Consumer Information for: BIVALIRUDIN FOR INJECTION

Consumer Information

Information about the product including what the product is used for, dosage, warnings, proper use and side effects. This summary will not tell you everything about the product. Contact your healthcare professional if you have any questions about the product.


What the medication is used for

Bivalirudin for Injection is an anti-coagulant, a medication that prevents blood from clotting. It is used to treat patients with STsegment 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. Bivalirudin for Injection is used instead of heparin in these cases when these patients must undergo PCI or cardiac surgery.

What it does

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

When it should not be used

Bivalirudin for Injection should not be used in patients with:

  • A history of any allergic or other severe reaction to Bivalirudin for Injection or any of its components (see ‘What the nonmedicinal ingredients are’ below)
  • Uncontrollable active bleeding
  • Major blood clotting disorders
  • Acute stomach or intestinal ulcer
  • Bleeding in the brain
  • Severe trauma to the brain or spine
  • Inflammation of the heart valves or inner layer of the heart wall caused by bacterial infections
  • Severe uncontrolled high blood pressure
  • An eye problem called “retinopathy” caused by diabetes or bleeding
  • A use of spinal/epidural anaesthesia
What the medicinal ingredient is

Bivalirudin

What the non-medicinal ingredients are

Mannitol, trifluoroacetate, sodium hydroxide

What dosage form it comes in

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

Warnings and precautions

Bivalirudin for Injection should not be administered into muscle

BEFORE you use Bivalirudin for Injection talk to your doctor or pharmacist if:

  • You are at risk of experiencing bleeding
  • You are pregnant, planning on becoming pregnant or are breast feeding. Bivalirudin for Injection should not be used during pregnancy, unless clearly necessary. Your doctor will decide whether or not this treatment is appropriate for you
  • 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 Bivalirudin for Injection in brachytherapy (a type of radiation therapy) has not been studied. Therefore, Bivalirudin for Injection 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 Bivalirudin for Injection or heparin during your medical procedure. In patients undergoing PCI, the need for transfusions is less common.

The safety and effectiveness of bivalirudin has not been studied in children

Interactions with this medication

No formal drug interaction studies have been carried out with bivalirudin. Use of Bivalirudin for Injection 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 Bivalirudin for Injection 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 Bivalirudin for Injection.

Solid particles can form when Bivalirudin for Injection is given in the same intravenous 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 Bivalirudin for Injection is not recommended.

Bivalirudin for Injection is administered via an intravenous line from a glass bottle or polyvinyl chloride bags.

Proper use of this medication

Bivalirudin for Injection is only administered by trained medical professionals through an intravenous line.

Bivalirudin for Injection 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, Bivalirudin for Injection 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 Bivalirudin for Injection 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:
Bivalirudin for Injection should be given as an intravenous bolus dose of 0.1 mg / kg followed by an infusion of 0.25 mg / kg / hr through the angiography procedure for as long as needed.

If you are going to undergo the PCI procedure, you will receive an additional intravenous bolus dose of 0.5 mg / kg at the start of the procedure, and this will be increased to 1.75 mg / kg / hr 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 intravenous bolus dose of 0.5 mg / kg just before surgery followed by a 1.75 mg / kg / hr 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:
Bivalirudin for Injection should be given as an intravenous bolus dose of 0.75 mg / kg followed by an infusion of 1.75 mg / kg / hr 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 / hr for 4-12 hours, as needed. Bivalirudin for Injection 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 mg / kg / hr. If you are on dialysis, the infusion rate should be reduced to 0.25 mg / kg / hr.

Cardiac Surgery:
On-pump Cardiac Surgery: Bivalirudin for Injection should be given as an intravenous bolus dose of 1 mg / kg followed by an infusion of 2.5 mg / kg / hr. Bivalirudin for Injection 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 intravenous bolus of 0.5 mg / kg should be administered and a 2.5 mg / kg / hr intravenous infusion restarted and continued until 15 minutes prior to the anticipated end of CPB

Off-pump Cardiac Surgery: Bivalirudin for Injection should be given as an intravenous bolus dose of 0.75 mg / kg followed by an infusion of 1.75 mg / kg / hr for the duration of the procedure.

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

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

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

Bivalirudin for Injection 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 Bivalirudin for Injection up to 7.5 mg / kg may result in increased bleeding or adverse events. If overdose occurs, Bivalirudin for Injection 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 Bivalirudin for Injection 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 bivalirudin. Bivalirudin for Injection is removed from the blood by dialysis

If you think you have taken too much Bivalirudin for Injection, contact your healthcare professional, hospital emergency department or regional Poison Control Centre immediately, even if there are no symptoms.

Missed Dose

Side effects and what to do about them

Side effects that have been observed with bivalirudin have also been observed with other drugs that prevent blood clotting such as heparin. Although the adverse events listed IMPORTANT: PLEASE READ Bivalirudin for Injection-Annotated Page 41 of 42 below have been reported when bivalirudin was used, it does not necessarily mean that bivalirudin 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 Bivalirudin for Injection 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 Bivalirudin for Injection 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 bivalirudin were: angina, collapsed lung, indigestion, nausea, nervousness, pain at the injection site, trouble sleeping, hematoma (localized swelling filled with blood) and vomiting

In clinical studies during and after cardiac surgery, common side effects with bivalirudin 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 bivalirudin 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 Bivalirudin for Injection, the following side effects have been reported: clot formation during PCI, and fatal bleeding.

Serious side effects, how often they happen and what to do about them
Symptom / effect Talk with your doctor, nurse, or pharmacist only if severe Talk with your doctor, nurse, or pharmacist in all cases Stop taking drug and talk with your doctor or pharmacist
Common
Anaemia   ✔  
Decreased blood pressure   ✔  
Difficulty urinating or decreased urine volume   ✔  
Fever (with or without cough and/or difficulty breathing)   ✔  
Headache   ✔  
Heart attack   ✔  
Heart rate changes (decreased, increased or irregular) which can be lifethreatening when not treated   ✔  
Increased blood pressure   ✔  
Pain (including back, pelvic/ abdominal, or chest pain)   ✔  
Swelling of the hands and/or feet   ✔  
Uncontrolled bleeding   ✔  
Wound secretion   ✔  
Uncommon
Allergic or hypersensitivity reactions   ✔  
Stroke   ✔  

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

How to store

Bivalirudin for Injection should be stored at controlled room temperature (15 C to 30 °C). Do not freeze. Discard any unused portion of the reconstituted solution remaining in the vial.

Do not freeze reconstituted or diluted Bivalirudin for Injection. Reconstituted material may be stored between 2 C and 8 C for up to 24 hours. Diluted Bivalirudin for Injection with a concentration of between 0.5 mg / mL and 5 mg / mL is stable at room temperature for up to 24 hours

Reporting side effects

You can report any suspected side effects associated with the use of health products to Health Canada by:

NOTE: Contact your health professional if you need information about how to manage your side effects. The Canada Vigilance Program does not provide medical advice.

More information

If you want more information about Bivalirudin for Injection:

  • Talk to your healthcare professional
  • Find the full product monograph that is prepared for healthcare professionals and includes this Consumer Information by visiting the Health Canada website (https://health-products.canada.ca/dpd-bdpp/indexeng.jsp); Fresenius Kabi Canada’s website (http://www.fresenius-kabi.com/en-ca/), or by contacting the sponsor, Fresenius Kabi Canada Ltd., at 1-877-821- 7724

This leaflet was prepared by:
Fresenius Kabi Canada Ltd.
165 Galaxy Blvd, Suite 100
Toronto, ON M9W 0C8

Last revised: April 18, 2019

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