Lorazepam Contraindications / Precautions
- abrupt discontinuation
- benzodiazepine hypersensitivity
- benzyl alcohol hypersensitivity
- breast-feeding
- chronic obstructive pulmonary disease (COPD)
- closed-angle glaucoma
- coma
- ethanol intoxication
- intraarterial administration
- obstetric delivery
- shock
- sleep apnea
- benzodiazepine dependence
- bipolar disorder
- children
- CNS depression
- dementia
- depression
- driving or operating machinery
- elderly
- GI disease
- hepatic disease
- hepatic encephalopathy
- infants
- mania
- myasthenia gravis
- neonates
- neuromuscular disease
- Parkinson’s disease
- pregnancy
- psychosis
- pulmonary disease
- renal failure
- renal impairment
- respiratory depression
- seizure disorder
- status epilepticus
- substance abuse
- suicidal ideation
Lorazepam Contraindications / Precautions
Occasionally, pre-existing depression may emerge or worsen with the use of benzodiazepines. Although lorazepam may be beneficial for patients with major depression or psychoses, the drug should be administered cautiously to patients with suicidal ideation. Large quantities of lorazepam should not be prescribed for patients with known suicidal ideation or a history of suicide attempt. Lorazepam should be used cautiously in patients with bipolar disorder because hypomania and mania have been reported in conjunction with the use of benzodiazepines in depressive disorders.
The use of injectable benzodiazepines in status epilepticus is often as an adjunct to other supportive therapies. In status epilepticus, ventilatory support and other life-saving measures should be readily available. Additional seizure maintenance medication should be ordered if required. The sedative effects of injectable benzodiazepines may add to the CNS depressive state seen in the postictal stage. Ventilatory support should also be available for the preanesthetic use of injectable benzodiazepines.
Injectable benzodiazepines are contraindicated for intraarterial administration due to the possibility of arteriospasm and resultant gangrene.
In general, use lorazepam with caution in patients with pulmonary disease. Lorazepam injection is contraindicated in patients with pulmonary disease that severely decreases respiratory function such as chronic obstructive pulmonary disease (COPD) or sleep apnea except in those patients receiving lorazepam for amnestic effects while being mechanically ventilated. Lorazepam injection should not be used in patients with preexisting respiratory depression or in cases of shock or coma because the drug can worsen CNS and respiratory depression. Lorazepam should be used cautiously in patients who snore regularly, because partial airway obstruction may convert to obstructive sleep apnea with benzodiazepine administration.
Due to CNS depression, patients should be cautioned against driving or operating machinery until they know how lorazepam may affect them. Some patients may experience excessive sedation and 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 lorazepam and other CNS depressant agents (lorazepam-interactions/">see Drug Interactions), and in patients with acute ethanol intoxication, organic brain syndromes (e.g., dementia), or psychosis. Patients with ethanol intoxication who have also consumed lorazepam are at increased risk of respiratory depression and coma.
Lorazepam is specifically contraindicated in cases of acute closed-angle glaucoma. According to most manufacturers, benzodiazepines are contraindicated in patients with acute closed-angle glaucoma. The mechanistic rational for this contraindication has been questioned, as benzodiazepines do not have antimuscarinic activity and do not raise intraocular pressure. Benzodiazepines may be used in patients with open-angle glaucoma who are receiving appropriate therapy.
Benzodiazepines should be administered cautiously to patients with renal impairment or renal failure, hepatic disease or hepatic encephalopathy; liver and renal function should be monitored regularly during prolonged therapy. As with all benzodiazepines, the use of lorazepam may worsen hepatic encephalopathy and should be used cautiously in severe hepatic impairment. Because lorazepam undergoes conjugative metabolism as opposed to oxidative metabolism, it is relatively safer to use in patients with hepatic dysfunction with careful clinical monitoring versus other benzodiazepines.
Lorazepam can cause physical and psychological dependence, and should be used with extreme caution in patients with known, suspected or a history of substance abuse. Generally, benzodiazepines should be prescribed for short periods (2 - 4 weeks) with continued reevaluation of the need for treatment. Tolerance (or tachyphylaxis) may develop to the sedative effects of benzodiazepines. Patients should be questioned about the need for escalating doses, and the clinician may need to intervene to prevent further tolerance or increased risk for addiction. Abrupt discontinuation of lorazepam after prolonged use should be avoided. Abrupt discontinuation of benzodiazepine therapy has been reported to cause withdrawal symptoms, especially following high dose or prolonged therapy (lorazepam-adverse-reactions/">see Adverse Effects). However, benzodiazepine dependence can occur following administration of therapeutic doses for as few as 1 - 2 weeks, and withdrawal symptoms may be seen following the discontinuation of therapy. Benzodiazepine withdrawal can be more intense with short-acting benzodiazepines such as lorazepam. 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 benzodiazepines due to the risk of precipitating a seizure. Benzodiazepines should be withdrawn slowly, using a gradual dosage-tapering schedule. During withdrawal, the greatest risk of seizure appears to be during the first 24 to 72 hours.
