Alprazolam (Xanax) Contraindications / Precautions
- abrupt discontinuation
- benzodiazepine hypersensitivity
- breast-feeding
- closed-angle glaucoma
- ethanol intoxication
- anxiety
- benzodiazepine dependence
- bipolar disorder
- children
- chronic obstructive pulmonary disease (COPD)
- CNS depression
- coma
- dementia
- depression
- driving or operating machinery
- elderly
- hepatic disease
- infants
- labor
- mania
- myasthenia gravis
- neonates
- obesity
- Parkinson’s disease
- porphyria
- pregnancy
- psychosis
- pulmonary disease
- renal failure
- renal impairment
- respiratory depression
- seizure disorder
- seizures
- shock
- sleep apnea
- status epilepticus
- substance abuse
- suicidal ideation
Alprazolam is contraindicated in any patient with a known alprazolam or other benzodiazepine hypersensitivity or known allergies to any component of the formulation.
Alprazolam can cause physical and psychological dependence, and should be used with caution in patients with known, suspected, or a history of substance abuse. The risk of dependence with alprazolam appears to be most probable with daily dosages greater than 4 mg and with a treatment period of more than 12 weeks. Abrupt discontinuation of alprazolam after prolonged use should be avoided. Abrupt discontinuation of benzodiazepine therapy has been reported to cause a withdrawal syndrome (alprazolam-xanax-adverse-reactions/">see Adverse Effects), especially following high dose or prolonged benzodiazepine therapy. However, benzodiazepine dependence can occur with therapeutic doses administered for as few as 1 - 2 weeks and withdrawal symptoms may be seen following the discontinuance of therapy. Benzodiazepine withdrawal also can be more intense if the benzodiazepine involved possesses a relatively short duration of action such as alprazolam. Panic rebound may be particularly problematic for patients receiving higher doses for panic disorder. Patients with a history of a seizure disorder or who are taking other drugs that lower the seizure threshold (i.e., TCAs, phenothiazines) should not be withdrawn abruptly from alprazolam due to the risk of precipitating seizures; status epilepticus has also been reported during therapy with immediate-release alprazolam. During withdrawal, the greatest risk of seizure appears to be during the first 24 to 72 hours. Seizures have also been reported with the use of the extended-release formulation of alprazolam, due to abrupt withdrawal and/or concomitant alcohol intake. Alprazolam (immediate-release or extended-release formulations) should be withdrawn slowly, using a gradual tapering schedule. Flumazenil, a benzodiazepine receptor antagonist, is indicated for partial or complete reversal of the depressive effects of benzodiazepines, and may be useful in overdose situations. The prescriber should be aware of the risk for seizure activity with flumazenil use, particularly in long-term users of benzodiazepines or patients presenting with a cyclic antidepressant overdose.
Worsening of daytime anxiety has been reported with the use of some hypnotic benzodiazepines as few as 10 days after continuous use. In some patients this may be due to interdose withdrawal. If increased daytime anxiety is observed, it may be advisable to discontinue treatment gradually.
Although alprazolam is occasionally beneficial for patients with major depression, the drug should be administered to these patients with careful monitoring. According to the manufacturer, alprazolam typically has no use in the treatment of psychosis; use with extreme caution if at all in patients with suicidal ideation. Alprazolam should be used cautiously in patients with bipolar disorder because mania and hypomania have been reported in conjunction with the use of alprazolam in depressive disorders.
Alprazolam should be avoided if possible in patients with respiratory depression, pulmonary disease such as severe chronic obstructive pulmonary disease (COPD), or sleep apnea because the drug can exacerbate ventilatory failure. In rare instances, death has occurred in patients with severe pulmonary disease shortly after the initiation of alprazolam.
Due to CNS depression, patients should be cautioned against driving or operating machinery until they know how alprazolam may affect them. Some patients may experience excessive sedation and an impaired ability to perform tasks; although this is usually less than that seen with intermediate- or long-acting benzodiazepines. Increased CNS effects may be seen with concurrent use of alprazolam and other CNS depressant agents (alprazolam-xanax-interactions/">see Drug Interactions), and in patients with acute ethanol intoxication, organic brain syndromes (i.e, dementia), or psychosis. Patients with ethanol intoxication who have also consumed alprazolam have an increased risk of respiratory depression and coma. Ethanol should be avoided during treatment with alprazolam. Benzodiazepines should be used cautiously in patients in shock or coma due to the increased risk of respiratory depression. Anterograde amnesia may occur with any short-acting benzodiazepine if given in sufficient doses.
