Hypertriglyceridemia (alternative agent) (adjunctive agent):
Note: For patients requiring fibrate therapy, fenofibrate is generally preferred. All patients should receive general measures (ie, address modifiable causes, manage atherosclerotic cardiovascular disease [ASCVD] risk, implement lifestyle modification [eg, dietary changes, reduction of alcohol consumption]) and optimal low-density lipoprotein lowering therapy for 4 to 12 weeks before considering triglyceride lowering therapy. For patients whose triglycerides remain ≥500 mg/dL and who do not warrant icosapent ethyl for additional ASCVD risk reduction, either a fibrate or any prescription strength omega-3 fatty acid (including icosapent ethyl) is reasonable (ACC [Virani 2021]).
Oral: 600 mg twice daily 30 minutes before breakfast and dinner.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Kidney Disease: Improving Global Outcomes guidelines recommend against the use of fibric acid derivatives in patients with chronic kidney disease (CKD), except for in the rare patient with severe hypertriglyceridemia who is at risk for pancreatitis (KDIGO 2013). Gemfibrozil has been associated with reversible elevations in SCr, although the clinical significance is unknown (Davidson 2007).
Altered kidney function: Oral:
CrCl ≥60 mL/minute: No dosage adjustment necessary (Evans 1987).
CrCl 30 to <60 mL/minute: No dosage adjustment is likely necessary based on pharmacokinetic data (Evans 1987; Kasiske 2004); however, gemfibrozil is poorly tolerated in patients with CKD (eg, significantly more GI-related adverse effects) (Dogra 2007) and increases in SCr have been reported (Tonelli 2004). Monitor patients closely.
CrCl <30 mL/minute: Use is contraindicated in severe kidney impairment (CrCl not specified) according to the manufacturer's labeling; however, if use of gemfibrozil is deemed necessary, initiate at a dose of 600 mg once daily with close monitoring. If the response is inadequate and risks outweigh benefits, may consider increasing the dose with extreme caution; not to exceed 600 mg twice daily with frequent monitoring for adverse effects (Evans 1987; Kasiske 2004; Knauf 1990; expert opinion).
Hemodialysis, intermittent (thrice weekly): Not likely to be significantly dialyzable (highly protein bound) (expert opinion):
Oral: Use is contraindicated in severe kidney impairment according to the manufacturer's labeling; however, if use of gemfibrozil is deemed necessary, dose as for CrCl <30 mL/minute (expert opinion).
Peritoneal dialysis: Not likely to be significantly dialyzable (highly protein bound) (expert opinion):
Oral: Use is contraindicated in severe kidney impairment according to the manufacturer's labeling; however, if use of gemfibrozil is deemed necessary, dose as for CrCl <30 mL/minute (expert opinion). One study found increases in creatine kinase with doses over 600 mg/day in patients on peritoneal dialysis (Chan 1989).
CRRT:
Oral: If necessary, dose as for CrCl <30 mL/minute with close monitoring for adverse effects (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration):
Oral: If necessary, dose as for CrCl <30 mL/minute with close monitoring for adverse effects (expert opinion).
There are no dosage adjustments provided in the manufacturer’s labeling; use is contraindicated.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Lopid: 600 mg [scored]
Generic: 600 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 300 mg
Tablet, Oral:
Generic: 600 mg
Administer 30 minutes prior to breakfast and dinner.
Hypertriglyceridemia: Treatment of hypertriglyceridemia in Fredrickson types IV and V hyperlipidemia for patients who are at greater risk for pancreatitis and who have not responded to dietary intervention; to reduce the risk of CHD development in Fredrickson type IIb patients without a history or symptoms of existing CHD who have not responded to dietary and other interventions (including pharmacologic treatment) and who have decreased HDL, increased LDL, and increased triglycerides.
