Tolvaptan Accord

Package leaflet: Information for the user

Tolvaptan Accord 7.5 mg tablets, 15 mg tablets, 30 mg tablets

tolvaptan
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 or pharmacist.
• This medicine has been prescribed for you only. Never give it to other people, 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, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Tolvaptan Accord is and what it is used for

Tolvaptan Accord, which contains the active substance tolvaptan, belongs to a group of medicines
called vasopressin antagonists. Vasopressin is a hormone that helps prevent water loss from the body
by reducing urine excretion. Antagonist means that it blocks vasopressin from acting on fluid retention.
This in turn reduces the amount of water in the body by increasing urine production, and consequently
increases the level or concentration of sodium in the blood.
Tolvaptan Accord is used to treat patients with low sodium concentrations in the blood. This medicine
has been prescribed for you because you suffer from low sodium levels in the blood due to a condition
called “syndrome of inappropriate antidiuretic hormone secretion” (SIADH), in which the kidneys retain
too much water. This disease causes inappropriate production of the hormone vasopressin, resulting in
sodium levels in the blood becoming too low (hyponatremia). This may cause difficulties with
concentration and memory, or in maintaining balance.

2. What you need to know before taking Tolvaptan Accord

Do not take Tolvaptan Accord

• if you are allergic to tolvaptan or to any of the other ingredients of this medicine (listed in section 6) or if you are allergic to benzazepine or derivatives of benzazepine (e.g., benazepril, conivaptan, mesylate fenoldopam, or mirtazapine)
• if your kidneys do not work (do not produce urine)
• if you have a condition causing high levels of salt in the blood ("hypernatremia")
• if you have a disorder associated with very low blood volume
• if you do not feel thirsty
• if you are pregnant
• if you are breastfeeding.

Warnings and precautions
Talk to your doctor or pharmacist before taking Tolvaptan Accord.

• if you are unable to drink enough water or if you have restrictions on fluid intake
• if you have difficulty urinating or if you have an enlarged prostate
• if you have liver disease
• if you have previously had an allergic reaction to benzazepine, tolvaptan, or other derivatives of benzazepine (e.g., benazepril, conivaptan, mesylate fenoldopam, or mirtazapine) or to any of the other ingredients of this medicine (listed in section 6)
• if you have a kidney disease called autosomal dominant polycystic kidney disease (ADPKD)
• if you have diabetes.

Drink enough water
Tolvaptan Accord causes water loss because it increases urine production. This water loss may cause
unwanted effects such as dry mouth and thirst, or even more serious side effects such as kidney problems (see section 4). Therefore, it is important that you have access to water and can drink enough whenever you feel thirsty.
Children and adolescents
Tolvaptan Accord is not suitable for children and adolescents (under 18 years of age).
Other medicines and Tolvaptan Accord
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.
The following medicines may increase the effect of this medicine:

• ketoconazole (for fungal infections),
• macrolide antibiotics,
• diltiazem (a treatment for high blood pressure and chest pain),
• other products that increase blood salt levels or contain large amounts of salt.

The following medicines may reduce the effects of this medicine:

• barbiturates (used to treat epilepsy/seizures and certain sleep disorders),
• rifampicin (for tuberculosis).

This medicine may increase the effects of the following medicines:

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

This medicine may reduce the effect of the following medicine:

• desmopressin (used to increase blood clotting factors).

There may be cases where it is still acceptable to take these medicines together with Tolvaptan
Accord. Your doctor will decide the appropriate treatment for you.
Tolvaptan Accord with food and drinks
Avoid drinking grapefruit juice when taking Tolvaptan Accord.
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, are planning a pregnancy, or are breastfeeding,
please consult your doctor or pharmacist before taking this medicine.
Do not take this medicine if you are pregnant or breastfeeding.
Adequate contraceptive methods must be used during treatment with this medicine.
Driving and using machines
It is unlikely that Tolvaptan Accord will negatively affect your ability to drive or operate machinery. However, you may occasionally experience dizziness or weakness, or brief episodes of fainting.
Tolvaptan Accord contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking
this medicine.

3. How to take Tolvaptan Accord

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.

