AA Pharma Nifedipine

AA Pharma Nifedipine

nifedipine

Manufacturer:

AA Pharma

Distributor:

Pharmaforte
Full Prescribing Info
Contents
Nifedipine.
Action
Pharmacology: AA Pharma Nifedipine is a calcium ion influx inhibitor (calcium entry blocker or calcium ion antagonist). The anti-anginal effect of this group of drugs, is believed to be related to their specific cellular action of selectively inhibiting transmembrane influx of calcium ions into cardiac muscle, and vascular smooth muscle. The contractile processes of these tissues are dependent upon the movement of extra-cellular calcium into the cells through specific ion channels.
Nifedipine blocks the transmembrane influx of calcium through the slow channel without affecting to any significant degree the transmembrane influx of sodium through the fast channel. This results in a reduction of free calcium ions available within cells of the above tissues. Nifedipine does not alter total serum calcium.
The specific mechanisms by which nifedipine relieves angina has not been fully determined but it is believed to be brought about largely by its vasodilatory action.
Nifedipine dilates the main coronary arteries and coronary arterioles both in normal and ischemic regions and is potent inhibitor of coronary artery spasm. This property increases myocardial oxygen delivery and is responsible for the effectiveness of nifedipine in vasospastic angina.
Nifedipine by its vasodilatory action on peripheral arterioles, reduces the total peripheral vascular resistance. This reduces the workload of the heart and thus reduces the myocardial energy consumption and oxygen requirements and probably accounts for the effectiveness of nifedipine in chronic stable angina.
The negative inotropic effect of nifedipine is usually not of major clinical significance because the drug's vasodilating properties evoke at therapeutic doses a baroreceptor-mediated reflex tachycardia which tends to counterbalance this negative inotropic effect.
At the usual therapeutic doses nifedipine does not possess antiarrhythmic properties.
In man, oral administration of 10 mg C14 nifedipine resulted in more than 90% absorption of the drug. Radioactivity was detectable in the serum 20 minutes after oral ingestion and peak serum levels were reached in 1 to 2 hours. 70 to 80% of the activity was eliminated via the kidneys and the remainder via the feces.
The bi-exponential analysis of the disappearance of nifedipine in the plasma yields an initial fast half-life (T1/2) of 2.5 to 3 hours and a terminal slow half-life (T1/2) of 5 hours.
A comparative bioavailability study was performed on Adalat 10 mg Capsules vs. AA Pharma Nifedipine 10 mg Capsules using 24 (twenty-four) normal volunteers. A single dose of 20 mg was administered. The results are as follows: (See Table 1.)

