Zonadine (Tablets) Instructions for Use

Marketing Authorization Holder

Pliva Hrvatska, d.o.o. (Croatia)

ATC Code

N05CF02 (Zolpidem)

Active Substance

Zolpidem (Rec.INN registered by WHO)

Dosage Form

Zonadine

Film-coated tablets, 10 mg: 10 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blister packs (1) – cardboard packs.

Clinical-Pharmacological Group

Hypnotic drug

Pharmacotherapeutic Group

Hypnotic agent

Pharmacological Action

Zolpidem is a hypnotic agent from the imidazopyridine group, a specific agonist of central ω₁-receptors. It shortens sleep onset time, reduces the number of nocturnal awakenings, increases total sleep duration, and improves sleep quality. It prolongs stage II sleep and deep sleep stages (III and IV), without affecting the duration of REM sleep.

It also has central muscle relaxant and anticonvulsant effects.

Pharmacokinetics

After oral administration, the peak plasma concentration (C_max) is reached within 0.5-3 hours. The bioavailability is about 70%.

Plasma protein binding is 92%. There is a linear relationship between the dose and the plasma concentration of the active substance. The volume of distribution (V_d) is 0.54±0.02 L/kg.

Zolpidem is metabolized in the liver and excreted as inactive metabolites in the urine (56%) and feces (37%). It does not induce hepatic microsomal enzymes.

The elimination half-life (T_1/2) ranges from 0.7 hours to 3.5 hours (average 2.4 hours).

In elderly individuals, the plasma clearance of zolpidem may decrease, while the T_1/2 increases slightly (on average up to 3 hours), C_max increases by 50%, and V_d decreases to 0.34±0.05 L/kg.

In patients with severe renal impairment, the clearance of zolpidem decreases slightly, while other pharmacokinetic parameters remain unchanged.

In patients with severe hepatic impairment, the bioavailability of zolpidem increases, clearance decreases somewhat, and T_1/2 increases up to 10 hours.

Indications

Episodic, transient, and chronic insomnia.

ICD codes

Dosage Regimen

Administer orally as a single dose immediately before bedtime.

For adults under 65 years, the standard dose is 10 mg.

For patients over 65 years or with hepatic impairment, initiate therapy at a reduced dose of 5 mg.

Do not exceed the maximum daily dose of 10 mg.

Limit the treatment course to several days up to 4 weeks to minimize the risk of tolerance and dependence.

Swallow the tablet whole; do not crush or chew.

Ensure you have a period of uninterrupted sleep of 7-8 hours after ingestion.

In case of severe renal impairment, no specific dose adjustment is required; however, exercise caution.

Discontinue treatment by gradually reducing the dose to prevent rebound insomnia.

Avoid consumption of alcohol and other central nervous system depressants during therapy.

Adverse Reactions

From the digestive system: in some cases – abdominal pain, nausea, vomiting, diarrhea.

From the central and peripheral nervous system: depending on the dose and individual sensitivity (especially in elderly patients) – dizziness, impaired balance, ataxia, headache, daytime drowsiness, attention disturbances, muscle weakness, diplopia, anterograde amnesia, paradoxical or psychopathological reactions; with high doses or long-term treatment, rebound insomnia is possible.

Allergic reactions: skin rash, itching.

Other: rarely – disturbances in libido; development of tolerance, formation of mental and physical dependence (with use over several weeks).

Contraindications

Severe respiratory failure, sleep apnea, severe hepatic failure, childhood and adolescence under 15 years, first trimester of pregnancy, lactation (breastfeeding), hypersensitivity to zolpidem.

Use in Pregnancy and Lactation

Zolpidem is contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in severe hepatic insufficiency. In cases of hepatic impairment, a dose reduction may be necessary.

Pediatric Use

Contraindicated in children and adolescents under 15 years of age.

Special Precautions

Use is not recommended in myasthenia gravis.

Use with caution in patients with respiratory failure. In cases of hepatic impairment, a dose reduction may be necessary.

When discontinuing therapy, the dose should be reduced gradually. The likelihood of developing tolerance increases with long-term use of zolpidem.

Avoid alcohol consumption during treatment.

Effect on ability to drive vehicles and operate machinery

During the treatment period, refrain from potentially hazardous activities requiring concentration of attention and high speed of psychomotor reactions.

Drug Interactions

Concomitant use with opioid analgesics, antitussives, barbiturates, antidepressants, sedatives, antihistamines, benzodiazepines, clonidine, neuroleptics, and ethanol may lead to symptoms of central nervous system and respiratory center depression.

Concomitant use with rifampicin decreases the plasma concentration of zolpidem, which is accompanied by a reduction in its hypnotic effect. This interaction is due to the induction of the CYP3A4 isoenzyme.

Concomitant use with inducers of the CYP3A4 isoenzyme (including carbamazepine, phenytoin) suggests the possibility of a decrease in the plasma concentration of zolpidem.

Concomitant use with clozapine increases the risk of collapse, circulatory arrest, and respiratory arrest.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.