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NIFEdipine


General


Pronunciation

(nye FED i peen)


Brand Names: U.S.

  • Adalat CC
  • Afeditab CR
  • Nifediac CC [DSC]
  • Nifedical XL
  • Procardia
  • Procardia XL

Indications


Use: Labeled Indications

Management of chronic stable or vasospastic angina; treatment of hypertension (sustained release products only)

The 2014 guideline for the management of high blood pressure in adults (JNC 8) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients (JNC 8 [James, 2013]):

- Patients ≥60 years of age with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg.

- Patients <60 years of age with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

- Patients ≥18 years of age with diabetes with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

- Patients ≥18 years of age with chronic kidney disease (CKD) with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

In patients with chronic kidney disease (CKD), regardless of race or diabetes status, the use of an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) as initial therapy is recommended to improve kidney outcomes. In the general nonblack population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic, calcium channel blocker, ACEI, or ARB. In the general black population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic or a calcium channel blocker instead of an ACEI or ARB.


Contraindications


Hypersensitivity to nifedipine or any component of the formulation; concomitant use with strong CYP3A4 inducers (eg, rifampin); cardiogenic shock

Note: Considered contraindicated in patients with ST-elevation myocardial infarction (STEMI) (ACCF/AHA [OGara, 2013]).

Canadian labeling: Additional contraindications (not in U.S. labeling): Severe hypotension; patients with a Kock pouch (ileostomy after proctocolectomy; extended release tablets only); breast-feeding; pregnancy or women of childbearing potential. Note: SOGC and ACOG guidelines recommend nifedipine as a preferred agent for maternal hypertension (ACOG, 2013; SOGC [Magee, 2014]).


Dosing and Administration


Dosing: Adult

Dosage adjustments should occur at 7- to 14-day intervals to allow for adequate assessment of new dose; however, if clinically indicated, titration may be done more rapidly with appropriate monitoring; when switching from immediate-release to sustained-release formulations, use same total daily dose.

Chronic stable or vasospastic angina: Oral:

Immediate release: Initial: 10 mg 3 times daily; usual dose: 10 to 20 mg 3 times daily; coronary artery spasm may require up to 20 to 30 mg 3 to 4 times daily; single doses >30 mg and total daily doses >120 mg are rarely needed; maximum: 180 mg daily (U.S. labeling) or 120 mg daily (Canadian labeling); Note: Do not use for acute anginal episodes; may precipitate myocardial infarction

Extended release:

US labeling: Initial: 30 or 60 mg once daily; titrate as clinically indicated. Doses >90 mg daily should be used with caution and only if necessary (maximum: 120 mg daily)

Canadian labeling: Initial: 30 mg once daily; titrate as clinically indicated (maximum dose: 90 mg daily)

Hypertension: Oral: Extended release:

U.S. labeling: Initial: 30 or 60 mg once daily; usual dosage range (ASH/ISH [Weber, 2014]): 30 to 90 mg daily; maximum: 90 to 120 mg daily

Canadian labeling: Initial: 20 or 30 mg once daily; usual maintenance: 30 to 60 mg once daily (maximum: 90 mg daily)

Hypertension emergency in pregnancy (systolic BP ≥160 mm Hg or diastolic BP ≥110 mm Hg) (off-label dose): Oral: Immediate release: 10 mg; may repeat with a 20 mg dose in 20 minutes if needed. Also refer to administration protocols developed by the American College of Obstetricians and Gynecologists (ACOG, 2015).

High altitude pulmonary edema (off-label use; Luks, 2010): Oral:

Prevention: Extended release: 30 mg every 12 hours starting the day before ascent and may be discontinued after staying at the same elevation for 5 days or if descent initiated

Treatment: Extended release: 30 mg every 12 hours

Pulmonary hypertension (off-label use; Galie, 2004): Oral: Extended release: Initial: 30 mg twice daily; may increase cautiously to 120 to 240 mg daily

Raynaud 's phenomenon (off-label use; Wigley, 2002): Oral: Extended release: Dosage range: 30 to 120 mg once daily


Dosing: Geriatric

Refer to adult dosing. In the management of hypertension, consider lower initial doses and titrate to response (Aronow, 2011).


