Drug Monograph
Gemfibrozil (Lopid)
gemfibrozil
Pharmacokinetic Profile
Half-Life
1.5 h (multiple doses)
Metabolism
Hepatic oxidation; glucuronidation; strong CYP2C8 inhibitor
Protein Binding
~97% (albumin)
Bioavailability
~97-100%
Volume of Distribution
~0.8 L/kg
Clinical Information
Drug Class
Fibric acid derivative
Available Doses
600 mg tablets
Route
Oral, twice daily
Renal Adjustment
Contraindicated in severe renal dysfunction
Hepatic Adjustment
Contraindicated in hepatic dysfunction
Pregnancy
Use only if benefit justifies risk
Lactation
Avoid; tumorigenicity concern from animal data
Schedule / Legal
Prescription only (not controlled)
Generic Available
Yes
Gemfibrozil Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Severe hypertriglyceridemia (Types IV and V) — patients with pancreatitis risk who do not respond adequately to dietary measures; typically TG >1000 mg/dL | Adults | Adjunctive to diet | FDA Approved |
| Reducing coronary heart disease risk (Type IIb) — patients without existing CHD who have the triad of low HDL-C, elevated LDL-C, and elevated TG after inadequate response to diet, exercise, and other agents | Adults | Adjunctive to diet; after failure of other agents | FDA Approved |
Gemfibrozil occupies a distinct position among fibrates: it is the only fibrate with positive cardiovascular outcome data from two major trials. The Helsinki Heart Study demonstrated a 34% relative reduction in coronary events in primary prevention (p=0.04), and VA-HIT showed a 22% relative risk reduction for CHD death or nonfatal MI in secondary prevention patients with low HDL-C (p=0.006). However, gemfibrozil carries a substantially higher drug interaction burden than fenofibrate due to its potent inhibition of CYP2C8, OATP1B1, and UGT enzymes, making it a poor choice for combination with statins.
Off-Label Uses
Secondary prevention in established CHD with low HDL-C (moderate evidence): Although not listed as an FDA-approved indication in the current label, the VA-HIT trial (n=2531) demonstrated significant cardiovascular benefit in men with CHD and HDL-C ≤40 mg/dL. Some clinicians use gemfibrozil for this population when statin therapy is not tolerated or not feasible.
Dosing
Adult Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Severe hypertriglyceridemia — TG >1000 mg/dL with pancreatitis risk | 600 mg BID | 600 mg BID | 1200 mg/day | Take 30 minutes before breakfast and dinner Reassess lipids; discontinue if inadequate response after 3 months |
| Atherogenic dyslipidemia (Type IIb) — primary CHD prevention with low HDL, high LDL, high TG | 600 mg BID | 600 mg BID | 1200 mg/day | Only after failure of diet, exercise, weight loss, and other agents (bile acid sequestrants, niacin) Not indicated for isolated LDL elevation or isolated low HDL |
| Low HDL-C with established CHD — secondary prevention (VA-HIT population) | 600 mg BID | 600 mg BID | 1200 mg/day | Supported by VA-HIT trial data; used as monotherapy (not with statins) Never co-administer with simvastatin; avoid with all statins if possible |
| Mild-to-moderate renal impairment | 600 mg once daily | 600 mg once daily | 600 mg/day | No formal dose-adjustment guidelines in PI; expert consensus suggests reduced dose with close monitoring Contraindicated in severe renal dysfunction |
Clinical Pearl — Timing of Administration
Gemfibrozil absorption is significantly affected by meal timing. Peak plasma concentrations (Cmax) are 50-60% higher when the drug is taken 30 minutes before meals compared to with meals or fasting. The FDA label recommends administration 30 minutes before breakfast and dinner. Unlike the TriCor formulation of fenofibrate which can be taken without regard to meals, gemfibrozil requires consistent pre-meal dosing for optimal therapeutic effect. There is only one tablet strength (600 mg), so dose titration is limited to frequency adjustment.
