SonNorm Duo (Tablets) Instructions for Use

Marketing Authorization Holder

Pharmstandard-Lexredstva OJSC (Russia)

ATC Code

N05CM (Other hypnotic and sedative drugs)

Active Substances

Peppermint oil (BP British Pharmacopoeia)

Melatonin (BP British Pharmacopoeia)

Leonuri herba (SP State Pharmacopoeia)

Dosage Form

SonNorm Duo

Film-coated tablets, 3 mg+1.16 mg+28 mg: 20, 30, or 50 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets from light blue to blue in color, round, biconvex; on the cross-section, the core is light brown in color with inclusions of darker and lighter color.

Excipients: lactose monohydrate – 42 mg, betadex – 41.84 mg, potato starch – 17 mg, microcrystalline cellulose PH101 – 11.5 mg, povidone K-30 (medium molecular weight polyvinylpyrrolidone) – 2.5 mg, talc – 1.5 mg, calcium stearate – 1.5 mg.

Inner film coating composition: partially hydrolyzed polyvinyl alcohol – 1.2 mg, titanium dioxide – 0.75 mg, macrogol – 0.606 mg, talc – 0.444 mg;
Or film coating Opadry II 85F18422 White – 3 mg [partially hydrolyzed polyvinyl alcohol – 1.2 mg, titanium dioxide – 0.75 mg, macrogol – 0.606 mg, talc – 0.444 mg].
Outer film coating composition: hypromellose – 4.868 mg, talc – 1.687 mg, povidone – 1.548 mg, titanium dioxide – 1.404 mg, polysorbate 80 – 0.44 mg, indigo carmine – 0.039 mg, brilliant blue – 0.012 mg, iron oxide yellow dye – 0.002 mg;
Or film coating Opadry II Blue 13A205000 – 10 mg [hypromellose – 4.868 mg, talc – 1.687 mg, povidone – 1.548 mg, titanium dioxide – 1.404 mg, polysorbate 80 – 0.440 mg, indigo carmine – 0.039 mg, brilliant blue – 0.012 mg, iron oxide yellow dye – 0.002 mg].

10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.

* the active pharmaceutical substance “Melatonin” is introduced into the composition of the outer film coating of this drug.

Clinical-Pharmacological Group

Adaptogenic agent

Pharmacotherapeutic Group

Hypnotic agent

Pharmacological Action

A combined medicinal product, the action of which is determined by the properties of its constituent substances.

Melatonin is a synthetic analogue of the pineal gland hormone; it has adaptogenic, sedative, and hypnotic effects.

It normalizes circadian rhythms. It increases the concentration of GABA and serotonin in the midbrain and hypothalamus, changes the activity of pyridoxal kinase involved in the synthesis of GABA, dopamine, and serotonin.

It regulates the sleep-wake cycle, daily changes in locomotor activity and body temperature, and has a positive effect on the intellectual and mnestic functions of the brain, and on the emotional and personal sphere.

It contributes to the organization of the biological rhythm and normalization of night sleep. It improves sleep quality, accelerates falling asleep, and regulates neuroendocrine functions. It adapts the bodies of weather-sensitive people to changes in weather conditions.

Peppermint leaf oil has a reflex vasodilating and antispasmodic effect.

The mechanism of action is associated with the ability to irritate the “cold” receptors of the oral mucosa and reflexively dilate mainly the vessels of the heart and brain.

Leonuri herba extract has a pronounced sedative effect, reduces the heart rate and increases the strength of heart contractions, and exhibits hypotensive properties.

Pharmacokinetics

Melatonin

Melatonin is rapidly absorbed from the gastrointestinal tract after oral administration.

In elderly patients, the absorption rate may be reduced by 50%. The kinetics of melatonin in the dose range of 2-8 mg is linear.

After oral administration of this combination at a dose of 6 mg, C_max in blood plasma reaches 19.670 ng/ml, AUC_o-t is 23.399 ng×h/ml.

T_max in blood serum is 0.56 h. After taking 3-6 mg of melatonin, C_max in blood serum is usually 10 times higher than endogenous melatonin in blood serum at night.

Concomitant food intake delays the absorption of melatonin. The bioavailability of melatonin when taken orally ranges from 9 to 33% (approximately 15%).

In in vitro studies, the binding of melatonin to plasma proteins is 60%.

Melatonin mainly binds to albumin, α₁-acid glycoprotein and HDL.

