Dafiro HCT

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 

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

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

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

Dafiro HCT 10 mg/160 mg/25 mg film-coated tablets 

Dafiro HCT 10 mg/320 mg/25 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

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

 

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

and 12.5 mg of hydrochlorothiazide. 

 

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

 

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

and 12.5 mg of hydrochlorothiazide. 

 

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

 

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

and 25 mg of hydrochlorothiazide. 

 

Dafiro HCT 10 mg/160 mg/25 mg film-coated tablets 

 

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

and 25 mg of hydrochlorothiazide. 

 

Dafiro HCT 10 mg/320 mg/25 mg film-coated tablets 

 

Each film-coated tablet contains 10 mg of amlodipine (as amlodipine besylate), 320 mg of valsartan 

and 25 mg of hydrochlorothiazide. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet (tablet) 

 

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

 

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

other side. Approximate size: 15 mm (length) x 5.9 mm (width). 

 

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

 

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

on the other side. Approximate size: 15 mm (length) x 5.9 mm (width). 

 

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

 

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

other side. Approximate size: 15 mm (length) x 5.9 mm (width). 



3 

 

Dafiro HCT 10 mg/160 mg/25 mg film-coated tablets 

 

Brown-yellow, ovaloid, biconvex tablets with bevelled edge, debossed “NVR” on one side and “VHL” 

on the other side. Approximate size: 15 mm (length) x 5.9 mm (width). 

 

Dafiro HCT 10 mg/320 mg/25 mg film-coated tablets 

 

Brown-yellow, ovaloid, biconvex tablets with bevelled edge, debossed “NVR” on one side and “VFL” 

on the other side. Approximate size: 19 mm (length) x 7.5 mm (width). 

 

 

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 Dafiro HCT is one tablet per day, to be taken preferably in the morning. 

 

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

taken at the same time. The dose of Dafiro HCT should be based on the doses of the individual 

components of the combination at the time of switching. 

 

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

 

Special populations 

Renal impairment 

Due to the hydrochlorothiazide component, Dafiro 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 m2) (see sections 4.3, 4.4 and 5.2). 

 

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

sections 4.4 and 5.2). 

 

Hepatic impairment 

Due to the valsartan component, Dafiro 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 Dafiro HCT is not 

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

have not been established in patients with mild to moderate hepatic impairment. When switching 

eligible hypertensive patients (see section 4.1) with hepatic impairment to Dafiro HCT, the lowest 

available dose of the amlodipine component should be used. 

 

Heart failure and coronary artery disease 

There is limited experience with the use of Dafiro 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 Dafiro HCT, 10 mg/320 mg/25 mg. 

 



4 

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 Dafiro HCT, 10 mg/320 mg/25 mg, since available data in this 

patient population are limited. When switching eligible elderly hypertensive patients (see section 4.1) 

to Dafiro HCT, the lowest available dose of the amlodipine component should be used. 

 

Paediatric population 

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

the indication of essential hypertension. 

 

Method of administration 

 

Oral use. 

Dafiro 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 listed in section 6.1. 

 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. 

 Concomitant use of Dafiro HCT with aliskiren-containing products in patients with diabetes 
mellitus or renal impairment (GFR <60 ml/min/1.73 m2) (see sections 4.5 and 5.1). 

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

 Severe hypotension. 

 Shock (including cardiogenic shock). 

 Obstruction of the outflow tract of the left ventricle (e.g. hypertrophic obstructive 
cardiomyopathy and high grade aortic stenosis). 

 Haemodynamically unstable heart failure after acute myocardial infarction. 
 

4.4 Special warnings and precautions for use 

 

The safety and efficacy of amlodipine in hypertensive crisis have not been established. 

 

Sodium- and/or volume-depleted patients 

 

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

the maximum dose of Dafiro 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 Dafiro HCT. Dafiro HCT should 

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

 

If excessive hypotension occurs with Dafiro 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. 

 



5 

Serum electrolyte changes 

 

Amlodipine/valsartan/hydrochlorothiazide 

In the controlled trial of Dafiro 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. 

 

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 Dafiro 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, Dafiro 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 Dafiro 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 Dafiro 

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

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

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

 

No dose adjustment of Dafiro HCT is required for patients with mild to moderate renal impairment 

(GFR ≥30 ml/min/1.73 m2). 

 

Renal artery stenosis 

 

Dafiro HCT should be used with caution to treat hypertension in patients with unilateral or bilateral 

renal artery stenosis or stenosis to a solitary kidney since blood urea and serum creatinine may 

increase in such patients. 

 

Kidney transplantation 

 

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

transplantation. 

 



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Hepatic impairment 

 

Valsartan is mostly eliminated unchanged via the bile. The half-life of amlodipine is prolonged and 

AUC values are higher in patients with impaired liver function; dose recommendations have not been 

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

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

patients (see sections 4.2, 4.3 and 5.2). 

 

Angioedema 

 

Angioedema, including swelling of the larynx and glottis, causing airway obstruction and/or swelling 

of the face, lips, pharynx, and/or tongue, has been reported in patients treated with valsartan. Some of 

these patients previously experienced angioedema with other medicinal products including ACE 

inhibitors. Dafiro HCT should be discontinued immediately in patients who develop angioedema and 

should not be re-administered. 

 

Heart failure and coronary artery disease/post-myocardial infarction 

 

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 

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. Evaluation of patients with heart failure or post-myocardial infarction should 

always include assessment of renal function. 

 

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. 

 

Calcium channel blockers, including amlodipine, should be used with caution in patients with 

congestive heart failure, as they may increase the risk of future cardiovascular events and mortality. 

 

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

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

is limited. 

