IFEX/MESNEX KIT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IFEX/MESNEX KIT (IFEX/MESNEX KIT).
Ifosfamide is an alkylating agent that requires metabolic activation by cytochrome P450 (CYP3A4) to active metabolites (e.g., ifosfamide mustard) that crosslink DNA, leading to cell cycle arrest and apoptosis. Mesna is a thiol compound that binds to and detoxifies urotoxic ifosfamide metabolites (e.g., acrolein) in the urinary tract, preventing hemorrhagic cystitis.
| Metabolism | Ifosfamide is extensively metabolized by hepatic CYP3A4 to active metabolites (ifosfamide mustard, 4-hydroxyifosfamide) and inactive metabolites (e.g., 2- and 3-dechloroethylifosfamide). Mesna is oxidized in the blood to dimesna and then reduced back to mesna in the kidneys. |
| Excretion | Ifosfamide: Renal excretion of unchanged drug (12-18%) and metabolites (primarily 4-hydroxyifosfamide, ifosforamide mustard, and chloroacetaldehyde). Biliary/fecal elimination is minimal (<2%). Mesna: Renal excretion as mesna and its disulfide dimer (dimesna), with >80% recovered in urine within 24 hours. |
| Half-life | Ifosfamide: Terminal elimination half-life of 4-7 hours at standard doses (1.2-2 g/m²), increasing to 10-15 hours at high doses (5 g/m²) due to saturable metabolism; clinically significant for dosing intervals and toxicity monitoring. Mesna: Terminal half-life of approximately 0.36 hours (22 minutes) for mesna and 1.17 hours for dimesna. |
| Protein binding | Ifosfamide: Minimal protein binding (<20%) and not concentration-dependent. Mesna: Approximately 69-75% bound to plasma proteins, primarily to albumin via disulfide bonds. |
| Volume of Distribution | Ifosfamide: Mean Vd of 0.6-0.8 L/kg, indicating extensive tissue distribution; crosses blood-brain barrier with CSF levels 20-60% of plasma. Mesna: Vd of 0.65 L/kg, limited to extracellular fluid; does not penetrate cells due to hydrophilic nature. |
| Bioavailability | Ifosfamide: Oral bioavailability is close to 100%, but intravenous administration is standard due to gastrointestinal toxicity; oral use is rare. Mesna: Oral bioavailability is 40-50% due to first-pass metabolism; oral mesna is available but typically used intravenously for this indication. |
| Onset of Action | Intravenous ifosfamide: Clinical antineoplastic effect is delayed, but distribution and metabolism begin immediately; peak plasma concentrations achieved at end of infusion. Intravenous mesna: Onset of uroprotective effect is immediate, as it binds acrolein in the urine. |
| Duration of Action | Ifosfamide: Antineoplastic effect persists for days, but dosing is typically given over 3-5 days per cycle; prolonged exposure increases cumulative toxicity. Mesna: Uroprotective effect lasts 8-12 hours; repeated doses are required (e.g., 0, 4, 8 hours post-ifosfamide) to maintain protection. |
| Molecular Weight | 261.09 |
IFEX (ifosfamide) 1.2 g/m2 intravenously daily for 5 consecutive days every 3 weeks, with MESNEX (mesna) given as 20% of the ifosfamide dose intravenously at the time of ifosfamide administration and 4 and 8 hours after each ifosfamide dose (total daily mesna dose = 60% of ifosfamide dose).
