Dafiro

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 



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1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 5 mg/80 mg film-coated tablets 

Dafiro 5 mg/160 mg film-coated tablets 

Dafiro 10 mg/160 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Dafiro 5 mg/80 mg film-coated tablets 

 

Each film-coated tablet contains 5 mg of amlodipine (as amlodipine besylate) and 80 mg of valsartan. 

 

Dafiro 5 mg/160 mg film-coated tablets 

 

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

 

Dafiro 10 mg/160 mg film-coated tablets 

 

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

valsartan. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet 

 

Dafiro 5 mg/80 mg film-coated tablets 

 

Dark yellow, round film-coated tablet with bevelled edges, imprinted with “NVR” on one side and 

“NV” on the other side. Approximate size: diameter 8.20 mm. 

 

Dafiro 5 mg/160 mg film-coated tablets 

 

Dark yellow, oval film-coated tablet, imprinted with “NVR” on one side and “ECE” on the other side. 

Approximate size: 14.2 mm (length) x 5.7 mm (width). 

 

Dafiro 10 mg/160 mg film-coated tablets 

 

Light yellow, oval film-coated tablet, imprinted with “NVR” on one side and “UIC” on the other side. 

Approximate size: 14.2 mm (length) x 5.7 mm (width). 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment of essential hypertension. 

 

Dafiro is indicated in adults whose blood pressure is not adequately controlled on amlodipine or 

valsartan monotherapy. 

 



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4.2 Posology and method of administration 

 

Posology 

 

The recommended dose of Dafiro is one tablet per day. 

 

Dafiro 5 mg/80 mg may be administered in patients whose blood pressure is not adequately controlled 

with amlodipine 5 mg or valsartan 80 mg alone. 

 

Dafiro 5 mg/160 mg may be administered in patients whose blood pressure is not adequately 

controlled with amlodipine 5 mg or valsartan 160 mg alone. 

 

Dafiro 10 mg/160 mg may be administered in patients whose blood pressure is not adequately 

controlled with amlodipine 10 mg or valsartan 160 mg alone or with Dafiro 5 mg/160 mg. 

 

Dafiro can be used with or without food. 

 

Individual dose titration with the components (i.e. amlodipine and valsartan) is recommended before 

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

to the fixed-dose combination may be considered. 

 

For convenience, patients receiving valsartan and amlodipine from separate tablets/capsules may be 

switched to Dafiro containing the same component doses. 

 

Renal impairment 

There are no available clinical data in severely renally impaired patients. No dosage adjustment is 

required for patients with mild to moderate renal impairment. Monitoring of potassium levels and 

creatinine is advised in moderate renal impairment. 

 

Hepatic impairment 

Dafiro is contraindicated in patients with severe hepatic impairment (see section 4.3). 

 

Caution should be exercised when administering Dafiro to patients with hepatic impairment or biliary 

obstructive disorders (see section 4.4). In patients with mild to moderate hepatic impairment without 

cholestasis, the maximum recommended dose is 80 mg valsartan. Amlodipine dosage 

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

When switching eligible hypertensive patients (see section 4.1) with hepatic impairment to amlodipine 

or Dafiro, the lowest available dose of amlodipine monotherapy or of the amlodipine component, 

respectively, should be used. 

 

Elderly (age 65 years or over) 

In elderly patients, caution is required when increasing the dosage. When switching eligible elderly 

hypertensive patients (see section 4.1) to amlodipine or Dafiro, the lowest available dose of 

amlodipine monotherapy or of the amlodipine component, respectively, should be used. 

 

Paediatric population 

The safety and efficacy of Dafiro in children aged below 18 years have not been established. No data 

are available. 

 

Method of administration 

 

Oral use. 

It is recommended to take Dafiro with some water. 

 



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4.3 Contraindications 

 

 Hypersensitivity to the active substances, to dihydropyridine derivatives, or to any of the 
excipients listed in section 6.1. 

 Severe hepatic impairment, biliary cirrhosis or cholestasis. 

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

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

 Severe hypotension. 

 Shock (including cardiogenic shock). 

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

 Haemodynamically unstable heart failure after acute myocardial infarction. 
 

4.4 Special warnings and precautions for use 

 

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

 

Pregnancy 

 

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

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

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

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

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

 

Sodium- and/or volume-depleted patients 

 

Excessive hypotension was seen in 0.4% of patients with uncomplicated hypertension treated with 

Dafiro in placebo-controlled studies. In patients with an activated renin-angiotensin system (such as 

volume- and/or salt-depleted patients receiving high doses of diuretics) who are receiving angiotensin 

receptor blockers, symptomatic hypotension may occur. Correction of this condition prior to 

administration of Dafiro or close medical supervision at the start of treatment is recommended. 

 

If hypotension occurs with Dafiro, the patient should be placed in the supine position and, if 

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

pressure has been stabilised. 

 

Hyperkalaemia 

 

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

potassium, or other medicinal products that may increase potassium levels (heparin, etc.) should be 

undertaken with caution and with frequent monitoring of potassium levels. 

 

Renal artery stenosis 

 

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

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

such patients. 

 

Kidney transplantation 

 

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

transplantation. 

 

  



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Hepatic impairment 

 

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

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

been established. Particular caution should be exercised when administering Dafiro to patients with 

mild to moderate hepatic impairment or biliary obstructive disorders. 

 

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

dose is 80 mg valsartan. 

 

Renal impairment 

 

No dosage adjustment of Dafiro is required for patients with mild to moderate renal impairment (GFR 

>30 ml/min/1.73 m2). Monitoring of potassium levels and creatinine is advised in moderate renal 

impairment. 

 

Primary hyperaldosteronism 

 

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

valsartan as their renin-angiotensin system is affected by the primary disease. 

 

Angioedema 

 

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

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

these patients previously experienced angioedema with other medicinal products, including ACE 

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

not be re-administered. 

 

Heart failure/post-myocardial infarction 

 

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

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

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

ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or 

progressive azotaemia and (rarely) with acute renal failure and/or death. Similar outcomes have been 

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

always include assessment of renal function. 

 

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

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

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

incidence of worsening heart failure as compared to placebo. 

 

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

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

 

Aortic and mitral valve stenosis 

 

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

significant aortic stenosis that is not high grade. 

 

  



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

 

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

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

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

recommended (see sections 4.5 and 5.1). 

 

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

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

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

 

Dafiro has not been studied in any patient population other than hypertension. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Interactions common to the combination 

 

No drug-drug interaction studies have been performed with Dafiro and other medicinal products. 

 

To be taken into account with concomitant use 

Other antihypertensive agents 

Commonly used antihypertensive agents (e.g. alpha blockers, diuretics) and other medicinal products 

which may cause hypotensive adverse effects (e.g. tricyclic antidepressants, alpha blockers for 

treatment of benign prostate hyperplasia) may increase the antihypertensive effect of the combination. 

