KAPOCIN 1 G

Indications

• Multiple-drug resistant pulmonary tuberculosis
• Tuberculosis resistant to first-line drugs

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidance.

Adults: Initially 1 g daily (maximum per dose 20 mg/kg) for 2-4 months, then reduced to 1 g 2-3 times a week.

Mechanism of action

Capreomycin is thought to inhibit protein synthesis by binding to the 70S ribosomal unit in bacteria, causing the production of abnormal proteins. This binding disrupts essential bacterial functions, ultimately resulting in bacterial cell death. Recent studies suggest that capreomycin also affects various cellular processes, including metabolism and respiration in Mycobacterium tuberculosis, enhancing its bactericidal activity against both replicating and non-replicating TB bacilli.

Pharmacodynamics

As a member of the aminoglycoside family, capreomycin exhibits broad-spectrum bactericidal activity, particularly against Mycobacterium tuberculosis. Its effectiveness is associated with its ability to irreversibly bind to ribosomal subunits, disrupting protein synthesis and leading to bacterial cell death. Capreomycin demonstrates unique activity against non-replicating TB bacilli, indicating its potential as a critical component in treating resistant TB strains.

Pharmacokinetics

Capreomycin is administered via deep intramuscular injection and is primarily excreted through renal pathways. It has a half-life that varies based on renal function, necessitating caution in patients with impaired renal function. Monitoring of renal function and electrolytes is recommended during treatment. The pharmacokinetic profile indicates that dosing adjustments may be necessary for individuals with varying degrees of renal impairment.

Contra-indications

• QTc interval more than 500 milliseconds (derived using Fridericia’s formula)
• ventricular arrhythmia

Adverse effects

• arthralgia
• diarrhoea
• dizziness
• headache
• myalgia
• nausea
• QT interval prolongation
• vomiting

Interactions

• Bedaquiline

Precautions

• Auditory impairment
• Caution in renal impairment (risk of nephrotoxicity and ototoxicity)
• Caution in hepatic impairment (avoid in severe impairment)
• Monitor renal, hepatic, auditory, and vestibular function and electrolytes

Pregnancy

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

Breast-feeding

Manufacturer advises caution-no information available.

Storage

Store in a cool, dry place away from light.

Formulations

• Gastro-resistant granules
• Deep intramuscular injection

Mechanism of action

Little is known about capreomycin's exact mechanism of action, but it is thought to inhibit protein synthesis by binding to the 70S ribosomal unit. Capreomycin also binds to components in the bacterial cell which result in the production of abnormal proteins. These proteins are necessary for the bacteria's survival. Therefore the production of these abnormal proteins is ultimately fatal to the bacteria. Aminoglycosides are usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/ Capreomycin is an important drug used for TB with multi-drug resistance. A recent study also indicates that this drug possesses unique bactericidal activity against non-replicating TB bacilli among known anti-TB drugs. Thus, there is an urgent need for investigating the full-spectrum action of capreomycin. Here /investigators/ conduct the first microarray-based study on capreomycin using the high-resolution Affymetrix oligonucleotide GeneChip system. The results indicate that capreomycin primarily acts on the information pathways but it also significantly affects cell wall, cell processes, intermediate metabolism and respiration in Mycobacterium tuberculosis. This study not only transcriptionally validates the specific molecular target, 16S rRNA, but also discovers potential new targets of capreomycin, including genes operating at the DNA level, such as Rv0054 (ssb) and Rv3715c (recR), as well as genes involved in cell division like Rv3260c (whiB2). In addition, the nuo gene cluster and the ATP synthase gene cluster are repressed.

Pharmacodynamics

Capreomycin is a member of the aminoglycoside family of antibiotics. These antibiotics have the ability to kill a wide variety of bacteria, including bacteria responsible for causing tuberculosis (TB).