Source: FDA, National Drug Code (US) Revision Year: 2020
Cathflo Activase should not be administered to patients with known hypersensitivity to Alteplase or any component of the formulation (see DESCRIPTION).
None.
The following adverse reactions are discussed in greater detail in Section PRECAUTIONS of the label:
In the clinical trials, the most serious adverse events reported after treatment were sepsis (see PRECAUTIONS, Infections), gastrointestinal bleeding, and venous thrombosis.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described for Trials 1 and 2 reflect exposure to Cathflo Activase in 1122 patients, of whom 880 received a single dose and 242 received two sequential doses of Cathflo Activase.
In the Cathflo Activase Trials 1 and 2, only limited, focused types of serious adverse events were recorded, including death, major hemorrhage, intracranial hemorrhage, pulmonary or arterial emboli, and other serious adverse events not thought to be attributed to underlying disease or concurrent illness. Major hemorrhage was defined as severe blood loss ( > 5 mL/kg), blood loss requiring transfusion, or blood loss causing hypotension. Non‑serious adverse events and serious events thought to be due to underlying disease or concurrent illness were not recorded. Patients were observed for serious adverse events until catheter function was deemed to be restored or for a maximum of 4 or 6 hours depending on study. For most patients the observation period was 30 minutes to 2 hours. Spontaneously reported deaths and serious adverse events that were not thought to be related to the patient’s underlying disease were also recorded during the 30 days following treatment.
Four catheter-related sepsis events occurred from 15 minutes to 1 day after treatment with Alteplase, and a fifth sepsis event occurred on Day 3 after Alteplase treatment. All 5 patients had positive catheter or peripheral blood cultures within 24 hours after symptom onset.
Three patients had a major hemorrhage from a gastrointestinal source from 2 to 3 days after Alteplase treatment. One case of injection site hemorrhage was observed at 4 hours after treatment in a patient with pre-existing thrombocytopenia. These events may have been related to underlying disease and treatments for malignancy, but a contribution to occurrence of the events from Alteplase cannot be ruled out. There were no reports of intracranial hemorrhage.
Three cases of subclavian and upper extremity deep venous thrombosis were reported 3 to 7 days after treatment. These events may have been related to underlying disease or to the long-term presence of an indwelling catheter, but a contribution to occurrence of the events from Alteplase treatment cannot be ruled out. There were no reports of pulmonary emboli.
There were no gender-related differences observed in the rates of adverse reactions. Adverse reactions profiles were similar across all age subgroups.
In Trial 3 all serious adverse events were recorded with a specific interest in intracranial hemorrhage, major hemorrhage, thrombosis, embolic events, sepsis and catheter related complications. Major hemorrhage was defined as severe blood loss (>5 mL/kg), blood loss requiring transfusion, or blood loss causing hypotension. Non-serious adverse events were not recorded. Patients were observed until catheter function was deemed to be restored or for a maximum of 4 hours after the first dose. Additionally, serious adverse events were elicited from patients at 48 hours (up to 96 hours) following completion of treatment.
No pediatric patients in Trial 3 experienced an intracranial hemorrhage, major hemorrhage, thrombosis, or an embolic event.
Three cases of sepsis occurred 2 to 44 hours after treatment with Cathflo Activase. All of these patients had evidence of infection prior to administration of Cathflo Activase. An additional patient developed fever and lethargy within one day of Cathflo Activase administration, which required outpatient intravenous antibiotics. In one subject, the lumen of the catheter, placed 2 years previously, ruptured with infusion of the study drug.
There were no gender-related differences observed in the rates of adverse reactions. Adverse reactions profiles were similar across all age groups.
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.
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.
Hypersensitivity, including urticaria, angioedema and anaphylaxis, has been reported in association with use of Cathflo Activase. Monitor patients treated with Cathflo Activase for signs of hypersensitivity and treat appropriately if necessary.
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.
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.
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.
Alteplase has been shown to have an embryocidal effect due to an increased postimplantation loss rate in rabbits when administered intravenously during organogenesis at a dose (3 mg/kg) approximately 50 times human exposure (based on AUC) at the dose for restoration of function to occluded CVADs. No maternal or fetal toxicity was evident at a dose (1 mg/kg) approximately 16 times human exposure at the dose for restoration of function to occluded CVADs.
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.
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.
A total of 432 subjects under age 17 have received Cathflo Activase in the three trials. Rates of serious adverse events were similar in the pediatric and adult patients, as were the rates of catheter function restoration.
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).
Potential interactions between Cathflo Activase and laboratory tests have not been studied.
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