Pharmacology
Mechanism of Action
Gemfibrozil is a fibric acid derivative whose precise mechanism has not been fully established. Its lipid-modifying effects are primarily mediated through activation of peroxisome proliferator-activated receptor alpha (PPARα), though it exhibits pharmacological properties distinct from other fibrates. Gemfibrozil inhibits peripheral lipolysis and decreases hepatic extraction of free fatty acids, thereby reducing hepatic triglyceride production. It suppresses synthesis and accelerates clearance of VLDL carrier apolipoprotein B, leading to decreased VLDL production. Gemfibrozil also increases activity of extrahepatic lipoprotein lipase, enhancing clearance of triglyceride-rich particles. This collectively shifts LDL composition toward larger, less atherogenic particles, raises HDL-C by stimulating apolipoprotein A-I and A-II synthesis, and increases both HDL2 and HDL3 subfractions.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Completely absorbed (~97-100%); Tmax 1-2 h; Cmax 50-60% higher when taken 30 min before meals vs with meals or fasting | Pre-meal dosing is critical for optimal absorption; AUC may be reduced 14-44% if taken after meals |
| Distribution | Vd ~0.8 L/kg; protein binding ~97% (albumin); crosses placenta (animal data) | High protein binding creates displacement interaction potential with warfarin and other highly bound drugs |
| Metabolism | Hepatic oxidation of ring methyl group to hydroxymethyl and carboxyl metabolites; glucuronide conjugation; strong inhibitor of CYP2C8, OATP1B1, UGT1A1/1A3; also inhibits CYP1A2, CYP2C9, CYP2C19 | Extensive enzyme and transporter inhibition profile creates major drug interaction risk; this is the key clinical difference from fenofibrate |
| Elimination | t½ 1.5 h; ~70% excreted in urine (mostly as glucuronide conjugates, <2% unchanged); 6% in feces; no accumulation with normal renal function | Short half-life necessitates twice-daily dosing; hemodialysis not considered effective due to high protein binding |
Side Effects
≥10%
Very Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Dyspepsia | 19.6% vs 11.9% placebo | Most common adverse effect; statistically significant excess over placebo in the Helsinki Heart Study; may improve over time |
1-10%
Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Abdominal pain | 9.8% vs 5.6% placebo | Statistically significant excess; consider biliary and pancreatic causes if severe or persistent |
| Diarrhea | Common (1-10%) | Dose-related GI effect; manage symptomatically |
| Nausea / Vomiting | Common (1-10%) | Usually mild and self-limiting; take 30 min before meals as directed |
| Flatulence / Constipation | Common (1-10%) | Part of the GI adverse effect profile common to the fibrate class |
| Headache / Dizziness | Common (1-10%) | Use caution when driving or operating machinery if dizziness occurs |
| Fatigue | Common (1-10%) | Generally mild; typically does not require discontinuation |
| Eczema / Rash / Dermatitis | Common (1-10%) | Probable causal relationship established from controlled trials |
| Acute appendicitis | 1.2% vs 0.6% placebo | Excess observed in Helsinki Heart Study; statistically significant in secondary prevention component (p=0.014) |
| Atrial fibrillation | 0.7% vs 0.1% placebo | Notable excess; mechanism unclear; monitor for palpitations |
Serious
Serious (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Rhabdomyolysis | Rare alone; markedly increased with statin co-use (reporting rate ~15x higher than fenofibrate-statin) | As early as 3 weeks or after several months of combined therapy | Immediate discontinuation; aggressive IV hydration; monitor CK, renal function, electrolytes, urine myoglobin; gemfibrozil-statin combination should generally be avoided |
