Sprimeo HCT

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 

 

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1. NAME OF THE MEDICINAL PRODUCT 
 

Sprimeo HCT 150 mg/12.5 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

Excipients: Each tablet contains 25 mg lactose monohydrate and 24.5 mg wheat starch. 

 

For a full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Film-coated tablet 

 

White, biconvex, ovaloid film-coated tablet imprinted with “LCI” on one side and “NVR” on the 

other. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Treatment of essential hypertension in adults. 

 

Sprimeo HCT is indicated in patients whose blood pressure is not adequately controlled on aliskiren or 

hydrochlorothiazide used alone. 

 

Sprimeo HCT is indicated as substitution therapy in patients adequately controlled with aliskiren and 

hydrochlorothiazide, given concurrently, at the same dose level as in the combination. 

 

4.2 Posology and method of administration 

 

The recommended dose of Sprimeo HCT is one tablet per day. Sprimeo HCT should be taken with a 

light meal once a day, preferably at the same time each day. Grapefruit juice should not be taken 

together with Sprimeo HCT. 

 

The antihypertensive effect is largely manifested within 1 week and the maximum effect is generally 

seen within 4 weeks. 

 

Posology in patients not adequately controlled with aliskiren or hydrochlorothiazide monotherapy 

Individual dose titration with each of the two components may be recommended before changing to 

the fixed combination. When clinically appropriate, direct change from monotherapy to the fixed 

combination may be considered. 

 

Sprimeo HCT 150 mg /12.5 mg may be administered in patients whose blood pressure is not 

adequately controlled with aliskiren 150 mg or hydrochlorothiazide 12.5 mg alone. 

 

If blood pressure remains uncontrolled after 2-4 weeks of therapy, the dose may be titrated up to a 

maximum of Sprimeo HCT 300 mg/25 mg daily. Dosing should be individualised and adjusted 

according to the patient’s clinical response. 

 

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Posology as substitution therapy 

For convenience, patients receiving aliskiren and hydrochlorothiazide from separate tablets may be 

switched to a fixed combination tablet of Sprimeo HCT containing the same component doses. 

 

Renal impairment 

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

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

use in patients with anuria and in patients with severe renal impairment (glomerular filtration rate 

(GFR) < 30 ml/min/1.73 m
2
). The concomitant use of Sprimeo HCT with angiotensin II receptor 

blockers (ARB) or angiotensin converting enzyme inhibitors (ACEI) is contraindicated in patients 

with renal impairment (GFR < 60 ml/min/1.73 m
2
) (see sections 4.3, 4.4 and 5.2). 

 

Hepatic impairment 

No adjustment of the initial dose is required for patients with mild to moderate hepatic impairment 

(see section 5.2). Sprimeo HCT is contraindicated in patients with severe hepatic impairment (see 

sections 4.3 and 4.4). 

 

Elderly patients (over 65 years) 

The recommended starting dose of aliskiren in elderly patients is 150 mg. No clinically meaningful 

additional blood pressure reduction is observed by increasing the dose to 300 mg in the majority of 

elderly patients. 

 

Paediatric patients 

Sprimeo HCT is not recommended for use in children and adolescents below age 18 due to a lack of 

data on safety and efficacy (see section 5.2). 

 

4.3 Contraindications 
 

 Hypersensitivity to the active substances or to any of the excipients (see section 6.1), or to other 
sulphonamide-derived substances. 

 History of angioedema with aliskiren. 

 Hereditary or idiopathic angioedema. 

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

 Anuria. 

 Severe renal impairment (GFR < 30 ml/min/1.73 m2). 

 Refractory hypokalaemia, hyponatraemia, hypercalcaemia and symptomatic hyperuricaemia. 

 Severe hepatic impairment. 

 The concomitant use of aliskiren with ciclosporin and itraconazole, two highly potent P-
glycoprotein (P-gp) inhibitors, and other potent P-gp inhibitors (e.g. quinidine), is 

contraindicated (see section 4.5). 

 The concomitant use of aliskiren with ARBs or ACEIs is contraindicated in patients with 
diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m

2
) (see sections 4.2, 4.4, 4.5 and 

5.1). 

 

4.4 Special warnings and precautions for use 
 

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

Hypotension, syncope, stroke, hyperkalaemia, and changes in renal function (including acute renal 

failure) have been reported in susceptible individuals, especially if combining medicinal products that 

affect this system (see section 5.1). Dual blockade of the renin-angiotensin-aldosterone system by 

combining aliskiren with an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin II 

receptor blocker (ARB) is therefore not recommended. 

 

The use of aliskiren in combination with ARBs or ACEIs is contraindicated in patients with diabetes 

mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) (see section 4.3). 

 

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Heart failure 

Aliskiren should be used with caution in patients with serious congestive heart failure (New York 

Heart Association (NYHA) functional class III-IV). Sprimeo HCT should be used with caution in 

patients with heart failure due to limited clinical efficacy and safety data. 

 

Angioedema 

As with other agents acting on the renin-angiotensin system, angioedema or symptoms suggestive of 

angioedema (swelling of the face, lips, throat and/or tongue) have been reported in patients treated 

with aliskiren. 

 

A number of these patients had a history of angioedema or symptoms suggestive of angioedema, 

which in some cases followed use of other medicines that can cause angioedema, including RAAS 

blockers (angiotensin converting enzyme inhibitors or angiotensin receptor blockers) (see section 4.8). 

 

Patients with a history of angioedema may be at increased risk of experiencing angioedema during 

treatment with aliskiren (see sections 4.3 and 4.8). Caution should therefore be exercised when 

prescribing aliskiren to patients with a history of angioedema, and such patients should be closely 

monitored during treatment (see section 4.8) especially at the beginning of the treatment. 

 

If angioedema occurs, Sprimeo HCT should be promptly discontinued and appropriate therapy and 

monitoring provided until complete and sustained resolution of signs and symptoms has occurred. 

Where there is involvement of the tongue, glottis or larynx adrenaline should be administered. In 

addition, measures necessary to maintain patent airways should be provided. 

 

Sodium- and/or volume-depleted patients 

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 Sprimeo HCT. Sprimeo HCT 

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

 

Electrolyte imbalance 

Treatment with Sprimeo 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 Sprimeo HCT should be discontinued until stable correction of the potassium balance. 

Although hypokalaemia may develop with the use of thiazide diuretics, concurrent therapy with 

aliskiren may reduce diuretic-induced hypokalaemia. The risk of hypokalaemia is greater in patients 

with cirrhosis of the liver, patients experiencing brisk diuresis, patients with inadequate oral 

electrolyte intake and patients receiving concomitant therapy with corticosteroids or 

adrenocorticotropic hormone (ACTH) (see sections 4.5 and 4.8). 

 

Conversely, increases in serum potassium have been observed with aliskiren in post-marketing 

experience and these may be exacerbated by concomitant use of other agents acting on the RAAS or 

by non-steroidal anti-inflammatory drugs (NSAIDs). Consistent with standard medical practice, 

periodic determination of renal function including serum electrolytes is advised if co-administration is 

considered necessary. The concomitant use of aliskiren and ACEIs or ARBs is contraindicated in 

patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) (see sections 4.3, 4.5 

and 4.8). 

 

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 Sprimeo HCT therapy, the treatment should be discontinued until 

normalisation of natraemia. 

 

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There is no evidence that Sprimeo HCT would reduce or prevent diuretic-induced hyponatraemia. 

Chloride deficit is generally mild and usually does not require treatment. 

 

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

electrolytes, particularly potassium, sodium and magnesium. 

 

Thiazides reduce urinary calcium excretion and may cause an intermittent and slight elevation of 

serum calcium in the absence of known disorders of calcium metabolism. Sprimeo HCT is 

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

existing hypercalcaemia. Sprimeo 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. 

 

Renal impairment and kidney transplantation 

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

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

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

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

 

No dosage adjustment is necessary in patients with mild to moderate renal impairment (GFR 

≥ 30 ml/min/1.73 m
2
). 

 

There is no experience regarding the administration of Sprimeo HCT in patients who have recently 

undergone kidney transplantation. 

 

As for other agents acting on the renin-angiotensin system, caution should be exercised when aliskiren 

is given in the presence of conditions pre-disposing to kidney dysfunction such as hypovolaemia (e.g. 

due to blood loss, severe or prolonged diarrhoea, prolonged vomiting, etc.), heart disease, liver 

disease, diabetes mellitus or kidney disease. The concomitant use of aliskiren and ACEIs or ARBs is 

contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m
2
). Acute renal failure, 

reversible upon discontinuation of treatment, has been reported in at-risk patients receiving aliskiren in 

post-marketing experience. In the event that any signs of renal failure occur, aliskiren should be 

promptly discontinued. 

 

Hepatic impairment 

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver 

disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. No 

adjustment of the initial dose is required for patients with mild to moderate hepatic impairment. No 

data are available for the use of Sprimeo HCT in patients with severe hepatic impairment. Due to the 

hydrochlorothiazide component, Sprimeo HCT is contraindicated in patients with severe hepatic 

impairment (see sections 4.3 and 5.2). 

 

There is no clinical experience with Sprimeo HCT in patients with hepatic impairment. 

 

Moderate P-gp inhibitors 

Co-administration of aliskiren 300 mg with ketoconazole 200 mg or verapamil 240 mg resulted in a 

76% or 97% increase in aliskiren AUC, respectively. Therefore caution should be exercised when 

aliskiren is administered with moderate P-gp inhibitors such as ketoconazole or verapamil (see section 

4.5). 

 

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy 

As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral 

stenosis, or obstructive hypertrophic cardiomyopathy. 

 

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Renal artery stenosis and renovascular hypertension 

No controlled clinical data are available on the use of Sprimeo HCT in patients with unilateral or 

bilateral renal artery stenosis, or stenosis to a solitary kidney. However, as with other agents acting on 

the renin-angiotensin system, there is an increased risk of renal insufficiency, including acute renal 

failure, when patients with renal artery stenosis are treated with aliskiren. Therefore caution should be 

exercised in these patients. If renal failure occurs, treatment should be discontinued. 

 

Systemic lupus erythematosus 

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

systemic lupus erythematosus. 

 

Metabolic and endocrine effects 

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

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

hypoglycaemic agents may be required. Concomitant use of Sprimeo HCT with ARBs or ACEIs is 

contraindicated in patients with diabetes mellitus (see section 4.3). 

 

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

hyperuricaemia (see section 4.3). 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 an intermittent and slight elevation of 

serum calcium in the absence of known disorders of calcium metabolism. Sprimeo HCT is 

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

existing hypercalcaemia. Sprimeo 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 Sprimeo HCT, it is recommended to stop the 

treatment. If a re-administration of the diuretic is deemed necessary, it is recommended to protect 

exposed areas to the sun or to artificial UVA. 

 

Acute angle-closure glaucoma 

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

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

visual acuity or ocular pain and typically occur within hours to weeks 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 

In the event of severe and persistent diarrhoea, Sprimeo HCT therapy should be stopped. 

 

As with any antihypertensive agent, excessive reduction of blood pressure in patients with ischaemic 

cardiopathy or ischaemic cardiovascular disease could result in a myocardial infarction or stroke. 

 

Hypersensitivity reactions to hydrochlorothiazide may occur in patients, but are more likely in patients 

with allergy and asthma. 

 

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Excipients 

Sprimeo HCT contains lactose. Patients with rare hereditary problems of galactose intolerance, the 

Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. 

 

Sprimeo HCT contains wheat starch. It is suitable for people with coeliac disease. Patients with wheat 

allergy (different from coeliac disease) should not take this medicine. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Information on Sprimeo HCT interactions 

Medicinal products affecting serum potassium levels: The potassium-depleting effect of 

hydrochlorothiazide is attenuated by the potassium-sparing effect of aliskiren. However, this effect of 

hydrochlorothiazide on serum potassium would be expected to be potentiated by other medicinal 

products associated with potassium loss and hypokalaemia (e.g. other kaliuretic diuretics, 

corticosteroids, laxatives, adrenocorticotropic hormone (ACTH), amphotericin, carbenoxolone, 

penicillin G, salicylic acid derivatives). Conversely, concomitant use of other agents affecting the 

RAAS, of NSAIDs or of agents that increase serum potassium levels (e.g. potassium-sparing diuretics, 

potassium supplements, salt substitutes containing potassium, heparin) may lead to increases in serum 

potassium. If co-medication with an agent affecting the level of serum potassium is considered 

necessary, caution is advisable. The combination of aliskiren with ARBs or ACEIs is contraindicated 

in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) and is not 

recommended in other patients (see sections 4.3, 4.4 and 5.1). 

 

Medicinal products affected by serum potassium disturbances: Periodic monitoring of serum 

potassium is recommended when Sprimeo HCT is administered with medicinal products affected by 

serum potassium disturbances (e.g. digitalis glycosides, antiarrhythmics). 

 

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors 

(COX-2 inhibitors), acetylsalicylic acid and non-selective NSAIDs: As with other agents acting on the 

renin-angiotensin system, NSAIDs may reduce the anti-hypertensive effect of aliskiren. NSAIDs may 

also weaken the diuretic and antihypertensive activity of hydrochlorothiazide. 

 

In some patients with compromised renal function (dehydrated patients or elderly patients) aliskiren 

and hydrochlorothiazide given concomitantly with NSAIDs may result in further deterioration of renal 

function, including possible acute renal failure, which is usually reversible. Therefore the use of 

Sprimeo HCT with an NSAID requires caution, especially in elderly patients. 

 

Other antihypertensive agents: The antihypertensive effect of Sprimeo HCT may be increased with 

the concomitant use of other antihypertensive agents. 

 

Additional information on aliskiren interactions 

The combination of aliskiren with ARBs or ACEIs is contraindicated in patients with diabetes mellitus 

or renal impairment (GFR < 60 ml/min/1.73 m
2
) and is not recommended in other patients (see 

sections 4.3, 4.4 and 5.1). 

 

Compounds that have been investigated in aliskiren clinical pharmacokinetic studies include 

acenocoumarol, atenolol, celecoxib, fenofibrate, pioglitazone, allopurinol, isosorbide-5-mononitrate, 

digoxin, metformin, amlodipine, atorvastatin, cimetidine and hydrochlorothiazide. No clinically 

relevant interactions have been identified. As a result no dose adjustment for aliskiren or these co-

administered medicinal products is necessary. 

 

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P-glycoprotein interactions: MDR1/Mdr1a/1b (P-gp) was found to be the major efflux system 

involved in intestinal absorption and biliary excretion of aliskiren in preclinical studies. Rifampicin, 

which is an inducer of P-gp, reduced aliskiren bioavailability by approximately 50% in a clinical 

study. Other inducers of P-gp (St. John’s wort) might decrease the bioavailability of aliskiren. 

Although this has not been investigated for aliskiren, it is known that P-gp also controls tissue uptake 

of a variety of substrates and P-gp inhibitors can increase the tissue-to-plasma concentration ratios. 

Therefore, P-gp inhibitors may increase tissue levels more than plasma levels. The potential for drug 

interactions at the P-gp site will likely depend on the degree of inhibition of this transporter. 

 

P-gp potent inhibitors: A single dose drug interaction study in healthy subjects has shown that 

ciclosporin (200 and 600 mg) increases Cmax of aliskiren 75 mg approximately 2.5-fold and AUC 

approximately 5-fold. The increase may be higher with higher aliskiren doses. In healthy subjects, 

itraconazole (100 mg) increases AUC and Cmax of aliskiren (150 mg) by 6.5-fold and 5.8-fold, 

respectively. Therefore, concomitant use of aliskiren and P-gp potent inhibitors is contraindicated (see 

section 4.3). 

 

Moderate P-gp inhibitors: Co-administration of ketoconazole (200 mg) or verapamil (240 mg) with 

aliskiren (300 mg) resulted in a 76% or 97% increase in aliskiren AUC, respectively. The change in 

plasma levels of aliskiren in the presence of ketoconazole or verapamil is expected to be within the 

range that would be achieved if the dose of aliskiren were doubled; aliskiren doses of up to 600 mg, or 

twice the highest recommended therapeutic dose, have been found to be well tolerated in controlled 

clinical trials. Preclinical studies indicate that aliskiren and ketoconazole co-administration enhances 

aliskiren gastrointestinal absorption and decreases biliary excretion. Therefore, caution should be 

exercised when aliskiren is administered with ketoconazole, verapamil or other moderate P-gp 

inhibitors (clarithromycin, telithromycin, erythromycin, amiodarone). 

 

P-gp substrates or weak inhibitors: No relevant interactions with atenolol, digoxin, amlodipine or 

cimetidine have been observed. When administered with atorvastatin (80 mg), steady-state aliskiren 

(300 mg) AUC and Cmax increased by 50%. 

 

Organic anion transporting polypeptide (OATP) inhibitors: Preclinical studies indicate that aliskiren 

might be a substrate of organic anion transporting polypeptides. Therefore, the potential exists for 

interactions between OATP inhibitors and aliskiren when administered concomitantly (see interaction 

with Grapefruit juice). 

 

Grapefruit juice: Administration of grapefruit juice with aliskiren resulted in a decrease in AUC and 

Cmax of aliskiren. Co-administration with aliskiren 150 mg resulted in a 61% decrease in aliskiren 

AUC and co-administration with aliskiren 300 mg resulted in a 38% decrease in aliskiren AUC. This 

decrease is likely due to an inhibition of organic anion transporting polypeptide-mediated uptake of 

aliskiren by grapefruit juice in the gastrointestinal tract. Therefore, because of the risk of therapeutic 

failure, grapefruit juice should not be taken together with Sprimeo HCT. 

 

Furosemide: When aliskiren was co-administered with furosemide, the AUC and Cmax of furosemide 

were reduced by 28% and 49%, respectively. It is therefore recommended to monitor the effects when 

initiating and adjusting furosemide therapy to avoid possible underutilisation in clinical situations of 

volume overload. 

 

Warfarin: The effects of aliskiren on warfarin pharmacokinetics have not been evaluated. 

 

Food interactions: Meals with a high fat content have been shown to reduce the absorption of aliskiren 

substantially. 

 

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Additional information on hydrochlorothiazide interactions 

When administered concurrently, the following medicinal products may interact with thiazide 

diuretics: 

 

Lithium: Renal clearance of lithium is reduced by thiazides, therefore the risk of lithium toxicity may 

be increased with hydrochlorothiazide. Co-administration of lithium and hydrochlorothiazide is not 

recommended. If this combination proves essential, careful monitoring of serum lithium level is 

recommended during concomitant use. 

 

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 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. 

 

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. 

 

Digoxine or other digitalis glycosides: Thiazide-induced hypokalaemia or hypomagnesaemia may 

occur as undesirable effects, favouring the onset of digitalis-induced cardiac arrhythmias. 

 

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. 

 

Antidiabetic agents (e.g. insulin and oral antidiabetic agents): Thiazides may alter glucose tolerance. 

Dose adjustment of the antidiabetic medicinal product may be necessary (see section 4.4). 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. 

 

Medicinal products used in the treatment of gout: 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. 

 

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. 

 

Amantadine: Thiazides, including hydrochlorothiazide, may increase the risk of adverse reactions 

caused by amantadine. 

 

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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. 

 

Cytotoxic agents: Thiazides, including hydrochlorothiazide, may reduce the renal excretion of 

cytotoxic agents (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects. 

 

Non-depolarising skeletal muscle relaxants: Thiazides, including hydrochlorothiazide, potentiate the 

action of skeletal muscle relaxants such as curare derivatives. 

 

Alcohol, barbiturates or narcotics: Concomitant administration of thiazide diuretics with subtances 

that also have a blood pressure lowering effect (e.g. by reducing sympathetic central nervous system 

activity or direct vasodilatation) may potentiate orthostatic hypotension. 

 

Methyldopa: There have been isolated reports of haemolytic anaemia occurring with concomitant use 

of hydrochlorothiazide and methyldopa. 

 

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 rehydrated before 

administration. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

There are no data on the use of aliskiren in pregnant women. Aliskiren was not teratogenic in rats or 

rabbits (see section 5.3). Other substances that act directly on the RAAS have been associated with 

serious foetal malformations and neonatal death when used during second and third trimesters. 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. 

 

Hydrochlorothiazide should not be used for gestational oedema, gestational hypertension or 

pre-eclampsia due to the risk of decreased plasma volume and placental hypoperfusion, without a 

beneficial effect on the course of the disease. 

 

Hydrochlorothiazide should not be used for essential hypertension in pregnant women except in rare 

situations where no other treatment could be used. 

 

No specific clinical studies have been performed with this combination, therefore Sprimeo HCT 

should not be used during the first trimester of pregnancy or in women planning to become pregnant 

and is contraindicated during the second and third trimesters (see section 4.3). A switch to a suitable 

alternative treatment should be carried out in advance of a planned pregnancy. If pregnancy is detected 

during therapy, Sprimeo HCT should be discontinued as soon as possible. 

 

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Breast-feeding 

It is not known whether aliskiren is excreted in human milk. Aliskiren was secreted in the milk of 

lactating rats. 

 

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

intense diuresis can inhibit milk production. 

 

The use of Sprimeo HCT during breast-feeding is not recommended. If Sprimeo HCT is used during 

breast-feeding, doses should be kept as low as possible. 

 

4.7 Effects on ability to drive and use machines 
 

No studies on the effect on the ability to drive and use machines have been performed. Sprimeo HCT 

is unlikely to affect the ability to drive and use machines. However, when driving vehicles or 

operating machinery it must be borne in mind that dizziness or drowsiness may occasionally occur 

when taking antihypertensive therapy. 

 

4.8 Undesirable effects 

 

Aliskiren/hydrochlorothiazide combination 

The safety of Sprimeo HCT has been evaluated in 9 clinical trials with more than 3,900 patients, 

including over 700 treated for over 6 months, and 190 for over 1 year. The incidence of adverse 

reactions showed no association with gender, age, body mass index, race or ethnicity. Treatment with 

Sprimeo HCT had an overall incidence of adverse experiences at doses up to 300 mg/25 mg similar to 

placebo. Adverse reactions have generally been mild and transient in nature and have only 

infrequently required discontinuation of therapy. The most common adverse drug reaction observed 

with Sprimeo HCT is diarrhoea. The adverse drug reactions previously reported with one of the 

individual components of Sprimeo HCT (aliskiren and hydrochlorothiazide) and listed in the 

respective paragraphs on the individual components may occur with Sprimeo HCT. 

 

The frequency of adverse reactions listed below is defined using the following convention: 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) and not known (cannot be estimated from the available data). 

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 

 

Gastrointestinal disorders 

 Common: Diarrhoea 

 

Diarrhoea: Diarrhoea is a dose-related adverse drug reaction for aliskiren. In controlled clinical trials, 

the incidence of diarrhoea in Sprimeo HCT-treated patients was 1.3% compared to 1.4% for aliskiren- 

or 1.9% for hydrochlorothiazide-treated patients. 

 

Serum potassium: In a large placebo-controlled clinical trial, the opposite effects of aliskiren (150 mg 

or 300 mg) and hydrochlorothiazide (12.5 mg or 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 potassium to detect possible electrolyte imbalance should be performed in 

patients at risk at appropriate intervals (see sections 4.4 and 4.5). 

 

Additional information on individual components 

Other adverse reactions previously reported with one of the individual components may occur with 

Sprimeo HCT even if not observed in clinical trials. 

 

Aliskiren 

Treatment with Aliskiren up to 300 mg resulted in an overall incidence of adverse reactions similar to 

placebo. Adverse reactions have generally been mild and transient in nature and have only 

infrequently required discontinuation of therapy. The most common adverse drug reaction is 

diarrhoea. 

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12 

 

The known aliskiren adverse drug reactions are presented in the table below using the same 

convention as described previously for the fixed combination. 

 

Nervous system disorders 

 Common: Dizziness 

Vascular disorders 

 Uncommon: Hypotension 

Gastrointestinal disorders 

 Common: Diarrhoea 

Immune system disorders 

 Rare: Hypersensitivity reactions 

Skin and subcutaneous tissue disorders 

 Uncommon: Rash, severe cutaneous adverse reactions (SCARs) including toxic 

epidermal necrolysis (TEN) and oral mucosal reactions 

 Rare: Angioedema 

Musculoskeletal and connective tissue disorders 

 Common: Arthralgia 

Renal and urinary disorders 
 Uncommon: Acute renal failure, renal impairment 

General disorders and administration site conditions 
 Uncommon: Oedema peripheral 

Investigations 
 Common: Hyperkalaemia 

 Rare: Haemoglobin decreased, haematocrit decreased 

 Rare: Blood creatinine increased 

 

Angioedema and hypersensitivity reactions have occurred during treatment with aliskiren. In 

controlled clinical trials, angioedema and hypersensitivity reactions occurred rarely during treatment 

with aliskiren with rates comparable to treatment with placebo or comparators. 

 

Cases of angioedema or symptoms suggestive of angioedema (swelling of the face, lips, throat and/or 

tongue) have also been reported in post-marketing experience. A number of these patients had a 

history of angioedema or symptoms suggestive of angioedema which in some cases was associated 

with the administration of other medicines known to cause angioedema, including RAAS blockers 

(ACE inhibitors or ARBs). 

 

Hypersensitivity reactions have also been reported in post-marketing experience. 

 

In the event of any signs suggesting a hypersensitivity reaction/angioedema (in particular difficulties 

in breathing or swallowing, rash, itching, hives or swelling of the face, extremities, eyes, lips and/or 

tongue, dizziness) patients should discontinue treatment and contact the physician (see section 4.4). 

 

Arthralgia has been reported in post-marketing experience. In some cases this occurred as part of a 

hypersensitivity reaction. 

 

Haemoglobin and haematocrit: Small decreases in haemoglobin and haematocrit (mean decreases of 

approximately 0.05 mmol/l and 0.16 volume percent, respectively) were observed. No patients 

discontinued therapy due to anaemia. This effect is also seen with other agents acting on the renin-

angiotensin system, such as ACEI and ARBs. 

 

Serum potassium: Increases in serum potassium have been observed with aliskiren and these may be 

exacerbated by concomitant use of other agents acting on the RAAS or by NSAIDs. Consistent with 

standard medical practice, periodic determination of renal function including serum electrolytes is 

advised if co-administration is considered necessary. The combination of aliskiren with ARBs or 

ACEIs is contraindicated in patients with diabetes mellitus or renal impairment (GFR 

< 60 ml/min/1.73 m
2
) and is not recommended in other patients (see sections 4.3, 4.4 and 5.1). 

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In post-marketing experience, renal dysfunction and cases of acute renal failure have been reported in 

patients at risk (see section 4.4). There have also been reports of peripheral oedema, increase in blood 

creatinine and severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis 

(TEN) and oral mucosal reactions. 

