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Mechanism of Action
US Drug Names
10 mg PO 3 times daily, initially. Increase the dose every 7 to 14 days until desired clinical response is achieved. May increase dose to 20 mg PO 3 times daily, then 30 mg PO 3 times daily over 3 days if needed or may increase dose by 10 mg/dose every 4 to 6 hours for hospitalized patients. Usual dose: 10 to 20 mg PO 3 times daily. Usual Max: 30 mg/dose and 120 mg/day. Max: 180 mg/day.
30 or 60 mg PO once daily, initially. Increase the dose every 7 to 14 days until desired clinical response is achieved. Usual Max: 90 mg/day. Max: 120 mg/day.
30 or 60 mg PO once daily, initially. May increase dose over 7 to 14 days if further control is needed. Usual dose range: 30 to 90 mg/day. Max: 120 mg/day.  
0.2 to 0.5 mg/kg/day PO in 1 to 2 divided doses. May increase dose if further control is needed. Max: 3 mg/kg/day.   A maximum of 120 mg/day PO has been recommended by pediatric hypertension guidelines; however, some experts recommend that doses up to 180 mg/day may be necessary in some clinical situations.  Extended-release tablets must be swallowed whole and are too large for young children.
0.2 to 0.5 mg/kg/dose (Max: 10 mg/dose) PO every 4 to 6 hours as needed. To avoid a precipitous and unexpected drop in blood pressure, some authors recommend initial doses less than 0.2 mg/kg and avoiding use in patients with CNS injury.  Mean doses of 0.22 to 0.23 mg/kg (range: 0.04 to 0.69 mg/kg) have been reported in retrospective studies (n = 299 pediatric patients 0.1 to 18.9 years).  NOTE: Per the FDA and manufacturers, immediate-release nifedipine dosage forms should not be used to treat hypertension and should only be used to treat patients with chronic stable angina or vasospastic angina. The immediate-release nifedipine formulation has been associated with serious side effects when used to treat adult patients with hypertension, hypertensive urgency, hypertensive emergency, or coexisting myocardial infarction. Although the use of immediate-release nifedipine for the treatment acute hypertensive episodes is still relatively common practice in pediatric patients, considerable controversy exists and caution should be used.
Conflicting data exist regarding the use of nifedipine for proteinuria associated with diabetic nephropathy. A significant increase in urinary albumin excretion was reported in 7 normotensive patients with diabetic nephropathy who were treated with slow-release nifedipine 20 mg PO twice daily and followed for 6 weeks. A significant increase in urinary albumin excretion was also reported in a crossover study of 14 non-insulin dependent diabetic patients during a 20-week trial. The mean study dose was 45 +/- 8 mg of long-acting nifedipine once daily. Conversely, in another study, 27 diabetics with persistent microalbuminuria received nifedipine 20 to 80 mg PO once daily for 12 months. These data demonstrated a decrease in urinary albumin excretion (UAE) during therapy, however, UAE increased to levels greater than baseline once therapy was discontinued.
See adult dosage. In general, initiate dosage at the lower end of the adult dosage range. Nifedipine plasma concentrations and half-life are significantly increased in geriatric patients. Adjust dosage based on clinical response.
Doses of 10 to 20 mg PO 3 times daily have been used.   
NOTE: Clinical practice guidelines recommend the use of a first line tocolytic (i.e., beta agonist, calcium channel blocker, or NSAID) for short-term use (up to 48 hours) to allow for administration of antenatal corticosteroids to enhance fetal lung maturation, magnesium sulfate for fetal neuroprotection, or transport to a tertiary facility, if indicated. There is no evidence that tocolytic therapy alone has any favorable effect on neonatal outcomes. Maintenance therapy with tocolytics is ineffective for preventing preterm birth and improving neonatal outcomes and is not recommended.
