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Lorazepam

What is lorazepam?

Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication often used to treat anxiety disorders. Lorazepam affects chemicals in the brain that may be unbalanced in people with anxiety. Lorazepam reduces anxiety, interferes with new memory formation, reduces agitation, induces sleep, treats seizures, treats nausea and vomiting, and relaxes muscles. Lorazepam is used for the short-term treatment of anxiety, trouble sleeping, acute seizures including status epilepticus, sedation of people in hospital, as well as sedation of aggressive patients. Due to tolerance and dependence, lorazepam is recommended for short-term use, up to two to four weeks only.

Among benzodiazepines, lorazepam has possible physical addiction potential Lorazepam also has misuse potential; the main types of misuse are for recreational purposes. Long-term effects of benzodiazepines include tolerance, dependence, benzodiazepine withdrawal syndrome, and cognitive impairments which may not completely reverse after stopping treatment. Withdrawal symptoms can range from anxiety and insomnia to seizures and psychosis. Adverse effects, including inability to form new memories, depression, and paradoxical effects, such as excitement or worsening of seizures, may occur. Children and the elderly are more sensitive to the adverse effects of benzodiazepines.Lorazepam impairs body balance and standing steadiness and is associated with falls and hip fractures in the elderly.

Lorazepam was initially patented in 1963 and went on sale in the United States in 1977. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.

Medical uses

Lorazepam has anxiety-reducing effects and its best-known indication is the short-term management of severe anxiety. In the US, the FDA advises against use of benzodiazepines such as lorazepam for longer than four weeks. It is fast acting, and useful in treating fast onset panic anxiety.

Lorazepam can effectively reduce agitation and induce sleep, and the duration of clinical effects from a single dose makes it an appropriate choice for the short-term treatment of insomnia, especially in the presence of severe anxiety or night terrors. It has a fairly short duration of action.

Withdrawal symptoms, including rebound insomnia and rebound anxiety, may occur after only seven days' administration of lorazepam.

Lorazepam is sometimes used for individuals receiving mechanical ventilation. However, in critically ill patients, propofol has been found to be superior to lorazepam both in effectiveness and overall cost; as a result, the use of propofol for this indication is now encouraged, whereas the use of lorazepam is discouraged.

Its relative effectiveness in preventing new memory formation, along with its ability to reduce agitation and anxiety makes lorazepam useful as premedication. It is given before a general anesthetic to reduce the amount of anesthetic agent required, or before unpleasant awake procedures, such as in dentistry or endoscopies, to reduce anxiety, to increase compliance, and to induce amnesia for the procedure. Oral lorazepam is given 90 to 120 minutes before procedures, and intravenous lorazepam as late as 10 minutes before procedures. Lorazepam is sometimes used as an alternative to midazolam in palliative sedation. In intensive care units lorazepam is sometimes used to produce anxiolysis, hypnosis, and amnesia.

Intravenous diazepam or lorazepam are first-line treatments for convulsive status epilepticus. Lorazepam is more effective than diazepam in the treatment of status epilepticus. However, phenobarbital has a superior success rate compared to lorazepam and other drugs, at least in the elderly.

Its marked anticonvulsant properties, and its pharmacokinetic profile, make intravenous lorazepam a reliable agent for stopping acute seizures, but it has relatively prolonged sedation after-effects. Oral lorazepam, and other benzodiazepines, have a role in long-term prophylactic treatment of resistant forms of petit mal epilepsy, but not as first-line therapies, mainly because of the development of tolerance to their effects.

Lorazepam's anticonvulsant and CNS depressant properties are useful for the treatment and prevention of alcohol withdrawal syndrome. In this setting, impaired liver function is not a hazard with lorazepam, since lorazepam does not require oxidation, hepatic or otherwise, for its metabolism.

Lorazepam is sometimes used as an alternative to haloperidol when there is the need for rapid sedation of violent or agitated individuals, but haloperidol plus promethazine is preferred due to better effectiveness and due to lorazepam's adverse effects on respiratory function. However, adverse effects such as behavioral disinhibition may make benzodiazepines inappropriate for some acutely psychotic patients. Acute delirium is sometimes treated with lorazepam, but as it can cause paradoxical effects, it is preferably given together with haloperidol. Lorazepam is absorbed relatively slowly if given intramuscularly, a common route in restraint situations.

