Tavneos

Patient Information Leaflet

Tavneos 10 mg hard capsules

avacopan
This medicinal product is subject to additional monitoring. This will allow for the rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Tavneos is and what it is used for
2. What you need to know before taking Tavneos
3. How to take Tavneos
4. Possible side effects
5. How to store Tavneos
6. Contents of the pack and other information

1. What Tavneos is and what it is used for

What is Tavneos?
Tavneos contains the active substance avacopan, which binds to a specific protein in the body called complement C5a receptor.
What is Tavneos used for?
Tavneos is used to treat adults with a progressively worsening disease caused by inflammation of small blood vessels, called granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA):

• Granulomatosis with polyangiitis mainly affects the small blood vessels and tissues of the kidneys, lungs, throat, nose, and paranasal sinuses, but also other organs. Patients develop small nodules (granulomas) inside and around blood vessels, formed by tissue damage caused by inflammation.
• Microscopic polyangiitis affects the smallest blood vessels, often the kidneys, but may also involve other organs.

The complement C5a receptor plays a key role in triggering inflammation. This medicine binds to it and prevents it from functioning, thereby reducing the blood vessel inflammation seen in these diseases.
Tavneos may be used in combination with other treatments prescribed by your doctor.

2. What you should know before taking Tavneos

Do not take Tavneos

• if you are allergic to avacopan or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor before taking Tavneos and during treatment if you have had or currently have:

• symptoms of liver injury such as feeling unwell (nausea or vomiting), fatigue, loss of appetite, yellowing of the skin or eyes, dark urine, itching, pain in the upper abdomen, increased levels of total bilirubin, the yellow breakdown product of blood pigment, or liver enzymes such as transaminases
• any infection, unexpected bruising and bleeding (these two are common signs of bone marrow failure)
• hepatitis B, hepatitis C, HIV infection or tuberculosis
• a heart condition, such as heart attack, heart failure, inflammation of the blood vessels of the heart
• any type of tumour.

Tavneos is not recommended in patients with

• active liver disease, or
• an active and severe infection.

Your doctor will perform blood tests before and, when necessary, during treatment to monitor:

• possible liver problems (by measuring liver enzymes and total bilirubin in the blood)
• the risk of developing infections (by measuring white blood cell count). Your doctor will decide whether to temporarily or permanently discontinue treatment.

Your doctor will also monitor you for signs and symptoms of an infection called Neisseria meningitidis. This is recommended for adult patients with GPA or MPA.
During treatment with Tavneos, prophylactic treatment for Pneumocystis jirovecii pneumonia is recommended.
Vaccinations are recommended before starting treatment with Tavneos or during periods of disease quiescence (granulomatosis with polyangiitis or microscopic polyangiitis).
During treatment with Tavneos, a severe swelling under the skin, often painful, mainly affecting the face, has been reported. If it affects the throat, it may compromise breathing. Stop treatment and consult a doctor urgently if you experience swelling of the face, lips, tongue or throat, or difficulty breathing.
Children and adolescents
Do not administer this medicine to children under 18 years of age, as there is insufficient evidence to demonstrate whether this medicine is safe and effective in this age group.
Other medicines and Tavneos
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
It is important to inform your doctor especially if you are taking any of the following medicines:

• carbamazepine, phenobarbital, phenytoin: medicines used to treat epilepsy and other conditions
• enzalutamide, mitotane: medicines used to treat cancer
• rifampicin: a medicine used to treat tuberculosis or certain other infections
• St John’s wort: a herbal medicine used for mild depression. If short-term use of any of these medicines cannot be avoided during treatment with Tavneos, your doctor may regularly monitor your condition to verify the effectiveness of Tavneos.

Tavneos may also affect or be affected by the following medicines:

• alfentanil: a painkiller used during anaesthesia
• boceprevir, telaprevir: medicines used to treat hepatitis C
• bosentan: a medicine used to treat high blood pressure in the lungs and skin ulcers on the fingers and toes known as scleroderma
• clarithromycin, telithromycin: antibiotic medicines used to treat bacterial infections
• conivaptan: a medicine used to treat low sodium levels in the blood
• ciclosporin: a medicine used to suppress the immune system and prevent transplant rejection, or to treat severe skin, eye or joint inflammation
• dabigatran: an anticoagulant medicine
• dihydroergotamine, ergotamine: medicines used to treat migraine
• fentanyl: a strong painkiller
• indinavir, efavirenz, etravirine, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir: medicines used to treat HIV infections
• itraconazole, posaconazole, voriconazole: medicines used to treat fungal infections
• ketoconazole: a medicine used to treat symptoms caused by excessive cortisol production by the body, known as Cushing's syndrome
• mibefradil: a medicine used to treat irregular heart rhythm and hypertension
• modafinil: a medicine used to treat excessive sleepiness
• nefazodone: medicines used to treat depression
• simvastatin: a medicine used to reduce total cholesterol, "bad" cholesterol (LDL cholesterol, an acronym for Low Density Lipoproteins), and blood fats called triglycerides
• sirolimus, tacrolimus: medicines used to suppress the immune system and prevent transplant rejection.

Tavneos with food and drink
During treatment with Tavneos, avoid consuming grapefruit and grapefruit juice, as they may affect the medicine’s action.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.

• Pregnancy This medicine is not recommended during pregnancy or in women of childbearing potential who are not using contraceptive measures.
• Breastfeeding It is not known whether avacopan is excreted in breast milk. The risk to breastfed infants cannot be ruled out. Your doctor will help you decide whether to discontinue Tavneos treatment or to stop breastfeeding.

