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Lorazepam - A Comprehensive Review on Its Uses, Dosage, Side Effects, Precautions, and Interactions

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Lorazepam is used to treat anxiety disorders. Learn about its uses, dosage, drug warnings, side effects, precautions, and drug interactions.

Medically reviewed by

Dr. Vishal Anilkumar Gandhi

Published At January 23, 2023
Reviewed AtJune 1, 2023

Overview:

Lorazepam is a benzodiazepine medication used as a sedative and treats anxiety disorder. Benzodiazepines are central nervous system depressants that slow down the activities in the nervous system. Benzodiazepines are available only on doctor's prescriptions and can be taken by adults and children aged 13 and above. Lorazepam is a Schedule IV controlled substance which means the drug has the potential for misuse and dependence.

How Does Lorazepam Work?

Lorazepam is a short-acting benzodiazepine, often referred to as a sedative or tranquilizer. These drugs work by relaxing the activities in the brain and the nerves. Lorazepam binds to the benzodiazepine receptors in the postsynaptic GABA (gamma-aminobutyric acid)-A ligand-gated chloride channel neuron at different sites of the central nervous system. This binding results in an increase in the GABA inhibitory effects, which translates as an increase in the flow of chloride ions into the cells, causing hyperpolarization and stabilization of the cellular plasma membrane.

Lorazepam is rapidly absorbed when given orally. The bioavailability of the drug is 90 percent. Lorazepam starts to work in around 20 to 30 minutes of oral administration. The drug reaches its full sedative effect after one to one and a half hours. Lorazepam is hepatically metabolized by the CYP450 isoenzymes and is eliminated mainly in the kidneys. It is recommended not to use Lorazepam for more than four weeks.

Uses of Lorazepam:

Lorazepam is Food and Drug Administration (FDA) approved for short-term relief of anxiety and anxiety associated with depressive symptoms such as insomnia (sleep disorder). It can be used as an anesthesia premedication in adults to relieve anxiety and treat status epilepticus.

Limitations:

  • Lorazepam is highly addictive and may be habit-forming. It is advised not to continue with Lorazepam for more than four weeks.

  • The risk of dependence on Lorazepam increases if the drug is given at higher doses and for longer. Addiction to Lorazepam affects the activity in the brain and impairs the ability to learn behavioral strategies and long-term episodic memory.

  • Prescription of Lorazepam should be reserved for patients with inadequate alternative treatment options.

  • Some patients may develop leukopenia (low white blood cells) and have elevated lactate dehydrogenase (LDH). Periodic blood count and liver function tests are recommended for patients on long-term therapy.

Route of Administration

  • Oral.

  • Injection.

Dosage Strengths

Tablets

  • 0.5 milligrams.

  • 1 milligram.

  • 2 milligrams.

Injectable Solution

  • 2 milligrams.

  • 4 milligrams.

Dosage Forms

  • Tablets.

  • Injection.

Typical Dosage

  • The starting oral dose for Lorazepam is two to three milligrams two to three times a day.

  • The recommended dose of injection usually is four milligrams given slowly.

  • The maximum dose of Lorazepam in 24 hours is 10 milligrams.

  • Lorazepam dosage depends on several factors, including the type and severity of the condition, the form of the drug, age, body weight, and other medical conditions.

  • Older adults may be given lower doses than usual as they have age-related liver or kidney problems.

adult-dosage-of-lorazepam

Special Considerations:

  • Pregnancy and Lactation - Lorazepam is considered a pregnancy category D drug which means that the drug carries known risks to pregnant women and their babies. The drug should be used with caution during pregnancy and while breastfeeding only if the benefits outweigh the risks of the drug. Lorazepam transfers through the placenta. Infants of mothers who have ingested the benzodiazepines for several weeks or more preceding delivery have been reported to have withdrawal symptoms during the postnatal period, with symptoms including hypoactivity, respiratory depression, apnea, and impaired metabolic response.

