Amlopine

Amlodipine besylate.

Amlopine: Each tablet contains amlodipine besylate equivalent to amlodipine 5 mg.
Amlopine 10: Each tablet contains amlodipine besylate equivalent to amlodipine 10 mg.

Pharmacodynamics: Mechanism of Action: Amlodipine besylate is a long-acting dihydropyridine calcium channel blocker that exerts its effect by blocking the transmembrane influx of calcium ions into cardiac and vascular smooth muscles. It also reduces peripheral vascular resistance and lowers blood pressure by causing a direct vasodilation in the peripheral arteries of the vascular smooth muscle. Its therapeutic effect on vasospastic angina is through inhibition of coronary spasm.
Pharmacokinetics: Onset and Duration: Onset: Initial Response: Hypertension, oral: 24 to 96 hours.
Duration: Multiple Dose: Hypertension, oral: 24 to 48 hours.
Drug Concentration Levels: Time to Peak Concentration: Oral, immediate release: 6 to 9 hours.
Mean peak serum levels are linear and age-independent.
Steady-state serum levels have been observed after 7 to 8 days of chronic administration.
Absorption: Bioavailability: 64% to 90%, not affected by food.
Distribution: Amlodipine has high tissue affinity with large volume of distribution (V_d), V_d: 21 L/kg.
Protein binding is 93% to 98%.
Metabolism: Extensively metabolized to inactive metabolites in the liver (>90%).
Excretion: Renal: 60% as metabolites, 5 to 10% unchanged.
Feces, 20% to 25%.
Elimination Half Life: About 30 to 50 hours.
Impaired hepatic function: 56 hours.

Treatment of hypertension; Treatment of myocardial ischemia whether due to fixed obstruction (chronic stable angina), vasospasm/vasoconstriction angina (Prinzmetal's or variant angina) of coronary vasculature; Reduce the risk of coronary revascularization and prevention of hospitalization due to angina with documented coronary artery disease (limited to patients without heart failure or ejection fraction <40%).

Recommended Doses: Adult: Hypertension: initial, 5 mg orally once daily; maintenance 5-10 mg orally once daily.
Stable angina: 5-10 mg orally once daily.
Variant angina: 5-10 mg orally once daily.
Coronary artery disease: 5-10 mg orally once daily.
Pediatric: Safety and efficacy not established in pediatric patients younger than 6 years of age.
Hypertension: 6 to 17 years of age, 2.5-5 mg orally once daily.
Dosage in Geriatric Patients: Begin therapy at 2.5 mg daily for hypertension and 5 mg for angina.
Dosage in Renal Failure: Dosage adjustments of amlodipine are not required in patients with renal impairment.
Dosage in Hepatic Insufficiency: Amlodipine is extensively metabolized in the liver, which results in a slight reduction of clearance in the presence of hepatic impairment. Dosage adjustments may be required in patients with liver disease. Begin therapy at 2.5 mg daily for hypertension and 5 mg for angina.
Dosage Adjustment During Dialysis: Hemodialysis: The pharmacokinetics of amlodipine have not been significantly altered in hemodialysis patients, and dosage adjustments do not appear to be required.
Peritoneal Dialysis: Dosage adjustments are not needed for chronic ambulatory peritoneal dialysis.
Mode of Administration: Oral: may be administered without regard to meals.

There is no specific treatment for over dosage, hence symptomatic and supportive treatment should be provided.

Amlodipine is contraindicated in those patients who are hypersensitive to amlodipine or any component of the formulation.

Increased angina and/or Myocardial Infarction (MI) has occurred with initiation or dosage titration of calcium channel blockers.
Symptomatic hypotension with or without syncope can rarely occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition.
Use caution in severe aortic stenosis and/or hypertrophic cardiomyopathy.
Use caution in patients with hepatic impairment.
The most common side effect is peripheral edema; occurs within 2-3 weeks of starting therapy. Reflex tachycardia may occur with use.
Dosage titration should occur after 7-14 days on a given dose.
Use in Children: Safety and efficacy have not been established in children <6 years of age.
Use in the Elderly: Initiate at a lower dose in the elderly.

Pregnancy: Category C.
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.
Lactation: It is not known whether amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while amlopine is administered to nursing women.

Very common Adverse Reaction (>10%): Cardiovascular: Dose dependent peripheral edema is the most common adverse effect of amlodipine: the incidence of edema was 10.8% at 10 mg daily, 3% at 5 mg daily, and 1.8% at 2.5 mg daily compared to 0.6% with placebo.
Common Adverse Reaction (1% to 10%): Cardiovascular: flushing, palpitation.
Central nervous system: headache, dizziness, fatigue, somnolence.
Dermatologic: rash, pruritus.
Endocrine & metabolic: male sexual dysfunction.
Gastrointestinal: nausea, abdominal pain, dyspepsia, gingival hyperplasia.
Neuromuscular & skeletal: muscle cramps, weakness.
Respiratory: dyspnea, pulmonary edema.
Common Adverse Reaction (<1%, limited to important or life-threatening): Abnormal dreams, agitation alopecia, amnesia, anxiety, apathy, arrhythmia, ataxia, bradycardia, cardiac failure, cholestasis, depersonalization, depression, erythema multiforme, exfoliative dermatitis, extrapyramidal symptoms, gastritis, gynecomastia, hepatitis, hypotension, purpura, rash, skin discoloration, Stevens-Johnson syndrome, syncope, thrombocytopenia, tinnitus, transaminases increased, urticaria, weight loss, vertigo, xerophthalmia.

Increased Effect/Toxicity: Amlodipine may increase the levels/effects of: amifostine, antihypertensives, CYP1A2 substrates, hypotensive agents, magnesium salts, neuromuscular-blocking agents (nondepolarizing), nitroprusside, phenytoin, rituximab, tacrolimus, tacrolimus systemic.
The levels/effects of amlodipine may be increased by: alpha1-blockers, antifungal agents (azole derivatives, systemic), calcium channel blockers (nondihydropyridine), cyclosporine, systemic, CYP3A4 inhibitors (moderate), CYP3A4 inhibitors (strong), dasatinib, diazoxide, fluconazole, grapefruit juice, herbs (hypotensive properties), macrolide antibiotics, magnesium salts, MAO inhibitors, pentoxifylline, phosphodiesterase-5 inhibitors, prostacyclin analogues, protease inhibitors, quinupristin.
Decreased Effect: Amlodipine may decrease the levels/effects of: clopidogrel, quinidine.
The levels/effects of amlodipine may be decreased by: barbiturates, calcium salts, carbamazepine, CYP3A4 inducers (strong), deferasirox, herbs (CYP3A4 inducers), herbs (hypertensive properties), methylphenidate, nafcillin, rifamycin derivatives, yohimbine.
Ethanol/Nutritional/Herb Interactions: Food: grapefruit juice may modestly increase amlodipine levels.
Herb/nutraceutical: St John's wort may decrease amlodipine levels. Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbine, ginseng (may worsen hypertension). Avoid garlic (may have increased antihypertensive effects).

Store below 30 °C.

Calcium Antagonists / Anti-Anginal Drugs

C08CA01 - amlodipine ; Belongs to the class of dihydropyridine derivative selective calcium-channel blockers with mainly vascular effects. Used in the treatment of cardiovascular diseases.

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