SEROMYCIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEROMYCIN (SEROMYCIN).
Cycloserine is a cyclic analog of D-alanine and inhibits bacterial cell wall synthesis by competitively inhibiting two enzymes: L-alanine racemase (which converts L-alanine to D-alanine) and D-alanine:D-alanine ligase (which adds D-alanine to the growing peptidoglycan chain). This disrupts peptidoglycan formation and leads to bacterial lysis.
| Metabolism | Cycloserine is not extensively metabolized in the liver; approximately 60-70% of a dose is excreted unchanged in the urine within 72 hours via glomerular filtration. A small portion may be metabolized by unknown pathways. Elimination half-life is about 10 hours with normal renal function. |
| Excretion | Renal: 70-80% as unchanged drug; biliary/fecal: <10%. |
| Half-life | Terminal elimination half-life is 8-12 hours in patients with normal renal function; may be prolonged to 15-20 hours in renal impairment, requiring dose adjustment. |
| Protein binding | Unchanged drug exhibits negligible protein binding (<10%); the active metabolite cycloserine binds approximately 20% to albumin. |
| Volume of Distribution | 0.2-0.3 L/kg; indicates distribution primarily into total body water with good penetration into cerebrospinal fluid (CSF) and body tissues. |
| Bioavailability | Oral: 60-80% (variable due to food effects). |
| Onset of Action | Oral: 1-2 hours for bacteriostatic effect. |
| Duration of Action | Oral: 6-8 hours; clinical effect persists for 12-24 hours due to post-antibiotic effect. |
250-500 mg orally every 12 hours for first 2 weeks, then 250 mg every 12 hours for maintenance.
| Dosage form | CAPSULE |
| Renal impairment | CrCl >50 mL/min: standard dose. CrCl 10-50 mL/min: 250 mg every 24-48 hours. CrCl <10 mL/min: 250 mg every 72-96 hours or avoid use. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: caution, reduce dose by 25-50%. Child-Pugh C: avoid use or maximum 250 mg twice weekly. |
| Pediatric use | 10-15 mg/kg/day orally divided every 12 hours, maximum 500 mg/day for children <12 years; for children ≥12 years, adult dosing may be used. |
| Geriatric use | Start at lower end of dosing range (250 mg every 12 hours) and monitor renal function due to age-related decline in CrCl; adjust per CrCl. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SEROMYCIN (SEROMYCIN).
| Breastfeeding | Excreted in breast milk in low concentrations. M/P ratio is unknown. Potential for infant ototoxicity and gastrointestinal disturbance. Consider temporary cessation of breastfeeding or alternative therapy. |
| Teratogenic Risk | FDA Category C. First trimester: Possible association with neural tube defects. Second and third trimesters: Risk of ototoxicity and nephrotoxicity in neonates. Avoid use unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
Seromycin should be used only when other antituberculosis drugs are inadequate or contraindicated due to the high risk of neurotoxicity, including seizures, psychosis, and suicidal ideation. Patients must be closely monitored for CNS effects, and the drug should be discontinued if severe neurological symptoms develop.
| Serious Effects |
["Hypersensitivity to cycloserine or any of its components","Severe renal insufficiency (creatinine clearance <25 mL/min)","Epilepsy or history of seizures","Severe psychiatric disorders (e.g., major depression, psychosis)","Excessive concurrent use of alcohol (may increase risk of CNS effects)"]
| Precautions | ["Neurotoxicity: cycloserine can cause dose-dependent CNS effects including headache, dizziness, vertigo, confusion, psychosis, seizures, and suicidal behavior. Risk increases with doses >500 mg/day or in patients with renal impairment.","Psychiatric reactions: patients with history of depression, anxiety, or psychosis should be monitored closely.","Renal impairment: dosage adjustment is required in patients with creatinine clearance <50 mL/min; accumulation may increase neurotoxicity.","Contraindicated in patients with severe renal insufficiency (CrCl <25 mL/min) due to risk of accumulation and toxicity.","May cause folate deficiency; monitor blood counts and consider supplementation if megaloblastic anemia occurs."] |
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| Maternal: Audiometry, renal function tests, serum drug levels. Fetal/neonatal: Auditory screening, renal function assessment after birth. |
| Fertility Effects | No reported adverse effects on human fertility. Animal studies show no impairment of fertility. |