  • Allergy - Therapy with Lorazepam can cause severe allergic reactions, with symptoms such as swelling of the throat, itching, hives or tongue, and trouble breathing. The drug should be avoided if the person has a history of an allergic reaction to any benzodiazepine (Alprazolam, Diazepam, Valium, and Versed).

  • Activities Requiring Mental Alertness - Therapy with Lorazepam can cause drowsiness, dizziness, and lack of concentration. It is advised to avoid driving or operating heavy machinery while taking Lorazepam.

  • Elderly - Therapy with Lorazepam should be administered with caution in the elderly, especially age above 65 years, as inadequate clinical studies are available. There can be an increased incidence of sedation and unsteadiness. Some elderly have age-related hepatic and renal problems that can increase their sensitivity to sedation.

  • Children - Treatment with Lorazepam is approved for children 12 years and older for short-term anxiety or insomnia.

Warnings and Contraindications

Contraindications:

  • Hypersensitivity - Lorazepam should not be given to people who have had an allergic reaction to the active component of the drug.

  • Acute Narrow-Angle Glaucoma - Treatment with Lorazepam is reported to increase intraocular pressure and cause visual disturbances, including diplopia (double vision). Lorazepam is contraindicated in patients with acute angle-closure glaucoma or untreated open-angle glaucoma (caused due to damage to the optic nerve).

  • Myasthenia Gravis - Lorazepam has the potential to produce respiratory depression in susceptible patients, such as with myasthenia gravis, by causing an increased risk for respiratory muscle weakness and distress.

Warnings and Precautions:

  • Obesity - The plasma half-life of benzodiazepine may be prolonged in obese patients due to increased distribution into fat. Therapy with Lorazepam should be administered with caution in obese patients with careful monitoring of the nervous system status.

  • Closed-Angle Glaucoma - Lorazepam is contraindicated in patients with acute angle-closure glaucoma. The user can be a risk factor for acute angle-closure glaucoma, an ophthalmic emergency.

  • Asthma - Caution should be exercised when taking Lorazepam in patients with asthma as it may exacerbate the condition and increase the likelihood of mortality following an exacerbation.

  • Drug Dependence - Prolonged use of benzodiazepines can cause dependence and abuse. Abrupt cessation following continued use for six weeks may precipitate withdrawal symptoms. Therapy with Lorazepam should be gradually tapered under close monitoring.

  • Respiratory Depression - High dosages or intravenous administration of Lorazepam may cause respiratory depression and apnea. Injectable formulations of benzodiazepines should be avoided in patients with sleep apnea, severe respiratory insufficiency, or hypoxia.

  • Seizures - Benzodiazepine therapy may precipitate or increase the incidence or onset of generalized tonic-clonic seizures in patients with a history of seizures. Cessation of Lorazepam should occur gradually with incrementally reduced dosage.

  • Prolonged Hypotension - Benzodiazepine should not be injected into patients in shock or coma; it may intensify the condition.

  • Depression - Therapy with benzodiazepines should be administered cautiously in patients with a history of depression or other psychiatric disorders.

For Patients

What Are Anxiety and Anxiety Disorders?

Anxiety is the body's response to stress. It develops a feeling of fear and apprehension in a person and stops them from doing certain things. Occasional anxiety is normal and may be due to health, money, or family problems. Anxiety disorders are the most common form of emotional disorder. It involves more than temporary worry or fear. The symptoms of anxiety disorders can interfere with a person’s day-to-day activities, such as at work, school, and relationships. Some anxiety disorders include panic disorder, social anxiety disorder, and phobia-related disorders.

Symptoms of Anxiety Disorders:

Some general symptoms of anxiety disorders include

  • Feeling restless.

  • Easily fatigued.

  • Being irritable.

  • Headaches, muscle aches, or unexplained aches.

  • Sweating.

  • Trembling.

  • Feeling out of control.

  • Pounding or racing heart.

  • Difficulty in making eye contact.

  • Irrational worry or excessive worry.

  • Phobia of heights, flying, blood, receiving injections, or specific animals.

