Flurazepam is a longer-acting benzodiazepine that is primarily used to treat patients with insomnia who have difficulty falling asleep or maintaining sleep.
Flurazepam Uses:
-
Insomnia:
-
- It is used to treat patients who have difficulty falling asleep, maintaining sleep, and/ o those who complain of early morning awakenings.
-
Flurazepam dose in Adults
Flurazepam dose in the treatment of Insomnia in Adults:
- The starting dose is 15 mg at bedtime for women, and 15 to 30 mg at bedtime for men;
- The dose may be increased to 30 mg at bedtime if required based on the individual’s response.
Flurazepam dose in Childrens
Flurazepam dose in the treatment of Insomnia in adolescents aged 15 years or more: Limited data available:
- 15 mg per oral at bedtime.
Pregnancy Risk Factor C
- All benzodiazepines are capable of crossing the placental boundary. There have been adverse fetal outcomes reported with many of them.
- A neonate may experience withdrawal symptoms as soon as they are born or the "floppy infant Syndrome" within days to weeks.
- However, some benzodiazepines may also have teratogenic effects. Data are limited.
- A maternal use of benzodiazepines in pregnancy has been linked to low birth weight, hypoglycemia, and respiratory depression among neonates.
- The infant's serum levels of N desalkylflurazepam was measured in the first four days after its use.
- Flurazepam is not recommended during pregnancy.
- It has been shown to be associated with neonatal depressive disorder in pregnant women who have taken it for more than ten days before giving birth.
Use flurazepam while breastfeeding
- Although information is scarce, it is possible that all benzodiazepines will be found in breastmilk.
- This could cause adverse effects such as lethargy, drowsiness, impaired feeding, and weight loss.
Dose in Kidney Disease:
- Use with caution in patients with kidney disease.
- The manufacture has not provided any recommendations regarding dosage adjustment in kidney impairment.
Dose in Liver disease:
- Use with caution in patients with liver disease.
- The manufacture has not provided any recommendations regarding dosage adjustment in hepatic impairment.
Side effects of Flurazepam:
-
Cardiovascular:
- Chest Pain
- Syncope
- Flushing
- Hypotension
- Palpitations
-
Central Nervous System:
- Abnormal Reflexes (Slowing)
- Confusion
- Depression
- Dizziness
- Drowsiness
- Drug Dependence
- Dysarthria
- Euphoria
- Apprehension
- Ataxia
- Bitter Taste
- Body Pain
- Falling
- Hallucination
- Hangover Effect
- Headache
- Irritability
- Memory Impairment
- Nervousness
- Paradoxical Reaction
- Restlessness
- Slurred Speech
- Staggering
- Talkativeness
-
Dermatologic:
- Diaphoresis
- Pruritus
- Skin Rash
-
Endocrine & Metabolic:
- Weight Gain
- Weight Loss
-
Gastrointestinal:
- Constipation
- Gastric Distress
- Gastrointestinal Pain
- Heartburn
- Increased Appetite
- Nausea
- Sialorrhea
- Vomiting
- Decreased Appetite
- Diarrhea
- Xerostomia
-
Hematologic & Oncologic:
- Granulocytopenia
- Leukopenia
-
Hepatic:
- Cholestatic Jaundice
- Increased Serum Alkaline Phosphatase
- Increased Serum ALT
- Abnormal Bilirubin Levels (Total Bilirubin Increased)
- Increased Serum AST
-
Neuromuscular & Skeletal:
- Arthralgia
- Weakness
-
Ophthalmic:
- Accommodation Disturbance
- Blurred Vision
- Burning Sensation Of Eyes
-
Respiratory:
- Apnea
- Dyspnea
Contraindication to Flurazepam Include:
- Hypersensitivity to flurazepam or other benzodiazepines or any component of this formulation
- Pregnancy
- Patients with a history of hypersensitivity reactions to one or more benzodiazepine drugs may be at risk for allergic cross-reactivity.
Warnings and precautions
-
Anterograde amnesia
- Memory loss (anterograde amnesia) has been linked to benzodiazepines.
-
Depression in the CNS:
- It can lead to CNS depression that may result in mental or physical impairments.
- Patients who are unable to perform tasks that require mental alertness should be warned about the dangers of using the drug.
-
Hypersensitivity reactions
- Flurazepam has been linked to hypersensitivity reactions including anaphylaxis, angioedema and anaphylaxis. Flurazepam should not be used on patients who have angioedema.
