No

Calcium Channel Blocker

Treatment of hypertension and angina

C

Teratogenic and embryotoxic effects have been demonstrated in small animals. No well controlled studies have been conducted in pregnant women. Use in pregnancy only when clearly needed and when the benefits outweigh the potential hazard to the fetus.

Breast-feeding/lactation: No data on crossing into breast milk

Hypersensitivity to amlodipine or any component

Increased angina and/or MI has occurred with initiation or dosage titration of calcium channel blockers. Use caution in severe aortic stenosis. Use caution in patients with severe hepatic impairment. Safety and efficacy in children have not been established. Dosage titration should occur after 7-14 days on a given dose.

>10%: Cardiovascular: Peripheral edema (1.8% to 14.6% dose-related)

1% to 10%:

Central nervous system: Flushing (0.7% to 2.6%), palpitations (0.7% to 4.5%), headache (7.3%; similar to placebo)

Dermatologic: Rash (1% to 2%), pruritus (1% to 2%)

Endocrine & metabolic: Male sexual dysfunction (1% to 2%)

Gastrointestinal: Nausea (2.9%), abdominal pain (1% to 2%), dyspepsia (1% to 2%), gingival hyperplasia

Neuromuscular & skeletal: Muscle cramps (1% to 2%), weakness (1% to 2%)

Respiratory: Shortness of breath (1% to 2%), pulmonary edema (15% from PRAISE trial, CHF population)

<1%: Hypotension, bradycardia, arrhythmias, syncope, tachycardia, vasculitis, nervousness, insomnia, malaise, weight gain, anorexia, diarrhea, pancreatitis, constipation, vomiting, xerostomia, flatulence, micturition disorder, joint stiffness, paresthesia, peripheral neuropathy, tremor, tinnitus, chest pain, hypotension, peripheral ischemia, postural hypotension, postural dizziness, hypoesthesia, vertigo, dysphagia, back pain, hot flushes, pain, rigors, arthrosis, myalgia, female sexual dysfunction, depression, abnormal dreams, anxiety, depersonalization, epistaxis, rash erythematous, angioedema, erythema multiforme, rash maculopapular, abnormal vision, conjunctivitis, diplopia, eye pain, micturition frequency, nocturia, increased sweating, thirst, hyperglycemia, purpura, allergic reactions, leukopenia, thrombocytopenia

<0.1% (Limited to important or life-threatening symptoms): Cardiac failure, pulse irregularity, extrasystoles, skin discoloration, urticaria, skin dryness, alopecia, dermatitis, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, coughing, rhinitis, dysuria, polyuria, parosmia, taste perversion, abnormal visual accommodation, xerophthalmia

Case reports: Nonthrombocytopenic purpura, leukocytoclastic vasculitis, EPS, gynecomastia, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis, dysosmia, phototoxicity

The primary cardiac symptoms of calcium blocker overdose includes hypotension and bradycardia. The hypotension is caused by peripheral vasodilation, myocardial depression, and bradycardia. Bradycardia results from sinus bradycardia, second- or third-degree atrioventricular block, or sinus arrest with junctional rhythm. Intraventricular conduction is usually not affected so QRS duration is normal (verapamil does prolong the P-R interval and bepridil prolongs the Q-T and may cause ventricular arrhythmias, including torsade de pointes).

In a few reported cases, overdose with calcium channel blockers has been associated with hypotension and bradycardia, initially refractory to atropine but becoming more responsive to this agent when larger doses (approaching 1 gram per hour for more than 24 hours) of calcium chloride was administered.

CYP3A3/4 enzyme substrate

Calcium may reduce the calcium channel blocker's effects, particularly hypotension.

Rifampin increases the metabolism of calcium channel blockers; adjust the dose of calcium channel blocker to maintain efficacy.

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

Onset of action: 30-50 minutes

Peak effect: 6-12 hours

Duration: 24 hours

Absorption: Oral: Well absorbed

Protein binding: 93%

Metabolism: Hepatic, >90% to inactive compound

Bioavailability: 64% to 90%

Half-life: 30-50 hours

Elimination: Metabolite and parent drug excreted renally

Adults: Oral:

Angina: Usual dose: 5-10 mg; use lower doses for elderly or those with hepatic insufficiency (eg, 2.5-5 mg).

Dialysis: Hemodialysis and peritoneal dialysis does not enhance elimination. Supplemental dose is not necessary.

Dosage adjustment in hepatic impairment: Administer 2.5 mg once daily.

Amlodipine therapy should be continued for 4-6 weeks before the dose is increased. Daily doses >10 mg are associated with an increase in side effects (eg, edema) without further reductions in blood pressure. Amlodipine may be used safely to treat hypertension and/or angina in patients with heart failure. In a study that addressed amlodipine therapy in severe heart failure, cardiovascular morbidity was decreased significantly in a subset of patients with nonischemic heart failure. This finding is being addressed in an ongoing trial (PRAISE-II).

May cause drowsiness; rarely may produce insomnia and nervousness

None reported

No information available to require special precautions

Calcium channel blockers (CCBs) cause gingival hyperplasia in ~1% of patients. There have been fewer reports with amlodipine than with other CCBs. The hyperplasia will usually disappear with cessation of drug therapy; consultation with physician is suggested.

Take as prescribed; do not stop abruptly without consulting prescriber. You may experience headache (if unrelieved, consult prescriber), nausea or vomiting (frequent small meals may help), or constipation (increased dietary bulk and fluids may help). May cause drowsiness; use caution when driving or engaging in tasks that require alertness until response to drug is known. Report unrelieved headache, vomiting, constipation, palpitations, peripheral or facial swelling, weight gain >5 lb/week, or respiratory changes. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Inform prescriber if breast-feeding.

Do not discontinue abruptly; report any dizziness, shortness of breath, palpitations, or edema

Tablet: 2.5 mg, 5 mg, 10 mg

A 1 mg/mL suspension was stable for 91 days when refrigerated or 56 days when kept at room temperature when compounded as follows:

Vehicle 1. Methylcellulose 1% (125 mL) and Simple Syrup N.F. (125 mL) mixed together in a graduate, or

Vehicle 2. Ora-Sweet® (125 mL) and Ora-Plus® (125 mL) mixed together in a graduate

Shake well before using and keep in refrigerator

Nahata MC, Morosco RS, and Hipple TF, Stability of Amlodipine in Two Liquid Dosage Forms, American Society of Health System Pharmacists Midyear Meeting, December 7-11, 1997.

Jorgensen MG, "Prevalence of Amlodipine-Related Gingival Hyperplasia," J Periodontol, 1997, 68(7):676-8.

Wynn RL, "An Update on Calcium Channel Blocker-Induced Gingival Hyperplasia," Gen Dent, 1995, 43(3):218-22.

Wynn RL, "Calcium Channel Blockers and Gingival Hyperplasia," Gen Dent, 1991, 39(4):240-3.