Manidipine Other names: Manidipine hydrochloride

Co-administration of manidipine with α-blockers (prazosin, alfuzosin, doxazosin, tamsulosin, terazosin) has an increased antihypertensive effect and an increased risk of orthostatic hypotension.

Co-administration of manidipine with corticosteroids reduces the antihypertensive effect (salt and water retention due to corticosteroids).

As occurs with other dihydropyridine calcium channel blockers, it is probable that manidipine metabolism is catalysed by the cytochrome P450 3A4. Caution should be exercised when manidipine is administered with drugs which which induce CYP 3A4, such as phenytoin, carbamazepine, phenobarbital and rifampicin and posology of manidipine should be adjusted if needed.

Co-administration of manidipine with tricyclic antidepressants has an increased antihypertensive effect and an increased risk of orthostatic hypotension.

As for all vasodilatory antihypertensives, caution is mandatory if alcohol is consumed concomitantly, as this can enhance their effects.

Grapefruit juice seems to inhibit the metabolism of dihydropyridines, with a resulting increase in its systemic bioavailability and its hypotensive effect. Manidipine must therefore not be administered with grapefruit juice.

In patients with mild to moderate renal impairment, caution should be taken in increasing the dose from 10 mg to 20 mg per day.

Due to manidipine’s extensive metabolism in the liver, dosage in patients with mild liver failure should not exceed 10 mg once a day.

The antihypertensive effect of manidipine can be increased by the concomitant administration of diuretics, betablockers and, in general, any other antihypertensive drugs.

As occurs with other dihydropyridine calcium channel blockers, it is probable that manidipine metabolism is catalysed by the cytochrome P450 3A4. Caution should be exercised when manidipine is administered with drugs which inhibit the CYP 3A4 enzyme, such as ketoconazole, itraconazole and posology of manidipine should be adjusted if needed.

Reversible biochemical changes in the head of spermatozoa which can impair fecundation have been reported in some patients treated by channel blockers.

Co-administration of amifostine with manidipine has an increased risk of antihypertensive effect.

Co-administration of manidipine with baclofen enhances the antihypertensive effect. Monitoring of blood pressure and renal function, and adjusting the dose of antihypertensive if necessary.

Concomitant administration of calcium antagonists with digoxin may lead to an increase in the concentration of the glycoside.

Co-administration of manidipine with tetracosactide reduces the antihypertensive effect.

Manidipine should be administered with caution in patients who have left ventricular outflow tract obstruction.

Manidipine should be administered with caution in patients with sick sinus syndrome (with no pacemaker).

Manidipine should be administered with caution in patients with isolated right heart failure.

No clinical data are available about the use of this medicinal product by pregnant women. Studies with manidipine on laboratory animals do not provide sufficient results on foetal development. Since other medicinal products in the dihydropyridine family have been shown to be teratogenic in animal species, and since the potential clinical risk is not known, manidipine should not be used during pregnancy.

Manidipine and its metabolites are excreted in large quantities in rat milk. It is not known whether or not manidipine is excreted in human milk. The use of manidipine must be avoided during lactation. If manidipine treatment is necessary, breast-feeding must be discontinued.

Fertility

Reversible biochemical changes in the head of spermatozoa which can impair fecundation have been reported in some patients treated by channel blockers.

Since dizziness may be experienced due to a reduced blood pressure, patients should be advised to take care while driving and operating machinery.

A number of undesirable effects have been observed during treatment with manidipine and other dihydropyridines, with the following frequencies: 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, including isolated cases.

The common adverse effects are dose-dependent and usually disappear later on during treatment.

Investigations

Uncommon: reversible increases in SGPT, SGOT, LDH, gamma-GT, alkaline phosphatase, BUN and serum creatinine

Cardiac disorders

Common: palpitations, oedema

Uncommon: tachycardia

Rare: chest pain, angina

Very rare: myocardial stroke and, in isolated cases, patients with pre-existent angina may experience increased frequency, duration and severity of these accidents.

Nervous system disorders

Common: headache, dizziness and vertigo

Uncommon: paresthesia

Rare: somnolence and drowsiness

Unknown: extrapyramidal syndrome has been reported with some calcium inhibitors

Respiratory, thoracic and mediastinal disorders

Uncommon: dyspnea

Gastrointestinal disorders

Uncommon: nausea, vomiting, constipation, dry mouth, digestive disorders

Rare: stomach ache, abdominal pain

Very rare: gingivitis and gingival hyperplasia, which generally disappeared with the withdrawal of the drug and need careful dental care.

Skin and subcutaneous disorders

Uncommon: rash, eczema

Rare: erythema, itching

Vascular disorders

Common: hot flushes

Uncommon: hypotension

Rare: hypertension

General disorders and administration site conditions

Uncommon: asthenia

Rare: irritability