ATROMID-S
Clinical safety rating
cautionComprehensive clinical and safety monograph for ATROMID-S (ATROMID-S).
Comprehensive clinical and safety monograph for ATROMID-S (ATROMID-S).
Type III hyperlipoproteinemiaHypertriglyceridemia (Fredrickson types IV and V) not responsive to diet
Inhibits hepatic triglyceride synthesis and increases lipoprotein lipase activity, leading to reduced VLDL and triglycerides.
| Metabolism | Hepatic via glucuronidation and oxidation; major metabolite is clofibric acid. |
| Excretion | Primarily renal excretion as glucuronide conjugates; approximately 60-70% of the dose is excreted in urine, 20-30% in feces via biliary elimination. |
| Half-life | Terminal elimination half-life is 6-8 hours in patients with normal renal function; may be prolonged to 12-24 hours in renal impairment. |
| Protein binding | >95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.11-0.14 L/kg; low Vd indicates limited extravascular distribution, consistent with high protein binding. |
| Bioavailability | Oral: approximately 60-70% due to first-pass metabolism; administered as clofibrate (prodrug) which is hydrolyzed to active clofibric acid. |
| Onset of Action | Oral: 2-4 weeks for significant reduction in serum lipids; maximal effect may take 1-2 months. |
| Duration of Action | Duration of lipid-lowering effect persists for several weeks after discontinuation; clinical effect returns to baseline over 4-6 weeks. |
| Molecular Weight | 242.7 |
500 mg to 1 g orally twice daily. Maximum dose 2 g/day.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-59 mL/min: 500 mg twice daily. GFR 15-29 mL/min: 250 mg twice daily. GFR <15 mL/min: avoid use. |
| Liver impairment | Child-Pugh Class B or C: avoid use or reduce dose by at least 50%; not recommended in severe hepatic impairment. |
| Pediatric use | Not recommended; safety and efficacy not established in pediatric patients. |
| Geriatric use | Start at lower end of dosing range (500 mg twice daily). Monitor renal function; adjust dose based on GFR. |
| 1st trimester | Avoid due to potential teratogenic effects; clofibrate has shown embryotoxicity in animal studies and is associated with placental insufficiency. |
| 2nd trimester | Not recommended; use only if potential benefit outweighs risk to mother and fetus; may cause fetal harm. |
| 3rd trimester | Not recommended; may cause placental insufficiency and neonatal complications; use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for ATROMID-S (ATROMID-S).
| Placental transfer | Crosses placenta in animals; limited human data suggest transfer; associated with placental insufficiency and fetal risk. |
| Breastfeeding | Clofibrate is excreted into breast milk in small amounts; potential for serious adverse effects in nursing infants (e.g., hepatotoxicity, gallbladder disease); manufacturer advises to discontinue nursing or the drug. |
| Lactation Rating | Avoid |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Potential for teratogenicity based on animal studies showing skeletal and visceral anomalies. Human data limited; use only if benefit outweighs risk. Second and third trimesters: May cause fetal harm due to placental transfer and potential for reduced fetal growth. |
| Fetal Monitoring | Monitor maternal liver function tests, renal function, and lipid profiles periodically. Fetal monitoring with ultrasound for growth and anatomy if used during pregnancy. |
| Fertility Effects | Animal studies suggest possible impairment of fertility; human data insufficient. Effects on spermatogenesis or ovulation not well documented. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to clofibrateSevere hepatic impairmentSevere renal impairment (e.g., creatinine clearance < 10 mL/min)Primary biliary cirrhosisGallbladder disease (cholelithiasis, cholecystitis)
| Precautions | Hepatotoxicity, Cholelithiasis, Renal impairment dose adjustment, Rhabdomyolysis risk with statins, Malignancy risk (hepatic, GI) |
| Food/Dietary | High-fat meals may reduce absorption; consistent timing of administration with food is recommended. Grapefruit juice may increase drug levels; avoid excessive intake. Alcohol may exacerbate hepatotoxicity. |
| Clinical Pearls | ATROMID-S (clofibrate) is a fibric acid derivative primarily indicated for hyperlipidemia but its use is now limited due to increased non-cardiovascular mortality and cholelithiasis risk. Monitor liver function and prothrombin time (potentiates warfarin). Not first-line; consider statins or fibrates like fenofibrate. |
| Patient Advice | Take with meals to reduce gastrointestinal upset. · Report unexplained muscle pain, tenderness, or weakness; may indicate myopathy. · Avoid alcohol as it may increase liver enzyme elevations. · Notify your doctor if you develop gallstones symptoms (e.g., right upper abdominal pain, nausea). · Use effective contraception as clofibrate may cause fetal harm. |
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