Angiomax

Name: Angiomax

Bivalirudin Dosage

Bivalirudin is injected into a vein through an IV. You will receive this injection during your angioplasty procedure in a clinic or hospital setting. The medicine must be given throughout the entire procedure.

Your doctor may want you to continue receiving bivalirudin for up to 20 hours after your angioplasty procedure.

Bivalirudin is usually given together with aspirin.

Because bivalirudin keeps your blood from coagulating (clotting) to prevent unwanted blood clots, it may be easier for you to bleed even from a minor injury. Contact your doctor or seek emergency medical attention if you have bleeding that will not stop.

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Because you will receive bivalirudin in a clinical setting, you are not likely to miss a dose.

Administration

IV Incompatibilities

No incompatibilities observed with glass bottles or polyvinyl chloride bags & administration sets

Y-site: alteplase, amiodarone, amphotericin B, chlorpromazine, diazepam, prochlorperazine, reteplase, streptokinase, vancomycin

IV Compatibilities

Solution: D5W, NS

Y-site: abciximab, alfentanil, ampicillin, ampicillin/sulbactam, azithromycin, ciprofloxacin, diphenhydramine, dobutamine(compatible at concentrations up to 4mg/ml; incompatible at 12.5mg/mL), dopamine, epinephrine, fentanyl, furosemide, heparin, lidocaine, lorazepam, MgSO4, midazolam, morphine SO4, KCl, NaHCO3, TMP-SMX, warfarin, most cephalosporins

IV Preparation

To each 250 mg vial add 5 mL SWI

Gently swirl until all material is dissolved

Dilute each vial in 50 mL of D5W or NS to yield a final concentration of 5 mg/mL

If low-rate infusion is used after initial infusion, a lower concentration bag should be prepared

Inspect for particulate matter and discoloration prior to administration

Do not use preparations containing particulate matter

Reconstituted drug will be a clear to slightly opalescent, colorless to slightly yellow solution

IV Administration

Initial bolus injection followed by cont infusion

Storage

Store bivalirudin dosage units at 20-25°C (68-77°F);Excursions of 15-30°C permitted

Do not freeze reconstituted or diluted bivalirudin

Reconstituted material may be stored at 2-8°C up to 24 hours

Diluted bivalirudin with a concentration between 0.5mg/mL and 5mg/mL is stable at room temperature for up to 24 hours

Discard any unused portion of reconstituted solution remaining in vial

Manufacturer

  • The Medicines Company

Angiomax Drug Class

Angiomax is part of the drug class:

  • Direct thrombin inhibitors

How is Angiomax (bivalirudin)given?

Bivalirudin is injected into a vein through an IV. You will receive this injection during your angioplasty procedure in a clinic or hospital setting. The medicine must be given throughout the entire procedure.

Your doctor may want you to continue receiving bivalirudin for up to 20 hours after your angioplasty procedure.

Bivalirudin is usually given together with aspirin.

Because bivalirudin keeps your blood from coagulating (clotting) to prevent unwanted blood clots, it may be easier for you to bleed even from a minor injury. Contact your doctor or seek emergency medical attention if you have bleeding that will not stop.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Bivalirudin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

250 mg

Angiomax

Medicines Company

Precautions While Using Angiomax

It is very important that your doctor check you at regular visits after you leave the hospital for any problems or unwanted effects that may be caused by this medicine. Be sure to keep all appointments.

Bivalirudin may increase your chance of bleeding. Check with your doctor right away if you notice any unusual bleeding or bruising; black, tarry stools; blood in the urine or stools; or pinpoint red spots on your skin. Avoid picking your nose. If you need to blow your nose, blow it gently.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Very bad dizziness or passing out.
  • Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
  • Very bad headache.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Description

Angiomax contains bivalirudin which is a specific and reversible direct thrombin inhibitor. Bivalirudin is a synthetic, 20 amino acid peptide, with the chemical name of D-phenylalanyl-L-prolyl-L-arginyl-L-prolyl-glycyl-glycyl-glycyl-glycyl-L-asparagyl-glycyl-L-aspartyl-L-phenylalanyl-L-glutamyl-L-glutamyl-L-isoleucyl-L-prolyl-L-glutamyl-L-glutamyl-L-tyrosyl-L-leucine. The active pharmaceutical ingredient is in the form of bivalirudin trifluoroacetate as a white to off-white powder. The chemical name for bivalirudin trifluoroacetate is D-phenylalanyl-L-prolyl-L-arginyl-L-prolyl-glycyl-glycyl-glycyl-glycyl-L-asparagyl-glycyl-L-aspartyl-L-phenylalanyl-L-glutamyl-L-glutamyl-L-isoleucyl-L-prolyl-L-glutamyl-L-glutamyl-L-tyrosyl-L-leucine trifluoroacetate (Figure 1). The molecular weight of bivalirudin is 2180 daltons (anhydrous free base peptide).

