Lorazepam

• Tablets: 0.5, 1, and 2 mg.
• Oral solution: 0.5 mg/5 ml, 2 mg/ml.
• Injection: 1 mg/0.5 ml, 2 mg/ml and 4 mg/ml

• Tablets should be kept at room temperature 15 C to 30 C (59 F to 86 F).
• Oral solutions should be refrigerated at 2 C to 8 C (36 F to 46 F).
• Injectable solutions should be refrigerated.

• Lorazepam is thought that excessive activity of nerves in the brain may cause anxiety and other psychological disorders. Gamma-aminobutyric acid (GABA) is a neurotransmitter, a chemical that nerves in the brain use to send messages to one another that reduces the activity of nerves in the brain. It is thought that lorazepam and other benzodiazepines may act by enhancing the effects of GABA in the brain to reduce activity. Because lorazepam is removed from the blood more rapidly than many other benzodiazepines, there is less chance that lorazepam concentrations in blood will reach high levels and become toxic. Lorazepam also has fewer interactions with other medications than most of the other benzodiazepines.

• The FDA approved lorazepam in March 1999.

Ativan (lorazepam), an antianxiety agent, has the chemical formula, 7-chloro-5-(o-chlorophenyl)-1,3- dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one:

C15H10Cl2N2O2     MW: 321.16

It is a nearly white powder almost insoluble in water. Each Ativan (lorazepam) tablet, to be taken orally, contains 0.5 mg, 1 mg, or 2 mg of lorazepam. The inactive ingredients present are lactose monohydrate, magnesium stearate, microcrystalline cellulose, and polacrilin potassium.

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at your next regularly scheduled time. Do not take extra medicine to make up the missed dose.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• alcohol
• antipsychotics such as aripiprazole (Abilify), haloperidol (Haldol), quetiapine (Seroquel), or clozapine (Clozaril)
• sedatives such as zolpidem (Ambien), eszopiclone (Lunesta), or zaleplon (Sonata)
• anxiolytics such as clonazepam (Klonopin), alprazolam (Xanax), or temazepam (Restoril)
• antidepressants such as fluoxetine (Prozac), escitalopram (Lexapro), or citalopram (Celexa)
• opioid analgesics such as oxycodone (OxyContin), morphine (MS Contin), or hydrocodone/acetaminophen (Norco), methadone (Methadose)
• antihistamines such as diphenhydramine (Benadryl) or promethazine (Phenergan)
• anticonvulsants such as phenytoin (Dilantin), carbamazepine (Tegretol, Equetro), or phenobarbital, valproate (Depakote)
• birth control pills
• probenecid; the dose of lorazepam should be reduced by 50% if also taking probenecid

Lorazepam Injection:

• You should tell your doctor if you are taking a drug called scopolamine, which may be used for gut problems or before an operation.

This is not a complete list of lorazepam drug interactions. Ask your doctor or pharmacist for more information.

Take lorazepam only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

lorazepam should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

Swallow the tablet whole. Do not crush, break, or chew it.

Measure the oral liquid using the marked medicine dropper that comes with the package. Dilute each dose with water, juice, soda, applesauce and puddings.

Dosing

The dose of lorazepam will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of lorazepam. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (oral solution):
  • For anxiety:
    • Adults and children 12 years of age and older—2 to 6 milligrams (mg) in divided doses per day. Your doctor may adjust your dose as needed.
    • Older adults—At first, 1 to 2 mg in divided doses per day. Your doctor may adjust your dose as needed.
    • Children younger than 12 years of age—Use and dose must be determined by your doctor.
• For oral dosage form (tablets):
  • For anxiety:
    • Adults and children 12 years of age and older—At first, 2 to 3 milligrams (mg) in divided doses per day. Your doctor may adjust your dose as needed.
    • Older adults—At first, 1 to 2 mg in divided doses per day. Your doctor may adjust your dose as needed and tolerated.
    • Children younger than 12 years of age—Use and dose must be determined by your doctor.
  • For insomnia caused by anxiety or transient situational stress:
    • Adults and children 12 years of age and older—2 to 4 milligrams (mg) taken as a single dose at bedtime. Your doctor may adjust your dose as needed.
    • Children younger than 12 years of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of lorazepam, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

It is very important that your doctor check your or your child's progress at regular visits to see if lorazepam is working and allow for changes in the dose. Blood tests may be needed to check for any unwanted effects.

