Amlodine HD

5 mg/20 mg: Each film-coated tablet contains: Amlodipine (as besilate) 5 mg, Atorvastatin (as calcium) 20 mg.
5 mg/40 mg: Each film-coated tablet contains: Amlodipine (as besilate) 5 mg, Atorvastatin (as calcium) 40 mg.
10 mg/20 mg: Each film-coated tablet contains: Amlodipine (as besilate) 10 mg, Atorvastatin (as calcium) 20 mg.
Amlodipine besilate and Atorvastatin calcium (AMLODINE HD) tablets combine the calcium channel blocker amlodipine besilate with the lipid-lowering agent atorvastatin calcium.
The amlodipine besilate component is chemically described as 3-ethyl-5methyl-(o-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylate, monobenzenesulphonate. Its empirical formula is C₂₀H₂₅ClN₂O₅-C₆H₆O₃S. The atorvastatin calcium component is chemically described as [R-(R*, R*)]2-(4- fluorophenyl)-βδ-dihydroxy-, 5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, calcium salt (2:1) trihydrate. Its empirical formula is (C₃₃H₃₄FN₂O₅)₂Ca-3H₂O.

Pharmacology: Pharmacokinetics: Amlodipine is well absorbed following oral administration with peak blood concentrations occurring after 6 to 12 hours. The bioavailability is 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.
Atorvastatin is rapidly absorbed from the gastrointestinal tract. It has low absolute bioavailability of about 12% due to presystemic clearance in the gastrointestinal mucosa and/or first-pass metabolism in the liver, its primary site of action. Atorvastatin is metabolized by the cytochrome P450 isoenzyme CYP3A4 to a number of compounds which are also active inhibitors of HMG-CoA reductase. The mean plasma elimination half-life of atorvastatin is about 14 hours although the half-life of inhibitory activity for HMG-CoA reductase is approximately 20 to 30 hours due to the contribution of the active metabolites. It is 98% bound to plasma proteins. Atorvastatin is excreted as metabolites, primarily in the bile.

For patients at increased cardiovascular risk due to the presence of hypertension & dyslipidemia, &/or symptomatic coronary heart disease expressed as angina & dyslipidemia. Prevention of cardiovascular complications in hypertensive patients eg. reduce risk of death, nonfatal myocardial infarction, stroke & risk of revascularization procedures & angina pectoris.

Individualize starting & maintenance doses. Dosage range of amlodipine/atorvastatin: 5 mg/20 mg, 10 mg/20 mg. Maximum amlodipine dose: 10 mg/day; maximum atorvastatin dose: 80 mg/day. Take this medication by mouth once daily with or without food.

Amlodipine: Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. If overdose should occur, begin active cardiac and respiratory monitoring. Perform frequent blood pressure measurements. Should hypotension occur, initiate cardiovascular support including elevation of the extremities and administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with specific attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.

Active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal. Pregnancy & lactation. Hypersensitivity.

Heart failure. Hepatic impairment & alcohol consumption. Skeletal muscle effects: Discontinue in patients w/ myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis.
Amlodipine should be used with caution in patients with hypotension, in patients whose cardiac reserve is poor, and in those with heart failure since deterioration of heart failure has been noted. It should not be used in cardiogenic shock, in patients who have recently suffered a myocardial infarction, or in acute unstable angina. It should not be used to treat an anginal attack in chronic stable angina. In patients with severe aortic stenosis it may increase the risk of developing heart failure. Sudden withdrawal might be associated with an exacerbation of angina. The dose may need to be reduced in patients with hepatic impairment. It should be discontinued in patients who experience ischaemic pain following its administration.
Atorvastatin should not be given to patients with active liver disease or unexplained persistently raised serum-aminotransferase concentrations and should be discontinued if marked or persistent increases in serum-aminotransferase concentrations occur. They should be avoided during pregnancy since there is a possibility that they could interfere with fetal sterol synthesis; there have been a number of reports of congenital abnormalities associated with statins. Statins may cause myopathy and rhabdomyolysis, especially at higher doses, and they should be used with caution in patient at risk of rhabdomyolysis, and particularly in patients taking drugs that increase plasma concentrations of the statin; the statin should be discontinued if creatine phosphokinase increases significantly or if myopathy is diagnosed. Some statins, such as fluvastatin, pravastatin, rosuvastatin, and simvastatin, should be used with caution in patients with severe renal impairment.