 

Hydrochlorothiazide 

Hydrochlorothiazide has been extensively prescribed for many years, frequently in higher doses than 

those contained in Sprimeo HCT. The following adverse reactions have been reported in patients 

treated with thiazide diuretics alone, including hydrochlorothiazide: 

 

Blood and lymphatic system disorders 

 Rare: Thrombocytopenia sometimes with purpura 

 Very rare: Agranulocytosis, bone marrow depression, haemolytic anaemia, 

leucopenia 

 Not known: Aplastic anaemia 
Immune system disorders 

 Very rare: Hypersensitivity 

Metabolism and nutrition disorders 

 Very common: Hypokalaemia 

 Common: Hyperuricaemia, hypomagnesaemia, hyponatraemia 

 Rare: Hypercalcaemia, hyperglycaemia, worsening of diabetic metabolic 

state 

 Very rare: Hypochloraemic alkalosis 

Psychiatric disorders 

 Rare: Depression, sleep disturbances 

Nervous system disorders 

 Rare: Dizziness, headache, paraesthesia 

Eye disorders 

 Rare: Visual impairment 

 Not known: Acute angle-closure glaucoma 

Cardiac disorders 

 Rare: Cardiac arrhythmias 

Vascular disorders 

 Common: Orthostatic hypotension 

Respiratory, thoracic and mediastinal disorders 

 Very rare: Respiratory distress (including pneumonitis and pulmonary oedema) 

Gastrointestinal disorders 

 Common: Decreased appetite, mild nausea and vomiting 

 Rare: Abdominal discomfort, constipation, diarrhoea 

 Very rare: Pancreatitis 

Hepatobiliary disorders 

 Rare: Intrahepatic cholestasis, jaundice 

Skin and subcutaneous tissue disorders 

 Common: Urticaria and other forms of rash 

 Rare: Photosensitivity reactions 

 Very rare: Cutaneous lupus erythematosus-like reactions, reactivation of 

cutaneous lupus erythematosus, vasculitis necrotising and toxic 

epidermal necrolysis 

 Not known: Erythema multiforme 

Musculoskeletal and connective tissue disorders 

 Not known: Muscle spasm 

Renal and urinary disorders 

 Not known: Renal dysfunction, acute renal failure 

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Reproductive system and breast disorders 

 Common: Impotence 

General disorders and administration site conditions 

 Not known: Asthenia, pyrexia 

Investigations 

 Very common: Increases in cholesterol and triglycerides 

 Rare: Glycosuria 

 

4.9 Overdose 
 

No information is available on the treatment of overdose with Sprimeo HCT. The most likely 

manifestation of overdose would be hypotension, related to the antihypertensive effect of aliskiren. 

 

Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, 

hypochloraemia, hyponatraemia) and dehydration 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 cardiac arrhythmias associated with the concomitant use of digitalis 

glycosides or certain antiarrhythmic medicinal products. If symptomatic hypotension should occur, 

supportive treatment should be initiated. 

 

In a study conducted in patients with end stage renal disease (ESRD) receiving haemodialysis, dialysis 

clearance of aliskiren was low (< 2% of oral clearance). Therefore dialysis is not adequate to treat 

aliskiren over-exposure. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Renin inhibitor (aliskiren) combinations with diuretics 

(hydrochlorothiazide), ATC code: C09XA52 

Sprimeo HCT combines two antihypertensive compounds to control blood pressure in patients with 

essential hypertension: Aliskiren belongs to the class of direct renin inhibitors and hydrochlorothiazide 

to the class of thiazide diuretics. The combination of these substances with complementary 

mechanisms of action provides an additive antihypertensive effect, reducing blood pressure to a 

greater degree than either component alone. 

 

Aliskiren 

Aliskiren is an orally active, non-peptide, potent and selective direct inhibitor of human renin. 

 

By inhibiting the enzyme renin, aliskiren inhibits the RAAS at the point of activation, blocking the 

conversion of angiotensinogen to angiotensin I and decreasing levels of angiotensin I and 

angiotensin II. Whereas other agents that inhibit the RAAS (angiotensin converting enzyme inhibitors 

(ACEI) and angiotension II receptor blockers (ARB)) cause a compensatory rise in plasma renin 

activity (PRA), treatment with aliskiren decreases PRA in hypertensive patients by approximately 50 

to 80%. Similar reductions were found when aliskiren was combined with other antihypertensive 

agents. The clinical implications of the effects on PRA are not known at the present time. 

 

In hypertensive patients, once-daily administration of aliskiren at doses of 150 mg and 300 mg 

provided dose-dependent reductions in both systolic and diastolic blood pressure that were maintained 

over the entire 24-hour dose interval (maintaining benefit in the early morning) with a mean peak to 

trough ratio for diastolic response of up to 98% for the 300 mg dose. 85 to 90% of the maximal blood-

pressure-lowering effect was observed after 2 weeks. The blood-pressure-lowering effect was 

sustained during long-term treatment (12 months), and was independent of age, gender, body mass 

index and ethnicity. 

 

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Combination therapy studies are available for aliskiren added to the diuretic hydrochlorothiazide, the 

calcium channel blocker amlodipine and the beta blocker atenolol. These combinations were 

efficacious and well tolerated. 

 

The efficacy and safety of aliskiren-based therapy were compared to ramipril-based therapy in a 9-

month non-inferiority study in 901 elderly patients (≥ 65 years) with essential systolic hypertension. 

Aliskiren 150 mg or 300 mg per day or ramipril 5 mg or 10 mg per day were administered for 

36 weeks with optional add-on therapy of hydrochlorothiazide (12.5 mg or 25 mg) at week 12, and 

amlodipine (5 mg or 10 mg) at week 22. Over the 12 week period, aliskiren monotherapy lowered 

systolic/diastolic blood pressure by 14.0/5.1 mmHg, compared to 11.6/3.6 mmHg for ramipril, 

consistent with aliskiren being non-inferior to ramipril at the dosages chosen and the differences in 

systolic and diastolic blood pressure were statistically significant. Tolerability was comparable in both 

treatment arms, however cough was more often reported with the ramipril regimen than the aliskiren 

regimen (14.2% vs. 4.4%), whilst diarrhoea was more common with the aliskiren regimen than for the 

ramipril regimen (6.6% vs. 5.0%). 

 

In a 8-week study in 754 hypertensive elderly (≥ 65 years) and very elderly patients (30% ≥ 75 years) 

aliskiren at doses of 75 mg, 150 mg and 300 mg provided statistically significant superior reduction in 

blood pressure (both systolic and diastolic) when compared to placebo. No additional blood pressure 

lowering effect was detected with 300 mg aliskiren compared to 150 mg aliskiren. All three doses 

were well tolerated in both elderly and very elderly patients. 

 

There has been no evidence of first-dose hypotension and no effect on pulse rate in patients treated in 

controlled clinical studies. With cessation of treatment, blood pressure gradually returned towards 

baseline levels over a period of several weeks, with no evidence of a rebound effect for blood pressure 

or PRA. 

 

In a 36-week study involving 820 patients with ischaemic left ventricular dysfunction, no changes in 

ventricular remodelling as assessed by left ventricular end systolic volume were detected with 

aliskiren compared to placebo on top of background therapy. 

 

The combined rates of cardiovascular death, hospitalisation for heart failure, recurrent heart attack, 

stroke and resuscitated sudden death were similar in the aliskiren group and the placebo group. 

However, in patients receiving aliskiren there was a significantly higher rate of hyperkalaemia, 

hypotension and kidney dysfunction when compared to the placebo group. 

 

Aliskiren was evaluated for cardiovascular and/or renal benefit in a double-blind placebo controlled 

randomised trial in 8,606 patients with type 2 diabetes and chronic kidney disease (evidenced by 

proteinuria and/or GFR < 60 ml/min/1.73 m
2
) with or without cardiovascular disease. In most patients 

arterial blood pressure was well controlled at baseline. The primary endpoint was a composite of 

cardiovascular and renal complications. 

 

In this study, aliskiren 300 mg was compared to placebo when added to standard of care which 

included either an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker. The 

study was discontinued prematurely because the participants were unlikely to benefit from aliskiren. 

Preliminary study results indicated a hazard ratio for the primary endpoint of 1.09 in favour of placebo 

(95% Confidence Interval: 0.97, 1.22, 2-sided p=0.17). In addition, an increased incidence of serious 

adverse outcomes was observed with aliskiren compared to placebo for renal complications (4.7% 

versus 3.3%), hyperkalaemia (36.9% versus 27.1%), hypotension (18.4% versus 14.6%) and stroke 

(2.7% versus 2.0%). The increased incidence of non-fatal stroke was greater in patients with renal 

insufficiency. 

 

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Hydrochlorothiazide 

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

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

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

action of thiazides is through inhibition of the Na+Cl- symporter 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. 

 

Aliskiren/hydrochlorothiazide 

Over 3,900 hypertensive patients received Sprimeo HCT once daily in clinical trials. 

 

In hypertensive patients, once-daily administration of Sprimeo HCT provided dose-dependent 

reductions in both systolic and diastolic blood pressure that were maintained over the entire 24-hour 

dose interval. The antihypertensive effect is largely manifested within 1 week and the maximum effect 

is generally seen within 4 weeks.The blood-pressure-lowering effect was sustained during long-term 

treatment, and was independent of age, gender, body mass index and ethnicity. The antihypertensive 

effect of a single dose of the combination persisted for 24 hours. Upon withdrawal of the aliskiren 

treatment (aliskiren with or without hydrochlorothiazide add-on), the return of blood pressure towards 

baseline was gradual (3-4 weeks) with no evidence of the rebound effect. 

 

Sprimeo HCT was studied in a placebo-controlled trial including 2,762 hypertensive patients with 

diastolic blood pressure ≥ 95 mmHg and < 110 mmHg (mean baseline blood pressure of 

153.6/99.2 mmHg). In this study, Sprimeo HCT in doses from 150 mg/12.5 mg to 300 mg/25 mg 

produced dose-dependent blood pressure reductions (systolic/diastolic) from 17.6/11.9 mmHg to 

21.2/14.3 mmHg, respectively, compared to 7.5/6.9 mmHg with placebo. The greater blood pressure 

reductions with these combination doses were also significantly greater than the respective doses of 

aliskiren and hydrochlorothiazide when used alone. The combination of aliskiren and 

hydrochlorothiazide neutralised the reactive increase of PRA caused by hydrochlorothiazide. 

 

When administered in hypertensive patients with markedly elevated blood pressure (systolic blood 

pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg), Sprimeo HCT in doses from 

150 mg/12.5 mg to 300 mg/25 mg administered without up-titration from monotherapy demonstrated 

significantly greater systolic/diastolic blood pressure control rates (< 140/90 mmHg) as compared to 

the respective monotherapies. In this population, Sprimeo HCT 150 mg/12.5 mg to 300 mg/25 mg 

provided dose-dependent systolic/diastolic blood pressure reduction from 20.6/12.4 mmHg to 

24.8/14.5 mmHg, which were significantly superior to the respective monotherapies. The safety of the 

combination therapy was similar to the respective monotherapies regardless of severity of 

hypertension or of the presence or absence of additional cardiovascular risk. Hypotension and related 

adverse events were uncommon with the combination treatment, with no increased incidence in 

elderly patients. 

 

In a study in 880 randomised patients not adequately responsive to aliskiren 300 mg treatment, the 

combination of aliskiren/hydrochlorothiazide 300 mg/25 mg produced systolic/diastolic blood 

pressure reductions of 15.8/11.0 mmHg, which were significantly greater than aliskiren 300 mg 

monotherapy. In a study in 722 randomised patients not adequately responsive to hydrochlorothiazide 

25 mg treatment, the combination of aliskiren/hydrochlorothiazide 300 mg/25 mg produced 

systolic/diastolic blood pressure reductions of 16.78/10.7 mmHg, which were significantly greater 

than hydrochlorothiazide 25 mg monotherapy. 

 

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In another clinical trial, the efficacy and safety of Sprimeo HCT were also assessed in 489 obese 

hypertensive patients who did not respond to hydrochlorothiazide 25 mg (baseline systolic/diastolic 

blood pressure 149.4/96.8 mmHg). In this difficult-to-treat population, Sprimeo HCT provided a blood 

pressure reduction (systolic/diastolic) of 15.8/11.9 mmHg compared to 15.4/11.3 mmHg for 

irbesartan/hydrochlorothiazide, 13.6/10.3 mmHg for amlodipine/hydrochlorothiazide and 

8.6/7.9 mmHg for hydrochlorothiazide monotherapy, with similar safety to hydrochlorothiazide 

monotherapy. 

 

In a study in 183 randomised patients with severe hypertension (mean sitting diastolic blood pressure 

≥ 105 and < 120 mmHg), aliskiren treatment regimen with optional addition of hydrochlorothiazide 

25 mg was shown to be safe and efficacious in reducing blood pressure. 

 

5.2 Pharmacokinetic properties 
 

Aliskiren 

Absorption 

Following oral absorption, peak plasma concentrations of aliskiren are reached after 1-3 hours. The 

absolute bioavailability of aliskiren is approximately 2-3%. Meals with a high fat content reduce Cmax 

by 85% and AUC by 70%. Steady-state-plasma concentrations are reached within 5-7 days following 

once-daily administration and steady-state levels are approximately 2-fold greater than with the initial 

dose. 

 

Distribution 

Following intravenous administration, the mean volume of distribution at steady state is approximately 

135 litres, indicating that aliskiren distributes extensively into the extravascular space. Aliskiren 

plasma protein binding is moderate (47-51%) and independent of the concentration. 

 

Metabolism and elimination 

The mean half-life is about 40 hours (range 34-41 hours). Aliskiren is mainly eliminated as unchanged 

compound in the faeces (oral radioactive dose recovery = 91%). Approximately 1.4% of the total oral 

dose is metabolised. The enzyme responsible for this metabolism is CYP3A4. Approximately 0.6% of 

the dose is recovered in urine following oral administration. Following intravenous administration, the 

mean plasma clearance is approximately 9 l/h. 

 

Linearity 

Exposure to aliskiren increased slightly more than in proportion to the increase in dose. After single 

dose administration in the dose range of 75 to 600 mg, a 2-fold increase in dose results in a ~2.3 and 

2.6-fold increase in AUC and Cmax, respectively. Mechanisms responsible for the deviation from dose 

proportionality have not been identified. A possible mechanism is saturation of transporters at the 

absorption site or at the hepatobiliary clearance route. 

 

Hydrochlorothiazide 

Absorption 

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

 

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Metabolism and elimination 

Hydrochlorothiazide is eliminated predominantly as unchanged compound. 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. There is more than 95% of the absorbed dose being excreted as 

unchanged compound in the urine. The renal clearance is composed of passive filtration and active 

secretion into the renal tubule. 

 

Aliskiren/hydrochlorothiazide 

Following oral administration of Sprimeo HCT tablets, the median peak plasma concentration time is 

within 1 hour for aliskiren and 2.5 hours for hydrochlorothiazide. 

 

The rate and extent of absorption of Sprimeo HCT are equivalent to the bioavailability of aliskiren and 

hydrochlorothiazide when administered as individual monotherapies. Similar food effect was observed 

for Sprimeo HCT as for the individual monotherapies. 

 

Characteristics in patients 

Sprimeo HCT has been shown to be effective as a once-a-day antihypertensive treatment in adult 

patients, regardless of gender, age, body mass index and ethnicity. 

 

The pharmacokinetics of aliskiren are not significantly affected in patients with mild to moderate liver 

disease. Consequently, no initial dose adjustment of Sprimeo HCT is required in patients with mild to 

moderate hepatic impairment. No data are available on patients with severe hepatic impairment treated 

by Sprimeo HCT. Sprimeo HCT is contraindicated in patients with severe hepatic impairment (see 

section 4.3). 

 

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

contraindicated in patients with anuria or severe renal impairment (GFR < 30 ml/min/1.73 m
2
) and the 

concomitant use of Sprimeo HCT with ARBs or ACEIs is contraindicated in patients with renal 

impairment (GFR < 60 ml/min/1.73 m
2
) (see section 4.3). 

 

The pharmacokinetics of aliskiren were evaluated in patients with end stage renal disease receiving 

haemodialysis. Administration of a single oral dose of 300 mg aliskiren was associated with very 

minor changes in the pharmacokinetics of aliskiren (change in Cmax of less than 1.2 fold; increase in 

AUC of up to 1.6 fold) compared to matched healthy subjects. Timing of haemodialysis did not 

significantly alter the pharmacokinetics of aliskiren in ESRD patients. Therefore, if administration of 

aliskiren in ESRD patients receiving haemodialysis is considered necessary, no dose adjustment is 

warranted in these patients. However, the use of aliskiren is not recommended in patients with severe 

renal impairment (see section 4.4). 

 

No initial dose adjustment of Sprimeo HCT is required in elderly patients. Limited data suggest that 

the systemic clearance of hydrochlorothiazide is reduced in both healthy and hypertensive elderly 

subjects compared to young healthy volunteers. 

 

No pharmacokinetic data are available in the paediatric population. 

 

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5.3 Preclinical safety data 
 

Safety pharmacology studies with aliskiren did not reveal any adverse effects on central nervous, 

respiratory or cardiovascular function. Findings during repeat-dose toxicity studies in animals were 

consistent with the known local irritation potential or the expected pharmacological effects of 

aliskiren. No carcinogenic potential for aliskiren was detected in a 2-year rat study and a 6-month 

transgenic mouse study. One colonic adenoma and one caecal adenocarcinoma recorded in rats at the 

dose of 1,500 mg/kg/day were not statistically significant. Aliskiren was devoid of any mutagenic 

potential, embryo-foetal toxicity or teratogenicity. Fertility, prenatal development and postnatal 

development were unaffected in rats. 

 

Preclinical evaluations to support the administration of hydrochlorothiazide in humans included in 

vitro genotoxicity assays and reproductive toxicity and carcinogenicity studies in rodents. Extensive 

clinical data are available for hydrochlorothiazide and these are reflected in the relevant sections. 

 

The findings observed in the 2-week and 13-week toxicity studies were consistent with those observed 

previously with aliskiren or hydrochlorothiazide monotherapies. There were no new or unexpected 

findings observed of relevance to human use. Increased cellular vacuolation of the adrenal gland zona 

glomerulosa was observed during the 13-week toxicity study in rats. The finding was observed in 

animals treated with hydrochlorothiazide but not in those animals receiving aliskiren alone or vehicle. 

There was no evidence that this finding was enhanced in the aliskiren/hydrochlorothiazide 

combination as it was only apparent at a minimal severity in all animals. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Tablet core: 

Cellulose microcrystalline 

Crospovidone 

Lactose monohydrate 

Wheat starch 

Povidone 

Magnesium stearate 

Silica colloidal anhydrous 

Talc 

 

Coating: 

Talc 

Hypromellose 

Macrogol 

Titanium dioxide (E171) 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

24 months 

 

6.4 Special precautions for storage 

 

Do not store above 30°C. 

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

 

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6.5 Nature and contents of container 

 

PA/Alu/PVC – Alu blisters: 

Single-packs containing 7, 14, 28, 30, 50 or 56 tablets. 

Multi-packs containing 90, 98 or 280 tablets. 

 

PVC/polychlorotrifluoroethylene (PCTFE) – Alu blisters: 

Single-packs containing 7, 14, 28, 30, 50, 56, 90 or 98 tablets. 

Single-packs (perforated unit dose blister) containing 56 x 1 tablets. 

Multi-packs containing 280 tablets. 

Multi-packs (perforated unit dose blister) containing 98 x 1 tablets. 

 

Not all pack sizes or strengths may be marketed. 

 

6.6 Special precautions for disposal 
 

Any unused product or waste material should be disposed of in accordance with local requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/001-020 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

23.06.2011 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

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

http://www.ema.europa.eu 

 
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21 

1. NAME OF THE MEDICINAL PRODUCT 
 

Sprimeo HCT 150 mg/25 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

Excipients: Each tablet contains 50 mg lactose monohydrate and 49 mg wheat starch. 

 

For a full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Film-coated tablet 

 

Pale yellow, biconvex, ovaloid film-coated tablet imprinted with “CLL” on one side and “NVR” on 

the other. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Treatment of essential hypertension in adults. 

 

Sprimeo HCT is indicated in patients whose blood pressure is not adequately controlled on aliskiren or 

hydrochlorothiazide used alone. 

 

Sprimeo HCT is indicated as substitution therapy in patients adequately controlled with aliskiren and 

hydrochlorothiazide, given concurrently, at the same dose level as in the combination. 

 

4.2 Posology and method of administration 

 

The recommended dose of Sprimeo HCT is one tablet per day. Sprimeo HCT should be taken with a 

light meal once a day, preferably at the same time each day. Grapefruit juice should not be taken 

together with Sprimeo HCT. 

 

The antihypertensive effect is largely manifested within 1 week and the maximum effect is generally 

seen within 4 weeks. 

 

Posology in patients not adequately controlled with aliskiren or hydrochlorothiazide monotherapy 

Individual dose titration with each of the two components may be recommended before changing to 

the fixed combination. When clinically appropriate, direct change from monotherapy to the fixed 

combination may be considered. 

 

Sprimeo HCT 150 mg /25 mg may be administered in patients whose blood pressure is not adequately 

controlled with aliskiren 150 mg or hydrochlorothiazide 25 mg alone or by Sprimeo HCT 

150 mg/12.5 mg. 

 

If blood pressure remains uncontrolled after 2-4 weeks of therapy, the dose may be titrated up to a 

maximum of Sprimeo HCT 300 mg/25 mg daily. Dosing should be individualised and adjusted 

according to the patient’s clinical response. 

 

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22 

Posology as substitution therapy 

For convenience, patients receiving aliskiren and hydrochlorothiazide from separate tablets may be 

switched to a fixed combination tablet of Sprimeo HCT containing the same component doses. 

 

Renal impairment 

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

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

use in patients with anuria and in patients with severe renal impairment (glomerular filtration rate 

(GFR) < 30 ml/min/1.73 m
2
). The concomitant use of Sprimeo HCT with angiotensin II receptor 

blockers (ARB) or angiotensin converting enzyme inhibitors (ACEI) is contraindicated in patients 

with renal impairment (GFR < 60 ml/min/1.73 m
2
) (see sections 4.3, 4.4 and 5.2). 

 

Hepatic impairment 

No adjustment of the initial dose is required for patients with mild to moderate hepatic impairment 

(see section 5.2). Sprimeo HCT is contraindicated in patients with severe hepatic impairment (see 

sections 4.3 and 4.4). 

 

Elderly patients (over 65 years) 

The recommended starting dose of aliskiren in elderly patients is 150 mg. No clinically meaningful 

additional blood pressure reduction is observed by increasing the dose to 300 mg in the majority of 

elderly patients. 

 

Paediatric patients 

Sprimeo HCT is not recommended for use in children and adolescents below age 18 due to a lack of 

data on safety and efficacy (see section 5.2). 

 

4.3 Contraindications 
 

 Hypersensitivity to the active substances or to any of the excipients (see section 6.1), or to other 
sulphonamide-derived substances. 

 History of angioedema with aliskiren. 

 Hereditary or idiopathic angioedema. 

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

 Anuria. 

 Severe renal impairment (GFR < 30 ml/min/1.73 m2). 

 Refractory hypokalaemia, hyponatraemia, hypercalcaemia and symptomatic hyperuricaemia. 

 Severe hepatic impairment. 

 The concomitant use of aliskiren with ciclosporin and itraconazole, two highly potent P-
glycoprotein (P-gp) inhibitors, and other potent P-gp inhibitors (e.g. quinidine), is 

contraindicated (see section 4.5). 

 The concomitant use of aliskiren with ARBs or ACEIs is contraindicated in patients with 
diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m

2
) (see sections 4.2, 4.4, 4.5 and 

5.1). 

 

4.4 Special warnings and precautions for use 
 

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

Hypotension, syncope, stroke, hyperkalaemia, and changes in renal function (including acute renal 

failure) have been reported in susceptible individuals, especially if combining medicinal products that 

affect this system (see section 5.1). Dual blockade of the renin-angiotensin-aldosterone system by 

combining aliskiren with an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin II 

receptor blocker (ARB) is therefore not recommended. 

 

The use of aliskiren in combination with ARBs or ACEIs is contraindicated in patients with diabetes 

mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) (see section 4.3). 

 

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Heart failure 

Aliskiren should be used with caution in patients with serious congestive heart failure (New York 

Heart Association (NYHA) functional class III-IV). Sprimeo HCT should be used with caution in 

patients with heart failure due to limited clinical efficacy and safety data. 

 

Angioedema 

As with other agents acting on the renin-angiotensin system, angioedema or symptoms suggestive of 

angioedema (swelling of the face, lips, throat and/or tongue) have been reported in patients treated 

with aliskiren. 

 

A number of these patients had a history of angioedema or symptoms suggestive of angioedema, 

which in some cases followed use of other medicines that can cause angioedema, including RAAS 

blockers (angiotensin converting enzyme inhibitors or angiotensin receptor blockers) (see section 4.8). 

 

Patients with a history of angioedema may be at increased risk of experiencing angioedema during 

treatment with aliskiren (see sections 4.3 and 4.8). Caution should therefore be exercised when 

prescribing aliskiren to patients with a history of angioedema, and such patients should be closely 

monitored during treatment (see section 4.8) especially at the beginning of the treatment. 

 

If angioedema occurs, Sprimeo HCT should be promptly discontinued and appropriate therapy and 

monitoring provided until complete and sustained resolution of signs and symptoms has occurred. 

Where there is involvement of the tongue, glottis or larynx adrenaline should be administered. In 

addition, measures necessary to maintain patent airways should be provided. 

 

Sodium- and/or volume-depleted patients 

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 Sprimeo HCT. Sprimeo HCT 

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

 

Electrolyte imbalance 

Treatment with Sprimeo 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 Sprimeo HCT should be discontinued until stable correction of the potassium balance. 

Although hypokalaemia may develop with the use of thiazide diuretics, concurrent therapy with 

aliskiren may reduce diuretic-induced hypokalaemia. The risk of hypokalaemia is greater in patients 

with cirrhosis of the liver, patients experiencing brisk diuresis, patients with inadequate oral 

electrolyte intake and patients receiving concomitant therapy with corticosteroids or 

adrenocorticotropic hormone (ACTH) (see sections 4.5 and 4.8). 

 

Conversely, increases in serum potassium have been observed with aliskiren in post-marketing 

experience and these may be exacerbated by concomitant use of other agents acting on the RAAS or 

by non-steroidal anti-inflammatory drugs (NSAIDs). Consistent with standard medical practice, 

periodic determination of renal function including serum electrolytes is advised if co-administration is 

considered necessary. The concomitant use of aliskiren and ACEIs or ARBs is contraindicated in 

patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) (see sections 4.3, 4.5 

and 4.8). 

 

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 Sprimeo HCT therapy, the treatment should be discontinued until 

normalisation of natraemia. 

 

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24 

There is no evidence that Sprimeo HCT would reduce or prevent diuretic-induced hyponatraemia. 

Chloride deficit is generally mild and usually does not require treatment. 

 

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

electrolytes, particularly potassium, sodium and magnesium. 

 

Thiazides reduce urinary calcium excretion and may cause an intermittent and slight elevation of 

serum calcium in the absence of known disorders of calcium metabolism. Sprimeo HCT is 

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

existing hypercalcaemia. Sprimeo 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. 

