Imprida HCT

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 

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1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 5 mg/160 mg/12.5 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains 5 mg of amlodipine (as amlodipine besylate), 160 mg of valsartan, 

and 12.5 mg of hydrochlorothiazide. 

 

For a full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet (tablet) 

 

White, ovaloid, biconvex tablets with bevelled edge, debossed “NVR” on one side and “VCL” on the 

other side. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment of essential hypertension as substitution therapy in adult patients whose blood pressure is 

adequately controlled on the combination of amlodipine, valsartan and hydrochlorothiazide (HCT), 

taken either as three single-component formulations or as a dual-component and a single-component 

formulation. 

 

4.2 Posology and method of administration 

 

Posology 

The recommended dose of Imprida HCT is one tablet per day, to be taken preferably in the morning. 

 

Before switching to Imprida HCT patients should be controlled on stable doses of the 

monocomponents taken at the same time. The dose of Imprida HCT should be based on the doses of 

the individual components of the combination at the time of switching. 

 

The maximum recommended dose of Imprida HCT is 10 mg/320 mg/25 mg. 

 

Special populations 

Renal impairment 

No adjustment of the initial dose is required for patients with mild to moderate renal impairment (see 

sections 4.4 and 5.2). Due to the hydrochlorothiazide component, Imprida HCT is contraindicated for 

use in patients with anuria (see section 4.3) and in patients with severe renal impairment (glomerular 

filtration rate (GFR) <30 ml/min/1.73 m
2
) (see sections 4.3, 4.4 and 5.2). 

 

Hepatic impairment 

Due to the valsartan component, Imprida HCT is contraindicated in patients with severe hepatic 

impairment (see section 4.3). In patients with mild to moderate hepatic impairment without 

cholestasis, the maximum recommended dose is 80 mg valsartan and therefore Imprida HCT is not 

suitable in this group of patients (see sections 4.3, 4.4 and 5.2). 

 

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Heart failure and coronary artery disease 

There is limited experience with the use of Imprida HCT, particulary at the maximum dose, in 

patients with heart failure and coronary artery disease. Caution is advised in patients with heart failure 

and coronary artery disease, particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg. 

 

Elderly (age 65 years or over) 

Caution, including more frequent monitoring of blood pressure, is recommended in elderly patients, 

particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in this 

patient population are limited. 

 

Paediatric population 

There is no relevant use of Imprida HCT in the paediatric population (patients below age 18 years) for 

the indication of essential hypertension. 

 

Method of administration 

Imprida HCT can be taken with or without food. The tablets should be swallowed whole with some 

water, at the same time of the day and preferably in the morning. 

 

4.3 Contraindications 

 

 Hypersensitivity to the active substances, to other sulphonamide derivatives, to dihydropyridine 

derivatives, or to any of the excipients. 

 Second and third trimesters of pregnancy (see sections 4.4 and 4.6). 

 Hepatic impairment, biliary cirrhosis or cholestasis. 

 Severe renal impairment (GFR <30 ml/min/1.73 m2), anuria and patients undergoing dialysis. 

 Refractory hypokalaemia, hyponatraemia, hypercalcaemia, and symptomatic hyperuricaemia. 

 

4.4 Special warnings and precautions for use 

 

Sodium- and/or volume-depleted patients 

Excessive hypotension, including orthostatic hypotension, was seen in 1.7% of patients treated with 

the maximum dose of Imprida HCT (10 mg/320 mg/25 mg) compared to 1.8% of 

valsartan/hydrochlorothiazide (320 mg/25 mg) patients, 0.4% of amlodipine/valsartan (10 mg/320 mg) 

patients, and 0.2% of hydrochlorothiazide/amlodipine (25 mg/10 mg) patients in a controlled trial in 

patients with moderate to severe uncomplicated hypertension. 

 

In sodium-depleted and/or volume-depleted patients, such as those receiving high doses of diuretics, 

symptomatic hypotension may occur after initiation of treatment with Imprida HCT. Imprida HCT 

should be used only after correction of any pre-existing sodium and/or volume depletion. 

 

If excessive hypotension occurs with Imprida HCT, the patient should be placed in the supine position 

and, if necessary, given an intravenous infusion of normal saline. Treatment can be continued once 

blood pressure has been stabilised. 

 

Serum electrolyte changes 

Amlodipine/valsartan/hydrochlorothiazide 

In the controlled trial of Imprida HCT, the counteracting effects of valsartan 320 mg and 

hydrochlorothiazide 25 mg on serum potassium approximately balanced each other in many patients. 

In other patients, one or the other effect may be dominant. Periodic determinations of serum 

electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals. 

 

Periodic determination of serum electrolytes and potassium in particular should be performed at 

appropriate intervals to detect possible electrolyte imbalance, especially in patients with other risk 

factors such as impaired renal function, treatment with other medicinal products or history of prior 

electrolyte imbalances. 

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Valsartan 

Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing 

potassium, or other medicinal products that may increase potassium levels (heparin, etc.) is not 

recommended. Monitoring of potassium should be undertaken as appropriate. 

 

Hydrochlorothiazide 

Treatment with Imprida HCT should only start after correction of hypokalaemia and any coexisting 

hypomagnesaemia. Thiazide diuretics can precipitate new onset hypokalaemia or exacerbate pre-

existing hypokalaemia. Thiazide diuretics should be administered with caution in patients with 

conditions involving enhanced potassium loss, for example salt-losing nephropathies and prerenal 

(cardiogenic) impairment of kidney function. If hypokalaemia develops during hydrochlorothiazide 

therapy, Imprida HCT should be discontinued until stable correction of the potassium balance. 

 

Thiazide diuretics can precipitate new onset hyponatraemia and hypochloroaemic alkalosis or 

exacerbate pre-existing hyponatraemia. Hyponatraemia, accompanied by neurological symptoms 

(nausea, progressive disorientation, apathy) has been observed. Treatment with hydrochlorothiazide 

should only be started after correction of pre-existing hyponatraemia. In case severe or rapid 

hyponatraemia develops during Imprida HCT therapy, the treatment should be discontinued until 

normalisation of natraemia. 

 

All patients receiving thiazide diuretics should be periodically monitored for imbalances in 

electrolytes, particularly potassium, sodium and magnesium. 

 

Renal impairment 

Thiazide diuretics may precipitate azotaemia in patients with chronic kidney disease. When Imprida 

HCT is used in patients with renal impairment periodic monitoring of serum electrolytes (including 

potassium), creatinine and uric acid serum levels is recommended. Imprida HCT is contraindicated in 

patients with severe renal impairment, anuria or undergoing dialysis (see section 4.3). 

 

No dosage adjustment of Imprida HCT is required for patients with mild to moderate renal 

impairment (GFR ≥30 ml/min/1.73 m
2
). 

 

Renal artery stenosis 

No data are available on the use of Imprida HCT in patients with unilateral or bilateral renal artery 

stenosis or stenosis to a solitary kidney. 

 

Kidney transplantation 

To date there is no experience of the safe use of Imprida HCT in patients who have had a recent 

kidney transplantation. 

 

Hepatic impairment 

Valsartan is mostly eliminated unchanged via the bile, whereas amlodipine is extensively metabolised 

by the liver. In patients with mild to moderate hepatic impairment without cholestasis, the maximum 

recommended dose is 80 mg valsartan, and therefore, Imprida HCT is not suitable in this group of 

patients (see sections 4.2, 4.3 and 5.2). 

 

Heart failure and coronary artery disease 

As a consequence of the inhibition of the renin-angiotensin-aldosterone system, changes in renal 

function may be anticipated in susceptible individuals. In patients with severe heart failure whose 

renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with 

angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been 

associated with oliguria and/or progressive azotaemia and (rarely) with acute renal failure and/or 

death. Similar outcomes have been reported with valsartan. 

 

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In a long-term, placebo-controlled study (PRAISE-2) of amlodipine in patients with NYHA (New 

York Heart Association Classification) III and IV heart failure of non-ischaemic aetiology, amlodipine 

was associated with increased reports of pulmonary oedema despite no significant difference in the 

incidence of worsening heart failure as compared to placebo. 

 

Caution is advised in patients with heart failure and coronary artery disease, particularly at the 

maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in these patient 

populations is limited. 

 

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy 

As with all other vasodilators, special caution is indicated in patients with aortic or mitral stenosis, or 

obstructive hypertrophic cardiomyopathy. 

 

Pregnancy 

Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless 

continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to 

alternative antihypertensive treatments which have an established safety profile for use in pregnancy. 

When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if 

appropriate, alternative therapy should be started (see sections 4.3 and 4.6). 

 

Primary hyperaldosteronism 

Patients with primary hyperaldosteronism should not be treated with the angiotensin II antagonist 

valsartan as their renin-angiotensin system is not activated. Therefore, Imprida HCT is not 

recommended in this population. 

 

Systemic lupus erythematosus 

Thiazide diuretics, including hydrochlorothiazide, have been reported to exacerbate or activate 

systemic lupus erythematosus. 

 

Other metabolic disturbances 

Thiazide diuretics, including hydrochlorothiazide, may alter glucose tolerance and raise serum levels 

of cholesterol, triglycerides and uric acid. In diabetic patients dosage adjustments of insulin or oral 

hypoglycaemic agents may be required. 

 

Due to the hydrochlorothiazide component, Imprida HCT is contraindicated in symptomatic 

hyperuricaemia. Hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of 

uric acid and may cause or exacerbate hyperuricaemia as well as precipitate gout in susceptible 

patients. 

 

Thiazides reduce urinary calcium excretion and may cause intermittant and slight elevation of serum 

calcium in the absence of known disorders of calcium metabolism. Imprida HCT is contraindicated in 

patients with hypercalcaemia and should only be used after correction of any pre-existing 

hypercalcaemia. Imprida HCT should be discontinued if hypercalcaemia develops during treatment. 

Serum levels of calcium should be periodically monitored during treatment with thiazides. Marked 

hypercalcaemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued 

before carrying out tests for parathyroid function. 

 

Photosensitivity 

Cases of photosensitivity reactions have been reported with thiazide diuretics (see section 4.8). If 

photosensitivity reaction occurs during treatment with Imprida HCT, it is recommended to stop the 

treatment. If a readministration of the diuretic is deemed necessary, it is recommended to protect 

exposed areas to the sun or to artificial UVA. 

 

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Acute angle-closure glaucoma 

Hydrochlorothiazide, a sulphonamide, has been associated with an idiosyncratic reaction resulting in 

acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased 

visual acuity or ocular pain and typically occur within hours to a week of treatment initiation. 

Untreated acute-angle closure glaucoma can lead to permanent vision loss. 

 

The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or 

surgical treatment may need to be considered if the intraocular pressure remains uncontrolled. Risk 

factors for developing acute angle closure glaucoma may include a history of sulphonamide or 

penicillin allergy. 

 

General 

Caution should be exercised in patients who have shown prior hypersensitivity to other angiotensin II 

receptor antagonists. Hypersensitivity reactions to hydrochlorothiazide are more likely in patients 

with allergy and asthma. 

 

Elderly (age 65 years or over) 

Caution, including more frequent monitoring of blood pressure, is recommended in elderly patients, 

particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in this 

patient population are limited. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

No formal interaction studies with other medicinal products were performed with Imprida HCT. Thus, 

only information on interactions with other medicinal products that are known for the individual 

active substances is provided in this section. 

 

However, it is important to take into account that Imprida HCT may increase the hypotensive effect of 

other antihypertensive agents. 

 

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Concomitant use not recommended 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Valsartan 

and 

HCT 

Lithium Reversible increases in serum lithium concentrations and 

toxicity have been reported during concurrent use of ACE 

inhibitors and thiazides such as hydrochlorothiazide. 

Despite the lack of experience with concomitant use of 

valsartan and lithium, this combination is not 

recommended. If the combination proves necessary, 

careful monitoring of serum lithium levels is 

recommended (see section 4.4). 

Valsartan Potassium-sparing 

diuretics, potassium 

supplements, salt 

substitutes containing 

potassium and other 

substances that may 

increase potassium 

levels 

If a medicinal product that affects potassium levels is 

considered necessary in combination with valsartan, 

frequent monitoring of potassium plasma levels is 

advised. 

Amlodipine Grapefruit or grapefruit 

juice 

Administration of amlodipine with grapefruit or grapefruit 

juice is not recommended as bioavailability may be 

increased in some patients, resulting in increased blood 

pressure lowering effects. 

 

Caution required with concomitant use 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Amlodipine CYP3A4 inhibitors 

(i.e. ketoconazole, 

itraconazole, ritonavir) 

Concomitant use of amlodipine with strong or moderate 

CYP3A4 inhibitors (protease inhibitors, azole antifungals, 

macrolides like erythromycin or clarithromycin, verapamil 

or diltiazem) may give rise to significant increase in 

amlodipine exposure. The clinical translation of these 

pharmacokinetic variations may be more pronounced in 

the elderly. Clinical monitoring and dose adjustment may 

thus be required. 

CYP3A4 inducers 

(anticonvulsant agents 

[e.g. carbamazepine, 

phenobarbital, 

phenytoin, 

fosphenytoin, 

primidone], rifampicin, 

Hypericum perforatum 

[St. John’s wort]) 

There is no data available regarding the effect of CYP3A4 

inducers on amlodipine. The concomitant use of CYP3A4 

inducers (e.g. rifampicin, Hypericum perforatum) may 

give a lower plasma concentration of amlodipine. 

Amlodipine should be used with caution together with 

CYP3A4 inducers. 

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 Simvastatin Co-administration of multiple doses of 10 mg amlodipine 

with 80 mg simvastatin resulted in a 77% increase in 

exposure to simvastatin compared to simvastatin alone. It 

is recommended to limit the dose of simvastatin to 20 mg 

daily in patients on amlodipine. 

Dantrolene (infusion) In animals, lethal ventricular fibrillation and 

cardiovascular collapse are observed in association with 

hyperkalaemia after administration of verapamil and 

intravenous dantrolene. Due to risk of hyperkalaemia, it is 

recommended that the co-administration of calcium 

channel blockers such as amlodipine be avoided in 

patients susceptible to malignant hyperthermia and in the 

management of malignant hyperthermia. 

Valsartan 

and HCT 

Non-steroidal anti-

inflammatory 

medicines (NSAIDs), 

including selective 

cyclooxygenase-2 

inhibitors (COX-2 

inhibitors), 

acetylsalicylic acid 

(>3 g/day), and non-

selective NSAIDs 

NSAIDS can attenuate the antihypertensive effect of both 

angiotensin II antagonists and hydrochlorothiazide when 

administered simultaneously. Furthermore, concomitant 

use of Imprida HCT and NSAIDs may lead to worsening 

of renal function and an increase in serum potassium. 

Therefore, monitoring of renal function at the beginning 

of the treatment is recommended, as well as adequate 

hydration of the patient. 

Valsartan Inhibitors of the uptake 

transporter (rifampicin, 

ciclosporin) or efflux 

transporter (ritonavir) 

The results of an in vitro study with human liver tissue 

indicate that valsartan is a substrate of the hepatic uptake 

transporter OATP1B1 and of the hepatic efflux 

transporter MRP2. Co-administration of inhibitors of the 

uptake transporter (rifampicin, ciclosporin) or efflux 

transporter (ritonavir) may increase the systemic exposure 

to valsartan. 

HCT Alcohol, barbiturates 

or narcotics 

Concomitant administration of thiazide diuretics with 

substances that also have a blood pressure lowering effect 

(e.g. by reducing sympathetic central nervous system 

activity or direct vasodilatation) may potentiate orthostatic 

hypotension. 

Amantadine Thiazides, including hydrochlorothiazide, may increase 

the risk of adverse reactions caused by amantadine. 

Anticholinergic agents 

and other medicinal 

products affecting 

gastric motility 

The bioavailability of thiazide-type diuretics may be 

increased by anticholinergic agents (e.g. atropine, 

biperiden), apparently due to a decrease in gastrointestinal 

motility and the stomach emptying rate. Conversely, it is 

anticipated that prokinetic substances such as cisapride 

may decrease the bioavailability of thiazide-type diuretics. 

Antidiabetic agents 

(e.g. insulin and oral 

antidiabetic agents) 

Thiazides may alter glucose tolerance. Dose adjustment of 

the antidiabetic medicinal product may be necessary. 

 Metformin Metformin should be used with caution because of the risk 

of lactic acidosis induced by possible functional renal 

failure linked to hydrochlorothiazide. 

Beta blockers and 

diazoxide 

Concomitant use of thiazide diuretics, including 

hydrochlorothiazide, with beta blockers may increase the 

risk of hyperglycaemia. Thiazide diuretics, including 

hydrochlorothiazide, may enhance the hyperglycaemic 

effect of diazoxide. 

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 Ciclosporin Concomitant treatment with ciclosporin may increase the 

risk of hyperuricaemia and gout-type complications. 

 Cytotoxic agents Thiazides, including hydrochlorothiazide, may reduce the 

renal excretion of cytotoxic agents (e.g. 

cyclophosphamide, methotrexate) and potentiate their 

myelosuppressive effects. 

 Digitalis glycosides Thiazide-induced hypokalaemia or hypomagnesaemia may 

occur as undesirable effects, favouring the onset of 

digitalis-induced cardiac arrhythmias. 

 Iodine contrasting 

agents 

In case of diuretic-induced dehydration, there is an 

increased risk of acute renal failure, especially with high 

doses of iodine products. Patients should be re-hydrated 

before the administration. 

 Ion exchange resins Absorption of thiazide diuretics, including 

hydrochlorothiazide, is decreased by cholestyramine or 

colestipol. This could result in sub-therapeutic effects of 

thiazide diuretics. However, staggering the dosage of 

hydrochlorothiazide and resin such that 

hydrochlorothiazide is administered at least 4 hours 

before or 4-6 hours after the administration of resins 

would potentially minimise the interaction. 

 Medicinal products 

affecting serum 

potassium level 

The hypokalaemic effect of hydrochlorothiazide may be 

increased by concomitant administration of kaliuretic 

diuretics, corticosteroids, laxatives, adrenocorticotropic 

hormone (ACTH), amphotericin, carbenoxolone, 

penicillin G and salicylic acid derivatives or 

antiarrhythmics. If these medicinal products are to be 

prescribed with the amlodipine /valsartan 

/hydrochlorothiazide combination, monitoring of 

potassium plasma levels is advised. 

 Medicinal products 

affecting serum sodium 

level 

The hyponatraemic effect of diuretics may be intensified 

by concomitant administration of medicinal products such 

as antidepressants, antipsychotics, antiepileptics, etc. 

Caution is indicated in long-term administration of these 

medicinal products. 

 Medicinal products 

that could induce 

torsades de pointes 

Due to the risk of hypokalaemia, hydrochlorothiazide 

should be administered with caution when associated with 

medicinal products that could induce torsades de pointes, 

in particular Class Ia and Class III antiarrhythmics and 

some antipsychotics. 

 Medicinal products 

used in the treatment of 

gout (probenecid, 

sulfinpyrazone and 

allopurinol) 

Dose adjustment of uricosuric medicinal products may be 

necessary as hydrochlorothiazide may raise the level of 

serum uric acid. Increase of dose of probenecid or 

sulfinpyrazone may be necessary. 

Co-administration of thiazide diuretics, including 

hydrochlorothiazide, may increase the incidence of 

hypersensitivity reactions to allopurinol. 

 Methyldopa There have been isolated reports of haemolytic anaemia 

occurring with concomitant use of hydrochlorothiazide 

and methyldopa. 

 Non-depolarising 

skeletal muscle 

relaxants (e.g. 

tubocurarine) 

Thiazides, including hydrochlorothiazide, potentiate the 

action of curare derivatives. 

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Other anti-hypertensive 

drugs 

Thiazides potentiate the antihypertensive action of other 

antihypertensive drugs (e.g. guanethidine, methyldopa, 

beta-blockers, vasodilators, calcium channel blockers, 

ACE inhibitors, ARBs and Direct Renin Inhibitors 

[DRIs]). 

Pressor amines (e.g. 

noradrenaline, 

adrenaline) 

Hydrochlorothiazide may reduce the response to pressor 

amines such as noradrenaline. The clinical significance of 

this effect is uncertain and not sufficient to preclude their 

use. 

Vitamin D and calcium 

salts 

Administration of thiazide diuretics, including 

hydrochlorothiazide, with vitamin D or with calcium salts 

may potentiate the rise in serum calcium. Concomitant use 

of thiazide type diuretics may lead to hypercalcaemia in 

patients pre-disposed for hypercalcaemia (e.g. 

hyperparathyroidism, malignancy or vitamin-D-mediated 

conditions) by increasing tubular calcium reabsorption. 

 

No interaction 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Valsartan  Others 

(cimetidine, warfarin, 

furosemide, digoxin, 

atenolol, indometacin, 

hydrochlorothiazide, 

amlodipine, 

glibenclamide) 

In monotherapy with valsartan, no interactions of clinical 

significance have been found with the following 

substances: cimetidine, warfarin, furosemide, digoxin, 

atenolol, indomethacin, hydrochlorothiazide, amlodipine, 

glibenclamide. 

 

Some of these substances could interact with the 

hydrochlorothiazide component of Imprida HCT (see 

interactions related to HCT). 

Amlodipine Others In clinical interaction studies, amlodipine did not affect 

the pharmacokinetics of atorvastatin, digoxin, warfarin or 

ciclosporin. 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

Amlodipine 

The safety of amlodipine in human pregnancy has not been established. In animal studies, 

reproductive toxicity was observed at high doses (see section 5.3). Use in pregnancy is only 

recommended when there is no safer alternative and when the disease itself carries greater risk for the 

mother and foetus. 

 

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Valsartan 

The use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during the first 

trimester of pregnancy (see section 4.4). The use of AIIRAs is contraindicated during the second and 

third trimesters of pregnancy (see sections 4.3 and 4.4). 

 

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors 

during the first trimester of pregnancy has not been conclusive; however a small increase in risk 

cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II 

Receptor Antagonists (AIIRAs), similar risks may exist for this class of drugs. Unless continued 

AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative 

antihypertensive treatments which have an established safety profile for use in pregnancy. When 

pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and if appropriate, 

alternative therapy should be started. 

 

Exposure to AIIRAs therapy during the second and third trimesters is known to induce human 

foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal 

toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3). 

 

Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check 

of renal function and skull is recommended. 

 

Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see sections 

4.3 and 4.4). 

 

Hydrochlorothiazide 

There is limited experience with hydrochlorothiazide during pregnancy, especially during the first 

trimester. Animal studies are insufficient. 

 

Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of 

hydrochlorothiazide, its use during the second and third trimester may compromise foeto-placental 

perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance 

and thrombocytopenia. 

 

Amlodipine/valsartan/hydrochlorothiazide 

There is no experience on the use of Imprida HCT in pregnant women. Based on the existing data 

with the components, the use of Imprida HCT is not recommended during first trimester and contra-

indicated during the second and third trimester of pregnancy (see sections 4.3 and 4.4). 

 

Breast-feeding 

No information is available regarding the use of valsartan and/or amlodipine during breast-feeding. 

Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing 

intense diuresis can inhibit milk production. The use of Imprida HCT during breast-feeding is not 

recommended. If Imprida HCT is used during breast-feeding, doses should be kept as low as possible. 

Alternative treatments with better established safety profiles during breast-feeding are preferable, 

especially while nursing a newborn or preterm infant. 

 

Fertility 

There are no clinical studies on fertility with Imprida HCT. 

 

Valsartan 

Valsartan had no adverse effects on the reproductive performance of male or female rats at oral doses 

up to 200 mg/kg/day. This dose is 6 times the maximum recommended human dose on a mg/m
2
 basis 

(calculations assume an oral dose of 320 mg/day and a 60-kg patient). 

 

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Amlodipine 

Reversible biochemical changes in the head of spermatozoa have been reported in some patients 

treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of 

amlodipine on fertility. In one rat study, adverse effects were found on male fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 

 

No studies on the effects on the ability to drive and use machines have been performed. When driving 

vehicles or using machines it should be taken into account that occasionally dizziness or weariness 

may occur. 

 

4.8 Undesirable effects 

 

The safety profile of Imprida HCT presented below is based on clinical studies performed with 

Imprida HCT and the known safety profile of the individual components amlodipine, valsartan and 

hydrochlorothiazide. 

 

Information on Imprida HCT 

The safety of Imprida HCT has been evaluated at its maximum dose of 10 mg/320 mg/25 mg in one 

controlled short-term (8 weeks) clinical study with 2,271 patients, 582 of whom received valsartan in 

combination with amlodipine and hydrochlorothiazide. Adverse reactions were generally mild and 

transient in nature and only infrequently required discontinuation of therapy. In this active controlled 

clinical trial, the most common reasons for discontinuation of therapy with Imprida HCT were 

dizziness and hypotension (0.7%). 

 

In the 8-week controlled clinical study, no significant new or unexpected adverse reactions were 

observed with triple therapy treatment compared to the known effects of the monotherapy or dual 

therapy components. 

 

In the 8-week controlled clinical study, changes in laboratory parameters observed with the 

combination of Imprida HCT were minor and consistent with the pharmacological mechanism of 

action of the monotherapy agents. The presence of valsartan in the triple combination attenuated the 

hypokalaemic effect of hydrochlorothiazide. 

 

The following adverse reactions, listed by MedDRA System Organ Class and frequency, concern 

Imprida HCT (amlodipine/valsartan/HCT) and amlodipine, valsartan and HCT individually. 

Very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1,000 to <1/100; rare: ≥1/10,000 to 

<1/1,000; very rare: <1/10,000, not known (cannot be estimated from the available data). 

 

MedDRA 

System Organ 

Class 

Adverse reactions Frequency    

Imprida 

HCT 

Amlodipine Valsartan HCT 

Blood and 

lymphatic system 

disorders 

Agranulocytosis, bone 

marrow depression 

-- -- -- Very rare 

Decrease in haemoglobin 

and in haematocrit 

-- -- Not known -- 

Haemolytic anaemia -- -- -- Very rare 

Leukopenia -- Very rare -- Very rare 

Neutropenia -- -- Not known -- 

Thrombocytopenia, 

sometimes with purpura 

-- Very rare Not known Rare 

Aplastic anaemia -- -- -- Not known 

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Immune system 

disorders 

Hypersensitivity -- Very rare Not known Very rare 

Metabolism and 

nutrition 

disorders 

Anorexia Uncommon -- -- -- 

Hypercalcaemia Uncommon -- -- Rare 

Hyperglycaemia -- Very rare -- Rare 

Hyperlipidaemia Uncommon -- -- -- 

Hyperuricaemia Uncommon -- -- Common 

Hypochloraemic alkalosis -- -- -- Very rare 

Hypokalaemia Common -- -- Very 

common 

Hypomagnesaemia -- -- -- Common 

Hyponatraemia Uncommon -- -- Common 

Worsening of diabetic 

metabolic state 

-- -- -- Rare 

Psychiatric 

disorders 

Depression -- -- -- Rare 

Insomnia/sleep disturbances Uncommon Uncommon -- Rare 

Mood swings -- Uncommon --  

Nervous system 

disorders 

Coordination abnormal Uncommon -- -- -- 

Dizziness Common Common -- Rare 

Dizziness postural, dizziness 

exertional 

Uncommon -- -- -- 

Dysgeusia Uncommon Uncommon -- -- 

Extrapyramidal syndrome -- Not known -- -- 

Headache Common Common -- Rare 

Hypertonia -- Very rare -- -- 

Lethargy Uncommon -- -- -- 

Paraesthesia Uncommon Uncommon -- Rare 

Peripheral neuropathy, 

neuropathy 

Uncommon Very rare -- -- 

Somnolence Uncommon Common -- -- 

Syncope Uncommon Uncommon -- -- 

Tremor -- Uncommon -- -- 

Eye disorders Acute angle-closure 

glaucoma 

-- -- -- Not known 

Visual impairment Uncommon Uncommon -- Rare 

Ear and labyrinth 

disorders 

Tinnitus -- Uncommon -- -- 

Vertigo Uncommon -- Uncommon -- 

Cardiac disorders Palpitations -- Common -- -- 

Tachycardia Uncommon -- -- -- 

Arrhythmias (including 

bradycardia, ventricular 

tachycardia, and atrial 

fibrillation) 

-- Very rare -- Rare 

Myocardial infarction -- Very rare -- -- 

Vascular 

disorders 

Flushing -- Common -- -- 

Hypotension Common Uncommon -- -- 

Orthostatic hypotension Uncommon -- -- Common 

Phlebitis, thrombophlebitis Uncommon -- -- -- 

Vasculitis -- Very rare Not known -- 

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Respiratory, 

thoracic and 

mediastinal 

disorders 

Cough Uncommon Very rare Uncommon -- 

Dyspnoea Uncommon Uncommon -- -- 

Respiratory distress, 

pulmonary oedema, 

pneumonitis 

-- -- -- Very rare 

Rhinitis -- Uncommon -- -- 

Throat irritation Uncommon -- -- -- 

Gastrointestinal 

disorders 

Abdominal discomfort, 

abdominal pain upper 

Uncommon Common Uncommon Rare 

Breath odour Uncommon -- -- -- 

Change of bowel habit -- Uncommon -- -- 

Constipation -- -- -- Rare 

Decreased appetite -- -- -- Common 

Diarrhoea Uncommon Uncommon -- Rare 

Dry mouth Uncommon Uncommon -- -- 

Dyspepsia Common Uncommon -- -- 

Gastritis -- Very rare -- -- 

Gingival hyperplasia -- Very rare -- -- 

Nausea Uncommon Common -- Common 

Pancreatitis -- Very rare -- Very rare 

Vomiting Uncommon Uncommon -- Common 

Hepatobiliary 

disorders 

Hepatic enzyme elevation, 

including increase of serum 

bilirubin 

-- Very rare Not known -- 

Hepatitis -- Very rare -- -- 

Intrahepatic cholestasis, 

jaundice 

-- Very rare -- Rare 

Skin and 

subcutaneous 

tissue disorders 

Alopecia -- Uncommon --  

Angioedema -- Very rare Not known -- 

Cutaneous lupus 

erythematosus-like 

reactions, reactivation of 

cutaneous lupus 

erythematosus 

-- -- -- Very rare 

Erythema multiforme -- Very rare -- Not known 

Exanthema -- Uncommon -- -- 

Hyperhidrosis Uncommon Uncommon -- -- 

Photosensitivity reaction* -- -- -- Rare 

Pruritus Uncommon Uncommon Not known -- 

Purpura -- Uncommon -- Rare 

Rash -- Uncommon Not known Common 

Skin discoloration -- Uncommon -- -- 

Urticaria and other forms of 

rash 

-- Very rare -- Common 

Vasculitis necrotising and 

toxic epidermal necrolysis 

-- -- -- Very rare 

Musculoskeletal 

and connective 

tissue disorders 

Arthralgia -- Uncommon -- -- 

Back pain Uncommon Uncommon -- -- 

Joint swelling Uncommon -- -- -- 

Muscle spasm Uncommon Uncommon -- Not known 

Muscular weakness Uncommon -- -- -- 

Myalgia Uncommon Uncommon Not known -- 

Pain in extremity Uncommon -- -- -- 

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Renal and 

urinary disorders 

Elevation of serum 

creatinine 

Uncommon -- Not known -- 

Micturition disorder  Uncommon   

Nocturia -- Uncommon -- -- 

Pollakiuria Common Uncommon   

Renal dysfunction -- -- -- Not known 

Renal failure acute Uncommon -- -- Not known 

Renal failure and 

impairment 

-- -- Not known Rare 

Reproductive 

system and 

breast disorders 

Impotence Uncommon Uncommon -- Common 

Gynaecomastia  Uncommon -- -- 

General 

disorders and 

administration 

site conditions 

Abasia, gait disturbance Uncommon -- -- -- 

Asthenia Uncommon Uncommon -- Not known 

Discomfort, malaise Uncommon Uncommon -- -- 

Fatigue Common Common Uncommon -- 

Non cardiac chest pain Uncommon Uncommon -- -- 

Oedema Common Common -- -- 

Pain -- Uncommon -- -- 

Pyrexia -- -- -- Not known 

Investigations Lipids increased  --  Very 

common 

Blood urea nitrogen 

increased 

Uncommon -- -- -- 

Blood uric acid increased Uncommon -- --  

Glycosuria    Rare 

Serum potassium decreased Uncommon  -- -- -- 

Serum potassium increased -- -- Not known -- 

Weight increase Uncommon Uncommon -- -- 

Weight decrease -- Uncommon -- -- 

 

* See section 4.4 Photosensitivity 

 

4.9 Overdose 

 

Symptoms 

There is no experience of overdose with Imprida HCT. The major symptom of overdose with 

valsartan is possibly pronounced hypotension with dizziness. Overdose with amlodipine may result in 

excessive peripheral vasodilation and, possibly, reflex tachycardia. Marked and potentially prolonged 

systemic hypotension, including shock with fatal outcome, have been reported with amlodipine. 

 

Treatment 

Amlodipine/Valsartan/Hydrochlorothiazide 

Clinically significant hypotension due to Imprida HCT overdose calls for active cardiovascular 

support, including frequent monitoring of cardiac and respiratory function, elevation of extremities, 

and attention to circulating fluid volume and urine output. A vasoconstrictor may be helpful in 

restoring vascular tone and blood pressure, provided that there is no contraindication to its use. 

Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. 

 

Amlodipine 

If ingestion is recent, induction of vomiting or gastric lavage may be considered. Administration of 

activated charcoal to healthy volunteers immediately or up to two hours after ingestion of amlodipine 

has been shown to significantly decrease amlodipine absorption. 

Amlodipine is unlikely to be removed by haemodialysis. 

 

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Valsartan 

Valsartan is unlikely to be removed by haemodialysis. 

 

Hydrochlorothiazide 

Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, 

hypochloraemia) and hypovolaemia resulting from excessive diuresis. The most common signs and 

symptoms of overdose are nausea and somnolence. Hypokalaemia may result in muscle spasms and or 

accentuate arrhythmia associated with the concomitant use of digitalis glycosides or certain anti-

arrhythmic medicinal products. 

The degree to which hydrochlorothiazide is removed by haemodialysis has not been established. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Angiotensin II antagonists, plain (valsartan), combinations with 

dihydropyridine derivatives (amlodipine) and thiazide diuretics (hydrochlorothiazide), ATC code: 

C09DX01 valsartan, amlodipine and hydrochlorothiazide. 

 

Imprida HCT combines three antihypertensive compounds with complementary mechanisms to 

control blood pressure in patients with essential hypertension: amlodipine belongs to the calcium 

antagonist class and valsartan to the angiotensin II antagonist class of medicines and 

hydrochlorothiazide belongs to the thiazide diuretics class of medicines. The combination of these 

substances has an additive antihypertensive effect. 

 

Amlodipine/Valsartan/Hydrochlorothiazide 

Imprida HCT was studied in a double-blind, active controlled study in hypertensive patients. A total 

of 2,271 patients with moderate to severe hypertension (mean baseline systolic/diastolic blood 

pressure was 170/107 mmHg) received treatments of amlodipine/valsartan/hydrochlorothiazide 

10 mg/320 mg/25 mg, valsartan/hydrochlorothiazide 320 mg/25 mg, amlodipine/valsartan 

10 mg/320 mg, or hydrochlorothiazide/amlodipine 25 mg/10 mg. At study initiation patients were 

assigned lower doses of their treatment combination and were titrated to their full treatment dose by 

week 2. 

 

At week 8, the mean reductions in systolic/diastolic blood pressure were 39.7/24.7 mmHg with 

Imprida HCT, 32.0/19.7 mmHg with valsartan/hydrochlorothiazide, 33.5/21.5 mmHg with 

amlodipine/valsartan, and 31.5/19.5 mmHg with amlodipine/hydrochlorothiazide. The triple 

combination therapy was statistically superior to each of the three dual combination treatments in 

reduction of diastolic and systolic blood pressures. The reductions in systolic/diastolic blood pressure 

with Imprida HCT were 7.6/5.0 mmHg greater than with valsartan/hydrochlorothiazide, 

6.2/3.3 mmHg greater than with amlodipine/valsartan, and 8.2/5.3 mmHg greater than with 

amlodipine/hydrochlorothiazide. The full blood pressure lowering effect was achieved 2 weeks after 

being on their maximal dose of Imprida HCT. Statistically greater proportions of patients achieved 

blood pressure control (<140/90 mmHg) with Imprida HCT (71%) compared to each of the three dual 

combination therapies (45-54%) (p<0.0001). 

 

In a subgroup of 283 patients focusing on ambulatory blood pressure monitoring, clinically and 

statistically superior reductions in 24-hour systolic and diastolic blood pressures were observed with 

the triple combination compared to valsartan/hydrochlorothiazide, valsartan/amlodipine, and 

hydrochlorothiazide/amlodipine. 

 

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Amlodipine 

The amlodipine component of Imprida HCT inhibits the transmembrane entry of calcium ions into 

cardiac and vascular smooth muscle. The mechanism of the antihypertensive action of amlodipine is 

due to a direct relaxant effect on vascular smooth muscle, causing reductions in peripheral vascular 

resistance and in blood pressure. Experimental data suggest that amlodipine binds to both 

dihydropyridine and non-dihydropyridine binding sites. The contractile processes of cardiac muscle 

and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into 

these cells through specific ion channels. 

 

Following administration of therapeutic doses to patients with hypertension, amlodipine produces 

vasodilation, resulting in a reduction of supine and standing blood pressures. These decreases in blood 

pressure are not accompanied by a significant change in heart rate or plasma catecholamine levels 

with chronic dosing. 

 

Plasma concentrations correlate with effect in both young and elderly patients. 

 

In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in a 

decrease in renal vascular resistance and increases in glomerular filtration rate and effective renal 

plasma flow, without change in filtration fraction or proteinuria. 

 

Valsartan 

Valsartan is an orally active, potent and specific angiotensin II receptor antagonist. It acts selectively 

on the receptor subtype AT1, which is responsible for the known actions of angiotensin II. 

 

Administration of valsartan to patients with hypertension results in a drop in blood pressure without 

affecting pulse rate. 

 

In most patients, after administration of a single oral dose, onset of antihypertensive activity occurs 

within 2 hours, and the peak drop in blood pressure is achieved within 4-6 hours. The 

antihypertensive effect persists over 24 hours after administration. During repeated administration, the 

maximum reduction in blood pressure with any dose is generally attained within 2-4 weeks. 

 

Hydrochlorothiazide 

The site of action of thiazide diuretics is primarily in the renal distal convoluted tubule. It has been 

shown that there is a high-affinity receptor in the renal cortex as the primary binding site for the 

thiazide diuretic action and inhibition of NaCl transport in the distal convoluted tubule. The mode of 

action of thiazides is through inhibition of the Na
+
Cl

-
 symporter perhaps by competing for the Cl

-
 site, 

thereby affecting electrolyte reabsorption mechanisms: directly increasing sodium and chloride 

excretion to an approximately equal extent, and indirectly, by this diuretic action, reducing plasma 

volume, with consequent increases in plasma renin activity, aldosterone secretion and urinary 

potassium loss, and a decrease in serum potassium. 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

Imprida HCT in all subsets of the paediatric population in essential hypertension. See section 4.2 for 

information on paediatric use. 

 

5.2 Pharmacokinetic properties 

 

Linearity 

Amlodipine, valsartan and hydrochlorothiazide exhibit linear pharmacokinetics. 

 

Amlodipine/valsartan/hydrochlorothiazide 

Following oral administration of Imprida HCT in normal healthy adults, peak plasma concentrations 

of amlodipine, valsartan and hydrochlorothiazide are reached in 6-8 hours, 3 hours, and 2 hours, 

respectively. The rate and extent of absorption of amlodipine, valsartan and hydrochlorothiazide from 

Imprida HCT are the same as when administered as individual dosage forms. 

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Amlodipine 

Absorption: After oral administration of therapeutic doses of amlodipine alone, peak plasma 

concentrations of amlodipine are reached in 6-12 hours. Absolute bioavailability has been calculated as 

between 64% and 80%. Amlodipine bioavailability is unaffected by food ingestion. 

 

Distribution: Volume of distribution is approximately 21 l/kg. In vitro studies with amlodipine have 

shown that approximately 97.5% of circulating drug is bound to plasma proteins. 

 

Biotransformation: Amlodipine is extensively (approximately 90%) metabolised in the liver to inactive 

metabolites. 

 

Elimination: Amlodipine elimination from plasma is biphasic, with a terminal elimination half-life of 

approximately 30 to 50 hours. Steady-state plasma levels are reached after continuous administration for 

7-8 days. Ten per cent of original amlodipine and 60% of amlodipine metabolites are excreted in urine. 

 

Valsartan 

Absorption: Following oral administration of valsartan alone, peak plasma concentrations of valsartan 

are reached in 2-4 hours. Mean absolute bioavailability is 23%. Food decreases exposure (as 

measured by AUC) to valsartan by about 40% and peak plasma concentration (Cmax) by about 50%, 

although from about 8 h post dosing plasma valsartan concentrations are similar for the fed and fasted 

groups. This reduction in AUC is not, however, accompanied by a clinically significant reduction in 

the therapeutic effect, and valsartan can therefore be given either with or without food. 

 

Distribution: The steady-state volume of distribution of valsartan after intravenous administration is 

about 17 litres, indicating that valsartan does not distribute into tissues extensively. Valsartan is 

highly bound to serum proteins (94-97%), mainly serum albumin. 

 

Biotransformation: Valsartan is not transformed to a high extent as only about 20% of dose is 

recovered as metabolites. A hydroxy metabolite has been identified in plasma at low concentrations 

(less than 10% of the valsartan AUC). This metabolite is pharmacologically inactive. 

 

Elimination: Valsartan is primarily eliminated in faeces (about 83% of dose) and urine (about 13% of 

dose), mainly as unchanged drug. Following intravenous administration, plasma clearance of valsartan 

is about 2 l/h and its renal clearance is 0.62 l/h (about 30% of total clearance). The half-life of 

valsartan is 6 hours. 

 

Hydrochlorothiazide 

Absorption: The absorption of hydrochlorothiazide, after an oral dose, is rapid (Tmax about 2 hours). 

The increase in mean AUC is linear and dose proportional in the therapeutic range. 

 

The effect of food on hydrochlorothiazide absorption, if any, has little clinical significance. Absolute 

bioavailability of hydrochlorothiazide is 70% after oral administration. 

 

Distribution: The apparent volume of distribution is 4-8 l/kg. Circulating hydrochlorothiazide is 

bound to serum proteins (40-70%), mainly serum albumin. Hydrochlorothiazide also accumulates in 

erythrocytes at approximately 3 times the level in plasma. 

 

Biotransformation: Hydrochlorothiazide is eliminated predominantly as unchanged compound. 

 

Elimination: Hydrochlorothiazide is eliminated from plasma with a half-life averaging 6 to 15 hours 

in the terminal elimination phase. There is no change in the kinetics of hydrochlorothiazide on 

repeated dosing, and accumulation is minimal when dosed once daily. More than 95% of the absorbed 

dose is being excreted as unchanged compound in the urine. The renal clearance is composed of 

passive filtration and active secretion into the renal tubule. 

 

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Special populations 

Paediatric patients (age below 18 years) 

No pharmacokinetic data are available in the paediatric population. 

 

Elderly (age 65 years or over) 

Time to peak plasma amlodipine concentrations is similar in young and elderly patients. In elderly 

patients, amlodipine clearance tends to decline, causing increases in the area under the curve (AUC) 

and elimination half-life. Mean systemic AUC of valsartan is higher by 70% in the elderly than in the 

young, therefore caution is required when increasing the dosage. 

 

Systemic exposure to valsartan is slightly elevated in the elderly as compared to the young, but this 

has not been shown to have any clinical significance. 

 

Limited data suggest that the systemic clearance of hydrochlorothiazide is reduced in both healthy and 

hypertensive elderly subjects compared to young healthy volunteers. 

 

Since the three components are equally well tolerated in younger and elderly patients, normal dose 

regimens are recommended (see section 4.2). 

 

Renal impairment 

The pharmacokinetics of amlodipine are not significantly influenced by renal impairment. As 

expected for a compound where renal clearance accounts for only 30% of total plasma clearance, no 

correlation was seen between renal function and systemic exposure to valsartan. 

 

Patients with mild to moderate renal impairment may therefore receive the usual initial dose (see 

sections 4.2 and 4.4). 

 

In the presence of renal impairment, mean peak plasma levels and AUC values of hydrochlorothiazide 

are increased and the urinary excretion rate is reduced. In patients with mild to moderate renal 

impairment, a 3-fold increase in hydrochlorothiazide AUC has been observed. In patients with severe 

renal impairment an 8-fold increase in AUC has been observed. Imprida HCT is contraindicated in 

patients with severe renal impairment, anuria or undergoing dialysis (see section 4.3). 

 

Hepatic impairment 

Patients with hepatic insufficiency have decreased clearance of amlodipine with resulting increase of 

approximately 40–60% in AUC. On average, in patients with mild to moderate chronic liver disease, 

exposure (measured by AUC values) to valsartan is twice that found in healthy volunteers (matched 

by age, sex and weight). Due to the valsartan component, Imprida HCT is contraindicated in patients 

with hepatic impairment (see sections 4.2 and 4.3). 

