The P-I-E-N-O Parkinsn's List Drug Database
lorazepam / AtivanTM
Description: Lorazepam is an oral and parenteral benzodiazepine used in the treatment of anxiety and status epilepticus. Other uses include perioperative sedation induction and anterograde amnesia. Intravenous lorazepam has replaced intravenous diazepam as the drug of choice for the treatment of status epilepticus because lorazepam persists in the CSF longer than diazepam. Some clinicians also prefer lorazepam over chlordiazepoxide or diazepam for controlling anxiety and agitation during ethanol withdrawal because lorazepam is not metabolized to active metabolites. Lorazepam was approved by the FDA in September 1977. It is a DEA schedule IV controlled substance.
Mechanism of Action: Benzodiazepines act at the level of the limbic, thalamic, and hypothalamic regions of the CNS, and can produce any level of CNS depression required including sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and coma. The action of these drugs is mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Central benzodiazepine receptors interact allosterically with GABA receptors, potentiating the effects of GABA and thereby increasing the inhibition of the ascending reticular activating system. Benzodiazepines block the cortical and limbic arousal that occurs following stimulation of the reticular pathways.
As an anticonvulsant, lorazepam has become the preferred parenteral benzodiazepine. Although lorazepam has a shorter elimination half-life than diazepam, lorazepam persists in the CNS longer than diazepam.
Pharmacokinetics: Lorazepam is administered orally and parenterally. It is absorbed rapidly following an oral dose, with wide distribution throughout the body tissues. Approximately 91% of lorazepam present in the blood is protein- bound. Lorazepam is conjugated to glucuronide by the liver to inactive metabolites. The half-life of lorazepam is approximately 42, 10.5, and 13 hours in neonates, older children, and adults, respectively. The plasma half-life is much longer in neonates because their glucuronidation pathways are not mature. The metabolites are excreted in the urine.
CONTRAINDICATIONS/PRECAUTIONS: Lorazepam should not be used in patients with preexisting respiratory depression or in cases of acute ethanol intoxication, shock, or coma because the drug can worsen CNS depression. Lorazepam should not be used in patients with diseases that decrease respiratory function such as chronic obstructive pulmonary disease (COPD).
Large quantities of lorazepam should not be prescribed for patients with known suicidal ideation or tendencies.
Lorazepam can impair mental ability and alertness, so patients should be warned not to drive a motor vehicle or operate heavy equipment while taking this drug.
Lorazepam is contraindicated in cases of acute closed-angle glaucoma because benzodiazepines can have anticholinergic effects.
Lorazepam is rarely beneficial for patients with depressive neurosis or psychosis and can induce paradoxical effects in these patients; the drug should therefore be administered very cautiously, if at all, to such patients.
Lorazepam can cause harm to the fetus when administered to pregnant women, so the drug is contraindicated during pregnancy.
Benzodiazepines should be administered cautiously to patients with renal impairment or hepatic disease; liver and renal function should be monitored regularly during prolonged therapy.
Abrupt discontinuation of lorazepam after prolonged use can cause seizures in susceptible patients. Abrupt discontinuation of benzodiazepine therapy has been reported to cause withdrawal symptoms including irritability, nervousness, and insomnia. Benzodiazepine withdrawal is more likely to occur following abrupt cessation after excessive or prolonged doses, but it can occur following the discontinuance of therapeutic doses administered for as few as 1-2 weeks. Benzodiazepine withdrawal also can be more intense if the benzodiazepine involved possesses a relatively short duration of action such as lorazepam. Abdominal cramps, confusion, depression, perceptual disturbances, sweating, nausea, vomiting, parasthesias, photophobia, hyperacusis, tachycardia, and trembling also occur during benzodiazepine withdrawal, but the incidence of these reactions is lower. Convulsions, hallucinations, delirium, and paranoia also can occur. Benzodiazepines should be withdrawn cautiously and slowly, using a very gradual dosage-tapering schedule.
The clearance and/or elimination of many drugs are reduced in the elderly. Delayed elimination can either intensify or prolong the actions of adverse reactions of the drug. Benzodiazepines have been associated with falls in the elderly and the consumer advocate group, Public Citizen, has recommended these drugs not be used in the elderly.
DRUG INTERACTIONS: Phenytoin can increase the hepatic metabolism of lorazepam, reducing lorazepam serum concentrations.
Patients receiving levodopa for Parkinson's disease can experience decreased control of the symptoms of this disease when benzodiazepines are added to their regimen. Benzodiazepines should be administered cautiously to such patients.
Cimetidine, erythromycin, or disulfiram can decrease the hepatic metabolism of lorazepam if administered concomitantly. Probenecid has also been shown to decrease lorazepam clearance and increase its elimination half-life although the clinical significance of this is unclear. Patients receiving lorazepam should be monitored for signs of altered benzodiazepine response when cimetidine, erythromycin, disulfiram, or possibly probenecid is initiated or discontinued.
Concomitant administration of lorazepam with CNS-depressant drugs, including opiate agonists, phenothiazines, barbiturates, ethanol, HA-blockers, general anesthetics, and tricyclic antidepressants, can potentiate the CNS effects (i.e., increased sedation or respiratory depression) of either agent.