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Studies in man, dog and rat showed that nifedipine is almost completely metabolized in the body. It is transformed into two pharmacologically inactive metabolities. The main metabolite is the hydroxycarboxylic acid derivative which represents about 95%, the other is the corresponding lactone, which represents about 5%. The acid form is mainly excreted in the urine. Protein binding of circulating nifedipine exceeds 90%.
Indications/Uses
1. Vasospastic angina pectoris (Prinzmetal's angina, variant angina or at-rest angina).
2. Chronic stable angina pectoris (effort angina).
3. Essential Hypertension.
4. Hypertensive emergency.
5. Raynaud's syndrome.
Dosage/Direction for Use
In all cases dosage should be adjusted to individual patient requirements.
The starting dose of AA Pharma Nifedipine is one 10 mg capsule, swallowed whole, 3 times/day. The usual effective dose range is 10-20 mg three times daily. Some patients, especially those with evidence of coronary artery spasm, respond only to higher doses, more frequent administration, or both. In such patients, doses of 20-30 mg three or four times daily may be effective. A maximum daily dose of 120 mg may be used.
In general there should be an interval of at least three days between increases in dose in order to adequately assess the response to a particular dose level. In hospitalized patients under close observation the titration phase may proceed more rapidly.
Nifedipine should be administered cautiously to elderly patients and the dosage should be carefully and gradually adjusted depending on patient tolerance and response. (See Precautions.)
AA Pharma Nifedipine 5 mg capsules provide for greater flexibility of dose titration, e.g. in elderly patients.
Overdosage
SYMPTOMS AND TREATMENT OF OVERDOSAGE: Although there is no well documented experience with AA Pharma Nifedipine overdosage, available data suggest that gross overdosage could result in excessive peripheral vasodilation with subsequent marked and probably prolonged systemic hypotension. Clinically significant hypotension due to nifedipine overdosage calls for active cardiovascular support including monitoring of cardiac and respiratory function, elevation of extremities, and attention to circulating fluid volume and urine output. A vasoconstrictor (such as norepinephrine) may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to its use.
Contraindications
1. AA Pharma Nifedipine is contraindicated in pregnancy and women of child-bearing potential. Fetal malformations and adverse effects on pregnancy have been reported in animals.
An increase in the number of fetal mortalities and resorptions occurred after the administration of 30 and 100 mg/kg nifedipine to pregnant mice, rats and rabbits. Fetal malformations occurred after the administration of 30 and 100 mg/kg nifedipine to pregnant mice and 100 mg/kg to pregnant rats.
2. Unstable angina pectoris.
3. Acute myocardial infarction (within the first 4 weeks).
4. Secondary prevention of myocardial infarction, as there is no convincing evidence of efficacy in these conditions and there are concerns about safety.
Warnings
AA Pharma Nifedipine should be used with care in the following conditions: 1. Beta Blocker Withdrawal: Patients recently withdrawn from beta blockers may develop a withdrawal syndrome with increased angina, probably related to increased sensitivity to catecholamines. Initiation of nifedipine treatment will not prevent this occurrence and might be expected to exacerbate it by provoking reflex catecholamine release. There have been occasional reports of increased angina in a setting of beta blocker withdrawal and nifedipine initiation. It is important to taper beta blockers if possible, rather than stopping them abruptly before beginning nifedipine.
2. Heart Failure: There have been reports of severe hypotension and a lowering of cardiac output after administration of nifedipine to patients with severe heart failure. Thus, nifedipine should be used cautiously in patients with heart failure. Rarely, patients usually receiving a beta blocker, have developed heart failure after beginning nifedipine.
Nifedipine should be used cautiously in patients with severe aortic stenosis. In such cases, nifedipine will not produce its usual afterload reducing effects, and there is a possibility that an unopposed negative inotropic action of nifedipine may produce heart failure if the end-diastolic pressure is raised.
3. Essential Hypertension and Chronic angina pectoris: In patients with essential (non-organ related) hypertension or chronic angina pectoris treated with regular or immediate release (short-acting) dosage forms of nifedipine, there is evidence to suggest a dose-related increase in complications of the cardiovascular system (eg. Myocardial Infarction) and increased mortality. Such preparations should therefore be used in these two conditions only if other drugs are not indicated.
The maximum dose is limited to 60mg.
Special Precautions
Because AA Pharma Nifedipine is an arterial and arteriolar vasodilator, blood pressure may be lowered, particularly in the hypertensive patient, and a compensatory increase in heart rate may occur. Thus, blood pressure and heart rate should be monitored carefully during nifedipine therapy. Close observation is especially recommended for patients already taking medications that are known to lower blood pressure. (See Warnings.)
Peripheral edema: Mild to moderate peripheral edema, typically associated with arterial vasodilation and not due to left ventricular dysfunction, has been reported to occur in patients treated with nifedipine. (See Adverse Reactions.) This edema occurs primarily in the lower extremities and usually responds to diuretic therapy. With patients whose angina is complicated by congestive heart failure, care should be taken to differentiate this peripheral edema from the effects of increasing left ventricular dysfunction.
Nifedipine should be administered cautiously to elderly patients, especially to those with a history of hypotension or cerebral vascular insufficiency.
The use of nifedipine in diabetic patients may require adjustment of their control.
Use In Pregnancy & Lactation
AA Pharma Nifedipine is contraindicated in pregnancy and women of child-bearing potential. Fetal malformations and adverse effects on pregnancy have been reported in animals.
An increase in the number of fetal mortalities and resorptions occurred after the administration of 30 and 100 mg/kg nifedipine to pregnant mice, rats and rabbits. Fetal malformations occurred after the administration of 30 and 100 mg/kg nifedipine to pregnant mice and 100 mg/kg to pregnant rats.
Adverse Reactions
A safety analysis from the world literature (controlled and open studies) was carried out in a heterogeneous group of 7146 patients who were treated with nifedipine. Adverse effects were reported in 27.9% of patients and required discontinuation of treatment in 5.5% of patients.
The most common adverse effects, which generally result from the vasodilating effects of nifedipine were: Headache (7.2%); dizziness, lightheadedness and giddiness (6.7%), nausea and vomiting and gastrointestinal distress (6.7%), flushing and heat sensation (5.8%); peripheral edema (3.7%) and hypotension (2.0%).
As a part of the previously mentioned analysis a more comprehensive safety evaluation (controlled and open studies) was carried out in 3074 patients, some of whom were severely ill and were receiving a variety of concomitant drugs, such as beta-blockers, nitrates, antiarrhythmics, cardiac glycosides, diuretics and anti-platelet drugs, etc.
The following adverse effects divided by systems were reported, in these 3074 patients: (See Table 2.)

