(nye fed' i peen)
P : Caution when used during pregnancy
|| See TERMINOLOGY & ABBREVIATIONS ||
|Indication(s) & Dosage||
Nifedipine is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.
|Administration||Immediate-release: May be taken with or without food. Avoid grapefruit juice.
Retard, GITS & OROS: May be taken with or without food. Avoid grapefruit juice. Swallow whole, do not chew/crush.
|Overdosage||Hypotension and bradycardia; hyperglycaemia, metabolic acidosis, coma. Management is mainly supportive and symptomatic.|
|Contraindications||Concomitant administration with strong P450 inducers, such as rifampin, are contraindicated since the efficacy of nifedipine tablets could be significantly reduced. Nifedipine must not be used in cases of cardiogenic shock.Adalat is contraindicated in patients with a known hypersensitivity to any component of the tablet.|
|Warning & Precautions||
Although in most patients the hypotensive effect of nifedipine is modest and well tolerated, occasional patients have had excessive and poorly tolerated hypotension. These responses have usually occurred during initial titration or at the time of subsequent upward dosage adjustment, and may be more likely in patients using concomitant beta-blockers.
Severe hypotension and/or increased fluid volume requirements have been reported in patients who received immediate release capsules together with a beta-blocking agent and who underwent coronary artery bypass surgery using high dose fentanyl anesthesia. The interaction with high dose fentanyl appears to be due to the combination of nifedipine and a beta-blocker, but the possibility that it may occur with nifedipine alone, with low doses of fentanyl, in other surgical procedures, or with other narcotic analgesics cannot be ruled out. In nifedipine-treated patients where surgery using high dose fentanyl anesthesia is contemplated, the physician should be aware of these potential problems and, if the patientâ€™s condition permits, sufficient time (at least 36 hours) should be allowed for nifedipine to be washed out of the body prior to surgery.
Increased Angina and/or Myocardial Infarction
Rarely, patients, particularly those who have severe obstructive coronary artery disease, have developed well-documented increased frequency, duration and/or severity of angina or acute myocardial infarction upon starting nifedipine or at the time of dosage increase. The mechanism of this effect is not established.
When discontinuing a beta-blocker it is important to taper its dose, if possible, rather than stopping abruptly before beginning nifedipine. 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 on occasion has been reported to increase it.
Congestive Heart Failure
Rarely, patients (usually while receiving a beta-blocker) have developed heart failure after beginning nifedipine. Patients with tight aortic stenosis may be at greater risk for such an event, as the unloading effect of nifedipine would be expected to be of less benefit to these patients, owing to their fixed impedance to flow across the aortic valve.
Hypotension, poor cardiac reserve, heart failure (deterioration has been noted), severe aortic stenosis, hepatic impairment, DM, porphyric patients, pregnancy. Avoid abrupt withdrawal (associated with exacerbation of angina). Discontinue if with ischaemic pain following administration.
|Adverse Drug Reaction(s)||Peripheral oedema, hypotension, palpitations, tachycardia, flushing, dizziness, headache, nausea, increased micturition frequency, lethargy, eye pain, mental depression, visual disturbances, gingival hyperplasia, myalgia, tremor, impotence, fever, paradoxical increase in ischaemic chest pain during initiation of treatment, rashes, abnormalities in liver function (including cholestasis), GI obstruction in some tablets covered in indigestable membrane.|
|Drug Interactions||Potentiates antihypertensives. Increases the effects of neuromuscular-blocking agents and CYP1A2 substrates (e.g. theophylline, aminophylline). Enhances toxic effects of magnesium. Enhanced antihypertensive effects with alpha 1-blockers, aldesleukin, and antipsychotics. Reduced effects with calcium. With concurrent use with quinidine, serum concentration is increased while reduced in quinidine. Decreased levels/effects with CYP3A4 inducers (e.g. carbamazepine, nafcillin, phenobarbital, phenytoin, and rifampicin). Increased levels/effects with CYP3A4 inhibitors (e.g. azole antifungals, cimetidine, erythromycin, and HIV-protease inhibitors). Please consult detailed drug interactions before prescribing.|
|Food Interaction||Serum levels may be decreased with food, St John's wort. Increased levels/effects with grapefruit juice, ethanol, garlic. Avoid ephedra, yohimbe, ginseng (may worsen hypertension).|
|Lab Interference||Falsely elevated spectrophotometric values of urinary vanillylmandelic acid.|
|Pregnancy Category (FDA) & use in specific population||
Pregnancy Category C.