Using lorazepam while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

lorazepam may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions.

lorazepam may cause drowsiness, trouble with thinking, trouble with controlling movements, or trouble with seeing clearly. Make sure you know how you react to lorazepam before you drive, use machines, or do anything else that could be dangerous if you are not alert or able to think or see well.

Do not stop taking it without checking with your doctor first. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This may help prevent a worsening of your condition and reduce the possibility of withdrawal symptoms, such as convulsions, hallucinations, headache, stomach or muscle cramps, tremors, trouble sleeping, or unusual behavior.

lorazepam will add to the effects of alcohol and other central nervous system (CNS) depressants. CNS depressants are medicines that slow down the nervous system, which may cause drowsiness or make you less alert. Some examples of CNS depressants are antihistamines or medicine for hay fever, allergies, or colds, sedatives, tranquilizers, or sleeping medicine, prescription pain medicine or narcotics, barbiturates or medicine for seizures, muscle relaxants, or anesthetics (numbing medicines), including some dental anesthetics. This effect may last for a few days after you stop taking lorazepam. Check with your doctor before taking any of the above while you are using lorazepam.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Drowsiness
• relaxed and calm
• sleepiness

• Abdominal or stomach pain
• aggressive, angry
• agitation
• attack, assault, or force
• black, tarry stools
• bleeding gums
• blood in the urine or stools
• bluish lips or skin
• blurred vision
• change in consciousness
• chills
• coma
• confusion
• confusion about identity, place, and time
• convulsions
• cough or hoarseness
• dark urine
• decreased urine output
• difficulty with breathing or swallowing
• difficulty with speaking
• discouragement
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• drooling
• dry mouth
• excitation
• false or unusual sense of well-being
• fast or irregular heartbeat
• feeling sad or empty
• fever with or without chills
• general feeling of tiredness or weakness
• headache
• hives, itching, or rash
• hyperventilation
• increased thirst
• irregular, fast or slow, or shallow breathing
• irritability
• loss of appetite
• loss of balance control
• loss of consciousness
• loss of interest or pleasure
• loss of memory
• lower back or side pain
• muscle pain or cramps
• muscle trembling, jerking, or stiffness
• nausea or vomiting
• not breathing
• painful or difficult urination
• pale or blue lips, fingernails, or skin
• pinpoint red spots on the skin
• problems with memory
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• reddening of the skin, especially around ears
• restlessness
• seeing, hearing, or feeling things that are not there
• seizures
• shaking
• shuffling walk
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• stiffness of the limbs
• sweating
• swelling of the eyes or inside of the nose
• swelling of the face, ankles, or hands
• swollen glands
• thoughts or attempts at killing oneself
• tightness in the chest
• trouble concentrating
• trouble sleeping
• twisting movements of body
• uncontrolled movements, especially of the face, neck, and back
• unexplained bleeding or bruising
• unpleasant breath odor
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting of blood
• yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur:

• Changes in patterns and rhythms of speech
• increased sweating
• loss of strength or energy
• nightmares
• shakiness and unsteady walk
• slurred speech
• trouble speaking
• unsteadiness, trembling, or other problems with muscle control or coordination
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
• unusual excitement, nervousness, restlessness, or irritability
• unusual paleness
• unusual weak feeling

