Adult: In patients with moderate or severe anxiety states, or anxiety associated with depression: As conventional tab, orally disintegrating tab or oral solution: Initially, 0.25-0.5 mg tid; may be increased as necessary every 3-4 days to a total of 3 or 4 mg daily (in divided doses). Max treatment duration: 8-12 weeks, including a tapering off period. Elderly: As conventional tab, orally disintegrating tab or oral solution: Initially, 0.25 mg 2-3 times daily; may be increased gradually if needed and tolerated.
Oral Panic disorder with or without agoraphobia
Adult: As conventional tab, orally disintegrating tab or oral solution: Initially, 0.5 mg tid; may be increased in increments of no more than 1 mg daily every 3-4 days. Doses of up to 10 mg daily may be used if required. As extended-release tab: Initially, 0.5-1 mg once daily; may be increased in increments of no more than 1 mg daily every 3-4 days according to response. Usual dosage range: 3-6 mg daily. Elderly: As conventional tab, orally disintegrating tab, oral solution: Initially, 0.25 mg 2-3 times daily. As extended-release tab: Initially, 0.5 mg once daily. All doses may be increased gradually if needed and tolerated.
Special Patient Group
Debilitated patients or patients with concomitant illness (e.g. severe pulmonary disease): As conventional tab, orally disintegrating tab or oral solution: 0.25 mg 2-3 times daily; may be increased gradually if needed and tolerated.
Patients taking ritonavir: In patients initiated with ritonavir and alprazolam together, or when ritonavir is initiated in a patient treated with alprazolam: Reduce alprazolam dose to half of the recommended dosage; increase to the target dose after 10-14 days of dosing ritonavir and alprazolam together. In patients who have been taking ritonavir for >10-14 days: No dose reduction is needed.
Hepatic Impairment
Severe: Contraindicated.
Administration
May be taken with or without food. Side effects eg, sleepiness/drowsiness may be reduced if taken immediately after meals.
Contraindications
Severe respiratory insufficiency, myasthenia gravis, sleep apnoea syndrome. Acute narrow-angle glaucoma. Severe hepatic impairment. Lactation. Concomitant use with strong CYP3A inhibitors, except ritonavir.
Special Precautions
Patient with depression or suicidal ideation, respiratory disease, history of alcohol or drug abuse. Debilitated patients or those with concomitant illness. Patients taking opioids or ritonavir. Avoid abrupt withdrawal. Renal and mild to moderate hepatic impairment. Elderly. Pregnancy.
Adverse Reactions
Significant: Anterograde amnesia, restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour, physical and emotional dependence. Eye disorders: Blurred vision. Gastrointestinal disorders: Dry mouth, constipation, nausea, increased salivation. General disorders and administration site conditions: Fatigue, lethargy. Investigations: Increased or decreased weight. Metabolism and nutrition disorders: Decreased appetite. Nervous system disorders: Sedation, somnolence, ataxia, memory impairment, dysarthria, dizziness, headache, balance disorder, abnormal coordination, tremors. Psychiatric disorders: Depression, confusional state, disorientation, anxiety, insomnia, hypersomnia, nervousness, disturbance in attention. Reproductive system and breast disorders: Increased or decreased libido, sexual dysfunction. Skin and subcutaneous tissue disorders: Dermatitis. Vascular disorders: Hypotension.
This drug may impair cognitive and motor functions, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor respiratory and CV status. Assess patients for risk of abuse, misuse, and addiction. Monitor for signs and symptoms of respiratory depression and sedation.
Overdosage
Symptoms: Mild cases: Drowsiness, mental confusion, lethargy, impaired coordination, diminished reflexes, slurred speech, dilated pupils, absent bowel sounds, tachycardia. Serious cases: Ataxia, hypotonia, hypotension, hypothermia, rhabdomyolysis, atrioventricular block, coma. Management: Supportive treatment with respiration, pulse rate and blood pressure monitoring. Induce vomiting (within 1 hour of ingestion) if the patient is conscious or perform gastric lavage if unconscious. Activated charcoal may be given to reduce absorption if gastric emptying is of no advantage. Administer IV fluids and maintain an adequate airway. Flumazenil may be considered with close monitoring for re-sedation, respiratory depression and other residual benzodiazepine effects.
Drug Interactions
Additive CNS depressant effects with other psychotropic drugs, anticonvulsants, anaesthetics, antihistamines and other drugs that produce CNS depression. Increased plasma concentrations with nefazodone, fluvoxamine, fluoxetine, oral contraceptives, diltiazem, macrolide antibiotics (e.g. erythromycin, clarithromycin), and cimetidine. Decreased plasma concentrations with CYP3A4 inducers (e.g. carbamazepine, phenytoin). May increase the concentration of digoxin. Potentially Fatal: Increased plasma concentrations with strong CYP3A inhibitors (e.g. ketoconazole, itraconazole). Concomitant use with opioids (e.g. propoxyphene) may result in profound sedation, respiratory depression and coma.
Food Interaction
Additive CNS depressant effects with alcohol. May increase plasma concentrations with grapefruit juice.
Action
Description: Mechanism of Action: Alprazolam is a short-acting benzodiazepine that has a high affinity for the benzodiazepine binding site in the brain. It enhances the inhibitory neurotransmitter action of GABA, which mediates both pre- and post-synaptic inhibition in the CNS. Pharmacokinetics: Absorption: Readily absorbed. Bioavailability: 84-92% (immediate-release); approx 90% (extended-release). Time to peak plasma concentration: 1-2 hours (immediate-release); approx 9 hours (extended-release); 1.5-2 hours (orally disintegrating tab). Distribution: Crosses placenta and enters breast milk. Volume of distribution: 0.84-1.42 L/kg (immediate-release). Plasma protein binding: 80%, mainly to albumin. Metabolism: Extensively metabolised in the liver, mainly by CYP3A4 into 2 major active metabolites (4-hydroxyalprazolam and α-hydroxyalprazolam), and an inactive benzophenone metabolite. Excretion: Mainly via urine, as unchanged drug and metabolites. Elimination half-life: 11.2 hours (range: immediate release: 6.3-26.9 hours; extended-release: 10.7-15.8 hours); orally disintegrating tab: 12.5 hours (range: 7.9-19.2 hours).
Chemical Structure
Alprazolam Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2118, Alprazolam. https://pubchem.ncbi.nlm.nih.gov/compound/2118. Accessed Aug. 26, 2022.
Storage
Store between 20-25°C. Protect from light and moisture.
N05BA12 - alprazolam ; Belongs to the class of benzodiazepine derivatives anxiolytics. Used in the management of anxiety, agitation or tension.
References
Alprazolam Solution, Concentrate (West-Ward Pharmaceuticals Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/06/2022.Alprazolam Tablet (Actavis Pharma, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/06/2022.Alprazolam Tablet, Extended Release (Actavis Pharma, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/06/2022.Alprazolam Tablet, Orally Disintegrating (Actavis Pharma, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/06/2022.Anon. Alprazolam. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 06/06/2022.Anon. Alprazolam. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/06/2022.Buckingham R (ed). Alprazolam. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/06/2022.Joint Formulary Committee. Alprazolam. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/06/2022.Pfizer New Zealand Ltd. Xanax 0.25 mg, 0.5 mg and 1.0 mg Tablets data sheet 27 December 2018. Medsafe. http://www.medsafe.govt.nz. Accessed 06/06/2022.Xanax (Viatris Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 14/08/2022.Xanax 500 microgram Tablets (Upjohn UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 06/06/2022.Xanax Tablets (Upjohn Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 06/06/2022.
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