Catatonia with inability to speak is responsive to lorazepam. Symptoms may recur and treatment for some days may be necessary. Catatonia due to abrupt or overly rapid withdrawal from benzodiazepines, as part of the benzodiazepine withdrawal syndrome, should also respond to lorazepam treatment. As lorazepam can have paradoxical effects, haloperidol is sometimes given at the same time.

It is sometimes used in chemotherapy in addition to medications used to treat nausea and vomiting, i.e. nausea and vomiting caused or worsened by psychological sensitization to the thought of being sick. It is also used as adjunct therapy for cyclic vomiting syndrome.

Important information

You should not use lorazepam if you have narrow-angle glaucoma or myasthenia gravis, or if you are allergic to Valium or a similar medicine.

Do not use lorazepam if you are pregnant. This medicine can cause birth defects or life-threatening withdrawal symptoms in a newborn.

Lorazepam may be habit-forming and should be used only by the person it was prescribed for. This medicine should never be shared with another person, especially someone who has a history of drug abuse or addiction. Keep the medication in a secure place where others cannot get to it.

Avoid using other medicines that make you sleepy. They can add to sleepiness caused by lorazepam.Do not drink alcohol while taking lorazepam. This medication can increase the effects of alcohol.

Before taking cheap Lorazepam Online

It is dangerous to purchase lorazepam from unknown sources on the Internet. Make sure you buy it from safe sources such as 24hrspharma.com  

You should not take this medicine 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; or
    •    a history of drug or alcohol addiction.

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.

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

How should I take lorazepam?

Take lorazepam exactly as it was prescribed for you. Follow all directions on your prescription label. Never use this medicine in larger amounts, or for longer than prescribed. Tell your doctor if the medicine seems to stop working as well in treating your symptoms.

Lorazepam may be habit-forming. Never share this medicine with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.
Misuse of habit-forming medicine can cause addiction, overdose, or death. Selling or giving away this medicine is against the law.

Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Lorazepam should be used for only a short time. Do not take this medicine for longer than your doctor recommends.
Do not stop using lorazepam suddenly or you could have unpleasant withdrawal symptoms, including a seizure (convulsions). Ask your doctor how to safely stop using this medicine.

Call your doctor if this medicine seems to stop working as well in treating your anxiety symptoms.
Store lorazepam at room temperature away from moisture, heat, and light.
Keep track of the amount of medicine used from each new bottle. Lorazepam is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.
Store the liquid form of this medicine in the refrigerator.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of lorazepam can be fatal. Overdose symptoms may include extreme drowsiness, confusion, muscle weakness, loss of balance or coordination, feeling light-headed, and fainting.

What should I avoid while taking lorazepam?

Do not drink alcohol while taking lorazepam. This medication can increase the effects of alcohol.
Lorazepam may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you. Dizziness or severe drowsiness can cause falls or other accidents.

Lorazepam side effects

Commonly reported side effects of lorazepam include tremor, agitation, and sedation. Other side effects include drowsiness, hypersomnia, and dizziness. See below for a comprehensive list of adverse effects.
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.

Lorazepam dosing information

Usual Adult Lorazepam Dose for Anxiety:

Tablets:
Initial dose: 2 to 3 mg orally per day administered 2 to 3 times per day
Maintenance dose: 1 to 2 mg orally 2 to 3 times a day
Parenteral:
IV: 2 mg total, or 0.044 mg/kg, whichever is smaller

Comments:
-The daily dosage may vary from 1 to 10 mg per day.
-The dosage should be increased gradually when needed to help avoid adverse effects.
-When higher dosage is indicated, the evening dose should be increased before the daytime doses.

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

Usual Adult Lorazepam Dose for Insomnia:

2 to 4 mg orally administered at bedtime

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

Use: Management of insomnia

Usual Geriatric Dose for Anxiety:

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.


What other drugs will affect lorazepam?

Taking this medicine with other drugs that make you sleepy or slow your breathing can cause dangerous or life-threatening side effects. Ask your doctor before taking lorazepam with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for depression or seizures.

Tell your doctor about all your current medicines and any you start or stop using, especially:
    •    any other medicines to treat anxiety;
    •    probenecid;
    •    aminophylline or theophylline;
    •    an antidepressant, or medicine to treat mental illness;
    •    a barbiturate such as phenobarbital;
    •    narcotic pain medicine;
    •    seizure medicine; or
    •    medicine that contains an antihistamine (such as sleep medicine, cold or allergy medicine).

