Each 12 hour extended release tablet contains: Nifedipine 10 mg.
Pharmacology: Nifedipine is a calcium antagonist of the 1,4-dihydropyridine type. Calcium antagonists reduce the transmembranal influx of calcium ions through the slow calcium channel into the cell. Nifedipine act particularly on the cells of the myocardium and the smooth muscle cells of the coronary arteries and the peripheral resistance vessels.
In the heart nifedipine dilates the coronary arteries, especially the large conductance vessels , even in the free wall segment of partially stenosed areas. Further, nifedipine reduces the vascular smooth muscle tone in coronary arteries and prevents vasospasm. The end-result is an increased poststenotic blood flow and an increased oxygen supply. Parallel to this, nifedipine reduces the oxygen requirement by lowering peripheral resistance (afterload). With long-term use, nifedipine can also prevent the development of new atherosclerotic lesions in the coronary arteries.
Nifedipine reduces the smooth muscle tone of the arterioles, thus lowering the increased peripheral resistance and consequently the blood pressure. At the beginning of the nifedipine treatment there may be a transient reflex increase in heart rate and thus in the cardiac output. However, this increase is not enough to compensate for the vasodilatation. In addition, nifedipine increases sodium and water excretion both in the short-term and long-term use. The blood-pressure-lowering effect of nifedipine is particularly pronounced in hypertensive patients.
Treatment of hypertension.
Treatment of coronary heart disease: Chronic stable angina pectoris (angina of effort); Post infarction angina pectoris (except in the first 8 days after acute myocardial infarction).
Dosage Regimen: As far as possible the treatment must be tailored to the needs of the individual. Depending on the clinical picture in each case, the basic dose must be introduced gradually. Unless otherwise prescribed, the following dosage guidelines are recommended for adults: See Table 1.
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In general therapy should be initiated with 30 mg once daily. A starting dose of 20 mg once daily may be considered when medically indicated. Depending on the severity of the disease and the patient's response the dose can be increased in stages up to 60 mg once daily.
If in angina pectoris an adequate therapeutic effects has not been achieved after 14 days of the treatment, the patient should change over the fast acting nifedipine tablet (10mg), if advised by doctor.
Duration of Treatment: The attending doctor will determine the duration of use.
Administration: The tablets must not be chewed or broken up.
As a rule the tablets are swallowed whole with a little liquid, irrespective of meal times.
Additional Information on Special Populations: Pediatric patients: The safety and efficacy of Farmalat ER in children below 18 years has not been established.
Geriatric patients: No dose adaptation in elderly people above 65 years is necessary.
Patients with hepatic impairment: In patients with mild, moderate impaired liver function careful monitoring and a dose reduction may be necessary.
Symptoms: The following symptoms are observed in cases of severe nifedipine intoxication. Disturbances of consciousness to the point of coma, a drop in blood pressure, tachycardiac/bradycardiac heart rhythm disturbances, hyperglycaemia, metabolic acidosis, hypoxia, cardiogenic shock with pulmonary oedema.
Management of Overdose in Man: As far as treatment is concerned, elimination of the active substance and the restoration of stable cardiovascular conditions have priority. After oral ingestion thorough gastric lavage is indicated, if necessary in combination with irrigation of the small intestine. Particularly in cases of intoxication with slow-released products must be as complete as possible, including the small intestine, to prevent the otherwise inevitable subsequent absorption of the active substance.
Haemodialysis serves no purpose, as nifedipine is not dialyzable, but plasmapheresis is advisable (high plasma protein binding, relatively low volume of distribution).
Bradycardiac heart rhythm disturbances may be treated symptomatically with 8-sympathomimetics, and in life-threatening bradycardiac disturbances of heart rhythm temporary pacemaker therapy can be advisable.
Hypotension as a result of cardiogenic shock and arterial vasodilatation can be treated with calcium (10-20 mL of a 10% calcium gluconate solution administered slowly IV and repeated if necessary). As a result, the serum calcium can reach the upper normal range to slightly elevated levels. If an insufficient increase in blood pressure is achieved with calcium, vasoconstricting sympathomimetics such as dopamine or noradrenaline are additionally administered. The dosage of these drugs is determined solely by the effect obtained.
Additional liquid or volume must be administered with caution because of the danger of overloading the heart.
Farmalat ER must not be used in cases of known hypersensitivity to nifedipine or to any of the excipients. Nifedipine is contraindicated in pregnancy before week 20 and during breastfeeding. Farmalat ER must not be used in cases of cardiovascular shock. Farmalat ER must not be used within the first 8 days after an acute episode of myocardial infraction. Nifedipine must not be used in combination with rifampicin because no efficient plasma levels of nifedipine may be obtained due to enzyme induction. Farmalat ER must not be used in patients with kock pouch (ileostomy after proctocolectomy).
