JINARC 30 mg + 90 mg TABLETS

2. What you need to know before you take Jinarc

Do not take Jinarc:

• If you are allergic to tolvaptan or any of the other ingredients of this medicinal product (listed in section 6) or if you are allergic to benzazepine or benzazepine derivatives (e.g. benazepril, conivaptan, fenoldopam mesylate or mirtazapine).

• If you have been told that you have elevated liver enzyme levels in your blood and this prevents you from receiving treatment with tolvaptan.
• If your kidneys do not function (no urine production)
• If you suffer from a disorder associated with very low blood volume (e.g. severe dehydration or bleeding).
• • If you have a disorder that increases the amount of sodium in your blood.
  • If you do not feel thirsty.
  • If you are pregnant (see "Pregnancy and breastfeeding").
  • If you are breastfeeding (see "Pregnancy and breastfeeding").

Warnings and precautions

Consult your doctor before starting treatment with Jinarc:

• If you have liver disease.

• If you are unable to drink enough water (see "Drinking enough water" below) or if you need to limit your fluid intake.
• • If you have difficulty urinating or benign prostatic hyperplasia (enlargement of the prostate gland).
  • If you have elevated or decreased sodium levels in your blood.
• If you have had an allergic reaction to benzazepine, tolvaptan, or other benzazepine derivatives (e.g. benazepril, conivaptan, fenoldopam mesylate or mirtazapine), or to any of the other ingredients of this medicinal product (listed in section 6).
• • If you have diabetes.
  • If you have been told that you have elevated uric acid levels in your blood (which may have caused gout).

Jinarc may cause your liver to not function properly. For this reason, please inform your doctor immediately if you experience signs that may indicate liver problems, such as:

• nausea
• vomiting
• fever
• fatigue
• loss of appetite
• abdominal pain
• dark urine
• jaundice (yellowing of the skin or eyes)
• itching (pruritus) of the skin
• pseudogripal syndrome (muscle and joint pain with fever)

During treatment with Jinarc, your doctor will ask you to have monthly blood tests to monitor changes in your liver function.

Drinking enough water

Jinarc causes water loss because it increases urine production. This water loss can lead to side effects such as dry mouth and thirst or more serious side effects such as kidney problems (see section 4). Therefore, it is essential that you have access to water and can drink enough fluid when you feel thirsty. Before going to bed, you should drink one or two glasses of water, even if you do not feel thirsty, and also drink water after urinating at night. You should be particularly careful if you have a disease that reduces adequate fluid intake or if you are at higher risk of dehydration, for example, if you have vomiting or diarrhea. Due to the increased urine production, it is also essential to always have a bathroom nearby.

Children and adolescents

Jinarc has not been studied in children and adolescents (under 18 years) and, therefore, is not recommended for use in this population.

Other medicines and Jinarc

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

In particular, inform your doctor if you are taking:

• treatments containing ketoconazole for fungal infections, macrolide antibiotics such as clarithromycin, or diltiazem for treating high blood pressure and chest pain.
• These medicines may increase the effects of Jinarc.
• medicines that increase sodium levels in the blood or contain large amounts of salt, such as effervescent tablets and antacids. These may increase the effects of Jinarc.
• digoxin (a medicine for treating irregular heartbeat and heart failure), dabigatran (used as a blood anticoagulant), rosuvastatin or pitavastatin (used to lower cholesterol levels in the blood), methotrexate (used to treat cancer and arthritis), ciprofloxacin (an antibiotic), sulfasalazine (for treating irritable bowel disease or rheumatoid arthritis), or metformin (for treating diabetes). Jinarc may increase the effect of these medicines.
• phenytoin or carbamazepine (medicines for treating epilepsy), rifampicin (a medicine for treating tuberculosis), or St. John's Wort (a herbal medicine for treating mild depression and anxiety). It is advisable to avoid using any of these medicines in combination with Jinarc, as they may reduce the effects of Jinarc.
• diuretics (used to increase urine production). When taken at the same time as Jinarc, these medicines may increase the risk of side effects due to water loss.
• diuretics or other medicines for treating high blood pressure. When taken at the same time as Jinarc, these medicines may increase the risk of low blood pressure when standing up or getting up.
• desmopressin (used to increase blood clotting factors or control urine production or urinary incontinence). Jinarc may reduce the effect of desmopressin.

