QUALITATIVE AND QUANTITATIVE COMPOSITION
Each prolonged-release tablet contains:
Active ingredients: Nifedipine: 30mg
Inactive ingredients: Talc purified, Polyvidone, Lactose monohydrate, Carbomer, Hypromellose, Silicon dioxide, colloidal, Magnesium stearate, Eudragit E, Titanium Dioxide, Iron oxide red, Macrogol 4000.
PHARMACODYNAMICS
Nifedipine belongs to the dihydropyridine group of calcium channel blocking agent. It inhibits calcium influx into the arterial smooth muscle, both in the coronary and peripheral circulation. As a result, it dilates coronary blood vessels and reduces peripheral resistance, allowing better blood perfusion to the surrounding tissue and achieving antihypertensive activity.
PHARMACOKINETICS
Macorel p.r tablets 30mg are a prolonged release formulation of nifedipine. It designs to provide less fluctuation of nifedipine blood concentrations than standard immediate release preparations
Nifedipine is highly protein bound. It undergoes hepatic oxidation to inactive metabolites which are excreted in urine (80%) and in faeces (20%).
INDICATIONS
Macorel p.r tablets 30mg are indicated in the treatment of hypertension
The symptomatic relief of chest pain caused by coronary disease, especially in effort associated angina. The vasospastic form of angina pectoris (Prinzmetal's angina)
Raynaud’s syndrome.
RECOMMENDED DOSAGE
Dosage should be individualized according to the severity of the condition and the patient’s response to medicine.
In hypertension: treatment should start with 30-60mg once daily. The usual maintenance dosage is 60-90mg daily.
In angina: treatment should start with 30-60mg daily. Dosage should be titrated according to the patient’s condition. Maximum dosage should not exceed 90mg/day.
Macorel p.r tablets 30mg should be swallowed whole, with a drink, without regards to meal. Concomitant food intake delays, but does not decrease the absorption.
Cessation of nifedipine treatment should be gradual.
SIDE EFFECTS
Side effects are usually observed in initiation of treatment and they are generally mild and transient. Many of these effects are related to the medicine’s pharmacologic action (vasodilation), they are not hazardous and subside immediately following withdrawal of medicine.
Side effects of this type are as follows
Headache, flushing, facial erythema, swollen ankle, tachycardia, dizziness, as well as polyuria, which however may be desirable for patients with high blood pressure. Other side effects include: fatigue, asthenia, nausea, diarrhea, constipation. More rarely the followings may occur: difficulty in breathing, muscle pain, tremor, nervousness, paraesthesia, postural hypotension and dermatologic reactions. Visual disturbance and chest pain have also been reported. In long-term treatment, gynaecomastia and gingival hyperplasia have been observed, which subside totally after withdrawal of treatment.
In isolated cases, the followings were reported: sleep disturbance, joint pain, fever, ear buzzing. Cases of fainting have been reported following initial dose due to decrease in blood pressure.
Inform doctors with side effects when using medicine
CONTRAINDICATIONS
Macorel p.r tablets 30mg is contraindicated to patients with known hypersensitivity to nifedipine or those with hypotension. Macorel p.r tablets 30mg should not be taken concomitantly with the antibiotic rifampicin. Macorel p.r tablets 30mg should not be used for the treatment of acute attacks of angina. Macorel p.r tablets 30mg should not used within 1 month following an acute myocardial infarction.
Cardiogenic shock, advanced aortic stenosis; unstable attacks of angina; porphyria.
USE IN PREGNANCY and LACTATION
Macorel p.r tablets are contraindicated during pregnancy
Nifedipine is excreted in breast milk. As there is no experience on the potential risk to the foetus, lactation should be discontinued if treatment with Macorel p.r tablets 30mg is considered essential.
PRECAUTIONS/WARNINGS
Macorel p.r tablets 30mg must be swallowed whole, under no circumstances should they be bitten, chewed or broken up.
Caution should be exercised in patients with very low blood pressure (systolic pressure < 90mmHg), as in case of manifest heart failure and severe aortic stenosis, as there is a risk of further reduction of blood pressure.
Macorel p.r tablets 30mg may be used in combination with beta-blocking drugs and other antihypertensive agents, but the possibility of an additive effect resulting in postural hypotension should be borne in mind.
In case of withdrawal of any previously prescribed beta-blockers, cessation should be gradual, preferably over 8 to 10 days to prevent possible rebound effects. Macorel p.r tablets 30mg should be used with caution in patients whose cardiac reserve is poor. Deterioration of heart failure has occasionally been observed with nifedipine. Ischaemic pain has been reported in a small proportion of patients following the introduction of nifedipine therapy. Patients experience this effect should discontinue nifedipine therapy.
In dialysis patients with maglinant hypertension and hypovolaemia, a marked decrease in blood pressure can occur due to the vasodilator effects of nifedipine. In patients with impaired liver function, careful monitoring and in severe cases, a dose reduction may be necessary.