Figure 1:  Structure formula for bivalirudin trifluoroacetate

Angiomax is supplied as a sterile white lyophilized cake, in single-dose vials. Each vial contains 250 mg bivalirudin, equivalent to an average of 275 mg of bivalirudin trifluoroactetate*, 125 mg mannitol, and sodium hydroxide to adjust the pH to 5-6 (equivalent of approximately 12.5 mg sodium). When reconstituted with Sterile Water for Injection, the product yields a clear to opalescent, colorless to slightly yellow solution, pH 5-6.

*The range of bivalirudin trifluoroacetate is 270 mg to 280 mg based on a range of trifluoroacetic acid composition of 1.7 to 2.6 equivalents.

What is bivalirudin (angiomax)?

Bivalirudin keeps the platelets in your blood from coagulating (clotting) to prevent unwanted blood clots that can occur with certain heart or blood vessel conditions.

Bivalirudin is used to prevent blood clots in people with severe chest pain or other conditions who are undergoing a procedure called angioplasty (to open blocked arteries).

Bivalirudin may also be used for purposes not listed in this medication guide.

What is the most important information i should know about bivalirudin (angiomax)?

You should not receive bivalirudin if you are allergic to it, or if you have any major bleeding from a surgery, injury, or other medical trauma.

Bivalirudin is not expected to be harmful to an unborn baby. However, aspirin is usually given with bivalirudin, and aspirin can cause bleeding when it is taken during the last 3 months of pregnancy. Aspirin can also cause side effects in a newborn baby.

Tell your doctor if you are pregnant before you are treated with bivalirudin and aspirin.

Before using bivalirudin, tell your doctor if you are allergic to any drugs, or if you have heart disease, kidney disease, or a bleeding or blood clotting disorder such as hemophilia.

Tell your doctor if you are using blood thinners or receiving any other medications to treat or prevent blood clots.

Because bivalirudin keeps your blood from coagulating (clotting) to prevent unwanted blood clots, it may be easier for you to bleed even from a minor injury. Contact your doctor or seek emergency medical attention if you have bleeding that will not stop.

Where can i get more information?

Your doctor or pharmacist can provide more information about bivalirudin.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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Side effects

Clinical Trials Experience

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.

Bleeding

In 6010 patients undergoing PCI treated in the REPLACE-2 trial, Angiomax patients exhibited statistically significantly lower rates of bleeding, transfusions, and thrombocytopenia as noted in Table 2.

Table 2: Major Hematologic Outcomes REPLACE-2 (Safety Population)

  ANGIOMAX with “provisional” GPI1
(n=2914)
HEPARIN + GPI
(n=2987)
Protocol defined major hemorrhage2 (%) 2.3% 4.0%
Protocol defined minor hemorrhage3 (%) 13.6% 25.8%
TIMI defined bleeding4
- Major 0.6% 0.9%
- Minor 1.3% 2.9%
Non-access site bleeding
- Retroperitoneal bleeding 0.2% 0.5%
- Intracranial bleeding <0.1% 0.1%
Access site bleeding
- Sheath site bleeding 0.9% 2.4%
Thrombocytopenia5
  <100,000 0.7% 1.7%
  <50,000 0.3% 0.6%
Transfusions
- RBC 1.3% 1.9%
- Platelets 0.3% 0.6%
1 GPIs were administered to 7.2% of patients in the Angiomax with provisional GPI group
2 Defined as the occurrence of any of the following: intracranial bleeding, retroperitoneal bleeding, a transfusion of ≥2 units of blood/blood products, a fall in hemoglobin > 4 g/dL, whether or not bleeding site is identified, spontaneous or non-spontaneous blood loss with a decrease in hemoglobin >3 g/Dl
3 Defined as observed bleeding that does not meet the criteria for major hemorrhage
4 TIMI major bleeding is defined as intracranial, or a fall in adjusted Hgb >5 g/dL or Hct of >15%: TIMI minor bleeding is defined as a fall in adjusted Hgb of 3 to <5 g/dL or a fall in adjusted Hct of 9 to <15%, with a bleeding site such as hematuria, hematemesis, hematomas, retroperitoneal bleeding or a decrease in Hgb of >4 g/dL with no bleeding site
5 If <100,000 and >25% reduction from baseline, or <50,000

In 4312 patients undergoing PTCA for treatment of unstable angina in 2 randomized, doubleblind studies comparing Angiomax to heparin, Angiomax patients exhibited lower rates of major bleeding and lower requirements for blood transfusions. The incidence of major bleeding is presented in Table 3. The incidence of major bleeding was lower in the Angiomax group than in the heparin group.