 

Interactions linked to amlodipine 

 

Concomitant use not recommended 

Grapefruit or grapefruit juice 

Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability 

may be increased in some patients, resulting in increased blood pressure lowering effects. 

 

Caution required with concomitant use 

CYP3A4 inhibitors 

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole 

antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to 

significant increase in amlodipine exposure. The clinical translation of these pharmacokinetic 

variations may be more pronounced in the elderly. Clinical monitoring and dose adjustment may thus 

be required. 

 

CYP3A4 inducers (anticonvulsant agents [e.g. carbamazepine, phenobarbital, phenytoin, 

fosphenytoin, primidone], rifampicin, Hypericum perforatum) 

Upon co-administration of known inducers of the CYP3A4, the plasma concentration of amlodipine 

may vary. Therefore, blood pressure should be monitored and dose regulation considered both during 

and after concomitant medication particularly with strong CYP3A4 inducers (e.g. rifampicin, 

hypericum perforatum). 

 

Simvastatin 

Co-administration of multiple doses of 10 mg amlodipine with 80 mg simvastatin resulted in a 77% 

increase in exposure to simvastatin compared to simvastatin alone. It is recommended to limit the dose 

of simvastatin to 20 mg daily in patients on amlodipine. 

 

  



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Dantrolene (infusion) 

In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with 

hyperkalaemia after administration of verapamil and intravenous dantrolene. Due to risk of 

hyperkalaemia, it is recommended that the co-administration of calcium channel blockers such as 

amlodipine be avoided in patients susceptible to malignant hyperthermia and in the management of 

malignant hyperthermia. 

 

To be taken into account with concomitant use 

Others 

In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, 

warfarin or ciclosporin. 

 

Interactions linked to valsartan 

 

Concomitant use not recommended 

Lithium 

Reversible increases in serum lithium concentrations and toxicity have been reported during 

concomitant administration of lithium with angiotensin converting enzyme inhibitors or angiotensin II 

receptor antagonists, including valsartan.. Therefore, careful monitoring of serum lithium levels is 

recommended during concomitant use. If a diurectic is also used, the risk of lithium toxicity may 

presumably be increased further with Dafiro. 

 

Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other 

substances that may increase potassium levels 

If a medicinal product that affects potassium levels is to be prescribed in combination with valsartan, 

monitoring of potassium plasma levels is advised. 

 

Caution required with concomitant use 

Non-steroidal anti-inflammatory medicines (NSAIDs), including selective COX-2 inhibitors, 

acetylsalicylic acid (>3 g/day), and non-selective NSAIDs 

When angiotensin II antagonists are administered simultaneously with NSAIDs attenuation of the 

antihypertensive effect may occur. Furthermore, concomitant use of angiotensin II antagonists and 

NSAIDs may lead to an increased risk of worsening of renal function and an increase in serum 

potassium. Therefore, monitoring of renal function at the beginning of the treatment is recommended, 

as well as adequate hydration of the patient. 

 

Inhibitors of the uptake transporter (rifampicin, ciclosporin) or efflux transporter (ritonavir) 

The results of an in vitro study with human liver tissue indicate that valsartan is a substrate of the 

hepatic uptake transporter OATP1B1 and of the hepatic efflux transporter MRP2. Co-administration 

of inhibitors of the uptake transporter (rifampicin, ciclosporin) or efflux transporter (ritonavir) may 

increase the systemic exposure to valsartan. 

 

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

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

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

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

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

 

Others 

In monotherapy with valsartan, no interactions of clinical significance have been found with the 

following substances: cimetidine, warfarin, furosemide, digoxin, atenolol, indometacin, 

hydrochlorothiazide, amlodipine, glibenclamide. 

 

  



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4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

 

Amlodipine 

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

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

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

mother and foetus. 

 

Valsartan 

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

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

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

 

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

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

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

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

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

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

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

alternative therapy should be started. 

 

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

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

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

 

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

of renal function and skull is recommended. 

 

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

sections 4.3 and 4.4). 

 

Breast-feeding 

 

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

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

amlodipine on infants is unknown. No information is available regarding the use of Dafiro during 

breast-feeding, therefore Dafiro is not recommended and alternative treatments with better established 

safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm 

infant. 

 

  



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Fertility 

 

There are no clinical studies on fertility with Dafiro. 

 

Valsartan 

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

up to 200 mg/kg/day. This dose is 6 times the maximum recommended human dose on a mg/m2 basis 

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

 

Amlodipine 

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

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

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

 

4.7 Effects on ability to drive and use machines 

 

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

or weariness may occasionally occur. 

 

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

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

impaired. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The safety of Dafiro has been evaluated in five controlled clinical studies with 5,175 patients, 2,613 of 

whom received valsartan in combination with amlodipine. The following adverse reactions were found 

to be the most frequently occurring or the most significant or severe: nasopharyngitis, influenza, 

hypersensitivity, headache, syncope, orthostatic hypotension, oedema, pitting oedema, facial oedema, 

oedema peripheral, fatigue, flushing, asthenia and hot flush. 

 

Tabulated list of adverse reactions 

 

Adverse reactions have been ranked under headings of frequency 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); not known (cannot be estimated from the available data). 

  



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MedDRA 

System organ 

class 

Adverse reactions Frequency 

Dafiro Amlodipine Valsartan 

Infections and 

infestations 

Nasopharyngitis Common -- -- 

Influenza Common -- -- 

Blood and 

lymphatic system 

disorders 

Haemoglobin and 

haematocrit decreased 

-- -- Not known 

Leukopenia -- Very rare -- 

Neutropenia -- -- Not known 

Thrombocytopenia, 

sometimes with purpura 

-- Very rare Not known 

Immune system 

disorders 

Hypersensitivity Rare Very rare Not known 

Metabolism and 

nutrition 

disorders 

Anorexia Uncommon -- -- 

Hypercalcaemia Uncommon -- -- 

Hyperglycaemia -- Very rare -- 

Hyperlipidaemia Uncommon -- -- 

Hyperuricaemia Uncommon -- -- 

Hypokalaemia Common -- -- 

Hyponatraemia Uncommon -- -- 

Psychiatric 

disorders 

Depression -- Uncommon -- 

Anxiety Rare -- -- 

Insomnia/sleep disorders -- Uncommon -- 

Mood swings -- Uncommon -- 

Confusion -- Rare -- 

Nervous system 

disorders 

Coordination abnormal Uncommon -- -- 

Dizziness Uncommon Common -- 

Dizziness postural Uncommon -- -- 

Dysgeusia -- Uncommon -- 

Extrapyramidal syndrome -- Not known -- 

Headache Common Common -- 

Hypertonia -- Very rare -- 

Paraesthesia Uncommon Uncommon -- 

Peripheral neuropathy, 

neuropathy 

-- Very rare -- 

Somnolence Uncommon Common -- 

Syncope -- Uncommon -- 

Tremor -- Uncommon -- 

Hypoesthesia -- Uncommon -- 

Eye disorders Visual disturbance Rare Uncommon -- 

Visual impairment Uncommon Uncommon -- 



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Ear and labyrinth 

disorders 

Tinnitus Rare Uncommon -- 

Vertigo Uncommon -- Uncommon 

Cardiac disorders Palpitations Uncommon Common -- 

Syncope Rare -- -- 

Tachycardia Uncommon -- -- 

Arrhythmias (including 

bradycardia, ventricular 

tachycardia, and atrial 

fibrillation) 