| Cholelithiasis / Cholecystitis | Gallstone prevalence 7.5% vs 4.9% placebo; gallbladder surgery 0.9% vs 0.5% (primary prevention) | Months to years | Gallbladder studies if suspected; discontinue gemfibrozil if gallstones confirmed |
| Hepatotoxicity (cholestatic jaundice, hepatitis) | Rare | Weeks to months | Monitor LFTs periodically; discontinue if persistent abnormalities |
| Pancreatitis | Rare; class-related risk | Variable; may reflect treatment failure in severe hypertriglyceridemia | Discontinue gemfibrozil; standard pancreatitis management |
| Severe hypoglycemia (with repaglinide co-use) | Dose-dependent; 8.1-fold increase in repaglinide AUC | Within days of co-administration | Combination is contraindicated; do not co-prescribe |
| Anaphylaxis / Angioedema / Laryngeal oedema | Very rare (postmarketing) | Any time | Emergency treatment; permanent discontinuation |
| Severe anaemia / Leucopenia / Thrombocytopenia | Rare | Variable | Monitor CBC; discontinue if clinically significant cytopenias develop |
Discontinuation
Discontinuation Rates
Helsinki Heart Study (5 years)
Not separately reported
Top reasons: GI intolerance (dyspepsia, abdominal pain), abnormal LFTs, musculoskeletal symptoms
Pediatric
N/A
No adequate studies in pediatric populations have been conducted
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Gastrointestinal intolerance | Most common | Dyspepsia (19.6%), abdominal pain (9.8%) are the primary tolerability concerns; GI effects may attenuate over time |
| Abnormal liver function tests | Probable causal relationship | Elevated AST/ALT; periodic monitoring recommended |
| Musculoskeletal symptoms | Probable causal relationship | Myalgia, myopathy; risk dramatically increased with statin co-use |
Managing GI Intolerance
Gastrointestinal symptoms are the dominant tolerability issue with gemfibrozil, with dyspepsia affecting roughly 1 in 5 patients. Data from the Helsinki Heart Study suggest these effects may diminish with continued therapy. Ensuring patients take the medication 30 minutes before meals (as directed) may reduce GI distress. If symptoms remain intolerable, switching to fenofibrate should be considered, as it has a more favourable GI tolerability profile and can be taken with or without food (TriCor formulation).
Drug Interactions
Gemfibrozil has a uniquely extensive enzyme and transporter inhibition profile among fibrates. It is a strong inhibitor of CYP2C8 and OATP1B1, and also inhibits CYP1A2, CYP2C9, CYP2C19, UGT1A1, and UGT1A3. This broad inhibition profile is the critical clinical distinction from fenofibrate, which does not undergo significant CYP450 metabolism and has minimal enzyme inhibition. The interaction burden of gemfibrozil substantially limits its use in combination therapy.
MajorSimvastatin
MechanismOATP1B1 inhibition increases simvastatin acid exposure; UGT inhibition impairs statin glucuronidation; additive myotoxicity
EffectMarkedly increased risk of rhabdomyolysis, acute renal failure, and death; reporting rate ~15x higher than fenofibrate-statin combinations
ManagementCombination is contraindicated (FDA PI); never co-prescribe
FDA PI / AHA 2016MajorRepaglinide
MechanismCYP2C8 and OATP1B1 inhibition; repaglinide AUC increased 8.1-fold; plasma concentration 28.6-fold higher at 7 hours
EffectSevere, prolonged hypoglycemia
ManagementCombination is contraindicated; use alternative hypoglycemic agent
FDA PIMajorDasabuvir
MechanismCYP2C8 inhibition; dasabuvir AUC increased 11.3-fold
EffectIncreased risk of QT prolongation
ManagementCombination is contraindicated
FDA PIMajorWarfarin / Coumarin Anticoagulants
MechanismCYP2C9 inhibition and protein-binding displacement of warfarin
EffectProlonged PT/INR; increased bleeding risk
ManagementReduce warfarin dose; monitor PT/INR frequently until stable
FDA PIMajorOther Statins (Atorvastatin, Rosuvastatin, Lovastatin, Pravastatin, etc.)
