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Crotalidae Polyvalent Immune Fab (Ovine)

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DOI: 10.1177/001857870103601108

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 Hospital Pharmacy
Volume 36, Number 11, pp 1174–1182
2001 Facts and Comparisons

DRUG REVIEWS FROM

THE FORMULARY

Crotalidae Polyvalent Immune Fab (Ovine)

Dennis J. Cada, PharmD, FASHP, FASCP* (Editor),
Terri Levien, PharmD†, and Danial E. Baker, PharmD, FASCP, FASHP**

The North American Crotalinae are

Each month, subscribers to The Formulary® Monograph Service receive
a subfamily of the Viperidae, previous
five to six well-documented monographs on drugs that are newly
known as Crotalidae. These pit vipers
released or are in late Phase III trials. The monographs are targeted to
include the North American species of
your Pharmacy and Therapeutics Committee. Subscribers also receive
Agkistrodon (copperhead and cotton-
monthly one-page summary monographs on the agents that are useful
mouth snakes), Crotalus (rattlesnakes),
for agendas and pharmacy/nursing in-services. A comprehensive target
and Sistrurus (massasauga and pigmy
drug utilization evaluation (DUE) is also provided each month. The
rattlesnakes).4
monographs are published in printed form and on diskettes that allow
At the time of the bite, the snake
customization. Subscribers to the The Formulary Monograph Service
injects its venom into the subcutaneous
also receive access to a pharmacy bulletin board, The Formulary Infor-
tissue via a hollow, movable fang locat-
mation Exchange (The F.I.X). All topics pertinent to clinical and hospital
ed in its anterior mouth. Occasionally,
pharmacy are discussed on The F.I.X.
the venom is injected intramuscularly or
Through the cooperation of The Formulary, Hospital Pharmacy pub-
intravenously. The bitten area generally
lishes selected reviews in this column. If you would like information
shows fang marks and local edema.
about The Formulary Monograph Service or The F.I.X., call The Formu-
The venom contains digestive enzymes
lary at 800-322-4349. The October 2001 Formulary monograph topics are
and spreading factors. If these
darbepoetin alfa, alteplase for CVAD clearance, cefditoren pivoxil, digox-
snakebites are left untreated, local tis-
in immune fab, and teriparatide injection. The DUE is on darbepoetin alfa.
sue destruction, pain, local edema,
ecchymosis, bullae, taste changes,
*Executive Editor, The Formulary; †Drug Information Pharmacist, Drug Information Cen-
myotoxicity (eg, compartment syn-
ter, Washington State University Spokane; **Director, Drug Information Center and Pro-
fessor of Pharmacy Practice; College of Pharmacy, Washington State University drome, rhabdomyolysis), severe coagu-
Spokane, 601 West First Avenue, Spokane, WA 99201-3899. lation abnormalities (eg, defibrination
with or without thrombocytopenia), fas-
ciculation, hypertension, hypotension,
talinae envenomation.1 Antivenin (Cro- pulmonary edema, cardiovascular col-
Generic Name:
talidae) polyvalent is approved for the lapse, shock, renal failure, appendage
CROTALIDAE POLYVALENT
management of patients with enveno- loss, or death can occur. The mortality
IMMUNE FAB (OVINE)
mation caused by crotalid snakes, rate is 2.6% without antivenom therapy
Proprietary Name:
including the Crotalids native to North, with rapid emergency medical system
CroFab (Protherics)
Central, and South America (eg, rat- transport and critical care therapy and
FDA Approval Rating: 1S
tlesnake, copperhead moccasin, cotton- 0.28% when antivenom is added to this
Therapeutic Class:
mouth [water] moccasin, fer-de-lance, treatment. The mortality rate was 5% to
Antivenom
tropical rattler, and the Cantil) and bush- 25% prior to the use of rapid emergency
Similar Drugs:
master of Central and South America.2 medical system transport and critical
Antivenin (Crotalidae)
Each year it is estimated there are care therapy.3
Polyvalent (equine)
45,000 snakebites in the US and Bites are classified based on the
300,000 to 400,000 bites worldwide. amount of envenomation. A dry bite
INDICATIONS Approximately 8000 of these snakebites shows local puncture wound marks but
Crotalidae polyvalent immune Fab involve venomous species. The majori- is associated with no systemic effects or
(ovine), an orphan drug, is approved for ty of people bitten are males and about laboratory abnormalities. A mild enven-
the management of patients with mini- 50% occur in the age group of 18 to 28 omation is one that has local effects
mal or moderate North American Cro- years.3 around the bite area (eg, swelling, pain,