-- Very rare -- 

Myocardial infarction -- Very rare -- 

Vascular 

disorders 

Flushing -- Common -- 

Hypotension Rare Uncommon -- 

Orthostatic hypotension Uncommon -- -- 

Vasculitis -- Very rare Not known 

Respiratory, 

thoracic and 

mediastinal 

disorders 

Cough Uncommon Very rare Uncommon 

Dyspnoea -- Uncommon -- 

Pharyngolaryngeal pain Uncommon -- -- 

Rhinitis -- Uncommon -- 

Gastrointestinal 

disorders 

Abdominal discomfort, 

abdominal pain upper 

Uncommon Common Uncommon 

Change of bowel habit -- Uncommon -- 

Constipation Uncommon -- -- 

Diarrhoea Uncommon Uncommon -- 

Dry mouth Uncommon Uncommon -- 

Dyspepsia -- Uncommon -- 

Gastritis -- Very rare -- 

Gingival hyperplasia -- Very rare -- 

Nausea Uncommon Common -- 

Pancreatitis -- Very rare -- 

Vomiting -- Uncommon -- 

Hepatobiliary 

disorders 

Liver function test abnormal, 

including blood bilirubin 

increase 

-- Very rare* Not known 

Hepatitis -- Very rare -- 

Intrahepatic cholestasis, 

jaundice 

-- Very rare -- 

Skin and 

subcutaneous 

tissue disorders 

Alopecia -- Uncommon -- 

Angioedema -- Very rare Not known 

Dermatitis bullous -- -- Not known 

Erythema Uncommon -- -- 

Erythema multiforme -- Very rare -- 

Exanthema Rare Uncommon -- 

Hyperhidrosis Rare Uncommon -- 

Photosensitivity reaction -- Uncommon -- 

Pruritus Rare Uncommon Not known 

Purpura -- Uncommon -- 

Rash Uncommon Uncommon Not known 

Skin discolouration -- Uncommon -- 

Urticaria and other forms of 

rash 

-- Very rare -- 

Exfoliative dermatitis -- Very rare -- 

Stevens-Johnson syndrome -- Very rare -- 

Quincke oedema -- Very rare -- 

Toxic Epidermal Necrolysis -- Not known -- 

  



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Musculoskeletal 

and connective 

tissue disorders 

Arthralgia Uncommon Uncommon -- 

Back pain Uncommon Uncommon -- 

Joint swelling Uncommon -- -- 

Muscle spasm Rare Uncommon -- 

Myalgia -- Uncommon Not known 

Ankle swelling -- Common -- 

Sensation of heaviness Rare -- -- 

Renal and 

urinary disorders 

Blood creatinine increased -- -- Not known 

Micturition disorder -- Uncommon -- 

Nocturia -- Uncommon -- 

Pollakiuria Rare Uncommon -- 

Polyuria Rare -- -- 

Renal failure and 

impairment 

-- -- Not known 

Reproductive 

system and 

breast disorders 

Impotence -- Uncommon -- 

Erectile dysfunction Rare -- -- 

Gynaecomastia -- Uncommon -- 

General disorders 

and 

administration 

site conditions 

Asthenia Common Uncommon -- 

Discomfort, malaise -- Uncommon -- 

Fatigue Common Common Uncommon 

Facial oedema Common -- -- 

Flushing, hot flush Common -- -- 

Non cardiac chest pain -- Uncommon -- 

Oedema Common Common -- 

Oedema peripheral Common -- -- 

Pain -- Uncommon -- 

Pitting oedema Common -- -- 

Investigations Blood potassium increased -- -- Not known 

Weight increase -- Uncommon -- 

Weight decrease -- Uncommon -- 

 

* Mostly consistent with cholestasis 

 

Additional information on the combination 

 

Peripheral oedema, a recognised side effect of amlodipine, was generally observed at a lower 

incidence in patients who received the amlodipine/valsartan combination than in those who received 

amlodipine alone. In double-blind, controlled clinical trials, the incidence of peripheral oedema by 

dose was as follows: 

 

% of patients who experienced peripheral 

oedema 

Valsartan (mg) 

0 40 80 160 320 

 

 

Amlodipine 

(mg) 

 

0 3.0 5.5 2.4 1.6 0.9 

2.5 8.0 2.3 5.4 2.4 3.9 

5 3.1 4.8 2.3 2.1 2.4 

10 10.3 NA NA 9.0 9.5 

 

The mean incidence of peripheral oedema evenly weighted across all doses was 5.1% with the 

amlodipine/valsartan combination. 

 



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Additional information on the individual components 

 

Adverse reactions previously reported with one of the individual components (amlodipine or 

valsartan) may be potential adverse reactions with Dafiro as well, even if not observed in clinical trials 

or during the post-marketing period. 

 

Amlodipine 

Common Somnolence, dizziness, palpitations, abdominal pain, nausea, ankle swelling. 

Uncommon Insomnia, mood changes (including anxiety), depression, tremor, dysgeusia, 

syncope, hypoesthesia, visual disturbance (including diplopia), tinnitus, 

hypotension, dyspnoea, rhinitis, vomiting, dyspepsia, alopecia, purpura, skin 

discolouration, hyperhidrosis, pruritus, exanthema, myalgia, muscle cramps, pain, 

micturition disorder, increased urinary frequency, impotence, gynaecomastia, 

chest pain, malaise, weight increase, weight decrease. 

Rare Confusion. 

Very rare Leukocytopenia, thrombocytopenia, allergic reactions, hyperglycaemia, 

hypertonia, peripheral neuropathy, myocardial infarction, arrhythmia (including 

bradycardia, ventricular tachycardia and atrial fibrillation), vasculitis, pancreatitis, 

gastritis, gingival hyperplasia, hepatitis, jaundice, hepatic enzymes increased*, 

angioedema, erythema multiforme, urticaria, exfoliative dermatitis, Stevens-

Johnson syndrome, Quincke oedema, photosensitivity. 

Not known Toxic Epidermal Necrolysis 

* mostly consistent with cholestasis 

 

Exceptional cases of extrapyramidal syndrome have been reported. 

