IVADANTIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IVADANTIN (IVADANTIN).
Ivadantin is a direct inhibitor of dihydrofolate reductase (DHFR), blocking the conversion of dihydrofolate to tetrahydrofolate, thereby inhibiting bacterial DNA synthesis.
| Metabolism | Hepatic metabolism via CYP3A4; minor contribution from CYP1A2 and CYP2C9. |
| Excretion | Approximately 30-40% excreted unchanged in urine via glomerular filtration and tubular secretion; the remainder is metabolized in the liver and eliminated via bile into feces, with negligible biliary excretion of parent drug. Total fecal elimination accounts for about 50-60% of the dose. |
| Half-life | Terminal elimination half-life is approximately 6-8 hours in patients with normal renal function. In severe renal impairment (CrCl <20 mL/min), it may be prolonged to >20 hours. Clinical context: Dosing interval is typically every 6-8 hours; renal adjustment required for CrCl <30 mL/min. |
| Protein binding | Approximately 70-80% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.5-0.7 L/kg, suggesting distribution primarily into extracellular fluid and well-perfused tissues, with moderate tissue penetration (e.g., lung, kidney). |
| Bioavailability | Oral bioavailability is approximately 50-70%, with interindividual variability due to first-pass metabolism and food effects (high-fat meals may decrease absorption). |
| Onset of Action | Oral administration: Onset of clinical effect (antibacterial activity) occurs within 1-2 hours after a dose, based on time to achieve therapeutic serum concentrations above MIC for susceptible organisms. |
| Duration of Action | Duration of antibacterial effect is approximately 6-8 hours, corresponding to the dosing interval. The drug exhibits time-dependent killing; serum concentrations should remain above MIC for at least 40-50% of the dosing interval for efficacy. |
| Molecular Weight | 369.49 Da |
100 mg orally twice daily for uncomplicated urinary tract infections; 200 mg orally three times daily for complicated urinary tract infections.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 50%; GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | 5 mg/kg/day divided every 12 hours, maximum 200 mg/day. |
| Geriatric use | Initiate at 50 mg twice daily; monitor renal function; avoid if CrCl <30 mL/min. |
| 1st trimester | Avoid due to risk of fetal thyroid dysfunction and potential teratogenicity. |
| 2nd trimester | Use only if clearly needed; monitor fetal thyroid function. |
| 3rd trimester | Avoid due to risk of neonatal hypothyroidism and goiter. |
Clinical note
Comprehensive clinical and safety monograph for IVADANTIN (IVADANTIN).
| Placental transfer | Crosses placenta; achieves fetal serum levels up to 50% of maternal levels. |
| Breastfeeding | Excreted in breast milk; use with caution. Monitor infant for thyroid suppression. Consider alternative therapies. |
| Lactation Rating | L3 (Moderately Safe) |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to ivadantin or its componentsSevere hepatic impairmentUntreated thyrotoxicosis
| Precautions | Monitor for hypersensitivity reactions; may cause acute interstitial nephritis; risk of QT prolongation; caution in renal impairment (CrCl <30 mL/min); use during pregnancy only if benefits outweigh risks (FDA Category C). |
| Food/Dietary | Take with meals or milk to enhance absorption and reduce gastrointestinal irritation. Avoid high-fat meals as they may delay absorption. No specific food-drug interactions; alcohol should be avoided to reduce potential disulfiram-like reaction (rare). |
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| Teratogenic Risk | FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; limited human data. First trimester: theoretical risk based on folate antagonism; avoid if possible. Second and third trimesters: use only if clearly needed; may cause neonatal hyperbilirubinemia and hemolytic anemia if used near term due to G6PD deficiency risk. |
| Fetal Monitoring | Monitor maternal CBC, renal function, and pulmonary symptoms (pulmonary fibrosis risk). Fetal monitoring: standard prenatal care; assess for hemolytic anemia in newborn if used near delivery. |
| Fertility Effects | No known adverse effects on fertility in animal or human studies. |
| Clinical Pearls |
| IVADANTIN is a brand name for nitrofurantoin, available as macrocrystals or macrocrystal-monohydrate. It achieves high urinary concentrations, making it effective for uncomplicated UTIs. It is avoided in G6PD deficiency, CrCl <30, and late pregnancy. Must be taken with food to reduce GI upset and enhance absorption. Therapeutic failure suggests resistance or complicated infection. Monitor for pulmonary, hepatic, and neurologic toxicity with prolonged use. |
| Patient Advice | Take with food or milk to reduce stomach upset and improve absorption. · Finish the full course even if symptoms improve to prevent resistance. · May cause harmless brownish discoloration of urine; inform patients it is not blood. · Avoid if you have kidney problems (low creatinine clearance), G6PD deficiency, or during late pregnancy (after 38 weeks). · Report immediately: difficulty breathing, chest pain, chills, fever, numbness/tingling, or severe fatigue. |