cycloserine capsule Eli Lilly and Company
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
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% of
a single dose of cycloserine can
be recovered in the urine within 72 hours after oral administration.
The remaining 35% is apparently metabolized to unknown substances.
The maximum excretion rate occurs 2 to 6 hours
after administration, with 50% of the drug eliminated in
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
determining the susceptibility of strains of mycobacteria. Cycloserine MICs for
susceptible strains are 25 μg/mL or lower.
INDICATIONS AND USAGE
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.
be effective in the treatment of acute urinary tract infections caused by
susceptible strains of gram–positive and gram–negative bacteria,
especially Enterobacter spp.
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
Administration is contraindicated in patients with any of the following:
severe anxiety, or psychosis
concurrent use of alcohol
Administration of Seromycin 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 Seromycin 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.
Before treatment with Seromycin is
initiated, cultures should be taken and the organism’s susceptibility
to the drug should be established. In tuberculous infections, the organism’s
susceptibility to the other antituberculosis agents in the regimen should
also be demonstrated.
Anticonvulsant drugs or sedatives may be effective in controlling symptoms
of CNS toxicity, such as convulsions, anxiety, and tremor.
Patients receiving more than 500 mg of Seromycin daily
should be closely observed for such symptoms. The value of pyridoxine in preventing
CNS toxicity from Seromycin has
not been proved.
Administration of Seromycin and
other antituberculosis drugs has been associated in a few instances with vitamin B12 and/or
folic–acid deficiency, megaloblastic anemia, and sideroblastic anemia.
If evidence of anemia develops during treatment, appropriate studies and therapy
should be instituted.
Blood levels should be determined at least weekly for patients with
reduced renal function, for individuals receiving a daily dosage of more than
500 mg, and for those showing signs and symptoms suggestive
of toxicity. The dosage should be adjusted to keep the blood level below 30 μg/mL.
Concurrent administration of ethionamide has been reported to potentiate
neurotoxic side effects.
Alcohol and Seromycin are
incompatible, especially during a regimen calling for large doses of the latter.
Alcohol increases the possibility and risk of epileptic episodes.
Concurrent administration of isoniazid may result in increased incidence
of CNS effects, such as dizziness or drowsiness. Dosage adjustments
may be necessary and patients should be monitored closely for signs of CNS toxicity.
Mutagenicity, and Impairment of Fertility
Studies have not been performed to determine potential for carcinogenicity.
The Ames test and unscheduled DNA repair test were negative.
A study in 2 generations of rats showed no impairment of
fertility relative to controls for the first mating but somewhat lower fertility
in the second mating.
A study in 2 generations of rats given doses up to
100 mg/kg/day demonstrated no teratogenic effect in offspring.
It is not known whether Seromycin can
cause fetal harm when administered to a pregnant woman or can affect reproduction
capacity. Seromycin should
be given to a pregnant woman only if clearly needed.
Because of the potential for serious adverse reactions in nursing infants
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.
in Pediatric Patients
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:
system symptoms (which appear to be related to higher dosages of
the drug, i.e., more than 500 mg daily)
Drowsiness and somnolence
Confusion and disorientation with loss of memory
Psychoses, possibly with suicidal tendencies
Major and minor (localized) clonic seizures
Sudden development of congestive heart failure
in patients receiving 1 to 1.5 g of Seromycin daily
has been reported
not related to dosage)
Elevated serum transaminase, especially in patients with preexisting
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
oral median lethal dose in mice is 5290 mg/kg.
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 listed 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.
of cycloserine have
been reported rarely. The following is provided to serve as a guide should
such an overdose be encountered.
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.
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.
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.
DOSAGE AND ADMINISTRATION
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.
Seromycin® is available as a 250 mg capsule with an opaque red cap and opaque gray
body imprinted with “Lilly” and “F04”
in edible black ink on both the cap and the body.
Bottles of 40
(No.12) NDC 0002-0604-40
Store at controlled room temperature, 20° to 25°C
(68° to 77°F) [see USP].
Dye WE: Laboratory methods for clinical and public health —
mycobacteriology. US Department of Health, Education and
Welfare, Public Health Service, 1967, pp 47–55,
Colorimetric determination of cycloserine, a new antibiotic. Anal