Cycloserine

Take the missed dose as soon as you remember. However, if it is almost time for your next regularly scheduled dose, skip the missed dose and take the next one as directed. Do not take a double dose of this medication.

Avoid alcohol while taking cycloserine. Alcohol will increase your risk of having a seizure during treatment with this medication. Also, alcohol will increase dizziness and drowsiness.

Use caution when driving, operating machinery, or performing other hazardous activities. Cycloserine may cause dizziness or drowsiness. If you experience dizziness or drowsiness, avoid these activities.

Administration

Oral Administration

Administer orally.102

Dosage

Should not be used alone for treatment of active (clinical) TB; must be given in conjunction with other antituberculosis agents.100 101 102

Data not available to date to support use of cycloserine in intermittent (e.g., 1-3 times weekly) multiple-drug TB regimens.100

Pediatric Patients

Children <15 years of age or weighing ≤40 kg†: 10–20 mg/kg daily (up to 1 g daily) given in 2 divided doses recommended by ATS, CDC, IDSA, and AAP.100 101

Children ≥15 years of age†: 10–15 mg/kg daily (up to 1 g daily) given in 2 divided doses recommended by ATS, CDC, and IDSA.100 Usual dosage is 500–750 mg daily given in 2 divided doses; toxicity is more common with dosages >500 mg daily.100 These experts suggest optimum dosage usually can be determined by maintaining peak cycloserine serum concentrations at 20–35 mcg/mL.100

Adults

10–15 mg/kg daily (up to 1 g daily) given in 2 divided doses recommended by ATS, CDC, and IDSA.100 Usual dosage is 500–750 mg daily given in 2 divided doses; toxicity is more common with dosages >500 mg daily.100 These experts suggest optimum dosage usually can be determined by maintaining peak cycloserine serum concentrations at 20–35 mcg/mL.100

Manufacturer states usual initial dosage is 250 mg every 12 hours for the first 2 weeks.102 Usual dosage is 0.5–1 g daily given in divided doses with serum concentration monitoring.102 Manufacturer recommends dosage be adjusted to maintain serum concentrations <30 mcg/mL.102

250 mg every 12 hours for 2 weeks.a

Prescribing Limits

Pediatric Patients

Maximum 1 g daily.100 101

Adults

Maximum 1 g daily.100 102

Special Populations

Renal Impairment

Contraindicated in severe renal insufficiency.102 In other patients, adjust dosage according to degree of renal impairment and monitor serum cycloserine concentrations.100 103 Maintain serum cycloserine concentrations <30 mcg/mL.102 (See Renal Impairment under Cautions.)

ATS, CDC, and IDSA state the drug should not be used in patients with Clcr <50 mL/minute unless they are undergoing hemodialysis.100 For those being treated for TB who are undergoing hemodialysis, these experts suggest a dosage of 500 mg 3 times weekly or 250 mg once daily (with close monitoring of serum cycloserine concentrations).100

Contraindications

• Hypersensitivity to cycloserine.102

• History of epilepsy, depression, severe anxiety, or psychosis.102

• Severe renal insufficiency.102 (See Renal Impairment under Cautions.)

• Excessive concurrent use of alcohol.102 (See CNS Effects under Cautions.)

Warnings/Precautions

Warnings

CNS effects are the most frequent adverse effects.a Drowsiness, somnolence, dizziness, headache, lethargy, depression, tremor, dysarthria, hyperreflexia, paresthesia, nervousness, anxiety, vertigo, confusion and disorientation (with loss of memory), paresis, major and minor clonic seizures, seizures, and coma have been reported.a Psychosis (possibly with suicidal tendencies), personality changes, hyperirritability, and aggression have also occurred.a

Increased risk of seizures in chronic alcoholics.102 (See Interactions.)

Adverse CNS effects appear to be dose related and occur within the first 2 weeks of therapy in about 30% of those receiving 500 mg daily.a Determine plasma concentrations at least once weekly in patients receiving >500 mg daily, in patients with reduced renal function, and in those with signs or symptoms of toxicity.a Adverse nervous system effects are minimized when plasma cycloserine concentrations are <30 mcg/mL.103 a

Some experts recommend that neuropsychiatric status be assessed at least once monthly and more frequently if symptoms develop.100 Patients with renal impairment should be closely monitored for evidence of neurotoxicity.100

If symptoms of CNS toxicity (e.g., seizures, psychosis, somnolence, depression, confusion, hyperreflexia, headache, tremor, vertigo, paresis, dysarthria) occur, reduce dosage or discontinue cycloserine.102 Symptoms generally disappear when the drug is discontinued.a

Sedatives may be effective in controlling anxiety or tremor; anticonvulsants may control seizures.102 a (See Interactions.)

Value of pyridoxine in preventing cycloserine-associated CNS toxicity has not been proven.102 Neurotoxic effects may be relieved or prevented by concomitant administration of pyridoxine hydrochloride (100–300 mg daily).100 102

Sensitivity Reactions

Rash and allergic reactions reported.102 Photosensitivity has occurred.a

If allergic dermatitis occurs, reduce dosage or discontinue cycloserine.102

General Precautions

Should not be used alone for treatment of active (clinical) TB; must be given in conjunction with other antituberculosis agents.100 101 102

Clinical specimens for microscopic examination and mycobacterial cultures and in vitro susceptibility testing should be obtained prior to initiation of antituberculosis therapy and periodically during treatment to monitor therapeutic response.100 102 The antituberculosis regimen should be modified as needed.100 Patients with positive cultures after 4 months of treatment should be considered to have failed treatment (usually as the result of noncompliance or drug-resistant TB).100 Cycloserine in vitro susceptibility testing may be technically difficult.100

