Gemfibrozil

(BAN, USAN, rINN)
Gemfibrozil Chemical formula
Synonyms: CI-719; Gemfibrotsiili; Gemfibrozilo; Gemfibrozilum; Gemfibrozyl. 2,2-Dimethyl-5-(2,5-xylyloxy)valeric acid.
Cyrillic synonym: Гемфиброзил.

💊 Chemical information

Chemical formula: C15H22O3 = 250.3.
CAS — 25812-30-0.
ATC — C10AB04.
ATC Vet — QC10AB04.

Pharmacopoeias.

In Chin., Eur., and US.

Ph. Eur. 6.2

(Gemfibrozil). A white or almost white, waxy, crystalline powder. M.p. 58° to 61°. Practically insoluble in water; freely soluble in dehydrated alcohol and in methyl alcohol; very soluble in dichloromethane. Protect from light.

USP 31

(Gemfibrozil). A white waxy crystalline solid. M.p. 58° to 61°. Practically insoluble in water; soluble in alcohol, in methyl alcohol, and in chloroform. Store in airtight containers.

💊 Adverse Effects and Precautions

As for Bezafibrate.

Incidence of adverse effects.

In the Helsinki Heart Study,111.3% of 2051 patients taking gemfibrozil reported various moderate to severe upper gastrointestinal tract symptoms during the first year of treatment compared with 7% of 2030 patients taking placebo. No differences were seen between gemfibrozil and placebo groups in haemoglobin concentrations, urinary-protein, or urinary-sugar concentrations. There was no significant difference in the total number of cancers between the gemfibrozil and placebo groups nor in the number of operations for gallstones or for cataract surgery. A higher number of deaths in the gemfibrozil group was mainly due to accident or violence and intracranial haemorrhage. A follow-up study2 reported that gastrointestinal symptoms remained more common in patients taking gemfibrozil. Although there was no significant difference between the gemfibrozil and placebo groups cholecystectomies were consistently more common in those receiving gemfibrozil during the entire 8.5-year observation period. Cancer occurred equally in both groups, but there was increased mortality attributable to cancer in the gemfibrozil group, mainly during the last 1.5 years of follow-up; this difference was no longer apparent after 18 years.3
1. Frick MH, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia: safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987; 317: 1237–45
2. Huttunen JK, et al. The Helsinki Heart Study: an 8.5-year safety and mortality follow-up. J Intern Med 1994; 235: 31–9
3. Tenkanen L, et al. Gemfibrozil in the treatment of dyslipidemia: an 18-year mortality follow-up of the Helsinki Heart Study. Arch Intern Med 2006; 166: 743–8.

Effects on the skin.

Psoriasis was exacerbated in a patient within 2 weeks of starting gemfibrozil therapy and recurred when gemfibrozil was subsequently reintroduced.1
1. Fisher DA, et al. Exacerbation of psoriasis by the hypolipidemic agent, gemfibrozil. Arch Dermatol 1988; 124: 854–5.

💊 Interactions

As for Bezafibrate. Gemfibrozil is an inhibitor of a number of cytochrome P450 isoenzymes, including CYP2C8, CYP2C9, CYP2C19, and CYP1A2 and may increase the plasma concentration of drugs metabolised by these isoenzymes; it also inhibits some UDP-glucuronosyltransferases. Increased plasma concentration of bexarotene, pioglitazone, and rosiglitazone have been reported with gemfibrozil, and use of gemfibrozil in patients receiving repaglinide is contra-indicated due to the risk of serious hypoglycaemia.

💊 Pharmacokinetics

Gemfibrozil is readily absorbed from the gastrointestinal tract; bioavailability is close to 100% and is highest when gemfibrozil is taken 30 minutes before food. Peak concentrations in plasma occur within 1 to 2 hours; the half-life is about 1.5 hours. Plasma protein binding of gemfibrozil is about 98%. About 70% of a dose is excreted in the urine mainly as glucuronide conjugates of gemfibrozil and its metabolites; little is excreted in the faeces.

💊 Uses and Administration

Gemfibrozil, a fibric acid derivative, is a lipid regulating drug with actions on plasma lipids similar to those of bezafibrate. Gemfibrozil is used to reduce total cholesterol and triglycerides in the management of hyperlipidaemias, including type IIa, type IIb, type III, type IV, and type V hyperlipoproteinaemias. It is also indicated for the primary prevention of ischaemic heart disease in hyperlipidaemic men: in the USA this use is restricted to type IIb patients who also have low HDL-cholesterol concentrations and who have not responded to dietary and other measures. The usual oral dose is 1.2 g daily in 2 divided doses given 30 minutes before the morning and evening meals. Alternatively, a single daily dose of 900 mg has been given 30 minutes before the evening meal.
1. Spencer CM, Barradell LB. Gemfibrozil: a reappraisal of its pharmacological properties and place in the management of dyslipidaemia. Drugs 1996; 51: 982–1018.