 

Aortic and mitral valve stenosis 

 

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

aortic stenosis that is not high grade. 

 

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, Dafiro HCT is not 

recommended in this population. 

 



7 

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, Dafiro 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. Dafiro HCT is contraindicated in 

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

hypercalcaemia. Dafiro 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 Dafiro 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. 

 

Choroidal effusion, acute myopia and secondary acute angle-closure glaucoma 

 

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

choroidal effusion with visual field defect, 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. 

 

  



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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 Dafiro HCT, 10 mg/320 mg/25 mg, since available data in this 

patient population are limited. 

 

Dual blockade of the renin-angiotensin-aldosterone system (RAAS) 

 

There is evidence that the concomitant use of ACE inhibitors, ARBs or aliskiren increases the risk of 

hypotension, hyperkalaemia, and decreased renal function (including acute renal failure). Dual 

blockage of RAAS through the combined use of ACE inhibitors, ARBs or aliskiren is therefore not 

recommended (see sections 4.5 and 5.1). 

 

If dual blockade therapy is considered absolutely necessary, this should only occur under specialist 

supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure. 

ACE inhibitors and ARBs should not be used concomitantly in patients with diabetic nephropathy. 

 

Non-melanoma skin cancer 

An increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous 

cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide exposure has been 

observed in two epidemiological studies based on the Danish National Cancer Registry. 

Photosensitising actions of hydrochlorothiazide could act as a possible mechanism for NMSC. 

 

Patients taking hydrochlorothiazide should be informed of the risk of NMSC and advised to regularly 

check their skin for any new lesions and promptly report any suspicious skin lesions. Possible 

preventive measures such as limited exposure to sunlight and UV rays and, in case of exposure, 

adequate protection should be advised to the patients in order to minimise the risk of skin cancer. 

Suspicious skin lesions should be promptly examined potentially including histological examinations 

of biopsies. The use of hydrochlorothiazide may also need to be reconsidered in patients who have 

experienced previous NMSC (see also section 4.8). 
 

  



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4.5 Interaction with other medicinal products and other forms of interaction 
 

No formal interaction studies with other medicinal products have been performed with Dafiro 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 Dafiro HCT may increase the hypotensive effect of 

other antihypertensive agents. 

 

Concomitant use not recommended 

 

Dafiro 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 concomitant 

administration of lithium with ACE inhibitors, angiotensin 

II receptor antagonists including valsartan or thiazides. 

Since renal clearance of lithium is reduced by thiazides, 

the risk of lithium toxicity may presumably be increased 

further with Dafiro HCT. Therefore careful monitoring of 

serum lithium concentrations is recommended during 

concomitant use. 

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. 

 

  



10 

Caution required with concomitant use 

 

Dafiro 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]) 

Upon co-administration of known inducers of the 

CYP3A4, the plasma concentration of amlodipine may 

vary. Therefore, blood pressure should be monitored and 

dose regulation considered both during and after 

concomitant medication particularly with strong CYP3A4 

inducers (e.g. rifampicin, hypericum perforatum). 

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 drugs 

(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 Dafiro 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. 



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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. 

 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. 



12 

 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. 

Other anti-hypertensive 

medicinal products 

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. 

 

Dual blockade of the RAAS with ARBs, ACE inhibitors or aliskiren 

Clinical trial data have shown that dual blockade of the RAAS through the combined use of ACE 

inhibitors, ARBs or aliskiren is associated with a higher frequency of adverse events such as 

hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to 

the use of a single RAAS-acting agent (see sections 4.3, 4.4 and 5.1). 

 

  



13 

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. 

 

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 Dafiro HCT in pregnant women. Based on the existing data with 

the components, the use of Dafiro 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). 

 



14 

Breast-feeding 

 

Amlodipine is excreted in human milk. The proportion of the maternal dose received by the infant has 

been estimated with an interquartile range of 3-7%, with a maximum of 15%. The effect of amlodipine 

on infants is unknown. No information is available regarding the use of valsartan 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 Dafiro HCT during breast-feeding is 

not recommended. If Dafiro 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 Dafiro 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/m2 basis 

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

 

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 
 

Patients taking Dafiro HCT and driving vehicles or using machines should take into account that 

dizziness or weariness may occasionally occur. 

 

Amlodipine can have mild or moderate influence on the ability to drive and use machines. If patients 

taking Dafiro HCT suffer from dizziness, headache, fatigue or nausea the ability to react may be 

impaired. 

 

4.8 Undesirable effects 

 

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

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

hydrochlorothiazide. 

 

Summary of the safety profile 

 

The safety of Dafiro 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 Dafiro 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 Dafiro 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. 



15 

 

Tabulated list of adverse reactions 

 

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

Dafiro 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    

Dafiro 

HCT 

Amlodipine Valsartan HCT 

Neoplasms 

benign, 

malignant and 

unspecified (incl 

cysts and polyps) 

Non-melanoma skin cancer 

(Basal cell carcinoma and 

Squamous cell carcinoma) 

-- -- -- Not known 

Blood and 

lymphatic system 

disorders 

Agranulocytosis, bone 

marrow failure 

-- -- -- Very rare 

Haemoglobin and 

haematocrit decreased 

-- -- 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 

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 -- Uncommon -- Rare 

Insomnia/sleep disorders Uncommon Uncommon -- Rare 

Mood swings -- Uncommon --  

Confusion -- Rare -- -- 



16 

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 -- -- 

Hypoesthesia -- Uncommon -- -- 

Eye disorders Acute angle-closure 

glaucoma 

-- -- -- Not known 

Visual disturbance -- Uncommon -- -- 

Visual impairment Uncommon Uncommon -- Rare 

Choroidal effusion -- -- -- Not Known 

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 -- 

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 -- -- -- 



17 

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 

Liver function test abnormal, 

including blood bilirubin 

increase 

-- 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 -- 

Dermatitis bullous -- -- 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* -- Very rare -- 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 