Why Is Lorazepam Prescribed For Anxiety Disorders?

Lorazepam belongs to a group of medicines called benzodiazepines that work by increasing the levels of a chemical, gamma-amino-butyric acid (GABA), in the brain. It makes one feel calm and relieves anxiety. The drug is quick-acting and effective in reducing anxiety caused by depression.

Facts One Should Know About Lorazepam:

  • Lorazepam is a Schedule IV controlled substance. Abuse and misuse of benzodiazepine involve using doses greater than the maximum recommended dosage and may produce physical dependence.

  • Lorazepam is known to be potentially addictive and causes both emotional and physical dependence. The drug should be started at the lowest dose and for the shortest possible time.

  • The most common side effect of Lorazepam is feeling sleepy during the daytime.

  • Do not drink alcohol while taking Lorazepam, as it can make one sleep very deeply.

  • Lorazepam can help one relax before an operation or dental treatment, as it is often prescribed for short-term use as a pre-med.

How Should One Take Lorazepam?

  • Lorazepam is available as a tablet, concentrate, and injection and may be taken with or without food.

  • It is prescribed for a short time. The dose is gradually reduced before stopping completely.

  • Lorazepam comes in 0.5 mg, 1 mg, 2.5 mg tablets, and liquid containing 1 mg for injection. Lorazepam is usually taken two to three times a day.

  • The Lorazepam concentrate comes with a specially marked dropper for measuring the dose.

  • The injectable Lorazepam may be given in hospitals.

  • Lorazepam must be stored in an airtight container away from children and pets. The medication should be stored at room temperature and away from heat, moisture, and direct sunlight.

  • Lorazepam should not be shared with another person, especially someone with a history of drug abuse or addiction.

  • In case of a missed dose, take it soon after one remembers. However, do not take two tablets together at once, as it may cause adverse reactions. Always space the doses at least eight hours apart.

Information to Be Given to the Doctor Before Taking Lorazepam:

  • Allergy - Therapy with Lorazepam should be avoided if the person has had allergic reactions such as hives, difficulty breathing, and swelling of the face.

  • Medical History - Before taking Lorazepam, inform the doctor of medical history and drug history. Tell the doctor about the prescription drugs, non-prescription, supplements, or herbal products that one may be taking.

  • Pregnancy and Breastfeeding - Lorazepam is a pregnancy category D drug. The use of Lorazepam is contraindicated in pregnancy as it may cause an increased risk of cleft lip, palate, birth defects, and miscarriages. The drug has low levels in breast milk.

  • Renal and Hepatic Disease - The liver metabolizes benzodiazepines, and the metabolites are excreted in the urine. These metabolites undergo biotransformation to inactive products before excretion by the kidneys. Therapy with benzodiazepines should be administered cautiously in patients with impaired renal or hepatic functions.

  • Children - Children can take Lorazepam above 13 years of age.

  • Elderly - Prolonged use of benzodiazepines can further worsen symptoms of older people with upper gastrointestinal disease and should be cautiously administered. Excessive drowsiness can increase the risk of falls or accidental injury. These people have age-related liver and kidney problems that may decrease drug clearance.

  • Mind Alertness - Lorazepam causes side effects like dizziness, drowsiness, and disorientation, which may affect the ability to drive or perform complex tasks.

Safety of Lorazepam:

Lorazepam is a safe drug when taken in the prescribed doses or at the recommended times. However, large doses of the medication may increase the risk of overdose. The drug slows down the activity in the brain and nerves. It may cause fatal consequences when combined with other drugs that suppress brain activity and vital organs. Patients should consult the physician before increasing the dose or abruptly discontinuing the drug. Periodic tests, such as blood counts and liver function tests, are usually advised for patients taking long-term Lorazepam therapy.

Effectiveness of Lorazepam:

Lorazepam is more effective in patients with worse anxiety symptoms. The drug helps the person to feel calm and reduces the feeling of anxiety. It also makes a person sleep in those having difficulty falling asleep and maintains sleep.