 

Renal impairment and kidney transplantation 

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

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

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

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

 

No dosage adjustment is necessary in patients with mild to moderate renal impairment (GFR 

≥ 30 ml/min/1.73 m
2
). 

 

There is no experience regarding the administration of Sprimeo HCT in patients who have recently 

undergone kidney transplantation. 

 

As for other agents acting on the renin-angiotensin system, caution should be exercised when aliskiren 

is given in the presence of conditions pre-disposing to kidney dysfunction such as hypovolaemia (e.g. 

due to blood loss, severe or prolonged diarrhoea, prolonged vomiting, etc.), heart disease, liver 

disease, diabetes mellitus or kidney disease. The concomitant use of aliskiren and ACEIs or ARBs is 

contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m
2
). Acute renal failure, 

reversible upon discontinuation of treatment, has been reported in at-risk patients receiving aliskiren in 

post-marketing experience. In the event that any signs of renal failure occur, aliskiren should be 

promptly discontinued. 

 

Hepatic impairment 

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver 

disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. No 

adjustment of the initial dose is required for patients with mild to moderate hepatic impairment. No 

data are available for the use of Sprimeo HCT in patients with severe hepatic impairment. Due to the 

hydrochlorothiazide component, Sprimeo HCT is contraindicated in patients with severe hepatic 

impairment (see sections 4.3 and 5.2). 

 

There is no clinical experience with Sprimeo HCT in patients with hepatic impairment. 

 

Moderate P-gp inhibitors 

Co-administration of aliskiren 300 mg with ketoconazole 200 mg or verapamil 240 mg resulted in a 

76% or 97% increase in aliskiren AUC, respectively. Therefore caution should be exercised when 

aliskiren is administered with moderate P-gp inhibitors such as ketoconazole or verapamil (see section 

4.5). 

 

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy 

As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral 

stenosis, or obstructive hypertrophic cardiomyopathy. 

 

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Renal artery stenosis and renovascular hypertension 

No controlled clinical data are available on the use of Sprimeo HCT in patients with unilateral or 

bilateral renal artery stenosis, or stenosis to a solitary kidney. However, as with other agents acting on 

the renin-angiotensin system, there is an increased risk of renal insufficiency, including acute renal 

failure, when patients with renal artery stenosis are treated with aliskiren. Therefore caution should be 

exercised in these patients. If renal failure occurs, treatment should be discontinued. 

 

Systemic lupus erythematosus 

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

systemic lupus erythematosus. 

 

Metabolic and endocrine effects 

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

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

hypoglycaemic agents may be required. Concomitant use of Sprimeo HCT with ARBs or ACEIs is 

contraindicated in patients with diabetes mellitus (see section 4.3). 

 

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

hyperuricaemia (see section 4.3). 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 an intermittent and slight elevation of 

serum calcium in the absence of known disorders of calcium metabolism. Sprimeo HCT is 

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

existing hypercalcaemia. Sprimeo 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 Sprimeo HCT, it is recommended to stop the 

treatment. If a re-administration of the diuretic is deemed necessary, it is recommended to protect 

exposed areas to the sun or to artificial UVA. 

 

Acute angle-closure glaucoma 

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

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

visual acuity or ocular pain and typically occur within hours to weeks 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 

In the event of severe and persistent diarrhoea, Sprimeo HCT therapy should be stopped. 

 

As with any antihypertensive agent, excessive reduction of blood pressure in patients with ischaemic 

cardiopathy or ischaemic cardiovascular disease could result in a myocardial infarction or stroke. 

 

Hypersensitivity reactions to hydrochlorothiazide may occur in patients, but are more likely in patients 

with allergy and asthma. 

 

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26 

Excipients 

Sprimeo HCT contains lactose. Patients with rare hereditary problems of galactose intolerance, the 

Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. 

 

Sprimeo HCT contains wheat starch. It is suitable for people with coeliac disease. Patients with wheat 

allergy (different from coeliac disease) should not take this medicine. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Information on Sprimeo HCT interactions 

Medicinal products affecting serum potassium levels: The potassium-depleting effect of 

hydrochlorothiazide is attenuated by the potassium-sparing effect of aliskiren. However, this effect of 

hydrochlorothiazide on serum potassium would be expected to be potentiated by other medicinal 

products associated with potassium loss and hypokalaemia (e.g. other kaliuretic diuretics, 

corticosteroids, laxatives, adrenocorticotropic hormone (ACTH), amphotericin, carbenoxolone, 

penicillin G, salicylic acid derivatives). Conversely, concomitant use of other agents affecting the 

RAAS, of NSAIDs or of agents that increase serum potassium levels (e.g. potassium-sparing diuretics, 

potassium supplements, salt substitutes containing potassium, heparin) may lead to increases in serum 

potassium. If co-medication with an agent affecting the level of serum potassium is considered 

necessary, caution is advisable. The combination of aliskiren with ARBs or ACEIs is contraindicated 

in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) and is not 

recommended in other patients (see sections 4.3, 4.4 and 5.1). 

 

Medicinal products affected by serum potassium disturbances: Periodic monitoring of serum 

potassium is recommended when Sprimeo HCT is administered with medicinal products affected by 

serum potassium disturbances (e.g. digitalis glycosides, antiarrhythmics). 

 

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors 

(COX-2 inhibitors), acetylsalicylic acid and non-selective NSAIDs: As with other agents acting on the 

renin-angiotensin system, NSAIDs may reduce the anti-hypertensive effect of aliskiren. NSAIDs may 

also weaken the diuretic and antihypertensive activity of hydrochlorothiazide. 

 

In some patients with compromised renal function (dehydrated patients or elderly patients) aliskiren 

and hydrochlorothiazide given concomitantly with NSAIDs may result in further deterioration of renal 

function, including possible acute renal failure, which is usually reversible. Therefore the use of 

Sprimeo HCT with an NSAID requires caution, especially in elderly patients. 

 

Other antihypertensive agents: The antihypertensive effect of Sprimeo HCT may be increased with 

the concomitant use of other antihypertensive agents. 

 

Additional information on aliskiren interactions 

The combination of aliskiren with ARBs or ACEIs is contraindicated in patients with diabetes mellitus 

or renal impairment (GFR < 60 ml/min/1.73 m
2
) and is not recommended in other patients (see 

sections 4.3, 4.4 and 5.1). 

 

Compounds that have been investigated in aliskiren clinical pharmacokinetic studies include 

acenocoumarol, atenolol, celecoxib, fenofibrate, pioglitazone, allopurinol, isosorbide-5-mononitrate, 

digoxin, metformin, amlodipine, atorvastatin, cimetidine and hydrochlorothiazide. No clinically 

relevant interactions have been identified. As a result no dose adjustment for aliskiren or these co-

administered medicinal products is necessary. 

 

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P-glycoprotein interactions: MDR1/Mdr1a/1b (P-gp) was found to be the major efflux system 

involved in intestinal absorption and biliary excretion of aliskiren in preclinical studies. Rifampicin, 

which is an inducer of P-gp, reduced aliskiren bioavailability by approximately 50% in a clinical 

study. Other inducers of P-gp (St. John’s wort) might decrease the bioavailability of aliskiren. 

Although this has not been investigated for aliskiren, it is known that P-gp also controls tissue uptake 

of a variety of substrates and P-gp inhibitors can increase the tissue-to-plasma concentration ratios. 

Therefore, P-gp inhibitors may increase tissue levels more than plasma levels. The potential for drug 

interactions at the P-gp site will likely depend on the degree of inhibition of this transporter. 

 

P-gp potent inhibitors: A single dose drug interaction study in healthy subjects has shown that 

ciclosporin (200 and 600 mg) increases Cmax of aliskiren 75 mg approximately 2.5-fold and AUC 

approximately 5-fold. The increase may be higher with higher aliskiren doses. In healthy subjects, 

itraconazole (100 mg) increases AUC and Cmax of aliskiren (150 mg) by 6.5-fold and 5.8-fold, 

respectively. Therefore, concomitant use of aliskiren and P-gp potent inhibitors is contraindicated (see 

section 4.3). 

 

Moderate P-gp inhibitors: Co-administration of ketoconazole (200 mg) or verapamil (240 mg) with 

aliskiren (300 mg) resulted in a 76% or 97% increase in aliskiren AUC, respectively. The change in 

plasma levels of aliskiren in the presence of ketoconazole or verapamil is expected to be within the 

range that would be achieved if the dose of aliskiren were doubled; aliskiren doses of up to 600 mg, or 

twice the highest recommended therapeutic dose, have been found to be well tolerated in controlled 

clinical trials. Preclinical studies indicate that aliskiren and ketoconazole co-administration enhances 

aliskiren gastrointestinal absorption and decreases biliary excretion. Therefore, caution should be 

exercised when aliskiren is administered with ketoconazole, verapamil or other moderate P-gp 

inhibitors (clarithromycin, telithromycin, erythromycin, amiodarone). 

 

P-gp substrates or weak inhibitors: No relevant interactions with atenolol, digoxin, amlodipine or 

cimetidine have been observed. When administered with atorvastatin (80 mg), steady-state aliskiren 

(300 mg) AUC and Cmax increased by 50%. 

 

Organic anion transporting polypeptide (OATP) inhibitors: Preclinical studies indicate that aliskiren 

might be a substrate of organic anion transporting polypeptides. Therefore, the potential exists for 

interactions between OATP inhibitors and aliskiren when administered concomitantly (see interaction 

with Grapefruit juice). 

 

Grapefruit juice: Administration of grapefruit juice with aliskiren resulted in a decrease in AUC and 

Cmax of aliskiren. Co-administration with aliskiren 150 mg resulted in a 61% decrease in aliskiren 

AUC and co-administration with aliskiren 300 mg resulted in a 38% decrease in aliskiren AUC. This 

decrease is likely due to an inhibition of organic anion transporting polypeptide-mediated uptake of 

aliskiren by grapefruit juice in the gastrointestinal tract. Therefore, because of the risk of therapeutic 

failure, grapefruit juice should not be taken together with Sprimeo HCT. 

 

Furosemide: When aliskiren was co-administered with furosemide, the AUC and Cmax of furosemide 

were reduced by 28% and 49%, respectively. It is therefore recommended to monitor the effects when 

initiating and adjusting furosemide therapy to avoid possible underutilisation in clinical situations of 

volume overload. 

 

Warfarin: The effects of aliskiren on warfarin pharmacokinetics have not been evaluated. 

 

Food interactions: Meals with a high fat content have been shown to reduce the absorption of aliskiren 

substantially. 

 

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Additional information on hydrochlorothiazide interactions 

When administered concurrently, the following medicinal products may interact with thiazide 

diuretics: 

 

Lithium: Renal clearance of lithium is reduced by thiazides, therefore the risk of lithium toxicity may 

be increased with hydrochlorothiazide. Co-administration of lithium and hydrochlorothiazide is not 

recommended. If this combination proves essential, careful monitoring of serum lithium level is 

recommended during concomitant use. 

 

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 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. 

 

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. 

 

Digoxine or other digitalis glycosides: Thiazide-induced hypokalaemia or hypomagnesaemia may 

occur as undesirable effects, favouring the onset of digitalis-induced cardiac arrhythmias. 

 

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. 

 

Antidiabetic agents (e.g. insulin and oral antidiabetic agents): Thiazides may alter glucose tolerance. 

Dose adjustment of the antidiabetic medicinal product may be necessary (see section 4.4). 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. 

 

Medicinal products used in the treatment of gout: 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. 

 

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. 

 

Amantadine: Thiazides, including hydrochlorothiazide, may increase the risk of adverse reactions 

caused by amantadine. 

 

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29 

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. 

 

Cytotoxic agents: Thiazides, including hydrochlorothiazide, may reduce the renal excretion of 

cytotoxic agents (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects. 

 

Non-depolarising skeletal muscle relaxants: Thiazides, including hydrochlorothiazide, potentiate the 

action of skeletal muscle relaxants such as curare derivatives. 

 

Alcohol, barbiturates or narcotics: Concomitant administration of thiazide diuretics with subtances 

that also have a blood pressure lowering effect (e.g. by reducing sympathetic central nervous system 

activity or direct vasodilatation) may potentiate orthostatic hypotension. 

 

Methyldopa: There have been isolated reports of haemolytic anaemia occurring with concomitant use 

of hydrochlorothiazide and methyldopa. 

 

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 rehydrated before 

administration. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

There are no data on the use of aliskiren in pregnant women. Aliskiren was not teratogenic in rats or 

rabbits (see section 5.3). Other substances that act directly on the RAAS have been associated with 

serious foetal malformations and neonatal death when used during second and third trimesters. 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. 

 

Hydrochlorothiazide should not be used for gestational oedema, gestational hypertension or 

pre-eclampsia due to the risk of decreased plasma volume and placental hypoperfusion, without a 

beneficial effect on the course of the disease. 

 

Hydrochlorothiazide should not be used for essential hypertension in pregnant women except in rare 

situations where no other treatment could be used. 

 

No specific clinical studies have been performed with this combination, therefore Sprimeo HCT 

should not be used during the first trimester of pregnancy or in women planning to become pregnant 

and is contraindicated during the second and third trimesters (see section 4.3). A switch to a suitable 

alternative treatment should be carried out in advance of a planned pregnancy. If pregnancy is detected 

during therapy, Sprimeo HCT should be discontinued as soon as possible. 

 

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Breast-feeding 

It is not known whether aliskiren is excreted in human milk. Aliskiren was secreted in the milk of 

lactating rats. 

 

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

intense diuresis can inhibit milk production. 

 

The use of Sprimeo HCT during breast-feeding is not recommended. If Sprimeo HCT is used during 

breast-feeding, doses should be kept as low as possible. 

 

4.7 Effects on ability to drive and use machines 
 

No studies on the effect on the ability to drive and use machines have been performed. Sprimeo HCT 

is unlikely to affect the ability to drive and use machines. However, when driving vehicles or 

operating machinery it must be borne in mind that dizziness or drowsiness may occasionally occur 

when taking antihypertensive therapy. 

 

4.8 Undesirable effects 

 

Aliskiren/hydrochlorothiazide combination 

The safety of Sprimeo HCT has been evaluated in 9 clinical trials with more than 3,900 patients, 

including over 700 treated for over 6 months, and 190 for over 1 year. The incidence of adverse 

reactions showed no association with gender, age, body mass index, race or ethnicity. Treatment with 

Sprimeo HCT had an overall incidence of adverse experiences at doses up to 300 mg/25 mg similar to 

placebo. Adverse reactions have generally been mild and transient in nature and have only 

infrequently required discontinuation of therapy. The most common adverse drug reaction observed 

with Sprimeo HCT is diarrhoea. The adverse drug reactions previously reported with one of the 

individual components of Sprimeo HCT (aliskiren and hydrochlorothiazide) and listed in the 

respective paragraphs on the individual components may occur with Sprimeo HCT. 

 

The frequency of adverse reactions listed below is defined using the following convention: 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) and not known (cannot be estimated from the available data). 

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 

 

Gastrointestinal disorders 

 Common: Diarrhoea 

 

Diarrhoea: Diarrhoea is a dose-related adverse drug reaction for aliskiren. In controlled clinical trials, 

the incidence of diarrhoea in Sprimeo HCT-treated patients was 1.3% compared to 1.4% for aliskiren- 

or 1.9% for hydrochlorothiazide-treated patients. 

 

Serum potassium: In a large placebo-controlled clinical trial, the opposite effects of aliskiren (150 mg 

or 300 mg) and hydrochlorothiazide (12.5 mg or 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 potassium to detect possible electrolyte imbalance should be performed in 

patients at risk at appropriate intervals (see sections 4.4 and 4.5). 

 

Additional information on individual components 

Other adverse reactions previously reported with one of the individual components may occur with 

Sprimeo HCT even if not observed in clinical trials. 

 

Aliskiren 

Treatment with Aliskiren up to 300 mg resulted in an overall incidence of adverse reactions similar to 

placebo. Adverse reactions have generally been mild and transient in nature and have only 

infrequently required discontinuation of therapy. The most common adverse drug reaction is 

diarrhoea. 

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31 

 

The known aliskiren adverse drug reactions are presented in the table below using the same 

convention as described previously for the fixed combination. 

 

Nervous system disorders 

 Common: Dizziness 

Vascular disorders 

 Uncommon: Hypotension 

Gastrointestinal disorders 

 Common: Diarrhoea 

Immune system disorders 

 Rare: Hypersensitivity reactions 

Skin and subcutaneous tissue disorders 

 Uncommon: Rash, severe cutaneous adverse reactions (SCARs) including toxic 

epidermal necrolysis (TEN) and oral mucosal reactions 

 Rare: Angioedema 

Musculoskeletal and connective tissue disorders 

 Common: Arthralgia 

Renal and urinary disorders 
 Uncommon: Acute renal failure, renal impairment 

General disorders and administration site conditions 
 Uncommon: Oedema peripheral 

Investigations 
 Common: Hyperkalaemia 

 Rare: Haemoglobin decreased, haematocrit decreased 

 Rare: Blood creatinine increased 

 

Angioedema and hypersensitivity reactions have occurred during treatment with aliskiren. In 

controlled clinical trials, angioedema and hypersensitivity reactions occurred rarely during treatment 

with aliskiren with rates comparable to treatment with placebo or comparators. 

 

Cases of angioedema or symptoms suggestive of angioedema (swelling of the face, lips, throat and/or 

tongue) have also been reported in post-marketing experience. A number of these patients had a 

history of angioedema or symptoms suggestive of angioedema which in some cases was associated 

with the administration of other medicines known to cause angioedema, including RAAS blockers 

(ACE inhibitors or ARBs). 

 

Hypersensitivity reactions have also been reported in post-marketing experience. 

 

In the event of any signs suggesting a hypersensitivity reaction/angioedema (in particular difficulties 

in breathing or swallowing, rash, itching, hives or swelling of the face, extremities, eyes, lips and/or 

tongue, dizziness) patients should discontinue treatment and contact the physician (see section 4.4). 

 

Arthralgia has been reported in post-marketing experience. In some cases this occurred as part of a 

hypersensitivity reaction. 

 

Haemoglobin and haematocrit: Small decreases in haemoglobin and haematocrit (mean decreases of 

approximately 0.05 mmol/l and 0.16 volume percent, respectively) were observed. No patients 

discontinued therapy due to anaemia. This effect is also seen with other agents acting on the renin-

angiotensin system, such as ACEI and ARBs. 

 

Serum potassium: Increases in serum potassium have been observed with aliskiren and these may be 

exacerbated by concomitant use of other agents acting on the RAAS or by NSAIDs. Consistent with 

standard medical practice, periodic determination of renal function including serum electrolytes is 

advised if co-administration is considered necessary. The combination of aliskiren with ARBs or 

ACEIs is contraindicated in patients with diabetes mellitus or renal impairment (GFR 

< 60 ml/min/1.73 m
2
) and is not recommended in other patients (see sections 4.3, 4.4 and 5.1). 

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32 

 

In post-marketing experience, renal dysfunction and cases of acute renal failure have been reported in 

patients at risk (see section 4.4). There have also been reports of peripheral oedema, increase in blood 

creatinine and severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis 

(TEN) and oral mucosal reactions. 

 

Hydrochlorothiazide 

Hydrochlorothiazide has been extensively prescribed for many years, frequently in higher doses than 

those contained in Sprimeo HCT. The following adverse reactions have been reported in patients 

treated with thiazide diuretics alone, including hydrochlorothiazide: 

 

Blood and lymphatic system disorders 

 Rare: Thrombocytopenia sometimes with purpura 

 Very rare: Agranulocytosis, bone marrow depression, haemolytic anaemia, 

leucopenia 

 Not known: Aplastic anaemia 
Immune system disorders 

 Very rare: Hypersensitivity 

Metabolism and nutrition disorders 

 Very common: Hypokalaemia 

 Common: Hyperuricaemia, hypomagnesaemia, hyponatraemia 

 Rare: Hypercalcaemia, hyperglycaemia, worsening of diabetic metabolic 

state 

 Very rare: Hypochloraemic alkalosis 

Psychiatric disorders 

 Rare: Depression, sleep disturbances 

Nervous system disorders 

 Rare: Dizziness, headache, paraesthesia 

Eye disorders 

 Rare: Visual impairment 

 Not known: Acute angle-closure glaucoma 

Cardiac disorders 

 Rare: Cardiac arrhythmias 

Vascular disorders 

 Common: Orthostatic hypotension 

Respiratory, thoracic and mediastinal disorders 

 Very rare: Respiratory distress (including pneumonitis and pulmonary oedema) 

Gastrointestinal disorders 

 Common: Decreased appetite, mild nausea and vomiting 

 Rare: Abdominal discomfort, constipation, diarrhoea 

 Very rare: Pancreatitis 

Hepatobiliary disorders 

 Rare: Intrahepatic cholestasis, jaundice 

Skin and subcutaneous tissue disorders 

 Common: Urticaria and other forms of rash 

 Rare: Photosensitivity reactions 

 Very rare: Cutaneous lupus erythematosus-like reactions, reactivation of 

cutaneous lupus erythematosus, vasculitis necrotising and toxic 

epidermal necrolysis 

 Not known: Erythema multiforme 

Musculoskeletal and connective tissue disorders 

 Not known: Muscle spasm 

Renal and urinary disorders 

 Not known: Renal dysfunction, acute renal failure 

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Reproductive system and breast disorders 

 Common: Impotence 

General disorders and administration site conditions 

 Not known: Asthenia, pyrexia 

Investigations 

 Very common: Increases in cholesterol and triglycerides 

 Rare: Glycosuria 

 

4.9 Overdose 
 

No information is available on the treatment of overdose with Sprimeo HCT. The most likely 

manifestation of overdose would be hypotension, related to the antihypertensive effect of aliskiren. 

 

Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, 

hypochloraemia, hyponatraemia) and dehydration 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 cardiac arrhythmias associated with the concomitant use of digitalis 

glycosides or certain antiarrhythmic medicinal products. If symptomatic hypotension should occur, 

supportive treatment should be initiated. 

 

In a study conducted in patients with end stage renal disease (ESRD) receiving haemodialysis, dialysis 

clearance of aliskiren was low (< 2% of oral clearance). Therefore dialysis is not adequate to treat 

aliskiren over-exposure. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Renin inhibitor (aliskiren) combinations with diuretics 

(hydrochlorothiazide), ATC code: C09XA52 

Sprimeo HCT combines two antihypertensive compounds to control blood pressure in patients with 

essential hypertension: Aliskiren belongs to the class of direct renin inhibitors and hydrochlorothiazide 

to the class of thiazide diuretics. The combination of these substances with complementary 

mechanisms of action provides an additive antihypertensive effect, reducing blood pressure to a 

greater degree than either component alone. 

 

Aliskiren 

Aliskiren is an orally active, non-peptide, potent and selective direct inhibitor of human renin. 

 

By inhibiting the enzyme renin, aliskiren inhibits the RAAS at the point of activation, blocking the 

conversion of angiotensinogen to angiotensin I and decreasing levels of angiotensin I and 

angiotensin II. Whereas other agents that inhibit the RAAS (angiotensin converting enzyme inhibitors 

(ACEI) and angiotension II receptor blockers (ARB)) cause a compensatory rise in plasma renin 

activity (PRA), treatment with aliskiren decreases PRA in hypertensive patients by approximately 50 

to 80%. Similar reductions were found when aliskiren was combined with other antihypertensive 

agents. The clinical implications of the effects on PRA are not known at the present time. 

 

In hypertensive patients, once-daily administration of aliskiren at doses of 150 mg and 300 mg 

provided dose-dependent reductions in both systolic and diastolic blood pressure that were maintained 

over the entire 24-hour dose interval (maintaining benefit in the early morning) with a mean peak to 

trough ratio for diastolic response of up to 98% for the 300 mg dose. 85 to 90% of the maximal blood-

pressure-lowering effect was observed after 2 weeks. The blood-pressure-lowering effect was 

sustained during long-term treatment (12 months), and was independent of age, gender, body mass 

index and ethnicity. 

 

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34 

Combination therapy studies are available for aliskiren added to the diuretic hydrochlorothiazide, the 

calcium channel blocker amlodipine and the beta blocker atenolol. These combinations were 

efficacious and well tolerated. 

 

The efficacy and safety of aliskiren-based therapy were compared to ramipril-based therapy in a 9-

month non-inferiority study in 901 elderly patients (≥ 65 years) with essential systolic hypertension. 

Aliskiren 150 mg or 300 mg per day or ramipril 5 mg or 10 mg per day were administered for 

36 weeks with optional add-on therapy of hydrochlorothiazide (12.5 mg or 25 mg) at week 12, and 

amlodipine (5 mg or 10 mg) at week 22. Over the 12 week period, aliskiren monotherapy lowered 

systolic/diastolic blood pressure by 14.0/5.1 mmHg, compared to 11.6/3.6 mmHg for ramipril, 

consistent with aliskiren being non-inferior to ramipril at the dosages chosen and the differences in 

systolic and diastolic blood pressure were statistically significant. Tolerability was comparable in both 

treatment arms, however cough was more often reported with the ramipril regimen than the aliskiren 

regimen (14.2% vs. 4.4%), whilst diarrhoea was more common with the aliskiren regimen than for the 

ramipril regimen (6.6% vs. 5.0%). 

 

In a 8-week study in 754 hypertensive elderly (≥ 65 years) and very elderly patients (30% ≥ 75 years) 

aliskiren at doses of 75 mg, 150 mg and 300 mg provided statistically significant superior reduction in 

blood pressure (both systolic and diastolic) when compared to placebo. No additional blood pressure 

lowering effect was detected with 300 mg aliskiren compared to 150 mg aliskiren. All three doses 

were well tolerated in both elderly and very elderly patients. 

 

There has been no evidence of first-dose hypotension and no effect on pulse rate in patients treated in 

controlled clinical studies. With cessation of treatment, blood pressure gradually returned towards 

baseline levels over a period of several weeks, with no evidence of a rebound effect for blood pressure 

or PRA. 

 

In a 36-week study involving 820 patients with ischaemic left ventricular dysfunction, no changes in 

ventricular remodelling as assessed by left ventricular end systolic volume were detected with 

aliskiren compared to placebo on top of background therapy. 

 

The combined rates of cardiovascular death, hospitalisation for heart failure, recurrent heart attack, 

stroke and resuscitated sudden death were similar in the aliskiren group and the placebo group. 

However, in patients receiving aliskiren there was a significantly higher rate of hyperkalaemia, 

hypotension and kidney dysfunction when compared to the placebo group. 

 

Aliskiren was evaluated for cardiovascular and/or renal benefit in a double-blind placebo controlled 

randomised trial in 8,606 patients with type 2 diabetes and chronic kidney disease (evidenced by 

proteinuria and/or GFR < 60 ml/min/1.73 m
2
) with or without cardiovascular disease. In most patients 

arterial blood pressure was well controlled at baseline. The primary endpoint was a composite of 

cardiovascular and renal complications. 

 

In this study, aliskiren 300 mg was compared to placebo when added to standard of care which 

included either an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker. The 

study was discontinued prematurely because the participants were unlikely to benefit from aliskiren. 

