nifedipine (Procardia, Procardia XL, Adalat CC, Nifedical XL, Adalat, Afeditab CR, Nifediac CC)

Dosing and uses of Procardia, Procardia XL (nifedipine)

• Adult
• Pediatric
• Geriatric

 

Adult dosage forms and strengths

capsule

• 10mg
• 20mg

tablet, extended release

• 30mg
• 60mg
• 90mg

 

Angina

10 mg (conventional) PO q8hr or 30-60 mg (extended release) PO once daily initially; may be increased every 7-14 days PRn

Maintenance: 10-20 mg (conventional) PO q8hr up to 20-30 mg PO q6-8hr; not to exceed 180 mg/day (conventional) or 120 mg/day (extended release)

 

Hypertension

30-60 mg (extended release) PO once daily; may be increased every 7-14 days PRN; not to exceed 90 mg/day (Adalat CC) or 120 mg/day (Procardia XL)

 

Pulmonary Hypertension

30 mg (extended-release) PO q12hr; may be increased to 120-240 mg/day (monitor)

 

Raynaud Phenomenon (Off-label)

30-120 mg (extended release) PO once daily

 

Anal Fissures (Off-label)

0.2% topical gel/ointment (extemporaneously compounded) q12hr for 3-6 weeks

20 mg sublinguaL

 

Dosing Modifications

Peritoneal dialysis (PD) or hemodialysis (HD): Supplemental dose not necessary

Cirrhosis: Consider dose adjustment

 

Administration

Take on empty stomach

 

Pediatric dosage forms and strengths

capsule

• 10mg
• 20mg

tablet, extended release

• 30mg
• 60mg
• 90mg

Not FDA approved for children

Potential toxic dose in children <6 years: 2 mg/kg

 

Hypertension (Off-label)

0.25-0.5 mg/kg/day (extended release) PO in 1 or 2 daily doses initially; not to exceed 3 mg/kg/day (120 mg/day)

 

Geriatric dosage forms and strengths

Avoid conventional (ie, immediate-release) product; potential for hypotension and risk of precipitating myocardial ischemia

 

Angina

10 mg (conventional) PO q8hr or 30-60 mg (extended release) PO once daily initially; may be increased every 7-14 days PRn

Maintenance: 10-20 mg (conventional) PO q8hr up to 20-30 mg PO q6-8hr; not to exceed 180 mg/day (conventional) or 120 mg/day (extended release)

 

Hypertension

30-60 mg (extended release) PO once daily; may be increased every 7-14 days PRN; not to exceed 90 mg/day (Adalat CC) or 120 mg/day (Procardia XL)

 

Procardia, Procardia XL (nifedipine) adverse (side) effects

Adverse effects differ between short-acting (conventional) and extended-release formulations, with the conventional preparations having more serious adverse drug reactions in some cases

 

>10%

Peripheral edema (10-30%)

Dizziness (23-27%)

Flushing (23-27%)

Headache (10-23%)

Heartburn (11%)

Nausea (11%)

 

1-10%

Muscle cramps (8%)

Mood change (7%)

Nervousness (7%)

Cough (6%)

Dyspnea (6%)

Palpitations (6%)

Wheezing (6%)

Hypotension, transient (5%)

Urticaria (2%)

Pruritus (2%)

Constipation (<2%)

Chest pain (<2%)

 

Frequency not defined

Gingival hyperplasia

Agranulocytosis

Erectile dysfunction

 

Postmarketing Reports

Exfoliative or bullous skin adverse events (eg, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis)

Photosensitivity reactions

Acute generalized exanthematous pustulosis

 

Warnings

Contraindications

Hypersensitivity to nifedipine or other calcium-channel blockers

Cardiogenic shock

Concomitant administration with strong CYP3A4 inducers (eg, rifampin, rifabutin, phenobarbital, phenytoin, carbamazepine, St John's wort) significantly reduces nifedipine efficacy

Immediate release preparation (sublingually or orally) for urgent or emergent hypertension

 

Cautions

Use with caution in (≤4 weeks) myocardial infarction (MI), congestive heart failure (CHF), advanced aortic stenosis, peripheral edema, symptomatic hypotension, unstable angina, concurrent use of beta blockers, hepatic or renal impairment, persistent progressive dermatologic reactions, exacerbation of angina (during initiation of treatment, after a dose increase, or after withdrawal of beta blocker)

Short-acting nifedipine may be less safe than other calcium-channel blockers in management of angina, hypertension, or acute MI

Use cautiously in combination with quinidine

Conventional (short-acting) form not indicated for hypertension

Use extended-release form with caution in severe GI stenosis; rare reports of GI obstructive symptoms in patients with known strictures or without history of GI obstruction in association with ingestion of long-acting nifedipine; bezoars can occur in very rare cases and may necessitate surgical intervention

Extended-release form contains lactose; thus, patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine

Cirrhosis: Clearance reduced and systemic exposure increased

CYP3A inhibitors (eg, ketoconazole, fluconazole, itraconazole clarithromycin, erythromycin, grapefruit, nefazodone, saquinavir, indinavir, nelfinavir, ritonavir) may inhibit nifedipine metabolism and result in increased exposure when coadministered

Strong CYP3A inducers (eg, rifampin, rifabutin, phenobarbital, phenytoin, carbamazepine, and St John’s wort) may enhance nifedipine metabolism and result in decreased exposure when coadministered

Avoid use in heart failure due to lack of benefit, and/or worse outcomes with calcium channel blockers in generaL

Use with caution in patients with hypertrophic cardiomyopathy and outflow tract obstruction; reduction in afterload may worsen symptoms associated with this condition

Avoid use of immediate release formulation in the elderly; may cause hypotension and risk precipitating myocardial ischemia

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Drug is distributed into breast milk; manufacturer suggests discontinuing drug or refraining from nursing (however, American Academy of Pediatrics states that drug is safe for nursing)

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Procardia, Procardia XL (nifedipine)

Mechanism of action

Calcium-channel blocker; inhibits transmembrane influx of extracellular calcium ions across myocardial and vascular smooth muscle cell membranes without changing serum calcium concentrations; this results in inhibition of cardiac and vascular smooth muscle contraction, thereby dilating main coronary and systemic arteries

Vasodilation with decreased peripheral resistance and increased heart rate

 

Absorption

Bioavailability: Conventional, 40-77%; extended release, 65-89%

Onset: Conventional, 20 min; extended release, 30 min

Duration: Conventional, 8 hr; extended release, 24 hr

Peak plasma time: Conventional, 30-120 min; extended release, 6 hr (Procardia XL) or 2.5-5 hr (Adalat CC)

 

Distribution

Protein bound: 92-98%

Vd: 1.42-2.2 L/kg

 

Metabolism

Metabolized in liver by CYP3A4

Metabolites: Nitropyridine analogue (inactive)

 

Elimination

Half-life: Conventional, 2-5 hr; 7 hr in cirrhosis

Dialyzable: No dose adjustments necessary in HD or Pd

Excretion: Urine (60-80%), feces (20-40%)