-- Not known -- Very rare 

Exfoliative dermatitis -- Very rare -- -- 

Stevens-Johnson syndrome -- Very rare -- -- 

Quincke oedema -- 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 -- -- -- 

Ankle swelling -- Common -- -- 



18 

Renal and 

urinary disorders 

Blood creatinine increased Uncommon -- Not known -- 

Micturition disorder  Uncommon   

Nocturia -- Uncommon -- -- 

Pollakiuria Common Uncommon   

Renal dysfunction -- -- -- Not known 

Acute renal failure 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 

Blood potassium decreased Uncommon  -- -- -- 

Blood potassium increased -- -- Not known -- 

Weight increase Uncommon Uncommon -- -- 

Weight decrease -- Uncommon -- -- 

 

* See section 4.4 Photosensitivity 

** Mostly consistent with cholestasis 

 

Description of selected adverse reactions 

 

Non-melanoma skin cancer: based on available data from epidemiological studies, cumulative 

dose-dependent association between hydrochlorothiazide and NMSC has been observed (see also 

sections 4.4 and 5.1). 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

  



19 

4.9 Overdose 

 

Symptoms 

 

There is no experience of overdose with Dafiro 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 Dafiro 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. 

 

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: Agents acting on the renin-angiotensin system, angiotensin II antagonists, 

other combinations, ATC code: C09DX01. 

 

Mechanism of action 

 

Dafiro 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. 

 



20 

Amlodipine/Valsartan/Hydrochlorothiazide 

 

Clinical efficacy and safety 

Dafiro 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 Dafiro 

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 Dafiro 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 Dafiro HCT. Statistically greater proportions of patients achieved 

blood pressure control (<140/90 mmHg) with Dafiro 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. 

 

Amlodipine 

 

Mechanism of action 

The amlodipine component of Dafiro 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. 

 

Pharmacodynamic effects 

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. 

 



21 

As with other calcium channel blockers, haemodynamic measurements of cardiac function at rest and 

during exercise (or pacing) in patients with normal ventricular function treated with amlodipine have 

generally demonstrated a small increase in cardiac index without significant influence on dP/dt or on 

left ventricular end diastolic pressure or volume. In haemodynamic studies, amlodipine has not been 

associated with a negative inotropic effect when administered in the therapeutic dose range to intact 

animals and humans, even when co-administered with beta blockers to humans. 

 

Amlodipine does not change sinoatrial nodal function or atrioventricular conduction in intact animals 

or humans. In clinical studies in which amlodipine was administered in combination with beta 

blockers to patients with either hypertension or angina, no adverse effects on electrocardiographic 

parameters were observed. 

 

Amlodipine has been studied in patients with chronic stable angina, vasospastic angina and 

angiographically documented coronary artery disease. 

 

Clinical efficacy and safety 

Use in patients with hypertension 

A randomised double-blind morbidity-mortality study called the Antihypertensive and Lipid-Lowering 

treatment to prevent Heart Attack Trial (ALLHAT) was performed to compare newer therapies: 

amlodipine 2.5-10 mg/day (calcium channel blocker) or lisinopril 10-40 mg/day (ACE-inhibitor) as 

first-line therapies to that of the thiazide-diuretic, chlorthalidone 12.5-25 mg/day in mild to moderate 

hypertension. 

 

A total of 33,357 hypertensive patients aged 55 or older were randomised and followed for a mean of 

4.9 years. The patients had at least one additional coronary heart disease risk factor, including: 

previous myocardial infarction or stroke (>6 months prior to enrollment) or documentation of other 

atherosclerotic cardiovascular disease (overall 51.5%), type 2 diabetes (36.1%), high density 

lipoprotein - cholesterol <35 mg/dl or <0.906 mmol/l (11.6%), left ventricular hypertrophy diagnosed 

by electrocardiogram or echocardiography (20.9%), current cigarette smoking (21.9%). 

 

The primary endpoint was a composite of fatal coronary heart disease or non-fatal myocardial 

infarction. There was no significant difference in the primary endpoint between amlodipine-based 

therapy and chlorthalidone-based therapy: risk ratio (RR) 0.98 95% CI (0.90-1.07) p=0.65. Among 

secondary endpoints, the incidence of heart failure (component of a composite combined 

cardiovascular endpoint) was significantly higher in the amlodipine group as compared to the 

chlorthalidone group (10.2% versus 7.7%, RR 1.38, 95% CI [1.25-1.52] p<0.001). However, there was 

no significant difference in all-cause mortality between amlodipine-based therapy and chlorthalidone-

based therapy RR 0.96 95% CI [0.89-1.02] p=0.20. 

 

Valsartan 

 

Mechanism of action 

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. 

 

Clinical efficacy and safety 

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. 

 



22 

Hydrochlorothiazide 

 

Mechanism of action 

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. 

 

Non-melanoma skin cancer 

Based on available data from epidemiological studies, cumulative dose-dependent association between 

hydrochlorothiazide and NMSC has been observed. One study included a population comprised of 

71,533 cases of BCC and of 8,629 cases of SCC matched to 1,430,833 and 172,462 population 

controls, respectively. High hydrochlorothiazide use (≥50000 mg cumulative) was associated with an 

adjusted odds ratio (OR) of 1.29 (95% CI: 1.23-1.35) for BCC and 3.98 (95% CI: 3.68-4.31) for SCC. 

