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DESCRIPCION Capastat Sulfate (capreomycin for injection) 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 sulfate is a parenteral antituberculosis agent. It is used as an adjunct agent in combination with at least one other antituberculosis agent and also in the treatment of other mycobacterial disease s. Capreomycin sulfate's mechanism of action is unknown, but it displays bacteriostatic activity. This agent usually is reserved as a last-line agent secondary to route of administration and side effect profile. Capreomycin is not absorbed in significant quantities from the gastrointestinal tract and must be administered parenterally. In 2 studies of 10 patients each, peak serum concentrations following 1 g of capreomycin given intramuscularly were achieved 1 to 2 hours after administration, and average peak levels reached were 28 and 32 µg/mL respectively (range, 20 to 47 µg/mL). Low serum concentrations were present at 24 hours. However, 1 g of capreomycin daily for 30 days or more produced no significant accumulation in subjects with normal renal function. Two patients with marked reduction of renal function had high serum concentrations 24 hours after administration of the drug. When a 1-g dose of capreomycin was given intramuscularly to normal volunteers, 52% was excreted in the urine within 12 hours. Lehmann, et al, examined the pharmacokinetics of single dose capreomycin (1.0 g) administered intramuscularly and by intravenous infusion (1 hour) in 6 healthy volunteers. The area under the serum concentration versus time curve was similar for the two routes of administration. Capreomycin peak concentrations after intravenous infusion were 30 ± 47% higher than after intramuscular administration.1,2 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. |
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Intravenously - For intravenous infusion, reconstituted Capastat Sulfate should be diluted in 100 mL of 0.9% Sodium Chloride Injection and administered over 60 minutes. Intramuscularly - Reconstituted Capastat Sulfate (capreomycin for injection) should be given by deep intramuscular injection into a large muscle mass, since superficial injection may be associated with increased pain and the development of sterile abscesses. Capastat Sulfate (capreomycin for injection) , which is to be used concomitantly with other appropriate antituberculosis agents, is indicated in pulmonary infections caused by capreomycin-susceptible strains of M. tuberculosis when the primary agents (isoniazid, rifampin, ethambutol, aminosalicylic acid, and streptomycin) have been ineffective or cannot be used because of toxicity or the presence of resistant tubercle bacilli. Susceptibility studies should be performed to determine the presence of a capreomycinsusceptible strain of M. tuberculosis.
Dosage: 1 g IM daily (not to exceed 20 mg/kg/day) for 60�120 days, followed by 1 g IM two to three times per week for 18�24 months. Patients with renal impairment: Dosage adjustment depending on the degree of renal impairment should be made to maintain a serum capreomycin concentration of 10 �g/ml. CrCl > 50 ml/min: no dosage adjustment needed. CrCl 25�50 ml/min: reduce recommended dose by 50%. CrCl 10�24 ml/min: reduce recommended dose by 50% and extend interval to every 48 hours. CrCl <= 10 ml/min: reduce recommended dose by 50% and administer twice per week.
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Contraindications/Precautions: Renal impairment, auditory impairment. Capastat Sulfate (capreomycin for injection) is contraindicated in patients who are hypersensitive to capreomycin. |
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Usage in Pregnancy - Pregnancy Category C Capastat Sulfate (capreomycin for injection) has been shown to be teratogenic in rats when given in doses 3 1/2 times the human dose. There are no adequate and well-controlled studies in pregnant women. Capastat Sulfate (capreomycin for injection) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus (see Boxed Warnings and Animal Pharmacology). Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Capastat Sulfate (capreomycin for injection) is administered to a nursing woman. |
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Nephrotoxic and ototoxic agents: Can have additive effects. | ||
dverse Reactions: Nephrotoxicity: In 36% of 722 patients treated with Capastat Sulfate (capreomycin for injection) , 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 (capreomycin for injection) (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 (capreomycin for injection) . 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 (capreomycin for injection) . 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 (capreomycin for injection) in combination with other antituberculosis agents that also are known to cause changes in hepatic function. The role of Capastat Sulfate (capreomycin for injection) 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 (capreomycin for injection) . 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 (capreomycin for injection) and other antituberculosis drugs were given concomitantly. Nephrotoxicity: tubular necrosis, azotemia, increases nonprotein nitrogen, decreased creatinine clearance, proteinuria, urinary sediments. Ototoxicity: auditory and vestibular portions of the eighth cranial nerve. Pain, induration, excessive bleeding, sterile abscesses at the injection site, leukocytosis, leukopenia, eosinophilia, thrombocytopenia, hypersensitivity reactions, abnormal liver function, hypokalemia. |
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Nephrotoxicity following the parenteral administration of
Capastat Sulfate (capreomycin for injection) is most closely related to
the area under the curve of the serum concentration versus time graph. The
elderly patient, patients with abnormal renal function or dehydration, and
patients receiving other nephrotoxic drugs are at much greater risk for
developing acute tubular necrosis.
Damage to the auditory and vestibular divisions of cranial nerve VIII has been associated with Capastat Sulfate (capreomycin for injection) given to patients with abnormal renal function or dehydration and in those receiving medications with additive auditory toxicities. These patients often experience dizziness, tinnitus, vertigo, and a loss of high-tone acuity. Neuromuscular blockage or respiratory paralysis may occur following rapid intravenous infusion. If capreomycin is ingested, toxicity would be unlikely because it is poorly absorbed (less than 1%) from an intact gastrointestinal system. Hypokalemia, hypocalcemia, hypomagnesemia, and an electrolyte disturbance resembling Bartter's syndrome have been reported The subcutaneous median lethal dose in mice was 514 mg/kg. Treatment To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians' Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient. Protect the patient's airway and maintain, within acceptable limits, the patient's Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal. Patients who have received an overdose of capreomycin and have normal renal function should be carefully hydrated to maintain a urine output of 3 to 5 mL/kg/h. Fluid balance, electrolytes, and creatinine clearance should be carefully monitored. Hemodialysis may be effectively used to remove capreomycin in patients with significant renal disease. |
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Capreomycin Capastat Sulfate� viales 1 g. de capreomicina | |
REFERENCIAS
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Monografía
creada el 12 de Noviembre de 2014.Equipo de redacci�n de IQB (Centro colaborador de La Administraci�n Nacional de Medicamentos, alimentos y Tecnolog�a M�dica -ANMAT - Argentina). . |
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