Side Effects Expected With Lorazepam:

Lorazepam may cause common side effects that may include:

  • Severe drowsiness.

  • Unusual changes in mood or behavior.

  • Sudden restless feeling or excitement.

  • Sleep problems.

  • Confusion.

  • Hallucinations (seeing imaginary things).

  • Vision changes.

  • Weakness.

  • Dark urine.

  • Nausea.

  • Diarrhea.

  • Changes in appetite.

  • Constipation.

  • Dry mouth.

  • Yellowing of the skin and eyes.

  • Suicidal thoughts.

Severe side effects may include:

  • Disoriented walking.

  • Tremors.

  • Fever.

  • Severe skin rash.

  • Irregular heartbeat.

Can One Stop Taking Lorazepam Suddenly Without the Doctors Approval?

  • Never stop taking medicines without talking to the doctor. The doctor will decrease the dose gradually.

  • Do not take the drug more than advised by the doctor.

  • Abruptly stopping Lorazepam causes withdrawal symptoms or relapse of the illness. Reported symptoms include headache, tension, depression, dizziness, irritability, confusion, involuntary movements, hallucinations, convulsions, tremors, palpitations, and short-term memory loss.

  • The doctor recommends that the drug dose should be gradually lowered.

Physical and Psychological Dependence of Lorazepam:

High doses and long-term use of Lorazepam increase the risk of dependency. It may further increase the risk in patients with a history of alcoholism or drug abuse, or significant personality disorders. Individuals prone to addiction, such as drug addicts, substance abusers, or alcoholics, should be under surveillance when receiving Lorazepam or other psychotropic agents.

Lorazepam should be prescribed for short periods, and the treatment should not be extended without reevaluating the need for continued treatment. Discontinuation of the drug should be gradual by tapering the dose.

Dietary Restrictions to Consider When Taking Lorazepam:

  • Alcohol - Drinking alcohol can increase the nervous system side effects of Lorazepam, such as dizziness, drowsiness, and difficulty concentrating, and should be avoided while being treated with Lorazepam.

  • Caffeine - It is advised to avoid taking caffeine or caffeine-containing foods or beverages like colas, coffee, or chocolates. Caffeine can cause anxiety and sleep loss and affect the drug's effectiveness.

Storage of Lorazepam:

  • Keep Lorazepam medicine in their original packaging.

  • Store at room temperature between 15 to 30 degrees. The injections before reconstitution may be stored at 20 to 25 degrees centigrade.

  • Direct contact with heat, air, and light may damage the medicines. Therefore, keep the medicines away from direct light and heat.

  • Keep all medicines out of reach of children and pets. Always lock the safety caps of the medication to protect small children from poisoning themselves.

Disposal of Lorazepam Medicines:

  • Do not keep outdated medicines or medicines that are no longer needed. Discard any unused portion of the reconstituted vial.

  • Likewise, unneeded Lorazepam tablets should not be disposed of by flushing or throwing them out with regular garbage.

  • Dispose of the medicine through the local medicine take-back program, which can be accessed or learned more about through the local pharmacist.

  • Some people may not have access to a drug take-back program. Ask the local pharmacist about any other drug disposal options available.

Overdose:

  • In case of an overdose, call the poison control helpline.

  • Call the emergency services if the person has collapsed or has trouble breathing.

  • Overdose symptoms include pale or bluish skin, over-sedation or drowsiness, slurred speech, memory loss, confusion, weakness, loss of coordination, or loss of consciousness.

  • An overdose of Lorazepam may end in death if the person is not given immediate medical attention.

  • Supportive treatment is initiated following the patient's clinical signs and symptoms.

For Doctors

Indications:

Lorazepam is approved for short-term (four months) relief of anxiety symptoms observed in anxiety-associated insomnia and as an anesthetic, premedication to produce sedation or amnesia. It is also used in treating status epilepticus. Doctors often prescribe Lorazepam (off-label or non-FDA-approved) for rapid tranquilization of agitated patients, alcohol withdrawal delirium, insomnia, panic disorder, or chemotherapy-associated nausea and vomiting.