Table 3: Major Bleeding and Transfusions in BAT Trial (all patients)*

  ANGIOMAX
(n=2161)
HEPARIN
(n=2151)
No. (%) Patients with Major hemorrhage1 79 (3.7) 199 (9.3)
-with >3 g/dL fall in Hgb 41 (1.9) 124 (5.8)
-with >5 g/dL fall in Hgb 14 (0.6) 47 (2.2)
-retroperitoneal bleeding 5 (0.2) 15 (0.7)
-intracranial bleeding 1 (<0.1) 2 (0.1)
-Required transfusions 43 (2.0) 123 (5.7)
* No monitoring of ACT (or PTT) was done after a target ACT was achieved.
1 Major hemorrhage was defined as the occurrence of any of the following, intracranial bleeding, retroperitoneal bleeding, clinically overt bleeding with a decrease in hemoglobin ≥3 g/dL or leading to a transfusion of ≥2 units of blood. This table includes data from the entire hospitalization period.

In the AT-BAT study, of the 51 patients with HIT/HITTS, 1 patient who did not undergo PCI had major bleeding during CABG on the day following angiography. Nine patients had minor bleeding (mostly due to access site bleeding), and 2 patients developed thrombocytopenia.

Other Adverse Reactions

Adverse reactions, other than bleeding, observed in clinical trials were similar between the Angiomax treated patients and the control groups.

Adverse reactions (related adverse events) seen in clinical studies in patients undergoing PCI and PTCA are shown in Tables 4 and 5.

Table 4: Most Frequent (>0.2%) Treatment-related Adverse Events (reactions)(through 30 days) in the REPLACE-2 Safety Population

  ANGIOMAX with “provisional”
GPI1 (n=2914)
HEPARIN + GPI
(n =2987)
Patients with at least one treatment-related AE n (%) n (%)
78 (2.7) 115 (3.9)
Thrombocytopenia 9 (0.3) 30 (1.0)
Nausea 15 (0.5) 7 (0.2)
Hypotension 7 (0.2) 11 (0.4)
Angina pectoris 5 (0.2) 12 (0.4)
Headache 6 (0.2) 5 (0.2)
Injection site pain 3 (0.1) 8 (0.3)
Nausea and vomiting 2 (0.1) 6 (0.2)
Vomiting 3 (0.1) 5 (0.2)
1 Note: A patient could have been more than one event in any category.
Abbreviation: AE = Adverse Event

Table 5: Adverse Reactions Other Than Bleeding Occurring In ≥ 5% of Patients in Either Treatment Group in BAT Trial

Event Treatment Groups
ANGIOMAX
(n=2161)
HEPARIN
(n=2151)
Number of Patients (%)
Cardiovascular
  Hypotension 262 (12) 371 (17)
  Hypertension 135 (6) 115 (5)
  Bradycardia 118 (5) 164 (8)
Gastrointestinal
  Nausea 318 (15) 347 (16)
  Vomiting 138 (6) 169 (8)
  Dyspepsia 100 (5) 111 (5)
Genitourinary
  Urinary retention 89 (4) 98 (5)
Miscellaneous
  Back pain 916 (42) 944 (44)
  Pain 330 (15) 358(17)
  Headache 264 (12) 225 (10)
  Injection site pain 174 (8) 274 (13)
  Insomnia. 142 (7) 139 (6)
  Pelvic pain 130 (6) 169 (8)
  Anxiety 127 (6) 140 (7)
  Abdominal pain 103 (5) 104 (5)
  Fever 103 (5) 108 (5)
  Nervousness 102 (5) 87 (4)

Serious, non-bleeding adverse events were experienced in 2% of 2161 Angiomax-treated patients and 2% of 2151 heparin-treated patients. The following individual serious non-bleeding adverse events were rare (>0.1% to <1%) and similar in incidence between Angiomax- and heparin-treated patients. These events are listed by body system: Body as a Whole: fever, infection, sepsis; Cardiovascular: hypotension, syncope, vascular anomaly, ventricular fibrillation; Nervous: cerebral ischemia, confusion, facial paralysis; Respiratory: lung edema; Urogenital: kidney failure, oliguria. In the BAT trial, there was no causality assessment for adverse events.

Immunogenicity/Re-Exposure

In in vitro studies, Angiomax exhibited no platelet aggregation response against sera from patients with a history of HIT/HITTS.

Among 494 subjects who received Angiomax in clinical trials and were tested for antibodies, 2 subjects had treatment-emergent positive bivalirudin antibody tests. Neither subject demonstrated clinical evidence of allergic or anaphylactic reactions and repeat testing was not performed. Nine additional patients who had initial positive tests were negative on repeat testing.

Postmarketing Experience

Because postmarketing adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been identified during postapproval use of Angiomax: fatal bleeding; hypersensitivity and allergic reactions including reports of anaphylaxis; lack of anticoagulant effect; thrombus formation during PCI with and without intracoronary brachytherapy, including reports of fatal outcomes; pulmonary hemorrhage; cardiac tamponade; and INR increased.

Read the entire FDA prescribing information for Angiomax (Bivalirudin)

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