This list is not complete. Other drugs may interact with lorazepam, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Tolerance and dependence

Dependence typified by a withdrawal syndrome occurs in about one-third of individuals who are treated for longer than four weeks with a benzodiazepine. Higher doses and longer periods of use increase the risk of developing a benzodiazepine dependence. Potent benzodiazepines, such as lorazepam, alprazolam, and triazolam, have the highest risk of causing a dependence. Tolerance to benzodiazepine effects develops with regular use. This is desirable with amnesic and sedative effects, but undesirable with anxiolytic, hypnotic, and anticonvulsant effects. Patients at first experience drastic relief from anxiety and sleeplessness, but symptoms gradually return, relatively soon in the case of insomnia, but more slowly in the case of anxiety symptoms. After four to six months of regular benzodiazepine use, evidence of continued efficacy declines.

If regular treatment is continued for longer than four to six months, dose increases may be necessary to maintain effects, but treatment-resistant symptoms may in fact be benzodiazepine withdrawal symptoms. Due to the development of tolerance to the anticonvulsant effects, benzodiazepines are generally not recommended for long-term use for the management of epilepsy. Increasing the dose may overcome tolerance, but tolerance may then develop to the higher dose and adverse effects may persist and worsen. The mechanism of tolerance to benzodiazepines is complex and involves GABAA receptor downregulation, alterations to subunit configuration of GABAA receptors, uncoupling and internalisation of the benzodiazepine binding site from the GABAA receptor complex as well as changes in gene expression.

The likelihood of dependence is relatively high with lorazepam compared to other benzodiazepines. Lorazepam's relatively short serum half-life, its confinement mainly to the vascular space, and its inactive metabolite, can result in interdose withdrawal phenomena and next-dose cravings, that may reinforce psychological dependence. Because of its high potency, the smallest lorazepam tablet strength of 0.5 mg is also a significant dose reduction (in the UK, the smallest tablet strength is 1.0 mg, which further accentuates this difficulty). To minimise the risk of physical/psychological dependence, lorazepam is best used only short-term, at the smallest effective dose. If any benzodiazepine has been used long-term, the recommendation is a gradual dose taper over a period of weeks, months or longer, according to dose and duration of use, degree of dependence and the individual.

Coming off long-term lorazepam use may be more realistically achieved by a gradual switch to an equivalent dose of diazepam and a period of stabilization on this, and only then initiating dose reductions. The advantage of switching to diazepam is that dose reductions are felt less acutely, because of the longer half-lives (20–200 hours) of diazepam and its active metabolites.

Withdrawal

On abrupt or overly rapid discontinuation of lorazepam, anxiety and signs of physical withdrawal have been observed, similar to those seen on withdrawal from alcohol and barbiturates. Lorazepam, as with other benzodiazepine drugs, can cause physical dependence, addiction, and benzodiazepine withdrawal syndrome.

The higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can, however, occur from standard dosages and also after short-term use. Benzodiazepine treatment should be discontinued as soon as possible via a slow and gradual dose reduction regimen. Rebound effects often resemble the condition being treated, but typically at a more intense level and may be difficult to diagnose. Withdrawal symptoms can range from mild anxiety and insomnia to more severe symptoms such as seizures and psychosis. The risk and severity of withdrawal is increased with long-term use, use of high doses, abrupt or over-rapid reduction, among other factors. Short-acting benzodiazepines such as lorazepam are more likely to cause a more severe withdrawal syndrome compared to longer-acting benzodiazepines.

Withdrawal symptoms can occur after taking therapeutic doses of Ativan for as little as one week. Withdrawal symptoms include headaches, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, dysphoria, dizziness, derealization, depersonalization, numbness/tingling of extremities, hypersensitivity to light, sound, and smell, perceptual distortions, nausea, vomiting, diarrhea, appetite loss, hallucinations, delirium, seizures, tremor, stomach cramps, myalgia, agitation, palpitations, tachycardia, panic attacks, short-term memory loss, and hyperthermia. It takes about 18–36 hours for the benzodiazepine to be removed from the body. The ease of addiction to lorazepam, (Ativan brand was particularly cited), and its withdrawal were brought to the attention of the British public during the early 1980s in Esther Rantzen's BBC TV series That's Life!, in a feature on the drug over a number of episodes.

