Each scored film- coated tablet contains Atorvastatin 20 mg and Amlodipine 5 mg.
The Amlodipine besylate is chemically described as 3- Ethyl-5- methyl(±) 2- [ (2-aminoethoxy)methyl] -4-(0-chlorophenyl)-1, 4-dihydro-6-methyl-3,5-pyridine dicarboxylate, monobenzensulphonate.Its empirical formula is C2O H25 CLN2O5.C6H6O3S. MW=567.1
The Atorvastatin calcium is chemically described as [R-(R*,R*)]-2-(4-flurophenyl)-B,6- dihydroxy -5-(1-methylethyl)-3-phenyl-4-[(phenylamino) carbonyl] -1H-pyrrole-1- heptanoic acid,calcium salf (2:1) trihydrate.Its empirical formula is (C33 H34 FN2O5) 2 Ca.3H2O MW=1209.42
Mechanism of Action :
The Amlodipine component of this tablet inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. The Atorvastatin component of this drug is a selective , competitive inhibitor of HMG-CoA reductase , the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl –coenzyme A to mevalonate , a precursor of sterols,including cholesterol. (PDR 2007)
- Absorption :
Amlodipine : Slowly and almost completely.
Atorvastatin: Rapidly absorbed.
- Bioavailability :
Amlodipine : 60-65%. Absorption not affected by food.
Atorvastatin : 14%
- Distribution :
Amlodipine: Ex vivo studies have shown that approximately 93% of the circulating Amlodipine drug is bound to plasma proteins in hypertensive patients.
Atorvastatin: Mean volume of distribution of Atorvastatin is approximately 381 liter
- Protein binding :
Amlodipine : 95-98%
Atorvastatin: >98% (USP DI 2005)
- Half life :
Amlodipine : 35 hours
Atorvastatin: 14 hours (USP DI 2005)
- Time to peak concentration :
Amlodipine : 6-9 hours
Atorvastatin : 1-2 hours (USP DI 2005)
- Elimination :
Amlodipine : (Biliary/fecal: 20- 25%,Renal: 59-62%)
Atorvastatin: Primarity fecal,Renal <2%
- Indications :
Amlodipine+Atorvastatin is indicated in patients for whom treatment with both Amlodipine and Atorvastatin is appropriate.
- Coronary artery disease (CAD): (Chronic stable angina,Vasospastic angina,Angiographically documented CAD.
- Prevention of cardiovascular disease .
- Heterozygous familial and nonfamilial hypercholesterolemia.
- Elevated serum TG levels.
- Primary dysbetalipoproteinemia
- Homozygous familial hypercholesterolemia
- Pediatric patients(reduce total-C, LDL- C, apo B)
Amlodipine + Atorvastatin is contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases.It is also contraindicated in patients with known hypersensitivity to any component of this medication.
- Rarely patients particularly those with severe obstructive coronary artery disease have developed documented increased frequency, duration and/or severity of angina or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase.
- Liver disfunction: It is recommended that liver function tests be performed prior to and at 12 weeks following both the initiation of therapy and any elevation of dose and periodically thereafter.
- In any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis, the therapy should be temporarity withheld or discontinued .
- Since the vasodilation induced by the Amlodipine component of this drug is gradual in onset, acute hypotension has rarely been reported after oral administration of Amlodipine. Nonetheless, caution should be exercised when administering this drug as with any other peripheral vasodilator particularly in patients with severe aortic stenosis.
- Use in patients with congestive heart failure .
- Withdrawal of beta – blockers should be by gradual reduction of the dose of beta- blocker.
- Caution should be exercised if an HMG- CoA reductase inhibitor is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones.
Pregnancy and breast feeding:
HMG- CoA reductase inhibitors are contraindicated during pregnancy and in nursing mother.
Amlodipine + Atorvastatin, which includes Atorvastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards. If the patient become pregnant while taking this drug, therapy should be discontinued and the patient apprised of the potential hazard to the fetus. ( PDR 2007(
No drug interaction studies have been conducted with Amlodipine + Atorvastatin and other drugs,although studies have been conducted in the individual Amlodipine and Atorvastatin componets, as described below: ( PRD 2007)
- Anesthetics,hydrocarbon inhalation,
- Anti- inflammatory drugs
- Beta- adrenergic blocking agents
- Highly protein- bound medications such as anticonvulsant
- Hypotension- producing medication
- Antacids, aluminum and magnesium hydroxide
- Azole antifungals
- Fibric acid derivatives
- Oral contraceptives
- Grape fruit juice in largc amounts
In general treatment with Amlodipine + Atorvastatin was well tolerated. Adverse experiences have been mild or moderate in severity. Adverse experiences are similar in terms of nature, severity and frequency to those reported previously with Amlodipine and Atorvastatin. ( PRD 2007)
Edema, dizziness, angina, bradycardia, hypotension, jaundice, orthostatic hypotension, Abdominal pain, Flushing, headache, somnolence, fatigue, nausea.
Allergic reaction,liver function abnormalities, muscle disorders (such as myalgia), anaphylaxis, bullous rashes, erythema multiforme, rhabdomyolysis, headache, Stevens-Johnson syndrom, sinusitis,infection, asthenia, back pain, constipation, diarrhea. (USP DI 2005)
Administration and dosage :
Dosage of Amlodipine and Atorvastatin must be individualized on the basis of both effectiveness and tolerance for each individual component in the treatment of hypertension/ angina and hyperlipidemia.
Adults: Usual initial antihypertensive oral dose is 5 mg once daily. Small, fragile or elderly individuals or patients with hepatic insufficiency may be started on 2.5 mg once daily.
The recommended dose of Amlodipine for chronic stable or vasospastic angina is 5-10 mg, and 5-10 once daily for patients with coronary artery disease.
In pediatric patients ages 6-17 years, 2.5-5 mg once daily is recommended.
- – Hypercholesterolemia ( Heterozygous familial and non-familial) and mixed dyslipidemia:
The recommended starting dose of Atorvastatin is 10 or 20 mg once daily Patients who require a large reduction in LDL-C (more than 45%), may be started at 40 mg once daily. The dosage range of Atorvastatin is 10-80 mg once daily .
- – Heterozygous familial hypercholesterolemia in pediatric patients (10-17 years of age).
The recommended starting dose of Atorvastatin is 10 mg/day, the maximum recommended dose is 20 mg /day.
- – Homozygous familial hypercholesteromia :
The dosage of Atorvastatin is 10-80 mg/day. ( PRD 2007)
Information for patients:
Due to the risk of myopathy drugs of the HMG- CoA reductase class, to which the Atorvastatin component of Amlodipine+ Atorvastatin belongs, patients should be advised to report promptly unexplained muscle pain, tenderness or weakness, particularly if accompained by malaise or fever.
Packagin and storage :
Store at 25°C (between 15-30°C) (PRD 2007)