Mechanism of effect
Depresses CNS activity by binding to barbiturate site at GABA-receptor complex enhancing GABA activity, depressing reticular activity system; higher doses may be gabamimetic.
Pharmacokinetics
Absorption: Well absorbed (90%)
Half-life elimination: 28 hr
Duration: 3-4 hr
Vd: 1.5 L/kg
Onset: 15-30 min (hypnosis)
Excretion: Urine
Protein Bound: 45-60%
Metabolism: hepatic microsomal enzymes, glucuronidationExcretion: mostly urine as metabolites (<5% unchanged)
Enzymes induced: Primarily CYP2C9/10; CYP2C8, CYP2C9
Time to Peak: Serum concentration: Oral: Within 2 to 4 hour
Duration of Action:Hypnosis: Oral: 3 to 4 hours with 100 mg dose
Drug indications
Hypnotic
Pre-procedure Sedation
Dosage
-Hypnotic
Short-term treatment:100 mg PO qHS
Do not administer for more than 2 weeks
-Pre-procedure Sedation
200-300 mg PO 1-2 hours before surgery
Drug contraindications
-Barbiturate hypersensitivity
-Porphyria
-Liver disease
-Severe respiratory disease
-Renal impairment
-Sleep apnea
-Alcoholism
-Drug dependence
-Suicidal tendencies
Side effects
Drowsiness , Abnormality in thinking, agitation, angioedema, anxiety, apnea, ataxia, bradycardia, central nervous system depression, sleep disorder (complex sleep-related behaviors, including cooking, driving, eating, and making phone calls while sleeping), confusion, constipation, dizziness, exfoliative dermatitis, fever, hallucination, headache, hepatotoxicity, hyperexcitability, hyperkinesis, hypotension, hypoventilation, insomnia, megaloblastic anemia, nausea, nervousness, nightmares, pain at injection site, skin rash, syncope, vomiting
Interactions
Protamine sulfat , fentanyl , Ranolazine , Sodium Oxybate , Tapentadol , Phenindione , Copanlisib , Tinzaparin , Dabrafenib , Fostamatinib , Acetaminophen and benzhydrocodone , Atenolol , Estrogen , Brimonidine , Pramipexole , Primidone , Thalidomide , Cannabis , Suvorexant , Alizapride , Cannabidiol , Blonanserin , lofexidine , Rotigotine , Chlorphenesin , Metipranolol , Clevidipine , Brexanolone , Bromperidol , Ulipristal , Doxylamine , Trimeprazine , Perampanel , Paraldehyde , Dyphylline , (Vitamin B6 (Pyridoxine , Droperidol , Teniposide , Hydrocodone , Felbamate , Orphenadrine , Azelastine , Buprenorphine , Levobunolol , Oxycodone , Serotonin , Methoxyflurane , Minocycline , Magnesium sulfate , Warfarin , Valproate sodium , Vitamin K , Chloramphenicol , Doxycycline , Ropinirole , Zolpidem , Cyclosporine , Griseofulvin , Lamotrigine , tezacaftor/ivacaftor , Oxymorphone , Abemaciclib , Triphasic , Ethchlorvynol , GefitinibAlcohol ,Alizapride ,Azelastine (Nasal),
Beta-Blockers Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol.
Blonanserin ,Blood Pressure Lowering Agents,
Brexanolone,Brimonidine (Topical),
Bromopride,Bromperidol,Buprenorphine,
Calcium Channel Blockers. Exceptions: Clevidipine. Monitor therapy
Cannabidiol ,Cannabis,Chloramphenicol (Systemic),
Chlormethiazole,Chlorphenesin Carbamate,
CNS Depressants ,CycloSPORINE (Systemic),
Dimethindene (Topical),Doxycycline,Doxylamine,
Dronabinol,Droperidol ,Esketamine ,Estrogen Derivatives ,Felbamate ,Flunitrazepam,Griseofulvin
Hemin,HYDROcodone ,HydrOXYzine ,Kava Kava ,
LamoTRIgine,Lemborexant ,Lofexidine ,Magnesium Sulfate ,Methotrimeprazine,Methoxyflurane,MetyroSINE,
Mianserin,Minocycline (Systemic),Multivitamins/Minerals (with ADEK, Folate, Iron),Nabilone,Opioid Agonists
Orphenadrine,Oxomemazine,OxyCODONE
Paraldehyde,Perampanel ,Piribedil,Pramipexole,
Primidone,Progestins,Propacetamol,Pyridoxine,
Rifamycin Derivatives,ROPINIRole,Rotigotine,
Rufinamide,Selective Serotonin Reuptake Inhibitors,
Sodium Oxybate,Somatostatin acetate,Suvorexant,Tapentadol,Teniposide,
Tetrahydrocannabinol:
Tetrahydrocannabinol and Cannabidiol ,
Thalidomide ,Theophylline Derivatives: Exceptions: Dyphylline. Monitor therapy ,Tricyclic Antidepressants,Trimeprazine ,Ulipristal ,Valproate Products ,Vitamin K Antagonists (eg, warfarin),Zolpidem
Alerts
-Causes CNS depression and impairs mental and physical abilities
-Paradoxical responses: Cay cause hyperactivity and agitation
-Use with caution in patients with depression, hepatic or renal impairment, cardiovascular diseases, or respiratory diseases
-Sleep-related activities: An increased risk for hazardous sleep-related activities such as sleep-driving; cooking and eating food, and making phone calls while asleep have also been noted
- Hypersensitivity reactions
-Abrupt cessation may precipitate withdrawal, including status epilepticus in epileptic patients.
Points of recommendation
-Discontinue treatment in patients who report a sleep-driving episode
-Effects may be potentiated when used with other sedative drugs or ethanol.
-Symptomatic treatment of insomnia should be initiated only after careful evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7-10 days may indicate psychiatric and/or medical illnes
Pregnancy level
DBreast feeding warning
secreted in breast milk; use with caution
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