SUMMARY CMI

SAMSCA^®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using SAMSCA?

SAMSCA contains the active ingredient tolvaptan. SAMSCA is used to treat hyponatraemia in adults, including patients who have conditions such as heart failure, and “syndrome of inappropriate antidiuretic hormone secretion” (SIADH).

For more information, see Section 1. Why am I using SAMSCA? in the full CMI.

2. What should I know before I take SAMSCA?

Do not use if you have ever had an allergic reaction to SAMSCA or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I take SAMSCA? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with SAMSCA and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take SAMSCA?

• Take SAMSCA once a day with or without food
• The dose can be from 15 mg to 60 mg once a day

More instructions can be found in Section 4. How do I take SAMSCA? in the full CMI.

5. What should I know while taking SAMSCA?

For more information, see Section 5. What should I know while taking SAMSCA? in the full CMI.

6. Are there any side effects?

Common side effects are thirst; dry mouth; making large amounts of urine and urinating often. Serious side effects include difficulty swallowing and speaking; seizures or convulsions; vomiting bright red blood; vomiting dark blood clots, or materials that looks like coffee-grounds; passing blood or stool mixed with blood; lethargy/fatigue (tiredness); mood changes; difficulty moving arms or legs, or uncontrollable movements.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

SAMSCA^®

Active ingredient(s): tolvaptan (tol-vap-tan)

Consumer Medicine Information (CMI)

This leaflet provides important information about using SAMSCA. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using SAMSCA.

Where to find information in this leaflet:

1. Why am I using SAMSCA?
2. What should I know before I take SAMSCA?
3. What if I am taking other medicines?
4. How do I take SAMSCA?
5. What should I know while taking SAMSCA?
6. Are there any side effects?
7. Product details

1. Why am I using SAMSCA?

SAMSCA contains the active ingredient tolvaptan.
SAMSCA belongs to a group of medicines called vasopressin antagonists. This means that it prevents vasopressin having its effect on water retention. This leads to a reduction in the amount of water in the body by increasing urine production and as a result it increases the concentration of sodium in your blood.

SAMSCA is used to treat hyponatraemia in adults, including patients who have conditions such as heart failure, and “syndrome of inappropriate antidiuretic hormone secretion” (SIADH). These conditions result in an inappropriate amount of the hormone vasopressin causing the sodium levels in your blood to get too low (hyponatraemia). That can lead to difficulties in concentration and memory, or in keeping your balance.

2. What should I know before I take SAMSCA?

Warnings

Do not take SAMSCA if:

• you are allergic to tolvaptan, any of the ingredients listed at the end of this leaflet, or any other similar medicine such as benzapine derivatives
• Always check the ingredients to make sure you can use this medicine.
• some of the symptoms of an allergic reaction may include:
  - shortness of breath
  - wheezing or difficulty breathing
  - swelling of the face, lips, tongue or other parts of the body
  - rash, itching or hives on the skin
• have any of the following medical conditions:
  - you cannot replace fluids by drinking
  - you cannot feel if you are thirsty
  - you have a condition which is associated with a very low blood volume
  - you are not producing or passing urine
• you are taking the following medicine(s):
  - medicines to treat fungal infections such as ketoconazole or itraconazole
  - medicines to treat bacterial infections such as clarithromycin or telithromycin
  - medicines to treat HIV infection such as saquinavir, nelfinavir or ritonavir
  - medicines to treat depression i.e. nefazodone
• you need to increase the sodium level in your blood right away - the safety and efficacy in these patients have not been studied

Check with your doctor if you:

• have any other medical conditions such as:
  - you cannot drink enough water or you are fluid restricted
  - difficulties in urination or have an enlarged prostate
  - liver disease including cirrhosis
  - diabetes
  - hypothyroidism (an underactive thyroid gland)
  - hypoadrenalism (an underactive adrenal gland)
• take any medicines for any other condition

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

It is not known if SAMSCA will harm your unborn baby or if it passes into breast milk. This medicine contains sugars as lactose.