 

5.3 Preclinical safety data 

 

Amlodipine/Valsartan/Hydrochlorothiazide 

In a variety of preclinical safety studies conducted in several animal species with amlodipine, 

valsartan, hydrochlorothiazide, valsartan/hydrochlorothiazide, amlodipine/valsartan and 

amlodipine/valsartan/hydrochlorothiazide (Imprida HCT), there was no evidence of systemic or target 

organ toxicity that would adversely affect the development of Imprida HCT for clinical use in 

humans. 

 

Preclinical safety studies of up to 13 weeks in duration were conducted with 

amlodipine/valsartan/hydrochlorothiazide in rats. The combination resulted in expected reduction of 

red blood cell mass (erythrocytes, haemoglobin, haematocrit, and reticulocytes), increase in serum 

urea, increase in serum creatinine, increase in serum potassium, juxtaglomerular (JG) hyperplasia in 

the kidney and focal erosions in the glandular stomach in rats. All these changes were reversible after 

a 4-week recovery period and were considered to be exaggerated pharmacological effects. 

 

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The amlodipine/valsartan/hydrochlorothiazide combination was not tested for genotoxicity or 

carcinogenicity as there was no evidence of any interaction between these substances, which have 

been on the market for a long time. However, amlodipine, valsartan and hydrochlorothiazide have 

been tested individually for genotoxicity and carcinogenicity with negative results. 

 

Amlodipine 

Reproductive toxicology 

Reproductive studies in rats and mice have shown delayed date of delivery, prolonged duration of 

labour and decreased pup survival at dosages approximately 50 times greater than the maximum 

recommended dosage for humans based on mg/kg. 

 

Impairment of fertility 

There was no effect on the fertility of rats treated with amlodipine (males for 64 days and females 

14 days prior to mating) at doses up to 10 mg/kg/day (8 times* the maximum recommended human 

dose of 10 mg on a mg/m
2
 basis). In another rat study in which male rats were treated with amlodipine 

besilate for 30 days at a dose comparable with the human dose based on mg/kg, decreased plasma 

follicle-stimulating hormone and testosterone were found as well as decreases in sperm density and in 

the number of mature spermatids and Sertoli cells. 

 

Carcinogenesis, mutagenesis 

Rats and mice treated with amlodipine in the diet for two years, at concentrations calculated to 

provide daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day showed no evidence of carcinogenicity. 

The highest dose (for mice, similar to, and for rats twice* the maximum recommended clinical dose of 

10 mg on a mg/m
2
 basis) was close to the maximum tolerated dose for mice but not for rats. 

 

Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels. 

 

* Based on patient weight of 50 kg 

 

Valsartan 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential. 

 

In rats, maternally toxic doses (600 mg/kg/day) during the last days of gestation and lactation led to 

lower survival, lower weight gain and delayed development (pinna detachment and ear-canal opening) 

in the offspring (see section 4.6). These doses in rats (600 mg/kg/day) are approximately 18 times the 

maximum recommended human dose on a mg/m
2 
basis (calculations assume an oral dose of 

320 mg/day and a 60-kg patient). 

 

In non-clinical safety studies, high doses of valsartan (200 to 600 mg/kg body weight) caused in rats a 

reduction of red blood cell parameters (erythrocytes, haemoglobin, haematocrit) and evidence of 

changes in renal haemodynamics (slightly raised plasma urea, and renal tubular hyperplasia and 

basophilia in males). These doses in rats (200 and 600 mg/kg/day) are approximately 6 and 18 times 

the maximum recommended human dose on a mg/m
2
 basis (calculations assume an oral dose of 

320 mg/day and a 60-kg patient). 

 

In marmosets at similar doses, the changes were similar though more severe, particularly in the kidney 

where the changes developed to a nephropathy which included raised urea and creatinine. 

 

Hypertrophy of the renal juxtaglomerular cells was also seen in both species. All changes were 

considered to be caused by the pharmacological action of valsartan which produces prolonged 

hypotension, particularly in marmosets. For therapeutic doses of valsartan in humans, the hypertrophy 

of the renal juxtaglomerular cells does not seem to have any relevance. 

 

 

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6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Tablet core 

Cellulose microcrystalline 

Crospovidone 

Silica, colloidal anhydrous 

Magnesium stearate 

 

Coating 

Hypromellose 

Titanium dioxide (E171) 

Macrogol 4000 

Talc 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

2 years 

 

6.4 Special precautions for storage 

 

Do not store above 30°C. 

 

Store in the original package in order to protect from moisture. 

 

6.5 Nature and contents of container 

 

PVC/PVDC blisters. One blister contains 7, 10 or 14 film-coated tablets. 

Pack sizes: 14, 28, 30, 56, 90, 98 or 280 film-coated tablets. 

Multipacks of 280 tablets, comprising 20 cartons, each containing 14 tablets. 

 

PVC/PVDC perforated unit dose blisters for hospital use: 

Pack sizes: 56, 98 or 280 film-coated tablets 

Multipacks of 280 tablets, comprising 4 cartons, each containing 70 tablets. 

 

Not all pack sizes or strengths may be marketed. 

 

6.6 Special precautions for disposal and other handling 

 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

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8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/001-012 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

15.10.2009 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

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23 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/160 mg/12.5 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains 10 mg of amlodipine (as amlodipine besylate), 160 mg of valsartan, 

and 12.5 mg of hydrochlorothiazide. 

 

For a full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet (tablet) 

 

Pale yellow, ovaloid, biconvex tablets with bevelled edge, debossed “NVR” on one side and “VDL” 

on the other side. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment of essential hypertension as substitution therapy in adult patients whose blood pressure is 

adequately controlled on the combination of amlodipine, valsartan and hydrochlorothiazide (HCT), 

taken either as three single-component formulations or as a dual-component and a single-component 

formulation. 

 

4.2 Posology and method of administration 

 

Posology 

The recommended dose of Imprida HCT is one tablet per day, to be taken preferably in the morning. 

 

Before switching to Imprida HCT patients should be controlled on stable doses of the 

monocomponents taken at the same time. The dose of Imprida HCT should be based on the doses of 

the individual components of the combination at the time of switching. 

 

The maximum recommended dose of Imprida HCT is 10 mg/320 mg/25 mg. 

 

Special populations 

Renal impairment 

No adjustment of the initial dose is required for patients with mild to moderate renal impairment (see 

sections 4.4 and 5.2). Due to the hydrochlorothiazide component, Imprida HCT is contraindicated for 

use in patients with anuria (see section 4.3) and in patients with severe renal impairment (glomerular 

filtration rate (GFR) <30 ml/min/1.73 m
2
) (see sections 4.3, 4.4 and 5.2). 

 

Hepatic impairment 

Due to the valsartan component, Imprida HCT is contraindicated in patients with severe hepatic 

impairment (see section 4.3). In patients with mild to moderate hepatic impairment without 

cholestasis, the maximum recommended dose is 80 mg valsartan and therefore Imprida HCT is not 

suitable in this group of patients (see sections 4.3, 4.4 and 5.2). 

 

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24 

Heart failure and coronary artery disease 

There is limited experience with the use of Imprida HCT, particulary at the maximum dose, in 

patients with heart failure and coronary artery disease. Caution is advised in patients with heart failure 

and coronary artery disease, particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg. 

 

Elderly (age 65 years or over) 

Caution, including more frequent monitoring of blood pressure, is recommended in elderly patients, 

particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in this 

patient population are limited. 

 

Paediatric population 

There is no relevant use of Imprida HCT in the paediatric population (patients below age 18 years) for 

the indication of essential hypertension. 

 

Method of administration 

Imprida HCT can be taken with or without food. The tablets should be swallowed whole with some 

water, at the same time of the day and preferably in the morning. 

 

4.3 Contraindications 

 

 Hypersensitivity to the active substances, to other sulphonamide derivatives, to dihydropyridine 

derivatives, or to any of the excipients. 

 Second and third trimesters of pregnancy (see sections 4.4 and 4.6). 

 Hepatic impairment, biliary cirrhosis or cholestasis. 

 Severe renal impairment (GFR <30 ml/min/1.73 m2), anuria and patients undergoing dialysis. 

 Refractory hypokalaemia, hyponatraemia, hypercalcaemia, and symptomatic hyperuricaemia. 

 

4.4 Special warnings and precautions for use 

 

Sodium- and/or volume-depleted patients 

Excessive hypotension, including orthostatic hypotension, was seen in 1.7% of patients treated with 

the maximum dose of Imprida HCT (10 mg/320 mg/25 mg) compared to 1.8% of 

valsartan/hydrochlorothiazide (320 mg/25 mg) patients, 0.4% of amlodipine/valsartan (10 mg/320 mg) 

patients, and 0.2% of hydrochlorothiazide/amlodipine (25 mg/10 mg) patients in a controlled trial in 

patients with moderate to severe uncomplicated hypertension. 

 

In sodium-depleted and/or volume-depleted patients, such as those receiving high doses of diuretics, 

symptomatic hypotension may occur after initiation of treatment with Imprida HCT. Imprida HCT 

should be used only after correction of any pre-existing sodium and/or volume depletion. 

 

If excessive hypotension occurs with Imprida HCT, the patient should be placed in the supine position 

and, if necessary, given an intravenous infusion of normal saline. Treatment can be continued once 

blood pressure has been stabilised. 

 

Serum electrolyte changes 

Amlodipine/valsartan/hydrochlorothiazide 

In the controlled trial of Imprida HCT, the counteracting effects of valsartan 320 mg and 

hydrochlorothiazide 25 mg on serum potassium approximately balanced each other in many patients. 

In other patients, one or the other effect may be dominant. Periodic determinations of serum 

electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals. 

 

Periodic determination of serum electrolytes and potassium in particular should be performed at 

appropriate intervals to detect possible electrolyte imbalance, especially in patients with other risk 

factors such as impaired renal function, treatment with other medicinal products or history of prior 

electrolyte imbalances. 

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25 

 

Valsartan 

Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing 

potassium, or other medicinal products that may increase potassium levels (heparin, etc.) is not 

recommended. Monitoring of potassium should be undertaken as appropriate. 

 

Hydrochlorothiazide 

Treatment with Imprida HCT should only start after correction of hypokalaemia and any coexisting 

hypomagnesaemia. Thiazide diuretics can precipitate new onset hypokalaemia or exacerbate pre-

existing hypokalaemia. Thiazide diuretics should be administered with caution in patients with 

conditions involving enhanced potassium loss, for example salt-losing nephropathies and prerenal 

(cardiogenic) impairment of kidney function. If hypokalaemia develops during hydrochlorothiazide 

therapy, Imprida HCT should be discontinued until stable correction of the potassium balance. 

 

Thiazide diuretics can precipitate new onset hyponatraemia and hypochloroaemic alkalosis or 

exacerbate pre-existing hyponatraemia. Hyponatraemia, accompanied by neurological symptoms 

(nausea, progressive disorientation, apathy) has been observed. Treatment with hydrochlorothiazide 

should only be started after correction of pre-existing hyponatraemia. In case severe or rapid 

hyponatraemia develops during Imprida HCT therapy, the treatment should be discontinued until 

normalisation of natraemia. 

 

All patients receiving thiazide diuretics should be periodically monitored for imbalances in 

electrolytes, particularly potassium, sodium and magnesium. 

 

Renal impairment 

Thiazide diuretics may precipitate azotaemia in patients with chronic kidney disease. When Imprida 

HCT is used in patients with renal impairment periodic monitoring of serum electrolytes (including 

potassium), creatinine and uric acid serum levels is recommended. Imprida HCT is contraindicated in 

patients with severe renal impairment, anuria or undergoing dialysis (see section 4.3). 

 

No dosage adjustment of Imprida HCT is required for patients with mild to moderate renal 

impairment (GFR ≥30 ml/min/1.73 m
2
). 

 

Renal artery stenosis 

No data are available on the use of Imprida HCT in patients with unilateral or bilateral renal artery 

stenosis or stenosis to a solitary kidney. 

 

Kidney transplantation 

To date there is no experience of the safe use of Imprida HCT in patients who have had a recent 

kidney transplantation. 

 

Hepatic impairment 

Valsartan is mostly eliminated unchanged via the bile, whereas amlodipine is extensively metabolised 

by the liver. In patients with mild to moderate hepatic impairment without cholestasis, the maximum 

recommended dose is 80 mg valsartan, and therefore, Imprida HCT is not suitable in this group of 

patients (see sections 4.2, 4.3 and 5.2). 

 

Heart failure and coronary artery disease 

As a consequence of the inhibition of the renin-angiotensin-aldosterone system, changes in renal 

function may be anticipated in susceptible individuals. In patients with severe heart failure whose 

renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with 

angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been 

associated with oliguria and/or progressive azotaemia and (rarely) with acute renal failure and/or 

death. Similar outcomes have been reported with valsartan. 

 

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26 

In a long-term, placebo-controlled study (PRAISE-2) of amlodipine in patients with NYHA (New 

York Heart Association Classification) III and IV heart failure of non-ischaemic aetiology, amlodipine 

was associated with increased reports of pulmonary oedema despite no significant difference in the 

incidence of worsening heart failure as compared to placebo. 

 

Caution is advised in patients with heart failure and coronary artery disease, particularly at the 

maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in these patient 

populations is limited. 

 

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy 

As with all other vasodilators, special caution is indicated in patients with aortic or mitral stenosis, or 

obstructive hypertrophic cardiomyopathy. 

 

Pregnancy 

Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless 

continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to 

alternative antihypertensive treatments which have an established safety profile for use in pregnancy. 

When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if 

appropriate, alternative therapy should be started (see sections 4.3 and 4.6). 

 

Primary hyperaldosteronism 

Patients with primary hyperaldosteronism should not be treated with the angiotensin II antagonist 

valsartan as their renin-angiotensin system is not activated. Therefore, Imprida HCT is not 

recommended in this population. 

 

Systemic lupus erythematosus 

Thiazide diuretics, including hydrochlorothiazide, have been reported to exacerbate or activate 

systemic lupus erythematosus. 

 

Other metabolic disturbances 

Thiazide diuretics, including hydrochlorothiazide, may alter glucose tolerance and raise serum levels 

of cholesterol, triglycerides and uric acid. In diabetic patients dosage adjustments of insulin or oral 

hypoglycaemic agents may be required. 

 

Due to the hydrochlorothiazide component, Imprida HCT is contraindicated in symptomatic 

hyperuricaemia. Hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of 

uric acid and may cause or exacerbate hyperuricaemia as well as precipitate gout in susceptible 

patients. 

 

Thiazides reduce urinary calcium excretion and may cause intermittant and slight elevation of serum 

calcium in the absence of known disorders of calcium metabolism. Imprida HCT is contraindicated in 

patients with hypercalcaemia and should only be used after correction of any pre-existing 

hypercalcaemia. Imprida HCT should be discontinued if hypercalcaemia develops during treatment. 

Serum levels of calcium should be periodically monitored during treatment with thiazides. Marked 

hypercalcaemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued 

before carrying out tests for parathyroid function. 

 

Photosensitivity 

Cases of photosensitivity reactions have been reported with thiazide diuretics (see section 4.8). If 

photosensitivity reaction occurs during treatment with Imprida HCT, it is recommended to stop the 

treatment. If a readministration of the diuretic is deemed necessary, it is recommended to protect 

exposed areas to the sun or to artificial UVA. 

 

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Acute angle-closure glaucoma 

Hydrochlorothiazide, a sulphonamide, has been associated with an idiosyncratic reaction resulting in 

acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased 

visual acuity or ocular pain and typically occur within hours to a week of treatment initiation. 

Untreated acute-angle closure glaucoma can lead to permanent vision loss. 

 

The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or 

surgical treatment may need to be considered if the intraocular pressure remains uncontrolled. Risk 

factors for developing acute angle closure glaucoma may include a history of sulphonamide or 

penicillin allergy. 

 

General 

Caution should be exercised in patients who have shown prior hypersensitivity to other angiotensin II 

receptor antagonists. Hypersensitivity reactions to hydrochlorothiazide are more likely in patients 

with allergy and asthma. 

 

Elderly (age 65 years or over) 

Caution, including more frequent monitoring of blood pressure, is recommended in elderly patients, 

particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in this 

patient population are limited. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

No formal interaction studies with other medicinal products were performed with Imprida HCT. Thus, 

only information on interactions with other medicinal products that are known for the individual 

active substances is provided in this section. 

 

However, it is important to take into account that Imprida HCT may increase the hypotensive effect of 

other antihypertensive agents. 

 

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Concomitant use not recommended 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Valsartan 

and 

HCT 

Lithium Reversible increases in serum lithium concentrations and 

toxicity have been reported during concurrent use of ACE 

inhibitors and thiazides such as hydrochlorothiazide. 

Despite the lack of experience with concomitant use of 

valsartan and lithium, this combination is not 

recommended. If the combination proves necessary, 

careful monitoring of serum lithium levels is 

recommended (see section 4.4). 

Valsartan Potassium-sparing 

diuretics, potassium 

supplements, salt 

substitutes containing 

potassium and other 

substances that may 

increase potassium 

levels 

If a medicinal product that affects potassium levels is 

considered necessary in combination with valsartan, 

frequent monitoring of potassium plasma levels is 

advised. 

Amlodipine Grapefruit or grapefruit 

juice 

Administration of amlodipine with grapefruit or grapefruit 

juice is not recommended as bioavailability may be 

increased in some patients, resulting in increased blood 

pressure lowering effects. 

 

Caution required with concomitant use 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Amlodipine CYP3A4 inhibitors 

(i.e. ketoconazole, 

itraconazole, ritonavir) 

Concomitant use of amlodipine with strong or moderate 

CYP3A4 inhibitors (protease inhibitors, azole antifungals, 

macrolides like erythromycin or clarithromycin, verapamil 

or diltiazem) may give rise to significant increase in 

amlodipine exposure. The clinical translation of these 

pharmacokinetic variations may be more pronounced in 

the elderly. Clinical monitoring and dose adjustment may 

thus be required. 

CYP3A4 inducers 

(anticonvulsant agents 

[e.g. carbamazepine, 

phenobarbital, 

phenytoin, 

fosphenytoin, 

primidone], rifampicin, 

Hypericum perforatum 

[St. John’s wort]) 

There is no data available regarding the effect of CYP3A4 

inducers on amlodipine. The concomitant use of CYP3A4 

inducers (e.g. rifampicin, Hypericum perforatum) may 

give a lower plasma concentration of amlodipine. 

Amlodipine should be used with caution together with 

CYP3A4 inducers. 

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29 

 

 Simvastatin Co-administration of multiple doses of 10 mg amlodipine 

with 80 mg simvastatin resulted in a 77% increase in 

exposure to simvastatin compared to simvastatin alone. It 

is recommended to limit the dose of simvastatin to 20 mg 

daily in patients on amlodipine. 

Dantrolene (infusion) In animals, lethal ventricular fibrillation and 

cardiovascular collapse are observed in association with 

hyperkalaemia after administration of verapamil and 

intravenous dantrolene. Due to risk of hyperkalaemia, it is 

recommended that the co-administration of calcium 

channel blockers such as amlodipine be avoided in 

patients susceptible to malignant hyperthermia and in the 

management of malignant hyperthermia. 

Valsartan 

and HCT 

Non-steroidal anti-

inflammatory 

medicines (NSAIDs), 

including selective 

cyclooxygenase-2 

inhibitors (COX-2 

inhibitors), 

acetylsalicylic acid 

(>3 g/day), and non-

selective NSAIDs 

NSAIDS can attenuate the antihypertensive effect of both 

angiotensin II antagonists and hydrochlorothiazide when 

administered simultaneously. Furthermore, concomitant 

use of Imprida HCT and NSAIDs may lead to worsening 

of renal function and an increase in serum potassium. 

Therefore, monitoring of renal function at the beginning 

of the treatment is recommended, as well as adequate 

hydration of the patient. 

Valsartan Inhibitors of the uptake 

transporter (rifampicin, 

ciclosporin) or efflux 

transporter (ritonavir) 

The results of an in vitro study with human liver tissue 

indicate that valsartan is a substrate of the hepatic uptake 

transporter OATP1B1 and of the hepatic efflux 

transporter MRP2. Co-administration of inhibitors of the 

uptake transporter (rifampicin, ciclosporin) or efflux 

transporter (ritonavir) may increase the systemic exposure 

to valsartan. 

HCT Alcohol, barbiturates 

or narcotics 

Concomitant administration of thiazide diuretics with 

substances that also have a blood pressure lowering effect 

(e.g. by reducing sympathetic central nervous system 

activity or direct vasodilatation) may potentiate orthostatic 

hypotension. 

Amantadine Thiazides, including hydrochlorothiazide, may increase 

the risk of adverse reactions caused by amantadine. 

Anticholinergic agents 

and other medicinal 

products affecting 

gastric motility 

The bioavailability of thiazide-type diuretics may be 

increased by anticholinergic agents (e.g. atropine, 

biperiden), apparently due to a decrease in gastrointestinal 

motility and the stomach emptying rate. Conversely, it is 

anticipated that prokinetic substances such as cisapride 

may decrease the bioavailability of thiazide-type diuretics. 

Antidiabetic agents 

(e.g. insulin and oral 

antidiabetic agents) 

Thiazides may alter glucose tolerance. Dose adjustment of 

the antidiabetic medicinal product may be necessary. 

 Metformin Metformin should be used with caution because of the risk 

of lactic acidosis induced by possible functional renal 

failure linked to hydrochlorothiazide. 

Beta blockers and 

diazoxide 

Concomitant use of thiazide diuretics, including 

hydrochlorothiazide, with beta blockers may increase the 

risk of hyperglycaemia. Thiazide diuretics, including 

hydrochlorothiazide, may enhance the hyperglycaemic 

effect of diazoxide. 

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 Ciclosporin Concomitant treatment with ciclosporin may increase the 

risk of hyperuricaemia and gout-type complications. 

 Cytotoxic agents Thiazides, including hydrochlorothiazide, may reduce the 

renal excretion of cytotoxic agents (e.g. 

cyclophosphamide, methotrexate) and potentiate their 

myelosuppressive effects. 

 Digitalis glycosides Thiazide-induced hypokalaemia or hypomagnesaemia may 

occur as undesirable effects, favouring the onset of 

digitalis-induced cardiac arrhythmias. 

 Iodine contrasting 

agents 

In case of diuretic-induced dehydration, there is an 

increased risk of acute renal failure, especially with high 

doses of iodine products. Patients should be re-hydrated 

before the administration. 

 Ion exchange resins Absorption of thiazide diuretics, including 

hydrochlorothiazide, is decreased by cholestyramine or 

colestipol. This could result in sub-therapeutic effects of 

thiazide diuretics. However, staggering the dosage of 

hydrochlorothiazide and resin such that 

hydrochlorothiazide is administered at least 4 hours 

before or 4-6 hours after the administration of resins 

would potentially minimise the interaction. 

 Medicinal products 

affecting serum 

potassium level 

The hypokalaemic effect of hydrochlorothiazide may be 

increased by concomitant administration of kaliuretic 

diuretics, corticosteroids, laxatives, adrenocorticotropic 

hormone (ACTH), amphotericin, carbenoxolone, 

penicillin G and salicylic acid derivatives or 

antiarrhythmics. If these medicinal products are to be 

prescribed with the amlodipine /valsartan 

/hydrochlorothiazide combination, monitoring of 

potassium plasma levels is advised. 

 Medicinal products 

affecting serum sodium 

level 

The hyponatraemic effect of diuretics may be intensified 

by concomitant administration of medicinal products such 

as antidepressants, antipsychotics, antiepileptics, etc. 

Caution is indicated in long-term administration of these 

medicinal products. 

 Medicinal products 

that could induce 

torsades de pointes 

Due to the risk of hypokalaemia, hydrochlorothiazide 

should be administered with caution when associated with 

medicinal products that could induce torsades de pointes, 

in particular Class Ia and Class III antiarrhythmics and 

some antipsychotics. 

 Medicinal products 

used in the treatment of 

gout (probenecid, 

sulfinpyrazone and 

allopurinol) 

Dose adjustment of uricosuric medicinal products may be 

necessary as hydrochlorothiazide may raise the level of 

serum uric acid. Increase of dose of probenecid or 

sulfinpyrazone may be necessary. 

Co-administration of thiazide diuretics, including 

hydrochlorothiazide, may increase the incidence of 

hypersensitivity reactions to allopurinol. 

 Methyldopa There have been isolated reports of haemolytic anaemia 

occurring with concomitant use of hydrochlorothiazide 

and methyldopa. 

 Non-depolarising 

skeletal muscle 

relaxants (e.g. 

tubocurarine) 

Thiazides, including hydrochlorothiazide, potentiate the 

action of curare derivatives. 

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Other anti-hypertensive 

drugs 

Thiazides potentiate the antihypertensive action of other 

antihypertensive drugs (e.g. guanethidine, methyldopa, 

beta-blockers, vasodilators, calcium channel blockers, 

ACE inhibitors, ARBs and Direct Renin Inhibitors 

[DRIs]). 

Pressor amines (e.g. 

noradrenaline, 

adrenaline) 

Hydrochlorothiazide may reduce the response to pressor 

amines such as noradrenaline. The clinical significance of 

this effect is uncertain and not sufficient to preclude their 

use. 

Vitamin D and calcium 

salts 

Administration of thiazide diuretics, including 

hydrochlorothiazide, with vitamin D or with calcium salts 

may potentiate the rise in serum calcium. Concomitant use 

of thiazide type diuretics may lead to hypercalcaemia in 

patients pre-disposed for hypercalcaemia (e.g. 

hyperparathyroidism, malignancy or vitamin-D-mediated 

conditions) by increasing tubular calcium reabsorption. 

 

No interaction 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Valsartan  Others 

(cimetidine, warfarin, 

furosemide, digoxin, 

atenolol, indometacin, 

hydrochlorothiazide, 

amlodipine, 

glibenclamide) 

In monotherapy with valsartan, no interactions of clinical 

significance have been found with the following 

substances: cimetidine, warfarin, furosemide, digoxin, 

atenolol, indomethacin, hydrochlorothiazide, amlodipine, 

glibenclamide. 

 

Some of these substances could interact with the 

hydrochlorothiazide component of Imprida HCT (see 

interactions related to HCT). 

Amlodipine Others In clinical interaction studies, amlodipine did not affect 

the pharmacokinetics of atorvastatin, digoxin, warfarin or 

ciclosporin. 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

Amlodipine 

The safety of amlodipine in human pregnancy has not been established. In animal studies, 

reproductive toxicity was observed at high doses (see section 5.3). Use in pregnancy is only 

recommended when there is no safer alternative and when the disease itself carries greater risk for the 

mother and foetus. 

 

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Valsartan 

The use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during the first 

trimester of pregnancy (see section 4.4). The use of AIIRAs is contraindicated during the second and 

third trimesters of pregnancy (see sections 4.3 and 4.4). 

 

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors 

during the first trimester of pregnancy has not been conclusive; however a small increase in risk 

cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II 

Receptor Antagonists (AIIRAs), similar risks may exist for this class of drugs. Unless continued 

AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative 

antihypertensive treatments which have an established safety profile for use in pregnancy. When 

pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and if appropriate, 

alternative therapy should be started. 

 

Exposure to AIIRAs therapy during the second and third trimesters is known to induce human 

foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal 

toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3). 

 

Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check 

of renal function and skull is recommended. 

 

Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see sections 

4.3 and 4.4). 

 

Hydrochlorothiazide 

There is limited experience with hydrochlorothiazide during pregnancy, especially during the first 

trimester. Animal studies are insufficient. 

 

Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of 

hydrochlorothiazide, its use during the second and third trimester may compromise foeto-placental 

perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance 

and thrombocytopenia. 

 

Amlodipine/valsartan/hydrochlorothiazide 

There is no experience on the use of Imprida HCT in pregnant women. Based on the existing data 

with the components, the use of Imprida HCT is not recommended during first trimester and contra-

indicated during the second and third trimester of pregnancy (see sections 4.3 and 4.4). 

 

Breast-feeding 

No information is available regarding the use of valsartan and/or amlodipine during breast-feeding. 

Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing 

intense diuresis can inhibit milk production. The use of Imprida HCT during breast-feeding is not 

recommended. If Imprida HCT is used during breast-feeding, doses should be kept as low as possible. 

Alternative treatments with better established safety profiles during breast-feeding are preferable, 

especially while nursing a newborn or preterm infant. 

 

Fertility 

There are no clinical studies on fertility with Imprida HCT. 

 

Valsartan 

Valsartan had no adverse effects on the reproductive performance of male or female rats at oral doses 

up to 200 mg/kg/day. This dose is 6 times the maximum recommended human dose on a mg/m
2
 basis 

(calculations assume an oral dose of 320 mg/day and a 60-kg patient). 

 

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Amlodipine 

Reversible biochemical changes in the head of spermatozoa have been reported in some patients 

treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of 

amlodipine on fertility. In one rat study, adverse effects were found on male fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 

 

No studies on the effects on the ability to drive and use machines have been performed. When driving 

vehicles or using machines it should be taken into account that occasionally dizziness or weariness 

may occur. 

 

4.8 Undesirable effects 

 

The safety profile of Imprida HCT presented below is based on clinical studies performed with 

Imprida HCT and the known safety profile of the individual components amlodipine, valsartan and 

hydrochlorothiazide. 

 

Information on Imprida HCT 

The safety of Imprida HCT has been evaluated at its maximum dose of 10 mg/320 mg/25 mg in one 

controlled short-term (8 weeks) clinical study with 2,271 patients, 582 of whom received valsartan in 

combination with amlodipine and hydrochlorothiazide. Adverse reactions were generally mild and 

transient in nature and only infrequently required discontinuation of therapy. In this active controlled 

clinical trial, the most common reasons for discontinuation of therapy with Imprida HCT were 

dizziness and hypotension (0.7%). 

 

In the 8-week controlled clinical study, no significant new or unexpected adverse reactions were 

observed with triple therapy treatment compared to the known effects of the monotherapy or dual 

therapy components. 

 

In the 8-week controlled clinical study, changes in laboratory parameters observed with the 

combination of Imprida HCT were minor and consistent with the pharmacological mechanism of 

action of the monotherapy agents. The presence of valsartan in the triple combination attenuated the 

hypokalaemic effect of hydrochlorothiazide. 

 

The following adverse reactions, listed by MedDRA System Organ Class and frequency, concern 

Imprida HCT (amlodipine/valsartan/HCT) and amlodipine, valsartan and HCT individually. 

Very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1,000 to <1/100; rare: ≥1/10,000 to 

<1/1,000; very rare: <1/10,000, not known (cannot be estimated from the available data). 

 

MedDRA 

System Organ 

Class 

Adverse reactions Frequency    

Imprida 

HCT 

Amlodipine Valsartan HCT 

Blood and 

lymphatic system 

disorders 

Agranulocytosis, bone 

marrow depression 

-- -- -- Very rare 

Decrease in haemoglobin 

and in haematocrit 

-- -- Not known -- 

Haemolytic anaemia -- -- -- Very rare 

Leukopenia -- Very rare -- Very rare 

Neutropenia -- -- Not known -- 

Thrombocytopenia, 

sometimes with purpura 

-- Very rare Not known Rare 

Aplastic anaemia -- -- -- Not known 

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Immune system 

disorders 

Hypersensitivity -- Very rare Not known Very rare 

Metabolism and 

nutrition 

disorders 

Anorexia Uncommon -- -- -- 

Hypercalcaemia Uncommon -- -- Rare 

Hyperglycaemia -- Very rare -- Rare 

Hyperlipidaemia Uncommon -- -- -- 

Hyperuricaemia Uncommon -- -- Common 

Hypochloraemic alkalosis -- -- -- Very rare 

Hypokalaemia Common -- -- Very 

common 

Hypomagnesaemia -- -- -- Common 

Hyponatraemia Uncommon -- -- Common 

Worsening of diabetic 

metabolic state 

-- -- -- Rare 

Psychiatric 

disorders 

Depression -- -- -- Rare 

Insomnia/sleep disturbances Uncommon Uncommon -- Rare 

Mood swings -- Uncommon --  

Nervous system 

disorders 

Coordination abnormal Uncommon -- -- -- 

Dizziness Common Common -- Rare 

Dizziness postural, dizziness 

exertional 

Uncommon -- -- -- 

Dysgeusia Uncommon Uncommon -- -- 

Extrapyramidal syndrome -- Not known -- -- 

Headache Common Common -- Rare 

Hypertonia -- Very rare -- -- 

Lethargy Uncommon -- -- -- 

Paraesthesia Uncommon Uncommon -- Rare 

Peripheral neuropathy, 

neuropathy 

Uncommon Very rare -- -- 

Somnolence Uncommon Common -- -- 

Syncope Uncommon Uncommon -- -- 

Tremor -- Uncommon -- -- 

Eye disorders Acute angle-closure 

glaucoma 

-- -- -- Not known 

Visual impairment Uncommon Uncommon -- Rare 

Ear and labyrinth 

disorders 

Tinnitus -- Uncommon -- -- 

Vertigo Uncommon -- Uncommon -- 

Cardiac disorders Palpitations -- Common -- -- 

Tachycardia Uncommon -- -- -- 

Arrhythmias (including 

bradycardia, ventricular 

tachycardia, and atrial 

fibrillation) 

-- Very rare -- Rare 

Myocardial infarction -- Very rare -- -- 

Vascular 

disorders 

Flushing -- Common -- -- 

Hypotension Common Uncommon -- -- 

Orthostatic hypotension Uncommon -- -- Common 

Phlebitis, thrombophlebitis Uncommon -- -- -- 

Vasculitis -- Very rare Not known -- 

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Respiratory, 

thoracic and 

mediastinal 

disorders 

Cough Uncommon Very rare Uncommon -- 

Dyspnoea Uncommon Uncommon -- -- 

Respiratory distress, 

pulmonary oedema, 

pneumonitis 

-- -- -- Very rare 

Rhinitis -- Uncommon -- -- 

Throat irritation Uncommon -- -- -- 

Gastrointestinal 

disorders 

Abdominal discomfort, 

abdominal pain upper 

Uncommon Common Uncommon Rare 

Breath odour Uncommon -- -- -- 

Change of bowel habit -- Uncommon -- -- 

Constipation -- -- -- Rare 

Decreased appetite -- -- -- Common 

Diarrhoea Uncommon Uncommon -- Rare 

Dry mouth Uncommon Uncommon -- -- 

Dyspepsia Common Uncommon -- -- 

Gastritis -- Very rare -- -- 

Gingival hyperplasia -- Very rare -- -- 

Nausea Uncommon Common -- Common 

Pancreatitis -- Very rare -- Very rare 

Vomiting Uncommon Uncommon -- Common 

Hepatobiliary 

disorders 

Hepatic enzyme elevation, 

including increase of serum 

bilirubin 

-- Very rare Not known -- 

Hepatitis -- Very rare -- -- 

Intrahepatic cholestasis, 

jaundice 

-- Very rare -- Rare 

Skin and 

subcutaneous 

tissue disorders 

Alopecia -- Uncommon --  

Angioedema -- Very rare Not known -- 

Cutaneous lupus 

erythematosus-like 

reactions, reactivation of 

cutaneous lupus 

erythematosus 

-- -- -- Very rare 

Erythema multiforme -- Very rare -- Not known 

Exanthema -- Uncommon -- -- 

Hyperhidrosis Uncommon Uncommon -- -- 

Photosensitivity reaction* -- -- -- Rare 

Pruritus Uncommon Uncommon Not known -- 

Purpura -- Uncommon -- Rare 

Rash -- Uncommon Not known Common 

Skin discoloration -- Uncommon -- -- 

Urticaria and other forms of 

rash 

-- Very rare -- Common 

Vasculitis necrotising and 

toxic epidermal necrolysis 

-- -- -- Very rare 

Musculoskeletal 

and connective 

tissue disorders 

Arthralgia -- Uncommon -- -- 

Back pain Uncommon Uncommon -- -- 

Joint swelling Uncommon -- -- -- 

Muscle spasm Uncommon Uncommon -- Not known 

Muscular weakness Uncommon -- -- -- 

Myalgia Uncommon Uncommon Not known -- 

Pain in extremity Uncommon -- -- -- 

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Renal and 

urinary disorders 

Elevation of serum 

creatinine 

Uncommon -- Not known -- 

Micturition disorder  Uncommon   

Nocturia -- Uncommon -- -- 

Pollakiuria Common Uncommon   

Renal dysfunction -- -- -- Not known 

Renal failure acute Uncommon -- -- Not known 

Renal failure and 

impairment 

-- -- Not known Rare 

Reproductive 

system and 

breast disorders 

Impotence Uncommon Uncommon -- Common 

Gynaecomastia  Uncommon -- -- 

General 

disorders and 

administration 

site conditions 

Abasia, gait disturbance Uncommon -- -- -- 

Asthenia Uncommon Uncommon -- Not known 

Discomfort, malaise Uncommon Uncommon -- -- 

Fatigue Common Common Uncommon -- 

Non cardiac chest pain Uncommon Uncommon -- -- 

Oedema Common Common -- -- 

Pain -- Uncommon -- -- 

Pyrexia -- -- -- Not known 

Investigations Lipids increased  --  Very 

common 

Blood urea nitrogen 

increased 

Uncommon -- -- -- 

Blood uric acid increased Uncommon -- --  

Glycosuria    Rare 

Serum potassium decreased Uncommon  -- -- -- 

Serum potassium increased -- -- Not known -- 

Weight increase Uncommon Uncommon -- -- 

Weight decrease -- Uncommon -- -- 

 

* See section 4.4 Photosensitivity 

 

4.9 Overdose 

 

Symptoms 

There is no experience of overdose with Imprida HCT. The major symptom of overdose with 

valsartan is possibly pronounced hypotension with dizziness. Overdose with amlodipine may result in 

excessive peripheral vasodilation and, possibly, reflex tachycardia. Marked and potentially prolonged 

systemic hypotension, including shock with fatal outcome, have been reported with amlodipine. 

 

Treatment 

Amlodipine/Valsartan/Hydrochlorothiazide 

Clinically significant hypotension due to Imprida HCT overdose calls for active cardiovascular 

support, including frequent monitoring of cardiac and respiratory function, elevation of extremities, 

and attention to circulating fluid volume and urine output. A vasoconstrictor may be helpful in 

restoring vascular tone and blood pressure, provided that there is no contraindication to its use. 

Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. 

 

Amlodipine 

If ingestion is recent, induction of vomiting or gastric lavage may be considered. Administration of 

activated charcoal to healthy volunteers immediately or up to two hours after ingestion of amlodipine 

has been shown to significantly decrease amlodipine absorption. 

Amlodipine is unlikely to be removed by haemodialysis. 

 

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Valsartan 

Valsartan is unlikely to be removed by haemodialysis. 

 

Hydrochlorothiazide 

Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, 

hypochloraemia) and hypovolaemia resulting from excessive diuresis. The most common signs and 

symptoms of overdose are nausea and somnolence. Hypokalaemia may result in muscle spasms and or 

accentuate arrhythmia associated with the concomitant use of digitalis glycosides or certain anti-

arrhythmic medicinal products. 

The degree to which hydrochlorothiazide is removed by haemodialysis has not been established. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Angiotensin II antagonists, plain (valsartan), combinations with 

dihydropyridine derivatives (amlodipine) and thiazide diuretics (hydrochlorothiazide), ATC code: 

C09DX01 valsartan, amlodipine and hydrochlorothiazide. 

 

Imprida HCT combines three antihypertensive compounds with complementary mechanisms to 

control blood pressure in patients with essential hypertension: amlodipine belongs to the calcium 

antagonist class and valsartan to the angiotensin II antagonist class of medicines and 

hydrochlorothiazide belongs to the thiazide diuretics class of medicines. The combination of these 

substances has an additive antihypertensive effect. 

 

Amlodipine/Valsartan/Hydrochlorothiazide 

Imprida HCT was studied in a double-blind, active controlled study in hypertensive patients. A total 

of 2,271 patients with moderate to severe hypertension (mean baseline systolic/diastolic blood 

pressure was 170/107 mmHg) received treatments of amlodipine/valsartan/hydrochlorothiazide 

10 mg/320 mg/25 mg, valsartan/hydrochlorothiazide 320 mg/25 mg, amlodipine/valsartan 

10 mg/320 mg, or hydrochlorothiazide/amlodipine 25 mg/10 mg. At study initiation patients were 

assigned lower doses of their treatment combination and were titrated to their full treatment dose by 

week 2. 

 

At week 8, the mean reductions in systolic/diastolic blood pressure were 39.7/24.7 mmHg with 

Imprida HCT, 32.0/19.7 mmHg with valsartan/hydrochlorothiazide, 33.5/21.5 mmHg with 

amlodipine/valsartan, and 31.5/19.5 mmHg with amlodipine/hydrochlorothiazide. The triple 

combination therapy was statistically superior to each of the three dual combination treatments in 

reduction of diastolic and systolic blood pressures. The reductions in systolic/diastolic blood pressure 

with Imprida HCT were 7.6/5.0 mmHg greater than with valsartan/hydrochlorothiazide, 

6.2/3.3 mmHg greater than with amlodipine/valsartan, and 8.2/5.3 mmHg greater than with 

amlodipine/hydrochlorothiazide. The full blood pressure lowering effect was achieved 2 weeks after 

being on their maximal dose of Imprida HCT. Statistically greater proportions of patients achieved 

blood pressure control (<140/90 mmHg) with Imprida HCT (71%) compared to each of the three dual 

combination therapies (45-54%) (p<0.0001). 

 

In a subgroup of 283 patients focusing on ambulatory blood pressure monitoring, clinically and 

statistically superior reductions in 24-hour systolic and diastolic blood pressures were observed with 

the triple combination compared to valsartan/hydrochlorothiazide, valsartan/amlodipine, and 

hydrochlorothiazide/amlodipine. 

 

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Amlodipine 

The amlodipine component of Imprida HCT inhibits the transmembrane entry of calcium ions into 

cardiac and vascular smooth muscle. The mechanism of the antihypertensive action of amlodipine is 

due to a direct relaxant effect on vascular smooth muscle, causing reductions in peripheral vascular 

resistance and in blood pressure. Experimental data suggest that amlodipine binds to both 

dihydropyridine and non-dihydropyridine binding sites. The contractile processes of cardiac muscle 

and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into 

these cells through specific ion channels. 

 

Following administration of therapeutic doses to patients with hypertension, amlodipine produces 

vasodilation, resulting in a reduction of supine and standing blood pressures. These decreases in blood 

pressure are not accompanied by a significant change in heart rate or plasma catecholamine levels 

with chronic dosing. 

 

Plasma concentrations correlate with effect in both young and elderly patients. 

 

In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in a 

decrease in renal vascular resistance and increases in glomerular filtration rate and effective renal 

plasma flow, without change in filtration fraction or proteinuria. 

 

Valsartan 

Valsartan is an orally active, potent and specific angiotensin II receptor antagonist. It acts selectively 

on the receptor subtype AT1, which is responsible for the known actions of angiotensin II. 

 

Administration of valsartan to patients with hypertension results in a drop in blood pressure without 

affecting pulse rate. 

 

In most patients, after administration of a single oral dose, onset of antihypertensive activity occurs 

within 2 hours, and the peak drop in blood pressure is achieved within 4-6 hours. The 

antihypertensive effect persists over 24 hours after administration. During repeated administration, the 

maximum reduction in blood pressure with any dose is generally attained within 2-4 weeks. 

 

Hydrochlorothiazide 

The site of action of thiazide diuretics is primarily in the renal distal convoluted tubule. It has been 

shown that there is a high-affinity receptor in the renal cortex as the primary binding site for the 

thiazide diuretic action and inhibition of NaCl transport in the distal convoluted tubule. The mode of 

action of thiazides is through inhibition of the Na
+
Cl

-
 symporter perhaps by competing for the Cl

-
 site, 

thereby affecting electrolyte reabsorption mechanisms: directly increasing sodium and chloride 

excretion to an approximately equal extent, and indirectly, by this diuretic action, reducing plasma 

volume, with consequent increases in plasma renin activity, aldosterone secretion and urinary 

potassium loss, and a decrease in serum potassium. 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

Imprida HCT in all subsets of the paediatric population in essential hypertension. See section 4.2 for 

information on paediatric use. 

 

5.2 Pharmacokinetic properties 

 

Linearity 

Amlodipine, valsartan and hydrochlorothiazide exhibit linear pharmacokinetics. 

 

Amlodipine/valsartan/hydrochlorothiazide 

Following oral administration of Imprida HCT in normal healthy adults, peak plasma concentrations 

of amlodipine, valsartan and hydrochlorothiazide are reached in 6-8 hours, 3 hours, and 2 hours, 

respectively. The rate and extent of absorption of amlodipine, valsartan and hydrochlorothiazide from 

Imprida HCT are the same as when administered as individual dosage forms. 

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39 

 

Amlodipine 

Absorption: After oral administration of therapeutic doses of amlodipine alone, peak plasma 

concentrations of amlodipine are reached in 6-12 hours. Absolute bioavailability has been calculated as 

between 64% and 80%. Amlodipine bioavailability is unaffected by food ingestion. 

 

Distribution: Volume of distribution is approximately 21 l/kg. In vitro studies with amlodipine have 

shown that approximately 97.5% of circulating drug is bound to plasma proteins. 

