Lovastatin

(BAN, USAN, rINN)
Lovastatin Chemical formula
Synonyms: L-154803; Lovastatiini; Lovastatina; Lovastatinas; Lovastatine; Lovastatinum; Lovasztatin; MB-530B; 6 Mevinolin; MK-803; Monacolin K; MSD-803. (3R,5R)-7{(1S,2S,6R,8S,8aR)-1,2,6,7,8,8a-Hexahydro-2,6-dimethyl-8-[(S)-2methylbutyryloxy]-1-naphthyl}-3-hydroxyheptan-5-olide.
Cyrillic synonym: Ловастатин.

💊 Chemical information

Chemical formula: C24H36O5 = 404.5.
CAS — 75330-75-5.
ATC — C10AA02.
ATC Vet — QC10AA02.

Pharmacopoeias.

In Eur. and US.

Ph. Eur. 6.2

(Lovastatin). A white or almost white crystalline powder. Practically insoluble in water; sparingly soluble in dehydrated alcohol; soluble in acetone. Store under nitrogen at a temperature of 2° to 8°.

USP 31

(Lovastatin). A white to off-white crystalline powder. Insoluble in water; sparingly soluble in alcohol; practically insoluble in petroleum spirit; freely soluble in chloroform; soluble in acetone, in acetonitrile, and in methyl alcohol. Store under nitrogen in airtight containers at a temperature not exceeding 8°.

💊 Adverse Effects and Precautions

As for Simvastatin.

Incidence of adverse effects.

Adverse effects led to withdrawal of lovastatin in 21 of 745 patients receiving the drug for about 5 years.1 They included asymptomatic elevation of hepatic aminotransferases in 10 patients, gastrointestinal symptoms in 3, rash in 2, myopathy in 2, myalgia in 1, arthralgia in 1, insomnia in 1, and weight gain in 1.
1. Lovastatin Study Groups. Lovastatin 5-year safety and efficacy study: Lovastatin Study Groups I through IV. Arch Intern Med 1993; 153: 1079–87.

💊 Interactions

As for Simvastatin. For specific dosage reductions in patients taking lovastatin with interacting drugs, see Uses and Administration, below.

💊 Pharmacokinetics

Lovastatin is absorbed from the gastrointestinal tract and must be hydrolysed to its active β-hydroxyacid form. Three other metabolites have also been isolated. Lovastatin is a substrate for the cytochrome P450 isoenzyme CYP3A4 and undergoes extensive firstpass metabolism in the liver, its primary site of action; less than 5% of an oral dose has been reported to reach the circulation. Peak plasma concentrations occur within 2 to 4 hours, and steady-state concentrations are achieved after 2 to 3 days with daily dosage. Both lovastatin and its β-hydroxyacid metabolite are more than 95% bound to plasma proteins. Lovastatin is mainly excreted in the bile as metabolites; about 85% of a dose has been recovered from the faeces and about 10% from the urine. The half-life of the active metabolite is 1 to 2 hours.
1. Desager J-P, Horsmans Y. Clinical pharmacokinetics of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. Clin Pharmacokinet 1996; 31: 348–71
2. Lennernäs H, Fager G. Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors: similarities and differences. Clin Pharmacokinet 1997; 32: 403–25.

💊 Uses and Administration

Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (a statin), is a lipid regulating drug with actions on plasma lipids similar to those of simvastatin. Lovastatin is used to reduce cholesterol in the treatment of hyperlipidaemias, particularly in type IIa and IIb hyperlipoproteinaemias. It is also given for cardiovascular risk reduction in both primary and secondary prevention of ischaemic heart disease. Lovastatin is given in an initial oral dose of 10 to 20 mg daily in the evening with food, increased, if necessary, at intervals of 4 weeks or more to 80 mg daily as a single dose or in 2 divided doses. Lower doses of lovastatin should be used in patients at risk of myopathy, including patients with severe renal impairment (see below) and those taking drugs that interact with lova statin; an initial dose of 10 mg daily is recommended in patients taking ciclosporin or danazol, and the daily dose should not exceed 20 mg in patients taking ciclosporin, danazol, fibric acid derivatives, or nicotinic acid, or 40 mg in those taking amiodarone or verapamil. For the use of lovastatin in children, see below.
1. Curran MP, Goa KL. Lovastatin extended release: a review of its use in the management of hypercholesterolaemia. Drugs 2003; 63: 685–99.

