Usage
- Flurazepam is prescribed for the short-term treatment of insomnia characterized by difficulty falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. It is not intended for long-term use.
- Pharmacological classification: Hypnotic, Benzodiazepine, GABAA receptor agonist
- Mechanism of Action: Flurazepam enhances the effect of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) by binding to the benzodiazepine site on the GABAA receptor complex. This leads to increased chloride influx into neurons, resulting in hyperpolarization and decreased neuronal excitability.
Alternate Names
- No widely used alternate names for the generic drug Flurazepam exist.
- Brand Name: Dalmane
How It Works
- Pharmacodynamics: Flurazepam exerts its hypnotic effect by potentiating GABAergic neurotransmission, leading to CNS depression. This results in decreased sleep latency, increased total sleep time, and reduced awakenings.
- Pharmacokinetics:
- Absorption: Flurazepam is rapidly absorbed after oral administration.
- Metabolism: Flurazepam is extensively metabolized in the liver, primarily by CYP3A4 and CYP2C19 enzymes, to several active metabolites, including desalkylflurazepam, which has a long half-life. This contributes to the drug’s prolonged duration of action.
- Elimination: Flurazepam and its metabolites are primarily excreted in the urine.
- Mode of Action: Flurazepam binds to the benzodiazepine site on the GABAA receptor complex, allosterically modulating the receptor and increasing the affinity of GABA for its binding site. This leads to enhanced GABA-mediated chloride influx, neuronal hyperpolarization, and reduced neuronal excitability.
- Elimination Pathways: Primarily renal excretion of metabolites after hepatic metabolism via CYP3A4 and CYP2C19.
Dosage
Standard Dosage
Adults:
- Initial dose: 15 mg orally once daily at bedtime for women; 15 mg or 30 mg orally once daily at bedtime for men.
- The dose can be increased to a maximum of 30 mg if necessary for efficacy.
- The lowest effective dose should be used to minimize the risk of dose-related side effects.
Children:
- Flurazepam is contraindicated in children under 15 years of age. Safety and efficacy have not been established in this population.
Special Cases:
- Elderly Patients: The initial dose should be limited to 15 mg due to increased sensitivity to the drug’s effects.
- Patients with Renal Impairment: Caution is advised; consider dosage reduction. Specific recommendations based on creatinine clearance may be necessary.
- Patients with Hepatic Dysfunction: Caution is advised; consider dosage reduction as metabolism may be impaired. Close monitoring is recommended.
- Patients with Comorbid Conditions: Use with caution in patients with respiratory insufficiency, sleep apnea, myasthenia gravis, severe liver disease, or a history of drug or alcohol abuse.
Clinical Use Cases
- Flurazepam is not indicated for use in settings requiring intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use is strictly limited to the short-term treatment of insomnia.
Dosage Adjustments
- Dosage adjustments may be necessary based on individual patient response, age, concomitant medications (especially CNS depressants), and the presence of renal or hepatic impairment.
Side Effects
Common Side Effects
- Drowsiness, dizziness, lightheadedness, ataxia, daytime sedation, fatigue, and cognitive impairment.
Rare but Serious Side Effects
- Severe allergic reactions (anaphylaxis), respiratory depression, paradoxical reactions (e.g., anxiety, agitation, hallucinations), and withdrawal symptoms upon discontinuation.
Long-Term Effects
- Cognitive impairment, dependence, tolerance, and withdrawal symptoms.
Adverse Drug Reactions (ADR)
- Angioedema, anaphylaxis, complex sleep-related behaviors (e.g., sleep-walking, sleep-driving, sleep-eating), and severe withdrawal symptoms (e.g., seizures, delirium).
Contraindications
- Hypersensitivity to flurazepam or other benzodiazepines.
- Severe respiratory insufficiency.
- Sleep apnea syndrome.
- Myasthenia gravis.
- Severe hepatic impairment.
Drug Interactions
- CNS depressants (e.g., alcohol, opioids, antihistamines): Increased risk of respiratory depression and excessive sedation.
- CYP3A4 and CYP2C19 inhibitors (e.g., cimetidine, erythromycin): May increase flurazepam plasma levels.
- CYP3A4 inducers (e.g., rifampin, St. John’s wort): May decrease flurazepam plasma levels.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X. Flurazepam is contraindicated in pregnancy due to the risk of fetal harm.
- Breastfeeding: Flurazepam is likely excreted in breast milk. Breastfeeding is not recommended while taking this medication.
Drug Profile Summary
- Mechanism of Action: GABAA receptor agonist, enhances GABAergic neurotransmission, leading to CNS depression.
- Side Effects: Drowsiness, dizziness, ataxia, confusion, daytime sedation. Rarely, paradoxical reactions, respiratory depression.
- Contraindications: Hypersensitivity, severe respiratory insufficiency, sleep apnea, myasthenia gravis, severe hepatic impairment, pregnancy.
- Drug Interactions: CNS depressants, CYP3A4 inhibitors/inducers.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy, not recommended during breastfeeding.
- Dosage: Adults: 15-30 mg orally at bedtime; elderly: 15 mg initially.
- Monitoring Parameters: Respiratory rate, mental status.
Popular Combinations
- Flurazepam is typically not used in combination with other medications for the treatment of insomnia.
Precautions
- Assess for risk of drug abuse, misuse, and addiction.
- Avoid abrupt discontinuation. Taper dose gradually to prevent withdrawal.
- Caution in patients with respiratory, hepatic, or renal impairment, and in elderly patients.
- Avoid alcohol and other CNS depressants.
- Caution patients about engaging in activities requiring alertness (e.g., driving).
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Flurazepam?
A: The recommended initial dose is 15 mg orally at bedtime for women and 15 mg or 30 mg for men. Elderly or debilitated patients should start with 15 mg.
Q2: How long can a patient take Flurazepam?
A: Flurazepam should be used for the shortest duration possible, typically not exceeding 7-10 consecutive days. Use for more than 2-3 weeks requires careful re-evaluation.
Q3: What are the common side effects of Flurazepam?
A: Common side effects include drowsiness, dizziness, lightheadedness, ataxia, and residual daytime sedation.
Q4: What are the contraindications for Flurazepam?
A: Flurazepam is contraindicated in patients with hypersensitivity to benzodiazepines, severe respiratory insufficiency, sleep apnea, myasthenia gravis, and severe hepatic impairment. It is also contraindicated during pregnancy.
Q5: Does Flurazepam interact with other medications?
A: Yes, Flurazepam interacts with CNS depressants (e.g., alcohol, opioids), CYP3A4 inhibitors (e.g., cimetidine), and CYP3A4 inducers (e.g., rifampin).
Q6: Can Flurazepam be used during pregnancy or breastfeeding?
A: Flurazepam is contraindicated during pregnancy (Pregnancy Category X) and is not recommended during breastfeeding.
Q7: What should be done in case of a Flurazepam overdose?
A: Flumazenil, a benzodiazepine receptor antagonist, can be used to reverse the effects of a Flurazepam overdose. Supportive care may also be necessary.
Q8: Are there any withdrawal symptoms associated with Flurazepam discontinuation?
A: Yes, abrupt discontinuation of Flurazepam can lead to withdrawal symptoms, including anxiety, insomnia, tremors, and seizures. The dose should be tapered gradually to minimize withdrawal effects.
Q9: How does Flurazepam compare to other hypnotic medications?
A: Flurazepam has a long duration of action compared to some other hypnotics due to its active metabolites. This can lead to residual daytime sedation. Other hypnotics, such as Zolpidem and Zaleplon, have shorter durations of action.