 

Valsartan 

Not known Decrease in haemoglobin, decrease in haematocrit, neutropenia, 

thrombocytopenia, increase of serum potassium, elevation of liver function values 

including increase of serum bilirubin, renal failure and impairment, elevation of 

serum creatinine, angioedema, myalgia, vasculitis, hypersensitivity including 

serum sickness. 

 

Reporting of suspected adverse reactions 

 

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

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

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

listed in Appendix V. 

 

4.9 Overdose 

 

Symptoms 

 

There is no experience of overdose with Dafiro. The major symptom of overdose with valsartan is 

possibly pronounced hypotension with dizziness. Overdose with amlodipine may result in excessive 

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

hypotension up to and including shock with fatal outcome have been reported. 

 

  

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14 

Treatment 

 

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

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

has been shown to significantly decrease amlodipine absorption. Clinically significant hypotension 

due to Dafiro overdose calls for active cardiovascular support, including frequent monitoring of 

cardiac and respiratory function, elevation of extremities, and attention to circulating fluid volume and 

urine output. A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, provided 

that there is no contraindication to its use. Intravenous calcium gluconate may be beneficial in 

reversing the effects of calcium channel blockade. 

 

Both valsartan and amlodipine are unlikely to be removed by haemodialysis. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

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

combinations; angiotensin II antagonists and calcium channel blockers, ATC code: C09DB01 

 

Dafiro combines two antihypertensive compounds with complementary mechanisms to control blood 

pressure in patients with essential hypertension: amlodipine belongs to the calcium antagonist class 

and valsartan to the angiotensin II antagonist class of medicines. The combination of these substances 

has an additive antihypertensive effect, reducing blood pressure to a greater degree than either 

component alone. 

 

Amlodipine/Valsartan 

 

The combination of amlodipine and valsartan produces dose-related additive reduction in blood 

pressure across its therapeutic dose range. The antihypertensive effect of a single dose of the 

combination persisted for 24 hours. 

 

Placebo-controlled trials 

Over 1,400 hypertensive patients received Dafiro once daily in two placebo-controlled trials. Adults 

with mild to moderate uncomplicated essential hypertension (mean sitting diastolic blood pressure 

95 and <110 mmHg) were enrolled. Patients with high cardiovascular risks – heart failure, type I and 

poorly controlled type II diabetes and history of myocardial infarction or stroke within one year – were 

excluded. 

 

Active-controlled trials in patients who were non-responders to monotherapy 

A multicentre, randomised, double-blind, active-controlled, parallel-group trial showed normalisation 

of blood pressure (trough sitting diastolic blood pressure <90 mmHg at the end of the trial) in patients 

not adequately controlled on valsartan 160 mg in 75% of patients treated with amlodipine/valsartan 

10 mg/160 mg and 62% of patients treated with amlodipine/valsartan 5 mg/160 mg, compared to 53% 

of patients remaining on valsartan 160 mg. The addition of amlodipine 10 mg and 5 mg produced an 

additional reduction in systolic/diastolic blood pressure of 6.0/4.8 mmHg and 3.9/2.9 mmHg, 

respectively, compared to patients who remained on valsartan 160 mg only. 
 
A multicentre, randomised, double-blind, active-controlled, parallel-group trial showed normalisation 

of blood pressure (trough sitting diastolic blood pressure <90 mmHg at the end of the trial) in patients 

not adequately controlled on amlodipine 10 mg in 78% of patients treated with amlodipine/valsartan 

10 mg/160 mg, compared to 67% of patients remaining on amlodipine 10 mg. The addition of 

valsartan 160 mg produced an additional reduction in systolic/diastolic blood pressure of 

2.9/2.1 mmHg compared to patients who remained on amlodipine 10 mg only. 

 



15 

Dafiro was also studied in an active-controlled study of 130 hypertensive patients with mean sitting 

diastolic blood pressure ≥110 mmHg and <120 mmHg. In this study (baseline blood pressure 

171/113 mmHg), a Dafiro regimen of 5 mg/160 mg titrated to 10 mg/160 mg reduced sitting blood 

pressure by 36/29 mmHg as compared to 32/28 mmHg with a regimen of 

lisinopril/hydrochlorothiazide 10 mg/12.5 mg titrated to 20 mg/12.5 mg. 

 

In two long-term follow-up studies the effect of Dafiro was maintained for over one year. Abrupt 

withdrawal of Dafiro has not been associated with a rapid increase in blood pressure. 

 

Age, gender, race or body mass index (≥30 kg/m2, <30 kg/m2) did not influence the response to 

Dafiro. 

 

Dafiro has not been studied in any patient population other than hypertension. Valsartan has been 

studied in patients with post myocardial infarction and heart failure. Amlodipine has been studied in 

patients with chronic stable angina, vasospastic angina and angiographically documented coronary 

artery disease. 

 

Amlodipine 

 

The amlodipine component of Dafiro inhibits the transmembrane entry of calcium ions into cardiac 

and vascular smooth muscle. The mechanism of the antihypertensive action of amlodipine is due to a 

direct relaxant effect on vascular smooth muscle, causing reductions in peripheral vascular resistance 

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

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

muscle are dependent upon the movement of extracellular calcium ions into these cells through 

specific ion channels. 

 

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

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

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

chronic dosing. 

 

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

 

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

decrease in renal vascular resistance and an increase in glomerular filtration rate and effective renal 

plasma flow, without change in filtration fraction or proteinuria. 

 

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

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

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

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

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

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

 

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

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

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

parameters were observed. 

 

Use in patients with hypertension 

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

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

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

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

hypertension. 

 



16 

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

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

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

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

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

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

 

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

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

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

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

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

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

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

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

 

Valsartan 

 

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

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

increased plasma levels of angiotensin II following AT1 receptor blockade with valsartan may 

stimulate the unblocked receptor subtype AT2, which appears to counterbalance the effect of the AT1 

receptor. Valsartan does not exhibit any partial agonist activity at the AT1 receptor and has much 

(about 20,000-fold) greater affinity for the AT1 receptor than for the AT2 receptor. 

 

Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin 

II and degrades bradykinin. Since there is no effect on ACE and no potentiation of bradykinin or 

substance P, angiotensin II antagonists are unlikely to be associated with coughing. In clinical trials 

where valsartan was compared with an ACE inhibitor, the incidence of dry cough was significantly (p 

<0.05) lower in patients treated with valsartan than in those treated with an ACE inhibitor (2.6% 

versus 7.9%, respectively). In a clinical trial of patients with a history of dry cough during ACE 

inhibitor therapy, 19.5% of trial subjects receiving valsartan and 19.0% of those receiving a thiazide 

diuretic experienced coughing, compared to 68.5% of those treated with an ACE inhibitor (p <0.05). 

Valsartan does not bind to or block other hormone receptors or ion channels known to be important in 

cardiovascular regulation. 

