peramivir

Peramivir is a medication administered intravenously to treat uncomplicated influenza in patients 6 months and older, who have had symptoms for no more than 2 days. Peramivir’s efficacy in treating hospitalized patients with serious influenza has not been studied. Peramivir controls influenza disease severity by preventing the release of new viral particles from the infected cells.

Influenza in humans is primarily caused by type A and B viruses of the Orthomyxoviridae family. The influenza virus is a single-stranded RNA that has 3 membrane proteins that help the virus enter into human cells, replicate and disperse to infect other cells:

• Hemagglutinin: The viral hemagglutinin protein enables the fusion with the cell membrane and entry into the cell
• Matrix protein: The matrix protein facilitates the release of viral particles into the interior of the cell where the viral RNA enters the cell nucleus and replicates.
• Neuraminidase: The replicated viral particles are assembled at the host cell membrane and neuraminidase protein facilitates their release from the infected cell and also helps virus movement through the airway mucus, promoting its infectivity.

Peramivir prevents the release of newly assembled viral particles by inhibiting the viral neuraminidase protein. Virus particles that lack the neuraminidase protein will be able to infect a cell and replicate within but will not be able to release newly assembled viral particles that can infect other cells.

• Do not administer peramivir to patients with hypersensitivity to any of its components.
• There have been rare reports of serious skin reactions including Steven-Johnson syndrome and erythema multiforme. Discontinue peramivir infusion immediately if a patient develops skin reactions, and initiate appropriate treatment.
• Discontinue peramivir infusion immediately if a patient develops severe allergic reactions (anaphylaxis) and institute appropriate supportive treatment.
• There have been rare reports of neurological and behavior symptoms such as hallucination, delirium and abnormal behavior in influenza patients, primarily among pediatric patients, sometimes with fatal outcomes. The contribution of peramivir to such reactions has not been established. Monitor the patients for neuropsychiatric symptoms.
• Serious bacterial infections may start with influenza-like symptoms and co-exist with influenza. Peramivir has no effect on any organisms other than influenza virus. Physicians should be alert for the possibility of bacterial infections, evaluate and treat with antibiotics as appropriate.

Common side effects of peramivir include:

• Low count of neutrophil immune cells (neutropenia)
• Diarrhea
• Constipation
• Vomiting
• Increase in blood glucose levels
• Increase in serum creatine phosphokinase (CPK)
• Increase in levels of liver enzyme alanine aminotransferase (ALT)
• Increase in levels of liver enzyme aspartate aminotransferase (AST)
• Protein excretion in urine (proteinuria)
• High blood pressure (hypertension)
• Insomnia
• Abnormal behavior
• Hallucination
• Delirium
• Severe skin reactions including:
  • Rash
  • Stevens-Johnson syndrome
  • Exfoliative dermatitis
  • Erythema multiforme
• Hypersensitivity reactions including:
  • Severe allergic reaction (anaphylaxis)
  • Nonimmune anaphylaxis

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

IV Solution

• 200 mg/20 mL (10 mg/mL)

Influenza

Adult:

• Indicated for treatment of acute uncomplicated influenza in patients who have been symptomatic for 2 days or less
• 600 mg intravenous (IV) as a single dose
• Dilute to recommended final volume before administering

Dosage Modifications

Renal impairment

• Creatinine clearance (CrCl) 50 mL/minute or above: No dosage adjustment necessary
• CrCl 30-49 mL/minute: 200 mg IV as a single dose
• CrCl 10-29 mL/minute: 100 mg IV as a single dose
• Hemodialysis: Administer after dialysis

Pediatric:

• Indicated for treatment of acute uncomplicated influenza in patients aged 6 months and above who have been symptomatic 2 days or less
• Children below 6 months: Safety and efficacy not established

Children 6 months and above

• Children 6 months to 12 years: 12 mg/kg IV as a single dose; not to exceed 600 mg/dose
• Children 13 years or above: 600 mg IV as a single dose
• Dilute to recommended final volume according to age and weight before administering

Dosage Modifications

Renal impairment

• Children 6 months to 2 years
  • CrCl above 50 mL/minute: No dosage adjustment necessary
  • CrCl below 50 mL/minute: Data are not available
• Children 2-12 years
  • CrCl above 50 mL/minute: No dosage adjustment necessary
  • CrCl 30-49 mL/minute: 4 mg/kg IV as a single dose
  • CrCl 10-29 mL/minute: 2 mg/kg IV as a single dose
• Children 13 years or above
  • CrCl above 50 mL/minute: No dosage adjustment necessary
  • CrCl 30-49 mL/minute: 200 mg IV as a single dose
  • CrCl 10-29 mL/minute: 100 mg IV as a single dose

Dosing Considerations

Limitations of use

• Efficacy based on clinical trials of naturally occurring influenza in which the predominant influenza infections were influenza A virus; a limited number of subjects infected with influenza B virus were enrolled
• Influenza viruses change over time and emergence of resistance substitutions could decrease drug effectiveness
• Efficacy not established in patients with serious influenza requiring hospitalization

Overdose

• There is no experience of peramivir overdose and no specific antidote. Peramivir overdose may be treated with supportive and symptomatic measures.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Peramivir has no known severe interactions with other drugs.
• Serious interactions with peramivir include:
  • influenza virus vaccine quadrivalent, intranasal
• Peramivir has moderate interactions with at least 30 different drugs.
• Peramivir has no known mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• There are no adequate and well-controlled studies on the safety of peramivir use in pregnant women. Use peramivir during pregnancy if clearly needed. Influenza during pregnancy is associated with fetal and maternal risks.
• It is not known if peramivir is present in human breastmilk, however the drug is excreted in animal milk. Decision to breastfeed should be based on the nursing mother’s clinical need, health and developmental benefits of breastfeeding, and the risks to the breastfed infant from exposure to the drug or the mother’s underlying condition.

• Inform your physician immediately if you develop severe skin reactions or hypersensitivity reaction after receiving peramivir infusion.
• Notify your physician if infection symptoms persist or do not improve. You may need to be evaluated for potential bacterial infection and treated appropriately.
• Inform your physician immediately if you notice any unusual changes in your behavior or experience hallucination.
• In case you suspect an overdose, notify your physician immediately.