SEROMYCIN^®
CYCLOSERINE CAPSULES, USP

Seromycin^® (Cycloserine Capsules, USP), 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. The structural formula of cycloserine is as follows:

Each capsule contains cycloserine, 250 mg (2.45 mmol); D&C Yellow No. 10, FD&C Blue No. 1, FD&C Red No. 3, FD&C Yellow No. 6, gelatin, iron oxide, talc, titanium dioxide, and other inactive ingredients.

Cycloserine inhibits cell–wall synthesis in susceptible strains of gram–positive and gram–negative bacteria and in Mycobacterium tuberculosis.

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.

Seromycin 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, Seromycin should be administered in conjunction with other effective chemotherapy and not as the sole therapeutic agent.

Seromycin 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 Seromycin 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.

Administration is contraindicated in patients with any of the following:

Because of the potential for serious adverse reactions in nursing infants from Seromycin, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Safety and effectiveness in pediatric patients have not been established.

Most adverse reactions occurring during therapy with Seromycin involve the nervous system or are manifestations of drug hypersensitivity. The following side effects have been observed in patients receiving Seromycin:

Acute toxicity from cycloserine can occur if more than 1 g is ingested by an adult. Chronic toxicity from cycloserine is dose related and can occur if more than 500 mg is administered daily. Patients with renal impairment will accumulate cycloserine and may develop toxicity if the dosing regimen is not modified. Patients with severe renal impairment should not receive the drug. The central nervous system is the most common organ system involved with toxicity. Toxic effects may include headache, vertigo, confusion, drowsiness, hyperirritability, paresthesias, dysarthria, and psychosis. Following larger ingestions, paresis, convulsions, and coma often occur. Ethyl alcohol may increase the risk of seizures in patients receiving cycloserine.

The oral median lethal dose in mice is 5290 mg/kg.

To obtain up–to–date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are uled in the Physicians’ Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.

Overdoses of cycloserine have been reported rarely. The following is provided to serve as a guide should such an overdose be encountered.

Protect the patient’s airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient’s vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient’s airway when employing gastric emptying or charcoal.

In adults, many of the neurotoxic effects of cycloserine can be both treated and prevented with the administration of 200 to 300 mg of pyridoxine daily.

The use of hemodialysis has been shown to remove cycloserine from the bloodstream. This procedure should be reserved for patients with life-threatening toxicity that is unresponsive to less invasive therapy.

Seromycin 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.

• Kubica GP, Dye WE: Laboratory methods for clinical and public health — mycobacteriology. US Department of Health, Education and Welfare, Public Health Service, 1967, pp 47–55, 66–70.

• Jones LR: Colorimetric determination of cycloserine, a new antibiotic. Anal Chem 1956;28:39.

Literature revised April 28, 2005

Eli Lilly and Company

Indianapolis, IN 46285, USA