Alprazolam (Dosing, Interaction, Side Effect, Administration, Etc..)

DRUG CLASS:
Anti Anxiety
Benzodiazepine

DOSING:

Adult Dose

:
Important Note:
Beers Criteria:

Use

caution or avoid

use as

potentially inappropriate in older adults.

General Dosage Information:
Decrease the daily dose by 0.5 mg every 3 days when discontinuing therapy
Patients receiving divided

doses of alprazolam

immediate-release tablets may be switched to alprazolam
extended-release tablets at the same total

daily dose

taken once daily

Anxiety:
(Immediate-release or orally disintegrating tablet)
0.25 to 0.5 mg orally 3 times a day; may increase every 3 to 4 days if necessary;

Maximum daily dose

; 4 mg in divided doses

Depression:
2.5 to 3 mg orally daily in divided doses (off-label dosage)

Panic disorder:
(Immediate-release or orally disintegrating tablet)
0.5 mg orally 3 times a day; may increase dosage by up to 1 mg/day every 3 to 4 days; usual dosage range; 1 to 10 mg/day (mean; 5 to 6 mg/day)

(Extended-release tablet)
0.5 to 1 mg orally once daily in the morning; may increase by up to 1 mg/day every 3 to 4 days; usual range is 3 to 6 mg/day

Pediatric Dose

:
Beers Criteria: Use caution or avoid use as potentially inappropriate in older adults.

INDICATIONS:
FDA LABELED INDICATIONS:
Anxiety
Panic disorder

NON FDA LABELED INDICATIONS:
Depression

MECHANISM OF ACTION:

Alprazolam

; a CNS drug from the 1; 4 benzodiazepine class; possesses an unknown mechanism of action. It presumably exerts its effects by binding to various stereo-specific receptors in the CNS. Alprazolam has also been reported to exhibit antidepressant properties; which are not characteristic of conventional benzodiazepine derivatives.

ADVERSE EFFECT:
Common:
Endocrine metabolic:
Decrease in appetite (7.3% to 27.8%)
Increased appetite (7% to 32.7%)
Weight increased (2.7% to 27.2%)

Gastrointestinal:
Constipation (8.1% to 26.2%)
Reduced salivation (32.8%)
Xerostomia (10.2% to 14.7%)

Neurologic:
Cognitive disorder (28.8%)
Confusion (1.5% to 10.4%)
Dysarthria (10.9% to 23.3%)
Incoordination (9.4% to 40.1%)
Lightheadedness (20.8%)
Memory impairment (15.4% to 33.1%)
Sedated (45.2%)
Somnolence (23% to 76.8%)

Psychiatric:
Irritability (immediate-release; 33.1%; extended-release 1% or more)

Reproductive:
Reduced libido (6% to 14.4%)

Other:
Fatigue (13.9% to 48.6%)

Serious:
Dermatologic:
Stevens-Johnson syndrome

Hepatic:
Liver failure

Neurologic:
Drug withdrawal seizure

CONTRAINDICATION:
Acute narrow angle glaucoma
Concomitant

use with itraconazole

or ketoconazole
Hypersensitivity to benzodiazepines

DRUG INTERACTION:
Use with Other CNS Depressants :
If

alprazolam Tablets

are to be combined with other psychotropic agents or anticonvulsant drugs, careful consideration should be given to the pharmacology of the agents to be employed, particularly with compounds which might potentiate the action of benzodiazepines. 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.

Use with Imipramine and Desipramine :
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 (CYP3A). Drugs which inhibit this metabolic pathway may have a profound effect on the

clearance of alprazolam

Drugs demonstrated to be CYP3A 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 demonstrated to be inducers of CYP3A :
Carbamazepine can increase alprazolam metabolism and therefore can decrease

plasma levels of alprazolam

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. However, data from an in vivo drug interaction study involving a

single dose of alprazolam

1 mg and steady state

dose

of sertraline (50 to 150 mg/day) did not reveal any clinically significant changes in the

