Sanval^® (Tablets) Instructions for Use

Marketing Authorization Holder

Sandoz, d.d. (Slovenia)

ATC Code

N05CF02 (Zolpidem)

Active Substance

Zolpidem (Rec.INN registered by WHO)

Dosage Forms

	Sanval®	Film-coated tablets, 5 mg: 20 pcs.
		Film-coated tablets, 10 mg: 10 or 20 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets light pink in color; round, biconvex.

Excipients: lactose monohydrate – 55 mg, microcrystalline cellulose – 42.4 mg, sodium carboxymethyl starch – 4.8 mg, povidone – 1.8 mg, colloidal silicon dioxide – 400 mcg, magnesium stearate – 600 mcg.

Shell composition hypromellose – 1.28 mg, hypromellose – 1.28 mg, macrogol 400 – 400 mcg, talc – 200 mcg, iron oxide red dye – 8 mcg, titanium dioxide – 832 mcg, carnauba wax – 90 mcg.

10 pcs. – blisters (2) – cardboard packs.

Film-coated tablets white or almost white, round, biconvex, with a score on one side.

Excipients: lactose monohydrate – 60 mg, microcrystalline cellulose – 42.4 mg, sodium carboxymethyl starch – 4.8 mg, povidone – 1.8 mg, colloidal silicon dioxide – 400 mcg, magnesium stearate – 600 mcg.

Shell composition hypromellose – 1.28 mg, hypromellose – 1.28 mg, macrogol 400 – 400 mcg, talc – 200 mcg, titanium dioxide – 840 mcg, carnauba wax – 90 mcg.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Hypnotic drug

Pharmacotherapeutic Group

Hypnotic agent

Pharmacological Action

A hypnotic drug belonging to the imidazopyridine group. It has a sedative effect, while anxiolytic, central muscle relaxant and anticonvulsant effects are insignificant.

It excites benzodiazepine ω-receptors in the alpha-subunit of GABA-receptor complexes localized in the area of the IV plate of the sensorimotor zones of the cortex, reticular parts of the substantia nigra, visual thalamus of the ventral thalamic complex, pons, globus pallidus, etc. Interaction with ω-receptors leads to the opening of neuronal ionophore channels for chloride ions.

The use of the drug shortens the time to fall asleep, reduces the number of nighttime awakenings, increases the total duration of sleep and improves its quality. It prolongs stage II sleep and deep sleep stages (III and IV).

The hypnotic effect develops rapidly. It does not cause daytime sleepiness.

Pharmacokinetics

Absorption and Distribution

After oral administration, Zolpidem is rapidly absorbed from the gastrointestinal tract. The time to reach C_max in blood plasma is 0.5 – 3 hours. The bioavailability of zolpidem reaches 70%.

There is a linear relationship between the dose of the drug and its plasma concentrations.

Plasma protein binding is 92%.

Metabolism and Excretion

It is metabolized in the liver to form three inactive metabolites. It does not induce liver enzymes.

Metabolites are excreted in the urine (56%) and in the feces (37%). T_1/2 is 0.7 – 3.5 hours.

Pharmacokinetics in Special Clinical Cases

In elderly individuals, plasma clearance may decrease without a significant increase in T_1/2 (on average 3 hours), while C_max increases by 50%.

In severe renal impairment, clearance increases slightly.

In liver function impairment, bioavailability increases, T_1/2 increases to 10 hours.

Indications

Sleep disorders

• Difficulty falling asleep;
• Early and nighttime awakenings.

ICD codes

Dosage Regimen

The drug is taken orally. Doses and duration of treatment are set individually.

The usual daily dose is 10 mg before bedtime; if necessary, the dose can be increased to 15 mg, however, it should not exceed 20 mg.

For patients over 65 years of age and with liver function impairment, the initial dose is 5 mg; if necessary, it can be increased to 10 mg.

Sanval^® should be taken immediately before bedtime. The course of treatment should not exceed 4 weeks.

Adverse Reactions

From the digestive system frequently (>1%) – abdominal pain, nausea, vomiting, diarrhea.

