A tranquilizer, a benzodiazepine derivative. It has anxiolytic, sedative, anticonvulsant, central muscle relaxant effect. The mechanism of action is associated with an increase in the inhibitory effect of GABA in the central nervous system. The muscle relaxant effect is also due to the inhibition of spinal reflexes. May cause anticholinergic effects.
Fast absorption. Cmax in plasma is noted after 90 minutes. Plasma protein binding is 98%. Penetrates through the placental barrier, into the cerebrospinal fluid, excreted in breast milk. Metabolized in the liver. Excreted by the kidneys - 70%.
Hypersensitivity to diazepam and other benzodiazepine derivatives, severe myasthenia gravis, coma, shock, angle-closure glaucoma, a history of addiction (drugs, alcohol, except for the treatment of alcohol withdrawal syndrome and delirium), sleep apnea syndrome, a state of acute alcohol intoxication with vital depression important functions, acute drug intoxication,that have a depressing effect on the central nervous system (narcotic, hypnotic and psychotropic drugs), severe chronic obstructive pulmonary disease (the risk of progression of respiratory failure), acute respiratory failure; pregnancy (especially the first trimester), the period of breastfeeding; for oral administration - children under 6 years of age; for parenteral use - children up to 5 weeks of age. Precautions: absence (petitmal) or Lennox-Gastaut syndrome; epilepsy, hepatic and / or renal failure, cerebral and spinal ataxia, hyperkinesis, a tendency to abuse psychotropic drugs, organic brain diseases (paradoxical reactions are possible), hypoproteinemia, old age, depression.
Pregnancy and lactation
Contraindicated for use during pregnancy (especially the first trimester) and during breastfeeding. Diazepam has a toxic effect on the fetus and increases the risk of developing congenital defects when used in the first trimester of pregnancy. Reception of therapeutic doses in later stages of pregnancy can cause depression of the central nervous system of the fetus. Continuous use during pregnancy can lead to physical dependence - possible withdrawal symptoms in a newborn. The use of diazepam in doses higher than 30 mg within 15 hours before delivery or during childbirth can cause respiratory depression (before apnea) in a newborn, decreased muscle tone, decreased blood pressure, hypothermia, weak sucking ("sluggish baby syndrome").
On the part of the nervous system: at the beginning of treatment (especially in elderly patients) - drowsiness, dizziness, increased fatigue, impaired concentration, ataxia, disorientation, slowing down of mental and motor reactions, anterograde amnesia; less often - headache, euphoria, decreased mood, tremor, catalepsy, confusion, dystonic extrapyramidal reactions (uncontrolled body movements),asthenia, muscle weakness, hyporeflexia, dysarthria; extremely rarely - paradoxical reactions (aggressive outbursts, psychomotor agitation, suicidal tendencies, muscle spasm, confusion, hallucinations, anxiety, sleep disturbances). After IV injection, hiccups are sometimes observed. With prolonged use, it is possible to develop drug dependence, memory impairment.From the hematopoietic system: leukopenia, neutropenia, agranulocytosis (chills, hyperthermia, sore throat, unusual fatigue or weakness), anemia, thrombocytopenia.From the digestive system: dry mouth or hypersalivation, heartburn, hiccups, gastralgia, nausea, vomiting, loss of appetite, constipation; liver dysfunction, increased activity of hepatic transaminases and alkaline phosphatase, jaundice. From the side of the cardiovascular system: palpitations, tachycardia, decreased blood pressure. From the reproductive system: rarely - increased or decreased libido, dysmenorrhea. From the urinary system: rarely - incontinence or urinary retention, impaired renal function. Allergic reactions: rarely - skin rash, itching.
Influence on the fetus: teratogenicity (especially the first trimester), inhibition of the central nervous system, respiratory failure and suppression of the sucking reflex in newborns whose mothers used the drug.
Others: addiction, drug dependence; rarely - depression of the respiratory center, visual impairment (diplopia), bulimia, weight loss.