Interactions

Lorazepam is not usually fatal in overdose, but may cause fatal respiratory depression if taken in overdose with alcohol. The combination also causes synergistic enhancement of the disinhibitory and amnesic effects of both drugs, with potentially embarrassing or criminal consequences. Some experts advise that patients should be warned against drinking alcohol while on lorazepam treatment, but such clear warnings are not universal. Synergistic adverse effects may also occur when lorazepam is administered with other drugs, such as opioids or other hypnotics. Lorazepam may also interact with rifabutin. Valproate inhibits the metabolism of lorazepam, whereas carbamazepine, lamotrigine, phenobarbital, phenytoin, and rifampin increase its rate of metabolism. Some antidepressants, antiepileptic drugs such as phenobarbital, phenytoin and carbamazepine, sedative antihistamines, opiates, antipsychotics and alcohol, when taken with lorazepam may result in enhanced sedative effects.

Overdose

In cases of a suspected lorazepam overdose, it is important to establish whether the patient is a regular user of lorazepam or other benzodiazepines, since regular use causes tolerance to develop. Also, one must ascertain whether other substances were also ingested.

Signs of overdose range through mental confusion, dysarthria, paradoxical reactions, drowsiness, hypotonia, ataxia, hypotension, hypnotic state, coma, cardiovascular depression, respiratory depression, and death.

Early management of alert patients includes emetics, gastric lavage, and activated charcoal. Otherwise, management is by observation, including of vital signs, support and, only if necessary, considering the hazards of doing so, giving intravenous flumazenil.

Patients are ideally nursed in a kind, nonfrustrating environment, since, when given or taken in high doses, benzodiazepines are more likely to cause paradoxical reactions. If shown sympathy, even quite crudely feigned, patients may respond solicitously, but they may respond with disproportionate aggression to frustrating cues. Opportunistic counseling has limited value here, as the patient is unlikely to recall this later, owing to drug-induced anterograde amnesia.

Detection in body fluids

Lorazepam may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest or to assist in a medicolegal death investigation. Blood or plasma concentrations are usually in a range of 10-300 μg/l in persons either receiving the drug therapeutically or in those arrested for impaired driving. Approximately 300-1000 μg/l is found in victims of acute overdosage.

Pharmacology

Lorazepam has anxiolytic, sedative, hypnotic, amnesic, anticonvulsant, and muscle relaxant properties. It is a high-potency and an intermediate-acting benzodiazepine, and its uniqueness, advantages, and disadvantages are largely explained by its pharmacokinetic properties (poor water and lipid solubility, high protein binding and anoxidative metabolism to a pharmacologically inactive glucuronide form) and by its high relative potency (lorazepam 1 mg is equal in effect to diazepam 10 mg).[70][71] The biological half-life of lorazepam is 10–20 hours.

History

1987 advertisement. "In a world where certainties are few...no wonder Ativan is prescribed by so many caring clinicians."

Historically, lorazepam is one of the "classical" benzodiazepines. Others include diazepam, clonazepam, oxazepam, nitrazepam, flurazepam, bromazepam, and clorazepate. Lorazepam was first introduced by Wyeth Pharmaceuticals in 1977 under the brand names Ativan and Temesta. The drug was developed by President of Research, D.J. Richards. Wyeth's original patent on lorazepam is expired in the United States, but the drug continues to be commercially viable.

Recreational use

Lorazepam is also used for other purposes, such as recreational use, wherein the drug is taken to achieve a high, or when the drug is continued long-term against medical advice.
In addition to recreational use, flunitrazepam, another member of the benzodiazepine family, may be taken to facilitate criminal activity. The anterograde amnesia and sedative-hypnotic effects of benzodiazepines such as lorazepam are sometimes used by predators on unwitting victims as date rape drugs, or for the purpose of robbery.
A large-scale, nationwide, U.S. government study of pharmaceutical-related emergency room (ER) visits by SAMHSA found sedative-hypnotics are the pharmaceuticals most frequently used outside of their prescribed medical purpose in the United States, with 35% of drug-related emergency room visits involving sedative-hypnotics. In this category, benzodiazepines are most commonly used. Males and females use benzodiazepines for nonmedical purposes equally. Of drugs used in attempted suicide, benzodiazepines are the most commonly used pharmaceutical drugs, with 26% of attempted suicides involving them. Lorazepam was the third-most-common benzodiazepine used outside of prescription in these ER visit statistics.

Legal status

Lorazepam is a Schedule IV drug under the Controlled Substances Act in the U.S. and internationally under the United Nations Convention on Psychotropic Substances. It is a Schedule IV drug under the Controlled Drugs and Substances Act in Canada. In the United Kingdom, it is a Class C, Schedule 4 Controlled Drug under the Misuse of Drugs Regulations 2001

 

 

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Lorazepam

What is lorazepam?

Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication often used to treat anxiety disorders. Lorazepam affects chemicals in the brain that may be unbalanced in people with anxiety.Lorazepam reduces anxiety, interferes with new memory formation, reduces agitation, induces sleep, treats seizures, treats nausea and vomiting, and relaxes muscles.Lorazepam is used for the short-term treatment of anxiety, trouble sleeping, acute seizures including status epilepticus, sedation of people in hospital, as well as sedation of aggressive patients.Due to tolerance and dependence, lorazepam is recommended for short-term use, up to two to four weeks only.

Among benzodiazepines, lorazepam has possible physical addiction potential Lorazepam also has misuse potential; the main types of misuse are for recreational purposes. Long-term effects of benzodiazepines include tolerance, dependence, benzodiazepine withdrawal syndrome, and cognitive impairments which may not completely reverse after stopping treatment. Withdrawal symptoms can range from anxiety and insomnia to seizures and psychosis. Adverse effects, including inability to form new memories, depression, and paradoxical effects, such as excitement or worsening of seizures, may occur. Children and the elderly are more sensitive to the adverse effects of benzodiazepines.Lorazepam impairs body balance and standing steadiness and is associated with falls and hip fractures in the elderly.

Lorazepam was initially patented in 1963 and went on sale in the United States in 1977.It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.

Medical uses

Lorazepam has anxiety-reducing effects and its best-known indication is the short-term management of severe anxiety. In the US, the FDA advises against use of benzodiazepines such as lorazepam for longer than four weeks.It is fast acting, and useful in treating fast onset panic anxiety.

Lorazepam can effectively reduce agitation and induce sleep, and the duration of clinical effects from a single dose makes it an appropriate choice for the short-term treatment of insomnia, especially in the presence of severe anxiety or night terrors. It has a fairly short duration of action.

Withdrawal symptoms, including rebound insomnia and rebound anxiety, may occur after only seven days' administration of lorazepam.

Lorazepam is sometimes used for individuals receiving mechanical ventilation. However, in critically ill patients, propofol has been found to be superior to lorazepam both in effectiveness and overall cost; as a result, the use of propofol for this indication is now encouraged, whereas the use of lorazepam is discouraged.

Its relative effectiveness in preventing new memory formation,along with its ability to reduce agitation and anxiety makes lorazepam useful as premedication. It is given before a general anesthetic to reduce the amount of anesthetic agent required, or before unpleasant awake procedures, such as in dentistry or endoscopies, to reduce anxiety, to increase compliance, and to induce amnesia for the procedure. Oral lorazepam is given 90 to 120 minutes before procedures, and intravenous lorazepam as late as 10 minutes before procedures.Lorazepam is sometimes used as an alternative to midazolam in palliative sedation.In intensive care units lorazepam is sometimes used to produce anxiolysis, hypnosis, and amnesia.

Intravenous diazepam or lorazepam are first-line treatments for convulsive status epilepticus.Lorazepam is more effective than diazepam in the treatment of status epilepticus.However, phenobarbital has a superior success rate compared to lorazepam and other drugs, at least in the elderly.

Its marked anticonvulsant properties, and its pharmacokinetic profile, make intravenous lorazepam a reliable agent for stopping acute seizures, but it has relatively prolonged sedation after-effects. Oral lorazepam, and other benzodiazepines, have a role in long-term prophylactic treatment of resistant forms of petit mal epilepsy, but not as first-line therapies, mainly because of the development of tolerance to their effects.

Lorazepam's anticonvulsant and CNS depressant properties are useful for the treatment and prevention of alcohol withdrawal syndrome. In this setting, impaired liver function is not a hazard with lorazepam, since lorazepam does not require oxidation, hepatic or otherwise, for its metabolism.

Lorazepam is sometimes used as an alternative to haloperidol when there is the need for rapid sedation of violent or agitated individuals, but haloperidol plus promethazine is preferred due to better effectiveness and due to lorazepam's adverse effects on respiratory function.However, adverse effects such as behavioral disinhibition may make benzodiazepines inappropriate for some acutely psychotic patients.Acute delirium is sometimes treated with lorazepam, but as it can cause paradoxical effects, it is preferably given together with haloperidol. Lorazepam is absorbed relatively slowly if given intramuscularly, a common route in restraint situations.

