Reteplase

Dosage Forms & Strengths

powder for injection

• 10.4 units (18.1mg)

Acute Myocardial Infarction

10 units IV bolus (over 2 minutes), THEN

Second dose given 30 minutes after first (for total cumulative dose of 20 units)

Treatment should be initiated ASAP after onset of AMI

Give each bolus injection via an IV line in which no other medication is being simultaneously injected or infused

Safety & efficacy not established

Follow your doctor's instructions about any restrictions on food, beverages, or activity while you are using retaplase.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Reteplase falls into category C:

In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans, though. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

OR

There are no well-controlled studies that have been done in pregnant women. Reteplase should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

OR

No studies have been done in animals, and no well-controlled studies have been done in pregnant women. Reteplase should be given to a pregnant woman only if clearly needed.

Acute MI

Management of selected cases of acute evolving transmural MI in conjunction with anticoagulants (e.g., heparin) and/or platelet-aggregation inhibitors (i.e., aspirin).1 2 3 7 15 Used to improve ventricular function and reduce the incidence of CHF, cardiogenic shock, and associated post-MI mortality.1 2 3 7 8

Clinical benefit diminishes as the time period from symptom onset to initiation of therapy increases.2 3 5 15 Administer as soon as possible, preferably within 3–6 hours of acute MI.1 3 5 ACC and AHA recommend administration within 30 minutes of hospital admission or first contact with the health-care system.15

AHA and ACC recommend use of any marketed thrombolytic agent (e.g., alteplase, reteplase, tenecteplase) in patients having ischemic symptoms characteristic of MI for ≤12 hours and ST-segment elevation or new or presumed new left bundle-branch block, unless contraindications exist.15

ACC and AHA state that thrombolytic therapy is reasonable within 12–24 hours of symptom onset in patients with persistent ischemic symptoms accompanied by ST-segment elevation, provided no contraindications exist.15

Thrombolytic therapy may be reasonable in patients with true posterior MI presenting within 12 hours after onset of symptoms.15

Acute PE

Has been used for the treatment of acute PE†.20 1005

The American College of Chest Physicians (ACCP) generally recommends against the use of systemic thrombolytic therapy in most patients with acute PE; however, in patients with acute PE associated with hypotension (e.g., systolic BP<90 mmHg), thrombolytic therapy may provide some benefit in terms of mortality reduction and is suggested as a possible treatment in patients without high risk of bleeding.1005

Specific Drugs

• Binds to fibrin and converts plasminogen to plasmin.1 Plasmin degrades the fibrin matrix of the thrombus.1

• Decreased fibrin affinity compared with alteplase.2 3 7 8 10

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• Very bad and sometimes deadly bleeding problems have happened with reteplase. Talk with the doctor.
• A very bad health problem called cholesterol embolism has happened with drugs like this one. Sometimes, this can be deadly. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• If you fall or hurt yourself, or if you hit your head, call your doctor right away. Talk with your doctor even if you feel fine.
• If you are 65 or older, use reteplase with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

• r-PA
• Recombinant Plasminogen Activator

Dosage kits should be stored at 2°C to 25°C (36°F to 77°F) and remain sealed until use in order to protect from light.

Applies to reteplase: intravenous kit

Hematologic

Hematologic side effects have been the most frequently reported side effects. In the INJECT trial, the overall incidence of bleeds from any site was 15.0%, of which 4.6% were clinically significant. Transfusion requirements have ranged from 1.0% (INJECT trial) to 12.4% (RAPID-2 trial). The types of bleeds associated with this drug (and thrombolytic therapy, in general) may be broadly categorized as either intracranial hemorrhage or other types of hemorrhage.

The overall incidence of intracranial hemorrhage has averaged 0.8%. This risk is increased in patients with advanced age or hypertension. The incidence of transient ischemic attack (TIA) or reversible ischemic neurologic deficit (RIND) in the INJECT trial averaged 0.20%, and the incidence of frank stroke in the RAPID-2 trial averaged 1.8%. The average incidence of nonintracranial hemorrhage ranged from 1.9% to 9.0%, depending on the trial, use of arterial catheterization, and whether the study was performed in the US or Europe.

The incidence of IV site bleeding ranged from 4.6% to 48.6%. Arterial and venous punctures should be minimized. Should serious bleeding in a critical location (intracranial, gastrointestinal, retroperitoneal, or pericardial) occur, any concomitant heparin should be terminated immediately, and the second bolus of reteplase should be withheld.[Ref]

The incidences of bleeding have been reported in the following sites within the following clinical trials, respectively (European INJECT study [n=2965], US RAPID-1 study [n=210], European RAPID-2 study [n=113]: injection site 4.6%, 48.6%, 19.5%; intracranial 1.2% (stroke), 0%, 1.8% (stroke); gastrointestinal 2.5%, 9.0%, 1.8%; genitourinary 1.6%, 9.5%, 0.9%; anemia 2.6%; 1.4%, 0.9%).

Since reteplase causes lysis of the fibrin plug, which is necessary to stop bleeding at puncture sites, careful attention should be paid to potential sites of bleeding during therapy (injection site, arterial puncture sites, catheter insertion sites, etc.).[Ref]

Cardiovascular

The following incidences were reported from the RAPID-2 trial: myocardial reinfarction 4.7%, congestive heart failure 9.5%, and ischemia or angina in 29.0%.

Cholesterol embolization--sometimes fatal--has been reported rarely in patients treated with thrombolytic agents. The exact incidence is unknown. Its relationship with lytic therapy might be coincidental as there is such risk associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy.

Reperfusion arrhythmias during thrombolytic therapy can be a sign of successful lytic therapy. These arrhythmias (e.g., sinus bradycardia, accelerated idioventricular rhythm, ventricular rhythm, ventricular premature depolarizations, ventricular tachycardia) may also be seen during the natural course of acute myocardial infarction, and they should be treated with standard antiarrhythmic measures, as indicated. It is recommended that antiarrhythmic therapy for bradycardia and/or ventricular irritability be available during reteplase therapy.[Ref]

Cardiovascular side effects are probably sequelae of myocardial infarction and not due to reteplase. These side effects have included hypotension, cardiogenic shock, arrhythmias (e.g., sinus bradycardia, accelerated idioventricular rhythm, premature ventricular depolarizations, supraventricular tachycardia, ventricular tachycardia, and ventricular fibrillation), AV block, pulmonary edema, heart failure, cardiac arrest, recurrent ischemia, reinfarction, myocardial rupture, mitral regurgitation, pericardial effusion, pericarditis, cardiac tamponade, venous thrombosis and embolism, and electromechanical dissociation.[Ref]

Hypersensitivity

Serious hypersensitivity reactions to reteplase have been rare. Among the 2,965 patients in the INJECT trial, such reactions were noted in 3 patients, with 1 patient experiencing dyspnea and hypotension. No cases of anaphylaxis were reported among the 3,856 patients treated with reteplase in initial clinical trials, but 2 cases of anaphylaxis were associated with the use of reteplase among approximately 2,500 patients in ongoing clinical trials.[Ref]

There are no data to demonstrate the formation of anti-reteplase antibodies among the approximately 2,400 patients who have been tested for the presence of such antibodies. Nevertheless, the use of reteplase (including the second bolus of reteplase) is not recommended if anaphylaxis has occurred with any prior use of reteplase in a given patient.[Ref]

Gastrointestinal

Gastrointestinal side effects have included nausea and vomiting.[Ref]

General

Fever, a general body side effect, has been reported.[Ref]

Some side effects of reteplase may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.