- ISCHEMIC HEART DISEASE DRUGS
- CARDIOVASCULAR DRUGS
- Pharmaceutical Form : Tablets
- Composition : Tab / Amlodipine (Besylate) 5 mg
- Active Substance : (Amlodipine (Besylate
Mechanism of action:
Amlodipine is a calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Serum calcium concentration is not affected by Amlodipine.
Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.
Amlodipine reduces the total peripheral resistance (afterload) against which the heart works and reduces the rate pressure product, and thus myocardial oxygen demand, at any given level of exercise. Vasospastic Angina: amlodipine has been demonstrated to block constriction and restore blood flow in coronary arteries and arterioles in response to calcium, potassium epinephrine, serotonin, and thromboxane A2 analog.
Absorption: Peak plasma concentrations of Amlodipine are reached 6-12 hours after administration of Amlodipine alone. Absolute bioavailability has been estimated to be between 64% and 90%. The bioavailability of Amlodipine is not altered by the presence of food.
Distribution: Approximately 93% of circulating Amlodipine is bound to plasma proteins in hypertensive patients.
Metabolism: Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine.
Elimination: Elimination of Amlodipine from the plasma is biphasic with a terminal elimination half-life of about 30-50 hours. Steady state plasma levels of Amlodipine are reached after 7-8 days of consecutive daily dosing.
Amlodipine is indicated for the treatment of these cases alone or in combination with other drugs:
- Coronary Artery Disease (CAD).
- Chronic Stable Angina.
- Vasospastic Angina (Prinzmetal’s or Variant Angina).
- Angiographically Documented CAD.
Amlodipine is contraindicated in patients with known sensitivity to amlodipine.
The most common side effects are headache and edema. incidence greater than 1.0% are : Headache , Fatigue , Nausea , Abdominal Pain ,Somnolence .
The following events occurred in <1% but >0.1% of patients in controlled clinical trials:
Cardiovascular: arrhythmia, bradycardia, chest pain, hypotension, peripheral ischemia, syncope, tachycardia, dizziness, and vasculitis.
Central and Peripheral Nervous System: hypoesthesia, neuropathy peripheral, paresthesia, tremor, and vertigo.
Gastrointestinal: anorexia, constipation, dyspepsia, 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 (male1 and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization.
Respiratory System: dyspnea, epistaxis.
Skin and Appendages: angioedema, erythema multiforme, pruritus, rash, erythematous rash maculopapular rash.
Special Senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus.
Urinary System: micturition frequency, micturition disorder, nocturia.
Autonomic Nervous System: dry mouth and sweating increased.
Metabolic and Nutritional: hyperglycemia, thirst.
Hemopoietic : leucopenia , purpura , thrombocytopenia.
Warning and precaution:
Hypotension: Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension is unlikely.
Increased Angina or Myocardial Infarction: Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of Amlodipine , particularly in patients with severe obstructive coronary artery disease.
Beta-Blocker Withdrawal: Amlodipine is not a beta-blocker and therefore gives no protection against the dangers of abrupt beta blocker withdrawal; any such withdrawal should be by gradual reduction of the dose of beta-blocker.
Patients with Hepatic Failure: Because Amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t1/2) is 56 hours in patients with impaired hepatic function, titrate slowly when administering Amlodipine to patients with severe hepatic impairment.
Pregnancy: Category C
There are no adequate and well-controlled studies in pregnant women. Amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
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 Amlodipine is administered.
In vitro data indicate Amlodipine has no effect on the human plasma protein binding of Digoxin, Phenytoin, Warfarin, and Indomethacin.
Simvastatin: Coadministration of Simvastatin with Amlodipine increases the systemic exposure of Simvastatin. Limit the dose of Simvastatin in patients on Amlodipine to 20 mg daily.
CYP3A4 Inhibitors: Coadministration with CYP3A4 inhibitors (moderate and strong) result in increased systemic exposure to Amlodipine warranting dose reduction. Monitor for symptoms of hypotension and edema in this coadministration withCYP3A4 inhibitors to determine the need for dose adjustment.
CYP3A4 Inducers: No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Blood pressure should be monitored when Amlodipine is coadministered with CYP3A4 inducers.
Cyclosporine: study in renal transplant patients showed on average of 40% increase in trough cyclosporine levels when concomitantly treated with amlodipine.
Dosage and administration:
Adults: The usual initial antihypertensive oral dose of Amlodipine is 5 mg once daily with a maximum dose of 10 mg once daily. Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily and this dose may be used when adding Amlodipine to other antihypertensive therapy.
Adjust dosage according to each patient’s need. In general, titration should proceed over 7 to 14 days so that the physician can fully assess the patient’s response to each dose level. Titration may proceed more rapidly, however, if clinically warranted, provided the patient is assessed frequently.
Angina: The recommended dose for chronic stable or vasospastic angina of Amlodipine is 5 to 10 mg, with the lower dose suggested in the elderly and in patients with hepatic insufficiency. Most patients will require 10 mg for adequate effect.
Coronary artery disease: The recommended dose range for patients with coronary artery disease is 5 to 10 mg once daily. In clinical studies, the majority of patients required 10 mg.
Children: The effective antihypertensive oral dose in pediatric patient’s ages 6 to 17 years is 2.5 mg to 5 mg once daily. Doses in excess of 5 mg daily have not been studied in pediatric patients.
Effect of Amlodipine on blood pressure in patients less than 6 years of age is not known.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing
range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of amlodipine with a resulting increase of AUC of approximately 40–60%, and a lower initial dose may be required.
Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia.
If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as Phenylephrine) with attention to circulating volume and urine output. As Amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.
How supplied: 30 tablets
Storage conditions :
Store at room tamperature less than 30°C.
Protect from light.