Cathflo

Generic name: Alteplase
Brand name: Activase, Cathflo Activase
Drug class: Thrombolytics

Cathflo (Alteplase) is a tissue plasminogen activator (t‑PA) produced by recombinant DNA technology. It is a sterile, purified glycoprotein of 527 amino acids. It is synthesized using the complementary DNA (cDNA) for natural human tissue‑type plasminogen activator (t‑PA) obtained from an established human cell line.

The manufacturing process involves secretion of the enzyme Alteplase into the culture medium by an established mammalian cell line (Chinese hamster ovary cells) into which the cDNA for Alteplase has been genetically inserted.¶

Cathflo for injection is a sterile, white to pale yellow, lyophilized powder for intracatheter installation for restoration of function to central venous access devices following reconstitution with Sterile Water for Injection, USP.

Each vial of Cathflo Activase contains 2.2 mg of Alteplase (which includes a 10% overfill), 77 mg of L‑arginine, 0.2 mg of polysorbate 80, and phosphoric acid for pH adjustment. Each reconstituted vial will deliver 2 mg of Cathflo Activase, at a pH of approximately 7.3.

What is Cathflo pharmacology?

Alteplase is an enzyme (serine protease) that has the property of fibrin-enhanced conversion of plasminogen to plasmin. It produces limited conversion of plasminogen in the absence of fibrin. Alteplase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin, thereby initiating local fibrinolysis

In patients with acute myocardial infarction administered 100 mg of Activase as an accelerated intravenous infusion over 90 minutes, plasma clearance occurred with an initial half‑life of less than 5 minutes and a terminal half‑life of 72 minutes. Clearance is mediated primarily by the liver.

When Cathflo Activase is administered for restoration of function to central venous access devices, circulating plasma levels of Alteplase is not expected to reach pharmacologic concentrations. If a 2 mg dose of Alteplase were administered by bolus injection directly into the systemic circulation (rather than instilled into the catheter), the concentration of circulating Alteplase would be expected to return to endogenous circulating levels of 5–10 ng/mL within 30 minutes

Indications and Usage

Cathflo is indicated for the restoration of function to central venous access devices as assessed by the ability to withdraw blood.

Contraindication

Cathflo Activase should not be administered to patients with known hypersensitivity to Alteplase or any component of the formulation

Precautions and warnings

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.¶
• 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, a 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 a 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 a 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 the aseptic technique.

Hypersensitivity

• 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.

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.

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 its 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.

Pregnancy

• 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 the 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.

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

• 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.

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

Cathflo side effects

 Allergy such as Hives and breathing problems and swelling of your lips, face, and tongue.

Consult your physician or seek medical attention in an emergency situation If you are experiencing indications of bleeding, for example:

• abrupt headache that is a sudden sensation of weakness or dizziness;
• bleeding gums, nosebleeds;
• easily bruising;
• bleeding from a wound incision, catheter, or needle injection
• Bloody or tarry stool, coughing up blood or vomit that appears like coffee grounds
• Pink or red urine;
• irregular menstrual cycles or vaginal bleeding or
• A sudden sensation of numbness or weakening (especially in one part of the back) as well as slurred speech. difficulties with balance or vision.

Make sure to contact your doctor at the earliest opportunity if you are suffering from:

• chest pain or a heavy feeling and pain that spreads into the shoulder or jaw, nausea, sweating, general discomfort;
• swelling with rapid weight gain very little or no urination
• severe nausea, stomach pain as well as severe stomach pain, nausea and vomiting;
• the discoloration becomes darker or more purple on your toes or fingers;
• extremely slow heartbeats, breathing shortness Feeling lightheaded,
• suddenly intense back pain in your back muscular weakness and numbness, or loss of sensation in your arms or legs;
• high blood pressure, severe headache fuzzy vision, the sound of pounding sensations in your ears or neck, anxiety, nosebleeds; or
• pancreatitis–severe discomfort in your upper stomach, which spreads into your lower back vomiting and nausea

Dosage and Administration

Cathflo is for instillation into the dysfunctional catheter at a concentration of 1 mg/mL.

If catheter function is not restored at 120 minutes after 1 dose of Cathflo Activase, a second dose may be instilled (see INSTRUCTIONS FOR ADMINISTRATION). There is no efficacy or safety information on dosing in excess of 2 mg per dose for this indication. Studies have not been performed with administration of total doses greater than 4 mg (two 2‑mg doses).

Instructions for Administration

Preparation of Solution

Reconstitute Cathflo Activase to a final concentration of 1 mg/mL:

1. Aseptically withdraw 2.2 mL of Sterile Water for Injection, USP (diluent is not provided). Do not use Bacteriostatic Water for Injection.

• 1. Inject the 2.2 mL of Sterile Water for Injection, USP, into the Cathflo Activase vial, directing the diluent stream into the powder. Slight foaming is not unusual; let the vial stand undisturbed to allow large bubbles to dissipate.
  2. Mix by gently swirling until the contents are completely dissolved. Complete dissolution should occur within 3 minutes. DO NOT SHAKE. The reconstituted preparation results in a colorless to pale yellow transparent solution containing 1 mg/mL Cathflo Activase at a pH of approximately 7.3.
  3. Cathflo Activase contains no antibacterial preservatives and should be reconstituted immediately before use. The solution may be used for intracatheter installation within 8 hours following reconstitution when stored at 2–30°C (36–86°F).

No other medication should be added to solutions containing Cathflo Activase.

Instillation of Solution into the Catheter

5. Inspect the product prior to administration for foreign matter and discoloration.

• 1. Withdraw 2 mL (2 mg) of solution from the reconstituted vial.
  2. Instill the appropriate dose of Cathflo Activasein to the occluded catheter.
  3. After 30 minutes of dwell time, assess catheter function by attempting to aspirate blood.
  4. After 120 minutes of dwell time, assess catheter function by attempting to aspirate blood and catheter contents. If the catheter is functional to Step 6.
  5. If catheter function is not restored after one dose of Cathflo Activase, a second dose of the equal amount may be instilled. Repeat the procedure beginning with Step 1 under Preparation of Solution.
  6. If catheter function has been restored, aspirate 4–5 mL of blood in patients ≥10 kg or 3 mL in patients <10 kg to remove Cathflo Activase and residual clot, and gently irrigate the catheter with 0.9% Sodium Chloride Injection, USP.

Any unused solution should be discarded.

Stability and Storage

Store lyophilized Cathflo Activase at refrigerated temperature (2–8°C/36–46°F). Do not use beyond the expiration date on the vial. Protect the lyophilized material during extended storage from excessive exposure to light.

How Supplied