Capastat

Administration

Administer by IV infusion or deep IM injection.102

IV Administration

Reconstitute 1-g vial by adding 2 mL of 0.9% sodium chloride injection or sterile water for injection.102 Alternatively, reconstitute 1-g vial with 2.15, 2.63, 3.3, or 4.3 mL of 0.9% sodium chloride injection or sterile water for injection to provide solutions containing approximately 370, 315, 260, or 210 mg/mL, respectively, taking into account the retention volume.102 Allow 2–3 minutes for complete dissolution.102

For IV infusion, reconstituted solution must be further diluted with 100 mL of 0.9% sodium chloride injection.102

Administer by IV infusion over 60 minutes.102

IM Administration

Administer by deep IM injection into a large muscle mass.102

Avoid superficial IM injections since they may be associated with increased pain and development of sterile abscesses.102

Reconstitute 1-g vial by adding 2 mL of 0.9% sodium chloride injection or sterile water for injection.102 Alternatively, reconstitute 1-g vial with 2.15, 2.63, 3.3, or 4.3 mL of 0.9% sodium chloride injection or sterile water for injection to provide solutions containing approximately 370, 315, 260, or 210 mg/mL, respectively, taking into account the retention volume.102 Allow 2–3 minutes for complete dissolution.102

Dosage

Available as capreomycin sulfate; dosage expressed in terms of capreomycin.102

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

Can be used in daily or intermittent (2 times weekly) multiple-drug TB regimens.100

Pediatric Patients

Children <15 years of age or weighing ≤40 kg†: 15–30 mg/kg daily (up to 1 g) 100 101 given once daily or twice weekly100 recommended by ATS, CDC, IDSA, and AAP.

Children ≥15 years of age†: 15 mg/kg daily (up to 1 g) given as a single daily dose 5–7 times weekly for the first 2–4 months or until culture conversion recommended by ATS, CDC, and IDSA; dosage can then be reduced to 15 mg/kg daily (up to 1 g) given 2 or 3 times weekly, depending on efficacy of the other drugs in the regimen.100

Adults

15 mg/kg daily (up to 1 g) given as a single daily dose 5–7 times weekly for the first 2–4 months or until culture conversion recommended by ATS, CDC, and IDSA; dosage can then be reduced to 15 mg/kg daily (up to 1 g) given 2 or 3 times weekly, depending on efficacy of the other drugs in the regimen.100

Manufacturer recommends 1 g (up to 20 mg/kg) daily for 60–120 days, followed by 1 g 2–3 times weekly.102

Prescribing Limits

Pediatric Patients

Maximum 1 g per dose in once-daily or 2- or 3-times weekly regimens.100 101

Adults

Maximum 1 g per dose in once-daily or 2- or 3-times weekly regimens.100 102

Adults >59 years of age: Maximum 750 mg per dose in once-daily or 2- or 3-times weekly regimens.100

Special Populations

Renal Impairment

Reduce dosage based on the degree of renal impairment.100 102 Use with caution and monitor serum capreomycin concentrations.100 102 (See Ototoxicity and Nephrotoxicity under Cautions.)

Manufacturer recommends that dosage in adults with renal impairment be based on Clcr and adjusted to maintain mean steady-state serum capreomycin concentrations of 10 mcg/mL.102 Consult manufacturer's literature for specific dosage recommendations for these patients.102

Some experts suggest a reduced dosage of 12–15 mg/kg given 2 or 3 times weekly.100

Doses in patients undergoing hemodialysis should be given after dialysis since the drug is removed by this procedure.100

Geriatric Patients

Manufacturer states no dosage adjustments except those related to renal impairment.102 Select dosage with caution (usually starting at low end of dosage range).102 (See Geriatric Use under Cautions.)

Adults >59 years of age: ATS, CDC, and IDSA recommend 10 mg/kg (up to 750 mg) per dose.100 (See Geriatric Use under Cautions.)

Storage

Parenteral

15–30°C.102

Following reconstitution with 0.9% sodium chloride injection or sterile water for injection, solutions may be stored for up to 24 hours in a refrigerator.102 Capreomycin solutions may develop a pale straw color and darken with time; this is not associated with loss of potency or development of toxicity.102

• 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 discontinuing therapy and informing clinicians if an allergic reaction occurs.102

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

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

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

The use of Capastat® Sulfate (Capreomycin for Injection, USP) in patients with renal insufficiency or preexisting auditory impairment must be undertaken with great caution, and the risk of additional cranial nerve VIII impairment or renal injury should be weighed against the benefits to be derived from therapy.

Refer to ANIMAL PHARMACOLOGY for additional information.

Since other parenteral antituberculosis agents (streptomycin, viomycin) also have similar and sometimes irreversible toxic effects, particularly on cranial nerve VIII and renal function, simultaneous administration of these agents with Capastat Sulfate is not recommended. Use with nonantituberculosis drugs (polymyxin A sulfate, colistin sulfate, amikacin, gentamicin, tobramycin, vancomycin, kanamycin, and neomycin) having ototoxic or nephrotoxic potential should be undertaken only with great caution.