 

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

affecting pulse rate. 

 

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

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

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

reduction in blood pressure with any dose is generally attained within 2–4 weeks and is sustained 

during long-term therapy. Abrupt withdrawal of valsartan has not been associated with rebound 

hypertension or other adverse clinical events. 

 

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

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

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

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

ARB. 

 

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

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

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

 



17 

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

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

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

results are also relevant for other ACE inhibitors and ARBs. 

 

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

nephropathy (see section 4.4). 

 

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

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

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

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

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

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

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

placebo group. 

 

5.2 Pharmacokinetic properties 

 

Linearity 

 

Amlodipine and valsartan exhibit linear pharmacokinetics. 

 

Amlodipine/Valsartan 

 

Following oral administration of Dafiro, peak plasma concentrations of valsartan and amlodipine are 

reached in 3 and 6–8 hours, respectively. The rate and extent of absorption of Dafiro are equivalent to 

the bioavailability of valsartan and amlodipine when administered as individual tablets. 

 

Amlodipine 

 

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

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

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

 

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

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

 

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

metabolites. 

 

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

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

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

 

Valsartan 

 

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

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

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

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

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

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

 

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

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

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



18 

 

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

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

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

 

Elimination: Valsartan shows multiexponential decay kinetics (t½α <1 h and t½ß about 9 h). Valsartan is 

primarily eliminated in faeces (about 83% of dose) and urine (about 13% of dose), mainly as 

unchanged drug. Following intravenous administration, plasma clearance of valsartan is about 2 l/h 

and its renal clearance is 0.62 l/h (about 30% of total clearance). The half-life of valsartan is 6 hours. 

 

Special populations 

 

Paediatric population (age below 18 years) 

No pharmacokinetic data are available in the paediatric population. 

 

Elderly (age 65 years or over) 

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

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

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

young therefore caution is required when increasing the dosage. 

 

Renal impairment 

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

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

was seen between renal function and systemic exposure to valsartan. 

 

Hepatic impairment 

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

impairment. Patients with hepatic impairment have decreased clearance of amlodipine with resulting 

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

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

(matched by age, sex and weight). Caution should be exercised in patients with liver disease (see 

section 4.2). 

 

5.3 Preclinical safety data 

 

Amlodipine/Valsartan 

 

Adverse reactions observed in animal studies with possible clinical relevance were as follows: 

Histopathological signs of inflammation of the glandular stomach was seen in male rats at an exposure 

of about 1.9 (valsartan) and 2.6 (amlodipine) times the clinical doses of 160 mg valsartan and 10 mg 

amlodipine. At higher exposures, there were ulceration and erosion of the stomach mucosa in both 

females and males. Similar changes were also seen in the valsartan alone group (exposure 8.5–

11.0 times the clinical dose of 160 mg valsartan). 

 

An increased incidence and severity of renal tubular basophilia/hyalinisation, dilation and casts, as 

well as interstitial lymphocyte inflammation and arteriolar medial hypertrophy were found at an 

exposure of 8–13 (valsartan) and 7–8 (amlodipine) times the clinical doses of 160 mg valsartan and 

10 mg amlodipine. Similar changes were found in the valsartan alone group (exposure 8.5–11.0 times 

the clinical dose of 160 mg valsartan). 

 

  



19 

In an embryo-foetal development study in the rat, increased incidences of dilated ureters, malformed 

sternebrae, and unossified forepaw phalanges were noticed at exposures of about 12 (valsartan) and 10 

(amlodipine) times the clinical doses of 160 mg valsartan and 10 mg amlodipine. Dilated ureters were 

also found in the valsartan alone group (exposure 12 times the clinical dose of 160 mg valsartan). 

There were only modest signs of maternal toxicity (moderate reduction of body weight) in this study. 

The no-observed-effect-level for developmental effects was observed at 3- (valsartan) and 4- 

(amlodipine) fold the clinical exposure (based on AUC). 

 

For the single compounds there was no evidence of mutagenicity, clastogenicity or carcinogenicity. 

 

Amlodipine 

 

Reproductive toxicology 

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

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

recommended dosage for humans based on mg/kg. 

 

Impairment of fertility 

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

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

dose of 10 mg on a mg/m2 basis). In another rat study in which male rats were treated with amlodipine 

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

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

the number of mature spermatids and Sertoli cells. 

 

Carcinogenesis, mutagenesis 

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

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

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

10 mg on a mg/m2 basis) was close to the maximum tolerated dose for mice but not for rats. 

 

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

 

* Based on patient weight of 50 kg 

 

Valsartan 

 

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

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction 

and development. 

 

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

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

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

maximum recommended human dose on a mg/m2 basis (calculations assume an oral dose of 

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

 

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

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

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

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

18 times the maximum recommended human dose on a mg/m2 basis (calculations assume an oral dose 

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

 



20 

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

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

creatinine. 

 

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

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

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

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

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Dafiro 5 mg/80 mg film-coated tablets 

 

Tablet core 

Cellulose microcrystalline 

Crospovidone (type A) 

Silica, colloidal anhydrous 

Magnesium stearate 

 

Coating 

Hypromellose, substitution type 2910 (3 mPa.s) 

Titanium dioxide (E171) 

Iron oxide, yellow (E172) 

Macrogol 4000 

Talc 

 

Dafiro 5 mg/160 mg film-coated tablets 

 

Tablet core 

Cellulose microcrystalline 

Crospovidone (type A) 

Silica, colloidal anhydrous 

Magnesium stearate 

 

Coating 

Hypromellose, substitution type 2910 (3 mPa.s) 

Titanium dioxide (E171) 

Iron oxide, yellow (E172) 

Macrogol 4000 

Talc 

 

Dafiro 10 mg/160 mg film-coated tablets 

 

Tablet core 

Cellulose microcrystalline 

Crospovidone (type A) 

Silica, colloidal anhydrous 

Magnesium stearate 

 



21 

Coating 

Hypromellose, substitution type 2910 (3 mPa.s) 

Titanium dioxide (E171) 

Iron oxide, yellow (E172) 

Iron oxide, red (E172) 

Macrogol 4000 

Talc 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

3 years. 

 

6.4 Special precautions for storage 

 

Do not store above 30°C. 

 

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

 

6.5 Nature and contents of container 

 

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

Pack sizes: 7, 14, 28, 30, 56, 90, 98 or 280 film-coated tablets and multipacks containing 280 (4x70 or 

20x14) film-coated tablets. 

 

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

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

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 

 

No special requirements. 

