Xofluza: Package Insert and Label Information

XOFLUZA- baloxavir marboxil tablet, film coated
A-S Medication Solutions

1 INDICATIONS AND USAGE

1.1 Treatment of Influenza

XOFLUZA is indicated for the treatment of acute uncomplicated influenza in patients 12 years of age and older who have been symptomatic for no more than 48 hours and who are:

1.2 Post-Exposure Prophylaxis of Influenza

XOFLUZA is indicated for post-exposure prophylaxis of influenza in persons 12 years of age and older following contact with an individual who has influenza [see Clinical Studies (14.3)].

1.3 Limitations of Use

Influenza viruses change over time, and factors such as the virus type or subtype, emergence of resistance, or changes in viral virulence could diminish the clinical benefit of antiviral drugs. Consider available information on drug susceptibility patterns for circulating influenza virus strains when deciding whether to use XOFLUZA [see Microbiology (12.4) and Clinical Studies (14)].

2 DOSAGE AND ADMINISTRATION

2.1 Dosage and Administration Overview

XOFLUZA is available in two dosage forms:

  • XOFLUZA tablets
  • XOFLUZA for oral suspension. This granule formulation is intended for patients who are unable to or have difficulty swallowing tablets, or those who require enteral administration [see Dosage and Administration (2.3)].

XOFLUZA should be taken as soon as possible after influenza symptom onset or exposure to influenza and may be taken with or without food. However, coadministration of XOFLUZA with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc) should be avoided [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

2.2 Recommended Dosage

Treatment of Acute Uncomplicated Influenza or Post-Exposure Prophylaxis in Adults and Adolescents (12 Years of Age and Older)

XOFLUZA should be taken as a single dose as soon as possible and within 48 hours of influenza symptom onset for treatment of acute uncomplicated influenza or following contact with an individual who has influenza. The recommended dosage of XOFLUZA in patients 12 years of age or older is a single weight-based dose displayed in Tables 1 and 2.

Table 1 Recommended XOFLUZA Tablet Dosage in Adults and Adolescents (12 Years of Age and Older)
Patient Body Weight (kg) Recommended Single Oral Dose (Tablets)
Less than 80 kg One 40 mg tablet(blister card contains one 40 mg tablet)
At least 80 kg One 80 mg tablet(blister card contains one 80 mg tablet)
Table 2 Recommended XOFLUZA Oral Suspension Dosage in Adults and Adolescents (12 Years of Age and Older)
Patient Body Weight (kg) Recommended Single Oral Dose (Suspension)
Less than 80 kg 40 mg/20 mL (1 bottle) taken as a single dose
At least 80 kg 80 mg/40 mL (2 bottles) taken as a single dose

2.3 Preparation of XOFLUZA for Oral Suspension by Healthcare Provider

Prior to dispensing to the patient, constitute XOFLUZA for oral suspension with 20 mL of drinking water or sterile water. After constitution, each bottle of XOFLUZA suspension contains 40 mg of baloxavir marboxil per 20 mL of volume for a final concentration of 2 mg/mL. This dosage form can be used for oral or enteral use.

Constituting XOFLUZA for Oral Suspension

Prepare the suspension at the time of dispensing. Administration must occur within 10 hours after constitution because the product does not contain a preservative.

  1. Gently tap the bottom of the bottle to loosen the granules.
  2. Constitute XOFLUZA for oral suspension with 20 mL of drinking water or sterile water.
  3. Gently swirl the suspension to ensure that the granules are evenly suspended. Do not shake.
  4. Write the expiration time and date on the bottle label in the space provided (10 hours from constitution time).

Important Information for the Healthcare Provider

  • Provide caregiver or patient with a measuring device (e.g., oral syringe, measuring cup) to deliver the prescribed dose of the suspension for oral use. For enteral administration (i.e., feeding tube), draw up suspension with an enteral syringe. Flush with 1 mL of water before and after enteral administration.
  • Instruct the caregiver or patient that the total prescribed dose of XOFLUZA for oral suspension may require more than one bottle (e.g., for adults and adolescents weighing at least 80 kg).

3 DOSAGE FORMS AND STRENGTHS

XOFLUZA Tablets:

XOFLUZA 40 mg tablets are white to light yellow, oblong-shaped, film-coated tablets debossed with “BXM40” on one side.

XOFLUZA 80 mg tablets are white to light yellow, oblong shaped, film-coated tablets debossed with “BXM80” on one side.

XOFLUZA for Oral Suspension:

XOFLUZA for oral suspension contains 40 mg/20 mL or 2 mg/mL baloxavir marboxil after constitution with 20 mL of drinking water or sterile water. The granules are white to light yellow. The constituted product is a white to light yellow opaque suspension with strawberry flavor.

4 CONTRAINDICATIONS

XOFLUZA is contraindicated in patients with a history of hypersensitivity to baloxavir marboxil or any of its ingredients. Serious allergic reactions have included anaphylaxis, angioedema, urticaria, and erythema multiforme [see Warnings and Precautions (5.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity

Cases of anaphylaxis, urticaria, angioedema, and erythema multiforme have been reported in postmarketing experience with XOFLUZA. Appropriate treatment should be instituted if an allergic-like reaction occurs or is suspected. The use of XOFLUZA is contraindicated in patients with known hypersensitivity to XOFLUZA [see Contraindications (4) and Adverse Reactions (6.2)].

5.2 Risk of Bacterial Infections

There is no evidence of efficacy of XOFLUZA in any illness caused by pathogens other than influenza viruses. Serious bacterial infections may begin with influenza-like symptoms or may coexist with, or occur as, a complication of influenza. XOFLUZA has not been shown to prevent such complications. Prescribers should be alert to potential secondary bacterial infections and treat them as appropriate.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The overall safety profile of XOFLUZA is based on data from 1,943 subjects 12 years of age and older in 4 controlled clinical trials who received XOFLUZA [see Clinical Studies (14)].

