Alprazolam Chemical formula
Synonyms: Alpratsolaami; Alprazolám; Alprazolamas; Alprazolamum; U-31889. 8-Chloro-1-methyl-6-phenyl-4H-1,2,4-triazolo[4,3a][1,4]benzodiazepine.
Cyrillic synonym: Алпразолам.

💊 Chemical information

Chemical formula: C17H13ClN4 = 308.8.
CAS — 28981-97-7 (alprazolam).
ATC — N0 5B A 12.
ATC Vet — QN05B A 12.


In Chin., Eur., Jpn, and US.

Ph. Eur. 6.2

(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.

USP 31

(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.1 It was not possible to say if this was due to alprazolam alone or a synergistic effect with phenelzine.
1. Roy-Byrne P, et al. Alprazolam-related hepatotoxicity. Lancet 1983; ii: 786–7.

Effects on the skin.

There have been some reports of alprazolam-induced photosensitivity.1,2
1. Kanwar AJ, et al. Photosensitivity due to alprazolam. Dermatologica 1990; 181: 75
2. Watanabe Y, et al. Photosensitivity due to alprazolam with positive oral photochallenge test after 17 days administration. J Am Acad Dermatol 1999; 40: 832–3.


A retrospective analysis1 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 of alprazolam 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 of alprazolam in overdosage, its increasing prescription to groups at risk of self-poisoning was of concern.
1. Isbister GK, et al. Alprazolam is relatively more toxic than other benzodiazepines in overdose. Br J Clin Pharmacol 2004; 58: 88–95.

💊 Precautions

As for Diazepam.


High doses of alprazolam taken after maintenance doses of methadone produced a ‘high’ without pronounced sedation; the drug was also misused by nonopioid-drug abusers.1 The usual urine toxicology screens for benzodiazepines often give falsenegative results for alprazolam because of the extremely low concentrations of metabolites excreted, making abuse difficult to detect. A subsequent review2 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.
1. Weddington WW, Carney AC. Alprazolam abuse during methadone maintenance therapy. JAMA 1987; 257: 3363
2. Rush CR, et al. Abuse liability of alprazolam relative to other commonly used benzodiazepines: a review. Neurosci Biobehav Rev 1993; 17: 277–85.

Breast feeding.

The American Academy of Pediatrics1 considers that, although the effect of alprazolam 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 study2 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 a maternal dose.
1. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108: 776–89. Correction. ibid.; 1029. Also available at: pediatrics%3b108/3/776 (accessed 28/04/04
2. Oo CY, et al. Pharmacokinetics in lactating women: prediction of alprazolam transfer into milk. Br J Clin Pharmacol 1995; 40: 231–6.


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.1 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.
1. Juhl RP, et al. Alprazolam pharmacokinetics in alcoholic liver disease. J Clin Pharmacol 1984; 24: 113–19.


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 α-hydroxyalprazolam, 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.
1. Greenblatt DJ, Wright CE. Clinical pharmacokinetics of alprazolam: therapeutic implications. Clin Pharmacokinet 1993; 24: 453–71
2. Wright CE, et al. Pharmacokinetics and psychomotor performance of alprazolam: concentration-effect relationship. J Clin Pharmacol 1997; 37: 321–9
3. Kaplan GB, et al. Single-dose pharmacokinetics and pharmacodynamics of alprazolam in elderly and young subjects. J Clin Pharmacol 1998; 38: 14–21
4. Park J-Y, et al. Effect of CYP3A5*3 genotype on the pharmacokinetics and pharmacodynamics of alprazolam in healthy subjects. Clin Pharmacol Ther 2006; 79: 590–9.

💊 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 of alprazolam daily have been used in the treatment of panic attacks. A modifiedrelease 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 contraindicated 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.

1. Cross-National Collaborative Panic Study, Second Phase Investigators. Drug treatment of panic disorder: comparative efficacy of alprazolam, imipramine, and placebo. Br J Psychiatry 1992; 160: 191–202
2. Lepola UM, et al. Three-year follow-up of patients with panic disorder after short-term treatment with alprazolam and imipramine. Int Clin Psychopharmacol 1993; 8: 115–18
3. Pollack MH, et al. Long-term outcome after acute treatment with alprazolam or clonazepam for panic disorder. J Clin Psychopharmacol 1993; 13: 257–63
4. Woodman CL, et al. Predictors of response to alprazolam and placebo in patients with panic disorder. J Affect Disord 1994; 30: 5–13
5. Spiegel DA. Efficacy studies of alprazolam in panic disorder. Psychopharmacol Bull 1998; 34: 191–5.


Although they may be useful for associated anxiety, benzodiazepines are not usually considered appropriate for treatment of depression; however, some drugs such as alprazolam have been tried for this indication.1
1. Kravitz HM, et al. Alprazolam and depression: a review of risks and benefits. J Clin Psychiatry 1993; 54: (suppl.): 78–84.