Diazepam has reportedly decreased the elimination of digoxin in some patients. Digoxin toxicity has occurred in a patient receiving alprazolam and digoxin. This interaction may be the result of increased protein binding of digoxin and/or an effect of benzodiazepines at the renal tubules that decreases the elimination of digoxin. Pending further clarification of this interaction, patients receiving a benzodiazepine and digoxin concurrently should be monitored for increased serum digoxin levels.
Oral contraceptives can increase the effects of lorazepam because oral contraceptives inhibit oxidative metabolism, thereby increasing serum concentrations of concomitantly administered benzodiazepines that undergo oxidation. Patients receiving oral contraceptive therapy should be observed for evidence of increased response to lorazepam.
Flumazenil and benzodiazepines are pharmacological opposites. Flumazenil is specifically used to reverse the actions of benzodiazepines. Clinicians should note that the duration of action for some benzodiazepines may be much longer than that of flumazenil and repeat doses of flumazenil may be necessary.
ADVERSE REACTIONS: Most of the CNS-related adverse effects associated with lorazepam therapy are dose-dependent. These include headache, drowsiness, ataxia, dizziness, confusion, depression, slurred speech, syncope, lightheadedness, fatigue, tremors, and vertigo. Occasionally, paradoxical CNS stimulation can occur, particularly in psychiatric patients and hyperactive children. Symptoms of paradoxical CNS stimulation include hostility, nightmares, talkativeness, excitement, mania, tremulousness, sleep disturbances, increased muscle spasticity, acute rage reactions, anxiety, restlessness, euphoria, and hyperflexia. Benzodiazepine therapy should be discontinued if any of the signs of paradoxical CNS excitement occur.
Other less frequently reported adverse reactions to lorazepam therapy include bradycardia, hypotension, rash, urticaria, blurred vision, diplopia, flushing, constipation, nausea/vomiting, libido decrease, hepatic dysfunction, and abdominal pain.
Apnea, hypotension, and cardiac arrest have been reported following parenteral administration of benzodiazepines to the elderly, to severely ill patients, or to patients with compromised respiratory function. Respiratory depression also has occurred in these pateints during benzodiazepine therapy, occasionally resulting in death.
Even after short-term use of lorazepam, there is evidence of physiological dependence and consequent adverse withdrawal symptoms. Abrupt withdrawal of benzodiazepine therapy has been reported to cause withdrawal symptoms including irritability, nervousness, and insomnia. Benzodiazepine withdrawal is more likely to occur following abrupt cessation of excessive or prolonged doses, but it can occur following the discontinuance of therapeutic doses that have been administered for as few as 1- 2 weeks. Abdominal cramps, confusion, depression, perceptual disturbances, sweating, nausea/vomiting, parasthesias, photophobia, hyperacusis, tachycardia, and trembling also occur during benzodiazepine withdrawal, but these reactions are less frequent. Convulsions, hallucinations, delirium, and paranoia also can occur. Benzodiazepines should be withdrawn cautiously and gradually, using a very gradual dosage-tapering schedule.
PATIENT INFORMATION:
What do lorazepam tablets do?
Lorazepam (AtivanTM ) is a benzodiazepine. Benzodiazepines belong to a group of medicines that slow down the central nervous system. Lorazepam relieves anxiety and nervousness. Federal law prohibits the transfer of clonazepam to any person other than the patient for whom it was prescribed. Do not share this medicine with anyone else. Generic lorazepam tablets are available.
What should my doctor or pharmacist know before I take lorazepam?
They need to know if you have any of these conditions:
How should I take this medicine?
Take lorazepam tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. If lorazepam upsets your stomach, take it with food or milk. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking except on your doctor's advice.
Special precautions for use in children:
The safe use of lorazepam in children under 12 years old has not been established.
Elderly patients over 65 years old may have a stronger reaction to this medicine.
What if I miss a dose?
If you miss a dose and remember within an hour, take it as soon as you can. If it is more than an hour since you missed a dose, skip that dose and go back to your regular schedule. Do not take double or extra doses.
What other medicines can interact with lorazepam?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking lorazepam?
Serious side effects with lorazepam include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with lorazepam include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take lorazepam?
Visit your doctor for regular checks on your progress. Your body may become dependent on lorazepam, ask your doctor if you still need to take it. However, if you have been taking lorazepam regularly for some time, do not suddenly stop taking it. You must gradually reduce the dose or you may get severe side effects. Ask your doctor for advice before increasing or decreasing the dose. Even after you stop taking lorazepam it can still affect your body for several days.
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how lorazepam affects you. To reduce the risk of dizzy and fainting spells, do not stand or sit up quickly, especially if you are an older patient. Alcohol may increase dizziness and drowsiness. Avoid alcoholic drinks.
Do not treat yourself for coughs, colds or allergies without asking your doctor or pharmacist for advice. Some ingredients can increase possible side effects.
If you are going to have surgery, tell your doctor or dentist that you are taking lorazepam.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature, approximately 25C (77F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.
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