Mode of action

Avacopan is a selective antagonist of a receptor for a protein in the blood called complement 5a (or C5a), which forms part of the immune system. When C5a attaches to its receptor, it activates neutrophils, which contribute to the inflammation of small blood vessels in GPA and MPA. By blocking the receptor for C5a, Tavneos is expected to reduce inflammation of blood vessels, thus improving the symptoms of the disease.

Posology

The recommended dose of Tavneos is 30mg (three hard capsules of 10mg each), taken orally morning and evening, with food.

Treatment should be initiated and monitored by healthcare professionals experienced in the diagnosis and treatment of GPA or MPA. Tavneos should be administered in combination with a rituximab or cyclophosphamide regimen. If a patient misses a dose, the missed dose is to be taken as soon as possible, unless it is within three hours of the next scheduled dose. If within three hours, then the missed dose is not to be taken. Treatment must be reassessed and temporarily stopped in the case of adverse reactions including liver function abnormalities, leukopenia, neutropenia, or serious infections, as described in the SPC.

Special warnings and precautions for use

• Avacopan can cause liver function abnormalities and must be avoided in patients with signs of liver disease. Hepatic transaminases and total bilirubin must be obtained prior to initiation of therapy and monitored thereafter;
• White blood cell count must be obtained prior to initiation and monitored thereafter. Patients must be advised to report any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow failure;
• Caution is required in treating patients with a history of TB, Hepatitis B, Hepatitis C, or HIV;
• The safety of immunisation with live vaccines following avacopan therapy has not been studied. Vaccinations should be administered prior to initiation of treatment or during quiescent phase of the disease;
• Angioedema has been reported in patients receiving avacopan. Patients must notify their doctor if they develop any symptoms such as swelling of the face, lips, or tongue, throat tightness, or difficulty breathing;
• The use of strong CYP3A4 enzyme inducers (for example, carbamazepine, phenobarbital, phenytoin, rifampicin, and St. John’s Wort), with avacopan is to be avoided. Patients requiring long-term administration of these medicinal products should not receive avacopan. If short-term co-administration cannot be avoided, the patient must be closely monitored in case of any reoccurrence of disease activity. Caution is required when using moderate CYP3A4 inducers;
• Strong CYP3A4 inhibitors (for example, clarithromycin, itraconazole) should be used with caution in patients treated with avacopan, due to potential increase of side effects due to increased exposure to avacopan. Grapefruit and grapefruit juice can increase the concentration of avaopan and should be avoided;
• Patients with GPA or MPA are at risk of cardiac disorders such as myocardial infarction, cardiac failure, and cardiac vasculitis. Serious cardiac adverse events have been reported in patients treated with avacopan;
• Immunomodulatory medicines such as avacopan may increase the risk for malignancies;
• Avacopan is not recommended during pregnancy and in women of childbearing potential not using contraception;
• 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; and
• The capsules contain macrogolglycerol hydroxystearate, which may cause stomach upset and diarrhoea.

Adverse reactions

• The most common adverse reactions are nausea, headache, decreased white blood cell count, upper respiratory tract infection, diarrhoea, vomiting, and nasopharyngitis; and
• The most common serious adverse reactions are liver function abnormalities and pneumonia.

EU authorisation and pack size details

Tavneos was authorised throughout the EU by the EMA in January 2022. This medicine is subject to additional monitoring (black triangle). Patients and healthcare professionals are strongly encouraged to report any suspected side effects with medicines displaying the black triangle, so that any new emerging information can be analysed efficiently.

Tavneos is available in Ireland currently in a pack size of 180 capsules (one month’s supply). This medicine does not require special temperature storage conditions but should be stored in the original bottle to protect it from light.

TAVNEOS 10MG HARD CAPSULES  180 hard capsules

High Tech Number: 89053