CYCLOSERINE - cycloserine capsule
Purdue GMP Center LLC dba The Chao Center
Cycloserine, 3-isoxazolidinone, 4-amino �, (R)� is a broad�spectrum antibiotic that is produced by a strain of Streptomyces orchidaceus and has also been synthesized. Cycloserine is a white to off�white powder that is soluble in water and stable in alkaline solution. It is rapidly destroyed at a neutral or acid pH.
Cycloserine has a pH between 5.5 and 6.5 in a solution containing 100 mg/mL. The molecular weight of cycloserine is 102.09, and it has an empirical formula of C3H6N2O2.
INACTIVE INGREDIENT SECTION
Each capsule contains cycloserine, 250 mg (2.45 mmol); D and C Yellow No. 10, FD and C Blue No. 1, FD and C Red No. 3, FD and C Yellow No. 6, gelatin, iron oxide, talc, titanium dioxide, and other inactive ingredients.
CLINICAL PHARMACOLOGY SECTION
After oral administration, cycloserine is readily absorbed from the gastrointestinal tract, with peak blood levels occurring in 4 to 8 hours.
Blood levels of 25 to 30 μg/mL can generally be maintained with the usual dosage of 250 mg twice a day, although the relationship of plasma levels to dosage is not always consistent. Concentrations in the cerebrospinal fluid, pleural fluid, fetal blood, and mother's milk approach those found in the serum. Detectable amounts are found in ascitic fluid, bile, sputum, amniotic fluid, and lung and lymph tissues. Approximately 65 percent of a single dose of cycloserine can be recovered in the urine within 72 hours after oral administration. The remaining 35 percent is apparently metabolized to unknown substances. The maximum excretion rate occurs 2 to 6 hours after administration, with 50 percent of the drug eliminated in 12 hours.
MICROBIOLOGY SECTION
Cycloserine inhibits cell�wall synthesis in susceptible strains of gram�positive and gram�negative bacteria and in Mycobacterium tuberculosis.
Susceptibility Tests
Cycloserine clinical laboratory standard powder is available for both direct and indirect methods1 of determining the susceptibility
of strains of mycobacteria. Cycloserine MICs for susceptible strains are 25 μg/mL or lower.
INDICATIONS & USAGE SECTION
Cycloserine is indicated in the treatment of active pulmonary and extrapulmonary tuberculosis (including renal disease) when the causative
organisms are susceptible to this drug and when treatment with the primary medications (streptomycin, isoniazid, rifampin, and ethambutol) has proved inadequate. Like all antituberculosis drugs, cycloserine should be administered in conjunction with other effective chemotherapy and not as the sole therapeutic agent.
Cycloserine may be effective in the treatment of acute urinary tract infections caused by susceptible strains of gram�positive and gram�negative bacteria, especially Enterobacter spp. and Escherichia coli. It is generally no more and is usually less effective than other antimicrobial agents in the treatment of urinary tract infections caused by bacteria other than mycobacteria. Use of cycloserine in these infections should be considered only when more conventional therapy has failed and when the organism has been demonstrated to be susceptible to the drug.
CONTRAINDICATIONS SECTION
Administration is contraindicated in patients with any of the
following:
Hypersensitivity to cycloserine
Epilepsy
Depression, severe anxiety, or psychosis
Severe renal insufficiency
Excessive concurrent use of alcohol
WARNINGS SECTION
Administration of cycloserine should be discontinued or the dosage reduced if the patient develops allergic dermatitis or symptoms of CNS toxicity, such as convulsions, psychosis, somnolence, depression, confusion, hyperreflexia, headache, tremor, vertigo, paresis, or dysarthria.
The toxicity of cycloserine is closely related to excessive blood levels (above 30 μg/mL), as determined by high dosage or inadequate renal clearance. The ratio of toxic dose to effective dose in tuberculosis is small.
The risk of convulsions is increased in chronic alcoholics.
Patients should be monitored by hematologic, renal excretion, blood level, and liver function studies.
DOSAGE & ADMINISTRATION SECTION
Cycloserine is effective orally and is currently administered only by this route. The usual dosage is 500 mg to 1 g daily in divided doses monitored by blood levels.2 The initial adult dosage most frequently given is 250 mg twice daily at 12�hour intervals for the first 2 weeks. A daily dosage of 1 g should not be exceeded.
HOW SUPPLIED SECTION
Cycloserine is available as a 250 mg capsule with an opaque red cap and opaque gray body imprinted with "CHAO" and "F04" in edible black ink on both the cap and the body.
Bottles of 40 NDC 13845-1201-3
Store at controlled room temperature, 20� to 25�C (68� to 77�F) [see USP].