Amlodine HD contains atorvastatin and is therefore contraindicated in women who are pregnant or may become pregnant. The atorvastatin component may cause fetal harm when administered to a pregnant woman. Amlodine HD should be administered to women of child-bearing potential only when such patients are highly unlikely to conceive and have been informed of the potential hazards. If the woman becomes pregnant while taking Amlodine HD, it should be discontinued immediately and the patient advised again as to the potential hazards to the fetus, and the lack of known clinical benefit with continued use during pregnancy.

Amlodipine: Flushing, fatigue, edema, dizziness, headache, abdominal pain, nausea, palpitations, somnolence. The most common adverse effects are associated with its vasodilator action and often diminish on continued therapy. They include dizziness, flushing, headache, hypotension, peripheral edema, tachycardia, and palpitations. Nausea and other gastrointestinal disturbances, increased micturition frequency, lethargy, eye pain, and mental depression have also occurred. A paradoxical increase in ischaemic chest pain may occur at the start of treatment and in a few patients excessive fall in blood pressure has led to cerebral or myocardial ischaemia or transient blindness. There have been reports of rashes (including erythema multiforme), fever, and abnormalities in liver function, including cholestasis, due to hypersensitivity reactions. Gingival hyperplasia, myalgia, tremor, and impotence have been reported. Overdosage may be associated with bradycardia and hypotension.
Atorvastatin: GI disorders, myalgia, asthenia, nasopharyngitis, hyperglycemia, pharyngolaryngeal pain, epistaxis, musculoskeletal & connective tissue disorders. The commonest adverse effects of therapy with Atorvastatin and other statins are gastrointestinal disturbances. Other adverse effects reported include headache, skin rashes, dizziness, blurred vision, insomnia, and dysgeusia. Reversible increases in serum-aminotransferase concentrations may occur and liver function should be assessed before treatment is initiated and then monitored periodically until one year after the last elevation in dose. Hepatitis and pancreatitis have been reported. Hypersensitivity reactions including anaphylaxis and angioedema have also occurred. Myopathy, characterized by myalgia and muscle weakness and associated with increased creatine phosphokinase concentrations, has been reported, especially in patients taking statins concurrently with ciclosporin, fibric acid derivatives, or nicotinic acid. Rarely, rhabdomyolysis with acute renal failure may develop.

May enhance the antihypertensive effects of other antihypertensive drugs such as beta blockers although the combination is generally well tolerated. Enhanced antihypertensive effects may also be seen with concomitant use of drugs such as aldesleukin and antipsychotics that cause hypotension. Nifedipine may modify insulin and glucose responses and therefore diabetic patients may need to adjust their antidiabetic treatment when receiving amlodipine. It is extensively metabolized in the liver by the cytochrome P450 enzyme system, and interactions may occur with other drugs such as quinidine sharing the same metabolic pathway, and with enzyme inducers such as carbamazepine, phenytoin, and rifampicin, and enzyme inhibitors, such as cimetidine and erythromycin. The most serious consequence of drug interactions with Atorvastatin and other statins is the development of myopathy and rhabdomyolysis. Drugs that can cause myopathy when given alone increase the risk of myopathy with all statins: these drugs includes fibric acid derivatives (fibrates or gemfibrozil), and nicotinic acid. Atorvastatin is metabolized by Cytochrome P450 isoenzyme CYP3A4, as are simvastatin and lovastatin, and interactions may occur with drugs that inhibit this enzyme, including ciclosporin, itraconazole, ketoconazole, erythromycin, clarithromycin, HIV-protease inhibitors, nefazodone, amiodarone, and verapamil; there may also be similar interaction with grapefruit juice.

Store at temperatures not exceeding 30°C.

Calcium Antagonists / Dyslipidaemic Agents

C10BX03 - atorvastatin and amlodipine ; Belongs to the class of HMG CoA reductase inhibitors, other combinations.

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