Actilyse Cathflo 2mg

Acute Ischemic Stroke

Actilyse Cathflo 2mg is indicated for the treatment of acute ischemic stroke.

Exclude intracranial hemorrhage as the primary cause of stroke signs and symptoms prior to initiation of treatment. Initiate treatment as soon as possible but within 3 hours after symptom onset.

Acute Myocardial Infarction

Actilyse Cathflo 2mg is indicated for use in acute myocardial infarction (AMI) for the reduction of mortality and reduction of the incidence of heart failure.

Limitation of Use: The risk of stroke may outweigh the benefit produced by thrombolytic therapy in patients whose AMI puts them at low risk for death or heart failure.

Pulmonary Embolism

Actilyse Cathflo 2mg is indicated for the lysis of acute massive pulmonary embolism, defined as:

• Acute pulmonary emboli obstructing blood flow to a lobe or multiple lung segments.
• Acute pulmonary emboli accompanied by unstable hemodynamics, e.g., failure to maintain blood pressure without supportive measures.

Actilyse Cathflo 2mg is a thrombolytic (THROM-bo-LIT-ik) drug, sometimes called a "clot-busting" drug. It helps your body produce a substance that dissolves unwanted blood clots.

Actilyse Cathflo 2mg is used to treat a stroke caused by a blood clot or other obstruction in in a blood vessel. Actilyse Cathflo 2mg is also used to prevent death from a heart attack (acute myocardial infarction).

Actilyse Cathflo 2mg is also used to treat a blood clot in the lung (pulmonary embolism).

Actilyse Cathflo 2mg is also used to dissolve blood clots that have formed in or around a catheter placed inside a blood vessel. This improve the flow of medicines injected in through the catheter, or blood drawn out through the catheter.

Actilyse Cathflo 2mg may also be used for purposes not listed in this medication guide.

Acute Ischemic Stroke

Administer Actilyse Cathflo 2mg as soon as possible but within 3 hours after onset of symptoms.

The recommended dose is 0.9 mg/kg (not to exceed 90 mg total dose), with 10% of the total dose administered as an initial intravenous bolus over 1 minute and the remainder infused over 60 minutes.

During and following Actilyse Cathflo 2mg administration for the treatment of acute ischemic stroke, frequently monitor and control blood pressure.

In patients without recent use of oral anticoagulants or heparin, Actilyse Cathflo 2mg treatment can be initiated prior to the availability of coagulation study results. Discontinue Actilyse Cathflo 2mg if the pretreatment International Normalized Ratio (INR) is greater than 1.7 or the activated partial thromboplastin time (aPTT) is elevated.

Acute Myocardial Infarction

Administer Actilyse Cathflo 2mg as soon as possible after the onset of symptoms.

The recommended total doses for acute myocardial infarction (AMI) is based on patient weight, not to exceed 100 mg, regardless of the selected administration regimen (accelerated or 3 hour, described below).

There are two Actilyse Cathflo 2mg dose regimens (accelerated and 3-hour) for use in the management of AMI; there are no controlled studies to compare clinical outcomes with these regimens.

Accelerated Infusion

The recommended accelerated infusion dose consists of an IV bolus followed by an IV infusion as set forth in Table 1.

Table 1: Accelerated Infusion Weight-Based Doses for Patients with AMI

The safety and efficacy of accelerated infusion of Actilyse Cathflo 2mg have only been investigated with concomitant administration of heparin and aspirin.

3-Hour Infusion

For patients weighing ≥ 65 kg, the recommended dose is 100 mg administered as 60 mg in the first hour (6-10 mg administered as a bolus), 20 mg over the second hour, and 20 mg over the third hour. For smaller patients (< 65 kg), a dose of 1.25 mg/kg administered over 3 hours may be used. Weight-based doses are shown in Table 2.

Table 2: 3-hour Infusion Weight-Based Doses for Patients with AMI

Pulmonary Embolism (PE)

The recommended dose is 100 mg administered by IV infusion over 2 hours.

Institute parenteral anticoagulation near the end of or immediately following the Actilyse Cathflo 2mg infusion when the partial thromboplastin time or thrombin time returns to twice normal or less.

