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Tecovirimat

Class: Antivirals, Miscellaneous
Chemical Name: Benzamide, N-[(3aR,4R,4aR,5aS,6S,6aS)-3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6 ethenocycloprop[f]isoindol-2(1H)-yl]-4-(trifluoromethyl), rel-(monohydrate)
Molecular Formula: C19H15F3N2O3•H2O
CAS Number: 816458-31-8
Brands: TPOXX

Medically reviewed by Drugs.com on March 29, 2021. Written by ASHP.

Introduction

Tecovirimat is an inhibitor of the orthopoxvirus VP37 envelope wrapping protein.

Uses for Tecovirimat

Tecovirimat has the following uses:

Tecovirimat is indicated for the treatment of human smallpox disease in adults and pediatric patients weighing at least 13 kg.

Tecovirimat has the following limitations of use:

The effectiveness of tecovirimat for treatment of smallpox disease has not been determined in humans because adequate and well-controlled field trials have not been feasible, and inducing smallpox disease in humans to study the drug’s efficacy is not ethical.

Tecovirimat efficacy may be reduced in immunocompromised patients based on studies demonstrating reduced efficacy in immunocompromised animal models.

Tecovirimat Dosage and Administration

General

Tecovirimat is available in the following dosage form(s) and strength(s):

Capsule: 200 mg (of anhydrous tecovirimat).

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Dosage of tecovirimat monohydrate is expressed in terms of anhydrous tecovirimat.

Tecovirimat should be taken within 30 minutes after a full meal of moderate or high fat.

Pediatric Patients

Dosage for Pediatric Patients Weighing 13 kg to less than 25 kg

The recommended dosage of tecovirimat in pediatric patients weighing 13 kg to less than 25 kg is 200 mg taken twice daily orally for 14 days.

Dosage for Pediatric Patients Weighing 25 kg to less than 40 kg

The recommended dosage of tecovirimat in pediatric patients weighing 25 kg to less than 40 kg is 400 mg (two 200-mg capsules) taken twice daily orally for 14 days.

Dosage for Pediatric Patients Weighing at Least 40 kg

The recommended dosage of tecovirimat in pediatric patients weighing at least 40 kg is 600 mg (three 200-mg capsules) taken twice daily orally for 14 days.

Adults

Dosage for Adults Weighing at Least 40 kg

The recommended dosage of tecovirimat in adults weighing at least 40 kg is 600 mg (three 200-mg capsules) taken twice daily orally for 14 days.

Pediatric Patients and Adults Who Cannot Swallow Capsules

For individuals who cannot swallow capsules, tecovirimat can be administered by carefully opening the capsules of the drug and mixing the entire contents in 30 mL of liquid (e.g., milk, chocolate milk) or soft food (e.g., applesauce, yogurt). The entire mixture should be administered within 30 minutes after preparation.

Table 1: Recommended Dosage and Preparation Instructions for Pediatric Patients and Adults Who Cannot Swallow Capsules

Body Weight

Dosage

Number of Tecovirimat 200-mg Capsules

Drug-Food Preparation for Each Dose

13 kg to less than 25 kg

200 mg twice daily

1 capsule twice daily

Mix contents of 1 capsule with 30 mL of liquid or soft food

Administer entire mixture

25 kg to less than 40 kg

400 mg twice daily

2 capsules twice daily

Mix contents of 2 capsules with 30 mL of liquid or soft food

Administer entire mixture

40 kg and above

600 mg twice daily

3 capsules twice daily

Mix contents of 3 capsules with 30 mL of liquid or soft food

Administer entire mixture

Cautions for Tecovirimat

Contraindications

None.

Warnings/Precautions

Hypoglycemia When Co-administered with Repaglinide

Co-administration of repaglinide and tecovirimat may cause mild to moderate hypoglycemia. Monitor blood glucose and monitor for hypoglycemic symptoms when administering tecovirimat with repaglinide.

In a drug interaction study, 10 of 30 healthy subjects experienced mild (6 subjects) or moderate (4 subjects) hypoglycemia following co-administration of repaglinide (2 mg) and tecovirimat. Symptoms resolved in all subjects after intake of food and/or oral glucose.

Specific Populations

Pregnancy

Risk Summary: No adequate and well-controlled studies in pregnant women were conducted; therefore, there are no human data to establish the presence or absence of tecovirimat-associated risk.

In animal reproduction studies, no embryofetal developmental toxicity was observed in mice during the period of organogenesis at tecovirimat exposures (area under the curve [AUC]) up to 23 times higher than human exposure at the recommended human dose (RHD). In rabbits, no embryofetal developmental toxicity was observed during organogenesis at tecovirimat exposures (AUC) less than human exposures at the RHD. In a mouse pre-/post-natal development study, no toxicities were observed at maternal tecovirimat exposures up to 24 times higher than human exposure at the RHD.

The background risk of major birth defects and miscarriage for the indicated population is unknown. 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.

Animal Data: Tecovirimat was administered orally to pregnant mice at doses up to 1000 mg/kg/day from gestation Days 6-15. No embryofetal toxicities were observed at doses up to 1000 mg/kg/day (approximately 23 times higher than human exposure at the RHD).