A clear cumulative dose response relationship was observed for both BCC and SCC. Another study 

showed a possible association between lip cancer (SCC) and exposure to hydrochlorothiazide: 

633 cases of lip cancer were matched with 63,067 population controls, using a risk-set sampling 

strategy. A cumulative dose-response relationship was demonstrated with an adjusted OR 2.1 (95% 

CI: 1.7-2.6) increasing to OR 3.9 (3.0-4.9) for high use (~25000 mg) and OR 7.7 (5.7-10.5) for the 

highest cumulative dose (~100000 mg) (see also section 4.4). 

 

Paediatric population 

 

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

Dafiro HCT in all subsets of the paediatric population in essential hypertension (see section 4.2 for 

information on paediatric use). 

 

Other: dual blockade of the renin-angiotensin-aldosterone system (RAAS) 

 

Two large randomised, controlled trials (ONTARGET [ONgoing Telmisartan Alone and in 

combination with Ramipril Global Endpoint Trial] and VA NEPHRON-D [The Veterans Affairs 

Nephropathy in Diabetes]) have examined the use of the combination of an ACE inhibitor with an 

ARB. 

 

ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular 

disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-

D was a study in patients with type 2 diabetes mellitus and diabetic nephropathy. 

 

These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and 

mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as 

compared to monotherapy was observed. Given their similar pharmacodynamic properties, these 

results are also relevant for other ACE inhibitors and ARBs. 

 

ACE inhibitors and ARBs should therefore not be used concomitantly in patients with diabetic 

nephropathy (see section 4.4). 

 



23 

ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) 

was a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE inhibitor 

or an ARB in patients with type 2 diabetes mellitus and chronic kidney disease, cardiovascular 

disease, or both. The study was terminated early because of an increased risk of adverse outcomes. 

Cardiovascular death and stroke were both numerically more frequent in the aliskiren group than in 

the placebo group and adverse events and serious adverse events of interest (hyperkalaemia, 

hypotension and renal dysfunction) were more frequently reported in the aliskiren group than in the 

placebo group. 

 

5.2 Pharmacokinetic properties 

 

Linearity 

 

Amlodipine, valsartan and hydrochlorothiazide exhibit linear pharmacokinetics. 

 

Amlodipine/valsartan/hydrochlorothiazide 

 

Following oral administration of Dafiro 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 

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

 

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. 

 



24 

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 shows multiexponential decay kinetics (t½α <1 h and t½ß about 9 h). 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. 

 

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). 

 



25 

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. Dafiro HCT is contraindicated in 

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

 

Hepatic impairment 

Very limited clinical data are available regarding amlodipine administration in patients with hepatic 

impairment. Patients with hepatic impairment 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, Dafiro 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 (Dafiro HCT), there was no evidence of systemic or target 

organ toxicity that would adversely affect the development of Dafiro 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. 

 

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/m2 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. 



26 

 

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/m2 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, toxicity to reproduction 

and development. 

 

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/m2 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 blood urea nitrogen, 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/m2 basis (calculations assume an oral dose 

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

 

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

kidney where the changes developed to a nephropathy including raised blood urea nitrogen 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. 

 

 

  



27 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

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

 

Tablet core 

Cellulose microcrystalline 

Crospovidone (type A) 

Silica, colloidal anhydrous 

Magnesium stearate 

 

Coating 

Hypromellose, substitution type 2910 (3 mPa.s) 

Macrogol 4000 

Talc 

Titanium dioxide (E171) 

Iron oxide, yellow (E172) 

Iron oxide, red (E172) 

 

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

 

Tablet core 

Cellulose microcrystalline 

Crospovidone (type A) 

Silica, colloidal anhydrous 

Magnesium stearate 

 

Coating 

Hypromellose, substitution type 2910 (3 mPa.s) 

Macrogol 4000 

Talc 

Titanium dioxide (E171) 

Iron oxide, yellow (E172) 

Iron oxide, red (E172) 

 

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

 

Tablet core 

Cellulose microcrystalline 

Crospovidone (type A) 

Silica, colloidal anhydrous 

Magnesium stearate 

 

Coating 

Hypromellose, substitution type 2910 (3 mPa.s) 

Macrogol 4000 

Talc 

Titanium dioxide (E171) 

Iron oxide, yellow (E172) 

 



28 

Dafiro HCT 10 mg/160 mg/25 mg film-coated tablets 

 

Tablet core 

Cellulose microcrystalline 

Crospovidone (type A) 

Silica, colloidal anhydrous 

Magnesium stearate 

 

Coating 

Hypromellose, substitution type 2910 (3 mPa.s) 

Macrogol 4000 

Talc 

Iron oxide, yellow (E172) 

 

Dafiro HCT 10 mg/320 mg/25 mg film-coated tablets 

 

Tablet core 

Cellulose microcrystalline 

Crospovidone (type A) 

Silica, colloidal anhydrous 

Magnesium stearate 

 

Coating 

Hypromellose, substitution type 2910 (3 mPa.s) 

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 may be marketed. 

 



29 

6.6 Special precautions for disposal and other handling 

 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

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

 

EU/1/09/574/001-012 

 

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

 

EU/1/09/574/013-024 

 

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

 

EU/1/09/574/025-036 

 

Dafiro HCT 10 mg/160 mg/25 mg film-coated tablets 

 

EU/1/09/574/037-048 

 

Dafiro HCT 10 mg/320 mg/25 mg film-coated tablets 

 

EU/1/09/574/049-060 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 04 November 2009 

Date of latest renewal: 04 July 2014 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

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

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

 

  



30 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 



31 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturer responsible for batch release 

 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nürnberg 

Germany 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to medical prescription. 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic Safety Update Reports 
 

The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Obligation to conduct post-authorisation measures 
 

The MAH shall complete, within the stated timeframe, the below measures: 

 

Conditions to the MA Due date 

The MAH must ensure that the manufacturing processes of the drug substances 

used for their drug products are reviewed for the potential risk of formation of 

N-nitrosamines and changed as necessary to minimise nitrosamine contamination 

as much as possible. 