In rodents, rabbits and monkeys, nifedipine has been shown to have a variety of embryotoxic, placentotoxic, teratogenic and fetotoxic effects, including stunted fetuses (rats, mice and rabbits), digital anomalies (rats and rabbits), rib deformities (mice), cleft palate (mice), small placentas and underdeveloped chorionic villi (monkeys), embryonic and fetal deaths (rats, mice and rabbits), prolonged pregnancy (rats; not evaluated in other species), and decreased neonatal survival (rats; not evaluated in other species). On a mg/kg or mg/m2 basis, some of the doses associated with these various effects are higher than the maximum recommended human dose and some are lower, but all are within an order of magnitude of it.
The digital anomalies seen in nifedipine-exposed rabbit pups are strikingly similar to those seen in pups exposed to phenytoin, and these are in turn similar to the phalangeal deformities that are the most common malformation seen in human children with in utero exposure to phenytoin.
From the clinical evidence available, a specific prenatal risk has not been identified. However, an increase in perinatal asphyxia, caesarean delivery, prematurity and intrauterine growth retardation have been reported.
Careful monitoring of blood pressure must be exercised in pregnant women, when administering nifedipine in combination with IV magnesium sulfate due to the possibility of an excessive fall in blood pressure which could harm the mother and fetus.
There are no adequate and well-controlled studies in pregnant women.
Nifedipine is excreted in human milk. Nursing mothers are advised not to breastfeed their babies when taking the drug.
The safety and effectiveness of Nifedipine in pediatric patients have not been established.
Although small pharmacokinetic studies have identified an increased half-life and increased Cmax and AUC, clinical studies of nifedipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Patients with Galactose Intolerance
Since this medicinal product contains lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Nifedipine is a calcium ion influx inhibitor (slow-channel blocker or calcium ion antagonist) which inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. The contractile processes of vascular smooth muscle and cardiac muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Nifedipine selectively inhibits calcium ion influx across the cell membrane of vascular smooth muscle and cardiac muscle without altering serum calcium concentrations.
Mechanism of Action
The mechanism by which nifedipine reduces arterial blood pressure involves peripheral arterial vasodilatation and, consequently, a reduction in peripheral vascular resistance. The increased peripheral vascular resistance, an underlying cause of hypertension, results from an increase in active tension in the vascular smooth muscle. Studies have demonstrated that the increase in active tension reflects an increase in cytosolic free calcium.
Nifedipine is a peripheral arterial vasodilator which acts directly on vascular smooth muscle. The binding of nifedipine to voltage-dependent and possibly receptor-operated channels in vascular smooth muscle results in an inhibition of calcium influx through these channels. Stores of intracellular calcium in vascular smooth muscle are limited and thus dependent upon the influx of extracellular calcium for contraction to occur. The reduction in calcium influx by nifedipine causes arterial vasodilation and decreased peripheral vascular resistance which results in reduced arterial blood pressure.
Pharmacokinetics and Metabolism
Nifedipine is completely absorbed after oral administration. The bioavailability of nifedipine as Nifedipine relative to immediate release nifedipine is in the range of 84%-89%. After ingestion of Nifedipine tablets under fasting conditions, plasma concentrations peak at about 2.5-5 hours with a second small peak or shoulder evident at approximately 6-12 hours post dose. The elimination half-life of nifedipine administered as Nifedipine is approximately 7 hours in contrast to the known 2 hour elimination half-life of nifedipine administered as an immediate release capsule.
When Nifedipine is administered as multiples of 30 mg tablets over a dose range of 30 mg to 90 mg, the area under the curve (AUC) is dose proportional; however, the peak plasma concentration for the 90 mg dose given as 3 x 30 mg is 29% greater than predicted from the 30 mg and 60 mg doses.
