Brincidofovir

Brincidofovir is a prescription medication used for the treatment of human smallpox disease caused by variola virus in adult and pediatric patients, including neonates.

• Brincidofovir is available under the following different brand names: Tembexa.

Common side effects of Brincidofovir include:

• diarrhea
• nausea
• vomiting
• abdominal pain

Serious side effects of Brincidofovir include:

• liver problems: swelling of the stomach, yellowing of the skin or the whites of the eyes, confusion, dark or brown urine
• dehydration: dry mouth, not urinating as much, lightheadedness, dizziness
• cancer: fever, extreme tiredness (fatigue), or weight loss

Rare side effects of Brincidofovir include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

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

Adult and pediatric dosage

Tablet

• 100 mg

Oral suspension

• 10 mg/mL

Smallpox

Adult dosage

• Weighing 48 kg and more (tablet or oral suspension): 200 mg orally every week for 2 doses (on days 1 and 8)
• Weighing less than 48 kg (oral suspension): 4 mg/kg orally every week for  2 doses (on days 1 and 8)

Pediatric dosage

• Weighing 48 kg and more (tablet or oral suspension): 200 mg orally every week for 2 doses (on days 1 and 8)
• Weighing between 10 and 48 kg (oral suspension): 4 mg/kg orally every week for 2 doses (on days 1 and 8)
• Weighing less than 10 kg (oral suspension): 6 mg/kg orally every week for 2 doses (on days 1 and 8)

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Brincidofovir has severe interactions with no other drugs
• Brincidofovir has serious interactions with no other drugs
• Brincidofovir has moderate interactions with the following drug:
  • ublituximab
• Brincidofovir has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Brincidofovir?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Brincidofovir?”

Cautions

• Increased mortality if used for a longer duration
• Not indicated for use in diseases other than human smallpox
• Increased mortality observed in a randomized, placebo-controlled phase 3 trial when evaluated for another disease (cytomegalovirus [CMV] infection)
• Increased risk of mortality is possible if used for a duration longer than at the recommended dosage on Days 1 and 8
• Elevated hepatic transaminases and bilirubin
  • Elevations in alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin observed
  • Perform hepatic laboratory testing in all patients before starting and during treatment, as clinically appropriate
  • Monitor patients who develop abnormal test results for the development of severe hepatic injury
  • Consider discontinuing if ALT levels remain persistently above 10x ULN
  • Do not give a second dose if ALT elevation is accompanied by clinical signs and symptoms of liver inflammation or increasing direct bilirubin, alkaline phosphatase, or international normalised ratio
• Diarrhea and GI adverse effects
  • Diarrhea common during treatment
  • Other GI effects include nausea, vomiting, and abdominal pain
  • Monitor for dehydration, and if necessary, do not give the second dose
• Embryofetal toxicity, carcinogenicity, and male infertility
  • Based on findings from animal reproduction studies, may cause fetal harm when administered to pregnant women
  • Considered a potential human carcinogen; mammary adenocarcinomas and squamous cell carcinomas occurred in rats at systemic exposures less than the expected human exposure based on the recommended dose
  • Based on testicular toxicity in animal studies, may irreversibly impair fertility in males of reproductive potential
• Drug interaction overview
  • Cidofovir
    • Do not coadminister with IV cidofovir
    • Brincidofovir, a lipid-linked derivative of cidofovir, is intracellularly converted to cidofovir
  • OATP 1B1 and 1B3 inhibitors
    • If possible, consider alternative medications that are not OATP1B1 or 1B3 inhibitors
    • If concomitant use is necessary, increase monitoring for adverse reactions associated with brincidofovir (elevations in transaminases and bilirubin, diarrhea, or other GI adverse events) and postpone dosing of OATP1B1 or 1B3 inhibitors for at least 3 hours after brincidofovir administration
  • Vaccines
    • No vaccine-drug interaction studies have been performed in humans; clinical impacts unknown
    • Animal studies suggest coadministration of brincidofovir at the same time as live smallpox vaccine (vaccinia virus) may reduce the immune response to the vaccine
    • Brincidofovir may reduce the immune response to replication-defective smallpox vaccine (modified vaccinia virus Ankara)

Pregnancy and Lactation

• Based on findings from animal reproduction studies, brincidofovir  may cause fetal harm when administered to pregnant women
• Perform pregnancy testing in individuals of childbearing potential before initiating
• Contraception
  • Females of childbearing potential: Use effective contraception during treatment and for at least 2 months after the last dose
  • Males: Advise sexually active individuals with partners of childbearing potential to use condoms during treatment and for at least 4 months after the last dose
• Male infertility
  • Based on testicular toxicity in animal studies, brincidofovir may irreversibly impair fertility in males of reproductive potential
• Lactation
  • Breastfeeding is not recommended in patients with smallpox
  • Data are not available on the presence of brincidofovir in human milk, its effects on breastfed infants, or milk production
  • Brincidofovir is present in animal milk