Riverside University Health System - Medical Center

Drug Monograph

Required Fields: Drug Name, Sentinel Events Advisories, US Boxed Warnings, REMS, Labeled Indication(s), Effectiveness/Clinical
Trials, NIOSH Category, Adverse Drug Reactions, Drug Interactions, Potential for Errors and Abuse, Other Risks, Population(s) Served
[e.g., pediatrics, geriatrics, etc.], Costs

Drug Generic Name Drug Trade Name

Crotalidae Immune F(ab)2 Anavip
Commercially Available Dosage Forms: Intravenous

US Boxed Warning:
 Thromboembolic risks, ischemic risks, cardiac arrest, and sudden deaths. 1

Risk Evaluation and Mitigation Strategy programs (REMS)

 No REMS component mandated

Sentinel Event Advisories

1. National Alert Network (NAN) Alerts
a. List all NAN alerts or None reported to date
b. Search: http://www.ismp.org/NAN/ > All NAN alerts should be reviewed to see if there is
anything pertaining to the medication that we should consider.
2. Sentinel Event Alerts
a. List all sentinel event alerts or None reported to date
b. Search: https://www.jointcommission.org/ > “Topics” > “Sentinel Event – Sentinel Event Alert” >
LEFT side in the “Sentinel Event Alert” box, click on view more
c. There have been a total of 56 Sentinel Event Alerts published to date (as of Jan 2017) since
TJC started publishing this information in 1998. The alerts usually talk about a topic and are
NOT medication-specific. Review all 56 to see if any of the alerts are applicable to the
medication being discussed. For example, if a medication is being introduced that increases the
risk for suicide ideation, Sentinel Event Alert 56: Detecting and treating suicide ideation in all
settings should be reviewed.

Statement of Need – Why Does RUHS Need This Medication?

 ANAVIP reduced the risk of late coagulopathy when compared with other FDA approved
treatments. An absolute risk reduction of 19.5-24.5% would suggest that 4-5 patients would
need to be treated with F(ab’)2 to result in fewer cases of late coagulopathy.
 Other anti-venom medications has serious bleeding complications after treatments, therefore,
Anavip can reduce late bleeding after snakebite, and the needed for repeated blood testing
after treatment could be reduced.
 Studies in Phase 2 has shown that Anavip was not associated with recurrent venom
antigenemia (antigen present in the blood) and a drop in platelet and fibrinogen levels (a drop
can cause bleeding).
 Has a long ½ life and does not need a maintenance therapy to prevent late coagulopathy.
 An affordable and less expensive anti-venom option compared to the other FDA approved
treatments

Sound-alike / Look-alike
P&T Approval Date:
This study source was downloaded by 100000857613368 from CourseHero.com on 01-23-2023 07:32:37 GMT -06:00
Page 1 of 9

https://www.coursehero.com/file/64495208/Anavip-Drug-Monographdoc/
  none

Pharmacologic Category / Mechanism of Action

 Drug Class: Antivenin
 Mechanism of Action: Contains venom-specific F(ab’)2 fragments of immunoglobulin G (IgG)
that bind and neutralize venom toxins, facilitating redistribution away from target tissues and
elimination from the body.
 Its administration following envenomation has been shown to prevent or reverse the
progression of local tissue damage and coagulopathy.
 Distribution: Vdss: 3.3 L
 Half-life: ~5.5 days
Use: Labeled Indication(s)
 Rattlesnake envenomation: Management of adult and pediatric patients with North American
rattlesnake envenomation
 Anavip [Crotalidae Immune F(ab’)2 (Equine)] is an equine-derived antivenin indicated for the
management of adult and pediatric patients with North American rattlesnake envenomation.
 Administration: IV
Infuse intravenously over 60 minutes. Infuse at a rate of 25 to 50 mL/hour for the first 10
minutes, carefully monitoring for any allergic reactions. If no reactions occur, increase the
infusion rate to 250 mL/hour until completion. Discontinue the infusion if any allergic reaction
occurs and institute appropriate emergency treatment. Reassess the risk to benefit ratio before
continuing the infusion.
 Administration: Pediatric
IV: Infuse intravenously over 60 minutes. Infuse at a rate of 25 to 50 mL/hour for the first
10 minutes, carefully monitoring for any allergic reactions. If no reactions occur, increase the
infusion rate to 250 mL/hour until completion. Discontinue the infusion if any allergic reaction
occurs and institute appropriate emergency treatment. Reassess the risk to benefit ratio before
continuing the infusion.