1174 Volume 36, November 2001


Comparison of Antivenin for North American Crotalinae Species
Property
Year marketed
Animal source
Immunoglobulin
(molecular weight)
Venoms used to
immunize animals
Total protein
Albumin
Total antibody
Purification method
Preservative
Viability
Onset
Duration
Sources: 1,2,4,7
ecchymosis) and no systemic or labora-
tory abnormalities. A moderate enveno-
mation shows local effects beyond the
immediate bite area (eg, swelling, pain,
ecchymosis), systemic effects (eg, vom-
iting, nausea, oral paresthesia, metallic
taste, mild hypotension, mild tachycar-
dia, tachypnea, fasciculations), and lab-
oratory abnormalities (eg, thrombocy-
topenia, decreased fibrinogen,
increased prothrombin time, and
increased creatine phosphokinase). A
severe envenomation shows local
effects (eg, swelling, pain, ecchymosis)
and may have compartment syndrome.
It is also associated with various sys-
temic effects (eg, severe hypotension,
shock, severe tachycardia, tachypnea,
respiratory insufficiency, diffuse or life-
threatening bleeding, renal failure, seri-
ous bleeding, severe threat of bleeding,
Drug Reviews From The Formulary
TABLE 1
Antivenin
(Crotalidae) Polyvalent
1954
Horse
IgG
(150,000 daltons)
Crotalus adamanteus
(Eastern diamondback);
C. atrox (Western diamondback);
C. durissus terrificus
(tropical rattlesnake);
Bothrops atrox (fer-de-lance)
2.1 g/vial
120 mg/vial (6% w/w)
IgG (18.9% w/w)
Ammonium sulfate
precipitation
Phenol, thimerosal
Inactive, passive, transient
Immediate (IV administration)
> 8 hours (IM injection)
< 15 days
and altered mental status). The labora-
tory abnormalities included thrombocy-
topenia, abnormal coagulation parame-
ters, rhabdomyolysis, and myoglobin-
uric renal failure. Administration of the
antivenom should be considered when
there are signs of envenomation pro-
gression or imminent risk of an acute
complication associated with enveno-
mation.1,3,4
CLINICAL PHARMACOLOGY
Crotalidae polyvalent immune Fab
(ovine) is harvested from the blood of
healthy sheep immunized with snake
venom from a North American Crotali-
nae (Crotalus atrox, Crotalus adaman-
teus, Crotalus scutulatus, or Agk-
istrodon piscivorus). The blood is frac-
tionated, the antibodies are digested
with papain, and the Fc fragments are
Crotalidae Polyvalent
Immune Fab (Ovine)
2001
Sheep
Fab
(50,000 daltons)
Crotalus adamanteus
(Eastern diamondback);
C. atrox (Western diamondback);
C. scutulatus (Mojave);
Agkistrodon piscivorus
(cottonmouth)
< 1 g/vial
< 1.5 g/vial (< 0.5% w/w)
Fab (> 85% w/w); Fc (< 3% w/w)
Sodium sulfate precipitation
and affinity purification
Thimerosal
Inactive, passive, transient
Immediate (IV administration)
Hours
removed and purified by ion exchange
and affinity chromatography. Once iso-
lated and purified, the monospecific
antivenins are combined to form a 4-
component antivenin.1,4,5,6
Wyeth’s antivenin is purified and
contains both the Fc and Fab fragments
of the IgG antibodies. See Table 1 for a
comparison of the two antivenins.2,6
Crotalidae polyvalent immune Fab
(ovine) should be given within 6 hours
of the snakebite to prevent clinical dete-
rioration and the occurrence of systemic
coagulation abnormalities. The Fab
antibody fragments work by binding and
neutralizing the toxic substances con-
tained in the venom of the crotalid
snakes. Once these toxic substances
are bound to the Fab antibody frag-
ments, it is redistributed away from the
target tissue and eliminated from the
Hospital Pharmacy 1175
Drug Reviews From The Formulary