Various regimens have been used. The recommended dose by the American College of Obstetrics and Gynecology (ACOG) is a 30-mg loading dose, followed by 10 to 20 mg every 4 to 6 hours. NOTE: A route of administration is not provided, although typically PO and/or SL is used for the loading dose and PO is used for subsequent dosing. Typical regimens for the loading dose include 10 mg SL with 20 mg PO, 30 mg PO, or 10 to 20 mg SL or PO every 15 to 20 minutes until contractions stop, up to a maximum of 30 to 40 mg over 1 hour. Although not definitive, typical duration of tocolysis for acute inhibition of premature labor is 24 to 72 hours. When compared to ritodrine or magnesium sulfate, nifedipine has generally demonstrated similar efficacy with similar or fewer maternal side effects. Although maintenance use of tocolytics after acute suppression of contractions has not been shown to prolong pregnancy, doses of 10 to 20 mg PO every 4 to 6 hours have been used. Additionally, some studies have used maintenance dosing with slow-release nifedipine (doses of 60 to 160 mg/day PO).     Magnesium sulfate therapy should not be given concurrently because of additive effects on maternal cardiac function.
10 to 30 mg PO, 30 to 45 minutes before meals, has been used. Nifedipine inhibits lower esophageal (LES) muscle contraction by blocking cellular calcium uptake and lowers the LES resting pressure by 30% to 60%; side effects (e.g., hypotension, headache, pedal edema) and tolerance may limit its utility. Reserve for patients who refuse or are not candidates for more definitive therapies (pneumatic dilation or surgical myotomy) or who fail to respond to botulinum toxin injections.
0.5 mg/kg/dose (Max: 20 mg/dose) PO every 8 hours until symptoms resolve. May consider further use if resuming ascent. Nifedipine is suggested in the rare case where response to oxygen and/or descent is unsatisfactory. The extended-release formulation is preferred over immediate-release.
30 mg PO every 12 hours or 20 mg PO every 8 hours until symptoms resolve.  Nifedipine is suggested as an adjunct to descent, oxygen, or portable hyperbaric therapy in the field setting where resources are limited; it may be used as primary therapy if these measures are not feasible.
0.5 mg/kg/dose (Max: 40 mg/dose) PO every 8 hours until symptoms resolve. May consider further use if resuming ascent. Nifedipine is suggested in the rare case where response to oxygen and/or descent is unsatisfactory.
30 mg PO every 12 hours or 20 mg PO every 8 hours starting the day before ascent and continuing for 5 days after reaching the target altitude or until descent is initiated.  Prophylactic medications should only be considered for individuals with a prior history of high altitude pulmonary edema.
20 mg PO twice daily for 6 to 8 weeks.   Guidelines suggest topical calcium channel blockers as first-line therapy. Given the higher incidence of adverse effects with oral calcium channel blockers, topical administration is preferred. 
Apply an almond-sized amount intra-anally every 8 to 12 hours for 2 to 8 weeks.    Guidelines suggest topical calcium channel blockers as first-line therapy. 
30 mg PO once daily, initially. Increase the dose to 60 to 120 mg PO twice daily as tolerated. 
0.3 to 0.6 mg/kg/dose PO once daily, initially. Increase dose as tolerated. Usual dose: 2 to 3 mg/kg/day. Max: 180 mg/day.
10 mg PO 3 times daily for 2 to 7 days, then 20 mg PO 3 times daily for up 8 to 12 weeks.  
90 mg/day PO for Procardia XL or 180 mg/day PO for immediate-release capsules for angina; 90 mg/day PO for most extended-release tabs and 120 mg/day PO for Procardia XL for hypertension.
Safety and efficacy have not been established; however, up to 3 mg/kg/day PO (not to exceed 180 mg/day) for extended-release tablets has been used off-label for hypertension; 0.5 mg/kg/dose (not to exceed 10 mg/dose) has been used off-label for hypertensive urgency/emergency.
Dosage reduction and close monitoring of blood pressure is advised in patients with hepatic impairment. Although no specific guidelines are available, the half-life and AUC of nifedipine is markedly increased in cirrhotic patients.