 

Biotransformation: Amlodipine is extensively (approximately 90%) metabolised in the liver to inactive 

metabolites. 

 

Elimination: Amlodipine elimination from plasma is biphasic, with a terminal elimination half-life of 

approximately 30 to 50 hours. Steady-state plasma levels are reached after continuous administration for 

7-8 days. Ten per cent of original amlodipine and 60% of amlodipine metabolites are excreted in urine. 

 

Valsartan 

Absorption: Following oral administration of valsartan alone, peak plasma concentrations of valsartan 

are reached in 2-4 hours. Mean absolute bioavailability is 23%. Food decreases exposure (as 

measured by AUC) to valsartan by about 40% and peak plasma concentration (Cmax) by about 50%, 

although from about 8 h post dosing plasma valsartan concentrations are similar for the fed and fasted 

groups. This reduction in AUC is not, however, accompanied by a clinically significant reduction in 

the therapeutic effect, and valsartan can therefore be given either with or without food. 

 

Distribution: The steady-state volume of distribution of valsartan after intravenous administration is 

about 17 litres, indicating that valsartan does not distribute into tissues extensively. Valsartan is 

highly bound to serum proteins (94-97%), mainly serum albumin. 

 

Biotransformation: Valsartan is not transformed to a high extent as only about 20% of dose is 

recovered as metabolites. A hydroxy metabolite has been identified in plasma at low concentrations 

(less than 10% of the valsartan AUC). This metabolite is pharmacologically inactive. 

 

Elimination: Valsartan is primarily eliminated in faeces (about 83% of dose) and urine (about 13% of 

dose), mainly as unchanged drug. Following intravenous administration, plasma clearance of valsartan 

is about 2 l/h and its renal clearance is 0.62 l/h (about 30% of total clearance). The half-life of 

valsartan is 6 hours. 

 

Hydrochlorothiazide 

Absorption: The absorption of hydrochlorothiazide, after an oral dose, is rapid (Tmax about 2 hours). 

The increase in mean AUC is linear and dose proportional in the therapeutic range. 

 

The effect of food on hydrochlorothiazide absorption, if any, has little clinical significance. Absolute 

bioavailability of hydrochlorothiazide is 70% after oral administration. 

 

Distribution: The apparent volume of distribution is 4-8 l/kg. Circulating hydrochlorothiazide is 

bound to serum proteins (40-70%), mainly serum albumin. Hydrochlorothiazide also accumulates in 

erythrocytes at approximately 3 times the level in plasma. 

 

Biotransformation: Hydrochlorothiazide is eliminated predominantly as unchanged compound. 

 

Elimination: Hydrochlorothiazide is eliminated from plasma with a half-life averaging 6 to 15 hours 

in the terminal elimination phase. There is no change in the kinetics of hydrochlorothiazide on 

repeated dosing, and accumulation is minimal when dosed once daily. More than 95% of the absorbed 

dose is being excreted as unchanged compound in the urine. The renal clearance is composed of 

passive filtration and active secretion into the renal tubule. 

 

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Special populations 

Paediatric patients (age below 18 years) 

No pharmacokinetic data are available in the paediatric population. 

 

Elderly (age 65 years or over) 

Time to peak plasma amlodipine concentrations is similar in young and elderly patients. In elderly 

patients, amlodipine clearance tends to decline, causing increases in the area under the curve (AUC) 

and elimination half-life. Mean systemic AUC of valsartan is higher by 70% in the elderly than in the 

young, therefore caution is required when increasing the dosage. 

 

Systemic exposure to valsartan is slightly elevated in the elderly as compared to the young, but this 

has not been shown to have any clinical significance. 

 

Limited data suggest that the systemic clearance of hydrochlorothiazide is reduced in both healthy and 

hypertensive elderly subjects compared to young healthy volunteers. 

 

Since the three components are equally well tolerated in younger and elderly patients, normal dose 

regimens are recommended (see section 4.2). 

 

Renal impairment 

The pharmacokinetics of amlodipine are not significantly influenced by renal impairment. As 

expected for a compound where renal clearance accounts for only 30% of total plasma clearance, no 

correlation was seen between renal function and systemic exposure to valsartan. 

 

Patients with mild to moderate renal impairment may therefore receive the usual initial dose (see 

sections 4.2 and 4.4). 

 

In the presence of renal impairment, mean peak plasma levels and AUC values of hydrochlorothiazide 

are increased and the urinary excretion rate is reduced. In patients with mild to moderate renal 

impairment, a 3-fold increase in hydrochlorothiazide AUC has been observed. In patients with severe 

renal impairment an 8-fold increase in AUC has been observed. Imprida HCT is contraindicated in 

patients with severe renal impairment, anuria or undergoing dialysis (see section 4.3). 

 

Hepatic impairment 

Patients with hepatic insufficiency have decreased clearance of amlodipine with resulting increase of 

approximately 40–60% in AUC. On average, in patients with mild to moderate chronic liver disease, 

exposure (measured by AUC values) to valsartan is twice that found in healthy volunteers (matched 

by age, sex and weight). Due to the valsartan component, Imprida HCT is contraindicated in patients 

with hepatic impairment (see sections 4.2 and 4.3). 

 

5.3 Preclinical safety data 

 

Amlodipine/Valsartan/Hydrochlorothiazide 

In a variety of preclinical safety studies conducted in several animal species with amlodipine, 

valsartan, hydrochlorothiazide, valsartan/hydrochlorothiazide, amlodipine/valsartan and 

amlodipine/valsartan/hydrochlorothiazide (Imprida HCT), there was no evidence of systemic or target 

organ toxicity that would adversely affect the development of Imprida HCT for clinical use in 

humans. 

 

Preclinical safety studies of up to 13 weeks in duration were conducted with 

amlodipine/valsartan/hydrochlorothiazide in rats. The combination resulted in expected reduction of 

red blood cell mass (erythrocytes, haemoglobin, haematocrit, and reticulocytes), increase in serum 

urea, increase in serum creatinine, increase in serum potassium, juxtaglomerular (JG) hyperplasia in 

the kidney and focal erosions in the glandular stomach in rats. All these changes were reversible after 

a 4-week recovery period and were considered to be exaggerated pharmacological effects. 

 

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The amlodipine/valsartan/hydrochlorothiazide combination was not tested for genotoxicity or 

carcinogenicity as there was no evidence of any interaction between these substances, which have 

been on the market for a long time. However, amlodipine, valsartan and hydrochlorothiazide have 

been tested individually for genotoxicity and carcinogenicity with negative results. 

 

Amlodipine 

Reproductive toxicology 

Reproductive studies in rats and mice have shown delayed date of delivery, prolonged duration of 

labour and decreased pup survival at dosages approximately 50 times greater than the maximum 

recommended dosage for humans based on mg/kg. 

 

Impairment of fertility 

There was no effect on the fertility of rats treated with amlodipine (males for 64 days and females 

14 days prior to mating) at doses up to 10 mg/kg/day (8 times* the maximum recommended human 

dose of 10 mg on a mg/m
2
 basis). In another rat study in which male rats were treated with amlodipine 

besilate for 30 days at a dose comparable with the human dose based on mg/kg, decreased plasma 

follicle-stimulating hormone and testosterone were found as well as decreases in sperm density and in 

the number of mature spermatids and Sertoli cells. 

 

Carcinogenesis, mutagenesis 

Rats and mice treated with amlodipine in the diet for two years, at concentrations calculated to 

provide daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day showed no evidence of carcinogenicity. 

The highest dose (for mice, similar to, and for rats twice* the maximum recommended clinical dose of 

10 mg on a mg/m
2
 basis) was close to the maximum tolerated dose for mice but not for rats. 

 

Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels. 

 

* Based on patient weight of 50 kg 

 

Valsartan 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential. 

 

In rats, maternally toxic doses (600 mg/kg/day) during the last days of gestation and lactation led to 

lower survival, lower weight gain and delayed development (pinna detachment and ear-canal opening) 

in the offspring (see section 4.6). These doses in rats (600 mg/kg/day) are approximately 18 times the 

maximum recommended human dose on a mg/m
2 
basis (calculations assume an oral dose of 

320 mg/day and a 60-kg patient). 

 

In non-clinical safety studies, high doses of valsartan (200 to 600 mg/kg body weight) caused in rats a 

reduction of red blood cell parameters (erythrocytes, haemoglobin, haematocrit) and evidence of 

changes in renal haemodynamics (slightly raised plasma urea, and renal tubular hyperplasia and 

basophilia in males). These doses in rats (200 and 600 mg/kg/day) are approximately 6 and 18 times 

the maximum recommended human dose on a mg/m
2
 basis (calculations assume an oral dose of 

320 mg/day and a 60-kg patient). 

 

In marmosets at similar doses, the changes were similar though more severe, particularly in the kidney 

where the changes developed to a nephropathy which included raised urea and creatinine. 

 

Hypertrophy of the renal juxtaglomerular cells was also seen in both species. All changes were 

considered to be caused by the pharmacological action of valsartan which produces prolonged 

hypotension, particularly in marmosets. For therapeutic doses of valsartan in humans, the hypertrophy 

of the renal juxtaglomerular cells does not seem to have any relevance. 

 

 

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6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Tablet core 

Cellulose microcrystalline 

Crospovidone 

Silica, colloidal anhydrous 

Magnesium stearate 

 

Coating 

Hypromellose 

Macrogol 4000 

Talc 

Titanium dioxide (E171) 

Iron oxide, yellow (E172) 

Iron oxide, red (E172) 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

2 years 

 

6.4 Special precautions for storage 

 

Do not store above 30°C. 

 

Store in the original package in order to protect from moisture. 

 

6.5 Nature and contents of container 

 

PVC/PVDC blisters. One blister contains 7, 10 or 14 film-coated tablets. 

Pack sizes: 14, 28, 30, 56, 90, 98 or 280 film-coated tablets. 

Multipacks of 280 tablets, comprising 20 cartons, each containing 14 tablets. 

 

PVC/PVDC perforated unit dose blisters for hospital use: 

Pack sizes: 56, 98 or 280 film-coated tablets 

Multipacks of 280 tablets, comprising 4 cartons, each containing 70 tablets. 

 

Not all pack sizes or strengths may be marketed. 

 

6.6 Special precautions for disposal and other handling 

 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

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43 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/013-024 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

15.10.2009 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

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1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 5 mg/160 mg/25 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains 5 mg of amlodipine (as amlodipine besylate), 160 mg of valsartan, 

and 25 mg of hydrochlorothiazide. 

 

For a full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet (tablet) 

 

Yellow, ovaloid, biconvex tablets with bevelled edge, debossed “NVR” on one side and “VEL” on the 

other side. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment of essential hypertension as substitution therapy in adult patients whose blood pressure is 

adequately controlled on the combination of amlodipine, valsartan and hydrochlorothiazide (HCT), 

taken either as three single-component formulations or as a dual-component and a single-component 

formulation. 

 

4.2 Posology and method of administration 

 

Posology 

The recommended dose of Imprida HCT is one tablet per day, to be taken preferably in the morning. 

 

Before switching to Imprida HCT patients should be controlled on stable doses of the 

monocomponents taken at the same time. The dose of Imprida HCT should be based on the doses of 

the individual components of the combination at the time of switching. 

 

The maximum recommended dose of Imprida HCT is 10 mg/320 mg/25 mg. 

 

Special populations 

Renal impairment 

No adjustment of the initial dose is required for patients with mild to moderate renal impairment (see 

sections 4.4 and 5.2). Due to the hydrochlorothiazide component, Imprida HCT is contraindicated for 

use in patients with anuria (see section 4.3) and in patients with severe renal impairment (glomerular 

filtration rate (GFR) <30 ml/min/1.73 m
2
) (see sections 4.3, 4.4 and 5.2). 

 

Hepatic impairment 

Due to the valsartan component, Imprida HCT is contraindicated in patients with severe hepatic 

impairment (see section 4.3). In patients with mild to moderate hepatic impairment without 

cholestasis, the maximum recommended dose is 80 mg valsartan and therefore Imprida HCT is not 

suitable in this group of patients (see sections 4.3, 4.4 and 5.2). 

 

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45 

Heart failure and coronary artery disease 

There is limited experience with the use of Imprida HCT, particulary at the maximum dose, in 

patients with heart failure and coronary artery disease. Caution is advised in patients with heart failure 

and coronary artery disease, particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg. 

 

Elderly (age 65 years or over) 

Caution, including more frequent monitoring of blood pressure, is recommended in elderly patients, 

particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in this 

patient population are limited. 

 

Paediatric population 

There is no relevant use of Imprida HCT in the paediatric population (patients below age 18 years) for 

the indication of essential hypertension. 

 

Method of administration 

Imprida HCT can be taken with or without food. The tablets should be swallowed whole with some 

water, at the same time of the day and preferably in the morning. 

 

4.3 Contraindications 

 

 Hypersensitivity to the active substances, to other sulphonamide derivatives, to dihydropyridine 

derivatives, or to any of the excipients. 

 Second and third trimesters of pregnancy (see sections 4.4 and 4.6). 

 Hepatic impairment, biliary cirrhosis or cholestasis. 

 Severe renal impairment (GFR <30 ml/min/1.73 m2), anuria and patients undergoing dialysis. 

 Refractory hypokalaemia, hyponatraemia, hypercalcaemia, and symptomatic hyperuricaemia. 

 

4.4 Special warnings and precautions for use 

 

Sodium- and/or volume-depleted patients 

Excessive hypotension, including orthostatic hypotension, was seen in 1.7% of patients treated with 

the maximum dose of Imprida HCT (10 mg/320 mg/25 mg) compared to 1.8% of 

valsartan/hydrochlorothiazide (320 mg/25 mg) patients, 0.4% of amlodipine/valsartan (10 mg/320 mg) 

patients, and 0.2% of hydrochlorothiazide/amlodipine (25 mg/10 mg) patients in a controlled trial in 

patients with moderate to severe uncomplicated hypertension. 

 

In sodium-depleted and/or volume-depleted patients, such as those receiving high doses of diuretics, 

symptomatic hypotension may occur after initiation of treatment with Imprida HCT. Imprida HCT 

should be used only after correction of any pre-existing sodium and/or volume depletion. 

 

If excessive hypotension occurs with Imprida HCT, the patient should be placed in the supine position 

and, if necessary, given an intravenous infusion of normal saline. Treatment can be continued once 

blood pressure has been stabilised. 

 

Serum electrolyte changes 

Amlodipine/valsartan/hydrochlorothiazide 

In the controlled trial of Imprida HCT, the counteracting effects of valsartan 320 mg and 

hydrochlorothiazide 25 mg on serum potassium approximately balanced each other in many patients. 

In other patients, one or the other effect may be dominant. Periodic determinations of serum 

electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals. 

 

Periodic determination of serum electrolytes and potassium in particular should be performed at 

appropriate intervals to detect possible electrolyte imbalance, especially in patients with other risk 

factors such as impaired renal function, treatment with other medicinal products or history of prior 

electrolyte imbalances. 

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46 

 

Valsartan 

Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing 

potassium, or other medicinal products that may increase potassium levels (heparin, etc.) is not 

recommended. Monitoring of potassium should be undertaken as appropriate. 

 

Hydrochlorothiazide 

Treatment with Imprida HCT should only start after correction of hypokalaemia and any coexisting 

hypomagnesaemia. Thiazide diuretics can precipitate new onset hypokalaemia or exacerbate pre-

existing hypokalaemia. Thiazide diuretics should be administered with caution in patients with 

conditions involving enhanced potassium loss, for example salt-losing nephropathies and prerenal 

(cardiogenic) impairment of kidney function. If hypokalaemia develops during hydrochlorothiazide 

therapy, Imprida HCT should be discontinued until stable correction of the potassium balance. 

 

Thiazide diuretics can precipitate new onset hyponatraemia and hypochloroaemic alkalosis or 

exacerbate pre-existing hyponatraemia. Hyponatraemia, accompanied by neurological symptoms 

(nausea, progressive disorientation, apathy) has been observed. Treatment with hydrochlorothiazide 

should only be started after correction of pre-existing hyponatraemia. In case severe or rapid 

hyponatraemia develops during Imprida HCT therapy, the treatment should be discontinued until 

normalisation of natraemia. 

 

All patients receiving thiazide diuretics should be periodically monitored for imbalances in 

electrolytes, particularly potassium, sodium and magnesium. 

 

Renal impairment 

Thiazide diuretics may precipitate azotaemia in patients with chronic kidney disease. When Imprida 

HCT is used in patients with renal impairment periodic monitoring of serum electrolytes (including 

potassium), creatinine and uric acid serum levels is recommended. Imprida HCT is contraindicated in 

patients with severe renal impairment, anuria or undergoing dialysis (see section 4.3). 

 

No dosage adjustment of Imprida HCT is required for patients with mild to moderate renal 

impairment (GFR ≥30 ml/min/1.73 m
2
). 

 

Renal artery stenosis 

No data are available on the use of Imprida HCT in patients with unilateral or bilateral renal artery 

stenosis or stenosis to a solitary kidney. 

 

Kidney transplantation 

To date there is no experience of the safe use of Imprida HCT in patients who have had a recent 

kidney transplantation. 

 

Hepatic impairment 

Valsartan is mostly eliminated unchanged via the bile, whereas amlodipine is extensively metabolised 

by the liver. In patients with mild to moderate hepatic impairment without cholestasis, the maximum 

recommended dose is 80 mg valsartan, and therefore, Imprida HCT is not suitable in this group of 

patients (see sections 4.2, 4.3 and 5.2). 

 

Heart failure and coronary artery disease 

As a consequence of the inhibition of the renin-angiotensin-aldosterone system, changes in renal 

function may be anticipated in susceptible individuals. In patients with severe heart failure whose 

renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with 

angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been 

associated with oliguria and/or progressive azotaemia and (rarely) with acute renal failure and/or 

death. Similar outcomes have been reported with valsartan. 

 

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47 

In a long-term, placebo-controlled study (PRAISE-2) of amlodipine in patients with NYHA (New 

York Heart Association Classification) III and IV heart failure of non-ischaemic aetiology, amlodipine 

was associated with increased reports of pulmonary oedema despite no significant difference in the 

incidence of worsening heart failure as compared to placebo. 

 

Caution is advised in patients with heart failure and coronary artery disease, particularly at the 

maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in these patient 

populations is limited. 

 

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy 

As with all other vasodilators, special caution is indicated in patients with aortic or mitral stenosis, or 

obstructive hypertrophic cardiomyopathy. 

 

Pregnancy 

Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless 

continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to 

alternative antihypertensive treatments which have an established safety profile for use in pregnancy. 

When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if 

appropriate, alternative therapy should be started (see sections 4.3 and 4.6). 

 

Primary hyperaldosteronism 

Patients with primary hyperaldosteronism should not be treated with the angiotensin II antagonist 

valsartan as their renin-angiotensin system is not activated. Therefore, Imprida HCT is not 

recommended in this population. 

 

Systemic lupus erythematosus 

Thiazide diuretics, including hydrochlorothiazide, have been reported to exacerbate or activate 

systemic lupus erythematosus. 

 

Other metabolic disturbances 

Thiazide diuretics, including hydrochlorothiazide, may alter glucose tolerance and raise serum levels 

of cholesterol, triglycerides and uric acid. In diabetic patients dosage adjustments of insulin or oral 

hypoglycaemic agents may be required. 

 

Due to the hydrochlorothiazide component, Imprida HCT is contraindicated in symptomatic 

hyperuricaemia. Hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of 

uric acid and may cause or exacerbate hyperuricaemia as well as precipitate gout in susceptible 

patients. 

 

Thiazides reduce urinary calcium excretion and may cause intermittant and slight elevation of serum 

calcium in the absence of known disorders of calcium metabolism. Imprida HCT is contraindicated in 

patients with hypercalcaemia and should only be used after correction of any pre-existing 

hypercalcaemia. Imprida HCT should be discontinued if hypercalcaemia develops during treatment. 

Serum levels of calcium should be periodically monitored during treatment with thiazides. Marked 

hypercalcaemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued 

before carrying out tests for parathyroid function. 

 

Photosensitivity 

Cases of photosensitivity reactions have been reported with thiazide diuretics (see section 4.8). If 

photosensitivity reaction occurs during treatment with Imprida HCT, it is recommended to stop the 

treatment. If a readministration of the diuretic is deemed necessary, it is recommended to protect 

exposed areas to the sun or to artificial UVA. 

 

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Acute angle-closure glaucoma 

Hydrochlorothiazide, a sulphonamide, has been associated with an idiosyncratic reaction resulting in 

acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased 

visual acuity or ocular pain and typically occur within hours to a week of treatment initiation. 

Untreated acute-angle closure glaucoma can lead to permanent vision loss. 

 

The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or 

surgical treatment may need to be considered if the intraocular pressure remains uncontrolled. Risk 

factors for developing acute angle closure glaucoma may include a history of sulphonamide or 

penicillin allergy. 

 

General 

Caution should be exercised in patients who have shown prior hypersensitivity to other angiotensin II 

receptor antagonists. Hypersensitivity reactions to hydrochlorothiazide are more likely in patients 

with allergy and asthma. 

 

Elderly (age 65 years or over) 

Caution, including more frequent monitoring of blood pressure, is recommended in elderly patients, 

particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in this 

patient population are limited. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

No formal interaction studies with other medicinal products were performed with Imprida HCT. Thus, 

only information on interactions with other medicinal products that are known for the individual 

active substances is provided in this section. 

 

However, it is important to take into account that Imprida HCT may increase the hypotensive effect of 

other antihypertensive agents. 

 

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Concomitant use not recommended 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Valsartan 

and 

HCT 

Lithium Reversible increases in serum lithium concentrations and 

toxicity have been reported during concurrent use of ACE 

inhibitors and thiazides such as hydrochlorothiazide. 

Despite the lack of experience with concomitant use of 

valsartan and lithium, this combination is not 

recommended. If the combination proves necessary, 

careful monitoring of serum lithium levels is 

recommended (see section 4.4). 

Valsartan Potassium-sparing 

diuretics, potassium 

supplements, salt 

substitutes containing 

potassium and other 

substances that may 

increase potassium 

levels 

If a medicinal product that affects potassium levels is 

considered necessary in combination with valsartan, 

frequent monitoring of potassium plasma levels is 

advised. 

Amlodipine Grapefruit or grapefruit 

juice 

Administration of amlodipine with grapefruit or grapefruit 

juice is not recommended as bioavailability may be 

increased in some patients, resulting in increased blood 

pressure lowering effects. 

 

Caution required with concomitant use 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Amlodipine CYP3A4 inhibitors 

(i.e. ketoconazole, 

itraconazole, ritonavir) 

Concomitant use of amlodipine with strong or moderate 

CYP3A4 inhibitors (protease inhibitors, azole antifungals, 

macrolides like erythromycin or clarithromycin, verapamil 

or diltiazem) may give rise to significant increase in 

amlodipine exposure. The clinical translation of these 

pharmacokinetic variations may be more pronounced in 

the elderly. Clinical monitoring and dose adjustment may 

thus be required. 

CYP3A4 inducers 

(anticonvulsant agents 

[e.g. carbamazepine, 

phenobarbital, 

phenytoin, 

fosphenytoin, 

primidone], rifampicin, 

Hypericum perforatum 

[St. John’s wort]) 

There is no data available regarding the effect of CYP3A4 

inducers on amlodipine. The concomitant use of CYP3A4 

inducers (e.g. rifampicin, Hypericum perforatum) may 

give a lower plasma concentration of amlodipine. 

Amlodipine should be used with caution together with 

CYP3A4 inducers. 

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50 

 

 Simvastatin Co-administration of multiple doses of 10 mg amlodipine 

with 80 mg simvastatin resulted in a 77% increase in 

exposure to simvastatin compared to simvastatin alone. It 

is recommended to limit the dose of simvastatin to 20 mg 

daily in patients on amlodipine. 

Dantrolene (infusion) In animals, lethal ventricular fibrillation and 

cardiovascular collapse are observed in association with 

hyperkalaemia after administration of verapamil and 

intravenous dantrolene. Due to risk of hyperkalaemia, it is 

recommended that the co-administration of calcium 

channel blockers such as amlodipine be avoided in 

patients susceptible to malignant hyperthermia and in the 

management of malignant hyperthermia. 

Valsartan 

and HCT 

Non-steroidal anti-

inflammatory 

medicines (NSAIDs), 

including selective 

cyclooxygenase-2 

inhibitors (COX-2 

inhibitors), 

acetylsalicylic acid 

(>3 g/day), and non-

selective NSAIDs 

NSAIDS can attenuate the antihypertensive effect of both 

angiotensin II antagonists and hydrochlorothiazide when 

administered simultaneously. Furthermore, concomitant 

use of Imprida HCT and NSAIDs may lead to worsening 

of renal function and an increase in serum potassium. 

Therefore, monitoring of renal function at the beginning 

of the treatment is recommended, as well as adequate 

hydration of the patient. 

Valsartan Inhibitors of the uptake 

transporter (rifampicin, 

ciclosporin) or efflux 

transporter (ritonavir) 

The results of an in vitro study with human liver tissue 

indicate that valsartan is a substrate of the hepatic uptake 

transporter OATP1B1 and of the hepatic efflux 

transporter MRP2. Co-administration of inhibitors of the 

uptake transporter (rifampicin, ciclosporin) or efflux 

transporter (ritonavir) may increase the systemic exposure 

to valsartan. 

HCT Alcohol, barbiturates 

or narcotics 

Concomitant administration of thiazide diuretics with 

substances that also have a blood pressure lowering effect 

(e.g. by reducing sympathetic central nervous system 

activity or direct vasodilatation) may potentiate orthostatic 

hypotension. 

Amantadine Thiazides, including hydrochlorothiazide, may increase 

the risk of adverse reactions caused by amantadine. 

Anticholinergic agents 

and other medicinal 

products affecting 

gastric motility 

The bioavailability of thiazide-type diuretics may be 

increased by anticholinergic agents (e.g. atropine, 

biperiden), apparently due to a decrease in gastrointestinal 

motility and the stomach emptying rate. Conversely, it is 

anticipated that prokinetic substances such as cisapride 

may decrease the bioavailability of thiazide-type diuretics. 

Antidiabetic agents 

(e.g. insulin and oral 

antidiabetic agents) 

Thiazides may alter glucose tolerance. Dose adjustment of 

the antidiabetic medicinal product may be necessary. 

 Metformin Metformin should be used with caution because of the risk 

of lactic acidosis induced by possible functional renal 

failure linked to hydrochlorothiazide. 

Beta blockers and 

diazoxide 

Concomitant use of thiazide diuretics, including 

hydrochlorothiazide, with beta blockers may increase the 

risk of hyperglycaemia. Thiazide diuretics, including 

hydrochlorothiazide, may enhance the hyperglycaemic 

effect of diazoxide. 

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 Ciclosporin Concomitant treatment with ciclosporin may increase the 

risk of hyperuricaemia and gout-type complications. 

 Cytotoxic agents Thiazides, including hydrochlorothiazide, may reduce the 

renal excretion of cytotoxic agents (e.g. 

cyclophosphamide, methotrexate) and potentiate their 

myelosuppressive effects. 

 Digitalis glycosides Thiazide-induced hypokalaemia or hypomagnesaemia may 

occur as undesirable effects, favouring the onset of 

digitalis-induced cardiac arrhythmias. 

 Iodine contrasting 

agents 

In case of diuretic-induced dehydration, there is an 

increased risk of acute renal failure, especially with high 

doses of iodine products. Patients should be re-hydrated 

before the administration. 

 Ion exchange resins Absorption of thiazide diuretics, including 

hydrochlorothiazide, is decreased by cholestyramine or 

colestipol. This could result in sub-therapeutic effects of 

thiazide diuretics. However, staggering the dosage of 

hydrochlorothiazide and resin such that 

hydrochlorothiazide is administered at least 4 hours 

before or 4-6 hours after the administration of resins 

would potentially minimise the interaction. 

 Medicinal products 

affecting serum 

potassium level 

The hypokalaemic effect of hydrochlorothiazide may be 

increased by concomitant administration of kaliuretic 

diuretics, corticosteroids, laxatives, adrenocorticotropic 

hormone (ACTH), amphotericin, carbenoxolone, 

penicillin G and salicylic acid derivatives or 

antiarrhythmics. If these medicinal products are to be 

prescribed with the amlodipine /valsartan 

/hydrochlorothiazide combination, monitoring of 

potassium plasma levels is advised. 

 Medicinal products 

affecting serum sodium 

level 

The hyponatraemic effect of diuretics may be intensified 

by concomitant administration of medicinal products such 

as antidepressants, antipsychotics, antiepileptics, etc. 

Caution is indicated in long-term administration of these 

medicinal products. 

 Medicinal products 

that could induce 

torsades de pointes 

Due to the risk of hypokalaemia, hydrochlorothiazide 

should be administered with caution when associated with 

medicinal products that could induce torsades de pointes, 

in particular Class Ia and Class III antiarrhythmics and 

some antipsychotics. 

 Medicinal products 

used in the treatment of 

gout (probenecid, 

sulfinpyrazone and 

allopurinol) 

Dose adjustment of uricosuric medicinal products may be 

necessary as hydrochlorothiazide may raise the level of 

serum uric acid. Increase of dose of probenecid or 

sulfinpyrazone may be necessary. 

Co-administration of thiazide diuretics, including 

hydrochlorothiazide, may increase the incidence of 

hypersensitivity reactions to allopurinol. 

 Methyldopa There have been isolated reports of haemolytic anaemia 

occurring with concomitant use of hydrochlorothiazide 

and methyldopa. 

 Non-depolarising 

skeletal muscle 

relaxants (e.g. 

tubocurarine) 

Thiazides, including hydrochlorothiazide, potentiate the 

action of curare derivatives. 

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Other anti-hypertensive 

drugs 

Thiazides potentiate the antihypertensive action of other 

antihypertensive drugs (e.g. guanethidine, methyldopa, 

beta-blockers, vasodilators, calcium channel blockers, 

ACE inhibitors, ARBs and Direct Renin Inhibitors 

[DRIs]). 

Pressor amines (e.g. 

noradrenaline, 

adrenaline) 

Hydrochlorothiazide may reduce the response to pressor 

amines such as noradrenaline. The clinical significance of 

this effect is uncertain and not sufficient to preclude their 

use. 

Vitamin D and calcium 

salts 

Administration of thiazide diuretics, including 

hydrochlorothiazide, with vitamin D or with calcium salts 

may potentiate the rise in serum calcium. Concomitant use 

of thiazide type diuretics may lead to hypercalcaemia in 

patients pre-disposed for hypercalcaemia (e.g. 

hyperparathyroidism, malignancy or vitamin-D-mediated 

conditions) by increasing tubular calcium reabsorption. 

 

No interaction 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Valsartan  Others 

(cimetidine, warfarin, 

furosemide, digoxin, 

atenolol, indometacin, 

hydrochlorothiazide, 

amlodipine, 

glibenclamide) 

In monotherapy with valsartan, no interactions of clinical 

significance have been found with the following 

substances: cimetidine, warfarin, furosemide, digoxin, 

atenolol, indomethacin, hydrochlorothiazide, amlodipine, 

glibenclamide. 

 

Some of these substances could interact with the 

hydrochlorothiazide component of Imprida HCT (see 

interactions related to HCT). 

Amlodipine Others In clinical interaction studies, amlodipine did not affect 

the pharmacokinetics of atorvastatin, digoxin, warfarin or 

ciclosporin. 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

Amlodipine 

The safety of amlodipine in human pregnancy has not been established. In animal studies, 

reproductive toxicity was observed at high doses (see section 5.3). Use in pregnancy is only 

recommended when there is no safer alternative and when the disease itself carries greater risk for the 

mother and foetus. 

 

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Valsartan 

The use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during the first 

trimester of pregnancy (see section 4.4). The use of AIIRAs is contraindicated during the second and 

third trimesters of pregnancy (see sections 4.3 and 4.4). 

 

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors 

during the first trimester of pregnancy has not been conclusive; however a small increase in risk 

cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II 

Receptor Antagonists (AIIRAs), similar risks may exist for this class of drugs. Unless continued 

AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative 

antihypertensive treatments which have an established safety profile for use in pregnancy. When 

pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and if appropriate, 

alternative therapy should be started. 

 

Exposure to AIIRAs therapy during the second and third trimesters is known to induce human 

foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal 

toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3). 

 

Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check 

of renal function and skull is recommended. 

 

Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see sections 

4.3 and 4.4). 

 

Hydrochlorothiazide 

There is limited experience with hydrochlorothiazide during pregnancy, especially during the first 

trimester. Animal studies are insufficient. 

 

Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of 

hydrochlorothiazide, its use during the second and third trimester may compromise foeto-placental 

perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance 

and thrombocytopenia. 

 

Amlodipine/valsartan/hydrochlorothiazide 

There is no experience on the use of Imprida HCT in pregnant women. Based on the existing data 

with the components, the use of Imprida HCT is not recommended during first trimester and contra-

indicated during the second and third trimester of pregnancy (see sections 4.3 and 4.4). 

 

Breast-feeding 

No information is available regarding the use of valsartan and/or amlodipine during breast-feeding. 

Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing 

intense diuresis can inhibit milk production. The use of Imprida HCT during breast-feeding is not 

recommended. If Imprida HCT is used during breast-feeding, doses should be kept as low as possible. 

Alternative treatments with better established safety profiles during breast-feeding are preferable, 

especially while nursing a newborn or preterm infant. 

 

Fertility 

There are no clinical studies on fertility with Imprida HCT. 

 

Valsartan 

Valsartan had no adverse effects on the reproductive performance of male or female rats at oral doses 

up to 200 mg/kg/day. This dose is 6 times the maximum recommended human dose on a mg/m
2
 basis 

(calculations assume an oral dose of 320 mg/day and a 60-kg patient). 

 

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Amlodipine 

Reversible biochemical changes in the head of spermatozoa have been reported in some patients 

treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of 

amlodipine on fertility. In one rat study, adverse effects were found on male fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 

 

No studies on the effects on the ability to drive and use machines have been performed. When driving 

vehicles or using machines it should be taken into account that occasionally dizziness or weariness 

may occur. 

 

4.8 Undesirable effects 

 

The safety profile of Imprida HCT presented below is based on clinical studies performed with 

Imprida HCT and the known safety profile of the individual components amlodipine, valsartan and 

hydrochlorothiazide. 

 

Information on Imprida HCT 

The safety of Imprida HCT has been evaluated at its maximum dose of 10 mg/320 mg/25 mg in one 

controlled short-term (8 weeks) clinical study with 2,271 patients, 582 of whom received valsartan in 

combination with amlodipine and hydrochlorothiazide. Adverse reactions were generally mild and 

transient in nature and only infrequently required discontinuation of therapy. In this active controlled 

clinical trial, the most common reasons for discontinuation of therapy with Imprida HCT were 

dizziness and hypotension (0.7%). 

 

In the 8-week controlled clinical study, no significant new or unexpected adverse reactions were 

observed with triple therapy treatment compared to the known effects of the monotherapy or dual 

therapy components. 

 

In the 8-week controlled clinical study, changes in laboratory parameters observed with the 

combination of Imprida HCT were minor and consistent with the pharmacological mechanism of 

action of the monotherapy agents. The presence of valsartan in the triple combination attenuated the 

hypokalaemic effect of hydrochlorothiazide. 

 

The following adverse reactions, listed by MedDRA System Organ Class and frequency, concern 

Imprida HCT (amlodipine/valsartan/HCT) and amlodipine, valsartan and HCT individually. 

Very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1,000 to <1/100; rare: ≥1/10,000 to 

<1/1,000; very rare: <1/10,000, not known (cannot be estimated from the available data). 

 

MedDRA 

System Organ 

Class 

Adverse reactions Frequency    

Imprida 

HCT 

Amlodipine Valsartan HCT 

Blood and 

lymphatic system 

disorders 

Agranulocytosis, bone 

marrow depression 

-- -- -- Very rare 

Decrease in haemoglobin 

and in haematocrit 

-- -- Not known -- 

Haemolytic anaemia -- -- -- Very rare 

Leukopenia -- Very rare -- Very rare 

Neutropenia -- -- Not known -- 

Thrombocytopenia, 

sometimes with purpura 

-- Very rare Not known Rare 

Aplastic anaemia -- -- -- Not known 

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Immune system 

disorders 

Hypersensitivity -- Very rare Not known Very rare 

Metabolism and 

nutrition 

disorders 

Anorexia Uncommon -- -- -- 

Hypercalcaemia Uncommon -- -- Rare 

Hyperglycaemia -- Very rare -- Rare 

Hyperlipidaemia Uncommon -- -- -- 

Hyperuricaemia Uncommon -- -- Common 

Hypochloraemic alkalosis -- -- -- Very rare 

Hypokalaemia Common -- -- Very 

common 

Hypomagnesaemia -- -- -- Common 

Hyponatraemia Uncommon -- -- Common 

Worsening of diabetic 

metabolic state 

-- -- -- Rare 

Psychiatric 

disorders 

Depression -- -- -- Rare 

Insomnia/sleep disturbances Uncommon Uncommon -- Rare 

Mood swings -- Uncommon --  

Nervous system 

disorders 

Coordination abnormal Uncommon -- -- -- 

Dizziness Common Common -- Rare 

Dizziness postural, dizziness 

exertional 

Uncommon -- -- -- 

Dysgeusia Uncommon Uncommon -- -- 

Extrapyramidal syndrome -- Not known -- -- 

Headache Common Common -- Rare 

Hypertonia -- Very rare -- -- 

Lethargy Uncommon -- -- -- 

Paraesthesia Uncommon Uncommon -- Rare 

Peripheral neuropathy, 

neuropathy 

Uncommon Very rare -- -- 

Somnolence Uncommon Common -- -- 

Syncope Uncommon Uncommon -- -- 

Tremor -- Uncommon -- -- 

Eye disorders Acute angle-closure 

glaucoma 

-- -- -- Not known 

Visual impairment Uncommon Uncommon -- Rare 

Ear and labyrinth 

disorders 

Tinnitus -- Uncommon -- -- 

Vertigo Uncommon -- Uncommon -- 

Cardiac disorders Palpitations -- Common -- -- 

Tachycardia Uncommon -- -- -- 

Arrhythmias (including 

bradycardia, ventricular 

tachycardia, and atrial 

fibrillation) 

-- Very rare -- Rare 

Myocardial infarction -- Very rare -- -- 

Vascular 

disorders 

Flushing -- Common -- -- 

Hypotension Common Uncommon -- -- 

Orthostatic hypotension Uncommon -- -- Common 

Phlebitis, thrombophlebitis Uncommon -- -- -- 

Vasculitis -- Very rare Not known -- 

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Respiratory, 

thoracic and 

mediastinal 

disorders 

Cough Uncommon Very rare Uncommon -- 

Dyspnoea Uncommon Uncommon -- -- 

Respiratory distress, 

pulmonary oedema, 

pneumonitis 

-- -- -- Very rare 

Rhinitis -- Uncommon -- -- 

Throat irritation Uncommon -- -- -- 

Gastrointestinal 

disorders 

Abdominal discomfort, 

abdominal pain upper 

Uncommon Common Uncommon Rare 

Breath odour Uncommon -- -- -- 

Change of bowel habit -- Uncommon -- -- 

Constipation -- -- -- Rare 

Decreased appetite -- -- -- Common 

Diarrhoea Uncommon Uncommon -- Rare 

Dry mouth Uncommon Uncommon -- -- 

Dyspepsia Common Uncommon -- -- 

Gastritis -- Very rare -- -- 

Gingival hyperplasia -- Very rare -- -- 

Nausea Uncommon Common -- Common 

Pancreatitis -- Very rare -- Very rare 

Vomiting Uncommon Uncommon -- Common 

Hepatobiliary 

disorders 

Hepatic enzyme elevation, 

including increase of serum 

bilirubin 

-- Very rare Not known -- 

Hepatitis -- Very rare -- -- 

Intrahepatic cholestasis, 

jaundice 

-- Very rare -- Rare 

Skin and 

subcutaneous 

tissue disorders 

Alopecia -- Uncommon --  

Angioedema -- Very rare Not known -- 

Cutaneous lupus 

erythematosus-like 

reactions, reactivation of 

cutaneous lupus 

erythematosus 

-- -- -- Very rare 

Erythema multiforme -- Very rare -- Not known 

Exanthema -- Uncommon -- -- 

Hyperhidrosis Uncommon Uncommon -- -- 

Photosensitivity reaction* -- -- -- Rare 

Pruritus Uncommon Uncommon Not known -- 

Purpura -- Uncommon -- Rare 

Rash -- Uncommon Not known Common 

Skin discoloration -- Uncommon -- -- 

Urticaria and other forms of 

rash 

-- Very rare -- Common 

Vasculitis necrotising and 

toxic epidermal necrolysis 

-- -- -- Very rare 

Musculoskeletal 

and connective 

tissue disorders 

Arthralgia -- Uncommon -- -- 

Back pain Uncommon Uncommon -- -- 

Joint swelling Uncommon -- -- -- 

Muscle spasm Uncommon Uncommon -- Not known 

Muscular weakness Uncommon -- -- -- 

Myalgia Uncommon Uncommon Not known -- 

Pain in extremity Uncommon -- -- -- 

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Renal and 

urinary disorders 

Elevation of serum 

creatinine 

Uncommon -- Not known -- 

Micturition disorder  Uncommon   

Nocturia -- Uncommon -- -- 

Pollakiuria Common Uncommon   

Renal dysfunction -- -- -- Not known 

Renal failure acute Uncommon -- -- Not known 

Renal failure and 

impairment 

-- -- Not known Rare 

Reproductive 

system and 

breast disorders 

Impotence Uncommon Uncommon -- Common 

Gynaecomastia  Uncommon -- -- 

General 

disorders and 

administration 

site conditions 

Abasia, gait disturbance Uncommon -- -- -- 

Asthenia Uncommon Uncommon -- Not known 

Discomfort, malaise Uncommon Uncommon -- -- 

Fatigue Common Common Uncommon -- 

Non cardiac chest pain Uncommon Uncommon -- -- 

Oedema Common Common -- -- 

Pain -- Uncommon -- -- 

Pyrexia -- -- -- Not known 

Investigations Lipids increased  --  Very 

common 

Blood urea nitrogen 

increased 

Uncommon -- -- -- 

Blood uric acid increased Uncommon -- --  

Glycosuria    Rare 

Serum potassium decreased Uncommon  -- -- -- 

Serum potassium increased -- -- Not known -- 

Weight increase Uncommon Uncommon -- -- 

Weight decrease -- Uncommon -- -- 

 

* See section 4.4 Photosensitivity 

 

4.9 Overdose 

 

Symptoms 

There is no experience of overdose with Imprida HCT. The major symptom of overdose with 

valsartan is possibly pronounced hypotension with dizziness. Overdose with amlodipine may result in 

excessive peripheral vasodilation and, possibly, reflex tachycardia. Marked and potentially prolonged 

systemic hypotension, including shock with fatal outcome, have been reported with amlodipine. 

 

Treatment 

Amlodipine/Valsartan/Hydrochlorothiazide 

Clinically significant hypotension due to Imprida HCT overdose calls for active cardiovascular 

support, including frequent monitoring of cardiac and respiratory function, elevation of extremities, 

and attention to circulating fluid volume and urine output. A vasoconstrictor may be helpful in 

restoring vascular tone and blood pressure, provided that there is no contraindication to its use. 

Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. 

 

Amlodipine 

If ingestion is recent, induction of vomiting or gastric lavage may be considered. Administration of 

activated charcoal to healthy volunteers immediately or up to two hours after ingestion of amlodipine 

has been shown to significantly decrease amlodipine absorption. 

Amlodipine is unlikely to be removed by haemodialysis. 

 

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Valsartan 

Valsartan is unlikely to be removed by haemodialysis. 

 

Hydrochlorothiazide 

Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, 

hypochloraemia) and hypovolaemia resulting from excessive diuresis. The most common signs and 

symptoms of overdose are nausea and somnolence. Hypokalaemia may result in muscle spasms and or 

accentuate arrhythmia associated with the concomitant use of digitalis glycosides or certain anti-

arrhythmic medicinal products. 

The degree to which hydrochlorothiazide is removed by haemodialysis has not been established. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Angiotensin II antagonists, plain (valsartan), combinations with 

dihydropyridine derivatives (amlodipine) and thiazide diuretics (hydrochlorothiazide), ATC code: 

C09DX01 valsartan, amlodipine and hydrochlorothiazide. 

 

Imprida HCT combines three antihypertensive compounds with complementary mechanisms to 

control blood pressure in patients with essential hypertension: amlodipine belongs to the calcium 

antagonist class and valsartan to the angiotensin II antagonist class of medicines and 

hydrochlorothiazide belongs to the thiazide diuretics class of medicines. The combination of these 

substances has an additive antihypertensive effect. 

 

Amlodipine/Valsartan/Hydrochlorothiazide 

Imprida HCT was studied in a double-blind, active controlled study in hypertensive patients. A total 

of 2,271 patients with moderate to severe hypertension (mean baseline systolic/diastolic blood 

pressure was 170/107 mmHg) received treatments of amlodipine/valsartan/hydrochlorothiazide 

10 mg/320 mg/25 mg, valsartan/hydrochlorothiazide 320 mg/25 mg, amlodipine/valsartan 

10 mg/320 mg, or hydrochlorothiazide/amlodipine 25 mg/10 mg. At study initiation patients were 

assigned lower doses of their treatment combination and were titrated to their full treatment dose by 

week 2. 