Two 30 mg Nifedipine tablets may be interchanged with a 60 mg Nifedipine tablet. Three 30 mg Nifedipine tablets, however, result in substantially higher Cmax values than those after a single 90 mg Nifedipine tablet. Three 30 mg tablets should, therefore, not be considered interchangeable with a 90 mg tablet.
Once daily dosing of Nifedipine under fasting conditions results in decreased fluctuations in the plasma concentration of nifedipine when compared to t.i.d. dosing with immediate release nifedipine capsules. The mean peak plasma concentration of nifedipine following a 90 mg Nifedipine tablet, administered under fasting conditions, is approximately 115 ng/mL. When Nifedipine is given immediately after a high fat meal in healthy volunteers, there is an average increase of 60% in the peak plasma nifedipine concentration, a prolongation in the time to peak concentration, but no significant change in the AUC. Plasma concentrations of nifedipine when Nifedipine is taken after a fatty meal result in slightly lower peaks compared to the same daily dose of the immediate release formulation administered in three divided doses. This may be, in part, because Nifedipine is less bioavailable than the immediate release formulation.
Nifedipine is extensively metabolized to highly water soluble, inactive metabolites accounting for 60% to 80% of the dose excreted in the urine. Only traces (less than 0.1% of the dose) of the unchanged form can be detected in the urine. The remainder is excreted in the feces in metabolized form, most likely as a result of biliary excretion.
Nifedipine is metabolized via the cytochrome P450 3A4 system. Drugs that are known to either inhibit or induce this enzyme system may alter the first pass or clearance of nifedipine.
No studies have been performed with Nifedipine in patients with renal failure; however, significant alterations in the pharmacokinetics of nifedipine immediate release capsules have not been reported in patients undergoing hemodialysis or chronic ambulatory peritoneal dialysis. Since the absorption of nifedipine from Nifedipine could be modified by renal disease, caution should be exercised in treating such patients.
Because nifedipine is metabolized via the cytochrome P450 3A4 system, its pharmacokinetics may be altered in patients with chronic liver disease. Nifedipine has not been studied in patients with hepatic disease; however, in patients with hepatic impairment (liver cirrhosis) nifedipine has a longer elimination half-life and higher bioavailability than in healthy volunteers.
The degree of protein binding of nifedipine is high (92%-98%). Protein binding may be greatly reduced in patients with renal or hepatic impairment.
After administration of Nifedipine to healthy elderly men and women (age > 60 years), the mean Cmax is 36% higher and the average plasma concentration is 70% greater than in younger patients.
In healthy subjects, the elimination half-life of a different sustained release nifedipine formulation was longer in elderly subjects (6.7 h) compared to young subjects (3.8 h) following oral administration. A decreased clearance was also observed in the elderly (348 mL/min) compared to young subjects (519 mL/min) following intravenous administration.
Co-administration of nifedipine with grapefruit juice results in up to a 2-fold increase in AUC and Cmax, due to inhibition of CYP3A related first-pass metabolism. Ingestion of grapefruit and grapefruit juice should be avoided while taking nifedipine.
Nifedipine produced dose-related decreases in systolic and diastolic blood pressure as demonstrated in two double-blind, randomized, placebo-controlled trials in which over 350 patients were treated with Nifedipine 30, 60 or 90 mg once daily for 6 weeks. In the first study, Nifedipine was given as monotherapy and in the second study, Nifedipine was added to a beta-blocker in patients not controlled on a beta-blocker alone.
It has little or no effect on cardiac conduction and rarely has negative inotropic activity.
|ATC Classification||C08CA05 - nifedipine; Belongs to the class of selective dihydropyridine derivative calcium-channel blockers with mainly vascular effects. Used in the treatment of cardiovascular diseases.|
|Brand Name||Manufacturer/Marketer||Composition||Dosage Form||Pack Size & Price|
|NIDIPINE 20||Square Pharmaceuticals Ltd.||Nifedipine 20mg||Tablet||10x10's: 64.00 MRP|
|NIFECAP||Drug International Ltd||Nifedipine 10mg||Capsule||30's: 63.00 MRP|
|NIFIN||The Acme Laboratories Ltd.||Nifedipine 10mg||Tablet (film-coated)||100's: 34.00 MRP|
Why is this medication prescribed?
