1. Rapivab™ - peramivir injection
Manufacturer:
BioCryst Pharmaceuticals
FDA Approval Date: 12/19/2014

2. Rapivab™ - peramivir injection Clinical Application
Indications:
Acute, uncomplicated influenza in patients 18 years and older who have been symptomatic for less than 2 days
Place in therapy:
Rapivab should be used in patients who:
test positive for the influenza virus
have symptoms for less than 48 hours AND
are unable to tolerate inhaled or PO medication

3. Rapivab™ - peramivir injection Clinical Application
Contraindications:
NONE
Warnings/ Precautions:
Serious skin and hypersensitivity reactions
Neuropsychiatric events
Risk of bacterial infections

4. Rapivab™ - peramivir injection Clinical Application
Pregnancy:
Category C
Lactation:
Not known if the drug is excreted in human breast milk

5. Rapivab™ - peramivir injection Drug Facts
Pharmacology:
An injectable neuraminidase inhibitor for the influenza virus. Through inhibition of the neuraminidase enzyme, peramivir prevents infected cells from releasing viral particles.

6. Rapivab™ - peramivir injection Drug Facts
Pharmacokinetics: A
100% bioavailability D
Vd: L
< 30% protein binding M
Not significantly metabolized E
T1/2: ~20 hours
eliminated via the kidney with 90% unchanged

7. Rapivab™ - peramivir injection Drug Interactions
Drug Interactions – Object Drugs:
Influenza Virus Vaccine  (variable %)

8. Rapivab™ - peramivir injection Drug Interactions
Drug Interactions – Precipitant Drugs:
NONE

9. Rapivab™ - peramivir injection Adverse Effects
Placebo
Diarrhea 8% 6%
Alanine Aminotransferase (> 2.5 x ULN) 3% 2%
Serum Glucose
(> 160 mg/dL) 5%
Creatine Phosphokinase
(≥ 6.0 x ULN) 4%
Neutrophils
(< x109 /L)

10. Rapivab™ - peramivir injection Monitoring Parameters
Efficacy Monitoring:
Resolution of influenza symptoms (headache, aches/pains, fatigue, cough, sore throat, nasal congestion)
Toxicity Monitoring:
Neurological abnormalities/abnormal behavior
Rash after administration

11. Rapivab™ - peramivir injection Prescription Information
Dosing: 600mg IV infusion over 15 minutes
Cost: No information at this time

12. Rapivab™ - peramivir injection Literature Review
Efficacy and Safety of Intravenous Peramivir for Treatment of Seasonal Influenza Virus Infection
Purpose: To determine the safety and efficacy of a single administration of peramivir in patients with the influenza virus in the outpatient setting
Design: Randomized, double-blind, placebo controlled trial
Kohno S et al. AAC Nov, 54(11):

13. Rapivab™ - peramivir injection Literature Review
Inclusion
Exclusion
20 – 64 year old, previously healthy
Respiratory dysfunction/ chronic respiratory disorder
Onset of influenza symptoms < 48 H
Convulsions or other neurological symptoms
Positive rapid antigen test
HIV
Fever > 38o C
Renal impairment requiring hemodialysis
Presence of at least 2 flu symptoms
Treatment with steroids/ other immunosuppressants or anti-influenza drugs within the previous 7 days
Women who are pregnant
Kohno S et al. AAC Nov, 54(11):

14. Rapivab™ - peramivir injection Literature Review
Peramivir 300mg
Peramivir 600mg
Placebo
Male
46 [46.5%]
53 [54.6%]
51 [51%]
Age
34.2
33.9
34.4
Symptom Onset
0 – 24 hours
59 [59.6%]
51 [52.6%]
48 [48%]
24 – 48 hours
40 [40.6%]
46 [47.4%]
52 [52%]
Composite symptom score
11.5
11.8
12.0
Body temperature
38.44
38.64
38.50
Influenza virus
A/H1
74 [74.7%]
69 [71.1%]
72 [72%]
A/H3
21 [21.2%]
25 [25.8%]
24 [24%]
A/-
2 [2.0%]
2 [2.1%]
4 [4%] B
2 [1.0%]
0 [0%]
Kohno S et al. AAC Nov, 54(11):

