Attrogy

Package leaflet: Information for the patient

Attrogy 250 mg film-coated tablets

diflunisal
Please read this leaflet carefully before using this medicine because it contains important information for you.

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

Contents of this leaflet

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

1. What Attrogy is and what it is used for

Attrogy contains the active substance diflunisal.
Attrogy is used:

• in adult patients for the treatment of stage 1 hereditary transthyretin amyloidosis with polyneuropathy, an inherited disease in which fibres called amyloid fibrils accumulate in body tissues, including around the nerves. In stage 1, patients experience symptoms such as tingling, numbness, or weakness, mainly in the legs or feet;
• in adult patients for the treatment of stage 2 hereditary transthyretin amyloidosis with polyneuropathy, an inherited disease in which fibres called amyloid fibrils accumulate in body tissues, including around the nerves. In stage 2, patients may experience more severe tingling, numbness, or weakness in the hands and feet, resulting in increasing difficulty walking or performing daily activities.

In patients with hereditary transthyretin amyloidosis, a protein called transthyretin is defective and easily degrades. The degraded protein forms a fibrous substance known as amyloid fibrils, which accumulate in tissues and organs throughout the body, impairing their normal function.
Attrogy binds to transthyretin, stabilizing it and preventing its breakdown. This action prevents the components of the abnormal protein from forming harmful amyloid fibrils.

2. What you need to know before using Attrogy

Do not use Attrogy

• if you are allergic to diflunisal or to any of the other ingredients of this medicine (listed in section 6);
• if you have previously experienced symptoms such as acute asthma, skin rash, runny nose, or skin swelling after taking medicines containing acetylsalicylic acid (a substance found in many medicines used to relieve pain and reduce fever) or non-steroidal anti-inflammatory drugs (NSAIDs) (e.g. ibuprofen, naproxen, diclofenac, celecoxib) used for fever, pain, and inflammation;
• if you have previously had gastrointestinal bleeding (bleeding from the stomach or intestine);
• if you suffer from heart failure;
• if you have severe kidney problems;
• if you have severe liver problems;
• if you are in the third trimester of pregnancy;
• if you are breastfeeding.

Warnings and precautions
Talk to your doctor before using Attrogy:

• if you are taking medicines known as NSAIDs (e.g. ibuprofen, naproxen, diclofenac, or celecoxib); discuss this with your doctor before taking this medicine, especially if you are over 65 years of age;
• if you have or have previously had stomach or intestinal ulcers;
• if you have had heart or circulatory problems, such as high blood pressure; if your heart does not pump blood properly, causing shortness of breath, fatigue, and swelling of the ankles; heart disease due to reduced or blocked blood vessels supplying the heart muscle; reduced blood flow in the arteries of the arms and legs; or problems with blood vessels supplying the brain;
• if you have elevated levels of lipids (e.g. cholesterol) in the blood, if you smoke and/or if you have a type of heart electrical activity disorder known as "long QT syndrome";
• if your kidneys have reduced function or if you have diabetes, as there is a risk of developing kidney problems in case of dehydration. For the same reason, consult your doctor before taking Attrogy if you have not taken in enough fluids or have lost fluids due to persistent vomiting or diarrhoea;
• if your heart or liver have reduced function or if liver function tests are abnormal; if you have blood clotting disorders or if you are taking medicines to thin the blood;
• if you develop signs or symptoms of an infection;
• if you have or develop eye problems, as eye examinations are recommended;
• if you have or have previously had asthma or breathing problems.

Children and adolescents
Attrogy is not indicated in children and adolescents under 18 years of age, as they do not present symptoms of transthyretin familial amyloidosis.