-
Paradoxical reactions
- Paradoxical reactions can occur, which may include aggressive or hyperactive behavior.
- Children and adolescents, patients who are older, patients with personality disorders or psychiatric disorders, and patients who have a history of such disorders, are at greater risk.
-
Activities that are sleep-related:
- The use of benzodiazepines has been linked to sleep-related dangerous activities like sleep-driving, cooking, eating, and making calls while asleep.
-
Depression
- Patients who have had a history of depression could be at greater risk for suicidal tendencies. This should be taken with caution.
- To avoid overdosing, patients with depression should only be given the lowest effective dose and for as short a time as possible.
- Some patients may experience a worsening in their depression when they are on benzodiazepine therapy.
-
Use of drugs:
- Patients who are addicted to drugs or alcoholics should be warned about the dangers of using benzodiazepines.
- Patients who abuse drugs and alcoholics are more likely to become dependent on drugs.
- Patients may develop tolerance to the drug or psychological dependence over time.
-
Hepatic impairment
- Patients with hepatic impairment should be cautious.
-
Renal impairment
- Patients with impaired renal function should be cautious.
-
Respiratory disease
- Patients with respiratory diseases should be cautious.
Flurazepam: Drug Interaction
|
Risk Factor C (Monitor therapy) |
|
|
Alcohol (Ethyl) |
CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). |
|
Alizapride |
May enhance the CNS depressant effect of CNS Depressants. |
|
Aprepitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Bosentan |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Brexanolone |
CNS Depressants may enhance the CNS depressant effect of Brexanolone. |
|
Brimonidine (Topical) |
May enhance the CNS depressant effect of CNS Depressants. |
|
Bromopride |
May enhance the CNS depressant effect of CNS Depressants. |
|
Cannabidiol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Cannabis |
May enhance the CNS depressant effect of CNS Depressants. |
|
Chlorphenesin Carbamate |
May enhance the adverse/toxic effect of CNS Depressants. |
|
Clofazimine |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
CNS Depressants |
May enhance the adverse/toxic effect of other CNS Depressants. |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
CYP3A4 Inhibitors (Moderate) |
May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). |
|
Deferasirox |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Dimethindene (Topical) |
May enhance the CNS depressant effect of CNS Depressants. |
|
Doxylamine |
May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. |
|
Dronabinol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Duvelisib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Erdafitinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Erdafitinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Esketamine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Fosamprenavir |
May increase the serum concentration of Flurazepam. |
|
Fosaprepitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Fosnetupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
HydrOXYzine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Ivosidenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Kava Kava |
May enhance the adverse/toxic effect of CNS Depressants. |
|
Larotrectinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Lofexidine |
May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Magnesium Sulfate |
May enhance the CNS depressant effect of CNS Depressants. |
|
Melatonin |
May enhance the sedative effect of Benzodiazepines. |
|
MetyroSINE |
CNS Depressants may enhance the sedative effect of MetyroSINE. |
|
Minocycline |
May enhance the CNS depressant effect of CNS Depressants. |
|
Mirtazapine |
CNS Depressants may enhance the CNS depressant effect of Mirtazapine. |
|
Nabilone |
May enhance the CNS depressant effect of CNS Depressants. |
|
Netupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Palbociclib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Piribedil |
CNS Depressants may enhance the CNS depressant effect of Piribedil. |
|
Pramipexole |
CNS Depressants may enhance the sedative effect of Pramipexole. |
|
Ritonavir |
May increase the serum concentration of Flurazepam. |
|
ROPINIRole |
CNS Depressants may enhance the sedative effect of ROPINIRole. |
|
Rotigotine |
CNS Depressants may enhance the sedative effect of Rotigotine. |
|
Rufinamide |
May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. |
|
Saquinavir |
May increase the serum concentration of Flurazepam. |
|
Sarilumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Selective Serotonin Reuptake Inhibitors |
CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. |
|
Siltuximab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Simeprevir |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Teduglutide |
May increase the serum concentration of Benzodiazepines. |
|
Tetrahydrocannabinol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Tetrahydrocannabinol and Cannabidiol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Tocilizumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Trimeprazine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Yohimbine |
