Lorazepam Medo 4 mg/ml

/ A.L. Medi-Market LTD,

Premedication
For a maximum beneficial effect, the dose should be calculated based on body weight (the usual dose is 2-4 mg) and administered as follows:
I.V. administration:
For an optimal effect, doses of 0.044 mg / kg to a maximum of 2 mg should be used, 15-20 minutes before the procedure.
This dose (I.V. administered) will be adequate for sedation of most adult patients and should not normally be exceeded in patients over 50 years of age.
Higher doses, up to 0.05 mg / kg with a maximum of 4 mg, can be administered.
The necessary airway equipment must be available immediately prior to the intravenous administration.
I.M. administration:
The optimal effect is reached by administrating 0.05mg/kg to a maximum 4mg, with minimum 2 hours before the forecasted procedure. The dose is individually adjusted.
In elderly or debilitated patients or in patients with impaired renal or hepatic function or with severe respiratory or cardiovascular disease, a dose reduction is recommended.
In case of local anesthesia and in diagnostic procedures requiring patient involvement, the simultaneous use of an analgesic may be appropriate.
The dose should be reduced in case of concomitant administration of central nervous system depressants. Should not be mixed with other drugs in the same syringe.
Symptomatic treatment of pathological anxiety and tension in patients who, for some reason, are unable to take oral medication
The recommended initial dose is 2-4 mg I.V. or 0.05 mg / kg I.M. (intravenous administration is preferred).
If necessary, the dose may be repeated after 2 hours. As soon as the acute symptomatology is controlled, the patient must receive appropriate treatment for the underlying condition.
The use of lorazepam tablets may be considered if further treatment with benzodiazepines is required.
Status epilepticus
Adults: 4 mg intravenously.
Elderly: The elderly may respond to lower doses; thus, half the normal adult dose may be sufficient.
Pediatric population (age 1 month and older): 0.1 mg/kg body weight intravenously. Maximum 4 mg/dose.
The infusion rate should not exceed 2 mg/min.
If the seizure lasts longer than 10-15 minutes, may decide to administer another dose. A maximum of 2 doses may be administered.
Pediatric population
The use in children under 12 years is contraindicated, except in the management of status epilepticus.
Elderly and debilitated patients
Clinical studies have shown that patients over 50 years of age have a deeper and prolonged sedation when lorazepam is administered intravenously.
In normal conditions, a starting dose of 2 mg should be sufficient unless a greater degree of sedation and / or preoperative impairment of memory is desired.
For elderly and debilitated patients reduce the initial dose by approximately 50% and adjust the dosage as needed and tolerated.
Patients with renal or hepatic insufficiency
This medical product is not recommended for use in patients with severe hepatic insufficiency. When it is used in patients with mild to moderate hepatic or renal insufficiency, a starting dose of 0.05 mg / kg (but not more than 2 mg) is recommended.

Adults and adolescents above 12 years of age:
• As premedication, before surgical procedures or prior to diagnostic procedures.
• For symptomatic treatment of pathological anxiety and tension in patients who, for some reason,
are unable to take oral medication.
Adults, adolescents, children and infants from 1 month of age:
• For the control of status epilepticus.

* Hypersensitivity to the active substance or to any of the excipients
* Intra-arterially. As with other injectable benzodiazepines, an intra-arterial injection may cause arterial spasm that causes gangrene and may require amputation.
* Sleep apnoea syndrome
* Severe respiratory insufficiency
* Hypersensitivity to benzodiazepines
* Myasthenia gravis
* Severe hepatic insufficiency
* Children under 12 years of age, except in the control of status epilepticus.