pharmacokinetics of alprazolam

. 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

Major:
Alfentanil (theoretical)
Amobarbital (probable)
Benzhydrocodone (theoretical)
Boceprevir (theoretical)
Bromazepam (theoretical)
Bromopride (theoretical)
Buprenorphine (theoretical)
Butabarbital (probable)
Butalbital (probable)
Butorphanol (theoretical)
Carbamazepine (probable)
Carbinoxamine (theoretical)
Carisoprodol (theoretical)
Ceritinib (theoretical)
Chloral Hydrate (theoretical)
Chlorzoxazone (theoretical)
Clarithromycin (established)
Cobicistat (theoretical)
Codeine (theoretical)
Conivaptan (theoretical)
Dantrolene (theoretical)
Dasabuvir (theoretical)
Digoxin (probable)
Domperidone (theoretical)
Doxylamine (theoretical)
Eliglustat (theoretical)
Ethchlorvynol (theoretical)
Fentanyl (theoretical)
Flibanserin (theoretical)
Fluconazole (theoretical)
Fosnetupitant (theoretical)
Fospropofol (theoretical)
Hydrocodone (theoretical)
Hydromorphone (theoretical)
Idelalisib (theoretical)
Levorphanol (theoretical)
Lofexidine (theoretical)
Loxapine (theoretical)
Meclizine (theoretical)
Meperidine (theoretical)
Mephenesin (theoretical)
Mephobarbital (probable)
Meprobamate (theoretical)
Metaxalone (theoretical)
Methadone (theoretical)
Methocarbamol (theoretical)
Methohexital (probable)
Metoclopramide (theoretical)
Mirtazapine (theoretical)
Morphine (theoretical)
Morphine Sulfate Liposome (theoretical)
Nalbuphine (theoretical)
Netupitant (theoretical)
Oxycodone (theoretical)
Oxymorphone (theoretical)
Pentobarbital (probable)
Periciazine (theoretical)
Phenobarbital (probable)
Piperaquine (theoretical)
Primidone (probable)
Propofol (theoretical)
Secobarbital (probable)
Sodium Oxybate (theoretical)
Sufentanil (theoretical)
Tapentadol (theoretical)
Thiopental (probable)
Tramadol (theoretical)
Voriconazole (theoretical)
Zolpidem (theoretical)

Moderate:
Amprenavir (probable)
Cimetidine (probable)
Desipramine (probable)
Desogestrel (probable)
Dienogest (probable)
Drospirenone (probable)
Erythromycin (probable)
Estradiol Cypionate (probable)
Estradiol Valerate (probable)
Ethinyl Estradiol (probable)
Ethynodiol Diacetate (probable)
Etonogestrel (probable)
Fluoxetine (probable)
Imipramine (probable)
Kava (probable)
Levonorgestrel (probable)
Mestranol (probable)
Mifepristone (probable)
Nefazodone (probable)
Norelgestromin (probable)
Norethindrone (probable)
Norgestimate (probable)
Norgestrel (probable)
Rifapentine (probable)
Roxithromycin (probable)
Sertraline (probable)
Telaprevir (established)
Theophylline (probable)
Troleandomycin (probable)

PHARMACOKINETICS:
Absorption:
Time for Maximum Plasma Concentration (Tmax): 11.2 hours (Range: 6.3–26.9 hours)
Absolute bioavailability: 90%
Relative bioavailability: 100%
Extended-release tablet: 5 to 11 hours; decreased by 1 hour with night dosing
Immediate release tablet: 1 to 2 hours
A high-fat meal given up to 2 hours before dosing with

Alprazolam Tablets

increased the mean Cmax by about 25%

Distribution:
Plasma Protein binding: 80%

Metabolism:
Hepatic: Extensive via CYP3A4

Excretion:
Renal: 80%; as unchanged drug and metabolites
Fecal: 7%
Renal clearance: 371 mL/hour
Total body clearance: 76 mL/min

Elimination:
Extended-release tablet: 10.7 to 15.8 hours
Orally disintegrating tablet: 12.5 hours
Immediate release tablet: 11.2 hours
Asians: 25% higher than Caucasian
Alcoholic liver disease: 19.7 hours
Elderly: 16.3 hours

PRECAUTION:
Access:
Patients receiving concomitant therapy with benzodiazepines or CNS depressants should not be denied access to medication-assisted treatment drugs (eg; methadone and buprenorphine); if concomitant use is necessary; careful management and monitoring recommended.