No dosage adjustment is needed.
Nifedipine is minimally removed by hemodialysis or hemoperfusion. Therefore, no supplemental dosage is needed following hemodialysis.
Description: Nifedipine is the prototype of the dihydropyridine class of calcium-channel antagonists. It is structurally and pharmacologically similar to other dihydropyridines including amlodipine, felodipine, isradipine, and nicardipine. In general, the dihydropyridine-type calcium-channel antagonists have more prominent effects on vasodilation and coronary flow relative to diltiazem and verapamil. Unlike both diltiazem and verapamil, however, nifedipine has negligible effects on AV nodal conduction. This difference is attributed to the fact that nifedipine binds to a different site in the calcium channel. Nifedipine is used in the treatment of Prinzmetal's angina, hypertension, and other vascular disorders such as Raynaud's phenomenon†. Nifedipine is available in immediate-release and extended-release dosage forms. The immediate-release nifedipine dosage forms should only be used to treat patients with chronic stable or vasospastic angina angina; the immediate-release formulation is associated with serious side effects when used to treat patients with hypertension, hypertensive urgency, hypertensive emergency, or coexisting myocardial infarction. Although its actions were described in 1972, nifedipine was not approved by the FDA until 1981.
For storage information, see the specific product information within the How Supplied section.
Extemporaneous compounding instructions for Nifedipine 0.5% rectal topical ointment
Although calcium-channel blockers are effective drugs for treating angina, nifedipine has rarely been associated with increased angina (<= 1%). This reaction may be a result of excessive lowering of blood pressure, coronary steal, or reflex tachycardia. Peripheral edema (4%—30%) has been attributed to nifedipine therapy and appears to be dose-related and related to the mechanism of action, which involves peripheral vasodilation. Peripheral edema occurred in about one in 25 patients (4%) at doses less than 60 mg/day, in about one in eight patients (12.5%) at >= 120 mg/day, and about 30% of patients at doses of 180 mg/day. This reaction reflects the potent vasodilatory effect of this drug because it occurs more frequently with nifedipine than with other calcium-channel blockers. This edema occurs primarily in the lower extremities and usually responds to diuretic therapy. Although not readily distinguishable from the natural history of disease, congestive heart failure (2%) was reported in large uncontrolled experience in patients with vasospastic or resistant angina pectoris (about half had concomitant treatment with beta-blockers). In a subgroup of approximately 250 patients with a diagnosis of congestive heart failure as well as angina, symptoms of congestive heart failure occurred in about 6.7% of patients. With patients whose angina is complicated by congestive heart failure, care should be taken to differentiate peripheral edema from the effects of increasing left ventricular dysfunction. In most patients the hypotensive effect of nifedipine is modest and well tolerated; however, some patients have had excessive and poorly tolerated hypotension (<1%—5%). These responses have usually occurred during initial titration or at the time of dose increase, and may be more likely in patients using concomitant beta-blockers. Other cardiovascular-related adverse events reported during nifedipine therapy include: flushing or heat sensation (< 3%—25%), palpitations (<1%—7%), syncope (0.5%—1%) (mostly with initial dosing and/or an increase in dose), erythromelalgia (0.5%), chest pain (unspecified) (<= 3%), substernal chest pain (< 1%), cardiac arrest (< 1%), phlebitis (< 1%), orthostatic hypotension (< 1%), cutaneous angiectases (< 1%), arrhythmia exacerbation (<= 1%), atrial fibrillation (< 1%), bradycardia (< 1%), sinus tachycardia (<= 1%), atrial or ventricular dysrhythmias (0.7%), extrasystole (i.e., premature ventricular contractions (PVCs))(< 1%), ventricular arrhythmias (< 0.5%), and conduction disturbances (0.5%).  