Alcohol: Tolerance for alcohol and other CNS depressants will be diminished in the presence of lorazepam, therefore patients should be advised to either avoid Lorazepam Medo 4 mg/ml or use a reduced dose.
Alcoholic beverages should not be used for at least 24 to 48 hours after receiving Lorazepam Medo 4 mg/ml, due to the general additive depressant effect of benzodiazepines on central nervous system.
Reduction of responsiveness / performance: It is recommended that patients treated with lorazepam, remain under observation for 24 hours after administration of the last dose.
If lorazepam is used for short-term procedures on an outpatient basis, the patient must be accompanied by a responsible adult at the time of discharge.
Patients should be warned not to drive vehicles or take activities requiring attention for 24-48 hours after administration.
A reduction in performance may persist for extended periods due to patient’s high age, concomitant use of other drugs, stress due to surgery, or the general condition of the patient. Patients should also be warned that premature walking (within 8 hours after lorazepam administration) may lead to injury due to traps.
Risk from concomitant use of opioids: Concomitant use of lorazepam and opioids may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of sedative medicines such as benzodiazepines or related drugs such as lorazepam with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe lorazepam concomitantly with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible.
Status epilepticus: Caution is required when administering lorazepam to patients with status epilepticus, especially patients who have received other central nervous system depressants or patients who are severely ill.
The possibility of respiratory depression or partial respiratory tract obstruction should be considered. Adequate resuscitation equipment must be available.
Psychotic or depressive disorders: Lorazepam is not intended for primary treatment of psychotic illness or depressive disorders, and should not be used as a monotherapy in depressed patients.
Benzodiazepines may have a disinhibiting effect and may release suicidal tendencies in depressed patients.
Long-term use of lorazepam: There are no data to support a long term use of lorazepam. Some patients have developed blood dyscrasia during the treatment with benzodiazepines; in some, an increase in the hepatic enzyme values was observed.
If prolonged treatment is considered clinically necessary, regular blood and hepatic function tests are recommended.
Prolonged treatment with benzodiazepines should be gradually reduced.
Elderly patients
As with any premedication, extreme caution is required when administering lorazepam in elderly or severely ill patients and patients with limited lung retention (COPD, sleep apnoea syndrome), due to the possibility of apnea and / or hypoxic heart failure. Resuscitation equipment for ventilation assistance must be readily available.
Lorazepam should be used with caution in elderly due to the risk of sedation and/or musculoskeletal weakness that can increase the risk of falls, with serious consequences in this population. Elderly patients should be given a reduced dose.
Impaired renal or hepatic function
Patients with impaired renal or hepatic function should be closely monitored and the dosage should be carefully adjusted according to their reactions. Lower doses may be sufficient in these patients.
The same precautions apply to elderly or debilitated patients and patients with chronic respiratory insufficiency. Lorazepam is not recommended for use in patients with renal insufficiency.
Paradoxical reactions
During treatment with benzodiazepines, paradoxical reactions such as restlessness, agitation, irritability, aggressiveness, despair, anger attacks, nightmares, hallucinations, psychoses and inappropriate behavior were occasionally reported. Such reactions are more likely to occur in children and in the elderly. Should these occur, use of the drug should be discontinued.
Anterograde amnesia
Benzodiazepines can cause anterograde amnesia. This usually occurs several hours after ingestion. Therefore, in order to reduce the risk, patients should be able to sleep continuously for 7/8 hours.
Paediatric population
The use of lorazepam is contraindicated in children under 12 years, except in the management of status epilepticus. After administration of lorazepam especially in neonates with very low birth weight, epileptic seizures and myoclonus were reported.
Drug abuse and dependence
There are no clinical data with regard to abuse or dependence. However, based upon experience with oral benzodiazepines, physicians should be aware that repeated administration of lorazepam over a long period of time may lead to physical and / or psychological dependence. The risk increases with higher doses and longer-term use and is further increased in patients with a history of alcoholism or drug abuse.
In case of physical dependence, abrupt discontinuation of treatment may be associated with withdrawal symptoms. Since the risk of withdrawal symptoms / rebound phenomena is greater if the treatment is abruptly stopped, it should be gradually decreased.
Information on excipients
Benzyl alcohol
Benzyl alcohol may cause allergic reactions. Intravenous administration of benzyl alcohol has been associated with serious adverse events and death in neonates (“gasping syndrome”). Although normal therapeutic doses of this product usually release amounts of benzyl alcohol significantly lower than doses reported in association with gasping syndrome, the minimum amount of benzyl alcohol at which toxicity may occur is not known.
Premature and low birth weight neonates are more likely to develop toxicity. Formulations containing benzyl alcohol should not be used for more than 1 week in children under 3 years of age, unless necessary.
Propylene glycol
Medical monitoring, including measurement of osmolar and/or anion gap, is required in patients with impaired renal or hepatic functions receiving ≥50 mg/kg/day propylene glycol. Various adverse events attributed to propylene glycol have been reported such as renal dysfunction (acute tubular necrosis), acute renal failure and liver dysfunction.
Prolonged administration of products containing propylene glycol, as well as co-administration with other substrates of alcohol dehydrogenase (e.g., ethanol), increase the risk of propylene glycol accumulation and toxicity, especially in patients with impaired hepatic or renal function.
Doses of propylene glycol 1 mg/kg/day may cause serious adverse reactions in neonates; doses of ≥50 mg/kg/day may cause side effects in children under 5 years of age, especially if the baby or child is receiving other medicines containing propylene glycol or alcohol.
Administration of ≥50 mg/kg/day propylene glycol to pregnant or breast-feeding women should only be considered on a case-by-case basis.
See prescribing information for full details.