V_d is about 35 l. It is rapidly distributed into saliva and crosses the blood-brain barrier, and is detected in the placenta.

The concentration in the cerebrospinal fluid is 2.5 times lower than in plasma.

Melatonin is metabolized mainly in the liver.

After oral administration, Melatonin undergoes significant transformation during the “first pass” through the liver, where it is hydroxylated and conjugated with sulfate and glucuronide to form 6-sulfatoxymelatonin; the level of presystemic metabolism can reach 85%, presumably, the isoenzymes CYP1A1, CYP1A2, CYP2C19 of the cytochrome P450 system are involved in the metabolism of melatonin.

The main metabolite of melatonin is 6-sulfatoxymelatonin, which is inactive.

Melatonin is excreted from the body by the kidneys.

After oral administration of 6 mg of this combination, the mean T_1/2 is 0.654 h, the elimination rate constant (K_el) is 1.133 h^-1.

Excretion is carried out with urine, about 90% in the form of sulfate and glucuronic conjugates of 6-hydroxymelatonin, and about 2-10% is excreted unchanged.

Pharmacokinetic parameters are influenced by age, caffeine intake, smoking, and oral contraceptive use.

In critical patients, accelerated absorption and impaired elimination are observed.

Elderly patients.

The metabolism of melatonin slows down with age. At different doses of melatonin, higher values of AUC and C_max were obtained in elderly patients, which reflects the reduced metabolism of melatonin in this group of patients.

Patients with impaired renal function.

No accumulation of melatonin was noted during long-term treatment. These data are consistent with the short T_1/2 of melatonin in humans.

Patients with impaired liver function.

The liver is the main organ involved in the metabolism of melatonin, so liver diseases lead to an increase in the concentration of endogenous melatonin. In patients with liver cirrhosis, the plasma concentration of melatonin during the daytime increased significantly.

Data on the pharmacokinetics of motherwort and peppermint components are not available.

Indications

Sleep disorders, disturbance of the circadian rhythm of sleep and wakefulness associated with a sharp change in time zones (desynchronosis).

ICD codes

Dosage Regimen

Take orally with water.

Administer one tablet once daily, 30-40 minutes before bedtime.

Ensure the timing aligns with your intended sleep period.

For sleep disturbances, use for the shortest duration necessary to restore normal sleep patterns.

For jet lag, initiate treatment on the day of travel and continue for 2-5 days after arrival at the destination.

The maximum course of treatment is 28 days.

Do not exceed the recommended dose.

Consult a physician if there is no improvement in sleep quality within a few days.

Use with caution in elderly patients due to potentially altered pharmacokinetics.

Avoid concomitant consumption of alcohol, which reduces efficacy.

Refrain from driving or operating machinery after taking the tablet due to potential drowsiness.

Adverse Reactions

Infections and infestations rarely – herpes zoster.

Blood and lymphatic system disorders rarely – leukopenia, thrombocytopenia.

Immune system disorders frequency unknown – hypersensitivity reactions.

Metabolism and nutrition disorders rarely – hypertriglyceridemia, hypokalemia, hyponatremia.

Psychiatric disorders infrequently – irritability, nervousness, restlessness, insomnia, unusual dreams, nightmares, anxiety; rarely – mood changes, aggression, agitation, tearfulness, stress symptoms, disorientation, early morning awakening, increased libido, depressed mood, depression.

Nervous system disorders infrequently – migraine, headache, lethargy, psychomotor hyperactivity, dizziness, somnolence; rarely – syncope, memory impairment, attention disturbance, delirium, restless legs syndrome, poor quality sleep, paresthesia.

Eye disorders rarely – reduced visual acuity, blurred vision, increased lacrimation.

Ear and labyrinth disorders rarely – vertigo, positional vertigo.

Cardiac disorders infrequently – arterial hypertension; rarely – “hot flushes”, exertional angina, palpitations.

Gastrointestinal disorders infrequently – abdominal pain, upper abdominal pain, dyspepsia, ulcerative stomatitis, dry mouth, nausea; rarely – gastroesophageal reflux disease, gastrointestinal disorder or upset, bullous stomatitis, ulcerative glossitis, vomiting, increased intestinal peristalsis, abdominal distension, hypersalivation, halitosis, abdominal discomfort, gastric dyskinesia, gastritis.

Hepatobiliary disorders infrequently – hyperbilirubinemia.

