Gemfibrozil

C10A - Cholesterol and triglyceride regulating preparations ATC C10AB04 Small molecule approved 1981 Oral Natural product

JFDA label: Low-lip F.C Tablets

Mechanism of Action

Agonist of Peroxisome proliferator-activated receptor alpha — Peroxisome proliferator-activated receptor alpha agonist

Target	Action	Gene / class
Peroxisome proliferator-activated receptor alpha efficacy	AGONIST	PPARA

Indications

Approved

Abdominal Pain — Abdominal pain
Cardiovascular Diseases — cardiovascular disease
Coronary Disease — coronary artery disease

Off-label

Alcoholism
Myocardial Ischemia
Parkinson Disease
Smoking Cessation
Tobacco Use Disorder

Contraindications

Source: Lexicomp

Additional contraindications (not in the US labeling): Renal dysfunction Absolute
Hypersensitivity to gemfibrozil or any component of the formulation Absolute
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 Absolute
concurrent use with cerivastatin Absolute
concurrent use with dasabuvir, repaglinide, or simvastatin Absolute
hepatic or severe renal dysfunction Absolute
preexisting gallbladder disease Absolute
primary biliary cirrhosis Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Common Atrial fibrillation

Nervous system disorders (2)

Common Fatigue · vertigo

Gastrointestinal disorders (2)

Common Abdominal pain · nausea and vomiting

Skin and subcutaneous tissue disorders (2)

Common Eczema · skin rash

Other (1)

Very Common Gastrointestinal: Dyspepsia

Dosing

Source: Lexicomp

Hyperlipidemia/hypertriglyceridemia: Oral: 600 mg twice daily 30 minutes before breakfast and dinner. Note: Discontinue if lipid response is inadequate after 3 months of therapy.

Refer to adult dosing.

Warnings & Precautions

Source: Lexicomp

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. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. 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.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events have been observed in animal reproduction studies. 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).

Lactation

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 indication

Monitoring

Clinical pearl	Serum cholesterol, LFTs periodically, CBC periodically (first year)

Chemistry & Properties

Formula	C15H22O3
Molecular weight	250.34 g/mol
IUPAC name	5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid
CAS	25812-30-0
PubChem CID	3463
InChIKey	`HEMJJKBWTPKOJG-UHFFFAOYSA-N`
logP	3.57 (XLogP 3.8)
Polar surface area	46.53 Å²
H-bond acceptors / donors	2 / 1
Drug-likeness (QED)	0.78
Lipinski violations	0

SMILES

Cc1ccc(C)c(OCCCC(C)(C)C(=O)O)c1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Inhibitor	—
CYP2C19	Inhibitor	—
CYP2C8	Inhibitor	IC₅₀ 33.32296899997401 µM
CYP2C9	Inhibitor	IC₅₀ 9.6 µM
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)OAT (Inhibitor)OAT3 (Inhibitor)OATP (Inhibitor)OATP1A2 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)OAT1 (Substrate)OAT2 (Substrate)OAT3 (Substrate)P-gp (Substrate)

Drug–drug interactions (63, DDInter)

Interacting drug	Severity	Management
Bexarotene	major
Dicoumarol	major
Elagolix	major
Eluxadoline	major
Irinotecan	major
Irinotecan (liposomal)	major
Loperamide	major
Ozanimod	major
Pioglitazone	major
Repaglinide	major
Rosuvastatin	major
Selexipag	major
Simvastatin	major
Siponimod	major
Warfarin	major
Acetohexamide	moderate
Apalutamide	moderate
Artesunate	moderate
Avatrombopag	moderate
Binimetinib	moderate
Celecoxib	moderate
Chenodeoxycholic acid	moderate
Chloroquine	moderate
Chlorpropamide	moderate
Cyclosporine	moderate
Dabrafenib	moderate
Diclofenac	moderate
Enzalutamide	moderate
Glimepiride	moderate
Glipizide	moderate
Glyburide	moderate
Hydroxychloroquine	moderate
Insulin aspart (aspart protamine)	moderate
Insulin aspart (aspart)	moderate
Insulin degludec	moderate
Insulin detemir	moderate
Insulin glargine	moderate
Insulin glulisine	moderate
Insulin human	moderate
Insulin human (inhalation, rapid acting)	moderate

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Registered Products (4)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Lipofor Tablet	Tablet 600 mg	30 tab	JAWEDA INT. DRUD STORE	4.410
Low-lip F.C Tablets	Film-Coated Tablet 600 mg	30 tab pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	5.220
Lopid	Tablet 600 mg	30 tab	Khoury Drug Store	6.300
Low-lip F.C Tablets	Film-Coated Tablet 600 mg	500 tab pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	63.080