Chemical formula: C₁₅H₁₀Cl₂N₂O₂ Molecular mass: 321.158 g/mol PubChem compound: 3958
Lorazepam interacts in the following cases:
CYP3A4 inducers may increase clearance of benzodiazepines.
Inhibitors (e.g. cimetidine, isoniazid; erythyromycin; omeprazole; esomeprazole) reduce clearance and may potentiate the action of benzodiazepines. Itraconazole, ketoconazole and to a lesser extent fluconazole and voriconazole are potent inhibitors of the cytochrome P450 isoenzyme CYP3A4 and may increase plasma levels of benzodiazepines. The effects of benzodiazepines may be increased and prolonged by concomitant use. A dose reduction of the benzodiazepine may be required.
Inhibition of CYP3A4 may increase the plasma concentration of lorazepam (possible increased sedation and amnesia). This interaction may be of little significance in healthy individuals, but it is not clear if other factors such as old age or liver cirrhosis increase the risk of adverse events with concurrent use.
Lorazepam should not be used together with alcohol (enhanced sedative effects; impaired ability to drive/operate machinery).
Concurrent use of antacids with lorazepam may delay absorption of lorazepam.
Oestrogen-containing contraceptives cause possible inhibition of hepatic metabolism of lorazepam.
Avoid concomitant use of lorazepam with HIV-protease inhibitors (increased risk of prolonged sedation).
When lorazepam taken with muscle relaxants, the overall muscle-relaxing effect may be increased (accumulative) therefore caution is advised, especially in elderly patients and at higher doses.
The concomitant use of sedative medicines such as benzodiazepines or related drugs such as lorazepam with opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dosage and duration of concomitant use should be limited. Enhancement of the euphoria may lead to increased psychological dependence.
Side effects may be more evident when lorazepam is co-administered with hydantoins or barbiturates.
Enhancement of the central depressive effect may occur if lorazepam is combined with drugs such as neuroleptics, antipsychotics, tranquillisers, antidepressants, hypnotics, analgesics, anaesthetics, barbiturates and sedative antihistamines. The elderly may require special supervision.
Concurrent use of lorazepam with caffeine may result in reduced sedative and anxiolytic effects of lorazepam.
Concomitant use of clozapine and lorazepam may produce marked sedation, excessive salivation, and ataxia.
There have been reports of apnoea, coma, bradycardia, heart arrest and death with the concomitant use of lorazepam injection solution and haloperidol.
Avoid concomitant use of lorazepam with sodium oxybate (enhanced effects of sodium oxybate).
The addition of scopolamine to lorazepam injection is not recommended, since their combination has been observed to cause an increased incidence of sedation, hallucination and irrational behaviour.
Possible antagonism of the effect of levodopa has been observed when co-administered with lorazepam.
Cases of excessive suppression and significant reduction in respiratory function have been reported when lorazepam and loxapine were co-administered.
Phenobarbital taken concomitantly with lorazepam may result in an additive CNS effect. Special care should be taken in adjusting the dose in the initial stages of treatment.
Concurrent administration of lorazepam with probenecid may result in reduced clearance, increased elimination half-life and increased concentrations of lorazepam. Therefore clinical monitoring is advised and lorazepam dosage should be reduced when appropriate.
Valproate may inhibit the glucuronidation of lorazepam (increased serum levels: increased risk of drowsiness).
Theophylline and aminophylline increase metabolism of lorazepam which possibly reduces the effect.
Increased clearance of zidovudine has been observed when co-administered with lorazepam.
Benzodiazepines should not be used during pregnancy, especially during the first and last trimesters. Benzodiazepines may cause foetal damage when administered to pregnant women.
If the drug is prescribed to a woman of childbearing potential, she should be warned to contact her physician about stopping the drug if she intends to become, or suspects that she is, pregnant.
Use of intravenous/intramuscular lorazepam during the late phase of pregnancy may require ventilation of the infant at birth.
If, for compelling medical reasons, the product is administered during the late phase of pregnancy, or during labour at high doses, effects on the neonate, such as hypothermia, hypotonia and moderate respiratory depression, can be expected, due to the pharmacological action of the compound.
There is a possibility that infants born to mothers who take benzodiazepines chronically during the later stages of pregnancy may develop physical dependence.
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 hypotonia, hypothermia, respiratory depression, apnoea, 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.
There are insufficient data regarding obstetrical safety of parenteral lorazepam, including use in caesarean section. Such use, therefore, is not recommended.
Benzyl alcohol can cross the placenta.
Lorazepam is excreted in small amounts in breast milk. Mothers who are breast-feeding should not take benzodiazepines. Sedation and inability to suckle have occurred in neonates of lactating mothers taking benzodiazepines.
Patients should be advised that sedation, amnesia, impaired concentration, dizziness, blurred vision and impaired muscular function may occur and that, if affected, they should not drive or to use machines, or take part in other activities where this would put themselves or others at risk. If insufficient sleep duration occurs, the likelihood of impaired alertness may be increased. Concurrent medication may increase these effects.