According to most manufacturers, benzodiazepines are contraindicated in patients with acute closed-angle glaucoma. However, the benzodiazepine may be used in patients with open-angle glaucoma who are receiving appropriate therapy. The mechanistic rational for this contraindication has been questioned, as benzodiazepines do not have antimuscarinic activity and do not raise intraocular pressure; few cases have been reported.
Alprazolam should be used with extreme caution in patients with myasthenia gravis because the drug can exacerbate this condition.
Patients with late stage Parkinson’s disease may experience worsening of their psychosis or impaired cognition with administration of benzodiazepines. Benzodiazepines may also cause incoordination or paradoxical reactions that may worsen symptoms of Parkinson’s disease.
The administration of alprazolam can exacerbate acute intermittent porphyria, so the drug should be used with caution in patients with this condition.
Alprazolam (including the extended-release formulation) is classified as FDA pregnancy risk category D because it could harm the fetus when administered to pregnant women. Positive evidence of human fetal risk exists based on investigational, marketing, or human studies, but the potential benefit to the mother may outweigh the potential risks to the fetus. It should be anticipated that neonates may experience withdrawal symptoms if the mother has been using benzodiazepines during pregnancy. Neonatal flaccidity has been reported in an infant whose mother was using benzodiazepines during pregnancy. Alprazolam has no established use in labor or obstetric delivery.
Many benzodiazepines distribute into breast milk. Because of the potential for adverse effects in the nursing infant, such as sedation, feeding difficulties, and weight loss, alprazolam generally is not recommended during breast-feeding.
Alprazolam should be administered cautiously to patients with severe hepatic disease because the elimination half-life of the drug can be prolonged, possibly resulting in toxicity. Patients with hepatic disease are more likely to experience adverse CNS reactions and should receive reduced initial dosages. Additionally, alprazolam is significantly metabolized via the hepatic microsomal P450 isoenzyme CYP3A4. Concomitant administration of alprazolam and potent inhibitors of CYP3A4 is contraindicated. Medications considered to be potent CYP3A4 inhibitors which should not be used concurrently with alprazolam include systemically-administered azole antifungals, some macrolide antibiotics, and anti-retroviral protease inhibitors (alprazolam-xanax-interactions/">see Drug Interactions). Other CYP3A4 inhibitors could potentially cause alprazolam toxicity (alprazolam-xanax-interactions/">see Drug Interactions). This list is not inclusive of all agents that may potently inhibit CYP3A4. Reduced elimination of alprazolam has also been reported in obesity.
Patients with renal impairment, including renal failure, should be carefully monitored during prolonged treatment with benzodiazepines to avoid the adverse reactions that may occur from drug accumulation.
The clearance and/or elimination of many drugs are reduced in the elderly or debilitated patient. The mean half-life of alprazolam is prolonged to 16.3 hours in the elderly compared to 11.2 hours in healthy subjects. Delayed elimination can either intensify or prolong the actions of adverse reactions of the drug. Benzodiazepines have been associated with falls in the elderly. The impairment of cognitive and motor function may be more marked in this patient group and a lower dosage is recommended together with close monitoring (alprazolam-xanax-indications-and-dosage/">see Dosage). Federal OBRA regulations recommend dosage limits for anxiolytic and hypnotic use in the nursing home resident (alprazolam-xanax-indications-and-dosage/">see Dosage).
The safe and effective use of alprazolam in children and infants under 18 years old has not been established. Children are generally more sensitive to the CNS effects of the benzodiazepines.
[ Last revised: 12/8/2003 4:50:00 PM ]
References
. Carter K, Faberowski LK, Sherwood MB, et al. A randomized trial of the effect of midazolam on intraocular pressure. J Glaucoma 1999;8:204 - 7.
. Gurvich T, Cunningham JA. Appropriate Use of Psychotropic Drugs in Nursing Homes. Am Fam Physician 2000;61:1437 - 46.
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