Bestrol - General Information
A triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of panic disorders, with or without agoraphobia, and in generalized anxiety disorders. (From AMA Drug Evaluations Annual, 1994, p238)
Pharmacology of Bestrol
Bestrol, a benzodiazepine, is used to treat panic disorder and anxiety disorder. Unlike chlordiazepoxide, clorazepate, and prazepam, alprazolam has a shorter half-life and metabolites with minimal activity. Like other triazolo benzodiazepines such as triazolam, alprazolam may have significant drug interactions involving the hepatic cytochrome P-450 3A4 isoenzyme. Clinically, all benzodiazepines cause a dose-related central nervous system depressant activity varying from mild impairment of task performance to hypnosis. Unlike other benzodiazepines, alprazolam may also have some antidepressant activity, although clinical evidence of this is lacking.
Bestrol for patients
Alprazolam is used for the treatment of anxiety, panic disorder, and insomnia. Inform your physican if you are pregnant or nursing. Alprazolam may cause dizziness and drowsiness; use caution while driving or operating hazardous machinery. Do not take any other sedating drugs or drink alcohol while taking this medication. Alprazolam may be habit forming. Withdrawal symptoms may occur after you stop taking it. Alprazolam may be taken with or without food.
For All Users of Alprazolam
To assure safe and effective use of benzodiazepines, all patients prescribed alprazolam should be provided with the following guidance. In addition, panic disorder patients, for whom doses greater than 4 mg/day are typically prescribed, should be advised about the risks associated with the use of higher doses.
1. Inform your physician about any alcohol consumption and medicine you are taking now, including medication you may buy without a prescription. Alcohol should generally not be used during treatment with benzodiazepines.
2. Not recommended for use in pregnancy. Therefore, inform your physician if you are pregnant, if you are planning to have a child, or if you become pregnant while you are taking this medication.
3. Inform your physician if you are nursing.
4. Until you experience how this medication affects you, do not drive a car or operate potentially dangerous machinery, etc.
5. Do not increase the dose even if you think the medication "does not work anymore" without consulting your physician. Benzodiazepines, even when used as recommended, may produce emotional and/or physical dependence.
6. Do not stop taking this medication abruptly or decrease the dose without consulting your physician, since withdrawal symptoms can occur.
Additional Advice for Panic Disorder Patients
The use of alprazolam at doses greater than 4 mg/day, often necessary to treat panic disorder, is accompanied by risks that you need to carefully consider. When used at high doses greater than 4 mg/day, which may or may not be required for your treatment, alprazolam has the potential to cause severe emotional and physical dependence in some patients and these patients may find it exceedingly difficult to terminate treatment. In two controlled trials of 6 to 8 weeks duration where the ability of patients to discontinue medication was measured, 7-29% of patients treated with alprazolam did not completely taper off therapy. In a controlled postmarketing discontinuation study of panic disorder patients, the patients treated with doses of alprazolam greater than 4 mg/day had more difficulty tapering to zero dose than patients treated with less than 4 mg/day. In all cases, it is important that your physician help you discontinue this medication in a careful and safe manner to avoid overly extended use of alprazolam.
In addition, the extended use at doses greater than 4 mg/day appears to increase the incidence and severity of withdrawal reactions when alprazolam is discontinued. These are generally minor but seizure can occur, especially if you reduce the dose too rapidly or discontinue the medication abruptly. Seizure can be life-threatening.
The benzodiazepines, including alprazolam, produce additive CNS depressant effects when co-administered with other psychotropic medications, anticonvulsants, antihistaminics, ethanol, and other drugs which themselves produce CNS depression.
The steady state plasma concentrations of imipramine and desipramine have been reported to be increased an average of 31% and 20%, respectively, by the concomitant administration of alprazolam tablets in doses up to 4 mg/day. The clinical significance of these changes is unknown.
Drugs That Inhibit Alprazolam Metabolism Via Cytochrome P450 3A: The initial step in alprazolam metabolism is hydroxylation catalyzed by cytochrome P450 3A (CYP 3A). Drugs which inhibit this metabolic pathway may have a profound effect on the clearance of alprazolam.
Drugs Demonstrated to be CYP 3A Inhibitors of Possible Clinical Significance on the Basis of Clinical Studies Involving Alprazolam (caution is recommended during coadministration with alprazolam):
- Fluoxetine: Coadministration of fluoxetine with alprazolam increased the maximum plasma concentration of alprazolam by 46%, decreased clearance by 21%, increased half-life by 17%, and decreased measured psychomotor performance.
- Propoxyphene: Coadministration of propoxyphene decreased the maximum plasma concentration of alprazolam by 6%, decreased clearance by 38%, and increased half-life by 58%.