Effectiveness/Clinical Trials
 Clinical Trials: Andexxa has been shown to reduce anti-factorXa activity to at least 80% within
2-5 minutes and maintaining that level for up to 2 hours. 2
 Effectiveness: Not applicable. This drug was approved on May 3, 2018. 2

Pharmacodynamics / Pharmacokinetics3

Absorption Not applicable

Distribution Andexxa is approximately equivalent to the blood volume of 5 L
Protein Binding Highly protein bound
Metabolism Not applicable
Half-life 5 to 7 hours ( clearance is approximately 4.3 L/hr )
Time to peak One minute
Excretion Urine ( refer to PI )
Duration of Refer to graph on PI
action

Administration and Dosage1

 Intravenous use only
P&T Approval Date:
This study source was downloaded by 100000857613368 from CourseHero.com on 01-23-2023 07:32:37 GMT -06:00
Page 2 of 9

https://www.coursehero.com/file/64495208/Anavip-Drug-Monographdoc/
  Initial: Ten vials; may repeat every hour as needed until local signs of envenomation are not
progressing, systemic symptoms are resolved and coagulation parameters have normalized or
are trending toward normal. There is no known maximum dose.
 Maintenance: Four vials as needed; may administer for any re-emerging symptoms, including
coagulopathies
 The initial dose of Anavip is 10 vials.
Reconstitute the contents of each vial with 10 milliliters (mL) of sterile normal saline.
Reconstitution time should be less than one minute.
Inspect the solution visually for particulate matter and discoloration prior to
administration. The solution is expected to be clear to yellow/green and opalescent. Do not use
if otherwise discolored or turbid.
Combine the contents of the reconstituted vials promptly and further dilute to a total
volume of 250 mL with sterile normal saline. Fluid volumes may need to be adjusted for very
small children or infants. Poison Control Centers are a helpful resource for individual treatment
advice.
Infuse intravenously over 60 minutes. For the first 10 minutes infuse at a 25-50
mL/hour rate, carefully monitoring for any allergic reactions, including an anaphylactic
reactions. Discontinue the infusion if any allergic reaction occurs and institute appropriate
emergency treatment.
Reassess the risk to benefit before continuing the infusion. If no reactions occur, the
infusion rate may be increased to the full 250 mL/hour rate until completion. If there is any
allergic reaction at any time, stop the infusion, treat accordingly, and reassess the need to
continue Anavip.
Following the completion of infusion, monitor the patient for at least 60 minutes for any
allergic reaction and to determine that local signs of envenomation are not progressing
(leading edge of local injury not progressing), systemic symptoms are resolved and
coagulation parameters have normalized or are trending toward normal.
Discard partially or unused reconstituted and diluted product.
 Additional Dosing to Achieve Initial Control:
Administer additional 10 vial doses if needed to arrest the progressive symptoms and repeat
every hour. There is no known maximum dose.
Repeat above steps for initial dose as many times as needed until local signs of envenomation are
not progressing, systemic symptoms are resolved and coagulation parameters have normalized or are
trending toward normal.
Prepare as described above for the initial dose.
Once initial control has been achieved, observe the patient to determine any need for further
dosing, as described below.
 Observation and Late Dosing
Monitor patients in a health care setting for at least 18 hours following initial control of signs and
symptoms. Re-emerging symptoms including coagulopathies may be suppressed with additional 4 vial
doses of Anavip as needed. Reconstitute each vial with 10 mL of sterile normal saline. Combine and
further dilute to a total of 250 mL. Infuse intravenously over 60 minutes.