Clinical studies of lorazepam generally were not adequate to determine whether elderly subjects respond differently than younger adults, however, elderly patients > 50 years of age may experience a greater incidence of central nervous system depression and more respiratory depression, particularly with preanesthetic use. Age does not appear to have a clinically significant effect on lorazepam kinetics. Clinical circumstances, some of which may be more common in the elderly, such as hepatic or renal impairment, should be considered. Greater sensitivity (e.g., sedation) of some elderly patients cannot be ruled out. Benzodiazepines have been associated with falls in the elderly; lorazepam should be used with caution in this population. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range (lorazepam-indications-and-dosage/">see dosage). Federal OBRA regulations recommend maximum dosage limits for anxiolytic and hypnotic use in the nursing home resident (lorazepam-indications-and-dosage/">see Dosage).
Lorazepam should be used with caution in patients with a neuromuscular disease, such as muscular dystrophy, myotonia, or myasthenia gravis as these conditions can be exacerbated. 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.
Lorazepam has not been shown to be effective for comorbid conditions associated with anxiety (i.e., cardiovascular or gastrointestinal disorders). Esophageal dilation has been shown to occur in rats with high doses (6 mg/kg/day) and prolonged therapy (> 1 year) of lorazepam. The effect was reversible only if therapy was stopped within 2 months of observation. Although the clinical significance is not known, patients utilizing lorazepam for prolonged periods should have frequent evaluation for symptoms of upper GI disease.
Lorazepam is classified in FDA pregnancy risk category D. In general, the use of benzodiazepines is not life-saving and thus should be avoided in pregnancy whenever possible. An increased risk of congenital malformations is associated with benzodiazepine use in the first trimester. Lorazepam is associated with teratogenic effects in animal models. Lorazepam injection should not be given to a pregnant women except in serious or life-threatening situations (e.g., status epilepticus). Lorazepam is not recommended for use in obstetrical procedures or obstetric delivery, including cesarean section. Neonatal flaccidity has been reported in an infant whose mother was using benzodiazepines during pregnancy.
Lorazepam is known to be excreted into human breast milk. Lorazepam should not be administered to breast-feeding mothers as the risk of serious adverse effects, including CNS and respiratory depression, exists.
Lorazepam is contraindicated in any patient with a known lorazepam or benzodiazepine hypersensitivity. Some formulations of lorazepam injection contain benzyl alcohol and are contraindicated in those patients with known benzyl alcohol hypersensitivity. Formulations with benzyl alcohol should not be used in large quantities in neonates. Benzyl alcohol has been associated with ‘gasping syndrome’ in neonatal populations, characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high blood and urine concentrations of benzyl alcohol and its metabolites. Additional symptoms may include gradual neurologic deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic failure, renal failure, hypotension, bradycardia, and cardiovascular collapse. Some formulations of lorazepam injection should not be used in patients who are hypersensitive to other ingredients in these products (i.e., propylene glycol or polyethylene glycol). Furthermore, too much propylene glycol can cause central nervous system toxicity such as seizures and intraventricular hemorrhage, unresponsiveness, tachypnea, tachycardia, and diaphoresis. Although normal therapeutic lorazepam injectable doses contain very small amounts of benzyl alcohol, propylene glycol, and polyethylene glycol, premature infants, low birth weight infants, and children who receive high doses may be more susceptible to their effects. Also, children are more susceptible to the effects of benzodiazepines. Safe and effective use of lorazepam tablets have not been established in children < 12 years old. According to the manufacturer’s information, injectable lorazepam has not been evaluated in infants or children < 18 years old. However, off-label dose guidelines exist for the use of lorazepam in children and infants for certain life-threatening indications, including status epilepticus (lorazepam-indications-and-dosage/">see Dosage).
[ Last revised: 2/27/2007 6:04:00 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.
. Drugs in Pregnancy and Lactation. A Reference Guide to Fetal and Neonatal Risk. Briggs GG, Freeman RK, Yaffe SJ, (eds.) 7th ed., Philadelphia. PA. Lippincott Williams and Wilkins. 2005; 942 - 3.
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