KEFLET
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KEFLET (KEFLET).
Keflet (warfarin) inhibits vitamin K epoxide reductase, preventing the recycling of vitamin K and thereby reducing the synthesis of clotting factors II, VII, IX, and X in the liver.
| Metabolism | Hepatic metabolism via CYP450 enzymes, primarily CYP2C9 (major), CYP3A4, CYP1A2, CYP2C19, and CYP2C8. |
| Excretion | Renal (80-90% unchanged via glomerular filtration and tubular secretion); biliary/fecal < 5%. |
| Half-life | 0.5-1 hour; prolonged in renal impairment (up to 20-30 hours in ESRD). |
| Protein binding | 5-15%, primarily to albumin. |
| Volume of Distribution | 0.2-0.3 L/kg; indicates distribution primarily in extracellular fluid. |
| Bioavailability | Oral: 50-70% (decreased by food). |
| Onset of Action | Oral: 0.5-1 hour; IV: immediate. |
| Duration of Action | 6-8 hours; shorter in hypermetabolic states. |
500 mg orally every 12 hours for 10-14 days; for uncomplicated UTI: 250 mg orally every 12 hours for 7 days.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-49 mL/min: 500 mg every 24 hours; CrCl 15-29 mL/min: 250 mg every 24 hours; CrCl <15 mL/min (not on dialysis): 250 mg every 48 hours. |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment; use with caution in severe impairment (Child-Pugh C) as data limited. |
| Pediatric use | For children ≥6 months: 30 mg/kg/day divided every 12 hours for 10 days; not to exceed 1000 mg/day. |
| Geriatric use | Initiate at 250 mg orally every 12 hours; monitor renal function and adjust based on CrCl. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KEFLET (KEFLET).
| Breastfeeding | Cephalexin is excreted into human milk in small amounts (M/P ratio approximately 0.06). The American Academy of Pediatrics considers it compatible with breastfeeding. Monitor infant for diarrhea, rash, and candidiasis; discontinue if infant develops adverse effects. |
| Teratogenic Risk | KEFLET (cephalexin) is classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, and there are no adequate well-controlled studies in pregnant women. First trimester: Limited data show no increased risk of major malformations. Second and third trimesters: No known fetal risks; used for maternal infections. Avoid use only if clearly needed. |
■ FDA Black Box Warning
Warfarin can cause major or fatal bleeding. Risk factors include high dose, advanced age, poor nutritional status, renal insufficiency, and certain genetic factors. Patients should be monitored regularly for INR. Concomitant use with NSAIDs, aspirin, or anticoagulants increases bleeding risk.
| Serious Effects |
Pregnancy (except in women with mechanical heart valves at high risk); active bleeding or bleeding disorders; recent or anticipated surgery of CNS or eye; malignant hypertension; hypersensitivity to warfarin or any component; inability to comply with monitoring; patients with hemorrhagic tendencies (e.g., hemophilia, thrombocytopenia).
| Precautions | Hemorrhage risk; necrosis or gangrene of skin or other tissues (calciphyaxis) on rare occasions; systemic atheroemboli and cholesterol microemboli; caution in patients with hepatic or renal impairment; caution in elderly; pregnancy: may cause fetal harm. |
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| Fetal Monitoring | No specific monitoring required beyond standard prenatal care. Monitor maternal renal function if high-dose or prolonged therapy. For fetal monitoring, assess for any signs of infection (e.g., maternal fever). |
| Fertility Effects | No known effects on human fertility. Animal studies have not demonstrated impaired fertility at therapeutic doses. |