Atorvastatin/Amlodipine

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[edit] BRAND NAMES

[edit] STRUCTURE

[edit] MECHANISM OF ACTION

It's a combination of two drugs, a dihydropyridine calcium channel blocker (amlodipine) and an HMG-CoA reductase inhibitor (atorvastatin);

Atorvastatin is a hypolipidemic belonging to the class of drugs called Statins.

Cholesterol is made mainly in the liver. Statins work by blocking a key liver enzyme involved in this process, thereby slowing down the production of cholesterol in the liver. This encourages the liver to take extra cholesterol, LDL cholesterol in particular, out of the bloodstream, by increasing the number of hepatic LDL receptors on the cell-surface and thus, causing the LDL cholesterol level to decrease .

Atorvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. As HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, this results in a decrease in mevalonate, a precursor of cholesterol. Atorvastatin reduces total-cholesterol, LDL-cholesterol, VLDL-cholesterol and TG and increases HDL-cholesterol (good cholesterol).


Amlodipine is a dihydropyridine calcium-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.

The decrease in intracellular calcium inhibits the contractile processes of the coronary arteries smooth muscle cells and systemic arteries, and thus increases oxygen delivery to the myocardial tissue and, decreases total peripheral resistance and systemic blood pressure.

[edit] INDICATIONS

Amlodipine and atorvastatin combination is indicated in patients for whom treatment with both amlodipine (Norvasc) and atorvastatin (Lipitor) is appropriate;

Amlodipine is used to treat hypertension, angina and coronary artery disease

Atorvastatin is used to lower cholesterol, triglycerides, risk for heart attack, stroke, coronary revascularization procedures (e.g. heart bypass, angioplasty), and angina (chest pain) in patients who have heart disease or risk factors for heart disease such as: age, smoking, hypertension, low levels of HDL-cholesterol (good cholesterol), heart disease in the family. Atorvastatin can also lower the risk for heart attack or stroke in patients with diabetes and risk factors such as: diabetic eye or kidney problems, smoking, or hypertension.

[edit] DOSAGE

Dosage must be individualized on the basis of both effectiveness and tolerance for each individual component in the treatment of hypertension/angina and hyperlipidemia.

Amlodipine: the recommended starting dose is 5 mg once daily with maximum dose 10 mg once daily. Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily.

Atorvastatin: Adult recommended starting dose is 10 or 20 mg once daily. Patients requiring large LDL-C reduction (>45%) may start at 40 mg once daily. Maximum: 80mg/day

[edit] CONTRAINDICATIONS

  • Known hypersensitivity to Atorvastatin or to Amlodipine
  • Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels
  • Women who may become pregnant, pregnancy and breastfeeding

[edit] WARNINGS AND PRECAUTIONS

  • Atorvastatin:
    • Skeletal Muscle Effects: Myalgia, myopathy and, rarely, rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including Atorvastatin. These risks can occur at any dose level, but are increased at the highest dose.
      Atorvastatin should be prescribed with caution in patients with predisposing factors for myopathy (e.g., age ≥ 65 years, inadequately treated hypothyroidism, renal impairment, personal or family history of hereditary muscular disorders, alcohol abuse).

      Concomitant use of cyclosporine, Fibrates, erythromycin, clarithromycin, the hepatitis C protease inhibitor telaprevir, combinations of HIV protease inhibitors, including saquinavir plus ritonavir, lopinavir plus ritonavir, tipranavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, and fosamprenavir plus ritonavir, niacin, or azole antifungal (e.g. Itraconazole, Ketoconazole), may increase the risk of myopathy. (see Interaction).

      Whilst on treatment, patients should be asked to report inexplicable muscle pain, weakness or cramps immediately, particularly if associated with malaise or fever. Creatine Kinase levels should be measured in these patients. Therapy should be discontinued if Creatine Kinase levels are markedly elevated.
    • Liver enzyme abnormalities and monitoring: As with other HMG-CoA reductase inhibitors, persistent elevations in hepatic transaminases can occur. Monitor liver enzymes prior to initiating therapy and repeat it when clinically indicated.
  • Amlodipine:
    • Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. However, acute hypotension is unlikely.
    • 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.
    • Amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t 1/2) is 56 hours in patients with impaired hepatic function. Titrate slowly in patients with severe hepatic impairment

[edit] INTERACTIONS

  • Strong Inhibitors of CYP3A4: Atorvastatin is metabolized by CYPP3A4. Concomitant administration of strong inhibitors of CYP3A4 can lead to increases in plasma concentrations of atorvastatin;
  • Cyclosporine: Combination increases Atorvastatin exposure. Avoid Atorvastatin
  • Concomitant lipid-lowering therapies:
    • Fibrates:
      • Gemfibrozil: Due to an increased risk of myopathy/rhabdomyolysis. concomitant administration of Atorvastatin with gemfibrozil should be avoided
      • Other fibrates: the risk of myopathy during treatment is increased with concurrent administration of other fibrates- Atorvastatin should be administered with caution
    • Niacin The risk of skeletal muscle effects may be enhanced. A reduction in Atorvastatin dosage should be considered
  • Oral Contraceptives: Co-administration of Atorvastatin and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol. These increases should be considered when selecting an oral contraceptive for a woman taking.
  • Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with atorvastatin co-administered with colchicine, and caution should be exercised when prescribing atorvastatin with colchicine.
  • Digoxin: When multiple doses of atorvastatin and digoxin were coadministered, steady state plasma digoxin concentrations increased by approximately 20%. Patients taking digoxin should be monitored appropriately.

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category X (US). Atorvastatin may cause fetal harm, therefore, it is contraindicated in women who are or may become pregnant
  • Nursing mothers who require Atorvastatin treatment should be advised not to nurse their infants.

[edit] SIDE EFFECTS

Most common adverse reactions to amlodipine are peripheral edema, fatigue, nausea, abdominal pain, and somnolence.

Most common adverse reactions to atorvastatin are nasopharyngitis (inflammation of the nasal passages, pain in the throat), nose bleed, joint pain, muscle pain, back pain, diarrhea, and urinary tract infection

[edit] RELATED LINKS

[edit] BIBLIOGRAPHY

Caduet prescribing information U.S. (revised 11/2013)

[edit] REFERENCES