cycloserine
Seromycin

Available forms
Available by prescription only
Capsules: 250 mg

Indications and dosages
 Adjunctive treatment in pulmonary or extrapulmonary tuberculosis. Adults: Initially, 250 mg P.O. q 12 hours for 2 weeks; then, if blood levels are below 25 to 30 mcg/ml and there are no clinical signs of toxicity, dosage is increased to 250 mg P.O. q 8 hours for 2 weeks. If optimum blood levels are still not achieved, and there are no signs of clinical toxicity, then dosage is increased to 250 mg P.O. q 6 hours. Maximum dose is 1 g daily. If CNS toxicity occurs, drug is discontinued for 1 week, then resumed at 250 mg daily for 2 weeks. If no serious toxic effects occur, dosage is increased by 250-mg increments q 10 days until blood levels reach 25 to 30 mcg/ml.
Children: 10 to 20 mg/kg (maximum, 750 to 1,000 mg) P.O. daily administered in two equally divided doses.
 Urinary tract infections. Adults: 250 mg P.O. q 12 hours for 2 weeks.

Pharmacodynamics
Antibiotic action: Cycloserine inhibits bacterial cell utilization of amino acids, thereby inhibiting cell wall synthesis. Its action is bacteriostatic or bactericidal, depending on organism susceptibility and drug concentration at infection site. Cycloserine is active against Mycobacterium tuberculosis, M. bovis, and some strains of M. kansasii, M. marinum, M. ulcerans, M. avium, M. smegmatis, and M. intracellulare. It’s also active against some gram-negative and gram-positive bacteria, including Staphylococcus aureus,Enterobacter, and Escherichia coli. Cycloserine is considered adjunctive therapy in tuberculosis and is combined with other antituberculotics to prevent or delay development of drug resistance by M. tuberculosis.

Pharmacokinetics
Absorption: About 80% of oral dose is absorbed from the GI tract.
Distribution: Distributed widely into body tissues and fluids, including CSF. Drug crosses the placental barrier; it doesn’t bind to plasma proteins.
Metabolism: May be metabolized partially.
Excretion: Excreted primarily in urine by glomerular filtration. Small amounts of drug are excreted in feces and breast milk. Elimination plasma half-life in adults is 10 hours. Drug is hemodialyzable.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with seizure disorders, depression or severe anxiety, psychosis, severe renal insufficiency, or excessive concurrent use of alcohol. Use cautiously in patients with impaired renal function.

Interactions
Drug-drug. Ethionamide, isoniazid: Increases hazard of CNS toxicity, drowsiness, and dizziness. Use with extreme caution.
Phenytoin: Inhibits phenytoin metabolism and causes risk of toxic blood levels. Dosage adjustment may be needed.
Drug-lifestyle. Alcohol use: Increases risk of seizures. Discourage alcohol use.

Adverse reactions
CNS: seizures, drowsiness, somnolence, headache, tremor, dysarthria, vertigo, confusion, memory loss, suicidal tendencies, psychosis, hyper-irritability, character changes, aggression, paresthesia, paresis, hyperreflexia, coma.
CV: sudden-onset heart failure.
Skin: rash.
Other: hypersensitivity reactions (allergic dermatitis).

Effects on lab test results
• May increase transaminase level.

Overdose and treatment
Signs and symptoms of overdose include CNS depression accompanied by dizziness, hyperreflexia, confusion, or seizures.
 Treat with gastric lavage and supportive care, including oxygen, I.V. fluids, pressor agents (for circulatory shock), and body temperature stabilization. Treat seizures with anticonvulsants and pyridoxine.

Special considerations
• Drug should be taken after meals to avoid gastric irritation.
• Specimens for culture and sensitivity testing will be taken before first dose, but therapy can begin pending test results; repeat testing periodically to detect drug resistance.
• Pyridoxine (200 to 300 mg daily) may be used to treat or prevent neurotoxic effects.
• Anticonvulsants, tranquilizers, or sedatives may be prescribed to relieve adverse reactions.
• Monitor hematologic, renal, and liver function test results before and periodically during therapy to minimize toxicity; toxic reactions may occur at blood levels above 30 mcg/ml.
• Assess level of consciousness and neurologic function; monitor patient for personality changes and other early signs of CNS toxicity.
Breast-feeding patients
• Drug appears in breast milk; use cautiously in breast-feeding women.
Geriatric patients
• Because elderly patients commonly have renal impairment, which decreases excretion of drugs, use drug with caution.

Patient education
• Explain rationale for long-term therapy.
• Teach signs and symptoms of hypersensitivity and other adverse reactions, and emphasize need to report unusual effects and rash promptly.
• Warn patient to avoid hazardous tasks that require mental alertness because drug may cause drowsiness or dizziness.
• Advise patient to take drug after meals to avoid gastric irritation.
• Urge patient to complete entire prescribed regimen, to comply with instructions for around-the-clock dosage, and not to discontinue drug without medical approval.
• Explain importance of follow-up appointments.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use