Premenstrual syndrome.

Alprazolam has been reported1-3 to have produced a marginal to good response in the premenstrual syndrome but others have not found it to be of benefit,4and 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.5 Withdrawal symptoms may be more severe after shortacting drugs such as alprazolam. Antidepressant drugs such as SSRIs may be preferred.
1. Smith S, et al. Treatment of premenstrual syndrome with alprazolam: results of a double-blind, placebo-controlled, randomized crossover clinical trial. Obstet Gynecol 1987; 70: 37–43
2. Harrison WM, et al. Treatment of premenstrual dysphoria with alprazolam: a controlled study. Arch Gen Psychiatry 1990; 47: 270–5
3. Freeman EW, et al. A double-blind trial of oral progesterone, alprazolam, and placebo in treatment of severe premenstrual syndrome. JAMA 1995; 274: 51–7
4. Evans SM, et al. Mood and performance changes in women with premenstrual dysphoric disorder: acute effects of alprazolam. Neuropsychopharmacology 1998; 19: 499–516
5. Mortola JF. A risk-benefit appraisal of drugs used in the management of premenstrual syndrome. Drug Safety 1994; 10: 160–9.


Alprazolam has been tried in the management of tinnitus.
1. Johnson RM, et al. Use of alprazolam for relief of tinnitus: a double-blind study. Arch Otolaryngol Head Neck Surg 1993; 119: 842–5
2. Huynh L, Fields S. Alprazolam for tinnitus. Ann Pharmacother 1995; 29: 311–12
3. Vernon JA, Meikle MB. Masking devices and alprazolam treatment for tinnitus. Otolaryngol Clin North Am 2003; 36: 307–20.

💊 Preparations

USP 31: Alprazolam Oral Suspension; Alprazolam Tablets.

Proprietary Preparations

Arg.: Alplax; Alprazol; Amziax; Ansielix; Aplacaina; Bayzolam; Becede; Bestrol; Calmol; Emeral; Isoproxal; Krama; Medronal; Nivelan N; Prenadona; Prinox; Psicosedol; PTA; Relaxten; Retan†; Rilow; Tensium; Thiprasolan; Tranquinal; Xanax; Austral.: Alprax; Kalma; Xanax; Austria: Alprastad; Alpratyrol†; Xanor; Belg.: Alpraz; Alprazomed; Docalprazo; Topazolam; Xanax; Braz.: Alfron; Altrox; Apraz; Constante; Frontal; Neozolam; Tranquinal; Canad.: Apo-Alpraz; Novo-Alprazol; Nu-Alpraz; Xanax; Chile: Adax; Grifoalpram; Prazam; Sanerva; Tricalma; Zotran; Cz.: Frontin; Helex; Neurol; Xanax; Denm.: Alprox; Tafil; Fin.: Alprox; Xanor; Fr.: Xanax; Ger.: Cassadan; Tafil; Xanax; Gr.: Antanax†; Saturnil; Xanax; Hong Kong: Alprax; Nalion; Renax; Xanax; Hung.: Frontin; Xanax; India: Alprax; Alprocontin; Anzilum†; Pacyl; Restyl; Tranax; Xycalm; Zolam; Indon.: Alganax; Alviz; Atarax; Calmlet; Feprax; Frixitas; Soxietas; Xanax; Zypraz; Irl.: Alprox; Calmax; Gerax; Xanax; Israel: Alpralid; Alprox; Xanagis; Xanax; Ital.: Alpravecs; Alprazig; Frontal; Ibizolam†; Mialin; Valeans; Xanax; Malaysia: Alpranax; Apo-Alpraz; Xanax; Mex.: Alzam; Farmapram; Irizz; Neupax; Tafil; Neth.: Xanax; Norw.: Xanor; NZ: Xanax; Philipp.: Xanor; Pol.: Afobam; Alprazomerck; Alprox; Neurol; Xanax; Zomiren; Port.: Alpronax†; Pazolam; Prazam; Unilan; Xanax; Rus.: Alzolam (Алзолам); Helex (Хелекс); Neurol (Неурол); Xanax (Ксанакс)†; S.Afr.: Alzam; Anxirid†; Azor; Drimpam†; Xanolam†; Xanor; Zopax; Singapore: Apo-Alpraz; Dizolam†; Xanax; Zacetin†; Spain: Tr an ki ma zi n; Swed.: Xanor; Switz.: Xanax; Thai.: Alcelam; Alnax; Alprax; Anax; Anpress; Anzion†; Dizolam; Marzolam; Mi tranax†; Pharnax; Siampraxol; Xanacine; Xanax; Xiemed; Turk.: Xanax; UK: Xanax; USA: Niravam; Xanax; Venez.: Abaxon; Alpram; Ansilan; Danox†; Tafil. Multi-ingredient: Arg.: 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.
Published October 22, 2018.