Preparation For Administration

Reconstitution

Use only the accompanying Sterile Water for Injection (SWFI), USP without preservatives. Do not use Bacteriostatic Water for Injection, USP.

Reconstitute using aseptic technique. Do not add other medication to solutions containing Actilyse Cathflo 2mg. Reconstitute Actilyse Cathflo 2mg no more than 8 hours before use, as it contains no antibacterial preservatives.

Slight foaming is not unusual; let stand undisturbed for several minutes to allow large bubbles to dissipate. Inspect parenteral drug products for particulate matter and discoloration prior to administration whenever solution and container permit.

Actilyse Cathflo 2mg may be administered as reconstituted at 1 mg/mL or further diluted immediately before administration in an equal volume of 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP, to yield a concentration of 0.5 mg/mL, using either polyvinyl chloride bags or glass vials.

Avoid excessive agitation during dilution; mix by gently swirling and/or slow inversion.

50 mg Vials

DO NOT USE IF VACUUM IS NOT PRESENT.

Using a large bore needle (e.g., 18 gauge) and a syringe, reconstitute by adding the contents of the accompanying 50 mL vial of SWFI to the 50 mg vial of Actilyse Cathflo 2mg, directing the SWFI stream into the lyophilized cake.

100 mg Vials

THE 100 mg VIALS DO NOT CONTAIN VACUUM.

Using the transfer device provided, reconstitute by adding the contents of the accompanying 100 mL vial of SWFI to the 100 mg vial of Actilyse Cathflo 2mg.

1. Use aseptic technique.
2. Remove the protective flip-caps from one vial of Actilyse Cathflo 2mg and one vial of SWFI.
3. Open the package containing the transfer device by peeling the paper label off the package.
4. Remove the protective cap from one end of the transfer device and keeping the vial of SWFI upright, insert the piercing pin vertically into the center of the stopper of the vial of SWFI.
5. Remove the protective cap from the other end of the transfer device. DO NOT INVERT THE VIAL OF SWFI.
6. Hold the vial of Actilyse Cathflo 2mg upside down, position it so that the center of the stopper is directly over the exposed piercing pin of the transfer device, and push the vial of Actilyse Cathflo 2mg down so that the piercing pin is inserted through the center of the Actilyse Cathflo 2mg vial stopper.
7. Invert the two vials so that the vial of Actilyse Cathflo 2mg is on the bottom (upright) and the vial of SWFI is upside-down, allowing the SWFI to flow down through the transfer device. Allow the entire contents of the vial of SWFI to flow into the Actilyse Cathflo 2mg vial (approximately 0.5 cc of SWFI will remain in the diluent vial).
8. Remove the transfer device and the empty SWFI vial from the Actilyse Cathflo 2mg vial and discard.
9. Swirl gently to dissolve the Actilyse Cathflo 2mg powder. DO NOT SHAKE.

Preparation Of Bolus Dose

• Prepare the bolus dose in one of the following ways: Remove the appropriate volume from the vial of reconstituted (1 mg/mL) Actilyse Cathflo 2mg using a syringe and needle. If this method is used with the 50 mg vials, the syringe should not be primed with air and the needle should be inserted into the Actilyse Cathflo 2mg vial stopper. If the 100 mg vial is used, the needle should be inserted away from the puncture mark made by the transfer device.
• Remove the appropriate volume from a port (second injection site) on the infusion line after the infusion set is primed.
• Program an infusion pump to deliver the appropriate volume as a bolus at the initiation of the infusion

Administration

Following bolus dose, if indicated :

• 50 mg vials - administer using either a polyvinyl chloride bag or glass vial and infusion set.
• 100 mg vials - remove from the vial any quantity of drug in excess of that specified for patient treatment. Insert the spike end of an infusion set through the same puncture site created by the transfer device in the stopper of the vial of reconstituted Actilyse Cathflo 2mg. Peel the clear plastic hanger from the vial label. Hang the Actilyse Cathflo 2mg vial from the resulting loop.

