General: Before treatment with cycloserine
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 cycloserine daily should be closely observed
for such symptoms. The value of pyridoxine in
preventing CNS toxicity from cycloserine has
not been proved.
Administration of cycloserine and other
antituberculosis drugs has been associated in
a few instances with vitamin B 12 and/or folic-
acid deficiency, megaloblastic anemia, and
sideroblastic anemia. If evidence of anemia
develops during treatment, appropriate studies
and therapy should be instituted.
Laboratory Tests: 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 mcg/mL.
Drug Interactions: Concurrent administration
of ethionamide has been reported to potentiate
neurotoxic side effects.
Alcohol and cycloserine 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.
Carcinogenesis, 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.
Pregnancy Category C: There are no
adequate and well-controlled studies with
the use of Cycloserine in pregnant women.
A study in 2 generations of rats given doses
up to 100 mg/kg/day (approximately equivalent
to the maximum recommended human dose
on a body surface area basis) demonstrated
no teratogenic effect in offspring. Cycloserine
should be used during pregnancy only if the
potential benefit justifies the potential risk to the
fetus.
Nursing Mothers: Because of the potential
for serious adverse reactions in nursing infants
from cycloserine, 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.
Usage in Pediatric Patients: Safety and
effectiveness in pediatric patients have not been
established.
Geriatric Use: Clinical studies of cycloserine
did not include sufficient numbers of subjects
aged 65 and over to determine whether they
responded differently from younger subjects.
Other reported clinical experience has not
identified differences in responses between
the elderly and younger patients. In general,
dose selection for an elderly patient should be
cautious, usually starting at the low end of the
dosing range, reflecting the greater frequency
of decreased hepatic, renal, or cardiac function,
and of concomitant disease or other drug
therapy.
This drug is known to be substantially excreted
by the kidney, and the risk of toxic reactions
to this drug may be greater in patients with
impaired renal function. Because elderly
patients are more likely to have decreased renal
function, care should be taken in dose selection,
and it may be useful to monitor renal function.
The toxicity of cycloserine is closely related
to excessive blood levels (above 30 mcg/mL)
as determined by high dosage or inadequate
renal clearance (see WARNINGS). 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 mcg/mL (see PRECAUTIONS,
Laboratory Tests).