15. Rapivab™ - peramivir injection Literature Review
Primary Endpoint: time from start of treatment to recovery (all influenza symptoms scores had been 0 or 1 for hours)
Other Endpoints:
Change in composite symptom scores
Proportion of afebrile subjects
Change in influenza titer from baseline
Time to resume usual activity
Incidence of influenza related illness
Kohno S et al. AAC Nov, 54(11):

16. Rapivab™ - peramivir injection Literature Review
Statistical Analysis:
Intention to Treat
67 subjects needed per group to have 80% power
Treatment Arms:
300 mg peramivir (n=99)
600 mg peramivir (n=97)
Placebo (n=100)
Kohno S et al. AAC Nov, 54(11):

17. Rapivab™ - peramivir injection Literature Review
Primary Endpoint:
Rapivab significantly reduced the time to alleviation of influenza symptoms compared to the placebo.
HR: (adjusted P value, ) in the 300 mg group
HR: (adjusted P value, ) in the 600 mg group
Patients reported shorter time in resumption of there usual activities
Kohno S et al. AAC Nov, 54(11):

18. Rapivab™ - peramivir injection Literature Review
Effect of Rapivab on viral shedding:
At baseline viral titers similar in all groups
At 3 days: virus positive patients were lower in the treatment arms
300 mg P: , 600 mg P:
At 9 days: virus was not detected in most patients
Kohno S et al. AAC Nov, 54(11):

19. Rapivab™ - peramivir injection Literature Review - Results
Population
Parameter
Peramivir 300 mg
Peramivir 600 mg
Placebo
Overall N
Median (hr) HR
Adjusted P 99
59.1
0.681
0.0092 97
59.9
0.666
100
81.8
Influenza
A/H1 74
52.5
0.779
0.145 69
62.6
0.899
0.5384 72
81.4
A/H3 21
76.1
0.542
0.0556 25
50.5
0.326
0.0008 24
81.0
Symptom duration
0 – 24 hr 59
57.2
0.653
0.0516 51
56.1
0.663 48
86.7
24-48 hr 40
69.1
0.708
0.1118 46
64.7
0.694 52
70.8
Kohno S et al. AAC Nov, 54(11):

20. Rapivab™ - peramivir injection Literature Review – Adverse Events
Parameter
Rapivab 300 mg
Rapivab 600 mg
Placebo
Number of Events
252
257
Increased Glucose
18 (18.25)
17 (17.2%)
18 (18%)
Decreased WBC
9 (9.1%)
7 (7.1%)
4 (4%)
Diarrhea
14 (14.1%)
15 (15.2%)
17 (17%)
Nausea
3 (3%)
6 (6.1%)
1 (1%)
Increase ALT
8 (8%)
Increase AST
6 (6%)
Prolonged QT Interval
2 (2%)
Kohno S et al. AAC Nov, 54(11):

21. Rapivab™ - peramivir injection Literature Review
Discussion:
Rapivab was well tolerated by most patients
Patients saw improvement in influenza symptoms within 24 hours of administration
Rapivab showed high activity against neuraminidase with a slow off rate
Plasma concentrations of Rapivab were higher than those from standard dose of Tamiflu
Kohno S et al. AAC Nov, 54(11):

22. Rapivab™ - peramivir injection Summary
Rapivab, peramivir, is a 600 mg, one time 15 minute IV infusion for patients who have uncomplicated influenza symptoms for less than 2 days
Not significantly metabolized, is renally cleared and should be administered at lower doses with impaired renal function
May decrease the efficacy of the influenza vaccine, and should not be used 48 hours prior to 2 weeks after vaccine administration
Can cause diarrhea, hyperglycemia or neutropenia. Rarely causes serious skin reactions or neurologic complications

23. Rapivab™ - peramivir injection References
Rapivab package insert. BioCryst Pharmaceuticals. December 2014.
Peramivir: Drug information. Lexicomp Drug Information. Accessed through UpToDate. Accessed on January 10, 2015.
Kohno S et al. AAC Nov, 54(11):