Inaqovi

Package leaflet: Information for the patient

Inaqovi 35 mg/100 mg film-coated tablets

decitabine/cedazuridine
(decitabinum /cedazuridinum)
This medicinal product is subject to additional monitoring. This will allow for 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 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, pharmacist, or nurse.
• 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, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Inaqovi is and what it is used for

What Inaqovi is
Inaqovi is an anticancer medicine that contains the active substances decitabine and cedazuridine.
What Inaqovi is used for
Inaqovi is used alone for the treatment of acute myeloid leukaemia (AML, acute myeloid leukaemia) in adults when chemotherapy is not considered a suitable treatment option. Inaqovi will be prescribed to you at the time of your initial AML diagnosis.
AML is a type of cancer affecting white blood cells called myeloid cells. In patients with AML, myeloid cells multiply and grow very rapidly in the bone marrow and blood.
How Inaqovi works
Inaqovi contains two active substances that work in different ways. Decitabine acts by blocking the growth of cancer cells and killing these cells. Cedazuridine does not directly affect cancer cells, but inhibits the breakdown of decitabine. This increases the amount of decitabine available in the body, thereby helping to enhance the effect of decitabine.

2. What you should know before taking Inaqovi

Do not take Inaqovi

• if you are allergic to decitabine or cedazuridine, or to any of the other ingredients of this medicine (listed in section 6);
• if you are breastfeeding (see section 2 “Breastfeeding”).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Inaqovi if:

• you have lung problems;
• you have liver problems;
• you have kidney problems;
• you have heart problems.

Myelosuppression and “differentiation syndrome”
Inaqovi can cause severe myelosuppression (a condition in which the bone marrow fails to produce an adequate number of blood cells) or a serious immune reaction called “differentiation syndrome”. Both of these reactions can be fatal.
Contact a doctor immediately if you notice any signs or symptoms (for symptoms, see section 4).

Cardiovascular disease
Talk to your doctor if you have a history of heart problems, so that you can be monitored for any signs or symptoms of heart failure.

Blood tests
You will need to have blood tests during treatment. These will be performed before starting treatment with Inaqovi, at the beginning of each treatment cycle, or whenever you notice signs or symptoms of myelosuppression. These tests are used to check:

• that you have an adequate number of blood cells;
• that your liver and kidneys are functioning properly.

Your doctor may adjust or delay your dose of Inaqovi. Your doctor may also prescribe medicines to prevent infections.

Children and adolescents
Inaqovi must not be taken by children and adolescents under 18 years of age. The medicine has not been studied in this age group.

Other medicines and Inaqovi
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines before starting treatment with Inaqovi. Inaqovi may affect the action of certain medicines, especially if you are taking the following medicines to treat:

• cancer, for example cytarabine, gemcitabine, or azacitidine.

Pregnancy, contraception, breastfeeding, and fertility
Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine.
You must not take Inaqovi during pregnancy, as the medicine may harm the unborn baby. If you are of childbearing age, a pregnancy test is recommended before starting treatment with Inaqovi.

Contraception
Women of childbearing potential must use effective contraceptive methods during treatment with Inaqovi and for 6 months after taking the last dose of Inaqovi.
Men with female partners of childbearing potential must use effective contraceptive methods during treatment with Inaqovi and for 3 months after taking the last dose.
Talk to your doctor about the most effective contraceptive methods.

Breastfeeding
Do not breastfeed during treatment with Inaqovi, as it is not known whether Inaqovi passes into breast milk and could harm the baby.

Male and female fertility
Inaqovi may impair fertility. It is not known whether the effect on fertility is permanent. Talk to your doctor before taking this medicine if you have concerns or wish to preserve sperm or freeze eggs before starting treatment.

Driving and using machines
Inaqovi may affect your ability to drive vehicles or operate tools and machinery. If you experience fatigue or dizziness after taking Inaqovi, avoid driving or using tools and machinery until you feel better.

Inaqovi contains lactose and sodium
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.

3. How to take Inaqovi

This medicine will be prescribed by a doctor experienced in the use of anticancer medicines. Always take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor.