Actilyse Cathflo 2mg is for intravenous administration only. Extravasation of Actilyse Cathflo 2mg infusion can cause ecchymosis or inflammation. If extravasation occurs, terminate the infusion at that IV site and apply local therapy.

Do not add any other medication to infusion solutions containing Actilyse Cathflo 2mg.

How supplied

Dosage Forms And Strengths

• 50 mg lyophilized powder per single use vial with 50 mL SWFI USP for reconstitution
• 100 mg lyophilized powder per single use vial with 100 mL SWFI USP for reconstitution

Storage And Handling

Actilyse Cathflo 2mg is supplied as a sterile, lyophilized powder in 50 mg vials containing vacuum and in 100 mg vials without vacuum.

Each 50 mg Actilyse Cathflo 2mg vial (29 million IU) is packaged with diluent for reconstitution (50 mL Sterile Water for Injection, USP): NDC 50242-044-13.

Each 100 mg Actilyse Cathflo 2mg vial (58 million IU) is packaged with diluent for reconstitution (100 Ml Sterile Water for Injection, USP), and one transfer device: NDC 50242-085-27.

Stability And Storage

Store lyophilized Actilyse Cathflo 2mg at controlled room temperature not to exceed 30°C (86°F), or under refrigeration (2-8°C/36-46°F). Protect the lyophilized material during extended storage from excessive exposure to light. If stored between 2-30°C (36-86°F), Actilyse Cathflo 2mg may be used within 8 hours following reconstitution. Discard any unused solution after administration is complete.

Do not use beyond the expiration date stamped on the vial.

Manufactured by: Genentech, Inc., A Member of the Roche Group, 1 DNA Way, South San Francisco, CA. Revised: Feb 2015

See also:
What is the most important information I should know about Actilyse Cathflo 2mg?

Known hypersensitivity to Actilyse Cathflo 2mg, gentamicin (a trace residue from the manufacturing process) or to any of the excipients of Actilyse Cathflo 2mg.

As with all thrombolytic agents, and generally, in all indications Actilyse Cathflo 2mg should not be used in cases where there is a high risk of haemorrhage eg, significant bleeding disorder at present or within the past 6 months, known haemorrhagic diathesis; patients receiving oral anticoagulants eg, warfarin sodium (INR >1.3); any history of central nervous system damage (ie, neoplasm, aneurysm, intracranial or spinal surgery); history or evidence or suspicion of intracranial haemorrhage including subarachnoid haemorrhage; severe uncontrolled arterial hypertension; major surgery or significant trauma in the past 10 days (this includes any trauma associated with the current acute myocardial infarction), recent trauma to head or cranium; prolonged or traumatic cardiopulmonary resuscitation (>2 min), obstetrical delivery, within the past 10 days, recent puncture of a non-compressible blood vessel (eg, subclavian or jugular vein puncture); severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis; bacterial endocarditis, pericarditis; acute pancreatitis; documented ulcerative gastrointestinal disease during the last 3 months; arterial aneurysms, arterial/venous malformations; neoplasm with increased bleeding risk.

In the indications of acute myocardial infarction and acute pulmonary embolism, the following contraindications apply in addition: Haemorrhagic stroke or stroke of unknown origin at any time; ischaemic stroke or transient ischaemic attack (TIA) in the preceding 6 months.

In the indication acute ischaemic stroke, the following contraindications apply in addition: Symptoms of ischaemic attack began >4.5 hrs prior to infusion start or when time of symptom onset is unknown; symptoms of acute ischaemic stroke that were either rapidly improving or only minor before start of infusion; severe stroke as assessed clinically (eg, NIHSS >25) and/or by appropriate imaging techniques; seizure at the onset of stroke; history of previous stroke or serious head trauma within 3 months; a combination of previous stroke and diabetes mellitus; administration of heparin within 48 hrs preceding the onset of stroke with an elevated activated partial thromboplastin time (aPTT) at presentation; platelet count of <100,000/mm³; systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, or aggressive management (IV medication) necessary to reduce blood pressure to these limits; blood glucose <50 or >400 mg/dL.