Although not readily distinguishable from the natural history of hypertensive disease, myocardial infarction (4%) was reported in large uncontrolled experience in patients with vasospastic or resistant angina pectoris (about half had concomitant treatment with beta-blockers). In a subgroup of approximately 250 patients with a diagnosis of CHF as well as angina, myocardial infarction occurred in about 6.7% of patients. Patients with angina should be observed for worsening symptoms when nifedipine therapy is begun, particularly if beta-blocker therapy is being withdrawn. Serious adverse effects have been reported with the use of immediate-release nifedipine, primarily due to the unpredictable rate and degree of blood pressure lowering. Profound hypotension, myocardial infarction, and death have been reported when immediate-release nifedipine is used to lower blood pressure acutely, especially when used in elderly patients. Due to the risks associated with the immediate-release nifedipine capsules, this dosage formulation should not be used in patients with chronic hypertension, acute hypertensive crisis, acute myocardial infarction, or in the setting of acute coronary syndrome.  
Common CNS-related adverse events reported during nifedipine therapy include: headache (10—23%; due to vasodilation) and dizziness or lightheadedness (4—27%) Other CNS-related adverse events reported during nifedipine therapy include weakness (10—12%), fatigue (4—5.9%), asthenia (< 1%—4%), tremor (<= 8%), paresthesias (<= 3%), vertigo (<= 3%), anxiety (<= 1%), nervousness; mood changes (<= 2%—7%), ataxia (<=1%), libido decrease (<= 1%), depression (<= 1%), hypertonia (<=1%), hypoesthesia (<=1%), migraine (<=1%), paroniria/nightmares (<= 1%), insomnia (< 3%), sleep disturbances (<= 2%), confusion (< 1%), drowsiness (< 3%), shakiness (<= 2%), jitteriness (<= 2%), difficulties in balance (<= 2%), and paranoia (<0.5%).  
Respiratory-related adverse reactions reported during nifedipine therapy include: nasal congestion (<=2%—6%), chest congestion (<= 2%), dyspnea (<= 2%—6%), cough (< 1%—6%), wheezing (6%), throat irritation (6%), epistaxis (<= 1%—3%), rhinitis (<= 3%), rales (< 1%), pharyngitis (< 1%), stridor (< 1%), upper respiratory tract infection (<= 1%), respiratory disorder (<= 1%), and sinusitis (<= 1%).  
Dermatologic and allergic adverse reactions reported during administration of nifedipine include: rash (unspecified) (<= 3%), pruritus (< 3%), dermatitis (<= 2%), urticaria (<= 2%), hyperhidrosis (<= 2%), photosensitivity reaction (< 1%), petechiae (< 1%), alopecia (<=1%), and purpura (<=1%). In post-marketing experience, there have been rare reports of exfoliative dermatitis (< 0.5%) caused by nifedipine. There have also been rare reports of exfoliative or bullous skin adverse events (such as erythema multiforme, Stevens-Johnson Syndrome, and toxic epidermal necrolysis). Angioedema (< 1%), allergic reaction (< 1%), cellulitis (< 1%), facial edema (<= 1%), and anaphylactoid reactions have been reported during nifedipine therapy.   Nifedipine has also been associated with acute generalized exanthematous pustulosis (AGEP). The nonfollicular, pustular, erythematous rash starts suddenly, is associated with elevated body temperature above 38 degrees C, and is distinct from pustular psoriasis, although biopsy results in each reveal spongiform subcorneal pustules. Drugs are the main cause of AGEP. A period of 2—3 weeks after an inciting drug exposure appears necessary for a first episode of AGEP. Unintentional reexposure may cause a second episode within 2 days. Clinical presentation is diverse with cutaneous lesions beyond erythema and pustules present in half of the cases. For example, bullous lesions, edema, purpura, itching, and mucosal erosions are possible. The mean duration of the pustules is 9.7 days followed by an annular desquamation, as long as the causative drug or factor is discontinued. The physiopathological mechanisms of AGEP have not been determined but the pathological criteria of edema, leukocytoclastic vasculitis, eosinophil exocytosis, and keratinocyte focal necrosis are distinctive. Pustule confluence or very small pustules may lead a clinician to make an incorrect diagnosis of TEN, of drug-induced erythroderma, or of staphylococcal scalded skin syndrome.