Nifedipine is used to treat high blood pressure and to control angina (chest pain). Nifedipine is in a class of medications called calcium-channel blockers. It works by relaxing the blood vessels so the heart does not have to pump as hard. It also increases the supply of blood and oxygen to the heart.
How should this medicine be used?
Nifedipine comes as a capsule and an extended-release (long-acting) tablet to take by mouth. The capsule is usually taken three or four times a day. The extended-release tablet should be taken once daily on an empty stomach, either 1 hour before or 2 hours after a meal. Take nifedipine at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor to explain any part you do not understand. Take nifedipine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Swallow the extended-release tablets whole; do not split, chew, or crush them.
Your doctor will probably start you on a low dose of nifedipine and gradually increase your dose, generally once every 7 to 14 days.
Nifedipine controls high blood pressure and chest pain (angina) but does not cure them. Continue to take nifedipine even if you feel well. Do not stop taking nifedipine without talking to your doctor. Your doctor will probably decrease your dose gradually.
Other uses for this medicine
Nifedipine is also used sometimes to treat preterm labor and Raynaud's syndrome. Talk to your doctor about the possible risks of using this medication for your condition.
This medication is sometimes prescribed for other uses; ask your doctor for more information.
What special precautions should I follow?
Before taking nifedipine,
- tell your doctor if you are allergic to nifedipine, any other medications, or any of the ingredients in nifedipine. Ask your pharmacist for a list of the ingredients.
- tell your doctor what other prescription and nonprescription medications, vitamins, nutritional supplements, you are taking or plan to take. Be sure to mention any of the following: acarbose; anticoagulants such as warfarin; antifungals such as fluconazole, itraconazole, and ketoconazole; beta blockers such as atenolol, labetalol, metoprolol, nadolol, propranolol, and timolol; carbamazepine; cimetidine; digoxin; diltiazem; doxazosin; erythromycin; fentanyl; flecainide; HIV protease inhibitors including amprenavir, atazanavir, delavirdine, fosamprenavir, indinavir, nelfinavir, and ritonavir; metformin; nefazodone; phenobarbital; phenytoin; quinidine; quinupristin and dalfopristin; rifampin; rifapentine; tacrolimus; valproic acid; and verapamil . Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor what herbal products you are taking, especially St. John's wort.
- tell your doctor if you have or have ever had a narrowing or blockage of your digestive system or any other condition that causes food to move through your digestive system more slowly; or heart, liver, or kidney disease. Also tell your doctor if you have had a myocardial infarction (MI) within the last 2 weeks.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking nifedipine, call your doctor.
talk to your doctor about the safe use of nifedipine capsules if you are 65 years of age or older. Older adults should not usually take nifedipine capsules because they are not as safe as other medications that can be used to treat the same condition.
- if you are having surgery, including dental surgery, tell your doctor or dentist that you are taking nifedipine.
- ask your doctor about the safe use of alcoholic beverages while you are taking nifedipine. Alcohol can make the side effects from nifedipine worse.
What special dietary instructions should I follow?
Do not drink grapefruit juice or eat grapefruit 3 days before and while taking nifedipine.
If your doctor prescribes a low-salt or low-sodium diet, follow these directions carefully.
What should I do if I forget a dose?
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Nifedipine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
dizziness or lightheadedness
flushing (feeling of warmth)
decreased sexual ability
Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:
swelling of the face, eyes, lips, tongue, hands, arms, feet, ankles, or lower legs
difficulty breathing or swallowing
yellowing of the skin or eyes
- increase in frequency or severity of chest pain (angina)
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature, away from light, and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
In case of emergency/overdose
In case of overdose, consult your doctor. If the victim has collapsed or is not breathing, consult local medical emergency services.
Symptoms of overdose may include:
flushing (feeling of warmth)
swelling of the hands, feet, ankles, or lower legs
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your response to this medicine.
Do not let anyone else use your medication. If you still have symptoms and need further treatment, consult your doctor.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
Ref: U.S. National Library of Medicine.
This information is provided for reference only and not a replacement for and should only be used in conjunction with full consultation with a registered medical practitioner. It may not contain all the available information you require and cannot substitute professional medical care, nor does it take into account all individual circumstances. Although great effort has been made to ensure content accuracy, mph-bd shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise.
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