Actilyse Cathflo 2mg is not indicated for the therapy of acute stroke in children and adolescents <18 years. For use in patients >80 years, see Precautions.

Use Actilyse Cathflo 2mg as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Actilyse Cathflo 2mg is usually administered at your doctor's office, hospital, or clinic. If you are using Actilyse Cathflo 2mg at home, carefully follow the procedures taught to you by your health care provider.
• If Actilyse Cathflo 2mg contains particles or is discolored, or if the vial is cracked or damaged in any way, do not use it.
• Mix Actilyse Cathflo 2mg by swirling gently. Do not shake.
• Throw away any unused medicine left in the vial.
• Do not reuse needles, syringes, or other materials. Dispose of properly after use. Ask your doctor or pharmacist to explain local regulations for selecting an appropriate container and properly disposing of the container when full.
• If you miss a dose of Actilyse Cathflo 2mg, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Actilyse Cathflo 2mg.

Use: Labeled Indications

Actilyse Cathflo 2mg:

Acute ischemic stroke: Treatment of acute ischemic stroke (AIS) as soon as possible but within 3 hours of symptom onset.

Pulmonary embolism: Management of acute massive pulmonary embolism (PE)

ST-elevation myocardial infarction: Management of ST-elevation myocardial infarction (STEMI) for the lysis of thrombi in coronary arteries.

Limitations of use: The risk of stroke may outweigh the benefit produced by thrombolytic therapy in patients whose acute myocardial infarction (MI) puts them at low risk for death or heart failure.

Recommended criteria for treatment:

STEMI (ACCF/AHA [O

See also:
What other drugs will affect Actilyse Cathflo 2mg?

No formal interaction studies with Actilyse Cathflo 2mg and medicinal products commonly administered in patients with acute myocardial infarction have been performed.

Medicinal products that affect coagulation or those that alter platelet function may increase the risk of bleeding prior to, during or after Actilyse Cathflo 2mg therapy.

Concomitant treatment with angiotensin-converting enzyme (ACE) inhibitors may enhance the risk of suffering an anaphylactoid reaction, as in the cases describing such reactions, a relatively larger proportion of patients were receiving ACE inhibitors concomitantly.

Incompatibilities: The reconstituted solution may be diluted further with sterile physiological saline solution (0.9%) up to a minimal concentration of Actilyse Cathflo 2mg 0.2 mg/mL since the occurrence of turbidity of the reconstituted solution cannot be excluded.

Further dilution with sterilised water for injections or the use of carbohydrate solutions is not recommended due to increasing formation of turbidity of the reconstituted solution.

Actilyse Cathflo 2mg should not be mixed with other drugs, neither in the same infusion-vial nor the same venous line (not even with heparin).

See also:
What are the possible side effects of Actilyse Cathflo 2mg?

In the clinical trials, the most serious adverse events reported after treatment were sepsis, 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.

Trials 1 and 2

The data described for Trials 1 and 2 reflect exposure to Actilyse Cathflo 2mg in 1122 patients, of whom 880 received a single dose and 242 received two sequential doses of Actilyse Cathflo 2mg.

In the Actilyse Cathflo 2mg 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 Actilyse Cathflo 2mg, and a fifth sepsis event occurred on Day 3 after Actilyse Cathflo 2mg 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 Actilyse Cathflo 2mg 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 Actilyse Cathflo 2mg 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 Actilyse Cathflo 2mg 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.

Trial 3

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 Actilyse Cathflo 2mg. All of these patients had evidence of infection prior to administration of Actilyse Cathflo 2mg. An additional patient developed fever and lethargy within one day of Actilyse Cathflo 2mg 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.

Allergic Reactions

No allergic-type reactions were observed in the trials in patients treated with Actilyse Cathflo 2mg. If an anaphylactic reaction occurs, appropriate therapy should be administered.

The reconstituted solution contains 1 mg Actilyse Cathflo 2mg per mL.

Excipients/Inactive Ingredients: L-arginine, phosphoric acid, polysorbate 80. Trace residue: gentamicin from manufacturing process.