HYDROXYSTILBAMIDINE ISETHIONATE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HYDROXYSTILBAMIDINE ISETHIONATE (HYDROXYSTILBAMIDINE ISETHIONATE).

How it works

Hydroxystilbamidine isethionate is an antiprotozoal agent that inhibits nucleic acid synthesis and disrupts polyamine metabolism by binding to DNA and RNA, particularly in kinetoplasts of Leishmania species.

What the body does with it

Metabolism	Not well characterized; likely hepatic.
Excretion	Renal: 10-15% as unchanged drug; biliary/fecal: 80-90% as metabolites and unchanged drug; negligible glomerular filtration due to high protein binding; prolonged presence in tissues.
Half-life	Terminal half-life: 24-48 hours; clinically, elimination is multiphasic with a slow tissue redistribution phase, requiring cautious dosing to avoid accumulation.
Protein binding	99% bound to albumin and alpha-1-acid glycoprotein; extensive tissue binding.
Volume of Distribution	Vd: 10-20 L/kg; indicates extensive tissue sequestration, particularly in liver, kidney, and reticuloendothelial system.
Bioavailability	IV: 100%; IM: 60-80% due to incomplete absorption and possible precipitation at injection site; not orally bioavailable.
Onset of Action	IV: 1-2 hours; IM: 3-5 hours; bioavailability after IM is slower due to depot formation.
Duration of Action	Single dose: 24-48 hours for antiprotozoal effect; tissue residues persist for weeks; clinical dosing typically every 24 hours for 10-14 days.

Classification & Brands

Dosing & administration

2-4 mg/kg/day intravenously every 24 hours for visceral leishmaniasis; 2-4 mg/kg intramuscularly every 24 hours for cutaneous leishmaniasis.

Dosage form	INJECTABLE
Renal impairment	CrCl 30-50 mL/min: reduce dose by 50% and extend interval to every 48 hours; CrCl <30 mL/min: contraindicated.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use.
Pediatric use	2-4 mg/kg/day intravenously or intramuscularly every 24 hours; maximum single dose 4 mg/kg.
Geriatric use	Start at low end of dosing range (2 mg/kg/day); monitor renal function and adjust based on CrCl; use with caution due to potential nephrotoxicity and hypotension.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for HYDROXYSTILBAMIDINE ISETHIONATE (HYDROXYSTILBAMIDINE ISETHIONATE).

Breastfeeding	No human data on excretion in breast milk. M/P ratio unknown. Due to potential for infant toxicity (hypotension, gastrointestinal effects), breastfeeding is not recommended during therapy. Discontinue nursing or drug.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: Potential teratogenic effects based on animal studies (cleft palate, skeletal anomalies). Second and third trimesters: Risk of fetal hypotension and hypoxia from maternal vasodilation. Avoid use unless maternal benefit outweighs fetal risk.

Warnings & precautions

■ FDA Black Box Warning

None specified.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to hydroxystilbamidine or any component","Severe hepatic or renal impairment","Pregnancy (avoid unless essential)","Lactation (discontinue nursing or drug)"]

Clinical Precautions

Precautions

["Nephrotoxicity (monitor renal function)","Hepatotoxicity (monitor liver enzymes)","Cardiotoxicity (QT prolongation, arrhythmias; monitor ECG)","Pancreatitis (monitor amylase/lipase)","Hypotension (especially with rapid infusion)","Anaphylaxis (have emergency measures available)","Carcinogenic and mutagenic potential (avoid in pregnancy unless benefit outweighs risk)"]

Clinical Tips & Counseling

Drug interactions

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HYDROXYSTILBAMIDINE ISETHIONATE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HYDROXYSTILBAMIDINE ISETHIONATE (HYDROXYSTILBAMIDINE ISETHIONATE).

How it works

What the body does with it

Metabolism	Not well characterized; likely hepatic.
Excretion	Renal: 10-15% as unchanged drug; biliary/fecal: 80-90% as metabolites and unchanged drug; negligible glomerular filtration due to high protein binding; prolonged presence in tissues.
Half-life	Terminal half-life: 24-48 hours; clinically, elimination is multiphasic with a slow tissue redistribution phase, requiring cautious dosing to avoid accumulation.
Protein binding	99% bound to albumin and alpha-1-acid glycoprotein; extensive tissue binding.
Volume of Distribution	Vd: 10-20 L/kg; indicates extensive tissue sequestration, particularly in liver, kidney, and reticuloendothelial system.
Bioavailability	IV: 100%; IM: 60-80% due to incomplete absorption and possible precipitation at injection site; not orally bioavailable.
Onset of Action	IV: 1-2 hours; IM: 3-5 hours; bioavailability after IM is slower due to depot formation.
Duration of Action	Single dose: 24-48 hours for antiprotozoal effect; tissue residues persist for weeks; clinical dosing typically every 24 hours for 10-14 days.

Classification & Brands

Dosing & administration

2-4 mg/kg/day intravenously every 24 hours for visceral leishmaniasis; 2-4 mg/kg intramuscularly every 24 hours for cutaneous leishmaniasis.

Dosage form	INJECTABLE
Renal impairment	CrCl 30-50 mL/min: reduce dose by 50% and extend interval to every 48 hours; CrCl <30 mL/min: contraindicated.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use.
Pediatric use	2-4 mg/kg/day intravenously or intramuscularly every 24 hours; maximum single dose 4 mg/kg.
Geriatric use	Start at low end of dosing range (2 mg/kg/day); monitor renal function and adjust based on CrCl; use with caution due to potential nephrotoxicity and hypotension.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for HYDROXYSTILBAMIDINE ISETHIONATE (HYDROXYSTILBAMIDINE ISETHIONATE).

Breastfeeding	No human data on excretion in breast milk. M/P ratio unknown. Due to potential for infant toxicity (hypotension, gastrointestinal effects), breastfeeding is not recommended during therapy. Discontinue nursing or drug.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: Potential teratogenic effects based on animal studies (cleft palate, skeletal anomalies). Second and third trimesters: Risk of fetal hypotension and hypoxia from maternal vasodilation. Avoid use unless maternal benefit outweighs fetal risk.

Warnings & precautions

■ FDA Black Box Warning

None specified.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to hydroxystilbamidine or any component","Severe hepatic or renal impairment","Pregnancy (avoid unless essential)","Lactation (discontinue nursing or drug)"]