Tecovirimat

Indications

Tecovirimat is used for: Human Smallpox Disease

Adult Dose

Human Smallpox Disease Antiviral agent indicated for treatment of human smallpox disease caused by variola virus >40 kg: 600 mg PO BID for 14 days Hepatic impairment Mild, moderate, or severe (Child-Pugh class A, B, or C): No dosage adjustment required

Child Dose

Human Smallpox Disease Indicated for treatment of human smallpox disease caused by variola virus in adults and children weighing ?13 kg <13 kg: Safety and efficacy not established 13 kg to <25 kg: 200 mg PO BID for 14 days 25 kg to <40 kg: 400 mg PO BID for 14 days >40 kg: 600 mg PO BID for 14 days

Renal Dose

Renal impairment Mild, moderate, severe, or patients with ESRD requiring hemodialysis: No dosage adjustment required

Administration

Administer within 30 minutes after a full meal of moderate or high fat

Contra Indications

Precautions

Coadministration with repaglinide (an antidiabetic agent) may cause mild-to-moderate hypoglycemia; monitor blood glucose and monitor for hypoglycemic symptoms when administering tecovirimat with repaglinide (see Drug interaction overview)

Pregnancy-Lactation

Pregnancy There are no available data regarding use in pregnant women Animal studies In animal reproduction studies, no embryofetal developmental toxicity was observed in mice and rabbits during the period of organogenesis at tecovirimat exposures (AUC) up to 23 and 24 times higher than human exposure at the recommended human dose Infertility No data are available regarding the effect on female and male reproductive potential in humans Decreased fertility due to testicular toxicity was observed in male mice Lactation The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition

Interactions

Vaccines No vaccine-drug interaction studies have been performed in humans Some animal studies have indicated that coadministration of tecovirimat at the same time as live smallpox vaccine (vaccinia virus) may reduce the immune response to the vaccine The clinical impact of this interaction on vaccine efficacy is unknown

Adverse Effects

Side effects of Tecovirimat : >10% Headache (12%) 1-10% Nausea (5%) Abdominal pain (2%) Vomiting (2%) <2% Gastrointestinal: Dry mouth, chapped lips, dyspepsia, eructation, oral paresthesia General and administration site: Pyrexia, pain, chills, malaise, thirst Investigations: Abnormal electroencephalogram, hematocrit decreased, hemoglobin decreased, heart rate increased Musculoskeletal and connective tissue: Arthralgia, osteoarthritis Nervous system: Migraine, disturbance in attention, dysgeusia, paresthesia Psychiatric: Depression, dysphoria, irritability, panic attack Respiratory, thoracic, and mediastinal disorders: Oropharyngeal pain Skin and subcutaneous tissue: Palpable purpura, rash, pruritic rash, facial redness, facial swelling, pruritus

Mechanism of Action

Antiviral agent; 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