). 2 Recommended Dose and Dosage Adjustment). , chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis) and cirrhosis. Consider the risks and benefits before administrating TAVNEOS to a patient with a liver disease.
1 Special Populations). Immune Angioedema TAVNEOS may cause angioedema (see 8 ADVERSE REACTIONS). In clinical trials, two cases of angioedema occurred, including one serious event requiring hospitalization. If angioedema occurs, discontinue TAVNEOS immediately, provide appropriate therapy, and monitor for airway compromise.
TAVNEOS must not be re-administered unless another cause has been established. Educate patients on recognizing the signs and symptoms of a hypersensitivity reaction and to seek immediate medical care should they develop. Immunization The safety of immunization with live vaccines, following avacopan has not been studied.
Administer vaccination preferably prior to initiation of treatment with avacopan. Infection Serious infections, including fatal infections, have been reported in patients receiving TAVNEOS. 8%). Avoid use of TAVNEOS in patients with an active serious infection, including localized infections.
Consider the risks and benefits of treatment prior to initiating TAVNEOS in patients: - With chronic or recurrent infections - Who have been exposed to tuberculosis - With a history of a serious or an opportunistic infection TAVNEOS avacopan Page 8 of 29 Unclassified / Non classifié - Who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or - With underlying conditions that may predispose them to infection.
Closely monitor patients for the development of signs and symptoms of infection during and after treatment with TAVNEOS. Interrupt TAVNEOS if a patient develops a serious or opportunistic infection and treat accordingly. TAVNEOS may be resumed once the infection is controlled.
Pneumocystis jirovecii pneumonia prophylaxis:
Pneumocystis jirovecii pneumonia prophylaxis is recommended for adult patients with GPA or MPA during TAVNEOS treatment, as appropriate according to local clinical practice guidelines. 1 Dosing Considerations and 7 WARNINGS AND PRECAUTIONS, Hepatic ).
1 Dosing Considerations and 7 WARNINGS AND PRECAUTIONS).
Reproductive Health:
Female and Male Potential • Fertility There are no data on the effects of avacopan on human fertility. Fertility/early embryo development, embryo/foetal development, and pre- and post-natal development studies conducted with avacopan in hamsters or rabbits generally showed no evidence of reproductive toxicity or teratogenicity, at doses up to 1,000 mg/kg/day in hamsters and 200 mg/kg/day in rabbits; the only exceptions were an increased incidence of skeletal variations at 1,000 mg/kg/day avacopan in hamster and of abortion at 200 mg/kg/day avacopan in rabbits (see 16 NON-CLINICAL TOXICOLOGY, Reproductive and Developmental Toxicology ).
1 Pregnant Women Avacopan is not recommended during pregnancy and in women of childbearing potential not using contraception. There are no data from the use of avacopan in pregnant women. In animal studies designed to assess effects of avacopan upon embryo-fetal development with pregnant hamsters (dosed by the oral route during the period of organogenesis from gestation day 6 to 12), there was an increased incidence of skeletal variations (short thoracolumbar supernumerary rib) at the highest dose tested (500 mg/kg BID, which is equivalent to an exposure of 5 times the maximum recommended human dose calculated on an AUC basis with 1000 mg/kg/day).
In a prenatal and postnatal development study with pregnant hamsters (orally dosed from gestation day 6 to lactation day 20), avacopan had no effects on the growth and development of offspring with exposures up to approximately 5 times the maximum recommended human dose (based on maternal doses of up to 1000 mg/kg/day).
An embryo-fetal development study with pregnant rabbits dosed by the oral route during the period of organogenesis from gestation day 6 to 18 was conducted. 6 times the maximum recommended human dose (based on AUCs with the maternal oral doses of 30 mg/kg/day and higher) (see 16 NON-CLINICAL TOXICOLOGY, Reproductive and Developmental Toxicology ).
2 Breast-feeding The safety of avacopan when used during pregnancy or breastfeeding has not been evaluated in humans. There are no data on the use of avacopan in lactating women and it is unknown whether avacopan is excreted in human milk.
37. The no-observed-adverse-effect-level (NOAEL) for viability, growth, and reproduction in F1 offspring was 1,000 mg/kg/day (500 mg/kg twice daily) (see 16 NON-CLINICAL TOXICOLOGY, Reproductive and […]