Gynecomastia has been reported in < 1% of patients receiving nifedipine. Breast enlargement or engorgement (< 1%) and breast pain or mastalgia (<= 1%) have also been reported.  
Gingival hyperplasia (<=1%) gum disorder (< 1%), and gum hemorrhage (< 1%) have been reported with nifedipine.  
Gastrointestinal-related adverse reactions reported during the use of all dosage forms of nifedipine include: nausea (2—11%), pyrosis (heartburn) (11%), diarrhea (< 3%), constipation (<= 3.3%), cramps (<= 2%), xerostomia (< 3%), dysphagia(< 1%), dyspepsia (< 3%), eructation (<= 1%), esophagitis (< 1%), flatulence (< 3%), gastrointestinal disorder (< 1%), GI bleeding (< 1%), vomiting (<= 1%), weight loss (< 1%), dysgeusia (<= 1%), abdominal pain (< 3%), gastrointestinal irritation (< 1%), gastroesophageal reflux (<= 1%), melena (<= 1%), and weight gain (<= 1%).   GI obstruction (even in patients with no prior history of gastrointestinal disease, see Contraindications), tablet adherence to the gastrointestinal wall resulting in peptic ulcer, and, rarely, bezoar have been reported in association with extended-release nifedipine formulations. In some cases, hospitalization and surgical intervention have been required.
Urogenital-related adverse reactions reported during nifedipine therapy include: sexual difficulties (<= 2%), impotence (erectile dysfunction) (< 1%—3%), nocturia (< 0.5%—1%), polyuria (< 3%), increased urinary frequency (<= 3%), pelvic pain (< 1%), dysuria (<= 1%), nephrolithiasis (< 1%), urogenital disorder (< 1%), gout (<= 1%), and hematuria (<= 1%).  
Musculoskeletal-related adverse reactions reported during nifedipine therapy include: muscle cramps (<= 2%—8%), inflammation (<= 2%), joint stiffness (<= 2%), arthritis with positive ANA (< 1%), myalgia (< 0.5—1%), pain (< 3%), leg pain (<= 3%), neck pain (< 1%), back pain (<= 1%), leg cramps (<= 3%), arthralgia (< 3%), joint disorder (< 1%), and myasthenia (< 1%).  
Clinically significant, but usually transient, elevated hepatic enzymes have been reported rarely during nifedipine therapy. A causal relationship to nifedipine has not been established. These laboratory abnormalities have rarely been associated with clinical symptoms; cholestasis with or without jaundice has been reported. Rare instances of allergic hepatitis have also been reported.  
Blurred vision (<= 2%), visual impairment (i.e., abnormal vision (<= 1%) or transient blindness at the peak of plasma level (< 0.5%)), amblyopia (< 1%), conjunctivitis (< 1%), diplopia (< 1%), eye disorder (< 1%), ocular hemorrhage (< 1%), periorbital edema (<= 1%), and abnormal lacrimation (<= 1%) have been reported during nifedipine therapy.  
Tinnitus (<= 1%) has been reported during nifedipine therapy.  
Hematologic changes have been reported with nifedipine therapy. Eosinophilia and lymphadenopathy have been reported in < 1% of nifedipine-treated patients. Thrombocytopenia, anemia, and leukopenia have been reported in < 0.5% of nifedipine-treated patients. Positive direct Coombs Test with/without hemolytic anemia has been reported but a causal relationship between nifedipine administration and positivity of this laboratory test, including hemolysis, could not be determined.  
General effects, such as fever (<= 2%), chills (<= 2%), malaise (<= 1%), and rigors (<= 1%) have been reported during nifedipine therapy.  
Nifedipine may produce hyperglycemia and may lead to loss of glucose control.
Hot flashes have been reported in <= 1% of nifedipine-treated patients, and may be related to vasodilation.
