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ph-1026

Anti-Influenza Agents Quantity Limit Program Summary

Policy Number: PH-1026

This program applies to Commercial, GenPlus, NetResults A series, Blue Partner, SourceRx and Health Insurance Marketplace formularies.

POLICY REVIEW CYCLE

Effective Date	Date of Origin
10-01-2024

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Relenza (zanamivir) Oral inhalation powder	Treatment of uncomplicated acute illness due to influenza type A and B infections in adult and pediatric patients aged 7 years and older who have been symptomatic for no more than 2 days. Prophylaxis of influenza in patients aged 5 years and older. Important limitations on use of zanamivir: Not a substitute for annual influenza vaccination Consider available information on influenza susceptibility patterns and treatment effects when deciding whether to use zanamivir Not recommended for treatment or prophylaxis of influenza in: Individuals with underlying airways disease Not proven effective for: Treatment in individuals with underlying airways disease. Prophylaxis in nursing home settings		1
Tamiflu^® (oseltamivir)* Capsule Oral suspension	Treatment of acute, uncomplicated influenza A and B in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours. Prophylaxis of influenza A and B in patients 1 year and older. Important limitations of use: Not a substitute for annual influenza vaccination Consider available information on influenza susceptibility patterns and treatment effects when deciding whether to use oseltamivir Not recommended for patients with end-stage renal disease not undergoing dialysis	* generic available	2
Xofluza^® (baloxavir marboxil) Tablet Oral suspension	Treatment of acute uncomplicated influenza in patients 5 years of age and older who have been symptomatic for no more than 48 hours and who are otherwise healthy or at high risk of developing influenza-related complications Post-exposure prophylaxis of influenza in persons 5 years of age and older following contact with an individual who has influenza. Limitations of use: Consider available information on drug susceptibility patterns for circulating virus strains when deciding whether to use Xofluza		4

See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Guidelines

Influenza

Antiviral treatment is recommended by the Centers for Disease Control and Prevention (CDC) as early as possible for any patient with confirmed or suspected influenza who: is hospitalized, has severe, complicated, or progressive illness, or is at higher risk for influenza complications. Antiviral treatment also can be considered for any previously healthy, symptomatic outpatient not at high risk for influenza complications, who is diagnosed with confirmed or suspected influenza, on the basis of clinical judgement, if treatment can be initiated within 48 hours of illness onset. Recommended duration for antiviral treatment is 5 days for oral oseltamivir or inhaled zanamivir. For the treatment of uncomplicated influenza with intravenous peramivir or oral baloxavir, a single dose is recommended. Longer daily dosing (oral oseltamivir or intravenous peramivir) can be considered for patients who remain severely ill after 5 days of treatment.(5)

The CDC does not recommend widespread or routine use of antiviral medications for chemoprophylaxis except as one of multiple interventions to control institutional influenza outbreaks. Routine use of post-exposure chemoprophylaxis is not recommended; one reason for this is to avoid sub-therapeutic treatment dosing if infection is already established, although the possibility of whether antiviral resistant viruses could emerge is unknown. Antiviral medications can be considered for chemoprophylaxis to prevent influenza in certain situations, such as: prevention in people at high risk to influenza complications during the first two weeks following vaccination after exposure to a person with influenza, prevention for people at high risk for complications from influenza who cannot receive influenza vaccine due to a contraindication after exposure to a person with influenza, and prevention for people with severe immune deficiencies or others who might not respond to influenza vaccination, such as people receiving immunosuppressive medications, after exposure to a person with influenza. To be effective as chemoprophylaxis, an antiviral medication must be taken each day for the duration of potential exposure to a person with influenza and continued for 7 days after the last known exposure. For persons taking antiviral chemoprophylaxis after inactivated influenza vaccination, the recommended duration is until immunity after vaccination develops (antibody development after vaccination takes about two weeks in adults and can take longer in children depending on age and vaccination history). For control of outbreaks in institutional settings (e.g., long-term care facilities for elderly people and children) and hospitals, CDC recommends antiviral chemoprophylaxis with oral oseltamivir or inhaled zanamivir for a minimum of 2 weeks and continuing up to 1 week after the last known case was identified. Antiviral chemoprophylaxis is recommended for all residents, including those who have received influenza vaccination. Baloxavir is approved for post-exposure prophylaxis (single-dose) of influenza in persons aged 5 years and older.(3)

COVID-19 (SARS-CoV-2) and Influenza

During periods of community co-circulation of influenza viruses and SARS-CoV-2, empiric antiviral treatment of influenza is recommended as soon as possible for the following priority groups: hospitalized patients with respiratory illness, outpatients with severe, complicated, or progressive respiratory illness, and outpatients at higher risk for influenza complications who present with any acute respiratory illness symptoms (with or without fever). Patients who require hospitalization and are suspected of having either or both viral infections should receive influenza antiviral treatment with oseltamivir as soon as possible without waiting for influenza testing results. Treatment for influenza is the same for all patients regardless of SARS-CoV-2 coinfection. Clinicians can consider starting early (less than or equal to 48 hours after illness onset) empiric antiviral treatment of non-high-risk outpatients with suspected influenza based upon clinical judgement. SARS-CoV-2 and other etiologies of influenza-like illness should also be considered.(5)