From the CNS headache, confusion, memory impairment, drowsiness, impaired coordination of movements, euphoria, nightmares, dizziness and diplopia; rarely (<1%) – agitation, hallucinations, paresthesia, stupor.

Allergic reactions: skin rash, itching.

Other rarely (<1%) – sweating, pallor, orthostatic hypotension.

With long-term use, the development of drug dependence is possible.

The frequency of side effects depends on the dose. Side effects are more common in women than in men.

Contraindications

• Hypersensitivity to zolpidem.

With caution Sanval^® should be prescribed for chronic obstructive pulmonary diseases (in the acute stage), respiratory failure, myasthenia gravis, hepatic/renal failure, alcoholism, history of drug abuse or drug dependence, depression.

Use in Pregnancy and Lactation

Sanval^® should be used with caution during pregnancy and breastfeeding.

In experimental studies on reproduction in animals, no risk of adverse effects on the fetus was identified.

Adequate and strictly controlled studies of the use of Sanval^® during pregnancy have not been conducted.

The patient should be warned that if she is planning a pregnancy or becomes pregnant during treatment with Sanval^®, and if she is breastfeeding, she must inform her doctor.

Use in Hepatic Impairment

^{Sanval® should be prescribed with caution for hepatic failure.}

Use in Renal Impairment

Sanval^® should be prescribed with caution for renal failure.

Pediatric Use

The drug is not prescribed to children under 15 years of age.

Geriatric Use

For patients over 65 years of age and with liver function impairment, the initial dose is 5 mg; if necessary, it can be increased to 10 mg.

Special Precautions

Due to the depressant effect on the central nervous system and the rapid onset of effect, Sanval^® should be taken immediately before bedtime.

Although clinical studies have not revealed a suppressive effect of zolpidem on respiration, caution should be exercised when prescribing the drug to patients with respiratory dysfunction. Sanval^®, as well as drugs of the benzodiazepine group, can cause respiratory disorders in patients suffering from sleep apnea.

Zolpidem may further reduce muscle tone in patients with myasthenia gravis, so such patients should be under close medical supervision during treatment with Sanval^®.

Medical supervision should be established for patients prone to depression, as the risk of suicidal behavior while using Sanval^® increases.

With long-term use of Sanval^®, the risk of developing addiction increases. The duration of taking hypnotic drugs should be limited, as a rule, to 2-3 weeks. The patient should be warned that if sleep does not improve during this time, they should consult a doctor again.

When used in recommended doses for more than 4 weeks, treatment withdrawal should be carried out gradually.

During treatment with Sanval^®, alcohol consumption should be avoided.

Use in pediatrics

The drug is not prescribed to children under 15 years of age.

Effect on the ability to drive vehicles and mechanisms

During treatment with Sanval^®, one should refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms impaired consciousness (from drowsiness to coma), respiratory depression, decreased blood pressure.

Treatment gastric lavage, the use of flumazenil is recommended as an antidote. Even with severe agitation, the administration of any sedative drugs is unacceptable. Hemodialysis is ineffective. If necessary, symptomatic therapy is carried out in a hospital setting.

Drug Interactions

With the simultaneous administration of Sanval^® and agents that depress the central nervous system, for example, opioid analgesics, antitussives, neuroleptics, hypnotics (barbiturates), some tranquilizers and antidepressants, antihistamines, clonidine, their depressant effect on the central nervous system may be enhanced.

Flumazenil eliminates the hypnotic effect of Sanval^®.

Anxiolytic agents (tranquilizers) benzodiazepine derivatives, used against the background of Sanval^® intake, increase the risk of developing drug dependence.

Sanval^® with simultaneous use enhances the effect of imipramine and chlorpromazine and prolongs the T_1/2 of chlorpromazine (chlorpromazine enhances drowsiness and the frequency of anterograde amnesia), reduces the C_max of imipramine.

Ketoconazole and ritonavir may enhance the sedative effect of Sanval^®, as they reduce the metabolism and clearance of zolpidem.

Rifampicin, on the contrary, reduces the concentration of zolpidem in plasma and, consequently, its effect (possibly due to increased metabolism).

Alcohol enhances the depressant effect of Sanval^® on the central nervous system.

Storage Conditions

List B. The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years.

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.