 

At week 8, the mean reductions in systolic/diastolic blood pressure were 39.7/24.7 mmHg with 

Imprida HCT, 32.0/19.7 mmHg with valsartan/hydrochlorothiazide, 33.5/21.5 mmHg with 

amlodipine/valsartan, and 31.5/19.5 mmHg with amlodipine/hydrochlorothiazide. The triple 

combination therapy was statistically superior to each of the three dual combination treatments in 

reduction of diastolic and systolic blood pressures. The reductions in systolic/diastolic blood pressure 

with Imprida HCT were 7.6/5.0 mmHg greater than with valsartan/hydrochlorothiazide, 

6.2/3.3 mmHg greater than with amlodipine/valsartan, and 8.2/5.3 mmHg greater than with 

amlodipine/hydrochlorothiazide. The full blood pressure lowering effect was achieved 2 weeks after 

being on their maximal dose of Imprida HCT. Statistically greater proportions of patients achieved 

blood pressure control (<140/90 mmHg) with Imprida HCT (71%) compared to each of the three dual 

combination therapies (45-54%) (p<0.0001). 

 

In a subgroup of 283 patients focusing on ambulatory blood pressure monitoring, clinically and 

statistically superior reductions in 24-hour systolic and diastolic blood pressures were observed with 

the triple combination compared to valsartan/hydrochlorothiazide, valsartan/amlodipine, and 

hydrochlorothiazide/amlodipine. 

 

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Amlodipine 

The amlodipine component of Imprida HCT inhibits the transmembrane entry of calcium ions into 

cardiac and vascular smooth muscle. The mechanism of the antihypertensive action of amlodipine is 

due to a direct relaxant effect on vascular smooth muscle, causing reductions in peripheral vascular 

resistance and in blood pressure. Experimental data suggest that amlodipine binds to both 

dihydropyridine and non-dihydropyridine binding sites. The contractile processes of cardiac muscle 

and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into 

these cells through specific ion channels. 

 

Following administration of therapeutic doses to patients with hypertension, amlodipine produces 

vasodilation, resulting in a reduction of supine and standing blood pressures. These decreases in blood 

pressure are not accompanied by a significant change in heart rate or plasma catecholamine levels 

with chronic dosing. 

 

Plasma concentrations correlate with effect in both young and elderly patients. 

 

In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in a 

decrease in renal vascular resistance and increases in glomerular filtration rate and effective renal 

plasma flow, without change in filtration fraction or proteinuria. 

 

Valsartan 

Valsartan is an orally active, potent and specific angiotensin II receptor antagonist. It acts selectively 

on the receptor subtype AT1, which is responsible for the known actions of angiotensin II. 

 

Administration of valsartan to patients with hypertension results in a drop in blood pressure without 

affecting pulse rate. 

 

In most patients, after administration of a single oral dose, onset of antihypertensive activity occurs 

within 2 hours, and the peak drop in blood pressure is achieved within 4-6 hours. The 

antihypertensive effect persists over 24 hours after administration. During repeated administration, the 

maximum reduction in blood pressure with any dose is generally attained within 2-4 weeks. 

 

Hydrochlorothiazide 

The site of action of thiazide diuretics is primarily in the renal distal convoluted tubule. It has been 

shown that there is a high-affinity receptor in the renal cortex as the primary binding site for the 

thiazide diuretic action and inhibition of NaCl transport in the distal convoluted tubule. The mode of 

action of thiazides is through inhibition of the Na
+
Cl

-
 symporter perhaps by competing for the Cl

-
 site, 

thereby affecting electrolyte reabsorption mechanisms: directly increasing sodium and chloride 

excretion to an approximately equal extent, and indirectly, by this diuretic action, reducing plasma 

volume, with consequent increases in plasma renin activity, aldosterone secretion and urinary 

potassium loss, and a decrease in serum potassium. 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

Imprida HCT in all subsets of the paediatric population in essential hypertension. See section 4.2 for 

information on paediatric use. 

 

5.2 Pharmacokinetic properties 

 

Linearity 

Amlodipine, valsartan and hydrochlorothiazide exhibit linear pharmacokinetics. 

 

Amlodipine/valsartan/hydrochlorothiazide 

Following oral administration of Imprida HCT in normal healthy adults, peak plasma concentrations 

of amlodipine, valsartan and hydrochlorothiazide are reached in 6-8 hours, 3 hours, and 2 hours, 

respectively. The rate and extent of absorption of amlodipine, valsartan and hydrochlorothiazide from 

Imprida HCT are the same as when administered as individual dosage forms. 

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60 

 

Amlodipine 

Absorption: After oral administration of therapeutic doses of amlodipine alone, peak plasma 

concentrations of amlodipine are reached in 6-12 hours. Absolute bioavailability has been calculated as 

between 64% and 80%. Amlodipine bioavailability is unaffected by food ingestion. 

 

Distribution: Volume of distribution is approximately 21 l/kg. In vitro studies with amlodipine have 

shown that approximately 97.5% of circulating drug is bound to plasma proteins. 

 

Biotransformation: Amlodipine is extensively (approximately 90%) metabolised in the liver to inactive 

metabolites. 

 

Elimination: Amlodipine elimination from plasma is biphasic, with a terminal elimination half-life of 

approximately 30 to 50 hours. Steady-state plasma levels are reached after continuous administration for 

7-8 days. Ten per cent of original amlodipine and 60% of amlodipine metabolites are excreted in urine. 

 

Valsartan 

Absorption: Following oral administration of valsartan alone, peak plasma concentrations of valsartan 

are reached in 2-4 hours. Mean absolute bioavailability is 23%. Food decreases exposure (as 

measured by AUC) to valsartan by about 40% and peak plasma concentration (Cmax) by about 50%, 

although from about 8 h post dosing plasma valsartan concentrations are similar for the fed and fasted 

groups. This reduction in AUC is not, however, accompanied by a clinically significant reduction in 

the therapeutic effect, and valsartan can therefore be given either with or without food. 

 

Distribution: The steady-state volume of distribution of valsartan after intravenous administration is 

about 17 litres, indicating that valsartan does not distribute into tissues extensively. Valsartan is 

highly bound to serum proteins (94-97%), mainly serum albumin. 

 

Biotransformation: Valsartan is not transformed to a high extent as only about 20% of dose is 

recovered as metabolites. A hydroxy metabolite has been identified in plasma at low concentrations 

(less than 10% of the valsartan AUC). This metabolite is pharmacologically inactive. 

 

Elimination: Valsartan is primarily eliminated in faeces (about 83% of dose) and urine (about 13% of 

dose), mainly as unchanged drug. Following intravenous administration, plasma clearance of valsartan 

is about 2 l/h and its renal clearance is 0.62 l/h (about 30% of total clearance). The half-life of 

valsartan is 6 hours. 

 

Hydrochlorothiazide 

Absorption: The absorption of hydrochlorothiazide, after an oral dose, is rapid (Tmax about 2 hours). 

The increase in mean AUC is linear and dose proportional in the therapeutic range. 

 

The effect of food on hydrochlorothiazide absorption, if any, has little clinical significance. Absolute 

bioavailability of hydrochlorothiazide is 70% after oral administration. 

 

Distribution: The apparent volume of distribution is 4-8 l/kg. Circulating hydrochlorothiazide is 

bound to serum proteins (40-70%), mainly serum albumin. Hydrochlorothiazide also accumulates in 

erythrocytes at approximately 3 times the level in plasma. 

 

Biotransformation: Hydrochlorothiazide is eliminated predominantly as unchanged compound. 

 

Elimination: Hydrochlorothiazide is eliminated from plasma with a half-life averaging 6 to 15 hours 

in the terminal elimination phase. There is no change in the kinetics of hydrochlorothiazide on 

repeated dosing, and accumulation is minimal when dosed once daily. More than 95% of the absorbed 

dose is being excreted as unchanged compound in the urine. The renal clearance is composed of 

passive filtration and active secretion into the renal tubule. 

 

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61 

Special populations 

Paediatric patients (age below 18 years) 

No pharmacokinetic data are available in the paediatric population. 

 

Elderly (age 65 years or over) 

Time to peak plasma amlodipine concentrations is similar in young and elderly patients. In elderly 

patients, amlodipine clearance tends to decline, causing increases in the area under the curve (AUC) 

and elimination half-life. Mean systemic AUC of valsartan is higher by 70% in the elderly than in the 

young, therefore caution is required when increasing the dosage. 

 

Systemic exposure to valsartan is slightly elevated in the elderly as compared to the young, but this 

has not been shown to have any clinical significance. 

 

Limited data suggest that the systemic clearance of hydrochlorothiazide is reduced in both healthy and 

hypertensive elderly subjects compared to young healthy volunteers. 

 

Since the three components are equally well tolerated in younger and elderly patients, normal dose 

regimens are recommended (see section 4.2). 

 

Renal impairment 

The pharmacokinetics of amlodipine are not significantly influenced by renal impairment. As 

expected for a compound where renal clearance accounts for only 30% of total plasma clearance, no 

correlation was seen between renal function and systemic exposure to valsartan. 

 

Patients with mild to moderate renal impairment may therefore receive the usual initial dose (see 

sections 4.2 and 4.4). 

 

In the presence of renal impairment, mean peak plasma levels and AUC values of hydrochlorothiazide 

are increased and the urinary excretion rate is reduced. In patients with mild to moderate renal 

impairment, a 3-fold increase in hydrochlorothiazide AUC has been observed. In patients with severe 

renal impairment an 8-fold increase in AUC has been observed. Imprida HCT is contraindicated in 

patients with severe renal impairment, anuria or undergoing dialysis (see section 4.3). 

 

Hepatic impairment 

Patients with hepatic insufficiency have decreased clearance of amlodipine with resulting increase of 

approximately 40–60% in AUC. On average, in patients with mild to moderate chronic liver disease, 

exposure (measured by AUC values) to valsartan is twice that found in healthy volunteers (matched 

by age, sex and weight). Due to the valsartan component, Imprida HCT is contraindicated in patients 

with hepatic impairment (see sections 4.2 and 4.3). 

 

5.3 Preclinical safety data 

 

Amlodipine/Valsartan/Hydrochlorothiazide 

In a variety of preclinical safety studies conducted in several animal species with amlodipine, 

valsartan, hydrochlorothiazide, valsartan/hydrochlorothiazide, amlodipine/valsartan and 

amlodipine/valsartan/hydrochlorothiazide (Imprida HCT), there was no evidence of systemic or target 

organ toxicity that would adversely affect the development of Imprida HCT for clinical use in 

humans. 

 

Preclinical safety studies of up to 13 weeks in duration were conducted with 

amlodipine/valsartan/hydrochlorothiazide in rats. The combination resulted in expected reduction of 

red blood cell mass (erythrocytes, haemoglobin, haematocrit, and reticulocytes), increase in serum 

urea, increase in serum creatinine, increase in serum potassium, juxtaglomerular (JG) hyperplasia in 

the kidney and focal erosions in the glandular stomach in rats. All these changes were reversible after 

a 4-week recovery period and were considered to be exaggerated pharmacological effects. 

 

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The amlodipine/valsartan/hydrochlorothiazide combination was not tested for genotoxicity or 

carcinogenicity as there was no evidence of any interaction between these substances, which have 

been on the market for a long time. However, amlodipine, valsartan and hydrochlorothiazide have 

been tested individually for genotoxicity and carcinogenicity with negative results. 

 

Amlodipine 

Reproductive toxicology 

Reproductive studies in rats and mice have shown delayed date of delivery, prolonged duration of 

labour and decreased pup survival at dosages approximately 50 times greater than the maximum 

recommended dosage for humans based on mg/kg. 

 

Impairment of fertility 

There was no effect on the fertility of rats treated with amlodipine (males for 64 days and females 

14 days prior to mating) at doses up to 10 mg/kg/day (8 times* the maximum recommended human 

dose of 10 mg on a mg/m
2
 basis). In another rat study in which male rats were treated with amlodipine 

besilate for 30 days at a dose comparable with the human dose based on mg/kg, decreased plasma 

follicle-stimulating hormone and testosterone were found as well as decreases in sperm density and in 

the number of mature spermatids and Sertoli cells. 

 

Carcinogenesis, mutagenesis 

Rats and mice treated with amlodipine in the diet for two years, at concentrations calculated to 

provide daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day showed no evidence of carcinogenicity. 

The highest dose (for mice, similar to, and for rats twice* the maximum recommended clinical dose of 

10 mg on a mg/m
2
 basis) was close to the maximum tolerated dose for mice but not for rats. 

 

Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels. 

 

* Based on patient weight of 50 kg 

 

Valsartan 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential. 

 

In rats, maternally toxic doses (600 mg/kg/day) during the last days of gestation and lactation led to 

lower survival, lower weight gain and delayed development (pinna detachment and ear-canal opening) 

in the offspring (see section 4.6). These doses in rats (600 mg/kg/day) are approximately 18 times the 

maximum recommended human dose on a mg/m
2 
basis (calculations assume an oral dose of 

320 mg/day and a 60-kg patient). 

 

In non-clinical safety studies, high doses of valsartan (200 to 600 mg/kg body weight) caused in rats a 

reduction of red blood cell parameters (erythrocytes, haemoglobin, haematocrit) and evidence of 

changes in renal haemodynamics (slightly raised plasma urea, and renal tubular hyperplasia and 

basophilia in males). These doses in rats (200 and 600 mg/kg/day) are approximately 6 and 18 times 

the maximum recommended human dose on a mg/m
2
 basis (calculations assume an oral dose of 

320 mg/day and a 60-kg patient). 

 

In marmosets at similar doses, the changes were similar though more severe, particularly in the kidney 

where the changes developed to a nephropathy which included raised urea and creatinine. 

 

Hypertrophy of the renal juxtaglomerular cells was also seen in both species. All changes were 

considered to be caused by the pharmacological action of valsartan which produces prolonged 

hypotension, particularly in marmosets. For therapeutic doses of valsartan in humans, the hypertrophy 

of the renal juxtaglomerular cells does not seem to have any relevance. 

 

 

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6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Tablet core 

Cellulose microcrystalline 

Crospovidone 

Silica, colloidal anhydrous 

Magnesium stearate 

 

Coating 

Hypromellose 

Macrogol 4000 

Talc 

Titanium dioxide (E171) 

Iron oxide, yellow (E172) 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

2 years 

 

6.4 Special precautions for storage 

 

Do not store above 30°C. 

 

Store in the original package in order to protect from moisture. 

 

6.5 Nature and contents of container 

 

PVC/PVDC blisters. One blister contains 7, 10 or 14 film-coated tablets. 

Pack sizes: 14, 28, 30, 56, 90, 98 or 280 film-coated tablets. 

Multipacks of 280 tablets, comprising 20 cartons, each containing 14 tablets. 

 

PVC/PVDC perforated unit dose blisters for hospital use: 

Pack sizes: 56, 98 or 280 film-coated tablets 

Multipacks of 280 tablets, comprising 4 cartons, each containing 70 tablets. 

 

Not all pack sizes or strengths may be marketed. 

 

6.6 Special precautions for disposal and other handling 

 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

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8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/025-036 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

15.10.2009 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

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65 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/160 mg/25 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains 10 mg of amlodipine (as amlodipine besylate), 160 mg of valsartan, 

and 25 mg of hydrochlorothiazide. 

 

For a full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet (tablet) 

 

Brown-yellow, ovaloid, biconvex tablets with bevelled edge, debossed “NVR” on one side and 

“VHL” on the other side. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment of essential hypertension as substitution therapy in adult patients whose blood pressure is 

adequately controlled on the combination of amlodipine, valsartan and hydrochlorothiazide (HCT), 

taken either as three single-component formulations or as a dual-component and a single-component 

formulation. 

 

4.2 Posology and method of administration 

 

Posology 

The recommended dose of Imprida HCT is one tablet per day, to be taken preferably in the morning. 

 

Before switching to Imprida HCT patients should be controlled on stable doses of the 

monocomponents taken at the same time. The dose of Imprida HCT should be based on the doses of 

the individual components of the combination at the time of switching. 

 

The maximum recommended dose of Imprida HCT is 10 mg/320 mg/25 mg. 

 

Special populations 

Renal impairment 

No adjustment of the initial dose is required for patients with mild to moderate renal impairment (see 

sections 4.4 and 5.2). Due to the hydrochlorothiazide component, Imprida HCT is contraindicated for 

use in patients with anuria (see section 4.3) and in patients with severe renal impairment (glomerular 

filtration rate (GFR) <30 ml/min/1.73 m
2
) (see sections 4.3, 4.4 and 5.2). 

 

Hepatic impairment 

Due to the valsartan component, Imprida HCT is contraindicated in patients with severe hepatic 

impairment (see section 4.3). In patients with mild to moderate hepatic impairment without 

cholestasis, the maximum recommended dose is 80 mg valsartan and therefore Imprida HCT is not 

suitable in this group of patients (see sections 4.3, 4.4 and 5.2). 

 

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66 

Heart failure and coronary artery disease 

There is limited experience with the use of Imprida HCT, particulary at the maximum dose, in 

patients with heart failure and coronary artery disease. Caution is advised in patients with heart failure 

and coronary artery disease, particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg. 

 

Elderly (age 65 years or over) 

Caution, including more frequent monitoring of blood pressure, is recommended in elderly patients, 

particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in this 

patient population are limited. 

 

Paediatric population 

There is no relevant use of Imprida HCT in the paediatric population (patients below age 18 years) for 

the indication of essential hypertension. 

 

Method of administration 

Imprida HCT can be taken with or without food. The tablets should be swallowed whole with some 

water, at the same time of the day and preferably in the morning. 

 

4.3 Contraindications 

 

 Hypersensitivity to the active substances, to other sulphonamide derivatives, to dihydropyridine 

derivatives, or to any of the excipients. 

 Second and third trimesters of pregnancy (see sections 4.4 and 4.6). 

 Hepatic impairment, biliary cirrhosis or cholestasis. 

 Severe renal impairment (GFR <30 ml/min/1.73 m2), anuria and patients undergoing dialysis. 

 Refractory hypokalaemia, hyponatraemia, hypercalcaemia, and symptomatic hyperuricaemia. 

 

4.4 Special warnings and precautions for use 

 

Sodium- and/or volume-depleted patients 

Excessive hypotension, including orthostatic hypotension, was seen in 1.7% of patients treated with 

the maximum dose of Imprida HCT (10 mg/320 mg/25 mg) compared to 1.8% of 

valsartan/hydrochlorothiazide (320 mg/25 mg) patients, 0.4% of amlodipine/valsartan (10 mg/320 mg) 

patients, and 0.2% of hydrochlorothiazide/amlodipine (25 mg/10 mg) patients in a controlled trial in 

patients with moderate to severe uncomplicated hypertension. 

 

In sodium-depleted and/or volume-depleted patients, such as those receiving high doses of diuretics, 

symptomatic hypotension may occur after initiation of treatment with Imprida HCT. Imprida HCT 

should be used only after correction of any pre-existing sodium and/or volume depletion. 

 

If excessive hypotension occurs with Imprida HCT, the patient should be placed in the supine position 

and, if necessary, given an intravenous infusion of normal saline. Treatment can be continued once 

blood pressure has been stabilised. 

 

Serum electrolyte changes 

Amlodipine/valsartan/hydrochlorothiazide 

In the controlled trial of Imprida HCT, the counteracting effects of valsartan 320 mg and 

hydrochlorothiazide 25 mg on serum potassium approximately balanced each other in many patients. 

In other patients, one or the other effect may be dominant. Periodic determinations of serum 

electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals. 

 

Periodic determination of serum electrolytes and potassium in particular should be performed at 

appropriate intervals to detect possible electrolyte imbalance, especially in patients with other risk 

factors such as impaired renal function, treatment with other medicinal products or history of prior 

electrolyte imbalances. 

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67 

 

Valsartan 

Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing 

potassium, or other medicinal products that may increase potassium levels (heparin, etc.) is not 

recommended. Monitoring of potassium should be undertaken as appropriate. 

 

Hydrochlorothiazide 

Treatment with Imprida HCT should only start after correction of hypokalaemia and any coexisting 

hypomagnesaemia. Thiazide diuretics can precipitate new onset hypokalaemia or exacerbate pre-

existing hypokalaemia. Thiazide diuretics should be administered with caution in patients with 

conditions involving enhanced potassium loss, for example salt-losing nephropathies and prerenal 

(cardiogenic) impairment of kidney function. If hypokalaemia develops during hydrochlorothiazide 

therapy, Imprida HCT should be discontinued until stable correction of the potassium balance. 

 

Thiazide diuretics can precipitate new onset hyponatraemia and hypochloroaemic alkalosis or 

exacerbate pre-existing hyponatraemia. Hyponatraemia, accompanied by neurological symptoms 

(nausea, progressive disorientation, apathy) has been observed. Treatment with hydrochlorothiazide 

should only be started after correction of pre-existing hyponatraemia. In case severe or rapid 

hyponatraemia develops during Imprida HCT therapy, the treatment should be discontinued until 

normalisation of natraemia. 

 

All patients receiving thiazide diuretics should be periodically monitored for imbalances in 

electrolytes, particularly potassium, sodium and magnesium. 

 

Renal impairment 

Thiazide diuretics may precipitate azotaemia in patients with chronic kidney disease. When Imprida 

HCT is used in patients with renal impairment periodic monitoring of serum electrolytes (including 

potassium), creatinine and uric acid serum levels is recommended. Imprida HCT is contraindicated in 

patients with severe renal impairment, anuria or undergoing dialysis (see section 4.3). 

 

No dosage adjustment of Imprida HCT is required for patients with mild to moderate renal 

impairment (GFR ≥30 ml/min/1.73 m
2
). 

 

Renal artery stenosis 

No data are available on the use of Imprida HCT in patients with unilateral or bilateral renal artery 

stenosis or stenosis to a solitary kidney. 

 

Kidney transplantation 

To date there is no experience of the safe use of Imprida HCT in patients who have had a recent 

kidney transplantation. 

 

Hepatic impairment 

Valsartan is mostly eliminated unchanged via the bile, whereas amlodipine is extensively metabolised 

by the liver. In patients with mild to moderate hepatic impairment without cholestasis, the maximum 

recommended dose is 80 mg valsartan, and therefore, Imprida HCT is not suitable in this group of 

patients (see sections 4.2, 4.3 and 5.2). 

 

Heart failure and coronary artery disease 

As a consequence of the inhibition of the renin-angiotensin-aldosterone system, changes in renal 

function may be anticipated in susceptible individuals. In patients with severe heart failure whose 

renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with 

angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been 

associated with oliguria and/or progressive azotaemia and (rarely) with acute renal failure and/or 

death. Similar outcomes have been reported with valsartan. 

 

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68 

In a long-term, placebo-controlled study (PRAISE-2) of amlodipine in patients with NYHA (New 

York Heart Association Classification) III and IV heart failure of non-ischaemic aetiology, amlodipine 

was associated with increased reports of pulmonary oedema despite no significant difference in the 

incidence of worsening heart failure as compared to placebo. 

 

Caution is advised in patients with heart failure and coronary artery disease, particularly at the 

maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in these patient 

populations is limited. 

 

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy 

As with all other vasodilators, special caution is indicated in patients with aortic or mitral stenosis, or 

obstructive hypertrophic cardiomyopathy. 

 

Pregnancy 

Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless 

continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to 

alternative antihypertensive treatments which have an established safety profile for use in pregnancy. 

When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if 

appropriate, alternative therapy should be started (see sections 4.3 and 4.6). 

 

Primary hyperaldosteronism 

Patients with primary hyperaldosteronism should not be treated with the angiotensin II antagonist 

valsartan as their renin-angiotensin system is not activated. Therefore, Imprida HCT is not 

recommended in this population. 

 

Systemic lupus erythematosus 

Thiazide diuretics, including hydrochlorothiazide, have been reported to exacerbate or activate 

systemic lupus erythematosus. 

 

Other metabolic disturbances 

Thiazide diuretics, including hydrochlorothiazide, may alter glucose tolerance and raise serum levels 

of cholesterol, triglycerides and uric acid. In diabetic patients dosage adjustments of insulin or oral 

hypoglycaemic agents may be required. 

 

Due to the hydrochlorothiazide component, Imprida HCT is contraindicated in symptomatic 

hyperuricaemia. Hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of 

uric acid and may cause or exacerbate hyperuricaemia as well as precipitate gout in susceptible 

patients. 

 

Thiazides reduce urinary calcium excretion and may cause intermittant and slight elevation of serum 

calcium in the absence of known disorders of calcium metabolism. Imprida HCT is contraindicated in 

patients with hypercalcaemia and should only be used after correction of any pre-existing 

hypercalcaemia. Imprida HCT should be discontinued if hypercalcaemia develops during treatment. 

Serum levels of calcium should be periodically monitored during treatment with thiazides. Marked 

hypercalcaemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued 

before carrying out tests for parathyroid function. 

 

Photosensitivity 

Cases of photosensitivity reactions have been reported with thiazide diuretics (see section 4.8). If 

photosensitivity reaction occurs during treatment with Imprida HCT, it is recommended to stop the 

treatment. If a readministration of the diuretic is deemed necessary, it is recommended to protect 

exposed areas to the sun or to artificial UVA. 

 

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Acute angle-closure glaucoma 

Hydrochlorothiazide, a sulphonamide, has been associated with an idiosyncratic reaction resulting in 

acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased 

visual acuity or ocular pain and typically occur within hours to a week of treatment initiation. 

Untreated acute-angle closure glaucoma can lead to permanent vision loss. 

 

The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or 

surgical treatment may need to be considered if the intraocular pressure remains uncontrolled. Risk 

factors for developing acute angle closure glaucoma may include a history of sulphonamide or 

penicillin allergy. 

 

General 

Caution should be exercised in patients who have shown prior hypersensitivity to other angiotensin II 

receptor antagonists. Hypersensitivity reactions to hydrochlorothiazide are more likely in patients 

with allergy and asthma. 

 

Elderly (age 65 years or over) 

Caution, including more frequent monitoring of blood pressure, is recommended in elderly patients, 

particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in this 

patient population are limited. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

No formal interaction studies with other medicinal products were performed with Imprida HCT. Thus, 

only information on interactions with other medicinal products that are known for the individual 

active substances is provided in this section. 

 

However, it is important to take into account that Imprida HCT may increase the hypotensive effect of 

other antihypertensive agents. 

 

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Concomitant use not recommended 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Valsartan 

and 

HCT 

Lithium Reversible increases in serum lithium concentrations and 

toxicity have been reported during concurrent use of ACE 

inhibitors and thiazides such as hydrochlorothiazide. 

Despite the lack of experience with concomitant use of 

valsartan and lithium, this combination is not 

recommended. If the combination proves necessary, 

careful monitoring of serum lithium levels is 

recommended (see section 4.4). 

Valsartan Potassium-sparing 

diuretics, potassium 

supplements, salt 

substitutes containing 

potassium and other 

substances that may 

increase potassium 

levels 

If a medicinal product that affects potassium levels is 

considered necessary in combination with valsartan, 

frequent monitoring of potassium plasma levels is 

advised. 

Amlodipine Grapefruit or grapefruit 

juice 

Administration of amlodipine with grapefruit or grapefruit 

juice is not recommended as bioavailability may be 

increased in some patients, resulting in increased blood 

pressure lowering effects. 

 

Caution required with concomitant use 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Amlodipine CYP3A4 inhibitors 

(i.e. ketoconazole, 

itraconazole, ritonavir) 

Concomitant use of amlodipine with strong or moderate 

CYP3A4 inhibitors (protease inhibitors, azole antifungals, 

macrolides like erythromycin or clarithromycin, verapamil 

or diltiazem) may give rise to significant increase in 

amlodipine exposure. The clinical translation of these 

pharmacokinetic variations may be more pronounced in 

the elderly. Clinical monitoring and dose adjustment may 

thus be required. 

CYP3A4 inducers 

(anticonvulsant agents 

[e.g. carbamazepine, 

phenobarbital, 

phenytoin, 

fosphenytoin, 

primidone], rifampicin, 

Hypericum perforatum 

[St. John’s wort]) 

There is no data available regarding the effect of CYP3A4 

inducers on amlodipine. The concomitant use of CYP3A4 

inducers (e.g. rifampicin, Hypericum perforatum) may 

give a lower plasma concentration of amlodipine. 

Amlodipine should be used with caution together with 

CYP3A4 inducers. 

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71 

 

 Simvastatin Co-administration of multiple doses of 10 mg amlodipine 

with 80 mg simvastatin resulted in a 77% increase in 

exposure to simvastatin compared to simvastatin alone. It 

is recommended to limit the dose of simvastatin to 20 mg 

daily in patients on amlodipine. 

Dantrolene (infusion) In animals, lethal ventricular fibrillation and 

cardiovascular collapse are observed in association with 

hyperkalaemia after administration of verapamil and 

intravenous dantrolene. Due to risk of hyperkalaemia, it is 

recommended that the co-administration of calcium 

channel blockers such as amlodipine be avoided in 

patients susceptible to malignant hyperthermia and in the 

management of malignant hyperthermia. 

Valsartan 

and HCT 

Non-steroidal anti-

inflammatory 

medicines (NSAIDs), 

including selective 

cyclooxygenase-2 

inhibitors (COX-2 

inhibitors), 

acetylsalicylic acid 

(>3 g/day), and non-

selective NSAIDs 

NSAIDS can attenuate the antihypertensive effect of both 

angiotensin II antagonists and hydrochlorothiazide when 

administered simultaneously. Furthermore, concomitant 

use of Imprida HCT and NSAIDs may lead to worsening 

of renal function and an increase in serum potassium. 

Therefore, monitoring of renal function at the beginning 

of the treatment is recommended, as well as adequate 

hydration of the patient. 

Valsartan Inhibitors of the uptake 

transporter (rifampicin, 

ciclosporin) or efflux 

transporter (ritonavir) 

The results of an in vitro study with human liver tissue 

indicate that valsartan is a substrate of the hepatic uptake 

transporter OATP1B1 and of the hepatic efflux 

transporter MRP2. Co-administration of inhibitors of the 

uptake transporter (rifampicin, ciclosporin) or efflux 

transporter (ritonavir) may increase the systemic exposure 

to valsartan. 

HCT Alcohol, barbiturates 

or narcotics 

Concomitant administration of thiazide diuretics with 

substances that also have a blood pressure lowering effect 

(e.g. by reducing sympathetic central nervous system 

activity or direct vasodilatation) may potentiate orthostatic 

hypotension. 

Amantadine Thiazides, including hydrochlorothiazide, may increase 

the risk of adverse reactions caused by amantadine. 

Anticholinergic agents 

and other medicinal 

products affecting 

gastric motility 

The bioavailability of thiazide-type diuretics may be 

increased by anticholinergic agents (e.g. atropine, 

biperiden), apparently due to a decrease in gastrointestinal 

motility and the stomach emptying rate. Conversely, it is 

anticipated that prokinetic substances such as cisapride 

may decrease the bioavailability of thiazide-type diuretics. 

Antidiabetic agents 

(e.g. insulin and oral 

antidiabetic agents) 

Thiazides may alter glucose tolerance. Dose adjustment of 

the antidiabetic medicinal product may be necessary. 

 Metformin Metformin should be used with caution because of the risk 

of lactic acidosis induced by possible functional renal 

failure linked to hydrochlorothiazide. 

Beta blockers and 

diazoxide 

Concomitant use of thiazide diuretics, including 

hydrochlorothiazide, with beta blockers may increase the 

risk of hyperglycaemia. Thiazide diuretics, including 

hydrochlorothiazide, may enhance the hyperglycaemic 

effect of diazoxide. 

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72 

 Ciclosporin Concomitant treatment with ciclosporin may increase the 

risk of hyperuricaemia and gout-type complications. 

 Cytotoxic agents Thiazides, including hydrochlorothiazide, may reduce the 

renal excretion of cytotoxic agents (e.g. 

cyclophosphamide, methotrexate) and potentiate their 

myelosuppressive effects. 

 Digitalis glycosides Thiazide-induced hypokalaemia or hypomagnesaemia may 

occur as undesirable effects, favouring the onset of 

digitalis-induced cardiac arrhythmias. 

 Iodine contrasting 

agents 

In case of diuretic-induced dehydration, there is an 

increased risk of acute renal failure, especially with high 

doses of iodine products. Patients should be re-hydrated 

before the administration. 

 Ion exchange resins Absorption of thiazide diuretics, including 

hydrochlorothiazide, is decreased by cholestyramine or 

colestipol. This could result in sub-therapeutic effects of 

thiazide diuretics. However, staggering the dosage of 

hydrochlorothiazide and resin such that 

hydrochlorothiazide is administered at least 4 hours 

before or 4-6 hours after the administration of resins 

would potentially minimise the interaction. 

 Medicinal products 

affecting serum 

potassium level 

The hypokalaemic effect of hydrochlorothiazide may be 

increased by concomitant administration of kaliuretic 

diuretics, corticosteroids, laxatives, adrenocorticotropic 

hormone (ACTH), amphotericin, carbenoxolone, 

penicillin G and salicylic acid derivatives or 

antiarrhythmics. If these medicinal products are to be 

prescribed with the amlodipine /valsartan 

/hydrochlorothiazide combination, monitoring of 

potassium plasma levels is advised. 

 Medicinal products 

affecting serum sodium 

level 

The hyponatraemic effect of diuretics may be intensified 

by concomitant administration of medicinal products such 

as antidepressants, antipsychotics, antiepileptics, etc. 

Caution is indicated in long-term administration of these 

medicinal products. 

 Medicinal products 

that could induce 

torsades de pointes 

Due to the risk of hypokalaemia, hydrochlorothiazide 

should be administered with caution when associated with 

medicinal products that could induce torsades de pointes, 

in particular Class Ia and Class III antiarrhythmics and 

some antipsychotics. 

 Medicinal products 

used in the treatment of 

gout (probenecid, 

sulfinpyrazone and 

allopurinol) 

Dose adjustment of uricosuric medicinal products may be 

necessary as hydrochlorothiazide may raise the level of 

serum uric acid. Increase of dose of probenecid or 

sulfinpyrazone may be necessary. 

Co-administration of thiazide diuretics, including 

hydrochlorothiazide, may increase the incidence of 

hypersensitivity reactions to allopurinol. 

 Methyldopa There have been isolated reports of haemolytic anaemia 

occurring with concomitant use of hydrochlorothiazide 

and methyldopa. 

 Non-depolarising 

skeletal muscle 

relaxants (e.g. 

tubocurarine) 

Thiazides, including hydrochlorothiazide, potentiate the 

action of curare derivatives. 

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Other anti-hypertensive 

drugs 

Thiazides potentiate the antihypertensive action of other 

antihypertensive drugs (e.g. guanethidine, methyldopa, 

beta-blockers, vasodilators, calcium channel blockers, 

ACE inhibitors, ARBs and Direct Renin Inhibitors 

[DRIs]). 

Pressor amines (e.g. 

noradrenaline, 

adrenaline) 

Hydrochlorothiazide may reduce the response to pressor 

amines such as noradrenaline. The clinical significance of 

this effect is uncertain and not sufficient to preclude their 

use. 

Vitamin D and calcium 

salts 

Administration of thiazide diuretics, including 

hydrochlorothiazide, with vitamin D or with calcium salts 

may potentiate the rise in serum calcium. Concomitant use 

of thiazide type diuretics may lead to hypercalcaemia in 

patients pre-disposed for hypercalcaemia (e.g. 

hyperparathyroidism, malignancy or vitamin-D-mediated 

conditions) by increasing tubular calcium reabsorption. 

 

No interaction 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Valsartan  Others 

(cimetidine, warfarin, 

furosemide, digoxin, 

atenolol, indometacin, 

hydrochlorothiazide, 

amlodipine, 

glibenclamide) 

In monotherapy with valsartan, no interactions of clinical 

significance have been found with the following 

substances: cimetidine, warfarin, furosemide, digoxin, 

atenolol, indomethacin, hydrochlorothiazide, amlodipine, 

glibenclamide. 

 

Some of these substances could interact with the 

hydrochlorothiazide component of Imprida HCT (see 

interactions related to HCT). 

Amlodipine Others In clinical interaction studies, amlodipine did not affect 

the pharmacokinetics of atorvastatin, digoxin, warfarin or 

ciclosporin. 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

Amlodipine 

The safety of amlodipine in human pregnancy has not been established. In animal studies, 

reproductive toxicity was observed at high doses (see section 5.3). Use in pregnancy is only 

recommended when there is no safer alternative and when the disease itself carries greater risk for the 

mother and foetus. 

 

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Valsartan 

The use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during the first 

trimester of pregnancy (see section 4.4). The use of AIIRAs is contraindicated during the second and 

third trimesters of pregnancy (see sections 4.3 and 4.4). 

 

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors 

during the first trimester of pregnancy has not been conclusive; however a small increase in risk 

cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II 

Receptor Antagonists (AIIRAs), similar risks may exist for this class of drugs. Unless continued 

AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative 

antihypertensive treatments which have an established safety profile for use in pregnancy. When 

pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and if appropriate, 

alternative therapy should be started. 

 

Exposure to AIIRAs therapy during the second and third trimesters is known to induce human 

foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal 

toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3). 

 

Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check 

of renal function and skull is recommended. 

 

Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see sections 

4.3 and 4.4). 

 

Hydrochlorothiazide 

There is limited experience with hydrochlorothiazide during pregnancy, especially during the first 

trimester. Animal studies are insufficient. 

 

Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of 

hydrochlorothiazide, its use during the second and third trimester may compromise foeto-placental 

perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance 

and thrombocytopenia. 

 

Amlodipine/valsartan/hydrochlorothiazide 

There is no experience on the use of Imprida HCT in pregnant women. Based on the existing data 

with the components, the use of Imprida HCT is not recommended during first trimester and contra-

indicated during the second and third trimester of pregnancy (see sections 4.3 and 4.4). 

 

Breast-feeding 

No information is available regarding the use of valsartan and/or amlodipine during breast-feeding. 

Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing 

intense diuresis can inhibit milk production. The use of Imprida HCT during breast-feeding is not 

recommended. If Imprida HCT is used during breast-feeding, doses should be kept as low as possible. 

Alternative treatments with better established safety profiles during breast-feeding are preferable, 

especially while nursing a newborn or preterm infant. 

 

Fertility 

There are no clinical studies on fertility with Imprida HCT. 

 

Valsartan 

Valsartan had no adverse effects on the reproductive performance of male or female rats at oral doses 

up to 200 mg/kg/day. This dose is 6 times the maximum recommended human dose on a mg/m
2
 basis 

(calculations assume an oral dose of 320 mg/day and a 60-kg patient). 

 

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Amlodipine 

Reversible biochemical changes in the head of spermatozoa have been reported in some patients 

treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of 

amlodipine on fertility. In one rat study, adverse effects were found on male fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 

 

No studies on the effects on the ability to drive and use machines have been performed. When driving 

vehicles or using machines it should be taken into account that occasionally dizziness or weariness 

may occur. 

 

4.8 Undesirable effects 

 

The safety profile of Imprida HCT presented below is based on clinical studies performed with 

Imprida HCT and the known safety profile of the individual components amlodipine, valsartan and 

hydrochlorothiazide. 

 

Information on Imprida HCT 

The safety of Imprida HCT has been evaluated at its maximum dose of 10 mg/320 mg/25 mg in one 

controlled short-term (8 weeks) clinical study with 2,271 patients, 582 of whom received valsartan in 

combination with amlodipine and hydrochlorothiazide. Adverse reactions were generally mild and 

transient in nature and only infrequently required discontinuation of therapy. In this active controlled 

clinical trial, the most common reasons for discontinuation of therapy with Imprida HCT were 

dizziness and hypotension (0.7%). 

 

In the 8-week controlled clinical study, no significant new or unexpected adverse reactions were 

observed with triple therapy treatment compared to the known effects of the monotherapy or dual 

therapy components. 

 

In the 8-week controlled clinical study, changes in laboratory parameters observed with the 

combination of Imprida HCT were minor and consistent with the pharmacological mechanism of 

action of the monotherapy agents. The presence of valsartan in the triple combination attenuated the 

hypokalaemic effect of hydrochlorothiazide. 

 

The following adverse reactions, listed by MedDRA System Organ Class and frequency, concern 

Imprida HCT (amlodipine/valsartan/HCT) and amlodipine, valsartan and HCT individually. 

Very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1,000 to <1/100; rare: ≥1/10,000 to 

<1/1,000; very rare: <1/10,000, not known (cannot be estimated from the available data). 

 

MedDRA 

System Organ 

Class 

Adverse reactions Frequency    

Imprida 

HCT 

Amlodipine Valsartan HCT 

Blood and 

lymphatic system 

disorders 

Agranulocytosis, bone 

marrow depression 

-- -- -- Very rare 

Decrease in haemoglobin 

and in haematocrit 

-- -- Not known -- 

Haemolytic anaemia -- -- -- Very rare 

Leukopenia -- Very rare -- Very rare 

Neutropenia -- -- Not known -- 

Thrombocytopenia, 

sometimes with purpura 

-- Very rare Not known Rare 

Aplastic anaemia -- -- -- Not known 

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Immune system 

disorders 

Hypersensitivity -- Very rare Not known Very rare 

Metabolism and 

nutrition 

disorders 

Anorexia Uncommon -- -- -- 

Hypercalcaemia Uncommon -- -- Rare 

Hyperglycaemia -- Very rare -- Rare 

Hyperlipidaemia Uncommon -- -- -- 

Hyperuricaemia Uncommon -- -- Common 

Hypochloraemic alkalosis -- -- -- Very rare 

Hypokalaemia Common -- -- Very 

common 

Hypomagnesaemia -- -- -- Common 

Hyponatraemia Uncommon -- -- Common 

Worsening of diabetic 

metabolic state 

-- -- -- Rare 

Psychiatric 

disorders 

Depression -- -- -- Rare 

Insomnia/sleep disturbances Uncommon Uncommon -- Rare 

Mood swings -- Uncommon --  

Nervous system 

disorders 

Coordination abnormal Uncommon -- -- -- 

Dizziness Common Common -- Rare 

Dizziness postural, dizziness 

exertional 

Uncommon -- -- -- 

Dysgeusia Uncommon Uncommon -- -- 

Extrapyramidal syndrome -- Not known -- -- 

Headache Common Common -- Rare 

Hypertonia -- Very rare -- -- 

Lethargy Uncommon -- -- -- 

Paraesthesia Uncommon Uncommon -- Rare 

Peripheral neuropathy, 

neuropathy 

Uncommon Very rare -- -- 

Somnolence Uncommon Common -- -- 

Syncope Uncommon Uncommon -- -- 

Tremor -- Uncommon -- -- 

Eye disorders Acute angle-closure 

glaucoma 

-- -- -- Not known 

Visual impairment Uncommon Uncommon -- Rare 

Ear and labyrinth 

disorders 

Tinnitus -- Uncommon -- -- 

Vertigo Uncommon -- Uncommon -- 

Cardiac disorders Palpitations -- Common -- -- 

Tachycardia Uncommon -- -- -- 

Arrhythmias (including 

bradycardia, ventricular 

tachycardia, and atrial 

fibrillation) 

-- Very rare -- Rare 

Myocardial infarction -- Very rare -- -- 

Vascular 

disorders 

Flushing -- Common -- -- 

Hypotension Common Uncommon -- -- 

Orthostatic hypotension Uncommon -- -- Common 

Phlebitis, thrombophlebitis Uncommon -- -- -- 

Vasculitis -- Very rare Not known -- 

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Respiratory, 

thoracic and 

mediastinal 

disorders 

Cough Uncommon Very rare Uncommon -- 

Dyspnoea Uncommon Uncommon -- -- 

Respiratory distress, 

pulmonary oedema, 

pneumonitis 

-- -- -- Very rare 

Rhinitis -- Uncommon -- -- 

Throat irritation Uncommon -- -- -- 

Gastrointestinal 

disorders 

Abdominal discomfort, 

abdominal pain upper 

Uncommon Common Uncommon Rare 

Breath odour Uncommon -- -- -- 

Change of bowel habit -- Uncommon -- -- 

Constipation -- -- -- Rare 

Decreased appetite -- -- -- Common 

Diarrhoea Uncommon Uncommon -- Rare 

Dry mouth Uncommon Uncommon -- -- 

Dyspepsia Common Uncommon -- -- 

Gastritis -- Very rare -- -- 

Gingival hyperplasia -- Very rare -- -- 

Nausea Uncommon Common -- Common 

Pancreatitis -- Very rare -- Very rare 

Vomiting Uncommon Uncommon -- Common 

Hepatobiliary 

disorders 

Hepatic enzyme elevation, 

including increase of serum 

bilirubin 

-- Very rare Not known -- 

Hepatitis -- Very rare -- -- 

Intrahepatic cholestasis, 

jaundice 

-- Very rare -- Rare 

Skin and 

subcutaneous 

tissue disorders 

Alopecia -- Uncommon --  

Angioedema -- Very rare Not known -- 

Cutaneous lupus 

erythematosus-like 

reactions, reactivation of 

cutaneous lupus 

erythematosus 

-- -- -- Very rare 

Erythema multiforme -- Very rare -- Not known 

Exanthema -- Uncommon -- -- 

Hyperhidrosis Uncommon Uncommon -- -- 

Photosensitivity reaction* -- -- -- Rare 

Pruritus Uncommon Uncommon Not known -- 

Purpura -- Uncommon -- Rare 

Rash -- Uncommon Not known Common 

Skin discoloration -- Uncommon -- -- 

Urticaria and other forms of 

rash 

-- Very rare -- Common 

Vasculitis necrotising and 

toxic epidermal necrolysis 

-- -- -- Very rare 

Musculoskeletal 

and connective 

tissue disorders 

Arthralgia -- Uncommon -- -- 

Back pain Uncommon Uncommon -- -- 

Joint swelling Uncommon -- -- -- 

Muscle spasm Uncommon Uncommon -- Not known 

Muscular weakness Uncommon -- -- -- 

Myalgia Uncommon Uncommon Not known -- 

Pain in extremity Uncommon -- -- -- 

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Renal and 

urinary disorders 

Elevation of serum 

creatinine 

Uncommon -- Not known -- 

Micturition disorder  Uncommon   

Nocturia -- Uncommon -- -- 

Pollakiuria Common Uncommon   

Renal dysfunction -- -- -- Not known 

Renal failure acute Uncommon -- -- Not known 

Renal failure and 

impairment 

-- -- Not known Rare 

Reproductive 

system and 

breast disorders 

Impotence Uncommon Uncommon -- Common 

Gynaecomastia  Uncommon -- -- 

General 

disorders and 

administration 

site conditions 

Abasia, gait disturbance Uncommon -- -- -- 

Asthenia Uncommon Uncommon -- Not known 

Discomfort, malaise Uncommon Uncommon -- -- 

Fatigue Common Common Uncommon -- 

Non cardiac chest pain Uncommon Uncommon -- -- 

Oedema Common Common -- -- 

Pain -- Uncommon -- -- 

Pyrexia -- -- -- Not known 

Investigations Lipids increased  --  Very 

common 

Blood urea nitrogen 

increased 

Uncommon -- -- -- 

Blood uric acid increased Uncommon -- --  

Glycosuria    Rare 

Serum potassium decreased Uncommon  -- -- -- 

Serum potassium increased -- -- Not known -- 

Weight increase Uncommon Uncommon -- -- 

Weight decrease -- Uncommon -- -- 

 

* See section 4.4 Photosensitivity 

 

4.9 Overdose 

 

Symptoms 

There is no experience of overdose with Imprida HCT. The major symptom of overdose with 

valsartan is possibly pronounced hypotension with dizziness. Overdose with amlodipine may result in 

excessive peripheral vasodilation and, possibly, reflex tachycardia. Marked and potentially prolonged 

systemic hypotension, including shock with fatal outcome, have been reported with amlodipine. 