Catatonia with inability to speak is responsive to lorazepam. Symptoms may recur and treatment for some days may be necessary. Catatonia due to abrupt or overly rapid withdrawal from benzodiazepines, as part of the benzodiazepine withdrawal syndrome, should also respond to lorazepam treatment. As lorazepam can have paradoxical effects, haloperidol is sometimes given at the same time.

It is sometimes used in chemotherapy in addition to medications used to treat nausea and vomiting, i.e. nausea and vomiting caused or worsened by psychological sensitization to the thought of being sick. It is also used as adjunct therapy for cyclic vomiting syndrome.

Important information

You should not use lorazepam if you have narrow-angle glaucoma or myasthenia gravis, or if you are allergic to Valium or a similar medicine.

Do not use lorazepam if you are pregnant. This medicine can cause birth defects or life-threatening withdrawal symptoms in a newborn.

Lorazepam may be habit-forming and should be used only by the person it was prescribed for. This medicine should never be shared with another person, especially someone who has a history of drug abuse or addiction. Keep the medication in a secure place where others cannot get to it.

Avoid using other medicines that make you sleepy. They can add to sleepiness caused by lorazepam.

Do not drink alcohol while taking lorazepam. This medication can increase the effects of alcohol.

Before taking this medicine

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 this medicine 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; or
  • a history of drug or alcohol addiction.

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.

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 this medicine.

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

 

How should I take lorazepam?

Take lorazepam exactly as it was prescribed for you. Follow all directions on your prescription label. Never use this medicine in larger amounts, or for longer than prescribed. Tell your doctor if the medicine seems to stop working as well in treating your symptoms.

Lorazepam may be habit-forming. Never share this medicine with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

Misuse of habit-forming medicine can cause addiction, overdose, or death. Selling or giving away this medicine is against the law.

Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Lorazepam should be used for only a short time. Do not take this medicine for longer than your doctor recommends.

Do not stop using lorazepam suddenly or you could have unpleasant withdrawal symptoms, including a seizure (convulsions). Ask your doctor how to safely stop using this medicine.

Call your doctor if this medicine seems to stop working as well in treating your anxiety symptoms.

Store lorazepam at room temperature away from moisture, heat, and light.

Keep track of the amount of medicine used from each new bottle. Lorazepam is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

Store the liquid form of this medicine in the refrigerator.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of lorazepam can be fatal. Overdose symptoms may include extreme drowsiness, confusion, muscle weakness, loss of balance or coordination, feeling light-headed, and fainting.

What should I avoid while taking lorazepam?

Do not drink alcohol while taking lorazepam. This medication can increase the effects of alcohol.

Lorazepam may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you. Dizziness or severe drowsiness can cause falls or other accidents.

Lorazepam side effects

Commonly reported side effects of lorazepam include tremor, agitation, and sedation. Other side effects include drowsiness, hypersomnia, and dizziness. See below for a comprehensive list of adverse effects.

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.

 

Lorazepam dosing information

Usual Adult Lorazepam Dose for Anxiety:

Tablets:
Initial dose: 2 to 3 mg orally per day administered 2 to 3 times per day
Maintenance dose: 1 to 2 mg orally 2 to 3 times a day
Parenteral:
IV: 2 mg total, or 0.044 mg/kg, whichever is smaller

Comments:
-The daily dosage may vary from 1 to 10 mg per day.
-The dosage should be increased gradually when needed to help avoid adverse effects.
-When higher dosage is indicated, the evening dose should be increased before the daytime doses.

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

Usual Adult Lorazepam Dose for Insomnia:

2 to 4 mg orally administered at bedtime

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

Use: Management of insomnia

Usual Geriatric Dose for Anxiety:

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

What other drugs will affect lorazepam?

Taking this medicine with other drugs that make you sleepy or slow your breathing can cause dangerous or life-threatening side effects. Ask your doctor before taking lorazepam with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for depression or seizures.

Tell your doctor about all your current medicines and any you start or stop using, especially:

  • any other medicines to treat anxiety;
  • probenecid;
  • aminophylline or theophylline;
  • an antidepressant, or medicine to treat mental illness;
  • a barbiturate such as phenobarbital;
  • narcotic pain medicine;
  • seizure medicine; or
  • medicine that contains an antihistamine (such as sleep medicine, cold or allergy medicine).

