ROHYPNOL

Indications

• Severe insomnia
• Premedication for surgical procedures

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations.

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Flunitrazepam binds nonspecifically to benzodiazepine receptors BNZ1 and BNZ2 in the central nervous system. This binding enhances the effects of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) at GABA-A receptors, increasing the affinity of GABA for its receptor. The resultant activation of the GABA-A receptor opens chloride channels, leading to hyperpolarization of the neuronal cell membrane, which inhibits neuronal excitability and induces sedative and anxiolytic effects.

Pharmacodynamics

Flunitrazepam exhibits significant hypnotic and sedative effects, making it effective for managing severe sleep disorders. Additionally, its anxiolytic properties reduce anxiety levels, while its muscle relaxant effects alleviate muscle tension. The drug's potency is associated with a high risk of dependence and potential for abuse, particularly due to its rapid onset and duration of action.

Pharmacokinetics

Flunitrazepam is well-absorbed following oral administration, with peak plasma concentrations typically reached within 1 to 2 hours. It undergoes extensive hepatic metabolism, primarily via cytochrome P450 enzymes, resulting in active metabolites. The elimination half-life of flunitrazepam varies, generally ranging from 18 to 26 hours, depending on individual metabolic differences. The drug is primarily excreted in urine as metabolites, and its pharmacokinetic profile can be affected by factors such as age, concomitant medications, and liver function.

Contra-indications

• Hypersensitivity to flunitrazepam or any of its components
• Severe respiratory insufficiency
• Sleep apnoea syndrome
• Myasthenia gravis
• Severe hepatic impairment

Adverse effects

• Drowsiness
• Confusion
• Amnesia
• Dizziness
• Ataxia
• Hypotension
• Respiratory depression
• Paradoxical reactions such as agitation or aggression

Interactions

• Other central nervous system depressants (e.g., alcohol, opioids, barbiturates) may enhance sedative effects
• CYP450 enzyme inhibitors may increase flunitrazepam plasma levels
• CYP450 enzyme inducers may decrease flunitrazepam plasma levels

Precautions

• Use with caution in elderly patients due to increased sensitivity and risk of falls
• Monitor for signs of dependency or abuse
• Caution in patients with a history of substance use disorders
• Gradual withdrawal recommended to avoid rebound insomnia or withdrawal symptoms

Pregnancy

Flunitrazepam is not recommended during pregnancy due to potential risks to the fetus, including withdrawal symptoms in newborns or teratogenic effects.

Breast-feeding

Flunitrazepam is excreted in breast milk, and caution is advised when administering to breastfeeding mothers due to potential effects on the infant.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Tablets
• Oral solutions

Mechanism of action

Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

Pharmacodynamics

Flunitrazepam is a powerful hypnotic drug that is a benzodiazepine derivative. It has powerful hypnotic, sedative, anxiolytic, and skeletal muscle relaxant properties. The drug is sometimes used as a date rape drug. In the United States, the drug has not been approved by the Food and Drug Administration for medical use, and is considered to be an illegal drug. It has however been approved in the United Kingdom and other countries.