WARNINGS
None.
PRECAUTIONS
GENERAL
Catheter dysfunction may be caused by a variety of conditions other than thrombus formation, such as catheter malposition, mechanical failure, constriction by a suture, and lipid deposits or drug precipitates within the catheter lumen. These types of conditions should be considered before treatment with Cathflo Activase.
Because of the risk of damage to the vascular wall or collapse of soft-walled catheters, vigorous suction should not be applied during attempts to determine catheter occlusion.
Excessive pressure should be avoided when Cathflo Activase is instilled into the catheter. Such force could cause rupture of the catheter or expulsion of the clot into the circulation.
BLEEDING
The most frequent adverse reaction associated with all thrombolytics in all approved indications is bleeding.3,4 Cathflo Activase has not been studied in patients known to be at risk for bleeding events that may be associated with the use of thrombolytics. Caution should be exercised with patients who have active internal bleeding or who have had any of the following within 48 hours: surgery, obstetrical delivery, percutaneous biopsy of viscera or deep tissues, or puncture of non-compressible vessels. In addition, caution should be exercised with patients who have thrombocytopenia, other hemostatic defects (including those secondary to severe hepatic or renal disease), or any condition for which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location, or who are at high risk for embolic complications (e.g., venous thrombosis in the region of the catheter). Death and permanent disability have been reported in patients who have experienced stroke and other serious bleeding episodes when receiving pharmacologic doses of a thrombolytic.
Should serious bleeding in a critical location (e.g., intracranial, gastrointestinal, retroperitoneal, pericardial) occur, treatment with Cathflo Activase should be stopped and the drug should be withdrawn from the catheter.
INFECTIONS
Cathflo Activase should be used with caution in the presence of known or suspected infection in the catheter. Using Cathflo Activase in patients with infected catheters may release a localized infection into the systemic circulation (see ADVERSE REACTIONS). As with all catheterization procedures, care should be used to maintain aseptic technique.
RE-ADMINISTRATION
In clinical trials, patients received up to two 2 mg/2 mL doses (4 mg total) of Alteplase. Additional re-administration of Cathflo Activase has not been studied. Antibody formation in patients receiving one or more doses of Cathflo Activase for restoration of function to CVADs has not been studied.
DRUG INTERACTIONS
The interaction of Cathflo Activase with other drugs has not been formally studied. Concomitant use of drugs affecting coagulation and/or platelet function has not been studied.
DRUG/LABORATORY TEST INTERACTIONS
Potential interactions between Cathflo Activase and laboratory tests have not been studied.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
Long-term studies in animals have not been performed to evaluate the carcinogenic potential or the effect on fertility. Short-term studies that evaluated tumorigenicity of Alteplase and effect on tumor metastases were negative in rodents. Studies to determine mutagenicity (Ames test) and chromosomal aberration assays in human lymphocytes were negative at all concentrations tested. Cytotoxicity, as reflected by a decrease in mitotic index, was evidenced only after prolonged exposure at high concentrations exceeding those expected to be achieved with Cathflo® Activase® (Alteplase).
PREGNANCY (CATEGORY C)
Alteplase has been shown to have an embryocidal effect due to an increased postimplantation loss rate in rabbits when administered intravenously at doses approximately 100 times (3 mg/kg) the human dose for restoration of function to occluded CVADs. No maternal or fetal toxicity was evident at 33 times (1 mg/kg) the human dose for restoration of function to occluded CVADs in pregnant rats and rabbits dosed during the period of organogenesis.
There are no adequate and well-controlled studies in pregnant women. Cathflo Activase should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
NURSING MOTHERS
It is not known whether Cathflo Activase is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Cathflo Activase is administered to a nursing woman.
PEDIATRIC USE
Cathflo Activase has not been studied in patients who are younger than 2 years of age or who weigh less than 10 kg. In Trials 1 and 2, 126 (11%) of 1135 patients treated were from 2 to 16 years of age. No study drug-related adverse events were observed in these patients. A total of 65 patients (6% of all patients treated in the studies) weighed >/=10 kg and <30 kg. These low body weight patients received up to two doses of Alteplase, with each dose equal to 110% of the internal lumen volume of the catheter (to a maximum dose of 2 mg). The rates of catheter function restoration in these subsets of patients were similar to those observed in adult patients. However, there was insufficient enrollment of pediatric patients to draw any conclusions regarding relative efficacy in the pediatric or low weight subgroups, relative efficacy related to catheter types used in these patients, or relative rates of adverse events.
GERIATRIC USE
In 312 patients enrolled who were age 65 years and over, no incidents of intracranial hemorrhage (ICH), embolic events, or major bleeding events were observed. One hundred three of these patients were age 75 years and over, and 12 were age 85 years and over. The effect of Alteplase on common age-related comorbidities has not been studied. In general, caution should be used in geriatric patients with conditions known to increase the risk of bleeding (see PRECAUTIONS, Bleeding).
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