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Especially at the start of therapy, patients may occasionally experience angina attacks or patients with pre-existing angina pectoris may occasionally experience an increase in the frequency, duration and severity of angina attacks. There have been isolated reports of myocardial infarction. (See Table 3.)

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Two cases of hypersensitivity have been reported resulting in an allergic hepatitis which resolved when the drug was discontinued. In one case recurrence was observed on re-challenge.
Nifedipine has been reported to cause in a small number of patients gingival hyperplasia similar to that caused by diphenylhydantoin. The lesions usually regressed on discontinuation of nifedipine. However, on occasion, gingivectomy was necessary.
Laboratory Tests: Rare, mild to moderate transient elevations of enzymes such as alkaline phosphatase, CPK, LDH, SGOT and SGPT have been noted.
Drug Interactions
The antihypertensive effect of beta-blockers may be augmented by nifedipine's reduction of peripheral vascular resistance. The concomitant administration of nifedipine with beta-adrenergic blocking drugs warrants caution and careful monitoring of the blood pressure and pulmonary signs and symptoms of congestive failure. (See Warnings.)
Long acting nitrates: Nifedipine may be safely co-administered with nitrates, but there have been no controlled studies to evaluate the antianginal effectiveness of this combination.
Antihypertensives: Nifedipine may potentiate the effects of hypotensive agents.
Concomitant use of nifedipine together with short acting nitrates, digitalis glycosides, furosemide and anticoagulants has shown no interaction or unusual toxic effects.
It has been reported that concurrent administration of cimetidine and nifedipine results in an almost doubling of peak nifedipine plasma, level. Patients receiving the two drugs concomitantly should be watched carefully for the possible exacerbation of effects of nifedipine, e.g. hypotension. Adjustment of the nifedipine may be necessary.
Storage
The capsules should be stored between 15 and 25°C. Avoid freezing. Protect from light.
MIMS Class
Calcium Antagonists
ATC Classification
C08CA05 - nifedipine ; Belongs to the class of dihydropyridine derivative selective calcium-channel blockers with mainly vascular effects. Used in the treatment of cardiovascular diseases.
Presentation/Packing
Cap 5 mg (mustard-coloured, opaque soft gelatin, imprinted 5) x 100's. 10 mg (mustard-coloured, opaque soft gelatin, imprinted 10) x 100's.
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