• Treatment with Tolvaptan Accord must begin in a hospital setting.
• For the treatment of low sodium levels (hyponatremia), your doctor will start with a dose of 15 mg and may subsequently increase it up to a maximum of 60 mg to achieve the desired sodium level. To monitor the effects of Tolvaptan Accord, your doctor will perform regular blood tests. In some cases, to reach the desired sodium level, your doctor may prescribe a lower dose of 7.5 mg.
• Swallow the tablet with a glass of water, without chewing.
• Take the tablets once daily, preferably in the morning, with or without food.

If you take more Tolvaptan Accord than you should
If you have taken more tablets than prescribed, drink plenty of water and contact your doctor or the nearest hospital immediately. Remember to bring the medicine package with you so that it is clear what you have taken.

If you forget to take Tolvaptan Accord
If you forget to take your dose, take it as soon as you remember, on the same day. If you miss a dose on a particular day, take your usual dose the next day. Do not take a double dose to make up for the missed dose.

If you stop taking Tolvaptan Accord
If you stop taking Tolvaptan Accord, this may lead to the recurrence of low sodium levels. Therefore, stop taking Tolvaptan Accord only if you experience side effects requiring urgent medical attention (see section 4), or if your doctor instructs you to do so.

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 everybody gets them.
If you notice any of the following side effects, you may urgently need medical treatment.
Stop taking Tolvaptan Accord and contact a doctor immediately, or go to the nearest hospital, if:

• you have difficulty urinating
• you notice swelling of the face, lips or tongue, itching, widespread skin rash, or severe wheezing or breathing difficulty (symptoms of an allergic reaction).

Consult your doctor if you develop symptoms such as fatigue, loss of appetite, discomfort in the upper right part of the abdomen, dark urine or jaundice (yellowing of the skin or eyes).
Other side effects
Very common (may affect more than 1 in 10 people)

• nausea
• thirst
• rapid increase in sodium levels.

Common (may affect up to 1 in 10 people)

• excessive water intake
• water loss
• high levels of sodium, potassium, creatinine, uric acid and blood sugar
• reduced blood sugar levels
• reduced appetite
• fainting
• headache
• dizziness
• low blood pressure when standing up
• constipation
• diarrhea
• dry mouth
• bruising
• itching
• increased need to urinate or need to urinate more frequently
• tiredness, general weakness
• fever
• feeling generally unwell
• blood in the urine
• elevated liver enzymes in the blood
• elevated creatinine levels in the blood.

Uncommon (may affect up to 1 in 100 people)

• altered taste
• kidney problems.

Not known (cannot be estimated from the available data)

• allergic reactions (see above)
• liver problems
• acute liver failure (acute liver failure, ALF)
• increased liver enzyme levels.

Reporting of side effects
If you get any side effect, 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 Tolvaptan Accord

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
each blister after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
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 Tolvaptan Accord contains

• The active substance is tolvaptan. Each Tolvaptan Accord 7.5 mg tablet contains 7.5 mg of tolvaptan. Each Tolvaptan Accord 15 mg tablet contains 15 mg of tolvaptan. Each Tolvaptan Accord 30 mg tablet contains 30 mg of tolvaptan.
• The other components are monohydrate lactose, maize starch, microcrystalline cellulose, magnesium stearate, sodium croscarmellose, hydroxypropylcellulose, indigo carmine aluminium lake (E132).

Description of the appearance of Tolvaptan Accord and package contents
Tolvaptan Accord 7.5 mg: tablets, light blue to blue in colour, round, biconvex, uncoated,
imprinted with "MT" on one side and "18" on the other, approximately 5.00 mm in size.
Tolvaptan Accord 15 mg: tablets, light blue to blue in colour, triangular, biconvex, uncoated,
imprinted with "MT" on one side and "7" on the other, approximately 6.7 x 6.3 x 3.3 mm in size.
Tolvaptan Accord 30 mg: tablets, light blue to blue in colour, round, biconvex, uncoated,
imprinted with "MT" on one side and "8" on the other, approximately 8.1 mm in size.
Tolvaptan Accord 7.5/15/30 mg tablets are available in boxes with PVC/Alu blisters, divisible into single doses, containing 7x1, 10x1, 28x1, or 30x1 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n,
Edifici Est, 6 Planta,
08039 Barcelona,
Spain

Manufacturer
Accord Healthcare Polska Sp. z.o.o.
ul. Lutomierska 50,
95-200 Pabianice, Poland
Pharmadox Healthcare Limited
KW20A Kordin Industrial Park,
Paola PLA 3000, Malta
Accord Healthcare B.V.
Winthontlaan 200,
3526 KV Utrecht, Netherlands

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