Samsca

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Samsca 7.5 mg tablets 
Samsca 15 mg tablets 
Samsca 30 mg tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Samsca 7.5 mg tablets 
Each tablet contains 7.5 mg tolvaptan. 
Excipient with known effect 
51 mg lactose (as monohydrate) per tablet 
 
Samsca 15 mg tablets 
Each tablet contains 15 mg tolvaptan. 
Excipient with known effect 
35 mg lactose (as monohydrate) per tablet 
 
Samsca 30 mg tablets 
Each tablet contains 30 mg tolvaptan. 
Excipient with known effect 
70 mg lactose (as monohydrate) per tablet 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Tablet 
 
Samsca 7.5 mg tablets 
Blue, rectangular, shallow-convex tablets with dimensions of 7.7 × 4.35 × 2.5 mm, debossed with 
“OTSUKA” and “7.5” on one side. 
 
Samsca 15 mg tablets 
Blue, triangular, shallow-convex tablets with dimensions of 6.58 × 6.2 × 2.7 mm, debossed with 
“OTSUKA” and “15” on one side. 
 
Samsca 30 mg tablets 
Blue, round, shallow-convex tablets with dimensions of Ø8 × 3.0 mm, debossed with “OTSUKA” and 
“30” on one side.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Samsca is indicated in adults for the treatment of hyponatremia secondary to the syndrome of 
inappropriate antidiuretic hormone secretion (SIADH). 
 
4.2 Posology and method of administration 
 
Due to the need for a dose titration phase with close monitoring of serum sodium and volume status 
(see section 4.4), treatment with Samsca has to be initiated in hospital. 
 



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Posology 
 
Tolvaptan has to be initiated at a dose of 15 mg 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. 
 
For patients at risk of overly rapid correction of sodium e.g. patients with oncological conditions, very 
low baseline serum sodium, taking diuretics, or taking sodium supplementation a dose of 7.5 mg 
should be considered (see section 4.4). 
 
During titration, patients must be monitored for serum sodium and volume status (see section 4.4). In 
case of inadequate improvement in serum sodium levels, other treatment options have to be 
considered, either in place of or in addition to tolvaptan. Use of tolvaptan in combination with other 
options may increase the risk of overly rapid correction of serum sodium (see sections 4.4 and 4.5). 
For patients with an appropriate increase in serum sodium, the underlying disease and serum sodium 
levels must be monitored at regular intervals to evaluate further need of tolvaptan treatment. In the 
setting of hyponatremia, the treatment duration is determined by the underlying disease and its 
treatment. Tolvaptan treatment is expected to last until the underlying disease is adequately treated or 
until such time that hyponatremia is no longer a clinical issue. 
Samsca must not be taken with grapefruit juice (see section 4.5). 
 
Special populations 
 
Renal impairment 
Tolvaptan is contraindicated in anuric patients (see section 4.3). 
Tolvaptan has not been studied in patients with severe renal failure. The efficacy and safety in this 
population is not well established. 
Based on the data available, no dose adjustment is required in those with mild to moderate renal 
impairment. 
 
Hepatic impairment 
No information is available in patients with severe hepatic impairment (Child-Pugh class C). In these 
patients dosing has to be managed cautiously and electrolytes and volume status must be monitored 
(see section 4.4). No dose adjustment is needed in patients with mild or moderate hepatic impairment 
(Child-Pugh classes A and B). 
 
Elderly 
No dose adjustment is needed in elderly patients. 
 
Paediatric population 
The safety and efficacy of tolvaptan in children and adolescents under the age of 18 years have not yet 
been established. Samsca is not recommended in the paediatric age group. 
 
Method of administration 
 
Oral use. 
 
Administration preferably in the morning, without regard to meals. Tablets must be swallowed without 
chewing with a glass of water. 
 
4.3 Contraindications 
 
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to 

benzazepine or benzazepine derivatives (see section 4.4) 
• Anuria 
• Volume depletion 
• Hypovolemic hyponatremia 
• Hypernatremia 



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• Patients who cannot perceive thirst 
• Pregnancy (see section 4.6) 
• Breast-feeding (see section 4.6) 
 
4.4 Special warnings and precautions for use 
 
Urgent need to raise serum sodium acutely 
 
Tolvaptan has not been studied in a setting of urgent need to raise serum sodium acutely. For such 
patients, alternative treatment has to be considered. 
 
Access to water 
 
Tolvaptan may cause adverse reactions related to water loss such as thirst, dry mouth and dehydration 
(see section 4.8). Therefore, patients must have access to water and be able to drink sufficient amounts 
of water. If fluid restricted patients are treated with tolvaptan, extra caution has to be exercised to 
ensure that patients do not become overly dehydrated. 
 
Dehydration 
 
Volume status must be monitored in patients taking tolvaptan because treatment with tolvaptan may 
result in severe dehydration, which constitutes a risk factor for renal dysfunction. If dehydration 
becomes evident, take appropriate action which may include the need to interrupt or reduce the dose of 
tolvaptan and increase fluid intake. 
 
Urinary outflow obstruction 
 
Urinary output must be secured. Patients with partial obstruction of urinary outflow, for example 
patients with prostatic hypertrophy or impairment of micturition, have an increased risk of developing 
acute retention. 
 
Fluid and electrolyte balance 
 
Fluid and electrolyte status has to be monitored in all patients and particularly in those with renal and 
hepatic impairment. Administration of tolvaptan may cause too rapid increases in serum sodium 
(≥ 12 mmol/L per 24 hours, please see below); therefore, monitoring of serum sodium in all patients 
must start no later than 4-6 hours after treatment initiation. During the first 1-2 days and until the 
tolvaptan dose is stabilised serum sodium and volume status must be monitored at least every 6 hours. 
 
Too rapid correction of serum sodium 
 
Patients with very low baseline serum sodium concentrations may be at greater risk for too rapid 
correction of serum sodium. 
Too rapid correction of hyponatremia (increase ≥ 12 mmol/L/24 hours) can cause osmotic 
demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic 
quadriparesis, seizures, coma or death. Therefore after initiation of treatment, patients have to be 
closely monitored for serum sodium and volume status (see above). 
In order to minimise the risk of too rapid correction of hyponatremia the increase of serum sodium 
should be less than 10-12 mmol/L/24 hours and less than 18 mmol/L/48 hours. Therefore, more 
precautionary limits apply during the early treatment phase. 
If sodium correction exceeds 6 mmol/L during the first 6 hours of administration or 8 mmol/L during 
the first 6-12 hours, respectively, the possibility that serum sodium correction may be overly rapid 
should be considered. These patients should be monitored more frequently regarding their serum 
sodium and administration of hypotonic fluid is recommended. In case serum sodium 
increases ≥ 12 mmol/L within 24 hours or ≥ 18 mmol/L within 48 hours, tolvaptan treatment is to be 
interrupted or discontinued followed by administration of hypotonic fluid. 



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In patients at higher risk of demyelination syndromes, for example those with hypoxia, alcoholism or 
malnutrition, the appropriate rate of sodium correction may be lower than that in patients without risk 
factors; these patients should be very carefully managed. 
 
Patients who received other treatment for hyponatremia or medicinal products which increase serum 
sodium concentration (see section 4.5) prior to initiation of treatment with Samsca must be managed 
very cautiously. These patients may be at higher risk for developing rapid correction of serum sodium 
during the first 1-2 days of treatment due to potential additive effects. 
Co-administration of Samsca with other treatments for hyponatremia, and medicinal products that 
increase serum sodium concentration, is not recommended during initial treatment or for other patients 
with very low baseline serum sodium concentrations (see section 4.5). 
 
Diabetes mellitus 
 
Diabetic patients with an elevated glucose concentration (e.g. in excess of 300 mg/dL) may present 
with pseudo-hyponatremia. This condition should be excluded prior and during treatment with 
tolvaptan. 
Tolvaptan may cause hyperglycemia (see section 4.8). Therefore, diabetic patients treated with 
tolvaptan should be managed cautiously. In particular this applies to patients with inadequately 
controlled type II diabetes. 
 
Idiosyncratic hepatic toxicity 
 
Liver injury induced by tolvaptan was observed in clinical trials investigating a different indication 
(autosomal dominant polycystic kidney disease [ADPKD]) with long-term use of tolvaptan at higher 
doses than for the approved indication (see section 4.8). 
 
In post-marketing experience with tolvaptan in ADPKD, acute liver failure requiring liver 
transplantation has been reported (see section 4.8). 
 
In these clinical trials, clinically significant increases (greater than 3 × Upper Limit of Normal) in 
serum alanine aminotransferase (ALT), along with clinically significant increases (greater than 2 × 
Upper Limit of Normal) in serum total bilirubin were observed in 3 patients treated with tolvaptan. In 
addition, an increased incidence of significant elevations of ALT was observed in patients treated with 
tolvaptan [4.4 % (42/958)] compared to those receiving placebo [1.0 % (5/484)]. Elevation 
(>3 × ULN) of serum aspartate aminotransferase (AST) was observed in 3.1 % (30/958) of patients on 
tolvaptan and 0.8 % (4/484) patients on placebo. Most of the liver enzyme abnormalities were 
observed during the first 18 months of treatment. The elevations gradually improved after 
discontinuation of tolvaptan. These findings may suggest that tolvaptan has the potential to cause 
irreversible and potentially fatal liver injury. 
 
In a post-authorisation safety study of tolvaptan in hyponatremia secondary to SIADH, several cases 
of hepatic disorders and elevated transaminases were observed (see section 4.8). 
 
Liver function tests must be promptly performed in patients taking tolvaptan who report symptoms 
that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark 
urine or jaundice. If liver injury is suspected, tolvaptan must be promptly discontinued, appropriate 
treatment has to be instituted, and investigations have to be performed to determine the probable 
cause. Tolvaptan must not be re-initiated in patients unless the cause for the observed liver injury is 
definitively established to be unrelated to treatment with tolvaptan. 
 
Anaphylaxis 
 
In post-marketing experience, anaphylaxis (including anaphylactic shock and generalised rash) has 
been reported very rarely following administration of tolvaptan. Patients have to be carefully 
monitored during treatment. Patients with known hypersensitivity reactions to benzazepine or 



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benzazepine derivatives (e.g. benazepril, conivaptan, fenoldopam mesylate or mirtazapine) may be at 
risk for hypersensitivity reaction to tolvaptan (see section 4.3 Contraindications). 
 
If an anaphylactic reaction or other serious allergic reactions occur, administration of tolvaptan must 
be discontinued immediately and appropriate therapy initiated. Since hypersensitivity is a 
contraindication (see section 4.3) treatment must never be restarted after an anaphylactic reaction or 
other serious allergic reactions. 
 
Lactose and galactose intolerance 
 
Samsca contains lactose as an excipient. Patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Co-administration with other treatments for hyponatremia and medicinal products that increase serum 
sodium concentration 
 
There is no experience from controlled clinical trials with concomitant use of Samsca and other 
treatments for hyponatremia such as hypertonic sodium chloride solution, oral sodium formulations, 
and medicinal products that increase serum sodium concentration. Medicinal products with high 
sodium content such as effervescent analgesic preparations and certain sodium containing treatments 
for dyspepsia may also increase serum sodium concentration. Concomitant use of Samsca with other 
treatments for hyponatremia or other medicinal products that increase serum sodium concentration 
may result in a higher risk for developing rapid correction of serum sodium (see section 4.4) and is 
therefore not recommended during initial treatment or for other patients with very low baseline serum 
sodium concentrations where rapid correction may represent a risk for osmotic demyelination (see 
section 4.4). 
 
CYP3A4 inhibitors 
 
Tolvaptan plasma concentrations have been increased by up to 5.4-fold area under time-concentration 
curve (AUC) after the administration of strong CYP3A4 inhibitors. Caution should be exercised in co-
administering CYP3A4 inhibitors (e.g. ketoconazole, macrolide antibiotics, diltiazem) with tolvaptan 
(see section 4.4). Co-administration of grapefruit juice and tolvaptan resulted in a 1.8-fold increase in 
exposure to tolvaptan. Patients taking tolvaptan should avoid ingesting grapefruit juice. 
 
CYP3A4 inducers 
 
Tolvaptan plasma concentrations have been decreased by up to 87 % (AUC) after the administration 
of CYP3A4 inducers. Caution has to be exercised in co-administering CYP3A4 inducers (e.g. 
rifampicin, barbiturates) with tolvaptan. 
 
CYP3A4 substrates 
 
In healthy subjects, tolvaptan, a CYP3A4 substrate, had no effect on the plasma concentrations of 
some other CYP3A4 substrates (e.g. warfarin or amiodarone). Tolvaptan increased plasma levels of 
lovastatin by 1.3- to 1.5-fold. Even though this increase has no clinical relevance, it indicates tolvaptan 
can potentially increase exposure to CYP3A4 substrates. 
 
Diuretics 
 
While there does not appear to be a synergistic or additive effect of concomitant use of tolvaptan with 
loop and thiazide diuretics, each class of agent has the potential to lead to severe dehydration, which 
constitutes a risk factor for renal dysfunction. If dehydration or renal dysfunction becomes evident, 
take appropriate action which may include the need to interrupt or reduce doses of tolvaptan and/or 



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diuretics, increase fluid intake, evaluate and address other potential causes of renal dysfunction or 
dehydration. 
 
Digoxin 
 
Steady state digoxin concentrations have been increased (1.3-fold increase in maximum observed 
plasma concentration [Cmax] and 1.2-fold increase in area under the plasma concentration-time curve 
over the dosing interval [AUCτ]) when co administered with multiple once daily 60 mg doses of 
tolvaptan. Patients receiving digoxin should therefore be evaluated for excessive digoxin effects when 
treated with tolvaptan. 
 
Co-administration with vasopressin analogues 
 
In addition to its renal aquaretic effect, tolvaptan is capable of blocking vascular vasopressin V2-
receptors involved in the release of coagulation factors (e.g., von Willebrand factor) from endothelial 
cells. Therefore, the effect of vasopressin analogues such as desmopressin may be attenuated in 
patients using such analogues to prevent or control bleeding when co-administered with tolvaptan. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of tolvaptan in pregnant women. Studies in 
animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. 
Samsca is contraindicated during pregnancy (see section 4.3). Women of childbearing potential have 
to use effective contraception during tolvaptan treatment. 
 
Breast-feeding 
 
It is unknown whether tolvaptan is excreted in human milk. 
Available pharmacodynamic/toxicological data in animals have shown excretion of tolvaptan in breast 
milk (for details see 5.3). 
The potential risk for humans is unknown. 
Samsca is contraindicated during breast-feeding (see section 4.3). 
 
Fertility 
 
Studies in animals showed effects on fertility (see section 5.3). The potential risk for humans is 
unknown. 
 
4.7 Effects on ability to drive and use machines 
 
Samsca has no or negligible influence on the ability to drive or use machines. However, when driving 
or using machines it should be taken into account that occasionally dizziness, asthenia or syncope may 
occur. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The adverse reaction profile of tolvaptan in SIADH is based on a clinical trials database of 
3,294 tolvaptan-treated patients and is consistent with the pharmacology of the active substance. The 
pharmaco-dynamically predictable and most commonly reported adverse reactions are thirst, dry 
mouth and pollakiuria occurring in approximately 18 %, 9 % and 6 % of patients. 
 
Tabulated list of adverse reactions 
 



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The frequencies of the adverse reactions from clinical trials correspond with very common (≥ 1/10), 
common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very 
rare (< 1/10,000) and not known (cannot be estimated from the available data). Within each frequency 
grouping, adverse reactions are presented in order of decreasing seriousness. 
 
The frequency of adverse reactions reported during post-marketing use cannot be determined as they 
are derived from spontaneous reports. Consequently, the frequency of these adverse reactions is 
qualified as "not known". 
 
System Organ 
Class 

Frequency 

 Very common Common Uncommon Not known 
Immune system 
disorders 

   Anaphylactic 
shock, 
Generalised rash 

Metabolism and 
nutrition disorders 

 Polydipsia, 
Dehydration, 
Hyperkalemia, 
Hyperglycemia, 
Hypoglycemia1, 
Hypernatremia1, 
Hyperuricemia1, 
Decreased 
appetite 
 

  

Nervous system 
disorders 

 Syncope1, 
Headache1, 
Dizziness1 
 

Dysgeusia  

Vascular 
disorders 

 Orthostatic 
hypotension 

  

Gastrointestinal 
disorders 

Nausea Constipation, 
Diarrhoea1, 
Dry mouth 

  

Skin and 
subcutaneous 
tissue disorders 

 Ecchymosis, 
Pruritus 

Pruritic rash1  

Renal and urinary 
disorders 

 Pollakiuria, 
Polyuria 

Renal impairment  

General disorders 
and 
administration site 
conditions 

Thirst Asthenia, 
Pyrexia, 
Malaise1 

  

Hepatobiliary 
disorders 

   Hepatic disorders2 
Acute hepatic 
failure3 

Investigations  Blood urine 
present1, 
Alanine 
aminotransferase 
increased (see 
section 4.4)1, 
Aspartate 
aminotransferase 
increased (see 
section 4.4)1, 
Blood creatinine 

Bilirubin 
increased (see 
section 4.4)1 

Elevated 
transaminases2 



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System Organ 
Class 

Frequency 

 Very common Common Uncommon Not known 
increased 

Surgical and 
medical 
procedures 

Rapid correction 
of hyponatremia, 
sometimes 
leading to 
neurological 
symptoms 

   

1 observed in clinical trials investigating other indications 
2 from post-authorisation safety study in hyponatremia secondary to SIADH 
3 observed in post-marketing with tolvaptan in ADPKD. Liver transplantation was necessary. 
 
Description of selected adverse reactions 
 
Rapid correction of hyponatremia  
In a post-authorisation safety study of tolvaptan in hyponatremia secondary to SIADH, including a 
high proportion of patients with tumours (especially Small Cell Lung Cancer), patients with low 
baseline serum sodium as well as patients with concomitant use of diuretics and/or sodium chloride 
solution the incidence of rapid correction of hyponatremia was found to be higher than in clinical 
trials. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Single doses up to 480 mg and multiple doses up to 300 mg per day for 5 days have been well 
tolerated in clinical trials in healthy volunteers. There is no specific antidote for tolvaptan intoxication. 
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/hypovolemia (profuse and prolonged aquaresis). 
 
In patients with suspected tolvaptan overdose, assessment of vital signs, electrolyte concentrations, 
ECG and fluid status is recommended. Appropriate replacement of water and/or electrolytes must 
continue until aquaresis abates. Dialysis may not be effective in removing tolvaptan because of its 
high binding affinity for human plasma protein (> 98 %). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Diuretics, vasopressin antagonists, ATC code: C03XA01 
 
Mechanism of action 
 
Tolvaptan is a selective vasopressin V2-receptor antagonist that specifically blocks the binding of 
arginine vasopressin (AVP) at the V2-receptor of the distal portions of the nephron. Tolvaptan affinity 
for the human V2-receptor is 1.8 times that of native AVP. 
 
In healthy adult subjects, oral administration of 7.5 to 120 mg doses of tolvaptan produced a increase 
in urine excretion rate within 2 hours of dosing. Following single oral doses of 7.5 to 60 mg, 24-hour 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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urine volume increased dose dependently with daily volumes ranging from 3 to 9 litres. For all doses, 
urine excretion rates returned to baseline levels after 24 hours. For single doses 60 mg to 480 mg, a 
mean of about 7 litres was excreted during 0 to 12 hours, independent of dose. Markedly higher doses 
of tolvaptan produce more sustained responses without affecting the magnitude of excretion, as active 
concentrations of tolvaptan are present for longer periods of time.  
 
