amlodipine (Rx)

>10%

Edema (1.8-10.8%)

1-10%

Headache (7.3%)

Fatigue (4.5%)

Palpitations (0.7-4.5%)

Dizziness (1.1-3.4%)

Nausea (2.9%)

Flushing (0.7-2.6%)

Abdominal pain (1.6%)

Somnolence (1.4%)

Asthenia (1-2%)

Pruritus (1-2%)

Skin rash (1-2%)

Muscle cramps (1-2%)

Male sexual dysfunction (1-2%)

<1%

Cardiovascular: Arrhythmia (eg, ventricular tachycardia, atrial fibrillation), bradycardia, chest pain, peripheral ischemia, syncope, tachycardia, vasculitis

Central and peripheral nervous system: Hypoesthesia, neuropathy peripheral, paresthesia, tremor, vertigo

Gastrointestinal: Anorexia, constipation, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia

General: Allergic reaction, asthenia, back pain, hot flushes, malaise, pain, rigors, weight gain, weight decrease

Musculoskeletal system: Arthralgia, arthrosis, muscle cramps, myalgia

Psychiatric: Sexual dysfunction (male and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization

Respiratory system: dyspnea, epistaxis

Skin and appendages: Angioedema, erythema multiforme, pruritus, rash, rash erythematous, rash maculopapular

Special senses: Abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus

Urinary system: Micturition frequency, micturition disorder, nocturia

Autonomic nervous system: Dry mouth, sweating increased

Metabolic and nutritional: hyperglycemia, thirst

Hemopoietic: leukopenia, purpura, thrombocytopenia

Frequency not defined

Pulmonary edema (higher incidence in heart failure patients)

Postmarketing Reports

Extrapyramidal disorder

Jaundice and hepatic enzyme elevations (mostly consistent with cholestasis or hepatitis)

Gynecomastia

Contraindications

Hypersensitivity

Cautions

Symptomatic hypotension is possible, particularly with severe aortic stenosis; owing to gradual onset of action, acute hypotension unlikely

Worsening of angina and acute myocardial infarction (MI) can develop after dose is started or increased, particularly with severe obstructive CAD

Extensively metabolized by the liver and plasma elimination half-life is 56 hr in patients with hepatic impairment; titrate slowly when treating patients with severe hepatic impairment

Drug interaction overview

• Sildenafil: Monitor for hypotension when sildenafil is coadministered with amlodipine

• CYP3A4 Inhibitors

  • Coadministration with moderate or strong CYP3A inhibitors may increase systemic exposure to amlodipine and may require dose reduction
  • Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors

• CYP3A4 inducers

  • No information available on the quantitative effects of CYP3A4 inducers on amlodipine
  • Closely monitor blood pressure when amlodipine is coadministered with CYP3A4 inducers

• Simvastatin

  • Coadministration of simvastatin with amlodipine increases the systemic exposure of simvastatin
  • Limit simvastatin dose in patients on amlodipine 20 mg/day

• Immunosuppressants

  • Amlodipine may increase systemic exposure of cyclosporine or tacrolimus when coadministered
  • Frequent monitoring trough blood levels of cyclosporine and tacrolimus and adjust dose when appropriate

Pregnancy

Limited available data based on postmarketing reports are insufficient to inform a drug-associated risk for major birth defects and miscarriage during pregnancy

Clinical considerations

• Hypertension in pregnancy increases maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (eg, need for cesarean section, postpartum hemorrhage)
• Hypertension increases fetal risk for intrauterine growth restriction and intrauterine death
• Carefully monitor pregnant women with hypertension and manage accordingly

Lactation

Limited available data from a published clinical lactation study reports that amlodipine is present in human milk at an estimated median relative infant dose

No adverse effects of amlodipine on breastfed infant reported

There is no available information on effects of amlodipine on milk production

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.

Mechanism of Action

Inhibits transmembrane influx of extracellular calcium ions across membranes of myocardial cells and vascular smooth muscle cells without changing serum calcium concentrations; this inhibits cardiac and vascular smooth muscle contraction, thereby dilating main coronary and systemic arteries

Increases myocardial oxygen delivery in patients with vasospastic angina

Absorption

Bioavailability: 64-90%

Onset: 24-96 hr

Duration: 24 hr (antihypertensive effect)

Peak plasma time: 6-12 hr

Steady-state plasma levels are reached after 7-8 days of consecutive dosing

Distribution

Protein bound: 93-98%

Vd: 21 L/kg

Metabolism

Extensively metabolized in liver by CYP3A4

Metabolites: Pyridine analogue (inactive)

Elimination

Half-life: 30-50 hr

Excretion: Urine (10% [parent]; 60% [inactive metabolites])

Oral Administration

Take with or without food

Suspension: Shake well before using

Storage

Tablets: Store bottles at controlled room temperature, 15-30°C (59-86°F) and dispense in tight, light-resistant containers

Oral suspension: Refrigerate at 2-8°C (36-46°F); avoid freezing and excessive heat; protect from light