Donormil

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT DONORMIL

Composition:

Active substance: doxylamine succinate;

1 tablet contains doxylamine succinate 15 mg;

Excipients: lactose monohydrate; sodium croscarmellose; microcrystalline cellulose; magnesium stearate; hypromellose; macrogol 6000; colouring dispersion containing hypromellose, titanium dioxide (E 171), propylene glycol, purified water.

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: white rectangular tablets with a biconvex scored line for division.

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 to improve the duration and quality of sleep.

Pharmacokinetics.

Maximum plasma concentration (Cmax) is reached on average within 2 hours (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 elimination half-life may be significantly prolonged in elderly individuals or in patients with renal or hepatic impairment.

Various metabolites formed during breakdown are not quantitatively significant, as 60% of the administered dose is excreted in urine in unchanged form as doxylamine.

Clinical characteristics.

Indications.

Episodic insomnia in adults.

Contraindications.

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

History or family history of acute angle-closure glaucoma.

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 or operating machinery.

Combinations to be taken into account.

With atropine and atropine-like medicinal products (tricyclic antidepressants such as imipramine, most atropine-like H1-antihistamines, anticholinergic antiparkinsonian agents, atropine-containing 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, non-benzodiazepine anxiolytics (meprobamate), other hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1-antihistamines, centrally-acting antihypertensives, and others: baclofen, thalidomide) due to enhanced central nervous system depression. Impaired reaction speed may lead to danger when driving or operating machinery.

With other hypnotic agents due to central nervous system depression.

Special precautions for use

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

The medicinal product contains lactose and is therefore contraindicated in patients with congenital galactosemia, glucose-galactose malabsorption syndrome, or lactase deficiency.

Like all hypnotic or sedative agents, doxylamine succinate may exacerbate sleep apnea syndrome (increasing the frequency and duration of breathing pauses).

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 on the medicinal product must be carefully monitored. The duration of treatment should not exceed 5 days. The medicinal product is not recommended for patients with a history of disorders caused by psychoactive substance use.

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

The half-life may be significantly 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., during nighttime awakenings), potentially leading to serious consequences 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 of the medicinal product is recommended.

To prevent daytime drowsiness, it is important to ensure that the duration of sleep following administration of the medicinal product is 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 atropine-like and sedative properties of this molecule should be taken into account when monitoring the newborn.

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

Effect on the ability to drive or operate machinery.

Caution should be exercised regarding the risk of daytime drowsiness, particularly in individuals who drive or operate machinery, which may occur following administration of this medicinal product. The risk of impaired reaction time is increased when sleep duration is insufficient.

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

Method of Administration and Dosage

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).

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 continued use of the medicinal product.

Children

The medicinal product must not be used in children under 18 years of age.

Overdose

The initial signs of acute poisoning include drowsiness and anticholinergic effects: excitation, mydriasis, paralysis of accommodation, dry mouth, facial and neck flushing, hyperthermia, and sinus tachycardia. Delirium, hallucinations, and athetoid movements are more commonly observed in children; these may sometimes precede rare complications of massive poisoning such as seizures or even coma. Even in the absence of seizures, acute poisoning with doxylamine may occasionally cause rhabdomyolysis, which can lead to acute renal failure. This muscular disorder is relatively common and warrants systematic screening by measuring 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 abuse and development of drug dependence have been reported.

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

Shelf life.

3 years.

Storage conditions.

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

Packaging.

10 or 30 tablets in a tube. 1 tube in a cardboard box.

Classification of supply.

No. 10 – over-the-counter;

No. 30 – prescription only.

Manufacturer.

UPSASAS, France.

Manufacturer's address and place of business.

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

304, avenue Docteur Jean Brudieux, 47000 Agen, France.