Baloxavir Marboxil – Antiviral Drug

Background

Baloxavir marboxil is an antiviral drug used to treat influenza. More specifically, it is a first-in-class cap-dependent endonuclease inhibitor that works to block influenza virus proliferation. It is a prodrug of baloxavir 6 with an improved absorption profile than its active metabolite due to the addition of a phenolic hydroxyl group to its structure. Baloxavir marboxil was first globally approved in Japan in February 2018, followed by the US approval in October, 2018. It was also approved by the European Commission on January 7, 2021.

Properties and Characteristics of Baloxavir marboxil

Drug class	Antiviral drug
Brand Names	Xofluza
Synonyms	Baloxavir marboxil, 1985606-14-1, Xofluza, baloxavir-marboxil Baloxavir marboxil [INN]
Molecular Formula	C27H23F2N3O7S
Molecular Weight	571.6 g/mol
IUPAC Names	[(3R)-2-[(11S)-7,8-difluoro-6,11-dihydrobenzo[c][1]benzothiepin-11-yl]-9,12-dioxo-5-oxa-1,2,8-triazatricyclo[8.4.0.03,8]tetradeca-10,13-dien-11-yl]oxymethyl methyl carbonate
Structural formula of main components
Pure active ingredient	Baloxavir marboxil
Appearance	White Powder
Boiling Point	712.8±70.0 °C at 760 mmHg
Solubility	0.015mg/mL
Excretion	Excreted in urine
Available as	Granule for solution, Powder, Tablet
Storage	Store at -20ºC
Prescription	Doctor prescription is required

Uses of Baloxavir Marboxil

Baloxavir marboxil is an antiviral medication used to treat the flu (influenza) if your symptoms started less than 48 hours ago. It helps make the symptoms (such as stuffy nose, cough, sore throat, fever/chills, aches, tiredness) less severe and may shorten the recovery time by 1 to 2 days. Baloxavir marboxil works by stopping the flu virus from growing. It will not treat other kinds of infection besides the flu virus. This medication may also be used to prevent the flu if you have been exposed to someone who already has the flu (such as a sick household member) or if there is a flu outbreak in the community. Talk to your doctor for more details. This medication should not be used in children younger than 5 since it may not be effective.Baloxavir marboxil is not a substitute for the flu vaccine.

What side effects may I notice from receiving this medication?

Side effects that you should report to your care team as soon as possible:

• Allergic reactions—skin rash, itching, hives, swelling of the face, lips, tongue, or throat

Side effects that usually do not require medical attention (report these to your care team if they continue or are bothersome):

• Diarrhea
• Headache
• Nausea
• Vomiting

This list may not describe all possible side effects. Call your doctor for medical advice about side effects.

Mechanism of Action

The influenza virus RNA polymerase complex is a heterotrimer made up of three protein subunits – polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), and polymerase acidic protein (PA). This polymerase complex is an influenza virus-specific enzyme essential for viral gene transcription and replication,6 with its subunits playing different roles in viral mRNA synthesis. The PB2 subunit binds to the cap of host cellular pre-messenger RNA, allowing the PA protein – a cap-dependent endonuclease – to cleave the capped pre-messenger RNA. This initial step of mRNA synthesis by the PA protein, also known as the “cap-snatching process,” provides an RNA primer for the PB1 subunit, which carries out its RNA-dependent RNA polymerase function to proceed with viral mRNA transcription.

After administration, the prodrug baloxavir marboxil is almost completely hydrolyzed by esterases in the gastrointestinal lumen, intestinal epithelium, liver and blood 3 to its active metabolite, baloxavir.6 Baloxavir selectively inhibits the PA protein,6 blocking the initiation of mRNA synthesis and ultimately influenza virus proliferation. Cap-dependent endonuclease is a highly conserved region across influenza strains;4 however, baloxavir is still vulnerable to resistance because amino acid substitutions in the PA protein can lead to reduced viral susceptibility to baloxavir.

Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aluminum
• Calcium
• Iron
• Magnesium
• Selenium
• Zinc

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Baloxavir marboxil dosage

Baloxavir marboxil is taken as a single, one-time dose that’s based on your body weight. The following information describes dosages that are commonly used or recommended. However, be sure to take the dosage your doctor prescribes for you. Your doctor will determine the best dosage to fit your needs.

Drug forms and strengths

Baloxavir marboxil comes as:

• These are taken by mouth and are available in two strengths: 20 mg and 40 mg.
• Granules that are made into a solution. Xofluza solution is taken by mouth and is available in one strength: 40 mg/20 mL.

Dosage for treating or preventing the flu

The recommended dosage of Xofluza is the same for either treating or preventing influenza (the flu). Dosages for Xofluza tablets and Xofluza solution are described below. With either form of the drug, you should take a single dose of Xofluza:

• Within 48 hours of when your flu symptoms start, or
• As soon as possible after you’re in contact with someone who has the flu

Dosage for Xofluza tablets

The recommended dosing instructions of Xofluza tablets for adults and children ages 12 years and older are as follows:

• People who weigh less than 80 kilograms (kg), or about 176 pounds (lb), should take a single dose of 40 mg (two 20-mg tablets)
• People who weigh 80 kg (176 lb) or more should take a single dose of 80 mg (two 40-mg tablets)

Dosage for Xofluza solution

The recommended dosing instructions of Xofluza solution for adults and children ages 12 years and older are as follows:

• people who weigh less than 80 kilograms (about 176 pounds) should take a single dose of 40 mg (one 40 mg/20 mL-bottle)
• people who weigh 80 kilograms or more should take a single dose of 80 mg (two 40 mg/20 mL-bottles)

Pediatric dosage

Xofluza is not approved for children under 12 years old. For children ages 12 years and older, see the recommended dosing instructions above.

Overdose or Toxicity

There is limited clinical experience with baloxavir overdose. In one ascending single-dose study involving healthy volunteers, up to 80 mg dose of baloxavir was administered without notable safety concerns. Treatment of an overdose of baloxavir marboxil 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 baloxavir marboxil. Baloxavir, the active ingredient, is unlikely to be significantly removed by dialysis due to high serum protein binding.

What special precautions should I follow?

Before taking baloxavir marboxil,

• Tell your doctor and pharmacist if you are allergic to baloxavir marboxil, any other medications, or any of the ingredients in baloxavir marboxil tablets or suspension. Ask your pharmacist for a list of the ingredients.
• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• do not take antacids or laxatives containing magnesium, aluminum, or calcium, calcium supplements, iron products, or vitamin or mineral supplements containing calcium, iron, zinc or selenium with baloxavir marboxil.
• Tell your doctor if you are pregnant or are breastfeeding.
• Tell your doctor if you have recently received or are scheduled to receive any vaccines.