Alprazolam

Drug Approvals

(British Approved Name, US Adopted Name, rINN)

INNs in other languages (French, Latin, and Spanish): Alpratsolaami; Alprazolam; Alprazolamas; Alprazolamum; U-31889

Note. The following terms have been used as ‘street names’ or slang names for various forms ofalprazolam: Benzo; Coffins; Dogbones; Fo’ Bars; Fo’s; Footballs; Forgetful Pills; Four Bars; French Fries; Gold Bars; Green Bars; Quad bar; School Buses; Sticks; Totem Poles; White Bars; X-Boxes; Xan-Bars; Xannies; Xanny; Zanny; Z-Bars; Zan-Bars; Zannies; Zan-ny-Bars.

Pharmacopoeias. In China, Europe, Japan, and US.

European Pharmacopoeia, 6th ed. (Alprazolam). A white or almost white, crystalline powder. It exhibits polymorphism. Practically insoluble in water sparingly soluble in alcohol and in acetone freely soluble in dichloromethane. Protect from light.

The United States Pharmacopeia 31, 2008 (Alprazolam). A white to off-white crystalline powder. Insoluble in water soluble in alcohol sparingly soluble in acetone freely soluble in chloroform slightly soluble in ethyl acetate.

Dependence and Withdrawal

As for Diazepam. Dependence may be a particular problem at the high doses used in the treatment of panic attacks.

Adverse Effects and Treatment

As for Diazepam.

Effects on the liver.

A patient receiving phenelzine for depression developed abnormal liver enzyme values on 2 occasions when alprazolam was added to the treatment. It was not possible to say if this was due to alprazolam alone or a synergistic effect with phenelzine.

Effects on the skin.

There have been some reports of alpra-zolam-induced photosensitivity.

Overdosage.

A retrospective analysis of 2063 hospital admissions for benzodiazepine overdosage in one region of Australia between January 1987 and October 2002 found that patients who took an overdose ofalprazolam were about twice as likely to require admission to intensive care. Flumazenil was required in 14% of the 131 alprazolam overdoses, and ventilation in 16%, which was significantly more than for other benzodiazepines. Given the apparently greater toxicity ofalprazolam in overdosage, its increasing prescription to groups at risk of self-poisoning was of concern.

Precautions

As for Diazepam

Abuse.

High doses ofalprazolam taken after maintenance doses of methadone produced a ‘high’ without pronounced sedation the drug was also misused by nonopioid-drug abusers. The usual urine toxicology screens for benzodiazepines often give false-negative results for alprazolam because of the extremely low concentrations of metabolites excreted, making abuse difficult to detect. A subsequent review considered that the literature did not support the widely held belief that alprazolam had a greater liability for abuse than other benzodiazepines, but the possibility could not be discounted.

Breast feeding.

The American Academy of Pediatrics considers that, although the effect ofalprazolam on breast-fed infants is unknown, its use by mothers during breast feeding may be of concern since anxiolytic drugs do appear in breast milk and thus could conceivably alter CNS function in the infant both in the short and long term.

From a study of the distribution of alprazolam into breast milk in 8 lactating women it was estimated that the average daily dose of alprazolam ingested by a breast-fed infant would range from 0.3 to 5 micrograms/kg or about 3% of amaternal dose.

Handling.

Care should be taken to prevent inhaling particles of alprazolam and exposing the skin to it.

Hepatic impairment.

Alprazolam 1 mg by mouth was absorbed more slowly in 17 patients with alcoholic cirrhosis with no ascites than in 17 healthy subjects. Mean peak alprazolam concentrations were achieved after 3.34 hours in the cirrhosis patients and 1.47 hours in the healthy subjects. Mean elimination half-life for cirrhosis patients was 19.7 hours compared with 11.4 hours for subjects from the healthy group. However, there were no significant differences in the maximum plasma concentrations achieved.

The results indicate that alprazolam, in common with other benzodiazepines that undergo oxidative metabolism, would accumulate to a greater extent in patients with alcoholic liver disease than in healthy subjects the daily dose of alprazolam may need to be reduced by half in this population. See also Administration in Hepatic or Renal Impairment, below.

Porphyria.

Alprazolam is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in in-vitro systems.

Interactions

As for Diazepam.

Pharmacokinetics

Alprazolam is well absorbed from the gastrointestinal tract after oral doses, peak plasma concentrations being achieved within 1 to 2 hours of a dose. The mean plasma half-life is 11 to 15 hours. Alprazolam is 70 to 80% bound to plasma proteins, mainly albumin. It is metabolised in the liver, primarily by the cytochrome P450 isoenzyme CYP3A4. Metabolites include a-hydroxy-alprazolam, which is reported to be about half as active as the parent compound, 4-hydroxyalprazolam, and an inactive benzophenone. Plasma concentrations of metabolites are very low. Alprazolam is excreted in urine as unchanged drug and metabolites.

