Avamax Special Precautions

Skeletal Muscle Effects: Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with atorvastatin and with other drugs in this class. A history of renal impairment may be a risk factor for the development of rhabdomyolysis. Closely monitor such patients for skeletal muscle effects.
Uncomplicated myalgia has been associated with atorvastatin. Myopathy, characterized by muscle aches or weakness with increases in creatine kinase (CK) values >10 times ULN, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness and/or marked elevation of CK. Patients should promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Treatment should be stopped if markedly elevated CK levels occur or myopathy is diagnosed or suspected.
Exercise caution in patients with predisposing factors for myopathy/rhabdomyolysis. Creatine kinase level should be measured before starting statin treatment in the following situations: elderly (age ≥65 years), renal impairment, hypothyroidism, personal or familial history of hereditary muscular disorders, previous history of muscular toxicity with a statin or fibrate, previous history of liver disease and/or where substantial quantities of alcohol are consumed, situations where an increase in plasma levels may occur, such as interactions and special populations including genetic subpopulations. In such situations, the risk of treatment should be considered in relation to possible benefit and clinical monitoring is recommended. If CK levels are significantly elevated (>5 times ULN) at baseline, do not start treatment with atorvastatin.
There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. Immune-mediated necrotizing myopathy is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents.
The risk of myopathy is increased with coadministration of atorvastatin with the following: ciclosporin, fibric acid derivatives, erythromycin, clarithromycin, niacin, azole antifungals, the HCV protease inhibitor telaprevir, fosamprenavir, and combinations of HIV protease inhibitors including saquinavir plus ritonavir, lopinavir plus ritonavir, tipranavir plus ritonavir, darunavir plus ritonavir, and fosamprenavir plus ritonavir. Physicians considering combined therapy with atorvastatin and fibric acid derivatives, erythromycin, clarithromycin, a combination of saquinavir plus ritonavir, lopinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, azole antifungals, or lipid-modifying doses of niacin should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs of symptoms of muscle pain, tenderness or weakness, particularly during the initial months of therapy and during any period of upward dosage titration of either drug. Consider lower starting and maintenance doses of atorvastatin when taken concomitantly with the aforementioned drugs (see Table 5 under Interactions). Periodic CK determinations may be considered in such situations, but there is no assurance that such monitoring will prevent the occurrence of severe myopathy.
Temporarily discontinue atorvastatin 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 elevations (>3 times ULN occurring on 2 or more occasions) in serum transaminases occurred in patients receiving atorvastatin.
It is recommended that liver enzyme tests be obtained prior to initiating therapy with atorvastatin and repeated as clinically indicated. There have been postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including atorvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during atorvastatin treatment, promptly interrupt therapy. If an alternate etiology is not found do not restart atorvastatin.
Use with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease.
Endocrine Function: Increases in glycosylated hemoglobin (HbA1c) and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including atorvastatin.
Statins as a class raise serum glucose levels and in some patients, at high risk of future diabetes, may produce a level of hyperglycemia where formal diabetes care is appropriate. This risk, however, is outweighed by the reduction in vascular risk with statins and therefore should not be a reason for stopping statin treatment. Patients at risk (raised serum glucose levels, history of hypertension, raised triglycerides and raised body mass) should be monitored both clinically and biochemically.
Statins interfere with cholesterol synthesis and may blunt adrenal and/or gonadal steroid production. In studies, 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 number of patients. The effects, if any, on the pituitary-gonadal axis in premenopausal women are unknown. Exercise caution if coadministered with other drugs that may decrease levels or activity of endogenous steroid hormones (e.g., ketoconazole, spironolactone, cimetidine).
Hemorrhagic Stroke: A post-hoc analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study in 4,731 patients without known CHD who had a recent (one to six months) stroke or TIA showed a higher incidence of hemorrhagic stroke in the atorvastatin 80 mg group compared with the placebo group. Subjects with prior hemorrhagic stroke or lacunar infarct on study entry appeared to be at increased risk for hemorrhagic stroke. The potential risk of a hemorrhagic stroke should be carefully considered before initiating atorvastatin treatment in patients with recent stroke or TIA.
Interstitial Lung Disease: Exceptional cases of interstitial lung disease have been reported with some statins, especially with long-term therapy. Presenting features may include dyspnea, nonproductive cough, deterioration in general health (fatigue, weight loss and fever). Discontinue statin therapy if it is suspected that a patient has developed interstitial lung disease.
Effects on Ability to Drive and Use Machines: Atorvastatin has negligible influence on the ability to drive and use machines.
Use in Children: Studies have not been conducted involving pre-pubertal patients or patients younger than 10 years old.
Use in the Elderly: There were no age-related differences in efficacy or safety profile of atorvastatin, however, greater sensitivity of some older individuals cannot be ruled out. Since advanced age (≥65 years) is a predisposing factor for myopathy, use with caution in the elderly.