Tecovirimat was administered orally to pregnant rabbits at doses up to 100 mg/kg/day from gestation Days 6-19. No embryofetal toxicities were observed at doses up to 100 mg/kg/day (0.4 times the human exposure at the RHD).

In the pre-/post-natal development study, tecovirimat was administered orally to pregnant mice at doses up to 1000 mg/kg/day from gestation Day 6 to post-natal Day 20. No toxicities were observed at doses up to 1000 mg/kg/day (approximately 24 times higher than human exposure at the RHD).

Lactation

Risk Summary: There are no data to assess the effect on milk production, the presence of the drug in human milk, and/or the effects on the breastfed child. When administered to lactating mice, tecovirimat was present in the milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tecovirimat and any potential adverse effects on the breastfed child from tecovirimat or from the underlying maternal condition.

Data: In a lactation study at doses up to 1000 mg/kg/day, mean tecovirimat milk to plasma ratios up to approximately 0.8 were observed at 6 and 24 hours post-dose when administered orally to mice on lactation Day 10 or 11.

Females and Males of Reproductive Potential

There are no data on the effect of tecovirimat on female and male reproductive potential in humans. Decreased fertility due to testicular toxicity was observed in male mice.

Pediatric Use

As in adults, the effectiveness of tecovirimat in pediatric patients is based solely on efficacy studies in animal models of orthopoxvirus disease. As exposure of healthy pediatric subjects to tecovirimat with no potential for direct clinical benefit is not ethical, pharmacokinetic simulation was used to derive dosing regimens that are predicted to provide pediatric patients with exposures comparable to the observed exposure in adults receiving 600 mg twice daily. The dosage for pediatric patients is based on weight.

Geriatric Use

Clinical studies of tecovirimat did not include sufficient numbers of subjects aged 65 and over to determine whether the safety profile of tecovirimat is different in this population compared to younger subjects. Of the 359 subjects in the clinical study of tecovirimat, 10% (36/359) were ≥65 years of age, and 1% (4/359) were ≥75 years of age. No alteration of dosing is needed for patients ≥65 years of age.

Renal Impairment

No dosage adjustment is required for patients with mild, moderate or severe renal impairment or patients with end stage renal disease (ESRD) requiring hemodialysis.

Hepatic Impairment

No dosage adjustment is required for patients with mild, moderate or severe hepatic impairment (Child-Pugh Class A, B, or C).

Common Adverse Effects

Common adverse reactions in healthy adult subjects (≥2%) were headache, nausea, abdominal pain, and vomiting.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Consult the full prescribing information prior to and during treatment for potential drug interactions.

Actions and Spectrum

Mechanism of Action

Tecovirimat is an antiviral agent active against variola (smallpox) virus. Tecovirimat targets and inhibits the activity of the orthopoxvirus VP37 protein (encoded by and highly conserved in all members of the orthopoxvirus genus) and blocks its interaction with cellular Rab9 GTPase and TIP47, which prevents the formation of egress-competent enveloped virions necessary for cell-to-cell and long-range dissemination of virus.

Spectrum

In cell culture assays, the effective concentrations of tecovirimat resulting in a 50% reduction in virus-induced cytopathic effect (EC50), were 0.016-0.067 µM, 0.014-0.039 µM, 0.015 µM, and 0.009 µM, for variola, monkeypox, rabbitpox, and vaccinia viruses, respectively. Ranges given for variola and monkeypox viruses are reflective of results from multiple strains assayed.

Resistance

There are no known instances of naturally occurring tecovirimat-resistant orthopoxviruses, although tecovirimat resistance may develop under drug selection. Tecovirimat has a relatively low resistance barrier, and certain amino acid substitutions in the target VP37 protein can confer large reductions in tecovirimat antiviral activity. The possibility of resistance to tecovirimat should be considered in patients who either fail to respond to therapy or who develop recrudescence of disease after an initial period of responsiveness.

Cross Resistance: There are no other antiviral drugs approved for the treatment of variola (smallpox) virus infection.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Efficacy Based on Animal Models Alone: Inform patients that the efficacy of tecovirimat is based solely on efficacy studies demonstrating a survival benefit in animals and that the effectiveness of tecovirimat has not been tested in humans with smallpox disease.

Important Dosage and Administration Information: Advise patients to take tecovirimat as directed within 30 minutes of eating a full meal of moderate or high fat. Inform patients to take tecovirimat for the entire duration without missing or skipping a dose.

Drug Interactions: Inform patients that tecovirimat may interact with other drugs. Advise patients to report to their healthcare provider the use of other prescription drugs. Co-administration of tecovirimat with repaglinide may cause hypoglycemia.

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Tecovirimat is stored in the US Strategic National Stockpile (SNS) and is not commercially available in the US. The SNS ensures that certain drugs and medical supplies are readily available to prevent or treat specific diseases, including during public health emergencies, and is managed by the US Department of Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response (ASPR). To request a drug from the SNS, state health departments can contact the US Centers for Disease Control and Prevention (CDC) Emergency Operations Center at 770-488-7100 or the HHS Secretary's Operations Center at 202-619-7800.

Tecovirimat

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsule

200 mg (of anhydrous tecovirimat)

TPOXX

SIGA Technologies Inc.

AHFS Drug Information. © Copyright 2021, Selected Revisions April 8, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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