(Information for professionals)
Trade name of the drug : Nitrazepam
The international non-proprietary name – Nitrazepam
Dosage form : pills
Composition per tablet :
Active substance: Nitrazepam – 5 mg
Auxiliary substances: milk sugar (lactose), potato starch, polyvinylpyrrolidone low molecular weight Medical (povidone), talc, magnesium stearate, Primogel (sodium carboxymethyl) – a sufficient amount to obtain a mass of pills 100 mg.
Description : Tablets white with yellowish-greenish tint, or a spherical shape with beveled ploskotsilindricheskoy.
Pharmacotherapeutic group : hypnotic
Code the ATX N05CD02
The drug belongs to the list of potent agents according to the protocol of the meeting PKKN.
Hypnotic of benzodiazepine has a depressant effect on the nervous system (CNS), realized mainly in the thalamus, hypothalamus and limbiche-tion system. It enhances the inhibitory action of gamma-aminobutyric acid (GABA), which is one of the major mediators of the pre- and post-synaptic inhibition of impulse transmission in the central nervous system.
The drug also has anxiolytic, sedative, muscle relaxant, and protivosudo-goad action. Hypnotic effect occurs within 20-40 minutes after ingestion and lasts 6-8 hours. Under the influence of the drug increases the depth and duration of sleep. Sleep and waking occur physiologically.
The drug was well pass through the blood-brain barrier, the placenta, enters the breast milk, which should be considered when administering the drug to pregnant and lactating women.
Absorption from the gastrointestinal tract – rapid and complete. Bioavailability – from 54% to 98% (depending on the dosage form). When taken together with food intake and slows down the maximum plasma concentration is reduced by about 30%. In a single oral dose of 10 mg nitrazepama average value of the maximum concentration of 0. 08-0.1 g / ml and is achieved within 1-4 hours. Relationship to plasma proteins – about 85-90%. The phase distribution of the active substance in the body varies greatly, ranging from 3.5 to 1. 7 h. The volume of distribution increases with age of patients 1 and 3-2. 6 L / kg. It penetrates through the blood-tissue barriers, including GEB and placental barrier, it is found in mother’s milk.
It is metabolized in the liver by reducing the nitro group and subsequent acetylated-tion with the formation of active acetyl derivatives. The half – 16-48 hours (depending on age and body weight of patients) of cerebrospinal fluid – 68 h main metabolites -. 7-amino-nitrazepam, 7-acetamino-nitrazepam, 2-amino-5-nitrobenzophenone and hydroxy-2- amino-5-nitrobenzophenone, the kidneys (65-71%) and feces (14-20%). Approximately 1-5% is excreted unchanged by the kidneys.
The accumulation during the second appointment – min (refers to benzodiazepines with short or medium half-life), excretion after cessation of treatment – fast.
- sleep disorders of various origins (difficulty falling asleep, frequent night and / or early morning awakening);
- some forms of seizures (especially in children), in Vol. h. West syndrome.Contraindications
- Hypersensitivity to benzodiazepines;
- coma, shock;
- angle-closure glaucoma (acute onset or predisposition);
- acute alcohol intoxication with the weakening of vital functions;
- acute intoxication of drugs, have a depressing effect on the central nervous system;
- severe depression (suicidal tendencies may occur);
- myasthenia gravis;
- drug or alcohol addiction;
- pregnancy, breast-feeding;
- acute respiratory failure;
- swallowing disorder in children;
- temporal lobe epilepsy;
- severe chronic obstructive pulmonary disease (risk of progression of the degree of respiratory failure)Carefully
- liver and / or kidney failure, respiratory failure, cerebral and spinal ataxia, hyperkinesis, drug dependency history, the propensity to abuse drugs, organic diseases of the brain, psychosis (possible paradoxical reactions), hypoproteinemia, sleep apnea (or suspected) , elderly age.Dosing and Administration
Inside. As a sedative 30 minutes before sleep:
– adult 2.5-5 mg nitrazepama, the maximum daily dose – 10 mg
– elderly patients and debilitated patients – 2.5 mg, the maximum daily dose – 5 mg.
For treatment West syndrome daily dose for children 1-2 years of age and infants – 2. 5-5 mg. Taken once daily dose, for administration to infants, a suitable amount of the drug is crushed and dissolved (suspended) in a convenient volume for receiving water.
On the part of the nervous system: at the beginning of treatment (particularly in elderly patients) – drowsiness, fatigue, dizziness, decreased concentration, ataxia, lethargy, blunting of emotions, mental retardation and motor responses; rarely – headache, euphoria, depression, tremors, catalepsy, anterograde amnesia, confusion, dystonic extrapyramidal reactions (uncontrolled movements of the body, including the eyes), muscle weakness, dysarthria, blurred speech; rarely -paradoksalnye reaction (aggressive outbursts, fear, suicidal tendencies, muscle spasms, hallucinations, agitation, irritability, anxiety, insomnia).
