Pharmacology: Lovastatin is converted in vivo by esterases to the corresponding open hydroxyacid which is a potent inhibitor of endogeneous cholesterol synthesis.
Lovastatin is a cholesterol-lowering agent isolated from a strain of A. terreus. After oral ingestion, lovastatin which is an inactive lactone, is hydrolysed to the corresponding β-hydroxyacid form. This principal metabolite is a specific inhibitor of 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase. This enzyme catalyses the conversion of HMG-CoA to mevalonate which is an early and rate-limiting step in the biosynthesis of cholesterol.
Lovastatin reduces cholesterol production by the liver and induces some changes in cholesterol transport and disposition in the blood and tissues. The mechanism of this effects is believed to involve both reduction of the synthesis of low-density lipoprotein (LDL) and in increase in LDL catabolism as a result of induction of the hepatic LDL receptors. The mechanism of the LDL-lowering effects of lovastatin may also involve reduction of the very low-density lipoprotein cholesterol concentration.
Pharmacokinetics: Following an oral dose of 14C-labeled lovastatin in man, 10% of the dose was excreted in the urine and 83% in the feces. The latter represents the absorbed as well as any unabsorbed drug that is excreted in the bile. As a consequence of extensive hepatic extraction of lovastatin, the availability of drug to the general circulation is low and variable.
Both lovastatin and β-hydroxyacid metabolite are highly bound (>95%) to human plasma proteins. The major active metabolites present in human are the β-hydroxyacid of lovastatin, it 6'-hydroxy derivative and 2 unidentified metabolites. Peak plasma concentrations of both active and total inhibitors were attained within 2-4 hrs of dose administration.
With a once-a-day dosing regimen, plasma concentrations of total inhibitors over a dosing interval achieved a steady state between the 2nd and 3rd days of therapy and were about 1.5 times those following a single dose.
For the reduction of elevated total and LDL-cholesterol levels in patients with primary hypercholesterolemia (type IIa and IIb), when the response to diet and other nonpharmacological measures alone has been inadequate. Lovastin may be useful to reduce elevated LDL-cholesterol levels in patients with combined hypercholesterolemia and hypertriglyceridemia.
Before instituting therapy with Lovastin, an attempt should be made to control hypercholesterolemia with appropriate diet, exercise, weight reduction in obese patients.
The patient should be placed on a standard cholesterol-lowering diet before receiving lovastatin and should continue on this diet during treatment with the drug. The usual starting dose is 20 mg/day given as a single dose with the evening meal. Adjustment of dosage, if required, should be made at intervals of not less than 4 weeks, to a maximum of 80 mg daily given in single doses or divided doses with morning and evening meals.
Concomitant Therapy: Preliminary evidence suggests that the cholesterol-lowering effects of lovastatin and the bile acid sequestrant, cholestyramine, are additive.
Patients with Renal Insufficiency: In patients with severe renal insufficiency (creatinine clearance <30 mL/min) dosage increases >20 mg/day should be carefully inserted and, if deemed necessary, implemented cautiously.
To be dispensed on physician's prescription.
No specific symptoms and all patients recovered without sequelae in a few reported cases of accidental overdosage. The maximum dosage taken was fifty-two 20-mg tablets (1.04 g).
Treatment: In the event of overdosage, treatment should be symptomatic and supportive, liver function should be monitored and appropriate therapy should be instituted. Until further experience is obtained, no specific therapy of overdosage can be recommended.
Hypersensitivity to any component of Lovastin.
Patients with active disease or unexplained persistent elevations of serum transaminases.
Use in pregnancy & lactation: Lovastin is contraindicated during pregnancy and lactation.
In controlled clinical trials, marked persistent increases (to >3 times the upper limit of normal) in serum transaminases occurred in 1.6% of adult patients who received lovastatin for at least 1 year. The increase usually appeared 3-12 months after the start of therapy. It is recommended that liver function tests be performed at baseline and every 4-6 weeks during the first 15 months of therapy with lovastatin and periodically thereafter in all patients. Lovastatin should be used with caution in patients with a history of liver disease.
Rhabdomyolysis has occurred rarely and should be considered in any patient with diffuse myalgias, muscle tenderness and/or marked elevation of creatine phosphokinase (10 times the upper limit of normal).
Most of the patients who have developed myopathy were receiving concomitant therapy with immunosuppressive drugs including cyclosporine, gemfibrozil or lipid-lowering doses of niacin.
Patients should be advised to report promptly unexplained muscle pain, tenderness, weakness, particularly if accompanied by malaise or fever.
Homozygous Familial Hypercholesterolemia: Lovastatin is less effective in patients with rare homozygous familial hypercholesterolemia and appears to be more likely to raise serum transaminase in this group of patients.
Eye: It is recommended that patients placed on lovastatin therapy be examined with a slit lamp before or shortly after initiation of treatment, and annually thereafter as new opacities was noted during clinical trial. However, this finding is inconclusive at the moment.
Use in children: Safety and effectiveness in children have not been established. Treatment of children with lovastatin is not recommended.
Lovastin is contraindicated during pregnancy and lactation.
Gastrointestinal: Constipation, diarrhea, dyspepsia, flatus, abdominal pain/cramps, nausea, heartburn.
Musculoskeletal: Muscle cramps, myalgia, myopathy, rhabdomyolysis.
CNS: Dizziness, headache, fatigue, sleep disorders, insomnia.
Skin: Rash, pruritus.
Special Senses: Blurred vision, dysgeusia.
Laboratory Test: Marked persistent increases of serum transaminases have been noted.
Immunosuppressive drugs, gemfibrozil, niacin (nicotinic acid), erythromycin and itraconazole.
When lovastatin and coumarin anticoagulants are administered concomitantly, prothrombin time may be increased in some patients. In patients taking anticoagulants, prothrombin time should be determined prior to starting therapy with lovastin and thereafter, monitored at the intervals usually recommended for patients on coumarin anticoagulants.
Myopathy or rhabdomyolysis has occurred in transplant and nontransplant patients receiving lovastatin following the initiation of treatment with the antifungal, itraconazole. This is probably related to metabolism of both drugs by the same P-450 isoform. Therapy with lovastatin should be temporarily interrupted if itraconazole therapy is required.
Store at temperatures between 15°C and 30°C. Keep in an airtight container. Protect from light and moisture.
Shelf-Life: 2 years.
C10AA02 - lovastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.
Tab 20 mg (light blue, octagonal, one side impressed with the mark "YUNG SHIN") x 10 x 6 x 10's.