Lovasterol - General Information
A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl COA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [PubChem]
Pharmacology of Lovasterol
Lovasterol, an antilipemic agent produced by fermentation of Aspergillus terreus, is the first of a class of lipid-lowering agents known as the HMG-CoA reductase inhibitors. Lovasterol is used to treat hypercholesterolemia, to slow coronary atherosclerosis, and to prevent myocardial infarction and stroke. Lovasterol, like simvastin and unlike pravastatin, is a prodrug, concentrating active drug in the liver during first-pass circulation.
Lovasterol for patients
Lovastatin is used to lower high cholesterol levels. This medication should
not be taken if you are pregnant, nursing, or have liver disease. Lovastatin
should be taken with the evening meal. This medication may cause increased
sensitivity to sunlight. Use sunscreens and wear protective clothing until
degree of sensitivity is determined. Notify your physician if you develop
blurred vision; skin rash; muscle pain, weakness, or cramps; unexplained fever,
or yellowing of the skin or eyes.
Patients should be advised about substances they should not take concomitantly
with lovastatin and be advised to report promptly unexplained muscle pain,
tenderness, or weakness (see list below and WARNINGS, Myopathy/Rhabdomyolysis ).
Patients should also be advised to inform other physicians prescribing a new
medication that they are taking MEVACOR.
Lovastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity;
therefore it is not expected to affect the plasma concentrations of other
drugs metabolized by CYP3A4. Potent inhibitors of CYP3A4 (below) increase
the risk of myopathy by reducing the elimination of lovastatin.
HIV protease inhibitors
Large quantities of grapefruit juice (>1 quart daily)
Interactions with lipid-lowering drugs that can cause myopathy when given
The risk of myopathy is also increased by the following lipid-lowering drugs
that are not potent CYP3A4 inhibitors, but which can cause myopathy when given
See WARNINGS, Myopathy/Rhabdomyolysis.
Niacin (nicotinic acid) (=1 g/day)
Other drug interactions
Danazol: The risk of myopathy/rhabdomyolysis is increased by concomitant
administration of danazol particularly with higher doses of lovastatin (see
Amiodarone or Verapamil: The risk of myopathy/rhabdomyolysis is increased when
either amiodarone or verapamil is used concomitantly with a closely related
member of the HMG-CoA reductase inhibitor class (see WARNINGS, Myopathy/Rhabdomyolysis).
Coumarin Anticoagulants: In a small clinical trial in which lovastatin was administered
to warfarin treated patients, no effect on prothrombin time was detected. However,
another HMG-CoA reductase inhibitor has been found to produce a less than two-second
increase in prothrombin time in healthy volunteers receiving low doses of warfarin.
Also, bleeding and/or increased prothrombin time have been reported in a few patients
taking coumarin anticoagulants concomitantly with lovastatin. It is recommended that in
patients taking anticoagulants, prothrombin time be determined before starting lovastatin
and frequently enough during early therapy to insure that no significant alteration of
prothrombin time occurs.
Once a stable prothrombin time has been documented, prothrombin times can be monitored
at the intervals usually recommended for patients on coumarin anticoagulants. If the
dose of lovastatin is changed, the same procedure should be repeated. Lovastatin therapy
has not been associated with bleeding or with changes in prothrombin time in patients not
Propranolol: In normal volunteers, there was no clinically significant pharmacokinetic or
pharmacodynamic interaction with concomitant administration of single doses of lovastatin
Digoxin: In patients with hypercholesterolemia, concomitant administration of lovastatin
and digoxin resulted in no effect on digoxin plasma concentrations.
Oral Hypoglycemic Agents: In pharmacokinetic studies of MEVACOR in hypercholesterolemic
noninsulin dependent diabetic patients, there was no drug interaction with glipizide or
Hypersensitivity to any component of this medication.
Active liver disease or unexplained persistent elevations of serum
Pregnancy and Lactation: Atherosclerosis is a chronic process and the
discontinuation of lipid-lowering drugs during pregnancy should have
little impact on the outcome of long-term therapy of primary hypercholesterolemia.