Very Common: Fatigue
Common: Sedation, drowsiness, dizziness, ataxia, muscle weakness
See prescribing information for full details.

Benzodiazepines, including lorazepam, produce additive CNS depressant effects when co-administered with other agents such as alcohol, barbiturates, antipsychotics, sedatives / hypnotics, anxiolytics, antidepressants, narcotic analgesics, sedative antihistamines, anticonvulsants and anesthetics.
Haloperidol: Cases of apnea, coma, bradycardia, cardiac arrest and death have been reported with concomitant use of lorazepam and haloperidol.
Scopolamine: Concomitant use of scopolamine showed an increased incidence of sedation, hallucinations and irrational behavior.
Clozapine: Concomitant use of clozapine and lorazepam may cause marked sedation, excessive salivation and ataxia.
Valproate: Valproate may inhibit the glucuronidation of lorazepam (increased serum levels: increased risk of drowsiness).
Probenecid: Probenecid increases the half-life of lorazepam and reduces the clearance due to inhibition of glucuronidation.
Opioids: 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.

Pregnancy: There are insufficient data on the use of lorazepam during pregnancy. When lorazepam is administered during pregnancy, hypothermia, respiratory depression and hypotonia (Floppy Infant Syndrome) may occur as a result of the pharmacological action of lorazepam in the newborn child.
In case of prolonged use, withdrawal symptoms may occur in the child. Lorazepam should only be used during pregnancy if strictly necessary for a period as short as possible and at the lowest possible dose. Administration of ≥50 mg/kg/day propylene glycol to pregnant women should only be considered on a case-by-case basis.
Lactation: Lorazepam passes in small amounts into breast milk. During Lorazepam use, breastfeeding is not recommended. Propylene glycol passes into breast milk and may be taken by mouth by a breastfed infant. Administration of ≥50 mg/kg/day of propylene glycol to breast-feeding women should only be considered on a case-by-case basis.           

Overdose will not cause a life-threatening situation, except in combination with other drugs with inhibitory effects on the central nervous system (including alcohol).
Attention should be paid to respiratory and cardiovascular functions on the intensive care.
Overdose with benzodiazepines usually results in different degrees of central nervous system dampening, ranging from sleepiness to coma. In mild cases, symptoms include sleepiness, mental confusion and lethargy. In severe cases, symptoms may occur such as ataxia, hypotension, hypotonia, respiratory depression, rarely coma (stages 1 to 3) and, very rarely, the patient’s death.
Flumazenil may be useful as antidote.
This medicinal product contains propylene glycol. Various side effects have been reported with high doses (500 mg/kg/day or more) or prolonged use of propylene glycol, such as hyperosmolality, lactic acidosis; impaired renal function (acute tubular necrosis), acute renal failure; cardiotoxicity (arrhythmia, hypotension); disorders of the central nervous system (depression, coma, seizures); respiratory depression, dyspnea; impaired liver function; hemolytic reaction (intravascular hemolysis) and hemoglobinuria; or multi-organ failure. Such exposure can be achieved if the dose of the product significantly exceeds the recommended dose. The risk of these symptoms is greater in patients with renal insufficiency and in children.