Skin and subcutaneous tissue disorders infrequently – dermatitis, night sweats, pruritus and generalized pruritus, rash, dry skin; rarely – eczema, erythema, hand dermatitis, psoriasis, generalized rash, pruritic rash, nail disorder; frequency unknown – angioedema, oral mucosal edema, tongue edema.

Musculoskeletal and connective tissue disorders infrequently – limb pain; rarely – arthritis, muscle spasm, neck pain, night cramps.

Renal and urinary disorders infrequently – glucosuria, proteinuria; rarely – polyuria, hematuria, nocturia.

Reproductive system and breast disorders infrequently – menopausal symptoms; rarely – priapism, prostatitis; frequency unknown – galactorrhea.

General disorders and administration site conditions infrequently – asthenia, chest pain; rarely – fatigue, pain, thirst.

Investigations infrequently – abnormal liver function tests, increased body weight; rarely – increased hepatic enzyme activity, abnormal blood electrolytes, abnormal laboratory test results.

Contraindications

Hypersensitivity to the components of the drug; severe impairment of renal and liver function; autoimmune diseases; lactose intolerance, lactase deficiency, glucose-galactose malabsorption; pregnancy; breastfeeding period; children under 18 years of age (efficacy and safety have not been established).

With caution

Renal failure (CrCl <30 ml/min); impaired liver function; elderly age.

Use in Pregnancy and Lactation

Use during pregnancy and breastfeeding is contraindicated.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with renal failure (CrCl <30 ml/min).

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in the elderly.

Special Precautions

Due to the possible development of photosensitization, it is necessary to limit sun exposure.

Women wishing to become pregnant should be informed about the weak contraceptive effect of this product.

There are no clinical data on the use of melatonin in patients with autoimmune diseases, therefore its use in this category of patients is not recommended.

Alcohol should not be consumed during the course of therapy.

Effect on ability to drive vehicles and operate machinery

This product causes drowsiness, therefore, during the treatment period, one should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

With the simultaneous use of this combination with drugs that depress the central nervous system (sedatives, hypnotics, neuroleptics, tranquilizers), mutual enhancement of effects is possible.

It enhances the effect of antispasmodic and analgesic agents.

Pharmacokinetic interaction

In concentrations significantly exceeding therapeutic ones, Melatonin induces the CYP3A isoenzyme in vitro. If signs of induction develop, the issue of reducing the dose of concurrently used medicinal products should be considered.

The combination with fluvoxamine, which increases the concentration of melatonin (increase in AUC by 17 times and C_max by 12 times) due to inhibition of its metabolism by cytochrome P450 (CYP) isoenzymes: CYP1A2 and CYPC19, should be avoided.

Caution should be exercised when taking the following medicinal products simultaneously

• 5- and 8-methoxypsoralen, which increases the concentration of melatonin due to inhibition of its metabolism;
• Cimetidine (inhibitor of CYP2D isoenzymes), which increases the plasma content of melatonin by inhibiting the latter;
• Estrogens, which increase the concentration of melatonin by inhibiting its metabolism by CYP1A1 and CYP1A2 isoenzymes;
• Inhibitors of CYPA2 isoenzymes (e.g., quinolones), which can increase the exposure of melatonin;
• Inducers of the CYP1A2 isoenzyme (e.g., carbamazepine and rifampicin), which can reduce the plasma concentration of melatonin.

Smoking can reduce the concentration of melatonin due to induction of the CYP1A2 isoenzyme.

Many data have been published on the effect of adrenergic and opioid receptor agonists/antagonists, antidepressants, prostaglandin inhibitors, benzodiazepines, tryptophan and alcohol on the secretion of endogenous melatonin. The study of the mutual influence of these drugs on the dynamics or kinetics of melatonin has not been conducted.

Pharmacodynamic interaction

Alcohol reduces the effectiveness of melatonin and may enhance the toxicity of this combination.

Melatonin enhances the sedative effect of benzodiazepine and non-benzodiazepine hypnotics such as zaleplon, zolpidem and zopiclone. Combined use may lead to progressive impairment of attention, memory and coordination compared to zolpidem monotherapy.

The use of melatonin together with thioridazine and imipramine may lead to an increased feeling of calmness and difficulty in performing certain tasks compared to imipramine monotherapy, as well as an increased feeling of “fogginess in the head” compared to thioridazine monotherapy.

Storage Conditions

Store at 8°C (46°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

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.