Donormil

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DONORMIL

Composition:

Active ingredient: doxylamine succinate;

1 tablet contains 15 mg of doxylamine succinate;

Excipients: sodium hydrocarbonate, anhydrous citric acid, anhydrous sodium hydrogen phosphate, anhydrous sodium sulfate, sodium benzoate (E 211), macrogol 6000.

Pharmaceutical form. Effervescent tablets.

Main physicochemical properties: cylindrical, flat, white tablets with a break line and bevelled edges, soluble in water with effervescence; minor chipping is acceptable.

Pharmacotherapeutic group.

Antihistamines for systemic use. ATC code R06AA09.

Hypnotics and sedatives. ATC code N05CM.

Pharmacological properties.

Pharmacodynamics.

Doxylamine succinate is an H1-histamine receptor antagonist of the ethanolamine class, which has sedative and atropine-like effects. It has been demonstrated to reduce the time required to fall asleep, as well as improve the duration and quality of sleep.

Pharmacokinetics.

Maximum plasma concentration (Cmax) is reached on average within 1 hour (Tmax) after administration of doxylamine succinate.

The average elimination half-life from plasma (T½) is approximately 10 hours.

Doxylamine succinate is partially metabolized in the liver via demethylation and N-acetylation. The various metabolites formed during the breakdown of the molecule are not quantitatively significant, as 60% of the administered dose is excreted in the urine in unchanged form.

Clinical characteristics.

Indications.

Episodic insomnia in adults.

Contraindications.

Hypersensitivity to doxylamine succinate or to excipients or to other antihistamines.

History of acute angle-closure glaucoma in the patient or in family history.

Urethroprostatic disorders with risk of urinary retention.

Interaction with other medicinal products and other forms of interaction.

Combinations to be avoided.

Alcohol enhances the sedative effect of most H1-antihistamines. Consumption of alcoholic beverages and medicinal products containing ethanol should be avoided.

Concomitant use with sodium oxybate should be avoided due to increased central nervous system depression. Impaired reaction speed may lead to danger when driving vehicles or operating machinery.

Combinations to be taken into consideration.

With atropine and atropine-like medicinal products (tricyclic antidepressants, most atropine-like H1-antihistamines, anticholinergic antiparkinsonian agents, atropine-like spasmolytics, disopyramide, phenothiazine neuroleptics, as well as clozapine) due to increased risk of adverse effects such as urinary retention, constipation, dry mouth;

With other sedative medicinal products (morphine derivatives (analgesics, antitussives, substitution therapy agents), neuroleptics; barbiturates, benzodiazepines; anxiolytics other than benzodiazepines (meprobamate); other hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine); sedative H1-antihistamines; centrally acting antihypertensives; others: baclofen, thalidomide) due to enhanced central nervous system depression. Impaired reaction speed may lead to danger when driving vehicles or operating machinery.

With other hypnotics, due to central nervous system depression.

Special precautions for use

Insomnia may have various causes that do not necessarily require medication; therefore, consultation with a physician is recommended before starting treatment with this medicinal product.

The medicinal product contains 563 mg of sodium per 1 tablet, corresponding to 28.15% of the maximum daily sodium intake recommended by the WHO. The maximum daily dose of the medicinal product is equivalent to 56.3% of the maximum daily sodium intake recommended by the WHO, which should be taken into account when prescribing the product to patients on a low-salt diet.

Like all hypnotics or sedatives, doxylamine succinate may exacerbate obstructive sleep apnea syndrome (increasing the number and duration of apneic episodes).

The risk of abuse and development of drug dependence is low. However, cases of abuse leading to drug dependence have been reported. Signs of abuse or dependence should be carefully monitored. The duration of treatment should not exceed 5 days. The medicinal product is not recommended for patients with a history of substance-related disorders.

Doxylamine succinate remains in the body for approximately 5 half-lives (see section "Pharmacokinetics").

The elimination half-life may be considerably prolonged in elderly patients or in patients with renal or hepatic impairment. With repeated administration, the drug or its metabolites reach steady-state concentrations much later and at higher levels. The efficacy and safety of the medicinal product can only be assessed after steady-state concentrations have been achieved.

Dosage adjustment may be required (see section "Dosage and administration").

H1-antihistamines should be used with caution in elderly patients due to the risk of cognitive disorders, sedative effects, slowed reaction time, and/or vertigo/dizziness, which may increase the risk of falls (e.g., when getting up at night), with consequences that are often serious in this patient population.

In elderly patients with renal or hepatic impairment, increased plasma concentrations of the drug and reduced plasma clearance have been observed. Dose reduction is recommended.

To prevent daytime drowsiness, it is important to remember that the duration of sleep after taking the medicinal product should be at least 7 hours.

Use during pregnancy or breastfeeding.

Based on available data, doxylamine may be used during pregnancy after consultation with a physician. If this medicinal product is used in late pregnancy, the anticholinergic and sedative properties of this molecule should be considered when monitoring the newborn.

It is unknown whether doxylamine is excreted in breast milk; therefore, the use of the medicinal product is not recommended during breastfeeding.

Effect on ability to drive and use machines.

The risk of daytime drowsiness should be considered, particularly in individuals who drive vehicles or operate machinery, as such effects may occur during treatment with this medicinal product. The risk of impaired reaction time is increased in cases of insufficient sleep duration.

See section "Interaction with other medicinal products and other forms of interaction".

Dosage and Administration.

For oral use. Administer 15–30 minutes before bedtime.

The recommended dose is 7.5–15 mg per day (½–1 tablet per day). If necessary, the dose may be increased to 30 mg per day (2 tablets per day). Dissolve the tablet in ½ glass of water before administration.

In elderly patients and patients with renal or hepatic impairment, a reduced dose is recommended.

The duration of treatment is 2–5 days.

If insomnia persists for more than 5 days, consult a physician regarding the appropriateness of continuing treatment.

Children.

The medicinal product is not intended for use in children under 18 years of age.

Overdose.

The initial signs of acute poisoning include drowsiness and anticholinergic effects: excitation, dilated pupils, accommodation paralysis, dry mouth, facial and neck flushing, hyperthermia, and sinus tachycardia. Delirium, hallucinations, and athetoid movements are more commonly observed in children; sometimes they precede seizures—a rare complication of massive poisoning—or even coma. Even in the absence of seizures, acute doxylamine poisoning may occasionally cause rhabdomyolysis, which can lead to acute renal failure. This type of muscle disorder is relatively common, necessitating systematic screening through measurement of creatine phosphokinase activity.

Treatment is symptomatic. In early stages of poisoning, activated charcoal is recommended (50 g for adults, 1 g/kg for children).

Side effects.

Anticholinergic effects: constipation, urinary retention, dry mouth, visual disturbances (accommodation disorders, blurred vision, hallucinations, visual defects), tachycardia, confusion.

Daytime drowsiness: if this effect occurs, the dose should be reduced.

Cases of drug abuse and development of drug dependence have been reported.

In addition, it is known that H1-antihistamine medicinal products cause sedative effects, cognitive disorders, and psychomotor activity impairment.

Shelf life.

3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in a place inaccessible to children.

Packaging.

10 tablets in a tube. 1 or 2 tubes in a cardboard box.

Classification of supply.

No. 10 – over-the-counter;

No. 20 – prescription only.

Manufacturer.

UPSA SAS, France.

Manufacturer's location and address of its business site.

979, avenue des Pyrénées, 47520 Le Passage, France.

304, avenue docteur Jean Bru, 47000 Agen, France.