Nifedipine decreases peripheral resistance and can worsen hypotension. Nifedipine should not be used in patients with systolic blood pressures of less than 90 mm Hg (i.e., severe hypotension). Nifedipine should be used with caution in patients with mild to moderate hypotension. Blood pressure should be monitored carefully in all patients receiving nifedipine.
Nifedipine is a dihydropyridine calcium-channel blocker and is contraindicated in patients with known serious dihydropyridine hypersensitivity.
There are no adequate and well-controlled studies of nifedipine use in pregnant women. In animal studies involving rats and rabbits, nifedipine has been shown to be teratogenic. Nifedipine was associated with various embryotoxic, placentotoxic, and fetotoxic effects, including stunted fetuses, embryonic deaths, and fetal deaths in rats, mice and rabbits; rib deformities and cleft palates in mice; small placentas and underdeveloped chorionic villi in monkeys; and prolonged pregnancy/decreased neonatal survival in rats. Nifedipine should only be used during pregnancy if the potential benefit justifies the potential risk. 
Because nifedipine is excreted in human milk, the manufacturer does not recommend breast-feeding during nifedipine therapy. Based off of data from a single mother-infant pair, it has been estimated that the amount of drug that would appear in the breast-milk is less than 5% of the maternal therapeutic dose. However, neonatal myocardium is very sensitive to changes in calcium status, and the therapeutic dose for a neonate is unknown. The authors further concluded that delaying breast-feeding or expressing milk for 3 to 4 hours after a dose would significantly reduce the amount of drug ingested by a nursing infant. Previous recommendations from The American Academy of Pediatrics (AAP) listed nifedipine as usually compatible with breast-feeding. Nifedipine has been used to treat Raynaud's phenomenon of the nipple to decrease the pain associated with breast-feeding.  Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Nifedipine should be used cautiously in patients with severe bradycardia. It also should be used cautiously in patients with congestive heart failure (or left ventricular dysfunction) because nifedipine can precipitate or exacerbate heart failure due to its negative inotropic effects, particularly in patients receiving concomitant beta-blocker therapy. The development or worsening of pulmonary edema is a marker for discontinuation of nifedipine. The manufacturer of Adalat CC (extended-release nifedipine) states that use in patients in cardiogenic shock is contraindicated. Immediate-release nifedipine should be avoided in certain coronary artery disease states which include cardiogenic shock or acute myocardial infarction (or other acute coronary syndromes such as unstable angina) due to its negative inotropic effects and the reflex sympathetic activation, tachycardia, and hypotension associated with its use. Although immediate-release nifedipine (including sublingual or 'bite and swallow' administration) was frequently used for the treatment of hypertensive urgencies prior to 1995, serious adverse effects have been reported with its use, primarily due to the unpredictable rate and degree of blood pressure lowering. Profound hypotension, myocardial infarction, and death have been reported when immediate-release nifedipine was used to lower blood pressure acutely. Therefore, according to recommendations of the Joint National Committee on Prevention, Detection Evaluation, and Treatment of High Blood Pressure (JNC-VI), nifedipine liquid-filled capsules are contraindicated in the setting of hypertensive urgency, hypertensive crisis, or hypertensive emergency. The routine, sporadic use of nifedipine liquid-filled capsules whenever blood pressure rises above a predetermined level is not considered appropriate. The immediate-release nifedipine dosage form is currently only indicated for the treatment of chronic stable angina or vasospastic angina.
