Gemfibrozil (Lopid, Gempid) 300 mg and 600 mg is used as a twice-daily oral medicine for the treatment of hypertriglyceridemia as an adjunct to dietary management.
Gemfibrozil Uses:
- It is used in the 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 management.
- It is also used to reduce the risk of coronary heart disease development in Fredrickson type IIb patients without a history and 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 triglyceride levels.
Gemfibrozil (Lopid) Dose in Adults
Gemfibrozil (Lopid) Dose in the treatment of Hyperlipidemia/ hypertriglyceridemia:
- It is given orally as 600 mg twice a day 30 minutes before breakfast and dinner.
Note:
- Discontinue if lipid response is inadequate after 3 months of therapy.
Use in Children:
Not indicated.
Gemfibrozil Pregnancy Category: C
- Studies on animal reproduction have revealed negative results.
- It can also cross the placenta.
- Triglyceride concentrations may rise during pregnancy and fetal growth.
- If the increase is more than anticipated, it's time to start supervised dietary intervention.
- Gemfibrozil may be an option for women with high levels of triglycerides or who are at higher risk of developing pancreatitis.
Gemfibrozil use during breastfeeding:
- It is unknown whether breast milk secretes it.
- Breast milk contains lipids, which are an acceptable component. Infant neurological development is normalized by the fatty acids.
- The mother's diet and other factors affect the composition of breast milk.
- Due to severe hypertriglyceridemia, the risk of pancreatitis is increased and gemfibrozil therapy can be considered.
- Other agents are preferred when treatment is required for other indications.
- The benefits of continuing therapy during pregnancy must be greater than the risks to both mother and baby's health.
Gemfibrozil (Lopid) Dose in Kidney disease:
-
Manufacturer's labeling:
- Mild-to-moderate impairment:
- According to the literature, there are no dose adjustments are required however caution is advised.
- Deterioration of renal function has been reported in patients with baseline serum creatinine >2 mg/dL
- Severe impairment:
- Its use is not recommended at all in severe renal impairment.
- Mild-to-moderate impairment:
-
Alternate recommendations:
- GFR >50 mL/minute: No dosage adjustment necessary.
- GFR 10 to 50 mL/minute: Administer 75% of dose.
- GFR <10 mL/minute: Administer 50% of dose.
- Intermittent hemodialysis: Supplemental dose is not necessary.
- Peritoneal dialysis: Administer 50% of the dose as a supplement for dialysis.
Dose in Liver disease:
Its use is contraindicated in severe liver impairment.
Common Side Effects of Gemfibrozil (Lopid):
-
Gastrointestinal:
- Dyspepsia
Less Common Side Effects of Gemfibrozil (Lopid):
-
Cardiovascular:
- Atrial fibrillation
-
Central nervous system:
- Fatigue
- Vertigo
-
Dermatologic:
- Eczema
- Skin rash
-
Gastrointestinal:
- Abdominal pain
- Nausea and vomiting
Contraindications to Gemfibrozil (Lopid):
- A contraindication is absolute hypersensitivity to gemfibrozil and any component of the formulation.
- Hepatic and severe renal dysfunction.
- Primary biliary dysfunction.
- Gallbladder disease that is already present
- Concurrent use of dasabuvir or repaglinide, simvastatin, selexipag, and repaglinide.
Canadian labeling: Additional contraindications not in the US labeling
- Renal dysfunction.
- Concurrent use of cerivastatin.
- Pregnancy.
- Breastfeeding
There is not much evidence of cross-reactivity between fibrates and allergens. Cross-sensitivity is possible due to similarities in chemical structure and pharmacologic characteristics.
Warnings and precautions
-
Cholelithiasis
- Cholelithiasis can be increased by using it. If gallstones are detected on gallbladder scans, the drug should be stopped.
-
Transaminases with elevated levels:
- Transaminitis is possible and it is important to monitor liver enzymes regularly.
-
Hematologic effects
- The initiation can cause anemia and a drop in the hematocrit. However, this usually resolves with long-term treatment.
- However, anemia, leukopenia and thrombocytopenia are rare. During the first year of therapy, frequent monitoring is recommended.
-
Malignancy
- Malignancy is more likely.
-
Myopathy/rhabdomyolysis:
- Rare myositis and rhabdomyolysis have been linked to it. It is important to monitor patients closely.
