Nitrosun (Tablets) Instructions for Use

ATC Code

N05CD02 (Nitrazepam)

Active Substance

Nitrazepam (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Hypnotic drug

Pharmacotherapeutic Group

Vasodilating agent – nitrate

Pharmacological Action

A hypnotic drug from the benzodiazepine group. It exerts a pronounced hypnotic effect, as well as anxiolytic, sedative, anticonvulsant, and central muscle relaxant actions.

The mechanism of action is associated with the enhancement of the inhibitory influence of GABA in the CNS by increasing the sensitivity of GABA receptors to the mediator as a result of the stimulation of benzodiazepine receptors.

It increases the depth and duration of sleep. Sleep usually occurs within 20-40 minutes after administration and lasts 6-8 hours. It moderately suppresses the REM sleep phase.

Pharmacokinetics

Absorption from the gastrointestinal tract is rapid and complete. Bioavailability ranges from 54% to 98% (depending on the dosage form). Plasma protein binding is about 85-90%.

It penetrates well through histohematic barriers, including the blood-brain barrier and the placental barrier. It is metabolized in the liver by reduction of the nitro group and subsequent acetylation with the formation of inactive acetyl derivatives.

The elimination half-life (T_1/2) is 16-48 hours (depends on the age and body weight of the patients). The main metabolites are excreted in the urine (65-71%) and in the feces (14-20%). About 1-5% is excreted unchanged by the kidneys.

Indications

Sleep disorders of various origins, somnambulism, premedication before surgical operations, encephalopathies accompanied by epileptic (myoclonic) seizures; epilepsy in children aged from 4 months to 1-2 years – West syndrome (infantile spasms or lightning nodding salaam seizures).

ICD codes

Dosage Regimen

Administer Nitrosun (Nitrazepam) tablets orally, typically as a single dose immediately before bedtime.

For adult insomnia, the usual dose is 5 mg to 10 mg.

Initiate therapy at the lowest effective dose for the shortest duration necessary.

For elderly or debilitated patients, use a reduced initial dose of 2.5 mg to 5 mg.

Adjust dosage cautiously based on patient response and tolerance.

For premedication before surgical procedures, administer a 5 mg to 10 mg dose on the preceding night and/or 1-2 hours before the procedure.

For pediatric use in epilepsy, specifically West syndrome, the dosage must be determined by a specialist; it is not a standard treatment for adult sleep disorders.

Do not exceed the maximum recommended daily dose.

The duration of treatment should generally not exceed 2-4 weeks, including a gradual dose reduction period.

Abrupt discontinuation is not recommended; always taper the dose gradually to avoid withdrawal symptoms.

Monitor patients closely for the development of tolerance and drug dependence, especially with prolonged use.

Adverse Reactions

From the nervous system: at the beginning of treatment (especially in elderly patients) – drowsiness, feeling of tiredness, dizziness, decreased ability to concentrate, ataxia, unsteady gait, lethargy, blunting of emotions, slowing of mental and motor reactions; headache, euphoria, depression, tremor, depressed mood, catalepsy, anterograde amnesia, confusion, dystonic, extrapyramidal reactions (uncontrolled body movements, including eyes), weakness, myasthenia, dysarthria; paradoxical reactions (aggressive outbursts, fear, suicidal tendency, muscle spasm, confusion, hallucinations, acute awakening, irritability, anxiety, insomnia).

From the hematopoietic system: leukopenia, neutropenia, agranulocytosis (chills, hyperthermia, sore throat, excessive fatigue or weakness), anemia, thrombocytopenia.

From the digestive system: dry mouth or salivation, heartburn, nausea, vomiting, decreased appetite, constipation or diarrhea; impaired liver function, increased activity of “liver” transaminases and alkaline phosphatase, jaundice.

From the urinary system: urinary incontinence, urinary retention, impaired renal function.

From the reproductive system: increased or decreased libido, dysmenorrhea.

Allergic reactions: skin rash, itching.

Effect on the fetus: teratogenicity, CNS depression, respiratory impairment and suppression of the sucking reflex in newborns whose mothers used Nitrazepam.