TABLE 2 used to measure the severity of the

envenomation. The ICA is based on the
Comparison of Dosing for Crotalidae Antivenoms investigator’s clinical judgment: nonre-
sponse was when the agent showed no
Antivenin (Crotalidae) Crotalidae effect on the patient’s condition, partial
Polyvalent Polyvalent Immune
response was a worsening of the signs
Fab (Ovine)
and symptoms but at a slower rate, and
Test dose Intradermal injection of None clinical response was a stoppage of the
0.02 to 0.03 mL of signs and symptoms of the envenoma-
1:10 dilution tion or improvement after treatment.1
Intravenous dose Eleven patients were treated with
Minimal envenomation 2 to 4 vials 4 to 6 vials an IV dose of four vials of Crotalidae
Moderate envenomation 5 to 9 vials 4 to 6 vials
polyvalent immune Fab (ovine) over 60
Severe envenomation 10 to 15 vials or more Not recommended
minutes. Each of these patients had a
Infusion rate 5 to 10 mL of diluted 25 to 50 mL/hr for the
minimal or moderate North American
antivenom infused first 10 min and
over the first 3 to 5 min; then increased to 250 crotalid envenomation in the 6 hours
the rate is increased to mL/hr if no signs and preceding treatment, were Ž 10 years
the maximum safe rate symptoms of allergic of age, and had progression of enveno-
of IV fluid administration reaction mation syndrome. Patients were
Intramuscular dose Large muscle mass None excluded from treatment if the
(eg, gluteal area); snakebite was from an Agkistrodon
avoid nerve trunk;
contortrix (copperhead snake), had lack
maximum blood
concentrations may of apparent envenomation or lack of
take > 8 hrs progression, severe venom poisoning,
Repeat dosing 10 to 50 mL Envenomation not infusion of more than one vial of
(1 to 5 vials) based on controlled with the first Antivenin (Crotalidae) Polyvalent, pres-
clinical response and dose: 4 to 6 vials ence of major organ disease or electro-
should cardiographic or radiographic abnor-
severity of the be given.
malities that would interfere with the
envenomation Once control is
established: 2-vial clinical evaluation, history of hypersen-
doses sitivity to any sheep-derived product,
every 6 hours for up to any use of systemic corticosteroids, or
18 hours. Then PRN if were pregnant or lactating. A second
necessary.
four-vial dose could be used if neces-
Sources: 1,2,7 sary. If the second dose failed to pro-
duce a positive clinical effect, the thera-
py was classified as a failure.
After the first hour, 90.9% of
body.1 The product labeling describes the patients had no change or a decrease in
results of two prospective, open-label, the SSS and had a clinical response
PHARMACOKINETICS multicenter trials. The patients had to be based on the ICA. Several of the
Limited data are available regard- healthy other than having been patients (54.5%) required an additional
ing the pharmacokinetics of Crotalidae snakebitten, and the envenomation had dose of Crotalidae polyvalent immune
polyvalent immune Fab (ovine). Its esti- to be classified as minimal to moderate Fab (ovine) to stem progressive or
mated half-life is 12 to 23 hours.1 and caused by a North American crotal- recurrent signs and symptoms. One of
id (except copperheads). A total of 42 these patients was classified as a failure
COMPARATIVE EFFICACY patients were enrolled in these two tri- and was then treated with 10 vials of
Safety and efficacy comparisons of als.1 Antivenin (Crotalidae) Polyvalent and
Crotalidae polyvalent immune Fab Efficacy was determined using two improved after the supplemental
(ovine) and antivenin (Crotalidae) poly- scales: the Snakebite Severity Score antivenom infusion.1,8
valent (equine) have not been conduct- (SSS) and the investigator’s clinical Thirty-one patients were treated in
ed. assessment (ICA). The SSS is a tool the second study. This group of patients

