Flurazepam

Oral
Short-term management of insomnia

Debilitated patients: Max initial dose: 15 mg to be taken at bedtime.

Severe: Contraindicated.

May be taken with or without food.

Severe respiratory insufficiency, sleep apnoea syndrome, respiratory depression, myasthenia gravis, chronic psychosis, phobic or obsessional states, spinal and cerebellar ataxia. Severe hepatic impairment. Children. Pregnancy.

Patient with chronic pulmonary insufficiency (e.g. COPD), depression, history of alcohol or drug abuse and psychiatric or personality disorders. Debilitated patients and those at risk of falls. Patients who are receiving opioids. Not recommended for long-term use. Avoid abrupt withdrawal. Renal and mild to moderate hepatic impairment. Elderly. Lactation.

Significant: CNS and respiratory depression, anterograde amnesia, confusion, depression, paradoxical reactions (e.g. anxiety, restlessness, agitation, delusion, excitement, hyperactive or aggressive behaviour, suicidal ideation); hazardous sleep-related activities (e.g. sleep-driving, making phone calls and cooking and eating food while asleep); rebound insomnia (when abruptly discontinued); tolerance, physical and psychological dependence, withdrawal syndrome.
Blood and lymphatic system disorders: Thrombocytopenia, leucopenia, agranulocytosis.
Cardiac disorders: Chest pain, palpitations.
Ear and labyrinth disorders: Rarely, vertigo.
Eye disorders: Blurred vision, burning sensation of eyes.
Gastrointestinal disorders: Nausea, vomiting, constipation, diarrhoea, abdominal discomfort, dry mouth, excessive salivation, dysgeusia.
General disorders and administration site conditions: Fatigue.
Investigations: Increased serum alkaline phosphatase, increased serum ALT/AST, abnormal bilirubin levels.
Musculoskeletal and connective tissue disorders: Muscle weakness, arthralgia.
Nervous system disorders: Somnolence, dizziness, headache, reduced alertness, ataxia, extrapyramidal disorder.
Psychiatric disorders: Nervousness, talkativeness.
Renal and urinary disorders: Rarely, urinary retention.
Reproductive system and breast disorders: Rarely, libido disorder.
Respiratory, thoracic and mediastinal disorders: Dyspnoea.
Skin and subcutaneous tissue disorders: Rash, pruritus, sweating.
Vascular disorders: Hypotension.
Potentially Fatal: Rarely, hypersensitivity reactions including anaphylaxis or angioedema.

PO: C

This drug may cause drowsiness and impaired alertness, if affected, do not drive or operate machinery.

Monitor respiratory rate, alertness during daytime, and behaviour profile. Closely assess for signs or symptoms of respiratory/CNS depression and hypersensitivity reaction.

Symptoms: Drowsiness, confusion, lethargy, dysarthria, ataxia, hypotonia, hypotension, respiratory depression, and rarely coma. Management: Symptomatic and supportive treatment. Induce vomiting if the patient is conscious or perform immediate gastric lavage with the airway protected for an unconscious patient. May consider administering activated charcoal to reduce absorption. Flumazenil may be cautiously given as an antidote. Monitor pulse, respiration and blood pressure and maintain adequate airway.

Additive CNS depressant effects with antipsychotics, anxiolytics, sedative/hypnotics, antidepressants, barbiturates, anticonvulsants, anaesthetics, sedating antihistamines, antihypertensives, and β-blockers. Muscle relaxants may enhance the relaxant effect of flurazepam. Sedative effect may be decreased by theophylline or aminophylline. Clearance may be reduced by hepatic enzyme inhibitors (e.g. cimetidine, disulfiram, omeprazole) and may be increased by hepatic enzyme inducers (e.g. rifampicin).
Potentially Fatal: May result in profound sedation, respiratory depression and coma with opioids.

May enhance CNS depressant effects with alcohol. May increase serum levels with grapefruit juice.

Description:
Mechanism of Action: Flurazepam is a long-acting benzodiazepine that binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron within the CNS (including the limbic system and reticular formation). It enhances the inhibitory actions of GABA on neuronal excitability by increasing neuronal membrane permeability to chloride ions, resulting in hyperpolarisation and stabilisation.
Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 30-60 minutes (flurazepam); 7.6-13.6 hours (N-desalkylflurazepam); approx 1 hour (N-hydroxyethylflurazepam).
Distribution: Crosses the placenta. Volume of distribution: 3.4 L/kg (flurazepam); 0.7 L/kg (N-desalkylflurazepam). Plasma protein binding: Approx 97% (flurazepam); approx 98% (N-desalkylflurazepam).
Metabolism: Metabolised in the liver into N-desalkylflurazepam (major active metabolite) and N-hydroxyethylflurazepam; undergoes extensive first-pass metabolism.
Excretion: Mainly via urine (22-55% as N-hydroxyethylflurazepam, <1% as N-desalkylflurazepam). Elimination half-life: 2.3 hours (flurazepam); 47-100 hours (N-desalkylflurazepam).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3393, Flurazepam. https://pubchem.ncbi.nlm.nih.gov/compound/Flurazepam. Accessed Oct. 24, 2023.

Store between 20-25°C. Protect from light.

Hypnotics & Sedatives

N05CD01 - flurazepam ; Belongs to the class of benzodiazepine derivatives. Used as hypnotics and sedatives.

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