Other medicines and Attrogy
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
It is particularly important if you are taking any of the following medicines:

• antacids containing aluminium hydroxide (medicines for heartburn). If you are taking antacids, you must leave a 2-hour interval between taking Attrogy and taking antacid medicines;
• acetazolamide (a medicine for glaucoma);
• methotrexate (a medicine for cancer and rheumatism);
• warfarin and other oral anticoagulant and antiplatelet medicines (to prevent blood clots);
• acetylsalicylic acid (a substance found in many medicines used to relieve pain and reduce fever);
• indomethacin and other NSAIDs (medicines to relieve fever, pain, and inflammation);
• cyclosporine and tacrolimus (medicines to prevent rejection of transplanted organs);
• medicines for high blood pressure or arrhythmias;
• diuretics, e.g. hydrochlorothiazide, furosemide, amiloride (medicines for fluid retention);
• lithium (a medicine for bipolar disorder);
• corticosteroids (used to treat inflammation);
• selective serotonin reuptake inhibitors (SSRIs) (medicines for depression).

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
You must not take Attrogy during the first 6 months of pregnancy unless absolutely necessary and advised by your doctor. Do not take Attrogy during the last 3 months of pregnancy.
This medicine may cause problems for the unborn baby or complications during delivery. It may cause kidney and heart problems in the unborn baby, affect the tendency to bleed in both you and the baby, and delay or prolong labour.
If you take this medicine for more than a few days from week 20 of pregnancy onwards, your doctor will recommend additional monitoring. This is because Attrogy may cause kidney problems in the unborn baby, which could reduce the levels of fluid surrounding the baby in the womb (oligohydramnios), or cause narrowing of a blood vessel (ductus arteriosus) in the baby's heart. You must stop taking this medicine before week 28 of pregnancy.

Breastfeeding
Do not use Attrogy if you are breastfeeding. The active substance in Attrogy, diflunisal, passes into human breast milk.

Fertility
The use of Attrogy may reduce female fertility and is not recommended for women intending to become pregnant.

Driving and using machines
This medicine is not expected to affect your ability to drive or use machinery.

Attrogy contains the colour sunset yellow FCF (E 110)
It may cause allergic reactions.

Attrogy contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. it is essentially "sodium-free".

3. How to use Attrogy

Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor.
The recommended dose is one 250 mg tablet to be taken twice daily.
It is recommended to swallow the tablets whole. Crushing or chewing the tablets is not advised due to the potential bitter taste. It is preferable to take the tablets with food to reduce the risk of unwanted effects on the stomach and intestines. If you are taking antacids, wait 2 hours before taking Attrogy tablets.
If you take more Attrogy than you should
Contact a doctor or pharmacist immediately for advice.
If you forget to take Attrogy
If you have missed a dose, wait until it is time to take the next dose and then take the tablet as usual.
Do not take a double dose to make up for the forgotten tablet.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Stop taking Attrogy and contact your doctor immediately if you experience any of the following side effects.
Uncommon (may affect up to 1 in 100 people)

• swelling of the face, lips, tongue, throat, arms or legs. These may be symptoms of angioedema (sudden swelling often caused by an allergic reaction);
• widespread severe skin rash with peeling of the skin, which may be accompanied by fever, flu-like symptoms, blisters in the mouth, eyes and/or genitals. These may be symptoms of a potentially life-threatening reaction known as Stevens-Johnson syndrome.

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

• signs of intestinal bleeding such as blood in the stools (formed or unformed), black stools; vomiting blood or dark clots resembling coffee grounds.

Other side effects
Very common (may affect more than 1 in 10 people)

• indigestion or heartburn (dyspepsia)

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

• viral stomach infection
• stomach and intestinal pain (gastrointestinal pain)
• diarrhoea
• nausea
• vomiting
• constipation
• flatulence
• tear (perforation) in the stomach or intestine
• bleeding in the stomach or intestine
• reflux of gastric acid into the tube connecting the mouth to the stomach (gastroesophageal reflux disease)
• feeling full after eating a small amount of food (early satiety)
• headache
• dizziness
• increased eye pressure (ocular hypertension)
• difficulty sleeping (insomnia)
• tiredness
• drowsiness
• rash
• sweating
• ringing in the ears (tinnitus)
• kidney failure
• heart failure
• chest pain
• skin inflammation (dermatitis)
• redness of the skin (erythema)
• high blood pressure (hypertension)
• fluid retention (oedema)
• decrease in the percentage of red blood cells (decreased haematocrit)
• blood not visible in the stools (positive for occult blood)
• abnormally high levels of protein in the urine (proteinuria)