| Dosage form | INJECTABLE |
| Renal impairment | CrCl > 60 mL/min: no adjustment; CrCl 30-60 mL/min: reduce ifosfamide dose by 25%; CrCl 10-29 mL/min: reduce ifosfamide dose by 50%; CrCl < 10 mL/min: use is not recommended. |
| Liver impairment | No specific dose adjustments provided for Child-Pugh classification in prescribing information; caution advised in severe hepatic impairment. |
| Pediatric use | For children, IFEX dose is 1.2-1.8 g/m2/day intravenously for 5 days every 3-4 weeks, with mesna dosing as per adult ratio (60% of ifosfamide daily dose divided into 3 doses). |
| Geriatric use | No specific dose adjustments; use with caution due to increased risk of renal and neurological toxicity; consider renal function for dose adjustment. |
| 1st trimester | Contraindicated. Ifosfamide is teratogenic; may cause fetal harm. |
| 2nd trimester | Contraindicated. Teratogenic and embryotoxic; avoid use. |
| 3rd trimester | Contraindicated. May cause fetal harm; consider alternative therapy. |
Clinical note
Comprehensive clinical and safety monograph for IFEX/MESNEX KIT (IFEX/MESNEX KIT).
| Placental transfer | Ifosfamide crosses the placenta; animal studies show fetal resorptions, malformations, and embryotoxicity. |
| Breastfeeding | Ifosfamide and mesna are excreted into breast milk. Potential for serious adverse reactions in nursing infants; discontinue breastfeeding or discontinue drug. |
| Lactation Rating |
■ FDA Black Box Warning
Ifosfamide can cause severe myelosuppression (leukopenia, thrombocytopenia, anemia) and dose-dependent hemorrhagic cystitis. Mesna is indicated to reduce the incidence of hemorrhagic cystitis. Ifosfamide is also associated with neurotoxicity (e.g., encephalopathy, confusion, coma) and nephrotoxicity (e.g., renal tubular acidosis, acute renal failure).
| Serious Effects |
Hypersensitivity to ifosfamide or mesnaSevere bone marrow suppressionActive infectionBreastfeeding
| Precautions | Myelosuppression (monitor blood counts), hemorrhagic cystitis (use mesna, adequate hydration, monitor urinalysis), neurotoxicity (discontinue if severe), nephrotoxicity (monitor renal function, avoid in pre-existing renal impairment), urotoxicity (ensure mesna administration), embryofetal toxicity (can cause fetal harm), and vaccination risks (avoid live vaccines during treatment). |
| Food/Dietary | Grapefruit and grapefruit juice should be avoided due to potential CYP3A4 inhibition. No other specific food restrictions; maintain adequate hydration. |
Loading safety data…
| L5 - Avoid |
| Teratogenic Risk | First trimester: Contraindicated due to major teratogenic effects (craniofacial, skeletal, visceral anomalies) and fetal loss. Second/third trimesters: Risk of fetal growth restriction, neurodevelopmental impairment, and neonatal myelosuppression. No effective chemotherapeutic alternative; if unavoidable, use only with maternal life-threatening condition. |
| Fetal Monitoring | Complete blood count, urinalysis for hematuria, renal function (BUN, creatinine), liver function tests. Fetal monitoring: serial ultrasound for growth, amniotic fluid volume. Consider fetal echocardiography if second/third trimester exposure. |
| Fertility Effects | Ifosfamide is highly gonadotoxic; causes ovarian failure (premature menopause, ovarian failure) and azoospermia/oligospermia in males. Mesna does not reduce gonadotoxicity. Preserve fertility options (cryopreservation) before therapy. |
| Clinical Pearls | Administer mesna concomitantly with ifosfamide to prevent hemorrhagic cystitis. Ensure adequate hydration (≥2 L/m²/day) and monitor urine output closely. Mesna dose is 60% of ifosfamide dose, given IV at 0, 4, and 8 hours after ifosfamide. Check urinalysis for hematuria before each dose. |
| Patient Advice | You will receive another medication (mesna) along with ifosfamide to protect your bladder. · Drink plenty of fluids (at least 8-10 glasses per day) unless instructed otherwise. · Report any blood in urine, pain with urination, or changes in urine color immediately. · This drug may cause nausea, hair loss, and lower your blood cell counts; notify your doctor if you develop fever, chills, or unusual bleeding. · Avoid grapefruit and grapefruit juice during treatment as it may affect drug metabolism. |