Pharmacology of Lorazepam

Description

Lorazepam is an antianxiety agent. That is short-acting and rapidly cleared benzodiazepine. It is a white powder that is almost insoluble in water.

Components

Active Ingredients - Lorazepam glucuronide.

Inactive Ingredients

  • Lactose monohydrate.

  • Magnesium stearate.

  • Microcrystalline cellulose.

  • Polacrilin potassium.

Clinical Pharmacology

A single high dose of Lorazepam has a tranquilizing action on the central nervous system with no appreciable effect on the respiratory or cardiovascular system.

Mechanism of Action

Lorazepam binds to the benzodiazepine receptors on the postsynaptic GABA-A ligand-gated chloride channel neuron at several sites within the central nervous system. It enhances the inhibitory effects of GABA, which increases the conductance of chloride ions in the cell. The shift of chloride ions results in hyperpolarization and stabilization of the cellular plasma membrane. The inhibitory action is beneficial in anxiety disorders.

Pharmacodynamics

The effect of Lorazepam on GABA-A receptors increases the frequency of the chloride ion channel opening. The anticonvulsant properties of Lorazepam are related to the binding to voltage-dependent sodium channels in which the sustained repetitive firing gets limited by the slow recovery of sodium channels due to the benzodiazepine effect.

Pharmacokinetics

  • The mean Cmax- 90 percent.

  • Median Tmax- Two hours.

[Cmax- Maximum concentration achieved by a drug in the blood, cerebrospinal fluid, or target organ after administration of a dose].

[Tmax- Time taken for a drug to reach maximum concentration after administration of a dose].

Pharmacokinetic Changes

Lorazepam is well absorbed after oral administration. Peak concentration is attained in two hours. The drug freely crosses the blood-brain barrier by passive diffusion.

A. Distribution

  • Steady-state Plasma Levels - Peak plasma concentration occurs approximately from a two-milligram dose is 20 ng/ml.

  • Mean Half-Life - 12 hours.

  • Protein Bound - 85 percent.

  • Time to Approach Steady-state Levels - One to one and a half hours.

  • Mean Volume of Distribution - 1.3 l/kg.

B. Metabolism

Metabolic Processes - Lorazepam is rapidly conjugated at its 3-hydroxy group into Lorazepam glucuronide, which is then excreted in the urine. There is no evidence of accumulation of Lorazepam on administration for up to six months.

C. Elimination -

The elimination half-life is 14 hours, and the clearance is 1.1 ml/min/ kg. The drug is excreted primarily 88 percent in the urine and seven percent in the feces.

Special Considerations

  • Pregnancy - Treatment with Lorazepam should be avoided during pregnancy, as it can increase the rate of preterm delivery and low birth weight in newborns.

  • Elderly - Debilitated patients and the elderly are more likely to be affected by the sedative effects of Lorazepam. Therefore, these patients should be monitored frequently and have their dosage adjusted carefully by the patient's response.

  • Children - The safety of Lorazepam has not been established in children under 12 years and should be given with caution.

  • Renal Impairment - Therapy with Lorazepam should be administered cautiously in patients with renal impairment, as it would compromise the clearance of the drug.

  • Hepatic Impairment - Lorazepam may worsen hepatic encephalopathy (decreased brain functioning due to severe liver disease). The drug should be used cautiously in patients with severe hepatic insufficiency and encephalopathy. The dosage must be adjusted according to the patient's response.

  • Alcohol - Alcohol can increase the nervous system side effects of Lorazepam, such as dizziness, drowsiness, and difficulty concentrating. Avoid or limit the use of alcohol while being treated with Lorazepam.

Drug Interactions

  • Diphenhydramine - Antihistamines such as Diphenhydramine should not be combined with Lorazepam as it can increase drowsiness and dizziness.