Safety

Zanamivir is contraindicated in patients with history of allergic reaction to any ingredient of Relenza, including milk proteins.(1)

REFERENCES

Number	Reference
1	Relenza prescribing information. GlaxoSmithKline. October 2021.
2	Tamiflu prescribing information. Gilead Sciences, Inc. August 2019.
3	Influenza Antiviral Medications: Summary for Clinicians. Center for Disease Control and Prevention. December 8, 2023. https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm.
4	Xofluza prescribing information. Genentech USA, Inc. March 2024.
5	Influenza and COVID-19. Center for Disease Control and Prevention. December 20, 2023. Available at: https://www.covid19treatmentguidelines.nih.gov/special-populations/influenza/

OBJECTIVE

The program accommodates for two rounds of influenza treatment or 20 days of prophylaxis in a 120-day period. Requests for larger quantities will be evaluated through the Clinical Review process when the prescriber provides evidence that dosing with higher quantities is appropriate for the patient.

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	QL Amount	Dose Form	Day Supply	Duration	Addtl QL Info	Allowed Exceptions	Targeted NDCs When Exclusions Exist

Relenza diskhaler	zanamivir aerosol powder breath activated	5 MG/BLISTER	40	Blisters	120	DAYS
Tamiflu	oseltamivir phosphate cap	30 MG ; 45 MG ; 75 MG	20	Capsules	120	DAYS
Tamiflu	Oseltamivir Phosphate Cap 30 MG (Base Equiv)	30 MG	40	Capsules	120	DAYS
Tamiflu	Oseltamivir Phosphate For Susp 6 MG/ML (Base Equiv)	6 MG/ML	300	mLs	120	DAYS
Xofluza	Baloxavir Marboxil Tab Therapy Pack	40 MG	2	Tablets	120	DAYS
Xofluza	Baloxavir Marboxil Tab Therapy Pack	80 MG	2	Tablets	120	DAYS
Xofluza	Baloxavir Marboxil Tab Therapy Pack 2 x 20 MG (40 MG Dose)	20 MG	4	Tablets	120	DAYS
Xofluza	Baloxavir Marboxil Tab Therapy Pack 2 x 40 MG (80 MG Dose)	40 MG	4	Tablets	120	DAYS

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
Relenza diskhaler	zanamivir aerosol powder breath activated	5 MG/BLISTER	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Tamiflu	oseltamivir phosphate cap	30 MG ; 45 MG ; 75 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Tamiflu	Oseltamivir Phosphate Cap 30 MG (Base Equiv)	30 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Tamiflu	Oseltamivir Phosphate For Susp 6 MG/ML (Base Equiv)	6 MG/ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Xofluza	Baloxavir Marboxil Tab Therapy Pack	40 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Xofluza	Baloxavir Marboxil Tab Therapy Pack	80 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Xofluza	Baloxavir Marboxil Tab Therapy Pack 2 x 20 MG (40 MG Dose)	20 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Xofluza	Baloxavir Marboxil Tab Therapy Pack 2 x 40 MG (80 MG Dose)	40 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
	Quantity limit for the Target Agent(s) will be approved when BOTH of the following are met: ONE of the following: The patient requires additional courses of therapy due to additional episodes of acute influenza infection OR The patient requires additional courses or increased duration of therapy for prophylaxis after exposure to an influenza infected person AND ONE of the following: There is no shortage of the requested agent and ONE of the following: ALL of the following: The requested quantity (dose) exceeds the program quantity limit AND The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit OR ALL of the following: The requested quantity (dose) exceeds the program quantity limit AND The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND There is support of therapy with a higher dose for the requested indication OR There is a shortage of the requested agent and ONE of the following: ALL of the following: The requested quantity (dose) exceeds the program quantity limit AND The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication OR ALL of the following: The requested quantity (dose) exceeds the program quantity limit AND The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND There is support of therapy with a higher dose for the requested indication Length of Approval: up to 4 months

Module

Clinical Criteria for Approval

Quantity limit for the Target Agent(s) will be approved when BOTH of the following are met:

ONE of the following:
1. The patient requires additional courses of therapy due to additional episodes of acute influenza infection OR
2. The patient requires additional courses or increased duration of therapy for prophylaxis after exposure to an influenza infected person AND
ONE of the following:
1. There is no shortage of the requested agent and ONE of the following:
  1. ALL of the following:
    1. The requested quantity (dose) exceeds the program quantity limit AND
    2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
    3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit OR
  2. ALL of the following:
    1. The requested quantity (dose) exceeds the program quantity limit AND
    2. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
    3. There is support of therapy with a higher dose for the requested indication OR
2. There is a shortage of the requested agent and ONE of the following:
  1. ALL of the following:
    1. The requested quantity (dose) exceeds the program quantity limit AND
    2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication OR
  2. ALL of the following:
    1. The requested quantity (dose) exceeds the program quantity limit AND
    2. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
    3. There is support of therapy with a higher dose for the requested indication

Length of Approval: up to 4 months

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

Commercial _ PS _ Anti-Influenza_Agents_QL _ProgSum_ 10-01-2024