MechanismOATP1B1 inhibition increases statin exposure; UGT inhibition impairs glucuronidation; additive pharmacodynamic myotoxicity
EffectSubstantially increased myopathy and rhabdomyolysis risk; FDA labels for all statins recommend avoiding gemfibrozil combination
ManagementAvoid combination; if fibrate-statin therapy is required, fenofibrate is strongly preferred; rosuvastatin labelling specifically states to avoid gemfibrozil co-use
AHA 2016 / FDA PIModerateCYP2C8 Substrates (Pioglitazone, Rosiglitazone, Enzalutamide, Paclitaxel, Montelukast)
MechanismStrong CYP2C8 inhibition increases exposure of substrates
EffectIncreased substrate toxicity (e.g., enzalutamide AUC +2.2-fold with increased seizure risk)
ManagementDose reduction of the CYP2C8 substrate; for enzalutamide, reduce dose if co-administration is necessary
FDA PIModerateBile Acid Sequestrants (Colestipol, Cholestyramine)
MechanismResin binding reduces gemfibrozil absorption; AUC reduced by 30% with simultaneous colestipol
EffectReduced gemfibrozil efficacy
ManagementSeparate administration by at least 2 hours
FDA PIModerateColchicine
MechanismAdditive myotoxicity; particularly in elderly and renally impaired patients
EffectMyopathy including rhabdomyolysis reported with chronic colchicine co-administration
ManagementUse with caution; monitor for muscle symptoms; avoid if possible in elderly or renally impaired patients
FDA PIMonitoring
-
Lipid Panel
Baseline, then periodically (every 3-6 months initially)
Routine Monitor TG, Total-C, LDL-C, HDL-C. Withdraw therapy if lipid response is inadequate after 3 months. Note: gemfibrozil may paradoxically increase LDL-C in some patients with high baseline TG (Type IV), which may require additional LDL-lowering therapy. -
Liver Function Tests
Baseline, then periodically
Routine AST, ALT, bilirubin, alkaline phosphatase. Abnormal LFTs have a probable causal relationship with gemfibrozil. Discontinue if persistent elevations develop. Contraindicated in hepatic dysfunction. -
CBC
Periodically during therapy
Routine Haematologic changes have a probable causal relationship with gemfibrozil. Monitor for anaemia (decreased haemoglobin/haematocrit), leucopenia, and thrombocytopenia. -
Renal Function
Baseline, then as clinically indicated
Routine Serum creatinine and eGFR. Gemfibrozil is contraindicated in severe renal dysfunction. VA-HIT subgroup analysis showed increased serum creatinine elevations with gemfibrozil (5.9% vs 2.8%, p=0.02) in patients with mild-to-moderate CKD. -
Creatine Kinase (CK)
If muscle symptoms develop
Trigger-based Assess CK in patients with unexplained muscle pain, tenderness, or weakness. Discontinue if myositis is suspected or CK is markedly elevated. Risk is dramatically higher with statin co-use — periodic CK monitoring does not reliably prevent severe myopathy. -
PT / INR
Frequently when co-prescribed with warfarin
Trigger-based Gemfibrozil potentiates warfarin effect via CYP2C9 inhibition and protein-binding displacement. Reduce warfarin dose and monitor PT/INR until definitively stabilised.
Contraindications & Cautions
Absolute Contraindications
- Hepatic dysfunction including primary biliary cirrhosis (FDA PI)
- Severe renal dysfunction (FDA PI)
- Pre-existing gallbladder disease — gemfibrozil increases biliary cholesterol excretion (FDA PI)
- Known hypersensitivity to gemfibrozil
- Concomitant simvastatin — contraindicated due to markedly increased rhabdomyolysis risk (FDA PI)
- Concomitant repaglinide — contraindicated due to 8.1-fold increase in repaglinide AUC causing severe hypoglycemia (FDA PI)
- Concomitant dasabuvir — contraindicated due to 11.3-fold increase in dasabuvir AUC with QT prolongation risk (FDA PI)
- Concomitant selexipag — contraindicated (FDA PI, 2018 update)
Relative Contraindications (Specialist Input Recommended)
- Concomitant use of any statin — while only simvastatin is a formal contraindication, FDA labels for all statins recommend avoiding gemfibrozil combination; if a fibrate-statin combination is required, fenofibrate is strongly preferred (AHA 2016)
- Concomitant anticoagulant therapy — requires careful warfarin dose reduction and frequent INR monitoring
- Type IIa hyperlipidemia with LDL elevation only — the PI explicitly states that the potential benefit does not outweigh the risks for this population
- Low HDL-C as the sole lipid abnormality — not indicated per FDA labelling
Use with Caution
- Mild to moderate renal impairment — increased adverse effects including GI intolerance; serum creatinine elevations observed in VA-HIT CKD subgroup
