Alprazolam

Alprazolam structure: Alprazolam in Kenya

Mechamism of Action:

Benzodiazepines bind to gamma aminobutyric acid (GABA) receptors in the brain and enhance GABA-mediated synaptic inhibition; such actions may be responsible for the efficacy of alprazolam in anxiety disorder and panic disorder.

Drug Label Information | Brands:

Alzolam , Sun Pharmaceutical Industries Limited
Atrest , Centaur Pharmaceuticals Pvt. Ltd.
Calmex, Cosmos Limited
Xanax ,Pfizer Laboratories Limited
Zolaram, Delorbis Pharmaceuticals Limited

INDICATIONS:

Alprazolam is indicated for the treatment of panic disorder, with or without agoraphobia.
Panic disorder (DSM-IV) is characterized by recurrent unexpected panic attacks, i.e., a discrete period of intense fear or discomfort in which four (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes:

  • palpitations, pounding heart, or accelerated heart rate;
  • sweating;
  • trembling or shaking;
  • sensations of shortness of breath or smothering;
  • feeling of choking;
  • chest pain or discomfort;
  • nausea or abdominal distress;
  • feeling dizzy, unsteady, lightheaded, or faint;
  • derealization (feelings of unreality) or depersonalization (being detached from oneself);
  • fear of losing control;
  • fear of dying;
  • paresthesias (numbness or tingling sensations);
  • chills or hot flushes.

CONTRAINDICATIONS:

Alprazolam is contraindicated in patients with known sensitivity to this drug or other benzodiazepines.

Alprazolam extended-release is contraindicated with ketoconazole and itraconazole, since these medications significantly impair the oxidative metabolism mediated by cytochrome P450 3A (CYP3A)

ADVERSE DRUG REACTIONS:

Cardiac Disorders: Frequent: palpitation; Infrequent: sinus tachycardia

Ear and Labyrinth Disorders: Frequent: Vertigo; Infrequent: tinnitus, ear pain

Eye Disorders: Frequent: blurred vision; Infrequent: mydriasis, photophobia

Gastrointestinal Disorders: Frequent: diarrhea, vomiting, dyspepsia, abdominal pain; Infrequent: dysphagia, salivary hypersecretion

General Disorders and Administration Site Conditions: Frequent: malaise, weakness, chest pains; Infrequent: fall, pyrexia, thirst, feeling hot and cold, edema, feeling jittery, sluggishness, asthenia, feeling drunk, chest tightness, increased energy, feeling of relaxation, hangover, loss of control of legs, rigors

Musculoskeletal and Connective Tissue Disorders: Frequent: back pain, muscle cramps, muscle twitching

Nervous System Disorders: Frequent: headache, dizziness, tremor; Infrequent: amnesia, clumsiness, syncope, hypotonia, seizures, depressed level of consciousness, sleep apnea syndrome, sleep talking, stupor

Psychiatric System Disorders: Frequent: irritability, insomnia, nervousness, derealization, libido increased, restlessness, agitation, depersonalization, nightmare; Infrequent: abnormal dreams, apathy, aggression, anger, bradyphrenia, euphoric mood, logorrhea, mood swings, dysphonia, hallucination, homicidal ideation, mania, hypomania, impulse control, psychomotor retardation, suicidal ideation

Renal and Urinary Disorders: Frequent: difficulty in micturition; Infrequent: urinary frequency, urinary incontinence

Respiratory, Thoracic, and Mediastinal Disorders: Frequent: nasal congestion, hyperventilation; Infrequent: choking sensation, epistaxis, rhinorrhea

Skin and Subcutaneous Tissue Disorders: Frequent: sweating increased; Infrequent: clamminess, rash, urticaria

Vascular Disorders: Infrequent: hypotension

DRUG INTERACTIONS:

The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists.

If alprazolam is 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 coadministered 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 in doses up to 4 mg/day. The clinical significance of these changes is unknown.

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

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%

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.

Carbamazepine can increase alprazolam metabolism and therefore can decrease plasma levels of alprazolam.

DRUG ABUSE AND DEPENDENCE

Physical and Psychological Dependence

Withdrawal symptoms similar in character to those noted with sedative/hypnotics and alcohol have occurred following discontinuance of benzodiazepines, including alprazolam. The symptoms can range from mild dysphoria and insomnia to a major syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. Distinguishing between withdrawal emergent signs and symptoms and the recurrence of illness is often difficult in patients undergoing dose reduction. The long-term strategy for treatment of these phenomena will vary with their cause and the therapeutic goal. When necessary, immediate management of withdrawal symptoms requires re-institution of treatment at doses of alprazolam sufficient to suppress symptoms. There have been reports of failure of other benzodiazepines to fully suppress these withdrawal symptoms. These failures have been attributed to incomplete cross-tolerance but may also reflect the use of an inadequate dosing regimen of the substituted benzodiazepine or the effects of concomitant medications.

Controlled Substance Class

Alprazolam is a controlled substance under the Controlled Substance Act by the Drug Enforcement