Preliminary study results indicated a hazard ratio for the primary endpoint of 1.09 in favour of placebo 

(95% Confidence Interval: 0.97, 1.22, 2-sided p=0.17). In addition, an increased incidence of serious 

adverse outcomes was observed with aliskiren compared to placebo for renal complications (4.7% 

versus 3.3%), hyperkalaemia (36.9% versus 27.1%), hypotension (18.4% versus 14.6%) and stroke 

(2.7% versus 2.0%). The increased incidence of non-fatal stroke was greater in patients with renal 

insufficiency. 

 

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35 

Hydrochlorothiazide 

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

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

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

action of thiazides is through inhibition of the Na+Cl- symporter 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. 

 

Aliskiren/hydrochlorothiazide 

Over 3,900 hypertensive patients received Sprimeo HCT once daily in clinical trials. 

 

In hypertensive patients, once-daily administration of Sprimeo HCT provided dose-dependent 

reductions in both systolic and diastolic blood pressure that were maintained over the entire 24-hour 

dose interval. The antihypertensive effect is largely manifested within 1 week and the maximum effect 

is generally seen within 4 weeks.The blood-pressure-lowering effect was sustained during long-term 

treatment, and was independent of age, gender, body mass index and ethnicity. The antihypertensive 

effect of a single dose of the combination persisted for 24 hours. Upon withdrawal of the aliskiren 

treatment (aliskiren with or without hydrochlorothiazide add-on), the return of blood pressure towards 

baseline was gradual (3-4 weeks) with no evidence of the rebound effect. 

 

Sprimeo HCT was studied in a placebo-controlled trial including 2,762 hypertensive patients with 

diastolic blood pressure ≥ 95 mmHg and < 110 mmHg (mean baseline blood pressure of 

153.6/99.2 mmHg). In this study, Sprimeo HCT in doses from 150 mg/12.5 mg to 300 mg/25 mg 

produced dose-dependent blood pressure reductions (systolic/diastolic) from 17.6/11.9 mmHg to 

21.2/14.3 mmHg, respectively, compared to 7.5/6.9 mmHg with placebo. The greater blood pressure 

reductions with these combination doses were also significantly greater than the respective doses of 

aliskiren and hydrochlorothiazide when used alone. The combination of aliskiren and 

hydrochlorothiazide neutralised the reactive increase of PRA caused by hydrochlorothiazide. 

 

When administered in hypertensive patients with markedly elevated blood pressure (systolic blood 

pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg), Sprimeo HCT in doses from 

150 mg/12.5 mg to 300 mg/25 mg administered without up-titration from monotherapy demonstrated 

significantly greater systolic/diastolic blood pressure control rates (< 140/90 mmHg) as compared to 

the respective monotherapies. In this population, Sprimeo HCT 150 mg/12.5 mg to 300 mg/25 mg 

provided dose-dependent systolic/diastolic blood pressure reduction from 20.6/12.4 mmHg to 

24.8/14.5 mmHg, which were significantly superior to the respective monotherapies. The safety of the 

combination therapy was similar to the respective monotherapies regardless of severity of 

hypertension or of the presence or absence of additional cardiovascular risk. Hypotension and related 

adverse events were uncommon with the combination treatment, with no increased incidence in 

elderly patients. 

 

In a study in 880 randomised patients not adequately responsive to aliskiren 300 mg treatment, the 

combination of aliskiren/hydrochlorothiazide 300 mg/25 mg produced systolic/diastolic blood 

pressure reductions of 15.8/11.0 mmHg, which were significantly greater than aliskiren 300 mg 

monotherapy. In a study in 722 randomised patients not adequately responsive to hydrochlorothiazide 

25 mg treatment, the combination of aliskiren/hydrochlorothiazide 300 mg/25 mg produced 

systolic/diastolic blood pressure reductions of 16.78/10.7 mmHg, which were significantly greater 

than hydrochlorothiazide 25 mg monotherapy. 

 

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36 

In another clinical trial, the efficacy and safety of Sprimeo HCT were also assessed in 489 obese 

hypertensive patients who did not respond to hydrochlorothiazide 25 mg (baseline systolic/diastolic 

blood pressure 149.4/96.8 mmHg). In this difficult-to-treat population, Sprimeo HCT provided a blood 

pressure reduction (systolic/diastolic) of 15.8/11.9 mmHg compared to 15.4/11.3 mmHg for 

irbesartan/hydrochlorothiazide, 13.6/10.3 mmHg for amlodipine/hydrochlorothiazide and 

8.6/7.9 mmHg for hydrochlorothiazide monotherapy, with similar safety to hydrochlorothiazide 

monotherapy. 

 

In a study in 183 randomised patients with severe hypertension (mean sitting diastolic blood pressure 

≥ 105 and < 120 mmHg), aliskiren treatment regimen with optional addition of hydrochlorothiazide 

25 mg was shown to be safe and efficacious in reducing blood pressure. 

 

5.2 Pharmacokinetic properties 
 

Aliskiren 

Absorption 

Following oral absorption, peak plasma concentrations of aliskiren are reached after 1-3 hours. The 

absolute bioavailability of aliskiren is approximately 2-3%. Meals with a high fat content reduce Cmax 

by 85% and AUC by 70%. Steady-state-plasma concentrations are reached within 5-7 days following 

once-daily administration and steady-state levels are approximately 2-fold greater than with the initial 

dose. 

 

Distribution 

Following intravenous administration, the mean volume of distribution at steady state is approximately 

135 litres, indicating that aliskiren distributes extensively into the extravascular space. Aliskiren 

plasma protein binding is moderate (47-51%) and independent of the concentration. 

 

Metabolism and elimination 

The mean half-life is about 40 hours (range 34-41 hours). Aliskiren is mainly eliminated as unchanged 

compound in the faeces (oral radioactive dose recovery = 91%). Approximately 1.4% of the total oral 

dose is metabolised. The enzyme responsible for this metabolism is CYP3A4. Approximately 0.6% of 

the dose is recovered in urine following oral administration. Following intravenous administration, the 

mean plasma clearance is approximately 9 l/h. 

 

Linearity 

Exposure to aliskiren increased slightly more than in proportion to the increase in dose. After single 

dose administration in the dose range of 75 to 600 mg, a 2-fold increase in dose results in a ~2.3 and 

2.6-fold increase in AUC and Cmax, respectively. Mechanisms responsible for the deviation from dose 

proportionality have not been identified. A possible mechanism is saturation of transporters at the 

absorption site or at the hepatobiliary clearance route. 

 

Hydrochlorothiazide 

Absorption 

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

 

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37 

Metabolism and elimination 

Hydrochlorothiazide is eliminated predominantly as unchanged compound. 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. There is more than 95% of the absorbed dose being excreted as 

unchanged compound in the urine. The renal clearance is composed of passive filtration and active 

secretion into the renal tubule. 

 

Aliskiren/hydrochlorothiazide 

Following oral administration of Sprimeo HCT tablets, the median peak plasma concentration time is 

within 1 hour for aliskiren and 2.5 hours for hydrochlorothiazide. 

 

The rate and extent of absorption of Sprimeo HCT are equivalent to the bioavailability of aliskiren and 

hydrochlorothiazide when administered as individual monotherapies. Similar food effect was observed 

for Sprimeo HCT as for the individual monotherapies. 

 

Characteristics in patients 

Sprimeo HCT has been shown to be effective as a once-a-day antihypertensive treatment in adult 

patients, regardless of gender, age, body mass index and ethnicity. 

 

The pharmacokinetics of aliskiren are not significantly affected in patients with mild to moderate liver 

disease. Consequently, no initial dose adjustment of Sprimeo HCT is required in patients with mild to 

moderate hepatic impairment. No data are available on patients with severe hepatic impairment treated 

by Sprimeo HCT. Sprimeo HCT is contraindicated in patients with severe hepatic impairment (see 

section 4.3). 

 

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

contraindicated in patients with anuria or severe renal impairment (GFR < 30 ml/min/1.73 m
2
) and the 

concomitant use of Sprimeo HCT with ARBs or ACEIs is contraindicated in patients with renal 

impairment (GFR < 60 ml/min/1.73 m
2
) (see section 4.3). 

 

The pharmacokinetics of aliskiren were evaluated in patients with end stage renal disease receiving 

haemodialysis. Administration of a single oral dose of 300 mg aliskiren was associated with very 

minor changes in the pharmacokinetics of aliskiren (change in Cmax of less than 1.2 fold; increase in 

AUC of up to 1.6 fold) compared to matched healthy subjects. Timing of haemodialysis did not 

significantly alter the pharmacokinetics of aliskiren in ESRD patients. Therefore, if administration of 

aliskiren in ESRD patients receiving haemodialysis is considered necessary, no dose adjustment is 

warranted in these patients. However, the use of aliskiren is not recommended in patients with severe 

renal impairment (see section 4.4). 

 

No initial dose adjustment of Sprimeo HCT is required in elderly patients. Limited data suggest that 

the systemic clearance of hydrochlorothiazide is reduced in both healthy and hypertensive elderly 

subjects compared to young healthy volunteers. 

 

No pharmacokinetic data are available in the paediatric population. 

 

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5.3 Preclinical safety data 
 

Safety pharmacology studies with aliskiren did not reveal any adverse effects on central nervous, 

respiratory or cardiovascular function. Findings during repeat-dose toxicity studies in animals were 

consistent with the known local irritation potential or the expected pharmacological effects of 

aliskiren. No carcinogenic potential for aliskiren was detected in a 2-year rat study and a 6-month 

transgenic mouse study. One colonic adenoma and one caecal adenocarcinoma recorded in rats at the 

dose of 1,500 mg/kg/day were not statistically significant. Aliskiren was devoid of any mutagenic 

potential, embryo-foetal toxicity or teratogenicity. Fertility, prenatal development and postnatal 

development were unaffected in rats. 

 

Preclinical evaluations to support the administration of hydrochlorothiazide in humans included in 

vitro genotoxicity assays and reproductive toxicity and carcinogenicity studies in rodents. Extensive 

clinical data are available for hydrochlorothiazide and these are reflected in the relevant sections. 

 

The findings observed in the 2-week and 13-week toxicity studies were consistent with those observed 

previously with aliskiren or hydrochlorothiazide monotherapies. There were no new or unexpected 

findings observed of relevance to human use. Increased cellular vacuolation of the adrenal gland zona 

glomerulosa was observed during the 13-week toxicity study in rats. The finding was observed in 

animals treated with hydrochlorothiazide but not in those animals receiving aliskiren alone or vehicle. 

There was no evidence that this finding was enhanced in the aliskiren/hydrochlorothiazide 

combination as it was only apparent at a minimal severity in all animals. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Tablet core: 

Cellulose microcrystalline 

Crospovidone 

Lactose monohydrate 

Wheat starch 

Povidone 

Magnesium stearate 

Silica colloidal anhydrous 

Talc 

 

Coating: 

Talc 

Hypromellose 

Macrogol 

Titanium dioxide (E171) 

Red iron oxide (E172) 

Yellow iron oxide (E172) 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

24 months 

 

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39 

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 

 

PA/Alu/PVC – Alu blisters: 

Single-packs containing 7, 14, 28, 30, 50 or 56 tablets. 

Multi-packs containing 90, 98 or 280 tablets. 

 

PVC/polychlorotrifluoroethylene (PCTFE) – Alu blisters: 

Single-packs containing 7, 14, 28, 30, 50, 56, 90 or 98 tablets. 

Single-packs (perforated unit dose blister) containing 56 x 1 tablets. 

Multi-packs containing 280 tablets. 

Multi-packs (perforated unit dose blister) containing 98 x 1 tablets. 

 

Not all pack sizes or strengths may be marketed. 

 

6.6 Special precautions for disposal 
 

Any unused product or waste material should be disposed of in accordance with local requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/021-040 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

23.06.2011 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

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

http://www.ema.europa.eu 

 

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40 

1. NAME OF THE MEDICINAL PRODUCT 
 

Sprimeo HCT 300 mg/12.5 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

Excipients: Each tablet contains 25 mg lactose monohydrate and 24.5 mg wheat starch. 

 

For a full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Film-coated tablet 

 

Violet white, biconvex, ovaloid film-coated tablet imprinted with “CVI” on one side and “NVR” on 

the other. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Treatment of essential hypertension in adults. 

 

Sprimeo HCT is indicated in patients whose blood pressure is not adequately controlled on aliskiren or 

hydrochlorothiazide used alone. 

 

Sprimeo HCT is indicated as substitution therapy in patients adequately controlled with aliskiren and 

hydrochlorothiazide, given concurrently, at the same dose level as in the combination. 

 

4.2 Posology and method of administration 

 

The recommended dose of Sprimeo HCT is one tablet per day. Sprimeo HCT should be taken with a 

light meal once a day, preferably at the same time each day. Grapefruit juice should not be taken 

together with Sprimeo HCT. 

 

The antihypertensive effect is largely manifested within 1 week and the maximum effect is generally 

seen within 4 weeks. 

 

Posology in patients not adequately controlled with aliskiren or hydrochlorothiazide monotherapy 

Individual dose titration with each of the two components may be recommended before changing to 

the fixed combination. When clinically appropriate, direct change from monotherapy to the fixed 

combination may be considered. 

 

Sprimeo HCT 300 mg /12.5 mg may be administered in patients whose blood pressure is not 

adequately controlled with aliskiren 300 mg or hydrochlorothiazide 12.5 mg alone or by Sprimeo HCT 

150 mg/12.5 mg. 

 

If blood pressure remains uncontrolled after 2-4 weeks of therapy, the dose may be titrated up to a 

maximum of Sprimeo HCT 300 mg/25 mg daily. Dosing should be individualised and adjusted 

according to the patient’s clinical response. 

 

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41 

Posology as substitution therapy 

For convenience, patients receiving aliskiren and hydrochlorothiazide from separate tablets may be 

switched to a fixed combination tablet of Sprimeo HCT containing the same component doses. 

 

Renal impairment 

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

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

use in patients with anuria and in patients with severe renal impairment (glomerular filtration rate 

(GFR) < 30 ml/min/1.73 m
2
). The concomitant use of Sprimeo HCT with angiotensin II receptor 

blockers (ARB) or angiotensin converting enzyme inhibitors (ACEI) is contraindicated in patients 

with renal impairment (GFR < 60 ml/min/1.73 m
2
) (see sections 4.3, 4.4 and 5.2). 

 

Hepatic impairment 

No adjustment of the initial dose is required for patients with mild to moderate hepatic impairment 

(see section 5.2). Sprimeo HCT is contraindicated in patients with severe hepatic impairment (see 

sections 4.3 and 4.4). 

 

Elderly patients (over 65 years) 

The recommended starting dose of aliskiren in elderly patients is 150 mg. No clinically meaningful 

additional blood pressure reduction is observed by increasing the dose to 300 mg in the majority of 

elderly patients. 

 

Paediatric patients 

Sprimeo HCT is not recommended for use in children and adolescents below age 18 due to a lack of 

data on safety and efficacy (see section 5.2). 

 

4.3 Contraindications 
 

 Hypersensitivity to the active substances or to any of the excipients (see section 6.1), or to other 
sulphonamide-derived substances. 

 History of angioedema with aliskiren. 

 Hereditary or idiopathic angioedema. 

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

 Anuria. 

 Severe renal impairment (GFR < 30 ml/min/1.73 m2). 

 Refractory hypokalaemia, hyponatraemia, hypercalcaemia and symptomatic hyperuricaemia. 

 Severe hepatic impairment. 

 The concomitant use of aliskiren with ciclosporin and itraconazole, two highly potent P-
glycoprotein (P-gp) inhibitors, and other potent P-gp inhibitors (e.g. quinidine), is 

contraindicated (see section 4.5). 

 The concomitant use of aliskiren with ARBs or ACEIs is contraindicated in patients with 
diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m

2
) (see sections 4.2, 4.4, 4.5 and 

5.1). 

 

4.4 Special warnings and precautions for use 
 

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

Hypotension, syncope, stroke, hyperkalaemia, and changes in renal function (including acute renal 

failure) have been reported in susceptible individuals, especially if combining medicinal products that 

affect this system (see section 5.1). Dual blockade of the renin-angiotensin-aldosterone system by 

combining aliskiren with an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin II 

receptor blocker (ARB) is therefore not recommended. 

 

The use of aliskiren in combination with ARBs or ACEIs is contraindicated in patients with diabetes 

mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) (see section 4.3). 

 

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42 

Heart failure 

Aliskiren should be used with caution in patients with serious congestive heart failure (New York 

Heart Association (NYHA) functional class III-IV). Sprimeo HCT should be used with caution in 

patients with heart failure due to limited clinical efficacy and safety data. 

 

Angioedema 

As with other agents acting on the renin-angiotensin system, angioedema or symptoms suggestive of 

angioedema (swelling of the face, lips, throat and/or tongue) have been reported in patients treated 

with aliskiren. 

 

A number of these patients had a history of angioedema or symptoms suggestive of angioedema, 

which in some cases followed use of other medicines that can cause angioedema, including RAAS 

blockers (angiotensin converting enzyme inhibitors or angiotensin receptor blockers) (see section 4.8). 

 

Patients with a history of angioedema may be at increased risk of experiencing angioedema during 

treatment with aliskiren (see sections 4.3 and 4.8). Caution should therefore be exercised when 

prescribing aliskiren to patients with a history of angioedema, and such patients should be closely 

monitored during treatment (see section 4.8) especially at the beginning of the treatment. 

 

If angioedema occurs, Sprimeo HCT should be promptly discontinued and appropriate therapy and 

monitoring provided until complete and sustained resolution of signs and symptoms has occurred. 

Where there is involvement of the tongue, glottis or larynx adrenaline should be administered. In 

addition, measures necessary to maintain patent airways should be provided. 

 

Sodium- and/or volume-depleted patients 

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 Sprimeo HCT. Sprimeo HCT 

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

 

Electrolyte imbalance 

Treatment with Sprimeo 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 Sprimeo HCT should be discontinued until stable correction of the potassium balance. 

Although hypokalaemia may develop with the use of thiazide diuretics, concurrent therapy with 

aliskiren may reduce diuretic-induced hypokalaemia. The risk of hypokalaemia is greater in patients 

with cirrhosis of the liver, patients experiencing brisk diuresis, patients with inadequate oral 

electrolyte intake and patients receiving concomitant therapy with corticosteroids or 

adrenocorticotropic hormone (ACTH) (see sections 4.5 and 4.8). 

 

Conversely, increases in serum potassium have been observed with aliskiren in post-marketing 

experience and these may be exacerbated by concomitant use of other agents acting on the RAAS or 

by non-steroidal anti-inflammatory drugs (NSAIDs). Consistent with standard medical practice, 

periodic determination of renal function including serum electrolytes is advised if co-administration is 

considered necessary. The concomitant use of aliskiren and ACEIs or ARBs is contraindicated in 

patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) (see sections 4.3, 4.5 

and 4.8). 

 

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 Sprimeo HCT therapy, the treatment should be discontinued until 

normalisation of natraemia. 

 

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43 

There is no evidence that Sprimeo HCT would reduce or prevent diuretic-induced hyponatraemia. 

Chloride deficit is generally mild and usually does not require treatment. 

 

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

electrolytes, particularly potassium, sodium and magnesium. 

 

Thiazides reduce urinary calcium excretion and may cause an intermittent and slight elevation of 

serum calcium in the absence of known disorders of calcium metabolism. Sprimeo HCT is 

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

existing hypercalcaemia. Sprimeo 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. 

 

Renal impairment and kidney transplantation 

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

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

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

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

 

No dosage adjustment is necessary in patients with mild to moderate renal impairment (GFR 

≥ 30 ml/min/1.73 m
2
). 

 

There is no experience regarding the administration of Sprimeo HCT in patients who have recently 

undergone kidney transplantation. 

 

As for other agents acting on the renin-angiotensin system, caution should be exercised when aliskiren 

is given in the presence of conditions pre-disposing to kidney dysfunction such as hypovolaemia (e.g. 

due to blood loss, severe or prolonged diarrhoea, prolonged vomiting, etc.), heart disease, liver 

disease, diabetes mellitus or kidney disease. The concomitant use of aliskiren and ACEIs or ARBs is 

contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m
2
). Acute renal failure, 

reversible upon discontinuation of treatment, has been reported in at-risk patients receiving aliskiren in 

post-marketing experience. In the event that any signs of renal failure occur, aliskiren should be 

promptly discontinued. 

 

Hepatic impairment 

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver 

disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. No 

adjustment of the initial dose is required for patients with mild to moderate hepatic impairment. No 

data are available for the use of Sprimeo HCT in patients with severe hepatic impairment. Due to the 

hydrochlorothiazide component, Sprimeo HCT is contraindicated in patients with severe hepatic 

impairment (see sections 4.3 and 5.2). 

 

There is no clinical experience with Sprimeo HCT in patients with hepatic impairment. 

 

Moderate P-gp inhibitors 

Co-administration of aliskiren 300 mg with ketoconazole 200 mg or verapamil 240 mg resulted in a 

76% or 97% increase in aliskiren AUC, respectively. Therefore caution should be exercised when 

aliskiren is administered with moderate P-gp inhibitors such as ketoconazole or verapamil (see section 

4.5). 

 

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy 

As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral 

stenosis, or obstructive hypertrophic cardiomyopathy. 

 

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44 

Renal artery stenosis and renovascular hypertension 

No controlled clinical data are available on the use of Sprimeo HCT in patients with unilateral or 

bilateral renal artery stenosis, or stenosis to a solitary kidney. However, as with other agents acting on 

the renin-angiotensin system, there is an increased risk of renal insufficiency, including acute renal 

failure, when patients with renal artery stenosis are treated with aliskiren. Therefore caution should be 

exercised in these patients. If renal failure occurs, treatment should be discontinued. 

 

Systemic lupus erythematosus 

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

systemic lupus erythematosus. 

 

Metabolic and endocrine effects 

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

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

hypoglycaemic agents may be required. Concomitant use of Sprimeo HCT with ARBs or ACEIs is 

contraindicated in patients with diabetes mellitus (see section 4.3). 

 

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

hyperuricaemia (see section 4.3). 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 an intermittent and slight elevation of 

serum calcium in the absence of known disorders of calcium metabolism. Sprimeo HCT is 

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

existing hypercalcaemia. Sprimeo 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 Sprimeo HCT, it is recommended to stop the 

treatment. If a re-administration of the diuretic is deemed necessary, it is recommended to protect 

exposed areas to the sun or to artificial UVA. 

 

Acute angle-closure glaucoma 

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

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

visual acuity or ocular pain and typically occur within hours to weeks 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 

In the event of severe and persistent diarrhoea, Sprimeo HCT therapy should be stopped. 

 

As with any antihypertensive agent, excessive reduction of blood pressure in patients with ischaemic 

cardiopathy or ischaemic cardiovascular disease could result in a myocardial infarction or stroke. 

 

Hypersensitivity reactions to hydrochlorothiazide may occur in patients, but are more likely in patients 

with allergy and asthma. 

 

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45 

Excipients 

Sprimeo HCT contains lactose. Patients with rare hereditary problems of galactose intolerance, the 

Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. 

 

Sprimeo HCT contains wheat starch. It is suitable for people with coeliac disease. Patients with wheat 

allergy (different from coeliac disease) should not take this medicine. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Information on Sprimeo HCT interactions 

Medicinal products affecting serum potassium levels: The potassium-depleting effect of 

hydrochlorothiazide is attenuated by the potassium-sparing effect of aliskiren. However, this effect of 

hydrochlorothiazide on serum potassium would be expected to be potentiated by other medicinal 

products associated with potassium loss and hypokalaemia (e.g. other kaliuretic diuretics, 

corticosteroids, laxatives, adrenocorticotropic hormone (ACTH), amphotericin, carbenoxolone, 

penicillin G, salicylic acid derivatives). Conversely, concomitant use of other agents affecting the 

RAAS, of NSAIDs or of agents that increase serum potassium levels (e.g. potassium-sparing diuretics, 

potassium supplements, salt substitutes containing potassium, heparin) may lead to increases in serum 

potassium. If co-medication with an agent affecting the level of serum potassium is considered 

necessary, caution is advisable. The combination of aliskiren with ARBs or ACEIs is contraindicated 

in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) and is not 

recommended in other patients (see sections 4.3, 4.4 and 5.1). 

 

Medicinal products affected by serum potassium disturbances: Periodic monitoring of serum 

potassium is recommended when Sprimeo HCT is administered with medicinal products affected by 

serum potassium disturbances (e.g. digitalis glycosides, antiarrhythmics). 

 

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors 

(COX-2 inhibitors), acetylsalicylic acid and non-selective NSAIDs: As with other agents acting on the 

renin-angiotensin system, NSAIDs may reduce the anti-hypertensive effect of aliskiren. NSAIDs may 

also weaken the diuretic and antihypertensive activity of hydrochlorothiazide. 

 

In some patients with compromised renal function (dehydrated patients or elderly patients) aliskiren 

and hydrochlorothiazide given concomitantly with NSAIDs may result in further deterioration of renal 

function, including possible acute renal failure, which is usually reversible. Therefore the use of 

Sprimeo HCT with an NSAID requires caution, especially in elderly patients. 

 

Other antihypertensive agents: The antihypertensive effect of Sprimeo HCT may be increased with 

the concomitant use of other antihypertensive agents. 

 

Additional information on aliskiren interactions 

The combination of aliskiren with ARBs or ACEIs is contraindicated in patients with diabetes mellitus 

or renal impairment (GFR < 60 ml/min/1.73 m
2
) and is not recommended in other patients (see 

sections 4.3, 4.4 and 5.1). 

 

Compounds that have been investigated in aliskiren clinical pharmacokinetic studies include 

acenocoumarol, atenolol, celecoxib, fenofibrate, pioglitazone, allopurinol, isosorbide-5-mononitrate, 

digoxin, metformin, amlodipine, atorvastatin, cimetidine and hydrochlorothiazide. No clinically 

relevant interactions have been identified. As a result no dose adjustment for aliskiren or these co-

administered medicinal products is necessary. 

 

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46 

P-glycoprotein interactions: MDR1/Mdr1a/1b (P-gp) was found to be the major efflux system 

involved in intestinal absorption and biliary excretion of aliskiren in preclinical studies. Rifampicin, 

which is an inducer of P-gp, reduced aliskiren bioavailability by approximately 50% in a clinical 

study. Other inducers of P-gp (St. John’s wort) might decrease the bioavailability of aliskiren. 

Although this has not been investigated for aliskiren, it is known that P-gp also controls tissue uptake 

of a variety of substrates and P-gp inhibitors can increase the tissue-to-plasma concentration ratios. 

Therefore, P-gp inhibitors may increase tissue levels more than plasma levels. The potential for drug 

interactions at the P-gp site will likely depend on the degree of inhibition of this transporter. 

 

P-gp potent inhibitors: A single dose drug interaction study in healthy subjects has shown that 

ciclosporin (200 and 600 mg) increases Cmax of aliskiren 75 mg approximately 2.5-fold and AUC 

approximately 5-fold. The increase may be higher with higher aliskiren doses. In healthy subjects, 

itraconazole (100 mg) increases AUC and Cmax of aliskiren (150 mg) by 6.5-fold and 5.8-fold, 

respectively. Therefore, concomitant use of aliskiren and P-gp potent inhibitors is contraindicated (see 

section 4.3). 