 

Treatment 

Amlodipine/Valsartan/Hydrochlorothiazide 

Clinically significant hypotension due to Imprida HCT overdose calls for active cardiovascular 

support, including frequent monitoring of cardiac and respiratory function, elevation of extremities, 

and attention to circulating fluid volume and urine output. A vasoconstrictor may be helpful in 

restoring vascular tone and blood pressure, provided that there is no contraindication to its use. 

Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. 

 

Amlodipine 

If ingestion is recent, induction of vomiting or gastric lavage may be considered. Administration of 

activated charcoal to healthy volunteers immediately or up to two hours after ingestion of amlodipine 

has been shown to significantly decrease amlodipine absorption. 

Amlodipine is unlikely to be removed by haemodialysis. 

 

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Valsartan 

Valsartan is unlikely to be removed by haemodialysis. 

 

Hydrochlorothiazide 

Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, 

hypochloraemia) and hypovolaemia resulting from excessive diuresis. The most common signs and 

symptoms of overdose are nausea and somnolence. Hypokalaemia may result in muscle spasms and or 

accentuate arrhythmia associated with the concomitant use of digitalis glycosides or certain anti-

arrhythmic medicinal products. 

The degree to which hydrochlorothiazide is removed by haemodialysis has not been established. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Angiotensin II antagonists, plain (valsartan), combinations with 

dihydropyridine derivatives (amlodipine) and thiazide diuretics (hydrochlorothiazide), ATC code: 

C09DX01 valsartan, amlodipine and hydrochlorothiazide. 

 

Imprida HCT combines three antihypertensive compounds with complementary mechanisms to 

control blood pressure in patients with essential hypertension: amlodipine belongs to the calcium 

antagonist class and valsartan to the angiotensin II antagonist class of medicines and 

hydrochlorothiazide belongs to the thiazide diuretics class of medicines. The combination of these 

substances has an additive antihypertensive effect. 

 

Amlodipine/Valsartan/Hydrochlorothiazide 

Imprida HCT was studied in a double-blind, active controlled study in hypertensive patients. A total 

of 2,271 patients with moderate to severe hypertension (mean baseline systolic/diastolic blood 

pressure was 170/107 mmHg) received treatments of amlodipine/valsartan/hydrochlorothiazide 

10 mg/320 mg/25 mg, valsartan/hydrochlorothiazide 320 mg/25 mg, amlodipine/valsartan 

10 mg/320 mg, or hydrochlorothiazide/amlodipine 25 mg/10 mg. At study initiation patients were 

assigned lower doses of their treatment combination and were titrated to their full treatment dose by 

week 2. 

 

At week 8, the mean reductions in systolic/diastolic blood pressure were 39.7/24.7 mmHg with 

Imprida HCT, 32.0/19.7 mmHg with valsartan/hydrochlorothiazide, 33.5/21.5 mmHg with 

amlodipine/valsartan, and 31.5/19.5 mmHg with amlodipine/hydrochlorothiazide. The triple 

combination therapy was statistically superior to each of the three dual combination treatments in 

reduction of diastolic and systolic blood pressures. The reductions in systolic/diastolic blood pressure 

with Imprida HCT were 7.6/5.0 mmHg greater than with valsartan/hydrochlorothiazide, 

6.2/3.3 mmHg greater than with amlodipine/valsartan, and 8.2/5.3 mmHg greater than with 

amlodipine/hydrochlorothiazide. The full blood pressure lowering effect was achieved 2 weeks after 

being on their maximal dose of Imprida HCT. Statistically greater proportions of patients achieved 

blood pressure control (<140/90 mmHg) with Imprida HCT (71%) compared to each of the three dual 

combination therapies (45-54%) (p<0.0001). 

 

In a subgroup of 283 patients focusing on ambulatory blood pressure monitoring, clinically and 

statistically superior reductions in 24-hour systolic and diastolic blood pressures were observed with 

the triple combination compared to valsartan/hydrochlorothiazide, valsartan/amlodipine, and 

hydrochlorothiazide/amlodipine. 

 

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Amlodipine 

The amlodipine component of Imprida HCT inhibits the transmembrane entry of calcium ions into 

cardiac and vascular smooth muscle. The mechanism of the antihypertensive action of amlodipine is 

due to a direct relaxant effect on vascular smooth muscle, causing reductions in peripheral vascular 

resistance and in blood pressure. Experimental data suggest that amlodipine binds to both 

dihydropyridine and non-dihydropyridine binding sites. The contractile processes of cardiac muscle 

and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into 

these cells through specific ion channels. 

 

Following administration of therapeutic doses to patients with hypertension, amlodipine produces 

vasodilation, resulting in a reduction of supine and standing blood pressures. These decreases in blood 

pressure are not accompanied by a significant change in heart rate or plasma catecholamine levels 

with chronic dosing. 

 

Plasma concentrations correlate with effect in both young and elderly patients. 

 

In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in a 

decrease in renal vascular resistance and increases in glomerular filtration rate and effective renal 

plasma flow, without change in filtration fraction or proteinuria. 

 

Valsartan 

Valsartan is an orally active, potent and specific angiotensin II receptor antagonist. It acts selectively 

on the receptor subtype AT1, which is responsible for the known actions of angiotensin II. 

 

Administration of valsartan to patients with hypertension results in a drop in blood pressure without 

affecting pulse rate. 

 

In most patients, after administration of a single oral dose, onset of antihypertensive activity occurs 

within 2 hours, and the peak drop in blood pressure is achieved within 4-6 hours. The 

antihypertensive effect persists over 24 hours after administration. During repeated administration, the 

maximum reduction in blood pressure with any dose is generally attained within 2-4 weeks. 

 

Hydrochlorothiazide 

The site of action of thiazide diuretics is primarily in the renal distal convoluted tubule. It has been 

shown that there is a high-affinity receptor in the renal cortex as the primary binding site for the 

thiazide diuretic action and inhibition of NaCl transport in the distal convoluted tubule. The mode of 

action of thiazides is through inhibition of the Na
+
Cl

-
 symporter perhaps by competing for the Cl

-
 site, 

thereby affecting electrolyte reabsorption mechanisms: directly increasing sodium and chloride 

excretion to an approximately equal extent, and indirectly, by this diuretic action, reducing plasma 

volume, with consequent increases in plasma renin activity, aldosterone secretion and urinary 

potassium loss, and a decrease in serum potassium. 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

Imprida HCT in all subsets of the paediatric population in essential hypertension. See section 4.2 for 

information on paediatric use. 

 

5.2 Pharmacokinetic properties 

 

Linearity 

Amlodipine, valsartan and hydrochlorothiazide exhibit linear pharmacokinetics. 

 

Amlodipine/valsartan/hydrochlorothiazide 

Following oral administration of Imprida HCT in normal healthy adults, peak plasma concentrations 

of amlodipine, valsartan and hydrochlorothiazide are reached in 6-8 hours, 3 hours, and 2 hours, 

respectively. The rate and extent of absorption of amlodipine, valsartan and hydrochlorothiazide from 

Imprida HCT are the same as when administered as individual dosage forms. 

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Amlodipine 

Absorption: After oral administration of therapeutic doses of amlodipine alone, peak plasma 

concentrations of amlodipine are reached in 6-12 hours. Absolute bioavailability has been calculated as 

between 64% and 80%. Amlodipine bioavailability is unaffected by food ingestion. 

 

Distribution: Volume of distribution is approximately 21 l/kg. In vitro studies with amlodipine have 

shown that approximately 97.5% of circulating drug is bound to plasma proteins. 

 

Biotransformation: Amlodipine is extensively (approximately 90%) metabolised in the liver to inactive 

metabolites. 

 

Elimination: Amlodipine elimination from plasma is biphasic, with a terminal elimination half-life of 

approximately 30 to 50 hours. Steady-state plasma levels are reached after continuous administration for 

7-8 days. Ten per cent of original amlodipine and 60% of amlodipine metabolites are excreted in urine. 

 

Valsartan 

Absorption: Following oral administration of valsartan alone, peak plasma concentrations of valsartan 

are reached in 2-4 hours. Mean absolute bioavailability is 23%. Food decreases exposure (as 

measured by AUC) to valsartan by about 40% and peak plasma concentration (Cmax) by about 50%, 

although from about 8 h post dosing plasma valsartan concentrations are similar for the fed and fasted 

groups. This reduction in AUC is not, however, accompanied by a clinically significant reduction in 

the therapeutic effect, and valsartan can therefore be given either with or without food. 

 

Distribution: The steady-state volume of distribution of valsartan after intravenous administration is 

about 17 litres, indicating that valsartan does not distribute into tissues extensively. Valsartan is 

highly bound to serum proteins (94-97%), mainly serum albumin. 

 

Biotransformation: Valsartan is not transformed to a high extent as only about 20% of dose is 

recovered as metabolites. A hydroxy metabolite has been identified in plasma at low concentrations 

(less than 10% of the valsartan AUC). This metabolite is pharmacologically inactive. 

 

Elimination: Valsartan is primarily eliminated in faeces (about 83% of dose) and urine (about 13% of 

dose), mainly as unchanged drug. Following intravenous administration, plasma clearance of valsartan 

is about 2 l/h and its renal clearance is 0.62 l/h (about 30% of total clearance). The half-life of 

valsartan is 6 hours. 

 

Hydrochlorothiazide 

Absorption: The absorption of hydrochlorothiazide, after an oral dose, is rapid (Tmax about 2 hours). 

The increase in mean AUC is linear and dose proportional in the therapeutic range. 

 

The effect of food on hydrochlorothiazide absorption, if any, has little clinical significance. Absolute 

bioavailability of hydrochlorothiazide is 70% after oral administration. 

 

Distribution: The apparent volume of distribution is 4-8 l/kg. Circulating hydrochlorothiazide is 

bound to serum proteins (40-70%), mainly serum albumin. Hydrochlorothiazide also accumulates in 

erythrocytes at approximately 3 times the level in plasma. 

 

Biotransformation: Hydrochlorothiazide is eliminated predominantly as unchanged compound. 

 

Elimination: Hydrochlorothiazide is eliminated from plasma with a half-life averaging 6 to 15 hours 

in the terminal elimination phase. There is no change in the kinetics of hydrochlorothiazide on 

repeated dosing, and accumulation is minimal when dosed once daily. More than 95% of the absorbed 

dose is being excreted as unchanged compound in the urine. The renal clearance is composed of 

passive filtration and active secretion into the renal tubule. 

 

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Special populations 

Paediatric patients (age below 18 years) 

No pharmacokinetic data are available in the paediatric population. 

 

Elderly (age 65 years or over) 

Time to peak plasma amlodipine concentrations is similar in young and elderly patients. In elderly 

patients, amlodipine clearance tends to decline, causing increases in the area under the curve (AUC) 

and elimination half-life. Mean systemic AUC of valsartan is higher by 70% in the elderly than in the 

young, therefore caution is required when increasing the dosage. 

 

Systemic exposure to valsartan is slightly elevated in the elderly as compared to the young, but this 

has not been shown to have any clinical significance. 

 

Limited data suggest that the systemic clearance of hydrochlorothiazide is reduced in both healthy and 

hypertensive elderly subjects compared to young healthy volunteers. 

 

Since the three components are equally well tolerated in younger and elderly patients, normal dose 

regimens are recommended (see section 4.2). 

 

Renal impairment 

The pharmacokinetics of amlodipine are not significantly influenced by renal impairment. As 

expected for a compound where renal clearance accounts for only 30% of total plasma clearance, no 

correlation was seen between renal function and systemic exposure to valsartan. 

 

Patients with mild to moderate renal impairment may therefore receive the usual initial dose (see 

sections 4.2 and 4.4). 

 

In the presence of renal impairment, mean peak plasma levels and AUC values of hydrochlorothiazide 

are increased and the urinary excretion rate is reduced. In patients with mild to moderate renal 

impairment, a 3-fold increase in hydrochlorothiazide AUC has been observed. In patients with severe 

renal impairment an 8-fold increase in AUC has been observed. Imprida HCT is contraindicated in 

patients with severe renal impairment, anuria or undergoing dialysis (see section 4.3). 

 

Hepatic impairment 

Patients with hepatic insufficiency have decreased clearance of amlodipine with resulting increase of 

approximately 40–60% in AUC. On average, in patients with mild to moderate chronic liver disease, 

exposure (measured by AUC values) to valsartan is twice that found in healthy volunteers (matched 

by age, sex and weight). Due to the valsartan component, Imprida HCT is contraindicated in patients 

with hepatic impairment (see sections 4.2 and 4.3). 

 

5.3 Preclinical safety data 

 

Amlodipine/Valsartan/Hydrochlorothiazide 

In a variety of preclinical safety studies conducted in several animal species with amlodipine, 

valsartan, hydrochlorothiazide, valsartan/hydrochlorothiazide, amlodipine/valsartan and 

amlodipine/valsartan/hydrochlorothiazide (Imprida HCT), there was no evidence of systemic or target 

organ toxicity that would adversely affect the development of Imprida HCT for clinical use in 

humans. 

 

Preclinical safety studies of up to 13 weeks in duration were conducted with 

amlodipine/valsartan/hydrochlorothiazide in rats. The combination resulted in expected reduction of 

red blood cell mass (erythrocytes, haemoglobin, haematocrit, and reticulocytes), increase in serum 

urea, increase in serum creatinine, increase in serum potassium, juxtaglomerular (JG) hyperplasia in 

the kidney and focal erosions in the glandular stomach in rats. All these changes were reversible after 

a 4-week recovery period and were considered to be exaggerated pharmacological effects. 

 

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The amlodipine/valsartan/hydrochlorothiazide combination was not tested for genotoxicity or 

carcinogenicity as there was no evidence of any interaction between these substances, which have 

been on the market for a long time. However, amlodipine, valsartan and hydrochlorothiazide have 

been tested individually for genotoxicity and carcinogenicity with negative results. 

 

Amlodipine 

Reproductive toxicology 

Reproductive studies in rats and mice have shown delayed date of delivery, prolonged duration of 

labour and decreased pup survival at dosages approximately 50 times greater than the maximum 

recommended dosage for humans based on mg/kg. 

 

Impairment of fertility 

There was no effect on the fertility of rats treated with amlodipine (males for 64 days and females 

14 days prior to mating) at doses up to 10 mg/kg/day (8 times* the maximum recommended human 

dose of 10 mg on a mg/m
2
 basis). In another rat study in which male rats were treated with amlodipine 

besilate for 30 days at a dose comparable with the human dose based on mg/kg, decreased plasma 

follicle-stimulating hormone and testosterone were found as well as decreases in sperm density and in 

the number of mature spermatids and Sertoli cells. 

 

Carcinogenesis, mutagenesis 

Rats and mice treated with amlodipine in the diet for two years, at concentrations calculated to 

provide daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day showed no evidence of carcinogenicity. 

The highest dose (for mice, similar to, and for rats twice* the maximum recommended clinical dose of 

10 mg on a mg/m
2
 basis) was close to the maximum tolerated dose for mice but not for rats. 

 

Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels. 

 

* Based on patient weight of 50 kg 

 

Valsartan 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential. 

 

In rats, maternally toxic doses (600 mg/kg/day) during the last days of gestation and lactation led to 

lower survival, lower weight gain and delayed development (pinna detachment and ear-canal opening) 

in the offspring (see section 4.6). These doses in rats (600 mg/kg/day) are approximately 18 times the 

maximum recommended human dose on a mg/m
2 
basis (calculations assume an oral dose of 

320 mg/day and a 60-kg patient). 

 

In non-clinical safety studies, high doses of valsartan (200 to 600 mg/kg body weight) caused in rats a 

reduction of red blood cell parameters (erythrocytes, haemoglobin, haematocrit) and evidence of 

changes in renal haemodynamics (slightly raised plasma urea, and renal tubular hyperplasia and 

basophilia in males). These doses in rats (200 and 600 mg/kg/day) are approximately 6 and 18 times 

the maximum recommended human dose on a mg/m
2
 basis (calculations assume an oral dose of 

320 mg/day and a 60-kg patient). 

 

In marmosets at similar doses, the changes were similar though more severe, particularly in the kidney 

where the changes developed to a nephropathy which included raised urea and creatinine. 

 

Hypertrophy of the renal juxtaglomerular cells was also seen in both species. All changes were 

considered to be caused by the pharmacological action of valsartan which produces prolonged 

hypotension, particularly in marmosets. For therapeutic doses of valsartan in humans, the hypertrophy 

of the renal juxtaglomerular cells does not seem to have any relevance. 

 

 

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6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Tablet core 

Cellulose microcrystalline 

Crospovidone 

Silica, colloidal anhydrous 

Magnesium stearate 

 

Coating 

Hypromellose 

Macrogol 4000 

Talc 

Iron oxide, yellow (E172) 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

2 years 

 

6.4 Special precautions for storage 

 

Do not store above 30°C. 

 

Store in the original package in order to protect from moisture. 

 

6.5 Nature and contents of container 

 

PVC/PVDC blisters. One blister contains 7, 10 or 14 film-coated tablets. 

Pack sizes: 14, 28, 30, 56, 90, 98 or 280 film-coated tablets. 

Multipacks of 280 tablets, comprising 20 cartons, each containing 14 tablets. 

 

PVC/PVDC perforated unit dose blisters for hospital use: 

Pack sizes: 56, 98 or 280 film-coated tablets 

Multipacks of 280 tablets, comprising 4 cartons, each containing 70 tablets. 

 

Not all pack sizes or strengths may be marketed. 

 

6.6 Special precautions for disposal and other handling 

 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

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8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/037-048 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

15.10.2009 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

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86 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/320 mg/25 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains 10 mg of amlodipine (as amlodipine besylate), 320 mg of valsartan 

and 25 mg of hydrochlorothiazide. 

 

For a full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet (tablet) 

 

Brown-yellow, ovaloid, biconvex tablets with bevelled edge, debossed “NVR” on one side and “VFL” 

on the other side. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment of essential hypertension as substitution therapy in adult patients whose blood pressure is 

adequately controlled on the combination of amlodipine, valsartan and hydrochlorothiazide (HCT), 

taken either as three single-component formulations or as a dual-component and a single-component 

formulation. 

 

4.2 Posology and method of administration 

 

Posology 

The recommended dose of Imprida HCT is one tablet per day, to be taken preferably in the morning. 

 

Before switching to Imprida HCT patients should be controlled on stable doses of the 

monocomponents taken at the same time. The dose of Imprida HCT should be based on the doses of 

the individual components of the combination at the time of switching. 

 

The maximum recommended dose of Imprida HCT is 10 mg/320 mg/25 mg. 

 

Special populations 

Renal impairment 

No adjustment of the initial dose is required for patients with mild to moderate renal impairment (see 

sections 4.4 and 5.2). Due to the hydrochlorothiazide component, Imprida HCT is contraindicated for 

use in patients with anuria (see section 4.3) and in patients with severe renal impairment (glomerular 

filtration rate (GFR) <30 ml/min/1.73 m
2
) (see sections 4.3, 4.4 and 5.2). 

 

Hepatic impairment 

Due to the valsartan component, Imprida HCT is contraindicated in patients with severe hepatic 

impairment (see section 4.3). In patients with mild to moderate hepatic impairment without 

cholestasis, the maximum recommended dose is 80 mg valsartan and therefore Imprida HCT is not 

suitable in this group of patients (see sections 4.3, 4.4 and 5.2). 

 

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87 

Heart failure and coronary artery disease 

There is limited experience with the use of Imprida HCT, particulary at the maximum dose, in 

patients with heart failure and coronary artery disease. Caution is advised in patients with heart failure 

and coronary artery disease, particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg. 

 

Elderly (age 65 years or over) 

Caution, including more frequent monitoring of blood pressure, is recommended in elderly patients, 

particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in this 

patient population are limited. 

 

Paediatric population 

There is no relevant use of Imprida HCT in the paediatric population (patients below age 18 years) for 

the indication of essential hypertension. 

 

Method of administration 

Imprida HCT can be taken with or without food. The tablets should be swallowed whole with some 

water, at the same time of the day and preferably in the morning. 

 

4.3 Contraindications 

 

 Hypersensitivity to the active substances, to other sulphonamide derivatives, to dihydropyridine 

derivatives, or to any of the excipients. 

 Second and third trimesters of pregnancy (see sections 4.4 and 4.6). 

 Hepatic impairment, biliary cirrhosis or cholestasis. 

 Severe renal impairment (GFR <30 ml/min/1.73 m2), anuria and patients undergoing dialysis. 

 Refractory hypokalaemia, hyponatraemia, hypercalcaemia, and symptomatic hyperuricaemia. 

 

4.4 Special warnings and precautions for use 

 

Sodium- and/or volume-depleted patients 

Excessive hypotension, including orthostatic hypotension, was seen in 1.7% of patients treated with 

the maximum dose of Imprida HCT (10 mg/320 mg/25 mg) compared to 1.8% of 

valsartan/hydrochlorothiazide (320 mg/25 mg) patients, 0.4% of amlodipine/valsartan (10 mg/320 mg) 

patients, and 0.2% of hydrochlorothiazide/amlodipine (25 mg/10 mg) patients in a controlled trial in 

patients with moderate to severe uncomplicated hypertension. 

 

In sodium-depleted and/or volume-depleted patients, such as those receiving high doses of diuretics, 

symptomatic hypotension may occur after initiation of treatment with Imprida HCT. Imprida HCT 

should be used only after correction of any pre-existing sodium and/or volume depletion. 

 

If excessive hypotension occurs with Imprida HCT, the patient should be placed in the supine position 

and, if necessary, given an intravenous infusion of normal saline. Treatment can be continued once 

blood pressure has been stabilised. 

 

Serum electrolyte changes 

Amlodipine/valsartan/hydrochlorothiazide 

In the controlled trial of Imprida HCT, the counteracting effects of valsartan 320 mg and 

hydrochlorothiazide 25 mg on serum potassium approximately balanced each other in many patients. 

In other patients, one or the other effect may be dominant. Periodic determinations of serum 

electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals. 

 

Periodic determination of serum electrolytes and potassium in particular should be performed at 

appropriate intervals to detect possible electrolyte imbalance, especially in patients with other risk 

factors such as impaired renal function, treatment with other medicinal products or history of prior 

electrolyte imbalances. 

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88 

 

Valsartan 

Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing 

potassium, or other medicinal products that may increase potassium levels (heparin, etc.) is not 

recommended. Monitoring of potassium should be undertaken as appropriate. 

 

Hydrochlorothiazide 

Treatment with Imprida HCT should only start after correction of hypokalaemia and any coexisting 

hypomagnesaemia. Thiazide diuretics can precipitate new onset hypokalaemia or exacerbate pre-

existing hypokalaemia. Thiazide diuretics should be administered with caution in patients with 

conditions involving enhanced potassium loss, for example salt-losing nephropathies and prerenal 

(cardiogenic) impairment of kidney function. If hypokalaemia develops during hydrochlorothiazide 

therapy, Imprida HCT should be discontinued until stable correction of the potassium balance. 

 

Thiazide diuretics can precipitate new onset hyponatraemia and hypochloroaemic alkalosis or 

exacerbate pre-existing hyponatraemia. Hyponatraemia, accompanied by neurological symptoms 

(nausea, progressive disorientation, apathy) has been observed. Treatment with hydrochlorothiazide 

should only be started after correction of pre-existing hyponatraemia. In case severe or rapid 

hyponatraemia develops during Imprida HCT therapy, the treatment should be discontinued until 

normalisation of natraemia. 

 

All patients receiving thiazide diuretics should be periodically monitored for imbalances in 

electrolytes, particularly potassium, sodium and magnesium. 

 

Renal impairment 

Thiazide diuretics may precipitate azotaemia in patients with chronic kidney disease. When Imprida 

HCT is used in patients with renal impairment periodic monitoring of serum electrolytes (including 

potassium), creatinine and uric acid serum levels is recommended. Imprida HCT is contraindicated in 

patients with severe renal impairment, anuria or undergoing dialysis (see section 4.3). 

 

No dosage adjustment of Imprida HCT is required for patients with mild to moderate renal 

impairment (GFR ≥30 ml/min/1.73 m
2
). 

 

Renal artery stenosis 

No data are available on the use of Imprida HCT in patients with unilateral or bilateral renal artery 

stenosis or stenosis to a solitary kidney. 

 

Kidney transplantation 

To date there is no experience of the safe use of Imprida HCT in patients who have had a recent 

kidney transplantation. 

 

Hepatic impairment 

Valsartan is mostly eliminated unchanged via the bile, whereas amlodipine is extensively metabolised 

by the liver. In patients with mild to moderate hepatic impairment without cholestasis, the maximum 

recommended dose is 80 mg valsartan, and therefore, Imprida HCT is not suitable in this group of 

patients (see sections 4.2, 4.3 and 5.2). 

 

Heart failure and coronary artery disease 

As a consequence of the inhibition of the renin-angiotensin-aldosterone system, changes in renal 

function may be anticipated in susceptible individuals. In patients with severe heart failure whose 

renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with 

angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been 

associated with oliguria and/or progressive azotaemia and (rarely) with acute renal failure and/or 

death. Similar outcomes have been reported with valsartan. 

 

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89 

In a long-term, placebo-controlled study (PRAISE-2) of amlodipine in patients with NYHA (New 

York Heart Association Classification) III and IV heart failure of non-ischaemic aetiology, amlodipine 

was associated with increased reports of pulmonary oedema despite no significant difference in the 

incidence of worsening heart failure as compared to placebo. 

 

Caution is advised in patients with heart failure and coronary artery disease, particularly at the 

maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in these patient 

populations is limited. 

 

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy 

As with all other vasodilators, special caution is indicated in patients with aortic or mitral stenosis, or 

obstructive hypertrophic cardiomyopathy. 

 

Pregnancy 

Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless 

continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to 

alternative antihypertensive treatments which have an established safety profile for use in pregnancy. 

When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if 

appropriate, alternative therapy should be started (see sections 4.3 and 4.6). 

 

Primary hyperaldosteronism 

Patients with primary hyperaldosteronism should not be treated with the angiotensin II antagonist 

valsartan as their renin-angiotensin system is not activated. Therefore, Imprida HCT is not 

recommended in this population. 

 

Systemic lupus erythematosus 

Thiazide diuretics, including hydrochlorothiazide, have been reported to exacerbate or activate 

systemic lupus erythematosus. 

 

Other metabolic disturbances 

Thiazide diuretics, including hydrochlorothiazide, may alter glucose tolerance and raise serum levels 

of cholesterol, triglycerides and uric acid. In diabetic patients dosage adjustments of insulin or oral 

hypoglycaemic agents may be required. 

 

Due to the hydrochlorothiazide component, Imprida HCT is contraindicated in symptomatic 

hyperuricaemia. Hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of 

uric acid and may cause or exacerbate hyperuricaemia as well as precipitate gout in susceptible 

patients. 

 

Thiazides reduce urinary calcium excretion and may cause intermittant and slight elevation of serum 

calcium in the absence of known disorders of calcium metabolism. Imprida HCT is contraindicated in 

patients with hypercalcaemia and should only be used after correction of any pre-existing 

hypercalcaemia. Imprida HCT should be discontinued if hypercalcaemia develops during treatment. 

Serum levels of calcium should be periodically monitored during treatment with thiazides. Marked 

hypercalcaemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued 

before carrying out tests for parathyroid function. 

 

Photosensitivity 

Cases of photosensitivity reactions have been reported with thiazide diuretics (see section 4.8). If 

photosensitivity reaction occurs during treatment with Imprida HCT, it is recommended to stop the 

treatment. If a readministration of the diuretic is deemed necessary, it is recommended to protect 

exposed areas to the sun or to artificial UVA. 

 

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Acute angle-closure glaucoma 

Hydrochlorothiazide, a sulphonamide, has been associated with an idiosyncratic reaction resulting in 

acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased 

visual acuity or ocular pain and typically occur within hours to a week of treatment initiation. 

Untreated acute-angle closure glaucoma can lead to permanent vision loss. 

 

The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or 

surgical treatment may need to be considered if the intraocular pressure remains uncontrolled. Risk 

factors for developing acute angle closure glaucoma may include a history of sulphonamide or 

penicillin allergy. 

 

General 

Caution should be exercised in patients who have shown prior hypersensitivity to other angiotensin II 

receptor antagonists. Hypersensitivity reactions to hydrochlorothiazide are more likely in patients 

with allergy and asthma. 

 

Elderly (age 65 years or over) 

Caution, including more frequent monitoring of blood pressure, is recommended in elderly patients, 

particularly at the maximum dose of Imprida HCT, 10 mg/320 mg/25 mg, since available data in this 

patient population are limited. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

No formal interaction studies with other medicinal products were performed with Imprida HCT. Thus, 

only information on interactions with other medicinal products that are known for the individual 

active substances is provided in this section. 

 

However, it is important to take into account that Imprida HCT may increase the hypotensive effect of 

other antihypertensive agents. 

 

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Concomitant use not recommended 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Valsartan 

and 

HCT 

Lithium Reversible increases in serum lithium concentrations and 

toxicity have been reported during concurrent use of ACE 

inhibitors and thiazides such as hydrochlorothiazide. 

Despite the lack of experience with concomitant use of 

valsartan and lithium, this combination is not 

recommended. If the combination proves necessary, 

careful monitoring of serum lithium levels is 

recommended (see section 4.4). 

Valsartan Potassium-sparing 

diuretics, potassium 

supplements, salt 

substitutes containing 

potassium and other 

substances that may 

increase potassium 

levels 

If a medicinal product that affects potassium levels is 

considered necessary in combination with valsartan, 

frequent monitoring of potassium plasma levels is 

advised. 

Amlodipine Grapefruit or grapefruit 

juice 

Administration of amlodipine with grapefruit or grapefruit 

juice is not recommended as bioavailability may be 

increased in some patients, resulting in increased blood 

pressure lowering effects. 

 

Caution required with concomitant use 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Amlodipine CYP3A4 inhibitors 

(i.e. ketoconazole, 

itraconazole, ritonavir) 

Concomitant use of amlodipine with strong or moderate 

CYP3A4 inhibitors (protease inhibitors, azole antifungals, 

macrolides like erythromycin or clarithromycin, verapamil 

or diltiazem) may give rise to significant increase in 

amlodipine exposure. The clinical translation of these 

pharmacokinetic variations may be more pronounced in 

the elderly. Clinical monitoring and dose adjustment may 

thus be required. 

CYP3A4 inducers 

(anticonvulsant agents 

[e.g. carbamazepine, 

phenobarbital, 

phenytoin, 

fosphenytoin, 

primidone], rifampicin, 

Hypericum perforatum 

[St. John’s wort]) 

There is no data available regarding the effect of CYP3A4 

inducers on amlodipine. The concomitant use of CYP3A4 

inducers (e.g. rifampicin, Hypericum perforatum) may 

give a lower plasma concentration of amlodipine. 

Amlodipine should be used with caution together with 

CYP3A4 inducers. 

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 Simvastatin Co-administration of multiple doses of 10 mg amlodipine 

with 80 mg simvastatin resulted in a 77% increase in 

exposure to simvastatin compared to simvastatin alone. It 

is recommended to limit the dose of simvastatin to 20 mg 

daily in patients on amlodipine. 

Dantrolene (infusion) In animals, lethal ventricular fibrillation and 

cardiovascular collapse are observed in association with 

hyperkalaemia after administration of verapamil and 

intravenous dantrolene. Due to risk of hyperkalaemia, it is 

recommended that the co-administration of calcium 

channel blockers such as amlodipine be avoided in 

patients susceptible to malignant hyperthermia and in the 

management of malignant hyperthermia. 

Valsartan 

and HCT 

Non-steroidal anti-

inflammatory 

medicines (NSAIDs), 

including selective 

cyclooxygenase-2 

inhibitors (COX-2 

inhibitors), 

acetylsalicylic acid 

(>3 g/day), and non-

selective NSAIDs 

NSAIDS can attenuate the antihypertensive effect of both 

angiotensin II antagonists and hydrochlorothiazide when 

administered simultaneously. Furthermore, concomitant 

use of Imprida HCT and NSAIDs may lead to worsening 

of renal function and an increase in serum potassium. 

Therefore, monitoring of renal function at the beginning 

of the treatment is recommended, as well as adequate 

hydration of the patient. 

Valsartan Inhibitors of the uptake 

transporter (rifampicin, 

ciclosporin) or efflux 

transporter (ritonavir) 

The results of an in vitro study with human liver tissue 

indicate that valsartan is a substrate of the hepatic uptake 

transporter OATP1B1 and of the hepatic efflux 

transporter MRP2. Co-administration of inhibitors of the 

uptake transporter (rifampicin, ciclosporin) or efflux 

transporter (ritonavir) may increase the systemic exposure 

to valsartan. 

HCT Alcohol, barbiturates 

or narcotics 

Concomitant administration of thiazide diuretics with 

substances that also have a blood pressure lowering effect 

(e.g. by reducing sympathetic central nervous system 

activity or direct vasodilatation) may potentiate orthostatic 

hypotension. 

Amantadine Thiazides, including hydrochlorothiazide, may increase 

the risk of adverse reactions caused by amantadine. 

Anticholinergic agents 

and other medicinal 

products affecting 

gastric motility 

The bioavailability of thiazide-type diuretics may be 

increased by anticholinergic agents (e.g. atropine, 

biperiden), apparently due to a decrease in gastrointestinal 

motility and the stomach emptying rate. Conversely, it is 

anticipated that prokinetic substances such as cisapride 

may decrease the bioavailability of thiazide-type diuretics. 

Antidiabetic agents 

(e.g. insulin and oral 

antidiabetic agents) 

Thiazides may alter glucose tolerance. Dose adjustment of 

the antidiabetic medicinal product may be necessary. 

 Metformin Metformin should be used with caution because of the risk 

of lactic acidosis induced by possible functional renal 

failure linked to hydrochlorothiazide. 

Beta blockers and 

diazoxide 

Concomitant use of thiazide diuretics, including 

hydrochlorothiazide, with beta blockers may increase the 

risk of hyperglycaemia. Thiazide diuretics, including 

hydrochlorothiazide, may enhance the hyperglycaemic 

effect of diazoxide. 

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 Ciclosporin Concomitant treatment with ciclosporin may increase the 

risk of hyperuricaemia and gout-type complications. 

 Cytotoxic agents Thiazides, including hydrochlorothiazide, may reduce the 

renal excretion of cytotoxic agents (e.g. 

cyclophosphamide, methotrexate) and potentiate their 

myelosuppressive effects. 

 Digitalis glycosides Thiazide-induced hypokalaemia or hypomagnesaemia may 

occur as undesirable effects, favouring the onset of 

digitalis-induced cardiac arrhythmias. 

 Iodine contrasting 

agents 

In case of diuretic-induced dehydration, there is an 

increased risk of acute renal failure, especially with high 

doses of iodine products. Patients should be re-hydrated 

before the administration. 

 Ion exchange resins Absorption of thiazide diuretics, including 

hydrochlorothiazide, is decreased by cholestyramine or 

colestipol. This could result in sub-therapeutic effects of 

thiazide diuretics. However, staggering the dosage of 

hydrochlorothiazide and resin such that 

hydrochlorothiazide is administered at least 4 hours 

before or 4-6 hours after the administration of resins 

would potentially minimise the interaction. 

 Medicinal products 

affecting serum 

potassium level 

The hypokalaemic effect of hydrochlorothiazide may be 

increased by concomitant administration of kaliuretic 

diuretics, corticosteroids, laxatives, adrenocorticotropic 

hormone (ACTH), amphotericin, carbenoxolone, 

penicillin G and salicylic acid derivatives or 

antiarrhythmics. If these medicinal products are to be 

prescribed with the amlodipine /valsartan 

/hydrochlorothiazide combination, monitoring of 

potassium plasma levels is advised. 

 Medicinal products 

affecting serum sodium 

level 

The hyponatraemic effect of diuretics may be intensified 

by concomitant administration of medicinal products such 

as antidepressants, antipsychotics, antiepileptics, etc. 

Caution is indicated in long-term administration of these 

medicinal products. 

 Medicinal products 

that could induce 

torsades de pointes 

Due to the risk of hypokalaemia, hydrochlorothiazide 

should be administered with caution when associated with 

medicinal products that could induce torsades de pointes, 

in particular Class Ia and Class III antiarrhythmics and 

some antipsychotics. 

 Medicinal products 

used in the treatment of 

gout (probenecid, 

sulfinpyrazone and 

allopurinol) 

Dose adjustment of uricosuric medicinal products may be 

necessary as hydrochlorothiazide may raise the level of 

serum uric acid. Increase of dose of probenecid or 

sulfinpyrazone may be necessary. 

Co-administration of thiazide diuretics, including 

hydrochlorothiazide, may increase the incidence of 

hypersensitivity reactions to allopurinol. 

 Methyldopa There have been isolated reports of haemolytic anaemia 

occurring with concomitant use of hydrochlorothiazide 

and methyldopa. 

 Non-depolarising 

skeletal muscle 

relaxants (e.g. 

tubocurarine) 

Thiazides, including hydrochlorothiazide, potentiate the 

action of curare derivatives. 

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Other anti-hypertensive 

drugs 

Thiazides potentiate the antihypertensive action of other 

antihypertensive drugs (e.g. guanethidine, methyldopa, 

beta-blockers, vasodilators, calcium channel blockers, 

ACE inhibitors, ARBs and Direct Renin Inhibitors 

[DRIs]). 

Pressor amines (e.g. 

noradrenaline, 

adrenaline) 

Hydrochlorothiazide may reduce the response to pressor 

amines such as noradrenaline. The clinical significance of 

this effect is uncertain and not sufficient to preclude their 

use. 

Vitamin D and calcium 

salts 

Administration of thiazide diuretics, including 

hydrochlorothiazide, with vitamin D or with calcium salts 

may potentiate the rise in serum calcium. Concomitant use 

of thiazide type diuretics may lead to hypercalcaemia in 

patients pre-disposed for hypercalcaemia (e.g. 

hyperparathyroidism, malignancy or vitamin-D-mediated 

conditions) by increasing tubular calcium reabsorption. 

 

No interaction 

 

Imprida 

HCT 

individual 

component 

Known interactions 

with the following 

agents 

Effect of the interaction with other medicinal products 

Valsartan  Others 

(cimetidine, warfarin, 

furosemide, digoxin, 

atenolol, indometacin, 

hydrochlorothiazide, 

amlodipine, 

glibenclamide) 

In monotherapy with valsartan, no interactions of clinical 

significance have been found with the following 

substances: cimetidine, warfarin, furosemide, digoxin, 

atenolol, indomethacin, hydrochlorothiazide, amlodipine, 

glibenclamide. 

 

Some of these substances could interact with the 

hydrochlorothiazide component of Imprida HCT (see 

interactions related to HCT). 

Amlodipine Others In clinical interaction studies, amlodipine did not affect 

the pharmacokinetics of atorvastatin, digoxin, warfarin or 

ciclosporin. 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

Amlodipine 

The safety of amlodipine in human pregnancy has not been established. In animal studies, 

reproductive toxicity was observed at high doses (see section 5.3). Use in pregnancy is only 

recommended when there is no safer alternative and when the disease itself carries greater risk for the 

mother and foetus. 

 

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Valsartan 

The use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during the first 

trimester of pregnancy (see section 4.4). The use of AIIRAs is contraindicated during the second and 

third trimesters of pregnancy (see sections 4.3 and 4.4). 

 

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors 

during the first trimester of pregnancy has not been conclusive; however a small increase in risk 

cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II 

Receptor Antagonists (AIIRAs), similar risks may exist for this class of drugs. Unless continued 

AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative 

antihypertensive treatments which have an established safety profile for use in pregnancy. When 

pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and if appropriate, 

alternative therapy should be started. 

 

Exposure to AIIRAs therapy during the second and third trimesters is known to induce human 

foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal 

toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3). 

 

Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check 

of renal function and skull is recommended. 

 

Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see sections 

4.3 and 4.4). 

 

Hydrochlorothiazide 

There is limited experience with hydrochlorothiazide during pregnancy, especially during the first 

trimester. Animal studies are insufficient. 

 

Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of 

hydrochlorothiazide, its use during the second and third trimester may compromise foeto-placental 

perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance 

and thrombocytopenia. 

 

Amlodipine/valsartan/hydrochlorothiazide 

There is no experience on the use of Imprida HCT in pregnant women. Based on the existing data 

with the components, the use of Imprida HCT is not recommended during first trimester and contra-

indicated during the second and third trimester of pregnancy (see sections 4.3 and 4.4). 

 

Breast-feeding 

No information is available regarding the use of valsartan and/or amlodipine during breast-feeding. 

Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing 

intense diuresis can inhibit milk production. The use of Imprida HCT during breast-feeding is not 

recommended. If Imprida HCT is used during breast-feeding, doses should be kept as low as possible. 

Alternative treatments with better established safety profiles during breast-feeding are preferable, 

especially while nursing a newborn or preterm infant. 

 

Fertility 

There are no clinical studies on fertility with Imprida HCT. 

 

Valsartan 

Valsartan had no adverse effects on the reproductive performance of male or female rats at oral doses 

up to 200 mg/kg/day. This dose is 6 times the maximum recommended human dose on a mg/m
2
 basis 

(calculations assume an oral dose of 320 mg/day and a 60-kg patient). 

 

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Amlodipine 

Reversible biochemical changes in the head of spermatozoa have been reported in some patients 

treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of 

amlodipine on fertility. In one rat study, adverse effects were found on male fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 

 

No studies on the effects on the ability to drive and use machines have been performed. When driving 

vehicles or using machines it should be taken into account that occasionally dizziness or weariness 

may occur. 

 

4.8 Undesirable effects 

 

The safety profile of Imprida HCT presented below is based on clinical studies performed with 

Imprida HCT and the known safety profile of the individual components amlodipine, valsartan and 

hydrochlorothiazide. 

 

Information on Imprida HCT 

The safety of Imprida HCT has been evaluated at its maximum dose of 10 mg/320 mg/25 mg in one 

controlled short-term (8 weeks) clinical study with 2,271 patients, 582 of whom received valsartan in 

combination with amlodipine and hydrochlorothiazide. Adverse reactions were generally mild and 

transient in nature and only infrequently required discontinuation of therapy. In this active controlled 

clinical trial, the most common reasons for discontinuation of therapy with Imprida HCT were 

dizziness and hypotension (0.7%). 

 

In the 8-week controlled clinical study, no significant new or unexpected adverse reactions were 

observed with triple therapy treatment compared to the known effects of the monotherapy or dual 

therapy components. 

