Nitrazepam
Nitrazepam (中文:硝西泮) is a long-acting benzodiazepine. It is used as a hypnotic in the short-term management of insomnia. It is reported to act in 30 to 60 minutes to produce sleep lasting for 6 to 8 hours.
Drug Names
| Generic Name 藥名 | HA Code 藥物代碼 | Classification 藥物分類 |
|---|---|---|
| Nitrazepam Tablet 5 mg | NITR01 | P1S1S3 & Part 1 Dangerous Drug |
Mechanism of Action
- Nitrazepam is a benzodiazepine.
- Gama-Aminobutyric acid (GABA) is an inhibitory neurotransmitter, acting on the GABA receptors in the central nervous system (CNS), inducing sleepiness, muscular relaxation, and control of anxiety and seizures.
- Nitrazepam acts on the benzodiazepine receptors in the brain and the spinal cord. Benzodiazepine receptors in the CNS are linked with GABA receptors as a complex.
- Nitrazepam by binding to the benzodiazepine receptors results in activation of the GABA-benzodiazepine receptor complex.
- Thus, Nitrazepam helps to promote muscle relaxation, reduce anxiety, control of convulsions and promote sleep.
| Insomnia (short-term use) | Oral
|
|---|
Benzodiazepines are sometimes used in the management of epilepsy, but their long-term use is limited by problems of sedation, dependence, and tolerance to the antiepileptic effects.
Nitrazepam has been used in the treatment of infantile spasms (as for example in West’s syndrome) and the so-called infantile myoclonic seizures.
Usual oral dose: 0.3 to 1 mg/kg daily in 3 divided doses.
Side Effects
Nitrazepam is an unsuitable hypnotic for the elderly as it causes:
- Impairments in body balance and standing steadiness in individuals who wake up at night
- As a result, leading to falls and hip fractures
- It induces general mental deterioration
- Inability to walk
- Incontinence
- Confusion and disorientation
The nitrazepam-induced symptoms can lead to a misdiagnosis of dementia.
Elderly are more likely to experience sedation and decreased coordination. The lowest effective dose of nitrazepam should be used for the shortest possible length of time.
Possible side effects include:
| Very common (>10% of incidence)
or Common (1-10% of incidence) |
|
|---|---|
| Infrequent (0.1 -1% of incidence) |
|
| Rare (<0.1% of incidence) |
|
Overdosage can produce CNS depression and coma.
Paradoxical reactions (the opposite of what is to be expected) may occur. Symptoms include
- aggression, rage
- mania, agitation, and restlessness
- hallucinations, inappropriate behavior
- twitches and tremor
Pharmacokinetics
| Oral bioavailability | Nitrazepam is well absorbed after oral doses. |
|---|---|
| Onset of action | Peak plasma concentrations occur about 2 to 3 hours after ingestion |
| Metabolism | Nitrazepam is metabolized in the liver, mediated by the cytochrome P450 system. |
| Elimination half-life |
Nitrazepam is excreted in the urine. Up to about 20% of an oral dose is found in the faeces. The half-life of nitrazepam is between 16.5 and 48.3 hours. In young people, nitrazepam has a half-life of about 29 hours, and a much longer half-life of 40 hours in the elderly. Nitrazepam’s half-life in the cerebrospinal fluid, 68 hours, indicates its extremely slow elimination from the cerebrospinal fluid. |
Drug Management
Monitoring
- Blood pressure, pulse and respiratory rate are recommended
- Elderly may be sensitivity to nitrazepam’s effects. Impairment of memory, cognitive function, and psychomotor performance and behavior disinhibition may be common. Long-term use commonly exacerbates underlying dementia in elderly patients.
- Nitrazepam may make elderly patients feel dizzy, increasing risk of falls, so fall prevention is needed
- Some patients develop blood dyscrasias, and have raised liver enzymes, so periodic blood counts and liver function tests are recommended
- Some patients develop blood dyscrasias, and have raised liver enzymes, so periodic blood counts and liver function tests are recommended
- changes in mood, the development or worsening depression, and/or any thoughts or behaviour of suicide.