P&T Approval Date:

This study source was downloaded by 100000857613368 from CourseHero.com on 01-23-2023 07:32:37 GMT -06:00
Page 3 of 9

https://www.coursehero.com/file/64495208/Anavip-Drug-Monographdoc/
 Monitoring Parameters1
 Vital signs; CBC, platelet count, prothrombin time, aPTT, fibrinogen levels, fibrin split products, clot
retraction, bleeding and coagulation times, BUN, electrolytes, bilirubin (prior to administration and
at regular intervals to gauge response to therapy and anticipate additional dosage requirement);
size of bite area (repeat every 15 to 30 minutes); intake and output; signs and symptoms of
anaphylaxis/allergy. Following the initial control of signs and symptoms, CBC, platelet counts, and
clotting studies are evaluated at 6- to 8-hour intervals until patient is stable (Lavonas 2011). The
manufacturer recommends monitoring patients in a health care setting for at least 18 hours
following initial control of signs and symptoms.
Reconstitution, Stability, and Storage1
 Store at room temperature (up to 25ºC [77ºF]). Brief temperature excursions are permitted up
to 40ºC (104ºF). Do not freeze. Discard partially used vials.
 Preparation for Administration: Adult
Reconstitute the contents of each vial with 10 mL of sterile normal saline; gently swirl to
mix. The solution should be clear to yellow/green and opalescent. Do not use if otherwise
discolored or turbid. Dilute dose (eg, 10 vials) to a total volume of 250 mL with sterile normal
saline.
 Preparation for Administration: Pediatric
Reconstitute the contents of each vial with 10 mL of sterile normal saline; gently swirl to
mix. The solution should be clear to yellow/green and opalescent. Do not use if otherwise
discolored or turbid. Dilute dose (Initial: 10 vials; maintenance: 4 vials) to a total volume of 250
mL with sterile normal saline. Fluid volumes may need to be adjusted for very small children or
infants.
National Institute for Occupational Safety and Health (NIOSH) Handling Category (Select One)
 Anti-Neoplastic
 Hazardous Non Anti-Neoplastic
 Reproductive Risk
 None

Contraindications
 None

Adverse Drug Reactions1

 Frequency not always defined.
 Cardiovascular: Peripheral edema (8%)
 Central nervous system: Headache (6%), chills (4%), anxiety (2%), insomnia (2%)
 Dermatologic: Pruritus (43%), skin rash (12%), skin blister (5%), erythema (4%)

P&T Approval Date:

This study source was downloaded by 100000857613368 from CourseHero.com on 01-23-2023 07:32:37 GMT -06:00
Page 4 of 9

https://www.coursehero.com/file/64495208/Anavip-Drug-Monographdoc/
  Endocrine & metabolic: Dehydration (2%)
 Gastrointestinal: Nausea (23%), vomiting (6%)
 Hematologic & oncologic: Thrombocytopenia (1%)
 Hypersensitivity: Hypersensitivity
 Neuromuscular & skeletal: Arthralgia (11%), myalgia (7%), limb pain (6%)
 Respiratory: Dyspnea (1%)
 Miscellaneous: Fever (5%)

Drug Interactions
 None

Warnings / Precautions1
 Acute hypersensitivity reactions: Derived from equine (horse) immune globulin
F(ab’)2 fragments; anaphylaxis and anaphylactoid reactions are possible, especially in patients
with known allergies to horse protein.
 Patients with known allergies to horse protein are particularly at risk for an anaphylactic
reaction. If signs or symptoms of anaphylaxis or hypersensitivity reactions (including urticaria,
rash, and tightness of the chest, wheezing, hypotension) occur, discontinue immediately and
institute appropriate treatment.
 Patients who have had previous treatment with Crotalidae immune F(ab’)2 or other equine-
derived antivenom/antitoxin may be at a higher risk for hypersensitivity reactions. In patients
who develop an anaphylactic reaction, discontinue the infusion and administer emergency
care.
Delayed serum sickness: Delayed serum sickness may occur, usually within 2 weeks; monitor
patients with follow-up visits for signs and symptoms (eg, arthralgia, fever, myalgia, pruritus,
rash, urticaria).
 Dosage form related issues:
Cresol: Product may contain small amounts of cresol resulting from the manufacturing
process; local reactions and generalized myalgias may occur.
Disease transmission: Product derived from equine (horse) plasma; may potentially
contain infectious agents (eg, viruses) which could transmit disease.

