Capreomycin

Capreomycin is an Antibiotic agent belonging to Aminoglycoside

Capreomycin is used in the treatment of Tuberculosis, pulmonary.

It is poorly absorbed from the GI tract and get excreted Via urine (approx 50%, as unchanged drug) by glomerular filtration w/in 12 hr.

The Tmax of Capreomycin was within 1-2 hour.

Capreomycin shows common side effects like swelling, rapid weight gain, little or no urinating, severe dizziness, spinning sensation, ringing or roaring

Capreomycin is available in the form of injection

Capreomycin is available in India, Germany, Canada, Italy.

Capreomycin is a cyclic polypeptide antimicrobial. It is administered as a mixture of capreomycin IA and capreomycin IB. The mechanism of action of capreomycin is not well understood. Mycobacterial species that have become resistant to other agents are usually still sensitive to the action of capreomycin. However, significant cross-resistance with viomycin, kanamycin, and neomycin occurs.

Capreomycin is available in the form of injection.

● IM: Administer by deep IM injection into a large muscle mass.

● IV: Administer over 60 minutes.

Capreomycin is used in the treatment of Tuberculosis, pulmonary.

Capreomycin is a cyclic polypeptide antimicrobial. It is bacteriostatic against various Mycobacteria, particularly those that have become resistant to primary anti-TB drugs.

Capreomycin is approved for use in the following clinical indications

Tuberculosis, pulmonary: Alternative agent for the treatment of pulmonary infections caused by capreomycin-susceptible strains of Mycobacterium tuberculosis, in combination with other appropriate antituberculosis agents, when other agents have been ineffective or cannot be used because of toxicity or the presence of resistant tubercle bacilli.

Capreomycin is available in various strengths as 1 g /vial.

Capreomycin is available in the form of injection.

● Dosage Adjustment for Pediatric Patients

Active tuberculosis infection; treatment multidrug resistant (MDR) (second-line therapy): Limited data available: Note: Always use as part of a multidrug regimen. Any regimens using less than once daily dosing should administer dosing as directly observed therapy (DOT). Treatment regimens for MDR TB are variable depending upon sensitivity and clinical response. Capreomycin frequency and dosing differs depending on treatment regimen selected; consult current drug-sensitive TB guidelines for detailed information

Primary pulmonary disease:

Once-daily therapy:

Infants, Children, and Adolescents <15 years, weighing ≤40 kg: Note: Suggested expert dosing range is large and variable : IM, IV: 15 to 30 mg/kg/dose once daily; some experts recommend an initial dose range of 15 to 20 mg/kg/dose once daily; maximum daily dose: 1,000 mg/day; monitor serum concentrations

Children and Adolescents <15 years weighing >40 kg or Adolescents ≥15 years: IM, IV: 15 mg/kg/dose once daily; maximum daily dose: 1,000 mg/day; monitor serum concentrations.

Three-times-weekly DOT: Children and Adolescents <15 years weighing >40 kg or Adolescents ≥15 years: IM, IV: 25 mg/kg/dose three times weekly; maximum dose: 1,000 mg/dose.

Twice-weekly DOT: Infants, Children, and Adolescents <15 years, weighing ≤40 kg: IM, IV: 25 to 30 mg/kg/dose twice weekly; maximum dose: 1,000 mg/dose

Meningitis (independent of HIV-status): Infants, Children, and Adolescents: Suggested expert dosing range is large and variable : IM, IV: 15 to 30 mg/kg/dose once daily; some experts recommend an initial range of 15 to 20 mg/kg/dose once daily; maximum daily dose: 1,000 mg/day; monitor serum concentrations

Hypersensitivity to Capreomycin and other aminoglycoside antibiotics. Myasthenia gravis. Concomitant or sequential administration of oral or topical drugs that are neurotoxic, ototoxic or nephrotoxic; concomitant use with potent diuretics.

Concerns related to adverse effects:

• Electrolyte imbalance: Hypocalcemia, hypokalemia, and hypomagnesemia have been reported with use. Monitor electrolytes periodically during treatment.

