Capreomycin is an injectable medicine used in the treatment of multidrug-resistant tuberculosis as a second line therapy. It is used in combination with other agents (like isoniazid, rifampin, ethambutol, and pyrazinamide) for the treatment of capreomycin-susceptible strains of Mycobacterium tuberculosis.

Capreomycin dose in Adults

Capreomycin use in the treatment of pulmonary Tuberculosis:

• 15 mg/kg Intramuscularly or intravenously once daily at a dose of up to 1 g for 5–7 days a week for 2–4 months, then 15 mg/kg twice or three times per week.

Capreomycin Dose in Children

Second-line medication for the treatment of active TB infections that are multidrug resistant (MDR).

Note: It should be added to a multidrug regimen. Consult experts prior to initiating therapy and follow relevant guidelines.

For the treatment of Primary pulmonary disease:

• Once a day therapy Infants, Children, and Adolescents less than 15 years and weighing 40 kgs or less:
  • 15 to 30 mg/kg/dose Intramuscular or intravenous once a day.
  • An initial dose range of 15 to 20 mg/kg/dose once a day to a maximum dose of 1,000 mg/day has been advised by some experts.
• Children and Adolescents less than 15 years weighing more than 40 kgs or Adolescents 15 years or more:
  • Daily administration:
    • 15 mg/kg/dose Intramuscular or intravenous once a day to a maximum dose of 1,000 mg/day. Serum concentration should be monitored.
  • Three-times weekly DOT therapy:
    • 25 mg/kg/dose Intramuscular or intravenous three times weekly to a maximum dose of 1,000 mg/dose.
  • Twice-weekly DOT:
    • • Infants, Children, and Adolescents less than 15 years and weighing 40 kgs or less:
        • 25 to 30 mg/kg/dose Intramuscular or intravenous twice a week to a maximum dose of 1,000 mg/dose.

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Meningitis caused by Mycobacterium Tuberculosis (independent of HIV-status):

• 15 to 30 mg/kg/dose Intramuscular or intravenous once a day.
• May use 15 to 20 mg/kg/dose once a day to a maximum daily dose of 1,000 mg/day.
• Monitor serum concentrations.

Pregnancy Risk Factor C

• [US Boxed Warn]: Safety for pregnant womenIt has not been established.
• Capreomycin should be avoided during pregnancy due to the possibility of congenital hearing loss and fetal nephrotoxicity.

Capreomycin use during breastfeeding:  

• Nursing mothers should use it with caution. It is not known if it will be excreted into breastmilk.

Capreomycin Dose in Renal Disease:

 Dose adjustment according to the Manufacturer's labeling (maximum dose: 1 g/dose):

• CrCl 110 mL/minute: 13.9 mg/kg one time a day
• CrCl 100 mL/minute: 12.7 mg/kg one time a day
• CrCl 80 mL/minute: 10.4 mg/kg one time a day
• CrCl 60 mL/minute: 8.2 mg/kg one time a day
• CrCl 50 mL/minute: 14 mg/kg every other day or 7 mg/kg once a day
• CrCl 40 mL/minute: 5.9 mg/kg or 11.7 mg/kg every other day, whichever comes first
• CrCl 30 mL/minute: 4.7 mg/kg once per day, 9.5 mg/kg each alternate day, or 14.2 mg/kg each subsequent day.
• CrCl 20 mL/minute: One dose of 3.6 mg/kg each day, two doses of 7.2 mg/kg, and three doses of 10.7 mg/kg.
• CrCl 10 mL/minute:  2.4 mg/kg once daily, 4.9 mg/kg twice daily, or 7.3 mg/kg three times each week.
• CrCl 0 mL/minute: Once daily at 1.3 mg/kg, twice daily at 2.6 mg/kg, and three times daily at 3.9 mg/kg.

Capreomycin Dose in Liver Disease:

The manufacturer has not recommended any dose adjustment in patients with liver disease.

Common Side Effects Of Capreomycin Include:

• Otic:
  • Ototoxicity
• 2.4 mg/kg once daily, 4.9 mg/kg twice daily, or 7.3 mg/kg three times each week.Genitourinary:
  • Nephrotoxicity

Less Common Side Effects Of Capreomycin Include:

• Hematologic:
  • Eosinophilia

Contraindication to capreomycin include:

• Allergy reactions to capreomycin and any other component of the formulation

Warnings & Precautions

• Electrolyte imbalance:
  • Hypocalcemia, hypokalemia and hypomagnesemia may occur.
  • During treatment, electrolytes should always be monitored.
• Nephrotoxicity:
  • Capreomycin can cause renaltoxicity. This includes tubular necrosis and elevated serum creatinine or BUN.
  • Before and during treatment, monitor your renal function.
  • If the patient experiences a rise in creatinine, BUN, or any other indication of reduced renal function, it is important to adjust or withhold therapy.
• Ototoxicity:
  • Capreomycin therapy may be used to treat vestibular dysfunction and ototoxicity that is irreversible due to impairment of the VIII cerebral nerve.
  • Therapy should include periodic audiometric assessments and vestibular function assessments.
• Superinfection
  • Capreomycin treatment for longer periods (over 2 months) can lead to superinfections, including fungal or bacterial superinfections. C. difficile-associated diarrhea, (CDAD), and pseudomembranous collitis can occur.
• Auditory impairment [US Boxed Warning]
  • Patients with an existing hearing impairment should be advised to take the drug with extreme caution.
• Renal impairment [US Boxed Warning]  
  • Preexisting renal dysfunction patients should be cautious when using it. Patients with kidney failure should adjust the dose.

Capreomycin: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Vestibular function and Audiometric measurements at baseline and periodically during therapy
• Renal function tests at baseline and once a week during therapy
• Serum electrolytes at baseline (including calcium, magnesium, and potassium) and periodically thereafter.
• Liver function tests at baseline and as needed during therapy.

How to administer capreomycin?

Intramuscular injection:

• Give a deep intramuscular injection into a sizable amount of muscle.
• If administered intravenously, it should be slowly infused over one hour. 

Mechanism of action of capreomycin:

• Capreomycin, a cyclic polypeptide antibiotic that can be used to treat mycobacterial infections that are sensitive to capreomycin, is known as Capreomycin. 
• Its mechanism of action remains a mystery. Cross-resistance is a significant problem with viomycin and kanamycin as well as neomycin.

It isn'tabsorbedWhen taken orally. 

When taken via the oral route. half-life eliminationPatients with normal renal function will take between 5 and 6 hours. Half-life elimination for patients with CrCl 50-80 mL/minute is 7-10 hours. For CrCl 20-40 mL/minute or less, it's 29 hours. After an event, it takes between 1 and 2 hours.IntramuscularInjection to reach thepeak serum concentration. 52 % of the drug can be excreted unchanged by urine.

International brands of Capreomycin:

• Capacin
• Capastat
• Kapocin

Capreomycin Brands in pakistan:

No brands available in the market in Pakistan. May be available in WHO specialized centres for the treatment of MDR TB.