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

• severe and sudden allergic reaction with excessive contraction of the airway muscles causing breathing difficulties (acute anaphylactic reaction with bronchospasm)
• fluid retention around the heart (angioedema)
• fever, chills, muscle or joint pain, abnormal liver or kidney function tests, abnormal blood tests, skin rashes or yellowing of the skin (hypersensitivity syndrome)
• ulcer in the stomach or small intestine (peptic ulcer)
• loss of appetite
• inflammation of the stomach lining (gastritis)
• vomiting blood (haematemesis)
• inflammation of small blood vessels due to allergic reactions (hypersensitivity vasculitis)
• potentially life-threatening reaction with flu-like symptoms and blistering of the skin, eyes and genitals (toxic epidermal necrolysis)
• skin reaction causing red spots or patches on the skin, which may look like a target with a dark red centre surrounded by rings of lighter red (erythema multiforme)
• severe skin condition causing widespread peeling and shedding of the upper layers of the skin with fever (exfoliative dermatitis), inflammation of the mouth and lips (ulcerative stomatitis)
• inflammation of the inner lining of the mouth (stomatitis)
• sensitivity to light (photosensitivity)
• dryness of moist body surfaces, such as the inner lining of the mouth (mucous membranes)
• inflammation around the kidney tubules (interstitial nephritis)
• yellowing of the skin and eyes (jaundice), sometimes with fever
• reduced bile flow from the liver due to obstruction (cholestasis)
• abnormal liver function
• inflammation of the liver (hepatitis)
• worsening of colon inflammation (exacerbation of colitis)
• worsening of Crohn's disease
• tingling or prickling sensation of the skin, hives
• painful urination (dysuria)
• kidney problems (renal impairment)
• a combination of symptoms including swelling, high blood pressure and reduced urine volume caused by inflammation of the kidney filters (nephritic syndrome)
• blood in the urine (haematuria)
• black stools (melena)
• feeling of weakness (asthenia)
• palpitations
• fainting (syncope)
• sensation of dizziness (vertigo)
• mild mental confusion
• shortness of breath (dyspnoea)
• feeling of nervousness
• depression
• hallucinations
• confusion
• transient visual disturbances, including blurred vision
• muscle cramps
• tingling (paraesthesia)
• low platelet levels, components that help blood clotting (thrombocytopenia)
• low levels of neutrophils, a type of white blood cells (neutropenia)
• very low levels of a type of white blood cells called granulocytes, important for fighting infections (agranulocytosis)
• cessation of production of new blood cells by the bone marrow (aplastic anaemia)
• excessive breakdown of red blood cells (haemolytic anaemia)

Very rare (may affect up to 1 in 10,000 people):

• runny nose (rhinitis)
• asthma
• increased levels of liver enzymes (transaminases) observed in blood tests
• inflammation of small blood vessels caused by allergy (allergic vasculitis).

Reporting of side effects
If you get any side effects, including ones 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 Attrogy

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the vial and outer packaging after "EXP.". The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature. Store in the original packaging to protect the medicine from light.
Do not dispose of any medicine 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 Attrogy contains

• The active substance is diflunisal. One tablet contains 250 mg of diflunisal.
• The other components are microcrystalline cellulose (E460), pregelatinized starch (E1422), sodium croscarmellose (E468), hydrophobic colloidal silica (E551), magnesium stearate,

hydroxypropylmethylcellulose (E464), macrogol 3350 (E1521), titanium dioxide (E171), sunset yellow FCF (E 110), purified water.
This medicine contains the colour sunset yellow FCF (E 110), see section 2.
Description of the appearance of Attrogy and package contents
This medicine is a light orange, biconvex, film-coated tablet, supplied in a plastic bottle with a plastic screw cap. It is available in packs of 100 tablets.
Marketing Authorization Holder
Purpose Pharma International AB
Grev Turegatan 13b
114 46 Stockholm
Sweden
E-mail: [email protected]
Manufacturer
SkyePharma Production S.A.S
Zone Industrielle Chesnes Ouest
55 Rue du Montmurier
38070 SAINT QUENTIN FALLAVIER
France
More detailed information on this medicine 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.