 

Moderate P-gp inhibitors: Co-administration of ketoconazole (200 mg) or verapamil (240 mg) with 

aliskiren (300 mg) resulted in a 76% or 97% increase in aliskiren AUC, respectively. The change in 

plasma levels of aliskiren in the presence of ketoconazole or verapamil is expected to be within the 

range that would be achieved if the dose of aliskiren were doubled; aliskiren doses of up to 600 mg, or 

twice the highest recommended therapeutic dose, have been found to be well tolerated in controlled 

clinical trials. Preclinical studies indicate that aliskiren and ketoconazole co-administration enhances 

aliskiren gastrointestinal absorption and decreases biliary excretion. Therefore, caution should be 

exercised when aliskiren is administered with ketoconazole, verapamil or other moderate P-gp 

inhibitors (clarithromycin, telithromycin, erythromycin, amiodarone). 

 

P-gp substrates or weak inhibitors: No relevant interactions with atenolol, digoxin, amlodipine or 

cimetidine have been observed. When administered with atorvastatin (80 mg), steady-state aliskiren 

(300 mg) AUC and Cmax increased by 50%. 

 

Organic anion transporting polypeptide (OATP) inhibitors: Preclinical studies indicate that aliskiren 

might be a substrate of organic anion transporting polypeptides. Therefore, the potential exists for 

interactions between OATP inhibitors and aliskiren when administered concomitantly (see interaction 

with Grapefruit juice). 

 

Grapefruit juice: Administration of grapefruit juice with aliskiren resulted in a decrease in AUC and 

Cmax of aliskiren. Co-administration with aliskiren 150 mg resulted in a 61% decrease in aliskiren 

AUC and co-administration with aliskiren 300 mg resulted in a 38% decrease in aliskiren AUC. This 

decrease is likely due to an inhibition of organic anion transporting polypeptide-mediated uptake of 

aliskiren by grapefruit juice in the gastrointestinal tract. Therefore, because of the risk of therapeutic 

failure, grapefruit juice should not be taken together with Sprimeo HCT. 

 

Furosemide: When aliskiren was co-administered with furosemide, the AUC and Cmax of furosemide 

were reduced by 28% and 49%, respectively. It is therefore recommended to monitor the effects when 

initiating and adjusting furosemide therapy to avoid possible underutilisation in clinical situations of 

volume overload. 

 

Warfarin: The effects of aliskiren on warfarin pharmacokinetics have not been evaluated. 

 

Food interactions: Meals with a high fat content have been shown to reduce the absorption of aliskiren 

substantially. 

 

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47 

Additional information on hydrochlorothiazide interactions 

When administered concurrently, the following medicinal products may interact with thiazide 

diuretics: 

 

Lithium: Renal clearance of lithium is reduced by thiazides, therefore the risk of lithium toxicity may 

be increased with hydrochlorothiazide. Co-administration of lithium and hydrochlorothiazide is not 

recommended. If this combination proves essential, careful monitoring of serum lithium level is 

recommended during concomitant use. 

 

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 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. 

 

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. 

 

Digoxine or other digitalis glycosides: Thiazide-induced hypokalaemia or hypomagnesaemia may 

occur as undesirable effects, favouring the onset of digitalis-induced cardiac arrhythmias. 

 

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. 

 

Antidiabetic agents (e.g. insulin and oral antidiabetic agents): Thiazides may alter glucose tolerance. 

Dose adjustment of the antidiabetic medicinal product may be necessary (see section 4.4). 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. 

 

Medicinal products used in the treatment of gout: 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. 

 

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. 

 

Amantadine: Thiazides, including hydrochlorothiazide, may increase the risk of adverse reactions 

caused by amantadine. 

 

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48 

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. 

 

Cytotoxic agents: Thiazides, including hydrochlorothiazide, may reduce the renal excretion of 

cytotoxic agents (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects. 

 

Non-depolarising skeletal muscle relaxants: Thiazides, including hydrochlorothiazide, potentiate the 

action of skeletal muscle relaxants such as curare derivatives. 

 

Alcohol, barbiturates or narcotics: Concomitant administration of thiazide diuretics with subtances 

that also have a blood pressure lowering effect (e.g. by reducing sympathetic central nervous system 

activity or direct vasodilatation) may potentiate orthostatic hypotension. 

 

Methyldopa: There have been isolated reports of haemolytic anaemia occurring with concomitant use 

of hydrochlorothiazide and methyldopa. 

 

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 rehydrated before 

administration. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

There are no data on the use of aliskiren in pregnant women. Aliskiren was not teratogenic in rats or 

rabbits (see section 5.3). Other substances that act directly on the RAAS have been associated with 

serious foetal malformations and neonatal death when used during second and third trimesters. 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. 

 

Hydrochlorothiazide should not be used for gestational oedema, gestational hypertension or 

pre-eclampsia due to the risk of decreased plasma volume and placental hypoperfusion, without a 

beneficial effect on the course of the disease. 

 

Hydrochlorothiazide should not be used for essential hypertension in pregnant women except in rare 

situations where no other treatment could be used. 

 

No specific clinical studies have been performed with this combination, therefore Sprimeo HCT 

should not be used during the first trimester of pregnancy or in women planning to become pregnant 

and is contraindicated during the second and third trimesters (see section 4.3). A switch to a suitable 

alternative treatment should be carried out in advance of a planned pregnancy. If pregnancy is detected 

during therapy, Sprimeo HCT should be discontinued as soon as possible. 

 

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49 

Breast-feeding 

It is not known whether aliskiren is excreted in human milk. Aliskiren was secreted in the milk of 

lactating rats. 

 

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

intense diuresis can inhibit milk production. 

 

The use of Sprimeo HCT during breast-feeding is not recommended. If Sprimeo HCT is used during 

breast-feeding, doses should be kept as low as possible. 

 

4.7 Effects on ability to drive and use machines 
 

No studies on the effect on the ability to drive and use machines have been performed. Sprimeo HCT 

is unlikely to affect the ability to drive and use machines. However, when driving vehicles or 

operating machinery it must be borne in mind that dizziness or drowsiness may occasionally occur 

when taking antihypertensive therapy. 

 

4.8 Undesirable effects 

 

Aliskiren/hydrochlorothiazide combination 

The safety of Sprimeo HCT has been evaluated in 9 clinical trials with more than 3,900 patients, 

including over 700 treated for over 6 months, and 190 for over 1 year. The incidence of adverse 

reactions showed no association with gender, age, body mass index, race or ethnicity. Treatment with 

Sprimeo HCT had an overall incidence of adverse experiences at doses up to 300 mg/25 mg similar to 

placebo. Adverse reactions have generally been mild and transient in nature and have only 

infrequently required discontinuation of therapy. The most common adverse drug reaction observed 

with Sprimeo HCT is diarrhoea. The adverse drug reactions previously reported with one of the 

individual components of Sprimeo HCT (aliskiren and hydrochlorothiazide) and listed in the 

respective paragraphs on the individual components may occur with Sprimeo HCT. 

 

The frequency of adverse reactions listed below is defined using the following convention: 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) and not known (cannot be estimated from the available data). 

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 

 

Gastrointestinal disorders 

 Common: Diarrhoea 

 

Diarrhoea: Diarrhoea is a dose-related adverse drug reaction for aliskiren. In controlled clinical trials, 

the incidence of diarrhoea in Sprimeo HCT-treated patients was 1.3% compared to 1.4% for aliskiren- 

or 1.9% for hydrochlorothiazide-treated patients. 

 

Serum potassium: In a large placebo-controlled clinical trial, the opposite effects of aliskiren (150 mg 

or 300 mg) and hydrochlorothiazide (12.5 mg or 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 potassium to detect possible electrolyte imbalance should be performed in 

patients at risk at appropriate intervals (see sections 4.4 and 4.5). 

 

Additional information on individual components 

Other adverse reactions previously reported with one of the individual components may occur with 

Sprimeo HCT even if not observed in clinical trials. 

 

Aliskiren 

Treatment with Aliskiren up to 300 mg resulted in an overall incidence of adverse reactions similar to 

placebo. Adverse reactions have generally been mild and transient in nature and have only 

infrequently required discontinuation of therapy. The most common adverse drug reaction is 

diarrhoea. 

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50 

 

The known aliskiren adverse drug reactions are presented in the table below using the same 

convention as described previously for the fixed combination. 

 

Nervous system disorders 

 Common: Dizziness 

Vascular disorders 

 Uncommon: Hypotension 

Gastrointestinal disorders 

 Common: Diarrhoea 

Immune system disorders 

 Rare: Hypersensitivity reactions 

Skin and subcutaneous tissue disorders 

 Uncommon: Rash, severe cutaneous adverse reactions (SCARs) including toxic 

epidermal necrolysis (TEN) and oral mucosal reactions 

 Rare: Angioedema 

Musculoskeletal and connective tissue disorders 

 Common: Arthralgia 

Renal and urinary disorders 
 Uncommon: Acute renal failure, renal impairment 

General disorders and administration site conditions 
 Uncommon: Oedema peripheral 

Investigations 
 Common: Hyperkalaemia 

 Rare: Haemoglobin decreased, haematocrit decreased 

 Rare: Blood creatinine increased 

 

Angioedema and hypersensitivity reactions have occurred during treatment with aliskiren. In 

controlled clinical trials, angioedema and hypersensitivity reactions occurred rarely during treatment 

with aliskiren with rates comparable to treatment with placebo or comparators. 

 

Cases of angioedema or symptoms suggestive of angioedema (swelling of the face, lips, throat and/or 

tongue) have also been reported in post-marketing experience. A number of these patients had a 

history of angioedema or symptoms suggestive of angioedema which in some cases was associated 

with the administration of other medicines known to cause angioedema, including RAAS blockers 

(ACE inhibitors or ARBs). 

 

Hypersensitivity reactions have also been reported in post-marketing experience. 

 

In the event of any signs suggesting a hypersensitivity reaction/angioedema (in particular difficulties 

in breathing or swallowing, rash, itching, hives or swelling of the face, extremities, eyes, lips and/or 

tongue, dizziness) patients should discontinue treatment and contact the physician (see section 4.4). 

 

Arthralgia has been reported in post-marketing experience. In some cases this occurred as part of a 

hypersensitivity reaction. 

 

Haemoglobin and haematocrit: Small decreases in haemoglobin and haematocrit (mean decreases of 

approximately 0.05 mmol/l and 0.16 volume percent, respectively) were observed. No patients 

discontinued therapy due to anaemia. This effect is also seen with other agents acting on the renin-

angiotensin system, such as ACEI and ARBs. 

 

Serum potassium: Increases in serum potassium have been observed with aliskiren and these may be 

exacerbated by concomitant use of other agents acting on the RAAS or by NSAIDs. Consistent with 

standard medical practice, periodic determination of renal function including serum electrolytes is 

advised if co-administration is considered necessary. The combination of aliskiren with ARBs or 

ACEIs is contraindicated in patients with diabetes mellitus or renal impairment (GFR 

< 60 ml/min/1.73 m
2
) and is not recommended in other patients (see sections 4.3, 4.4 and 5.1). 

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51 

 

In post-marketing experience, renal dysfunction and cases of acute renal failure have been reported in 

patients at risk (see section 4.4). There have also been reports of peripheral oedema, increase in blood 

creatinine and severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis 

(TEN) and oral mucosal reactions. 

 

Hydrochlorothiazide 

Hydrochlorothiazide has been extensively prescribed for many years, frequently in higher doses than 

those contained in Sprimeo HCT. The following adverse reactions have been reported in patients 

treated with thiazide diuretics alone, including hydrochlorothiazide: 

 

Blood and lymphatic system disorders 

 Rare: Thrombocytopenia sometimes with purpura 

 Very rare: Agranulocytosis, bone marrow depression, haemolytic anaemia, 

leucopenia 

 Not known: Aplastic anaemia 
Immune system disorders 

 Very rare: Hypersensitivity 

Metabolism and nutrition disorders 

 Very common: Hypokalaemia 

 Common: Hyperuricaemia, hypomagnesaemia, hyponatraemia 

 Rare: Hypercalcaemia, hyperglycaemia, worsening of diabetic metabolic 

state 

 Very rare: Hypochloraemic alkalosis 

Psychiatric disorders 

 Rare: Depression, sleep disturbances 

Nervous system disorders 

 Rare: Dizziness, headache, paraesthesia 

Eye disorders 

 Rare: Visual impairment 

 Not known: Acute angle-closure glaucoma 

Cardiac disorders 

 Rare: Cardiac arrhythmias 

Vascular disorders 

 Common: Orthostatic hypotension 

Respiratory, thoracic and mediastinal disorders 

 Very rare: Respiratory distress (including pneumonitis and pulmonary oedema) 

Gastrointestinal disorders 

 Common: Decreased appetite, mild nausea and vomiting 

 Rare: Abdominal discomfort, constipation, diarrhoea 

 Very rare: Pancreatitis 

Hepatobiliary disorders 

 Rare: Intrahepatic cholestasis, jaundice 

Skin and subcutaneous tissue disorders 

 Common: Urticaria and other forms of rash 

 Rare: Photosensitivity reactions 

 Very rare: Cutaneous lupus erythematosus-like reactions, reactivation of 

cutaneous lupus erythematosus, vasculitis necrotising and toxic 

epidermal necrolysis 

 Not known: Erythema multiforme 

Musculoskeletal and connective tissue disorders 

 Not known: Muscle spasm 

Renal and urinary disorders 

 Not known: Renal dysfunction, acute renal failure 

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52 

 

Reproductive system and breast disorders 

 Common: Impotence 

General disorders and administration site conditions 

 Not known: Asthenia, pyrexia 

Investigations 

 Very common: Increases in cholesterol and triglycerides 

 Rare: Glycosuria 

 

4.9 Overdose 
 

No information is available on the treatment of overdose with Sprimeo HCT. The most likely 

manifestation of overdose would be hypotension, related to the antihypertensive effect of aliskiren. 

 

Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, 

hypochloraemia, hyponatraemia) and dehydration 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 cardiac arrhythmias associated with the concomitant use of digitalis 

glycosides or certain antiarrhythmic medicinal products. If symptomatic hypotension should occur, 

supportive treatment should be initiated. 

 

In a study conducted in patients with end stage renal disease (ESRD) receiving haemodialysis, dialysis 

clearance of aliskiren was low (< 2% of oral clearance). Therefore dialysis is not adequate to treat 

aliskiren over-exposure. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Renin inhibitor (aliskiren) combinations with diuretics 

(hydrochlorothiazide), ATC code: C09XA52 

Sprimeo HCT combines two antihypertensive compounds to control blood pressure in patients with 

essential hypertension: Aliskiren belongs to the class of direct renin inhibitors and hydrochlorothiazide 

to the class of thiazide diuretics. The combination of these substances with complementary 

mechanisms of action provides an additive antihypertensive effect, reducing blood pressure to a 

greater degree than either component alone. 

 

Aliskiren 

Aliskiren is an orally active, non-peptide, potent and selective direct inhibitor of human renin. 

 

By inhibiting the enzyme renin, aliskiren inhibits the RAAS at the point of activation, blocking the 

conversion of angiotensinogen to angiotensin I and decreasing levels of angiotensin I and 

angiotensin II. Whereas other agents that inhibit the RAAS (angiotensin converting enzyme inhibitors 

(ACEI) and angiotension II receptor blockers (ARB)) cause a compensatory rise in plasma renin 

activity (PRA), treatment with aliskiren decreases PRA in hypertensive patients by approximately 50 

to 80%. Similar reductions were found when aliskiren was combined with other antihypertensive 

agents. The clinical implications of the effects on PRA are not known at the present time. 

 

In hypertensive patients, once-daily administration of aliskiren at doses of 150 mg and 300 mg 

provided dose-dependent reductions in both systolic and diastolic blood pressure that were maintained 

over the entire 24-hour dose interval (maintaining benefit in the early morning) with a mean peak to 

trough ratio for diastolic response of up to 98% for the 300 mg dose. 85 to 90% of the maximal blood-

pressure-lowering effect was observed after 2 weeks. The blood-pressure-lowering effect was 

sustained during long-term treatment (12 months), and was independent of age, gender, body mass 

index and ethnicity. 

 

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53 

Combination therapy studies are available for aliskiren added to the diuretic hydrochlorothiazide, the 

calcium channel blocker amlodipine and the beta blocker atenolol. These combinations were 

efficacious and well tolerated. 

 

The efficacy and safety of aliskiren-based therapy were compared to ramipril-based therapy in a 9-

month non-inferiority study in 901 elderly patients (≥ 65 years) with essential systolic hypertension. 

Aliskiren 150 mg or 300 mg per day or ramipril 5 mg or 10 mg per day were administered for 

36 weeks with optional add-on therapy of hydrochlorothiazide (12.5 mg or 25 mg) at week 12, and 

amlodipine (5 mg or 10 mg) at week 22. Over the 12 week period, aliskiren monotherapy lowered 

systolic/diastolic blood pressure by 14.0/5.1 mmHg, compared to 11.6/3.6 mmHg for ramipril, 

consistent with aliskiren being non-inferior to ramipril at the dosages chosen and the differences in 

systolic and diastolic blood pressure were statistically significant. Tolerability was comparable in both 

treatment arms, however cough was more often reported with the ramipril regimen than the aliskiren 

regimen (14.2% vs. 4.4%), whilst diarrhoea was more common with the aliskiren regimen than for the 

ramipril regimen (6.6% vs. 5.0%). 

 

In a 8-week study in 754 hypertensive elderly (≥ 65 years) and very elderly patients (30% ≥ 75 years) 

aliskiren at doses of 75 mg, 150 mg and 300 mg provided statistically significant superior reduction in 

blood pressure (both systolic and diastolic) when compared to placebo. No additional blood pressure 

lowering effect was detected with 300 mg aliskiren compared to 150 mg aliskiren. All three doses 

were well tolerated in both elderly and very elderly patients. 

 

There has been no evidence of first-dose hypotension and no effect on pulse rate in patients treated in 

controlled clinical studies. With cessation of treatment, blood pressure gradually returned towards 

baseline levels over a period of several weeks, with no evidence of a rebound effect for blood pressure 

or PRA. 

 

In a 36-week study involving 820 patients with ischaemic left ventricular dysfunction, no changes in 

ventricular remodelling as assessed by left ventricular end systolic volume were detected with 

aliskiren compared to placebo on top of background therapy. 

 

The combined rates of cardiovascular death, hospitalisation for heart failure, recurrent heart attack, 

stroke and resuscitated sudden death were similar in the aliskiren group and the placebo group. 

However, in patients receiving aliskiren there was a significantly higher rate of hyperkalaemia, 

hypotension and kidney dysfunction when compared to the placebo group. 

 

Aliskiren was evaluated for cardiovascular and/or renal benefit in a double-blind placebo controlled 

randomised trial in 8,606 patients with type 2 diabetes and chronic kidney disease (evidenced by 

proteinuria and/or GFR < 60 ml/min/1.73 m
2
) with or without cardiovascular disease. In most patients 

arterial blood pressure was well controlled at baseline. The primary endpoint was a composite of 

cardiovascular and renal complications. 

 

In this study, aliskiren 300 mg was compared to placebo when added to standard of care which 

included either an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker. The 

study was discontinued prematurely because the participants were unlikely to benefit from aliskiren. 

Preliminary study results indicated a hazard ratio for the primary endpoint of 1.09 in favour of placebo 

(95% Confidence Interval: 0.97, 1.22, 2-sided p=0.17). In addition, an increased incidence of serious 

adverse outcomes was observed with aliskiren compared to placebo for renal complications (4.7% 

versus 3.3%), hyperkalaemia (36.9% versus 27.1%), hypotension (18.4% versus 14.6%) and stroke 

(2.7% versus 2.0%). The increased incidence of non-fatal stroke was greater in patients with renal 

insufficiency. 

 

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54 

Hydrochlorothiazide 

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

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

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

action of thiazides is through inhibition of the Na+Cl- symporter 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. 

 

Aliskiren/hydrochlorothiazide 

Over 3,900 hypertensive patients received Sprimeo HCT once daily in clinical trials. 

 

In hypertensive patients, once-daily administration of Sprimeo HCT provided dose-dependent 

reductions in both systolic and diastolic blood pressure that were maintained over the entire 24-hour 

dose interval. The antihypertensive effect is largely manifested within 1 week and the maximum effect 

is generally seen within 4 weeks.The blood-pressure-lowering effect was sustained during long-term 

treatment, and was independent of age, gender, body mass index and ethnicity. The antihypertensive 

effect of a single dose of the combination persisted for 24 hours. Upon withdrawal of the aliskiren 

treatment (aliskiren with or without hydrochlorothiazide add-on), the return of blood pressure towards 

baseline was gradual (3-4 weeks) with no evidence of the rebound effect. 

 

Sprimeo HCT was studied in a placebo-controlled trial including 2,762 hypertensive patients with 

diastolic blood pressure ≥ 95 mmHg and < 110 mmHg (mean baseline blood pressure of 

153.6/99.2 mmHg). In this study, Sprimeo HCT in doses from 150 mg/12.5 mg to 300 mg/25 mg 

produced dose-dependent blood pressure reductions (systolic/diastolic) from 17.6/11.9 mmHg to 

21.2/14.3 mmHg, respectively, compared to 7.5/6.9 mmHg with placebo. The greater blood pressure 

reductions with these combination doses were also significantly greater than the respective doses of 

aliskiren and hydrochlorothiazide when used alone. The combination of aliskiren and 

hydrochlorothiazide neutralised the reactive increase of PRA caused by hydrochlorothiazide. 

 

When administered in hypertensive patients with markedly elevated blood pressure (systolic blood 

pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg), Sprimeo HCT in doses from 

150 mg/12.5 mg to 300 mg/25 mg administered without up-titration from monotherapy demonstrated 

significantly greater systolic/diastolic blood pressure control rates (< 140/90 mmHg) as compared to 

the respective monotherapies. In this population, Sprimeo HCT 150 mg/12.5 mg to 300 mg/25 mg 

provided dose-dependent systolic/diastolic blood pressure reduction from 20.6/12.4 mmHg to 

24.8/14.5 mmHg, which were significantly superior to the respective monotherapies. The safety of the 

combination therapy was similar to the respective monotherapies regardless of severity of 

hypertension or of the presence or absence of additional cardiovascular risk. Hypotension and related 

adverse events were uncommon with the combination treatment, with no increased incidence in 

elderly patients. 

 

In a study in 880 randomised patients not adequately responsive to aliskiren 300 mg treatment, the 

combination of aliskiren/hydrochlorothiazide 300 mg/25 mg produced systolic/diastolic blood 

pressure reductions of 15.8/11.0 mmHg, which were significantly greater than aliskiren 300 mg 

monotherapy. In a study in 722 randomised patients not adequately responsive to hydrochlorothiazide 

25 mg treatment, the combination of aliskiren/hydrochlorothiazide 300 mg/25 mg produced 

systolic/diastolic blood pressure reductions of 16.78/10.7 mmHg, which were significantly greater 

than hydrochlorothiazide 25 mg monotherapy. 

 

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55 

In another clinical trial, the efficacy and safety of Sprimeo HCT were also assessed in 489 obese 

hypertensive patients who did not respond to hydrochlorothiazide 25 mg (baseline systolic/diastolic 

blood pressure 149.4/96.8 mmHg). In this difficult-to-treat population, Sprimeo HCT provided a blood 

pressure reduction (systolic/diastolic) of 15.8/11.9 mmHg compared to 15.4/11.3 mmHg for 

irbesartan/hydrochlorothiazide, 13.6/10.3 mmHg for amlodipine/hydrochlorothiazide and 

8.6/7.9 mmHg for hydrochlorothiazide monotherapy, with similar safety to hydrochlorothiazide 

monotherapy. 

 

In a study in 183 randomised patients with severe hypertension (mean sitting diastolic blood pressure 

≥ 105 and < 120 mmHg), aliskiren treatment regimen with optional addition of hydrochlorothiazide 

25 mg was shown to be safe and efficacious in reducing blood pressure. 

 

5.2 Pharmacokinetic properties 
 

Aliskiren 

Absorption 

Following oral absorption, peak plasma concentrations of aliskiren are reached after 1-3 hours. The 

absolute bioavailability of aliskiren is approximately 2-3%. Meals with a high fat content reduce Cmax 

by 85% and AUC by 70%. Steady-state-plasma concentrations are reached within 5-7 days following 

once-daily administration and steady-state levels are approximately 2-fold greater than with the initial 

dose. 

 

Distribution 

Following intravenous administration, the mean volume of distribution at steady state is approximately 

135 litres, indicating that aliskiren distributes extensively into the extravascular space. Aliskiren 

plasma protein binding is moderate (47-51%) and independent of the concentration. 

 

Metabolism and elimination 

The mean half-life is about 40 hours (range 34-41 hours). Aliskiren is mainly eliminated as unchanged 

compound in the faeces (oral radioactive dose recovery = 91%). Approximately 1.4% of the total oral 

dose is metabolised. The enzyme responsible for this metabolism is CYP3A4. Approximately 0.6% of 

the dose is recovered in urine following oral administration. Following intravenous administration, the 

mean plasma clearance is approximately 9 l/h. 

 

Linearity 

Exposure to aliskiren increased slightly more than in proportion to the increase in dose. After single 

dose administration in the dose range of 75 to 600 mg, a 2-fold increase in dose results in a ~2.3 and 

2.6-fold increase in AUC and Cmax, respectively. Mechanisms responsible for the deviation from dose 

proportionality have not been identified. A possible mechanism is saturation of transporters at the 

absorption site or at the hepatobiliary clearance route. 

 

Hydrochlorothiazide 

Absorption 

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

 

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56 

Metabolism and elimination 

Hydrochlorothiazide is eliminated predominantly as unchanged compound. 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. There is more than 95% of the absorbed dose being excreted as 

unchanged compound in the urine. The renal clearance is composed of passive filtration and active 

secretion into the renal tubule. 

 

Aliskiren/hydrochlorothiazide 

Following oral administration of Sprimeo HCT tablets, the median peak plasma concentration time is 

within 1 hour for aliskiren and 2.5 hours for hydrochlorothiazide. 

 

The rate and extent of absorption of Sprimeo HCT are equivalent to the bioavailability of aliskiren and 

hydrochlorothiazide when administered as individual monotherapies. Similar food effect was observed 

for Sprimeo HCT as for the individual monotherapies. 

 

Characteristics in patients 

Sprimeo HCT has been shown to be effective as a once-a-day antihypertensive treatment in adult 

patients, regardless of gender, age, body mass index and ethnicity. 

 

The pharmacokinetics of aliskiren are not significantly affected in patients with mild to moderate liver 

disease. Consequently, no initial dose adjustment of Sprimeo HCT is required in patients with mild to 

moderate hepatic impairment. No data are available on patients with severe hepatic impairment treated 

by Sprimeo HCT. Sprimeo HCT is contraindicated in patients with severe hepatic impairment (see 

section 4.3). 

