Donormyl^® (Tablets) Instructions for Use

Marketing Authorization Holder

UPSA, SAS (France)

Contact Information

BRISTOL-MYERS SQUIBB (USA)

ATC Code

R06AA09 (Doxylamine)

Active Substance

Doxylamine (Rec.INN registered by WHO)

Dosage Form

Donormyl®

Film-coated tablets, 15 mg: 10 or 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, rectangular, with a score on both sides.

Excipients : lactose monohydrate – 100 mg, croscarmellose sodium – 9 mg, microcrystalline cellulose – 15 mg, magnesium stearate – 2 mg.

Film coating composition macrogol 6000 – 1 mg, hypromellose – 2.3 mg, Sepispers AP 7001 (hypromellose – 2-4%, titanium dioxide CI 77891 – 25-31%, propylene glycol – 30-40%, water – up to 100%) – 0.7 mg.

10 pcs. – polypropylene tubes (1) – cardboard packs.
30 pcs. – polypropylene tubes (1) – cardboard packs.

Clinical-Pharmacological Group

Hypnotic drug

Pharmacotherapeutic Group

Histamine H1-receptor antagonist

Pharmacological Action

A histamine H₁-receptor blocker from the ethanolamines group. The drug has a hypnotic, sedative and m-anticholinergic blocking effect.

It reduces the time to fall asleep, increases the duration and quality of sleep, without changing the phases of sleep. The duration of action is 6-8 hours.

Pharmacokinetics

Absorption and Distribution

C_max is reached on average 2 hours after oral administration. Absorption is high.

Metabolism and Excretion

Penetrates well through histohematic barriers (including the BBB). Metabolized in the liver. T_1/2 – about 10 hours.

Excreted 60% by the kidneys unchanged, partially through the gastrointestinal tract.

Pharmacokinetics in Special Patient Groups

In patients over 65 years of age, as well as in hepatic and renal insufficiency, T_1/2 may be prolonged.

When repeating courses of treatment, the stable concentration of the drug and its metabolites in the blood plasma is reached later and at a higher level.

Indications

• Transient sleep disorders.

ICD codes

Dosage Regimen

Orally. 1/2-1 tablet/day, with a small amount of liquid, 15-30 minutes before bedtime. If treatment is ineffective, the dose may be increased to 2 tablets on the recommendation of a doctor.

The duration of treatment is from 2 to 5 days; if insomnia persists, it is necessary to consult a doctor.

Patients with renal and hepatic impairment: due to data on increased plasma concentration and decreased plasma clearance of doxylamine, dose adjustment towards a decrease is recommended.

Elderly patients over 65 years of age: histamine H₁-receptor blockers should be prescribed with caution to this group of patients due to possible dizziness and slow reactions with the risk of falling (for example, during nighttime awakenings after taking sleeping pills).

In view of data on increased plasma concentration, decreased plasma clearance and increased T_1/2, dose adjustment towards a decrease is recommended.

Adverse Reactions

From the digestive system: constipation, dry mouth.

From the cardiovascular system: palpitations.

From the organ of vision: visual and accommodation disturbances, blurred vision.

From the urinary system: urinary retention.

From the nervous system: daytime sleepiness (in this case, the dose of the drug should be reduced); confusion, hallucinations.

From the musculoskeletal system: rhabdomyolysis.

From laboratory parameters: increased CPK level.

If any of the above side effects worsen or other side effects not listed in the instructions appear, the patient should inform the doctor.

Contraindications

• Hypersensitivity to doxylamine and other components of the drug, or to other antihistamines;
• Closed-angle glaucoma or family history of closed-angle glaucoma;
• Diseases of the urethra and prostate gland accompanied by impaired urine outflow;
• Congenital galactosemia, glucose-galactose malabsorption, lactase deficiency;
• Childhood and adolescence under 15 years of age.

With caution: in patients with a history of apnea – due to the fact that doxylamine succinate may worsen the syndrome of nocturnal apnea (sudden cessation of breathing during sleep); in patients over 65 years of age – due to possible dizziness and slow reactions with the risk of falling (for example, during nighttime awakenings after taking sleeping pills), as well as due to a possible increase in T_1/2; in patients with renal and hepatic insufficiency (T_1/2 may increase).