Diabetic patients taking Macorel p.r tablets 30mg may require adjustment of their diabetic therapy. Effects on the ability to drive or operate machinery: reactions to Macorel p.r tablets 30mg vary in intensity from individual to individual, can impair the ability to drive or operate machinery. This applies particularly at the start of therapy, on medication and in combination of alcohol
DRUG INTERACTIONS
Known interactions
Grapefruit juice: As with other dihydropyridines, nifedipine should not be taken with grapefruit juice as elevated plasma concentrations occur, due to a decreased first pass metabolism. As a consequence, the blood pressure lowering effects of nifedipine may be increased.
Cimetidine: The antihypertensive effect of nifedipine may be potentiated by simultaneous administration of cimetidine.
Quinidine: When used in combination with nifedipine, serum quinidine levels have beeb shown to be suppressed regardless of dosage of quinidine. Therefore, monitoring of quinidine plasma levels and if necessary, adjustment of quinidine dosage is recommended.
Digoxin: Simultaneous administration of nifedipine and digoxin may lead to reduced digoxin clearance, hence, increases digoxin plasma level. Digoxin plasma level should be monitored when use in concomitant with nifedipine, and if necessary, reduce the digoxin dosage.
Phenytoin: The bioavailability of nifedipine is reduced with co-administration with phenytoin. The clinical response to nifedipine should be monitored, and if necessary, increase the nifedipine dosage.
Diltiazem: Diltiazem decreases clearance of nifedipine. Reduction of nifedipine dosage may be necessary if both drugs are administered concomitantly.
Rifampicin: Nifedipine should not be administered concomitantly with rifampicin since effective plasma levels of nifedipine may not achieve owing to enzyme induction.
Others: Nifedipine may cause false increase in the spectrophometric values of urinary vanillylmandellic acid. However, HPLC measurements are unaffected.
Theoretical interactions
Nifedipine is metabolized via the cytochrome P450 3A4 system, therefore, there are theoretical interactions for drugs which are known to inhibit this enzyme system. Co-administration of the followings may increase nifedipine plasma concentration:
Erythromycin, ketoconazole, itraconazole, fluconazole, fluoxetine, indinavir, nelfinavir, ritonavir, amprenavir and saquinavir.
Blood pressure should therefore be monitored, and if necessary, reduce nifedipine dosage.
Tacrolimus has been shown to be metabolized via P450 3A4 system. Upon co-administration of both drugs, if necessary, consider reduction of tacrolimus dosage. Carbamazepine, phenobarbitone have shown to decrease, whilst valproic acid increase plasma levels of a structurally similar calcium channel blocker, hence an alteration in efficacy cannot be excluded.
Drugs shown not to interact with nifedipine
Aspirin, benazepril, candesartan cilexetil, debrisoquine, doxazocin, irbesartan, omeprazole, orlistat, pantoprazole, ranitidine, risiglitazone, talinolol and triamterene hydrochlorothiazide have been shown to have no effect on pharmacokinetics of nifedipine when administered concomitantly.
OVERDOSE:
Symptoms and signs
The following symptoms are observed in cases of severe nifedipine intoxication: disturbance of consiousness to the point of coma, drop in blood pressure, tachycardia, bradycardia, hyperglycemia, metabolic acidosia, hypoxia, cardiogenic shock with pulmonary oedema.
Treatment
As far as treatment is concerned, elimination of nifedipine and restoration of stable cardiovascular conditions have priority. Elimination must be as complete as possible, including the small intestine to prevent the otherwise subsequent absorption of the active substance
Elimination of nifedipine
Consider activated charcoal (50g for adults, 1g/kg for children) if the patient presents within 1 hour of ingestion of a potentially toxic amount.
Alternatively consider gastric lavage in adults within 1 hour of potentially life-threatening overdose.
Consider further doses of activated charcoal every 4 hours if a clinically significant amount of a prolonged release preparation has been ingested with a single dose of an osmotic laxative (e.g. sorbitol, lactulose or magnesium sulphate).
A symptomatic patients should be observed for at least 12 hours after ingestion.
Haemodialysis serves no purpose as nifedipine is not dialyzable.
Restoration of cardiovascular conditions
Hypotension as s result of cardiogenic shock and arterial vasodilation can be treated with calcium (10-20ml of a 10% calcium gluconate solution administered intravenously over 5-10 minutes). If the effects are inadequate, the treatment can be continued, with ECG monitoring.
If an insufficient increase in blood pressure is achieved with calcium, vasoconstricting sympathomimetic such as dopamine or noradrenaline should be administered. The dosage of these drugs should be determined by the patient’s response.
Symptomatic bradycardia may be treated with atropine, beta-sympathomimetics or a temporary cardiac pacemaker, as required.
Additional fluids should be administered with caution to avoid cardiac overload.
STORAGE
Nifedipine is photosensitive. Therefore you should avoid direct contact with sunlight.
Store the product in a dry place below 25oC
SPECIFICATION: EP
USE TERM: 3 years since the manufacturing date
HOW SUPPLIED: Box of 10 blisters x 10 tablets
WARNING
Read carefully the leaflet before use.
For further information, please contact your doctor.
This drug is dispensed on prescription only.
Keep out of reach of children.
Manufactured by:
VALPHARMA COMPANY, SAN MARINO
Via Ranco 112- Serravalle 47899, Marino
Packed by:
ELPEN PHARMACEUTICALS CO. INC.
95, Marathonos Ave., 190 09 Pikermi, Attica, Greece