Within 

2 years after 

Commission 

Decision. 

N-nitrosodimethylamine (NDMA) 

After the transitional period of 2 years, a limit for NDMA of maximum 0.03 ppm 

should be implemented. 

Within 

2 years after 

Commission 

Decision. 

 

  



32 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



33 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



34 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

280 film-coated tablets 

56 x 1 film-coated tablet (unit dose) 

98 x 1 film-coated tablet (unit dose) 

280 x 1 film-coated tablet (unit dose) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 



35 

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. 

 

 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/001 14 film-coated tablets 

EU/1/09/574/002 28 film-coated tablets 

EU/1/09/574/003 30 film-coated tablets 

EU/1/09/574/004 56 film-coated tablets 

EU/1/09/574/005 90 film-coated tablets 

EU/1/09/574/006 98 film-coated tablets 

EU/1/09/574/007 280 film-coated tablets 

EU/1/09/574/008 56 x 1 film-coated tablet (unit dose) 

EU/1/09/574/009 98 x 1 film-coated tablet (unit dose) 

EU/1/09/574/010 280 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 

 

 



36 

16. INFORMATION IN BRAILLE 

 

Dafiro HCT 5 mg/160 mg/12.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



37 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

 

Film-coated tablet 

 

14 film-coated tablets. Component of a multipack. Not to be sold separately. 

70x1 film-coated tablets. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach 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. 

 



38 

 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/012 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/574/011 280 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 

 

Dafiro HCT 5 mg/160 mg/12.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

 

  



39 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

Multipack: 280 (20 packs of 14) film-coated tablets. 

Multipack: 280 (4 packs of 70x1) film-coated tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach 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. 

 

 



40 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/012 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/574/011 280 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 

 

Dafiro HCT 5 mg/160 mg/12.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



41 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

  



42 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

280 film-coated tablets 

56 x 1 film-coated tablet (unit dose) 

98 x 1 film-coated tablet (unit dose) 

280 x 1 film-coated tablet (unit dose) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 



43 

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. 

 

 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/013 14 film-coated tablets 

EU/1/09/574/014 28 film-coated tablets 

EU/1/09/574/015 30 film-coated tablets 

EU/1/09/574/016 56 film-coated tablets 

EU/1/09/574/017 90 film-coated tablets 

EU/1/09/574/018 98 film-coated tablets 

EU/1/09/574/019 280 film-coated tablets 

EU/1/09/574/020 56 x 1 film-coated tablet (unit dose) 

EU/1/09/574/021 98 x 1 film-coated tablet (unit dose) 

EU/1/09/574/022 280 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 

 

 



44 

16. INFORMATION IN BRAILLE 

 

Dafiro HCT 10 mg/160 mg/12.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



45 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

14 film-coated tablets. Component of a multipack. Not to be sold separately. 

70x1 film-coated tablets. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach 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. 

 

 



46 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/024 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/574/023 280 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 

 

Dafiro HCT 10 mg/160 mg/12.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

 

  



47 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

Multipack: 280 (20 packs of 14) film-coated tablets. 

Multipack: 280 (4 packs of 70x1) film-coated tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach 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. 

 

 



48 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/024 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/574/023 280 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 

 

Dafiro HCT 10 mg/160 mg/12.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



49 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

  



50 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

280 film-coated tablets 

56 x 1 film-coated tablet (unit dose) 

98 x 1 film-coated tablet (unit dose) 

280 x 1 film-coated tablet (unit dose) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 



51 

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. 

 

 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/025 14 film-coated tablets 

EU/1/09/574/026 28 film-coated tablets 

EU/1/09/574/027 30 film-coated tablets 

EU/1/09/574/028 56 film-coated tablets 

EU/1/09/574/029 90 film-coated tablets 

EU/1/09/574/030 98 film-coated tablets 

EU/1/09/574/031 280 film-coated tablets 

EU/1/09/574/032 56 x 1 film-coated tablet (unit dose) 

EU/1/09/574/033 98 x 1 film-coated tablet (unit dose) 

EU/1/09/574/034 280 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 

 

 



52 

16. INFORMATION IN BRAILLE 

 

Dafiro HCT 5 mg/160 mg/25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



53 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

14 film-coated tablets. Component of a multipack: Not to be sold separately. 

70x1 film-coated tablets. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach 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. 

 

 



54 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/036 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/574/035 280 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 

 

Dafiro HCT 5 mg/160 mg/25 mg 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

 

  



55 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

Multipack: 280 (20 packs of 14) film-coated tablets. 

Multipack: 280 (4 packs of 70x1) film-coated tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach 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. 

 

 



56 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/036 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/574/035 280 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 

 

Dafiro HCT 5 mg/160 mg/25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



57 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

  



58 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

280 film-coated tablets 

56 x 1 film-coated tablet (unit dose) 

98 x 1 film-coated tablet (unit dose) 

280 x 1 film-coated tablet (unit dose) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 



59 

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. 