• Nephrotoxicity: May cause nephrotoxicity, including tubular necrosis, increased BUN or serum creatinine, and abnormal urinary sediment; slight elevations in BUN and serum creatinine with urinary RBCs, WBCs, and casts have been observed with prolonged treatment. Monitor renal function at baseline and periodically during treatment. A BUN >30 mg/dL or other evidence of decreasing renal function should prompt clinical evaluation and dosage adjustment or therapy discontinuation.

• Ototoxicity: May cause impairment of cranial nerve VIII, which may be irreversible; perform audiometric assessment and assessment of vestibular function prior to initiation and periodically during treatment.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Allergies: Use with caution in patients who demonstrate some form of allergy.

• Auditory impairment: [US Boxed Warning]: Use in patients with preexisting auditory impairment must be undertaken with great caution, and the risk of additional cranial nerve VIII impairment should be weighed against the benefits to be derived from therapy.

• Renal impairment: [US Boxed Warning]: Use in patients with renal impairment must be undertaken with great caution, and the risk of additional renal injury should be weighed against the benefits to be derived from therapy. Dosage reductions are recommended for known or suspected renal impairment.

Capreomycin may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

It is not known if capreomycin is present in breast milk.

Capreomycin is not significantly absorbed when administered orally, limiting any potential exposure via breast milk. The manufacturer recommends that caution be exercised when administering capreomycin to breastfeeding women. Patients with multidrug-resistant tuberculosis and a sputum smear-positive test should avoid breastfeeding when possible.

Immediate release: Food delays rate, but not extent of absorption; Extended release: Food increases Capreomycin AUC by ~30% relative to fasting conditions. Management: Administer immediate release products without regard to meals. Administer extended release products with food.

• Common Adverse effects

Ototoxicity; hypokalaemia, hypocalcaemia, hypomagnesaemia and an electrolyte disturbance resembling Bartter’s syndrome; leukocytosis, leucopenia, eosinophilia.

• Less Common Adverse effects:

hypersensitivity reactions (e.g. urticaria, photosensitivity, maculopapular rash) associated w/ fever; abnormal LFT results; partial neuromuscular blockade

• Rare Adverse effects

Pain, induration, excessive bleeding and sterile abscess on inj site.

Additive neurotoxic, ototoxic or nephrotoxic effects with amphotericin B, bacitracin, cisplatin, ciclosporin, cephaloridine, paromomycin, polymyxin B, colistin, tacrolimus, vancomycin, viomycin, IV mannitol, or other aminoglycosides. Increased risk of ototoxicity with potent diuretics (e.g. ethacrynic acid or furosemide); may increase risk of toxicity with IV diuretics. May increase risk of respiratory paralysis with anaesthetics or neuromuscular blocking agents (e.g. tubocurarine, succinylcholine, decamethonium, atracurium, rocuronium, vecuronium, opioid analgesic, massive transfusions with citrated anticoagulated blood). Increased risk of nephrotoxicity and may increase serum creatinine levels with cephalosporins. May reduce antibacterial activity with penicillins. Increased risk of hypocalcaemia with bisphosphonates. Increased risk of nephrotoxicity and ototoxicity with platinum drugs. May increase serum concentration with indomethacin in neonates.

The common side effects of Capreomycin include the following swelling, rapid weight gain, little or no urinating; · severe dizziness, spinning sensation, ringing or roaring

Symptoms: Hypokalaemia, hypocalcaemia, hypomagnesaemia and an electrolyte disturbance resembling Bartter’s syndrome; nephrotoxicity (e.g. acute tubular necrosis) and ototoxicity (e.g. dizziness, tinnitus, vertigo, loss of high-tone acuity).

Management: Symptomatic and supportive treatment. May administer activated charcoal to reduce absorption.

Pharmacodynamic

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).

Pharmacokinetics

• Absorption: Poorly absorbed from the GI tract. Time to peak plasma concentration: 1-2 hr (IM).
• Excretion: Via urine (approx 50%, as unchanged drug) by glomerular filtration w/in 12 hr.

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
• https://reference.medscape.com/drug/colestid-Capreomycin -342452
• https://go.drugbank.com/drugs/DB00375
• https://www.sciencedirect.com/topics/medicine-and-dentistry/Capreomycin
• https://europepmc.org/article/med/6988203