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Being forgetful
• clumsiness
• constipation
• decreased interest in sexual intercourse
• disturbed color perception
• dizziness or lightheadedness
• double vision
• drowsiness
• feeling of constant movement of self or surroundings
• hair loss or thinning of the hair
• halos around lights
• inability to have or keep an erection
• increased in sexual ability, desire, drive, or performance
• increased interest in sexual intercourse
• lack or loss of self-control
• lethargy
• loss in sexual ability, desire, drive, or performance
• muscle aches, twitching, or weakness
• night blindness
• overbright appearance of lights
• rapid weight gain
• sensation of spinning
• shakiness in the legs, arms, hands, or feet
• shivering
• stupor
• trembling or shaking of the hands or feet
• tunnel vision
• weak or feeble pulse

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

In patients with depression, a possibility for suicide should be borne in mind; benzodiazepines should not be used in such patients without adequate anti-depressant therapy.

Lorazepam should be used with caution in patients with compromised respiratory function (e.g. COPD, sleep apnea syndrome).

Elderly or debilitated patients may be more susceptible to the sedative effects of Lorazepam. Therefore these patients should be monitored frequently and have their dosage adjusted carefully according to patient response; the initial dosage should not exceed 2 mg.

Paradoxical reactions have been occasionally reported during benzodiazepine use. Such reactions may be more likely to occur in children and the elderly. Should these occur, use of the drug should be discontinued.

The usual precautions for treating patients with impaired renal or hepatic function should be observed. As with all benzodiazepines, the use of Lorazepam may worsen hepatic encephalopathy; therefore, Lorazepam should be used with caution in patients with severe hepatic insufficiency and/or encephalopathy. Dosage for patients with severe hepatic insufficiency should be adjusted carefully according to patient response; lower doses may be sufficient in such patients.

In patients where gastrointestinal or cardiovascular disorders coexist with anxiety, it should be noted that Lorazepam has not been shown to be of significant benefit in treating the gastrointestinal or cardiovascular component.

Esophageal dilation occurred in rats treated with Lorazepam for more than one year at 6 mg/kg/day. The no-effect dose was 1.25 mg/kg/day (approximately 6 times the maximum human therapeutic dose of 10 mg per day). The effect was reversible only when the treatment was withdrawn within two months of first observation of the phenomenon. The clinical significance of this is unknown. However, use of Lorazepam for prolonged periods and in geriatric patients requires caution, and there should be frequent monitoring for symptoms of upper G.I. disease.

Safety and effectiveness of Lorazepam in children of less than 12 years have not been established.

Information for Patients

To assure the safe and effective use of Lorazepam, patients should be informed that, since benzodiazepines may produce psychological and physical dependence, it is advisable that they consult with their physician before either increasing the dose or abruptly discontinuing this drug.

Essential Laboratory Tests

Some patients on Lorazepam have developed Leucopenia, and some have had elevations of LDH. As with other benzodiazepines, periodic blood counts and liver-function tests are recommended for patients on long-term therapy.

Clinically Significant Drug Interactions

The benzodiazepines, including Lorazepam, produce increased CNS-depressant effects when administered with other CNS depressants such as alcohol, barbiturates, antipsychotics, sedative/hypnotics, anxiolytics, antidepressants, narcotic analgesics, sedative antihistamines, anticonvulsants, and anesthetics.

Concomitant use of clozapine and Lorazepam may produce marked sedation, excessive salivation, hypotension, ataxia, delirium and respiratory arrest.

Concurrent administration of Lorazepam with valproate may result in increased plasma concentrations and reduced clearance of Lorazepam. Lorazepam dosage should be reduced to approximately 50% when coadministered with valproate.

Concurrent administration of Lorazepam with probenecid may result in a more rapid onset or prolonged effect of Lorazepam due to increased half-life and decreased total clearance. Lorazepam dosage needs to be reduced by approximately 50% when coadministered with probenecid.

The effects of probenecid and valproate on Lorazepam may be due to inhibition of glucuronidation.

Administration of theophylline or aminophylline may reduce the sedative effects of benzodiazepines, including Lorazepam.