The recommended dose is 1 tablet once daily for the first 5 days of a treatment cycle. This will be followed by a 23-day period during which you must not take the medicine. A treatment cycle lasts 28 days.

• Swallow the tablets whole with water, approximately at the same time each day.
• Do not chew, crush, or break the tablets to avoid skin contact or dispersion of the medicine into the air.
• Since taking Inaqovi with food may reduce the medicine’s effectiveness, Inaqovi must be taken on an empty stomach. Take Inaqovi 2 hours before or 2 hours after a meal.

You will generally need to take Inaqovi for at least 4 cycles. Your doctor will regularly perform blood tests to monitor your response to treatment. Based on your response, your doctor may delay the next dose and adjust the total number of treatment cycles.

If you vomit
If you vomit after taking a dose, do not take an additional dose on the same day. Take the next dose at the usual time the following day.
Your doctor may prescribe another medicine to take before each dose of Inaqovi to help prevent nausea or vomiting during treatment.

If you take more Inaqovi than you should
Overdose may cause myelosuppression, sepsis, or pulmonary infection (see section 4 “Possible side effects”). If you take more Inaqovi than you should, seek immediate medical advice.

If you forget to take Inaqovi
If you miss a dose and the delay in taking it is less than 12 hours, take the missed dose as soon as possible and then continue with your regular daily dosing schedule.
If you miss a dose and the delay is 12 hours or more, do not take the missed dose; instead, take the next dose at the usual time the following day. Extend the administration period by one day for each missed dose. Make sure you take a total of 5 daily doses (one dose per day) in each cycle.

If you stop taking Inaqovi
If you stop taking this medicine, the cancer may no longer be controlled and symptoms may return. Therefore, you should only stop taking this medicine on the advice of your doctor.

If you have any doubts about how to take this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Immediately inform your doctor, pharmacist or nurse if you notice one or more of the following serious
side effects:

• fever: could be a sign of an infection due to low levels of white blood cells (very common: may affect more than 1 in 10 people)
• chest pain or shortness of breath (with or without fever or cough): these could be signs of a lung infection (very common: may affect more than 1 in 10 people) or inflamed lungs (lung interstitial disease; frequency not known)
• bleeding, including blood in the stools, nosebleeds or bruises that form more easily: these could be signs of low levels of blood cells (platelets and red blood cells) (common: may affect up to 1 in 10 people)
• difficulty moving, speaking, understanding or seeing; sudden severe headache, seizure, numbness or weakness in any part of the body: these could be signs of bleeding in the brain (common: may affect up to 1 in 10 people)
• dizziness or fainting, confusion or disorientation, weakness, shortness of breath, reduced need to urinate, diarrhoea, nausea/vomiting, fever, tremors or feeling very cold, moist skin or sweating, or cough: these could be signs and symptoms of a blood infection (sepsis) (very common: may affect more than 1 in 10 people)
• fever, cough, difficulty breathing, rash, reduced urine output, hypotension (low blood pressure), swelling of the arms or legs and rapid weight gain: these could be signs of a severe immune reaction (differentiation syndrome; frequency not known).

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

• urinary tract infection
• infection caused by bacteria, viruses or fungi
• high blood glucose levels
• development of mouth or tongue ulcers due to painful inflammation of the membrane lining the mouth
• diarrhoea
• nausea and vomiting
• changes in liver function tests (increased ALT, AST, alkaline phosphatase and bilirubin)

Common (may affect up to 1 in 10 people)

• inflammation of the sinuses
• headache
• inflamed intestine (neutropenic colitis)

Uncommon (may affect up to 1 in 100 people)

• decrease in the number of red blood cells, white blood cells and platelets
• sudden fever with multiple red or red-blue raised and painful skin lesions, usually on the arms, legs, trunk, face or neck (“acute febrile neutrophilic dermatosis” or “Sweet’s syndrome”)
• heart muscle disease

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. 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 Inaqovi

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 carton after “Exp.” and on the blister after “EXP”. The expiry date refers to the last day of that month.
Store in the original packaging to protect the medicine from moisture.
This medicine does not require any special storage temperature.
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 Inaqovi contains

• The active substances are decitabine and cedazuridine. Each film-coated tablet contains 35 mg of decitabine and 100 mg of cedazuridine.
• The other components are: Inaqovi contains lactose and sodium, see section 2. Tablet core: lactose monohydrate, hypromellose (E464), croscarmellose sodium (E466), anhydrous colloidal silica, magnesium stearate (E572). Film coating: polyvinyl alcohol (E1203), titanium dioxide (E171), polyethylene glycol (E1521), talc (E553b), iron oxide red (E172).

Description of the appearance of Inaqovi and contents of the pack
Inaqovi is presented as red, oval biconvex film-coated tablets, 14 mm in diameter, smooth on one side and marked with "H35" on the other side.
The tablets are supplied in aluminum blisters containing 5 tablets.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Otsuka Pharmaceutical Netherlands B.V.
Herikerbergweg 292
1101 CT Amsterdam
The Netherlands

Manufacturer
Skyepharma Production S.A.S.
Zone Industrielle Chesnes Ouest
55 Rue Du Montmurier
38070 Saint-Quentin-Fallavier
France
BSP Pharmaceuticals S.p.A.
Via Appia Km. 65,561
04013 Latina Scalo (LT)
Italy
R-PHARM Germany GmbH
Heinrich-Mack-Straße 35
89257 Illertissen
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Otsuka Pharmaceutical Netherlands B.V. Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555 Tel: +31 (0) 20 85 46 555

България Luxembourg/Luxemburg
Otsuka Pharmaceutical Netherlands B.V. Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555 Tel: +31 (0) 20 85 46 555

Česká republika Magyarország
Otsuka Pharmaceutical Netherlands B.V. Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555 Tel: +31 (0) 20 85 46 555

Danmark Malta
Otsuka Pharma Scandinavia AB Otsuka Pharmaceutical Netherlands B.V.
Tlf: +46 (0) 8 545 286 60 Tel: +31 (0) 20 85 46 555

Deutschland Nederland
Otsuka Pharma GmbH Otsuka Pharmaceutical Netherlands B.V.
Tel: +49 (0) 69 1700 860 Tel: +31 (0) 20 85 46 555

Eesti Norge
Otsuka Pharmaceutical Netherlands B.V. Otsuka Pharma Scandinavia AB
Tel: +31 (0) 20 85 46 555 Tlf: +46 (0) 8 545 286 60

Ελλάδα Österreich
Otsuka Pharmaceutical Netherlands B.V. Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555 Tel: +31 (0) 20 85 46 555

España Polska
Otsuka Pharmaceutical, S.A. Otsuka Pharmaceutical Netherlands B.V.
Tel: +34 93 550 01 00 Tel: +31 (0) 20 85 46 555

France Portugal
Otsuka Pharmaceutical France SAS Otsuka Pharmaceutical Netherlands B.V.
Tél: +33 (0)1 47 08 00 00 Tel: +31 (0) 20 85 46 555

Hrvatska România
Otsuka Pharmaceutical Netherlands B.V. Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555 Tel: +31 (0) 20 85 46 555

Ireland Slovenija
Otsuka Pharmaceutical Netherlands B.V. Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555 Tel: +31 (0) 20 85 46 555

Ísland Slovenská republika
Vistor hf. Otsuka Pharmaceutical Netherlands B.V.
Sími: +354 (0) 535 7000 Tel: +31 (0) 20 85 46 555

Italia Suomi/Finland
Otsuka Pharmaceutical Italy S.r.l. Otsuka Pharma Scandinavia AB
Tel: +39 (0) 2 0063 2710 Tlf: +46 (0) 8 545 286 60

Κύπρος Sverige
Otsuka Pharmaceutical Netherlands B.V. Otsuka Pharma Scandinavia AB
Tel: +31 (0) 20 85 46 555 Tlf: +46 (0) 8 545 286 60

Latvija
Otsuka Pharmaceutical Netherlands B.V.
Tel: +31 (0) 20 85 46 555

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/. Links to other websites on rare diseases and their therapeutic treatments are also provided.
This leaflet is available in all languages of the European Union/European Economic Area on the European Medicines Agency website.