With simultaneous use with drugs that have a depressing effect on the central nervous system (including with neuroleptics, sedatives, hypnotics, opioid analgesics, anesthetics), the depressing effect on the central nervous system, on the respiratory center, severe arterial hypotension increases.With simultaneous use with tricyclic antidepressants (including with amitriptyline), it is possible to increase the inhibitory effect on the central nervous system, increase the concentration of antidepressants and increase the cholinergic action. In patients who have received long-term antihypertensive drugs of central action, beta-blockers, anticoagulants, cardiac glycosides, the degree and mechanisms of drug interactions are unpredictable.With simultaneous use with muscle relaxants, the effect of muscle relaxants increases, the risk of apnea increases.With simultaneous use with oral contraceptives, the effects of diazepam may be enhanced. The risk of developing breakthrough bleeding increases.With simultaneous use with bupivacaine, an increase in the concentration of bupivacaine in blood plasma is possible; with diclofenac - increased dizziness is possible; with isoniazid - reducing the elimination of diazepam from the body.Drugs causing the induction of liver enzymes, incl. antiepileptic drugs (carbamazepine, phenytoin) can accelerate the elimination of diazepam.When used simultaneously with caffeine, the sedative and possibly anxiolytic effect of diazepam decreases.With simultaneous use with clozapine, severe arterial hypotension, respiratory depression, loss of consciousness are possible; with levodopa - suppression of antiparkinsonian action is possible; with lithium carbonate - a case of the development of a coma is described; with metoprolol - a decrease in visual acuity, deterioration of psychomotor reactions are possible.With simultaneous use with paracetamol, it is possible to reduce the elimination of diazepam and its metabolite (desmethyldiazepam); with risperidone - cases of ZNS development are described. With simultaneous use with rifampicin, the excretion of diazepam increases due to a significant increase in its metabolism under the influence of rifampicin.Theophylline in low doses distorts the sedative effect of diazepam.
With simultaneous use in rare cases, diazepam inhibits metabolism and enhances the effect of phenytoin. Phenobarbital and phenytoin can speed up the metabolism of diazepam.
With the simultaneous use of fluvoxamine increases plasma concentration and side effects of diazepam.
With simultaneous use with cimetidine, omeprazole, disulfiram, an increase in the intensity and duration of action of diazepam is possible.
With the simultaneous administration of ethanol, ethanol-containing drugs, the inhibitory effect on the central nervous system (mainly on the respiratory center) increases, and a syndrome of pathological intoxication may also occur.
Dosage and administration
Administered orally, intramuscularly, intravenously, rectally. The daily dose ranges from 500 mcg to 60 mg. A single dose, frequency and duration of use are set individually, depending on the indications and dosage form.
Special care is required when prescribing diazepam for severe depression, because diazepam can be used for suicidal purposes.
With renal / hepatic insufficiency, as well as with long-term treatment, it is necessary to control the peripheral blood picture and hepatic enzymes.
The risk of drug dependence increases with the use of high doses of diazepam, a significant duration of treatment, in patients who have previously abused alcohol or drugs. It should not be used for a long time without special instructions. Abrupt discontinuation of treatment is unacceptable because of the risk of "withdrawal syndrome"
If patients develop such reactions as increased aggressiveness, psychomotor agitation, anxiety, fear, suicidal thoughts, hallucinations, increased muscle cramps, difficulty falling asleep, superficial sleep in patients with diazepam, treatment should be discontinued.
Use with extreme caution in patients with heart and respiratory failure, organic changes in the brain (in such cases, it is recommended to avoid parenteral administration of diazepam), with angle-closure glaucoma and predisposition to it, with myasthenia gravis.
Special care is required when using diazepam, especially at the beginning of treatment, in patients who have been receiving centrally acting antihypertensive drugs, beta-blockers, anticoagulants, cardiac glycosides for a long time. When discontinuing therapy, the dose should be reduced gradually. With a sudden cancellation of diazepam after prolonged use, anxiety, agitation, tremors, convulsions are possible. The initiation of diazepam treatment or its abrupt withdrawal in patients with epilepsy or with a history of epileptic seizures can accelerate the development of seizures or status epilepticus. After i / m injection of diazepam, an increase in the activity of CPK in the blood plasma is possible (which should be taken into account in the differential diagnosis of myocardial infarction).Avoid IV injection.
During the period of treatment, avoid alcohol consumption.
Influence on the ability to drive vehicles and use mechanisms
Diazepam can slow down the speed of psychomotor reactions, which should be taken into account in patients engaged in potentially hazardous activities.