If cycloserine is added as a new drug to a regimen in patients experiencing treatment failure who have proven or suspected drug-resistant TB, at least 2 (preferably 3) new drugs known or expected to be active against the resistant strain should be added at the same time.100

Compliance with the full course of antituberculosis therapy and all drugs included in the multiple-drug regimen is critical.100 Missed doses increase the risk of treatment failure and increase the risk that M. tuberculosis will develop resistance to the antituberculosis regimen.100

To ensure compliance, ATS, CDC, IDSA, and AAP recommend that directly observed (supervised) therapy (DOT) be used for treatment of active TB whenever possible, especially when intermittent regimens are used, when the patient is immunocompromised or infected with HIV, or when drug-resistant M. tuberculosis is involved.100 101

Vitamin B12 and/or folic acid deficiency, megaloblastic anemia, and sideroblastic anemia have been reported in patients receiving cycloserine in conjunction with other antituberculosis agents.102

If anemia occurs, initiate appropriate studies and therapy.102

Monitor renal, hepatic, and hematologic function.102

Monitor cycloserine concentrations; measure concentrations at least once weekly in those with reduced renal function, in those receiving >500 mg daily, and in those showing signs and symptoms that suggest toxicity.102 Adjust dosage to maintain serum concentrations <30 mcg/mL.102

Specific Populations

Category C.102

Because cycloserine crosses the placenta and data are limited regarding safety of the drug in pregnant women, ATS, CDC, and IDSA state the drug should be used for treatment of TB during pregnancy only when there are no suitable alternatives.100

Distributed into milk.102 Discontinue nursing or the drug.102

Safety and efficacy not established in children.102

ATS, CDC, IDSA, and AAP consider cycloserine one of several second-line antituberculosis agents that can be used in children†.100 101

Caution in patients with alcohol-related hepatitis.100 (See Interactions.)

Use caution in patients with renal impairment;100 103 contraindicated in those with severe renal insufficiency.102

Symptoms of acute toxicity may occur if usual dosage is used in patients with renal impairment.a Adjust dosage according to the degree of renal impairment and serum cycloserine concentrations.100 102 103 Closely monitor patients with renal impairment for evidence of neurotoxicity.100

Determine serum cycloserine concentrations at least once weekly in patients with reduced renal function; adjust dosage to maintain concentrations <30 mcg/mL.102 (See CNS Effects under Cautions.)

Common Adverse Effects

CNS effects (seizures, drowsiness, somnolence, dizziness, headache, tremor, dysarthria, hyperreflexia, paresthesia, nervousness, anxiety, vertigo, confusion, disorientation with loss of memory, paresis, coma); hypersensitivity reactions.102 a

• Advise patients that poor compliance with antituberculosis regimens can result in treatment failure and development of drug-resistant TB, which can be life-threatening and lead to other serious health risks.100

• Importance of avoiding excessive concurrent use of alcohol.102

• Importance of notifying clinicians if allergic dermatitis or symptoms of CNS toxicity (seizures, psychosis, somnolence, depression, confusion, hyperreflexia, headache, tremor, vertigo, paresis, dysarthria) occur.102

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.102

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.102

• Importance of informing patients of other important precautionary information.102 (See Cautions.)

Cycloserine belongs to the family of medicines called antibiotics. It is used to treat tuberculosis (TB). When cycloserine is used for TB, it is given with other medicines for TB. Cycloserine may also be used for other conditions as determined by your doctor.

To help clear up your tuberculosis (TB) completely, you must keep taking cycloserine for the full time of treatment, even if you begin to feel better. This is very important. It is also important that you do not miss any doses.

Cycloserine is available only with your doctor's prescription.

It is very important that your doctor check your progress at regular visits.

If your symptoms do not improve within 2 to 3 weeks, or if they become worse, check with your doctor.

If cycloserine causes you to feel very depressed or to have thoughts of suicide, check with your doctor immediately. Your doctor will probably want to change your medicine.

cycloserine may cause some people to become dizzy, drowsy, or less alert than they are normally. Make sure you know how you react to cycloserine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or are not alert. If these reactions are especially bothersome, check with your doctor.

Some of cycloserine's side effects (for example, convulsions [seizures]) may be more likely to occur if you drink alcoholic beverages regularly while you are taking cycloserine. Therefore, you should not drink alcoholic beverages while you are taking cycloserine.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Anxiety
• confusion
• dizziness
• drowsiness
• increased irritability
• increased restlessness
• mental depression
• muscle twitching or trembling
• nervousness
• nightmares
• other mood or mental changes
• speech problems
• thoughts of suicide

• Convulsions (seizures)
• numbness, tingling, burning pain, or weakness in the hands or feet
• skin rash

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Headache

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Tuberculosis: Treatment of active pulmonary or extrapulmonary tuberculosis, in combination with other agents, when treatment with primary tuberculosis therapy has proved inadequate

Urinary tract infections: May be effective in treatment of acute urinary tract infections caused by susceptible strains of gram-positive and gram-negative bacteria, especially Enterobacter spp. and Escherichia coli. Note: Should be considered only when more conventional therapy has failed and when the organism has been demonstrated to be susceptible to the drug.

Refer to adult dosing.

Alcohol (Ethyl): May enhance the neurotoxic effect of CycloSERINE. Specifically, the risk for seizures may be increased. Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

Ethionamide: May enhance the adverse/toxic effect of CycloSERINE. Monitor therapy

Isoniazid: May enhance the adverse/toxic effect of CycloSERINE. Specifically, CNS toxicity may be enhanced. Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Prothionamide: May enhance the adverse/toxic effect of CycloSERINE. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect 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. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

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 C 3 H 6 N 2 O 2 . The structural formula of cycloserine is as follows:

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