Uses and Administration

Alprazolam is a short-acting benzodiazepine with general properties similar to those of diazepam. It is used in the short-term treatment of anxiety disorders in oral doses of 250 to 500 micrograms three times daily, increased where necessary to a total daily dose of 3 or 4 mg. In elderly or debilitated patients, an initial dose of 250 micrograms two or three times daily has been suggested. For doses in patients with hepatic or renal impairment, see below.

Doses of up to 10 mg ofalprazolam daily have been used in the treatment of panic attacks. A modified-release preparation of alprazolam is also available for once-daily dosing.

Administration in hepatic or renal impairment.

UK licensed product information advises caution when using alprazolam in patients with hepatic or renal impairment it is contra-indicated in those with severe hepatic impairment. In the USA, licensed product information states that patients with advanced liver disease may be given an initial dose of 250 micrograms two or three times daily.

Anxiety disorders.

The management of anxiety disorders, including the use of benzodiazepines.

Depression.

Although they may be useful for associated anxiety, benzodiazepines are not usually considered appropriate for treatment of depression (p.373) however, some drugs such as alprazolam have been tried for this indication.

Premenstrual syndrome.

Alprazolam has been reported to have produced a marginal to good response in the premenstrual syndrome but others have not found it to be of benefit, and the role of benzodiazepines is limited by their adverse effects. If benzodiazepines are selected it is recommended that in order to reduce the risk of dependence and withdrawal symptoms they should be carefully restricted to the luteal phase in selected patients. Withdrawal symptoms may be more severe after short-acting drugs such as alprazolam. Antidepressant drugs such as SSRIs may be preferred.

Tinnitus.

Alprazolam has been tried in the management of tinnitus.

Preparations

The United States Pharmacopeia 31, 2008: Alprazolam Oral Suspension Alprazolam Tablets.

Proprietary Preparations

Argentina: Alplax Alprazol Amziax Ansielix Aplacaina Bayzolam Becede Bestrol Calmol Emeral Isoproxal Krama Medronal Nivelan N Prenadona Prinox Psicosedol PTA Relaxten Retanf Rilow Tensium Thiprasolan Tranquinal Xanax

Australia: Alprax Kalma Xanax

Austria: Alprastad Alpratyrol Xanor

Belgium: Alpraz Alprazomed Docalprazo Topazolam Xanax

Brazil: Alfron Altrox Apraz Constante Frontal Neozolam Tranquinal

Canada: Apo-Alpraz Novo-Alprazol Nu-Alpraz Xanax

Chile: Adax Grifoalpram Prazam Sanerva Tricalma Zotran

Czech Republic: Frontin Helex Neural Xanax

Denmark: Alprax Tafil

Finland: Alprax Xanor

France: Xanax

Germany: Cassadan Tafil Xanax

Greece: Antanax Saturnil Xanax

Hong Kong: Alprax Nalion Renax Xanax

Hungary: Frontin Xanax

India: Alprax Alprocontin Anzilum Pacyl Restyl Tranax Xycalm Zolam

Indonesia: Alganax Alviz Atarax Calmlet Feprax Frixitas Soxietas Xanax Zypraz

Ireland: Alprax Calmax Gerax Xanax

Israel: Alpralid Alprax Xanagis Xanax

Italy: Alpravecs Alprazig Frontal Ibizolam Mialin Valeans Xanax

Malaysia: Alpranax Apo-Alpraz Xanax

Mexico: Alzam Farmapram Irizz Neupax Tafil

The Netherlands: Xanax

Norway: Xanor

New Zealand: Xanax

Philippines: Xanor

Poland: Afobam Alprazomerck Alprax Neural Xanax Zomiren

Portugal: Alpronax Pazolam Prazam Unilan Xanax

Russia: Alzolam Helex Neural Xanax

South Africa: Alzam Anxiridf Azor Drimpam Xanolamf Xanor Zopax

Singapore: Apo-Alpraz Dizolam Xanax Zacetin

Spain: Trankimazin

Sweden: Xanor

Switzerland: Xanax

Thailand: Alcelam Alnax Alprax Anax Anpress Anzionf Dizolam Marzolam Mitranax Pharnax Siampraxol Xanacine Xanax Xiemed

Turkey: Xanax

United Kingdom: Xanax

USA: Niravam Xanax

Venezuela: Abaxon Alpram Ansilan Danox Tafil

Multi-ingredient

Argentina: Alplax Digest Alplax Net Ansielix Digest Euciton Stress Novo Vegestabil Sidomal Tensium Gastric Tranquinal Soma

India: Fludep Plus Restyl Forte Restyl Plus Stresnil Zopax Plus