The use of nifedipine immediate-release dosage forms in geriatric patients (aged 71 years and older) for the treatment of hypertension has been associated with a nearly 4-fold increase in risk for all-cause mortality when compared to other antihypertensives (beta-blockers, ACE inhibitors, or non-dihydropyridine calcium channel blockers). Nifedipine plasma concentrations are significantly increased in elderly patients. This patient population may be at greater risk for drug accumulation and toxicity; initiate dosage cautiously. Small pharmacokinetic studies have identified an increase in the half-life, Cmax, and AUC in elderly populations. In healthy subjects, the clearance of nifedipine after intravenous administration was decreased by 33% in the elderly compared to younger subjects. These changes are not due to changes in renal function. According to the Beers Criteria, immediate-release nifedipine is considered a potentially inappropriate medication (PIM) in geriatric patients; avoid use due to the potential for hypotension and the risk of precipitating myocardial ischemia. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities; antihypertensive regimens should be individualized to achieve the desired outcome while minimizing adverse effects. Antihypertensives may cause dizziness, postural hypotension, fatigue, and there is an increased risk for falls. Calcium channel blockers may cause peripheral edema and clinically significant constipation; some agents may cause generalized aching, headache, and muscle pain. OBRA states that short acting/immediate-release nifedipine increases the risk of cardiac complications and should not be used.
Nifedipine should be avoided in patients with advanced aortic stenosis because the drug can worsen the abnormal pressure gradient associated with this condition.
Because calcium channel blockers relax the lower esophageal sphincter, nifedipine should be used cautiously in patients with gastroesophageal reflux disease (GERD) or hiatal hernia associated with reflux esophagitis. Nifedipine extended-release formulations have been associated with rare reports of obstructive symptoms in patients with known strictures as well as in patients with no known gastrointestinal disease. In some cases hospitalization and surgical intervention have been necessary. Use caution in patients at increased risk of GI obstruction including those with an alteration in gastrointestinal anatomy such as severe gastrointestinal narrowing (e.g., esophageal stricture), gastric cancer, colon cancer, small bowel obstruction, bowel resection, gastric bypass, vertical banded gastroplasty, colostomy, diverticulitis, diverticulosis, and inflammatory bowel disease), hypomotility disorders (constipation, gastroesophageal reflux disease (GERD), ileus, obesity, hypothyroidism, and diabetes mellitus) and aggravating concomitant medications (H2-histamine blockers, opiate agonists, nonsteroidal anti-inflammatory drugs, laxatives, anticholinergic agents, levothyroxine, and neuromuscular blocking agents).
The safety and efficacy of nifedipine use in infants, children, and adolescents has not been established.
Nifedipine plasma concentrations are significantly increased in patients with hepatic disease such as cirrhosis. These patients may be at greater risk for drug accumulation and toxicity. It is unknown how systemic exposure may be altered in patients with moderate or severe hepatic impairment. Careful monitoring and dose reduction may be necessary; consider initiating therapy with the lowest dose available (see Dosage).
According to the manufacturer of Adalat CC, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take nifedipine formulations that contain lactose.
The manufacturer also notes a report of reversible reduction in the ability of human sperm obtained from a limited number of infertile men taking recommended doses of nifedipine to bind to and fertilize an ovum in vitro. There are published reports of reversible infertility in men taking nifedipine for hypertension. 
Mechanism of Action: Like other calcium-channel antagonists, nifedipine inhibits the influx of extracellular calcium through myocardial and vascular membrane pores, which are selective for specific ions. Serum calcium levels remain unchanged. It is believed that nifedipine inhibits this influx by physically plugging the channel. While verapamil and diltiazem exert balanced effects on calcium channels in the SA node, AV node, and vasculature, nifedipine and other members of the dihydropyridine group act predominantly on the vasculature, making these agents more potent peripheral vasodilators. The decrease in intracellular calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries. This results in increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Although these drugs originally were believed to improve oxygen supply, it now appears that their effectiveness as anti-ischemic agents arises from their ability to alter the systemic balance between supply and demand. Reduced afterload and reduced myocardial wall tension lead to reduced myocardial oxygen demand, which now seems to best explain the benefit of nifedipine and other dihydropyridines in the treatment of angina. Thus, nifedipine increases myocardial oxygen supply (secondary to coronary vasodilation) and decreases myocardial oxygen demand (secondary to decreased afterload). Nifedipine appears particularly effective in treating variant angina (i.e., vasospastic angina) due to this ability to increase myocardial oxygen supply by inducing coronary vasodilation. The effectiveness of nifedipine in treating chronic stable angina, on the other hand, is related to the decrease in myocardial oxygen demand secondary to decreased afterload.