Gemfibrozil may be confused with gabapentin
Lopid may be confused with Levbid, Lipitor, Lodine
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Gastrointestinal: Dyspepsia (20%)
1% to 10%:
Cardiovascular: Atrial fibrillation (1%)
Central nervous system: Fatigue (4%), vertigo (2%)
Dermatologic: Eczema (2%), skin rash (2%)
Gastrointestinal: Abdominal pain (10%), nausea and vomiting (3%)
<1%, postmarketing and/or case reports (probable causation): Anemia, angioedema, arthralgia, blurred vision, bone marrow depression, cholecystitis, cholelithiasis, cholestatic jaundice, decreased libido, depression, dermatitis, dermatomyositis, dizziness, drowsiness, dysgeusia, eosinophilia, exfoliative dermatitis, headache, hypoesthesia, hypokalemia, impotence, increased creatine phosphokinase, increased serum alkaline phosphatase, increased serum bilirubin, increased serum transaminases, laryngeal edema, leukopenia, limb pain, myalgia, myasthenia, myopathy, nephrotoxicity, paresthesia, peripheral neuritis, polymyositis, pruritus, Raynaud phenomenon, rhabdomyolysis, synovitis, urticaria
Reports where causal relationship has not been established: Alopecia, anaphylaxis, cataract, colitis, confusion, extrasystoles, hepatic neoplasm, intracranial hemorrhage, lupus-like syndrome, pancreatitis, peripheral vascular disease, positive ANA titer, reduced fertility (male), renal insufficiency, retinal edema, seizure, skin photosensitivity, syncope, thrombocytopenia, vasculitis, weight loss
Hypersensitivity to gemfibrozil or any component of the formulation; hepatic or severe renal dysfunction; primary biliary cirrhosis; preexisting gallbladder disease; concurrent use with dasabuvir, repaglinide, selexipag, or simvastatin.
Canadian labeling: Additional contraindications (not in the US labeling): Renal dysfunction; concurrent use with cerivastatin; pregnancy; breastfeeding.
Documentation of allergenic cross-reactivity for fibrates is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Concerns related to adverse effects:
• Cholelithiasis: May increase risk of cholelithiasis; discontinue if gallstones are found upon gallbladder studies.
• Elevated transaminases: Elevations in serum transaminases may be seen with use; periodic monitoring recommended.
• Hematologic effects: May cause mild decreases in hemoglobin, hematocrit, and WBC upon initiation which usually stabilizes with long-term therapy. Anemia, leukopenia, thrombocytopenia, and bone marrow hypoplasia have rarely been reported. Periodic monitoring recommended during the first year of therapy.
• Malignancy: Possible increased risk of malignancy.
• Myopathy/rhabdomyolysis: Has been associated with rare myositis or rhabdomyolysis; patients should be monitored closely. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine.
Disease-related concerns:
• Renal impairment: Use with caution in patients with mild-to-moderate renal impairment; contraindicated in patients with severe impairment. Deterioration has been seen when used in patients with a serum creatinine >2 mg/dL.
Other warnings/precautions:
• Appropriate use: Secondary causes of hyperlipidemia should be ruled out prior to therapy. Be careful in patient selection, this is not a first- or second-line choice; other agents may be more suitable. Discontinue if lipid response not seen.
Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C8 (strong), OAT1/3, OATP1B1/1B3 (SLCO1B1/1B3)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acipimox: May enhance the myopathic (rhabdomyolysis) effect of Fibric Acid Derivatives. Risk C: Monitor therapy
Alitretinoin (Systemic): CYP2C8 Inhibitors (Strong) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP2C8 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP2C8 inhibitor. Risk D: Consider therapy modification
Amiodarone: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Amiodarone. Risk C: Monitor therapy
Amodiaquine: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Amodiaquine. Risk X: Avoid combination
Apalutamide: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Apalutamide. Risk C: Monitor therapy
Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Risk X: Avoid combination
Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Atogepant. Management: The recommended dose of atogepant when coadministered with OATP1B1/1B3 inhibitors is 10 mg once daily or 30 mg once daily. Risk D: Consider therapy modification
Atorvastatin: Gemfibrozil may enhance the myopathic (rhabdomyolysis) effect of Atorvastatin. Gemfibrozil may increase the serum concentration of Atorvastatin. Risk X: Avoid combination
Bexarotene (Systemic): Gemfibrozil may increase the serum concentration of Bexarotene (Systemic). Risk X: Avoid combination
Bile Acid Sequestrants: May decrease the absorption of Fibric Acid Derivatives. Management: Separate doses by at least 2 hours to minimize this interaction; fenofibric acid labeling recommends administration one hour prior to or 4-6 hours after a bile acid sequestrant. Risk D: Consider therapy modification
Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider therapy modification
Ciprofibrate: May enhance the adverse/toxic effect of Fibric Acid Derivatives. Risk X: Avoid combination
Clofarabine: OAT1/3 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy
Colchicine: Fibric Acid Derivatives may enhance the myopathic (rhabdomyolysis) effect of Colchicine. Risk C: Monitor therapy
CycloSPORINE (Systemic): May enhance the nephrotoxic effect of Fibric Acid Derivatives. Fibric Acid Derivatives may decrease the serum concentration of CycloSPORINE (Systemic). Management: Careful consideration of the risks and benefits should be undertaken prior to use of this combination; extra monitoring of renal function and cyclosporine concentrations will likely be required. Adjustment of cyclosporine dose may be necessary. Risk D: Consider therapy modification
Dabrafenib: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Dabrafenib. Management: Consider alternatives to strong CYP2C8 inhibitors in patients being treated with dabrafenib. If such a combination cannot be avoided, monitor closely for evidence of dabrafenib-related adverse effects. Risk D: Consider therapy modification
Dasabuvir: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Dasabuvir. Risk X: Avoid combination
Desloratadine: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Desloratadine. Risk C: Monitor therapy
Dichlorphenamide: OAT1/3 Inhibitors may increase the serum concentration of Dichlorphenamide. Risk C: Monitor therapy
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Risk X: Avoid combination
Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid combination
Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased eluxadoline effects/toxicities. Risk D: Consider therapy modification
Enzalutamide: CYP2C8 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Enzalutamide. CYP2C8 Inhibitors (Strong) may increase the serum concentration of Enzalutamide. Management: Avoid concurrent use of strong CYP2C8 inhibitors and enzalutamide if possible. If the combination must be used, reduce enzalutamide to 80 mg once daily. Once the inhibitor is discontinued, return enzalutamide to the dose used prior to inhibitor initiation Risk D: Consider therapy modification
Ezetimibe: Fibric Acid Derivatives may enhance the adverse/toxic effect of Ezetimibe. Specifically, the risk of myopathy and cholelithiasis may be increased. Fibric Acid Derivatives may increase the serum concentration of Ezetimibe. Risk X: Avoid combination
Fluvastatin: Gemfibrozil may enhance the myopathic (rhabdomyolysis) effect of Fluvastatin. Risk X: Avoid combination
Imatinib: Gemfibrozil may decrease serum concentrations of the active metabolite(s) of Imatinib. Specifically N-desmethylimatinib concentrations may be decreased. Gemfibrozil may decrease the serum concentration of Imatinib. Risk C: Monitor therapy
Lovastatin: Gemfibrozil may increase the serum concentration of Lovastatin. More specifically, gemfibrozil may increase the serum concentrations of lovastatin acid (active form of parent drug). Risk X: Avoid combination
Montelukast: Gemfibrozil may increase the serum concentration of Montelukast. Risk C: Monitor therapy
OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors): Gemfibrozil may increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Specifically, the concentrations of the dasabuvir component may be increased. Risk X: Avoid combination
Ozanimod: CYP2C8 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ozanimod. Risk X: Avoid combination
PACLitaxel (Conventional): CYP2C8 Inhibitors (Strong) may increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP2C8 Inhibitors (Strong) may increase the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy
Pioglitazone: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Pioglitazone. Management: Limit the pioglitazone dose to 15 mg daily and monitor for increased pioglitazone toxicities (eg, hypoglycemia) when used in combination with strong CYP2C8 inhibitors. Risk D: Consider therapy modification
Pitavastatin: Gemfibrozil may enhance the myopathic (rhabdomyolysis) effect of Pitavastatin. Gemfibrozil may increase the serum concentration of Pitavastatin. Risk X: Avoid combination
Pravastatin: Gemfibrozil may enhance the myopathic (rhabdomyolysis) effect of Pravastatin. Gemfibrozil may increase the serum concentration of Pravastatin. Risk X: Avoid combination
Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of Fibric Acid Derivatives. Risk C: Monitor therapy
Red Yeast Rice: Gemfibrozil may increase the serum concentration of Red Yeast Rice. Risk X: Avoid combination
Repaglinide: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Risk X: Avoid combination
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Risk X: Avoid combination
