Avacopan

Avacopan (Tavneos) is used to treat two forms of ANCA-associated vasculitis, both granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Avacopan is an add-on treatment used with other medicines for adults with active and severe symptoms.

Avacopan brand name is Tavneos, there is no generic avacopan available.

Avacopan capsules are taken twice daily with food. They should be swallowed whole and not crushed, chewed, or opened.

Avacopan works by blocking a receptor called complement 5a (or C5a), which is part of the immune system. When Avacopan blocks the C5a receptor, it helps reduce blood vessel inflammation, improving disease symptoms. Avacopan is called a complement 5a receptor (C5aR) antagonist.

Avacopan was developed by ChemoCentryx, a biopharmaceutical company specializing in oral medications for autoimmune diseases, inflammatory disorders, and cancers. ChemoCentryx was acquired by Amgen, a leading independent biotechnology company, on October 20, 2022.

Avacopan FDA approval was received on October 7, 2021, under the brand name Tavneos by ChemoCentryx, Inc. Tavneos is FDA-approved as a treatment for adults with severe active ANCA-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis) when used together with standard therapy, including glucocorticoids.

Avacopan FDA approval was granted after positive results from the Phase III ADVOCATE trial (NCT02994927), published in The New England Journal of Medicine (NEJM).

Anti-neutrophil cytoplasmic autoantibody-associated vasculitis (ANCA-associated vasculitis) is a rare autoimmune disease that causes inflammation and damage to small or medium-sized blood vessels, affecting various organs, including airways, kidneys, and lungs. Two forms of ANCA-associated vasculitis are granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

Granulomatosis with polyangiitis (GPA), previously called Wegener’s granulomatosis, mainly affects the respiratory tract and the kidneys, leading to sinusitis, nosebleeds, and kidney disease.

Microscopic polyangiitis (MPA) mainly affects the kidneys and lungs and, compared to GPA, less often involves the upper respiratory tract.

Avacopan mechanism of action is as a C5a receptor antagonist that blocks complement 5a (C5aR), a key part of the immune system responsible for inflammation. The complement cascade is a part of the immune system that, when overactive, may mistakenly attack and damage your cells. By inhibiting this receptor, avacopan calms down the overactive immune system, helping to reduce inflammation of blood vessels, relieve symptoms, and prevent further damage to blood vessels.

Take avacopan (Tavneos) capsules twice a day (morning and evening) with food.

Swallow the capsule whole with water. Do not crush, chew, break, or open the capsules.

Take this medicine exactly as your healthcare provider tells you how to take it. Do not stop treatment unless your healthcare provider tells you to. Check with your healthcare provider or pharmacist if you are not sure how to take this medicine.

This medicine may cause serious side effects, including severe liver problems such as vanishing bile duct syndrome (VBDS), which can lead to death. Call your doctor at once if you have unexplained symptoms such as yellowing of your skin or eyes (jaundice), itchy skin, pain on the upper right side of your stomach area, feeling tired, dark or brown urine, easy bleeding or bruising, or loss of appetite.

Your healthcare provider will do blood tests to check for hepatitis B and to see how well your liver is working before starting and during your treatment with this medicine. If you are of Japanese descent, your healthcare provider may recommend additional liver function testing and monitoring.

You should not use this medicine if you are allergic to avacopan or any inactive ingredients. Tell your doctor if you have ever had:

• liver problems or abnormal liver function tests;
• hepatitis B or C; or
• if you currently have an infection.

Pregnancy

Talk to your healthcare provider if you are pregnant, are planning a pregnancy, or become pregnant, as it is not known if these capsules will harm your unborn baby.

Breastfeeding

Talk to your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if this medicine can pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Tavneos.

Common avacopan side effects

Common avacopan side effects include:

• Nausea 39%
• Headache 34%
• High blood pressure 30%
• Diarrhea 25%
• Vomiting 25%
• Rash 19%
• Tiredness 17%
• Stomach pain 11%
• Dizziness 11%
• Increase blood creatinine levels 10%
• pins and needles (tingling or numbness) 9%.

These are the common side effects that occurred in 5% or more of patients in the Phase 3 clinical trial (NCT02994927) who received Tavneos 30 mg avacopan twice daily for 52 weeks.

Serious avacopan side effects

Get emergency medical help if you have signs of a serious allergic reaction, including shortness of breath or trouble breathing, swelling of your face, lips, tongue, or throat, trouble swallowing, chest pain, feeling dizzy or faint, or moderate or severe stomach pain or vomiting. Do not take this medicine if you are allergic to the active ingredient avacopan or any inactive ingredients.

Avacopan may cause other serious side effects. Call your doctor at once if you have:

• signs of liver problems - loss of appetite, pain or swelling in your stomach, swelling in your legs, easy bleeding, drowsiness, confusion, or jaundice (yellowing of the skin or eyes);
• signs of serious infections - fever, cold symptoms (runny nose or sore throat), flu symptoms (cough, tiredness, and body aches), earache or headache, painful urination, cold sores in mouth or throat; or
• signs of hepatitis B reactivation - worsening tiredness or yellowing of your skin or the white part of your eyes.

Also, see the Warning section.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Usual Adult Avacopan Dose: 30 mg (three 10 mg capsules) twice daily (morning and night), with food.

Dose modification: Reduce avacopan dose to 30 mg once daily when used together with medications that are strong CYP3A4 inhibitors.

Use: adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. Tavneos does not eliminate glucocorticoid use.

Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Tell your healthcare provider about all the other medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Avacopan and certain other medicines may affect each other and cause side effects. Keep a list of all the medicines that you take, and show it to your healthcare provider and pharmacist.

• Some medicines should not be taken with avacopan.
• Your healthcare provider may prescribe other medicines to treat your disease.

Strong and moderate CYP3A4 enzyme inducers: Avoid use.

Strong CYP3A4 enzyme inhibitors: Reduce avacopan dose to 30 mg once daily.

CYP3A4 substrates: Consider dose reduction of CYP3A4 substrates when co-administering avacopan with CYP3A4 substrates.

Not all possible drug interactions are listed here.

Store at room temperature between 68°F to 77°F (20°C to 25°C).

Keep all medicines out of reach of children and pets.

Active ingredient: avacopanInactive ingredients: polyethylene glycol 4000 (PEG-4000), Polyoxyl-40 hydrogenated castor oil.

Avacopan ChemoCentryx, Inc.

Avacopan Amgen (acquired ChemoCentryx in October 2022)

One Amgen Center Drive, Thousand Oaks, CA 91320-1799