Nifedipine has no clinical effect on AV conduction, which may be due to its inhibition of phosphodiesterase. This intracellular mechanism of nifedipine actually enhances calcium inflow and counteracts its own inhibitory effects on calcium influx at the membrane surface. Also, phosphodiesterase inhibition causes additional relaxation of vascular smooth muscle. Thus, nifedipine is more potent than verapamil as a peripheral vasodilator but has negligible effects on AV nodal conduction. Negative inotropic effects rarely are noted clinically, presumably due to a reflex increase in heart rate in response to nifedipine's vasodilatory activity. Nifedipine therapy usually does not affect cardiovascular parameters in patients with normal ventricular function, but patients with decreased left ventricular function can experience an increase in ejection fraction and a decrease in left ventricular filling pressures. In general, calcium-channel blockers exert favorable effects on LVH, and do not worsen insulin resistance or exert detrimental effects on the lipid profile.
Nifedipine is administered orally and sublingually. It is relatively well distributed, including into breast milk. Nifedipine is protein-bound in a concentration-dependent way, ranging from 92% to 98%. Hepatic metabolism is rapid and complete, causing the formation of 2 inactive metabolites that, along with the parent drug, are excreted primarily in the urine and, to a lesser extent, the feces. Less than 5% is eliminated as unchanged drug. The elimination half-life of nifedipine is approximately 2 to 5 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
Nifedipine is a CYP3A4 substrate, and its metabolism may be affected by CYP3A4 inhibitors or inducers.
Nifedipine is rapidly and well absorbed (90%) following an oral dose but undergoes extensive first-pass metabolism, resulting in a bioavailability of 50% to 70%. The bioavailability of the sustained-release tablet ("gastrointestinal therapeutic system [GITS]") relative to the capsule is 86% after chronic administration. The bioavailability of nifedipine does not appear to be affected by food. Co-administration of nifedipine with grapefruit juice increases the AUC and peak plasma concentrations of nifedipine by 2-fold, with no change in half-life. Bioavailability is substantially increased (up to a 100% increase) in the presence of hepatic impairment. Decreases in gastrointestinal transit time can significantly alter the absorption characteristics of the sustained-release formulation in a relatively unpredictable fashion by increasing the time available for the osmotically driven release to occur.
Sublingual administration of nifedipine liquid (expressed from regular-release capsules) to achieve rapid decreases in blood pressure, such as in the case of hypertensive urgency, has generated much controversy and confusion and is not recommended. There is little difference in the bioavailability when nifedipine capsules are swallowed whole or if they are bitten and swallowed, or bitten and held sublingually. Biting through the capsule does, however, result in slightly earlier plasma concentrations (within 10 minutes) than if capsules were swallowed intact.
Onset of hypotensive effects occurs in 30 minutes to 1 hour after administration of regular-release capsules, with peak effects occurring within 30 minutes to 2 hours. With the sustained-release tablet, serum concentrations do not peak for 6 hours, and hypotensive effects are correspondingly delayed. Duration of pharmacodynamic activity for the immediate-release preparation is approximately 8 hours. The extended-release tablet is designed to release nifedipine continuously in a zero-order process. Once-daily dosing is possible with this dosage form.
Bioavailability is substantially increased (up to a 100% increase) in the presence of hepatic impairment. Protein binding is significantly reduced in patients with hepatic dysfunction. In patients with clinically significant hepatic impairment, the half-life increases to an average of 7 hours with accumulation of plasma nifedipine concentrations.
Protein binding is significantly reduced in patients with hepatic dysfunction. Nifedipine is minimally removed by hemodialysis or hemoperfusion.
Age significantly affects the pharmacokinetics of nifedipine. In healthy subjects, the clearance of nifedipine after intravenous administration was decreased by 33% in the elderly compared to younger subjects. These changes are not due to changes in renal function.
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