If you have been told by your doctor that you have an intolerance to some sugars, tell your doctor before taking SAMSCA.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with SAMSCA and affect how it works. These include:

• medicines to treat fungal infections such as ketoconazole, itraconazole or fluconazole
• macrolide antibiotics such as clarithromycin or telithromycin or erythromycin
• treatments for high blood pressure and chest pain such as diltiazem or verapamil
• treatments of irregularities of heart beat and heart failure such as digoxin
• treatments for epilepsy/seizures and some sleep disorders such as barbiturates, phenytoin or carbamazepine
• medicines to treat tuberculosis such as rifampicin rifabutin or rifapentin
• medicines to immunosuppressant therapy such as cyclosporine
• treatments used to prevent or control bleeding, i.e. vasopressin analogs
• treatments of HIV infection such as saquinavir, nelfinavir or ritonavir; and
• medicines used to treat depression, i.e. nefazodone or St. John's Wort
• other medicines that increase the level of sodium in your blood or which contain large amounts of salt, such as tablets that dissolve in water and indigestion remedies

These medicines may be affected by SAMSCA or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor will have more information on medicines to be careful with or avoid while taking SAMSCA.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect SAMSCA.

4. How do I take SAMSCA?

Treatment with SAMSCA should be started and re-started only in a hospital, where the sodium levels in your blood can be monitored closely.

If your doctor or pharmacist tells you to keep taking SAMSCA after you leave a hospital, it is important that you do not stop and restart SAMSCA on your own.

You may need to go back to a hospital to re-start SAMSCA. Talk to your doctor right away if you stop taking SAMSCA for any reason.

It is important to stay under the care of your doctor while taking SAMSCA and follow their instructions.

If you do not understand the instructions, ask your doctor or pharmacist for help.

How much to take

• Take SAMSCA once a day
• You can take SAMSCA with or without food
• Tablets should be swallowed without chewing and with a glass of water
• Do not take SAMSCA with grapefruit juice
• The dose can be from 15 mg to 60 mg once a day. Your doctor will start with a dose of 15 mg and may then increase it to a maximum of 60 mg to achieve the desired level of serum sodium.
• Ask your doctor of pharmacist if you are unsure of the correct dose for you, they will tell you exactly how much to take
• Follow the instructions provided and use SAMSCA until your doctor tells you to stop
• SAMSCA should not be taken for longer than 30 days
• If you take the wrong dose, SAMSCA may not work as well and your problem may not improve
• Do not take more than the dose your doctor has recommended

When to take SAMSCA

• SAMSCA should be taken the same time each day, preferably in the morning
• This will help you remember when to take the medicine
• Certain medicines or illnesses may keep you from drinking fluids or may cause you to lose too much body fluid, such as vomiting or diarrhoea. If you have these problems, call your doctor right away.

If you forget to take SAMSCA

SAMSCA should be used regularly at the same time each day. If you miss your dose at the usual time, take it as soon as you remember and then go back to taking your medicine as you would normally.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

• This may increase the chance of you getting an unwanted side effect

If you are not sure what to do, ask your doctor or pharmacist

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much SAMSCA

If you think that you have taken too much SAMSCA, you may need urgent medical attention.

You should immediately:

• phone the Poisons Information Centre
  (by calling 13 11 26), or
• contact your doctor, or
• go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention. Remember to take the medicine pack with you so that it is clear what you have taken.

Symptoms of an overdose may include:

• thirst
• dehydration
• passing more urine than normal
• low blood volume causing very low blood pressure
• a rise in concentration of sodium concentration the blood

If your doctor tells you to stop taking SAMSCA, follow their instructions about limiting the amount of fluid you should drink.

5. What should I know while taking SAMSCA?

Things you should do

Make sure you have access to water and continue to drink when thirsty.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking SAMSCA.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine.

It may affect other medicines used during surgery.

If you are about to have any blood tests, tell your doctor that you are taking this medicine.

It may interfere with the results of some tests.

Call your doctor straight away if you:

• become pregnant while taking this medicine

Remind any doctor, dentist or pharmacist you visit that you are using SAMSCA.

Things you should not do

• Do not use SAMSCA to treat any complaint other than that directed by your doctor
• Do not give SAMSCA to someone else even if their symptoms are the same
• Do not stop taking SAMSCA or lower the dose unless you notice side effects requiring urgent medical attention or if your doctor tells you to do so. This may lead to reoccurrence of your low sodium.

Drinking enough water

• SAMSCA causes water loss because it increases your urine production. This water loss commonly results in dry mouth and thirst, and less commonly severe side effects such as kidney problems. It is therefore important that you have access to water and that you are able to drink sufficient amounts when you feel thirsty.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how SAMSCA affects you.

SAMSCA may occasionally make you feel dizzy or weak or you may faint for a short period.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

• Store SAMSCA below 25°C and away from light and moisture.
• Do not leave it in the car on hot or cold days. Heat, cold and dampness can destroy some medicines.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

• in the bathroom or near a sink, or
• in the car or on window sills.

Keep it where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep SAMSCA in the pack until it is time to take your dose. If it is removed from the pack, it may not keep well.

Getting rid of any unwanted medicine

If your doctor tells you to stop taking SAMSCA or it is out of date, ask your doctor what to do with any SAMSCA that is left.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Serious side effects

SAMSCA may affect your liver function. Therefore, please inform your doctor at any time if you have signs that could indicate potential liver problems such as:

• unusual exhaustion
• loss of appetite
• pain in your right upper stomach
• dark urine
• jaundice (yellowing of your skin or the whites of your eyes)

During treatment with SAMSCA, your doctor may arrange blood tests to check for changes in your liver function or electrolytes (salts).

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What SAMSCA contains

SAMSCA tablets contain 15 mg of tolvaptan.

Do not take this medicine if you are allergic to any of these ingredients.

What SAMSCA looks like

SAMSCA is supplied as 15 mg tablets in a PVC/aluminium perforated unit dose blister pack of 10 tablets.

The 15 mg tablet is blue, triangular, shallow-convex, debossed with “OTSUKA” and “15” on one side.

(Aust R 176602).

Who distributes SAMSCA

Otsuka Australia Pharmaceutical Pty Ltd
Suite 2.03, Level 2
9 Help Street
Chatswood NSW 2067

This leaflet was prepared in June 2022.

SAMSCA^® is a registered trademark of Otsuka Pharmaceutical Co., Ltd.

Published by MIMS August 2022

1 Name of Medicine

Tolvaptan.

2 Qualitative and Quantitative Composition

Samsca tablets for oral use contain 15 mg or 30 mg of tolvaptan.
Excipients with known effect: sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Samsca is supplied as 15 mg and 30 mg tolvaptan tablets.
The 15 mg tablet is blue, triangular, shallow-convex, debossed with "OTSUKA" and "15" on one side.
The 30 mg tablet is blue, round, shallow-convex, debossed with "OTSUKA" and "30" on one side.

4 Clinical Particulars

4.1 Therapeutic Indications

Samsca is indicated for the treatment of clinically significant hypervolaemic or euvolaemic hyponatraemia (serum sodium less than 125 mmol/L, or less marked hyponatraemia that is symptomatic and has resisted correction with fluid restriction) including patients with heart failure and syndrome of inappropriate antidiuretic hormone (SIADH).

Important limitations.