From the side of hematopoiesis: leukopenia, neutropenia, agranulocytosis (chills, pyrexia, sore throat, unusual tiredness or weakness), anemia, thrombocytopenia. From the digestive system: dry mouth or salivation, heartburn, nausea, vomiting, decreased or increased appetite, constipation or diarrhea; abnormal liver function, increased activity of “liver” transaminases and alkaline phosphatase, jaundice. From the urogenital system: urinary incontinence, urinary retention, renal dysfunction, increased or decreased libido, dysmenorrhea. Allergic reactions: skin rash, pruritus. Effect on the fetus: central nervous system depression, respiratory failure and suppression of sucking reflex in infants whose mothers used the drug during pregnancy.
Other: addiction, drug dependency; lowering blood pressure; rarely – depression of the respiratory center, blurred vision (diplopia), bulimia, weight loss, tachycardia. With a sharp decrease in dose or cessation of reception – syndrome “cancel” (irritability, headache, anxiety, agitation, anxiety, sleep disturbances, dysphoria, a spasm of smooth muscles of internal organs and skeletal muscles, depersonalization, increased sweating, depression, nausea, vomiting , tremors, disorders of perception, incl hyperacusis, hyperesthesia, paresthesia, photophobia, tachycardia, convulsions, hallucinations, rare -… acute psychosis).
Symptoms: drowsiness, depression of consciousness of varying severity (up to coma), paradoxical excitement, reduced reflexes, decreased response to pain stimuli, deep sleep, dysarthria, ataxia, blurred vision (nystagmus), tremor, bradycardia, dyspnea or shortness of breath, severe weakness, decreased blood pressure, collapse, depression of cardiac and respiratory activity. Treatment: gastric lavage, forced diuresis, administration of activated charcoal. Symptomatic therapy (maintenance of respiration and blood pressure). As a specific antagonist flumazenil is used (in a hospital). Hemodialysis – is ineffective.
reduces the effectiveness of levodopa in patients with Parkinson’s disease.
The mutual reinforcement of action when combined with psychotropic drugs, lithium, drugs, narcotic analgesics, general anesthetics, alcohol, muscle relaxants, antihistamines and sedatives, clonidine, barbiturates and anxiolytic-cal drugs (tranquilizers).
The effect is amplified and lengthened cimetidine, oral contraceptives estrogensoderjath (launch delay and extension perioda.poluvyvedeniya).
inhibitors of microsomal oxidation lengthen the half-life to increase the risk of toxic effects of the drug.
Inductors microsomal liver enzymes decrease the efficiency nitrazepama.
Narcotic analgesics increase the euphoria, leading to an increase in drug addiction.
Antihypertensive funds may increase the severity of blood pressure reduction.
On the background of the simultaneous appointment of clozapine may increase the respiratory depression.
It may increase the toxicity of zidovudine.
valproic acid, probably enhances the effect nitrazepama in children with epilepsy.
requires particular caution when assigning nitrazepama with severe depression, t. To. The drug can be used for the implementation of suicidal intentions.
In the period of treatment should refrain from vehicles and Occupation of driving potentially hazardous activities that require high concentration and psychomotor speed reactions.
during treatment the patient is strictly prohibited alcohol.
Without specific instructions, should not be used for a long time.
If, before the start of treatment nitrazepama sick for a long time held the therapy with other drugs, the treatment begins with caution.
In renal / hepatic failure and long-term treatment is required picture control peripheral blood and “liver” enzymes.
The risk of drug dependence increases when using large doses, a significant duration of treatment in patients who previously abused alcohol or drugs.
Nitrazepam has primary potential addictive.
Even at a daily intake of it for a few weeks, there is a danger the development of physical and psychological dependence. This effect occurs not only when nitrazepama abuse, particularly high doses, but when it is used in usual therapeutic doses. Therefore, treatment should be continued to carry out only for health reasons, after carefully weighing the benefit of therapy with the risk of addiction to the drug, and depending on it.
Remove the drug should be made gradually to avoid the syndrome of “cancellation”.
If you have patients with such unusual reactions such as aggression, agitation, fear, suicidal thoughts, hallucinations, increased muscle cramps, difficulty falling asleep, shallow sleep, treatment nitrazepama should be discontinued.
If, despite the fact that the drug is contraindicated during pregnancy, it is often used – may develop physical dependence (syndrome of “cancellation”) the newborn.
Using just before birth or during labor may cause neonatal respiratory depression, decreased muscle tone, decreased blood pressure, hypothermia, and a weak act of sucking ( “sluggish baby syndrome”).
in young children, there is increased production of mucus and sputum in airways, so you should take steps to ensure airway patency good (given the dampening effect of the drug).
10 tablets in blisters. At 1, 2 or 5 contour cell packages with instruction on the medical application in a carton box. 20 or 50 tablets in a jar lighting glass or polymer. In one bank, along with instructions for use in a carton box.
List number 1 PKKN potent substances. In a dry, protected from light, out of reach of children.
3 years. Do not use after the expiration date printed on the packaging.
Conditions of supply of pharmacies