Usage in Pregnancy: The safety of the use of Capastat Sulfate in pregnancy has not been determined.

Pediatric Usage: Safety and effectiveness in pediatric patients have not been established.

Capastat Sulfate is a polypeptide antibiotic isolated from Streptomyces capreolus. It is a complex of 4 microbiologically active components which have been characterized in part; however, complete structural determination of all the components has not been established.

Capreomycin is supplied as the disulfate salt and is soluble in water. In complete solution, it is almost colorless.

Each vial contains the equivalent of 1 g capreomycin activity.

The structural formula is as follows:

Nephrotoxicity: In 36% of 722 patients treated with Capastat Sulfate, elevation of the BUN above 20 mg/100 mL has been observed. In many instances, there was also depression of PSP excretion and abnormal urine sediment. In 10% of this series, the BUN elevation exceeded 30 mg/100 mL.

Toxic nephritis was reported in 1 patient with tuberculosis and portal cirrhosis who was treated with Capastat Sulfate (1 g) and aminosalicylic acid daily for 1 month. This patient developed renal insufficiency and oliguria and died. Autopsy showed subsiding acute tubular necrosis.

Electrolyte disturbances including hypokalemia, hypomagnesemia and hypocalcemia, sometimes serious in nature, have been reported.

Ototoxicity: Subclinical auditory loss was noted in approximately 11% of 722 patients undergoing treatment with Capastat Sulfate. This was a 5– to 10–decibel loss in the 4000– to 8000–CPS range. Clinically apparent hearing loss occurred in 3% of the 722 subjects. Some audiometric changes were reversible. Other cases with permanent loss were not progressive following withdrawal of Capastat Sulfate.

Tinnitus and vertigo have occurred.

Liver: Serial tests of liver function have demonstrated a decrease in BSP excretion without change in AST (SGOT) or ALT (SGPT) in the presence of preexisting liver disease. Abnormal results in liver function tests have occurred in many persons receiving Capastat Sulfate in combination with other antituberculosis agents that also are known to cause changes in hepatic function. The role of Capastat Sulfate in producing these abnormalities is not clear; however, periodic determinations of liver function are recommended.

Blood: Leukocytosis and leukopenia have been observed. The majority of patients treated have had eosinophilia exceeding 5% while receiving daily injections of Capastat Sulfate. This has subsided with reduction of the Capastat Sulfate dosage to 2 or 3 g weekly.

Pain and induration at the injection site have been observed. Excessive bleeding at the injection site has been reported. Sterile abscesses have been noted. Rare cases of thrombocytopenia have been reported.

Hypersensitivity: Urticaria and maculopapular skin rashes associated in some cases with febrile reactions have been reported when Capastat Sulfate and other antituberculosis drugs were given concomitantly.

Capastat® Sulfate, Capreomycin for Injection, USP, is available in:

Vials: 1 g1, 10 mL size (No. 718) (1s) NDC 0002-1485-01

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Store at controlled room temperature 15° to 30°C (59° to 86°F) prior to reconstitution.

In addition to renal and cranial nerve VIII toxicity demonstrated in animal toxicology studies, cataracts developed in 2 dogs on doses of 62 mg/kg and 100 mg/kg for prolonged periods.

In teratology studies, a low incidence of “wavy ribs” was noted in litters of female rats treated with daily doses of 50 mg/kg or more of capreomycin.

Applies to capreomycin: intramuscular powder for injection

Renal

Renal side effects have included dose-related nephrotoxicity, including BUN elevations (greater than 20 mg/dL) (36%), BUN elevations (greater than 30 mg/dL) (10%), depression of PSP excretion, abnormal urine sediment, renal insufficiency, and oliguria. At least one case of toxic nephritis and acute tubular necrosis has been reported.[Ref]

A patient with tuberculosis and portal cirrhosis experienced toxic nephritis and acute tubular necrosis coincident with capreomycin therapy. The patient was treated with capreomycin therapy (1 g) and aminosalicylic acid daily for 1 month. The patient developed renal insufficiency and oliguria and died. The autopsy showed subsiding acute tubular necrosis.[Ref]

Nervous system

Nervous system side effects have included ototoxicity and vestibular toxicity including subclinical auditory loss (11%), clinically apparent hearing loss (3%), vertigo, and tinnitus.[Ref]

Local

Local side effects have included pain, induration, and excessive bleeding at the injection site.[Ref]

Hematologic

Hematologic side effects have included leukocytosis, leukopenia, and eosinophilia. Thrombocytopenia has also been reported rarely.[Ref]

Hepatic

Hepatic side effects have included decreased BSP excretion.[Ref]

Metabolic

Metabolic side effects including hypokalemia, hypocalcemia, hypomagnesemia, and electrolyte disturbances resembling Bartter's syndrome have been reported.[Ref]

Some side effects of Capastat may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.