Administration in children.

Lovastatin reduces plasma-cholesterol concentrations in children and adolescents with heterozygous familial hypercholesterolaemia1-3 and has been given safely for up to 48 weeks in boys,2 and up to 24 weeks in girls.3In the USA it is licensed in children aged 10 to 17 years and is given orally in an initial dose of 10 to 20 mg once daily, increased at intervals of 4 weeks or more, if necessary, to a maximum dose of 40 mg once daily.
1. Lambert M, et al. Canadian Lovastatin in Children Study Group. Treatment of familial hypercholesterolemia in children and adolescents: effect of lovastatin. Pediatrics 1996; 97: 619–28
2. Stein EA, et al. Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial. JAMA 1999; 281: 137–44
3. Clauss SB, et al. Efficacy and safety of lovastatin therapy in adolescent girls with heterozygous familial hypercholesterolemia. Pediatrics 2005; 116: 682–8.

Administration in renal impairment.

Patients with renal impairment may be at increased risk of myopathy and US licensed product information states that doses of lovastatin above 20 mg daily should be used cautiously in patients with a creatinine clearance below 30 mL/minute.

Adrenoleucodystrophy.

A preliminary study1 has shown that lovastatin may be useful in the treatment of adrenoleucodystrophy. Lovastatin reduced the plasma levels of very-long-chain fatty acids which are known to be elevated in patients with this rare metabolic disorder.
1. Pai GS, et al. Lovastatin therapy for X-linked adrenoleukodystrophy: clinical and biochemical observations on 12 patients. Mol Genet Metab 2000; 69: 312–22.

💊 Preparations

USP 31: Lovastatin Tablets.

Proprietary Preparations

Arg.: Hipovastin; Loriter†; Mevlor; Sivlor†; Austria: Mevacor; Braz.: Lipoclin; Lovast†; Lovaton†; Lovax†; Mevacor; Mevalip; Minor†; Neolipid†; Reducol; Canad.: Mevacor; Chile: Colevix†; Hiposterol; Lispor; Lovacol; Mevacor†; Nij-Terol†; Sanelor; Cz.: Holetar; Lovacard†; Medostatin; Mevacor; Rancor; Denm.: Lovacodan; Mevacor; Fin.: Lovacol; Mevacor; Ger.: Lova†; Lovabeta; Lovadura; Lovagamma; Lovahexal; Mevinacor; Gr.: Aurostatin; B-Lovatin†; Cecural; Ilopar; Liferzit; Lipidless; Lostin; Lovadrug; Lovapen; Lovasten; Lovatex; Lovatop; Lowlipid; Medovascin; Mevacor; Mevastin; Mevinol†; Misodomin; Nabicortin; Terveson; Velkalov; Viking; Hong Kong: Ellanco; Lofacol†; Lomar; Medostatin; Mevacor; Hung.: Mevacor; Stoplip; India: Lovacard; Pro-HDL; Rovacor; Indon.: Cholvastin; Lipovas; Lofacol; Lotyn; Lovatrol; Israel: Lovalip†; Ital.: Lovinacor; Rextat; Tavacor; Malaysia: Lestric; Lostatin; Lovarem; Lovastin; Medostatin; Mevacor†; Mex.: Casbame; Dilucid; Liperol; Mevacor; Norw.: Mevacor; Pol.: Anlostin; Apo-Lova; Liprox; Lovasterol; Lovastin; Port.: Flozul; Lipdaune; Lipus; Mevinacor; Mevlor; Tecnolip; Rus.: Cardiostatin (Кардиостатин); Holetar (Холетар); Lovasterol (Ловастерол); Medostatin (Медостатин); Rovacor (Ровакор); S.Afr.: Lovachol; Singapore: Elstatin; Lostatin; Lovastin; Medostatin; Rovacor; Spain: Aterkey; Colesvir; Lipofren†; Liposcler; Mevacor; Mevasterol; Nergadan; Taucor; USA: Altoprev; Mevacor; Venez.: Dislipin†; Levistan; Lostatin†; Lovanil; Lovas†; Mevacor. Multi-ingredient: USA: Advicor.
Published May 08, 2019.