Pfizer Limited

Concurrent administration of lorazepam with sodium valproate may result in increased plasma concentrations and reduced clearance (20 to 40%) and increased concentrations of lorazepam. Lorazepam dosage should be reduced to approximately 50% when co-administered with valproate Therefore clinical monitoring is advised and lorazepam dosage should be reduced when appropriate.

Concurrent administration of lorazepam with probenecid may result in a more rapid onset or prolonged effect of lorazepam due toreduced clearance, increased elimination half-life and decreased total clearance. Lorazepam dosage needs to be reduced by approximately 50% when co-administered with probenecidincreased concentrations of lorazepam.  Therefore clinical monitoring is advised and lorazepam dosage should be reduced when appropriate.

10 x 1ml solution (in 2ml ampoules) (Type I glass) with a yellow snap ring in per pack sizes of 10.

4.5  Interaction with other Medicaments medicinal products and other forms of interaction

Not recommended:  ConcommitantConcomitant intake with alcohol

The sedative effects may be enhanced when the product is used in combination with alcohol.  This affects the ability to drive or use machines.

The benzodiazepines, including Ativan Injection, produce additive CNS depressant effects when co-administered with other medications which themselves produce CNS depression, e.g. barbiturates, antipsychotics, sedatives/hypnotics, anxiolytics, antidepressants, narcotic analgesics, sedative antihistamines, anticonvulsants and anaesthetics.

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 co-administered 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 co-administered with probenecid.

An enhancement of the euphoria induced by narcotic analgesics may occur with benzodiazepine use, leading to an increase in psychic dependence.

Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines.  To a lesser degree this also applies to benzodiazepines which are metabolised only by conjugation.

The addition of scopolamine to Ativan Injection is not recommended, since their combination has been observed to cause an increased incidence of sedation, hallucination and irrational behaviour.

Concomitant use of clozapine and lorazepam may produce marked sedation, excessive salivation, and ataxia.

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

There have been reports of apnoea, coma, bradycardia, heart arrest and death with the concomitant use of lorazepam injection solution and haloperidol.

1. TRADE NAME OF THE MEDICINAL PRODUCT

Ativan*® Injection

Ativan Injection contains the active ingredient lorazepam BP at a concentration of 4mg/ml.

Lorazepam (INN, BAN) is chemically defined as 7-chloro-5-(o-chlorphenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one.

Solution for injection

Ativan Injection is a  Clear, colourless solution supplied in clear glass ampoules containing 4 mg lorazepam in 1 ml of solution.

Polyethylene glycol 400

, b Benzyl alcohol

, p Propylene glycol

The use of benzodiazepines, including lorazepam, may lead to physical and psychological dependence.

Severe anaphylactic/anaphylactoid reactions have been reported with the use of benzodiazepines. Cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of benzodiazepines. Some patients taking benzodiazepines have had additional symptoms such as dyspnoea, throat closing, or nausea and vomiting. Some patients have required medical therapy in the emergency department. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with a benzodiazepine should not be rechallenged with the drug.

Extreme care must be taken in administering Ativan Injection to elderly or very ill patients and to those with limited pulmonary reserve or compromised respiratory function (eg, chronic obstructive pulmonary disease [COPD], sleep apnoea syndrome),because of the possibility that apnoea and/or cardiac arrest may occur.  Care should also be exercised when administering Ativan Injection to a patient with status epilepticus, especially when the patient has received other central nervous system depressants.

Withdrawal symptoms (eg, rebound insomnia) can appear following cessation of recommended doses after as little as one week of therapy.

As with all benzodiazepines, the use of lorazepam may worsen hepatic encephalopathy.

unless the expected benefit to the woman outweighs the potential risk to the infant.