Angiomax: Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

Angiomax is an anticoagulant, a medication that prevents blood from clotting. It is used to treat patients with ST-segment elevation myocardial infarction [STEMI (a severe type of heart attack)] undergoing Percutaneous Coronary Intervention (PCI), (a procedure that unblocks narrowed coronary arteries without having to perform surgery). It is also used to treat patients with moderate- to high-risk acute coronary syndromes (ACS) due to unstable angina or non-ST segment elevation myocardial infarction (a type of heart attack) undergoing PCI, or who will be managed with medicines only, or who will have cardiac (heart) surgery called a Coronary Artery Bypass Graft (CABG) (sometimes referred to as “bypass” surgery). Heparin is also a drug that prevents blood from clotting and is commonly used in patients with cardiovascular disease during PCI or cardiac surgery. Rarely, a patient can develop antibodies to heparin that put them at risk for developing a clot if exposed to heparin. Angiomax is used instead of heparin in these cases when these patients must undergo PCI or cardiac surgery.

What it does:

Angiomax is a direct thrombin-inhibitor that prevents blood from clotting during and after PCI or cardiac surgery.

When it should not be used:

Angiomax should not be used in patients with:

x A history of any allergic or other severe reaction to Angiomax

or any of its components (see ‘What the nonmedicinal ingredients are’ below)

x Uncontrollable active bleeding

x Major blood clotting disorders

x Acute stomach or intestinal ulcer

x Bleeding in the brain

x Severe trauma to the brain or spine

x Inflammation of the heart valves or inner layer of the heart

wall caused by bacterial infections

x Severe uncontrolled high blood pressure

x An eye problem called “retinopathy” caused by diabetes or

bleeding

x A use of spinal/epidural anaesthesia

What the medicinal ingredient is:

Bivalirudin

What the nonmedicinal ingredients are:

Mannitol, sodium hydroxide, trifluoroacetate

What dosage forms it comes in:

Angiomax is available as a powder (250 mg) for intravenous (IV) injection after dilution.

WARNINGS AND PRECAUTIONS

Angiomax (bivalirudin) should not be administered into muscle.

BEFORE you use Angiomax talk to your doctor or pharmacist if: x You are at risk of experiencing bleeding x You are pregnant, planning on becoming pregnant or are breast feeding. Angiomax should not be used during pregnancy, unless clearly necessary. Your doctor will decide whether or not this treatment is appropriate for you. x You are taking blood thinners or medicines to prevent blood clots (anticoagulants e.g., warfarin, dabigatran, apixaban, rivaroxaban, ASA, clopidogrel, prasugrel, ticagrelor).

The safety and effectiveness of Angiomax in brachytherapy (a type of radiation therapy) has not been studied. Therefore, Angiomax is not recommended for use in brachytherapy procedures.

As with any drug that prevents blood from clotting, bleeding may occur during or after your PCI or cardiac surgery. You may be at an increased risk for bleeding if you are elderly, female or are being given other drugs also known to cause bleeding like heparin or warfarin. Early signs of bleeding include nose or gum bleeds, blood in urine or stool, bruising easily and/or the appearance of a rash of round, red spots under the skin. If you are concerned about your risk for bleeding or experience any of these symptoms after your PCI or cardiac surgery, talk to your doctor immediately.

In patients undergoing cardiac surgery it is often necessary to receive a blood transfusion. This is true whether the doctor uses Angiomax or heparin during your medical procedure. In patients undergoing PCI, the need for transfusions is less common.

The safety and effectiveness of Angiomax has not been studied in children.

INTERACTIONS WITH THIS MEDICATION

No formal drug interaction studies have been carried out with bivalirudin. Use of Angiomax together with heparin, warfarin, thrombolytics (drugs that break up blood clots) or glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors (drugs that prevent platelets from binding together) is associated with an increased risk of bleeding events.

Solid particles form when Angiomax is given in the same intravenous (IV) line as alteplase, amiodarone HCl, amphotericin B, chlorpromazine HCl, diazepam, prochlorperazine edisylate, reteplase, streptokinase, and vancomycin HCl. Therefore, they should not be administered in the same intravenous line with Angiomax.

Solid particles can form when Angiomax is given in the same IV line as Dobutamine HCl, Famotidine, Haloperidol lactate, Labetalol HCl, Lorazepam, and Promethazine HCl. Therefore, the administration of these medicinal products in the same intravenous line as Angiomax is not recommended.

Angiomax is administered via an intravenous line from a glass bottle or polyvinyl chloride bags.

PROPER USE OF THIS MEDICATION

Angiomax is only administered by trained medical professionals through an intravenous line.

Angiomax will be administered to you after it has been dissolved in sterile water and diluted to a final concentration of 5 mg/mL.

As with all intravenous (IV) mixtures, Angiomax should be inspected visually for clarity, solid particles, discolouration and leakage prior to administration whenever solution and container permit. Solutions showing haziness, solid particles, discolouration or leakage should not be used. Discard unused portion.

Usual dose:

The dose of Angiomax you will receive will be based on your weight and will depend on what procedure, PCI or cardiac surgery, you are going to have.

ACS:

Angiomax should be given as an IV bolus dose of 0.1 mg/kg followed by an infusion of 0.25 mg/kg/h through the angiography procedure for as long as needed.

If you are going to undergo the PCI procedure, you will receive an additional IV bolus dose of 0.5 mg/kg at the start of the procedure, and this will be increased to 1.75 mg/kg/h for the entire procedure. After the procedure, your doctor may decide to give you a reduced infusion dose for as long as needed.

