47/18. Baloxavir Marboxil- (XOFLUZA)- @- (Oct- 2018)- for the treatment of acute uncomplicated influenza
Drug Name:47/18. Baloxavir Marboxil- (XOFLUZA)- @- (Oct- 2018)- for the treatment of acute uncomplicated influenza
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS
1. Effect of Other Drugs on XOFLUZA
Co-administration with polyvalent cation-containing products may decrease plasma concentrations of baloxavir which may reduce XOFLUZA efficacy. Avoid co-administration of XOFLUZA with polyvalent cationcontaining laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc).
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.
Indication:
BRIEF SUMMARY
BALOXAVIR MARBOXIL- (Dec 2019)
Indn- For the treatment of acute uncomplicated influenza in patients who have been symptomatic for no more than 48 hours
Comp- Tablets 20mg and 40mg e a single dose of XOFLUZA orally within 48 hours of symptom onset with or without food.
Avoid co-administration of XOFLUZA with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc). The dose of XOFLUZA depends on weight.
ADR-
CI-
Pat Inform-
================================================================
U.S. FDA APPROVED DRUGS DURING 2018
Sr.No- 47
Name of the Drug- XOFLUZA
Active Ingredient - Baloxavir Marboxil
Pharmacological Classification-
For the treatment of acute uncomplicated influenza in patients who have been symptomatic for no more than 48 hours
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
XOFLUZA safely and effectively.
See full prescribing information for XOFLUZA.
XOFLUZATM (baloxavir marboxil) tablets, for oral use
Initial U.S. Approval: 2018
INDICATIONS AND USAGE-------------------------XOFLUZATM is a polymerase acidic (PA) endonuclease inhibitor 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. (1) 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. (1)
------------------------DOSAGE AND ADMINISTRATION---------------------Take a single dose of XOFLUZA orally within 48 hours of symptom onset with or without food. Avoid co-administration of XOFLUZA with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc). The dose of XOFLUZA depends on weight. (2)
---------------------DOSAGE FORMS AND STRENGTHS---------------------
Tablets 20mg and 40mg
Date of Approval - 10/24/2018
(Ref- FDA approved List 2018)
Take a single dose of XOFLUZA orally within 48 hours of symptom onset with or without food.
Avoid co-administration of XOFLUZA with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc). The dose of XOFLUZA depends on weight.
Adverse Reaction:
ADVERSE REACTIONS
Adverse events reported in at least 1% of adult and adolescent subjects treated with XOFLUZA included diarrhea (3%), bronchitis (2%), nasopharyngitis (1%), headache (1%) and nausea (1%).
.
Contra-Indications:
CONTRAINDICATIONS
XOFLUZA is contraindicated in patients with a history of hypersensitivity to baloxavir marboxil or any of its ingredients.
WARNINGS AND PRECAUTIONS
Risk of Bacterial Infection: Serious bacterial infections may begin with influenza-like symptoms, 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.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
XOFLUZATM is a polymerase acidic (PA) endonuclease inhibitor 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.
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.
DOSAGE AND ADMINISTRATION-
Take a single dose of XOFLUZA orally within 48 hours of symptom onset with or without food.
Avoid co-administration of XOFLUZA with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc). The dose of XOFLUZA depends on weight.
DOSAGE FORMS AND STRENGTHS
Tablets 20mg and 40mg
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Important Dosing Information
Instruct patients to begin treatment with XOFLUZA as soon as possible at the first appearance of influenza symptoms, within 48 hours of onset of symptoms.
XOFLUZA can be taken with or without food, but advise patients not to take with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc).
Influenza Vaccines
Because of the potential for antivirals to decrease the effectiveness of live attenuated influenza vaccine, advise patients to consult their healthcare provider prior to receiving a live attenuated influenza vaccine after taking XOFLUZA
Distributed by: Genentech USA, Inc. A Member of the Roche Group 1 DNA Way South San Francisco, CA 94080-4990
Manufactured by: Shionogi & Co., Ltd. 2-5-1 Mishima, Settsu Osaka 566-0022, Japan
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Baloxavir marboxil is an antiviral drug with activity against influenza virus [see Microbiology (12.4)].
2. Pharmacodynamics
Cardiac Electrophysiology At twice the expected exposure from recommended dosing, XOFLUZA did not prolong the QTc interval. Exposure-Response Relationships.
No change in the baloxavir exposure-response (time to alleviation of symptoms) relationship was observed at the recommended dosing.
3. Pharmacokinetics
Baloxavir marboxil is a prodrug that is almost completely converted to its active metabolite, baloxavir, following oral administration.