Potential for Errors and Abuse1

 Should not be used for more than 2 hours

Other Risks
 Pregnancy risk factor: C

Pregnancy and Lactation1

 Pregnancy Considerations
Animal reproduction studies have not been conducted. In general, the health and
prognosis of the mother should be taken into consideration when using medications as
antidotes; they should be administered to pregnant women if there is a clear indication for use
and should not be withheld because of fears of teratogenicity. Experience with the use of
P&T Approval Date:
This study source was downloaded by 100000857613368 from CourseHero.com on 01-23-2023 07:32:37 GMT -06:00
Page 5 of 9

https://www.coursehero.com/file/64495208/Anavip-Drug-Monographdoc/
 antivenom in pregnancy is limited; however, treatment with antivenom should be considered in
snake envenomation in which it is usually required as definitive management or in
envenomations refractory to supportive care (Brown 2013).
 Breast-Feeding Considerations
It is not known if Crotalidae Immune F(ab’)2 (Equine) is excreted in breast milk. The
manufacturer recommends that caution be exercised when administering this antivenin to
nursing women.
Population(s) Served [e.g., pediatrics, geriatrics, etc.] 1
 Geriatric: refer to adult dosing
 Dosing: Renal Impairment: Adult
There are no dosage adjustments provided in the manufacturer’s labeling
 Dosing: Hepatic Impairment: Adult
There are no dosage adjustments provided in the manufacturer’s labeling
 Dosing: Pediatric
Note: Initiate therapy as soon as possible after a rattlesnake bite in patients exhibiting
any signs of envenomation.
 Rattlesnake envenomation: Infants, Children, and Adolescents: IV:
Initial: Ten vials; may repeat every hour as needed until local signs of envenomation are
not progressing, systemic symptoms are resolved, and coagulation parameters have
normalized or are trending toward normal.
Maintenance: Four vials as needed; may administer for any reemerging symptoms,
including coagulopathies
 Dosing: Renal Impairment: Pediatric
There are no dosage adjustments provided in the manufacturer's labeling.
 Dosing: Hepatic Impairment: Pediatric
There are no dosage adjustments provided in the manufacturer's labeling.

Costs (Consider WAC, GPO, 340B)

Date Obtained: 06/11/2018
Source: AmerisourceBergen (Cindra, ASD)

Strength/Concentratio WAC GPO 340B

n and Volume
Andexxa 100 mg/vial 11000.00 N/A N/A
(4 pack)

 Currently, there are only 20 hospitals across the nation that currently has access to Andexxa. It
may not be until 2019 that the manufacturer opens this item up to more hospitals. (Shareef
Mohamed, AmerisourceBergen)

Product Return and Replacement Opportunity Details (applicable for expensive medications)
 Contact manufacturer: Portola Pharmaceuticals, Inc

P&T Approval Date:

This study source was downloaded by 100000857613368 from CourseHero.com on 01-23-2023 07:32:37 GMT -06:00
Page 6 of 9

https://www.coursehero.com/file/64495208/Anavip-Drug-Monographdoc/
 Comparison to Formulary Medications

Strength/Concentration WAC GPO 340B

and Volume
Kcentra 540 IU 874.80 874.80 N/A

Activated 50 g (8 oz) 32.99 25.23 28.01

Charcoal

Criteria of Use
 Reversal of anticoagulation from Apixaban or Rivaroxaban: Reversal of anticoagulation in
patients with apixaban or rivaroxaban experiencing life-threatening or uncontrolled bleeding. 1
 Life-threatening bleed referring to all bleeds associated with hemodynamic compromise,
occurring in an anatomically critical site (e.g., intracranial), or associated with a decrease of
hemoglobin >2 g/dL (when baseline is known) or requiring transfusion of >2 U of packed
RBCs.11

Recommendation(s) (Inpatient/Outpatient/MISP, Dosage Forms, Restrictions)