Other: tolerance, drug dependence; decreased blood pressure; depression of the respiratory center, visual impairment (diplopia), bulimia, weight loss, tachycardia. With a sharp dose reduction or discontinuation – withdrawal syndrome.

Contraindications

Hypersensitivity to benzodiazepines; coma, shock, acute alcohol intoxication with weakening of vital functions, acute intoxication with drugs that have a depressant effect on the CNS (including narcotic analgesics and hypnotics); drug addiction, alcoholism; myasthenia gravis; closed-angle glaucoma (acute attack); temporal lobe epilepsy, severe COPD (progression of the degree of respiratory failure), acute respiratory failure, hypercapnia, severe depression (suicidal tendencies may be noted); pregnancy (especially the first trimester), lactation (breastfeeding). During treatment, the consumption of ethanol is strictly prohibited for patients.

With caution hepatic and/or renal insufficiency, respiratory failure, cerebral and spinal ataxias, hyperkinesis, history of drug dependence, tendency to abuse psychoactive drugs, organic brain diseases, psychosis (paradoxical reactions are possible), hypoproteinemia, nocturnal apnea (established or suspected); children and adolescents under 18 years of age; elderly age.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy (especially in the first trimester) and during lactation (breastfeeding). If it is necessary to use during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Should be used with caution in hepatic insufficiency.

Use in Renal Impairment

Should be used with caution in renal insufficiency.

Pediatric Use

Should be used with caution in children and adolescents under 18 years of age – strictly according to indications, in doses and dosage forms recommended for the respective age. It is necessary to strictly follow the instructions in the nitrazepam drug labels regarding contraindications for the use of specific nitrazepam dosage forms in children of different ages.

Geriatric Use

Should be used with caution in elderly patients.

Special Precautions

In renal/hepatic insufficiency and during long-term treatment, monitoring of the peripheral blood picture and liver enzyme parameters is necessary.

The risk of drug dependence formation increases with the use of large doses (20 mg), significant duration of treatment in patients who previously abused ethanol or drugs. With prolonged use, tolerance may occur.

In the case of drug dependence development, abrupt withdrawal of nitrazepam is accompanied by a withdrawal syndrome (headache, myalgia, anxiety, tension, confusion, irritability, agitation, excitement, feeling of fear, nervousness, sleep disturbances, increased sweating, depression, nausea, vomiting, tremor; in severe cases – derealization, depersonalization, hyperacusis, photophobia, paresthesia in the limbs; hallucinations and epileptic seizures, tachycardia, convulsions, hallucinations, rarely – acute psychosis).

Withdrawal of nitrazepam should be carried out gradually.

Effect on the ability to drive vehicles and machinery

During the treatment period, patients are prohibited from driving any vehicles and engaging in other activities requiring high concentration of attention and speed of psychomotor reactions.

Drug Interactions

The effect of nitrazepam is enhanced and prolonged with simultaneous use with cimetidine, oral estrogen-containing contraceptives (delayed excretion and prolongation of T_1/2).

Inhibitors of hepatic microsomal enzymes prolong the T_1/2 of nitrazepam, increasing the risk of toxic effects.

With simultaneous use, Nitrazepam reduces the effectiveness of levodopa in patients with parkinsonism.

Mutual enhancement of action occurs with simultaneous use with drugs affecting the CNS, including lithium preparations, narcotic analgesics, agents for general anesthesia, ethanol, H₁-receptor blockers, sedative drugs, clonidine, barbiturates and other anxiolytic agents (tranquilizers), muscle relaxants.

With simultaneous use, inducers of hepatic microsomal enzymes reduce the effectiveness of nitrazepam. Narcotic analgesics enhance euphoria, leading to an increase in drug dependence.

With simultaneous use with nitrazepam, the effect of antihypertensive agents is potentiated.

Against the background of simultaneous use with clozapine, increased respiratory depression is possible.

With simultaneous use with nitrazepam, the toxicity of zidovudine may increase.

With simultaneous use with nitrazepam, valproic acid may enhance the effect of nitrazepam in children with epilepsy.

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.