Activase

 

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

 

Actilyse (Activase) 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 Activase into the culture medium by an established mammalian cell line (Chinese hamster ovary cells) into which the cDNA for Activase has been genetically inserted.¶

Activase injection is a sterile, white to pale yellow, lyophilized powder for intravenous administration following reconstitution with Sterile Water for Injection, USP.

Pharmacology

Activase 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. Activase 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.

Mechanism of action

• Activase is a serine protease that helps plasminogen into plasmin. In the absence of fibrin, it converts plasminogen to plasmin.
• When injected into the bloodstream, Activase binds to fibrin and transforms plasminogen into plasmin. This causes local fibrinolysis and mild systemic proteolysis.

Indications and Usage

Acute Ischemic Stroke

• The drug Activase is used to treat acute ischemic stroke. Before starting treatment, rule out cerebral bleeding as the major cause of stroke signs and symptoms.
• Start treatment as soon as feasible, but no later than 3 hours following the onset of symptoms.

Acute Myocardial Infarction

• Activase is prescribed for the treatment of acute myocardial infarction (AMI) to reduce mortality and the occurrence of heart failure.
• Limitation of Use: In patients whose AMI puts them at low risk for mortality or heart failure, the danger of stroke may outweigh the benefit of thrombolytic therapy.

Pulmonary Embolism

• Activase is used to treat acute massive pulmonary embolism, which is characterized as:
• Acute pulmonary emboli block blood flow to one or more lobes or segments of the lungs.
  Acute pulmonary emboli with unsteady hemodynamics, such as inability to maintain blood pressure without the use of supportive measures.

Contraindication

Activase should not be administered to patients with known hypersensitivity to Activase 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 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 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.¶
• 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 v should be stopped and the drug should be withdrawn from the catheter.

Infections

• Activase should be used with caution in the presence of a known or suspected infection in the catheter. Using Alteplase in patients with infected catheters may release a localized infection into the systemic circulation  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 the use of Activase. Monitor patients treated with 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 Activase. Additional re-administration of Activase has not been studied. Antibody formation in patients receiving one or more doses of Activase for restoration of function to CVADs has not been studied.

Drug Interactions

• The interaction of 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 the tumorigenicity of Activase 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 Activase.

Pregnancy

• Activase 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 on pregnant women. 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 Alteplase is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Alteplase is administered to a nursing woman.

Pediatric Use

• A total of 432 subjects under age 17 have received 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 Activase 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

Activase 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

Acute Ischemic Stroke

• The suggested dose is 0.9 mg/kg (maximum total dose of 90 mg) delivered intravenously over 60 minutes, with 10% of the total dose given as an initial bolus over 1 minute.

Acute Myocardial Infarction

• The suggested dose is based on patient weight, not to exceed 100 mg.

Acute Massive Pulmonary Embolism

• The recommended dose is 100 mg administered by IV infusion over 2 hours.
• Do not add other medications to infusions containing Activase

Stability and Storage

Store lyophilized 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.

If I don’t take the dose?

Since you’ll be receiving Activase in a medical environment, you’re less likely to skip the dose.

If I consume too much?

Get medical attention immediately or contact for help at the Poison Help line at 1-800-222-1222.

What other medications can affect the action of Actilyse?

Discuss with your doctor all other medications including:

• Any medication that is employed for treating or preventing blood clots
• A blood thinner ( heparin, warfarin, Coumadin, Jantoven) or
• The NSAIDs (nonsteroidal anti-inflammatory drugs)–aspirin Ibuprofen (Advil, Motrin), naproxen (Aleve), and celecoxib. diclofenac, indomethacinand meloxicam and many more.

This list isn’t complete. Other medications can affect Activase, which includes medications that are prescribed and available over the counter, vitamins, and herbal products. There are many possible interactions between drugs that are included here.

Additional details

Be sure to keep this medication and other medications out of reach of children. Never give your medication to anyone else and take this medication only for the purpose prescribed.

Always consult your doctor to confirm that the information provided on this site is appropriate to your particular situation.

How Supplied