 

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

contraindicated in patients with anuria or severe renal impairment (GFR < 30 ml/min/1.73 m
2
) and the 

concomitant use of Sprimeo HCT with ARBs or ACEIs is contraindicated in patients with renal 

impairment (GFR < 60 ml/min/1.73 m
2
) (see section 4.3). 

 

The pharmacokinetics of aliskiren were evaluated in patients with end stage renal disease receiving 

haemodialysis. Administration of a single oral dose of 300 mg aliskiren was associated with very 

minor changes in the pharmacokinetics of aliskiren (change in Cmax of less than 1.2 fold; increase in 

AUC of up to 1.6 fold) compared to matched healthy subjects. Timing of haemodialysis did not 

significantly alter the pharmacokinetics of aliskiren in ESRD patients. Therefore, if administration of 

aliskiren in ESRD patients receiving haemodialysis is considered necessary, no dose adjustment is 

warranted in these patients. However, the use of aliskiren is not recommended in patients with severe 

renal impairment (see section 4.4). 

 

No initial dose adjustment of Sprimeo HCT is required in elderly patients. Limited data suggest that 

the systemic clearance of hydrochlorothiazide is reduced in both healthy and hypertensive elderly 

subjects compared to young healthy volunteers. 

 

No pharmacokinetic data are available in the paediatric population. 

 

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5.3 Preclinical safety data 
 

Safety pharmacology studies with aliskiren did not reveal any adverse effects on central nervous, 

respiratory or cardiovascular function. Findings during repeat-dose toxicity studies in animals were 

consistent with the known local irritation potential or the expected pharmacological effects of 

aliskiren. No carcinogenic potential for aliskiren was detected in a 2-year rat study and a 6-month 

transgenic mouse study. One colonic adenoma and one caecal adenocarcinoma recorded in rats at the 

dose of 1,500 mg/kg/day were not statistically significant. Aliskiren was devoid of any mutagenic 

potential, embryo-foetal toxicity or teratogenicity. Fertility, prenatal development and postnatal 

development were unaffected in rats. 

 

Preclinical evaluations to support the administration of hydrochlorothiazide in humans included in 

vitro genotoxicity assays and reproductive toxicity and carcinogenicity studies in rodents. Extensive 

clinical data are available for hydrochlorothiazide and these are reflected in the relevant sections. 

 

The findings observed in the 2-week and 13-week toxicity studies were consistent with those observed 

previously with aliskiren or hydrochlorothiazide monotherapies. There were no new or unexpected 

findings observed of relevance to human use. Increased cellular vacuolation of the adrenal gland zona 

glomerulosa was observed during the 13-week toxicity study in rats. The finding was observed in 

animals treated with hydrochlorothiazide but not in those animals receiving aliskiren alone or vehicle. 

There was no evidence that this finding was enhanced in the aliskiren/hydrochlorothiazide 

combination as it was only apparent at a minimal severity in all animals. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Tablet core: 

Cellulose microcrystalline 

Crospovidone 

Lactose monohydrate 

Wheat starch 

Povidone 

Magnesium stearate 

Silica colloidal anhydrous 

Talc 

 

Coating: 

Talc 

Hypromellose 

Macrogol 

Titanium dioxide (E171) 

Red iron oxide (E172) 

Black iron oxide (E172) 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

24 months 

 

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58 

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 

 

PA/Alu/PVC – Alu blisters: 

Single-packs containing 7, 14, 28, 30, 50 or 56 tablets. 

Multi-packs containing 90, 98 or 280 tablets. 

 

PVC/polychlorotrifluoroethylene (PCTFE) – Alu blisters: 

Single-packs containing 7, 14, 28, 30, 50, 56, 90 or 98 tablets. 

Single-packs (perforated unit dose blister) containing 56 x 1 tablets. 

Multi-packs containing 280 tablets. 

Multi-packs (perforated unit dose blister) containing 98 x 1 tablets. 

 

Not all pack sizes or strengths may be marketed. 

 

6.6 Special precautions for disposal 
 

Any unused product or waste material should be disposed of in accordance with local requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/041-060 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

23.06.2011 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

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

http://www.ema.europa.eu 

 

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59 

1. NAME OF THE MEDICINAL PRODUCT 
 

Sprimeo HCT 300 mg/25 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

Excipients: Each tablet contains 50 mg lactose monohydrate and 49 mg wheat starch. 

 

For a full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Film-coated tablet 

 

Light yellow, biconvex, ovaloid film-coated tablet imprinted with “CVV” on one side and “NVR” on 

the other. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Treatment of essential hypertension in adults. 

 

Sprimeo HCT is indicated in patients whose blood pressure is not adequately controlled on aliskiren or 

hydrochlorothiazide used alone. 

 

Sprimeo HCT is indicated as substitution therapy in patients adequately controlled with aliskiren and 

hydrochlorothiazide, given concurrently, at the same dose level as in the combination. 

 

4.2 Posology and method of administration 

 

The recommended dose of Sprimeo HCT is one tablet per day. Sprimeo HCT should be taken with a 

light meal once a day, preferably at the same time each day. Grapefruit juice should not be taken 

together with Sprimeo HCT. 

 

The antihypertensive effect is largely manifested within 1 week and the maximum effect is generally 

seen within 4 weeks. 

 

Posology in patients not adequately controlled with aliskiren or hydrochlorothiazide monotherapy 

Individual dose titration with each of the two components may be recommended before changing to 

the fixed combination. When clinically appropriate, direct change from monotherapy to the fixed 

combination may be considered. 

 

Sprimeo HCT 300 mg /25 mg may be administered in patients whose blood pressure is not adequately 

controlled with aliskiren 300 mg or hydrochlorothiazide 25 mg alone or by Sprimeo HCT 

300 mg/12.5 mg or Sprimeo HCT 150 mg/25 mg. 

 

If blood pressure remains uncontrolled after 2-4 weeks of therapy, the dose may be titrated up to a 

maximum of Sprimeo HCT 300 mg/25 mg daily. Dosing should be individualised and adjusted 

according to the patient’s clinical response. 

 

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60 

Posology as substitution therapy 

For convenience, patients receiving aliskiren and hydrochlorothiazide from separate tablets may be 

switched to a fixed combination tablet of Sprimeo HCT containing the same component doses. 

 

Renal impairment 

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

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

use in patients with anuria and in patients with severe renal impairment (glomerular filtration rate 

(GFR) < 30 ml/min/1.73 m
2
). The concomitant use of Sprimeo HCT with angiotensin II receptor 

blockers (ARB) or angiotensin converting enzyme inhibitors (ACEI) is contraindicated in patients 

with renal impairment (GFR < 60 ml/min/1.73 m
2
) (see sections 4.3, 4.4 and 5.2). 

 

Hepatic impairment 

No adjustment of the initial dose is required for patients with mild to moderate hepatic impairment 

(see section 5.2). Sprimeo HCT is contraindicated in patients with severe hepatic impairment (see 

sections 4.3 and 4.4). 

 

Elderly patients (over 65 years) 

The recommended starting dose of aliskiren in elderly patients is 150 mg. No clinically meaningful 

additional blood pressure reduction is observed by increasing the dose to 300 mg in the majority of 

elderly patients. 

 

Paediatric patients 

Sprimeo HCT is not recommended for use in children and adolescents below age 18 due to a lack of 

data on safety and efficacy (see section 5.2). 

 

4.3 Contraindications 
 

 Hypersensitivity to the active substances or to any of the excipients (see section 6.1), or to other 
sulphonamide-derived substances. 

 History of angioedema with aliskiren. 

 Hereditary or idiopathic angioedema. 

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

 Anuria. 

 Severe renal impairment (GFR < 30 ml/min/1.73 m2). 

 Refractory hypokalaemia, hyponatraemia, hypercalcaemia and symptomatic hyperuricaemia. 

 Severe hepatic impairment. 

 The concomitant use of aliskiren with ciclosporin and itraconazole, two highly potent P-
glycoprotein (P-gp) inhibitors, and other potent P-gp inhibitors (e.g. quinidine), is 

contraindicated (see section 4.5). 

 The concomitant use of aliskiren with ARBs or ACEIs is contraindicated in patients with 
diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m

2
) (see sections 4.2, 4.4, 4.5 and 

5.1). 

 

4.4 Special warnings and precautions for use 
 

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

Hypotension, syncope, stroke, hyperkalaemia, and changes in renal function (including acute renal 

failure) have been reported in susceptible individuals, especially if combining medicinal products that 

affect this system (see section 5.1). Dual blockade of the renin-angiotensin-aldosterone system by 

combining aliskiren with an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin II 

receptor blocker (ARB) is therefore not recommended. 

 

The use of aliskiren in combination with ARBs or ACEIs is contraindicated in patients with diabetes 

mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) (see section 4.3). 

 

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61 

Heart failure 

Aliskiren should be used with caution in patients with serious congestive heart failure (New York 

Heart Association (NYHA) functional class III-IV). Sprimeo HCT should be used with caution in 

patients with heart failure due to limited clinical efficacy and safety data. 

 

Angioedema 

As with other agents acting on the renin-angiotensin system, angioedema or symptoms suggestive of 

angioedema (swelling of the face, lips, throat and/or tongue) have been reported in patients treated 

with aliskiren. 

 

A number of these patients had a history of angioedema or symptoms suggestive of angioedema, 

which in some cases followed use of other medicines that can cause angioedema, including RAAS 

blockers (angiotensin converting enzyme inhibitors or angiotensin receptor blockers) (see section 4.8). 

 

Patients with a history of angioedema may be at increased risk of experiencing angioedema during 

treatment with aliskiren (see sections 4.3 and 4.8). Caution should therefore be exercised when 

prescribing aliskiren to patients with a history of angioedema, and such patients should be closely 

monitored during treatment (see section 4.8) especially at the beginning of the treatment. 

 

If angioedema occurs, Sprimeo HCT should be promptly discontinued and appropriate therapy and 

monitoring provided until complete and sustained resolution of signs and symptoms has occurred. 

Where there is involvement of the tongue, glottis or larynx adrenaline should be administered. In 

addition, measures necessary to maintain patent airways should be provided. 

 

Sodium- and/or volume-depleted patients 

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 Sprimeo HCT. Sprimeo HCT 

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

 

Electrolyte imbalance 

Treatment with Sprimeo 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 Sprimeo HCT should be discontinued until stable correction of the potassium balance. 

Although hypokalaemia may develop with the use of thiazide diuretics, concurrent therapy with 

aliskiren may reduce diuretic-induced hypokalaemia. The risk of hypokalaemia is greater in patients 

with cirrhosis of the liver, patients experiencing brisk diuresis, patients with inadequate oral 

electrolyte intake and patients receiving concomitant therapy with corticosteroids or 

adrenocorticotropic hormone (ACTH) (see sections 4.5 and 4.8). 

 

Conversely, increases in serum potassium have been observed with aliskiren in post-marketing 

experience and these may be exacerbated by concomitant use of other agents acting on the RAAS or 

by non-steroidal anti-inflammatory drugs (NSAIDs). Consistent with standard medical practice, 

periodic determination of renal function including serum electrolytes is advised if co-administration is 

considered necessary. The concomitant use of aliskiren and ACEIs or ARBs is contraindicated in 

patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) (see sections 4.3, 4.5 

and 4.8). 

 

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 Sprimeo HCT therapy, the treatment should be discontinued until 

normalisation of natraemia. 

 

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62 

There is no evidence that Sprimeo HCT would reduce or prevent diuretic-induced hyponatraemia. 

Chloride deficit is generally mild and usually does not require treatment. 

 

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

electrolytes, particularly potassium, sodium and magnesium. 

 

Thiazides reduce urinary calcium excretion and may cause an intermittent and slight elevation of 

serum calcium in the absence of known disorders of calcium metabolism. Sprimeo HCT is 

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

existing hypercalcaemia. Sprimeo 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. 

 

Renal impairment and kidney transplantation 

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

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

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

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

 

No dosage adjustment is necessary in patients with mild to moderate renal impairment (GFR 

≥ 30 ml/min/1.73 m
2
). 

 

There is no experience regarding the administration of Sprimeo HCT in patients who have recently 

undergone kidney transplantation. 

 

As for other agents acting on the renin-angiotensin system, caution should be exercised when aliskiren 

is given in the presence of conditions pre-disposing to kidney dysfunction such as hypovolaemia (e.g. 

due to blood loss, severe or prolonged diarrhoea, prolonged vomiting, etc.), heart disease, liver 

disease, diabetes mellitus or kidney disease. The concomitant use of aliskiren and ACEIs or ARBs is 

contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m
2
). Acute renal failure, 

reversible upon discontinuation of treatment, has been reported in at-risk patients receiving aliskiren in 

post-marketing experience. In the event that any signs of renal failure occur, aliskiren should be 

promptly discontinued. 

 

Hepatic impairment 

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver 

disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. No 

adjustment of the initial dose is required for patients with mild to moderate hepatic impairment. No 

data are available for the use of Sprimeo HCT in patients with severe hepatic impairment. Due to the 

hydrochlorothiazide component, Sprimeo HCT is contraindicated in patients with severe hepatic 

impairment (see sections 4.3 and 5.2). 

 

There is no clinical experience with Sprimeo HCT in patients with hepatic impairment. 

 

Moderate P-gp inhibitors 

Co-administration of aliskiren 300 mg with ketoconazole 200 mg or verapamil 240 mg resulted in a 

76% or 97% increase in aliskiren AUC, respectively. Therefore caution should be exercised when 

aliskiren is administered with moderate P-gp inhibitors such as ketoconazole or verapamil (see section 

4.5). 

 

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy 

As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral 

stenosis, or obstructive hypertrophic cardiomyopathy. 

 

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Renal artery stenosis and renovascular hypertension 

No controlled clinical data are available on the use of Sprimeo HCT in patients with unilateral or 

bilateral renal artery stenosis, or stenosis to a solitary kidney. However, as with other agents acting on 

the renin-angiotensin system, there is an increased risk of renal insufficiency, including acute renal 

failure, when patients with renal artery stenosis are treated with aliskiren. Therefore caution should be 

exercised in these patients. If renal failure occurs, treatment should be discontinued. 

 

Systemic lupus erythematosus 

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

systemic lupus erythematosus. 

 

Metabolic and endocrine effects 

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

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

hypoglycaemic agents may be required. Concomitant use of Sprimeo HCT with ARBs or ACEIs is 

contraindicated in patients with diabetes mellitus (see section 4.3). 

 

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

hyperuricaemia (see section 4.3). 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 an intermittent and slight elevation of 

serum calcium in the absence of known disorders of calcium metabolism. Sprimeo HCT is 

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

existing hypercalcaemia. Sprimeo 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 Sprimeo HCT, it is recommended to stop the 

treatment. If a re-administration of the diuretic is deemed necessary, it is recommended to protect 

exposed areas to the sun or to artificial UVA. 

 

Acute angle-closure glaucoma 

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

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

visual acuity or ocular pain and typically occur within hours to weeks 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 

In the event of severe and persistent diarrhoea, Sprimeo HCT therapy should be stopped. 

 

As with any antihypertensive agent, excessive reduction of blood pressure in patients with ischaemic 

cardiopathy or ischaemic cardiovascular disease could result in a myocardial infarction or stroke. 

 

Hypersensitivity reactions to hydrochlorothiazide may occur in patients, but are more likely in patients 

with allergy and asthma. 

 

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64 

Excipients 

Sprimeo HCT contains lactose. Patients with rare hereditary problems of galactose intolerance, the 

Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. 

 

Sprimeo HCT contains wheat starch. It is suitable for people with coeliac disease. Patients with wheat 

allergy (different from coeliac disease) should not take this medicine. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Information on Sprimeo HCT interactions 

Medicinal products affecting serum potassium levels: The potassium-depleting effect of 

hydrochlorothiazide is attenuated by the potassium-sparing effect of aliskiren. However, this effect of 

hydrochlorothiazide on serum potassium would be expected to be potentiated by other medicinal 

products associated with potassium loss and hypokalaemia (e.g. other kaliuretic diuretics, 

corticosteroids, laxatives, adrenocorticotropic hormone (ACTH), amphotericin, carbenoxolone, 

penicillin G, salicylic acid derivatives). Conversely, concomitant use of other agents affecting the 

RAAS, of NSAIDs or of agents that increase serum potassium levels (e.g. potassium-sparing diuretics, 

potassium supplements, salt substitutes containing potassium, heparin) may lead to increases in serum 

potassium. If co-medication with an agent affecting the level of serum potassium is considered 

necessary, caution is advisable. The combination of aliskiren with ARBs or ACEIs is contraindicated 

in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) and is not 

recommended in other patients (see sections 4.3, 4.4 and 5.1). 

 

Medicinal products affected by serum potassium disturbances: Periodic monitoring of serum 

potassium is recommended when Sprimeo HCT is administered with medicinal products affected by 

serum potassium disturbances (e.g. digitalis glycosides, antiarrhythmics). 

 

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors 

(COX-2 inhibitors), acetylsalicylic acid and non-selective NSAIDs: As with other agents acting on the 

renin-angiotensin system, NSAIDs may reduce the anti-hypertensive effect of aliskiren. NSAIDs may 

also weaken the diuretic and antihypertensive activity of hydrochlorothiazide. 

 

In some patients with compromised renal function (dehydrated patients or elderly patients) aliskiren 

and hydrochlorothiazide given concomitantly with NSAIDs may result in further deterioration of renal 

function, including possible acute renal failure, which is usually reversible. Therefore the use of 

Sprimeo HCT with an NSAID requires caution, especially in elderly patients. 

 

Other antihypertensive agents: The antihypertensive effect of Sprimeo HCT may be increased with 

the concomitant use of other antihypertensive agents. 

 

Additional information on aliskiren interactions 

The combination of aliskiren with ARBs or ACEIs is contraindicated in patients with diabetes mellitus 

or renal impairment (GFR < 60 ml/min/1.73 m
2
) and is not recommended in other patients (see 

sections 4.3, 4.4 and 5.1). 

 

Compounds that have been investigated in aliskiren clinical pharmacokinetic studies include 

acenocoumarol, atenolol, celecoxib, fenofibrate, pioglitazone, allopurinol, isosorbide-5-mononitrate, 

digoxin, metformin, amlodipine, atorvastatin, cimetidine and hydrochlorothiazide. No clinically 

relevant interactions have been identified. As a result no dose adjustment for aliskiren or these co-

administered medicinal products is necessary. 

 

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P-glycoprotein interactions: MDR1/Mdr1a/1b (P-gp) was found to be the major efflux system 

involved in intestinal absorption and biliary excretion of aliskiren in preclinical studies. Rifampicin, 

which is an inducer of P-gp, reduced aliskiren bioavailability by approximately 50% in a clinical 

study. Other inducers of P-gp (St. John’s wort) might decrease the bioavailability of aliskiren. 

Although this has not been investigated for aliskiren, it is known that P-gp also controls tissue uptake 

of a variety of substrates and P-gp inhibitors can increase the tissue-to-plasma concentration ratios. 

Therefore, P-gp inhibitors may increase tissue levels more than plasma levels. The potential for drug 

interactions at the P-gp site will likely depend on the degree of inhibition of this transporter. 

 

P-gp potent inhibitors: A single dose drug interaction study in healthy subjects has shown that 

ciclosporin (200 and 600 mg) increases Cmax of aliskiren 75 mg approximately 2.5-fold and AUC 

approximately 5-fold. The increase may be higher with higher aliskiren doses. In healthy subjects, 

itraconazole (100 mg) increases AUC and Cmax of aliskiren (150 mg) by 6.5-fold and 5.8-fold, 

respectively. Therefore, concomitant use of aliskiren and P-gp potent inhibitors is contraindicated (see 

section 4.3). 

 

Moderate P-gp inhibitors: Co-administration of ketoconazole (200 mg) or verapamil (240 mg) with 

aliskiren (300 mg) resulted in a 76% or 97% increase in aliskiren AUC, respectively. The change in 

plasma levels of aliskiren in the presence of ketoconazole or verapamil is expected to be within the 

range that would be achieved if the dose of aliskiren were doubled; aliskiren doses of up to 600 mg, or 

twice the highest recommended therapeutic dose, have been found to be well tolerated in controlled 

clinical trials. Preclinical studies indicate that aliskiren and ketoconazole co-administration enhances 

aliskiren gastrointestinal absorption and decreases biliary excretion. Therefore, caution should be 

exercised when aliskiren is administered with ketoconazole, verapamil or other moderate P-gp 

inhibitors (clarithromycin, telithromycin, erythromycin, amiodarone). 

 

P-gp substrates or weak inhibitors: No relevant interactions with atenolol, digoxin, amlodipine or 

cimetidine have been observed. When administered with atorvastatin (80 mg), steady-state aliskiren 

(300 mg) AUC and Cmax increased by 50%. 

 

Organic anion transporting polypeptide (OATP) inhibitors: Preclinical studies indicate that aliskiren 

might be a substrate of organic anion transporting polypeptides. Therefore, the potential exists for 

interactions between OATP inhibitors and aliskiren when administered concomitantly (see interaction 

with Grapefruit juice). 

 

Grapefruit juice: Administration of grapefruit juice with aliskiren resulted in a decrease in AUC and 

Cmax of aliskiren. Co-administration with aliskiren 150 mg resulted in a 61% decrease in aliskiren 

AUC and co-administration with aliskiren 300 mg resulted in a 38% decrease in aliskiren AUC. This 

decrease is likely due to an inhibition of organic anion transporting polypeptide-mediated uptake of 

aliskiren by grapefruit juice in the gastrointestinal tract. Therefore, because of the risk of therapeutic 

failure, grapefruit juice should not be taken together with Sprimeo HCT. 

 

Furosemide: When aliskiren was co-administered with furosemide, the AUC and Cmax of furosemide 

were reduced by 28% and 49%, respectively. It is therefore recommended to monitor the effects when 

initiating and adjusting furosemide therapy to avoid possible underutilisation in clinical situations of 

volume overload. 

 

Warfarin: The effects of aliskiren on warfarin pharmacokinetics have not been evaluated. 

 

Food interactions: Meals with a high fat content have been shown to reduce the absorption of aliskiren 

substantially. 

 

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Additional information on hydrochlorothiazide interactions 

When administered concurrently, the following medicinal products may interact with thiazide 

diuretics: 

 

Lithium: Renal clearance of lithium is reduced by thiazides, therefore the risk of lithium toxicity may 

be increased with hydrochlorothiazide. Co-administration of lithium and hydrochlorothiazide is not 

recommended. If this combination proves essential, careful monitoring of serum lithium level is 

recommended during concomitant use. 

 

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 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. 

 

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. 

 

Digoxine or other digitalis glycosides: Thiazide-induced hypokalaemia or hypomagnesaemia may 

occur as undesirable effects, favouring the onset of digitalis-induced cardiac arrhythmias. 

 

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. 

 

Antidiabetic agents (e.g. insulin and oral antidiabetic agents): Thiazides may alter glucose tolerance. 

Dose adjustment of the antidiabetic medicinal product may be necessary (see section 4.4). 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. 

 

Medicinal products used in the treatment of gout: 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. 

 

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. 

 

Amantadine: Thiazides, including hydrochlorothiazide, may increase the risk of adverse reactions 

caused by amantadine. 

 

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67 

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. 

 

Cytotoxic agents: Thiazides, including hydrochlorothiazide, may reduce the renal excretion of 

cytotoxic agents (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects. 

 

Non-depolarising skeletal muscle relaxants: Thiazides, including hydrochlorothiazide, potentiate the 

action of skeletal muscle relaxants such as curare derivatives. 

 

Alcohol, barbiturates or narcotics: Concomitant administration of thiazide diuretics with subtances 

that also have a blood pressure lowering effect (e.g. by reducing sympathetic central nervous system 

activity or direct vasodilatation) may potentiate orthostatic hypotension. 

 

Methyldopa: There have been isolated reports of haemolytic anaemia occurring with concomitant use 

of hydrochlorothiazide and methyldopa. 

 

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 rehydrated before 

administration. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

There are no data on the use of aliskiren in pregnant women. Aliskiren was not teratogenic in rats or 

rabbits (see section 5.3). Other substances that act directly on the RAAS have been associated with 

serious foetal malformations and neonatal death when used during second and third trimesters. 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. 

 

Hydrochlorothiazide should not be used for gestational oedema, gestational hypertension or 

pre-eclampsia due to the risk of decreased plasma volume and placental hypoperfusion, without a 

beneficial effect on the course of the disease. 

 

Hydrochlorothiazide should not be used for essential hypertension in pregnant women except in rare 

situations where no other treatment could be used. 

 

No specific clinical studies have been performed with this combination, therefore Sprimeo HCT 

should not be used during the first trimester of pregnancy or in women planning to become pregnant 

and is contraindicated during the second and third trimesters (see section 4.3). A switch to a suitable 

alternative treatment should be carried out in advance of a planned pregnancy. If pregnancy is detected 

during therapy, Sprimeo HCT should be discontinued as soon as possible. 

 

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68 

Breast-feeding 

It is not known whether aliskiren is excreted in human milk. Aliskiren was secreted in the milk of 

lactating rats. 

 

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

intense diuresis can inhibit milk production. 

 

The use of Sprimeo HCT during breast-feeding is not recommended. If Sprimeo HCT is used during 

breast-feeding, doses should be kept as low as possible. 

 

4.7 Effects on ability to drive and use machines 
 

No studies on the effect on the ability to drive and use machines have been performed. Sprimeo HCT 

is unlikely to affect the ability to drive and use machines. However, when driving vehicles or 

operating machinery it must be borne in mind that dizziness or drowsiness may occasionally occur 

when taking antihypertensive therapy. 

 

4.8 Undesirable effects 

 

Aliskiren/hydrochlorothiazide combination 

The safety of Sprimeo HCT has been evaluated in 9 clinical trials with more than 3,900 patients, 

including over 700 treated for over 6 months, and 190 for over 1 year. The incidence of adverse 

reactions showed no association with gender, age, body mass index, race or ethnicity. Treatment with 

Sprimeo HCT had an overall incidence of adverse experiences at doses up to 300 mg/25 mg similar to 

placebo. Adverse reactions have generally been mild and transient in nature and have only 

infrequently required discontinuation of therapy. The most common adverse drug reaction observed 

with Sprimeo HCT is diarrhoea. The adverse drug reactions previously reported with one of the 

individual components of Sprimeo HCT (aliskiren and hydrochlorothiazide) and listed in the 

respective paragraphs on the individual components may occur with Sprimeo HCT. 

 

The frequency of adverse reactions listed below is defined using the following convention: 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) and not known (cannot be estimated from the available data). 

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 

 

Gastrointestinal disorders 

 Common: Diarrhoea 

 

Diarrhoea: Diarrhoea is a dose-related adverse drug reaction for aliskiren. In controlled clinical trials, 

the incidence of diarrhoea in Sprimeo HCT-treated patients was 1.3% compared to 1.4% for aliskiren- 

or 1.9% for hydrochlorothiazide-treated patients. 

