Source: Health Products Regulatory Authority (IE) Revision Year: 2015 Publisher: Astellas Pharma Co. Ltd, 5 Waterside, Citywest Business Campus, Naas Road, Dublin 24, Ireland
Nivadil should not be used in cases of cardiovascular shock, in case of pronounced aortic stenosis, during and in the first 4 weeks after acute myocardial infarction, in case of unstable angina pectoris.
Nivadil should not be used in cases of proven hypersensitivity to the active substance or to any of the excipients listed in 6.1.
Nivadil should not be used in patients with severe renal insufficiency (creatinine clearance <30 ml/min, dialysis patients) since as yet only insufficient therapeutic experience has been gained in this regard.
Nivadil is contraindicated in pregnancy and lactation.
Safety and efficacy of Nivadil have not been established in children
Nivadil, like any calcium antagonist, should not be administered concurrently with dantrolene infusion because of the risk of ventricular fibrillation.
Cimetidine and, to a lesser extent, other histamine H2-antagonists may lead to an increase in the Nilvadipine plasma concentration. Therefore, the daily dose of 1 × 8 mg Nilvadipine (equivalent to 1 Nivadil 8 mg prolonged release capsule) should not be exceeded.
Nilvadipine should be administrated with care in patients with severe hepatic impairment (liver cirrhosis) the dose should not be increased because Nivadil has a higher bio-availability in such patients. In patients with severe renal insufficiency (creatinine clearance <30 ml/min, dialysis patients) this product should be administered only under very close supervision and with extreme caution since as yet only insufficient therapeutic experience has been gained in this regard.
Care should also be taken in cases of decompensated cardiac insufficiency. Patients with mild bradycardia, first degree AV block or prolonged PR interval should be observed closely.
The concurrent administration of Nilvadipine and other anti-hypertensive drugs or tricyclic anti-depressive agents may result in an additional anti-hypertensive effect. Clinical studies have not yielded any indication of a negative inotropic effect; nevertheless, patients concomitantly treated with Nivadil and a beta-receptor blocker should be particularly carefully monitored, since drugs from this class of substances may result in heart failure when administered in combination with beta-receptor blockers.
Certain structurally related drugs may amplify the negative inotropic action of anti-arrhythmic agents like amiodarone and quinidine. In isolated cases simultaneous treatment with other drugs of the same pharmacological class has led to the observation of a decrease in the plasma quinidine level; monitoring of the plasma quinidine level is therefore recommended in patients on combination therapy. Similar observations have not been made with Nivadipine. Since in rare cases Nilvadipine may cause an increase in plasma digoxin level, monitoring of this parameter is recommended
Other dihydropyridine calcium entry blockers have been reported to increase the plasma concentration of concomitantly administered cyclosporin. Until further clinical data concerning the concomitant administration of Nilvadipine and cyclosporin are available, it is recommended that cyclosporin plasma levels are monitored during a comedication of Nivadil and cyclosporin.
Since Nivadil is metabolised by cytochrome P-450, drugs or food constituents that induce or inhibit this system may affect plasma concentrations of Nivadil.
In vitro studies show that Nilvadipine is metabolised by cytochrome P450 3A4 (CYP3A4). Nilvadipine should be administered with care when coadministered with CYP3A4 inhibitors, like: antiproteases, ketoconazole, itraconazole, erythromycin, and clarithromycin.
Anticonvulsants which induce cytochrome P-450 have been reported to decrease the bio-availability of dihydropyridines. Although there is no experience in this regard with Nivadil, it is recommended not to use Nivadil in patients concomitantly treated with enzyme- inducing anticonvulsants such as phenytoin, carbamazepine or phenobarbital.
Concurrent dosing of Cimetidine, and, to a lesser extent, other structurally related substances, Nilvadipine in a specific interaction study led on average to a doubling of Nilvadipine plasma levels. A daily dose of 1 × 8 mg Nilvadipine should not be exceeded when Nilvadipine and cimetidine are used concomitantly.
Taking Nivadil after a high fat breakfast increase bio-availability by 42%. The patient should be informed that taking Nivadil in the fasted state may decrease its bio-availability.
As with other calcium channel blockers of the dihydropyridine group, a stronger increase in Nilvadipine concentrations in the blood has been reported when Nilvadipine was taken together with grapefruit juice than when it was taken with water.
Nilvadipine should not be taken with grapefruit juice because its metabolism may be inhibited.
In an animal study, concomitant use of verapamil and intravenous dantrolene resulted in hyperkalemia accompanied by ventricular fibration and circulatory collapse. The relevance of these results for Nilvadipine is not known, but a risk that these events occur clinically cannot be excluded when Nilvadipine is used concomitantly with dantrolene.
No clinical experience with Nilvadipine in pregnancy or lactation is present. Preclinical investigations have not yielded any indication of a damaging potential of the substance on the foetus. The class of dihydropyridines has shown the potential to prolong delivery and parturition, which was not observed with Nilvadipine. As a consequence, Nilvadipine could be used in pregnancy only if the benefit justifies the potential risk to the foetus.
The results of animal tests have shown that Nilvadipine (or its metabolites) is excreted in human milk. Therefore, breast feeding is not advised during use of Nilvadipine. Since there has yet been no experience gained regarding the possible effects of the substance on the suckling infant, the child should be weaned from the breast in cases in which treatment of the nursing mother with Nivadil is regarded as necessary.
No studies on the effects on the ability to drive and use machines have been performed with Nilvadipine. However, caution should be exercised because dizziness may occur during antihypertensive treatment.
The management of hypertension with this drug requires regular checks by the physician. The occurrence of reactions, which may differ in severity from one person to another, may impair the patient’s ability to drive vehicles and to operate machinery. This precaution applies particularly at the beginning of therapy, or when dosage is changed, or with concurrent consumption of alcohol.
The frequency of adverse reactions is defined as follows: 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Rare: Anaemia
Very rare: Leukopenia, Thrombocytopenia
Rare: Appetite disorder
Common: Headache, Dizziness
Rare: Tinnitus, Nervousness, Insomnia
Rare: Increased intraocular pressure, Blurred vision
Rare: Epistaxis, Dry mouth
Uncommon: Tachycardia, Palpitations, Angina Pectoris
Very rare: Myocardial infarction
Common: Flushing
Uncommon: Hypotension, Hypertensive crisis
Rare: Dyspnoea
Uncommon: Nausea, Abdominal discomfort, Abdominal distension, Constipation, Diarrhoea
Rare: Vomiting, Increased weight, Decreased weight
Very rare: Gingival hyperplasia
Uncommon: Transaminases increased, Blood alkaline phosphatase increased
Uncommon: Hypersensitivity reactions, Rash, Pruritus, Erythema
Rare: Paraesthesia
Very rare: Peripheral coldness, Alopecia
Uncommon: Tremor, Myalgia, Arthralgia, Sensation of heaviness
Rare: Neck pain, Chest discomfort
Rare: Pollakiuria
Rare: Erectile dysfunction
Very rare: Gynaecomastia
Common: Peripheral oedema
Uncommon: Fatigue
Rare: Hyperhidrosis
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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.
Not applicable.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.