Gelicon

Approved indications

• Severe hypertriglyceridemia — to reduce serum triglyceride (TG) levels and lower the risk of pancreatitis in patients with markedly elevated TGs (typically ≥500 mg/dL) when diet and other measures are insufficient.
• Mixed dyslipidemia — treatment of patients with elevated triglycerides and low HDL cholesterol where reduction of TG and modest increases in HDL are desired.
• Type III hyperlipoproteinemia (dysbetalipoproteinemia) — used in patients with this specific disorder characterized by elevated β-VLDL/remnant lipoproteins when lifestyle interventions alone are inadequate.

Clinically accepted / off-label uses

• Adjunctive therapy in select patients with residual hypertriglyceridemia despite other lipid-lowering therapies (used cautiously because of interaction risk).
• Short-term therapy where rapid triglyceride lowering is required to reduce pancreatitis risk (combined with dietary measures and other supportive care).

Usual adult dose

• 600 mg orally twice daily, given 30 minutes before the morning and evening meals (or as directed by product labeling). Do not exceed recommended dose.

Special populations

• Elderly: no routine dosage reduction required solely for age, but start with standard dose and monitor closely for adverse effects (myopathy, hepatic dysfunction, drug interactions).
• Pediatrics: safety and efficacy not established for routine pediatric use; if considered for adolescents, use under specialist guidance.
• Renal impairment: use with caution; no well-established dose reduction algorithm—monitor renal function and adverse effects.
• Hepatic impairment: generally avoid in severe hepatic dysfunction; check LFTs before initiating and periodically; use alternative lipid agents if significant hepatic disease.
• Pregnancy & lactation: not routinely recommended — see Section 5.

Administration notes

• Take consistently relative to meals (30 minutes before) for predictable absorption.
• Continue lifestyle measures (diet, weight management, exercise, alcohol avoidance) while on therapy.
• When initiating or stopping interacting drugs (e.g., statins, repaglinide, warfarin), reassess doses and monitoring needs.

Gemfibrozil is a fibric acid derivative (a fibrate) that lowers triglyceride levels primarily by activating peroxisome proliferator-activated receptor-alpha (PPAR-α) in hepatocytes. PPAR-α activation increases expression of lipoprotein lipase and other enzymes involved in fatty acid oxidation, enhances catabolism of triglyceride-rich lipoproteins (VLDL), reduces hepatic VLDL production, and increases HDL particle levels. The net effect is decreased plasma triglycerides, modest increases in HDL cholesterol, and variable effects on LDL cholesterol.

• Absorption: Well absorbed orally; bioavailability influenced by formulation and food.
• Time to peak (Tmax): typically within 1–3 hours after dosing.
• Distribution: Highly protein bound (a large fraction binds to plasma proteins).
• Metabolism: Extensively metabolized in the liver primarily by glucuronidation to acyl glucuronide metabolites (active/inhibitory metabolites contribute to pharmacologic and interaction profile).
• Elimination: Metabolites excreted largely in the urine; small amounts in feces.
• Half-life: relatively short parent drug half-life (hours), but pharmacologic effects persist due to metabolites and PPAR-α–mediated gene expression changes.
• Steady state: achieved in a few days with twice-daily dosing.

• Pregnancy: Use is not recommended in pregnancy. Lipid-lowering therapy should generally be withheld during pregnancy except in rare, high-risk situations; insulin and dietary management are preferred for metabolic control if needed. If gemfibrozil use is contemplated in pregnancy, it should be discussed with a specialist and only used if the potential benefit justifies the potential risk to the fetus.
• Lactation: Gemfibrozil is excreted into breast milk in limited quantities; because of potential for adverse effects in the nursing infant (including effects on lipid metabolism), breastfeeding is generally not recommended during treatment. Discuss alternatives with the clinician.

• Primary class: Antilipemic agent — fibrate.
• Subclass: Fibric acid derivative; PPAR-α agonist.

• Known hypersensitivity to gemfibrozil or any component of the formulation.
• Severe hepatic dysfunction (active liver disease, unexplained persistent elevations of hepatic transaminases).
• Severe renal impairment in some settings (use caution and specialist judgment).
• Gallbladder disease or a history of gallstones — fibrates may increase biliary cholesterol saturation and risk of cholelithiasis.
• Concomitant use with certain statins (see Section 10): gemfibrozil should not be coadministered with simvastatin or other statins where a high risk of severe myopathy exists unless no acceptable alternatives and with extreme caution—current practice generally avoids combining gemfibrozil with most statins because of marked interaction risk.

