GANTANOL-DS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for GANTANOL-DS (GANTANOL-DS).

How it works

Sulfamethoxazole is a sulfonamide that inhibits bacterial dihydrofolate synthesis by competing with para-aminobenzoic acid, thereby blocking folate synthesis. Trimethoprim inhibits bacterial dihydrofolate reductase, converting dihydrofolate to tetrahydrofolate. This sequential blockade produces bactericidal activity.

What the body does with it

Metabolism	Sulfamethoxazole is metabolized primarily by N-acetylation and glucuronidation; trimethoprim is metabolized by oxidation and conjugation. Both undergo hepatic metabolism with involvement of CYP450 enzymes.
Excretion	Primarily renal (70-100%) as unchanged drug and inactive metabolites (sulfamethoxazole N4-acetyl and glucuronide conjugates); <5% biliary/fecal.
Half-life	10-12 hours (sulfamethoxazole component); prolonged in renal impairment (up to 30 hours with CrCl <15 mL/min).
Protein binding	Sulfamethoxazole: 65-70% bound (primarily albumin); trimethoprim: 40-45% bound.
Volume of Distribution	0.2-0.4 L/kg (sulfamethoxazole); 1.5-2.0 L/kg (trimethoprim, indicating extensive tissue penetration).
Bioavailability	Oral: 85-95% (sulfamethoxazole); 90-100% (trimethoprim).
Onset of Action	Oral: 1-2 hours (peak serum concentration); clinical effect within 24-48 hours for susceptible infections.
Duration of Action	12-24 hours (dosing every 12 hours recommended); sustained with once-daily dosing for urinary tract infections.

Classification & Brands

Dosing & administration

2 g (DS strength: 2 g sulfamethoxazole/400 mg trimethoprim) orally every 12 hours for 14-21 days for Pneumocystis jirovecii pneumonia.

Dosage form	TABLET
Renal impairment	CrCl 15-30 mL/min: decrease dose by 50% (e.g., 1 g PO q12h); CrCl <15 mL/min: contraindicated unless hemodialysis; use with caution and monitor levels.
Liver impairment	Child-Pugh Class A: no adjustment; Class B: reduce dose by 50% (e.g., 1 g PO q12h); Class C: avoid use or use with extreme caution.
Pediatric use	For PCP: 75-100 mg/kg/day of sulfamethoxazole (Bactrim component) divided every 6-8 hours, PO or IV. Weight-based: sulfamethoxazole 20 mg/kg/dose (max 2 g/dose) q8h.
Geriatric use	Start at lower end of dosing (e.g., 1 g DS PO q12h) due to age-related renal decline; monitor renal function and serum potassium; adjust per renal function.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for GANTANOL-DS (GANTANOL-DS).

Breastfeeding	Excreted in breast milk; M/P ratio approximately 0.4. Potential for kernicterus in neonates, especially with G6PD deficiency or hyperbilirubinemia. Avoid breastfeeding or use with caution.
Teratogenic Risk	First trimester: Avoid due to risk of neural tube defects and congenital malformations. Second/Third trimester: Risk of kernicterus and hemolytic anemia in G6PD-deficient fetuses; avoid near term.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Fatal hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias have been reported.

Side Effect Profile

Serious Effects

Absolute Contraindications

Known hypersensitivity to sulfonamides or trimethoprim, megaloblastic anemia due to folate deficiency, pregnancy at term and nursing mothers, severe hepatic or renal failure, concomitant use with dofetilide.

Clinical Precautions

Precautions

Hypersensitivity reactions, severe dermatologic reactions, hematologic toxicity, folate deficiency, glucose-6-phosphate dehydrogenase deficiency, renal/hepatic impairment, elderly patients, pregnancy (contraindicated at term), lactation, phototoxicity, hyperkalemia (high-dose trimethoprim).

Clinical Tips & Counseling

Drug interactions

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GANTANOL-DS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for GANTANOL-DS (GANTANOL-DS).

How it works

What the body does with it

Metabolism	Sulfamethoxazole is metabolized primarily by N-acetylation and glucuronidation; trimethoprim is metabolized by oxidation and conjugation. Both undergo hepatic metabolism with involvement of CYP450 enzymes.
Excretion	Primarily renal (70-100%) as unchanged drug and inactive metabolites (sulfamethoxazole N4-acetyl and glucuronide conjugates); <5% biliary/fecal.
Half-life	10-12 hours (sulfamethoxazole component); prolonged in renal impairment (up to 30 hours with CrCl <15 mL/min).
Protein binding	Sulfamethoxazole: 65-70% bound (primarily albumin); trimethoprim: 40-45% bound.
Volume of Distribution	0.2-0.4 L/kg (sulfamethoxazole); 1.5-2.0 L/kg (trimethoprim, indicating extensive tissue penetration).
Bioavailability	Oral: 85-95% (sulfamethoxazole); 90-100% (trimethoprim).
Onset of Action	Oral: 1-2 hours (peak serum concentration); clinical effect within 24-48 hours for susceptible infections.
Duration of Action	12-24 hours (dosing every 12 hours recommended); sustained with once-daily dosing for urinary tract infections.

Classification & Brands

Dosing & administration

2 g (DS strength: 2 g sulfamethoxazole/400 mg trimethoprim) orally every 12 hours for 14-21 days for Pneumocystis jirovecii pneumonia.

Dosage form	TABLET
Renal impairment	CrCl 15-30 mL/min: decrease dose by 50% (e.g., 1 g PO q12h); CrCl <15 mL/min: contraindicated unless hemodialysis; use with caution and monitor levels.
Liver impairment	Child-Pugh Class A: no adjustment; Class B: reduce dose by 50% (e.g., 1 g PO q12h); Class C: avoid use or use with extreme caution.
Pediatric use	For PCP: 75-100 mg/kg/day of sulfamethoxazole (Bactrim component) divided every 6-8 hours, PO or IV. Weight-based: sulfamethoxazole 20 mg/kg/dose (max 2 g/dose) q8h.
Geriatric use	Start at lower end of dosing (e.g., 1 g DS PO q12h) due to age-related renal decline; monitor renal function and serum potassium; adjust per renal function.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for GANTANOL-DS (GANTANOL-DS).

Breastfeeding	Excreted in breast milk; M/P ratio approximately 0.4. Potential for kernicterus in neonates, especially with G6PD deficiency or hyperbilirubinemia. Avoid breastfeeding or use with caution.
Teratogenic Risk	First trimester: Avoid due to risk of neural tube defects and congenital malformations. Second/Third trimester: Risk of kernicterus and hemolytic anemia in G6PD-deficient fetuses; avoid near term.
Fetal Monitoring