Administration in renal impairment.

Gemfibrozil is contra-indicated in patients with severe renal impairment. However, UK licensed prescribing information allows its use in patients with mild to moderate impairment (glomerular filtration rate 30 to 80 mL/minute per 1.73 m2); the initial dose should be reduced to 900 mg daily and renal function should be assessed before increasing the dose. In a study1 of the pharmacokinetics of gemfibrozil in 17 patients with stable chronic renal failure the mean plasma half-life was 1.8 and 1.9 hours after multiple and single doses respectively, which was comparable with that reported in patients with normal renal function. Gemfibrozil clearance was independent of renal function, but the kinetics of gemfibrozil metabolites were not evaluated. Beneficial responses2 were seen in lipid and lipoprotein concentrations in 5 of 6 uraemic patients treated with gemfibrozil 1.2 g daily for six months and in 6 nephrotic patients given gemfibrozil 800 mg daily for 4 months. No significant adverse effects or signs of organ toxicity were seen. Results of a secondary prevention study3 also suggested that gemfibrozil at a dose of 1.2 g daily was safe and effective in patients with mild to moderate renal impairment.
1. Evans JR, et al. The effect of renal function on the pharmacokinetics of gemfibrozil. J Clin Pharmacol 1987; 27: 994–1000
2. Manninen V, et al. Gemfibrozil treatment of dyslipidaemias in renal failure with uraemia or in the nephrotic syndrome. Res Clin Forums 1982; 4: 113–18
3. Tonelli M, et al. for the Veterans’ Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) Investigators. Gemfibrozil for secondary prevention of cardiovascular events in mild to moderate chronic renal insufficiency. Kidney Int 2004; 66: 1123–30.

💊 Preparations

BP 2008: Gemfibrozil Capsules; Gemfibrozil Tablets; USP 31: Gemfibrozil Capsules; Gemfibrozil Tablets.

Proprietary Preparations

Arg.: Gedun; Hipolixan; Lopid; Austral.: Ausgem; Gemhexal; Jezil; Lipazil; Lopid; Austria: Gevilon; Braz.: Lopid; Lozil; Canad.: Lopid; Chile: Grifogemzilo; Lipotril; Lopid; Cz.: Gevilon†; Innogem†; Ipolipid†; Denm.: Lopid; Fin.: Gevilon; Lopid; Fr.: Lipur; Ger.: Gemfi; Gevilon; Lipox Gemfi†; Gr.: Adratan†; Amedran; Antilipid; Cholhepan; Clipostat; Dosamont; Drisofal†; Eklipid; Entianthe†; Fibrolip; Fibrospes; Gebrozil†; Gedizil; Gemfolid; Gemlipid; Gineton; Hobatolex; Lisolip; Lopid; Noxobran†; Parnoxil; Prelisin; Renolip; Solulip; Terostrant; Tiazam; Hong Kong: Gemzil; Ipolipid; Lipison; Lipistorol; Lipofor; Lopid; Lowin; Marbrozil; Qualipid; Saffid; Synbrozil; Hung.: Innogem; Minilip; India: Lopid; Normolip; Indon.: Detrichol; Fetinor; Fibralip; Hypofil; Inobes; Lapibroz; Lifibron; Lipira; Lipitrop; Lokoles; Lopid; Lowlip; Mersikol; Nufalemzil; Progemzal; Renabrazin; Scantipid; Zilop; Irl.: Lopid; Ital.: Fibrocit; Gemlipid; Genlip; Genozil; Lipogen; Lipozid; Lopid; Malaysia: Brozil; Fibrol†; Ipolipid; Lipistorol†; Lipofor; Lopid†; Mariston†; Mex.: Apo-Fide; Lopid; Raypid; Neth.: Lopid; NZ: Gemizol†; Philipp.: Lipigem; Lipison; Lipizile; Lipozid; Lopid; Reducel; Port.: Lipoite; Lopid; Rus.: Ipolipid (Иполипид); S.Afr.: Lopid; Singapore: Brozil; Gemd†; Hidil; Ipolipid; Lipison†; Lipofor; Lopid†; Recozil; Spain: Bolutol†; Decrelip†; Lopid; Pilder; Trialmin; Swed.: Lopid; Switz.: Gevilon; Thai.: Bisil; Chlorestrol†; Deopid†; Dropid; Gemfibril; GFB; Gozid; Hidil; Lipidys; Lipison; Lipolo; Lipozil; Locholes; Lopid; Manobrozil; Mariston; Norpid; Pharzil; PoliFibrozil; Polyxit; Tiba; Turk.: Lopid; UK: Lopid; USA: Lopid; Venez.: Lipontal; Lopid.
Published March 20, 2019.