Use in Pregnancy and Lactation

Based on adequate and well-controlled studies, Doxylamine can be used in pregnant women throughout the entire period of pregnancy.

If the drug is prescribed in the later stages of pregnancy, the atropine-like and sedative properties of doxylamine should be taken into account when monitoring the condition of the newborn.

It is not known whether Doxylamine passes into breast milk. Due to the possibility of developing a sedative or excitatory effect in the child, breastfeeding should not be done while using the drug.

Use in Hepatic Impairment

Use with caution in patients with hepatic insufficiency (T_1/2 may increase).

Use in Renal Impairment

Use with caution in patients with renal insufficiency (T_1/2 may increase).

Pediatric Use

Contraindicated in children and adolescents under 15 years of age.

Geriatric Use

With caution: in patients over 65 years of age – due to possible dizziness and slow reactions with the risk of falling (for example, during nighttime awakenings after taking sleeping pills).

Special Precautions

It should be taken into account that insomnia can be caused by a number of reasons for which there is no need to prescribe this drug.

The drug has a sedative effect, suppresses cognitive abilities and slows psychomotor reactions.

The first generation of histamine H₁-receptor blockers may have m-anticholinergic, α-adrenergic blocking and antiserotonin effects, which can cause dry mouth, constipation, urinary retention, accommodation and vision disorders.

Like all sleeping pills or sedatives, doxylamine succinate may worsen the syndrome of nocturnal apnea (sudden cessation of breathing during sleep) – increasing the number and duration of apnea attacks.

Possible abuse of first-generation histamine H₁-receptor blockers, including Doxylamine, can lead to physical and psychological dependence, which has been reported against the background of deliberate intake of higher doses of the drug than recommended.

One tablet of the drug contains 100 mg of lactose monohydrate, which should be taken into account in patients with rare congenital galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption.

Effect on the ability to drive vehicles and mechanisms

Due to possible daytime sleepiness, driving vehicles, working with mechanisms and other activities requiring quick mental and motor reactions should be avoided.

Overdose

Symptoms: daytime sleepiness, agitation, pupil dilation (mydriasis), accommodation disturbances, dry mouth, redness of the skin of the face and neck (hyperemia), increased body temperature (hyperthermia), sinus tachycardia, confusion, hallucinations, low mood, anxiety, impaired coordination of movements, trembling (tremor), involuntary movements (athetosis), convulsions (epileptic syndrome), coma.

Involuntary movements are sometimes precursors of convulsions, which may indicate a severe degree of poisoning. Even in the absence of convulsions, severe doxylamine poisoning can cause the development of rhabdomyolysis, which is often accompanied by acute renal failure. In such cases, standard therapy with constant monitoring of CPK levels is indicated.

If symptoms of poisoning appear, you should immediately consult a doctor.

Treatment symptomatic (m-cholinomimetics, etc.), as a first aid measure, taking activated charcoal (in the amount of 50 g – for adults and 1 g/kg of body weight for children) is indicated.

Drug Interactions

When taking the drug Donormyl^® simultaneously with sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), barbiturates, benzodiazepines, clonidine, morphine derivatives (analgesics, antitussives), neuroleptics, anxiolytics, histamine H₁-receptor blockers with sedative effect, central antihypertensive drugs, thalidomide, baclofen, pizotifen, the inhibitory effect on the central nervous system is enhanced.

When taken simultaneously with m-anticholinergic agents (atropine, imipramine antidepressants, antiparkinsonian drugs, atropine antispasmodics, disopyramide, phenothiazine neuroleptics), the risk of such side effects as urinary retention, constipation, dry mouth increases.

Since alcohol enhances the sedative effect of most histamine H₁-receptor blockers, including the drug Donormyl^®, it is necessary to avoid its simultaneous use with alcoholic beverages and medicines containing alcohol.

Storage Conditions

The drug should be stored out of the reach of children at a temperature of 15 to 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.