This list is not complete. Other drugs may interact with lorazepam, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Tolerance and dependence

Dependence typified by a withdrawal syndrome occurs in about one-third of individuals who are treated for longer than four weeks with a benzodiazepine. Higher doses and longer periods of use increase the risk of developing a benzodiazepine dependence. Potent benzodiazepines, such as lorazepam, alprazolam, and triazolam, have the highest risk of causing a dependence. Tolerance to benzodiazepine effects develops with regular use. This is desirable with amnesic and sedative effects, but undesirable with anxiolytic, hypnotic, and anticonvulsant effects. Patients at first experience drastic relief from anxiety and sleeplessness, but symptoms gradually return, relatively soon in the case of insomnia, but more slowly in the case of anxiety symptoms. After four to six months of regular benzodiazepine use, evidence of continued efficacy declines.

If regular treatment is continued for longer than four to six months, dose increases may be necessary to maintain effects, but treatment-resistant symptoms may in fact be benzodiazepine withdrawal symptoms.Due to the development of tolerance to the anticonvulsant effects, benzodiazepines are generally not recommended for long-term use for the management of epilepsy. Increasing the dose may overcome tolerance, but tolerance may then develop to the higher dose and adverse effects may persist and worsen. The mechanism of tolerance to benzodiazepines is complex and involves GABAA receptor downregulation, alterations to subunit configuration of GABAA receptors, uncoupling and internalisation of the benzodiazepine binding site from the GABAA receptor complex as well as changes in gene expression.

The likelihood of dependence is relatively high with lorazepam compared to other benzodiazepines. Lorazepam's relatively short serum half-life, its confinement mainly to the vascular space, and its inactive metabolite, can result in interdose withdrawal phenomena and next-dose cravings, that may reinforce psychological dependence. Because of its high potency, the smallest lorazepam tablet strength of 0.5 mg is also a significant dose reduction (in the UK, the smallest tablet strength is 1.0 mg, which further accentuates this difficulty). To minimise the risk of physical/psychological dependence, lorazepam is best used only short-term, at the smallest effective dose. If any benzodiazepine has been used long-term, the recommendation is a gradual dose taper over a period of weeks, months or longer, according to dose and duration of use, degree of dependence and the individual.

Coming off long-term lorazepam use may be more realistically achieved by a gradual switch to an equivalent dose of diazepam and a period of stabilization on this, and only then initiating dose reductions. The advantage of switching to diazepam is that dose reductions are felt less acutely, because of the longer half-lives (20–200 hours) of diazepam and its active metabolites.

Withdrawal

On abrupt or overly rapid discontinuation of lorazepam, anxiety and signs of physical withdrawal have been observed, similar to those seen on withdrawal from alcohol and barbiturates. Lorazepam, as with other benzodiazepine drugs, can cause physical dependence, addiction, and benzodiazepine withdrawal syndrome. The higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can, however, occur from standard dosages and also after short-term use. Benzodiazepine treatment should be discontinued as soon as possible via a slow and gradual dose reduction regimen.Rebound effects often resemble the condition being treated, but typically at a more intense level and may be difficult to diagnose. Withdrawal symptoms can range from mild anxiety and insomnia to more severe symptoms such as seizures and psychosis. The risk and severity of withdrawal is increased with long-term use, use of high doses, abrupt or over-rapid reduction, among other factors. Short-acting benzodiazepines such as lorazepam are more likely to cause a more severe withdrawal syndrome compared to longer-acting benzodiazepines.

Withdrawal symptoms can occur after taking therapeutic doses of Ativan for as little as one week. Withdrawal symptoms include headaches, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, dysphoria, dizziness, derealization, depersonalization, numbness/tingling of extremities, hypersensitivity to light, sound, and smell, perceptual distortions, nausea, vomiting, diarrhea, appetite loss, hallucinations, delirium, seizures, tremor, stomach cramps, myalgia, agitation, palpitations, tachycardia, panic attacks, short-term memory loss, and hyperthermia. It takes about 18–36 hours for the benzodiazepine to be removed from the body.The ease of addiction to lorazepam, (Ativan brand was particularly cited), and its withdrawal were brought to the attention of the British public during the early 1980s in Esther Rantzen's BBC TV series That's Life!, in a feature on the drug over a number of episodes.