1176 Volume 36, November 2001

 Drug Reviews From The Formulary

TABLE 3

Comparison of the Storage and Reconstitution Recommendations

for Antivenin for North American Crotalinae Species

Property Antivenin (Crotalidae) Polyvalent Crotalidae Polyvalent

Immune Fab (Ovine)

Dating period 60 months 30 months

Storage temperature
for above dating
Freezing
Dilution procedure
tion
should
Time to maximum level
of antivenom protein after
reconstitution
Median time for
reconstitution of dose
Stability after dilution
Sources: 1,7,13,14
Ž 37ºC (98.6º F)
Can tolerate up to three freeze/thaw cycles
Reconstitute the powder with 10 mL diluent
(Bacteriostatic Water for Injection with
0.001% phenylmercuric nitrate) and mix
by continuous gentle swirling. The contents
of the vial should be withdrawn and then
mixed with 0.9% Sodium Chloride USP or
5% Dextrose Injection and mixed by
gently swirling.
45 minutes
> 90 minutes
Room temperature for up to 48 hours
for the reconstituted solution and
12 hours for the final dilution.
2º to 8º C (36º to 46º F)
No
Reconstitute the lyophilized powder
with 10 mL of Sterile Water for Injec-
USP and mix by continuous gentle
swirling. The contents of the vial
be withdrawn and then mixed with
250 mL of 0.9% Sodium Chloride USP
and mixed by gently swirling.
25 minutes
40 minutes
Room temperature for up to 4 hours

were treated using two different dosing
schedules: One group was treated
using three doses at 6-hour intervals for
the first 18 hours of therapy (scheduled
group) and the other group was treated
as needed after the administration of
the first antivenin. The clinical response
based on ICA was 96.8% after 1 hour,
80.7% after 6 hours, and 83.9% after 12
hours. The SSS was decreased after 1,
6, and 12 hours in both groups.
Details of the number of patients
enrolled in each group and the number
of repeat doses in the as needed group
were not provided. However, the sum-
mary data indicate that the scheduled
group had a lower incidence of coagula-
tion abnormalities, and repeat doses
were required in the as needed group.
Both of these finding are indicators that
there is a need for continued antivenin
administration for adequate treatment.1
Successful therapy of crotalid-
induced neurotoxicity with Crotalidae
polyvalent immune Fab (ovine) was
noted in a case report of three patients.9
CONTRAINDICATIONS
Patients with a hypersensitivity to
papaya or papain should not use the
Crotalidae polyvalent immune Fab
(ovine) unless the benefits outweigh the
risks. If such a patient does receive the
antivenin, they need to be watched for
signs and symptoms of anaphylaxis and
managed accordingly.1
WARNINGS AND PRECAU-
TIONS
Skin testing is not necessary with
Crotalidae polyvalent immune Fab
(ovine), whereas skin testing must be
performed with patients scheduled to
receive the antivenin (Crotalidae) poly-
valent.2,3,7
Repeat administration of the
antivenin may be necessary to control
recurrent coagulopathy associated with
the envenomation. The patient may
experience an initial improvement and
then develop decreased fibrinogen,
decreased platelets, and elevated pro-
thrombin time. This is probably the
result of the short persistence of the
antivenin in the blood, redistribution of
the venom from depot sites over a pro-
longed period of time, and possible
unbinding of the venom from the
antivenom. The risk of recurrent coagu-
lopathy may persist for 1 to 2 weeks or
more after the snakebite.1,8,10,11,12
Patients should be monitored for at
least 1 week after treatment to deter-