Dosing: Pediatric

High altitude pulmonary edema (off-label use; Pollard, 2001): Oral: Note: Treatment with NIFEdipine is only necessary if response to oxygen and/or descent is unsatisfactory; extended release preparation is preferred, but with proper dose and frequency adjustment:

Immediate release: 0.5 mg/kg/dose (maximum: 20 mg/dose) every 8 hours

Hypertension (off-label use): Oral: Children 1 to 17 years: Extended release tablet: Initial: 0.2 to 0.5 mg/kg/day once daily or in 2 divided doses; maximum: 3 mg/kg/day up to 120 mg daily


Dosing: Renal Impairment

There are no dosage adjustments provided in manufacturer 's labeling (has not been studied); the pharmacokinetics of nifedipine are not significantly influenced by the degree of renal impairment (only trace amounts of unchanged drug are found in urine).

Hemodialysis: Supplemental dose is not necessary.

Peritoneal dialysis effects: Supplemental dose is not necessary.


Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer 's labeling (has not been studied); use with caution. Clearance of nifedipine is reduced in cirrhotic patients, which may lead to increased systemic exposure; monitor closely for adverse effects/toxicity and consider dose adjustments.


Administration

Immediate release: In general, may be administered with or without food.

Extended release: Tablets should be swallowed whole; do not crush, split, or chew.

Adalat CC, Afeditab CR, Nifediac CC: Administer on an empty stomach (per manufacturer). Other extended release products may not have this recommendation; consult product labeling.


Dietary Considerations

Avoid grapefruit juice with all products.

Immediate release: Capsule is rapidly absorbed orally if it is administered without food, but may result in vasodilator side effects; if flushing is problematic, administration with low-fat meals may decrease. In general, can take with or without food.

Extended release: Adalat CC, Afeditab CR, Nifediac CC: Take on an empty stomach (manufacturers labeling). Other extended release products may not have this recommendation; consult product labeling.


Storage

Adalat CC, Afeditab CR, Procardia XL: Store below 30 � �C (86 � �F); protect from light and moisture.

Nifediac CC, Nifedical XL: Store at 25 � �C (77 � �F); excursions permitted to 15 � �C to 30 � �C (59 � �F to 86 � �F); protect from light and moisture.

Immediate release capsules (Procardia): Store at 15 � �C to 25 � �C (59 � �F to 77 � �F); prevent capsules from freezing; protect from light and moisture.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Procardia: 10 mg

Generic: 10 mg, 20 mg

Tablet Extended Release 24 Hour, Oral:

Adalat CC: 30 mg, 60 mg, 90 mg

Afeditab CR: 30 mg, 60 mg

Nifediac CC: 30 mg [DSC], 60 mg [DSC]

Nifediac CC: 90 mg [DSC] [contains tartrazine (fd&c yellow #5)]

Nifedical XL: 30 mg, 60 mg

Procardia XL: 30 mg, 60 mg, 90 mg

Generic: 30 mg, 60 mg, 90 mg


Extemporaneously Prepared

A 4 mg/mL oral suspension may be made with liquid capsules (Note: Concentration inside capsule may vary depending on manufacturer. Procardia: 10 mg capsule contains a concentration of 10 mg/0.34 mL [29.4 mg/mL]). Puncture the top of twelve 10 mg liquid capsules with one needle to create a vent. Insert a second needle attached to a syringe and extract the liquid; transfer to a calibrated bottle and add sufficient quantity of a 1:1 mixture of Ora-Sweet and Ora-Plus to make 30 mL. Label shake well". Stable 90 days under refrigeration or at room temperature.

Nahata MC, Morosco RS, and Willhite EA, "Stability of Nifedipine in Two Oral Suspensions Stored at Two Temperatures," J Am Pharm Assoc, 2002, 42(6):865-7.

Drug Interactions

Alcohol (Ethyl): May increase the serum concentration of NIFEdipine. Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs. Management: Concurrent use of felodipine or nisoldipine with itraconazole is specifically contraindicated. Frequent monitoring is warranted with any such combination; calcium channel blocker dose reductions may be required. Exceptions: Fluconazole; Isavuconazonium Sulfate. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Beta-Blockers: NIFEdipine may enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Monitor therapy

Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Management: Consider alternatives to cimetidine. If no suitable alternative exists, monitor for increased effects of calcium channel blockers following cimetidine initiation/dose increase, and decreased effects following cimetidine discontinuation/dose decrease. Consider therapy modification

Cisapride: May increase the serum concentration of NIFEdipine. Reported with sustained release nifedipine product. Monitor therapy

Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CycloSPORINE (Systemic): May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of NIFEdipine. Avoid combination

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Monitor therapy

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Digoxin: NIFEdipine may increase the serum concentration of Digoxin. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Efavirenz: May decrease the serum concentration of Calcium Channel Blockers. Monitor therapy

Fluconazole: May increase the serum concentration of Calcium Channel Blockers. Monitor therapy

FLUoxetine: May enhance the adverse/toxic effect of NIFEdipine. Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Grapefruit Juice: May increase the serum concentration of NIFEdipine. Avoid combination

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification

Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nafcillin: May increase the metabolism of Calcium Channel Blockers. Consider therapy modification

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phenytoin: NIFEdipine may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of NIFEdipine. Avoid combination

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

QuiNIDine: Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

St Johns Wort: May decrease the serum concentration of NIFEdipine. Avoid combination

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

VinCRIStine: NIFEdipine may increase the serum concentration of VinCRIStine. Monitor therapy

VinCRIStine (Liposomal): NIFEdipine may increase the serum concentration of VinCRIStine (Liposomal). Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy


Monitoring Parameters

Heart rate, blood pressure, signs and symptoms of CHF, peripheral edema


Adverse Reactions


>10%:

Cardiovascular: Flushing (10% to 25%; extended release products 3% to 4%), peripheral edema (dose related 7% to 30%)

Central nervous system: Dizziness/lightheadedness/giddiness (10% to 27%), headache (10% to 23%)

Gastrointestinal: Nausea/heartburn (10% to 11%)

≥1% to 10%:

Cardiovascular: Palpitation ( ≤2% to 7%), transient hypotension (dose related 5%), CHF (2%)

Central nervous system: Nervousness/mood changes ( ≤2% to 7%), fatigue (6%), shakiness ( ≤2%), jitteriness ( ≤2%), sleep disturbances ( ≤2%), difficulties in balance ( ≤2%), fever ( ≤2%), chills ( ≤2%)

Dermatologic: Dermatitis ( ≤2%), pruritus ( ≤2%), urticaria ( ≤2%)

Endocrine & metabolic: Sexual difficulties ( ≤2%)

Gastrointestinal: Diarrhea ( ≤2%), constipation ( ≤2%), cramps ( ≤2%), flatulence ( ≤2%), gingival hyperplasia ( ≤10%)

Neuromuscular & skeletal: Muscle cramps/tremor ( ≤2% to 8%), weakness (<3%), inflammation ( ≤2%), joint stiffness ( ≤2%)

Ocular: Blurred vision ( ≤2%)

Respiratory: Cough/wheezing (6%), nasal congestion/sore throat ( ≤2% to 6%), chest congestion ( ≤2%), dyspnea ( ≤2%)

Miscellaneous: Diaphoresis ( ≤2%)

<1% (Limited to important or life-threatening): Agranulocytosis, allergic hepatitis, alopecia, anemia, angina, angioedema, aplastic anemia, arrhythmia, arthritis with positive ANA, bezoars (Procardia XL � �), cerebral ischemia, depression, dysosmia, epistaxis, EPS, erectile dysfunction, erythema multiforme, erythromelalgia, exanthematous pustulosis, exfoliative dermatitis, facial edema, gastroesophageal reflux, gastrointestinal obstruction (Procardia XL � �), gastrointestinal ulceration (Procardia XL � �), gynecomastia, hematuria, ischemia, leukopenia, lip cancer (Friedman, 2012), memory dysfunction, migraine, myalgia, myoclonus, nocturia, paranoid syndrome, parotitis, periorbital edema, photosensitivity, polyuria, purpura, Stevens-Johnson syndrome, syncope, tachycardia, taste perversion, thrombocytopenia, tinnitus, toxic epidermal necrolysis, transient blindness, ventricular arrhythmia

Reported with use of sublingual short-acting nifedipine: Acute MI, cerebrovascular ischemia, ECG changes, fetal distress, heart block, severe hypotension, sinus arrest, stroke, syncope


Warnings/Precautions


Special Populations: Elderly

Mean Cmax is 36% higher and plasma concentration is 70% greater in elderly patients.


Warnings/Precautions

Concerns related to adverse effects:

- Angina/MI: Increased angina and/or MI have occurred with initiation or dosage titration of dihydropyridine calcium channel blockers. Reflex tachycardia may occur resulting in angina and/or MI in patients with obstructive coronary disease, especially in the absence of concurrent beta-blockade. In patients with unstable angina/non-STEMI, the use of immediate-release nifedipine is not recommended except with concomitant beta-blockade (ACCF/AHA [Anderson, 2013]).

