Skeletal Muscle: Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with atorvastatin and with other drugs in this class. Atorvastatin therapy should be temporarily withheld or discontinued 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 (e.g., severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures).
Liver Dysfunction: Statins, like some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function. Persistent elevation ( > 3 times the upper limit of normal [ULN] occurring on 2 or more occasions) in serum transaminases occurred in 0.7% of patients who received atorvastatin in clinical trials. The incidence of these abnormalities was 0.2%, 0.2%, 0.6%, and 2.3% for 10, 20, 40, and 80 mg, respectively.
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 (e.g., semiannually) thereafter. Liver enzyme changes generally occur in the first 3 months of treatment with atorvastatin. Patients who develop increased transaminase levels should be monitored until the abnormalities resolve. Should an increase in ALT or AST of > 3 times ULN persist, reduction of dose or withdrawal of atorvastatin is recommended.
Atorvastatin should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. Active liver disease or unexplained persistent transaminase elevations are contraindications to the use of atorvastatin.
Endocrine Function: Statins interfere with cholesterol synthesis and theoretically might blunt adrenal and/or gonadal steroid production. Clinical studies have shown that atorvastatin does not reduce basal plasma cortisol concentration or impair adrenal reserve. The effects of statins on male fertility have not been studied in adequate numbers of patients. The effects, if any, on the pituitary-gonadal axis in premenopausal women are unknown. Caution should be exercised if a statin is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone, and cimetidine.
Use in Patients with Recent Stroke or TIA: In a post-hoc analysis of stroke subtypes in patients without CHD who had a recent stroke or TIA, there was a higher incidence of hemorrhagic stroke in patients initiated on atorvastatin 80 mg compared to placebo. The increased risk was particularly noted in patients with prior haemorrhagic risk or lacunar infarct at study entry. For patients with prior haemorrhagic stroke or lacunar infarct, the balance of risks and benefits of atorvastatin 80 mg is uncertain and the potential risk of haemorrhagic stroke should be carefully considered before initiating treatment.
Muscle Pain: All patients starting therapy with atorvastatin should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness, or weakness. The risk of this occurring is increased when taking certain types of medication or consuming larger quantities (> 1 liter) of grapefruit juice. The patient should discuss all medication, both prescription and over the counter, with their healthcare professional.
Liver Enzymes: 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 (e.g., semiannually) thereafter.
Effects on ability to drive and use machines: There is no pattern of reported adverse events suggesting that patients taking Atorvastatin will have any impairment of ability to drive and use hazardous machinery.
Use in Pregnancy: Women of childbearing age should be advised to use an effective method of birth control to prevent pregnancy while using atorvastatin. Discuss future pregnancy plans with patients, and discuss when to stop atorvastatin if patients are trying to conceive. Patients who become pregnant should be advised to stop taking atorvastatin and call their healthcare professional.
Use in Lactation: Women who are breastfeeding should be advised to not use atorvastatin. Patients who have a lipid disorder and are breastfeeding, should be advised to discuss the options with their healthcare professional.
Atorvastatin is contraindicated in pregnancy and while breast-feeding. Women of child-bearing potential should use appropriate contraceptive measures.
An interval if 1 month should be allowed from stopping Atorvastatin treatment to conception in the event of planning a pregnancy.
In animal studies, atorvastatin had no effect on fertility and was not teratogenic, however, at maternally toxic doses, foetal toxicity was observed in rats and rabbits. The development of the rat offspring was delayed and post-natal survival reduced during exposure of the dams to atorvastatin equivalent to 6 and 21 times that expected in man, respectively.
It is not known whether this drug or its metabolites is excreted in human milk.
Use in Children: Safety and effectiveness in patients 10-17 years of age with heterozygous familial hypercholesterolemia have been evaluated in a controlled clinical trial of 6 months’ duration in adolescent boys and postmenarchal girls. Patients treated with atorvastatin had an adverse experience profile generally similar to that of patients treated with placebo. The most common adverse experiences observed in both groups, regardless of causality assessment, were infections. Doses greater than 20 mg have not been studied in this patient population. Atorvastatin has not been studied in controlled clinical trials involving pre-pubertal patients or patients younger than 10 years of age.