Lower risk of late coagulopathy after initial control1
- Late coagulopathy was seen at 1 study site using ANAVIP and 7 study sites using Fab Comparator1
- ANAVIP significantly improved lowest mean platelet countc and lowest mean fibrinogen leveld vs Fab Comparator1
- ANAVIP required a 3.5- to 6-fold lower maximum protein load than Fab Comparator to neutralize toxins1
- Treatment effect for ANAVIP was statistically significant in an exact logistic regression analysis adjusting for baseline coagulopathic effect and region5,b
ANAVIP reduced the risk of late coagulopathy seen with Fab Comparator1
Study design: In a randomized, prospective, blinded, controlled, multicenter study of 121 patients experiencing envenomation in the United States, two ANAVIP regimens were compared with the approved regimen for the Fab Comparator. After achieving initial control, maintenance dosing was administered every 6 hr with either blinded study drug (Group 1 and Group 3) or placebo (Group 2). The efficacy endpoint was the proportion of patients experiencing a coagulopathic effect (defined as absolute platelet levels <150,000/mm3, fibrinogen levels <150 mg/dL, or clinical coagulopathy requiring intervention) on Day 5 or Day 8.5
ap<0.05, Fisher’s exact test, Group 1 and Group 2 compared with Group 3. bOdds ratio adjusted for baseline coagulopathy vs Group 3 (95% confidence interval) for Group 1 was 0.184 (0.033, 0.794) and for Group 2 was 0.121 (0.010, 0.764). cMean platelet nadir (253.4 +/- 80.3 [103/mm3] for Group 1 and 247.5 +/- 62.6 [103/mm3] for Group 2 vs 208 +/- 76.9 [103/mm3] for Group 3; p<0.05). dMean fibrinogen nadir (340.0 +/- 70.0 mg/dL for Group 1 and 367.8 +/- 93.9 mg/dL for Group 2 vs 309.9 +/- 116.4 mg/dL for Group 3; p<0.05). Significance was only demonstrated in Group 2. eThe efficacy analysis did not meet the pre-specified statistically defined superiority criterion. However, the percentages of subjects showing prespecified criteria for coagulopathic effect on either Day 5 and/or Day 8 were 10.3% and 5.3% in the Groups 1 and 2 when compared to 29.7% in Group 3 indicating efficacy of ANAVIP in management of coagulopathic effect in patients with North American rattlesnake envenomation.
Important Safety Information
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.
The most common adverse reactions observed in more than 2 percent of patients in the clinical trials for ANAVIP were: pruritus, nausea, rash, arthralgia, peripheral edema, erythema, headache, myalgia, pain in extremity, and vomiting.
WARNINGS AND PRECAUTIONS
ANAVIP may cause allergic reactions.
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, tightness of the chest, wheezing, hypotension) occur, discontinue immediately and institute appropriate treatment.
Monitor patients with follow-up visits for signs and symptoms of delayed allergic reactions or serum sickness (rash, fever, myalgia, arthralgia, pruritus, urticarial rash) and treat appropriately if necessary.
Transmissible Infectious Agents
ANAVIP is made from equine (horse) plasma and may therefore carry a risk of transmitting infectious agents, e.g., viruses.
Reactions to Cresol
Trace amounts of cresol from the manufacturing process are contained in ANAVIP. Localized reactions and generalized myalgias have been reported with the use of cresol as an injectable excipient.