 

 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/037 14 film-coated tablets 

EU/1/09/574/038 28 film-coated tablets 

EU/1/09/574/039 30 film-coated tablets 

EU/1/09/574/040 56 film-coated tablets 

EU/1/09/574/041 90 film-coated tablets 

EU/1/09/574/042 98 film-coated tablets 

EU/1/09/574/043 280 film-coated tablets 

EU/1/09/574/044 56 x 1 film-coated tablet (unit dose) 

EU/1/09/574/045 98 x 1 film-coated tablet (unit dose) 

EU/1/09/574/046 280 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 

 

 



60 

16. INFORMATION IN BRAILLE 

 

Dafiro HCT 10 mg/160 mg/25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



61 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

14 film-coated tablets. Component of a multipack. Not to be sold separately. 

70x1 film-coated tablets. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach 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. 

 

 



62 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/048 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/574/047 280 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 

 

Dafiro HCT 10 mg/160 mg/25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

 

  



63 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

Multipack: 280 (20 packs of 14) film-coated tablets. 

Multipack: 280 (4 packs of 70x1) film-coated tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach 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. 

 

 



64 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/048 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/574/047 280 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 

 

Dafiro HCT 10 mg/160 mg/25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



65 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

  



66 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

280 film-coated tablets 

56 x 1 film-coated tablet (unit dose) 

98 x 1 film-coated tablet (unit dose) 

280 x 1 film-coated tablet (unit dose) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 



67 

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. 

 

 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/049 14 film-coated tablets 

EU/1/09/574/050 28 film-coated tablets 

EU/1/09/574/051 30 film-coated tablets 

EU/1/09/574/052 56 film-coated tablets 

EU/1/09/574/053 90 film-coated tablets 

EU/1/09/574/054 98 film-coated tablets 

EU/1/09/574/055 280 film-coated tablets 

EU/1/09/574/056 56 x 1 film-coated tablet (unit dose) 

EU/1/09/574/057 98 x 1 film-coated tablet (unit dose) 

EU/1/09/574/058 280 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 

 

 



68 

16. INFORMATION IN BRAILLE 

 

Dafiro HCT 10 mg/320 mg/25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



69 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

14 film-coated tablets. Component of a multipack: Not to be sold separately. 

70x1 film-coated tablets. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach 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. 

 

 



70 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/060 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/574/059 280 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 

 

Dafiro HCT 10 mg/320 mg/25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

 

  



71 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

Film-coated tablet 

 

Multipack: 280 (20 packs of 14) film-coated tablets. 

Multipack: 280 (4 packs of 70x1) film-coated tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach 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. 

 

 



72 

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 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/574/060 280 film-coated tablets (multipack, 20 cartons of 14 tablets) 

EU/1/09/574/059 280 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 

 

Dafiro HCT 10 mg/320 mg/25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



73 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 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 

 

  



74 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 
 



75 

Package leaflet: Information for the user 

 

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

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

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

Dafiro HCT 10 mg/160 mg/25 mg film-coated tablets 

Dafiro 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 because it contains 

important information for you. 
- 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 only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. See section 4. 

 

 

What is in this leaflet 

 

1. What Dafiro HCT is and what it is used for 

2. What you need to know before you take Dafiro HCT 

3. How to take Dafiro HCT 

4. Possible side effects 

5. How to store Dafiro HCT 

6. Contents of the pack and other information 

 

 

1. What Dafiro HCT is and what it is used for 

 

Dafiro 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. 

 

Dafiro HCT is used to treat high blood pressure in adult patients whose blood pressure is already 

controlled while taking amlodipine, valsartan and hydrochlorothiazide and who may benefit from 

taking one tablet containing all three substances. 

 

 

  



76 

2. What you need to know before you take Dafiro HCT 

 

Do not take Dafiro HCT 

 if you are more than 3 months pregnant. (It is also recommended to avoid Dafiro HCT in early 
pregnancy – see Pregnancy section.) 

 if you are allergic to amlodipine or to any other calcium channel blockers, valsartan, 
hydrochlorothiazide, sulphonamide-derived medicines (medicines used to treat chest or urinary 

infections), or any of the other ingredients of this medicine (listed in section 6). 

If you think you may be allergic, do not take Dafiro 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). 

 if the level of potassium or sodium in your blood is too low despite treatment to increase the 
potassium or sodium levels in your blood. 

 if the level of calcium in your blood is too high despite treatment to reduce the calcium levels in 
your blood. 

 if you have gout (uric acid crystals in the joints). 

 if you have severe low blood pressure (hypotension). 

 if you have narrowing of the aortic valve (aortic stenosis) or cardiogenic shock (a condition 
where your heart is unable to supply enough blood to the body). 

 if you suffer from heart failure after a heart attack. 

 if you have diabetes or impaired kidney function and you are treated with a blood pressure 
lowering medicine containing aliskiren. 

If any of the above applies to you, do not take Dafiro HCT and talk to your doctor. 

 

Warnings and precautions 

Talk to your doctor or pharmacist before taking Dafiro 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 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 
prescribed the maximum dose of Dafiro HCT (10 mg/320 mg/25 mg). 

 if you have experienced a heart attack. Follow your doctor’s instructions for the starting dose 
carefully. Your doctor may also check your kidney function. 

 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 Dafiro 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). 