Carcinogenesis and Mutagenesis

No evidence of carcinogenic potential emerged in rats during an 18-month study with Lorazepam. No studies regarding mutagenesis have been performed.

Pregnancy

Reproductive studies in animals were performed in mice, rats, and two strains of rabbits. Occasional anomalies (reduction of tarsals, tibia, metatarsals, malrotated limbs, gastroschisis, malformed skull, and microphthalmia) were seen in drug-treated rabbits without relationship to dosage. Although all of these anomalies were not present in the concurrent control group, they have been reported to occur randomly in historical controls. At doses of 40 mg/kg and higher, there was evidence of fetal resorption and increased fetal loss in rabbits which was not seen at lower doses.

The clinical significance of the above findings is not known. However, an increased risk of congenital malformations associated with the use of minor tranquilizers (chlordiazepoxide, diazepam, and meprobamate) during the first trimester of pregnancy has been suggested in several studies. Because the use of these drugs is rarely a matter of urgency, the use of Lorazepam during this period should be avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. Patients should be advised that if they become pregnant, they should communicate with their physician about the desirability of discontinuing the drug.

In humans, blood levels obtained from umbilical cord blood indicate placental transfer or Lorazepam and Lorazepam glucuronide. Infants of mothers who ingested benzodiazepines for several weeks or more preceding delivery have been reported to have withdrawal symptoms during the postnatal period. Symptoms such as hypoactivity, hypotonia, hypothermia, respiratory depression, apnea, feeding problems, and impaired metabolic response to cold stress have been reported in neonates born of mothers who have received benzodiazepines during the late phase of pregnancy or at delivery.

Nursing Mothers

Lorazepam has been detected in human breast milk; therefore, it should not be administered to breast-feeding women, unless the expected benefit to the woman outweighs the potential risk to the infant.

Sedation and inability to suckle have occurred in neonates of lactating mothers taking benzodiazepines. Infants of lactating mothers should be observed for pharmacological effects (including sedation and irritability).

Geriatric Use

Clinical studies of Lorazepam generally were not adequate to determine whether subjects aged 65 and over respond differently than younger subjects; however, the incidence of sedation and unsteadiness was observed to increase with age (see ADVERSE REACTIONS).

Age does not appear to have a significant effect on Lorazepam kinetics (see CLINICAL PHARMACOLOGY).

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 older individuals cannot be ruled out. In general, dose selection for an elderly patient should be cautious, and lower doses may be sufficient in these patients (see DOSAGE AND ADMINISTRATION).

In postmarketing experience, overdose with Lorazepam has occurred predominantly in combination with alcohol and/or other drugs. Therefore, in the management of overdosage, it should be borne in mind that multiple agents may have been taken.

Symptoms

Overdosage of benzodiazepines is usually manifested by varying degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion, paradoxical reactions, dysarthria and lethargy. In more serious cases, and especially when other drugs or alcohol were ingested, symptoms may include ataxia, hypotonia, hypotension, cardiovascular depression, respiratory depression, hypnotic state, coma, and death.

Management

General supportive and symptomatic measures are recommended; vital signs must be monitored and the patient closely observed. When there is a risk of aspiration, induction of emesis is not recommended. Gastric lavage may be indicated if performed soon after ingestion or in symptomatic patients. Administration of activated charcoal may also limit drug absorption.  Hypotension, though unlikely, usually may be controlled with norepinephrine bitartrate injection.  Lorazepam is poorly dialyzable. Lorazepam glucuronide, the inactive metabolite, may be highly dialyzable.