- Elderly patients — increased risk for myopathy and renal impairment, particularly with colchicine co-use
- Pregnancy — no adequate human studies; adverse developmental effects in animals at human-equivalent doses; use only if benefit justifies risk
- CYP2C8 substrate co-administration — dose reduction of the substrate may be required
- Patients with hypothyroidism — secondary cause of dyslipidemia; optimise thyroid function before initiating
FDA Class-Wide Regulatory Warning
Fibrate Class Safety Concerns
The Lopid FDA labelling carries an extensive safety warning based on class-related toxicity signals from clofibrate trials. The WHO clofibrate study demonstrated a statistically significant 44% higher age-adjusted all-cause mortality in the clofibrate-treated group versus placebo, driven by non-cardiovascular causes including malignancy, post-cholecystectomy complications, and pancreatitis. The Helsinki Heart Study showed a non-significant 20% relative excess in cumulative all-cause mortality (4.9% vs 4.1%) at 8.5 years in the group originally randomised to gemfibrozil, with excess noncoronary deaths primarily due to cancer. The FDA warns that gemfibrozil should be administered only to patients meeting the approved indications, and therapy should be discontinued if significant lipid response is not obtained.
Patient Counselling
Purpose of Therapy
Gemfibrozil is a lipid-lowering medication prescribed to reduce very high triglyceride levels and, in certain patients, to help prevent heart disease. It works alongside diet, exercise, and weight management, and is not a substitute for these lifestyle changes. Patients should continue all prescribed dietary modifications throughout treatment.
How to Take
Take one 600 mg tablet 30 minutes before breakfast and one 600 mg tablet 30 minutes before dinner. This timing is important for proper absorption of the medication. If a dose is missed, take it as soon as remembered. However, if it is almost time for the next dose, skip the missed dose and resume the normal schedule. Do not double the dose.
Stomach Upset
Tell patientIndigestion and stomach discomfort are the most common side effects, affecting roughly 1 in 5 patients. These symptoms often improve after the first few weeks of treatment. Taking the medication consistently 30 minutes before meals may help reduce stomach upset.
Call prescriberIf stomach pain becomes severe, persistent, or is accompanied by nausea, vomiting, or yellowing of the skin, as this could indicate gallbladder problems or other serious conditions.
Muscle Pain or Weakness
Tell patientGemfibrozil can rarely cause serious muscle problems, especially if taken with certain cholesterol-lowering medications called statins. It is critical that all healthcare providers know you are taking gemfibrozil before prescribing any new medication.
Call prescriberReport immediately any unexplained muscle pain, tenderness, or weakness, especially if accompanied by fever, unusual tiredness, or dark-coloured urine. These may be signs of a rare but serious muscle condition.
Gallbladder Problems
Tell patientGemfibrozil may increase the risk of developing gallstones. This risk is a known class effect of fibrate medications.
Call prescriberSeek medical attention for sudden, severe pain in the upper right part of your abdomen, pain between your shoulder blades, nausea with vomiting, or pain after eating fatty foods.
Drug Interactions
Tell patientGemfibrozil interacts with many medications including blood thinners (warfarin), diabetes medications (repaglinide), cholesterol medications (statins), and others. Always inform every healthcare provider, pharmacist, and dentist that you are taking gemfibrozil before starting any new medication.
Call prescriberBefore starting any new prescription or over-the-counter medication, contact your prescriber to check for interactions with gemfibrozil.
Pregnancy & Breastfeeding
Tell patientThe safety of gemfibrozil in pregnancy has not been established. Animal studies have shown adverse developmental effects. Breastfeeding is not recommended during gemfibrozil therapy due to the potential risk of tumorigenicity observed in animal studies.
Call prescriberInform your prescriber immediately if you become pregnant, plan to become pregnant, or are breastfeeding.
Sources
Regulatory (PI / SmPC)
- Lopid (gemfibrozil tablets, USP) — Full Prescribing Information. Pfizer (Parke-Davis). Revised 2017. FDA Label Primary source for indications, dosing, contraindications, adverse reactions, and pharmacokinetic data cited in this monograph.