Interactions

Lorazepam is not usually fatal in overdose, but may cause fatal respiratory depression if taken in overdose with alcohol. The combination also causes synergistic enhancement of the disinhibitory and amnesic effects of both drugs, with potentially embarrassing or criminal consequences. Some experts advise that patients should be warned against drinking alcohol while on lorazepam treatment,but such clear warnings are not universal.Synergistic adverse effects may also occur when lorazepam is administered with other drugs, such as opioids or other hypnotics.Lorazepam may also interact with rifabutin.Valproate inhibits the metabolism of lorazepam, whereas carbamazepine, lamotrigine, phenobarbital, phenytoin, and rifampin increase its rate of metabolism. Some antidepressants, antiepileptic drugs such as phenobarbital, phenytoin and carbamazepine, sedative antihistamines, opiates, antipsychotics and alcohol, when taken with lorazepam may result in enhanced sedative effects.

Overdose

See also: Benzodiazepine overdose

In cases of a suspected lorazepam overdose, it is important to establish whether the patient is a regular user of lorazepam or other benzodiazepines, since regular use causes tolerance to develop. Also, one must ascertain whether other substances were also ingested.

Signs of overdose range through mental confusion, dysarthria, paradoxical reactions, drowsiness, hypotonia, ataxia, hypotension, hypnotic state, coma, cardiovascular depression, respiratory depression, and death.

Early management of alert patients includes emetics, gastric lavage, and activated charcoal. Otherwise, management is by observation, including of vital signs, support and, only if necessary, considering the hazards of doing so, giving intravenous flumazenil.

Patients are ideally nursed in a kind, nonfrustrating environment, since, when given or taken in high doses, benzodiazepines are more likely to cause paradoxical reactions. If shown sympathy, even quite crudely feigned, patients may respond solicitously, but they may respond with disproportionate aggression to frustrating cues.Opportunistic counseling has limited value here, as the patient is unlikely to recall this later, owing to drug-induced anterograde amnesia.

Detection in body fluids

Lorazepam may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest or to assist in a medicolegal death investigation. Blood or plasma concentrations are usually in a range of 10-300 μg/l in persons either receiving the drug therapeutically or in those arrested for impaired driving. Approximately 300-1000 μg/l is found in victims of acute overdosage.

Pharmacology

Lorazepam has anxiolytic, sedative, hypnotic, amnesic, anticonvulsant, and muscle relaxant properties. It is a high-potency and an intermediate-acting benzodiazepine, and its uniqueness,advantages, and disadvantages are largely explained by its pharmacokinetic properties (poor water and lipid solubility, high protein binding and anoxidative metabolism to a pharmacologically inactive glucuronide form) and by its high relative potency (lorazepam 1 mg is equal in effect to diazepam 10 mg).[70][71] The biological half-life of lorazepam is 10–20 hours.

History

 

1987 advertisement. "In a world where certainties are few...no wonder Ativan is prescribed by so many caring clinicians."

Historically, lorazepam is one of the "classical" benzodiazepines. Others include diazepam, clonazepam, oxazepam, nitrazepam, flurazepam, bromazepam, and clorazepate.Lorazepam was first introduced by Wyeth Pharmaceuticals in 1977 under the brand names Ativan and Temesta. The drug was developed by President of Research, D.J. Richards. Wyeth's original patent on lorazepam is expired in the United States, but the drug continues to be commercially viable.

Recreational use

Lorazepam is also used for other purposes, such as recreational use, wherein the drug is taken to achieve a high, or when the drug is continued long-term against medical advice.

In addition to recreational use, flunitrazepam, another member of the benzodiazepine family, may be taken to facilitate criminal activity. The anterograde amnesia and sedative-hypnotic effects of benzodiazepines such as lorazepam are sometimes used by predators on unwitting victims as date rape drugs, or for the purpose of robbery.

A large-scale, nationwide, U.S. government study of pharmaceutical-related emergency room (ER) visits by SAMHSA found sedative-hypnotics are the pharmaceuticals most frequently used outside of their prescribed medical purpose in the United States, with 35% of drug-related emergency room visits involving sedative-hypnotics. In this category, benzodiazepines are most commonly used. Males and females use benzodiazepines for nonmedical purposes equally. Of drugs used in attempted suicide, benzodiazepines are the most commonly used pharmaceutical drugs, with 26% of attempted suicides involving them. Lorazepam was the third-most-common benzodiazepine used outside of prescription in these ER visit statistics.

Legal status

Lorazepam is a Schedule IV drug under the Controlled Substances Act in the U.S. and internationally under the United Nations Convention on Psychotropic Substances. It is a Schedule IV drug under the Controlled Drugs and Substances Act in Canada. In the United Kingdom, it is a Class C, Schedule 4 Controlled Drug under the Misuse of Drugs Regulations 2001.

 



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