 

 

  



22 

7. MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

Dafiro 5 mg/80 mg film-coated tablets 

 

EU/1/06/371/001 

EU/1/06/371/002 

EU/1/06/371/003 

EU/1/06/371/004 

EU/1/06/371/005 

EU/1/06/371/006 

EU/1/06/371/007 

EU/1/06/371/008 

EU/1/06/371/025 

EU/1/06/371/026 

EU/1/06/371/027 

EU/1/06/371/034 

EU/1/06/371/037 

 

Dafiro 5 mg/160 mg film-coated tablets 

 

EU/1/06/371/009 

EU/1/06/371/010 

EU/1/06/371/011 

EU/1/06/371/012 

EU/1/06/371/013 

EU/1/06/371/014 

EU/1/06/371/015 

EU/1/06/371/016 

EU/1/06/371/028 

EU/1/06/371/029 

EU/1/06/371/030 

EU/1/06/371/035 

EU/1/06/371/038 

 



23 

Dafiro 10 mg/160 mg film-coated tablets 

 

EU/1/06/371/017 

EU/1/06/371/018 

EU/1/06/371/019 

EU/1/06/371/020 

EU/1/06/371/021 

EU/1/06/371/022 

EU/1/06/371/023 

EU/1/06/371/024 

EU/1/06/371/031 

EU/1/06/371/032 

EU/1/06/371/033 

EU/1/06/371/036 

EU/1/06/371/039 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 16 January 2007 

Date of latest renewal: 21 November 2011 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

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

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

 

  

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


24 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 



25 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

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

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to medical prescription. 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic Safety Update Reports 
 

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

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

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

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Obligation to conduct post-authorisation measures 
 

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

 

Conditions to the MA Due date 

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

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

N-nitrosamines and changed as necessary to minimise nitrosamine contamination 

as much as possible. 

Within 

2 years after 

Commission 

Decision. 

N-nitrosodimethylamine (NDMA) 

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

should be implemented. 

Within 

2 years after 

Commission 

Decision. 

 

  



26 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



27 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

  



28 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 5 mg/80 mg film-coated tablets 

amlodipine/valsartan 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg amlodipine (as amlodipine besylate) and 80 mg valsartan. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

280 film-coated tablets 

56x1 film-coated tablet (unit dose) 

98x1 film-coated tablet (unit dose) 

280x1 film-coated tablet (unit dose) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 



29 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/371/001 7 film-coated tablets 

EU/1/06/371/002 14 film-coated tablets 

EU/1/06/371/003 28 film-coated tablets 

EU/1/06/371/004 30 film-coated tablets 

EU/1/06/371/005 56 film-coated tablets 

EU/1/06/371/006 90 film-coated tablets 

EU/1/06/371/007 98 film-coated tablets 

EU/1/06/371/008 280 film-coated tablets 

EU/1/06/371/025 56x1 film-coated tablet (unit dose) 

EU/1/06/371/026 98x1 film-coated tablet (unit dose) 

EU/1/06/371/027 280x1 film-coated tablet (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

  



30 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Dafiro 5 mg/80 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



31 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 5 mg/80 mg film-coated tablets 

amlodipine/valsartan 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg amlodipine (as amlodipine besylate) and 80 mg valsartan. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

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

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

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 



32 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/371/034 280 film-coated tablets (4x70) 

EU/1/06/371/037 280 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 

 

Dafiro 5 mg/80 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

 

  



33 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 5 mg/80 mg film-coated tablets 

amlodipine/valsartan 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg amlodipine (as amlodipine besylate) and 80 mg valsartan. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

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

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

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 



34 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/371/034 280 film-coated tablets (4x70) 

EU/1/06/371/037 280 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 

 

Dafiro 5 mg/80 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



35 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 5 mg/80 mg film-coated tablets 

amlodipine/valsartan 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



36 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 5 mg/160 mg film-coated tablets 

amlodipine/valsartan 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg amlodipine (as amlodipine besylate) and 160 mg valsartan. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

280 film-coated tablets 

56x1 film-coated tablet (unit dose) 

98x1 film-coated tablet (unit dose) 

280x1 film-coated tablet (unit dose) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 



37 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/371/009 7 film-coated tablets 

EU/1/06/371/010 14 film-coated tablets 

EU/1/06/371/011 28 film-coated tablets 

EU/1/06/371/012 30 film-coated tablets 

EU/1/06/371/013 56 film-coated tablets 

EU/1/06/371/014 90 film-coated tablets 

EU/1/06/371/015 98 film-coated tablets 

EU/1/06/371/016 280 film-coated tablets 

EU/1/06/371/028 56x1 film-coated tablet (unit dose) 

EU/1/06/371/029 98x1 film-coated tablet (unit dose) 

EU/1/06/371/030 280x1 film-coated tablet (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

  



38 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Dafiro 5 mg/160 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



39 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 5 mg/160 mg film-coated tablets 

amlodipine/valsartan 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg amlodipine (as amlodipine besylate) and 160 mg valsartan. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

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

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

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 



40 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/371/035 280 film-coated tablets (4x70) 

EU/1/06/371/038 280 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 

 

Dafiro 5 mg/160 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

 

  



41 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 5 mg/160 mg film-coated tablets 

amlodipine/valsartan 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg amlodipine (as amlodipine besylate) and 160 mg valsartan. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

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

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

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 



42 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/371/035 280 film-coated tablets (4x70) 

EU/1/06/371/038 280 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 

 

Dafiro 5 mg/160 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



43 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 5 mg/160 mg film-coated tablets 

amlodipine/valsartan 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



44 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 10 mg/160 mg film-coated tablets 

amlodipine/valsartan 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg amlodipine (as amlodipine besylate) and 160 mg valsartan. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

280 film-coated tablets 

56x1 film-coated tablet (unit dose) 

98x1 film-coated tablet (unit dose) 

280x1 film-coated tablet (unit dose) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 



45 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/371/017 7 film-coated tablets 

EU/1/06/371/018 14 film-coated tablets 

EU/1/06/371/019 28 film-coated tablets 

EU/1/06/371/020 30 film-coated tablets 

EU/1/06/371/021 56 film-coated tablets 

EU/1/06/371/022 90 film-coated tablets 

EU/1/06/371/023 98 film-coated tablets 

EU/1/06/371/024 280 film-coated tablets 

EU/1/06/371/031 56x1 film-coated tablet (unit dose) 

EU/1/06/371/032 98x1 film-coated tablet (unit dose) 

EU/1/06/371/033 280x1 film-coated tablet (unit dose) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

  



46 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Dafiro 10 mg/160 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



47 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 10 mg/160 mg film-coated tablets 

amlodipine/valsartan 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg amlodipine (as amlodipine besylate) and 160 mg valsartan. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

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

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

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 



48 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/371/036 280 film-coated tablets (4x70) 

EU/1/06/371/039 280 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 

 

Dafiro 10 mg/160 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

 

  



49 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 10 mg/160 mg film-coated tablets 

amlodipine/valsartan 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg amlodipine (as amlodipine besylate) and 160 mg valsartan. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

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

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

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

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

 

 



50 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/371/036 280 film-coated tablets (4x70) 

EU/1/06/371/039 280 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 

 

Dafiro 10 mg/160 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



51 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dafiro 10 mg/160 mg film-coated tablets 

amlodipine/valsartan 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



52 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

 



53 

Package leaflet: Information for the user 

 

Dafiro 5 mg/80 mg film-coated tablets 

Dafiro 5 mg/160 mg film-coated tablets 

Dafiro 10 mg/160 mg film-coated tablets 

amlodipine/valsartan 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

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

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

-  
 

 

What is in this leaflet 

 

1. What Dafiro is and what it is used for 

2. What you need to know before you take Dafiro 

3. How to take Dafiro 

4. Possible side effects 

5. How to store Dafiro 

6. Contents of the pack and other information 

 

 

1. What Dafiro is and what it is used for 

 

Dafiro tablets contain two substances called amlodipine and valsartan. Both of these substances help 

to control high blood pressure. 