4.2 Dose and Method of Administration

Due to the need for a dose titration phase with close monitoring of serum sodium and volume status, treatment with Samsca should be initiated and reinitiated in hospital.
Treatment with Samsca should be initiated at a dose of 15 mg, orally, once daily. The dose may be increased to a maximum of 60 mg once daily as tolerated to achieve the desired level of serum sodium. Increase from the starting dose should be done incrementally (first to 30 mg and then to 60 mg if required) at intervals ≥ 24 hours. During titration, patients should be monitored for serum sodium and volume status.
For patients with an appropriate increase in serum sodium, the underlying disease and serum sodium levels should be monitored at regular intervals to evaluate further need of Samsca treatment. Do not administer Samsca for more than 30 days to minimise the risk of liver injury (see Section 4.4 Special Warnings and Precautions for Use).
Samsca tablets should be taken orally, preferably in the morning, without regard to meals. Tablets should be swallowed without chewing with a glass of water.
Samsca tablets should not be taken with grapefruit juice.

Patient monitoring.

Hyperkalaemia or drugs that increase serum potassium.

Drug withdrawal.

4.3 Contraindications

Samsca is contraindicated in:
Patients hypersensitive to the active substance, benzazepine derivatives or any of the excipients.
Patients who are unable to sense or appropriately respond to thirst.
Patients suffering from hypovolaemic hyponatraemia.
Patients with anuria.
Urgent need to raise serum sodium acutely. Samsca has not been studied in a setting of urgent need to raise serum sodium acutely.
Ketoconazole and other strong CYP3A inhibitors. See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

4.4 Special Warnings and Precautions for Use

Heart failure.

Hypothyroidism and hypoadrenalism.

Liver injury.

Too rapid increases in serum sodium.

Hypernatremia.

Dehydration and hypovolaemia.

Hyperkalaemia or drugs that increase serum potassium.

Urinary outflow obstruction.

Lactose and galactose intolerance.

Use in hepatic impairment.

Use in renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Ketoconazole and other strong CYP3A inhibitors.

Moderate CYP3A inhibitors.

Grapefruit juice.

Rifampin and other CYP3A inducers.

P-glycoprotein (P-gp) inhibitors.

Lovastatin, warfarin, amiodarone, frusemide, and hydrochlorothiazide.

Digoxin.

Coadministration with hypertonic saline.

Coadministration with vasopressin analogs.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

When driving vehicles or using machines it should be taken into account that occasionally dizziness, asthenia or syncope may occur.

4.8 Adverse Effects (Undesirable Effects)

In multiple dose, placebo controlled trials, 607 hyponatraemic patients (serum sodium < 135 mmol/L) were treated with Samsca. The mean age of these patients was 62 years; 70% of patients were male and 82% were Caucasian. One hundred eighty nine (189) Samsca treated patients had a serum sodium < 130 mmol/L, and 52 patients had a serum sodium < 125 mmol/L. Hyponatraemia was attributed to cirrhosis in 17% of patients, heart failure in 68% and SIADH/ other in 16%. Of these patients, 223 were treated with the recommended dose titration (15 mg titrated to 60 mg as needed to raise serum sodium).
Overall, over 4000 patients have been treated with oral doses of Samsca in open label or placebo controlled clinical trials. Approximately 650 of these patients had hyponatraemia; approximately 219 of these hyponatraemic patients were treated with Samsca for 6 months or more.
The most common adverse reactions (incidence ≥ 5% more than placebo) seen in two 30 day, double blind, placebo controlled hyponatraemia trials in which Samsca was administered in titrated doses (15 mg to 60 mg once daily) were thirst, dry mouth, asthenia, constipation, pollakiuria or polyuria and hyperglycemia. In these trials, 10% (23/223) of Samsca treated patients discontinued treatment because of an adverse event, compared to 12% (26/220) of placebo treated patients; no adverse reaction resulting in discontinuation of trial medication occurred at an incidence of > 1% in tolvaptan treated patients.
Table 1 lists the adverse reactions reported in Samsca treated patients with hyponatraemia (serum sodium < 135 mmol/L) and at a rate at least 2% greater than placebo treated patients in two 30 day, double blind, placebo controlled trials. In these studies, 223 patients were exposed to tolvaptan (starting dose 15 mg, titrated to 30 and 60 mg as needed to raise serum sodium). Adverse events resulting in death in these trials were 6% in Samsca treated patients and 6% in placebo treated patients.
In a subgroup of patients with hyponatraemia (N = 475, serum sodium < 135 mmol/L) enrolled in a double blind, placebo controlled trial (mean duration of treatment was 9 months) of patients with worsening heart failure, the following adverse reactions occurred in tolvaptan treated patients at a rate at least 2% greater than placebo: mortality (42% tolvaptan, 38% placebo), nausea (21% tolvaptan, 16% placebo), thirst (12% tolvaptan, 2% placebo), dry mouth (7% tolvaptan, 2% placebo) and polyuria or pollakiuria (4% tolvaptan, 1% placebo).
The following adverse reactions occurred in < 2% of hyponatraemic patients treated with Samsca and at a rate greater than placebo in double blind placebo controlled trials (N = 607 tolvaptan; N = 518 placebo) or in < 2% of patients in an uncontrolled trial of patients with hyponatraemia (N = 111) and are not mentioned elsewhere in the label.

Blood and lymphatic system disorders.

Cardiac disorders.

Investigations.

Gastrointestinal disorders.

Metabolism and nutrition disorders.

Musculoskeletal and connective tissue disorders.

Nervous system.

Renal and urinary disorders.

Reproductive system and breast disorders (female).

Respiratory, thoracic, and mediastinal disorders.

Vascular disorder.

Gastrointestinal bleeding in patients with cirrhosis.

Postmarketing experience.

Reporting suspected adverse reactions.

4.9 Overdose

Contact the Poisons Information Centre on telephone 13 11 26 for advice on management of overdose.
Single oral doses up to 480 mg and multiple doses up to 300 mg of Samsca, taken once daily for 5 days have been well tolerated in studies in healthy subjects.
There is no specific antidote for Samsca overdose. The signs and symptoms of an acute overdose can be anticipated to be those of excessive pharmacologic effect: a rise in serum sodium concentration, polyuria, thirst, and dehydration/ hypovolaemia.
The oral LD₅₀ of tolvaptan in rats and dogs is > 2000 mg/kg. No mortality was observed in rats or dogs following single oral doses of 2000 mg/kg (maximum feasible dose). A single oral dose of 2000 mg/kg was lethal in mice, and symptoms of toxicity in affected mice included decreased locomotor activity, staggering gait, tremor and hypothermia.
If overdose occurs, estimation of the severity of poisoning is an important first step. A thorough history and details of overdose should be obtained, and a physical examination should be performed. The possibility of multiple drug involvement should be considered.
Treatment should involve symptomatic and supportive care, with respiratory, ECG and blood pressure monitoring and water/ electrolyte supplements as needed. A profuse and prolonged aquaresis should be anticipated, which, if not matched by oral fluid ingestion, should be replaced with intravenous hypotonic fluids, while closely monitoring electrolytes and fluid balance.
ECG monitoring should begin immediately and continue until ECG parameters are within normal ranges. Dialysis may not be effective in removing tolvaptan because of its high binding affinity for human plasma protein (> 99%). Close medical supervision and monitoring should continue until the patient recovers.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Tolvaptan is a Vasopressin antagonist: ATC code C03XA01.

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

Absorption and distribution.

Metabolism.

Linearity.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Maize starch, hyprolose, lactose monohydrate, magnesium stearate, microcrystalline cellulose and indigo carmine aluminium lake.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.
Protect from light and moisture.

6.5 Nature and Contents of Container

Samsca is supplied as 15 mg and 30 mg tolvaptan tablets in PVC/aluminium perforated unit dose blister packs of 10 or 30 tablets each.
Not all presentations and pack sizes may be available in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Tolvaptan is (±)-4'-[(7-chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl) carbonyl]-o-tolu-m-toluidide. The empirical formula is C₂₆H₂₅ClN₂O₃. Molecular weight is 448.94.

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

Schedule 4: Prescription Only Medicine (S4).

Summary Table of Changes