Vasodip

/ Dexcel

The recommended dosage is 10 mg orally once a day at least 15 minutes before meals,; the dose may be increased to 20 mg depending on the individual patient’s response.
Dose titration should be gradual, because it may take about 2 weeks before the maximal antihypertensive effect is apparent.
Some individuals, not adequately controlled on a single antihypertensive agent, may benefit from the addition of Vasodip to therapy with a beta-adrenoceptor blocking drug (atenolol), a diuretic (hydrochlorothiazide) or an angiotensin converting enzyme inhibitor (captopril or enalapril).
Since the dose-response curve is steep with a plateau at doses between 20-30 mg, it is unlikely that efficacy will be improved by higher doses; whereas side effects may increase.
Elderly patients: Although the pharmacokinetic data and clinical experience suggest that no adjustment of the daily dosage is required, special care should be exercised when initiating treatment in the elderly.
Paediatric population: The safety and efficacy of Vasodip in children aged up to 18 years have not been established. No data are available.
Patients with renal or hepatic impairment: special care should be exercised when treatment is commenced in patients with mild to moderate renal or hepatic dysfunction. Although the usually recommended dose schedule may be tolerated by these subgroups, an increase in dose to 20 mg daily must be approached with caution.The antihypertensive effect may be enhanced in patients with hepatic impairment and consequently an adjustment of the dosage should be considered. Vasodip is not recommended for use in patients with severe hepatic impairment or in patients with severe renal impairment (GFR < 30 ml/min).
Method of administration: Precautions to be taken before handling or administering the medicinal product: Treatment should be preferably administered in the morning at least 15 minutes before a meal. This product should not be administered with grapefruit juice.

Treatment of mild to moderate essential hypertension.

Hypersensitivity to the active substance, lercanidipine, to any dihydropyridine or to any of the excipients. Pregnancy and lactation. Women of child-bearing potential unless effective contraception is used. Left ventricular outflow tract obstruction. Untreated congestive cardiac failure. Unstable angina pectoris.
Severe renal or hepatic impairment. Within 1 month of a myocardial infarction.
Co-administration with: strong inhibitors of CYP3A4, o cyclosporin, Grapefruit juice.

Special care should be exercised when Vasodip is used in patients with sick sinus syndrome (if a pacemaker is not in situ). Although hemodynamic controlled studies revealed no impairment of ventricular function, care is also required in patients with LV dysfunction. It has been suggested that some short-acting dihydropyridines may be associated with increased cardiovascular risk in patients with ischaemic heart disease. Although Vasodip is long-acting, caution is required in such patients.
Some dihydropyridines may rarely lead to precordial pain or angina pectoris. Very rarely patients with preexisting angina pectoris may experience increased frequency, duration or severity of these attacks. Isolated cases of myocardial infarction may be observed.
Use in renal or hepatic dysfunction: special care should be exercised when treatment is commenced in patients with mild to moderate renal or hepatic dysfunction.
Although the usually recommended dose schedule may be tolerated by these subgroups, an increase in dose to 20 mg daily must be approached with caution. The antihypertensive effect may be enhanced in patients with hepatic impairment and consequently an adjustment of the dosage should be considered.
Vasodip is not recommended for use in patients with severe hepatic impairment or in patients with severe renal impairment (GFR < 30 ml/min).
Alcohol should be avoided since it may potentiate the effect of vasodilating antihypertensive drugs.
Inducers of CYP3A4 like anticonvulsants (e.g. phenytoin, carbamazepine) and rifampicin may reduce lercanidipine’s plasma levels and therefore the efficacy of lercanidipine may be less than expected.
One tablet of Vasodip (10 mg) contains 30 mg lactose and 1 tablet of Vasodip 20 contains 60 mg lactose and therefore should not be administered to patients with Lapp lactase insufficiency, galactosaemia or glucose/galactose malabsorption syndrome.

most common: About 1.8% of treated patients experienced adverse reactions. The table below shows the incidence of adverse drug reactions, at least possibly causally related, grouped by MedDRA System Organ Class classification, and ranked by frequency (uncommon, rare).
As shown in the table, the most commonly occurring adverse drug reactions reported in controlled clinical trials are headache, dizziness, peripheral oedema, tachycardia, palpitations, flushing, each occurring in less than 1% of patients.