May diminish the therapeutic effect of Antianxiety Agents. |
|
Risk Factor D (Consider therapy modification) |
|
|
Blonanserin |
CNS Depressants may enhance the CNS depressant effect of Blonanserin. |
|
Buprenorphine |
CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. |
|
Chlormethiazole |
May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. |
|
CloZAPine |
Benzodiazepines may enhance the adverse/toxic effect of CloZAPine. Management: Consider decreasing the dose of (or possibly discontinuing) benzodiazepines prior to initiating clozapine. |
|
CYP3A4 Inducers (Strong) |
May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
|
CYP3A4 Inhibitors (Strong) |
May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). |
|
Dabrafenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
|
Droperidol |
May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Enzalutamide |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. |
|
Flunitrazepam |
CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. |
|
HYDROcodone |
CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
Lorlatinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
|
Methadone |
Benzodiazepines may enhance the CNS depressant effect of Methadone. Management: Clinicians should generally avoid concurrent use of methadone and benzodiazepines when possible; any combined use should be undertaken with extra caution. |
|
Methotrimeprazine |
CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. |
|
MiFEPRIStone |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. |
|
Mitotane |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. |
|
Opioid Agonists |
CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
OxyCODONE |
CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
Perampanel |
May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. |
|
Pitolisant |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. |
|
St John's Wort |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
|
Stiripentol |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. |
|
Suvorexant |
CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. |
|
Tapentadol |
May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
Theophylline Derivatives |
May diminish the therapeutic effect of Benzodiazepines. |
|
Zolpidem |
CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. |
|
Risk Factor X (Avoid combination) |
|
|
Azelastine (Nasal) |
CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). |
|
Bromperidol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Conivaptan |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Fusidic Acid (Systemic) |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Idelalisib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
OLANZapine |
May enhance the adverse/toxic effect of Benzodiazepines. Management: Avoid concomitant use of parenteral benzodiazepines and IM olanzapine due to risks of additive adverse events (e.g., cardiorespiratory depression). Olanzapine prescribing information provides no specific recommendations regarding oral administration. |
|
Orphenadrine |
CNS Depressants may enhance the CNS depressant effect of Orphenadrine. |
|
Oxomemazine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Paraldehyde |
CNS Depressants may enhance the CNS depressant effect of Paraldehyde. |
|
Sodium Oxybate |
Benzodiazepines may enhance the CNS depressant effect of Sodium Oxybate. |
|
Thalidomide |
CNS Depressants may enhance the CNS depressant effect of Thalidomide. |
Monitoring parameters:
- Daytime alertness;
- respiratory rate;
- behavior profile
How to administer Flurazepam?
- It should be taken at bedtime without regard to meals.
Mechanism of action of Flurazepam:
- It binds to stereospecific GABA neuron postsynaptic GABA receptors at multiple sites in the central nervous system including the limbic and reticular systems.
- Increased neuronal membrane permeability for chloride ions is possible by enhancing the inhibitory effect GABA has on neuronal excitability.
- This shift in the chloride ions leads to hyperpolarization (a state that is less excitable) and stabilization.
- Benzodiazepine effects and receptors appear to be linked with the GABA-A receptors. Benzodiazepines don't bind to GABAB receptors.
Absorption:
- Rapid
Protein binding:
- Flurazepam: ~97 percent; N-desalkylflurazepam: ~98 percent.
Metabolism:
- Hepatic to N-desalkylflurazepam (active) and N-hydroxyethylflurazepam
Half-life elimination:
- Flurazepam: 2.3 hours
- N-desalkylflurazepam:
- Adults:
- Single dose: 74 to 90 hours;
- Multiple doses: 111 to 113 hours
- Elderly (61 to 85 years):
- Single dose: 120 to 160 hours;
- Multiple doses: 126 to 158 hours
- Adults:
Time to peak, serum:
- Flurazepam: 30 to 60 minutes
- N-desalkylflurazepam: 10.6 hours (range: 7.6 to 13.6 hours)
- N-hydroxyethylflurazepam: ~1 hour
Excretion:
- Urine: N-hydroxyethylflurazepam (22 percent to 55 percent );
- N-desalkylflurazepam (<1%)
International Brand Names of Flurazepam:
- BIO-Flurazepam
- Dalmane 15
- Fordrim
- Insumin
- Manlsum
- Nergart
- Noctosom
- Slipam
- Somlan
- Dalmane 30
- PMS-Flurazepam
- Som-Pam
- Aluctin
- Dalmadorm
- Dalmane
- Dalmapam
- Dalpam
- Dormodor
- Felison
- Florapam
- Flunox
- Fluralema
- Fluraz
- Fluzepam
- Staurodorm
- Valdorm
Flurazepam Brand Names in Pakistan:
Flurazepam (HCl) Tablets 15 mg in Pakistan |
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