 

In the 8-week controlled clinical study, changes in laboratory parameters observed with the 

combination of Imprida HCT were minor and consistent with the pharmacological mechanism of 

action of the monotherapy agents. The presence of valsartan in the triple combination attenuated the 

hypokalaemic effect of hydrochlorothiazide. 

 

The following adverse reactions, listed by MedDRA System Organ Class and frequency, concern 

Imprida HCT (amlodipine/valsartan/HCT) and amlodipine, valsartan and HCT individually. 

Very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1,000 to <1/100; rare: ≥1/10,000 to 

<1/1,000; very rare: <1/10,000, not known (cannot be estimated from the available data). 

 

MedDRA 

System Organ 

Class 

Adverse reactions Frequency    

Imprida 

HCT 

Amlodipine Valsartan HCT 

Blood and 

lymphatic system 

disorders 

Agranulocytosis, bone 

marrow depression 

-- -- -- Very rare 

Decrease in haemoglobin 

and in haematocrit 

-- -- Not known -- 

Haemolytic anaemia -- -- -- Very rare 

Leukopenia -- Very rare -- Very rare 

Neutropenia -- -- Not known -- 

Thrombocytopenia, 

sometimes with purpura 

-- Very rare Not known Rare 

Aplastic anaemia -- -- -- Not known 

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Immune system 

disorders 

Hypersensitivity -- Very rare Not known Very rare 

Metabolism and 

nutrition 

disorders 

Anorexia Uncommon -- -- -- 

Hypercalcaemia Uncommon -- -- Rare 

Hyperglycaemia -- Very rare -- Rare 

Hyperlipidaemia Uncommon -- -- -- 

Hyperuricaemia Uncommon -- -- Common 

Hypochloraemic alkalosis -- -- -- Very rare 

Hypokalaemia Common -- -- Very 

common 

Hypomagnesaemia -- -- -- Common 

Hyponatraemia Uncommon -- -- Common 

Worsening of diabetic 

metabolic state 

-- -- -- Rare 

Psychiatric 

disorders 

Depression -- -- -- Rare 

Insomnia/sleep disturbances Uncommon Uncommon -- Rare 

Mood swings -- Uncommon --  

Nervous system 

disorders 

Coordination abnormal Uncommon -- -- -- 

Dizziness Common Common -- Rare 

Dizziness postural, dizziness 

exertional 

Uncommon -- -- -- 

Dysgeusia Uncommon Uncommon -- -- 

Extrapyramidal syndrome -- Not known -- -- 

Headache Common Common -- Rare 

Hypertonia -- Very rare -- -- 

Lethargy Uncommon -- -- -- 

Paraesthesia Uncommon Uncommon -- Rare 

Peripheral neuropathy, 

neuropathy 

Uncommon Very rare -- -- 

Somnolence Uncommon Common -- -- 

Syncope Uncommon Uncommon -- -- 

Tremor -- Uncommon -- -- 

Eye disorders Acute angle-closure 

glaucoma 

-- -- -- Not known 

Visual impairment Uncommon Uncommon -- Rare 

Ear and labyrinth 

disorders 

Tinnitus -- Uncommon -- -- 

Vertigo Uncommon -- Uncommon -- 

Cardiac disorders Palpitations -- Common -- -- 

Tachycardia Uncommon -- -- -- 

Arrhythmias (including 

bradycardia, ventricular 

tachycardia, and atrial 

fibrillation) 

-- Very rare -- Rare 

Myocardial infarction -- Very rare -- -- 

Vascular 

disorders 

Flushing -- Common -- -- 

Hypotension Common Uncommon -- -- 

Orthostatic hypotension Uncommon -- -- Common 

Phlebitis, thrombophlebitis Uncommon -- -- -- 

Vasculitis -- Very rare Not known -- 

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Respiratory, 

thoracic and 

mediastinal 

disorders 

Cough Uncommon Very rare Uncommon -- 

Dyspnoea Uncommon Uncommon -- -- 

Respiratory distress, 

pulmonary oedema, 

pneumonitis 

-- -- -- Very rare 

Rhinitis -- Uncommon -- -- 

Throat irritation Uncommon -- -- -- 

Gastrointestinal 

disorders 

Abdominal discomfort, 

abdominal pain upper 

Uncommon Common Uncommon Rare 

Breath odour Uncommon -- -- -- 

Change of bowel habit -- Uncommon -- -- 

Constipation -- -- -- Rare 

Decreased appetite -- -- -- Common 

Diarrhoea Uncommon Uncommon -- Rare 

Dry mouth Uncommon Uncommon -- -- 

Dyspepsia Common Uncommon -- -- 

Gastritis -- Very rare -- -- 

Gingival hyperplasia -- Very rare -- -- 

Nausea Uncommon Common -- Common 

Pancreatitis -- Very rare -- Very rare 

Vomiting Uncommon Uncommon -- Common 

Hepatobiliary 

disorders 

Hepatic enzyme elevation, 

including increase of serum 

bilirubin 

-- Very rare Not known -- 

Hepatitis -- Very rare -- -- 

Intrahepatic cholestasis, 

jaundice 

-- Very rare -- Rare 

Skin and 

subcutaneous 

tissue disorders 

Alopecia -- Uncommon --  

Angioedema -- Very rare Not known -- 

Cutaneous lupus 

erythematosus-like 

reactions, reactivation of 

cutaneous lupus 

erythematosus 

-- -- -- Very rare 

Erythema multiforme -- Very rare -- Not known 

Exanthema -- Uncommon -- -- 

Hyperhidrosis Uncommon Uncommon -- -- 

Photosensitivity reaction* -- -- -- Rare 

Pruritus Uncommon Uncommon Not known -- 

Purpura -- Uncommon -- Rare 

Rash -- Uncommon Not known Common 

Skin discoloration -- Uncommon -- -- 

Urticaria and other forms of 

rash 

-- Very rare -- Common 

Vasculitis necrotising and 

toxic epidermal necrolysis 

-- -- -- Very rare 

Musculoskeletal 

and connective 

tissue disorders 

Arthralgia -- Uncommon -- -- 

Back pain Uncommon Uncommon -- -- 

Joint swelling Uncommon -- -- -- 

Muscle spasm Uncommon Uncommon -- Not known 

Muscular weakness Uncommon -- -- -- 

Myalgia Uncommon Uncommon Not known -- 

Pain in extremity Uncommon -- -- -- 

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Renal and 

urinary disorders 

Elevation of serum 

creatinine 

Uncommon -- Not known -- 

Micturition disorder  Uncommon   

Nocturia -- Uncommon -- -- 

Pollakiuria Common Uncommon   

Renal dysfunction -- -- -- Not known 

Renal failure acute Uncommon -- -- Not known 

Renal failure and 

impairment 

-- -- Not known Rare 

Reproductive 

system and 

breast disorders 

Impotence Uncommon Uncommon -- Common 

Gynaecomastia  Uncommon -- -- 

General 

disorders and 

administration 

site conditions 

Abasia, gait disturbance Uncommon -- -- -- 

Asthenia Uncommon Uncommon -- Not known 

Discomfort, malaise Uncommon Uncommon -- -- 

Fatigue Common Common Uncommon -- 

Non cardiac chest pain Uncommon Uncommon -- -- 

Oedema Common Common -- -- 

Pain -- Uncommon -- -- 

Pyrexia -- -- -- Not known 

Investigations Lipids increased  --  Very 

common 

Blood urea nitrogen 

increased 

Uncommon -- -- -- 

Blood uric acid increased Uncommon -- --  

Glycosuria    Rare 

Serum potassium decreased Uncommon  -- -- -- 

Serum potassium increased -- -- Not known -- 

Weight increase Uncommon Uncommon -- -- 

Weight decrease -- Uncommon -- -- 

 

* See section 4.4 Photosensitivity 

 

4.9 Overdose 

 

Symptoms 

There is no experience of overdose with Imprida HCT. The major symptom of overdose with 

valsartan is possibly pronounced hypotension with dizziness. Overdose with amlodipine may result in 

excessive peripheral vasodilation and, possibly, reflex tachycardia. Marked and potentially prolonged 

systemic hypotension, including shock with fatal outcome, have been reported with amlodipine. 

 

Treatment 

Amlodipine/Valsartan/Hydrochlorothiazide 

Clinically significant hypotension due to Imprida HCT overdose calls for active cardiovascular 

support, including frequent monitoring of cardiac and respiratory function, elevation of extremities, 

and attention to circulating fluid volume and urine output. A vasoconstrictor may be helpful in 

restoring vascular tone and blood pressure, provided that there is no contraindication to its use. 

Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. 

 

Amlodipine 

If ingestion is recent, induction of vomiting or gastric lavage may be considered. Administration of 

activated charcoal to healthy volunteers immediately or up to two hours after ingestion of amlodipine 

has been shown to significantly decrease amlodipine absorption. 

Amlodipine is unlikely to be removed by haemodialysis. 

 

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Valsartan 

Valsartan is unlikely to be removed by haemodialysis. 

 

Hydrochlorothiazide 

Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, 

hypochloraemia) and hypovolaemia resulting from excessive diuresis. The most common signs and 

symptoms of overdose are nausea and somnolence. Hypokalaemia may result in muscle spasms and or 

accentuate arrhythmia associated with the concomitant use of digitalis glycosides or certain anti-

arrhythmic medicinal products. 

The degree to which hydrochlorothiazide is removed by haemodialysis has not been established. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Angiotensin II antagonists, plain (valsartan), combinations with 

dihydropyridine derivatives (amlodipine) and thiazide diuretics (hydrochlorothiazide), ATC code: 

C09DX01 valsartan, amlodipine and hydrochlorothiazide. 

 

Imprida HCT combines three antihypertensive compounds with complementary mechanisms to 

control blood pressure in patients with essential hypertension: amlodipine belongs to the calcium 

antagonist class and valsartan to the angiotensin II antagonist class of medicines and 

hydrochlorothiazide belongs to the thiazide diuretics class of medicines. The combination of these 

substances has an additive antihypertensive effect. 

 

Amlodipine/Valsartan/Hydrochlorothiazide 

Imprida HCT was studied in a double-blind, active controlled study in hypertensive patients. A total 

of 2,271 patients with moderate to severe hypertension (mean baseline systolic/diastolic blood 

pressure was 170/107 mmHg) received treatments of amlodipine/valsartan/hydrochlorothiazide 

10 mg/320 mg/25 mg, valsartan/hydrochlorothiazide 320 mg/25 mg, amlodipine/valsartan 

10 mg/320 mg, or hydrochlorothiazide/amlodipine 25 mg/10 mg. At study initiation patients were 

assigned lower doses of their treatment combination and were titrated to their full treatment dose by 

week 2. 

 

At week 8, the mean reductions in systolic/diastolic blood pressure were 39.7/24.7 mmHg with 

Imprida HCT, 32.0/19.7 mmHg with valsartan/hydrochlorothiazide, 33.5/21.5 mmHg with 

amlodipine/valsartan, and 31.5/19.5 mmHg with amlodipine/hydrochlorothiazide. The triple 

combination therapy was statistically superior to each of the three dual combination treatments in 

reduction of diastolic and systolic blood pressures. The reductions in systolic/diastolic blood pressure 

with Imprida HCT were 7.6/5.0 mmHg greater than with valsartan/hydrochlorothiazide, 

6.2/3.3 mmHg greater than with amlodipine/valsartan, and 8.2/5.3 mmHg greater than with 

amlodipine/hydrochlorothiazide. The full blood pressure lowering effect was achieved 2 weeks after 

being on their maximal dose of Imprida HCT. Statistically greater proportions of patients achieved 

blood pressure control (<140/90 mmHg) with Imprida HCT (71%) compared to each of the three dual 

combination therapies (45-54%) (p<0.0001). 

 

In a subgroup of 283 patients focusing on ambulatory blood pressure monitoring, clinically and 

statistically superior reductions in 24-hour systolic and diastolic blood pressures were observed with 

the triple combination compared to valsartan/hydrochlorothiazide, valsartan/amlodipine, and 

hydrochlorothiazide/amlodipine. 

 

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101 

Amlodipine 

The amlodipine component of Imprida HCT inhibits the transmembrane entry of calcium ions into 

cardiac and vascular smooth muscle. The mechanism of the antihypertensive action of amlodipine is 

due to a direct relaxant effect on vascular smooth muscle, causing reductions in peripheral vascular 

resistance and in blood pressure. Experimental data suggest that amlodipine binds to both 

dihydropyridine and non-dihydropyridine binding sites. The contractile processes of cardiac muscle 

and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into 

these cells through specific ion channels. 

 

Following administration of therapeutic doses to patients with hypertension, amlodipine produces 

vasodilation, resulting in a reduction of supine and standing blood pressures. These decreases in blood 

pressure are not accompanied by a significant change in heart rate or plasma catecholamine levels 

with chronic dosing. 

 

Plasma concentrations correlate with effect in both young and elderly patients. 

 

In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in a 

decrease in renal vascular resistance and increases in glomerular filtration rate and effective renal 

plasma flow, without change in filtration fraction or proteinuria. 

 

Valsartan 

Valsartan is an orally active, potent and specific angiotensin II receptor antagonist. It acts selectively 

on the receptor subtype AT1, which is responsible for the known actions of angiotensin II. 

 

Administration of valsartan to patients with hypertension results in a drop in blood pressure without 

affecting pulse rate. 

 

In most patients, after administration of a single oral dose, onset of antihypertensive activity occurs 

within 2 hours, and the peak drop in blood pressure is achieved within 4-6 hours. The 

antihypertensive effect persists over 24 hours after administration. During repeated administration, the 

maximum reduction in blood pressure with any dose is generally attained within 2-4 weeks. 

 

Hydrochlorothiazide 

The site of action of thiazide diuretics is primarily in the renal distal convoluted tubule. It has been 

shown that there is a high-affinity receptor in the renal cortex as the primary binding site for the 

thiazide diuretic action and inhibition of NaCl transport in the distal convoluted tubule. The mode of 

action of thiazides is through inhibition of the Na
+
Cl

-
 symporter perhaps by competing for the Cl

-
 site, 

thereby affecting electrolyte reabsorption mechanisms: directly increasing sodium and chloride 

excretion to an approximately equal extent, and indirectly, by this diuretic action, reducing plasma 

volume, with consequent increases in plasma renin activity, aldosterone secretion and urinary 

potassium loss, and a decrease in serum potassium. 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

Imprida HCT in all subsets of the paediatric population in essential hypertension. See section 4.2 for 

information on paediatric use. 

 

5.2 Pharmacokinetic properties 

 

Linearity 

Amlodipine, valsartan and hydrochlorothiazide exhibit linear pharmacokinetics. 

 

Amlodipine/valsartan/hydrochlorothiazide 

Following oral administration of Imprida HCT in normal healthy adults, peak plasma concentrations 

of amlodipine, valsartan and hydrochlorothiazide are reached in 6-8 hours, 3 hours, and 2 hours, 

respectively. The rate and extent of absorption of amlodipine, valsartan and hydrochlorothiazide from 

Imprida HCT are the same as when administered as individual dosage forms. 

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102 

 

Amlodipine 

Absorption: After oral administration of therapeutic doses of amlodipine alone, peak plasma 

concentrations of amlodipine are reached in 6-12 hours. Absolute bioavailability has been calculated as 

between 64% and 80%. Amlodipine bioavailability is unaffected by food ingestion. 

 

Distribution: Volume of distribution is approximately 21 l/kg. In vitro studies with amlodipine have 

shown that approximately 97.5% of circulating drug is bound to plasma proteins. 

 

Biotransformation: Amlodipine is extensively (approximately 90%) metabolised in the liver to inactive 

metabolites. 

 

Elimination: Amlodipine elimination from plasma is biphasic, with a terminal elimination half-life of 

approximately 30 to 50 hours. Steady-state plasma levels are reached after continuous administration for 

7-8 days. Ten per cent of original amlodipine and 60% of amlodipine metabolites are excreted in urine. 

 

Valsartan 

Absorption: Following oral administration of valsartan alone, peak plasma concentrations of valsartan 

are reached in 2-4 hours. Mean absolute bioavailability is 23%. Food decreases exposure (as 

measured by AUC) to valsartan by about 40% and peak plasma concentration (Cmax) by about 50%, 

although from about 8 h post dosing plasma valsartan concentrations are similar for the fed and fasted 

groups. This reduction in AUC is not, however, accompanied by a clinically significant reduction in 

the therapeutic effect, and valsartan can therefore be given either with or without food. 

 

Distribution: The steady-state volume of distribution of valsartan after intravenous administration is 

about 17 litres, indicating that valsartan does not distribute into tissues extensively. Valsartan is 

highly bound to serum proteins (94-97%), mainly serum albumin. 

 

Biotransformation: Valsartan is not transformed to a high extent as only about 20% of dose is 

recovered as metabolites. A hydroxy metabolite has been identified in plasma at low concentrations 

(less than 10% of the valsartan AUC). This metabolite is pharmacologically inactive. 

 

Elimination: Valsartan is primarily eliminated in faeces (about 83% of dose) and urine (about 13% of 

dose), mainly as unchanged drug. Following intravenous administration, plasma clearance of valsartan 

is about 2 l/h and its renal clearance is 0.62 l/h (about 30% of total clearance). The half-life of 

valsartan is 6 hours. 

 

Hydrochlorothiazide 

Absorption: The absorption of hydrochlorothiazide, after an oral dose, is rapid (Tmax about 2 hours). 

The increase in mean AUC is linear and dose proportional in the therapeutic range. 

 

The effect of food on hydrochlorothiazide absorption, if any, has little clinical significance. Absolute 

bioavailability of hydrochlorothiazide is 70% after oral administration. 

 

Distribution: The apparent volume of distribution is 4-8 l/kg. Circulating hydrochlorothiazide is 

bound to serum proteins (40-70%), mainly serum albumin. Hydrochlorothiazide also accumulates in 

erythrocytes at approximately 3 times the level in plasma. 

 

Biotransformation: Hydrochlorothiazide is eliminated predominantly as unchanged compound. 

 

Elimination: Hydrochlorothiazide is eliminated from plasma with a half-life averaging 6 to 15 hours 

in the terminal elimination phase. There is no change in the kinetics of hydrochlorothiazide on 

repeated dosing, and accumulation is minimal when dosed once daily. More than 95% of the absorbed 

dose is being excreted as unchanged compound in the urine. The renal clearance is composed of 

passive filtration and active secretion into the renal tubule. 

 

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103 

Special populations 

Paediatric patients (age below 18 years) 

No pharmacokinetic data are available in the paediatric population. 

 

Elderly (age 65 years or over) 

Time to peak plasma amlodipine concentrations is similar in young and elderly patients. In elderly 

patients, amlodipine clearance tends to decline, causing increases in the area under the curve (AUC) 

and elimination half-life. Mean systemic AUC of valsartan is higher by 70% in the elderly than in the 

young, therefore caution is required when increasing the dosage. 

 

Systemic exposure to valsartan is slightly elevated in the elderly as compared to the young, but this 

has not been shown to have any clinical significance. 

 

Limited data suggest that the systemic clearance of hydrochlorothiazide is reduced in both healthy and 

hypertensive elderly subjects compared to young healthy volunteers. 

 

Since the three components are equally well tolerated in younger and elderly patients, normal dose 

regimens are recommended (see section 4.2). 

 

Renal impairment 

The pharmacokinetics of amlodipine are not significantly influenced by renal impairment. As 

expected for a compound where renal clearance accounts for only 30% of total plasma clearance, no 

correlation was seen between renal function and systemic exposure to valsartan. 

 

Patients with mild to moderate renal impairment may therefore receive the usual initial dose (see 

sections 4.2 and 4.4). 

 

In the presence of renal impairment, mean peak plasma levels and AUC values of hydrochlorothiazide 

are increased and the urinary excretion rate is reduced. In patients with mild to moderate renal 

impairment, a 3-fold increase in hydrochlorothiazide AUC has been observed. In patients with severe 

renal impairment an 8-fold increase in AUC has been observed. Imprida HCT is contraindicated in 

patients with severe renal impairment, anuria or undergoing dialysis (see section 4.3). 

 

Hepatic impairment 

Patients with hepatic insufficiency have decreased clearance of amlodipine with resulting increase of 

approximately 40–60% in AUC. On average, in patients with mild to moderate chronic liver disease, 

exposure (measured by AUC values) to valsartan is twice that found in healthy volunteers (matched 

by age, sex and weight). Due to the valsartan component, Imprida HCT is contraindicated in patients 

with hepatic impairment (see sections 4.2 and 4.3). 

 

5.3 Preclinical safety data 

 

Amlodipine/Valsartan/Hydrochlorothiazide 

In a variety of preclinical safety studies conducted in several animal species with amlodipine, 

valsartan, hydrochlorothiazide, valsartan/hydrochlorothiazide, amlodipine/valsartan and 

amlodipine/valsartan/hydrochlorothiazide (Imprida HCT), there was no evidence of systemic or target 

organ toxicity that would adversely affect the development of Imprida HCT for clinical use in 

humans. 

 

Preclinical safety studies of up to 13 weeks in duration were conducted with 

amlodipine/valsartan/hydrochlorothiazide in rats. The combination resulted in expected reduction of 

red blood cell mass (erythrocytes, haemoglobin, haematocrit, and reticulocytes), increase in serum 

urea, increase in serum creatinine, increase in serum potassium, juxtaglomerular (JG) hyperplasia in 

the kidney and focal erosions in the glandular stomach in rats. All these changes were reversible after 

a 4-week recovery period and were considered to be exaggerated pharmacological effects. 

 

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The amlodipine/valsartan/hydrochlorothiazide combination was not tested for genotoxicity or 

carcinogenicity as there was no evidence of any interaction between these substances, which have 

been on the market for a long time. However, amlodipine, valsartan and hydrochlorothiazide have 

been tested individually for genotoxicity and carcinogenicity with negative results. 

 

Amlodipine 

Reproductive toxicology 

Reproductive studies in rats and mice have shown delayed date of delivery, prolonged duration of 

labour and decreased pup survival at dosages approximately 50 times greater than the maximum 

recommended dosage for humans based on mg/kg. 

 

Impairment of fertility 

There was no effect on the fertility of rats treated with amlodipine (males for 64 days and females 

14 days prior to mating) at doses up to 10 mg/kg/day (8 times* the maximum recommended human 

dose of 10 mg on a mg/m
2
 basis). In another rat study in which male rats were treated with amlodipine 

besilate for 30 days at a dose comparable with the human dose based on mg/kg, decreased plasma 

follicle-stimulating hormone and testosterone were found as well as decreases in sperm density and in 

the number of mature spermatids and Sertoli cells. 

 

Carcinogenesis, mutagenesis 

Rats and mice treated with amlodipine in the diet for two years, at concentrations calculated to 

provide daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day showed no evidence of carcinogenicity. 

The highest dose (for mice, similar to, and for rats twice* the maximum recommended clinical dose of 

10 mg on a mg/m
2
 basis) was close to the maximum tolerated dose for mice but not for rats. 

 

Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels. 

 

* Based on patient weight of 50 kg 

 

Valsartan 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential. 

 

In rats, maternally toxic doses (600 mg/kg/day) during the last days of gestation and lactation led to 

lower survival, lower weight gain and delayed development (pinna detachment and ear-canal opening) 

in the offspring (see section 4.6). These doses in rats (600 mg/kg/day) are approximately 18 times the 

maximum recommended human dose on a mg/m
2 
basis (calculations assume an oral dose of 

320 mg/day and a 60-kg patient). 

 

In non-clinical safety studies, high doses of valsartan (200 to 600 mg/kg body weight) caused in rats a 

reduction of red blood cell parameters (erythrocytes, haemoglobin, haematocrit) and evidence of 

changes in renal haemodynamics (slightly raised plasma urea, and renal tubular hyperplasia and 

basophilia in males). These doses in rats (200 and 600 mg/kg/day) are approximately 6 and 18 times 

the maximum recommended human dose on a mg/m
2
 basis (calculations assume an oral dose of 

320 mg/day and a 60-kg patient). 

 

In marmosets at similar doses, the changes were similar though more severe, particularly in the kidney 

where the changes developed to a nephropathy which included raised urea and creatinine. 

 

Hypertrophy of the renal juxtaglomerular cells was also seen in both species. All changes were 

considered to be caused by the pharmacological action of valsartan which produces prolonged 

hypotension, particularly in marmosets. For therapeutic doses of valsartan in humans, the hypertrophy 

of the renal juxtaglomerular cells does not seem to have any relevance. 

 

 

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105 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Tablet core 

Cellulose microcrystalline 

Crospovidone 

Silica, colloidal anhydrous 

Magnesium stearate 

 

Coating 

Hypromellose 

Macrogol 4000 

Talc 

Iron oxide, yellow (E172) 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

2 years 

 

6.4 Special precautions for storage 

 

Do not store above 30°C. 

 

Store in the original package in order to protect from moisture. 

 

6.5 Nature and contents of container 

 

PVC/PVDC blisters. One blister contains 7, 10 or 14 film-coated tablets. 

Pack sizes: 14, 28, 30, 56, 90, 98 or 280 film-coated tablets. 

Multipacks of 280 tablets, comprising 20 cartons, each containing 14 tablets. 

 

PVC/PVDC perforated unit dose blisters for hospital use: 

Pack sizes: 56, 98 or 280 film-coated tablets 

Multipacks of 280 tablets, comprising 4 cartons, each containing 70 tablets. 

 

Not all pack sizes or strengths may be marketed. 

 

6.6 Special precautions for disposal and other handling 

 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

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8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/049-060 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

15.10.2009 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

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107 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURING AUTHORISATION HOLDER 

RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OF THE MARKETING AUTHORISATION 

 

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108 

A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH 

RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nürnberg 

Germany 

 

 

B. CONDITIONS OF THE MARKETING AUTHORISATION 

 

 CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON 

THE MARKETING AUTHORISATION HOLDER 

 

Medicinal product subject to medical prescription. 

 

 CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

Not applicable. 

 

 OTHER CONDITIONS 
 

Pharmacovigilance system 

The MAH must ensure that the system of pharmacovigilance, presented in Module 1.8.1. of the 

Marketing Authorisation, is in place and functioning before and whilst the product is on the market. 

 

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109 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

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110 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

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111 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 5 mg/160 mg/12.5 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiaziade 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg amlodipine (as amlodipine besylate), 160 mg valsartan and 12.5 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

56 film-coated tablets 

56 x 1 film-coated tablet (unit dose) 

90 film-coated tablets 

98 film-coated tablets 

98 x 1 film-coated tablet (unit dose) 

280 film-coated tablets 

280 x 1 film-coated tablet (unit dose) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

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112 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/001 14 film-coated tablets 

EU/1/09/570/002 28 film-coated tablets 

EU/1/09/570/003 30 film-coated tablets 

EU/1/09/570/004 56 film-coated tablets 

EU/1/09/570/005 90 film-coated tablets 

EU/1/09/570/006 98 film-coated tablets 

EU/1/09/570/007 280 film-coated tablets 

EU/1/09/570/008 56 x 1 film-coated tablet (unit dose) 

EU/1/09/570/009 98 x 1 film-coated tablet (unit dose) 

EU/1/09/570/010 280 x 1 film-coated tablet (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 5 mg/160 mg/12.5 mg 

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113 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 5 mg/160 mg/12.5 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg amlodipine (as amlodipine besylate), 160 mg valsartan and 12.5 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 cartons, each containing 14 tablets. 

70 film-coated tablets 

Component of a multipack comprising 4 cartons, each containing 70 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

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114 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/012 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/570/011 280 film-coated tablets (multipack, 4 cartons of 70 tablets) (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 5 mg/160 mg/12.5 mg 

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115 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 5 mg/160 mg/12.5 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg amlodipine (as amlodipine besylate), 160 mg valsartan and 12.5 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

280 film-coated tablets 

Multipack comprising 20 cartons each containing 14 tablets. 

Multipack comprising 4 cartons, each containing 70 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

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116 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/012 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/570/011 280 film-coated tablets (multipack, 4 cartons of 70 tablets) (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 5 mg/160 mg/12.5 mg 

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117 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 5 mg/160 mg/12.5 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/160 mg/12.5 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiaziade 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg amlodipine (as amlodipine besylate), 160 mg valsartan and 12.5 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

56 film-coated tablets 

56 x 1 film-coated tablet (unit dose) 

90 film-coated tablets 

98 film-coated tablets 

98 x 1 film-coated tablet (unit dose) 

280 film-coated tablets 

280 x 1 film-coated tablet (unit dose) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

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9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/013 14 film-coated tablets 

EU/1/09/570/014 28 film-coated tablets 

EU/1/09/570/015 30 film-coated tablets 

EU/1/09/570/016 56 film-coated tablets 

EU/1/09/570/017 90 film-coated tablets 

EU/1/09/570/018 98 film-coated tablets 

EU/1/09/570/019 280 film-coated tablets 

EU/1/09/570/020 56 x 1 film-coated tablet (unit dose) 

EU/1/09/570/021 98 x 1 film-coated tablet (unit dose) 

EU/1/09/570/022 280 x 1 film-coated tablet (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 10 mg/160 mg/12.5 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/160 mg/12.5 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg amlodipine (as amlodipine besylate), 160 mg valsartan and 12.5 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 cartons, each containing 14 tablets. 

70 film-coated tablets 

Component of a multipack comprising 4 cartons, each containing 70 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/024 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/570/023 280 film-coated tablets (multipack, 4 cartons of 70 tablets) (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 10 mg/160 mg/12.5 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/160 mg/12.5 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg amlodipine (as amlodipine besylate), 160 mg valsartan and 12.5 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

280 film-coated tablets 

Multipack comprising 20 cartons each containing 14 tablets. 

Multipack comprising 4 cartons, each containing 70 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/024 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/570/023 280 film-coated tablets (multipack, 4 cartons of 70 tablets) (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 10 mg/160 mg/12.5 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/160 mg/12.5 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 5 mg/160 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiaziade 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg amlodipine (as amlodipine besylate), 160 mg valsartan and 25 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

56 film-coated tablets 

56 x 1 film-coated tablet (unit dose) 

90 film-coated tablets 

98 film-coated tablets 

98 x 1 film-coated tablet (unit dose) 

280 film-coated tablets 

280 x 1 film-coated tablet (unit dose) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

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9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/025 14 film-coated tablets 

EU/1/09/570/026 28 film-coated tablets 

EU/1/09/570/027 30 film-coated tablets 

EU/1/09/570/028 56 film-coated tablets 

EU/1/09/570/029 90 film-coated tablets 

EU/1/09/570/030 98 film-coated tablets 

EU/1/09/570/031 280 film-coated tablets 

EU/1/09/570/032 56 x 1 film-coated tablet (unit dose) 

EU/1/09/570/033 98 x 1 film-coated tablet (unit dose) 

EU/1/09/570/034 280 x 1 film-coated tablet (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 5 mg/160 mg/25 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 5 mg/160 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg amlodipine (as amlodipine besylate), 160 mg valsartan and 25 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 cartons, each containing 14 tablets. 

70 film-coated tablets 

Component of a multipack comprising 4 cartons, each containing 70 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/036 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/570/035 280 film-coated tablets (multipack, 4 cartons of 70 tablets) (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 5 mg/160 mg/25 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 5 mg/160 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg amlodipine (as amlodipine besylate), 160 mg valsartan and 25 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

280 film-coated tablets 

Multipack comprising 20 cartons each containing 14 tablets. 

Multipack comprising 4 cartons, each containing 70 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/036 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/570/035 280 film-coated tablets (multipack, 4 cartons of 70 tablets) (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 5 mg/160 mg/25 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 5 mg/160 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/160 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiaziade 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg amlodipine (as amlodipine besylate), 160 mg valsartan and 25 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

56 film-coated tablets 

56 x 1 film-coated tablet (unit dose) 

90 film-coated tablets 

98 film-coated tablets 

98 x 1 film-coated tablet (unit dose) 

280 film-coated tablets 

280 x 1 film-coated tablet (unit dose) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

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9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/037 14 film-coated tablets 

EU/1/09/570/038 28 film-coated tablets 

EU/1/09/570/039 30 film-coated tablets 

EU/1/09/570/040 56 film-coated tablets 

EU/1/09/570/041 90 film-coated tablets 

EU/1/09/570/042 98 film-coated tablets 

EU/1/09/570/043 280 film-coated tablets 

EU/1/09/570/044 56 x 1 film-coated tablet (unit dose) 

EU/1/09/570/045 98 x 1 film-coated tablet (unit dose) 

EU/1/09/570/046 280 x 1 film-coated tablet (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 10 mg/160 mg/25 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/160 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg amlodipine (as amlodipine besylate), 160 mg valsartan and 25 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 cartons, each containing 14 tablets. 

70 film-coated tablets 

Component of a multipack comprising 4 cartons, each containing 70 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/048 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/570/047 280 film-coated tablets (multipack, 4 cartons of 70 tablets) (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 10 mg/160 mg/25 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/160 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg amlodipine (as amlodipine besylate), 160 mg valsartan and 25 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

280 film-coated tablets 

Multipack comprising 20 cartons each containing 14 tablets. 

Multipack comprising 4 cartons, each containing 70 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/048 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/570/047 280 film-coated tablets (multipack, 4 cartons of 70 tablets) (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 10 mg/160 mg/25 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/160 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/320 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiaziade 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg amlodipine (as amlodipine besylate), 320 mg valsartan and 25 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

56 film-coated tablets 

56 x 1 film-coated tablet (unit dose) 

90 film-coated tablets 

98 film-coated tablets 

98 x 1 film-coated tablet (unit dose) 

280 film-coated tablets 

280 x 1 film-coated tablet (unit dose) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

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9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/049 14 film-coated tablets 

EU/1/09/570/050 28 film-coated tablets 

EU/1/09/570/051 30 film-coated tablets 

EU/1/09/570/052 56 film-coated tablets 

EU/1/09/570/053 90 film-coated tablets 

EU/1/09/570/054 98 film-coated tablets 

EU/1/09/570/055 280 film-coated tablets 

EU/1/09/570/056 56 x 1 film-coated tablet (unit dose) 

EU/1/09/570/057 98 x 1 film-coated tablet (unit dose) 

EU/1/09/570/058 280 x 1 film-coated tablet (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 10 mg/320 mg/25 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/320 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg amlodipine (as amlodipine besylate), 320 mg valsartan and 25 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 cartons, each containing 14 tablets. 

70 film-coated tablets 

Component of a multipack comprising 4 cartons, each containing 70 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/060 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/570/059 280 film-coated tablets (multipack, 4 cartons of 70 tablets) (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 10 mg/320 mg/25 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/320 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg amlodipine (as amlodipine besylate), 320 mg valsartan and 25 mg 

hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

280 film-coated tablets 

Multipack comprising 20 cartons each containing 14 tablets. 

Multipack comprising 4 cartons, each containing 70 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/570/060 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/570/059 280 film-coated tablets (multipack, 4 cartons of 70 tablets) (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Imprida HCT 10 mg/320 mg/25 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Imprida HCT 10 mg/320 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

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B. PACKAGE LEAFLET 

 

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PACKAGE LEAFLET: INFORMATION FOR THE USER 

 

Imprida HCT 5 mg/160 mg/12.5 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

Read all of this leaflet carefully before you start taking this medicine. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or pharmacist. 

- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 

- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 

 

 

In this leaflet: 

1. What Imprida HCT is and what it is used for 

2. Before you take Imprida HCT 

3. How to take Imprida HCT 

4. Possible side effects 

5. How to store Imprida HCT 

6. Further information 

 

 

1. WHAT IMPRIDA HCT IS AND WHAT IT IS USED FOR 

 

Imprida HCT tablets contain three substances called amlodipine, valsartan and hydrochlorothiazide. 

All of these substances help to control high blood pressure. 

 Amlodipine belongs to a group of substances called “calcium channel blockers”. Amlodipine 

stops calcium from moving into the blood vessel wall, which stops the blood vessels from 

tightening. 

 Valsartan belongs to a group of substances called “angiotensin-II receptor antagonists”. 

Angiotensin II is produced by the body and makes the blood vessels tighten, thus increasing the 

blood pressure. Valsartan works by blocking the effect of angiotensin II. 

 Hydrochlorothiazide belongs to a group of substances called “thiazide diuretics”. 

Hydrochlorothiazide increases urine output, which also lowers blood pressure. 

As a result of all three mechanisms, the blood vessels relax and blood pressure is lowered. 

 

Imprida HCT is used to treat high blood pressure in adult patients who are already taking amlodipine, 

valsartan and hydrochlorothiazide and who may benefit from taking one tablet containing all three 

substances. 

 

 

2. BEFORE YOU TAKE IMPRIDA HCT 

 

Do not take Imprida HCT 

 if you are more than 3 months pregnant. (It is also better to avoid Imprida HCT in early 

pregnancy – see Pregnancy section). 

 if you are allergic (hypersensitive) to amlodipine, valsartan, hydrochlorothiazide, 

sulphonamide-derived medicines (medicines used to treat chest or urinary infections), or any of 

the other ingredients of Imprida HCT (see section 6, “What Imprida HCT contains”). 

If you think you may be allergic, do not take Imprida HCT and talk to your doctor. 

 if you have liver disease, destruction of the small bile ducts within the liver (biliary cirrhosis) 

leading to the build up of bile in the liver (cholestasis). 

 if you have severe kidney problems or if you are having dialysis. 

 if you are unable to produce urine (anuria). 

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 if the level of potassium or sodium in your blood is too low despite treatment. 

 if the level of calcium in your blood is too high despite treatment. 

 if you have gout (uric acid crystals in the joints). 

If any of the above applies to you, do not take Imprida HCT and talk to your doctor. 

 

Take special care with Imprida HCT 

 if you have a low level of potassium or magnesium in your blood (with or without symptoms 

such as muscle weakness, muscle spasms, abnormal heart rhythm). 

 if you have a low level of sodium in your blood (with or without symptoms such as tiredness, 

confusion, muscle twitching, convulsions). 

 if you have a high level of calcium in your blood (with or without symptoms such as nausea, 

vomiting, constipation, stomach pain, frequent urination, thirst, muscle weakness and 

twitching). 

 if you are taking medicines or substances that increase the amount of potassium in your blood. 

These include potassium supplements or salt substitutes containing potassium, potassium-

sparing medicines and heparin. It may be necessary to check the amount of potassium in your 

blood at regular intervals. 

 if you have kidney problems, have had a kidney transplant or if you had been told that you have 

a narrowing of your kidney arteries. 

 if you have liver problems. 

 if you have or have had heart failure or coronary artery disease, particularly if you are taking 
the maximum dose of Imprida HCT (10 mg/320 mg/25 mg) 

 if your doctor has told you that you have a narrowing of the valves in your heart (called “aortic 

or mitral stenosis”) or that the thickness of your heart muscle is abnormally increased (called 

“obstructive hypertrophic cardiomyopathy”). 

 if you suffer from aldosteronism. This is a disease in which the adrenal glands make too much 

of the hormone aldosterone If this applies to you, the use of Imprida HCT is not recommended. 

 if you suffer from a disease called systemic lupus erythematosus (also called “lupus” or 

“SLE”). 

 if you have diabetes (high level of sugar in your blood). 

 if you have high levels of cholesterol or triglycerides in your blood. 

 if you experience skin reactions such as rash after sun exposure. 

 if you had an allergic reaction to other high blood pressure medicines or diuretics (a type of 

medicine also known as “water tablets”), especially if you suffer from asthma and allergies 

 if you have been sick (vomiting or diarrhoea). 

 if you experience dizziness and/or fainting during treatment with Imprida HCT, tell your doctor 

as soon as possible. 

 if you experience a decrease in vision or eye pain. These could be symptoms of an increase of 

pressure in your eye and can happen within hours to a week of taking Imprida HCT. This can 

lead to permanent vision impairment, if not treated. 

If any of these apply to you, talk to your doctor. 

 

You must tell your doctor if you think that you are (or might become) pregnant. Imprida HCT is not 

recommended in early pregnancy and must not be taken if you are more than 3 months pregnant, as it 

may cause serious harm to your baby if used at this stage (see section “Pregnancy and breast-

feeding”). 

 

The use of Imprida HCT in children and adolescents under 18 years of age is not recommended. 

 

Imprida HCT and older people (age 65 years and older) 

Imprida HCT can be used by people aged 65 years and over at the same dose as for other adults and in 

the same way as they have already taken the three substances called amlodipine, valsartan and 

hydrochlorothiazide. Elderly patients, particularly those taking the maximum dose of Imprida HCT 

(10 mg/320 mg/25 mg), should have their blood pressure checked regularly. 

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Using other medicines 

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 

including medicines obtained without a prescription. Your doctor may need to change the dose or take 

other precautions. In some cases you may have to stop using one of the medicines. This is especially 

important if you are using any of the medicines listed below: 

 

Do not take together with: 

• lithium (a medicine used to treat some types of depression); 

• medicines or substances that increase the amount of potassium in your blood. These include 

potassium supplements or salt substitutes containing potassium, potassium-sparing medicines 

and heparin. 

Caution should be used with: 

• alcohol, sleeping pills and anaesthetics (medicines allowing patients to undergo surgery and 

other procedures); 

• amantadine (anti-Parkinson therapy, also used to treat or prevent certain illnesses caused by 

viruses); 

• anticholinergic agents (medicines used to treat a variety of disorders such as gastrointestinal 

cramps, urinary bladder spasm, asthma, motion sickness, muscular spasms, Parkinson's disease 

and as an aid to anaesthesia); 

• anticonvulsant medicines and mood-stabilising medicines used to treat epilepsy and bipolar 

disorder (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone); 

• cholestyramine, colestipol or other resins (substances used mainly to treat high levels of lipids 

in the blood); 

• simvastatin (a medicine used to control high cholesterol levels); 

• ciclosporin (a medicine used in transplantation to prevent organ rejection or for other 

conditions, e.g: rheumatoid arthritis or atopic dermatitis); 

• cytotoxic medicines (used to treat cancer), such as methotrexate or cyclophosphamide; 

• digoxin or other digitalis glycosides (medicines used to treat heart problems); 

• verapamil, diltiazem (heart medicines); 

• iodine contrast media (agents used for imaging examinations); 

• medicines for the treatment of diabetes (oral agents such as metformin or insulins); 

• medicines for the treatment of gout, such as allopurinol; 

• medicines that may increase blood sugar levels (beta blockers, diazoxide); 

• medicines that may induce “torsades de pointes” (irregular heart beat), such as antiarrhythmics 

(medicines used to treat heart problems) and some antipsychotics; 

• medicines that may reduce the amount of sodium in your blood, such as antidepressants, 

antipsychotics, antiepileptics; 

• medicines that may reduce the amount of potassium in your blood, such as diuretics (water 

tablets), corticosteroids, laxatives, amphotericin or penicillin G; 

• medicines to increase blood pressure such as adrenaline or noradrenaline; 

• medicines used for HIV/AIDS (e.g. ritonavir, indinavir, nelfinavir); 

• medicines used to treat fungal infections (e.g. ketoconazole, itraconazole); 

• medicines used for oesophageal ulceration and inflammation (carbenoxolone); 

• medicines used to relieve pain or inflammation, especially non-steroidal anti-inflammatory 

agents (NSAIDs), including selective cyclooxygenase-2 inhibitors (Cox-2 inhibitors); 

• muscle relaxants (medicines to relax the muscles which are used during operations); 

• nitroglycerin and other nitrates, or other substances called “vasodilators”; 

• other medicines to treat high blood pressure, including methyldopa; 

• rifampicin (used, for example, to treat tuberculosis); 

• St. John’s wort; 

• dantrolene (infusion for severe body temperature abnormalities); 

• vitamin D and calcium salts. 

 

Talk to your doctor before drinking alcohol. Alcohol may make your blood pressure fall too much 

and/or increase the possibility of dizziness or fainting. 

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Taking Imprida HCT with food and drink 

You can take Imprida HCT with or without food. Grapefruit and grapefruit juice should not be 

consumed by people who are taking Imprida HCT. This is because grapefruit and grapefruit juice can 

lead to an increase in the blood levels of the active substance amlodipine, which can cause an 

unpredictable increase in the blood pressure lowering effect of Imprida HCT. 

 

Pregnancy and breast-feeding 

Pregnancy 

You must tell your doctor if you think you are (or might become) pregnant. Your doctor will 

normally advise you to stop taking Imprida HCT before you become pregnant or as soon as you know 

you are pregnant and will advise you to take another medicine instead of Imprida HCT. Imprida HCT 

is not recommended in early pregnancy and must not be taken when more than 3 months pregnant, as 

it may cause serious harm to your baby if used after the third month of pregnancy. 

 

Breast-feeding 

Tell your doctor if you are breast-feeding or about to start breast-feeding. Imprida HCT is not 

recommended for mothers who are breast-feeding, and your doctor may choose another treatment for 

you if you wish to breast-feed, especially if your baby is a newborn, or was born prematurely. 

 

Ask your doctor or pharmacist for advice before taking any medicine. 

 

Driving and using machines 

As with many other medicines used to treat high blood pressure, this medicine may make you feel 

dizzy. If you experience this symptom, do not drive or use tools or machines. 

 

 

3. HOW TO TAKE IMPRIDA HCT 

 

Always take this medicine exactly as your doctor has told you. You should check with your doctor if 

you are not sure. This will help you get the best results and lower the risk of side effects. 

