Chemical formula: C₁₅H₂₂O₃ Molecular mass: 250.333 g/mol PubChem compound: 3463
Gemfibrozil interacts in the following cases:
The interaction profile of gemfibrozil is complex. In vivo studies indicate that gemfibrozil and its metabolite gemfibrozil 1-O-β-glucuronide are potent inhibitors of CYP2C8 (an enzyme important for the metabolism of e.g. dabrafenib, enzalutamide, loperamide, montelukast, repaglinide, rosiglitazone, pioglitazone, dasabuvir, selexipag and paclitaxel). Co-administration of gemfibrozil with repaglinide, dasabuvir or selexipag is contraindicated. In addition, dosing reduction of drugs that are mainly metabolised by CYP2C8 enzyme may be required when gemfibrozil is used concomitantly.
Gemfibrozil 1-O-β-glucuronide also inhibits OATP1B1.
In vitro studies have shown that gemfibrozil is a strong inhibitor of CYP2C9 (an enzyme involved in the metabolism of e.g. warfarin and glimepiride), but also of CYP2C19, CYP1A2, OATP1B1 and UGTA1 and UGTA3.
In patients with mild to moderate renal impairment (Glomerular filtration rate 50 – 80 and 30 - < 50 ml/min/1.73 m², respectively), start treatment at 900 mg daily and assess renal function before increasing dose. Gemfibrozil should not be used in patients with severely impaired renal function.
Gemfibrozil may potentiate the effects of coumarin type vitamin K antagonist anticoagulants such as warfarin, acenocoumarol, or phenprocoumon. The concomitant administration of gemfibrozil with these anticoagulants necessitates careful monitoring of prothrombin time (INR – International Normalised Ratio). Caution should be exercised when such a coumarin type vitamin K antagonist anticoagulant is given concomitantly with gemfibrozil. The dosage of the anticoagulant may need to be reduced to maintain desired prothrombin time levels.
Reduced bioavailability of gemfibrozil may result when given simultaneously with resin-granule drugs such as colestipol. Administration of the products two hours or more apart is recommended.
Reversible decreases in male fertility have been observed in reproductive toxicity studies in rats.
Concomitant administration of gemfibrozil with bexarotene is not recommended. A population analysis of plasma bexarotene concentrations in patients with cutaneous T-cell lymphoma (CTCL) indicated that concomitant administration of gemfibrozil resulted in substantial increases in plasma concentrations of bexarotene.
Risk of myopathy and rhabdomyolysis may be increased with concomitant administration of colchicine and gemfibrozil. This risk may be increased in the elderly and in patients with hepatic or renal dysfunction. Clinical and biological monitoring are recommended, especially at the start of combined treatment.
In healthy volunteers given a single 160 mg dose of enzalutamide after gemfibrozil 600 mg twice daily, the AUC of enzalutamide plus active metabolite (N-desmethyl enzalutamide) was increased by 2.2-fold and corresponding Cmax was decreased by 16%. Increased enzalutamide exposure may increase the risk of seizures. Concomitant treatment of gemfibrozil and enzalutamide should be avoided; if co-administration is considered necessary, the dose of enzalutamide should be reduced.
The combination of gemfibrozil with rosiglitazone should be approached with caution. Co-administration with rosiglitazone has resulted in 2.3-fold increase in rosiglitazone systemic exposure, probably by inhibition of the CYP2C8 isozyme.
There are no adequate data on use of gemfibrozil in pregnant women. Animal studies are insufficiently clear to allow conclusions to be drawn on pregnancy and foetal development. The potential risk for humans is unknown. Gemfibrozil should not be used during pregnancy unless it is clearly necessary.
There are no data on excretion of gemfibrozil in milk. Gemfibrozil should not be used when breast-feeding.
Reversible decreases in male fertility have been observed in reproductive toxicity studies in rats.
No studies on the effects on the ability to drive and use machines have been performed. In isolated cases dizziness and visual disturbances can occur which may negatively influence driving.
Most commonly reported adverse reactions are of gastrointestinal character and are seen in approximately 7% of the patients. These adverse reactions do not usually lead to discontinuation of the treatment.
Adverse reactions are ranked according to frequency using the following convention: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), including isolated reports:
Rare: Bone marrow failure, severe anaemia, thrombocytopenia, leukopenia, eosinophilia
Rare: Depression, decreased libido
Common: Vertigo, headache
Rare: Neuropathy peripheral, paraesthesia, dizziness, somnolence
Rare: Vision blurred
Uncommon: Atrial fibrillation
Rare: Laryngeal oedema
Very common: Dyspepsia
Common: Diarrhoea, vomiting, nausea, abdominal pain constipation, flatulence
Rare: Pancreatitis, appendicitis
Rare: Jaundice cholestatic, hepatitis, cholelithiasis, cholecystitis, hepatic function abnormal
Common: Eczema, rash
Rare: Angioedema, dermatitis exfoliative, urticaria, dermatitis, alopecia, photosensitivity reaction, pruritus
Rare: Rhabdomyolysis, myopathy, myositis, muscular weakness, synovitis, myalgia, arthralgia, pain in extremity
Rare: Erectile dysfunction
Common: Fatigue
Rare: Haemoglobin decreased, haematocrit decreased, white blood cell count decreased, blood creatine phosphokinase increased
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