This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:
Sedation, amnesia, impaired concentration and impaired muscular function may adversely affect the ability to drive or use machines. Therefore, patients should not drive or operate machinery within 24-48 hours of intravenous/intramuscular administration of lorazepam and should be advised not to take alcohol.
Frequency not known: Thrombocytopenia, agranulocytosis, pancytopenia
Frequency not known: Hypersensitivity reactions, anaphylactic/oid reactions
Frequency not known: SIADH
Frequency not known: Hyponatremia
Common: Confusion depression, unmasking of depression
Uncommon: Change in libido, decreased orgasm
Frequency not known: Disinhibition, euphoria, suicidal ideation/attempt, paradoxical reactions, including anxiety, agitation, excitation, hostility, aggression, rage, sleep disturbances/insomnia, sexual arousal, hallucinations
Very Common: Sedation, drowsiness
Common: Ataxia, dizziness
Frequency not known: Extrapyramidal symptoms, tremor, dysarthria/slurred speech, headache, convulsions/seizures, amnesia, coma, impaired attention/concentration, balance disorder
Frequency not known: Visual disturbances (including diplopia and blurred vision)
Frequency not known: Vertigo
Frequency not known: Hypotension, lowering in blood pressure
Frequency not known: Respiratory depressionβ, apnea, worsening of sleep apnea, worsening of obstructive pulmonary disease
Uncommon: Nausea
Frequency not known: Constipation
Frequency not known: Jaundice
Frequency not known: Angioedema, allergic skin reactions, alopecia
Common: Muscle weakness
Uncommon: Impotence
Very Common: Fatigue
Common: Asthenia
Frequency not known: Hypothermia
Frequency not known: Increase in bilirubin, increase in liver transaminases, increase in alkaline phosphatase
± Benzodiazepine effects on the CNS are dose-dependent, with more severe CNS depression occurring with high doses.
β The extent of respiratory depression with benzodiazepines is dose-dependent, with more severe depression occurring with high doses.
Tolerance at the injection site is generally good although, rarely, pain and redness have been reported after lorazepam injection.
Transient anterograde amnesia or memory impairment may occur using therapeutic doses, the risk increasing at higher doses.
Paradoxical reactions may be more likely to occur in children and the elderly.
Adverse reactions, when they occur, are usually observed at the beginning of therapy and generally decrease in severity or disappear with continued use or upon decreasing the dose.
Most frequently reported adverse reactions associated with benzodiazepines include daytime drowsiness, dizziness, muscle weakness, and ataxia.
Adverse reactions are listed by frequency: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000); not known (cannot be estimated from the available data).
Very rare: Thrombocytopenia, leucopenia, agranulocytosis, pancytopenia
Very rare: Hypersensitivity including anaphylaxis/anaphylactoid reactions
Very rare: Inappropriate antidiuretic hormone secretion, hyponatraemia
Rare: Confusion, depression and unmasking of depression, numbed emotions, disinhibition, euphoria, appetite changes, sleep disturbance, change in libido, decreased orgasm.
Unknown: Dependence, Suicidal ideation/attempt
Paradoxical reactions such as restlessness, agitation, irritability, aggressiveness, delusion, rage, insomnia, nightmares, hallucinations, psychoses, sexual arousal, and inappropriate behaviour have been occasionally reported during use.
Very common: Daytime drowsiness, sedation
Common: Dizziness, ataxia
Rare: headache, reduced alertness, dysarthria/slurred speech, transient anterograde amnesia or memory impairment.
Very rare: Tremor, extrapyramidal reactions, Coma
Rare: Visual disturbances (diplopia, blurred vision)
Rare: Hypotension
Rare: Apnoea, worsening of sleep apnoea, worsening of obstructive pulmonary disease. Respiratory depression
Rare: Nausea, constipation, salivation changes
Rare: Abnormal liver function test values (increases in bilirubin, transaminases, alkaline phosphatise), jaundice
Rare: Rash, allergic dermatitis
Common: Muscle weakness
Rare: Impotence
Common: Asthenia, fatigue
Very rare: Hypothermia
Symptoms reported following discontinuation of benzodiazepines include headaches, muscle pain, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, and the occurrence of “rebound” phenomena whereby the symptoms that led to treatment with benzodiazepines recur in an enhanced form. These symptoms may be difficult to distinguish from the original symptoms for which the drug was prescribed.
In severe cases the following symptoms may occur: derealisation; depersonalisation; hyperacusis; tinnitus; numbness and tingling of the extremities; hypersensitivity to light, noise, and physical contact; involuntary movements; hyperreflexia, tremor, nausea, vomiting; diarrhoea, abdominal cramps, loss of appetite, agitation, palpitations, tachycardia, panic attacks, vertigo, short-term memory loss, hallucinations/delirium; catatonia; hyperthermia, convulsions. Convulsions may be more common in patients with pre-existing seizure disorders or who are taking other drugs that lower the convulsive threshold such as antidepressants.
Not known: Fall
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