Fertility: In single cases fertilization calcium antagonists like nifedipine have been associated with reversible biochemical changes in the spermatozoa's head section that may result in impaired sperm function. In those men who are repeatedly unsuccessful in fathering a child by in-vitro fertilization, and where no other explanation can be found, calcium antagonists like nifedipine should be considered as possible causes.
Care must be exercised in patients with very low blood pressure (severe hypotension with systolic pressure less then 90 mm Hg), In case of manifest heart failure and in the case of severe aortic stenosis.
There are not safety and efficacy data from studies in pregnant women.
The available information is inadequate to rule out adverse drug effects on the unborn and newborn child. Therefore any use in pregnancy after week 20 requires a very careful individual risk benefit assessment and should only be considered if all other treatment options are either not indicated or have failed to be efficacious. Careful monitoring of blood pressure must be exercised, also when administered nifedipine with i.v magnesium sulfate, owing to the possibility of an excessive fall in blood pressure which could harm both mother and fetus. As with other non-deformable material care should be used when administering Farmalat ER in patients with pre-existing severe gastrointestinal narrowing because obstructive symptoms may occur. Bezoars can occur in very rare cases and may require surgical intervention. In single cases obstructive symptoms have been described without known history of gastrointestinal disorders.
When doing barium contrast X-ray Farmalat ER may cause false positive effects (e.g. filling defects interpreted as polyp). In patients with mild, moderate impaired liver function careful monitoring and a dose reduction may be necessary. The pharmacokinetics of nifedipine has not been investigated in patients with severe hepatic impairment. Therefore, nifedipine should be used with caution in patients with severe hepatic impairment. In the presence of coronary spasms (Prinzmetal angina, angina at rest) and particularly severe forms of coronary heart diseases or in the case of impending anginal attack or acute hypertension crisis which all require onset on effect, Farmalat ER which marked by rapid action should be taken. Farmalat ER should be used in with caution in patients whose cardiac reserve is poor.
Effect on Ability to Drive and Use Machines: Reactions to the drug, which vary in intensity from individual to individual, can impair the ability to drive or to operate machinery. This applies particularly at the start of the treatment, on changing the medication and in combination with alcohol.
Pregnancy: Nifedipine is contraindicated in pregnancy before week 20. There are no adequate and well-controlled studies in pregnant women.
Lactation: Nifedipine passes into the breast milk. As there is no experience of possible effects on infants, breastfeeding should first be stopped if nifedipine treatment becomes necessary during the breastfeeding period.
(See Table 2.)
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Drugs that affect nifedipine: Nifedipine is metabolized via the cytochrome P450 3A4 system, located both in the intestinal mucosa and in the liver. Drugs that are known to either inhibit or to induce this enzyme system may therefore alter the first pass (after oral administration) or the clearance of nifedipine.
The extent as well as the duration of interactions should be taken into account when administering nifedipine together with the following drugs: Blood pressure lowering drugs: The blood pressure lowering effect of nifedipine may be potentiated upon co-administration of other hypertensive drugs.
When nifedipine is administered simultaneously with 8-receptor blockers, the patient should be carefully monitored, since fairly severe hypotension can occur. Deterioration of heart failure is also known to develop in isolated cases.
Nifedipine is metabolized via the cytochrome P450 3A4 system, located both in the intestinal mucosa and in the liver. Drugs that are known to either inhibit or to induce this enzyme system may therefore alter the first pass (after oral administration) or the clearance of nifedipine.
Digoxin: the simultaneous administration of nifedipine and digoxin may lead to reduced digoxin clearance and hence an increase in plasma concentrations of digoxin. The patient should therefore be checked for symptoms of digoxin overdose as a precaution and, if necessary, the glycoside dose should be reduced taking account of the plasma concentration of digoxin.
Cytochrome P450 3A4 system-inducing anti-epileptic drugs, such as phenytoin, carbamazepine and phenobarbitone: Upon co-administration with phenytoin, the bioavailability of nifedipine is reduced and thus its efficacy weakened. When both drugs are concomitantly administered, the clinical response to nifedipine should be monitored and, if necessary, an increase of the nifedipine dose considered. If the dose of nifedipine is increased during co-admnistration of both drugs, a reduction of the nifedipine dose should be considered when the treatment with phenytoin is discontinued.
Quinidine: When nifedipine and quinidine have been administered simultaneously, lowered quinidine or after discontinuation of nifedipine, a distinct increase in plasma concentrations of quinidine have been observed in individual cases. For this reason, when nifedipine is either additionally administered or discontinued, monitoring of the quinidine dose are recommended. Some author reported increased plasma concentrations of nifedipine upon co-administration of both drugs, while others did not observe an alteration in the pharmacokinetics of nifedipine. Therefore, the blood pressure should be carefully monitored, If quinidine added to an existing therapy with nifedipine. If necessary, the dose of nifedipine should be decreased.
Quinupristin/Dalfopristin: Simultaneous administration of quinupristin/dalfopristin and nifedipine may lead to increased plasma concentrations of nifedipine.