- Patients should be taught to report any unexplained pain, tenderness or weakness in their muscles.
-
Renal impairment
- Patients with moderate-to-severe renal impairment should exercise caution. It is not recommended for patients with severe impairment.
- Patients with serum creatinine levels above 2 mg/dL have shown worsening of RFTs.
Gemfibrozil: Drug Interaction
|
Risk Factor C (Monitor therapy) |
|
|
Acipimox |
May enhance the myopathic (rhabdomyolysis) effect of Fibric Acid Derivatives. |
|
Apalutamide |
CYP2C8 Inhibitors (Strong) may increase the serum concentration of Apalutamide. |
|
Chenodiol |
Fibric Acid Derivatives may diminish the therapeutic effect of Chenodiol. Management: Monitor clinical response to chenodiol closely when used together with any fibric acid derivative. |
|
Colchicine |
Fibric Acid Derivatives may enhance the myopathic (rhabdomyolysis) effect of Colchicine. |
|
Desloratadine |
CYP2C8 Inhibitors (Strong) may increase the serum concentration of Desloratadine. |
|
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. |
|
Montelukast |
Gemfibrozil may increase the serum concentration of Montelukast. |
|
OATP1B1/1B3 (SLCO1B1/1B3) Substrates |
Gemfibrozil may increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. See separate drug interaction monographs for agents listed as exceptions. Exceptions: AtorvaSTATin; Eluxadoline; Ezetimibe; Fluvastatin; Pitavastatin; Pravastatin; Repaglinide; Rosuvastatin; Simvastatin. |
|
Raltegravir |
May enhance the myopathic (rhabdomyolysis) effect of Fibric Acid Derivatives. |
|
Sulfonylureas |
Fibric Acid Derivatives may enhance the hypoglycemic effect of Sulfonylureas. |
|
Ursodiol |
Fibric Acid Derivatives may diminish the therapeutic effect of Ursodiol. |
|
Risk Factor D (Consider therapy modification) |
|
|
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. |
|
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. Exceptions: Colesevelam. |
|
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. |
|
CYP2C8 Substrates (High risk with Inhibitors) |
CYP2C8 Inhibitors (Strong) may decrease the metabolism of CYP2C8 Substrates (High risk with Inhibitors). |
|
Eluxadoline |
Gemfibrozil may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with gemfibrozil and monitor patients for increased eluxadoline effects/toxicities. |
|
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. |
|
Pioglitazone |
CYP2C8 Inhibitors (Strong) may increase the serum concentration of Pioglitazone. Management: Limit pioglitazone adult maximum dose to 15 mg/day when used in combination with any strong CYP2C8 inhibitor. |
|
Thiazolidinediones |
Gemfibrozil may decrease the metabolism of Thiazolidinediones. Management: Limit pioglitazone maximum adult dose to 15 mg/day, and consider dose reduction of rosiglitazone, when used in combination with gemfibrozil. |
|
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. |
|
Vitamin K Antagonists (eg, warfarin) |
Fibric Acid Derivatives may enhance the anticoagulant effect of Vitamin K Antagonists. |
|
Risk Factor X (Avoid combination) |
|
|
Amodiaquine |
CYP2C8 Inhibitors (Strong) may increase the serum concentration of Amodiaquine. |
|
Asunaprevir |
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. |
|
AtorvaSTATin |
Gemfibrozil may enhance the myopathic (rhabdomyolysis) effect of AtorvaSTATin. Gemfibrozil may increase the serum concentration of AtorvaSTATin. |
|
Bexarotene (Systemic) |
Gemfibrozil may increase the serum concentration of Bexarotene (Systemic). |
|
Ciprofibrate |
May enhance the adverse/toxic effect of Fibric Acid Derivatives. |
|
Dabrafenib |
CYP2C8 Inhibitors (Strong) may increase the serum concentration of Dabrafenib. |
|
Dasabuvir |
CYP2C8 Inhibitors (Strong) may increase the serum concentration of Dasabuvir. |
|
Elagolix |
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. |
|
Ezetimibe |
