|
|
| Line 1: |
Line 1: |
| __NOTOC__
| | #redirect [[Lovastatin#Warnings]] |
| {{Lovastatin}}
| |
| {{CMG}}; {{AE}} {{SS}}
| |
| | |
| ==Warnings and Precautions==
| |
| | |
| ===Skeletal Muscle Effects===
| |
| | |
| Cases of [[myopathy]] and [[rhabdomyolysis]] with acute renal failure secondary to [[myoglobinuria]] have been reported with [[HMG-CoA]] reductase inhibitors, including Altoprev®. These risks can occur at any dose level, but increase in a dose-dependent manner. Predisposing factors for [[myopathy]] include advanced age (≥65 years), female gender, renal impairment, and inadequately treated [[hypothyroidism]]. In a clinical study (EXCEL) in which patients were carefully monitored and some interacting drugs were excluded, there was one case of [[myopathy]] among 4933 patients randomized to lovastatin20-40 mg daily for 48 weeks, and 4 among 1649 patients randomized to 80 mg daily.
| |
| | |
| There have been rare reports of immune-mediated necrotizing [[myopathy]] (IMNM), an autoimmune [[myopathy]], associated with [[statin]]use. IMNM 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.
| |
| | |
| All patients starting therapy with Altoprev®, or whose dose of Altoprev® is being increased, should be advised of the risk of [[myopathy]], including [[rhabdomyolysis]], and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by [[malaise]] or fever or if muscle signs and symptoms persist after discontinuing Altoprev. Altoprev therapy should be discontinued immediately if [[myopathy]] is diagnosed or suspected.
| |
| | |
| Altoprev® therapy should be discontinued if markedly elevated creatine kinase (CK) levels occur or [[myopathy]] is diagnosed or suspected. Altoprev® therapy should also be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to [[rhabdomyolysis]], e.g., [[sepsis]]; [[hypotension]]; [[dehydration]]; major surgery; trauma; severe metabolic, endocrine, and electrolyte disorders; or uncontrolled [[epilepsy]].
| |
| | |
| • Drug Interactions that can cause skeletal muscle effects
| |
| | |
| '''Strong CYP3A Inhibitors''': The risk of [[myopathy]] and [[rhabdomyolysis]] is increased by high levels of [[statin]]activity in plasma. lovastatinis metabolized by the [[cytochrome]] P450 isoform 3A4. Certain drugs which inhibit this metabolic pathway can raise the plasma levels of lovastatinand may increase the risk of [[myopathy]]. Co-administration of these drugs with Altoprev is contraindicated. If treatment with strong CYP3A inhibitors is unavoidable, therapy with Altoprev should be suspended during the course of treatment (see Contraindications (4); Clinical Pharmacology, Pharmacokinetics (12.3); Drug Interactions (7.1)].
| |
| | |
| '''[[erythromycin]]''': Co-administration of [[erythromycin]] with Altoprev is contraindicated. If treatment with [[erythromycin]] is unavoidable, therapy with Altoprev should be suspended during the course of treatment (see Contraindications (4); Drug Interactions (7.2)]
| |
| | |
| '''[[Gemfibrozil]]''': Avoid the combined use of Altoprev with [[gemfibrozil]].
| |
| | |
| '''Other lipid-lowering drugs (other fibrates, or lipid-lowering doses (≥ 1 g/day) of niacin''': Use caution when prescribing other fibrates or lipid-lowering doses (≥ 1 g/day) of niacin with Altoprev, as these agents can cause [[myopathy]] when given alone and the risk is increased when they are coadministered with Altoprev. Carefully weigh the expected benefit of further alterations in lipid levels by the combined use of lovastatinwith other fibrates or niacin against the potential risks of these combinations [see Drug Interactions (7.3)].
| |
| | |
| '''[[Cyclosporine]]''': Avoid the combined use of Altoprev with cyclosporine [see Drug Interactions (7.4)].
| |
| | |
| [[Danazol]], [[diltiazem]], [[dronedarone]] or [[verapamil]] with higher doses of lovastatin: Do not exceed 20 mg of Altoprev daily in patients receiving concomitant therapy with [[danazol]], [[diltiazem]], [[dronedarone]] or [[verapamil]]. Weigh carefully the benefits of the use of Altoprev in patients receiving [[danazol]], [[diltiazem]], [[dronedarone]] or [[verapamil]] against the risks of these combinations [see Drug Interactions (7.5)].
| |
| | |
| '''Amiodarone''': Do not exceed 40 mg of Altoprev daily in patients receiving concomitant therapy with [[amiodarone]]. Avoid the combined use of Altoprev at doses exceeding 40 mg daily with [[amiodarone]] unless the clinical benefit is likely to outweigh the increased risk of [[myopathy]]. The concomitant use of higher doses of a closely related member of the [[HMG-CoA]] reductase inhibitor class with [[amiodarone]] increased the risk of [[myopathy]]/[[rhabdomyolysis]] [see Drug Interactions (7.6)] .