Driving and using machines
Tavneos is considered unlikely to affect the ability to drive or operate machinery.
Tavneos contains macrogol glycerol hydroxystearate
This may cause stomach discomfort and diarrhoea.

3. How to take Tavneos

Take this medicine exactly as instructed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
The recommended dose is 3 capsules in the morning and 3 capsules in the evening.
Method of administration
Swallow the capsules whole with a glass of water. Do not crush, chew or open the capsules. Take the
capsules during a meal, 3 capsules in the morning and 3 capsules in the evening.
If you take more Tavneos than you should
Contact your doctor immediately.
If you forget to take Tavneos
If there are more than 3 hours remaining until your next scheduled dose, take the missed dose as
soon as possible, then take the next dose at the usual time.
If there are less than 3 hours remaining until your next scheduled dose, do not take the missed dose. Take the
next dose at the usual time.
Do not take a double dose to make up for a forgotten dose.
If you stop taking Tavneos
Stop treatment and consult a doctor urgently if you experience swelling of the face,
lips, tongue or throat, or breathing difficulties. In all other cases, do not stop taking
this medicine without talking to your doctor.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Contact your doctor immediately if you experience any of the following serious side effects:
Very common (may affect more than 1 in 10 people)

• blood test showing increased levels of
  • liver enzymes (a sign of liver problems)
  • bilirubin: a yellow substance produced from the breakdown of a blood pigment.

Common (may affect up to 1 in 10 people):

• lung inflammation (symptoms may include wheezing, difficulty breathing, or chest pain).

Uncommon (may affect up to 1 in 100 people):

• severe allergic reaction causing subcutaneous swelling, mainly of the face, which may cause breathing difficulties (angioedema).

Frequency not known (frequency cannot be estimated from the available data)

• severe liver and bile duct injury (symptoms may include feeling unwell (nausea or vomiting), feeling tired, loss of appetite, yellowing of the skin or eyes, dark urine, itching, or pain in the upper stomach). (See section 2).

Other side effects may occur with the following frequencies:
Very common

• upper respiratory tract infection
• irritated and inflamed throat and nose
• headache
• nausea
• diarrhoea
• vomiting
• decreased white blood cell count observed in blood tests.

Common

• inflammation of the nasal mucosa causing sneezing, itching, runny or blocked nose
• urinary tract infections
• inflammation of the sinuses or bronchial tubes
• inflammation of the stomach and intestinal wall
• lower respiratory tract infections
• cellulitis
• Herpes Zoster
• influenza
• fungal or herpes infection of the mouth due to Candida or herpes
• middle ear infection
• reduced number of white blood cells called neutrophils (symptoms may include infections, fever, or painful swallowing)
• pain in the upper abdomen
• increased blood levels of the enzyme creatine phosphokinase (symptoms may include chest pain, confusion, muscle pain and discomfort, sudden weakness or numbness of the body).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Tavneos

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature conditions. Store in the original vial to protect from light.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Tavneos contains

• The active substance is avacopan. Each hard capsule contains 10 mg of avacopan.
• The other components are:
  • macrogol glycerol hydroxystearate
  • macrogol (4000)
  • gelatin
  • polysorbate 80
  • iron oxide red (E172), iron oxide yellow (E172), iron oxide black (E172)
  • titanium dioxide (E171)
  • shellac
  • potassium hydroxide.

Description of the appearance of Tavneos and contents of the pack
Tavneos hard capsules have a yellow body and a light orange cap, printed with “CCX168” in black ink.
The capsules are 22 mm long and have a diameter of 8 mm.
The capsules are packaged in plastic bottles with child-resistant closures.
Tavneos is available in:

• packs containing 30 hard capsules, or
• packs containing 180 hard capsules, or
• multiple packs containing 540 hard capsules (3 individual packs of 180 hard capsules each).

Not all pack sizes may be marketed.
Marketing Authorisation Holder:
Vifor Fresenius Medical Care Renal Pharma France
100–101 Terrasse Boieldieu
Tour Franklin La Défense 8
92042 Paris la Défense Cedex
France
Manufacturer
Vifor France
100–101 Terrasse Boieldieu
Tour Franklin La Défense 8
92042 Paris la Défense Cedex
France
For further information about this medicinal product, please contact the Marketing Authorisation Holder.
Other sources of information
More detailed information about this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.
More detailed information about this medicinal product is also available at the following link:
https://www.tavneos-patient.eu.
Annex IV
Scientific conclusions and grounds for the variation to the terms of the marketing authorisations
Scientific conclusions
Taking into account the evaluation by the Pharmacovigilance Risk Assessment Committee (PRAC) of the Periodic Safety Update Reports (PSURs) for avacopan, the PRAC's scientific conclusions are as follows:
In view of the available data on the timing of abnormal liver function tests, the serious cases of drug-induced liver injury (DILI), including fatal outcomes reported in the post-marketing context, and the absence of recommendations regarding the frequency or interval of liver function monitoring in the most recent guidelines from the European Alliance of Associations for Rheumatology (EULAR) for the management of antineutrophil cytoplasmic antibody-associated vasculitis, the PRAC considers that the frequency of liver function monitoring (i.e., hepatic transaminases and total bilirubin) should be further specified in the product information. The PRAC has concluded that the product information for medicinal products containing avacopan should be amended accordingly.
Having reviewed the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the general conclusions and rationale of the recommendation.
Grounds for the variation to the terms of the marketing authorisations
Based on the scientific conclusions for avacopan, the CHMP considers that the benefit-risk balance of the medicinal product containing avacopan remains unchanged, subject to the proposed amendments to the product information.
The CHMP recommends a variation to the terms of the marketing authorisations.