77 

 if you have experienced swelling, particularly of the face and throat, while taking other 
medicines (including angiotensin converting enzyme inhibitors). If you get these symptoms, 

stop taking Dafiro HCT and contact your doctor straight away. You should never take Dafiro 

HCT again. 

 if you experience dizziness and/or fainting during treatment with Dafiro HCT, tell your doctor 
as soon as possible. 

 if you experience a decrease in vision or eye pain. These could be symptoms of fluid 
accumulation in the vascular layer of the eye (choroidal effusion) or an increase of pressure in 

your eye and can happen within hours to a week of taking Dafiro HCT. This can lead to 

permanent vision impairment, if not treated. 

 if you are taking any of the following medicines used to treat high blood pressure: 

 an ACE inhibitor (for example enalapril, lisinopril, ramipril), in particular if you have 
diabetes-related kidney problems. 

 aliskiren. 

 if you have had skin cancer or if you develop an unexpected skin lesion during the treatment. 
Treatment with hydrochlorothiazide, particularly long term use with high doses, may increase 

the risk of some types of skin and lip cancer (non-melanoma skin cancer). Protect your skin 

from sun exposure and UV rays while taking Dafiro HCT. 

 

Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. 

potassium) in your blood at regular intervals. 

 

See also information under the heading “Do not take Dafiro HCT”. 

 

If any of these apply to you, talk to your doctor. 
 

Children and adolescents 

The use of Dafiro HCT in children and adolescents under 18 years of age is not recommended. 

 

Elderly people (age 65 years and older) 

Dafiro 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 Dafiro HCT 

(10 mg/320 mg/25 mg), should have their blood pressure checked regularly. 

 

Other medicines and Dafiro HCT 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. Your doctor may need to change your dose and/or to 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; 

• ACE inhibitors or aliskiren –(see also information under the headings “Do not take Dafiro 

HCT” and “Warnings and precautions”) . 

 

  



78 

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), erythromycin, clarithromycin (antibiotics); 

• St. John’s wort; 

• dantrolene (infusion for severe body temperature abnormalities); 

• vitamin D and calcium salts. 

 

Dafiro HCT with food, drink and alcohol 

Grapefruit and grapefruit juice should not be consumed by people who are prescribed Dafiro 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 Dafiro HCT. 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. 

 

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 Dafiro HCT before you become pregnant or as soon as you know 

you are pregnant and will advise you to take another medicine instead of Dafiro HCT. Dafiro 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. 

 



79 

Breast-feeding 

Tell your doctor if you are breast-feeding or about to start breast-feeding. Amlodipine has been 

shown to pass into breast milk in small amounts. Dafiro 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 

This medicine may make you feel dizzy, drowsy, nauseous or have a headache. If you experience 

these symptoms, do not drive or use tools or machines. 

 

 

3. How to take Dafiro HCT 
 

Always take this medicine exactly as your doctor has told you. 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 Dafiro 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 Dafiro HCT with or without food. Do not take Dafiro HCT with grapefruit or 
grapefruit juice. 

 

Depending on how you respond to the treatment, your doctor may suggest a higher or lower dose. 

 

Do not exceed the prescribed dose. 

 

If you take more Dafiro HCT than you should 

If you have accidentally taken too many Dafiro HCT tablets, talk to a doctor immediately.You may 

require medical attention. 

 

If you forget to take Dafiro 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 Dafiro HCT 

Stopping your treatment with Dafiro HCT may cause your disease to get worse. Do not stop taking 

your medicine unless your doctor tells you to. 

 

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 medicine, ask your doctor or pharmacist. 

 

 

  



80 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

As for any combination containing three active substances, side effects associated with each individual 

component cannot be excluded. The side effects reported with Dafiro HCT or one of its three active 

substances (amlodipine, valsartan and hydrochlorothiazide) are listed below and may occur with the 

use of Dafiro HCT. 

 

Some side effects can be serious and need immediate medical attention. 

Consult a doctor immediately if you experience any of the following serious side effects after 

taking this medicine: 

Common (may affect up to 1 in 10 people): 

 dizziness 

 low blood pressure (feeling of faintness, light-headedness, sudden loss of consciousness) 
 

Uncommon (may affect up to 1 in 100 people): 

 severely decreased urine output (decreased kidney function) 
 

Rare (may affect up to 1 in 1,000 people): 

 spontaneous bleeding 

 irregular heart beat 

 liver disorder 
 

Very rare (may affect up to 1 in 10,000 people): 

 sudden wheeziness, chest pain, shortness of breath or difficulty breathing 

 swelling of eyelids, face or lips 

 swelling of the tongue and throat which causes great difficulty breathing 

 severe skin reactions including intense skin rash, hives, reddening of the skin over your whole 
body, severe itching, blistering, peeling and swelling of the skin, inflammation of the mucous 

membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis) or other allergic reactions 

 heart attack 

 inflamed pancreas, which may cause severe abdominal and back pain accompanied with feeling 
of being very unwell 

 weakness, bruising, fever and frequent infections 

 stiffness 
 

Other side effects may include: 
Very common (may affect more than 1 in 10 people): 

 low level of potassium in the blood 

 increase of lipids in the blood 
 

Common (may affect up to 1 in 10 people): 

 sleepiness 

 palpitations (awareness of your heart beat) 

 flushing 

 ankle swelling (oedema) 

 abdominal pain 

 stomach discomfort after meal 

 tiredness 

 headache 

 frequent urination 

 high level of uric acid in the blood 

 low level of magnesium in the blood 

 low level of sodium in the blood 



81 

 dizziness, fainting on standing up 

 reduced appetite 

 nausea and vomiting 

 itchy rash and other types of rash 

 inability to achieve or maintain erection 
 

Uncommon (may affect up to 1 in 100 people): 

 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 

 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 

 sudden, temporary loss of consciousness 

 low blood pressure on standing up 

 cough 

 breathlessness 

 throat irritation 

 excessive sweating 

 itching 

 swelling, reddening and pain along a vein 

 skin reddening 

 trembling 

 mood changes 

 anxiety 

 depression 

 sleeplessness 

 taste abnormalities 

 fainting 

 loss of pain sensation 

 visual disturbances 

 visual impairment 

 ringing in the ears 

 sneezing/runny nose caused by inflammation of the lining of the nose (rhinitis) 



