Summary of Product Characteristics
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SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT *IPERTEN/ARTEDIL/MANYPER 10mg tablets IPERTEN/ARTEDIL/MANYPER 20mg tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION IPERTEN/ARTEDIL/MANYPER 10 mg tablets Each tablet contains: Manidipine hydrochloride 10mg Excipient with known effect: 119,61 mg lactose monohydrate/tablet IPERTEN/ARTEDIL/MANYPER 20 mg tablets Each tablet contains: Manidipine hydrochloride 20mg Excipient with known effect: 131,80 mg lactose monohydrate/tablet For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Tablet IPERTEN/ARTEDIL/MANYPER 10mg: pale yellow, round, scored tablet; IPERTEN/ARTEDIL/MANYPER 20mg: yellow-orange, oblong, scored tablet. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Mild to moderate essential hypertension 4.2 Posology and method of administration The recommended starting dose is 10 mg once a day. Should the antihypertensive effect be still insufficient after 2-4 weeks of treatment, it is advisable to increase the dosage to the usual maintenance dose of 20 mg once a day. Elderly In view of the slowing down of metabolism in the elderly, the recommended dose is 10mg once daily. This dosage is sufficient in most elderly patients; the risk/benefit of any dose increase should be considered with caution on an individual basis. Renal impairment In patients with mild to moderate renal dysfunction care should be taken when increasing the dosage from 10 to 20mg once a day. Hepatic impairment Due to the extensive hepatic metabolisation of manidipine, patients with mild hepatic dysfunction should not exceed 10mg once a day (see also Section 4.3 Contraindications). Tablet must be swallowed in the morning after breakfast, without chewing it, with a few liquid. Paediatric population Iperten is contraindicated in pediatric age (see section 4.3). *IPERTEN is the current trade mark in Italy and France, ARTEDIL in Spain, MANYPER in Greece and in Germany. SmPC (V 3.1) 2019-05 Page 1/6 4.3 Contraindications -Hypersensitivity to the active substance manidipine or to any dihydropyridine agents or to any of the excipients listed in section 6.1. -Paediatric age. -Unstable angina pectoris or myocardial infarction (in the first 4 weeks). -Untreated heart failure. Severe renal dysfunction (creatinine clearance <10ml/min). -Moderate to severe hepatic dysfunction. 4.4 Special warnings and precautions for use In patients with mild hepatic impairment, the product should be cautiously administered since its antihypertensive effect might be strengthened (see also section 4.2 "Posology"). Considering the slowing down of metabolic processes, in elderly patients an adjustment of the dosage is required (see also section 4.2 “Posology”). Manidipine should be used with caution in patients with left ventricular dysfunction, in patients suffering from obstruction of the outflow channel of the left ventricle, in patients with isolated right-sided heart failure and in patients with sick sinus (if a pacemaker is not in situ). As no results of studies in stable coronary patients are available, caution is required in such patients because of the possible increased coronary risk (see section 4.8). As in vivo interaction studies on the effect of drugs which inhibit or induce the CYP3A4 on the pharmacokinetics of manidipine are not available, IPERTEN/ARTEDIL/MANYPER should not be administered with CYP3A4 inhibitors, such as antiproteases, cimetidine, ketoconazole, itraconazole, erythromycin and clarithromycin as well as with CYP3A4 inducers, such as phenitoin, carbamazepine, phenobarbital and rifampicine (see also section 4.5). Caution should be exercised when manidipine is co-prescribed with other substrates of CYP3A4, like terfenadine, astemizole, quinidine and class III antiarythmic drug such as amiodarone (see also section 4.5). Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. 4.5 Interaction with other medicinal products and other forms of interaction Manidipine antihypertensive effect can be strengthened with the association of diuretics, -blockers and generally with other antihypertensive drugs. In vitro studies show that the inhibitory potential on cytochrome P450 of manidipine may be clinically insignificant. Similarly to other dihydropyridines calcium-channel blockers, it is likely that manidipine metabolism is catalysed by the cytochrome P4503A4. As in vivo interaction studies on the effect of drugs which inhibit or induce the CYP3A4 on the pharmacokinetics of manidipine are not available, IPERTEN/ARTEDIL/MANYPER should not be administered with CYP3A4 inhibitors, such as antiproteases, cimetidine, ketoconazole, itraconazole, erythromycin, and clarithromycin, as well as with CYP3A4 inducers, such as phenitoin, carbamazepine, phenobarbital and rifampicine (see also section 4.4). Caution should be exercised when manidipine is co-prescribed with other substrates of CYP3A4, like terfenadine, astemizole, quinidine and class III antiarrythmic drug such as amiodarone (see also section 4.4). and quinidin. Furthermore, concomitant administration of calcium-channel blockers with digoxin can lead to an increase of glucoside concentrations. Alcohol: as with all vasodilating antihypertensive agents caution should be exercised when alcohol is taken concomitantly, as it may potentiate their effect. Grapefruit juice: dihydropyridines appear to be particularly sensitive to inhibition of metabolism by grapefruit juice, with a consequent rise in their systemic availability and increased hypotensive effect. Therefore, manidipine should not be taken simultaneously with grapefruit juice. No interaction phenomena have been observed with oral hypoglycemic drugs. 4.6 Fertility, pregnancy and lactation Pregnancy SmPC (V 3.1) 2019-05 Page 2/6 No clinical data on exposed pregnancies are available. Animals studies with manidipine hydrochloride are insufficient with respect to embryo-fetal development (see section 5.3). As other dihydropyridine compounds have been found to be teratogenic in animals and the potential risk for humans is unknown, for safety reason, manidipine hydrochloride should not be used during pregnancy. Breast-feeding Manidipine and its metabolites are excreted in high amounts into the milk of lactating rats. Since it is not known whether manidipine hydrochloride is excreted into human milk, manidipine hydrochloride must be avoided during lactation. If treatment with manidipine hydrochloride is unavoidable, breast feeding must be stopped. 4.7 Effects on ability to drive and use machines Since dizziness due to pressure reduction might occur, patients should be warned to pay attention in driving and in using machinery. 4.8 Undesirable Effects The most common (>1% and <10%) adverse reactions are palpitations, hot flush, headache, oedema, vertigo and dizziness. All these adverse reactions are ascribable to the vasodilating properties of manidipine. They are dose-depending and usually resolve spontaneously on continued therapy. The following undesirable effects have been observed and reported during treatment with IPERTEN/ARTEDIL/MANYPER and other dihydropyridines with the following frequencies: Very common ≥1/10 Common 1/100 and <1/10 Uncommon 1/1,000 and <1/100 Rare 1/10,000 and <1/1,000 Very rare <1/10,000 Not known cannot be estimated from the available data System Organ Class Adverse Reaction Frequency Nervous system disorders Vertigo, dizziness, headache Common Paraesthesia Uncommon Somnolence Rare Cardiac disorders Palpitations Common Tachycardia Uncommon Chest pain, Angina pectoris Rare Myocardial infarction Very rare Patients with pre-existing angina pectoris may Very rare experience increased frequency, duration or severity of these attacks. Vascular disorders Hot flush Common Hypotension Uncommon Hypertension Rare Respiratory, thoracic and Dyspnoea Uncommon mediastinal disorders Nausea, Vomiting, Constipation, Dry mouth, Uncommon Gastrointestinal disorders Gastrointestinal disorder SmPC (V 3.1) 2019-05 Page 3/6 Gastralgia, Abdominal pain, Diarrhea, Anorexia Rare Gingivitis and Gingival hyperplasia, which are Very rare often regressive at therapy withdrawal and requiring a careful dental care Hepatobiliary disorders Jaundice Rare Rash, eczema Uncommon Skin and subcutaneous Erythema, pruritus Rare tissue disorders Erythema multiforme, Dermatitis exfoliative Not known Musculoskeletal and Myalgia Not known connective tissue disorders Reproductive system and Gynaecomastia Not known breast disorders Oedema Common General disorders and administration site Asthenia Uncommon conditions Irritability Rare The following reversible increases have been Uncommon observed: Alanine aminotransferase increased, Aspartate aminotransferase increased, Blood lactate dehydrogenase increased, Gamma- Investigations glutamyltransferase increased, Blood alkaline phosphatase increased, Blood urea nitrogen increased and Blood creatinine increased Blood bilirubin increased Rare 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 There is no experience with IPERTEN/ARTEDIL/MANYPER overdosage. As with other dihydropyridines, overdosage might be expected to cause excessive peripheral vasodilation