 

The usual dose of Imprida HCT is one tablet per day. 

 It is best to take the tablet at the same time each day. Morning is the best time. 

 Swallow the tablet whole with a glass of water. 

 You can take Imprida HCT with or without food. Do not take Imprida HCT with grapefruit or 

grapefruit juice. 

 

Depending on how you respond to the treatment, your doctor may suggest a higher or lower dose. 

 

If you take more Imprida HCT than you should 

If you have accidentally taken too many Imprida HCT tablets, talk to a doctor immediately.You may 

require medical attention. 

 

If you forget to take Imprida HCT 

If you forget to take a dose of this medicine, take it as soon as you remember and then take the next 

dose at its usual time. If it is almost time for your next dose you should simply take the next tablet at 

the usual time. Do not take a double dose (two tablets at once) to make up for a forgotten tablet. 

 

If you stop taking Imprida HCT 

Stopping your treatment with Imprida HCT may cause your disease to get worse. Do not stop taking 

your medecine unless your doctor tells you to. 

 

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Always take this medicine, even if you are feeling well 

People who have high blood pressure often do not notice any signs of the problem. Many feel normal. 

It is very important that you take this medicine exactly as your doctor tells you to get the best results 

and reduce the risk of side effects. Keep your appointments with the doctor even if you are feeling 

well. 

 

If you have any further questions on the use of this product ask your doctor or pharmacist. 

 

 

4. POSSIBLE SIDE EFFECTS 

 

Like all medicines, Imprida HCT can cause side effects, although not everybody gets them. 

These side effects may occur with certain frequencies, which are defined as follows: 

very common: affects more than 1 user in 10 

common: affects 1 to 10 users in 100 

uncommon: affects 1 to 10 users in 1,000 

rare: affects 1 to 10 users in 10,000 

very rare: affects less than 1 user in 10,000 

not known: frequency cannot be estimated from the available data 

 

Some side effects can be serious and need immediate medical attention: 

 

You should see your doctor immediately if you experience any of the following symptoms: 

Common 

 dizziness 

 low blood pressure (feeling of faintness, light-headedness, sudden loss of consciousness) 

 

Uncommon 

 severely decreased urine output (decreased kidney function) 

 

Rare 

 spontaneous bleeding 

 irregular heart beat 

 liver disorder 

 

Very rare 

 allergic reaction with symptoms such as rash, itching 

 angioedema: swelling of face or lips or tongue, difficulty of breathing 

 crushing/tight chest pain that gets worse or that does not go away 

 weakness, bruising, fever and frequent infections 

 stiffness 

 

Other possible side effects of Imprida HCT: 

Common 

 stomach discomfort after meal 

 tiredness 

 swelling 

 low level of potassium in the blood 

 headache 

 frequent urination 

 

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Uncommon 

 fast heart beat 

 spinning sensation 

 vision disorder 

 stomach discomfort 

 chest pain 

 increase of urea nitrogen, creatinine and uric acid in the blood 

 high level of calcium, fat or sodium in the blood 

 decrease of potassium in the blood 

 breath odour 

 diarrhoea 

 dry mouth 

 nausea 

 vomiting 

 abdominal pain 

 weight increase 

 loss of appetite 

 disturbed sense of taste 

 back pain 

 joint swelling 

 muscle cramps/weakness/pain 

 pain in extremity 

 inability to either stand or walk in a normal manner 

 weakness 

 abnormal coordination 

 dizziness on standing up or after exercising 

 lack of energy 

 sleep disturbances 

 tingling or numbness 

 neuropathy 

 sleepiness 

 sudden, temporary loss of consciousness 

 low blood pressure on standing up 

 impotence 

 cough 

 breathlessness 

 throat irritation 

 excessive sweating 

 itching 

 swelling, reddening and pain along a vein 

 skin reddening 

 trembling 

 

Not known 

 changes in blood tests for kidney function, increase of potassium in your blood, low level of red 

blood cells 

 

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Side effects reported with amlodipine or valsartan or hydrochlorothiazide alone, but not 

observed with Imprida HCT or observed in a higher frequency: 

 

Amlodipine 

Common 

 palpitations 

 abdominal pain 

 nausea 

 sleepiness 

 hot flushes 

 

Uncommon 

 ringing noise in ears 

 change of bowel habit 

 pain 

 weight decrease 

 joint pain 

 trembling 

 mood swings 

 urination disorders 

 urination at night 

 breast enlargement in men 

 runny nose 

 hair loss 

 skin eruption 

 purple skin patches 

 rash 

 skin discoloration 

 

Very rare 

 low level of white blood cells and blood platelets 

 irregular heart beat 

 heart attack 

 inflammation of the stomach lining or of the pancreas, gingival overgrowth, abnormal liver 

function test 

 liver disorder which can occur together with yellow skin and eyes, or dark-coloured urine 

 allergic reaction including swelling deeper in the skin and difficulty breathing 

 high level of sugar in the blood 

 increased muscle stiffness 

 skin reaction with skin reddening and peeling, blistering of lips, eyes or mouth 

 itchy rash 

 inflammation of blood vessels 

 

Not known 

 stiff limbs and trembling hands 

 

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Valsartan 

Not known 

 abnormal red blood cell test 

 low level of a certain type of white blood cell and blood platelet 

 increase of potassium in the blood 

 increase of creatinine in the blood 

 abnormal liver function test 

 allergic reaction including swelling deeper in the skin and difficulty breathing 

 muscle pain 

 severely decreased urine output 

 itching 

 rash 

 inflammation of blood vessels 

 

Hydrochlorothiazide 

Very common 

 low level of potassium in the blood 

 increase of lipids in the blood 

 

Common 

 high level of uric acid in the blood 

 low level of magnesium in the blood 

 low level of sodium in the blood 

 dizziness, fainting on standing up 

 reduced appetite 

 nausea and vomiting 

 itchy rash and other types of rash 

 inability to achieve or maintain erection 

 

Rare 

 low level of blood platelets (sometimes with bleeding or bruising underneath the skin) 

 sugar in the urine 

 high level of sugar in the blood 

 worsening of the diabetic metabolic state 

 sad mood (depression) 

 irregular heart beat 

 abdominal discomfort 

 constipation 

 liver disorders which can occur together with yellow skin and eyes, or dark-coloured urine 

(haemolytic anaemia) 

 increased sensitivity of skin to sun 

 purple skin patches 

 kidney disorders 

 

Very rare 

 fever, sore throat or mouth ulcers, more frequent infections (lack or low level of white blood 

cells) 

 pale skin, tiredness, breathlessness, dark-coloured urine (haemolytic anaemia, abnormal 

breakdown of red blood cells either in the blood vessels or elsewhere in the body) 

 confusion, tiredness, muscle twitching and spasm, rapid breathing (hypochloraemic alkalosis) 

 severe upper stomach ache (inflammation of the pancreas) 

 rash, itching, hives, difficulty breathing or swallowing, dizziness (hypersensitivity reactions) 

 difficulty breathing with fever, coughing, wheezing, breathlessness (respiratory distress, 

pulmonary oedema, pneumonitis) 

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 facial rash, joint pain, muscle disorder, fever (lupus erythematosus) 

 inflammation of blood vessels with symptoms such as rash, purplish-red spots, fever (vasculitis) 

 severe skin disease that causes rash, red skin, blistering of the lips, eyes or mouth, skin peeling, 

fever (toxic epidermal necrolysis) 

 

Not known 

 weakness, bruising and frequent infections (aplastic anaemia) 

 decrease in vision or pain in your eyes due to high pressure (possible signs of acute angle-

closure glaucoma) 

 breathlessness 

 severely decreased urine output (possible signs of renal disorder or renal failure) 

 severe skin disease that causes rash, red skin, blistering of the lips, eyes or mouth, skin peeling, 

fever (erythema multiforme) 

 muscle spasm 

 fever (pyrexia) 

 

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 

 

 

5. HOW TO STORE IMPRIDA HCT 

 

Keep out of the reach and sight of children. 

Do not use Imprida HCT after the expiry date which is stated on the carton and blister after EXP. The 

expiry date refers to the last day of that month. 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

Do not use any Imprida HCT pack that is damaged or shows signs of tampering. 

 

 

6. FURTHER INFORMATION 

 

What Imprida HCT contains 

 The active substances of Imprida HCT are amlodipine (as amlodipine besylate), valsartan and 

hydrochlorothiazide. 

 

 Imprida HCT 5 mg/160 mg/12.5 mg film-coated tablets: Each film-coated tablet contains 5 mg 

amlodipine (as amlodipine besylate), 160 mg valsartan and 12.5 mg hydrochlorothiazide. The 

other ingredients are cellulose microcrystalline; crospovidone; silica, colloidal anhydrous; 

magnesium stearate; hypromellose, macrogol 4000, talc, titanium dioxide (E171). 

 

What Imprida HCT looks like and contents of the pack 

 Imprida HCT 5 mg/160 mg/12.5 mg film-coated tablets are white, oval tablets with “NVR” on 

one side and “VCL” on the other side. 

 

Imprida HCT is available in packs containing 14, 28, 30, 56, 90, 98 or 280 film-coated tablets, in 

multipacks of 280 tablets (comprising 4 cartons, each containing 70 tablets, or 20 cartons, each 

containing 14 tablets), and in hospital packs containing 56, 98 or 280 tablets in single unit blisters. 

Not all pack sizes may be available in your country. 

 

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Marketing Authorisation Holder 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

България 

Novartis Pharma Services Inc. 

Тел.: +359 2 976 98 28 

 

Magyarország 

Novartis Hungária Kft. Pharma 

Tel.: +36 1 457 65 00 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2298 3217 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 26 37 82 111 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 

Eesti 

Novartis Pharma Services Inc. 

Tel: +372 66 30 810 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

España 

Lacer, S.A. 

Tel: +34 93 446 53 00 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

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Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

Novartis Pharma Services Inc. 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

Lietuva 

Novartis Pharma Services Inc. 

Tel: +370 5 269 16 50 

 

 

 

This leaflet was last approved in 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

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PACKAGE LEAFLET: INFORMATION FOR THE USER 

 

Imprida HCT 10 mg/160 mg/12.5 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

Read all of this leaflet carefully before you start taking this medicine. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or pharmacist. 

- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 

- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 

 

 

In this leaflet: 

1. What Imprida HCT is and what it is used for 

2. Before you take Imprida HCT 

3. How to take Imprida HCT 

4. Possible side effects 

5. How to store Imprida HCT 

6. Further information 

 

 

1. WHAT IMPRIDA HCT IS AND WHAT IT IS USED FOR 

 

Imprida HCT tablets contain three substances called amlodipine, valsartan and hydrochlorothiazide. 

All of these substances help to control high blood pressure. 

 Amlodipine belongs to a group of substances called “calcium channel blockers”. Amlodipine 

stops calcium from moving into the blood vessel wall, which stops the blood vessels from 

tightening. 

 Valsartan belongs to a group of substances called “angiotensin-II receptor antagonists”. 

Angiotensin II is produced by the body and makes the blood vessels tighten, thus increasing the 

blood pressure. Valsartan works by blocking the effect of angiotensin II. 

 Hydrochlorothiazide belongs to a group of substances called “thiazide diuretics”. 

Hydrochlorothiazide increases urine output, which also lowers blood pressure. 

As a result of all three mechanisms, the blood vessels relax and blood pressure is lowered. 

 

Imprida HCT is used to treat high blood pressure in adult patients who are already taking amlodipine, 

valsartan and hydrochlorothiazide and who may benefit from taking one tablet containing all three 

substances. 

 

 

2. BEFORE YOU TAKE IMPRIDA HCT 

 

Do not take Imprida HCT 

 if you are more than 3 months pregnant. (It is also better to avoid Imprida HCT in early 

pregnancy – see Pregnancy section). 

 if you are allergic (hypersensitive) to amlodipine, valsartan, hydrochlorothiazide, 

sulphonamide-derived medicines (medicines used to treat chest or urinary infections), or any of 

the other ingredients of Imprida HCT (see section 6, “What Imprida HCT contains”). 

If you think you may be allergic, do not take Imprida HCT and talk to your doctor. 

 if you have liver disease, destruction of the small bile ducts within the liver (biliary cirrhosis) 

leading to the build up of bile in the liver (cholestasis). 

 if you have severe kidney problems or if you are having dialysis. 

 if you are unable to produce urine (anuria). 

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 if the level of potassium or sodium in your blood is too low despite treatment. 

 if the level of calcium in your blood is too high despite treatment. 

 if you have gout (uric acid crystals in the joints). 

If any of the above applies to you, do not take Imprida HCT and talk to your doctor. 

 

Take special care with Imprida HCT 

 if you have a low level of potassium or magnesium in your blood (with or without symptoms 

such as muscle weakness, muscle spasms, abnormal heart rhythm). 

 if you have a low level of sodium in your blood (with or without symptoms such as tiredness, 

confusion, muscle twitching, convulsions). 

 if you have a high level of calcium in your blood (with or without symptoms such as nausea, 

vomiting, constipation, stomach pain, frequent urination, thirst, muscle weakness and 

twitching). 

 if you are taking medicines or substances that increase the amount of potassium in your blood. 

These include potassium supplements or salt substitutes containing potassium, potassium-

sparing medicines and heparin. It may be necessary to check the amount of potassium in your 

blood at regular intervals. 

 if you have kidney problems, have had a kidney transplant or if you had been told that you have 

a narrowing of your kidney arteries. 

 if you have liver problems. 

 if you have or have had heart failure or coronary artery disease, particularly if you are taking 
the maximum dose of Imprida HCT (10 mg/320 mg/25 mg) 

 if your doctor has told you that you have a narrowing of the valves in your heart (called “aortic 

or mitral stenosis”) or that the thickness of your heart muscle is abnormally increased (called 

“obstructive hypertrophic cardiomyopathy”). 

 if you suffer from aldosteronism. This is a disease in which the adrenal glands make too much 

of the hormone aldosterone If this applies to you, the use of Imprida HCT is not recommended. 

 if you suffer from a disease called systemic lupus erythematosus (also called “lupus” or 

“SLE”). 

 if you have diabetes (high level of sugar in your blood). 

 if you have high levels of cholesterol or triglycerides in your blood. 

 if you experience skin reactions such as rash after sun exposure. 

 if you had an allergic reaction to other high blood pressure medicines or diuretics (a type of 

medicine also known as “water tablets”), especially if you suffer from asthma and allergies 

 if you have been sick (vomiting or diarrhoea). 

 if you experience dizziness and/or fainting during treatment with Imprida HCT, tell your doctor 

as soon as possible. 

 if you experience a decrease in vision or eye pain. These could be symptoms of an increase of 

pressure in your eye and can happen within hours to a week of taking Imprida HCT. This can 

lead to permanent vision impairment, if not treated. 

If any of these apply to you, talk to your doctor. 

 

You must tell your doctor if you think that you are (or might become) pregnant. Imprida HCT is not 

recommended in early pregnancy and must not be taken if you are more than 3 months pregnant, as it 

may cause serious harm to your baby if used at this stage (see section “Pregnancy and breast-

feeding”). 

 

The use of Imprida HCT in children and adolescents under 18 years of age is not recommended. 

 

Imprida HCT and older people (age 65 years and older) 

Imprida HCT can be used by people aged 65 years and over at the same dose as for other adults and in 

the same way as they have already taken the three substances called amlodipine, valsartan and 

hydrochlorothiazide. Elderly patients, particularly those taking the maximum dose of Imprida HCT 

(10 mg/320 mg/25 mg), should have their blood pressure checked regularly. 

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Using other medicines 

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 

including medicines obtained without a prescription. Your doctor may need to change the dose or take 

other precautions. In some cases you may have to stop using one of the medicines. This is especially 

important if you are using any of the medicines listed below: 

 

Do not take together with: 

• lithium (a medicine used to treat some types of depression); 

• medicines or substances that increase the amount of potassium in your blood. These include 

potassium supplements or salt substitutes containing potassium, potassium-sparing medicines 

and heparin. 

Caution should be used with: 

• alcohol, sleeping pills and anaesthetics (medicines allowing patients to undergo surgery and 

other procedures); 

• amantadine (anti-Parkinson therapy, also used to treat or prevent certain illnesses caused by 

viruses); 

• anticholinergic agents (medicines used to treat a variety of disorders such as gastrointestinal 

cramps, urinary bladder spasm, asthma, motion sickness, muscular spasms, Parkinson's disease 

and as an aid to anaesthesia); 

• anticonvulsant medicines and mood-stabilising medicines used to treat epilepsy and bipolar 

disorder (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone); 

• cholestyramine, colestipol or other resins (substances used mainly to treat high levels of lipids 

in the blood); 

• simvastatin (a medicine used to control high cholesterol levels); 

• ciclosporin (a medicine used in transplantation to prevent organ rejection or for other 

conditions, e.g: rheumatoid arthritis or atopic dermatitis); 

• cytotoxic medicines (used to treat cancer), such as methotrexate or cyclophosphamide; 

• digoxin or other digitalis glycosides (medicines used to treat heart problems); 

• verapamil, diltiazem (heart medicines); 

• iodine contrast media (agents used for imaging examinations); 

• medicines for the treatment of diabetes (oral agents such as metformin or insulins); 

• medicines for the treatment of gout, such as allopurinol; 

• medicines that may increase blood sugar levels (beta blockers, diazoxide); 

• medicines that may induce “torsades de pointes” (irregular heart beat), such as antiarrhythmics 

(medicines used to treat heart problems) and some antipsychotics; 

• medicines that may reduce the amount of sodium in your blood, such as antidepressants, 

antipsychotics, antiepileptics; 

• medicines that may reduce the amount of potassium in your blood, such as diuretics (water 

tablets), corticosteroids, laxatives, amphotericin or penicillin G; 

• medicines to increase blood pressure such as adrenaline or noradrenaline; 

• medicines used for HIV/AIDS (e.g. ritonavir, indinavir, nelfinavir); 

• medicines used to treat fungal infections (e.g. ketoconazole, itraconazole); 

• medicines used for oesophageal ulceration and inflammation (carbenoxolone); 

• medicines used to relieve pain or inflammation, especially non-steroidal anti-inflammatory 

agents (NSAIDs), including selective cyclooxygenase-2 inhibitors (Cox-2 inhibitors); 

• muscle relaxants (medicines to relax the muscles which are used during operations); 

• nitroglycerin and other nitrates, or other substances called “vasodilators”; 

• other medicines to treat high blood pressure, including methyldopa; 

• rifampicin (used, for example, to treat tuberculosis); 

• St. John’s wort; 

• dantrolene (infusion for severe body temperature abnormalities); 

• vitamin D and calcium salts. 

 

Talk to your doctor before drinking alcohol. Alcohol may make your blood pressure fall too much 

and/or increase the possibility of dizziness or fainting. 

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Taking Imprida HCT with food and drink 

You can take Imprida HCT with or without food. Grapefruit and grapefruit juice should not be 

consumed by people who are taking Imprida HCT. This is because grapefruit and grapefruit juice can 

lead to an increase in the blood levels of the active substance amlodipine, which can cause an 

unpredictable increase in the blood pressure lowering effect of Imprida HCT. 

 

Pregnancy and breast-feeding 

Pregnancy 

You must tell your doctor if you think you are (or might become) pregnant. Your doctor will 

normally advise you to stop taking Imprida HCT before you become pregnant or as soon as you know 

you are pregnant and will advise you to take another medicine instead of Imprida HCT. Imprida HCT 

is not recommended in early pregnancy and must not be taken when more than 3 months pregnant, as 

it may cause serious harm to your baby if used after the third month of pregnancy. 

 

Breast-feeding 

Tell your doctor if you are breast-feeding or about to start breast-feeding. Imprida HCT is not 

recommended for mothers who are breast-feeding, and your doctor may choose another treatment for 

you if you wish to breast-feed, especially if your baby is a newborn, or was born prematurely. 

 

Ask your doctor or pharmacist for advice before taking any medicine. 

 

Driving and using machines 

As with many other medicines used to treat high blood pressure, this medicine may make you feel 

dizzy. If you experience this symptom, do not drive or use tools or machines. 

 

 

3. HOW TO TAKE IMPRIDA HCT 

 

Always take this medicine exactly as your doctor has told you. You should check with your doctor if 

you are not sure. This will help you get the best results and lower the risk of side effects. 

 

The usual dose of Imprida HCT is one tablet per day. 

 It is best to take the tablet at the same time each day. Morning is the best time. 

 Swallow the tablet whole with a glass of water. 

 You can take Imprida HCT with or without food. Do not take Imprida HCT with grapefruit or 

grapefruit juice. 

 

Depending on how you respond to the treatment, your doctor may suggest a higher or lower dose. 

 

If you take more Imprida HCT than you should 

If you have accidentally taken too many Imprida HCT tablets, talk to a doctor immediately.You may 

require medical attention. 

 

If you forget to take Imprida HCT 

If you forget to take a dose of this medicine, take it as soon as you remember and then take the next 

dose at its usual time. If it is almost time for your next dose you should simply take the next tablet at 

the usual time. Do not take a double dose (two tablets at once) to make up for a forgotten tablet. 

 

If you stop taking Imprida HCT 

Stopping your treatment with Imprida HCT may cause your disease to get worse. Do not stop taking 

your medecine unless your doctor tells you to. 

 

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Always take this medicine, even if you are feeling well 

People who have high blood pressure often do not notice any signs of the problem. Many feel normal. 

It is very important that you take this medicine exactly as your doctor tells you to get the best results 

and reduce the risk of side effects. Keep your appointments with the doctor even if you are feeling 

well. 

 

If you have any further questions on the use of this product ask your doctor or pharmacist. 

 

 

4. POSSIBLE SIDE EFFECTS 

 

Like all medicines, Imprida HCT can cause side effects, although not everybody gets them. 

These side effects may occur with certain frequencies, which are defined as follows: 

very common: affects more than 1 user in 10 

common: affects 1 to 10 users in 100 

uncommon: affects 1 to 10 users in 1,000 

rare: affects 1 to 10 users in 10,000 

very rare: affects less than 1 user in 10,000 

not known: frequency cannot be estimated from the available data 

 

Some side effects can be serious and need immediate medical attention: 

 

You should see your doctor immediately if you experience any of the following symptoms: 

Common 

 dizziness 

 low blood pressure (feeling of faintness, light-headedness, sudden loss of consciousness) 

 

Uncommon 

 severely decreased urine output (decreased kidney function) 

 

Rare 

 spontaneous bleeding 

 irregular heart beat 

 liver disorder 

 

Very rare 

 allergic reaction with symptoms such as rash, itching 

 angioedema: swelling of face or lips or tongue, difficulty of breathing 

 crushing/tight chest pain that gets worse or that does not go away 

 weakness, bruising, fever and frequent infections 

 stiffness 

 

Other possible side effects of Imprida HCT: 

Common 

 stomach discomfort after meal 

 tiredness 

 swelling 

 low level of potassium in the blood 

 headache 

 frequent urination 

 

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Uncommon 

 fast heart beat 

 spinning sensation 

 vision disorder 

 stomach discomfort 

 chest pain 

 increase of urea nitrogen, creatinine and uric acid in the blood 

 high level of calcium, fat or sodium in the blood 

 decrease of potassium in the blood 

 breath odour 

 diarrhoea 

 dry mouth 

 nausea 

 vomiting 

 abdominal pain 

 weight increase 

 loss of appetite 

 disturbed sense of taste 

 back pain 

 joint swelling 

 muscle cramps/weakness/pain 

 pain in extremity 

 inability to either stand or walk in a normal manner 

 weakness 

 abnormal coordination 

 dizziness on standing up or after exercising 

 lack of energy 

 sleep disturbances 

 tingling or numbness 

 neuropathy 

 sleepiness 

 sudden, temporary loss of consciousness 

 low blood pressure on standing up 

 impotence 

 cough 

 breathlessness 

 throat irritation 

 excessive sweating 

 itching 

 swelling, reddening and pain along a vein 

 skin reddening 

 trembling 

 

Not known 

 changes in blood tests for kidney function, increase of potassium in your blood, low level of red 

blood cells 

 

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Side effects reported with amlodipine or valsartan or hydrochlorothiazide alone, but not 

observed with Imprida HCT or observed in a higher frequency: 

 

Amlodipine 

Common 

 palpitations 

 abdominal pain 

 nausea 

 sleepiness 

 hot flushes 

 

Uncommon 

 ringing noise in ears 

 change of bowel habit 

 pain 

 weight decrease 

 joint pain 

 trembling 

 mood swings 

 urination disorders 

 urination at night 

 breast enlargement in men 

 runny nose 

 hair loss 

 skin eruption 

 purple skin patches 

 rash 

 skin discoloration 

 

Very rare 

 low level of white blood cells and blood platelets 

 irregular heart beat 

 heart attack 

 inflammation of the stomach lining or of the pancreas, gingival overgrowth, abnormal liver 

function test 

 liver disorder which can occur together with yellow skin and eyes, or dark-coloured urine 

 allergic reaction including swelling deeper in the skin and difficulty breathing 

 high level of sugar in the blood 

 increased muscle stiffness 

 skin reaction with skin reddening and peeling, blistering of lips, eyes or mouth 

 itchy rash 

 inflammation of blood vessels 

 

Not known 

 stiff limbs and trembling hands 

 

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Valsartan 

Not known 

 abnormal red blood cell test 

 low level of a certain type of white blood cell and blood platelet 

 increase of potassium in the blood 

 increase of creatinine in the blood 

 abnormal liver function test 

 allergic reaction including swelling deeper in the skin and difficulty breathing 

 muscle pain 

 severely decreased urine output 

 itching 

 rash 

 inflammation of blood vessels 

 

Hydrochlorothiazide 

Very common 

 low level of potassium in the blood 

 increase of lipids in the blood 

 

Common 

 high level of uric acid in the blood 

 low level of magnesium in the blood 

 low level of sodium in the blood 

 dizziness, fainting on standing up 

 reduced appetite 

 nausea and vomiting 

 itchy rash and other types of rash 

 inability to achieve or maintain erection 

 

Rare 

 low level of blood platelets (sometimes with bleeding or bruising underneath the skin) 

 sugar in the urine 

 high level of sugar in the blood 

 worsening of the diabetic metabolic state 

 sad mood (depression) 

 irregular heart beat 

 abdominal discomfort 

 constipation 

 liver disorders which can occur together with yellow skin and eyes, or dark-coloured urine 

(haemolytic anaemia) 

 increased sensitivity of skin to sun 

 purple skin patches 

 kidney disorders 

 

Very rare 

 fever, sore throat or mouth ulcers, more frequent infections (lack or low level of white blood 

cells) 

 pale skin, tiredness, breathlessness, dark-coloured urine (haemolytic anaemia, abnormal 

breakdown of red blood cells either in the blood vessels or elsewhere in the body) 

 confusion, tiredness, muscle twitching and spasm, rapid breathing (hypochloraemic alkalosis) 

 severe upper stomach ache (inflammation of the pancreas) 

 rash, itching, hives, difficulty breathing or swallowing, dizziness (hypersensitivity reactions) 

 difficulty breathing with fever, coughing, wheezing, breathlessness (respiratory distress, 

pulmonary oedema, pneumonitis) 

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 facial rash, joint pain, muscle disorder, fever (lupus erythematosus) 

 inflammation of blood vessels with symptoms such as rash, purplish-red spots, fever (vasculitis) 

 severe skin disease that causes rash, red skin, blistering of the lips, eyes or mouth, skin peeling, 

fever (toxic epidermal necrolysis) 

 

Not known 

 weakness, bruising and frequent infections (aplastic anaemia) 

 decrease in vision or pain in your eyes due to high pressure (possible signs of acute angle-

closure glaucoma) 

 breathlessness 

 severely decreased urine output (possible signs of renal disorder or renal failure) 

 severe skin disease that causes rash, red skin, blistering of the lips, eyes or mouth, skin peeling, 

fever (erythema multiforme) 

 muscle spasm 

 fever (pyrexia) 

 

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 

 

 

5. HOW TO STORE IMPRIDA HCT 

 

Keep out of the reach and sight of children. 

Do not use Imprida HCT after the expiry date which is stated on the carton and blister after EXP. The 

expiry date refers to the last day of that month. 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

Do not use any Imprida HCT pack that is damaged or shows signs of tampering. 

 

 

6. FURTHER INFORMATION 

 

What Imprida HCT contains 

 The active substances of Imprida HCT are amlodipine (as amlodipine besylate), valsartan and 

hydrochlorothiazide. 

 

 Imprida HCT 10 mg/160 mg/12.5 mg film-coated tablets: Each film-coated tablet contains 

10 mg amlodipine (as amlodipine besylate),160 mg valsartan, and 12.5 mg hydrochlorothiazide. 

The other ingredients are cellulose microcrystalline; crospovidone; silica, colloidal anhydrous; 

magnesium stearate; hypromellose, macrogol 4000, talc, titanium dioxide (E171), yellow iron 

oxide (E172), red iron oxide (E172). 

 

What Imprida HCT looks like and contents of the pack 

 Imprida HCT 10 mg/160 mg/12.5 mg film-coated tablets are pale yellow, oval tablets with 

“NVR” on one side and “VDL” on the other side. 

 

Imprida HCT is available in packs containing 14, 28, 30, 56, 90, 98 or 280 film-coated tablets, in 

multipacks of 280 tablets (comprising 4 cartons, each containing 70 tablets, or 20 cartons, each 

containing 14 tablets), and in hospital packs containing 56, 98 or 280 tablets in single unit blisters. 

Not all pack sizes may be available in your country. 

 

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Marketing Authorisation Holder 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

България 

Novartis Pharma Services Inc. 

Тел.: +359 2 976 98 28 

 

Magyarország 

Novartis Hungária Kft. Pharma 

Tel.: +36 1 457 65 00 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2298 3217 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 26 37 82 111 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 

Eesti 

Novartis Pharma Services Inc. 

Tel: +372 66 30 810 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

España 

Lacer, S.A. 

Tel: +34 93 446 53 00 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

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Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

Novartis Pharma Services Inc. 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

Lietuva 

Novartis Pharma Services Inc. 

Tel: +370 5 269 16 50 

 

 

 

This leaflet was last approved in 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

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PACKAGE LEAFLET: INFORMATION FOR THE USER 

 

Imprida HCT 5 mg/160 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

Read all of this leaflet carefully before you start taking this medicine. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or pharmacist. 

- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 

- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 

 

 

In this leaflet: 

1. What Imprida HCT is and what it is used for 

2. Before you take Imprida HCT 

3. How to take Imprida HCT 

4. Possible side effects 

5. How to store Imprida HCT 

6. Further information 

 

 

1. WHAT IMPRIDA HCT IS AND WHAT IT IS USED FOR 

 

Imprida HCT tablets contain three substances called amlodipine, valsartan and hydrochlorothiazide. 

All of these substances help to control high blood pressure. 

 Amlodipine belongs to a group of substances called “calcium channel blockers”. Amlodipine 

stops calcium from moving into the blood vessel wall, which stops the blood vessels from 

tightening. 

 Valsartan belongs to a group of substances called “angiotensin-II receptor antagonists”. 

Angiotensin II is produced by the body and makes the blood vessels tighten, thus increasing the 

blood pressure. Valsartan works by blocking the effect of angiotensin II. 

 Hydrochlorothiazide belongs to a group of substances called “thiazide diuretics”. 

Hydrochlorothiazide increases urine output, which also lowers blood pressure. 

As a result of all three mechanisms, the blood vessels relax and blood pressure is lowered. 

 

Imprida HCT is used to treat high blood pressure in adult patients who are already taking amlodipine, 

valsartan and hydrochlorothiazide and who may benefit from taking one tablet containing all three 

substances. 

 

 

2. BEFORE YOU TAKE IMPRIDA HCT 

 

Do not take Imprida HCT 

 if you are more than 3 months pregnant. (It is also better to avoid Imprida HCT in early 

pregnancy – see Pregnancy section). 

 if you are allergic (hypersensitive) to amlodipine, valsartan, hydrochlorothiazide, 

sulphonamide-derived medicines (medicines used to treat chest or urinary infections), or any of 

the other ingredients of Imprida HCT (see section 6, “What Imprida HCT contains”). 

If you think you may be allergic, do not take Imprida HCT and talk to your doctor. 

 if you have liver disease, destruction of the small bile ducts within the liver (biliary cirrhosis) 

leading to the build up of bile in the liver (cholestasis). 

 if you have severe kidney problems or if you are having dialysis. 

 if you are unable to produce urine (anuria). 

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 if the level of potassium or sodium in your blood is too low despite treatment. 

 if the level of calcium in your blood is too high despite treatment. 

 if you have gout (uric acid crystals in the joints). 

If any of the above applies to you, do not take Imprida HCT and talk to your doctor. 

 

Take special care with Imprida HCT 

 if you have a low level of potassium or magnesium in your blood (with or without symptoms 

such as muscle weakness, muscle spasms, abnormal heart rhythm). 

 if you have a low level of sodium in your blood (with or without symptoms such as tiredness, 

confusion, muscle twitching, convulsions). 

 if you have a high level of calcium in your blood (with or without symptoms such as nausea, 

vomiting, constipation, stomach pain, frequent urination, thirst, muscle weakness and 

twitching). 

 if you are taking medicines or substances that increase the amount of potassium in your blood. 

These include potassium supplements or salt substitutes containing potassium, potassium-

sparing medicines and heparin. It may be necessary to check the amount of potassium in your 

blood at regular intervals. 

 if you have kidney problems, have had a kidney transplant or if you had been told that you have 

a narrowing of your kidney arteries. 

 if you have liver problems. 

 if you have or have had heart failure or coronary artery disease, particularly if you are taking 
the maximum dose of Imprida HCT (10 mg/320 mg/25 mg) 

 if your doctor has told you that you have a narrowing of the valves in your heart (called “aortic 

or mitral stenosis”) or that the thickness of your heart muscle is abnormally increased (called 

“obstructive hypertrophic cardiomyopathy”). 

 if you suffer from aldosteronism. This is a disease in which the adrenal glands make too much 

of the hormone aldosterone If this applies to you, the use of Imprida HCT is not recommended. 

 if you suffer from a disease called systemic lupus erythematosus (also called “lupus” or 

“SLE”). 

 if you have diabetes (high level of sugar in your blood). 

 if you have high levels of cholesterol or triglycerides in your blood. 

 if you experience skin reactions such as rash after sun exposure. 

 if you had an allergic reaction to other high blood pressure medicines or diuretics (a type of 

medicine also known as “water tablets”), especially if you suffer from asthma and allergies 

 if you have been sick (vomiting or diarrhoea). 

 if you experience dizziness and/or fainting during treatment with Imprida HCT, tell your doctor 

as soon as possible. 

 if you experience a decrease in vision or eye pain. These could be symptoms of an increase of 

pressure in your eye and can happen within hours to a week of taking Imprida HCT. This can 

lead to permanent vision impairment, if not treated. 

If any of these apply to you, talk to your doctor. 

 

You must tell your doctor if you think that you are (or might become) pregnant. Imprida HCT is not 

recommended in early pregnancy and must not be taken if you are more than 3 months pregnant, as it 

may cause serious harm to your baby if used at this stage (see section “Pregnancy and breast-

feeding”). 

 

The use of Imprida HCT in children and adolescents under 18 years of age is not recommended. 

 

Imprida HCT and older people (age 65 years and older) 

Imprida HCT can be used by people aged 65 years and over at the same dose as for other adults and in 

the same way as they have already taken the three substances called amlodipine, valsartan and 

hydrochlorothiazide. Elderly patients, particularly those taking the maximum dose of Imprida HCT 

(10 mg/320 mg/25 mg), should have their blood pressure checked regularly. 

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Using other medicines 

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 

including medicines obtained without a prescription. Your doctor may need to change the dose or take 

other precautions. In some cases you may have to stop using one of the medicines. This is especially 

important if you are using any of the medicines listed below: 

 

Do not take together with: 

• lithium (a medicine used to treat some types of depression); 

• medicines or substances that increase the amount of potassium in your blood. These include 

potassium supplements or salt substitutes containing potassium, potassium-sparing medicines 

and heparin. 

Caution should be used with: 

• alcohol, sleeping pills and anaesthetics (medicines allowing patients to undergo surgery and 

other procedures); 

• amantadine (anti-Parkinson therapy, also used to treat or prevent certain illnesses caused by 

viruses); 

• anticholinergic agents (medicines used to treat a variety of disorders such as gastrointestinal 

cramps, urinary bladder spasm, asthma, motion sickness, muscular spasms, Parkinson's disease 

and as an aid to anaesthesia); 

• anticonvulsant medicines and mood-stabilising medicines used to treat epilepsy and bipolar 

disorder (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone); 

• cholestyramine, colestipol or other resins (substances used mainly to treat high levels of lipids 

in the blood); 

• simvastatin (a medicine used to control high cholesterol levels); 

• ciclosporin (a medicine used in transplantation to prevent organ rejection or for other 

conditions, e.g: rheumatoid arthritis or atopic dermatitis); 

• cytotoxic medicines (used to treat cancer), such as methotrexate or cyclophosphamide; 

• digoxin or other digitalis glycosides (medicines used to treat heart problems); 

• verapamil, diltiazem (heart medicines); 

• iodine contrast media (agents used for imaging examinations); 

• medicines for the treatment of diabetes (oral agents such as metformin or insulins); 

• medicines for the treatment of gout, such as allopurinol; 

• medicines that may increase blood sugar levels (beta blockers, diazoxide); 

• medicines that may induce “torsades de pointes” (irregular heart beat), such as antiarrhythmics 

(medicines used to treat heart problems) and some antipsychotics; 

• medicines that may reduce the amount of sodium in your blood, such as antidepressants, 

antipsychotics, antiepileptics; 

• medicines that may reduce the amount of potassium in your blood, such as diuretics (water 

tablets), corticosteroids, laxatives, amphotericin or penicillin G; 

• medicines to increase blood pressure such as adrenaline or noradrenaline; 

• medicines used for HIV/AIDS (e.g. ritonavir, indinavir, nelfinavir); 

• medicines used to treat fungal infections (e.g. ketoconazole, itraconazole); 

• medicines used for oesophageal ulceration and inflammation (carbenoxolone); 

• medicines used to relieve pain or inflammation, especially non-steroidal anti-inflammatory 

agents (NSAIDs), including selective cyclooxygenase-2 inhibitors (Cox-2 inhibitors); 

• muscle relaxants (medicines to relax the muscles which are used during operations); 

• nitroglycerin and other nitrates, or other substances called “vasodilators”; 

• other medicines to treat high blood pressure, including methyldopa; 

• rifampicin (used, for example, to treat tuberculosis); 

• St. John’s wort; 

• dantrolene (infusion for severe body temperature abnormalities); 

• vitamin D and calcium salts. 

 

Talk to your doctor before drinking alcohol. Alcohol may make your blood pressure fall too much 

and/or increase the possibility of dizziness or fainting. 

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Taking Imprida HCT with food and drink 

You can take Imprida HCT with or without food. Grapefruit and grapefruit juice should not be 

consumed by people who are taking Imprida HCT. This is because grapefruit and grapefruit juice can 

lead to an increase in the blood levels of the active substance amlodipine, which can cause an 

unpredictable increase in the blood pressure lowering effect of Imprida HCT. 

 

Pregnancy and breast-feeding 

Pregnancy 

You must tell your doctor if you think you are (or might become) pregnant. Your doctor will 

normally advise you to stop taking Imprida HCT before you become pregnant or as soon as you know 

you are pregnant and will advise you to take another medicine instead of Imprida HCT. Imprida HCT 

is not recommended in early pregnancy and must not be taken when more than 3 months pregnant, as 

it may cause serious harm to your baby if used after the third month of pregnancy. 

 

Breast-feeding 

Tell your doctor if you are breast-feeding or about to start breast-feeding. Imprida HCT is not 

recommended for mothers who are breast-feeding, and your doctor may choose another treatment for 

you if you wish to breast-feed, especially if your baby is a newborn, or was born prematurely. 

 

Ask your doctor or pharmacist for advice before taking any medicine. 

 

Driving and using machines 

As with many other medicines used to treat high blood pressure, this medicine may make you feel 

dizzy. If you experience this symptom, do not drive or use tools or machines. 

 

 

3. HOW TO TAKE IMPRIDA HCT 

 

Always take this medicine exactly as your doctor has told you. You should check with your doctor if 

you are not sure. This will help you get the best results and lower the risk of side effects. 

 

The usual dose of Imprida HCT is one tablet per day. 

 It is best to take the tablet at the same time each day. Morning is the best time. 

 Swallow the tablet whole with a glass of water. 

 You can take Imprida HCT with or without food. Do not take Imprida HCT with grapefruit or 

grapefruit juice. 

 

Depending on how you respond to the treatment, your doctor may suggest a higher or lower dose. 

 

If you take more Imprida HCT than you should 

If you have accidentally taken too many Imprida HCT tablets, talk to a doctor immediately.You may 

require medical attention. 

 

If you forget to take Imprida HCT 

If you forget to take a dose of this medicine, take it as soon as you remember and then take the next 

dose at its usual time. If it is almost time for your next dose you should simply take the next tablet at 

the usual time. Do not take a double dose (two tablets at once) to make up for a forgotten tablet. 

 

If you stop taking Imprida HCT 

Stopping your treatment with Imprida HCT may cause your disease to get worse. Do not stop taking 

your medecine unless your doctor tells you to. 

 

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Always take this medicine, even if you are feeling well 

People who have high blood pressure often do not notice any signs of the problem. Many feel normal. 

It is very important that you take this medicine exactly as your doctor tells you to get the best results 

and reduce the risk of side effects. Keep your appointments with the doctor even if you are feeling 

well. 

 

If you have any further questions on the use of this product ask your doctor or pharmacist. 

 

 

4. POSSIBLE SIDE EFFECTS 

 

Like all medicines, Imprida HCT can cause side effects, although not everybody gets them. 

These side effects may occur with certain frequencies, which are defined as follows: 

very common: affects more than 1 user in 10 

common: affects 1 to 10 users in 100 

uncommon: affects 1 to 10 users in 1,000 

rare: affects 1 to 10 users in 10,000 

very rare: affects less than 1 user in 10,000 

not known: frequency cannot be estimated from the available data 

 

Some side effects can be serious and need immediate medical attention: 

 

You should see your doctor immediately if you experience any of the following symptoms: 

Common 

 dizziness 

 low blood pressure (feeling of faintness, light-headedness, sudden loss of consciousness) 

 

Uncommon 

 severely decreased urine output (decreased kidney function) 

 

Rare 

 spontaneous bleeding 

 irregular heart beat 

 liver disorder 

 

Very rare 

 allergic reaction with symptoms such as rash, itching 

 angioedema: swelling of face or lips or tongue, difficulty of breathing 

 crushing/tight chest pain that gets worse or that does not go away 

 weakness, bruising, fever and frequent infections 

 stiffness 

 

Other possible side effects of Imprida HCT: 

Common 

 stomach discomfort after meal 

 tiredness 

 swelling 

 low level of potassium in the blood 

 headache 

 frequent urination 

 

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Uncommon 

 fast heart beat 

 spinning sensation 

 vision disorder 

 stomach discomfort 

 chest pain 

 increase of urea nitrogen, creatinine and uric acid in the blood 

 high level of calcium, fat or sodium in the blood 

 decrease of potassium in the blood 

 breath odour 

 diarrhoea 

 dry mouth 

 nausea 

 vomiting 

 abdominal pain 

 weight increase 

 loss of appetite 

 disturbed sense of taste 

 back pain 

 joint swelling 

 muscle cramps/weakness/pain 

 pain in extremity 

 inability to either stand or walk in a normal manner 

 weakness 

 abnormal coordination 

 dizziness on standing up or after exercising 

 lack of energy 

 sleep disturbances 

 tingling or numbness 

 neuropathy 

 sleepiness 

 sudden, temporary loss of consciousness 

 low blood pressure on standing up 

 impotence 

 cough 

 breathlessness 

 throat irritation 

 excessive sweating 

 itching 

 swelling, reddening and pain along a vein 

 skin reddening 

 trembling 

 

Not known 

 changes in blood tests for kidney function, increase of potassium in your blood, low level of red 

blood cells 

 

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Side effects reported with amlodipine or valsartan or hydrochlorothiazide alone, but not 

observed with Imprida HCT or observed in a higher frequency: 

 

Amlodipine 

Common 

 palpitations 

 abdominal pain 

 nausea 

 sleepiness 

 hot flushes 

 

Uncommon 

 ringing noise in ears 

 change of bowel habit 

 pain 

 weight decrease 

 joint pain 

 trembling 

 mood swings 

 urination disorders 

 urination at night 

 breast enlargement in men 

 runny nose 

 hair loss 

 skin eruption 

 purple skin patches 

 rash 

 skin discoloration 

 

Very rare 

 low level of white blood cells and blood platelets 

 irregular heart beat 

 heart attack 

 inflammation of the stomach lining or of the pancreas, gingival overgrowth, abnormal liver 

function test 

 liver disorder which can occur together with yellow skin and eyes, or dark-coloured urine 

 allergic reaction including swelling deeper in the skin and difficulty breathing 

 high level of sugar in the blood 

 increased muscle stiffness 

 skin reaction with skin reddening and peeling, blistering of lips, eyes or mouth 

 itchy rash 

 inflammation of blood vessels 

 

Not known 

 stiff limbs and trembling hands 

 

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Valsartan 

Not known 

 abnormal red blood cell test 

 low level of a certain type of white blood cell and blood platelet 

 increase of potassium in the blood 

 increase of creatinine in the blood 

 abnormal liver function test 

 allergic reaction including swelling deeper in the skin and difficulty breathing 

 muscle pain 

 severely decreased urine output 

 itching 

 rash 

 inflammation of blood vessels 

 

Hydrochlorothiazide 

Very common 

 low level of potassium in the blood 

 increase of lipids in the blood 

 

Common 

 high level of uric acid in the blood 

 low level of magnesium in the blood 

 low level of sodium in the blood 

 dizziness, fainting on standing up 

 reduced appetite 

 nausea and vomiting 

 itchy rash and other types of rash 

 inability to achieve or maintain erection 

 

Rare 

 low level of blood platelets (sometimes with bleeding or bruising underneath the skin) 

 sugar in the urine 

 high level of sugar in the blood 

 worsening of the diabetic metabolic state 

 sad mood (depression) 

 irregular heart beat 

 abdominal discomfort 

 constipation 

 liver disorders which can occur together with yellow skin and eyes, or dark-coloured urine 

(haemolytic anaemia) 

 increased sensitivity of skin to sun 

 purple skin patches 

 kidney disorders 

 

Very rare 

 fever, sore throat or mouth ulcers, more frequent infections (lack or low level of white blood 

cells) 

 pale skin, tiredness, breathlessness, dark-coloured urine (haemolytic anaemia, abnormal 

breakdown of red blood cells either in the blood vessels or elsewhere in the body) 

 confusion, tiredness, muscle twitching and spasm, rapid breathing (hypochloraemic alkalosis) 

 severe upper stomach ache (inflammation of the pancreas) 

 rash, itching, hives, difficulty breathing or swallowing, dizziness (hypersensitivity reactions) 

 difficulty breathing with fever, coughing, wheezing, breathlessness (respiratory distress, 

pulmonary oedema, pneumonitis) 

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 facial rash, joint pain, muscle disorder, fever (lupus erythematosus) 

 inflammation of blood vessels with symptoms such as rash, purplish-red spots, fever (vasculitis) 

 severe skin disease that causes rash, red skin, blistering of the lips, eyes or mouth, skin peeling, 

fever (toxic epidermal necrolysis) 

 

Not known 

 weakness, bruising and frequent infections (aplastic anaemia) 

 decrease in vision or pain in your eyes due to high pressure (possible signs of acute angle-

closure glaucoma) 

 breathlessness 

 severely decreased urine output (possible signs of renal disorder or renal failure) 

 severe skin disease that causes rash, red skin, blistering of the lips, eyes or mouth, skin peeling, 

fever (erythema multiforme) 

 muscle spasm 

 fever (pyrexia) 

 

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 

 

 

5. HOW TO STORE IMPRIDA HCT 

 

Keep out of the reach and sight of children. 