The benzodiazepine antagonist flumazenil may be used in hospitalized patients as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert including “CONTRAINDICATIONS”, “WARNINGS”, and “PRECAUTIONS” should be consulted prior to use.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Concentrate, Oral:

LORazepam Intensol: 2 mg/mL (30 mL) [alcohol free, dye free, sugar free; unflavored flavor]

Generic: 2 mg/mL (30 mL)

Solution, Injection:

Ativan: 2 mg/mL (1 mL, 10 mL); 4 mg/mL (1 mL, 10 mL) [contains benzyl alcohol, polyethylene glycol, propylene glycol]

Generic: 2 mg/mL (1 mL, 10 mL); 4 mg/mL (1 mL, 10 mL)

Solution, Intravenous:

Generic: 100 mg/100 mL in NaCl 0.9% (100 mL); 60 mg/60 mL in NaCl 0.9% (60 mL [DSC])

Tablet, Oral:

Ativan: 0.5 mg, 1 mg [DSC]

Ativan: 1 mg [scored]

Ativan: 2 mg [DSC]

Ativan: 2 mg [scored]

Generic: 0.5 mg, 1 mg, 2 mg

Agitation in the ICU patient

Based on the American Society of Critical Care Medicine guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit (ICU), intravenous lorazepam may be given for the management of agitation in these patients; however, in mechanically-ventilated patients, nonbenzodiazepine sedation may be preferred due to suggested increases in duration of mechanical ventilation, ICU length of stay, and incidence of delirium with benzodiazepines.

Alcohol withdrawal delirium

Based on the American Society of Addiction Medicine guidelines for the management of alcohol withdrawal delirium, lorazepam has been recommended for the management of this condition [Mayo-Smith 2004].

Alcohol withdrawal syndrome

Based on the American Society of Addiction Medicine guidelines for the treatment of alcohol withdrawal syndrome, lorazepam given for alcohol withdrawal is effective and recommended in the management of this condition [Mayo-Smith 1997].

Chemotherapy-associated nausea and vomiting (adjunct or breakthrough) (adults)

Based on the American Society of Clinical Oncology antiemetic guidelines for chemotherapy associated nausea and vomiting, lorazepam may be given as an adjunct for the management of chemotherapy-associated nausea and vomiting and for breakthrough episodes in adults [Basch 2011].

Chemotherapy-associated nausea and vomiting (adjunct or breakthrough) (children/adolescents)

For pediatrics, clinical experience suggests the utility of lorazepam in managing breakthrough nausea and vomiting [Dupuis 2003]; however, additional data may be necessary to further define the role of lorazepam in children for chemotherapy-associated nausea and vomiting.

Chemotherapy-associated nausea and vomiting (anticipatory) (children/adolescents)

Based on the Pediatric Oncology Group of Ontario (POGO) Guidelines for Prevention and Treatment of Anticipatory Nausea and Vomiting Due to Chemotherapy in Pediatric Cancer Patients, lorazepam may be given to prevent or treat anticipatory nausea and vomiting in children [Dupuis 2014].

Partial complex seizures (refractory)

Data from a limited number of patients studied suggests that adjunctive use of lorazepam may be beneficial for the treatment of partial complex seizures [Walker 1984]; additional data may be necessary to further define the role of lorazepam in this condition.

Psychogenic catatonia

Data from a limited number of patients in a small number of studies suggest that lorazepam may be beneficial for the treatment of psychogenic catatonia [Bush 1996], [Rosebush 1990]; clinical experience also suggests the utility of lorazepam in managing psychogenic catatonia [England 2011], [Rosebush 2010]. Additional data may be necessary to further define the role of lorazepam in this condition.

Rapid tranquilization of the agitated patient

Based on the Expert Consensus Guidelines on the Treatment of Behavioral Emergencies, lorazepam may be given to rapidly tranquilize the agitated patient [Allen 2005]. Based on the American Association for Emergency Psychiatry Project BETA Psychopharmacology Workgroup, benzodiazepines are recommended as first-line for agitation due to alcohol or benzodiazepine withdrawal or intoxication due to a CNS stimulant (eg, amphetamines) and second-line for agitation associated with psychosis in patients with known psychiatric disorders [Wilson 2012].