If you are going to undergo off-pump cardiac surgery, you will receive an additional IV bolus dose of 0.5 mg/kg just before surgery followed by a 1.75 mg/kg/h dose during the entire procedure.

If you are going to undergo on-pump cardiac surgery, the initial infusion will be continued until 1 hour before the procedure at which point you will be treated with unfractionated heparin.

PCI:

Angiomax should be given as an IV bolus dose of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the entire procedure. Your doctor may decide to continue the infusion for 4 hours after your procedure, and you may be continued on an infusion at a reduced dose of 0.25 mg/kg/h for 4-12 hours, as needed.

Angiomax is intended for use with acetylsalicylic acid (ASA) and

may be used with clopidogrel. If you have severe kidney disease, the infusion dose may have to be reduced to 1.0 mg/kg/h. If you are on dialysis, the infusion rate should be reduced to 0.25 mg/kg/h.

Cardiac Surgery:

On-pump Cardiac Surgery: Angiomax should be given as an IV bolus dose of 1.0 mg/kg followed by an infusion of 2.5 mg/kg/h. Angiomax infusion may be terminated approximately 15 minutes prior to the anticipated end of cardiopulmonary bypass (CPB). If CPB is not terminated within 20 minutes or if you need to go back on bypass, a bivalirudin IV bolus of 0.5 mg/kg should be administered and a 2.5 mg/kg/h IV infusion restarted and continued until 15 minutes prior to the anticipated end of CPB.

Off-pump Cardiac Surgery: Angiomax should be given as an IV bolus dose of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure.

Patients with severe kidney disease have not been studied in cardiac surgery using Angiomax.

Angiomax can be started 30 minutes after discontinuation of unfractionated heparin and 8 hours after discontinuation of low molecular weight heparin.

Angiomax can be used with a glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor (drug that prevents platelets from binding together).

Overdose:

Overdosage with single bolus doses of Angiomax up to 7.5 mg/kg may result in increased bleeding or adverse events. If overdose occurs, Angiomax should be discontinued and the patient should be monitored closely for signs of bleeding. Supportive therapy to treat any symptoms should be started as needed. Once the administration of Angiomax has been stopped, there is a gradual reduction in the risk for bleeding as the body breaks down the drug. There is no known antidote to Angiomax. Angiomax is removed from the blood by dialysis.

In case of drug overdose, contact a health care practitioner, hospital emergency department or regional Poison Control Centre immediately, even if there are no symptoms.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

Side effects that have been observed with Angiomax have also been observed with other drugs that prevent blood clotting such as heparin. Although the adverse events listed below have been reported when Angiomax was used, it does not necessarily mean that Angiomax caused the event. The side effects listed below are for your information and if you have any concerns or think you are experiencing an adverse reaction, talk to your doctor or pharmacist immediately.

Common side effects:

The most common serious side effect of treatment with Angiomax is major bleeding which could occur anywhere inside the body [e.g., stomach, digestive system (including vomiting blood or passing blood with the stools), abdomen, lungs, groin, bladder, heart, eye, ear, nose, or brain). This may rarely result in a stroke or be fatal. Swelling or pain in the groin or the arm, back pain, bruising, headache, coughing blood, pink or red urine, sweating, feeling faint or sick or dizzy due to low blood pressure may be signs of internal bleeding. Bleeding is more likely to occur when Angiomax is used in combination with other anticoagulant or antithrombotic medicines (see INTERACTIONS WITH THIS MEDICINE).

In clinical studies during and after PCI, common side effects reported with Angiomax were: angina, collapsed lung, indigestion, nausea, nervousness, pain at the injection site, trouble sleeping, haematoma (localized swelling filled with blood) and vomiting.

In clinical studies during and after cardiac surgery, common side effects with Angiomax were: anxiety, constipation, fluid build-up in the chest cavity, nausea, and vomiting.

Uncommon side effects:

Thrombosis (blood clot) which may result in serious or fatal complications such as heart attack.

Rare side effects:

Other side effects that occurred rarely with Angiomax included: decreased platelet count, hives, rash, and coronary artery thrombosis (blood clot in the heart arteries or within a stent being felt as a heart attack) which can also be fatal and/or thrombosis in the catheter.

During routine medical use with Angiomax, the following side effects have been reported: clot formation during PCI, and fatal bleeding.

Common

This is not a complete list of side effects. For any unexpected effects while taking Angiomax, contact your doctor or pharmacist.

HOW TO STORE IT

As Angiomax is a hospital product only, storage of Angiomax is the responsibility of healthcare professionals.

Store at controlled room temperature (15–25°C). Do not freeze. Discard any unused portion of the reconstituted solution remaining in the vial.

REPORTING SUSPECTED SIDE EFFECTS

You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:

-------------------------------------------------------------------------- x Report online at www.healthcanada.gc.ca/medeffect x Call toll-free at 1-866-234-2345

x Complete a Canada Vigilance Reporting Form and:

• Fax toll-free to 1-866-678-6789, or

• Mail to: Canada Vigilance Program

  Health Canada

  Postal Locator 0701E Ottawa, Ontario K1A 0K9

Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect^™ Canada Web site at www.healthcanada.gc.ca/medeffect.

NOTE: Should you require information related to the management of side effects, contact your health professional. The Canada Vigilance Program does not provide medical advice.

MORE INFORMATION

This document plus the full product monograph, prepared for health professionals can be found by contacting the sponsor, Sandoz Canada Inc., at:

1-800-361-3062

or by written request at:

145 Jules-Léger

Boucherville, Québec, Canada

J4B 7K8

Or by e-mail at :

medinfo@sandoz.com

Last revised: September 28, 2016