• Myopathy and rhabdomyolysis: Risk increases substantially when gemfibrozil is combined with statins or other myotoxic drugs. Monitor for muscle pain, weakness, or dark urine. Check baseline and periodic creatine kinase (CK) if symptoms develop. Avoid combining with statins when possible; if combination is unavoidable, use the lowest effective statin dose and monitor closely.
• Hepatic dysfunction: Elevated liver enzymes or hepatotoxicity can occur; obtain baseline LFTs and monitor periodically; discontinue for persistent transaminase elevations or signs of liver injury.
• Renal effects: Monitor renal function in those with pre-existing renal disease; avoid in severe renal impairment unless specialist-managed.
• Cholelithiasis: Fibrate therapy is associated with increased risk of gallstones; investigate biliary colic symptoms.
• Hypersensitivity / hematologic effects: Rare blood dyscrasias have been reported; evaluate unexplained fatigue, infections, or bleeding.
• Drug interactions: See Section 10 — gemfibrozil interacts through inhibition of drug-metabolizing pathways (glucuronidation) and certain CYP enzymes (notably CYP2C8), producing clinically important interactions.

Very common / common

• Dyspepsia, abdominal pain, flatulence.
• Elevated liver enzymes (transaminases) — usually asymptomatic but monitor.

Less common

• Musculoskeletal: myalgia; rarely myositis.
• Gallbladder: cholelithiasis (gallstones) or biliary colic.
• Dermatologic: rash, urticaria.
• Hematologic: rare anemia, leucopenia, thrombocytopenia.
• Neurologic: headache, dizziness.

Serious / rare

• Rhabdomyolysis (especially when combined with statins or other interacting agents).
• Severe hepatotoxicity (rare).
• Severe allergic reactions (rare).

Timing & dose dependence

• Adverse effects may occur at any time but risk of hepatic enzyme elevations and muscle complaints commonly appears within weeks to months of therapy initiation or with dose escalation or interacting co-medications.

Gemfibrozil has several clinically important interactions — exercise caution and monitor when coadministered with the following:

• Statins (HMG-CoA reductase inhibitors): Significant interaction risk. Gemfibrozil increases plasma concentrations of many statins (notably simvastatin, lovastatin and to varying extents others) by inhibiting glucuronidation and affecting hepatic uptake, markedly increasing the risk of myopathy and rhabdomyolysis. Concomitant use is generally avoided; if lipid lowering requires a fibrate and statin, fenofibrate is often preferred over gemfibrozil when a fibrate is necessary with statin because fenofibrate has a lower interaction profile (but still carries risk).
• Repaglinide: Gemfibrozil markedly increases repaglinide exposure (CYP2C8 inhibition), leading to severe hypoglycaemia; coadministration is contraindicated.
• Warfarin (and other oral anticoagulants): Gemfibrozil can potentiate anticoagulant effects (changes in protein binding and metabolism), increasing bleeding risk and INR variability; more frequent INR monitoring and possible dose adjustment are required if used together.
• CYP and UGT substrates: Gemfibrozil inhibits CYP2C8 and certain UGT enzymes (glucuronidation), which can raise concentrations of drugs metabolized by these pathways (e.g., certain statins, repaglinide, cerivastatin historically). Review concomitant medications metabolized by CYP2C8 and UGTs.
• Other interactions: caution with drugs that cause myopathy (colchicine, certain antivirals), or that are highly protein bound (displacement interactions possible). Also monitor interactions with immunosuppressants and other narrow therapeutic index drugs.

Clinical actions

• Avoid coadministration with repaglinide and many statins; if warfarin is necessary, intensify INR monitoring. Review the full medication list for potential interactions before starting gemfibrozil.

• Therapeutic context: Contemporary lipid-management guidelines prioritize statins for cardiovascular risk reduction. Fibrates (including gemfibrozil) are used primarily to treat severe hypertriglyceridemia to reduce pancreatitis risk or in specific dyslipidemias (e.g., type III) where triglyceride lowering helps.
• Combination therapy caution: Current guidance advises caution combining fibrates with statins because of myopathy risk; if combination lipid lowering is required, careful selection (often fenofibrate preferred if a fibrate is needed) and close safety monitoring are recommended.
• Risk-benefit focus: Use gemfibrozil when clear benefit in TG lowering (reduction of pancreatitis risk) outweighs interaction and adverse-effect risks; consider alternatives when cardiovascular risk reduction is the primary goal.

• Store tablets at room temperature, generally 15–30°C (59–86°F), in a dry place away from light and moisture.
• Keep in original container, tightly closed, and out of reach of children.
• Do not use beyond printed expiration date.