Do not use Imprida HCT after the expiry date which is stated on the carton and blister after EXP. The 

expiry date refers to the last day of that month. 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

Do not use any Imprida HCT pack that is damaged or shows signs of tampering. 

 

 

6. FURTHER INFORMATION 

 

What Imprida HCT contains 

 The active substances of Imprida HCT are amlodipine (as amlodipine besylate), valsartan and 

hydrochlorothiazide. 

 

 Imprida HCT 5 mg/160 mg/25 mg film-coated tablets: Each film-coated tablet contains 5 mg 

amlodipine (as amlodipine besylate), 160 mg valsartan and 25 mg hydrochlorothiazide. The 

other ingredients are cellulose microcrystalline; crospovidone; silica, colloidal anhydrous, 

magnesium stearate, hypromellose, macrogol 4000, talc, titanium dioxide (E171), yellow iron 

oxide (E172). 

 

What Imprida HCT looks like and contents of the pack 

 Imprida HCT 5 mg/160 mg/25 mg film-coated tablets are yellow, oval tablets with “NVR” on 

one side and “VEL” on the other side. 

 

Imprida HCT is available in packs containing 14, 28, 30, 56, 90, 98 or 280 film-coated tablets, in 

multipacks of 280 tablets (comprising 4 cartons, each containing 70 tablets, or 20 cartons, each 

containing 14 tablets), and in hospital packs containing 56, 98 or 280 tablets in single unit blisters. 

Not all pack sizes may be available in your country. 

 

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Marketing Authorisation Holder 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

България 

Novartis Pharma Services Inc. 

Тел.: +359 2 976 98 28 

 

Magyarország 

Novartis Hungária Kft. Pharma 

Tel.: +36 1 457 65 00 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2298 3217 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 26 37 82 111 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 

Eesti 

Novartis Pharma Services Inc. 

Tel: +372 66 30 810 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

España 

Lacer, S.A. 

Tel: +34 93 446 53 00 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

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Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

Novartis Pharma Services Inc. 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

Lietuva 

Novartis Pharma Services Inc. 

Tel: +370 5 269 16 50 

 

 

 

This leaflet was last approved in 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

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PACKAGE LEAFLET: INFORMATION FOR THE USER 

 

Imprida HCT 10 mg/160 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

Read all of this leaflet carefully before you start taking this medicine. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or pharmacist. 

- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 

- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 

 

 

In this leaflet: 

1. What Imprida HCT is and what it is used for 

2. Before you take Imprida HCT 

3. How to take Imprida HCT 

4. Possible side effects 

5. How to store Imprida HCT 

6. Further information 

 

 

1. WHAT IMPRIDA HCT IS AND WHAT IT IS USED FOR 

 

Imprida HCT tablets contain three substances called amlodipine, valsartan and hydrochlorothiazide. 

All of these substances help to control high blood pressure. 

 Amlodipine belongs to a group of substances called “calcium channel blockers”. Amlodipine 

stops calcium from moving into the blood vessel wall, which stops the blood vessels from 

tightening. 

 Valsartan belongs to a group of substances called “angiotensin-II receptor antagonists”. 

Angiotensin II is produced by the body and makes the blood vessels tighten, thus increasing the 

blood pressure. Valsartan works by blocking the effect of angiotensin II. 

 Hydrochlorothiazide belongs to a group of substances called “thiazide diuretics”. 

Hydrochlorothiazide increases urine output, which also lowers blood pressure. 

As a result of all three mechanisms, the blood vessels relax and blood pressure is lowered. 

 

Imprida HCT is used to treat high blood pressure in adult patients who are already taking amlodipine, 

valsartan and hydrochlorothiazide and who may benefit from taking one tablet containing all three 

substances. 

 

 

2. BEFORE YOU TAKE IMPRIDA HCT 

 

Do not take Imprida HCT 

 if you are more than 3 months pregnant. (It is also better to avoid Imprida HCT in early 

pregnancy – see Pregnancy section). 

 if you are allergic (hypersensitive) to amlodipine, valsartan, hydrochlorothiazide, 

sulphonamide-derived medicines (medicines used to treat chest or urinary infections), or any of 

the other ingredients of Imprida HCT (see section 6, “What Imprida HCT contains”). 

If you think you may be allergic, do not take Imprida HCT and talk to your doctor. 

 if you have liver disease, destruction of the small bile ducts within the liver (biliary cirrhosis) 

leading to the build up of bile in the liver (cholestasis). 

 if you have severe kidney problems or if you are having dialysis. 

 if you are unable to produce urine (anuria). 

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 if the level of potassium or sodium in your blood is too low despite treatment. 

 if the level of calcium in your blood is too high despite treatment. 

 if you have gout (uric acid crystals in the joints). 

If any of the above applies to you, do not take Imprida HCT and talk to your doctor. 

 

Take special care with Imprida HCT 

 if you have a low level of potassium or magnesium in your blood (with or without symptoms 

such as muscle weakness, muscle spasms, abnormal heart rhythm). 

 if you have a low level of sodium in your blood (with or without symptoms such as tiredness, 

confusion, muscle twitching, convulsions). 

 if you have a high level of calcium in your blood (with or without symptoms such as nausea, 

vomiting, constipation, stomach pain, frequent urination, thirst, muscle weakness and 

twitching). 

 if you are taking medicines or substances that increase the amount of potassium in your blood. 

These include potassium supplements or salt substitutes containing potassium, potassium-

sparing medicines and heparin. It may be necessary to check the amount of potassium in your 

blood at regular intervals. 

 if you have kidney problems, have had a kidney transplant or if you had been told that you have 

a narrowing of your kidney arteries. 

 if you have liver problems. 

 if you have or have had heart failure or coronary artery disease, particularly if you are taking 
the maximum dose of Imprida HCT (10 mg/320 mg/25 mg) 

 if your doctor has told you that you have a narrowing of the valves in your heart (called “aortic 

or mitral stenosis”) or that the thickness of your heart muscle is abnormally increased (called 

“obstructive hypertrophic cardiomyopathy”). 

 if you suffer from aldosteronism. This is a disease in which the adrenal glands make too much 

of the hormone aldosterone If this applies to you, the use of Imprida HCT is not recommended. 

 if you suffer from a disease called systemic lupus erythematosus (also called “lupus” or 

“SLE”). 

 if you have diabetes (high level of sugar in your blood). 

 if you have high levels of cholesterol or triglycerides in your blood. 

 if you experience skin reactions such as rash after sun exposure. 

 if you had an allergic reaction to other high blood pressure medicines or diuretics (a type of 

medicine also known as “water tablets”), especially if you suffer from asthma and allergies 

 if you have been sick (vomiting or diarrhoea). 

 if you experience dizziness and/or fainting during treatment with Imprida HCT, tell your doctor 

as soon as possible. 

 if you experience a decrease in vision or eye pain. These could be symptoms of an increase of 

pressure in your eye and can happen within hours to a week of taking Imprida HCT. This can 

lead to permanent vision impairment, if not treated. 

If any of these apply to you, talk to your doctor. 

 

You must tell your doctor if you think that you are (or might become) pregnant. Imprida HCT is not 

recommended in early pregnancy and must not be taken if you are more than 3 months pregnant, as it 

may cause serious harm to your baby if used at this stage (see section “Pregnancy and breast-

feeding”). 

 

The use of Imprida HCT in children and adolescents under 18 years of age is not recommended. 

 

Imprida HCT and older people (age 65 years and older) 

Imprida HCT can be used by people aged 65 years and over at the same dose as for other adults and in 

the same way as they have already taken the three substances called amlodipine, valsartan and 

hydrochlorothiazide. Elderly patients, particularly those taking the maximum dose of Imprida HCT 

(10 mg/320 mg/25 mg), should have their blood pressure checked regularly. 

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Using other medicines 

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 

including medicines obtained without a prescription. Your doctor may need to change the dose or take 

other precautions. In some cases you may have to stop using one of the medicines. This is especially 

important if you are using any of the medicines listed below: 

 

Do not take together with: 

• lithium (a medicine used to treat some types of depression); 

• medicines or substances that increase the amount of potassium in your blood. These include 

potassium supplements or salt substitutes containing potassium, potassium-sparing medicines 

and heparin. 

Caution should be used with: 

• alcohol, sleeping pills and anaesthetics (medicines allowing patients to undergo surgery and 

other procedures); 

• amantadine (anti-Parkinson therapy, also used to treat or prevent certain illnesses caused by 

viruses); 

• anticholinergic agents (medicines used to treat a variety of disorders such as gastrointestinal 

cramps, urinary bladder spasm, asthma, motion sickness, muscular spasms, Parkinson's disease 

and as an aid to anaesthesia); 

• anticonvulsant medicines and mood-stabilising medicines used to treat epilepsy and bipolar 

disorder (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone); 

• cholestyramine, colestipol or other resins (substances used mainly to treat high levels of lipids 

in the blood); 

• simvastatin (a medicine used to control high cholesterol levels); 

• ciclosporin (a medicine used in transplantation to prevent organ rejection or for other 

conditions, e.g: rheumatoid arthritis or atopic dermatitis); 

• cytotoxic medicines (used to treat cancer), such as methotrexate or cyclophosphamide; 

• digoxin or other digitalis glycosides (medicines used to treat heart problems); 

• verapamil, diltiazem (heart medicines); 

• iodine contrast media (agents used for imaging examinations); 

• medicines for the treatment of diabetes (oral agents such as metformin or insulins); 

• medicines for the treatment of gout, such as allopurinol; 

• medicines that may increase blood sugar levels (beta blockers, diazoxide); 

• medicines that may induce “torsades de pointes” (irregular heart beat), such as antiarrhythmics 

(medicines used to treat heart problems) and some antipsychotics; 

• medicines that may reduce the amount of sodium in your blood, such as antidepressants, 

antipsychotics, antiepileptics; 

• medicines that may reduce the amount of potassium in your blood, such as diuretics (water 

tablets), corticosteroids, laxatives, amphotericin or penicillin G; 

• medicines to increase blood pressure such as adrenaline or noradrenaline; 

• medicines used for HIV/AIDS (e.g. ritonavir, indinavir, nelfinavir); 

• medicines used to treat fungal infections (e.g. ketoconazole, itraconazole); 

• medicines used for oesophageal ulceration and inflammation (carbenoxolone); 

• medicines used to relieve pain or inflammation, especially non-steroidal anti-inflammatory 

agents (NSAIDs), including selective cyclooxygenase-2 inhibitors (Cox-2 inhibitors); 

• muscle relaxants (medicines to relax the muscles which are used during operations); 

• nitroglycerin and other nitrates, or other substances called “vasodilators”; 

• other medicines to treat high blood pressure, including methyldopa; 

• rifampicin (used, for example, to treat tuberculosis); 

• St. John’s wort; 

• dantrolene (infusion for severe body temperature abnormalities); 

• vitamin D and calcium salts. 

 

Talk to your doctor before drinking alcohol. Alcohol may make your blood pressure fall too much 

and/or increase the possibility of dizziness or fainting. 

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Taking Imprida HCT with food and drink 

You can take Imprida HCT with or without food. Grapefruit and grapefruit juice should not be 

consumed by people who are taking Imprida HCT. This is because grapefruit and grapefruit juice can 

lead to an increase in the blood levels of the active substance amlodipine, which can cause an 

unpredictable increase in the blood pressure lowering effect of Imprida HCT. 

 

Pregnancy and breast-feeding 

Pregnancy 

You must tell your doctor if you think you are (or might become) pregnant. Your doctor will 

normally advise you to stop taking Imprida HCT before you become pregnant or as soon as you know 

you are pregnant and will advise you to take another medicine instead of Imprida HCT. Imprida HCT 

is not recommended in early pregnancy and must not be taken when more than 3 months pregnant, as 

it may cause serious harm to your baby if used after the third month of pregnancy. 

 

Breast-feeding 

Tell your doctor if you are breast-feeding or about to start breast-feeding. Imprida HCT is not 

recommended for mothers who are breast-feeding, and your doctor may choose another treatment for 

you if you wish to breast-feed, especially if your baby is a newborn, or was born prematurely. 

 

Ask your doctor or pharmacist for advice before taking any medicine. 

 

Driving and using machines 

As with many other medicines used to treat high blood pressure, this medicine may make you feel 

dizzy. If you experience this symptom, do not drive or use tools or machines. 

 

 

3. HOW TO TAKE IMPRIDA HCT 

 

Always take this medicine exactly as your doctor has told you. You should check with your doctor if 

you are not sure. This will help you get the best results and lower the risk of side effects. 

 

The usual dose of Imprida HCT is one tablet per day. 

 It is best to take the tablet at the same time each day. Morning is the best time. 

 Swallow the tablet whole with a glass of water. 

 You can take Imprida HCT with or without food. Do not take Imprida HCT with grapefruit or 

grapefruit juice. 

 

Depending on how you respond to the treatment, your doctor may suggest a higher or lower dose. 

 

If you take more Imprida HCT than you should 

If you have accidentally taken too many Imprida HCT tablets, talk to a doctor immediately.You may 

require medical attention. 

 

If you forget to take Imprida HCT 

If you forget to take a dose of this medicine, take it as soon as you remember and then take the next 

dose at its usual time. If it is almost time for your next dose you should simply take the next tablet at 

the usual time. Do not take a double dose (two tablets at once) to make up for a forgotten tablet. 

 

If you stop taking Imprida HCT 

Stopping your treatment with Imprida HCT may cause your disease to get worse. Do not stop taking 

your medecine unless your doctor tells you to. 

 

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Always take this medicine, even if you are feeling well 

People who have high blood pressure often do not notice any signs of the problem. Many feel normal. 

It is very important that you take this medicine exactly as your doctor tells you to get the best results 

and reduce the risk of side effects. Keep your appointments with the doctor even if you are feeling 

well. 

 

If you have any further questions on the use of this product ask your doctor or pharmacist. 

 

 

4. POSSIBLE SIDE EFFECTS 

 

Like all medicines, Imprida HCT can cause side effects, although not everybody gets them. 

These side effects may occur with certain frequencies, which are defined as follows: 

very common: affects more than 1 user in 10 

common: affects 1 to 10 users in 100 

uncommon: affects 1 to 10 users in 1,000 

rare: affects 1 to 10 users in 10,000 

very rare: affects less than 1 user in 10,000 

not known: frequency cannot be estimated from the available data 

 

Some side effects can be serious and need immediate medical attention: 

 

You should see your doctor immediately if you experience any of the following symptoms: 

Common 

 dizziness 

 low blood pressure (feeling of faintness, light-headedness, sudden loss of consciousness) 

 

Uncommon 

 severely decreased urine output (decreased kidney function) 

 

Rare 

 spontaneous bleeding 

 irregular heart beat 

 liver disorder 

 

Very rare 

 allergic reaction with symptoms such as rash, itching 

 angioedema: swelling of face or lips or tongue, difficulty of breathing 

 crushing/tight chest pain that gets worse or that does not go away 

 weakness, bruising, fever and frequent infections 

 stiffness 

 

Other possible side effects of Imprida HCT: 

Common 

 stomach discomfort after meal 

 tiredness 

 swelling 

 low level of potassium in the blood 

 headache 

 frequent urination 

 

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Uncommon 

 fast heart beat 

 spinning sensation 

 vision disorder 

 stomach discomfort 

 chest pain 

 increase of urea nitrogen, creatinine and uric acid in the blood 

 high level of calcium, fat or sodium in the blood 

 decrease of potassium in the blood 

 breath odour 

 diarrhoea 

 dry mouth 

 nausea 

 vomiting 

 abdominal pain 

 weight increase 

 loss of appetite 

 disturbed sense of taste 

 back pain 

 joint swelling 

 muscle cramps/weakness/pain 

 pain in extremity 

 inability to either stand or walk in a normal manner 

 weakness 

 abnormal coordination 

 dizziness on standing up or after exercising 

 lack of energy 

 sleep disturbances 

 tingling or numbness 

 neuropathy 

 sleepiness 

 sudden, temporary loss of consciousness 

 low blood pressure on standing up 

 impotence 

 cough 

 breathlessness 

 throat irritation 

 excessive sweating 

 itching 

 swelling, reddening and pain along a vein 

 skin reddening 

 trembling 

 

Not known 

 changes in blood tests for kidney function, increase of potassium in your blood, low level of red 

blood cells 

 

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Side effects reported with amlodipine or valsartan or hydrochlorothiazide alone, but not 

observed with Imprida HCT or observed in a higher frequency: 

 

Amlodipine 

Common 

 palpitations 

 abdominal pain 

 nausea 

 sleepiness 

 hot flushes 

 

Uncommon 

 ringing noise in ears 

 change of bowel habit 

 pain 

 weight decrease 

 joint pain 

 trembling 

 mood swings 

 urination disorders 

 urination at night 

 breast enlargement in men 

 runny nose 

 hair loss 

 skin eruption 

 purple skin patches 

 rash 

 skin discoloration 

 

Very rare 

 low level of white blood cells and blood platelets 

 irregular heart beat 

 heart attack 

 inflammation of the stomach lining or of the pancreas, gingival overgrowth, abnormal liver 

function test 

 liver disorder which can occur together with yellow skin and eyes, or dark-coloured urine 

 allergic reaction including swelling deeper in the skin and difficulty breathing 

 high level of sugar in the blood 

 increased muscle stiffness 

 skin reaction with skin reddening and peeling, blistering of lips, eyes or mouth 

 itchy rash 

 inflammation of blood vessels 

 

Not known 

 stiff limbs and trembling hands 

 

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Valsartan 

Not known 

 abnormal red blood cell test 

 low level of a certain type of white blood cell and blood platelet 

 increase of potassium in the blood 

 increase of creatinine in the blood 

 abnormal liver function test 

 allergic reaction including swelling deeper in the skin and difficulty breathing 

 muscle pain 

 severely decreased urine output 

 itching 

 rash 

 inflammation of blood vessels 

 

Hydrochlorothiazide 

Very common 

 low level of potassium in the blood 

 increase of lipids in the blood 

 

Common 

 high level of uric acid in the blood 

 low level of magnesium in the blood 

 low level of sodium in the blood 

 dizziness, fainting on standing up 

 reduced appetite 

 nausea and vomiting 

 itchy rash and other types of rash 

 inability to achieve or maintain erection 

 

Rare 

 low level of blood platelets (sometimes with bleeding or bruising underneath the skin) 

 sugar in the urine 

 high level of sugar in the blood 

 worsening of the diabetic metabolic state 

 sad mood (depression) 

 irregular heart beat 

 abdominal discomfort 

 constipation 

 liver disorders which can occur together with yellow skin and eyes, or dark-coloured urine 

(haemolytic anaemia) 

 increased sensitivity of skin to sun 

 purple skin patches 

 kidney disorders 

 

Very rare 

 fever, sore throat or mouth ulcers, more frequent infections (lack or low level of white blood 

cells) 

 pale skin, tiredness, breathlessness, dark-coloured urine (haemolytic anaemia, abnormal 

breakdown of red blood cells either in the blood vessels or elsewhere in the body) 

 confusion, tiredness, muscle twitching and spasm, rapid breathing (hypochloraemic alkalosis) 

 severe upper stomach ache (inflammation of the pancreas) 

 rash, itching, hives, difficulty breathing or swallowing, dizziness (hypersensitivity reactions) 

 difficulty breathing with fever, coughing, wheezing, breathlessness (respiratory distress, 

pulmonary oedema, pneumonitis) 

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 facial rash, joint pain, muscle disorder, fever (lupus erythematosus) 

 inflammation of blood vessels with symptoms such as rash, purplish-red spots, fever (vasculitis) 

 severe skin disease that causes rash, red skin, blistering of the lips, eyes or mouth, skin peeling, 

fever (toxic epidermal necrolysis) 

 

Not known 

 weakness, bruising and frequent infections (aplastic anaemia) 

 decrease in vision or pain in your eyes due to high pressure (possible signs of acute angle-

closure glaucoma) 

 breathlessness 

 severely decreased urine output (possible signs of renal disorder or renal failure) 

 severe skin disease that causes rash, red skin, blistering of the lips, eyes or mouth, skin peeling, 

fever (erythema multiforme) 

 muscle spasm 

 fever (pyrexia) 

 

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 

 

 

5. HOW TO STORE IMPRIDA HCT 

 

Keep out of the reach and sight of children. 

Do not use Imprida HCT after the expiry date which is stated on the carton and blister after EXP. The 

expiry date refers to the last day of that month. 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

Do not use any Imprida HCT pack that is damaged or shows signs of tampering. 

 

 

6. FURTHER INFORMATION 

 

What Imprida HCT contains 

 The active substances of Imprida HCT are amlodipine (as amlodipine besylate), valsartan and 

hydrochlorothiazide. 

 

 Imprida HCT 10 mg/160 mg/25 mg film-coated tablets: Each film-coated tablet contains 10 mg 

amlodipine (as amlodipine besylate), 160 mg valsartan, and 25 mg hydrochlorothiazide. The 

other ingredients are cellulose microcrystalline; crospovidone; silica, colloidal anhydrous, 

magnesium stearate, hypromellose, macrogol 4000, talc, yellow iron oxide (E172). 

 

What Imprida HCT looks like and contents of the pack 

 Imprida HCT 10 mg/160 mg/25 mg film-coated tablets are brown-yellow, oval tablets with 

“NVR” on one side and “VHL” on the other side. 

 

Imprida HCT is available in packs containing 14, 28, 30, 56, 90, 98 or 280 film-coated tablets, in 

multipacks of 280 tablets (comprising 4 cartons, each containing 70 tablets, or 20 cartons, each 

containing 14 tablets), and in hospital packs containing 56, 98 or 280 tablets in single unit blisters. 

Not all pack sizes may be available in your country. 

 

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Marketing Authorisation Holder 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

България 

Novartis Pharma Services Inc. 

Тел.: +359 2 976 98 28 

 

Magyarország 

Novartis Hungária Kft. Pharma 

Tel.: +36 1 457 65 00 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2298 3217 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 26 37 82 111 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 

Eesti 

Novartis Pharma Services Inc. 

Tel: +372 66 30 810 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

España 

Lacer, S.A. 

Tel: +34 93 446 53 00 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

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Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

Novartis Pharma Services Inc. 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

Lietuva 

Novartis Pharma Services Inc. 

Tel: +370 5 269 16 50 

 

 

 

This leaflet was last approved in 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

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PACKAGE LEAFLET: INFORMATION FOR THE USER 

 

Imprida HCT 10 mg/320 mg/25 mg film-coated tablets 

amlodipine/valsartan/hydrochlorothiazide 

 

Read all of this leaflet carefully before you start taking this medicine. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or pharmacist. 

- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 

- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 

 

 

In this leaflet: 

1. What Imprida HCT is and what it is used for 

2. Before you take Imprida HCT 

3. How to take Imprida HCT 

4. Possible side effects 

5. How to store Imprida HCT 

6. Further information 

 

 

1. WHAT IMPRIDA HCT IS AND WHAT IT IS USED FOR 

 

Imprida HCT tablets contain three substances called amlodipine, valsartan and hydrochlorothiazide. 

All of these substances help to control high blood pressure. 

 Amlodipine belongs to a group of substances called “calcium channel blockers”. Amlodipine 

stops calcium from moving into the blood vessel wall, which stops the blood vessels from 

tightening. 

 Valsartan belongs to a group of substances called “angiotensin-II receptor antagonists”. 

Angiotensin II is produced by the body and makes the blood vessels tighten, thus increasing the 

blood pressure. Valsartan works by blocking the effect of angiotensin II. 

 Hydrochlorothiazide belongs to a group of substances called “thiazide diuretics”. 

Hydrochlorothiazide increases urine output, which also lowers blood pressure. 

As a result of all three mechanisms, the blood vessels relax and blood pressure is lowered. 

 

Imprida HCT is used to treat high blood pressure in adult patients who are already taking amlodipine, 

valsartan and hydrochlorothiazide and who may benefit from taking one tablet containing all three 

substances. 

 

 

2. BEFORE YOU TAKE IMPRIDA HCT 

 

Do not take Imprida HCT 

 if you are more than 3 months pregnant. (It is also better to avoid Imprida HCT in early 

pregnancy – see Pregnancy section). 

 if you are allergic (hypersensitive) to amlodipine, valsartan, hydrochlorothiazide, 

sulphonamide-derived medicines (medicines used to treat chest or urinary infections), or any of 

the other ingredients of Imprida HCT (see section 6, “What Imprida HCT contains”). 

If you think you may be allergic, do not take Imprida HCT and talk to your doctor. 

 if you have liver disease, destruction of the small bile ducts within the liver (biliary cirrhosis) 

leading to the build up of bile in the liver (cholestasis). 

 if you have severe kidney problems or if you are having dialysis. 

 if you are unable to produce urine (anuria). 

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 if the level of potassium or sodium in your blood is too low despite treatment. 

 if the level of calcium in your blood is too high despite treatment. 

 if you have gout (uric acid crystals in the joints). 

If any of the above applies to you, do not take Imprida HCT and talk to your doctor. 

 

Take special care with Imprida HCT 

 if you have a low level of potassium or magnesium in your blood (with or without symptoms 

such as muscle weakness, muscle spasms, abnormal heart rhythm). 

 if you have a low level of sodium in your blood (with or without symptoms such as tiredness, 

confusion, muscle twitching, convulsions). 

 if you have a high level of calcium in your blood (with or without symptoms such as nausea, 

vomiting, constipation, stomach pain, frequent urination, thirst, muscle weakness and 

twitching). 

 if you are taking medicines or substances that increase the amount of potassium in your blood. 

These include potassium supplements or salt substitutes containing potassium, potassium-

sparing medicines and heparin. It may be necessary to check the amount of potassium in your 

blood at regular intervals. 

 if you have kidney problems, have had a kidney transplant or if you had been told that you have 

a narrowing of your kidney arteries. 

 if you have liver problems. 

 if you have or have had heart failure or coronary artery disease, particularly if you are taking 
the maximum dose of Imprida HCT (10 mg/320 mg/25 mg) 

 if your doctor has told you that you have a narrowing of the valves in your heart (called “aortic 

or mitral stenosis”) or that the thickness of your heart muscle is abnormally increased (called 

“obstructive hypertrophic cardiomyopathy”). 

 if you suffer from aldosteronism. This is a disease in which the adrenal glands make too much 

of the hormone aldosterone If this applies to you, the use of Imprida HCT is not recommended. 

 if you suffer from a disease called systemic lupus erythematosus (also called “lupus” or 

“SLE”). 

 if you have diabetes (high level of sugar in your blood). 

 if you have high levels of cholesterol or triglycerides in your blood. 

 if you experience skin reactions such as rash after sun exposure. 

 if you had an allergic reaction to other high blood pressure medicines or diuretics (a type of 

medicine also known as “water tablets”), especially if you suffer from asthma and allergies 

 if you have been sick (vomiting or diarrhoea). 

 if you experience dizziness and/or fainting during treatment with Imprida HCT, tell your doctor 

as soon as possible. 

 if you experience a decrease in vision or eye pain. These could be symptoms of an increase of 

pressure in your eye and can happen within hours to a week of taking Imprida HCT. This can 

lead to permanent vision impairment, if not treated. 

If any of these apply to you, talk to your doctor. 

 

You must tell your doctor if you think that you are (or might become) pregnant. Imprida HCT is not 

recommended in early pregnancy and must not be taken if you are more than 3 months pregnant, as it 

may cause serious harm to your baby if used at this stage (see section “Pregnancy and breast-

feeding”). 

 

The use of Imprida HCT in children and adolescents under 18 years of age is not recommended. 

 

Imprida HCT and older people (age 65 years and older) 

Imprida HCT can be used by people aged 65 years and over at the same dose as for other adults and in 

the same way as they have already taken the three substances called amlodipine, valsartan and 

hydrochlorothiazide. Elderly patients, particularly those taking the maximum dose of Imprida HCT 

(10 mg/320 mg/25 mg), should have their blood pressure checked regularly. 

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Using other medicines 

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 

including medicines obtained without a prescription. Your doctor may need to change the dose or take 

other precautions. In some cases you may have to stop using one of the medicines. This is especially 

important if you are using any of the medicines listed below: 

 

Do not take together with: 

• lithium (a medicine used to treat some types of depression); 

• medicines or substances that increase the amount of potassium in your blood. These include 

potassium supplements or salt substitutes containing potassium, potassium-sparing medicines 

and heparin. 

Caution should be used with: 

• alcohol, sleeping pills and anaesthetics (medicines allowing patients to undergo surgery and 

other procedures); 

• amantadine (anti-Parkinson therapy, also used to treat or prevent certain illnesses caused by 

viruses); 

• anticholinergic agents (medicines used to treat a variety of disorders such as gastrointestinal 

cramps, urinary bladder spasm, asthma, motion sickness, muscular spasms, Parkinson's disease 

and as an aid to anaesthesia); 

• anticonvulsant medicines and mood-stabilising medicines used to treat epilepsy and bipolar 

disorder (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone); 

• cholestyramine, colestipol or other resins (substances used mainly to treat high levels of lipids 

in the blood); 

• simvastatin (a medicine used to control high cholesterol levels); 

• ciclosporin (a medicine used in transplantation to prevent organ rejection or for other 

conditions, e.g: rheumatoid arthritis or atopic dermatitis); 

• cytotoxic medicines (used to treat cancer), such as methotrexate or cyclophosphamide; 

• digoxin or other digitalis glycosides (medicines used to treat heart problems); 

• verapamil, diltiazem (heart medicines); 

• iodine contrast media (agents used for imaging examinations); 

• medicines for the treatment of diabetes (oral agents such as metformin or insulins); 

• medicines for the treatment of gout, such as allopurinol; 

• medicines that may increase blood sugar levels (beta blockers, diazoxide); 

• medicines that may induce “torsades de pointes” (irregular heart beat), such as antiarrhythmics 

(medicines used to treat heart problems) and some antipsychotics; 

• medicines that may reduce the amount of sodium in your blood, such as antidepressants, 

antipsychotics, antiepileptics; 

• medicines that may reduce the amount of potassium in your blood, such as diuretics (water 

tablets), corticosteroids, laxatives, amphotericin or penicillin G; 

• medicines to increase blood pressure such as adrenaline or noradrenaline; 

• medicines used for HIV/AIDS (e.g. ritonavir, indinavir, nelfinavir); 

• medicines used to treat fungal infections (e.g. ketoconazole, itraconazole); 

• medicines used for oesophageal ulceration and inflammation (carbenoxolone); 

• medicines used to relieve pain or inflammation, especially non-steroidal anti-inflammatory 

agents (NSAIDs), including selective cyclooxygenase-2 inhibitors (Cox-2 inhibitors); 

• muscle relaxants (medicines to relax the muscles which are used during operations); 

• nitroglycerin and other nitrates, or other substances called “vasodilators”; 

• other medicines to treat high blood pressure, including methyldopa; 

• rifampicin (used, for example, to treat tuberculosis); 

• St. John’s wort; 

• dantrolene (infusion for severe body temperature abnormalities); 

• vitamin D and calcium salts. 

 

Talk to your doctor before drinking alcohol. Alcohol may make your blood pressure fall too much 

and/or increase the possibility of dizziness or fainting. 

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Taking Imprida HCT with food and drink 

You can take Imprida HCT with or without food. Grapefruit and grapefruit juice should not be 

consumed by people who are taking Imprida HCT. This is because grapefruit and grapefruit juice can 

lead to an increase in the blood levels of the active substance amlodipine, which can cause an 

unpredictable increase in the blood pressure lowering effect of Imprida HCT. 

 

Pregnancy and breast-feeding 

Pregnancy 

You must tell your doctor if you think you are (or might become) pregnant. Your doctor will 

normally advise you to stop taking Imprida HCT before you become pregnant or as soon as you know 

you are pregnant and will advise you to take another medicine instead of Imprida HCT. Imprida HCT 

is not recommended in early pregnancy and must not be taken when more than 3 months pregnant, as 

it may cause serious harm to your baby if used after the third month of pregnancy. 

 

Breast-feeding 

Tell your doctor if you are breast-feeding or about to start breast-feeding. Imprida HCT is not 

recommended for mothers who are breast-feeding, and your doctor may choose another treatment for 

you if you wish to breast-feed, especially if your baby is a newborn, or was born prematurely. 

 

Ask your doctor or pharmacist for advice before taking any medicine. 

 

Driving and using machines 

As with many other medicines used to treat high blood pressure, this medicine may make you feel 

dizzy. If you experience this symptom, do not drive or use tools or machines. 

 

 

3. HOW TO TAKE IMPRIDA HCT 

 

Always take this medicine exactly as your doctor has told you. You should check with your doctor if 

you are not sure. This will help you get the best results and lower the risk of side effects. 

 

The usual dose of Imprida HCT is one tablet per day. 

 It is best to take the tablet at the same time each day. Morning is the best time. 

 Swallow the tablet whole with a glass of water. 

 You can take Imprida HCT with or without food. Do not take Imprida HCT with grapefruit or 

grapefruit juice. 

 

Depending on how you respond to the treatment, your doctor may suggest a higher or lower dose. 

 

If you take more Imprida HCT than you should 

If you have accidentally taken too many Imprida HCT tablets, talk to a doctor immediately.You may 

require medical attention. 

 

If you forget to take Imprida HCT 

If you forget to take a dose of this medicine, take it as soon as you remember and then take the next 

dose at its usual time. If it is almost time for your next dose you should simply take the next tablet at 

the usual time. Do not take a double dose (two tablets at once) to make up for a forgotten tablet. 

 

If you stop taking Imprida HCT 

Stopping your treatment with Imprida HCT may cause your disease to get worse. Do not stop taking 

your medecine unless your doctor tells you to. 

 

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Always take this medicine, even if you are feeling well 

People who have high blood pressure often do not notice any signs of the problem. Many feel normal. 

It is very important that you take this medicine exactly as your doctor tells you to get the best results 

and reduce the risk of side effects. Keep your appointments with the doctor even if you are feeling 

well. 

 

If you have any further questions on the use of this product ask your doctor or pharmacist. 

 

 

4. POSSIBLE SIDE EFFECTS 

 

Like all medicines, Imprida HCT can cause side effects, although not everybody gets them. 

These side effects may occur with certain frequencies, which are defined as follows: 

very common: affects more than 1 user in 10 

common: affects 1 to 10 users in 100 

uncommon: affects 1 to 10 users in 1,000 

rare: affects 1 to 10 users in 10,000 

very rare: affects less than 1 user in 10,000 

not known: frequency cannot be estimated from the available data 

 

Some side effects can be serious and need immediate medical attention: 

 

You should see your doctor immediately if you experience any of the following symptoms: 

Common 

 dizziness 

 low blood pressure (feeling of faintness, light-headedness, sudden loss of consciousness) 

 

Uncommon 

 severely decreased urine output (decreased kidney function) 

 

Rare 

 spontaneous bleeding 

 irregular heart beat 

 liver disorder 

 

Very rare 

 allergic reaction with symptoms such as rash, itching 

 angioedema: swelling of face or lips or tongue, difficulty of breathing 

 crushing/tight chest pain that gets worse or that does not go away 

 weakness, bruising, fever and frequent infections 

 stiffness 

 

Other possible side effects of Imprida HCT: 

Common 

 stomach discomfort after meal 

 tiredness 

 swelling 

 low level of potassium in the blood 

 headache 

 frequent urination 

 

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Uncommon 

 fast heart beat 

 spinning sensation 

 vision disorder 

 stomach discomfort 

 chest pain 

 increase of urea nitrogen, creatinine and uric acid in the blood 

 high level of calcium, fat or sodium in the blood 

 decrease of potassium in the blood 

 breath odour 

 diarrhoea 

 dry mouth 

 nausea 

 vomiting 

 abdominal pain 

 weight increase 

 loss of appetite 

 disturbed sense of taste 

 back pain 

 joint swelling 

 muscle cramps/weakness/pain 

 pain in extremity 

 inability to either stand or walk in a normal manner 

 weakness 

 abnormal coordination 

 dizziness on standing up or after exercising 

 lack of energy 

 sleep disturbances 

 tingling or numbness 

 neuropathy 

 sleepiness 

 sudden, temporary loss of consciousness 

 low blood pressure on standing up 

 impotence 

 cough 

 breathlessness 

 throat irritation 

 excessive sweating 

 itching 

 swelling, reddening and pain along a vein 

 skin reddening 

 trembling 

 

Not known 

 changes in blood tests for kidney function, increase of potassium in your blood, low level of red 

blood cells 

 

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Side effects reported with amlodipine or valsartan or hydrochlorothiazide alone, but not 

observed with Imprida HCT or observed in a higher frequency: 

 

Amlodipine 

Common 

 palpitations 

 abdominal pain 

 nausea 

 sleepiness 

 hot flushes 

 

Uncommon 

 ringing noise in ears 

 change of bowel habit 

 pain 

 weight decrease 

 joint pain 

 trembling 

 mood swings 

 urination disorders 

 urination at night 

 breast enlargement in men 

 runny nose 

 hair loss 

 skin eruption 

 purple skin patches 

 rash 

 skin discoloration 

 

Very rare 

 low level of white blood cells and blood platelets 

 irregular heart beat 

 heart attack 

 inflammation of the stomach lining or of the pancreas, gingival overgrowth, abnormal liver 

function test 

 liver disorder which can occur together with yellow skin and eyes, or dark-coloured urine 

 allergic reaction including swelling deeper in the skin and difficulty breathing 

 high level of sugar in the blood 

 increased muscle stiffness 

 skin reaction with skin reddening and peeling, blistering of lips, eyes or mouth 

 itchy rash 

 inflammation of blood vessels 

 

Not known 

 stiff limbs and trembling hands 

 

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Valsartan 

Not known 

 abnormal red blood cell test 

 low level of a certain type of white blood cell and blood platelet 

 increase of potassium in the blood 

 increase of creatinine in the blood 

 abnormal liver function test 

 allergic reaction including swelling deeper in the skin and difficulty breathing 

 muscle pain 

 severely decreased urine output 

 itching 

 rash 

 inflammation of blood vessels 

 

Hydrochlorothiazide 

Very common 

 low level of potassium in the blood 

 increase of lipids in the blood 

 

Common 

 high level of uric acid in the blood 

 low level of magnesium in the blood 

 low level of sodium in the blood 

 dizziness, fainting on standing up 

 reduced appetite 

 nausea and vomiting 

 itchy rash and other types of rash 

 inability to achieve or maintain erection 

 

Rare 

 low level of blood platelets (sometimes with bleeding or bruising underneath the skin) 

 sugar in the urine 

 high level of sugar in the blood 

 worsening of the diabetic metabolic state 

 sad mood (depression) 

 irregular heart beat 

 abdominal discomfort 

 constipation 

 liver disorders which can occur together with yellow skin and eyes, or dark-coloured urine 

(haemolytic anaemia) 

 increased sensitivity of skin to sun 

 purple skin patches 

 kidney disorders 

 

Very rare 

 fever, sore throat or mouth ulcers, more frequent infections (lack or low level of white blood 

cells) 

 pale skin, tiredness, breathlessness, dark-coloured urine (haemolytic anaemia, abnormal 

breakdown of red blood cells either in the blood vessels or elsewhere in the body) 

 confusion, tiredness, muscle twitching and spasm, rapid breathing (hypochloraemic alkalosis) 

 severe upper stomach ache (inflammation of the pancreas) 

 rash, itching, hives, difficulty breathing or swallowing, dizziness (hypersensitivity reactions) 

 difficulty breathing with fever, coughing, wheezing, breathlessness (respiratory distress, 

pulmonary oedema, pneumonitis) 

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 facial rash, joint pain, muscle disorder, fever (lupus erythematosus) 

 inflammation of blood vessels with symptoms such as rash, purplish-red spots, fever (vasculitis) 

 severe skin disease that causes rash, red skin, blistering of the lips, eyes or mouth, skin peeling, 

fever (toxic epidermal necrolysis) 

 

Not known 

 weakness, bruising and frequent infections (aplastic anaemia) 

 decrease in vision or pain in your eyes due to high pressure (possible signs of acute angle-

closure glaucoma) 

 breathlessness 

 severely decreased urine output (possible signs of renal disorder or renal failure) 

 severe skin disease that causes rash, red skin, blistering of the lips, eyes or mouth, skin peeling, 

fever (erythema multiforme) 

 muscle spasm 

 fever (pyrexia) 

 

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 

 

 

5. HOW TO STORE IMPRIDA HCT 

 

Keep out of the reach and sight of children. 

Do not use Imprida HCT after the expiry date which is stated on the carton and blister after EXP. The 

expiry date refers to the last day of that month. 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

Do not use any Imprida HCT pack that is damaged or shows signs of tampering. 

 

 

6. FURTHER INFORMATION 

 

What Imprida HCT contains 

 The active substances of Imprida HCT are amlodipine (as amlodipine besylate), valsartan and 

hydrochlorothiazide. 

 

 Imprida HCT 10 mg/320 mg/25 mg film-coated tablets: Each film-coated tablet contains 10 mg 

amlodipine (as amlodipine besylate), 320 mg valsartan, and 25 mg hydrochlorothiazide. The 

other ingredients are cellulose microcrystalline; crospovidone; silica, colloidal anhydrous, 

magnesium stearate, hypromellose, macrogol 4000, talc, yellow iron oxide (E172). 

 

What Imprida HCT looks like and contents of the pack 

 Imprida HCT 10 mg/320 mg/25 mg film-coated tablets are brown-yellow, oval tablets with 

“NVR” on one side and “VFL” on the other side. 

 

Imprida HCT is available in packs containing 14, 28, 30, 56, 90, 98 or 280 film-coated tablets, in 

multipacks of 280 tablets (comprising 4 cartons, each containing 70 tablets, or 20 cartons, each 

containing 14 tablets), and in hospital packs containing 56, 98 or 280 tablets in single unit blisters. 

Not all pack sizes may be available in your country. 

 

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Marketing Authorisation Holder 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

България 

Novartis Pharma Services Inc. 

Тел.: +359 2 976 98 28 

 

Magyarország 

Novartis Hungária Kft. Pharma 

Tel.: +36 1 457 65 00 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2298 3217 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 26 37 82 111 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 

Eesti 

Novartis Pharma Services Inc. 

Tel: +372 66 30 810 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

España 

Lacer, S.A. 

Tel: +34 93 446 53 00 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

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Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

Novartis Pharma Services Inc. 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

Lietuva 

Novartis Pharma Services Inc. 

Tel: +370 5 269 16 50 

 

 

 

This leaflet was last approved in 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET