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1.3.1 SPC, Labeling and Package Leaflet DE

SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET

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1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE

SUMMARY OF PRODUCT CHARACTERISTICS

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1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE

1. NAME OF THE MEDICINAL PRODUCT

25 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 25 mg doxylamine hydrogen succinate.

Excipients with known effect Each film-coated tablet contains 158.34 mg lactose (as monohydrate) and 0.61 mg – 1.36 mg sodium.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet

White to almost white, oval, biconvex, one side scored film-coated tablets. Tablet dimension: 12 mm x 6 mm. The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Short-term symptomatic treatment of occasional insomnia (problems with falling asleep and midnight awakenings) in adults.

4.2 Posology and method of administration

Posology

Adults:  25 mg doxylamine hydrogen succinate daily  50 mg doxylamine hydrogen succinate daily as the maximum dose in severe sleep disturbances

The tablets should be taken about half an hour to one hour before bedtime.

In acute sleep disturbances, treatment should be limited to single doses, if possible. The duration of treatment should be as short as possible. In general, the length of treatment can vary from a few days to one week. Treatment should be discontinued at the latest after two weeks of daily use.

Special populations In patients with reduced kidney or function, elderly or weakened patients, who are more sensitive to the effects of doxylamine, the dose should be reduced. For doses not feasible with this medicinal product, other products are available.

Paediatric population The safety and efficacy of doxylamine as a night time sleep aid in children and adolescents under 18

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1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE years of age has not been established. Therefore doxylamine should not be used in children and adolescents under 18 years of age.

Method of administration Oral use. The tablet should be taken with a glass of water.

4.3 Contraindications

- Hypersensitivity to the active substance, other or to any of the excipients listed in section 6.1 - Acute asthma attack - Angle-closure - Phaeochromocytoma - Prostatic hypertrophy with urinary retention - Acute intoxication with , sleep or pain medicinal products and psychotropic medicinal products (neuroleptics, tranquillizers, antidepressants, lithium) - Epilepsy - Concomitant treatment with MAO inhibitors (see section 4.5)

4.4 Special warnings and precautions for use

should be used with caution in: - Hepatic impairment - Renal impairment - Pre-existing cardiac impairment and hypertension - Chronic respiratory problems and asthma - Gastroesophageal reflux - Stenosing peptic ulcer - Pyloroduodenal obstruction

Particular caution should be exercised in patients with neurologically apparent cerebral injuries in the cerebral cortex and a history of convulsions, because already by taking small doses of doxylamine grand mal seizures can be triggered. EEG controls are recommended. An existing treatment of seizures should not be discontinued during treatment with .

During treatment with antihistamines, ECG changes, in particular repolarization disorders, have been reported, so regular monitoring of the heart function is recommended. This is especially true for elderly patients and patients with pre-existing cardiac impairment. Special care should also be taken in patients with arterial hypertension, as antihistamines may cause an increase in blood pressure.

Caution is required in patients over 65 years of age, due to their greater sensitivity to the appearance of adverse reactions to this medication (see section 4.2). Increased risk for fall has also been described in older patients (see section 4.8).

Patients must ensure a sufficient sleep time (a period of at least 8 hours) after taking so that their ability to react is not impaired the following morning.

Interference with diagnostic tests Doxylamine may interfere with allergen tests: - Inhalation-challenge testing with histamine or antigen: Possible suppression of test response - Antigen skin testing: Possible suppression of wheal and flare reactions It is advisable to suspend this medication three days before undergoing such tests.

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1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE

contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose- galactose malabsorption should not take this medicinal product. This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

Contraindicated combinations

During concomitant use of doxylamine and monoamine oxidase inhibitors, hypotension and increased depression of the central nervous system and respiratory function may occur. Therefore, concomitant treatment with MAO inhibitors is contraindicated (see also section 4.3).

Combinations which require precautions for use

When used together, the CNS depressant effects of doxylamine and other medicinal products can be increased (e.g. some neuroleptics, tranquilizers, antidepressants, hypnotics, analgesics, anaesthetics, antiepileptics, muscle relaxants, other antihistamines). Alcohol can change the effect of doxylamine unpredictably and should be avoided. When used together, the effects of doxylamine and other medicinal products with activity (e.g. , biperiden, tricyclic antidepressants), can be increased, which could lead to e.g. paralytic , urinary retention or acute glaucoma.

The efficacy of the following medicinal products can be decreased - Phenytoin, - Neuroleptics.

During concomitant use of doxylamine - and antihypertensives with centrally active effects, such as guanabenz, clonidine, -, increased sedation may occur. - the symptoms of an incipient inner ear damage caused by ototoxic medicinal products (e.g. aminoglycosides, salicylates, diuretics) may be decreased. - false negative skin test results may be obtained. - epinephrine should not be administered, as it may lead to a paradoxical further drop in blood pressure (adrenaline reversal). Severe shock conditions can be treated with norepinephrine (see section 4.9). Therefore, concomitant treatment with epinephrine should be avoided.

4.6 Fertility, and lactation

Pregnancy Epidemiological studies with doxylamine succinate did not provide evidence for congenital malformations in humans. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of during pregnancy.

Breastfeeding Since the active substance is excreted into breast milk, breast-feeding should be discontinued during treatment with .

Fertility No data are available on the possible effects of doxylamine on human fertility. Studies in animals have

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1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE demonstrated no effects upon fertility even at doses far higher than those recommended in clinical practice (see section 5.3).

4.7 Effects on ability to drive and use machines

has major influence on the ability to drive and use machines. Even when used as recommended, this medicinal product may alter the ability to react to such an extent that the ability to participate actively in road traffic or to operate machinery is impaired. This applies even more in combination with alcohol.

Therefore, driving, operating machinery or engaging in other dangerous activities – at least during the first phase of the treatment – should be completely omitted.

4.8 Undesirable effects

Adverse reactions are listed below in frequency using the following conventions: 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), not known (cannot be estimated from the available data).

Blood and lymphatic system disorders Very rare: Blood count changes in the form of leukopenia, thrombocytopenia, haemolytic anaemia, aplastic anaemia and agranulocytosis

Endocrine disorders Not known: In patients with phaeochromocytoma, the administration of antihistamines can lead to catecholamine release.

Metabolism and nutrition disorders Not known: loss of appetite or increased appetite

Psychiatric disorders Not known: Impaired concentration, depression, prolonged reaction time. There is also the possibility of "paradoxical" reactions, such as restlessness, excitement, tension, insomnia, nightmares, confusion, hallucinations, . After prolonged daily use, intensified sleep disturbances may reoccur in case of abrupt discontinuation of treatment.

Nervous system disorders Rare: seizures Not known: , drowsiness,

Eye disorders Not known: difficulty focusing, increased intraocular pressure

Ear and labyrinth disorders Not known: , tinnitus

Cardiac disorders Not known: , arrhythmia, worsening of an existing heart failure and ECG changes

Vascular disorders Not known: Hypotension, hypertension

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1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE

Respiratory, thoracic and mediastinal disorders Not known: Respiratory function can be impaired by secretion thickening, bronchial obstruction and bronchospasm. Feeling of nasal congestion.

Gastrointestinal disorders Very rare: life-threatening paralytic ileus. Not known: , nausea, vomiting, diarrhoea, epigastric pain, dry mouth

Hepatobiliary disorders Not known: liver dysfunction (cholestatic jaundice)

Skin and subcutaneous tissue disorders Not known: allergic skin reactions and photosensitivity

Musculoskeletal and connective tissue disorders Not known: Muscle weakness

Renal and urinary disorders Not known: micturition disorders

General disorders and administration site conditions Not known: weakness, disturbances of body temperature regulation

Note: The frequency and severity of undesirable effects can be reduced by careful and individual adjustment of the daily doses. The risk of undesirable effects is greater in elderly patients, and the risk of falling can also be increased in this population.

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

In principle, the possibility of multiple-drug intoxication, for example, when taking several medicinal products with a suicidal intention, should always be considered.

Symptoms of overdose and intoxication - to coma, sometimes excitement and delirious confusion - Anticholinergic effects: blurred vision, acute glaucoma, absence of intestinal motility, urinary retention - Cardiovascular: hypotension, tachycardia or bradycardia, ventricular tachyarrhythmia, cardiac and circulatory failure - or hypothermia - Seizures - Respiratory complications: cyanosis, respiratory depression, respiratory arrest, aspiration

Management of overdose Treatment is symptomatic and supportive, based on the general principles of the procedure for overdose, with the following special features:

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1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE

- In the case of oral intake of larger quantities, early gastric lavage or induced vomiting. - Analeptics are contraindicated because doxylamine may lower the seizure threshold and thus increase the risk of seizures. - In hypotension, epinephrine-like substances should not be used, due to the paradoxical reaction, but norepinephrine-like substances (e.g. norepinephrine continuous infusion) or angiotensinamide. Beta agonists should be avoided because they increase vasodilatation. - Anticholinergic symptoms may be treated by administering salicylate (1–2 mg IV) (possibly repeated); however, routine use should be avoided due to severe undesirable effects. - In the case of repeated epileptic seizures, anticonvulsants are indicated, provided artificial respiration is possible because of the risk of respiratory depression. - Forced diuresis is of low efficacy because antihistamines are only found in small amounts in the urine. However, haemodialysis and peritoneal dialysis can be useful if mixed intoxications cannot be ruled out.

In very rare cases, rhabdomyolysis which could lead to renal failure was observed after overdosing. Consequently, systematic evaluation is warranted, based on the determination of creatine phosphokinase (CPK) activity. These serious adverse reactions have not been described at therapeutic dosing, i.e. the dose attributed to the occurrence of rhabdomyolysis and death are 13 mg/kg and 25 mg/kg, respectively, which is nearly 100 times the therapeutic range. Early detection and treatment of rhabdomyolysis is necessary to minimise kidney damage. Treatment of rhabdomyolysis induced by doxylamine overdose is by aggressive hydration and urine alkalisation. Aggressive hydration with intravenous crystalloids such as sodium chloride solution 9 mg/ml (0.9%) or lactated Ringer’s solution at a rate of 300–500 ml/h in an adult is essential. To date, it has been believed that there is no difference in effectiveness between sodium chloride solution and lactated Ringer’s solution. The therapeutic measures depend on the symptoms.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antihistamines for systemic use, aminoalkyl ethers, ATC code: R06AA09.

Mechanism of action and pharmacodynamic effects Doxylamine is an ethanolamine derivative with blocking activity on the H1 histamine receptor. It thereby reduces the stimulation of H1 receptors, which leads to vasodilatation, increased permeability of the capillary walls and sensitization of pain receptors.

In addition to blocking the H1 receptor-mediated effect, doxylamine has sedative effects. It has been shown to reduce the time to fall asleep (sleep latency) and improve the duration and quality of sleep.

5.2 Pharmacokinetic properties

Absorption After oral administration, doxylamine is absorbed rapidly and almost completely. The onset of action is within 30 minutes, peak serum concentrations were measured at 99 ng/ml 2.4 hours after oral administration of a single dose of 25 mg, the effect lasts for 3–6 hours.

Biotransformation The metabolism occurs primarily in the liver. N-desmethyldoxylamine, N,N-didesmethyldoxylamine and their N-acetyl conjugates were detected.

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1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE

Elimination Doxylamine has an elimination half-life of about 10-13 hours in healthy young adults, increasing to about 12-16 hours in the elderly. The active substance is primarily excreted in the urine as unchanged doxylamine (approximately 60%), and as nordoxylamine and dinordoxylamine metabolites. In humans, only small amounts are excreted in the faeces. Data is lacking on the of doxylamine in patients with impaired renal and hepatic function. Increased active substance exposure is however expected

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of chronic toxicity, genotoxicity, reproductive and developmental toxicity. Repeat-dose oral toxicity studies in mice and rats revealed that the liver is a target organ of toxicity in rodents. In carcinogenicity studies, doxylamine induced liver tumours in mice and rats, and thyroid tumours in mice. The induction of CYP450 enzymes and thyroxine glucuronidation, with subsequent decrease in serum thyroxine levels and increase in thyroid stimulating hormones, respectively, are the most probable mechanisms underlying the liver toxicity and induction of tumours in rodents. This mechanism is not considered relevant for humans.

No effects on the fertility of rats were observed even at doses far higher than those recommended in clinical practice. Doxylamine crosses the placental barrier and has been detected in embryos at concentrations above pregnant female plasma levels. Doxylamine succinate showed no teratogenic effects in embryotoxicity studies. Potential effects on peri- and postnatal development have not been investigated.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core: Lactose monohydrate Croscarmellose sodium Cellulose, microcrystalline Magnesium stearate

Film-coating: Hypromellose Titanum dioxide (E171) Macrogol 400

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

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1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Blister (OPA/Alu/PVC)/Alu Pack sizes: 7, 10, 14 and 20 film-coated tablets, in a box.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

[To be completed nationally]

8. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

[To be completed nationally]

10. DATE OF REVISION OF THE TEXT

[To be completed nationally]

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LABELLING

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1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BOX

1. NAME OF THE MEDICINAL PRODUCT

25 mg film-coated tablets doxylamine hydrogen succinate

For use in adults

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film-coated tablet contains 25 mg doxylamine hydrogen succinate.

3. LIST OF EXCIPIENTS

Contains lactose and sodium. See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS film-coated tablet

7 film-coated tablets 10 film-coated tablets 14 film coated-tablets 20 film-coated tablets

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

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1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE

EXP

9. SPECIAL STORAGE CONDITIONS

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

[To be completed nationally]

12. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

[To be completed nationally]

15. INSTRUCTIONS ON USE

Only for OTC status:

Short-term symptomatic treatment of occasional insomnia (problems with falling asleep and midnight awakenings) in adults.

Posology: Recommended dose is 1 tablet with a glass of water about half an hour to one hour before bedtime. In cases of severe sleep disturbances, 2 tablets can be taken as the maximum dose.

Read the package leaflet before use.

16. INFORMATION IN BRAILLE

25 mg

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17. UNIQUE IDENTIFIER – 2D BARCODE

Only for OTC status: Not applicable.

Only for Rx status: 2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

Only for OTC status: Not applicable.

Only for Rx status: PC: SN:

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1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER

1. NAME OF THE MEDICINAL PRODUCT

25 mg film-coated tablets doxylamine hydrogen succinate

2. NAME OF THE MARKETING AUTHORISATION HOLDER

[To be completed nationally]

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

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PACKAGE LEAFLET

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1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE

Package leaflet: Information for the patient

25 mg film-coated tablets doxylamine hydrogen succinate

For use in adults

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.

Only for OTC status: Read all of this leaflet carefully before you start taking this medicine because it contains important information for you. Always take this medicine exactly as described in this leaflet or as your doctor or pharmacist have told you. - Keep this leaflet. You may need to read it again. - Ask your pharmacist if you need more information or advice. 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. - You must talk to a doctor or pharmacist if you do not feel better or if you feel worse after 14 days.

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

1. What is and what it is used for

is a medicine with sedative properties (an , a sedative).

is used for short-term symptomatic treatment of occasional insomnia (problems with falling asleep and midnight awakenings) in adults.

Only for OTC status: Note: Not all states of restlessness that interfere with falling asleep and sleeping require medical treatment. They are often an expression of a physical or mental illness and can be influenced by other measures or treatment of the underlying disease. Therefore, long-term sleep disturbances should not be treated with . Your doctor should be consulted instead.

2. What you need to know before you take SmPCPIL090533_9 23.05.2017 – Updated: 11.09.2018 Page 17 of 22

1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE

Do not take : - if you are allergic to doxylamine, other antihistamines or any of the other ingredients of this medicine (listed in section 6), - in cases of acute asthma attack, - if you have narrow-angle glaucoma, - if you have adrenal tumour (phaeochromocytoma), - if you have enlargement of the prostate (prostatic hypertrophy) with urinary retention, - in acute poisoning with alcohol, sleep or pain medicines or psychotropic medicines (neuroleptics, tranquilizers, antidepressants, lithium), - if you have epilepsy, - if you are taking any medicines known as monoamine oxidase inhibitors (MAOIs) (medicines used to treat depression, Parkinson's Disease or other conditions, such as moclobemide, phenelzine, and tranylcypromine, isocarboxazid, linezoid, , procarbazine, and ).

Warnings and precautions Talk to your doctor or pharmacist before taking if: - you have liver or kidney impairment, - you have pre-existing heart disorder and high blood pressure (as maybe regular monitoring of the heart function will be needed), - you have chronic breathing problems and asthma, - you have inadequate closure of the stomach entrance with reflux of food into the oesophagus (gastro-oesophageal reflux), - you have erosion of the stomach or beginning of the intestine wall or pyloroduodenal obstruction (difficulty passing food from the stomach into the intestine).

Ensure a sufficient sleep time (at least 8 hours) so that your ability to react is not impaired the following morning.

Special care should also be taken in patients with neurologically recognizable brain injuries in the cerebral cortex and a history of convulsions, because already by taking small amounts of doxylamine grand mal seizures can be triggered.

If you are over 65 years you may be more likely to experience side effects. In addition, there is an increased risk of falls.

Interference with diagnostic tests This medicine may interfere with skin tests that are performed for the diagnosis of allergy, so it is recommended to discontinue the medication at least three days before the tests and to inform your doctor.

Children and adolescents Children and adolescents should not be treated with ,because the safety and efficacy of doxylamine as a night time sleep aid in children and adolescents under 18 years of age has not been established.

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

Do not take together with monoamine oxidase inhibitors. During concomitant use of and monoamine oxidase inhibitors, decreased blood pressure, increased depression SmPCPIL090533_9 23.05.2017 – Updated: 11.09.2018 Page 18 of 22

1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE of the central nervous system and breathing may occur.

When used together, the effects of and the following medicines can be increased: - Centrally acting medicines (such as psychotropic medicines, sleep medicines, pain medicines, anaesthetics, anti-seizure medicines) - Other medicines with anticholinergic activity (e.g. biperiden in Parkinson’s disease and tricyclic antidepressants for the treatment of depression), which leads to e.g. life-threatening intestinal paralysis, urinary retention, acute elevation of pressure inside the eye.

The effect of the following medicines can be decreased: - Phenytoin (for the treatment of seizures) - Neuroleptics

During concomitant use of : - with medicines for high blood pressure that act on the central nervous system (guanabenz, clonidine, alpha-methyldopa), increased tiredness and weakness may occur. - the symptoms of a beginning inner ear damage caused by other medicines (e.g. aminoglycoside antibiotics, some painkillers, some diuretics) may be masked. - false negative skin test results may be obtained. - epinephrine should not be administered (as it may lead to widening of the blood vessels, decreased blood pressure and accelerated heart rate).

with food and drink and alcohol Alcohol can change the effect of doxylamine unpredictably. During treatment with , alcohol consumption should be avoided.

Pregnancy and breast-feeding and fertility 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.

You should only take during pregnancy when explicitly advised by your doctor.

As the active substance passes into breast milk, breast-feeding should be interrupted for the duration of treatment.

Driving and using machines Even when used as recommended, this medicine may alter the ability to react to such an extent that the ability to participate actively in road traffic or to operate machinery is impaired. This applies even more in combination with alcohol. You can no longer react to unexpected and sudden events quickly and purposefully enough.

Do not drive a car or other vehicles. Do not operate any electrical tools or machinery. Do not work without a secure foothold.

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.

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

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3. How to take

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Only for OTC status: Always take this medicine exactly as described in this leaflet or as your doctor or pharmacist have told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose is: Adults should take 1 tablet (equivalent to 25 mg doxylamine succinate) about half an hour to one hour before bedtime. In cases of severe sleep disturbances, 2 tablets (equivalent to 50 mg doxylamine succinate) can be taken as the maximum dose.

Only for OTC status: The treatment of acute sleep disturbances should be limited to single doses, if possible. The duration of treatment should be as short as possible. In general, the length of treatment can vary from a few days to one week. Treatment should be discontinued at the latest after two weeks of daily use.

In patients with reduced kidney or liver function, elderly or weakened patients, who are more sensitive to the effects of doxylamine, a lower dose should be used. For doses not feasible with this medicinal product, other products are available.

Method of administration is for oral use. The tablet should be taken with a glass of water. The score line is only there to help you break the tablet if you have difficulty swallowing it whole.

If you take more than you should Initial signs of overdose can be central nervous system symptoms, such as restlessness, increased muscle reflexes, unconsciousness, depression of breathing and heart arrest. Other signs of overdose are dilated pupils, accelerated heart rate (tachycardia), fever, hot, red skin and dry mucous membranes. If these symptoms occur, a doctor should be contacted immediately. In addition, breakdown of muscle fibres (rhabdomyolysis) has been reported after overdose. Your doctor will decide what to do. In cases of gastrointestinal complaints, central nervous disorders, dry mouth, bladder emptying disorders (micturition disorders) and visual disturbances, appropriate measures must be taken by your doctor depending on the symptom.

If you forget to take Do not take a double dose to make up for a forgotten tablet dose.

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.

Rare side effects (may affect up to 1 in 1,000 people): - seizures.

Very rare side effects (may affect up to 1 in 10,000 people): SmPCPIL090533_9 23.05.2017 – Updated: 11.09.2018 Page 20 of 22

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- blood cell disorders (such as abnormal breakdown of red blood cells, decrease of platelets in blood or white blood cells), - life-threatening intestinal paralysis,

Not known (frequency cannot be estimated from the available data): - in patients with adrenal tumour (phaeochromocytoma), substances that have a very strong effect on the cardiovascular system may be released from the tumour, - impaired concentration, depression, prolonged reaction time, - "paradoxical" reactions, such as restlessness, excitement, tension, sleeplessness, nightmares, confusion, hallucinations, shaking, - dizziness, drowsiness, headache, - vegetative side effects, such as difficulty focusing, dry mouth, feeling of nasal congestion, increased pressure inside the eye, constipation, urinary disorders, nausea, vomiting, diarrhoea, loss of appetite or increased appetite, stomach pain. - vertigo, ringing in the ears, - accelerated or irregular heartbeat, worsening of an existing heart failure, ECG changes, - high or low blood pressure, - breathing function can be impaired by the thickening of mucus, obstruction or narrowing of the bronchi, - liver dysfunction (cholestatic jaundice), - allergic skin reactions and photosensitivity (avoid direct exposure to the sun), - muscle weakness, - weakness, disturbances of body temperature regulation.

After prolonged daily use, intensified sleep disturbances may reoccur in case of abrupt discontinuation of treatment.

Note: The frequency and severity of side effects can be reduced by careful and individual adjustment of the daily doses. The risk of side effects is greater in elderly patients, and the risk of falling can also be increased in this population.

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

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 blister and the carton after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

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

SmPCPIL090533_9 23.05.2017 – Updated: 11.09.2018 Page 21 of 22

1.3.1 Doxylamine SPC, Labeling and Package Leaflet DE

What contains The active substance is doxylamine hydrogen succinate. Each film-coated tablet contains 25 mg doxylamine hydrogen succinate. The other ingredients are: lactose monohydrate, croscarmellose sodium, microcrystalline cellulose, magnesium stearate in the core and hypromellose, titanum dioxide (E171), macrogol 400, in the film coating. See section 2 " contains lactose", " contains sodium".

What looks like and contents of the pack

film-coated tablets are white to almost white, oval, biconvex, one side scored. Tablet dimension: 12 mm x 6 mm. The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

is available in cartoon boxes of 7, 10, 14 and 20 film-coated tablets in blisters.

Not all pack sizes may be marketed.

Marketing Authorisation Holder [To be completed nationally]

Manufacturer [To be completed nationally]

This medicinal product is authorised in the Member States of the EEA under the following names:

Bulgaria, Слийпзон Czech Republic, Germany, Spain, Portugal, Dornite Romania, Slovakia Poland Nitedor Estonia, Croatia, Calmesan Hungary, Latvia, Lithuania, Slovenia Noctiben

This leaflet was last revised in [To be completed nationally]

SmPCPIL090533_9 23.05.2017 – Updated: 11.09.2018 Page 22 of 22