Lercanidipine is known to be methabolised by the CYP3A4 enzyme and therefore inhibitors and inducers of CYP3A4 administered concurrently may interact with the metabolism and elimination of lercanidipine.
Co-prescription of Vasodip with inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, ritonavir, erythromycin, troleandomycin) should be avoided.
An interaction study with a strong CYP3A4 inhibitor, Ketoconazole, has shown a considerable increase in plasma levels of lercanidipine (a 15-fold increase of the AUC and an 8-fold increase of the Cmax for the eutomer S-lercanidipine).
Cyclosporin and lercanidipine should not be administered together. Increased plasma levels of both lercanidipine and cyclosporin have been observed following concomitant administration. A study in young healthy volunteers has shown that when cyclosporin was administered 3 hours after the lercanidipine intake the plasma levels of lercanidipine did not change, while the AUC of cyclosporin increased by 27%. However, the co-administration of Vasodip with cyclosporin has caused a 3-fold increase of the plasma levels of lercanidipine and a 21% increase of the cyclosporin AUC.
Lercanidipine should not be taken with grapefruit juice.
As for other dihydropiridines, lercanidipine is sensitive to inhibition of metabolism by grapefruit juice, with a consequent rise in its systemic availability and increased hypotensive effect.
When concominantly administered at a dose of 20 mg with midazolam p.o. to elderly volunteers, lercanidipine’s absorption was increased (by approximately 40%) and the rate of absorption was decreased (tmax was delayed from 1.75 to 3 hours). Midazolam concentrations were not modified.
Caution should be exercised when Vasodip is co-prescribed with other substrates of CYP3A4, like terfenadine, astemizole, class III antiarrhythmic drugs such as amiodarone and quinidine.
Co-administration of Vasodip with CYP3A4 inducers like anticonvulsants (e.g. phenytoin,carbamazepine) and rifampicin should be approached with caution since the antihypertensive effect may be reduced and blood pressure should be monitored more frequently than usual. When Vasodip was co-administered with metoprolol, a β-blocker eliminated mainly by the liver, the bioavailability of metoprolol was not changed while that of lercanidipine was reduced by 50%. This effect may be due to the reduction in the hepatic blood flow caused by β-blockers and may therefore occur with other drugs of this class. Consequently, lercanidipine may be safely administered with beta-adrenoceptor blocking drugs, but dose adjustment may be required.
An interaction study with fluoxetine (an inhibitor of CYP2D6 and CYP3A4), conducted in volunteers of an age of 65 ± 7 years (mean ± s.d.), has shown no clinically relevant modification of the pharmacokinetics of lercanidipine.
Concomitant administration of cimetidine 800 mg daily does not cause significant modifications in plasma levels of lercanidipine, but at higher doses caution is required since the bioavailability and the hypotensive effect of lercanidipine may be increased.
Co-administration of 20 mg lercanidipine in patients chronically treated with β-methyldigoxin showed no evidence of pharmacokinetic interaction. Healthy volunteers treated with digoxin following dosing with 20 mg lercanidipine given fasted, showed a mean increase of 33 % in digoxin Cmax while AUC and renal clearance were not significantly modified. Patients on concomitant digoxin treatment should be closely monitored clinically for signs of digoxin toxicity.
When a dose of 20 mg of Vasodip was repeatedly co-administered with 40 mg of simvastatin, the AUC of lercanidipine was not significantly modified, while simvastatin’s AUC increased by 56% and that of its active metabolite β-hydroxyacid by 28%. It is unlikely that such changes are of clinical relevance. No interaction is expected when lercanidipine is administered in the morning and simvastatin in the evening, as indicated for such drug.
The co-administration of 20 mg lercanidipine to healthy volunteers given fasted did not alter the pharmacokinetics of warfarin.
Vasodip has been safely administered with diuretics and ACE inhibitors.
Alcohol should be avoided since it may potentiate the effect of vasodilating antihypertensive drugs .

Pregnancy: Data for lercanidipine provide no evidence of a teratogenic effect in the rat and the rabbit and reproductive performance in the rat was unimpaired. Nevertheless, since there is no clinical experience with lercanidipine in pregnancy and lactation, and other dihydropyridine compounds have been found teratogenic in animals, Vasodip should not be administered during pregnancy or to women with child-bearing potential unless effective contraception is used.
Breast-feeding: It is unknown whether lercanidipine/metabolites are excreted in human milk. A risk in the newborns/infants cannot be excluded. Vasodip is contraindicated during breastfeeding.

In the post-marketing experience, some cases of overdose were reported (from 40 up to 800 mg of lercanidipine including reports of suicide attempt).
Symptoms: As with other dihydropyridines, overdosage might be expected to cause excessive peripheral vasodilatation. Symptoms associated to overdose include marked hypotension and reflex tachycardia.
Treatment: In case of severe hypotension, bradycardia and unconsciousness, cardiovascular support could be helpful, with intravenous atropine for bradycardia. In view of the prolonged pharmacological effect of lercanidipine, it is essential that the cardiovascular status of patients who take an overdose is monitored for 24 hours at least. There is no information on the value of dialysis. Since the drug is highly lipophilic, it is most probable that plasma levels are no guide to the duration of the period of risk and dialysis may not be effective.