- Lopid (gemfibrozil tablets, USP) — Full Prescribing Information. Pfizer. Revised 2018 (selexipag update). FDA Label (2018) Updated label adding selexipag contraindication and additional CYP2C8 substrate interaction data.
Key Clinical Trials
- Frick MH, Elo O, Haapa K, 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(20):1237-1245. doi:10.1056/NEJM198711123172001 Landmark primary prevention trial (n=4081 men) demonstrating 34% relative reduction in coronary events with gemfibrozil; source for all Helsinki Heart Study adverse events data.
- Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol (VA-HIT). N Engl J Med. 1999;341(6):410-418. doi:10.1056/NEJM199908053410604 VA-HIT trial (n=2531 men with CHD and HDL-C ≤40 mg/dL) demonstrating 22% relative risk reduction in CHD events with gemfibrozil; key evidence for secondary prevention in low-HDL patients.
- Robins SJ, Collins D, Wittes JT, et al. Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA. 2001;285(12):1585-1591. doi:10.1001/jama.285.12.1585 VA-HIT post-hoc analysis showing that HDL-C increase during gemfibrozil treatment predicted reduced CHD events, though the benefit extended beyond lipid changes alone.
- Tenkanen L, Manttari M, Manninen V. Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil: experience from the Helsinki Heart Study. Circulation. 1995;92(7):1779-1785. doi:10.1161/01.CIR.92.7.1779 Helsinki Heart Study subgroup analysis showing greatest gemfibrozil benefit in patients with features of the metabolic syndrome (high TG, low HDL-C, elevated BMI).
Guidelines
- Wiggins BS, Saseen JJ, Page RL, et al. Recommendations for management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2016;134(21):e468-e495. doi:10.1161/CIR.0000000000000456 Authoritative AHA statement on statin-fibrate interactions; source for rhabdomyolysis reporting rate comparisons between gemfibrozil and fenofibrate.
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC Guideline on the Management of Blood Cholesterol. Circulation. 2019;139(25):e1082-e1143. doi:10.1161/CIR.0000000000000625 Current ACC/AHA cholesterol guideline; recommends fenofibrate over gemfibrozil if fibrate-statin combination is considered necessary.
Mechanistic / Basic Science
- Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation. 1998;98(19):2088-2093. doi:10.1161/01.CIR.98.19.2088 Foundational review of PPARα-mediated mechanisms underlying fibrate effects on lipid metabolism.
- Niemi M, Backman JT, Granfors M, Laitila J, Neuvonen M, Neuvonen PJ. Gemfibrozil considerably increases the plasma concentrations of rosiglitazone. Diabetologia. 2003;46(10):1319-1323. doi:10.1007/s00125-003-1195-4 Key pharmacokinetic study characterising gemfibrozil as a strong CYP2C8 inhibitor and its clinical implications for drug interactions.
Pharmacokinetics / Special Populations
- Todd PA, Ward A. Gemfibrozil: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in dyslipidaemia. Drugs. 1988;36(3):314-339. doi:10.2165/00003495-198836030-00004 Comprehensive pharmacokinetic and pharmacodynamic review of gemfibrozil including absorption, distribution, metabolism, and elimination parameters.
- Tonelli M, Collins D, Robins S, Bloomfield H, Curhan GC. Gemfibrozil for secondary prevention of cardiovascular events in mild to moderate chronic renal insufficiency. Kidney Int. 2004;66(3):1123-1130. doi:10.1111/j.1523-1755.2004.00862.x VA-HIT CKD subgroup analysis showing gemfibrozil efficacy in mild-to-moderate renal impairment but increased serum creatinine elevations (5.9% vs 2.8%).
- Backman JT, Kyrklund C, Neuvonen M, Neuvonen PJ. Gemfibrozil greatly increases plasma concentrations of cerivastatin. Clin Pharmacol Ther. 2002;72(6):685-691. doi:10.1067/mcp.2002.128469 Landmark study demonstrating the mechanism of gemfibrozil-statin interaction via CYP2C8 and glucuronidation inhibition, leading to cerivastatin’s withdrawal.