| |
| | |
| '''Colchicine''': There have been cases of [[myopathy]], including [[rhabdomyolysis]], reported in patients receiving lovastatincoadministered with colchicine. Use caution when prescribing Altoprev with colchicine [see Drug Interactions (7.8)].
| |
| | |
| Ranolazine: Concomitant use of ranolazine and Altoprev may increase the risk of [[myopathy]], including [[rhabdomyolysis]]. Consider dose adjustment of Altoprev if coadministering with ranolazine [see Drug Interactions (7.9)].
| |
| | |
| Prescribing recommendations for interacting agents are summarized in Table 1.
| |
| | |
| ===Liver Enzyme Abnormalities===
| |
| | |
| Increases in serum transaminases (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) have been reported with [[HMG-CoA]] reductase inhibitors, including Altoprev®.
| |
| | |
| Persistent increases (to more than 3 times the upper limit of normal) in serum transaminases occurred in 1.9% of adult patients who received lovastatinfor at least one year in early clinical trials [see Adverse Reactions (6.1)]. When the drug was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels.
| |
| | |
| It is recommended that liver enzyme tests be obtained prior to initiating therapy with Altoprev and repeated as clinically indicated. There have been rare postmarketing reports of fatal and non-fatal [[hepatic failure]] in patients taking [[statins]], including lovastatin. If serious liver injury with clinical symptoms and/or [[hyperbilirubinemia]] or jaundice occurs during treatment with Altoprev, promptly interrupt therapy. If an alternate etiology is not found, do not restart Altoprev.
| |
| | |
| The drug should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease. Active liver disease or unexplained transaminase elevations are contraindications to the use of Altoprev®.
| |
| | |
| Altoprev®
| |
| In controlled clinical trials (467 patients treated with Altoprev® and 329 patients treated with lovastatinimmediate-release) no meaningful differences in transaminase elevations between the two treatments were observed.
| |
| | |
| Lovastatin | |
| In the EXCEL study [see Clinical Studies (14)], the incidence of persistent increases in serum transaminases over 48 weeks was 0.1% for placebo, 0.1% at 20 mg/day, 0.9% at 40 mg/day, and 1.5% at 80 mg/day in patients on lovastatin. However, in post-marketing experience with lovastatinimmediate-release, symptomatic liver disease has been reported rarely at all dosages [see Adverse Reactions (6.2)].
| |
| | |
| In AFCAPS/TexCAPS, the number of participants with consecutive elevations of either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (>3 times the upper limit of normal), over a median of 5.1 years of follow-up, was not significantly different between the lovastatinimmediate-release and placebo groups [18 (0.6%) vs. 11 (0.3%)]. Elevated transaminases resulted in discontinuation of 6 (0.2%) participants from therapy in the lovastatinimmediate-release group (n=3,304) and 4 (0.1%) in the placebo group (n=3,301).
| |
| | |
| ===Endocrine Effects===
| |
| | |
| Increases in HbA1c and fasting serum glucose levels have been reported with [[HMG-CoA]] reductase inhibitors, including lovastatin.
| |
| | |
| [[HMG-CoA]] reductase inhibitors interfere with cholesterol synthesis and as such might theoretically blunt adrenal and/or gonadal steroid production. Results of clinical trials with drugs in this class have been inconsistent with regard to drug effects on basal and reserve steroid levels. However, clinical studies have shown that lovastatindoes not reduce basal plasma cortisol concentration or impair adrenal reserve, and does not reduce basal plasma testosterone concentration. Another [[HMG-CoA]] reductase inhibitor has been shown to reduce the plasma testosterone response to HCG. The effects of [[HMG-CoA]] reductase inhibitors on male fertility have not been studied in adequate numbers of male patients. The effects, if any, on the pituitary-gonadal axis in premenopausal women are unknown. Patients treated with lovastatinwho develop clinical evidence of endocrine dysfunction should be evaluated appropriately. Caution should also be exercised if an [[HMG-CoA]] reductase inhibitor or other agent used to lower cholesterol levels is administered to patients also receiving other drugs (e.g., spironolactone, cimetidine) that may decrease the levels or activity of endogenous steroid hormones.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = ALTOPREV (LOVASTATIN) TABLET, EXTENDED RELEASE [SHIONOGI INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=e8b6ccc2-e6e7-45fd-ab66-c312bcbe2b01 | publisher = | date = | accessdate = 13 February 2014 }}</ref>
| |
| | |
| ==References==
| |
| {{Reflist|2}}
| |
| | |
| {{[[statins]]}}
| |
|
| |
|
| [[Category:[[statins]]]] | | [[Category:[[statins]]]] |
| [[Category:Carboxylate esters]] | | [[Category:Carboxylate esters]] |
| [[Category:Lactones]] | | [[Category:Lactones]] |
| [[Category:Cardiovascular Drug]] | | [[Category:Cardiovascular Drugs]] |
| [[Category:Drug]] | | [[Category:Drug]] |