 Add to inpatient/Medically Indigent Services Program (MISP) formulary
 Dosage Form: Intravenous3
 Restrictions: The safety of ANDEXXA has not been evaluated in patients who experienced
thromboembolic events or disseminated intravascular coagulation within two weeks prior to the life-
threatening bleeding event requiring treatment with ANDEXXA. Safety of ANDEXXA also has not
been evaluated in patients who received prothrombin complex concentrates, recombinant factor
VIIa, or whole blood products within seven days prior to the bleeding event. 1

P&T Approval Date:

This study source was downloaded by 100000857613368 from CourseHero.com on 01-23-2023 07:32:37 GMT -06:00
Page 7 of 9

https://www.coursehero.com/file/64495208/Anavip-Drug-Monographdoc/
  Anti-FXa activity was measured prior to and after ANDEXXA or placebo administration. 2
 Dashed lines indicate the end of the bolus or infusion. A break in the x-axis is added to better
visualize the immediate, short-term dynamics of anti-FXa activity following ANDEXXA
treatment. The points on the graph represent the mean anti-FXa activity level; error bars
illustrate standard error. There was a statistically significant difference (p < 0.05) in the percent
change of anti-FXa activity normalized to pre-bolus between ANDEXXA and placebo until 2
hours after administration of infusion.2
A. Apixaban – with ANDEXXA 400 mg IV bolus plus 4 mg/min infusion for 120 minutes.
B. Rivaroxaban – with ANDEXXA 800 mg IV bolus plus 8 mg/min infusion for 120 minutes.

P&T Approval Date:

This study source was downloaded by 100000857613368 from CourseHero.com on 01-23-2023 07:32:37 GMT -06:00
Page 8 of 9

https://www.coursehero.com/file/64495208/Anavip-Drug-Monographdoc/
 References(s)

1. Dietrich, Scott, et al. “Anavip: Is the Juice Worth the Squeeze?” EM PharmD, 16 Jan. 2020,
empharmd.com/2019/12/07/anavip-is-the-juice-worth-the-squeeze/.
2. Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet Alfa for the Reversal of Factor Xa
Inhibitor Activity. New England Journal of Medicine. 2015;373(25):2413-2424.
doi:10.1056/NEJMoa1510991
3. Andexanet Alfa. Lexicomp Online.
https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6640361. Accessed June 18, 2017.
4. Xarelto (rivaroxaban) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc;
May 2016.
5. Eliquis (Apixaban) [prescribing information]. Princeton, NJ: Bristol-Myers Quibb Company; Dec
2012.
6. Apixaban. Lexicomp Online.
https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/3804162. Accessed June 18, 2017.
7. Frontera JA, Lewin III JJ, Rabinstein AA, et al. Guideline for Reversal of Antithrombotics in
Intracranial Hemorrhage: A Statement for Healthcare Professionals from the Neurocritical Care
Society and Society of Critical Care Medicine. Neurocritical Care. 2016;24(1):6-46.
doi:10.1007/s12028-015-0222-x
8. Summers RL, Sterling SA. Emergent Bleeding in Patients Receiving Direct Oral
Anticoagulants. Air Medical Journal. 2016;35(3):148-155. doi:10.1016/j.amj.2016.01.001
9. Hellenbart E, Faulkenberg K, Finks S. Evaluation of bleeding in patients receiving direct oral
anticoagulants. Vascular Health and Risk Management. 2017;Volume 13:325-342.
doi:10.2147/VHRM.S121661
10. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline
and expert panel report. Chest. 2016;149(2):315–352.
11. Tomaselli GF, Mahaffey KW, Cuker A, et al. 2017 ACC Expert Consensus Decision Pathway on
Management of Bleeding in Patients on Oral Anticoagulants. Journal of the American College
of Cardiology. 2017;70(24):3042-3067. doi:10.1016/j.jacc.2017.09.1085

P&T Approval Date:

This study source was downloaded by 100000857613368 from CourseHero.com on 01-23-2023 07:32:37 GMT -06:00
Page 9 of 9

https://www.coursehero.com/file/64495208/Anavip-Drug-Monographdoc/
Powered by TCPDF (www.tcpdf.org)