Gemfibrozil may enhance the adverse/toxic effect of Ezetimibe. Specifically, the risk of myopathy and cholelithiasis may be increased. Gemfibrozil may increase the serum concentration of Ezetimibe. |
|
Fluvastatin |
Gemfibrozil may enhance the myopathic (rhabdomyolysis) effect of Fluvastatin. |
|
Grazoprevir |
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Grazoprevir. |
|
Lovastatin |
Gemfibrozil may enhance the myopathic (rhabdomyolysis) effect of 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). |
|
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir |
CYP2C8 Inhibitors (Strong) may increase the serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Specifically, the serum concentrations of dasabuvir may increase significantly. |
|
Pitavastatin |
Gemfibrozil may enhance the myopathic (rhabdomyolysis) effect of Pitavastatin. Gemfibrozil may increase the serum concentration of Pitavastatin. |
|
Pravastatin |
Gemfibrozil may enhance the myopathic (rhabdomyolysis) effect of Pravastatin. Gemfibrozil may increase the serum concentration of Pravastatin. |
|
Repaglinide |
Gemfibrozil may increase the serum concentration of Repaglinide. The addition of itraconazole may augment the effect of gemfibrozil on repaglinide. |
|
Revefenacin |
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. |
|
Rosuvastatin |
Gemfibrozil may enhance the myopathic (rhabdomyolysis) effect of Rosuvastatin. Gemfibrozil may increase the serum concentration of Rosuvastatin. Management: If possible, avoid concomitant use of rosuvastatin with gemfibrozil. If concomitant can not be avoided, limit rosuvastatin to 10 mg/day (US recommendation) or 20 mg/day (Canadian recommendation). Monitor for signs/symptoms of rhabdomyolysis. |
|
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. |
|
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. |
|
Voxilaprevir |
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. |
Monitoring parameters:
- Serum cholesterol.
- LFTs periodically.
- CBC periodically during the first year of use
How to administer Gemfibrozil?
Administer 30 minutes prior to breakfast and dinner.
Mechanism of action of Gemfibrozil (Lopid):
- Gemfibrozil's exact mechanism of action is not known. However, there are many theories about the VLDL effect.
- It can inhibit lipolysis and reduce subsequent hepatic fat acid uptake, as well as inhibiting hepatic secretion VLDL.
- These actions together decrease serum VLDL levels, and increase HDL cholesterol levels. It is not known what causes HDL elevation.
The onset of action:
- It may require several days.
Absorption:
- Well absorbed
Protein binding:
- 99%
Metabolism:
- It has hepatic metabolism via oxidation to two inactive metabolites. It undergoes enterohepatic recycling.
Half-life elimination:
- 1.5 hours
Time to peak, serum:
- 1 to 2 hours
Excretion:
- Urine (~70% primarily as conjugated drug).
- via feces (6%)
International Brands of Gemfibrozil:
- Lopid
- APO-Gemfibrozil
- DOM-Gemfibrozil
- Gemfibrozil-600
- MYLAN-Gemfibrozil
- PHL-Gemfibrozil
- PMS-Gemfibrozil
- TEVA-Gemfibrozil
- Antalip
- Ausgem
- Brezimed
- Brozil
- Cell
- Clearol
- Detrichol
- Elmogan
- Fetinor
- Fibropid
- F.B.-600
- Gedum
- Gem-S
- Gemd
- Gemfi
- Gemfibril
- Gemfil
- Gemnpid
- Gevilon
- Goprozil
- Gozid
- Hidil
- Hipolixan
- Innogem
- Ipolipid
- Lesdown
- Lifibron
- Lipazil
- Lipicap
- Lipigem
- Lipison
- Lipistorol
- Lipitrop
- Lipizile
- Lipofor
- Lipolo
- Lipres
- Lipur
- Loceride
- Lopid
- Lopid OD
- Low-Lip
- Lozil
- Manobrozil
- Mersikol
- Minilip
- Normolip
- Polyxit
- Qualipid
- Reducel
- Regulip
- Ronox
- Synbrozil
- Tgil
- Trialmin
- Triglizil
- Weijiangzhi
Gemfibrozil Brand Names in Pakistan:
Gemfibrozil Capsules 300 mg in Pakistan |
|
| Gemzil | Zafa Pharmaceutical Laboratories (Pvt) Ltd. |
Gemfibrozil Capsules 600 mg in Pakistan |
|
| Gempid | Atco Laboratories Limited |
| Gemzil | Zafa Pharmaceutical Laboratories (Pvt) Ltd. |