- Hypotension/syncope: Symptomatic hypotension with or without syncope can rarely occur; blood pressure must be lowered at a rate appropriate for the patients clinical condition. The use of immediate release nifedipine (sublingually or orally) in hypertensive emergencies and urgencies is neither safe nor effective. Serious adverse events (eg, death, cerebrovascular ischemia, syncope, stroke, acute myocardial infarction, and fetal distress) have been reported. Immediate release nifedipine should not be used for acute blood pressure reduction.

- Peripheral edema: The most common side effect is peripheral edema; occurs within 2-3 weeks of starting therapy.

Disease-related concerns:

- Aortic stenosis: Use with extreme caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in myocardial ischemia.

- Gastrointestinal strictures: Alterations in gastrointestinal anatomy (eg, severe gastrointestinal narrowing, history of GI cancer, obstruction, bowel resection, gastric bypass, vertical banded gastroplasty) and underlying hypomotility disorders have led to bezoar formation with extended release forms.

- Heart failure (HF): The ACCF/AHA heart failure guidelines recommend to avoid use in patients with heart failure due to lack of benefit and/or worse outcomes with calcium channel blockers in general (Yancy, 2013).

- Hepatic impairment: Use with caution in patients with hepatic impairment. Clearance of nifedipine is reduced in cirrhotic patients leading to increased systemic exposure; monitor closely for adverse effects/toxicity and consider dose adjustments.

- Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

- Extended release formulation: Consists of drug within a nondeformable matrix; following drug release/absorption, the matrix/shell is expelled in the stool. The use of nondeformable products in patients with known stricture/narrowing of the GI tract (eg, severe gastrointestinal narrowing, colon cancer, obstruction, bowel resection, gastric bypass, vertical banded gastroplasty) has been associated with symptoms of obstruction (pharmacobezoar).

- Immediate release formulation: Immediate release formulations should not be used to manage primary hypertension, adequate studies to evaluate outcomes have not been conducted.

- Lactose: Adalat CC tablets contain lactose; do not use with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndromes.

Other warnings/precautions:

- Surgery: Use with caution before major surgery. Cardiopulmonary bypass, intraoperative blood loss or vasodilating anesthesia may result in severe hypotension and/or increased fluid requirements. Consider withdrawing nifedipine (>36 hours) before surgery if possible.

- Withdrawal: Abrupt withdrawal may cause rebound angina in patients with CAD.


Pregnancy Risk Factor

C


Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Nifedipine crosses the placenta and small amounts can be detected in the urine of newborn infants (Manninen, 1991; Silberschmidt, 2008). An increase in perinatal asphyxia, cesarean delivery, prematurity, and intrauterine growth retardation have been reported following maternal use. Untreated chronic maternal hypertension is also associated with adverse events in the fetus, infant, and mother. If treatment for chronic hypertension during pregnancy is needed, nifedipine is one of the preferred agents (ACOG, 2013; SOGC [Magee, 2014]). Nifedipine is also recommended for the management of acute onset, severe hypertension (systolic BP ≥160 mm Hg or diastolic BP ≥110 mm Hg) with preeclampsia or eclampsia in pregnant and postpartum women (ACOG, 2015; Magee, 2014).

Nifedipine has also been evaluated for the treatment of preterm labor. Tocolytics may be used for the short-term (48 hour) prolongation of pregnancy to allow for the administration of antenatal steroids and should not be used prior to fetal viability or when the risks of use to the fetus or mother are greater than the risk of preterm birth (ACOG, 2012). Nifedipine is ineffective for maintenance tocolytic therapy (ACOG, 2012; Roos, 2013).


Actions


Pharmacology

Inhibits calcium ion from entering the "slow channels " � or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing a relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina; also reduces peripheral vascular resistance, producing a reduction in arterial blood pressure.


Metabolism

Hepatic via CYP3A4 to inactive metabolites


Excretion

Urine (60% to 80% as inactive metabolites); feces


Onset of Action

Immediate release: ~20 minutes


Half-Life Elimination

Adults: Healthy: 2 to 5 hours; Cirrhosis: 7 hours; Elderly: 7 hours (extended release tablet)


Protein Binding

Concentration dependent: 92% to 98%; Note: Protein-binding may be significantly decreased in patients with renal or hepatic impairment


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?

- Patient may experience headache, flushing, heartburn, nausea, loss of strength and energy, anxiety, or tablet shell in stool. Have patient report immediately to prescriber severe dizziness; passing out; arrhythmia; mood changes; shortness of breath; excessive weight gain; swelling of arms or legs; muscle pain; muscle cramps; tremors; severe abdominal pain; black, tarry, or bloody stools; or vomiting blood (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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