Cimetidine: due to its inhibition of cytochrome P450 3A4, cimetidine elevates the plasma concentrations of nifedipine and may potentiate the antihypertensive effect.
Rifampicin: strongly induces the cytochrome P450 3A4 system. Upon co-administration with rifampicin, the bioavailability of nifedipine is distinctly reduced and thus its efficacy weakened. The use of nifedipine in combination with rifampicin is therefore contra-indicated.
Diltiazem: decreases the clearance of nifedipine. The combination of both drugs should be administered with caution and a reduction of the nifedipine dose may be considered.
Cisapride: simultaneous administration of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine. Upon co-administration of both drugs, the blood pressure should be monitored and, if necessary, a reduction of the nifedipine dose considered.
Drug-food interactions: Grapefruit juice: Grapefruit juice inhibits the cytochrome P450 3A4 system. Administration of nifedipine together with grapefruit juice thus results in elevated plasma concentrations and prolonged action of nifedipine due to a decreased first pass metabolism or reduced clearance. As a consequence, the blood pressure lowering effect may be increased. After regular intake of grapefruit juice this effect may last for at least 3 days after the last ingestion of grapefruit juice.
Theoretical Potential Interactions: Macrolide antibiotics (e.g., erythromycin): No interaction studies have been carried out between nifedipine and erythromycin. Erythromycin is known to inhibit the cytochrome P450 3A4 mediated metabolism of other drugs. Therefore the potential for an increase of nifedipine plasma concentrations upon co-administration of both drugs cannot be excluded.
Fluoxetine: A clinical study investigating the potential of a drug interaction between nifedipine and fluoxetine has not yet been performed. Fluoxetine has been shown to inhibit in-vitro the cytochrome P450 3A4 mediated metabolism of nifedipine. Therefore an increase of nifedipine plasma concentrations upon co-administration of both drugs cannot be excluded.
Anti-HIV protease inhibitors (e.g., ritonavir): A clinical study investigating the potential of a drug interaction between nifedipine and certain anti-HIV protease inhibitors has not yet been performed. Drug of this class are known to inhibit the cytochrome P450 3A4 system. In addition drug of this class have been shown to inhibit in vitro the cytochrome P450 3A4 mediated metabolism of nifedipine. When administered together with nifedipine, a substantial increase in plasma concentrations of nifedipine due to a decreased first pass metabolism and a decreased elimination cannot be excluded.
Azole anti-mycotics (e.g., ketoconazole): This drug interaction between nifedipine and ketoconazole, itraconazole or fluconazole has not yet been performed. Drugs of this class are known to inhibit the cytochrome P450 3A4 system. When administered orally together with nifedipine, a substantial increase in systemic bioavailability of nifedipine due to an increased absorption cannot be excluded. Upon co-administration, the blood pressure should be monitored and, if necessary, a reduction in the nifedipine dose considered.
Nefazodone: Nefazodone is a drug interaction between nifedipine and nefazodone has not yet been performed. Nefazodone is known to inhibit the cytochrome P450-3A4 mediated metabolism of other drugs. Therefore an increase of nifedipine plasma concentrations upon co-administration or both drugs cannot be excluded.
Tacrolimus: Tacrolimus has been shown to be metabolized via cytochrome P450-3A4 system. Data recently published indicate that the dose of nifedipine administered simultaneously with tacrolimus may be reduced in individual cases. Upon co-administration of both drugs, the tacrolimus plasma concentrations should be monitored and, if necessary, a reduction in the tacrolimus dose considered.
Carbamazepine-Phenobarbitone: No formal studies have been performed to investigate the potential interaction between nifedipine and carbamazepine or phenobarbitone. As both drugs have been shown to reduce the plasma concentrations of the structurally similar calcium channel blocker nimodipine due to enzyme induction, a decrease in nifedipine plasma concentrations and hence a decrease in efficacy cannot be excluded.
Valproic acid: No formal studies have been performed to investigate the potential interaction between nifedipine and valproic acid. As valproic acid has been shown to reduce the plasma concentrations of the structurally similar calcium channel blocker nimodipine due to enzyme induction, an increase in nifedipine plasma concentrations and hence an increase in efficacy cannot be excluded.
Other forms of interaction: Nifedipine may cause falsely increased spectrophotometirc values of urinary vanillyl-mandelic acid. However, measurement with HPLC is unaffected. Antagonists like nifedipine should be considered as possible causes.
Instruction for Use/Handling: The light sensitive active substance contained in Farmalat ER is protected from light inside and outside its packaging. The tablet must be protected from humidity and must therefore only be removed from the foil immediately before use.
Incompatibilities: None.
C08CA05 - nifedipine ; Belongs to the class of dihydropyridine derivative selective calcium-channel blockers with mainly vascular effects. Used in the treatment of cardiovascular diseases.
Farmalat ER 12 hr ER tab 10 mg
100's (Rp80,000/boks)
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