Stadovas 5/Stadovas 10

Amlodipine besylate.

Each Stadovas 5 and Stadovas 10 tablet contains amlodipine (besylate) 5 mg and 10 mg, respectively.

Pharmacology: Pharmacodynamics: Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. 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.
Pharmacokinetics: Amlodipine is well absorbed following oral administration with peak blood concentrations occurring after 6 to 12 hours. The bioavailability varies but is usually about 60 to 65%. Amlodipine is reported to be about 97.5% bound to plasma proteins. It has a prolonged terminal elimination half-life of 35 to 50 hours and steady-state plasma concentrations are not achieved until after 7 to 8 days of administration. Amlodipine is extensively metabolised in the liver; metabolites are mostly excreted in urine together with less than 10% of a dose as unchanged drug. Amlodipine is not removed by dialysis.

Amlodipine is used alone or in combination with other classes of antihypertensive agents in the management of hypertension.
Amlodipine also is used for the management of Prinzmetal variant angina and chronic stable angina pectoris. The drug has been used alone or in combination with other antianginal agents.

Administration: Stadovas 5/Stadovas 10 is administered orally and may be given without regard to meals.
Dosage: Hypertension: Adults: The usual initial dosage of amlodipine is 2.5 - 5 mg once daily. In geriatric and small frail individuals, an initial dosage of 2.5 mg once daily is recommended. Subsequent dosage of amlodipine should be adjusted according to the patient's blood pressure response and tolerance and usually should not exceed 10 mg once daily. The usual maintenance dosage of amlodipine for the management of hypertension in adults is 5-10 mg once daily.
Children 6 years of age and older: The usual effective dosage of amlodipine is 2.5 - 5 mg once daily.
Angina: For the management of Prinzmetal variant angina or chronic stable angina, the usual adult dosage is 5-10 mg once daily. In geriatric patients, the lower dosage of 5 mg once daily is recommended. Maintenance dosage is 10 mg daily.

Single oral doses of amlodipine equivalent to 40 mg/kg and 100 mg/kg in mice and rats, respectively, caused deaths. Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia.
If massive overdosage occurs, active cardiac and respiratory monitoring should be instituted. 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, administration of vasopressors (such as phenylephrine) should be considered with attention to circulating volume and urine output. Intravenous calcium gluconate may help to reverse the effects of calcium entry blockade. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.

Patients who are hypersensitive to amlodipine, to any other calcium antagonist, or any ingredient in the formulation.

Amlodipine should be used with caution in patients with hypotension, poor cardiac reserve, heart failure.
The drug should not be used in cardiogenic shock, in patients who have suffered a myocardial infarction in the previous 2 to 4 weeks, or in acute unstable angina, in treatment of an anginal attack in chronic stable angina.
In patients with severe aortic stenosis, amlodipine may increase the risk of developing heart failure. Sudden withdrawal of amlodipine might be associated with an exacerbation of angina.
The dose may need to be reduced in patients with hepatic impairment.

No clinical experience with the preparation in pregnancy or lactation. Accordingly, amlodipine should not be administered during pregnancy, or lactation, or to women of childbearing potential unless effective contraception is used.

Common: Ankle oedema, flushing, headache, skin rash, and fatigue.
Uncommon: Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, hypotension, peripheral ischemia, syncope, tachycardia, postural dizziness, postural hypotension, vasculitis.
Central and peripheral nervous system: hypoesthesia, neuropathy peripheral, paresthesia, tremor, vertigo.
Gastrointestinal: anorexia, constipation, dyspepsia, 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, 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.

Amlodipine has been safely administered with thiazide diuretics, alpha blockers, beta-blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual glyceryl trinitrate, non-steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycaemic drugs.
Effect of other agents on amlodipine: Cimetidine, grapefruit juice, antacid: Co-administration of amlodipine and those had no significant effect on the pharmacokinetics of amlodipine.
Sildenafil: When amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect.
Effect of amlodipine on other agents: Atorvastatin, ethanol (alcohol): Co-administration of amlodipine with 80 mg atorvastatin or ethanol resulted in no significant change in the steady-state pharmacokinetics parameters of atorvastatin or ethanol.
Digoxin: Co-administration of amlodipine with digoxin did not change serum digoxin levels or digoxin renal clearance.
Warfarin: Co-administration of amlodipine with warfarin did not change the warfarin prothrombin response time.
Cyclosporine: Pharmacokinetics studies with cyclosporine have demonstrated that amlodipine does not significantly alter the pharmacokinetics of cyclosporine.

Store in a well-closed container, in a dry place, protect from light.
Do not store above 30°C.
Shelf-life: 36 months from the date of manufacturing.

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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