Treatment of Acute Uncomplicated Influenza

Adult and Adolescent Subjects:

The safety of XOFLUZA in adult and adolescent subjects is based on data from 3 placebo-controlled trials in which a total of 1,640 subjects received XOFLUZA: 1,334 (81%) subjects were 18 to 64 years of age, 209 (13%) subjects were adults 65 years of age or older, and 97 (6%) subjects were adolescents 12 to 17 years of age. These trials included otherwise healthy adults and adolescents (N=910) and subjects at high risk of developing complications associated with influenza (N=730). Of these, 1,440 subjects received XOFLUZA at the recommended dose [see Clinical Studies (14.1, 14.2)]. Trial 1 was a phase 2 dose-finding placebo-controlled trial where otherwise healthy adult subjects 20 to 64 years of age received single oral dose of XOFLUZA or placebo. Trial 2 was a placebo- and active-controlled trial in otherwise healthy adults and adolescents 12 to 64 years of age; subjects received weight-based XOFLUZA or placebo as a single oral dose on Day 1 or oseltamivir twice a day for 5 days. Trial 3 was a randomized, double-blind, placebo- and active-controlled trial where adults and adolescents at high risk of influenza complications 12 years of age and older received either XOFLUZA, placebo or oseltamivir.

Table 3 displays the most common adverse events (regardless of causality assessment) reported in at least 1% of adult and adolescent subjects who received XOFLUZA at the recommended dose in Trials 1, 2, and 3.

Table 3 Incidence of Adverse Events Occurring in at Least 1% of Adult and Adolescent Subjects Receiving XOFLUZA in the Acute Uncomplicated Influenza Trials 1, 2, and 3
Adverse Event XOFLUZA(N=1,440) Placebo(N=1,136)
Diarrhea 3% 4%
Bronchitis 3% 4%
Nausea 2% 3%
Sinusitis 2% 3%
Headache 1% 1%

Post-Exposure Prophylaxis of Influenza

The safety of XOFLUZA in adult and adolescent subjects is based on data from one placebo-controlled clinical trial in which 374 subjects, of which 303 were adult and adolescent subjects ≥ 12 years, received XOFLUZA: eight (3%) subjects were adults 65 years of age or older, and 12 (4%) subjects were adolescents 12 to 17 years of age. The most frequently reported AE in the total study population was nasopharyngitis which occurred in 6% of subjects who received XOFLUZA and 7% on placebo [see Clinical Studies (14.3)].

6.2 Postmarketing Experience

The following adverse reactions have been identified during postmarketing use of XOFLUZA. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to XOFLUZA exposure.

Immune System Disorders: Anaphylactic reactions, anaphylactic shock, anaphylactoid reactions, hypersensitivity reactions, angioedema (swelling of face, eyelids, tongue and lips)

Skin and Subcutaneous Tissue Disorders: Rash, urticaria, erythema multiforme

Gastrointestinal Disorders: Vomiting, hematochezia, melena, colitis

Psychiatric Disorders: Delirium, abnormal behavior, hallucinations

7 DRUG INTERACTIONS

7.1 Effect of Other Drugs on XOFLUZA

Baloxavir may form a chelate with polyvalent cations such as calcium, aluminum, or magnesium. Coadministration with polyvalent cation-containing products may decrease plasma concentrations of baloxavir [see Clinical Pharmacology (12.3)], which may reduce XOFLUZA efficacy. Avoid coadministration of XOFLUZA with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc).

7.2 Vaccines

The concurrent use of XOFLUZA with intranasal live attenuated influenza vaccine (LAIV) has not been evaluated. Concurrent administration of antiviral drugs may inhibit viral replication of LAIV and thereby decrease the effectiveness of LAIV vaccination. Interactions between inactivated influenza vaccines and XOFLUZA have not been evaluated.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no adequate and well-controlled studies with XOFLUZA in pregnant women to inform a drug-associated risk of adverse developmental outcomes. There are risks to the mother and fetus associated with influenza virus infection in pregnancy [see Clinical Considerations]. In animal reproduction studies, no adverse developmental effects were observed in rats or rabbits with oral administration of baloxavir marboxil at exposures approximately 5 (rats) and 7 (rabbits) times the systemic baloxavir exposure at the maximum recommended human dose (MRHD) [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes, including maternal death, stillbirth, birth defects, preterm delivery, low birth weight, and small for gestational age.

Data

Animal Data

Baloxavir marboxil was administered orally to pregnant rats (20, 200, or 1,000 mg/kg/day from gestation day 6 to 17) and rabbits (30, 100, or 1,000 mg/kg/day from gestation day 7 to 19). No adverse embryo-fetal effects were observed in rats up to the highest dose of baloxavir marboxil (1,000 mg/kg/day), resulting in systemic baloxavir exposure (AUC) of approximately 5 times the exposure at the MRHD. In rabbits, fetal skeletal variations occurred at a maternally toxic dose (1,000 mg/kg/day) resulting in 2 abortions out of 19 pregnancies. No adverse maternal or embryo-fetal effects were observed in rabbits at the middle dose (100 mg/kg/day) resulting in systemic baloxavir exposure (AUC) approximately 7 times the exposure at the MRHD.

In the prenatal and postnatal development study in rats, baloxavir marboxil was administered orally at 20, 200, or 1,000 mg/kg/day from gestation day 6 to postpartum/lactation day 20. No significant effects were observed in the offspring at maternal systemic baloxavir exposure (AUC) approximately 5 times the exposure at the MRHD.

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