CYCLOSERINE 250MG CAPSULE

Indications

• Tuberculosis resistant to first-line drugs
• Multidrug-resistant pulmonary tuberculosis

Dosage

Children: For children aged 12-17 years: Initially 250 mg every 12 hours for 2 weeks, then adjusted according to blood concentration and response. For children under 12 years, consult BNF for Children for specific dosing guidance.

Adults: Initially 250 mg every 12 hours for 2 weeks, then increased if necessary up to 500 mg every 12 hours, based on blood concentration and response.

Mechanism of action

Cycloserine is an analog of the amino acid D-alanine. It inhibits bacterial cell wall synthesis by competitively inhibiting two enzymes: L-alanine racemase, which converts L-alanine to D-alanine, and D-alanylalanine synthetase, which incorporates D-alanine into the pentapeptide necessary for peptidoglycan formation. This action weakens the bacterial cell wall, leading to cell death.

Pharmacodynamics

Cycloserine may exhibit either bactericidal or bacteriostatic effects, depending on its concentration at the infection site and the susceptibility of the bacteria. It inhibits the formation of peptidoglycans, essential components of the bacterial cell wall, and therefore compromises bacterial integrity, leading to cell lysis and death.

Pharmacokinetics

Cycloserine is well absorbed from the gastrointestinal tract. It penetrates the central nervous system (CNS) effectively. The drug is metabolized in the liver and excreted primarily through the kidneys. Dose adjustments may be necessary in renal impairment. Serum levels should be monitored to ensure efficacy and minimize toxicity, particularly when used in conjunction with other drugs that may prolong the QT interval.

Contra-indications

• Optic neuritis
• Poor vision
• QTc interval more than 500 milliseconds (derived using Fridericia’s formula)
• Ventricular arrhythmia

Adverse effects

• Dizziness
• Headache
• Nausea
• Vomiting
• Diarrhoea
• Myalgia
• Arthralgia
• Hepatic function abnormal
• QT interval prolongation

Interactions

• Cycloserine + isoniazid: Moderate (increases risk of CNS toxicity)
• Other drugs known to prolong the QT interval

Precautions

• Caution in renal impairment, especially if creatinine clearance is less than 30 mL/min
• Caution in hepatic impairment, particularly in moderate to severe cases
• Auditory impairment monitoring required
• Monitor serum potassium, calcium, and magnesium
• Obtain ECG before starting treatment and monitor monthly

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk; teratogenic in animal studies.

Breast-feeding

Manufacturer advises caution; no information available regarding excretion in human milk.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• 250 mg tablets
• 500 mg tablets

Mechanism of action

Cycloserine is an analog of the amino acid D-alanine. It interferes with an early step in bacterial cell wall synthesis in the cytoplasm by competitive inhibition of two enzymes, L-alanine racemase, which forms D-alanine from L-alanine, and D-alanylalanine synthetase, which incorporates D-alanine into the pentapeptide necessary for peptidoglycan formation and bacterial cell wall synthesis. EXCRETION OF B-ALANINE & D-BETA-AMINOISOBUTYRIC ACID WAS INCR IN PT WITH TUBERCULOSIS RECEIVING CLINICAL DOSES OF D-CYCLOSERINE. Cycloserine is inhibitory for Mycobacterium tuberculosis in concentrations of 5 to 20 ug/ml in vitro. There is no cross-resistance between cycloserine and other tuberculostatic agents. While the antibiotic is effective in experimental infections caused by other microorganisms, studies in vitro reveal no suppression of growth in cultures made in conventional media, which contain D-alanine; this amino acid blocks the antibacterial activity of cycloserine. ... Cycloserine inhibits reactions in which D-alanine is involved in bacterial cell-wall synthesis. The use of media free of D-alanine reveals that the antibiotic inhibits the growth in vitro of enterococci, E. coli, Staph. aureus, Nocardia species, and Chlamydia.

Pharmacodynamics

Cycloserine, a broad-spectrum antibiotic, may be bactericidal or bacteriostatic, depending on its concentration at the site of infection and the susceptibility of the organism. Cycloserine works by blocking the formation of these peptidoglycans. By doing this the walls of the bacteria become weak and it results in the death of the bacteria