Hospital Pharmacy 1177

Drug Reviews From The Formulary
mine the need for repeat administration.
In addition, the need for anticoagulants
or antiplatelet drugs should be carefully
assessed during this time frame.1
Trace amounts of papain or inacti-
vated papain residues may be present
in the antivenin. Patients allergic to
papain, chymopapain, other papaya
extracts, or the pineapple enzyme
bromelain may react to the antivenin. A
risk of cross reactivity may also be pre-
sent with allergies to dust mite allergens
and some latex allergens.1
Mercury can be found in the
antivenin in the form of ethyl mercury.
Its origin is the thimerosal that is used
as a preservative. Each vial contains
0.11 mg of mercury; the total average
dose used in clinical trials contained 1.9
mg of mercury.
All patients need to be monitored
for signs and symptoms of anaphylaxis,
anaphylactoid reactions, and allergic
reactions to the antivenin.1,6
The risk of coagulation may be
increased in patients with a coagulation
defects from another conditions (eg,
cancer, collagen disease, congestive
heart failure, diarrhea, elevated temper-
ature, hepatic disorders, hy-
perthyroidism, poor nutritional state,
steatorrhea, vitamin K deficiency).1
No information is available about
whether the efficacy or toxicity of Cro-
talidae polyvalent immune Fab (ovine)
is altered in patients who are pregnant,
breastfeeding, or in the geriatric or pedi-
atric age groups.
ADVERSE REACTIONS
The most common adverse effects
associated with Crotalidae polyvalent
immune Fab (ovine) therapy are
urticaria, rash, pruritus, and nausea.
The number of adverse events for a
given condition is small because of the
number of patients that have been treat-
ed with Crotalidae polyvalent immune
Fab (ovine). The number of patients
experiencing a specific adverse event in
the 42 patients treated with Crotalidae
polyvalent immune Fab (ovine) ranged
1178 Volume 36, November 2001
from 1 to 7 patients.1
DRUG INTERACTIONS
Drug interaction studies have not
been conducted with Crotalidae polyva-
lent immune Fab (ovine). Caution
should be used with drugs that might
cause coagulation defects.
RECOMMENDED MONITOR-
ING
Patients should be monitored
throughout therapy and for at least 1
week for signs and symptoms associat-
ed with the envenomation. If the signs
and symptoms worsen, a repeat course
of Crotalidae polyvalent immune Fab
(ovine) may be necessary.1,12
DOSING
The dose of Crotalidae polyvalent
immune Fab (ovine) is four to six vials
for patients with a minimal or moderate
envenomation caused by a North Amer-
ican crotalid. The antivenin should be
administered within 6 hours of the
snakebite to prevent clinical deteriora-
tion and the occurrence of systemic
coagulation abnormalities (see Table
2).1,7
One hour after the completion of
the first dose, a determination should be
made if the first dose of the antivenin
has controlled the envenomation. If not,
an additional dose of four to six vials
should be given. Once control is estab-
lished, additional two-vial doses of Cro-
talidae polyvalent immune Fab (ovine)
should be given every 6 hours for up to
18 hours. Additional doses may be nec-
essary after the first 18 hours based on
the patient’s clinical course.1,7
No dosing recommendations are
available for severe envenomation,
because no clinical data support the
efficacy of Crotalidae polyvalent
immune Fab (ovine) in this situation.1
Each vial should be reconstituted
with 10 mL of Sterile Water for Injection
USP and mixed by continuous gentle
swirling. The contents of the vial should
be withdrawn and then mixed with 250
mL of 0.9% Sodium Chloride USP and
mixed by gently swirling. The diluted
solution should be used within 4 hours.1
The total dose should be given
over 60 minutes as an infusion. The
infusion rate should be 25 to 50 mL/hr
for the first 10 minutes and then
increased to 250 mL/hr if no signs and
symptoms of allergic reaction occur.1
PRODUCT AVAILABILITY
Crotalidae polyvalent immune Fab
(ovine) is manufactured in Wales and
imported to the United States. Savage
Laboratories, a division of Altana Inc.,
will market and distribute CroFab in the
United States.1,13 See Table 3 for a com-
parison of the storage and reconstitu-
tion recommendations for antivenin for
North American Crotalinae species.
It may be possible to store the
antivenin in the field for a limited time.
The Crotalidae polyvalent immune Fab
(ovine) is heat stable at 50°C for 60
days and loses some potency when
stored at 70° C for 30 days.15
POSTMARKETING
REQUIREMENTS
Protherics is required by the FDA
to conduct a Phase 4 study to monitor a
surrogate clinical endpoint to determine
whether it can be used as a quality con-
trol parameter to detect changes in
product quality, measure residual
papain, evaluate the consistency of per-
formance of the antivenin, and validate
studies of its column lifetime and repro-
cessing procedures. In addition, studies
need to be conducted to develop a
matrix storage solution that does not
contain thimerosal.13
CONCLUSION
The Crotalidae polyvalent immune
Fab (ovine) is an effective means of
management for patients with minimal
or moderate North American Crotalinae
envenomation. It should be considered
an alternative to antivenin (Crotalidae)
polyvalent for most envenomation
caused by crotalid snakes. Both