It may not be a problem to take these medicines at the same time as Jinarc. Your doctor will decide what is best for you.

Using Jinarc with drinks and alcohol

Do not drink grapefruit juice while taking Jinarc.

Pregnancy and breastfeeding

Do nottake this medicine if you are pregnant or breastfeeding.

Women of childbearing potential should use reliable contraceptive methods while being treated with this medicine.

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

Some people may feel dizzy, weak, or tired after taking Jinarc. If you experience these effects, do not drive or use tools or machines.

Jinarc contains lactose.

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Jinarc

Only specialized doctors in the treatment of ADPKD can prescribe Jinarc. Follow your doctor's instructions for taking this medicine exactly. If you are unsure, consult your doctor or pharmacist again.

Dose

The daily dose of Jinarc should be divided into two doses, one higher than the other. The higher dose should be taken in the morning when getting up, at least 30 minutes before breakfast, while the lower dose should be taken 8 hours later.

The dose combinations are:

45 mg + 15 mg

60 mg + 30 mg

90 mg + 30 mg

Normally, your treatment will start with a dose of 45 mg in the morning and 15 mg 8 hours later. Your doctor may gradually increase your dose up to a maximum combination of 90 mg when getting up and 30 mg 8 hours later. To determine the best dose for you, your doctor will regularly check how you tolerate the prescribed dose. You should always take the highest tolerable dose combination prescribed by your doctor.

If you are taking other medicines that may increase the effects of Jinarc, you may receive lower doses. In this case, your doctor may prescribe Jinarc tablets with 30 or 15 mg of tolvaptan, which you should take once a day in the morning.

Method of administration

Swallow the tablets whole with a glass of water.

The morning dose should be taken at least 30 minutes before breakfast. The second daily dose can be taken with or without food.

If you take more Jinarc than you should

If you have taken more tablets than the prescribed dose, drink plenty of water and contact your doctor or the nearest hospital immediately.Remember to take the medicine package with you so that it is clear what you have taken. If you take the higher dose too late, you may need to go to the bathroom more frequently at night.

If you forget to take Jinarc

If you forget to take your medicine, take the dose as soon as you remember on the same day. If you have not taken the tablets for a day, take the normal dose the next day. Do nottake a double dose to make up for the missed individual doses.

If you stop taking Jinarc

If you stop taking Jinarc, kidney cysts may grow as quickly as before starting treatment with this medicine. Therefore, you should only stop taking Jinarc if you experience side effects that require urgent medical attention (see section 4) or if your doctor tells you to do so.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects:

If you experience any of the following side effects, you may need urgent medical attention. Stop taking Jinarc and contact a doctor or go to the nearest hospital immediately if:

• you have difficulty urinating;

• your face, lips, or tongue swell, you feel itchy, have a rash all over your body, or have wheezing (whistling sound when you breathe) or difficulty breathing (symptoms of an allergic reaction).

Jinarc may cause your liver to not function properly.

Tell your doctor if you experience symptoms of nausea, vomiting, fever, fatigue, loss of appetite, abdominal pain, dark urine, jaundice (yellowing of the skin or eyes), itching (pruritus) of the skin, or muscle and joint pain with fever.

Other side effects:

Very common: may affect more than 1 in 10 people

• thirst (need to drink excessive amounts of water)
• headache
• dizziness
• diarrhea
• dry mouth
• increased need to urinate, urinate at night, or urinate more frequently
• fatigue

Common: may affect up to 1 in 10 people

• dehydration
• elevated sodium, uric acid, and sugar levels in the blood
• gout
• decreased appetite
• difficulty sleeping
• palpitations
• breathing difficulties
• abdominal pain
• feeling full, bloated, or uncomfortable in the stomach
• constipation

• heartburn
• abnormal liver function
• rash
• itching
• muscle spasms
• general weakness
• increased liver enzyme levels in the blood
• weight loss

Uncommon: may affect up to 1 in 100 people

• increased bilirubin levels in the blood (a substance that can cause yellowing of the skin or eyes)

Frequency not known: cannot be estimated from the available data

• allergic reactions (see above)
• acute liver failure

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Jinarc

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 outer carton, blister pack, and on the blister strip after "EXP". The expiry date refers to the last day of the month shown.

Store in the original package to protect from light and moisture.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Package Contents and Additional Information

Jinarc Composition

The active ingredient is tolvaptan.

Each 15 mg Jinarc tablet contains 15 mg of tolvaptan.

Each 30 mg Jinarc tablet contains 30 mg of tolvaptan.

Each 45 mg Jinarc tablet contains 45 mg of tolvaptan.

Each 60 mg Jinarc tablet contains 60 mg of tolvaptan.

Each 90 mg Jinarc tablet contains 90 mg of tolvaptan.

The other ingredients are lactose monohydrate (see section 2), cornstarch, microcrystalline cellulose, hydroxypropylcellulose, magnesium stearate, and aluminum lake of indigo carmine.

Appearance of Jinarc and Package Contents

The different doses of Jinarc tablets have different shapes and engravings:

15 mg tablet: blue, triangular, engraved with "OTSUKA" and "15" on one side.

30 mg tablet: blue, round, engraved with "OTSUKA" and "30" on one side.

45 mg tablet: blue, square, engraved with "OTSUKA" and "45" on one side.

60 mg tablet: blue, modified rectangular, engraved with "OTSUKA" and "60" on one side.

90 mg tablet: blue, pentagonal, engraved with "OTSUKA" and "90" on one side.

The medication is supplied with the following package sizes:

Jinarc 15 mg tablets: blisters with 7 or 28 tablets

Jinarc 30 mg tablets: blisters with 7 or 28 tablets

Jinarc 45 mg tablets + Jinarc 15 mg tablets: blisters with or without a carton box containing

14 (7 tablets of the highest dose + 7 tablets of the lowest dose),

28 (14 tablets of the highest dose + 14 tablets of the lowest dose) or

56 (28 tablets of the highest dose + 28 tablets of the lowest dose) tablets.

Jinarc 60 mg tablets + Jinarc 30 mg tablets: blisters with or without a carton box containing 14 (7 tablets of the highest dose + 7 tablets of the lowest dose),

28 (14 tablets of the highest dose + 14 tablets of the lowest dose) or

56 (28 tablets of the highest dose + 28 tablets of the lowest dose) tablets.

Jinarc 90 mg tablets + Jinarc 30 mg tablets: blisters with or without a carton box containing

14 (7 tablets of the highest dose + 7 tablets of the lowest dose),

28 (14 tablets of the highest dose + 14 tablets of the lowest dose) or

56 (28 tablets of the highest dose + 28 tablets of the lowest dose) tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder

Otsuka Pharmaceutical Netherlands B.V.

Herikerbergweg 292

1101 CT, Amsterdam

Netherlands

Manufacturer

AndersonBrecon (UK) Limited

Units 2-7, Wye Valley Business Park, Brecon Road, Hay-on-Wye

Hereford - HR3 5PG

United Kingdom

Almac Pharma Services Ltd.

Almac House, 20 Seagoe Industrial Estate

Craigavon - BT63 5QD

United Kingdom

Almac Pharma Service (Ireland) Limited

Finnabair Industrial Estate, Dundalk,

Co. Louth - A91 P9KD

Ireland

Millmount Healthcare Limited

Block-7, City North Business Campus, Stamullen, Co.

Meath, K32 YD60

Ireland

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Date of the last revision of this leaflet: MM/YYYY.

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/.