Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date:...
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Transcript of Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date:...
Rapivab™ - peramivir injection
Manufacturer:
BioCryst Pharmaceuticals
FDA Approval Date: 12/19/2014
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
Rapivab™ - peramivir injection
Clinical Application
• Contraindications:• NONE
• Warnings/ Precautions:• Serious skin and hypersensitivity
reactions
• Neuropsychiatric events
• Risk of bacterial infections
Rapivab™ - peramivir injection
Clinical Application
• Pregnancy:• Category C
• Lactation:• Not known if the drug is excreted in
human breast milk
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.
Rapivab™ - peramivir injection
Drug Facts
• Pharmacokinetics:
A 100% bioavailability
DVd: 12.56 L < 30% protein binding
M Not significantly metabolized
ET1/2: ~20 hourseliminated via the kidney with 90% unchanged
Rapivab™ - peramivir injection
Drug Interactions
• Drug Interactions – Object Drugs: • Influenza Virus Vaccine (variable %)
Rapivab™ - peramivir injection
Drug Interactions
• Drug Interactions – Precipitant Drugs: • NONE
Rapivab™ - peramivir injection
Adverse Effects
Rapivab (peramivir) Placebo
Diarrhea 8% 6%
Alanine Aminotransferase
(> 2.5 x ULN) 3% 2%
Serum Glucose (> 160 mg/dL)
5% 3%
Creatine Phosphokinase (≥ 6.0 x ULN)
4% 2%
Neutrophils (< 1.000 x109 /L)
8% 6%
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
Rapivab™ - peramivir injection
Prescription Information
• Dosing: 600mg IV infusion over 15 minutes
• Cost: No information at this time
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. 2010 Nov, 54(11): 4568-4574
Rapivab™ - peramivir injection
Literature Review
Inclusion Exclusion
20 – 64 year old, previously healthy Respiratory dysfunction/ chronic
respiratory disorder
Onset of influenza symptoms < 48 HConvulsions or other neurological
symptoms
Positive rapid antigen test HIV
Fever > 38o CRenal 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. 2010 Nov, 54(11): 4568-4574
Rapivab™ - peramivir injection
Literature ReviewPeramivir 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 [2.0%] 2 [1.0%] 0 [0%]
Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574
Rapivab™ - peramivir injection
Literature Review
• Primary Endpoint: time from start of treatment to recovery (all influenza symptoms scores had been 0 or 1 for 21.5 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. 2010 Nov, 54(11): 4568-4574
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. 2010 Nov, 54(11): 4568-4574
Rapivab™ - peramivir injection
Literature Review
• Primary Endpoint:
• Rapivab significantly reduced the time to alleviation of influenza symptoms compared to the placebo. • HR: 0.681 (adjusted P value, 0.0092) in the 300 mg
group
• HR: 0.666 (adjusted P value, 0.0092) in the 600 mg group
• Patients reported shorter time in resumption of there usual activities
Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574
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: 0.0485, 600 mg P: 0.0003
• At 9 days: virus was not detected in most patients
Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574
Rapivab™ - peramivir injection
Literature Review - Results
Population Parameter Peramivir 300 mg Peramivir 600 mg Placebo
Overall NMedian (hr)
HRAdjusted P
9959.1
0.6810.0092
9759.9
0.6660.0092
10081.8
Influenza
A/H1 NMedian (hr)
HRAdjusted P
7452.5
0.7790.145
6962.6
0.8990.5384
7281.4
A/H3 NMedian (hr)
HRAdjusted P
2176.1
0.5420.0556
2550.5
0.3260.0008
2481.0
Symptom duration
0 – 24 hr NMedian (hr)
HRAdjusted P
5957.2
0.6530.0516
5156.1
0.6630.0516
4886.7
24-48 hr NMedian (hr)
HRAdjusted P
4069.1
0.7080.1118
4664.7
0.6940.1118
5270.8
Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574
Rapivab™ - peramivir injection Literature Review – Adverse Events
Parameter Rapivab 300 mg Rapivab 600 mg Placebo
Number of Events 252 252 257
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 4 (4%) 7 (7.1%) 8 (8%)
Increase AST 1 (1%) 7 (7.1%) 6 (6%)
Prolonged QT Interval 2 (2%) 3 (3%) 3 (3%)
Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574
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. 2010 Nov, 54(11): 4568-4574
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
Rapivab™ - peramivir injection
References
1. http://www.rapivab.com
2. Rapivab package insert. BioCryst Pharmaceuticals. December 2014.
3. Peramivir: Drug information. Lexicomp Drug Information. Accessed through UpToDate. Accessed on January 10, 2015.
4. Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574