 

Serum potassium: In a large placebo-controlled clinical trial, the opposite effects of aliskiren (150 mg 

or 300 mg) and hydrochlorothiazide (12.5 mg or 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 potassium to detect possible electrolyte imbalance should be performed in 

patients at risk at appropriate intervals (see sections 4.4 and 4.5). 

 

Additional information on individual components 

Other adverse reactions previously reported with one of the individual components may occur with 

Sprimeo HCT even if not observed in clinical trials. 

 

Aliskiren 

Treatment with Aliskiren up to 300 mg resulted in an overall incidence of adverse reactions similar to 

placebo. Adverse reactions have generally been mild and transient in nature and have only 

infrequently required discontinuation of therapy. The most common adverse drug reaction is 

diarrhoea. 

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69 

 

The known aliskiren adverse drug reactions are presented in the table below using the same 

convention as described previously for the fixed combination. 

 

Nervous system disorders 

 Common: Dizziness 

Vascular disorders 

 Uncommon: Hypotension 

Gastrointestinal disorders 

 Common: Diarrhoea 

Immune system disorders 

 Rare: Hypersensitivity reactions 

Skin and subcutaneous tissue disorders 

 Uncommon: Rash, severe cutaneous adverse reactions (SCARs) including toxic 

epidermal necrolysis (TEN) and oral mucosal reactions 

 Rare: Angioedema 

Musculoskeletal and connective tissue disorders 

 Common: Arthralgia 

Renal and urinary disorders 
 Uncommon: Acute renal failure, renal impairment 

General disorders and administration site conditions 
 Uncommon: Oedema peripheral 

Investigations 
 Common: Hyperkalaemia 

 Rare: Haemoglobin decreased, haematocrit decreased 

 Rare: Blood creatinine increased 

 

Angioedema and hypersensitivity reactions have occurred during treatment with aliskiren. In 

controlled clinical trials, angioedema and hypersensitivity reactions occurred rarely during treatment 

with aliskiren with rates comparable to treatment with placebo or comparators. 

 

Cases of angioedema or symptoms suggestive of angioedema (swelling of the face, lips, throat and/or 

tongue) have also been reported in post-marketing experience. A number of these patients had a 

history of angioedema or symptoms suggestive of angioedema which in some cases was associated 

with the administration of other medicines known to cause angioedema, including RAAS blockers 

(ACE inhibitors or ARBs). 

 

Hypersensitivity reactions have also been reported in post-marketing experience. 

 

In the event of any signs suggesting a hypersensitivity reaction/angioedema (in particular difficulties 

in breathing or swallowing, rash, itching, hives or swelling of the face, extremities, eyes, lips and/or 

tongue, dizziness) patients should discontinue treatment and contact the physician (see section 4.4). 

 

Arthralgia has been reported in post-marketing experience. In some cases this occurred as part of a 

hypersensitivity reaction. 

 

Haemoglobin and haematocrit: Small decreases in haemoglobin and haematocrit (mean decreases of 

approximately 0.05 mmol/l and 0.16 volume percent, respectively) were observed. No patients 

discontinued therapy due to anaemia. This effect is also seen with other agents acting on the renin-

angiotensin system, such as ACEI and ARBs. 

 

Serum potassium: Increases in serum potassium have been observed with aliskiren and these may be 

exacerbated by concomitant use of other agents acting on the RAAS or by NSAIDs. Consistent with 

standard medical practice, periodic determination of renal function including serum electrolytes is 

advised if co-administration is considered necessary. The combination of aliskiren with ARBs or 

ACEIs is contraindicated in patients with diabetes mellitus or renal impairment (GFR 

< 60 ml/min/1.73 m
2
) and is not recommended in other patients (see sections 4.3, 4.4 and 5.1). 

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70 

 

In post-marketing experience, renal dysfunction and cases of acute renal failure have been reported in 

patients at risk (see section 4.4). There have also been reports of peripheral oedema, increase in blood 

creatinine and severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis 

(TEN) and oral mucosal reactions. 

 

Hydrochlorothiazide 

Hydrochlorothiazide has been extensively prescribed for many years, frequently in higher doses than 

those contained in Sprimeo HCT. The following adverse reactions have been reported in patients 

treated with thiazide diuretics alone, including hydrochlorothiazide: 

 

Blood and lymphatic system disorders 

 Rare: Thrombocytopenia sometimes with purpura 

 Very rare: Agranulocytosis, bone marrow depression, haemolytic anaemia, 

leucopenia 

 Not known: Aplastic anaemia 
Immune system disorders 

 Very rare: Hypersensitivity 

Metabolism and nutrition disorders 

 Very common: Hypokalaemia 

 Common: Hyperuricaemia, hypomagnesaemia, hyponatraemia 

 Rare: Hypercalcaemia, hyperglycaemia, worsening of diabetic metabolic 

state 

 Very rare: Hypochloraemic alkalosis 

Psychiatric disorders 

 Rare: Depression, sleep disturbances 

Nervous system disorders 

 Rare: Dizziness, headache, paraesthesia 

Eye disorders 

 Rare: Visual impairment 

 Not known: Acute angle-closure glaucoma 

Cardiac disorders 

 Rare: Cardiac arrhythmias 

Vascular disorders 

 Common: Orthostatic hypotension 

Respiratory, thoracic and mediastinal disorders 

 Very rare: Respiratory distress (including pneumonitis and pulmonary oedema) 

Gastrointestinal disorders 

 Common: Decreased appetite, mild nausea and vomiting 

 Rare: Abdominal discomfort, constipation, diarrhoea 

 Very rare: Pancreatitis 

Hepatobiliary disorders 

 Rare: Intrahepatic cholestasis, jaundice 

Skin and subcutaneous tissue disorders 

 Common: Urticaria and other forms of rash 

 Rare: Photosensitivity reactions 

 Very rare: Cutaneous lupus erythematosus-like reactions, reactivation of 

cutaneous lupus erythematosus, vasculitis necrotising and toxic 

epidermal necrolysis 

 Not known: Erythema multiforme 

Musculoskeletal and connective tissue disorders 

 Not known: Muscle spasm 

Renal and urinary disorders 

 Not known: Renal dysfunction, acute renal failure 

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71 

 

Reproductive system and breast disorders 

 Common: Impotence 

General disorders and administration site conditions 

 Not known: Asthenia, pyrexia 

Investigations 

 Very common: Increases in cholesterol and triglycerides 

 Rare: Glycosuria 

 

4.9 Overdose 
 

No information is available on the treatment of overdose with Sprimeo HCT. The most likely 

manifestation of overdose would be hypotension, related to the antihypertensive effect of aliskiren. 

 

Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, 

hypochloraemia, hyponatraemia) and dehydration 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 cardiac arrhythmias associated with the concomitant use of digitalis 

glycosides or certain antiarrhythmic medicinal products. If symptomatic hypotension should occur, 

supportive treatment should be initiated. 

 

In a study conducted in patients with end stage renal disease (ESRD) receiving haemodialysis, dialysis 

clearance of aliskiren was low (< 2% of oral clearance). Therefore dialysis is not adequate to treat 

aliskiren over-exposure. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Renin inhibitor (aliskiren) combinations with diuretics 

(hydrochlorothiazide), ATC code: C09XA52 

Sprimeo HCT combines two antihypertensive compounds to control blood pressure in patients with 

essential hypertension: Aliskiren belongs to the class of direct renin inhibitors and hydrochlorothiazide 

to the class of thiazide diuretics. The combination of these substances with complementary 

mechanisms of action provides an additive antihypertensive effect, reducing blood pressure to a 

greater degree than either component alone. 

 

Aliskiren 

Aliskiren is an orally active, non-peptide, potent and selective direct inhibitor of human renin. 

 

By inhibiting the enzyme renin, aliskiren inhibits the RAAS at the point of activation, blocking the 

conversion of angiotensinogen to angiotensin I and decreasing levels of angiotensin I and 

angiotensin II. Whereas other agents that inhibit the RAAS (angiotensin converting enzyme inhibitors 

(ACEI) and angiotension II receptor blockers (ARB)) cause a compensatory rise in plasma renin 

activity (PRA), treatment with aliskiren decreases PRA in hypertensive patients by approximately 50 

to 80%. Similar reductions were found when aliskiren was combined with other antihypertensive 

agents. The clinical implications of the effects on PRA are not known at the present time. 

 

In hypertensive patients, once-daily administration of aliskiren at doses of 150 mg and 300 mg 

provided dose-dependent reductions in both systolic and diastolic blood pressure that were maintained 

over the entire 24-hour dose interval (maintaining benefit in the early morning) with a mean peak to 

trough ratio for diastolic response of up to 98% for the 300 mg dose. 85 to 90% of the maximal blood-

pressure-lowering effect was observed after 2 weeks. The blood-pressure-lowering effect was 

sustained during long-term treatment (12 months), and was independent of age, gender, body mass 

index and ethnicity. 

 

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72 

Combination therapy studies are available for aliskiren added to the diuretic hydrochlorothiazide, the 

calcium channel blocker amlodipine and the beta blocker atenolol. These combinations were 

efficacious and well tolerated. 

 

The efficacy and safety of aliskiren-based therapy were compared to ramipril-based therapy in a 9-

month non-inferiority study in 901 elderly patients (≥ 65 years) with essential systolic hypertension. 

Aliskiren 150 mg or 300 mg per day or ramipril 5 mg or 10 mg per day were administered for 

36 weeks with optional add-on therapy of hydrochlorothiazide (12.5 mg or 25 mg) at week 12, and 

amlodipine (5 mg or 10 mg) at week 22. Over the 12 week period, aliskiren monotherapy lowered 

systolic/diastolic blood pressure by 14.0/5.1 mmHg, compared to 11.6/3.6 mmHg for ramipril, 

consistent with aliskiren being non-inferior to ramipril at the dosages chosen and the differences in 

systolic and diastolic blood pressure were statistically significant. Tolerability was comparable in both 

treatment arms, however cough was more often reported with the ramipril regimen than the aliskiren 

regimen (14.2% vs. 4.4%), whilst diarrhoea was more common with the aliskiren regimen than for the 

ramipril regimen (6.6% vs. 5.0%). 

 

In a 8-week study in 754 hypertensive elderly (≥ 65 years) and very elderly patients (30% ≥ 75 years) 

aliskiren at doses of 75 mg, 150 mg and 300 mg provided statistically significant superior reduction in 

blood pressure (both systolic and diastolic) when compared to placebo. No additional blood pressure 

lowering effect was detected with 300 mg aliskiren compared to 150 mg aliskiren. All three doses 

were well tolerated in both elderly and very elderly patients. 

 

There has been no evidence of first-dose hypotension and no effect on pulse rate in patients treated in 

controlled clinical studies. With cessation of treatment, blood pressure gradually returned towards 

baseline levels over a period of several weeks, with no evidence of a rebound effect for blood pressure 

or PRA. 

 

In a 36-week study involving 820 patients with ischaemic left ventricular dysfunction, no changes in 

ventricular remodelling as assessed by left ventricular end systolic volume were detected with 

aliskiren compared to placebo on top of background therapy. 

 

The combined rates of cardiovascular death, hospitalisation for heart failure, recurrent heart attack, 

stroke and resuscitated sudden death were similar in the aliskiren group and the placebo group. 

However, in patients receiving aliskiren there was a significantly higher rate of hyperkalaemia, 

hypotension and kidney dysfunction when compared to the placebo group. 

 

Aliskiren was evaluated for cardiovascular and/or renal benefit in a double-blind placebo controlled 

randomised trial in 8,606 patients with type 2 diabetes and chronic kidney disease (evidenced by 

proteinuria and/or GFR < 60 ml/min/1.73 m
2
) with or without cardiovascular disease. In most patients 

arterial blood pressure was well controlled at baseline. The primary endpoint was a composite of 

cardiovascular and renal complications. 

 

In this study, aliskiren 300 mg was compared to placebo when added to standard of care which 

included either an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker. The 

study was discontinued prematurely because the participants were unlikely to benefit from aliskiren. 

Preliminary study results indicated a hazard ratio for the primary endpoint of 1.09 in favour of placebo 

(95% Confidence Interval: 0.97, 1.22, 2-sided p=0.17). In addition, an increased incidence of serious 

adverse outcomes was observed with aliskiren compared to placebo for renal complications (4.7% 

versus 3.3%), hyperkalaemia (36.9% versus 27.1%), hypotension (18.4% versus 14.6%) and stroke 

(2.7% versus 2.0%). The increased incidence of non-fatal stroke was greater in patients with renal 

insufficiency. 

 

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73 

Hydrochlorothiazide 

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

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

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

action of thiazides is through inhibition of the Na+Cl- symporter 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. 

 

Aliskiren/hydrochlorothiazide 

Over 3,900 hypertensive patients received Sprimeo HCT once daily in clinical trials. 

 

In hypertensive patients, once-daily administration of Sprimeo HCT provided dose-dependent 

reductions in both systolic and diastolic blood pressure that were maintained over the entire 24-hour 

dose interval. The antihypertensive effect is largely manifested within 1 week and the maximum effect 

is generally seen within 4 weeks.The blood-pressure-lowering effect was sustained during long-term 

treatment, and was independent of age, gender, body mass index and ethnicity. The antihypertensive 

effect of a single dose of the combination persisted for 24 hours. Upon withdrawal of the aliskiren 

treatment (aliskiren with or without hydrochlorothiazide add-on), the return of blood pressure towards 

baseline was gradual (3-4 weeks) with no evidence of the rebound effect. 

 

Sprimeo HCT was studied in a placebo-controlled trial including 2,762 hypertensive patients with 

diastolic blood pressure ≥ 95 mmHg and < 110 mmHg (mean baseline blood pressure of 

153.6/99.2 mmHg). In this study, Sprimeo HCT in doses from 150 mg/12.5 mg to 300 mg/25 mg 

produced dose-dependent blood pressure reductions (systolic/diastolic) from 17.6/11.9 mmHg to 

21.2/14.3 mmHg, respectively, compared to 7.5/6.9 mmHg with placebo. The greater blood pressure 

reductions with these combination doses were also significantly greater than the respective doses of 

aliskiren and hydrochlorothiazide when used alone. The combination of aliskiren and 

hydrochlorothiazide neutralised the reactive increase of PRA caused by hydrochlorothiazide. 

 

When administered in hypertensive patients with markedly elevated blood pressure (systolic blood 

pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg), Sprimeo HCT in doses from 

150 mg/12.5 mg to 300 mg/25 mg administered without up-titration from monotherapy demonstrated 

significantly greater systolic/diastolic blood pressure control rates (< 140/90 mmHg) as compared to 

the respective monotherapies. In this population, Sprimeo HCT 150 mg/12.5 mg to 300 mg/25 mg 

provided dose-dependent systolic/diastolic blood pressure reduction from 20.6/12.4 mmHg to 

24.8/14.5 mmHg, which were significantly superior to the respective monotherapies. The safety of the 

combination therapy was similar to the respective monotherapies regardless of severity of 

hypertension or of the presence or absence of additional cardiovascular risk. Hypotension and related 

adverse events were uncommon with the combination treatment, with no increased incidence in 

elderly patients. 

 

In a study in 880 randomised patients not adequately responsive to aliskiren 300 mg treatment, the 

combination of aliskiren/hydrochlorothiazide 300 mg/25 mg produced systolic/diastolic blood 

pressure reductions of 15.8/11.0 mmHg, which were significantly greater than aliskiren 300 mg 

monotherapy. In a study in 722 randomised patients not adequately responsive to hydrochlorothiazide 

25 mg treatment, the combination of aliskiren/hydrochlorothiazide 300 mg/25 mg produced 

systolic/diastolic blood pressure reductions of 16.78/10.7 mmHg, which were significantly greater 

than hydrochlorothiazide 25 mg monotherapy. 

 

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74 

In another clinical trial, the efficacy and safety of Sprimeo HCT were also assessed in 489 obese 

hypertensive patients who did not respond to hydrochlorothiazide 25 mg (baseline systolic/diastolic 

blood pressure 149.4/96.8 mmHg). In this difficult-to-treat population, Sprimeo HCT provided a blood 

pressure reduction (systolic/diastolic) of 15.8/11.9 mmHg compared to 15.4/11.3 mmHg for 

irbesartan/hydrochlorothiazide, 13.6/10.3 mmHg for amlodipine/hydrochlorothiazide and 

8.6/7.9 mmHg for hydrochlorothiazide monotherapy, with similar safety to hydrochlorothiazide 

monotherapy. 

 

In a study in 183 randomised patients with severe hypertension (mean sitting diastolic blood pressure 

≥ 105 and < 120 mmHg), aliskiren treatment regimen with optional addition of hydrochlorothiazide 

25 mg was shown to be safe and efficacious in reducing blood pressure. 

 

5.2 Pharmacokinetic properties 
 

Aliskiren 

Absorption 

Following oral absorption, peak plasma concentrations of aliskiren are reached after 1-3 hours. The 

absolute bioavailability of aliskiren is approximately 2-3%. Meals with a high fat content reduce Cmax 

by 85% and AUC by 70%. Steady-state-plasma concentrations are reached within 5-7 days following 

once-daily administration and steady-state levels are approximately 2-fold greater than with the initial 

dose. 

 

Distribution 

Following intravenous administration, the mean volume of distribution at steady state is approximately 

135 litres, indicating that aliskiren distributes extensively into the extravascular space. Aliskiren 

plasma protein binding is moderate (47-51%) and independent of the concentration. 

 

Metabolism and elimination 

The mean half-life is about 40 hours (range 34-41 hours). Aliskiren is mainly eliminated as unchanged 

compound in the faeces (oral radioactive dose recovery = 91%). Approximately 1.4% of the total oral 

dose is metabolised. The enzyme responsible for this metabolism is CYP3A4. Approximately 0.6% of 

the dose is recovered in urine following oral administration. Following intravenous administration, the 

mean plasma clearance is approximately 9 l/h. 

 

Linearity 

Exposure to aliskiren increased slightly more than in proportion to the increase in dose. After single 

dose administration in the dose range of 75 to 600 mg, a 2-fold increase in dose results in a ~2.3 and 

2.6-fold increase in AUC and Cmax, respectively. Mechanisms responsible for the deviation from dose 

proportionality have not been identified. A possible mechanism is saturation of transporters at the 

absorption site or at the hepatobiliary clearance route. 

 

Hydrochlorothiazide 

Absorption 

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

 

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75 

Metabolism and elimination 

Hydrochlorothiazide is eliminated predominantly as unchanged compound. 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. There is more than 95% of the absorbed dose being excreted as 

unchanged compound in the urine. The renal clearance is composed of passive filtration and active 

secretion into the renal tubule. 

 

Aliskiren/hydrochlorothiazide 

Following oral administration of Sprimeo HCT tablets, the median peak plasma concentration time is 

within 1 hour for aliskiren and 2.5 hours for hydrochlorothiazide. 

 

The rate and extent of absorption of Sprimeo HCT are equivalent to the bioavailability of aliskiren and 

hydrochlorothiazide when administered as individual monotherapies. Similar food effect was observed 

for Sprimeo HCT as for the individual monotherapies. 

 

Characteristics in patients 

Sprimeo HCT has been shown to be effective as a once-a-day antihypertensive treatment in adult 

patients, regardless of gender, age, body mass index and ethnicity. 

 

The pharmacokinetics of aliskiren are not significantly affected in patients with mild to moderate liver 

disease. Consequently, no initial dose adjustment of Sprimeo HCT is required in patients with mild to 

moderate hepatic impairment. No data are available on patients with severe hepatic impairment treated 

by Sprimeo HCT. Sprimeo HCT is contraindicated in patients with severe hepatic impairment (see 

section 4.3). 

 

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

contraindicated in patients with anuria or severe renal impairment (GFR < 30 ml/min/1.73 m
2
) and the 

concomitant use of Sprimeo HCT with ARBs or ACEIs is contraindicated in patients with renal 

impairment (GFR < 60 ml/min/1.73 m
2
) (see section 4.3). 

 

The pharmacokinetics of aliskiren were evaluated in patients with end stage renal disease receiving 

haemodialysis. Administration of a single oral dose of 300 mg aliskiren was associated with very 

minor changes in the pharmacokinetics of aliskiren (change in Cmax of less than 1.2 fold; increase in 

AUC of up to 1.6 fold) compared to matched healthy subjects. Timing of haemodialysis did not 

significantly alter the pharmacokinetics of aliskiren in ESRD patients. Therefore, if administration of 

aliskiren in ESRD patients receiving haemodialysis is considered necessary, no dose adjustment is 

warranted in these patients. However, the use of aliskiren is not recommended in patients with severe 

renal impairment (see section 4.4). 

 

No initial dose adjustment of Sprimeo HCT is required in elderly patients. Limited data suggest that 

the systemic clearance of hydrochlorothiazide is reduced in both healthy and hypertensive elderly 

subjects compared to young healthy volunteers. 

 

No pharmacokinetic data are available in the paediatric population. 

 

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76 

5.3 Preclinical safety data 
 

Safety pharmacology studies with aliskiren did not reveal any adverse effects on central nervous, 

respiratory or cardiovascular function. Findings during repeat-dose toxicity studies in animals were 

consistent with the known local irritation potential or the expected pharmacological effects of 

aliskiren. No carcinogenic potential for aliskiren was detected in a 2-year rat study and a 6-month 

transgenic mouse study. One colonic adenoma and one caecal adenocarcinoma recorded in rats at the 

dose of 1,500 mg/kg/day were not statistically significant. Aliskiren was devoid of any mutagenic 

potential, embryo-foetal toxicity or teratogenicity. Fertility, prenatal development and postnatal 

development were unaffected in rats. 

 

Preclinical evaluations to support the administration of hydrochlorothiazide in humans included in 

vitro genotoxicity assays and reproductive toxicity and carcinogenicity studies in rodents. Extensive 

clinical data are available for hydrochlorothiazide and these are reflected in the relevant sections. 

 

The findings observed in the 2-week and 13-week toxicity studies were consistent with those observed 

previously with aliskiren or hydrochlorothiazide monotherapies. There were no new or unexpected 

findings observed of relevance to human use. Increased cellular vacuolation of the adrenal gland zona 

glomerulosa was observed during the 13-week toxicity study in rats. The finding was observed in 

animals treated with hydrochlorothiazide but not in those animals receiving aliskiren alone or vehicle. 

There was no evidence that this finding was enhanced in the aliskiren/hydrochlorothiazide 

combination as it was only apparent at a minimal severity in all animals. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Tablet core: 

Cellulose microcrystalline 

Crospovidone 

Lactose monohydrate 

Wheat starch 

Povidone 

Magnesium stearate 

Silica colloidal anhydrous 

Talc 

 

Coating: 

Talc 

Hypromellose 

Macrogol 

Titanium dioxide (E171) 

Red iron oxide (E172) 

Yellow iron oxide (E172) 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

24 months 

 

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77 

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 

 

PA/Alu/PVC – Alu blisters: 

Single-packs containing 7, 14, 28, 30, 50 or 56 tablets. 

Multi-packs containing 90, 98 or 280 tablets. 

 

PVC/polychlorotrifluoroethylene (PCTFE) – Alu blisters: 

Single-packs containing 7, 14, 28, 30, 50, 56, 90 or 98 tablets. 

Single-packs (perforated unit dose blister) containing 56 x 1 tablets. 

Multi-packs containing 280 tablets. 

Multi-packs (perforated unit dose blister) containing 98 x 1 tablets. 

 

Not all pack sizes or strengths may be marketed. 

 

6.6 Special precautions for disposal 
 

Any unused product or waste material should be disposed of in accordance with local requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/061-080 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

23.06.2011 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

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

http://www.ema.europa.eu 

 

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78 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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 
 

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79 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturer responsible for batch release 

 

Novartis Farma S.p.A. 

Via Provinciale Schito 131 

IT-80058 Torre Annunziata/NA 

Italy 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 

Medicinal product subject to medical prescription. 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

Pharmacovigilance system 

The MAH must ensure that the system of pharmacovigilance, presented in Module 1.8.1 of the 

Marketing Authorisation, is in place and functioning before and whilst the medicinal product is on the 

market. 

 

Risk Management Plan (RMP) 

The MAH shall perform the pharmacovigilance activities detailed in the Pharmacovigilance Plan, as 

agreed in the RMP presented in Module 1.8.2 of the Marketing Authorisation and any subsequent 

updates of the RMP agreed by the Committee for Medicinal Products for Human Use (CHMP). 

 

As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the 

updated RMP should be submitted at the same time as the next Periodic Safety Update Report 

(PSUR). 

 

In addition, an updated RMP should be submitted: 

 When new information is received that may impact on the current Safety Specification, 
Pharmacovigilance Plan or risk minimisation activities 

 Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being 
reached 

 At the request of the European Medicines Agency. 
 

 CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

Not applicable. 

 

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80 

 OBLIGATION TO CONDUCT POST-AUTHORISATION MEASURES 
 

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

 

Description Due date 

The MAH shall submit the final results and study report for the active treatment 

phase of the ALTITUDE study when available 

31 July 2012 

The MAH shall submit an updated risk management plan (RMP) that adequately 

describes all the safety concerns, the pharmacovigilance activities and the 

interventions designed to identify, characterise, prevent or minimise the risks. 

Within a month 

following the 

Commission 

Decision 

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ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

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82 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

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83 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK CONTAINING PVC/PCTFE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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84 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/010 7 film-coated tablets 

EU/1/11/683/011 14 film-coated tablets 

EU/1/11/683/012 28 film-coated tablets 

EU/1/11/683/013 30 film-coated tablets 

EU/1/11/683/014 50 film-coated tablets 

EU/1/11/683/015 56 film-coated tablets 

EU/1/11/683/016 56 film-coated tablets (56x1; perforated unit dose blister) 

EU/1/11/683/017 90 film-coated tablets 

EU/1/11/683/018 98 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 150 mg/12.5 mg 

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85 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK CONTAINING PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

56 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

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86 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/001 7 film-coated tablets 

EU/1/11/683/002 14 film-coated tablets 

EU/1/11/683/003 28 film-coated tablets 

EU/1/11/683/004 30 film-coated tablets 

EU/1/11/683/005 50 film-coated tablets 

EU/1/11/683/006 56 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 150 mg/12.5 mg 

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87 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS (PVC/PCTFE OR PA/ALU/PVC) 

BLISTER (CALENDAR) (PVC/PCTFE OR PA/ALU/PVC) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

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88 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) CONTAINING 

PVC/PCTFE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 packs, each containing 14 tablets. 

49 film-coated tablets 

Component of a multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

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89 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/020 280 film-coated tablets (20x14) 

EU/1/11/683/019 98 film-coated tablets (2x49; perforated unit dose blister) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 150 mg/12.5 mg 

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90 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) CONTAINING 

PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 packs, each containing 14 tablets. 

30 film-coated tablets 

Component of a multipack comprising 3 packs, each containing 30 tablets. 

49 film-coated tablets 

Component of a multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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91 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/009 280 film-coated tablets (20x14) 

EU/1/11/683/007 90 film-coated tablets (3x30) 

EU/1/11/683/011 98 film-coated tablets (2x49) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 150 mg/12.5 mg 

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92 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) CONTAINING 

PVC/PCTFE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

98 film-coated tablets 

Multipack comprising 2 packs, each containing 49 tablets. 