  • Morphine - Narcotic pain medications such as Morphine, Oxycodone, and Hydrocodone can cause dangerous interactions and central nervous system depression, including respiratory distress, coma, and even death.

  • Opioid Cough Medications - Taking medications, such as Codeine cough syrup, increases the risk of respiratory depression, as it acts on different sites in the central nervous system.

  • Zolpidem - Sleeping medications such as Zolpidem, when used together with Lorazepam, can increase side effects, such as drowsiness, confusion, and difficulty in concentration.

  • Droperidol - Treatment with Droperidol causes excessive slow heart rate and low blood pressure. Combining it with Lorazepam can increase the risk of an irregular heart rhythm that can be life-threatening.

  • S Ketamine - Using Lorazepam with S Ketamine may increase the side effects, such as drowsiness, dizziness, and difficulty concentrating.

  • Valproate - Valproate (used for epilepsy and bipolar disorder) with Lorazepam can decrease the excretion of benzodiazepine and increase the side effects.

  • Probenecid - Combining the use of Probenecid (used for gout) may result in a more rapid onset or prolonged effect of Lorazepam due to increased half-life and decreased total clearance. The dosage may need to be reduced by 50 percent when coadministered with Probenecid.

  • Theophylline - Bronchodilators, such as Theophylline and Aminophylline, may reduce the sedative effects of benzodiazepines, including Lorazepam.

What Have Clinical Trials Shown About Lorazepam?

Trial 1:

Objective - To study the effectiveness of Lorazepam for the treatment of out-of-hospital status epilepticus in comparison to Diazepam and placebo.

  • A randomized, double-blind trial to evaluate intravenous benzodiazepines for treating status epilepticus.

  • There were 205 participants, of which 68 received Diazepam, 66 received Lorazepam, and 71 received a placebo. Participants included adults with prolonged or repetitive generalized convulsive seizures who have received intravenous Diazepam (5 mg), Lorazepam (2 mg), or a placebo.

Primary Outcome Endpoint - Status epilepticus had terminated on arrival at the emergency department in more patients treated with Lorazepam or Diazepam than patients were given a placebo.

Secondary Outcome End Point - The rates of respiratory or circulatory complications after study treatment was administered were more in the placebo group (22.5 percent) than in the Lorazepam group (10.6 percent) and Diazepam group (10.3 percent).

Results - Benzodiazepines are effective and safe when administered by paramedics for out-the-hospital status epilepticus in adults. Lorazepam is likely to be a better therapy than Diazepam.

Trial 2:

Objective - A study to compare the efficacy and adverse effects of intranasal versus intravenous Lorazepam in children aged 6 to 14 who presented with acute seizures.

  • A randomized open-label study in a hospital on one hundred forty-one children presenting with convulsions in an emergency was included.

  • Children were randomly given either intravenous or intranasal Lorazepam.

Primary Outcome Measure - Clinical seizure remission within ten days of drug administration was found to be 80 percent in the intravenous group compared to 83.1 percent in the intranasal group.

Secondary Outcome Measure - Persistent cessation of seizure activity for one hour.

Result - Intranasal administration of Lorazepam is not inferior to intravenous administration to terminate acute convulsive seizures in children.

Complications or Side Effects:

  • Drowsiness - Consuming alcohol with Lorazepam should be avoided, as it can tire one. Avoid driving and operating heavy machinery, as Lorazepam can make the person drowsy or sleepy.

  • Dizziness - Initial doses of Lorazepam may make one feel dizzy. The problem wears off when one gets used to the medicine. Avoid standing up suddenly after a long-time sitting or lying position. Wait until the dizziness subsides.

  • Rash - Lorazepam can cause rashes and allergic reactions, which may require the person to take antihistamines.

  • Dependence - Lorazepam may produce emotional and physical dependence even if it is taken in the recommended dose. It can develop after two or more weeks of daily use.

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Dr. Vishal Anilkumar Gandhi
Dr. Vishal Anilkumar Gandhi

Psychiatry

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