In the phase 3 trial, at the recommended dose of 40 mg for subjects weighing less than 80 kg, the mean (CV%) values of baloxavir Cmax and AUC0-inf were 96.4 ng/mL (45.9%) and 6160 ng·hr/mL (39.2%), respectively.
At the recommended dose of 80 mg for subjects weighing 80 kg and more, the mean (CV%) values of baloxavir Cmax and AUC0-inf were 107 ng/mL (47.2%) and 8009 ng·hr/mL (42.4%), respectively.
3 Pharmacokinetic Parameters of Plasma Baloxavir
Absorption Tmax (hr)a 4 Effect of food (relative to fasting)b Cmax: 48%, AUC0-inf; %
Distribution % Bound to human serum proteinsc 92.9 - 93.9 Ratio of blood cell to blood 48.5% - 54.4% Volume of distribution (V/F, L)d 1180 (20.8%)
Elimination Major route of elimination
Metabolism Clearance (CL/F, L/hr)d 10.3 (22.5%) t1/2 (hr) d, e 79.1 (22.4%) Metabolism Metabolic pathwaysf UGT1A3, CYP3A4
Excretion % of dose excreted in urineg 14.7 (Total radioactivity), 3.3 (Baloxavir) % of dose excreted in fecesg 80.1 (Total radioactivity)
a Median
b Meal: approximately 400 to 500 kcal including 150 kcal from fat
c in vitro
d Geometric mean (geometric CV%)
e Apparent terminal elimination half-life
f Baloxavir is primarily metabolized by UGT1A3 with minor contribution from CYP3A4
g Ratio of radioactivity to radio-labeled [14C]-baloxavir marboxil dose in mass balance study
Specific Populations
There were no clinically significant differences in the pharmacokinetics of baloxavir based on age (adolescents as compared to adults), or sex.
Patients with Renal Impairment
A population pharmacokinetic analysis did not identify a clinically meaningful effect of renal function on the pharmacokinetics of baloxavir in patients with creatinine clearance (CrCl) 50 mL/min and above.
The effects of severe renal impairment on the pharmacokinetics of baloxavir marboxil or its active metabolite, baloxavir, have not been evaluated.
Patients with Hepatic Impairment
In a clinical study comparing pharmacokinetics of baloxavir in subjects with moderate hepatic impairment (Child-Pugh class B) to subjects with normal hepatic function, no clinically meaningful differences in the pharmacokinetics of baloxavir were observed.
The pharmacokinetics in patients with severe hepatic impairment have not been evaluated.
Body Weight Body weight had a significant effect on the pharmacokinetics of baloxavir (as body weight increases, baloxavir exposure decreases). When dosed with the recommended weight-based dosing, no clinically significant difference in exposure was observed between body weight groups.
Race/Ethnicity Based on a population pharmacokinetic analysis, baloxavir exposure is approximately 35% lower in nonAsians as compared to Asians; this difference is not considered clinically significant when the recommended dose was administered.
Drug Interaction Studies
Clinical Studies- No clinically significant changes in the pharmacokinetics of baloxavir marboxil and its active metabolite, baloxavir, were observed when co-administered with itraconazole (combined strong CYP3A and P-gp inhibitor), probenecid (UGT inhibitor), or oseltamivir.
No clinically significant changes in the pharmacokinetics of the following drugs were observed when coadministered with baloxavir marboxil: midazolam (CYP3A4 substrate), digoxin (P-gp substrate), rosuvastatin (BCRP substrate), or oseltamivir.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy Risk Summary
There are no available data on XOFLUZA use 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.
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)
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.
2 Lactation Risk Summary
There are no data on the presence of baloxavir marboxil in human milk, the effects on the breastfed infant, or the effects on milk production. Baloxavir and its related metabolites were present in the milk of lactating rats (see Data).
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for XOFLUZA and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.
3.Pediatric Use
The safety and effectiveness of XOFLUZA for the treatment of influenza have been established in pediatric patients 12 years of age and older weighing at least 40 kg.
The safety and effectiveness of XOFLUZA have not been established in pediatric patients less than 12 years of age.
4.Geriatric Use
Clinical trials of XOFLUZA did not include subjects 65 years of age and older to determine whether they respond differently from younger subjects.
OVERDOSAGE
There have been no reports of XOFLUZA overdoses. Treatment of an overdose of XOFLUZA should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.
There is no specific antidote for overdose with XOFLUZA. Baloxavir is unlikely to be significantly removed by dialysis due to high serum protein binding.