Clinical efficacy and safety 
 
Hyponatremia 
In 2 pivotal, double-blind, placebo-controlled, clinical trials, a total of 424 patients with euvolemic or 
hypervolemic hyponatremia (serum sodium < 135 mEq/L) due to a variety of underlying causes (heart 
failure [HF], liver cirrhosis, SIADH and others) were treated for 30 days with tolvaptan (n = 216) or 
placebo (n = 208) at an initial dose of 15 mg/day. The dose could be increased to 30 and 60 mg/day 
depending on response using a 3 day titration scheme. The mean serum sodium concentration at trial 
entry was 129 mEq/L (range 114-136). 
 
The primary endpoint for these trials was the average daily AUC for change in serum sodium from 
baseline to Day 4 and baseline to Day 30. Tolvaptan was superior to placebo (p < 0.0001) for both 
periods in both studies. This effect was seen in all patients, the severe (serum sodium: < 130 mEq/L) 
and mild (serum sodium: 130 -< 135 mEq/L) subsets and for all disease aetiology subsets (e.g. HF, 
cirrhosis, SIADH/other). At 7 days after discontinuing treatment, sodium values decreased to levels of 
placebo treated patients. 
 
Following 3 days of treatment, the pooled analysis of the two trials revealed five-fold more tolvaptan 
than placebo patients achieved normalisation of serum sodium concentrations (49 % vs. 11 %). This 
effect continued as on Day 30, when more tolvaptan than placebo patients still had normal 
concentrations (60 % vs. 27 %). These responses were seen in patients independent of the underlying 
disease. The results of self-assessed health status using the SF-12 Health Survey for the mental scores 
showed statistically significant and clinically relevant improvements for tolvaptan treatment compared 
to placebo. 
 
Data on the long-term safety and efficacy of tolvaptan were assessed for up to 106 weeks in a clinical 
trial in patients (any aetiology) who had previously completed one of the pivotal hyponatremia trials. 
A total of 111 patients started tolvaptan treatment in an open-label, extension trial, regardless of their 
previous randomisation. Improvements in serum sodium levels were observed as early as the first day 
after dosing and continued for on-treatment assessments up to Week 106. When treatment was 
discontinued, serum sodium concentrations decreased to approximately baseline values, despite the 
reinstatement of standard care therapy. 
 
In a pilot, randomized (1:1:1), double-blind trial in 30 patients with hyponatremia secondary to 
SIADH, the pharmacodynamics of tolvaptan following single doses of 3.75, 7.5 and 15 mg were 
assessed. Results were highly variable with large overlap between dose groups; changes were not 
significantly correlated with tolvaptan exposure. Mean maximal changes in serum sodium were 
highest following the 15 mg dose (7.9 mmol/L) but median maximal changes were highest for the 
7.5 mg dose (6.0 mmol/L). Individual maximal increases in serum sodium were negatively correlated 
with fluid balance; mean change in fluid balance showed a dose dependent decrease. Mean change 
from baseline in cumulative urine volume and urine excretion rates was 2-fold higher for the 15 mg 
dose compared to the 7.5 and 3.75 mg doses, which showed similar responses. 
 
Heart failure 
EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan) 
was a long-term outcome, double-blind, controlled clinical trial in patients hospitalised with worsening 
HF and signs and symptoms of volume overload. In the long-term outcome trial, a total of 
2,072 patients received 30 mg tolvaptan with standard of care (SC) and 2,061 received placebo with 
SC. The primary objective of the study was to compare the effects of tolvaptan + SC with placebo + 
SC on the time to all-cause mortality and on the time to first occurrence of cardiovascular (CV) 
mortality or hospitalisation for HF. Tolvaptan treatment had no statistically significant favourable or 



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unfavourable effects on overall survival or the combined endpoint of CV mortality or HF 
hospitalisation, and did not provide convincing evidence for clinically relevant benefit. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Samsca in one or more subsets of the paediatric population in treatment of dilutional hyponatremia 
(see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
After oral administration, tolvaptan is rapidly absorbed with peak plasma concentrations occurring 
about 2 hours after dosing. The absolute bioavailability of tolvaptan is about 56 %. Co-administration 
of a 60 mg dose with a high-fat meal increases peak concentrations 1.4 fold with no change in AUC 
and no change in urine output. Following single oral doses of ≥ 300 mg, peak plasma concentrations 
appear to plateau, possibly due to saturation of absorption. 
 
Distribution 
 
Tolvaptan binds reversibly (98 %) to plasma proteins. 
 
Biotransformation 
 
Tolvaptan is extensively metabolised by the liver. Less than 1 % of intact active substance is excreted 
unchanged in the urine. 
 
Elimination 
 
The terminal elimination half-life is about 8 hours and steady-state concentrations of tolvaptan are 
obtained after the first dose. 
 
Radio labelled tolvaptan experiments showed that 40 % of the radioactivity was recovered in the urine 
and 59 % was recovered in the faeces where unchanged tolvaptan accounted for 32 % of radioactivity. 
Tolvaptan is only a minor component in plasma (3 %). 
 
Linearity 
 
Tolvaptan has linear pharmacokinetics for doses of 7.5 to 60 mg. 
 
Pharmacokinetics in special patient groups 
 
Age 
Clearance of tolvaptan is not significantly affected by age. 
 
Hepatic impairment 
The effect of mildly or moderately impaired hepatic function (Child-Pugh classes A and B) on the 
pharmacokinetics of tolvaptan was investigated in 87 patients with liver disease of various origins. No 
clinically significant changes have been seen in clearance for doses ranging from 5 to 60 mg. Very 
limited information is available in patients with severe hepatic impairment (Child-Pugh class C). 
 
In a population pharmacokinetic analysis in patients with hepatic oedema, AUC of tolvaptan in 
severely (Child-Pugh class C) and mildly or moderately (Child-Pugh classes A and B) hepatic 
impaired patients were 3.1 and 2.3 times higher than that in healthy subjects. 
 
Renal impairment 
In an analysis on population pharmacokinetics for patients with heart failure, tolvaptan concentrations 
of patients with mildly (creatinine clearance [Ccr] 50 to 80 mL/min) or moderately (Ccr 20 to 



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50 mL/min) impaired renal function were not significantly different to tolvaptan concentrations in 
patients with normal renal function (Ccr 80 to 150 mL/min). The efficacy and safety of tolvaptan in 
those with a creatinine clearance < 10 mL/min has not been evaluated and is therefore unknown. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity or carcinogenic potential. 
 
Teratogenicity was noted in rabbits given 1,000 mg/kg/day (up to 15 times the exposure in humans at 
the 60 mg dose, based on AUC). No teratogenic effects were seen in rabbits at 300 mg/kg/day (up to 
5 times the exposure in humans at the 60 mg dose, based on AUC). 
In a peri-and post-natal study in rats, delayed ossification and reduced pup bodyweight were seen at 
the high dose of 1,000 mg/kg/day. 
Two fertility studies in rats showed effects on the parental generation (decreased food consumption 
and body weight gain, salivation), but tolvaptan did not affect reproductive performance in males and 
there were no effects on the foetuses. In females, abnormal oestrus cycles were seen in both studies. 
The no observed adverse effects level (NOAEL) for effects on reproduction in females 
(100 mg/kg/day) was about 8-times the total daily dose of 60 mg/day on a mg/m2 basis. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Maize starch 
Hydroxypropylcellulose 
Lactose monohydrate 
Magnesium stearate 
Microcrystalline cellulose 
Indigo carmine aluminium lake (E 132) 
 
6.2 Incompatibilities 
 
Not applicable 
 
6.3 Shelf life 
 
Samsca 7.5 mg tablets 
5 years 
 
Samsca 15 mg tablets and Samsca 30 mg tablets 
4 years 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from light and moisture. 
 
6.5 Nature and contents of container 
 
Samsca 7.5 mg tablets 
10 tablets in PP/Alu blisters 
30 tablets in PP/Alu blisters 
10 × 1 tablet in PVC/Alu perforated unit dose blisters 
30 × 1 tablet in PVC/Alu perforated unit dose blisters 
 
Samsca 15 mg and Samsca 30 mg tablets 



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10 × 1 tablet in PVC/Alu perforated unit dose blisters 
30 × 1 tablet in PVC/Alu perforated unit dose blisters 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
Samsca 7.5 mg tablets 
EU/1/09/539/005 (10 tablets) 
EU/1/09/539/006 (30 tablets) 
EU/1/09/539/007 (10 × 1 tablet) 
EU/1/09/539/008 (30 × 1 tablet) 
 
Samsca 15 mg tablets 
EU/1/09/539/001 (10 × 1 tablet) 
EU/1/09/539/002 (30 × 1 tablet) 
 
Samsca 30 mg tablets 
EU/1/09/539/003 (10 × 1 tablet) 
EU/1/09/539/004 (30 × 1 tablet) 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 03 August 2009 
Date of latest renewal: 19 June 2014 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 
SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



15 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
AndersonBrecon (UK) Ltd. 
Units 2-7, 
Wye Valley Business Park, 
Brecon Road, 
Hay-on-Wye 
Hereford, HR3 5PG 
United Kingdom 
 
Millmount Healthcare Limited 
Block-7, City North Business Campus, Stamullen, Co. 
Meath, K32 YD60 
Ireland 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



18 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Samsca 7.5 mg tablets 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 7.5 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose.  
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
10 tablets 
30 tablets 
10 × 1 tablet 
30 × 1 tablet 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 



19 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/539/005 (10 tablets) 
EU/1/09/539/006 (30 tablets) 
EU/1/09/539/007 (10 × 1 tablet) 
EU/1/09/539/008 (30 × 1 tablet) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Samsca 7.5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



20 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS AND PERFORATED UNIT DOSE BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Samsca 7.5 mg tablets 
tolvaptan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



21 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Samsca 15 mg tablets 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 15 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose.  
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
10 × 1 tablet 
30 × 1 tablet 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 
 
 



22 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/539/001 (10 × 1 tablet) 
EU/1/09/539/002 (30 × 1 tablet) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Samsca 15 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



23 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
PERFORATED UNIT DOSE BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Samsca 15 mg tablets 
tolvaptan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Samsca 30 mg tablets 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 30 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose.  
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
10 × 1 tablet 
30 × 1 tablet 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 
 
 



25 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/539/003 (10 × 1 tablet) 
EU/1/09/539/004 (30 × 1 tablet) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Samsca 30 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



26 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
PERFORATED UNIT DOSE BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Samsca 30 mg tablets 
tolvaptan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



28 

Package leaflet: Information for the user 
 

Samsca 7.5 mg tablets 
Samsca 15 mg tablets 
Samsca 30 mg tablets 

tolvaptan 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- 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. 
 
What is in this leaflet 
 
1. What Samsca is and what it is used for  
2. What you need to know before you take Samsca  
3. How to take Samsca  
4. Possible side effects  
5. How to store Samsca 
6. Contents of the pack and other information 
 
 
1. What Samsca is and what it is used for 
 
Samsca, which contains the active substance tolvaptan, belongs to a group of medicines called 
vasopressin antagonists. Vasopressin is a hormone that helps prevent the loss of water from the body 
by reducing urine output. Antagonist 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 level or concentration of sodium in your blood. 
 
Samsca is used to treat low serum sodium levels in adults. You have been prescribed this medicine 
because you have a lowered sodium level in your blood as a result of a disease called “syndrome of 
inappropriate antidiuretic hormone secretion” (SIADH) where the kidneys retain too much water. This 
disease causes an inappropriate production of the hormone vasopressin which has caused the sodium 
levels in your blood to get too low (hyponatremia). That can lead to difficulties in concentration and 
memory, or in keeping your balance. 
 
 
2. What you need to know before you take Samsca 
 
Do not take Samsca 
• 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 your kidneys do not work (no urine production) 
• if you have a condition which increases the salt in your blood (“hypernatremia”) 
• if you have a condition which is associated with a very low blood volume 
• if you do not realise when you are thirsty 
• if you are pregnant 
• if you are breast-feeding. 
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking Samsca: 



29 

• if you cannot drink enough water or if you are fluid restricted 
• if you have difficulties in urination or have an enlarged prostate 
• if you suffer from liver disease 
• 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 suffer from a kidney disease called autosomal dominant polycystic kidney disease 
(ADPKD) 

• if you have diabetes. 
 
Drinking enough water 
Samsca 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. 
 
Children and adolescents 
Samsca is not suitable for children and adolescents (under age 18). 
 
Other medicines and Samsca 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. This includes all medicines obtained without a prescription. 
 
The following medicines may increase the effect of this medicine: 
• ketoconazole (against fungal infections), 
• macrolide antibiotics, 
• diltiazem (treatment for high blood pressure and chest pain), 
• other products which increase the salt in your blood or which contain large amounts of salt. 
 
The following medicines may lower the effect of this medicine: 
• barbiturates (used to treat epilepsy/seizures and some sleep disorders), 
• rifampicin (against tuberculosis). 
 
This medicine may increase the effect of the following medicines: 
• digoxin (used for treatment of irregularities of heart beat and heart failure). 
 
This medicine may lower the effect of the following medicines: 
• desmopressin (used to increase blood clotting factors). 
 
It may still be alright for you to take these medicines and Samsca together. Your doctor will be able to 
decide what is suitable for you. 
 
Samsca with food and drink 
Avoid drinking grapefruit juice when taking Samsca. 
 
Pregnancy and breast-feeding 
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. 
 
Do not take this medicine if you are pregnant or breast-feeding. 
 
Adequate contraceptive measures must be used during use of this medicine. 
 
Driving and using machines 
Samsca is unlikely to adversely affect your ability to drive or to operate machinery. However, you 
may occasionally feel dizzy or weak or you may faint for a short period. 
 



30 

Samsca contains lactose 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicine. 
 
 
3. How to take Samsca 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
• Treatment with Samsca will be initiated in hospital. 
• For treatment of your low sodium (hyponatremia), 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. 
To monitor the effects of Samsca your doctor will do regular blood tests. To achieve the desired 
level of serum sodium your doctor can give in some instances a lower dose of 7.5 mg. 

• Swallow the tablet without chewing, with a glass of water. 
• Take the tablets once a day preferably in the morning with or without food. 
 
If you take more Samsca than you should 
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 forget to take Samsca 
If you forget to take your medicine you have to take the dose as soon as you remember on the same 
day. If you do not take your tablet on one day, take your normal dose on the next day. Do not take a 
double dose to make up for a forgotten dose. 
 
If you stop taking Samsca 
If you stop taking Samsca this may lead to reoccurrence of your low sodium. Therefore, you should 
only stop taking Samsca if you notice side effects requiring urgent medical attention (see section 4) or 
if your doctor tells you to. 
 
If you have any further questions on the use of this medicine, ask 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 need urgent medical attention. Stop 
taking Samsca and immediately contact a doctor or go to the nearest hospital if you: 
 
• find it difficult to urinate 
• find a swelling of the face, lips or tongue, itching, generalised rash, or severe wheezing or 

breathlessness (symptoms of an allergic reaction). 
 
Consult your doctor if symptoms of fatigue, loss of appetite, right upper abdominal discomfort, dark  
urine or jaundice (yellowing of skin or eyes) occur. 
 
Other side effects 
 
Very common (may affect more than 1 in 10 people) 
• feeling sick 
• thirst 
• rapid rise in level of sodium. 
 



31 

Common (may affect up to 1 in 10 people) 
• excessive drinking of water 
• water loss 
• high levels of sodium, potassium, creatinine, uric acid and blood sugar 
• decrease in level of blood sugar 
• decreased appetite 
• fainting 
• headache 
• dizziness 
• low blood pressure when standing up 
• constipation 
• diarrhoea 
• dry mouth 
• patchy bleeding in the skin 
• itching 
• increased need to urinate, or to urinate more frequently 
• tiredness, general weakness 
• fever 
• general feeling of being unwell 
• blood in urine 
• raised levels of liver enzymes in the blood 
• raised levels of creatinine in the blood. 
 
Uncommon (may affect up to 1 in 100 people) 
• sense of taste altered 
• kidney problems 
 
Not known (cannot be estimated from the available data) 
• allergic reactions (see above) 
• liver problems 
• acute liver failure (ALF) 
• increase in liver enzymes. 
 
Reporting of side effects 
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 national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Samsca 
 
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 and blister after EXP. The 
expiry date refers to the last day of that month. 
 
Store in the original package in order to protect from light and moisture. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Samsca contains 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


32 

• The active substance is tolvaptan 
Each Samsca 7.5 mg tablet contains 7.5 mg tolvaptan. 
Each Samsca 15 mg tablet contains 15 mg tolvaptan. 
Each Samsca 30 mg tablet contains 30 mg tolvaptan. 

 
• The other ingredients are lactose monohydrate, maize starch, microcrystalline cellulose, 

hydroxypropylcellulose, magnesium stearate, indigo carmine aluminium lake (E 132). 
 
What Samsca looks like and contents of the pack 
Samsca 7.5 mg: Blue, rectangular, shallow-convex tablets with dimensions of 7.7 × 4.35 × 2.5 mm, 
debossed with “OTSUKA” and “7.5” on one side. 
Samsca 15 mg: Blue, triangular, shallow-convex tablets with dimensions of 6.58 × 6.2 × 2.7 mm, 
debossed with “OTSUKA” and “15” on one side. 
Samsca 30 mg: Blue, round, shallow-convex tablets with dimensions of Ø8 × 3.0 mm, debossed with 
“OTSUKA” and “30” on one side. 
 
Samsca 7.5 mg tablets are available as 
10 tablets in PP/Alu blisters 
30 tablets in PP/Alu blisters 
10 × 1 tablet in PVC/Alu perforated unit dose blisters 
30 × 1 tablet in PVC/Alu perforated unit dose blisters 
 
Samsca 15 mg and Samsca 30 mg tablets are available as 
10 × 1 tablet in PVC/Alu perforated unit dose blisters 
30 × 1 tablet in PVC/Alu perforated unit dose blisters 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands  
 
Manufacturer 
AndersonBrecon (UK) Ltd. 
Units 2-7, 
Wye Valley Business Park, 
Brecon Road, 
Hay-on-Wye 
Hereford, HR3 5PG 
United Kingdom 
 
Millmount Healthcare Limited 
Block-7, City North Business Campus, Stamullen, Co.Meath, K32 YD60 
Ireland 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Otsuka Pharmaceutical Netherlands B.V. 
Tél/Tel: +31 (0) 20 85 46 555 
 

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



33 

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

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

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

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

Danmark 
Otsuka Pharma Scandinavia AB 
Tlf: +46854 528 660 
 

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

Deutschland 
Otsuka Pharma GmbH 
Tel: +49691 700 860 
 

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

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

Norge 
Otsuka Pharma Scandinavia AB 
Tlf: +46854 528 660 
 

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

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

España 
Otsuka Pharmaceutical S.A 
Tel: +3493 2081 020 
 

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

France 
Otsuka Pharmaceutical France SAS 
Tél: +33147 080 000 
 

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

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

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

Ireland 
Otsuka Pharmaceuticals (UK) Ltd 
Tel: +44 (0)203 747 5300 
 

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

Ísland 
Otsuka Pharma Scandinavia AB 
Sími: +46854 528 660 
 

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

Italia 
Otsuka Pharmaceutical Italy S.r.l. 
Tel: +39 02 00 63 27 10 
 

Suomi/Finland 
Otsuka Pharma Scandinavia AB 
Tel/ Puh: +46854 528 660 
 

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

Sverige 
Otsuka Pharma Scandinavia AB 
Tel: +46854 528 660 
 

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

United Kingdom 
Otsuka Pharmaceuticals (UK) Ltd 
Tel: +44 (0)203 747 5300 
 

 



34 

This leaflet was last revised in {MM/YYYY} 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET