Version July 2025
Tuberculosis disease [active tuberculosis]; drug resistant (alternative agent): Limited data available: Note: Consider dosage adjustment based on serum concentration monitoring to minimize toxicity (Ref). Concomitant pyridoxine is recommended to prevent neurologic adverse events (Ref). Always use in combination with other antitubercular drugs; expert consultation for optimal regimen and duration of treatment is advised (Ref).
ATS/CDC/IDSA guideline dosing:
Infants, Children, and Adolescents: Oral: 10 to 20 mg/kg/day once daily; maximum daily dose: 1,000 mg/day. Usual adult dose: 250 to 750 mg/day in 1 or 2 divided doses (Ref). Note: Some patients may be unable to tolerate recommended doses; consider dividing daily dose twice daily. May also begin with a low once-daily dose and gradually increase as tolerated. Adolescents may require dosing on the lower end of the range (eg, 10 to 15 mg/kg/day) to avoid high exposures that may contribute to toxicity (Ref).
WHO dosing:
Infants, Children, and Adolescents:
3 to <5 kg: Oral: 25 mg once daily (Ref). Note: Dosing lower than previously recommended due to high exposures observed in pharmacokinetic models (Ref).
5 to <7 kg: Oral: 50 mg once daily (Ref). Note: Dosing lower than previously recommended due to high exposures observed in pharmacokinetic models; some experts still recommend higher dosing (Ref).
7 to <30 kg: Oral: 15 to 20 mg/kg/dose once daily; maximum dose: 1,000 mg/day. May divide dose twice daily to improve tolerability; doses >750 mg may not be tolerated (Ref).
≥30 kg: Oral: 10 to 15 mg/kg/dose once daily; maximum dose: 1,000 mg/day. May divide dose twice daily to improve tolerability; doses >750 mg may not be tolerated (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. In adults with severe kidney impairment, use is contraindicated. Based on experience in adult patients, dosage adjustment suggested when CrCl <30 mL/minute; eg, start with low doses, adjust based on serum concentration monitoring; monitor closely for toxicity (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Cycloserine: Drug information")
Tuberculosis, drug resistant: Note: Expert consultation for optimal regimen and duration of treatment is advised. Some neurotoxic effects may be treated or prevented by concomitant administration of pyridoxine ≥100 mg daily or 50 mg of pyridoxine per 250 mg of cycloserine (Ref).
Oral: 10 to 15 mg/kg/day (maximum: 1 g/day), usually 250 to 750 mg/day in 1 or 2 divided doses as part of an appropriate combination regimen (Ref). Note: Some experts recommend the following 2-week dose titration: 250 mg once daily for 3 to 4 days, 250 mg twice daily for 3 to 4 days, then 250 mg in the morning and 500 mg in the evening (Ref). Adjust based on serum concentration (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; use is contraindicated in severe impairment. However, the following adjustments have been used by some clinicians:
ATS/CDC/IDSA guidelines: CrCl <30 mL/minute or hemodialysis: 250 mg once daily or 500 mg 3 times per week. Note: The appropriateness of 250 mg daily doses has not been established, and careful monitoring is necessary for evidence of neurotoxicity. Monitor serum concentrations to minimize toxicity (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
Frequency not defined:
Cardiovascular: Heart failure
Endocrine & metabolic: Vitamin B12 deficiency
Hepatic: Increased serum transaminases
Nervous system: Amnesia, behavioral changes, coma, confusion, disorientation, drowsiness, dysarthria, hyperreflexia, paresis, paresthesia, seizure, tremor, vertigo
Postmarketing:
Dermatologic: Lichenoid eruption (Kim 2017), Stevens-Johnson syndrome (Akula 1997)
Endocrine & metabolic: Folate deficiency (Klipstein 1967)
Hematologic & oncologic: Megaloblastic anemia (Klipstein 1967), sideroblastic anemia (Klipstein 1967)
Nervous system: Encephalopathy (Kwon 2008), headache (Singanamala 2019), psychiatric disturbance (including aggressive behavior, depression, hallucination, hyperirritability, mania, psychosis, and suicidal tendencies) (Bakhla 2013; Intini 2019; Singanamala 2019)
Hypersensitivity to cycloserine or any component of the formulation; epilepsy; depression, severe anxiety, or psychosis; severe renal insufficiency; excessive concurrent use of alcohol
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• CNS effects: Has been associated with dose-related CNS toxicity, including seizures, psychosis, depression, and confusion; decrease dosage or discontinue use if occurs. Pyridoxine may be coadministered to prevent/treat CNS effects.
• Skin reactions: Allergic dermatitis may occur; reduce dose or discontinue use if allergic dermatitis develops.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Alcoholism: Use with caution in patients with a history of chronic alcoholism; increased risk of seizures.
• Mental illness: Use with caution in patients with depression, severe anxiety, and/or psychosis.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be necessary. Use is contraindicated in severe renal insufficiency.
Special populations:
• Patients with potential for vitamin deficiency: Use with caution in patients with potential vitamin B12 and/or folate deficiency (malnourished, chronic antiseizure medication therapy, or elderly).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 250 mg
Yes
Capsules (cycloSERINE Oral)
250 mg (per each): $91.88
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: May administer without regard to meals; absorption is best on an empty stomach but may negatively impact GI tolerability (Ref). For smaller doses (eg, <250 mg), dissolve capsule contents in 10 mL of water and administer the appropriate dose aliquot using calibrated measuring device (eg, dissolve 250 mg capsule in 10 mL to create a 25 mg/mL solution; administer appropriate volume to equal patient-specific dose) (Ref).
Oral: Administer in divided doses with or without food.
Store at 20°C to 25°C (68°F to 77°F).
Treatment of pulmonary or extrapulmonary tuberculosis in conjunction with other effective agents when treatment with primary tuberculosis therapy has proven inadequate (FDA approved in adults); treatment of acute urinary tract infections caused by susceptible organisms (FDA approved in adults). Note: Should be considered only when more conventional therapy has failed and when the organism has been demonstrated to be susceptible to the drug.
CycloSERINE may be confused with cyclobenzaprine, cycloPHOSphamide, cycloSPORINE
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Alcohol (Ethyl): May increase neurotoxic effects of CycloSERINE. Specifically, the risk for seizures may be increased. Risk X: Avoid
Bacillus clausii: Antibiotics may decrease therapeutic effects of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider Therapy Modification
BCG (Intravesical): Antibiotics may decrease therapeutic effects of BCG (Intravesical). Risk X: Avoid
BCG Vaccine (Immunization): Antibiotics may decrease therapeutic effects of BCG Vaccine (Immunization). Risk C: Monitor
Cholera Vaccine: Antibiotics may decrease therapeutic effects of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid
Ethionamide: May increase adverse/toxic effects of CycloSERINE. Risk C: Monitor
Fecal Microbiota (Live) (Oral): May decrease therapeutic effects of Antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Rectal): Antibiotics may decrease therapeutic effects of Fecal Microbiota (Live) (Rectal). Risk X: Avoid
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Isoniazid: May increase adverse/toxic effects of CycloSERINE. Specifically, CNS toxicity may be enhanced. Risk C: Monitor
Lactobacillus and Estriol: Antibiotics may decrease therapeutic effects of Lactobacillus and Estriol. Risk C: Monitor
Mycophenolate: Antibiotics may decrease active metabolite exposure of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor
Prothionamide: May increase adverse/toxic effects of CycloSERINE. Risk C: Monitor
Sodium Picosulfate: Antibiotics may decrease therapeutic effects of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider Therapy Modification
Typhoid Vaccine: Antibiotics may decrease therapeutic effects of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider Therapy Modification
May increase vitamin B12 and folic acid dietary requirements. Management: Vitamin B12 and folic acid supplementation may be needed.
May be taken with food; may increase vitamin B12 and folic acid dietary requirements.
Evaluate pregnancy status prior to treatment of multidrug resistant tuberculosis in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment for multidrug-resistant tuberculosis (Esmail 2018).
Cycloserine crosses the placenta and can be detected in the fetal blood and amniotic fluid.
Tuberculosis (TB) disease (active TB) is associated with adverse fetal outcomes, including intrauterine growth restriction, low birth weight, preterm birth, and perinatal death (Esmail 2018; Miele 2020), as well as adverse maternal outcomes, including increased risks for anemia and cesarean delivery. Placental transmission may rarely occur with active maternal disease (Miele 2020).
Data are limited for use of second-line drugs in pregnancy (ie, cycloserine). The treatment of multidrug-resistant tuberculosis in pregnant patients should be individualized; evidence to support a specific regimen is not available (ATS/CDC/ERS/IDSA [Nahid 2019]; WHO 2020).
Kidney and liver function, CBC, serum cycloserine concentrations. Monitor for CNS toxicity (eg, inability to concentrate, depression, anxiety, hallucinations, psychosis, suicidal ideation); screen for depression using an appropriate tool at baseline and monthly during treatment (Ref).
Obtain concentrations within first 1 to 2 weeks and monitor routinely during therapy (Ref). Peak concentrations are routinely recommended for monitoring, though samples may be obtained at 2 to 3 and 6 to 7 hours postdose to determine overall exposure (Ref).
Peak concentration:
Timing: 2 to 3 hours post-dose (Ref).
Target: 20 to 35 mg/L (Ref); some prefer <30 mg/L (Ref). Peak concentrations >35 mg/L are associated with CNS toxicity, though CNS adverse effects may also occur at lower concentrations (Ref).
Inhibits bacterial cell wall synthesis by competing with amino acid (D-alanine) for incorporation into the bacterial cell wall; bacteriostatic or bactericidal
Absorption: ~70% to 90% from GI tract (WHO 2008). Absorption is delayed and Cmax lowered when administered with high-fat meal compared to fasting, but AUC not impacted (Zhu 2001).
Distribution: Widely to most body fluids and tissues including CSF, bile, sputum, lymph tissue, lungs, and ascitic, pleural, and synovial fluids (WHO 2008)
Protein binding: Not plasma protein bound
Metabolism: Hepatic
Half-life elimination: Normal renal function: 12 hours
Time to peak, serum: 4 to 8 hours
Excretion: Urine (~65% as unchanged drug) within 72 hours; Feces (small amounts); remainder metabolized
