Rapivab

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Health-System Edition, May 2016, Volume 5, Issue 3

Rapivab was approved by the FDA in December 2014 to treat acute and uncomplicated influenza in adults.

Rapivab (peramivir), manufactured by BioCryst Pharmaceuticals, was approved by the FDA in December 2014 to treat acute and uncomplicated influenza in adults. Rapivab is 1 of 3 FDA-approved neuraminidase inhibitors indicated for influenza treatment and is the only intravenous formulation. The CDC estimates that 5% to 20% of Americans get the flu yearly, and approximately 200,000 of these patients are hospitalized. Although treatment should not supplant preventive annual vaccination, Rapivab may be an option for some patients who get the flu.1,2

PHARMACOLOGY/ PHARMACOKINETICS1,3

Neuraminidase is an enzyme that releases viral particles from infected cells. Rapivab binds to the active site and inhibits neuraminidase of several influenza A and B strains. Once neuraminidase is inhibited, infected cells cannot release viral progeny and the flu infection cannot spread.

Rapivab is less than 30% proteinbound, has a volume of distribution of 12.56 L, and demonstrates a Cmax of 46.8 mcg/mL after a 600-mg IV dose over 30 minutes. Rapivab is minimally metabolized and is neither an inducer nor an inhibitor of CYP enzymes or P-glycoprotein—mediated transport; Rapivab is not involved in any significant drug interactions. The elimination half-life is 20 hours, and the clearance is 7.58 L/hr. The kidneys are responsible for most elimination, as 90% of the drug is excreted unchanged.

DOSING AND ADMINISTRATION1,3-6

According to the package insert, Rapivab may be used within 2 days of symptom onset in patients 18 years and older who have acute and uncomplicated influenza. Rapivab is FDAapproved as a single 600-mg dose in patients without renal impairment, administered as a 15- to 30-minute IV infusion. Although Rapivab is not FDAapproved for hospitalized patients with serious influenza, the CDC recommends dosing Rapivab for at least 5 days (600 mg daily) if it must be used in patients unable to receive oral oseltamivir. Rapivab should be diluted to a maximum volume of 100 mL with 0.9% or 0.45% sodium chloride, 5% dextrose, or lactated Ringer’s solution.

CLINICAL EFFICACY3,5-7

Kohno and colleagues completed a multicenter, randomized, doubleblind, placebo-controlled trial to compare the efficacy and safety of Rapivab to a placebo. This trial was the basis of approval for Rapivab. Patients were 20 to 64 years of age and presented within 48 hours of symptom onset. An influenza diagnosis was confirmed based on a positive result from a rapid antigen test, the presence of fever, and at least 2 self-reported influenza symptoms (headache, myalgia, feverishness, fatigue, cough, sore throat, nasal congestion). Patients were randomized to receive Rapivab 300 mg (n = 99), Rapivab 600 mg (n = 97), or placebo (n = 100). Time to symptom relief, the primary end point, was defined as the number of hours from treatment initiation until all 7 symptoms were absent or “mild” for at least 21.5 hours.

The time to symptom relief was significantly reduced by Rapivab compared with placebo. The median time to alleviation of symptoms was 59.1, 59.9, and 81.8 hours in the Rapivab 300-mg, Rapivab 600-mg, and placebo groups, respectively. The hazard ratio compared with placebo for the time to alleviation of symptoms was 0.681 (95% CI, 0.511-0.909; P = .0092) in the 300-mg group and 0.666 (95% CI, 0.499-0.890; P = .0092) in the 600- mg group. Patients receiving Rapivab resumed usual activities earlier than patients receiving placebo (43.6 and 41.7 hours earlier in the 300-mg and 600-mg groups, respectively). Efficacy end points were not influenced by influenza virus subtype or the duration of symptoms before the study; however, the package labeling warns that few subjects with influenza type B were included. The tolerability of peramivir was also evaluated. Adverse events (AEs), generally mild to moderate, were comparable to that of placebo. One patient (receiving placebo) withdrew from the study due to an AE. Gastrointestinal AEs, such as diarrhea and nausea, were the most common in this trial. Although IV Rapivab may shorten influenza symptom duration by 21 hours, patients and health care providers should consider the clinical benefit versus the cost.

Rapivab is not FDA-approved for serious influenza in patients requiring hospitalization, but some studies have evaluated use in this population. De Jong et al failed to demonstrate clinical benefit of IV Rapivab 600 mg for 5 days versus placebo and terminated the study after a preplanned analysis.5 Ison et al demonstrated that 5 days of IV Rapivab (either 300 mg twice daily or 600 mg once daily) may be associated with clinical improvement; however, this was an uncontrolled, open-label trial. Although there is insufficient evidence that Rapivab is effective against serious influenza in hospitalized patients, it is likely welltolerated.

MEDICATION SAFETY/ADVERSE EFFECTS1,7

Rapivab is generally well-tolerated. In rare instances, serious skin reactions and neuropsychiatric events (hallucinations, delirium, and abnormal behavior) have been reported in postmarketing experience. The most common AE observed in clinical trials was diarrhea, which occurred at a rate similar to that for placebo (8% for Rapivab vs 7% for placebo).

AVAILABILITY AND COST1,7

Rapivab is a clear and colorless solution supplied in a clear glass vial containing 200 mg/20 mL. Vials should be stored between 20°C and 25°C before diluting. The suggested average wholesale price of a carton of 3 vials (1 dose) is $1140; the wholesale acquisition cost is $950.a

aPricing obtained from RedBook.

Jennifer L. Cruz, PharmD, BCPS, is an assistant professor of clinical education at UNC Eshelman School of Pharmacy.Katherine Summers is a PharmD candidate at UNC Eshelman School of Pharmacy.

References

  • Rapivab [package insert]. Durham, NC: BioCryst Pharmaceuticals, Inc; updated December 2014.
  • FDA approves Rapivab to treat flu infection [news release; December 22, 2014.]. FDA website. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427755.htm. Accessed March 21, 2016.
  • Peramivir. Micromedex [online database]. Greenwood Village, CO: Truven Health Analytics; updated August 20, 2015.
  • Influenza antiviral medications: summary for clinicians. Centers for Disease Control and Prevention website. cdc.gov/flu/professionals/antivirals/summary-clinicians.htm. Accessed March 28, 2016.
  • de Jong MD, Ison MG, Monto AS, et al. Evaluation of intravenous peramivir for treatment of influenza in hospitalized patients. Clin Infect Dis. 2014;59(12):172-185. doi: 10.1093/cid/ciu632.
  • Ison MG, Fraiz J, Heller B, et al. Intravenous peramivir for treatment of influenza in hospitalized patients. Antivir Ther. 2014;19(4):349-361. doi: 10.3851/IMP2680.
  • Kohno S, Kida H, Mizuguchi M, Shimada J; S-021812 Clinical Study Group. Efficacy and safety of intravenous peramivir for treatment of seasonal influenza virus infection. Antimicrob Agents Chemother. 2010;54(11):4568-4574. doi: 10.1128/AAC.00474-10.