antivenoms are given when there are
signs of envenomation progression or
imminent risk of an acute complication
associated with envenomation. The
Crotalidae polyvalent immune Fab
(ovine) can be used in patients with
documented allergies to equine pro-
teins. Neither one of these antivenoms
is a complete replacement for the other
agent. For example the Crotalidae poly-
valent immune Fab (ovine) has activity
against Agkistrodon piscivorus (cotton-
mouth), whereas this is not a compo-
nent of Antivenin (Crotalidae) Polyva-
lent.
REFERENCES
1. CroFab product labeling. Protherics;
December 2000.
2. McEvoy GK, Ed. American Hospital
Formulary Service: Drug Information
2001. Bethesda, MD: American Society
of Hospital Pharmacists; 2001.
3. Bush SP. Snake envenomations, rat-
tle from emergency medicine/environ-
mental. emedicine: Instant Access to
the Minds of Medicine; May 17, 2001.
w w w . e m e d i c i n e .
com/emerg/topic540.htm. Accessed on
May 22, 2001.
4. Dart RC, McNally J. Efficacy, safety,
and use of snake antivenoms in the
United States. Ann Emerg Med.
2001;37:181–8.
Drug Reviews From The Formulary
5. Consroe P, et al. Comparison of a Guidelines for clinical management with
new ovine antigen binding fragment crotaline Fab antivenom. Ann Emerg
(Fab) antivenin for United States Crotal- Med. 2001;37:196–201.
idae with the commercial antivenin for
protection against venom-induced 13.Product approval information: Cro-
lethality in mice. Am J Trop Med Hyg. talidae polyvalent immune Fab (Ovine).
FDA. October 2, 2000.
1995;53:507–10.
www.fda.gov/CBER/ approvaltr/cro-
6. Heard K, et al. Antivenom therapy in pro1002001.htm. Accessed on May 14,
the Americas. Drugs. 1999;58:5–15. 2001.
7. Grabenstein JD, ed. ImmunoFacts: 14.Hill RE, et al. Time to reconstitution:
Vaccines and Immunologic Drugs. St. Purified Fab antivenom vs unpurified
Louis, MO: Facts and Comparisons, IgG antivenom. Toxicon.
Inc.; 2001. 2001;39:729–31.
8. Dart RC, et al. Affinity-purified, 15.Decker WW, et al. Heat and motion
mixed monospecific crotalid antivenom stability of polyvalent Crotalidae
ovine Fab for the treatment of crotalid antivenin, ovine FAB. Toxicon.
venom poisoning. Ann Emerg Med. 1998;36:377–82.
1997;30:33–9.
9. Clark RF, et al. Successful treatment
of crotalid-induced neurotoxicity with a
new polyspecific crotalid Fab antiven-
om. Ann Emerg Med. 1997;30:54–7.
10.Seifert SA, et al. Relationship of
venom effects to venom antigen and
antivenom serum concentrations in a
patient with Crotalus atrox envenoma-
tion treated with a Fab antivenom. Ann
Emerg Med. 1997;30:49–53.
11. Seifert SA, Boyer LV. Recurrence
phenomena after immunoglobulin ther-
apy for snake envenomations: Part 1.
Pharmacokinetics and pharmacody-
namics of immunoglobulin antivenoms
and related antibodies. Ann Emerg
Med. 2001; 37:189–95.
12.Boyer LV, et al. Recurrence phe-
nomena after immunoglobulin therapy
for snake envenomations: Part 2.
Hospital Pharmacy 1179
Drug Reviews From The Formulary