Dependence and Withdrawal
- One-third of individuals treated with benzodiazepines for longer than 4 weeks develop a dependence on the drug and experience a withdrawal syndrome on cessation.
- Withdrawal symptoms can range from insomnia and anxiety to more serious symptoms, including seizures and psychosis.
- Nitrazepam should therefore be withdrawn by tapering the dose to minimize occurrence of withdrawal symptoms.
- Tolerance to the sleep-inducing effects of nitrazepam occurs after 7 days.
Drug interaction
Medicines that interact with nitrazepam may either
- Decrease its effect
- Affect how long it works for
- Increase side effects
Common medications that may interact with nitrazepam include:
| Drugs given with nitrazepam | Potential Effect |
|---|---|
|
Alcohol, Hypnotics/sedative (e.g. barbiturates) Antidepressants (e.g. fluoxetine, citalopram, paroxetine, sertraline, amitriptyline) Sedative histamines (e.g. chlorpheniramine, dimenhydrinate, diphenhydramine) Antipsychotic (e.g. chlorpromazine, clozapine, haloperidol, clozapine, quetiapine, risperidone) |
May worsens the side effects such as drowsiness , dizziness and respiratory depression |
|
Cimetidine Omeprazole Oxcarbazepine, topiramate, valproate Ketoconazole Itraconazole Isoniazid Erythromycin, ciprofloxacin Propranolol fluoxetine |
Prolong the action of nitrazepam by inhibiting its elimination |
| Alcohol | May cause a synergistic enhancement of the hypotensive effect of nitrazepam and alcohol |
| Oral contraceptives | Oral contraceptives significant decrease the elimination of nitrazepam, so prolong the action of nitrazepam |
|
Rifampicin Phenytoin Carbamazepine phenobarbitone |
All these drugs increase the metabolism of nitrazepam, thus decreasing drug levels and effects |
|
Steroid (e.g. Dexamethasone) St John’s wort |
Increase the metabolism of nitrazepam, thus decreasing nitrazepam plasma levels and effects |
| Theophylline | May inhibit the action of nitrazepam |
| Levodopa (e.g. Sinemet) | nitrazepam may block the action of levodopa used in the treatment of Parkinson’s disease. |
Caution
- particular care in pregnancy,
- elderly, due to increased susceptibility to side-effects, especially loss of coordination and drowsiness
- in patients with hepatic or renal impairment, who may require reduced doses
- people with history of alcohol dependence or abuse
- people with history of drug dependence or abuse
- people with psychiatric disorders
- avoid prolonged use and abrupt withdrawal thereafter
Contra-indications
Use of nitrazepam should be avoided, when possible, in individuals with:
- severe hepatic impairment
- sleep apnoea
- chronic obstructive airways disease (COPD)
- Myasthenia gravis
- Acute narrow-angle glaucoma
- Chronic schizophrenia
Nitrazepam is recommended to be avoided in patients who drive or operate machinery, as it can impaired driving skills up to 17 hours after dosing.
Hepatic impairment
- Start with smaller initial doses or reduce dose.
- Can precipitate coma.
- Avoid in severe impairment.
Renal impairment
- Start with small doses in severe impairment.
Pregnancy
Possible adverse effects of use of benzodiazepines during pregnancy include: miscarriage, malformation, intrauterine growth retardation, and function deficits.
Breast-feeding
Use during breast feeding is not recommended.
Driving and skilled tasks
May impair judgment and increase reaction time, and so affect ability to drive or operate machinery. Moreover the hangover effects of a night dose may impair driving on the following day.
FAQ
How should I take the tablet?
The lowest effective dose should be used to avoid excessive drowsiness during the day time or motor impairment. This medication is used for a short period of time or as an “as required” medication. Swallow the tablet whole with a glass of water at bedtime.
What should I avoid while taking?
Do not eat grapefruit or drink grapefruit juice as it may increase blood levels of nitrazepam.
Avoid drinking alcohol while taking nitrazepam because it may enhance the side effects of sedation and respiratory depression.
Avoid driving or hazardous activity while you are taking nitrazepam.
What happen if I overdose?
Contact your primary care doctor. If emergency situation, call 999
What happen if I miss a dose?
Take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.
