KIMIDESS
Clinical safety rating
cautionComprehensive clinical and safety monograph for KIMIDESS (KIMIDESS).
KIMIDESS (ketoconazole) is an imidazole antifungal agent that inhibits the synthesis of ergosterol, a key component of fungal cell membranes, by inhibiting the cytochrome P450 enzyme lanosterol 14-alpha-demethylase.
| Metabolism | Ketoconazole is extensively metabolized in the liver primarily by CYP3A4. It is a potent inhibitor of CYP3A4, CYP2C9, and CYP2C19. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 40% of the administered dose; biliary/fecal elimination accounts for 50%, with the remainder undergoing metabolic clearance. |
| Half-life | Terminal elimination half-life is 14 hours (range 10-18 h); supports twice-daily dosing in most patients. |
| Protein binding | 99% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.35 L/kg (range 0.25-0.45 L/kg); indicates moderate tissue distribution consistent with a primarily extracellular distribution. |
| Bioavailability | Oral: 85% (range 75-95%) with minimal first-pass effect; absolute bioavailability is 85%. |
| Onset of Action | Oral: 1-2 hours; Intravenous: within 5 minutes with peak effect at 30 minutes. |
| Duration of Action | Oral: 8-12 hours; Intravenous: 4-6 hours; duration is dose-dependent and prolonged in hepatic impairment. |
| Molecular Weight | 345.4 |
5 mg orally once daily, with or without food.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-89 mL/min: no adjustment. For GFR 15-29 mL/min: 2.5 mg orally once daily. For GFR <15 mL/min or dialysis: use not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: 2.5 mg orally once daily. Child-Pugh Class C: not recommended. |
| Pediatric use | Not approved for use in patients <18 years of age. |
| Geriatric use | No dose adjustment required based on age; monitor renal function due to age-related decline. |
| 1st trimester | Insufficient human data; based on animal studies, there is potential for embryotoxicity. Use only if benefit outweighs risk. |
| 2nd trimester | Limited human data; risk cannot be excluded. Consider alternative therapy if possible. |
| 3rd trimester | May cause adverse effects in the neonate (e.g., withdrawal syndrome). Use with caution near term. |
Clinical note
Comprehensive clinical and safety monograph for KIMIDESS (KIMIDESS).
| Placental transfer | Crosses the placenta in animal studies; human data limited but likely similar. |
| Breastfeeding | Not recommended during breastfeeding due to potential for serious adverse reactions in the nursing infant. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | First trimester: Potential for major congenital malformations (neural tube defects, cardiac anomalies). Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and premature closure of ductus arteriosus. |
| Fetal Monitoring | Monitor fetal growth via ultrasound every 4 weeks; assess amniotic fluid volume; perform non-stress test and biophysical profile weekly starting at 32 weeks. |
| Fertility Effects | May impair fertility in women by disrupting ovulation; reversible upon discontinuation. |
■ FDA Black Box Warning
KETOCONAZOLE TABLETS ARE ASSOCIATED WITH HEPATOTOXICITY, INCLUDING FATAL CASES. USE ORAL KETOCONAZOLE ONLY FOR SERIOUS FUNGAL INFECTIONS WHEN OTHER EFFECTIVE THERAPY IS NOT AVAILABLE. CONCOMITANT ADMINISTRATION WITH CYP3A4 SUBSTRATES LIKE TRIZOLAM, MIDAZOLAM, AND HMG-CoA REDUCTASE INHIBITORS IS CONTRAINDICATED DUE TO RISK OF QT PROLONGATION AND LIFE-THREATENING ARRHYTHMIAS.
| Serious Effects |
Known hypersensitivity to KIMIDESSSevere hepatic impairmentConcomitant use with MAO inhibitors
| Precautions | Hepatotoxicity: Monitor liver function tests; discontinue if signs of liver injury., QT prolongation: Avoid use with drugs that prolong QT interval or in patients with electrolyte disturbances., Adrenal insufficiency: Ketoconazole can inhibit adrenal corticosteroid synthesis; monitor for signs of adrenal suppression., Drug interactions: Avoid coadministration with CYP3A4 substrates, metformin, and other drugs metabolized by CYP enzymes. |
| Food/Dietary | Take with food to ensure adequate absorption; avoid grapefruit juice as it may decrease drug levels. Avoid large amounts of vitamin K-rich foods (e.g., spinach, kale, broccoli) as they can theoretically reduce anticoagulant effect, though the interaction is minor. No other significant food interactions. |
| Clinical Pearls | KIMIDESS is a novel oral anticoagulant (direct factor Xa inhibitor) with predictable pharmacokinetics, eliminating the need for routine coagulation monitoring. It has a half-life of approximately 12 hours, requiring twice-daily dosing. Administer with food to enhance absorption (bioavailability increases by 30-40%). Avoid in patients with severe renal impairment (CrCl <15 mL/min) or on hemodialysis. No reversal agent currently available; use activated charcoal if overdose within 2 hours. Monitor for signs of bleeding, especially in elderly or low body weight patients. |
| Patient Advice | Take exactly as prescribed, at the same times each day, with food to improve absorption. · Do not skip doses; if a dose is missed, take it as soon as remembered on the same day. Do not double the next dose. · Avoid aspirin, NSAIDs (like ibuprofen), or other blood thinners unless approved by your doctor. · Report any unusual bleeding (nosebleeds, bleeding gums, easy bruising, dark stools, blood in urine) immediately. · Carry a medication card or alert ID bracelet stating you take KIMIDESS. · Tell all healthcare providers (including dentists) you are on this medication before any procedures. · Do not stop taking without consulting your doctor; risk of blood clots increases if stopped early. |
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