gemfibrozil
Brand: Lopid
Prototype: fenofibrate
Drug Class: fibrate
Drug Family: antilipemic
Subclass: PPAR-alpha agonist
Organ Systems: cardiovascular
Mechanism of Action
PPAR-alpha agonist; additionally inhibits CYP2C8 and OATP1B1 transporters causing significant statin interactions.
PPAR-alpha
Indications
- hypertriglyceridemia
- mixed dyslipidemia
- secondary prevention in Type IIb dyslipidemia (Helsinki Heart Study)
Contraindications
- severe renal impairment
- pre-existing gallbladder disease
- concurrent repaglinide (CYP2C8 inhibition — hypoglycemia)
Adverse Effects
Common
- GI upset
- dyspepsia
- myalgia
Serious
- rhabdomyolysis (especially with statins via CYP2C8/OATP1B1 inhibition)
- gallstones
Pharmacokinetics (ADME)
| Absorption | ~97% oral |
| Distribution | large Vd |
| Metabolism | hepatic conjugation |
| Excretion | renal 70% |
| Half-life | 1.3-1.5 hours |
| Onset | 1-2 hours |
| Peak | 1-2 hours |
| Duration | 12 hours |
| Protein Binding | 97% |
| Vd | 9 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| statins | OATP1B1 + CYP2C8 inhibition — markedly increases all statins; avoid combination | major |
| repaglinide | CYP2C8 inhibition — 8-fold increase in repaglinide exposure; severe hypoglycemia — CONTRAINDICATED | major |
| warfarin | increases INR | major |
Nursing Considerations
- AVOID concurrent statin use if possible (markedly increases rhabdomyolysis risk)
- Take 30 minutes before breakfast and dinner
- Gemfibrozil + repaglinide is CONTRAINDICATED (severe hypoglycemia)
- Helsinki Heart Study: reduced CV events in primary prevention
Clinical Pearls
- Helsinki Heart Study: reduced MI and CV events in primary prevention
- More drug interactions than fenofibrate due to CYP2C8 and OATP1B1 inhibition — fenofibrate preferred for combination with statins
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.