Amlodipine + Atorvastatin


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO HTN or angina and hyperlipidaemia As combination tab containing Amlodipine (mg)/Atorvastatin (mg): 2.5/10, 2.5/20, 2.5/40, 5/10, 5/20, 5/40, 5/80, 10/10, 10/20, 10/40, 10/80. Amlodipine: Initially 5 mg once daily, titrate over 1-2 wk; max: 10 mg/day. Atorvastatin: Initially 10-20 mg once daily (anytime of the day), patients who require >45 % reduction in LDL cholesterol may be initiated at 40 mg once daily. Titrate dose at intervals of at least 4 week; max: 80 mg/day.
Dosage Details
Oral
Hypertension or angina and hyperlipidaemia
Adult: As combination tab containing Amlodipine (mg)/Atorvastatin (mg): 2.5/10, 2.5/20, 2.5/40, 5/10, 5/20, 5/40, 5/80, 10/10, 10/20, 10/40, 10/80. May be used to substitute individual titrated components; or to provide additional therapy for patients currently receiving one of its components; or as initial therapy in patients whom treatment with both Amlodipine and Atorvastatin is appropriate. Amlodipine: Initially 5 mg once daily, titrate over 1-2 wk to maximum of 10 mg once daily. Atorvastatin: Initially 10-20 mg once daily (anytime of the day), patients who require >45 % reduction in LDL cholesterol may be initiated at 40 mg once daily. Titrate dose at intervals of at least 4 week to maximum of 80 mg once daily.
Child: HTN: Amlodipine: 2.5-5 mg once daily in children ages 6-17 yr. Heterozygous familial hypercholesterolaemia: Atorvastatin: Initially 10 mg once daily in children ages 10-17 yr; maximum recommended dose is 20 mg once daily.
Elderly: May initiate Amlodipine component at 2.5 mg once daily.
Special Patient Group
In patients receiving concomitant cyclosporine: Do not exceed 10 mg Atorvastatin daily. In patients receiving concomitant strong CYP3A4 inhibitors (e.g. Clarithromycin, itraconazole, HIV protease inhibitors): Caution when doses > 20 mg Atorvastatin daily are used.
Hepatic Impairment
May initiate Amlodipine component at 2.5 mg once daily.
Administration
May be taken with or without food.
Contraindications
Active liver disease or unexplained persistent elevated hepatic transaminases. Pregnancy and lactation.
Special Precautions
Atorvastatin may cause myopathy, and rarely rhabdomyolysis with acute renal failure secondary to myoglobinuria especially at high doses or in patients with history of renal impairment. Caution when used with CYP3A4 inhibitors which may increase plasma concentrations of Atorvastatin. Withhold/discontinue Atorvastatin if symptoms suggestive of myopathy or rhabdomyolysis are observed. Atorvastatin has been associated with biochemical abnormalities of liver; LFT should be monitored prior to and at 12 wk following treatment initiation and dosage increment; caution in patients who consume large amounts of alcohol or with history of liver disease. Worsening of angina and/or myocardial infarction has been reported with use of dihydrophyridine calcium channel blockers, especially in patients with severe obstructive coronary artery disease. Amlodipine may cause dose-dependent peripheral oedema. Caution in patients with severe aortic stenosis, symptomatic hypotension may occur. Elderly.
Adverse Reactions
Amlodipine: Headache, dizziness, fatigue, somnolence, peripheral oedema, flushing, palpitations, nausea, abdominal pain; rarely pruritus, rash, dyspnoea, asthenia and muscle cramps. Atorvastatin: Nasopharyngitis, arthralgia, diarrhoea, pain in extremity, UTI, dyspepsia, nausea, musculoskeletal pain, muscle spasms, myalgia, insomnia, increased transaminases, abnormal liver function test, increased creatinine phosphokinase, thrombocytopenia, malaise, hepatitis, cholestasis, bullous rashes.
Potentially Fatal: Rhabdomyolysis with acute renal failure.
Overdosage
Amlodipine overdosage may cause marked hypotension and possibly reflex tachycardia due to excessive peripheral vasodilation. Actively monitor cardiac and respiratory function, provide CV support if hypotension occur. Both Amlodipine and Atorvastatin are highly protein bound, haemodialysis is unlikely to be useful to enhance clearance.
Drug Interactions
Rifamycins may increase the metabolism of both Amlodipine and Atorvastatin. Atorvastatin may increase AUC of norethindrone and ethinyl estradiol.
Potentially Fatal: Atorvastatin: Increased risk of myopathy when used concurrently with fibric acid derivatives, lipid-modifying doses of niacin, cyclosporine or strong CYP3A4 inhibitors (e.g. clarithromycin, HIV protease inhibitors, itraconazole). Cyclosporine (OATP1B1 inhibitor) may significantly increase bioavailability of Atorvastatin.
Food Interaction
The serum levels of both Amlodipine and Atorvastatin may be increased by grapefuit juice (especially with excessive consumption >1.2 L daily). St John's wort may decrease Atorvastatin levels. Patients receiving Atorvastatin should avoid consumption of large amounts of alcohol.
Action
Description: Amlodipine is a dihydropyridine calcium channel blocker which relaxes peripheral and coronary vascular smooth muscle. It produces coronary vasodilation by inhibiting the entry of Ca ions into the voltage-sensitive channels of the vascular smooth muscle and myocardium during depolarisation. It reduces peripheral vascular resistance and hence resulting in a reduction of blood pressure. In vasospastic angina, Amlodipine also inhibits coronary spasm in patients with vasopastic angina. Atorvastatin selectively and competitively inhibits HMG-CoA reductase, the enzyme that catalyses the conversion of HMG-CoA to mevalonate which is a rate-limiting step in cholesterol biosynthesis.
Pharmacokinetics:
Absorption: Amlodipine: Plasma concentrations peak between 6-12 hr; absolute bioavailability: About 64- 90%. Atorvastatin: Rapidly absorbed; plasma concentrations peak within 1-2 hr; absolute bioavailability of parent drug (Atorvastatin): About 14%.
Distribution: Amlodipine: Protein-binding: Abt 93%; steady-state concentrations reached after 7-8 days of consecutive daily dosing. Atorvastatin: Vd: 381 L; Protein-binding: ≥98 %.
Metabolism: Amlodipine: About 90% is metabolised to inactive metabolite in the liver. Atorvastatin: Extensively metabolised mainly by CYP3A4 in the liver to ortho- and parahydroxylated derivatives (active metabolites); and various beta-oxidation products.
Excretion: Amlodipine: Biphasic elimination; terminal half-life: About 30-50 hr. Atorvastatin: Atorvastatin and its metabolites are removed mainly in the bile; mean elimination half-life: About 14 hr (parent drug), 20-30 hr (equipotent active metabolites).
Storage
Store at 15 to 30°C.
Disclaimer: This information is independently developed by MIMS based on Amlodipine + Atorvastatin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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