Tolvaptan 15mg Tablets and Tolvaptan 45mg Tablets

• Keep this leaflet. You may need to read it again
• If you have any further questions, ask your doctor or pharmacist
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

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

• if you are allergic to tolvaptan or any of the other ingredients of this medicine (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 raised levels of liver enzymes in your blood which do not allow treatment with tolvaptan
• if your kidneys do not work (no urine production)
• if you have a condition which is associated with a very low blood volume (e.g. severe dehydration or bleeding)
• if you have a condition which increases the sodium in your blood
• if you do not realise when you are thirsty
• if you are pregnant
• if you are breastfeeding.

Talk to your doctor before taking tolvaptan:

• if you suffer from liver disease
• if you cannot drink enough water (see “drinking enough water” below) or if you have to restrict your fluid intake
• if you have difficulties urinating (e.g. have an enlarged prostate)
• if you suffer from too high or too low blood sodium
• if you had an allergic reaction in the past to benzazepine, tolvaptan or other benzazepine derivatives (e.g. benazepril, conivaptan, fenoldopam mesylate or mirtazapine), or to any of the other ingredients of this medicine (listed in section 6)
• if you have diabetes
• if you have been told you have high levels of a chemical called uric acid in your blood (which may have caused attacks of gout)
• if you have advanced kidney disease.

This medicine may cause your liver to not work properly. Therefore, please inform your doctor immediately if you have signs that could indicate potential liver problems such as:

• nausea
• vomiting
• fever
• tiredness
• loss of appetite
• pain in the abdomen
• dark urine
• jaundice (yellowing of skin or eyes)
• itching of your skin
• flu-like syndrome (joint and muscle pain with fever).

During treatment with this medicine, your doctor will arrange monthly blood tests to check for changes in your liver function.

Drinking enough water

This medicine causes water loss because it increases your urine production. This water loss may result in side effects such as dry mouth and thirst or even more severe side effects like kidney problems (see section 4). It is therefore important that you have access to water and that you are able to drink sufficient amounts when you feel thirsty. Before bed-time you must drink 1 or 2 glasses of water even if you do not feel thirsty and you must also drink water after you urinate at night. Special care must be taken if you have a disease that reduces appropriate fluid intake or if you are at an increased risk of water loss e.g. in case of vomiting or diarrhoea. Due to the increased urine production it is also important that you always have access to a toilet.

Do not give this medicine to children and adolescents (under age of 18 years) because it has not been studied in these age groups.

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

The following medicines may increase the effect of tolvaptan:

• amprenavir, atazanavir, darunavir/ritonavir and fosamprenavir (used to treat HIV/AIDS)
• aprepitant (used to avoid nausea and vomiting in chemotherapy)
• crizotinib and imatinib (used to treat cancer)
• ketoconazole, fluconazole or itraconazole (used to treat fungal infections)
• macrolide antibiotics like erythromycin or clarithromycin
• verapamil (used to treat heart diseases and high blood pressure)
• ciprofloxacin (an antibiotic)
• diltiazem (used to treat high blood pressure and chest pain).

The following medicines may lower the effect of tolvaptan:

• phenytoin or carbamazepine (used to treat epilepsy)
• rifampicin, rifabutin or rifapentine (used to treat tuberculosis)
• St. John’s Wort (a traditional herbal medicinal product for the relief of slightly low mood and mild anxiety).

Tolvaptan may increase the effect of the following medicines:

• digoxin (used to treat irregular heart beat and heart failure)
• dabigatran (used to thin the blood)
• sulfasalazine (used to treat inflammatory bowel disease or rheumatoid arthritis)
• metformin (used to treat diabetes).

Tolvaptan may lower the effect of the following medicines:

• vasopressin analogues such as desmopressin (used to increase blood clotting factors or to control urine output or bedwetting).

These medicines can affect or be affected by Tolvaptan:

• diuretics (used to influence the production of urine). Taken with tolvaptan these may increase the risk of side effects due to water loss or may cause kidney problems
• diuretics or other medicines for the treatment of high blood pressure. Taken with tolvaptan these may increase the risk of low blood pressure when you stand up from sitting or lying down
• medicines which increase the level of sodium in your blood or which contain large amounts of salt (e.g. tablets that dissolve in water and indigestion remedies). These may increase the effect of tolvaptan. There is a risk that this may lead to too much sodium in your blood.

It may still be alright for you to take these medicines and tolvaptan together. Your doctor will be able to decide what is suitable for you.

Do not drink grapefruit juice when taking this medicine.

Do not take this medicine if you are pregnant or breast-feeding.

Women of childbearing age must use reliable contraceptive measures during use of this medicine.

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

Some people may feel dizzy, weak or tired after being given tolvaptan. If this happens to you, do not drive or use any tools or machines.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

This medicine contains less than 1mmol sodium (23mg) per tablet, that is to say essentially ‘sodium-free’.

If you have taken more tablets than your prescribed dose, drink plenty of water and contact your doctor or your local hospital immediately. Remember to take the medicine pack with you so that it is clear what you have taken. If you take the higher dose very late in the day you may have to go to the toilet at night more frequently.

If you forget to take your medicine you should take the dose as soon as you remember on the same day. If you do not take your tablets on one day, take your normal dose on the next day. DO NOT take a double dose to make up for forgotten individual doses.

If you stop taking this medicine your kidney cysts may grow as fast as they did before you started treatment with tolvaptan. Therefore, you should only stop taking tolvaptan if you notice side effects requiring urgent medical attention (see section 4) or if your doctor tells you to.

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

• find it difficult to urinate
• experience swelling of the face, lips or tongue, itching, generalised rash, or severe wheezing or breathlessness (symptoms of an allergic reaction).

Tolvaptan may cause your liver not to work properly.

Consult your doctor if symptoms of nausea, vomiting, fever, tiredness, loss of appetite, pain in the abdomen, dark urine, jaundice (yellowing of skin or eyes), itching of your skin or joint and muscle pain with fever occur.

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

• thirst (requiring excessive drinking of water)
• headache
• dizziness
• diarrhoea
• dry mouth
• increased need to urinate, to urinate at night, or to urinate more frequently
• fatigue.

Common (may affect up to 1 in 10 people)

• dehydration
• high levels of sodium, uric acid and blood sugar
• decreased appetite
• taste changes
• gout
• difficulty sleeping
• fainting
• heart pounding
• shortness of breath
• belly pain
• full or bloated or uncomfortable feeling in the stomach
• constipation
• heartburn
• liver function abnormal
• dry skin
• rash
• itching
• hives
• joint pain
• muscle spasms
• muscle pain
• general weakness
• raised levels of liver enzymes in the blood
• weight loss
• weight gain.

Uncommon (may affect up to 1 in 100 people)

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

Not known (frequency cannot be estimated from the available data)

• allergic reactions (see above)
• generalised rash
• acute liver failure (ALF).

If you get 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 via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is tolvaptan
  Each Tolvaptan 15mg tablet contains 15mg tolvaptan
  Each Tolvaptan 30mg tablet contains 30mg tolvaptan
  Each Tolvaptan 45mg tablet contains 45mg tolvaptan
  Each Tolvaptan 60mg tablet contains 60mg tolvaptan
  Each Tolvaptan 90mg tablet contains 90mg tolvaptan
• The other ingredients are lactose monohydrate (see section 2), sodium laurilsulfate, povidone, microcrystalline cellulose, croscarmellose sodium, magnesium stearate.

The different strengths of Tolvaptan tablets have different shapes and embossing:

15mg tablet: white to off-white round shaped uncoated tablets with notch, having break-line on both sides and debossed with “A” and “3” on either side of break-line on one side. Diameter of approximately 5.50 mm

30mg tablet: white to off-white, round shaped uncoated tablets, debossed with “T5” on one side and plain on the other side, with diameter of approximately 6.80 mm

45mg tablet: white to off-white, square shaped uncoated tablets, debossed with “T8” on one side and plain on the other side, with dimensions of approximately 7.70 mm x 7.70 mm

60mg tablet: white to off-white, barrel shaped uncoated tablets, debossed with “A0” on one side and plain on the other side, with dimensions of approximately 10.60 mm x 6.30 mm

90mg tablet: white to off-white, pentagon shaped uncoated tablets, debossed with “AT” on one side and plain on the other side, with dimensions of approximately 11.27 mm x 11.00 mm.

Your medicine is supplied in cartons containing blisters consist of:

• PVC/Aclar/PVC forming foil and lidding Paper/PET/Aluminum foil
• PVC/Aclar/PVC forming foil and lidding Aluminum foil
• OPA/Aluminum/PVC forming foil and lidding Paper/PET/Aluminium foil.

Your medicine is supplied in the following pack sizes:

Tolvaptan 15mg tablets: packs containing 7 or 28 tablets

Tolvaptan 30mg tablets: packs containing 7 or 28 tablets

Tolvaptan 45mg tablets + Tolvaptan 15mg tablets: packs (blister with or without wallet card) containing

14 tablets (7 tablets of the higher strength + 7 tablets of the lower strength)

28 tablets (14 tablets of the higher strength + 14 tablets of the lower strength)

or

56 tablets (28 tablets of the higher strength + 28 tablets of the lower strength)

Tolvaptan 60mg tablets + Tolvaptan 30mg tablets: packs (blister with or without wallet card) containing

14 tablets (7 tablets of the higher strength + 7 tablets of the lower strength)

28 tablets (14 tablets of the higher strength + 14 tablets of the lower strength)

Or

56 tablets (28 tablets of the higher strength + 28 tablets of the lower strength)

Tolvaptan 90mg tablets + Tolvaptan 30mg tablets: packs (blister with or without wallet card) containing

14 tablets (7 tablets of the higher strength + 7 tablets of the lower strength)

28 tablets (14 tablets of the higher strength + 14 tablets of the lower strength)

or

56 tablets (28 tablets of the higher strength + 28 tablets of the lower strength)

Not all pack sizes may be marketed.