Tavneos

/ CTS

The recommended dose is 30 mg Avacopan (3 hard capsules of 10 mg each) taken orally twice daily, morning and evening, with food.
See prescribing information for full details

Avacopan, in combination with a rituximab or cyclophosphamide regimen, is indicated for the treatment of adult patients with severe, active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).

Hypersensitivity to the active substance or to any of the excipients.

Hepatotoxicity
Serious adverse reactions of elevated hepatic transaminases with elevated total bilirubin have been observed in patients receiving avacopan in combination with cyclophosphamide (followed by azathioprine or mycophenolate) or rituximab, and trimethoprim and sulfamethoxazole.
In the post-marketing setting, drug-induced liver injury and vanishing bile duct syndrome (VBDS), including cases with fatal outcomes, have been reported.
Avacopan must be avoided in patients with signs of liver disease, such as elevated AST, ALT, alkaline phosphatase (ALP), or total bilirubin > 3 times ULN.
Hepatic transaminases and total bilirubin must be obtained prior to initiation of therapy. Patients must be monitored for hepatic transaminases and total bilirubin as clinically indicated and as part of the routine follow-up of patient’s underlying condition.
Blood and immune system
White blood cell (WBC) count must be obtained prior to initiation of therapy and patients must be monitored as clinically indicated and as part of the routine follow-up of patient’s underlying condition. Treatment with avacopan must not be initiated if WBC count is < 3.5 × 109/L, or neutrophil count < 1.5 × 109/L, or lymphocyte count < 0.5 × 109/L. Patients receiving avacopan must be instructed to report immediately any evidence of infection, unexpected bruising, bleeding, or any other manifestations of bone marrow failure.
Serious infections
Serious infections have been reported in patients receiving combination agents for treatment of GPA or MPA, including avacopan in combination with rituximab or cyclophosphamide. Patients must be assessed for any serious infections.
Avacopan has not been studied in patients with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infections. Before and during treatment, patients must notify their physician if they have been diagnosed with tuberculosis, hepatitis B, hepatitis C, or HIV infection. Be cautious when treating patients with a history of tuberculosis, hepatitis B, hepatitis C, or HIV infection.
Avacopan does not decrease the formation of the membrane attack complex (C5b-9) or terminal complement complex (TCC). No cases of Neisseria meningitidis have been identified in the avacopan clinical program. Monitor patients treated for ANCA-associated vasculitis according to standard practice for clinical signs and symptoms of Neisseria infections.
Pneumocystis jirovecii pneumonia prophylaxis
Pneumocystis jirovecii pneumonia prophylaxis is recommended for adult patients with GPA or MPA during avacopan treatment, as appropriate according to local clinical practice guidelines.
Immunisation
The safety of immunization with live vaccines, following avacopan therapy has not been studied. Administer vaccinations preferably prior to initiation of treatment with avacopan or during quiescent phase of the disease.
Angioedema
Patients must notify their physician if they develop any symptoms such as swelling of the face, lips, or tongue, throat tightness, or difficulty breathing.
Avacopan must be withheld in cases of angioedema.
Interaction with strong CYP3A4 inducers
The use of strong CYP3A4 enzyme inducers (e.g., carbamazepine, enzalutamide, mitotane, phenobarbital, phenytoin, rifampicin, and St. John’s Wort) with avacopan is to be avoided. Patients anticipated to require long-term administration of these medicinal products are not to be treated with avacopan. If short-term co-administration cannot be avoided in a patient already using avacopan, the patient must be closely monitored in case of any reoccurrence of disease activity.
Cardiac disorders
Patients with GPA or MPA are at risk of cardiac disorders such as myocardial infarction, cardiac failure, and cardiac vasculitis.
Serious adverse events (SAEs) of cardiac disorder have been reported in patients treated with avacopan. A treatment regimen based on the combination with cyclophosphamide followed by azathioprine may carry an increased risk for cardiac disorders as compared to a regimen based on the combination with rituximab.
See prescribing information for full details.

The most common adverse reactions are nausea (23.5%), headache (20.5%), white blood cell count decreased (18.7%), upper respiratory tract infection (14.5%), diarrhoea (15.1%), vomiting (15.1%), and nasopharyngitis (15.1%).
The most common serious adverse reactions are liver function abnormalities (5.4%) and pneumonia (4.8%).
See prescribing information for full details

Avacopan is a substrate of CYP3A4. Co-administration of inducers or inhibitors of this enzyme may affect the pharmacokinetics of avacopan.
Effect of avacopan on other medicinal products
Avacopan is a weak inhibitor of CYP3A4 in vivo and may increase the plasma exposures of concomitant medicinal products that are CYP3A4 substrates with a narrow therapeutic index (e.g., alfentanil, ciclosporin, dihydroergotamine, ergotamine, fentanyl, sirolimus and tacrolimus). Be cautious when these medicinal products are used with avacopan.
Effect of macrogolglycerol hydroxystearate on sensitive P-glycoprotein (P-gp) substrates: A clinically relevant effect of the excipient macrogolglycerol hydroxystearate on sensitive P-gp substrates with relatively low bioavailability (e.g., dabigatran etexilate) cannot be excluded. Exercise caution when using low-bioavailability P-gp substrates in patients who are being treated with avacopan.
See prescribing information for full details

Pregnancy: Women of childbearing potential/Pregnancy There are no data on the use of avacopan in pregnant women.
Lactation: A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy with avacopan, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility:
There are no data on the effects of avacopan on human fertility. Animal data did not indicate any impairment of male or female fertility.

Avacopan was studied in healthy subjects at a maximum total daily dose of 200 mg (given as 100 mg twice daily) for 7 days without evidence of dose limiting toxicities. In case of an overdose, it is recommended that the patient is monitored for any signs or symptoms of adverse effects, and appropriate symptomatic treatment and supportive care are provided.