 Amlodipine belongs to a group of substances called “calcium channel blockers”. Amlodipine 
stops calcium from moving into the blood vessel wall which stops the blood vessels from 

tightening. 

 Valsartan belongs to a group of substances called “angiotensin-II receptor antagonists”. 
Angiotensin II is produced by the body and makes the blood vessels tighten, thus increasing the 

blood pressure. Valsartan works by blocking the effect of angiotensin II. 

This means that both of these substances help to stop the blood vessels tightening. As a result, the 

blood vessels relax and blood pressure is lowered. 

 

Dafiro is used to treat high blood pressure in adults whose blood pressure is not controlled enough 

with either amlodipine or valsartan on its own. 

 

 

  



54 

2. What you need to know before you take Dafiro 

 

Do not take Dafiro 

 if you are allergic to amlodipine or to any other calcium channel blockers. This may involve 
itching, reddening of the skin or difficulty in breathing. 

 if you are allergic to valsartan or any of the other ingredients of Dafiro this medicine (listed in 
section 6). If you think you may be allergic, talk to your doctor before taking Dafiro. 

 if you have severe liver problems or bile problems such as biliary cirrhosis or cholestasis. 

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

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

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

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

 if you have diabetes or impaired kidney function and you are treated with a blood 

pressure lowering medicine containing aliskiren. 
If any of the above applies to you, do not take Dafiro and talk to your doctor. 

 

Warnings and precautions 

Talk to your doctor before taking Dafiro: 

 if you have been sick (vomiting or diarrhoea). 

 if you have liver or kidney problems. 

 if you have had a kidney transplant or if you had been told that you have a narrowing of your 
kidney arteries. 

 if you have a condition affecting the renal glands called “primary hyperaldosteronism”. 

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

 if your doctor has told you that you have a narrowing of the valves in your heart (called “aortic 
or mitral stenosis”) or that the thickness of your heart muscle is abnormally increased (called 

“obstructive hypertrophic cardiomyopathy”). 

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

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

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

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

 aliskiren. 

 

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

potassium) in your blood at regular intervals. 

 

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

If any of these apply to you, tell your doctor before taking Dafiro. 

 

Children and adolescents 

The use of Dafiro in children and adolescents is not recommended (aged below 18 years old). 

 

  



55 

Other medicines and Dafiro 

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

medicines. Your doctor may need to change your dose and/or to take other precautions. In some cases 

you may have to stop taking one of the medicines. This applies especially to the medicines listed 

below: 

 ACE inhibitors or aliskiren (see also information under the headings “Do not take Dafiro” and 
“Warnings and precautions”); 

 diuretics (a type of medicine also called “water tablets” which increases the amount of urine you 
produce); 

 lithium (a medicine used to treat some types of depression); 
 potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and 

other substances that may increase potassium levels; 

 certain types of painkillers called non-steroidal anti-inflammatory medicines (NSAIDs) or 

selective cyclooxygenase-2 inhibitors (COX-2 inhibitors). Your doctor may also check your 

kidney function; 

 anticonvulsant agents (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone); 

 St. John’s wort; 

 nitroglycerin and other nitrates, or other substances called “vasodilators”; 

 medicines used for HIV/AIDS (e.g. ritonavir, indinavir, nelfinavir); 

 medicines used to treat fungal infections (e.g. ketoconazole, itraconazole); 

 medicines used to treat bacterial infections (such as rifampicin, erythromycin, clarithromycin, 
talithromycin); 

 verapamil, diltiazem (heart medicines); 

 simvastatin (a medicine used to control high cholesterol levels); 

 dantrolene (infusion for severe body temperature abnormalities); 

 medicines used to protect against transplant rejection (ciclosporin). 
 

Dafiro with food and drink 

Grapefruit and grapefruit juice should not be consumed by people who are taking Dafiro. This is 

because grapefruit and grapefruit juice can lead to an increase in the blood levels of the active 

substance amlodipine, which can cause an unpredictable increase in the blood pressure lowering effect 

of Dafiro. 

 

Pregnancy and breast-feeding 

Pregnancy 

You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally 

advise you to stop taking Dafiro before you become pregnant or as soon as you know you are pregnant 

and will advise you to take another medicine instead of Dafiro. Dafiro is not recommended in early 

pregnancy (first 3 months), 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. Amlodipine has been shown 

to pass into breast milk in small amounts. Dafiro is not recommended for mothers who are breast-

feeding, and your doctor may choose another treatment for you if you wish to breast-feed, especially if 

your baby is newborn, or was born prematurely. 

 

Ask your doctor or pharmacist for advice before taking any medicine. 

 

Driving and using machines 

This medicine may make you feel dizzy. This can affect how well you can concentrate. So, if you are 

not sure how this medicine will affect you, do not drive, use machinery, or do other activities that you 

need to concentrate on. 

 

 

  



56 

3. How to take Dafiro 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not 

sure. This will help you get the best results and lower the risk of side effects. 

 

The usual dose of Dafiro is one tablet per day. 

 It is preferable to take your medicine at the same time each day. 

 Swallow the tablets with a glass of water. 

 You can take Dafiro with or without food. Do not take Dafiro with grapefruit or grapefruit juice. 
 

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

 

Do not exceed the prescribed dose. 

 

Dafiro and older people (age 65 years or over) 

Your doctor should exercise caution when increasing your dose. 

 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

 

If you take more Dafiro than you should 

If you have taken too many tablets of Dafiro, or if someone else has taken your tablets, consult a 

doctor immediately. 

 

If you forget to take Dafiro 

If you forget to take this medicine, take it as soon as you remember. Then take your next dose at its 

usual time. However, if it is almost time for your next dose, skip the dose you missed. Do not take a 

double dose to make up for a forgotten tablet. 

 

If you stop taking Dafiro 

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

medicine unless your doctor tells you to. 

 

 

4. Possible side effects 

 

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

 

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

A few patients have experienced these serious side effects (may affect up to 1 in 1,000 people). If any 

of the following happen, tell your doctor straight away: 

Allergic reaction with symptoms such as rash, itching, swelling of face or lips or tongue, difficulty 

breathing, low blood pressure (feeling of faintness, light-headedness). 

 

Other possible side effects of Dafiro: 

Common (may affect up to 1 in 10 people): Influenza (flu); blocked nose, sore throat and discomfort 

when swallowing; headache; swelling of arms, hands, legs, ankles or feet; tiredness; asthenia 

(weakness); redness and warm feeling of the face and/or neck. 

Uncommon (may affect up to 1 in 100 people): Dizziness; nausea and abdominal pain; dry mouth; 

drowsiness, tingling or numbness of the hands or feet; vertigo; fast heart beat including palpitations; 

dizziness on standing up; cough; diarrhoea; constipation; skin rash, redness of the skin; joint swelling, 

back pain; pain in joints. 

Rare (may affect up to 1 in 1,000 people): Feeling anxious; ringing in the ears (tinnitus); fainting; 

passing more urine than normal or feeling more of an urge to pass urine; inability to get or maintain an 

erection; sensation of heaviness; low blood pressure with symptoms such as dizziness, light-

headedness; excessive sweating; skin rash all over your body; itching; muscle spasm. 

  



57 

If any of these affect you severely, tell your doctor. 

 

Side effects reported with amlodipine or valsartan alone and either not observed with Dafiro or 

observed with a higher frequency than with Dafiro: 

 

Amlodipine 

Consult a doctor immediately if you experience any of the following very rare, severe side effects 

after taking this medicine: 

- Sudden wheeziness, chest pain, shortness of breath or difficulty in breathing. 
- Swelling of eyelids, face or lips. 
- Swelling of the tongue and throat which causes great difficulty breathing. 
- Severe skin reactions including intense skin rash, hives, reddening of the skin over your whole 

body, severe itching, blistering, peeling and swelling of the skin, inflammation of the mucous 

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

- Heart attack, abnormal heart beat. 
- Inflamed pancreas, which may cause severe abdominal and back pain accompanied with feeling 

of being very unwell. 

 

The following side effects have been reported. If any of these cause you problems or if they last for 

more than one week, you should contact your doctor. 

Common (may affect up to 1 in 10 people): Dizziness, sleepiness; palpitations (awareness of your heart 

beat); flushing, ankle swelling (oedema); abdominal pain, feeling sick (nausea). 

Uncommon (may affect up to 1 in 100 people): Mood changes, anxiety, depression, sleeplessness, 

trembling, taste abnormalities, fainting, loss of pain sensation; visual disturbances, visual impairment, 

ringing in the ears; low blood pressure; sneezing/runny nose caused by inflammation of the lining of 

the nose (rhinitis); indigestion, vomiting (being sick); hair loss, increased sweating, itchy skin, skin 

discolouration; disorder in passing urine, increased need to urinate at night, increased number of times 

of passing urine; inability to obtain an erection, discomfort or enlargement of the breasts in men, pain, 

feeling unwell, muscle pain, muscle cramps; weight increase or decrease. 

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

Very rare (may affect up to 1 in 10,000 people): Decreased number of white blood cells, decrease in 

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

sugar in blood (hyperglycaemia); swelling of the gums, abdominal bloating (gastritis); abnormal liver 

function, inflammation of the liver (hepatitis), yellowing of the skin (jaundice), liver enzyme increase 

which may have an effect on some medical tests; increased muscle tension; inflammation of blood 

vessels often with skin rash, sensitivity to light; disorders combining rigidity, tremor and/or movement 

disorders. 

 

Valsartan 

Not known (frequency cannot be estimated from the available data): Decrease in red blood cells, fever, 

sore throat or mouth sores due to infections; spontaneous bleeding or bruising; high level of potassium 

in the blood; abnormal liver test results; decreased renal functions and severely decreased renal 

functions; swelling mainly of the face and the throat; muscle pain; rash, purplish-red spots; fever; 

itching; allergic reaction; blistering skin (sign of a condition called dermatitis bullous). 

 

If you experience any of these, tell your doctor straight away. 

 

Reporting of side effects 

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

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

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

this medicine. 

 

 

  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


58 

5. How to store Dafiro 

 

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

 

Do not use this medicine after the expiry date which is stated on the carton and blister. 

 

Do not store above 30°C. 

 

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

 

Do not use any Dafiro pack that is damaged or shows signs of tampering. 

 

 

6. Contents of the pack and other information 

 

What Dafiro contains 

 

Dafiro 5 mg/80 mg film-coated tablets 

The active substances of Dafiro are amlodipine (as amlodipine besylate) and valsartan. Each tablet 

contains 5 mg amlodipine and 80 mg valsartan. 

 

The other ingredients are cellulose microcrystalline; crospovidone (type A); silica, colloidal 

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

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

 

Dafiro 5 mg/160 mg film-coated tablets 

The active substances of Dafiro are amlodipine (as amlodipine besylate) and valsartan. Each tablet 

contains 5 mg amlodipine and 160 mg valsartan. 

 

The other ingredients are cellulose microcrystalline; crospovidone (type A); silica, colloidal 

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

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

 

Dafiro 10 mg/160 mg film-coated tablets 

The active substances of Dafiro are amlodipine (as amlodipine besylate) and valsartan. Each tablet 

contains 10 mg amlodipine and 160 mg valsartan. 

 

The other ingredients are cellulose microcrystalline; crospovidone (type A); silica, colloidal 

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

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

 

What Dafiro looks like and contents of the pack 

Dafiro 5 mg/80 mg tablets are round and dark yellow with “NVR” on one side and “NV” on the other 

side. Approximate size: diameter 8.20 mm. 

 

Dafiro 5 mg/160 mg tablets are oval and dark yellow “NVR” on one side and “ECE” on the other side. 

Approximate size: 14.2 mm (length) x 5.7 mm (width). 

 

Dafiro 10 mg/160 mg tablets are oval and light yellow with “NVR” on one side and “UIC” on the 

other side. Approximate size: 14.2 mm (length) x 5.7 mm (width). 

 

Dafiro is available in packs containing 7, 14, 28, 30, 56, 90, 98 or 280 tablets and in multipacks 

comprising 4 cartons, each containing 70 tablets, or 20 cartons, each containing 14 tablets. All packs 

are available with standard blisters; the 56, 98 and 280 tablet packs are additionally available with 

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

 



59 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 

SIA „Novartis Baltics“ Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 976 98 28 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 26 37 82 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 

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

Τηλ: +30 210 281 17 12 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Esteve Pharmaceuticals, S.A. 

Tel: +34 93 446 60 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 



60 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

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 

 

Latvija 

SIA “Novartis Baltics” 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 

 

Other sources of information 

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

http://www.ema.europa.eu 

 

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

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