82 

 altered bowel habits 

 indigestion 

 hair loss 

 itchy skin 

 skin discolouration 

 disorder in passing urine 

 increased need to urinate at night 

 increased number of times of passing urine 

 discomfort or enlargement of the breasts in men 

 pain 

 feeling unwell 

 weight decrease 
 

Rare (may affect up to 1 in 1,000 people): 

 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 

 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 

 confusion 
 

Very rare (may affect up to 1 in 10,000 people): 

 decreased number of white blood cells 

 decrease in blood platelets which may result in unusual brusing or easy bleeding (red blood cell 
damage) 

 swelling of the gums 

 abdominal bloating (gastritis) 

 inflammation of the liver (hepatitis) 

 yellowing of the skin (jaundice) 

 liver enzyme increase which may have an effect on some medical tests 

 increased muscle tension 

 inflammation of blood vessels often with skin rash 

 sensitivity to light 

 disorders combining rigidity, tremor and/or movement disorders 

 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) 

 difficulty breathing with fever, coughing, wheezing, breathlessness (respiratory distress, 
pulmonary oedema, pneumonitis) 

 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) 

 



83 

Not known (frequency cannot be estimated from the available data): 

 changes in blood tests for kidney function, increase of potassium in your blood, low level of red 
blood cells 

 abnormal red blood cell test 

 low level of a certain type of white blood cell and blood platelet 

 increase of creatinine in the blood 

 abnormal liver function test 

 severely decreased urine output 

 inflammation of blood vessels 

 weakness, bruising and frequent infections (aplastic anaemia) 

 decrease in vision or pain in your eyes due to high pressure (possible signs of fluid 
accumulation in the vascular layer of the eye (choroidal effusion) or 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) 

 blistering skin (sign of a condition called dermatitis bullous) 

 skin and lip cancer (non-melanoma skin cancer) 
 

Reporting of side effects 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. By reporting side effects you can help provide more information on the safety of 

this medicine. 

 

 

5. How to store Dafiro HCT 
 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine 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 Dafiro HCT pack that is damaged or shows signs of tampering. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

 

 

  



84 

6. Contents of the pack and other information 

 

What Dafiro HCT contains 

 

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

The active substances of Dafiro HCT are amlodipine (as amlodipine besylate), valsartan and 

hydrochlorothiazide. 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 (type A); silica, colloidal 

anhydrous; magnesium stearate; hypromellose (substitution type 2910 (3 mPa.s)), macrogol 4000, talc, 

titanium dioxide (E171). 

 

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

The active substances of Dafiro HCT are amlodipine (as amlodipine besylate), valsartan and 

hydrochlorothiazide. 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 (type A); silica, colloidal 

anhydrous; magnesium stearate; hypromellose (substitution type 2910 (3 mPa.s)), macrogol 4000, talc, 

titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172). 

 

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

The active substances of Dafiro HCT are amlodipine (as amlodipine besylate), valsartan and 

hydrochlorothiazide. 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 (type A); silica, colloidal 

anhydrous, magnesium stearate, hypromellose (substitution type 2910 (3 mPa.s)), macrogol 4000, talc, 

titanium dioxide (E171), yellow iron oxide (E172). 

 

Dafiro HCT 10 mg/160 mg/25 mg film-coated tablets 

The active substances of Dafiro HCT are amlodipine (as amlodipine besylate), valsartan and 

hydrochlorothiazide. 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 (type A); silica, colloidal 

anhydrous, magnesium stearate, hypromellose (substitution type 2910 (3 mPa.s)), macrogol 4000, talc, 

yellow iron oxide (E172). 

 

Dafiro 10 mg/320 mg/25 mg film-coated tablets 

The active substances of Dafiro HCT are amlodipine (as amlodipine besylate), valsartan and 

hydrochlorothiazide. 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 (type A); silica, colloidal 

anhydrous, magnesium stearate, hypromellose (substitution type 2910 (3 mPa.s)), macrogol 4000, talc, 

yellow iron oxide (E172). 

 

  



85 

What Dafiro HCT looks like and contents of the pack 

Dafiro 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. Approximate size: 15 mm (length) x 5.9 mm (width). 

 

Dafiro 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. Approximate size: 15 mm (length) x 5.9 mm (width). 

 

Dafiro 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. Approximate size: 15 mm (length) x 5.9 mm (width). 

 

Dafiro 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. Approximate size: 15 mm (length) x 5.9 mm (width). 

 

Dafiro 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. Approximate size: 19 mm (length) x 7.5 mm (width). 

 

Dafiro 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 perforated dose 

blisters. Not all pack sizes may be available in your country. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

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 

 

Lietuva 

SIA „Novartis Baltics“ Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 



86 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Nederland 

Novartis Pharma B.V. 

Tel: +31 26 37 82 111 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

Deutschland 

Novartis Pharma GmbH           
Tel: +49 911 273 0 

Eesti 

SIA Novartis Baltics Eesti filiaal 
Tel: +372 66 30 810 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

España 

Esteve Pharmaceuticals, S.A. 
Tel: +34 93 446 60 00 

France 

Novartis Pharma S.A.S. 
Tél: +33 1 55 47 66 00 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

Ireland 

Novartis Ireland Limited 
Tel: +353 1 260 12 55 

Ísland 

Vistor hf. 
Sími: +354 535 7000 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Κύπρος 

Novartis Pharma Services Inc. 
Τηλ: +357 22 690 690 

Latvija 

SIA “Novartis Baltics” 
Tel: +371 67 887 070 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

This leaflet was last revised in 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET