Tecovirimat

Tecovirimat (^TPOXX®) is an antiviral agent with activity against orthopox viruses such as smallpox and monkeypox.

Average half-life: approx. 19.0 hours.

Tecovirimat inhibits the activity of the VP37 protein of orthopoxviruses, which is encoded by a highly conserved gene in all members of the orthopoxvirus genus. Here, tecovirimat blocks the interaction of VP37 with the cellular Rab9 GTPase and TIP47, which prevents the formation of exit-competent enveloped virions required for cell-to-cell spread of the virus.

Average half-life: approx. 19.0 hours;

Q0 value: 0.0

Tecovirimat is available in the form of hard capsules for oral administration and should be taken as soon as possible after diagnosis. Ideally, it should be taken within 30 minutes of a moderately or heavily fatty meal.

Tecovirimat is indicated for the treatment of the following viral infections:

• smallpox
• monkeypox
• cowpox

Tecovirimat can also be used to treat complications due to replication of the vaccinia virus after smallpox vaccination in adults and children weighing at least 13 kg.

Pregnancy: To date, there is neither experience with the use of tecovirimat in pregnant women nor sufficient animal studies with regard to reproductive toxicity. The use of tecovirimate during pregnancy is therefore not recommended.

Lactation: It is not known whether tecovirimat/metabolites pass into breast milk. The available toxicological/safety data from animals showed that tecovirimate passes into milk. Since a risk to the newborn/infant cannot be excluded, breastfeeding should be discontinued during treatment with tecovirimate.

The recommended dose depends on the patient's weight:

• 13 kg body weight to less than 25 kg body weight: 200 mg every 12 hours for 14 days
• 25 kg body weight to less than 40 kg body weight: 400 mg every 12 hours for 14 days
• 40 kg body weight and more: 600 mg every 12 hours for 14 days.

Special patient groups

• Elderly patients: No dose adjustment is necessary (see section 5.2).
• Impaired renal function: No dose adjustment is necessary (see section 5.2).
• Hepatic impairment: No dose adjustment is necessary (see section 5.2).
• Children and adolescents: Tecovirimate should not be given to children weighing less than 13 kg. No dosage recommendations have been established.

Tecovirimat is available in the form of hard capsules for oral administration and should be taken as soon as possible after diagnosis. Ideally, it should be taken within 30 minutes after a moderately or heavily fatty meal.

The most common side effects associated with the use of Tecovirimat are:

• headache
• dizziness
• Pain in the upper abdomen
• Abdominal discomfort
• diarrhea
• Nausea
• Vomiting
• Skin manifestations: Possible skin reactions include: macular exanthema, urticaria, in very rare cases angioedema (lips, eyelid areas); pruritus;

Note: If vomiting occurs within 30 minutes after taking Tecovirimat hard capsules, another dose can be used immediately. If vomiting occurs later than 30 minutes after taking Tecovirimat hard capsules, no further dose should be used and intake should be continued as usual after 12 hours.

The following interactions must be considered when using tecovirimate:

• Sensitive CYP3A4 or CYP2B6 substrates: Tecovirimate and its M4 metabolite are inducers of cytochrome P450 (CYP)3A and CYP2B6, therefore decreased plasma exposure of sensitive CYP3A4 or CYP2B6 substrates may occur.
• Sensitive CYP2C8 or CYP2C19 substrates: Concomitant use with tecovirimate may lead to increased plasma exposure of sensitive CYP2C8 or CYP2C19 substrates, which may result in increased adverse reactions.
• Live smallpox vaccine: Some animal studies indicate that concomitant administration of tecovirimat and live smallpox vaccine (vaccinia virus) may reduce the immune response to the vaccine.

Tecovirimat must not be used in case of hypersensitivity to the active substance.

There are no known cases of naturally occurring orthopoxviruses with resistance to tecovirimat, although tecovirimat resistance may develop as a result of drug selection.

Tecovirimat has a relatively low resistance barrier, and certain amino acid substitutions in the target protein VP37 can greatly reduce the antiviral activity of tecovirimat. The possibility of resistance to tecovirimat should be considered in patients who either do not respond to therapy or who experience a new onset of disease after an initial response phase.

Tecovirimat has a minor influence on the ability to drive and use machines, as dizziness may occur during use.

1. Brüssow H (2023) Pandemic potential of poxviruses: From an ancient killer causing smallpox to the surge of monkeypox. Microb Biotechnol 16:1723-1735
2. Duraffour S et al. (2010) Tecovirimat, a p37 envelope protein inhibitor for the treatment of smallpox infection. IDrugs 13:181-191.
3. Halani S et al. (2022) Tecovirimat for monkeypox. CMAJ 194:E1573.
4. Khan M et al. (2023) Managing Monkeypox Virus: Characterizing Common Cutaneous Manifestations and Antiviral Efficacy. J Drugs Dermatol 22:282-287.
5. Karagoz A et al. (2023) Monkeypox (mpox) virus: Classification, origin, transmission, genome organization, antiviral drugs, and molecular diagnosis. J Infect Public Health 16:531-541.