IVADANTIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for IVADANTIN (IVADANTIN).

How it works

Ivadantin is a direct inhibitor of dihydrofolate reductase (DHFR), blocking the conversion of dihydrofolate to tetrahydrofolate, thereby inhibiting bacterial DNA synthesis.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for IVADANTIN (IVADANTIN).

Breastfeeding	Excreted in breast milk in low concentrations; M/P ratio not established. Considered compatible with breastfeeding by AAP; monitor infant for diarrhea, rash, and hemolysis in G6PD-deficient infants. Use caution in nursing mothers of infants with G6PD deficiency.
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.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to ivadantin or any component; severe hepatic impairment; concomitant use with strong CYP3A4 inhibitors.

Clinical Precautions

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).

Clinical Tips & Counseling

Drug interactions

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IVADANTIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for IVADANTIN (IVADANTIN).

How it works

Ivadantin is a direct inhibitor of dihydrofolate reductase (DHFR), blocking the conversion of dihydrofolate to tetrahydrofolate, thereby inhibiting bacterial DNA synthesis.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for IVADANTIN (IVADANTIN).

Breastfeeding	Excreted in breast milk in low concentrations; M/P ratio not established. Considered compatible with breastfeeding by AAP; monitor infant for diarrhea, rash, and hemolysis in G6PD-deficient infants. Use caution in nursing mothers of infants with G6PD deficiency.
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.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to ivadantin or any component; severe hepatic impairment; concomitant use with strong CYP3A4 inhibitors.