Beers Criteria:
Avoid use in elderly due to greater benzodiazepine sensitivity; especially in patients with a history of falls or fractures (unless safer alternatives are not available); cognitive impairment or dementia; or with delirium or at high risk for delirium. May increase risk of syncope; falls fractures; ataxia; cognitive or psychomotor impairment; motor vehicle accidents; delirium; or other adverse CNS effects (may be appropriate for seizure disorders; rapid eye movement sleep disorders; benzodiazepine or ethanol withdrawal; severe generalized anxiety disorder; periprocedural anesthesia; and end-of-life care).

Concomitant Use:
Concomitant use with potent CYP3A inhibitors not recommended

Debilitated:
Patients may be at increased risk of ataxia or oversedation; dose adjustment recommended

Hepatic:
Advanced hepatic disease may increase systemic exposure; dose adjustment recommended
Alcoholic liver disease or obesity may increase systemic exposure

Neurologic:
Risk of seizure recurrence upon rapid discontinuation; slow taper recommended for patients with history of seizures

Psychiatric:
Suicidality risk in patients with history of or current suicidal behavior
Depression; increased risk of hypomania and mania; and may increase suicidality
Increased risk of physical and psychological dependence at doses greater than 4 mg/day or with prolonged use
Drug abuse and dependence risk in patients with history of alcohol or drug abuse; monitoring recommended

Reproductive:
Birth defect risk in newborns when

used by pregnant women

; avoid use during first trimester

Respiratory:
Severe pulmonary disease may increase the risk of adverse events; including rare fatalities

Withdrawal of Therapy:
Withdrawal symptoms; including life-threatening seizures; may occur with missed doses; abrupt dose reduction; or discontinuation; gradual dose reduction

PREGNANCY CATEGORY:
D (FDA)
C (AUS)

BREAST FEEDING:
AAP:
Drugs for which the effect on nursing infants is unknown but may be of concern

MONITORING:
Reduction in symptoms of anxiety or panic disorder indicates efficacy
Blood counts; urinalysis; and blood chemistry; periodically during chronic therapy
Respiratory depression or sedation; in patients using concomitant opioids

HOW TO TAKE OR ADMINISTRATION:
Oral:
(Extended-release tablets)
Do not break, chew, or crush
Administration in the morning is preferred

(Disintegrating tablets)
Remove tablet from bottle with dry hands
Consume tablet immediately once it is removed from the bottle; allow tablet to disintegrate on top of the tongue, then swallow with saliva Discard any unused portion of an orally disintegrating tablet, as it may not remain stable

DOSAGE FORM:
Oral Tablet:
0.25 MG
0.5 MG
1 MG
2 MG

Oral Tablet; Disintegrating:
0.25 MG
0.5 MG
1 MG
2 MG

Oral Tablet; Extended Release:
0.5 MG
1 MG
2 MG
3 MG

TOXICOLOGY:
Deaths from benzodiazepine

overdose

are extremely rare. A patient with multiple severe medical problems expired following an overdose of

7.5 mg of alprazolam

. In general; the toxic-to-therapeutic ratio is very high for benzodiazepines; making them remarkably safe medications

TREATMENTS:
Supportive care with attention to the airway; breathing; and circulation is the mainstay of treatment. Benzodiazepine overdose as a single agent may cause coma but generally does not cause loss of airway reflexes. However; when combined with other sedating drugs (eg; ethanol; opioids; muscle relaxants; antipsychotics; anticonvulsants); airway protection may be necessary. Even with large

overdoses

; patients generally remain hemodynamically stable.

MANAGEMENT OF MILD TO MODERATE TOXICITY:
Supportive care

MANAGEMENT OF SEVERE TOXICITY:
Coma and respiratory depression require intubation. Hypotension responds to fluids and rarely vasopressors.

PATIENT COUNSELING OR CLINICAL TEACHING:
Patient should avoid activities requiring mental alertness or coordination until drug effects are realized.
This drug may cause increased appetite; changes in weight; constipation; dizziness; dysarthria; memory impairment; somnolence; depression; or reduced libido.
Advise patient and family to monitor for confusion with use; especially with elderly patients.
Advise patient against abrupt discontinuation of drug to prevent withdrawal symptoms.
Patient should avoid alcohol while taking drug.
Patient should not eat grapefruit or drink grapefruit juice while taking drug.




Disclaimer:
For the Registered Medical Practitioner Only. We are not recommended for self medication. self medication is may harmful for health. We are only information about medicine.