Rosiglitazone: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Rosiglitazone. Risk C: Monitor therapy
Rosuvastatin: Gemfibrozil may enhance the myopathic (rhabdomyolysis) effect of Rosuvastatin. Gemfibrozil may increase the serum concentration of Rosuvastatin. Management: Avoid combination if possible. If combination cannot be avoided, initiate rosuvastatin at 5 mg/day and limit rosuvastatin to 10 mg/day. Monitor for signs/symptoms of rhabdomyolysis. Risk D: Consider therapy modification
Roxadustat: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Roxadustat. Risk C: Monitor therapy
Selexipag: CYP2C8 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Selexipag. CYP2C8 Inhibitors (Strong) may increase the serum concentration of Selexipag. Risk X: Avoid combination
Simvastatin: Gemfibrozil may enhance the myopathic (rhabdomyolysis) effect of Simvastatin. Gemfibrozil may increase the serum concentration of Simvastatin. Concentrations of the active simvastatin acid metabolite may also be increased by gemfibrozil. Risk X: Avoid combination
Sulfonylureas: Fibric Acid Derivatives may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Taurursodiol. Risk X: Avoid combination
TiaGABine: Gemfibrozil may increase the serum concentration of TiaGABine. Both total and unbound concentrations may be increased. Risk C: Monitor therapy
Treprostinil: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Treprostinil. Management: Reduce the initial treprostinil extended release tablet dose to 0.125 mg twice daily, titrating by 0.125 mg twice daily every 3 to 4 days. No preemptive dose adjustment is recommended for other treprostinil products. Risk D: Consider therapy modification
Tucatinib: CYP2C8 Inhibitors (Strong) may increase the serum concentration of Tucatinib. Management: Combined use not recommended. If the combo cannot be avoided, reduce tucatinib to 100 mg twice daily. After stopping the strong CYP2C8 inhibitor, wait 3 half-lives of the discontinued inhibitor and resume the tucatinib dose taken prior to the inhibitor. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Fibric Acid Derivatives may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Consider reducing the oral anticoagulant dose by 25% to 33% when initiating a fibric acid derivative. Monitor for toxic or reduced anticoagulant effects if a fibric acid derivative is initiated/dose increased, or discontinued/dose decreased, respectively. Risk D: Consider therapy modification
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Risk X: Avoid combination
When given after meals, the AUC of gemfibrozil is decreased. Management: Administer 30 minutes prior to breakfast and dinner.
Gemfibrozil crosses the placenta (Tsai 2004).
Triglyceride concentrations increase during pregnancy as required for normal fetal development. When increases are greater than expected, supervised dietary intervention should be initiated. In women who develop very severe hypertriglyceridemia and are at risk for pancreatitis, use of gemfibrozil beginning in the second trimester is one intervention that may be considered (Avis 2009; Berglund 2012; Jacobson 2015; Wong 2015).
It is not known if gemfibrozil is present in breast milk.
Lipids are a normal component of breast milk and the fatty acid component is required for normal infant neurologic development. Maternal diet, as well as other factors, may influence the fatty acid composition (Innis 2014). When treatment for very severe hypertriglyceridemia in breastfeeding women at risk for pancreatitis is needed, therapy with gemfibrozil may be considered (Jacobson 2015). When treatment is needed for other indications, agents other than gemfibrozil are preferred (Jacobson 2015; NICE 2008). Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.
Before initiation of therapy, patients should be placed on a standard cholesterol-lowering diet for 3 to 6 months and the diet should be continued during drug therapy. Administer 30 minutes prior to breakfast and dinner
Serum cholesterol, LFTs periodically, CBC periodically (first year)
The exact mechanism of action of gemfibrozil is unknown, however, several theories exist regarding the VLDL effect; it can inhibit lipolysis and decrease subsequent hepatic fatty acid uptake as well as inhibit hepatic secretion of VLDL; together these actions decrease serum VLDL levels; increases HDL-cholesterol; the mechanism behind HDL elevation is currently unknown
Onset of action: May require several days
Absorption: Well absorbed
Protein binding: 99%
Metabolism: Hepatic via oxidation to two inactive metabolites; undergoes enterohepatic recycling
Half-life elimination: 1.5 hours
Time to peak, serum: 1 to 2 hours
Excretion: Urine (~70% primarily as conjugated drug); feces (6%)
Tablets (Gemfibrozil Oral)
600 mg (per each): $0.14 - $2.43
Tablets (Lopid Oral)
600 mg (per each): $1.55
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.