Moreover, cholesterol and other products of the cholesterol biosynthesis
pathway are essential components for fetal development, including synthesis
of steroids and cell membranes. Because of the ability of inhibitors of
HMG-CoA reductase such as lovastatin to decrease the synthesis of cholesterol
and possibly other products of the cholesterol biosynthesis pathway, lovastatin
is contraindicated during pregnancy and in nursing mothers. Lovastatin should
be administered to women of childbearing age only when such patients are highly
unlikely to conceive. If the patient becomes pregnant while taking this drug,
lovastatin should be discontinued immediately and the patient should be apprised
of the potential hazard to the fetus
Additional information about Lovasterol
Lovasterol Indication: For management as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia; For primary prevention of coronary heart disease
Mechanism Of Action: Lovasterol is a lactone that is readily hydrolyzed in vivo to the corresponding b-hydroxyacid, a potent inhibitor of HMG-CoA reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate. The conversion of HMG-CoA to mevalonate is an early step in the biosynthetic pathway for cholesterol.
Drug Interactions: Amprenavir Amprenavir can possibly increase the statin toxicity
Anisindione The statin increases the anticoagulant effect
Acenocoumarol The statin increases the anticoagulant effect
Dicumarol The statin increases the anticoagulant effect
Warfarin The statin increases the anticoagulant effect
Atazanavir Increased risk of myopathy/rhabdomyolysis
Azithromycin Azithromycin can possibly increase the statin toxicity
Bezafibrate Increased risk of myopathy/rhabdomyolysis
Bosentan Bosentan could decrease the statin effect
Carbamazepine Carbamazepine decreases the effect of the statin
Colchicine Increased risk of rhabdomyolysis with this combination
Cyclosporine Possible myopathy and rhabdomyolysis
Danazol Risk of severe myopathy/rhabdomyolysis with this combination
Diltiazem Diltiazem increases the effect and toxicity of the statin
Fenofibrate Increased risk of myopathy/rhabdomyolysis
Fluconazole Increased risk of myopathy/rhabdomyolysis
Fosamprenavir Amprenavir can possibly increase the statin toxicity
Gemfibrozil Increased risk of myopathy/rhabdomyolysis
Imatinib Imatinib increases the effect and toxicity of statin
Itraconazole Increased risk of myopathy/rhabdomyolysis
Ketoconazole Increased risk of myopathy/rhabdomyolysis
Nefazodone Nefazodone increases the effect and toxicity of the statin
Nelfinavir Nelfinavir increases the effect and toxicity of the statin
Niacin Risk of severe myopathy/rhabdomyolysis with this combination
Quinupristin This combination presents an increased risk of toxicity
Ritonavir Ritonavir increases the effect and toxicity of the statin
Verapamil Verapamil increases the effect and toxicity of statin
Telithromycin Telithromycin may possibly increase statin toxicity
Tacrolimus Tacrolimus increases the effect and toxicity of the statin
Clarithromycin The macrolide possibly increases the statin toxicity
Erythromycin The macrolide possibly increases the statin toxicity
Josamycin The macrolide possibly increases the statin toxicity
Delavirdine The NNRT inhibitor increases the effect and toxicity of the statin
Efavirenz The NNRT inhibitor increases the effect and toxicity of the statin
Nevirapine The NNRT inhibitor increases the effect and toxicity of the statin
Rifabutin The rifamycin decreases the effect of statin drug
Rifampin The rifamycin decreases the effect of statin drug
Food Interactions: Avoid drastic changes in dietary habit.
Take with food, 50% increase in bioavailability when taken with food.
Avoid taking with grapefruit juice.
Generic Name: Lovastatin
Synonyms: Lovastatina [Spanish]; Lovastatine [French]; Lovastatinum [Latin]; 6 alpha-Methylcompactin
Drug Category: Antineoplastic Agents; Anticholesteremic Agents; HMG-CoA Reductase Inhibitors
Drug Type: Small Molecule; Approved
Other Brand Names containing Lovastatin: Altocor; Altoprev; Artein; Belvas; Cholestra; Closterol; Colevix; Hipolip; Hipovastin; Lestatin; Lipdip; Lipivas; Lipofren; Lovalip; Lovalord; Lovasterol; Lovastin; Lozutin; Mevacor; Mevinacor; Mevlor; Monacolin K; Nergadan; Paschol; Rodatin; Rovacor; Sivlor; Taucor; Tecnolip; Teroltrat;
Toxicity (Overdose): LD50>1000 mg/kg (orally in mice)
Protein Binding: >95%
Half Life: 5.3 hours
Dosage Forms of Lovasterol: Tablet Oral
Chemical IUPAC Name: [(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate
Chemical Formula: C24H36O5
Lovastatin on Wikipedia: https://en.wikipedia.org/wiki/Lovastatin
Organisms Affected: Humans and other mammals