Continuing Education Quiz

Goal — The goal of this program is to inform the participant about Crotali- 7. A severe envenomation is character-
dae polyvalent immune Fab (ovine). ized by:
A. No systemic effects
Objectives — At the completion of this program, the participant will be able B. Swelling and ecchymosis
to: around the bite mark, but no
1. Describe the pharmacology of Crotalidae polyvalent immune Fab laboratory abnormalities
(ovine). C. Mild hypotension and tachycar-
2. Apply the information on Crotalidae polyvalent immune Fab (ovine) to a dia along with pain at the bite
case study. mark
3. Discuss the risk associated with the use of Crotalidae polyvalent D. Respiratory insufficiency, com-
immune Fab (ovine). partment syndrome, and
4. Be able to discuss the potential benefit of Crotalidae polyvalent immune hypotension
Fab (ovine) in the treatment of a patient’s condition.
8. Administration of antivenom should
Key Words — antivenom; Crofab; Crotalidae polyvalent immune Fab be considered when:
(ovine); North American Crotalidae envenomation; pit viper bites A. Signs of envenomation get
worse
B. Risks of acute complications
Note: To answer some of the CE D. None of the above are apparent
questions, you may need to consult an C. Swelling and pain intensify and
additional reference (eg, Drug Facts 4. If untreated, an envenomation may ecchymosis occurs
and Comparisons). lead to: D. Any of the above occur
A. Local tissue destruction and
1. Crotalidae polyvalent immune Fab pain 9. Crotalidae polyvalent immune Fab
(ovine) is approved for the treatment B. Ecchymosis, bullae, and local (ovine) is harvested from:
of patients with: edema A. Horses
A. Minimal to moderate enveno- C. Myotoxicity and local edema B. Rabbits
mation D. All of the above C. Sheep
B. Moderate to severe envenoma- D. Snakes
tion 5. Administration of the correct
C. Severe envenomation antivenom can result in a _____-fold 10. Crotalidae polyvalent immune Fab
D. All of the above reduction in mortality. (ovine) contains:
A. 2.7 A. Fc fragments
2. Crotalidae polyvalent immune Fab B. 5.5 B. Whole antivenom antibodies
(ovine) is approved for use in the C. 7.2 C. Digestive enzymes
treatment of envenomations caused D. 9.3 D. All of the above
by:
A. Various pit vipers 6. A dry bite is characterized by: 11. The preservative used in Crotalidae
B. Constrictive snakes A. Local puncture wound marks polyvalent immune Fab (ovine) is:
C. Bull snakes but no systemic effects A. Phenol
D. All of the above B. Local effects around the bite B. Thimerosal
area C. Phenol and thimerosal
3. Envenomation generally involves: C. Swelling around the bite area D. Benzyl alcohol
A. Subcutaneous tissue D. Compartment syndrome and
B. Muscular tissue thrombocytopenia 12. The duration of the Crotalidae poly-
C. Intravenous administration valent immune Fab (ovine) antiven-