- Oral Contraceptives: Coadministration of oral contraceptives increased the maximum plasma concentration of alprazolam by 18%, decreased clearance by 22%, and increased half-life by 29%.
Drugs and other substances demonstrated to be CYP 3A inhibitors on the basis of clinical studies involving benzodiazepines metabolized similarly to alprazolam or on the basis of in vitro studies with alprazolam or other benzodiazepines (caution is recommended during coadministration with alprazolam): Available data from clinical studies of benzodiazepines other than alprazolam suggest a possible drug interaction with alprazolam for the following: diltiazem, isoniazid, macrolide antibiotics such as erythromycin and clarithromycin, and grapefruit juice. Data from in vitro studies of alprazolam suggest a possible drug interaction with alprazolam for the following: sertraline and paroxetine. Data from in vitro studies of benzodiazepines other than alprazolam suggest a possible drug interaction for the following: ergotamine, cyclosporine, amiodarone, nicardipine, and nifedipine. Caution is recommended during the coadministration of any of these with alprazolam.
Alprazolam tablets are contraindicated in patients with known sensitivity to this drug or other benzodiazepines. Alprazolam may be used in patients with open angle glaucoma who are receiving appropriate therapy, but is contraindicated in patients with acute narrow angle glaucoma.
Alprazolam is contraindicated with ketaconazole and itraconzole, since these medications significantly impair the oxidative metabolism mediated by cytochrome P450 3A (CYP 3A).
Additional information about Bestrol
Bestrol Indication: For the management of anxiety disorder or the short-term relief of symptoms of anxiety and for the treatment of panic disorder, with or without agoraphobia.
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.
Drug Interactions: Amprenavir Increases the effect and toxicity of benzodiazepine
Aprepitant Increases the effect and toxicity of benzodiazepine
Carbamazepine Reduces the effect of the benzodiazepine
Cimetidine Increases the effect of the benzodiazepine
Clarithromycin The macrolide increases the effect of the benzodiazepine
Clozapine Increased risk of toxicity
Delavirdine The antiviral agent increases the effect and toxicity of benzodiazepine
Digoxin The benzodiazepine increases the effect
Efavirenz The antiviral agent increases the effect and toxicity of benzodiazepine
Erythromycin The macrolide increases the effect of the benzodiazepine
Ethotoin Possible increased levels of the hydantoin, decrease of benzodiazepine
Fluconazole Increases the effect of the benzodiazepine
Indinavir The protease inhibitor increases the effect of the benzodiazepine
Itraconazole The imidazole increase the effect of the benzodiazepine
Ketoconazole The imidazole increases the effect of the benzodiazepine
Mephenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine
Nelfinavir The protease inhibitor increases the effect of the benzodiazepine
Omeprazole Increases the effect of the benzodiazepine
Phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine
Ritonavir The protease inhibitor increases the effect of the benzodiazepine
Saquinavir The protease inhibitor increases the effect of the benzodiazepine
Telithromycin Increases the effect/toxicity of the benzodiazepine
Voriconazole The imidazole increases the effect of the benzodiazepine
Erythromycin The macrolide increases the effect of the benzodiazepine
Fosamprenavir Amprenavir increases the effect and toxicity of benzodiazepine
Fosphenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine
Josamycin The macrolide increases the effect of the benzodiazepine
Kava Kava increases the effect of the benzodiazepine
St. John's Wort St. John's Wort could reduce the benzodiazepine effect
Food Interactions: Avoid alcohol.
Take with food.
Avoid excessive quantities of coffee or tea (Caffeine).
Avoid taking with grapefruit juice.
Generic Name: Alprazolam
Drug Category: Anti-anxiety Agents; GABA Modulators; Hypnotics and Sedatives; Benzodiazepines
Drug Type: Small Molecule; Illicit; Approved
Absorption: Readily absorbed from the gastrointestinal tract. Bioavailability is 80-90%.
Toxicity (Overdose): Oral, mouse: LD50=1020 mg/kg. Symptoms of overdose include confusion, coma, impaired coordination, sleepiness, and slowed reaction time.
Protein Binding: 80% (mainly to albumin)
Biotransformation: Hepatic. Hydroxylated in the liver to α-hydroxyalprazolam, which is also active. This and other metabolites are later excreted in urine as glucuronides.
Half Life: 6.3-26.9 hours
Dosage Forms of Bestrol: Tablet Oral
Chemical IUPAC Name: 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
Chemical Formula: C17H13ClN4
Alprazolam on Wikipedia: https://en.wikipedia.org/wiki/Alprazolam
Organisms Affected: Humans and other mammals