Atorvastatin

Indications

Atorvastatin is used for: Primary hypercholesterolemia (heterozygous familial and nonfamilial), Mixed Dyslipidemia, Homozygous familial hypercholesterolemia, Hypertriglyceridemia, Familial hypercholesterolemia, Cardiovascular event prevention, Primary dysbetalipoproteinemia

Adult Dose

Oral Mixed dyslipidaemia, Heterozygous familial hypercholesterolaemia, Nonfamilial hypercholesterolaemia Adult: Initially, 10 or 20 mg once daily, may be adjusted at 4-wk interval. May initiate 40 mg once daily in patients who require >45% reduction in LDL-cholesterol. Max: 80 mg/day. Elderly: No dosage adjustment needed.

Child Dose

Oral Mixed dyslipidaemia, Heterozygous familial hypercholesterolaemia, Nonfamilial hypercholesterolaemia Child: Heterozygous familial hypercholesterolaemia: 10-17 yr 10 mg once daily, may increase at intervals of at least 4 wk to max 20 mg/day.

Renal Dose

Renal Insufficiency: Renal disease does not affect the plasma concentrations or LDL-C reduction of atorvastatin; thus, dosage adjustment in patients with renal dysfunction is not necessary.

Administration

Atorvastatin can be administered as a single dose at any time of the day, with or without food. Avoid excessive consumption (>1 L/day) of grapefruit juice.

Contra Indications

Hypersensitivity, active liver disease or unexplained persistent elevations of serum transaminase, porphyria, pregnancy, lactation.

Precautions

Patients who consume substantial quantities of alcohol. History of liver disease. Patients with risk factors for myopathy or rhabdomyolysis. Hypothyroidism should be properly managed prior to starting statin therapy. Children <10 yr. Premenarcheal females. Lactation: Because of the potential for adverse reactions in nursing infants, women taking this drug should not breastfeed; contraindicated in nursing mothers.

Pregnancy-Lactation

Pregnancy Contraindicated for use in pregnant women since safety in pregnant women has not been established and there is no apparent benefit of lipid lowering drugs during pregnancy; because HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, therapy may cause fetal harm when administered to a pregnant woman; discontinue therapy as soon as pregnancy is recognized; limited published data are insufficient to determine a drug-associated risk of major congenital malformations or miscarriage Contraception Advise females of reproductive potential to use effective contraception during treatment Lactation Use is contraindicated during breastfeeding; there is no available information on effects of drug on breastfed infant or on milk production.; not known whether atorvastatin is present in human milk; it has been shown that another drug in this class passes into human milk and atorvastatin is present in rat milk; because of potential for serious adverse reactions in breastfed infant, advise women that breastfeeding is not recommended during treatment

Interactions

May increase risk of myopathy and rhabdomyolysis w/ CYP3A4 potent inhibitor (e.g. HIV or HCV protease inhibitors, itraconazole, clarithromycin), fenofibrate, colchicines, fixed combination of lopinavir/ritonavir. May decrease plasma concentration w/ CYP3A4 inducer (e.g. rifampicin, efavirenz). May significantly increase AUC and peak plasma concentration of digoxin. Increased AUC for norethindrone and ethinyl estradiol. Potentially Fatal: Increased risk of myopathy or rhabdomyolysis w/ ciclosporin, gemfibrozil, telaprevir, tipranavir.

Adverse Effects

Side effects of Atorvastatin : >10% Diarrhea (5-14%), Nasopharyngitis (4-13%), Arthralgia (4-12%) 1-10% Insomnia (1-5%), Urinary tract infection (4-8%), Nausea (4-7%), Dyspepsia (3-6%), Increased transaminases (2-3%), Muscle spasms (2-5%), Musculoskeletal pain (2-5%), Myalgia (3-8%), Limb pain (3-8%), Pharyngolaryngeal pain (1-4%) Frequency Not Defined Angina, Syncope, Dyspnea, Myopathy, Anaphylaxis, Stevens-Johnson syndrome, Myositis Potentially Fatal: Thrombocytopenia. Rhabdomyolysis with acute renal failure.

Mechanism of Action

Atorvastatin competitively inhibits HMG-CoA reductase, the enzyme that catalyses the conversion of HMG-CoA to mevalonate. This results in the induction of the LDL receptors and stimulation of LDL catabolism, leading to lowered LDL-cholesterol levels.