1180 Volume 36, November 2001


om is:
A. 5 hours
B. 5 days
C. < 15 days
D. 30 days
13. The effectiveness of Crotalidae poly-
valent immune Fab (ovine):
A. Is greater than antivenin (Cro-
talidae) polyvalent (equine)
B. Is less than antivenin (Crotali-
dae) polyvalent (equine)
C. Is equal to antivenin (Crotali-
dae) polyvalent (equine)
D. Compared with antivenin, (Cro-
talidae) polyvalent (equine) is
unknown
14. The efficacy of Crotalidae polyvalent
immune Fab (ovine) in the treatment
of snakebite has been assessed by:
A. Snakebite severity scores
B. Investigator’s clinical assess-
ment
C. Avoiding laboratory changes
D. All of the above
15. Crotalidae polyvalent immune Fab
(ovine) should not be used in
patients with:
A. Hypersensitivity reactions to
Drug Reviews From The Formulary
papaya associated with Crotalidae polyva-
B. Hypersensitivity reactions to lent immune Fab (ovine) administra-
benzyl alcohol tion are:
C. Hypersensitivity reactions to A. Urticaria and rash
phenol B. Hypotension and thrombocy-
D. All of the above topenia
C. Nausea and headaches
16. Skin testing is required prior to the D. Burning at the site of injection
administration of Crotalidae polyva-
lent immune Fab (ovine). 20. Crotalidae polyvalent immune Fab
A. True (ovine) should be given within
B. False _______ of the snakebite.
A. 2 hours
17. Patients should be monitored for at B. 6 hours
least _______ after treatment with C. 12 hours
Crotalidae polyvalent immune Fab D. 24 hours
(ovine) to determine the need for
repeat administration.
A. 1 hour
B. 24 hours
C. 72 hours
D. 1 week
18. The risk of coagulation is increased
in patients with:
A. Cancer
B. Heart failure
C. Hepatic disorders
D. All of the above
19. The most common adverse effects
Hospital Pharmacy 1181
Drug Reviews From The Formulary

Drug Evaluations: order to receive continuing education credit for this pro-
Crotalidae Polyvalent Immune Fab (Ovine) gram, you need a minimum correct response rate of
ACPE No. 071-999-01-049-H01 (0.2 CEU) 70%.
Program Expires: November 2004
To receive continuing education credit, complete this PROGRAM EVALUATION
form and mail with your $7 processing fee (made
Please rate our continuing education offering by
payable to WSU College of Pharmacy) to:
responding to the following questions:
Continuing Education Department
College of Pharmacy 1. Were the educational objectives met?
Washington State University Spokane n completely n fairly well n not at all
Health Sciences Building
Riverpoint Higher Education Campus 2. The overall quality of the program was:
310 North Riverpoint Boulevard n excellent n good n fair n poor
Spokane, WA 99202-1675
3. Was the content of this article relevant to the
Tel: (509) 358-7660
practice of pharmacy?
Print clearly or type. Please allow 4 weeks for process- n excellent n good n fair n poor
ing.
4. How long did it take you to complete this continuing
Name: _____________________________________ education program? _______ hours

___________________________________________ 5. What other continuing education programs or topics

_____ would you like to see?
Address: ___________________________________
_________________________________________
City: _______________ State: ______ Zip: _____
____
Note: Your answer sheet will be graded confidentially
and you will receive prompt notification of your score. In
_________________________________________

Answer Key
1. A B C D 11. A B C D

2. A B C D 12. A B C D

3. A B C D 13. A B C D

4. A B C D 14. A B C D
The Washington State Uni-
5. A B C D 15. A B C D versity College of Pharmacy is
approved by the American
6. A B C D 16. A B C D Council on Pharmaceutical
Education (ACPE) as a pro-
7. A B C D 17. A B C D vider of continuing pharmaceu-
tical education.
8. A B C D 18. A B C D

9. A B C D 19. A B C D

10. A B C D 20. A B C D

1182 Volume 36, November 2001

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