Clinical experience also suggests the utility of lorazepam in managing the agitated patient [Battaglia 2005], [ De Fruyt 2004], [Zeller 2010].

Status epilepticus (infants, children, and adolescents)

Based on the American Society of Pediatrics Statement on Drugs for Pediatric Emergencies, Neurocritical Care Society Guidelines for the Evaluation and Management of Status Epilepticus, and American Epilepsy Society Guidelines for the Treatment of Convulsive Status Epilepticus in Children and Adults, lorazepam is effective and recommended in the management of status epilepticus in infants, children, and adolescents.

Chemotherapy-associated nausea and vomiting (off-label use):

Anticipatory nausea/vomiting (prevention and treatment): Infants ≥1 month, Children, and Adolescents: Oral: 0.04 to 0.08 mg/kg/dose (maximum dose: 2 mg) once at bedtime the evening prior to chemotherapy and once the next day before chemotherapy (Dupuis 2014)

Breakthrough nausea/vomiting: Children ≥2 years and Adolescents: IV: 0.025 to 0.05 mg/kg/dose (maximum dose: 2 mg) every 6 hours as needed (Dupuis 2003); however, additional data may be necessary to further define the role of lorazepam in children for chemotherapy-associated nausea and vomiting

Status epilepticus: Infants, Children, and Adolescents (off-label use):

American Epilepsy Society and Neurocritical Care Society recommendations: IV: 0.1 mg/kg (maximum dose: 4 mg) given at a maximum rate of 2 mg/minute; may repeat in 5 to 10 minutes (AES [Glauser 2016]; NCS [Brophy 2012]). Note: Dilute dose 1:1 with saline.

American Academy of Pediatrics recommendation: IV, IM: 0.05 to 0.1 mg/kg (maximum dose: 4 mg); may repeat dose every 10 to 15 minutes if seizure continues (AAP [Hegenbarth 2008])

Dosage adjustment for lorazepam with concomitant medications: Probenecid or valproic acid: Reduce lorazepam dose by 50%

Note: Commercial oral solution is available (2 mg/mL)

Two different 1 mg/mL oral suspensions may be made from different generic lorazepam tablets (Mylan Pharmaceuticals or Watson Laboratories), sterile water, Ora-Sweet, and Ora-Plus.

Mylan tablets: Place one-hundred-eighty 2 mg tablets in a 12-ounce amber glass bottle; add 144 mL of sterile water to disperse the tablets; shake until slurry is formed. Add 108 mL Ora-Plus in incremental proportions; then add a quantity of Ora-Sweet sufficient to make 360 mL. Label "shake well" and "refrigerate". Stable for 91 days when stored in amber glass prescription bottles at room temperature or refrigerated (preferred).

Watson tablets: Place one-hundred-eighty 2 mg tablets in a 12-ounce amber glass bottle; add 48 mL sterile water to disperse the tablets; shake until slurry is formed. Add 156 mL of Ora-Plus in incremental proportions; then add a quantity of Ora-Sweet sufficient to make 360 mL. Label "shake well" and "refrigerate". Store in amber glass prescription bottles. Stable for 63 days at room temperature or 91 days refrigerated.

Parenteral: Intact vials should be refrigerated (room temperature storage information may be available; contact product manufacturer to obtain current recommendations). Protect from light. Parenteral admixture in D5W, LR, or NS is stable at room temperature (25°C) for 24 hours (consult parenteral admixture resource for additional detail).

Oral concentrate: Store at colder room temperature or refrigerate at 2°C to 8°C (36°F to 46°F). Discard open bottle after 90 days.

Oral tablet: Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Sublingual tablet [Canadian product]: Store at 15°C to 25°C (59°F to 77°F). Protect from light.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, headache, or injection site irritation. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or illogical thinking), hallucinations, behavioral changes, change in balance, confusion, memory impairment, severe loss of strength and energy, severe dizziness, passing out, vision changes, muscle weakness, dark urine, jaundice, difficulty breathing, slow breathing, or shallow breathing (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

It is dangerous to purchase lorazepam on the Internet or from vendors outside the United States. Medications distributed from Internet sales may contain dangerous ingredients, or may not be distributed by a licensed pharmacy. The sale and distribution of lorazepam outside the U.S. does not comply with the regulations of the Food and Drug Administration (FDA) for the safe use of this medication.

You should not take lorazepam if you have:

• narrow-angle glaucoma;

• myasthenia gravis; or

• a history of allergic reaction to any benzodiazepine, such as diazepam (Valium), chlordiazepoxide, clonazepam, flurazepam, and others.

To make sure lorazepam is safe for you, tell your doctor if you have:

• seizures or epilepsy;

• kidney or liver disease (especially alcoholic liver disease);

• asthma or other breathing disorder;

• open-angle glaucoma;

• a history of depression or suicidal thoughts or behavior;

• a history of drug or alcohol addiction; or

• if you use a narcotic (opioid) medication.

Do not use lorazepam if you are pregnant. This medicine can cause birth defects. Your baby could also become dependent on the drug. This can cause life-threatening withdrawal symptoms in the baby after it is born. Babies born dependent on habit-forming medicine may need medical treatment for several weeks. Tell your doctor if you are pregnant or plan to become pregnant. Use effective birth control to prevent pregnancy while you are taking lorazepam.

Lorazepam can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using this medicine.

Lorazepam is not approved for use by anyone younger than 18 years old.

The sedative effects of lorazepam may last longer in older adults. Accidental falls are common in elderly patients who take benzodiazepines. Use caution to avoid falling or accidental injury while you are taking lorazepam.

Get emergency medical help if you have signs of an allergic reaction to lorazepam: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe drowsiness;

• thoughts of suicide or hurting yourself;

• unusual changes in mood or behavior;

• confusion, aggression, hallucinations;

• worsened sleep problems;

• sudden restless feeling or excitement;

• muscle weakness, drooping eyelids, trouble swallowing;

• vision changes; or

• upper stomach pain, dark urine, jaundice (yellowing of the skin or eyes).

Common lorazepam side effects may include:

• dizziness, drowsiness;

• weakness;

• slurred speech, lack of balance or coordination;

• memory problems; or

• feeling unsteady.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

IM: 0.05 mg/kg up to a maximum of 4 mg
IV: 2 mg total, or 0.044 mg/kg, whichever is smaller

Comments:
-Doses of other injectable central-nervous-system depressant drugs should be reduced.
-For optimum effect, intramuscular drug should be administered at least 2 hours before the anticipated operative procedure.
-Narcotic analgesics should be administered at their usual preoperative time.
-IV: This dose should not ordinarily be exceeded in patients over 50 years of age.
-IV: Larger doses as high as 0.05 mg/kg up to a total of 4 mg may be administered.
-For optimum effect, intravenous drug should be administered 15 to 20 minutes before the anticipated operative procedure.

Use:
-Preanesthetic medication for adult patients, producing sedation (sleepiness or drowsiness), relief of anxiety, and a decreased ability to recall events related to the day of surgery

0.1 mg/kg IV up to 4 mg per dose; may repeat in 5 to 10 minutes
Maximum dose: 8 mg

Comments:
-Vital signs should be monitored, an unobstructed airway should be maintained, and artificial ventilation equipment should be available.
-When an intravenous port is not available, the IM route may prove useful.

Use: Treatment of status epilepticus

Elderly or debilitated patients:
1 to 2 mg orally per day in divided doses

Comments:
-The dosage should be increased gradually when needed to help avoid adverse effects.

Use: Management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms

Administration advice:
-The manufacturer product information should be consulted.

Storage requirements:
-Injection: Protect from light; store in a refrigerator at 2 to 8 C (36 to 46 F)
-Tablets: Store in a cool, dry place

Reconstitution/preparation techniques:
-The manufacturer product information should be consulted.