TECOVIRIMAT SIGA Hard capsule Ref.[28350] Active ingredients: Tecovirimat

Co-administration of other medicinal products

Co-administration of repaglinide and tecovirimat may cause mild to moderate hypoglycaemia, (see section 4.5). Blood glucose and hypoglycaemic symptoms should be monitored when administering tecovirimat with repaglinide.

Co-administration of midazolam and tecovirimat may reduce the effectiveness of midazolam (see section 4.5). Effectiveness of midazolam should be monitored when administering tecovirimat with midazolam.

Renal impairment

Tecovirimat should be used with caution in patients with severe renal impairment as there is limited clinical data in this population and higher unbound drug and metabolites levels may be observed. (see sections 4.2 and 5.2).

Hepatic impairment

Tecovirimat should be used with caution in patients with severe hepatic impairment as there is limited clinical data in this population and higher unbound drug and metabolite levels may be observed (see sections 4.2 and 5.2).

Immunocompromised population

The safety and efficacy of tecovirimat has not been evaluated in immunocompromised individuals. Nonclinical studies using animal models indicate that tecovirimat may have reduced efficacy in immunocompromised individuals. (See section 5.1).

Excipients

This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicine contains sunset yellow (E110). May cause allergic reactions.

Effect of other medicinal products on tecovirimat

Tecovirimat is a substrate of UGT1A1, 1A3 and 1A4. Co-administration of tecovirimat with strong inhibitors or inducers of these UGTs is not expected to have a clinically important effect on tecovirimat exposures.

Effect of tecovirimat on other medicinal products

Tecovirimat and its M4 metabolite are inducers of cytochrome P450 (CYP)3A and CYP2B6. Co-administration with tecovirimat may lead to reduced plasma exposures of sensitive substrates of CYP3A4 or CYP2B6, potentially leading to reduced effects. Monitoring is advised during co-administration of tecovirimat with CYP3A4 and CYP2B6 substrates that have narrow therapeutic windows. See Table 2 for some examples.

Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Co-administration with tecovirimat may lead to increased plasma exposures of sensitive substrates of CYP2C8 or CYP2C19, potentially leading to increased adverse effects. Monitoring is advised during co-administration of tecovirimat with CYP2C8 and CYP2C19 substrates that have narrow therapeutic windows. See Table 2 for some examples.

Table 2. Interactions and dose recommendations with other medicinal products:

^a These interactions have been studied in healthy adults to evaluate the effect of repeated doses of tecovirimat 600 mg twice daily on the single-dose PK of probe substrates.

Vaccine

No vaccine-drug interaction studies have been performed in human subjects. Some animal studies have indicated that co-administration of tecovirimat at the same time as live smallpox vaccine (vaccinia virus) may reduce the immune response to the vaccine.

Paediatric population

Interaction studies have only been performed in adults.

Pregnancy

There are no data from the use of tecovirimat in pregnant women.

Animal studies are insufficient with respect to reproductive toxicity (see section 5.3).

Tecovirimat is not recommended during pregnancy.

Breast-feeding

It is unknown whether tecovirimat/metabolites are excreted in human milk.

Available toxicological/safety data in animals have shown excretion of tecovirimat in milk (see section 5.3).

A risk to the newborns/infants cannot be excluded.

Breast-feeding should be discontinued during treatment with tecovirimat.

Fertility

The effects of tecovirimat on fertility in humans have not been studied.

Tecovirimat caused decreased fertility due to testicular toxicity in male mice (see section 5.3).

Tecovirimat has minor influence on the ability to drive and use machines. Patients should be informed about the possible occurrence of dizziness and should be cautoned about driving or operating machines until they know how tecovirimat will affect them.

Summary of the safety profile

The most frequently reported adverse drug reactions were headache (12.3%) and nausea (4.5%).

Tabulated summary of adverse reactions

Adverse reactions are classified according to System Organ Class and frequency. Frequency categories are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

Table 3. Frequency of Adverse Reactions by System Organ Class from Clinical Trials:

Paediatric population

Tecovirimat has not been studied in the paediatric population.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.