SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT

Unipine XL / Cardilate XL 30mg Tablets.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Circular, biconvex, red, film-coated tablets marked “UXL 30” on one side and blank on the other side containing 30 mg Nifedipine Ph. Eur.

3. PHARMACEUTICAL FORM

Nifedipine (30 mg) in tablet form for oral administration. It is a sustained release preparation.

4.    CLINICAL PARTICULARS

4.1.    Therapeutic Indications

Unipine XL / CardilateXL 30mg is indicated for the treatment hypertension.

4.2. Posology and Method of Administration

Adults and elderly

The recommended starting dose of nifedipine is 30 mg every 24 hours swallowed with water with subsequent titration of dosage according to response. The dose may be adjusted to 60 mg every 24 hours.

Nifedipine should be taken with a little water. Tablets should be swallowed whole. Do not chew. Not to be taken with or immediately after food.

The pharmacokinetics of nifedipine are altered in the elderly so that lower maintenance doses of nifedipine may be required compared to younger patients.

Nifedipine is metabolised primarily by the liver and therefore patients with liver dysfunction should be carefully monitored. Patients with renal impairment should not require adjustment of dosage.

Children

Nifedipine is not recommended for use in children.

4.3. Contra-Indications

Hypersensitivity to nifedipine or other dihydropyridines because of the theoretical risk of cross reactivity.

Nifedipine should not be used in clinically significant aortic stenosis, unstable angina, or during or within one month of a myocardial infarction.

Nifedipine should not be used for the treatment of acute attacks of angina.

The safety of nifedipine in malignant hypertension has not been established.

Nifedipine should not be used for secondary prevention of myocardial infarction.

Nifedipine should not be administered concomitantly with rifampicin since effective plasma

levels of nifedipine may not be achieved owing to enzyme induction.

4.4. Special Warnings and Special Precautions for Use

Unipine XL / CardilateXL 30mg should be used with caution in patients whose cardiac reserve is poor and in patients with hepatic impairment. A marked decrease in blood pressure may occur in dialysis patients with malignant hypertension and hypovolaemia.

Unipine XL/ CardilateXL 30mg should be discontinued in patients who experience ischaemic pain following its administration.

4.5. Interaction with other Medicinal Products and other Forms of Interaction

When Unipine XL / CardilateXL 30mg is used in combination with beta blocking drugs and other anti-hypertensive drugs, there is the possibility of an additive effect resulting in postural hypotension.

Decreased plasma quinidine and increased plasma phenytoin, theophylline concentrations have been reported when nifedipine is administered concomitantly.

Adjustment of hypoglycaemic medication may be required in diabetic patients.

There may be potentiation of the antihypertensive action of nifedipine when administered simultaneously with cimetidine. Unipine XL / CardilateXL 30mg is not a beta-blocker and therefore gives no protection against the dangers of abrupt beta-blocker withdrawal. Any such withdrawal should be by gradual reduction of the dose of beta-blocker preferably over 8 to 10 days. Unipine XL / CardilateXL 30mg will not prevent possible rebound effects after cessation of anti-hypertensive therapy.

The simultaneous administration of nifedipine and digoxin may lead to reduced digoxin clearance and hence an increase in the plasma digoxin. Digoxin levels should be monitored and, if necessary the digoxin dose reduced.

Nifedipine should not be administered concomitantly with rifampicin since effective plasma levels of nifedipine, may not be achieved to owing to enzyme induction (see Contraindications).

As with other dihydropyridines, nifedipine should not be taken with grapefruit juice because bioavailability is increased.

4.6. Pregnancy and Lactation

Unipine XL / CardilateXL 30mg should not be administered to women who are pregnant, women of child-bearing potential or to nursing mothers.

4.7. Effects on Ability to Drive and Use Machines

Not applicable.

4.8. Undesirable Effects

Side effects, mainly associated with the vasodilatory action of nifedipine include headache, dizziness, flushing and gravitational oedema. These effects usually disappear with continued treatment. Common side effects include rash, nausea, lethargy, increased frequency of micturition, hypersensitivity type jaundice and gingival hyperplasia.

As with other sustained release dihydropyridines, exacerbation of angina pectoris may occur rarely at the start of treatment with sustained release formulations of nifedipine. The occurrence of myocardial infarction has been described although it is not possible to distinguish such an event from the natural course of ischaemic heart disease.

4.9. Overdose

Following overdosage, the stomach should be emptied by aspiration and lavage and charcoal instillation. Standard measures such as atropine and noradrenaline may be used for resultant bradycardia and hypotension. Intravenous calcium gluconate may be of benefit combined with metaraminol.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Nifedipine is a potent and specific Class II calcium antagonist. The main action is to reduce contraction of vascular smooth muscle in both the coronary and peripheral circulation resulting in a reduction in blood pressure.

5.2. Pharmacokinetic Properties

Nifedipine is absorbed over the whole length of the gastrointestinal tract the majority of an oral dose being absorbed in the jejunum. There is however considerable inter-individual variation in the rate and extent to which nifedipine is absorbed. It undergoes extensive yet variable first pass metabolism. The absorption of nifedipine from Nifedipine (30 mg) SR Tablets occurs over several hours which is typical of a sustained release preparation. At steady state C_max was approximately 20 mg/ml with T_max of 7 hours. At 24 hours the mean plasma concentration was approximately 8 ng/ml supporting once daily administration. In a single dose study the mean elimination half life was shown to be 10 hours (range 3.5-16.5 hours) in the fasting state.

5.3. Pre-clinical Safety Data

The LD₅₀ of oral nifedipine has been found to be 494 mg/kg in mice and 1022 mg/kg in rats. Reproductive studies have shown reduced fertility in male and female rats dosed 100 mg/kg/day nifedipine for 10 weeks. Pregnant rats and rabbits receiving 30 mg/kg/day nifedipine showed increased rates of resorption and abortion. In pregnant mice dosed at 24 mg/kg/day nifedipine caused a low incidence of embryo lethality and a dosage-related reduction in foetal weight.

Nifedipine showed no mutagenic activity in the dominant lethal or micronucleus tests in mice, or in an in vivo cytogenic study in hamsters. Nor was it carcinogenic in rats.

The widespread clinical usage of nifedipine in accordance with the data sheet has established its safety and efficacy in man in the treatment of hypertension.

6. PHARMACEUTICAL PARTICULARS

6.1.    List of Excipients

Povidone, Ammoniomethacrylate copolymer, Lactose, Hydrogenated castor oil, Talc, Colours E110, E171, E120, E132

6.2.    Incompatibilities

Unipine XL / CardilateXL 30mg should not be taken with cimetidine as this causes potentiation of the anti-hypertensive action of nifedipine.

6.3.    Shelf-Life

2 years.

6.4.    Special Precautions for Storage

Unipine XL / CardilateXL 30mg should be protected from light and stored below 25°C, in a dry place in the manufacturers original container.

6.5.    Nature and Contents of Container

Unipine XL / CardilateXL 30mg is available in blister packs each containing 28 tablets.

6.6. Instructions for Use, Handling and Disposal

No special instructions.

7 MARKETING AUTHORISATION HOLDER

Genus Pharmaceuticals Limited

T/A Genus Pharmaceuticals

Linthwaite

Huddersfield

HD75QH

UK

8. MARKETING AUTHORIZATION NUMBER(S)

PL 06831/0047

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

19/02/2009

10 DATE OF REVISION OF THE TEXT

12/08/2014