280 film-coated tablets 

Multipack comprising 20 packs, each containing 14 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

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93 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/019 98 film-coated tablets (2x49; perforated unit dose blister) 

EU/1/11/683/020 280 film-coated tablets (20x14) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 150 mg/12.5 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) CONTAINING 

PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

98 film-coated tablets 

Multipack comprising 2 packs, each containing 49 tablets. 

280 film-coated tablets 

Multipack comprising 20 packs, each containing 14 tablets. 

90 film-coated tablets 

Multipack comprising 3 packs, each containing 30 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/008 98 film-coated tablets (2x49) 

EU/1/11/683/009 280 film-coated tablets (20x14) 

EU/1/11/683/007 90 film-coated tablets (3x30) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 150 mg/12.5 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK CONTAINING PVC/PCTFE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/030 7 film-coated tablets 

EU/1/11/683/031 14 film-coated tablets 

EU/1/11/683/032 28 film-coated tablets 

EU/1/11/683/033 30 film-coated tablets 

EU/1/11/683/034 50 film-coated tablets 

EU/1/11/683/035 56 film-coated tablets 

EU/1/11/683/036 56 film-coated tablets (56x1; perforated unit dose blister) 

EU/1/11/683/037 90 film-coated tablets 

EU/1/11/683/038 98 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 150 mg/25 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK CONTAINING PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

56 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/021 7 film-coated tablets 

EU/1/11/683/022 14 film-coated tablets 

EU/1/11/683/023 28 film-coated tablets 

EU/1/11/683/024 30 film-coated tablets 

EU/1/11/683/025 50 film-coated tablets 

EU/1/11/683/026 56 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 150 mg/25 mg 

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100 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS (PVC/PCTFE OR PA/ALU/PVC) 

BLISTER (CALENDAR) (PVC/PCTFE OR PA/ALU/PVC) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

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101 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) CONTAINING 

PVC/PCTFE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 packs, each containing 14 tablets. 

49 film-coated tablets 

Component of a multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

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102 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/040 280 film-coated tablets (20x14) 

EU/1/11/683/039 98 film-coated tablets (2x49; perforated unit dose blister) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 150 mg/25 mg 

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103 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) CONTAINING 

PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 packs, each containing 14 tablets. 

30 film-coated tablets 

Component of a multipack comprising 3 packs, each containing 30 tablets. 

49 film-coated tablets 

Component of a multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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104 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/029 280 film-coated tablets (20x14) 

EU/1/11/683/027 90 film-coated tablets (3x30) 

EU/1/11/683/028 98 film-coated tablets (2x49) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 150 mg/25 mg 

Me
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rod
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t n
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on
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105 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) CONTAINING 

PVC/PCTFE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

98 film-coated tablets 

Multipack comprising 2 packs, each containing 49 tablets. 

280 film-coated tablets 

Multipack comprising 20 packs, each containing 14 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

Me
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106 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/039 98 film-coated tablets (2x49; perforated unit dose blister) 

EU/1/11/683/040 280 film-coated tablets (20x14) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 150 mg/25 mg 

Me
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ina
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rod
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t n
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on
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107 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) CONTAINING 

PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 150 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

98 film-coated tablets 

Multipack comprising 2 packs, each containing 49 tablets. 

280 film-coated tablets 

Multipack comprising 20 packs, each containing 14 tablets. 

90 film-coated tablets 

Multipack comprising 3 packs, each containing 30 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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108 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/028 98 film-coated tablets (2x49) 

EU/1/11/683/029 280 film-coated tablets (20x14) 

EU/1/11/683/027 90 film-coated tablets (3x30) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 150 mg/25 mg 

Me
dic

ina
l p

rod
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t n
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on
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109 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK CONTAINING PVC/PCTFE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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110 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/050 7 film-coated tablets 

EU/1/11/683/051 14 film-coated tablets 

EU/1/11/683/052 28 film-coated tablets 

EU/1/11/683/053 30 film-coated tablets 

EU/1/11/683/054 50 film-coated tablets 

EU/1/11/683/055 56 film-coated tablets 

EU/1/11/683/056 56 film-coated tablets (56x1; perforated unit dose blister) 

EU/1/11/683/057 90 film-coated tablets 

EU/1/11/683/058 98 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 300 mg/12.5 mg 

Me
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ina
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111 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK CONTAINING PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

56 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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112 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/041 7 film-coated tablets 

EU/1/11/683/042 14 film-coated tablets 

EU/1/11/683/043 28 film-coated tablets 

EU/1/11/683/044 30 film-coated tablets 

EU/1/11/683/045 50 film-coated tablets 

EU/1/11/683/046 56 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 300 mg/12.5 mg 

Me
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ina
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rod
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t n
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on
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113 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS (PVC/PCTFE OR PA/ALU/PVC) 

BLISTER (CALENDAR) (PVC/PCTFE OR PA/ALU/PVC) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

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114 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) CONTAINING 

PVC/PCTFE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 packs, each containing 14 tablets. 

49 film-coated tablets 

Component of a multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

Me
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ina
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t n
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on
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115 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/060 280 film-coated tablets (20x14) 

EU/1/11/683/059 98 film-coated tablets (2x49; perforated unit dose blister) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 300 mg/12.5 mg 

Me
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ina
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rod
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t n
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on
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r a
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ori
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116 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) CONTAINING 

PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 packs, each containing 14 tablets. 

30 film-coated tablets 

Component of a multipack comprising 3 packs, each containing 30 tablets. 

49 film-coated tablets 

Component of a multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/049 280 film-coated tablets (20x14) 

EU/1/11/683/047 90 film-coated tablets (3x30) 

EU/1/11/683/048 98 film-coated tablets (2x49) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 300 mg/12.5 mg 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
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ori
se

d



 

118 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) CONTAINING 

PVC/PCTFE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

98 film-coated tablets 

Multipack comprising 2 packs, each containing 49 tablets. 

280 film-coated tablets 

Multipack comprising 20 packs, each containing 14 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
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ori
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119 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/059 98 film-coated tablets (2x49; perforated unit dose blister) 

EU/1/11/683/060 280 film-coated tablets (20x14) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 300 mg/12.5 mg 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

120 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) CONTAINING 

PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/12.5 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

98 film-coated tablets 

Multipack comprising 2 packs, each containing 49 tablets. 

280 film-coated tablets 

Multipack comprising 20 packs, each containing 14 tablets. 

90 film-coated tablets 

Multipack comprising 3 packs, each containing 30 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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121 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/048 98 film-coated tablets (2x49) 

EU/1/11/683/049 280 film-coated tablets (20x14) 

EU/1/11/683/047 90 film-coated tablets (3x30) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 300 mg/12.5 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK CONTAINING PVC/PCTFE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/070 7 film-coated tablets 

EU/1/11/683/071 14 film-coated tablets 

EU/1/11/683/072 28 film-coated tablets 

EU/1/11/683/073 30 film-coated tablets 

EU/1/11/683/074 50 film-coated tablets 

EU/1/11/683/075 56 film-coated tablets 

EU/1/11/683/076 56 film-coated tablets (56x1; perforated unit dose blister) 

EU/1/11/683/077 90 film-coated tablets 

EU/1/11/683/078 98 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 300 mg/25 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK CONTAINING PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

56 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/061 7 film-coated tablets 

EU/1/11/683/062 14 film-coated tablets 

EU/1/11/683/063 28 film-coated tablets 

EU/1/11/683/064 30 film-coated tablets 

EU/1/11/683/065 50 film-coated tablets 

EU/1/11/683/066 56 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 300 mg/25 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS (PVC/PCTFE OR PA/ALU/PVC) 

BLISTER (CALENDAR) (PVC/PCTFE OR PA/ALU/PVC) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) CONTAINING 

PVC/PCTFE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 packs, each containing 14 tablets. 

49 film-coated tablets 

Component of a multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/080 280 film-coated tablets (20x14) 

EU/1/11/683/079 98 film-coated tablets (2x49; perforated unit dose blister) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 300 mg/25 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) CONTAINING 

PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 packs, each containing 14 tablets. 

30 film-coated tablets 

Component of a multipack comprising 3 packs, each containing 30 tablets. 

49 film-coated tablets 

Component of a multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/069 280 film-coated tablets (20x14) 

EU/1/11/683/067 90 film-coated tablets (3x30) 

EU/1/11/683/068 98 film-coated tablets (2x49) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 300 mg/25 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) CONTAINING 

PVC/PCTFE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

98 film-coated tablets 

Multipack comprising 2 packs, each containing 49 tablets. 

280 film-coated tablets 

Multipack comprising 20 packs, each containing 14 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/079 98 film-coated tablets (2x49; perforated unit dose blister) 

EU/1/11/683/080 280 film-coated tablets (20x14) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 300 mg/25 mg 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) CONTAINING 

PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sprimeo HCT 300 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose and wheat starch. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

98 film-coated tablets 

Multipack comprising 2 packs, each containing 49 tablets. 

280 film-coated tablets 

Multipack comprising 20 packs, each containing 14 tablets. 

90 film-coated tablets 

Multipack comprising 3 packs, each containing 30 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

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

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/683/068 98 film-coated tablets (2x49) 

EU/1/11/683/069 280 film-coated tablets (20x14) 

EU/1/11/683/067 90 film-coated tablets (3x30) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Sprimeo HCT 300 mg/25 mg 

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B. PACKAGE LEAFLET 

 

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PACKAGE LEAFLET: INFORMATION FOR THE USER 

 

Sprimeo HCT 150 mg/12.5 mg film-coated tablets 

Sprimeo HCT 150 mg/25 mg film-coated tablets 

Sprimeo HCT 300 mg/12.5 mg film-coated tablets 

Sprimeo HCT 300 mg/25 mg film-coated tablets 

Aliskiren/hydrochlorothiazide 

 

 

Read all of this leaflet carefully before you start taking this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 

- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 
please tell your doctor or pharmacist. 

 

 

In this leaflet: 

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

2. Before you take Sprimeo HCT 

3. How to take Sprimeo HCT 

4. Possible side effects 

5. How to store Sprimeo HCT 

6. Further information 

 

 

1. WHAT SPRIMEO HCT IS AND WHAT IT IS USED FOR 

 

Sprimeo HCT tablets contain two active substances, called aliskiren and hydrochlorothiazide. Both of 

these substances help to control high blood pressure (hypertension). 

 

Aliskiren is a substance that belongs to a new group of medicines called renin inhibitors. These reduce 

the amount of angiotensin II the body can make. Angiotensin II causes blood vessels to tighten, which 

makes blood pressure higher. Lowering the amount of angiotensin II allows the blood vessels to relax; 

this lowers blood pressure. 

 

Hydrochlorothiazide belongs to a group of medicines called thiazide diuretics. Hydrochlorothiazide 

increases urine output, which also lowers blood pressure. 

 

High blood pressure increases the workload of the heart and arteries. If this continues for a long time, 

it can damage the blood vessels of the brain, heart and kidneys, and may result in a stroke, heart 

failure, heart attack or kidney failure. Lowering the blood pressure to a normal level reduces the risk of 

developing these disorders. 

 

Sprimeo HCT is used to treat high blood pressure. 

 

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2. BEFORE YOU TAKE SPRIMEO HCT 

 

Do not take Sprimeo HCT 
- if you are allergic (hypersensitive) to aliskiren or hydrochlorothiazide, to sulphonamide-derived 

medicines (medicines used to treat chest or urinary infections) or to any of the other ingredients 

of Sprimeo HCT. If you think you may be allergic, do not take Sprimeo HCT and ask your 

doctor for advice. 

- if you have experienced the following forms of angioedema (difficulties in breathing or 
swallowing, or swelling of the face, hands and feet, eyes, lips and/or tongue): 

- angioedema when taking aliskiren 
- hereditary angioedema 
- angioedema without any known cause. 

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

- if you are between three and nine months pregnant. 
- if you have serious liver or serious kidney problems. 
- if you are unable to produce urine (anuria). 
- if the level of potassium or sodium in your blood is too low despite treatment. 
- if the level of calcium in your blood is too high despite treatment. 
- if you have gout (uric acid crystals in the joints). 
- if you are taking ciclosporin (a medicine used in transplantation to prevent organ rejection or for 

other conditions, e.g. rheumatoid arthritis or atopic dermatitis), itraconazole (a medicine used to 

treat fungal infections) or quinidine (a medicine used to correct heart rhythm). 

- if you have diabetes mellitus or impaired kidney function and you are treated with either of the 
following classes of medicines used to treat high blood pressure: 

- an “angiotensin converting enzyme inhibitor” such as enalapril, lisinopril, ramipril etc. 
or 

- an “angiotensin 2 receptor blocker” such as valsartan, telmisartan, irbesartan etc. 
If any of the above applies to you, do not take Sprimeo HCT and talk to your doctor. 
 

Take special care with Sprimeo HCT 
- if you have impaired kidney function, your doctor will carefully consider whether Sprimeo HCT 

is suitable for you and may wish to monitor you carefully. 

- if you have had a kidney transplant. 
- if you suffer from liver problems. 
- if you suffer from heart problems. 
- if you experience angioedema (difficulties in breathing, or swallowing, or swelling of the face, 

hands and feet, eyes, lips and/or tongue). If this happens, stop taking Sprimeo HCT and contact 

your doctor. 

- if you have diabetes (high level of sugar in your blood). 
- if you have a high level of cholesterol or triglycerides in your blood. 
- if you suffer from a disease called lupus erythematosus (also called “lupus” or “SLE”). 
- if you suffer from allergy or asthma. 
- if you are taking either of the following classes of medicines used to treat high blood pressure: 

- an “angiotensin converting enzyme inhibitor” such as enalapril, lisinopril, ramipril etc. 

or 

- an “angiotensin 2 receptor blocker” such as valsartan, telmisartan, irbesartan etc. 

- if you are on a low-salt diet. 
- if you have signs and symptoms such as abnormal thirst, dry mouth, general weakness, 

drowsiness, muscle pain or cramps, nausea, vomiting, or an abnormally fast heart beat which 

may indicate an excessive effect of hydrochlorothiazide (contained in Sprimeo HCT). 

- if you experience skin reactions such as rash after sun exposure. 
- if you experience a decrease in vision or eye pain. These could be symptoms of an increase of 

pressure in your eye and can happen within hours to weeks of taking Sprimeo HCT. This can 

lead to permanent vision impairment, if not treated. 

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Tell your doctor if any of the above applies to you. 

 

You must tell your doctor if you think you are (or might become) pregnant. Sprimeo HCT is not 

recommended in early pregnancy, and must not be taken if you are more than 3 months pregnant, as it 

may cause serious harm to your baby if used at that stage (see Pregnancy section). 

 

The use of Sprimeo HCT in children and adolescents up to 18 years of age is not recommended. 

 

Using other medicines 

Please tell your doctor or pharmacist if you are taking or have recently taken any other 

medicines, including medicines obtained without a prescription. 

 

It is especially important to tell your doctor if you are using the following medicines: 

- 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. 

- medicines that may reduce the amount of potassium in your blood, such as diuretics (water 
tablets), corticosteroids, laxatives, carbenoxolone, amphotericin or penicillin G. 

- 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 (carbamazepine). 

- pain killers such as non-steroidal anti-inflammatory agents (NSAIDs), including selective 
cyclooxygenase-2 inhibitors (Cox-2 inhibitors). 

- medicines to reduce blood pressure, including methyldopa. 
- medicines to increase blood pressure, such as noradrenaline or adrenaline. 
- digoxin or other digitalis glycosides (medicines used to treat heart problems). 
- vitamin D and calcium salts. 
- medicines for the treatment of diabetes (oral agents such as metformin or insulins). 
- medicines that may increase blood sugar level, such as beta blockers and diazoxide. 
- medicines for the treatment of gout, such as allopurinol. 
- 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). 

- amantadine (a medicine used to treat Parkinson’s disease, also used to treat or prevent certain 
illnesses caused by viruses). 

- cholestyramine, colestipol or other resins (substances used mainly to treat high levels of lipids 
in the blood). 

- cytotoxic medicines (used to treat cancer), such as methotrexate or cyclophosphamide. 
- muscle relaxants (medicines to relax the muscles which are used during operations). 
- alcohol, sleeping pills and anaesthetics (medicines allowing patients to undergo surgery and 

other procedures). 

- iodine contrast media (agents used for imaging examinations). 
- arthritis medicines. 
 

Your doctor may need to change your dose and/or take other precautions if you are taking one 

of the following medicines: 

- furosemide, a medicine belonging to the type known as diuretics, or water tablets, which is used 
to increase the amount of urine you produce. 

- some medicines used to treat infections, such as ketoconazole. 
- verapamil, a medicine used to lower high blood pressure, to correct heart rhythm or to treat 

angina pectoris. 

 

Taking Sprimeo HCT with food and drink 
You should take Sprimeo HCT with a light meal once a day, preferably at the same time each day. 

You should not take Sprimeo HCT together with grapefruit juice. 

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Pregnancy 

You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally 

advise you to stop taking Sprimeo HCT before you become pregnant or as soon as you know you are 

pregnant and will advise you to take another medicine instead of Sprimeo HCT. Sprimeo HCT is not 

recommended during pregnancy, and must not be taken when more than 3 months pregnant, as it may 

cause serious harm to your baby if used after the third month of pregnancy. 

 

Breast-feeding 

Tell your doctor if you are breast-feeding or about to start breast-feeding. Sprimeo 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. 

 

Ask your doctor or pharmacist for advice before taking any medicine. 

 

Driving and using machines 
As with many other medicines used to treat high blood pressure, this medicine may make you feel 

dizzy. If you experience this symptom, do not drive or use tools or machines. 

 

Important information about some of the ingredients of Sprimeo HCT 

Sprimeo HCT contains lactose (milk sugar). If you have been told by your doctor that you have an 

intolerance to some sugars, contact your doctor before taking this medicine. 

 

Sprimeo HCT contains wheat starch. It is suitable for people with coeliac disease. Patients with wheat 

allergy (different from coeliac disease) should not take this medicine. 

 

 

3. HOW TO TAKE SPRIMEO HCT 

 

Always take Sprimeo HCT exactly as your doctor has told you. You should check with your doctor or 

pharmacist if you are not sure. 

 

The usual dose of Sprimeo HCT is one tablet a day. Swallow the tablet whole with some water. You 

should take Sprimeo HCT with a light meal once a day, preferably at the same time each day. You 

should not take Sprimeo HCT together with grapefruit juice. During your treatment, your doctor may 

adjust your dose depending on your blood pressure response. 

 

Sprimeo HCT may have been prescribed to you because your previous treatment did not lower your 

blood pressure enough. If this is the case, your doctor will tell you how to switch from that treatment 

to Sprimeo HCT. 

 

If you take more Sprimeo HCT than you should 
If you have accidentally taken too many Sprimeo HCT tablets, talk to a doctor immediately. You may 

require medical attention. 

 

If you forget to take Sprimeo 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. 

 

Do not stop taking this medicine, even if you are feeling well (unless your doctor tells you to do so). 

People who have high blood pressure often do not notice any signs of the problem. Many may feel 

quite 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 further questions on the use of this product, ask your doctor or pharmacist. 

 

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4. POSSIBLE SIDE EFFECTS 
 

Like all medicines, Sprimeo HCT can cause side effects, although not everybody gets them. 

 

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 

tell your doctor or pharmacist. You may need to stop Sprimeo HCT. 

 

Side effects reported in clinical studies for patients treated with Sprimeo HCT were: 

Common (affecting less than 1 in 10 patients): 

 Diarrhoea 
 

As for any combination of two active substances, side effects associated with each individual 

component cannot be excluded. 

Aliskiren: 

Common (affecting less than 1 in 10 patients): 

 Diarrhoea 

 Joint pain (arthralgia) 

 High level of potassium in the blood 

 Dizziness 
 

Uncommon (affecting less than 1 in 100 patients): 

 Skin rash (this may also be a sign of allergic reactions or angioedema – see “Rare” side effects 
below) 

 Kidney problems including acute renal failure (severely decreased urine output) 

 Swelling of hands, ankles or feet (peripheral oedema) 

 Severe skin reactions (toxic epidermal necrolysis and/or oral mucosal reactions - red skin, 
blistering of the lips, eyes or mouth, skin peeling, fever) 

 Low blood pressure 
 

Rare (affecting less than 1 in 1,000 patients): 

 Allergic reactions (hypersensitivity) and angioedema (the symptoms of which can include 
difficulties in breathing or swallowing, rash, itching, hives or swelling of the face, hands and 

feet, eyes, lips and/or tongue, dizziness) 

 Increased level of creatinine in the blood 
 

Hydrochlorothiazide: 

Very common (affecting more than 1 in 10 patients): 

 Low level of potassium in the blood 

 Increase of lipids in the blood 
 

Common (affecting less than 1 in 10 patients): 

 High level of uric acid in the blood 

 Low level of magnesium in the blood 

 Low level of sodium in the blood 

 Dizziness, fainting on standing up 

 Reduced appetite 

 Nausea and vomiting 

 Itchy rash and other types of rash 

 Inability to achieve or maintain erection 
 

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141 

Rare (affecting less than 1 in 1,000 patients): 

 Low level of blood platelets (sometimes with bleeding or bruising underneath the skin) 

 High level of calcium in the blood 

 High level of sugar in the blood 

 Worsening of the diabetic metabolic state 

 Sad mood (depression) 

 Sleep disturbances 

 Dizziness 

 Headache 

 Tingling or numbness 

 Vision disorder 

 Irregular heart beat 

 Abdominal discomfort 

 Constipation 

 Diarrhoea 

 Liver disorders which can occur together with yellow skin and eyes 

 Increased sensitivity of skin to the sun 

 Sugar in the urine 
 

Very rare (affecting less than 1 in 10,000 patients): 

 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) 

 Rash, itching, hives, difficulty breathing or swallowing, dizziness (hypersensitivity reactions) 

 Confusion, tiredness, muscle twitching and spasm, rapid breathing (hypochloraemic alkalosis) 

 Difficulty breathing with fever, coughing, wheezing, breathlessness (respiratory distress 
including pneumonitis and pulmonary oedema) 

 Severe upper stomach pain (pancreatitis) 

 Facial rash, joint pain, muscle disorder, fever (lupus erythematosus) 

 Inflammation of blood vessels with symptoms such as rash, purplish-red spots, fever (vasculitis) 

 Severe skin disease that causes rash, red skin, blistering of the lips, eyes or mouth, skin peeling, 
fever (toxic epidermal necrolysis) 

 

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

 Weakness 

 Bruising and frequent infections (aplastic anaemia) 

 Decrease in vision or pain in your eyes due to high pressure (possible signs of acute-angle 
closure glaucoma) 

 Severe skin disease that causes rash, red skin, blistering of the lips, eyes or mouth, skin peeling, 
fever (erythema multiforme) 

 Muscle spasm 

 Severely decreased urine output (possible signs of renal disorder or renal failure), weakness 
(asthenia) 

 Fever 
 

 

5. HOW TO STORE SPRIMEO HCT 
 

Keep out of the reach and sight of children. 

Do not use Sprimeo HCT after the expiry date which is stated on the carton. 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. 

 

 

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6. FURTHER INFORMATION 

 

What Sprimeo HCT contains 

- Each Sprimeo HCT 150 mg/12.5 mg film-coated tablet contains 150 mg aliskiren (as 
hemifumarate) and 12.5 mg hydrocholorothiazide. The other ingredients are: cellulose 

microcrystalline, crospovidone, lactose monohydrate, wheat starch, povidone, magnesium 

stearate, silica colloidal anhydrous, talc, hypromellose, macrogol, titanium dioxide (E171). 

- Each Sprimeo HCT 150 mg/25 mg film-coated tablet contains 150 mg aliskiren (as 
hemifumarate) and 25 mg hydrocholorothiazide. The other ingredients are: cellulose 

microcrystalline, crospovidone, lactose monohydrate, wheat starch, povidone, magnesium 

stearate, silica colloidal anhydrous, talc, hypromellose, macrogol, titanium dioxide (E171), red 

iron oxide (E172), yellow iron oxide (E172). 

- Each Sprimeo HCT 300 mg/12.5 mg film-coated tablet contains 300 mg aliskiren (as 
hemifumarate) and 12.5 mg hydrocholorothiazide. The other ingredients are: cellulose 

microcrystalline, crospovidone, lactose monohydrate, wheat starch, povidone, magnesium 

stearate, silica colloidal anhydrous, talc, hypromellose, macrogol, titanium dioxide (E171), red 

iron oxide (E172), black iron oxide (E172). 

- Each Sprimeo HCT 300 mg/25 mg film-coated tablet contains 300 mg aliskiren (as 
hemifumarate) and 25 mg hydrocholorothiazide. The other ingredients are: cellulose 

microcrystalline, crospovidone, lactose monohydrate, wheat starch, povidone, magnesium 

stearate, silica colloidal anhydrous, talc, hypromellose, macrogol, titanium dioxide (E171), red 

iron oxide (E172), yellow iron oxide (E172). 

 

What Sprimeo HCT looks like and contents of the pack 

Sprimeo HCT 150 mg/12.5 mg film-coated tablets are white, oval film-coated tablets imprinted with 

“LCI” on one side and “NVR” on the other. 

Sprimeo HCT 150 mg/25 mg film-coated tablets are pale yellow, oval film-coated tablets imprinted 

with “CLL” on one side and “NVR” on the other. 

Sprimeo HCT 300 mg/12.5 mg film-coated tablets are violet white, oval film-coated tablets imprinted 

with “CVI” on one side and “NVR” on the other. 

Sprimeo HCT 300 mg/25 mg film-coated tablets are light yellow, oval film-coated tablets imprinted 

with “CVV” on one side and “NVR” on the other. 

 

Sprimeo HCT is available in packs containing 7, 14, 28, 30, 50, 56, 90,or 98 tablets. 

Packs containing 90 (3x30), 98 (2x49) or 280 (20x14) tablets are multi-packs. 

 

Not all pack sizes or strengths may be available in your country. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

Manufacturer 

Novartis Farma S.p.A. 

Via Provinciale Schito 131 

I-80058 Torre Annunziata/NA 

Italy 

 

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For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Luxembourg/Luxemburg 
Novartis Pharma GmbH 

Tél/Tel: +49 911 273 0 

 

България 

Novartis Pharma Services Inc. 

Тел.: +359 2 489 98 28 

 

Magyarország 

Novartis Hungária Kft. Pharma 

Tel.: +36 1 457 65 00 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2298 3217 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 26 37 82 111 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Eesti 

Novartis Pharma Services Inc. 

Tel: +372 66 30 810 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

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

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

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Latvija 

Novartis Pharma Services Inc. 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

Lietuva 
Novartis Pharma Services Inc. 

Tel: +370 5 269 16 50 

 

 

 

This leaflet was last approved in 

 

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

http://www.ema.europa.eu 

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	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
	A. LABELLING
	B. PACKAGE LEAFLET