SAPHIRA

Posology Treatment to be given: • under close medical supervision • at the lowest effective dose • for the shortest possible duration (not exceeding 4 weeks) Doses should be individualised. Extension of use should not take place without further clinical evaluation.

4). When treatment is started the patient should be informed that: • treatment will be of limited duration • the dosage will be progressively decreased • there is a possibility of rebound phenomena. 4). Treatment should be initiated at the lowest available dose and given for the shortest possible duration.

If this medicine is being used for the treatment of epilepsy, it should be used for as long as the prescriber considers necessary. 25 mg, 3 to 4 times per day. May be increased if needed until a clinical response is achieved up to 4 mg total daily dose.

25 mg as a single dose before retiring, increased as required until a clinical response is achieved; up to 2 mg. Pre-medication before operative dentistry or general surgery: 2-3 mg the night before operation, 2-4 mg one to two hours before the procedure.

4). 5mg according to weight, not less than one hour before operation. 4). 6). Method of administration For oral use.

4 Special warnings and precautions). 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.

Injury, poisoning and procedural complications Not known:

Fall Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

9 Overdose Patients should be informed of the signs and symptoms of overdose and to ensure that family and friends are also aware of these signs and to seek immediate medical help if they occur. In the management of overdosage with any drug, it should be borne in mind that multiple agents may have been taken.

Overdose of benzodiazepines is usually manifested by degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion, and lethargy. In more serious cases, and especially when other CNS-depressant drugs or alcohol are ingested, symptoms may include ataxia, hypotension, hypotonia, respiratory depression, coma, and very rarely, death.

If ingestion was recent, induced vomiting and/or gastric lavage should be undertaken followed by general supportive care, monitoring of vital signs and close observation of the patient. If there is no advantage in emptying the stomach, activated charcoal may be effective in reducing absorption.

Hypotension, though unlikely, may be controlled with noradrenaline. Lorazepam is poorly dialysable. The benzodiazepine antagonist, flumazenil may be useful in hospitalised patients for the management of benzodiazepine overdosage. Flumazenil product information should be consulted prior to use.

1 Pharmacodynamic properties Pharmacotherapeutic group: Nervous system; psycholeptics; anxiolytics; benzodiazepine derivatives ATC code: N05BA06 Lorazepam is a benzodiazepine with anxiolytic, sedative, hypnotic properties. 2 Pharmacokinetic properties Lorazepam is almost completely absorbed from the gastrointestinal tract and peak serum levels are reached in 2 hours.

It is metabolised by a simple one- step process to a pharmacologically inert glucuronide. There are no major active metabolites. The elimination half-life is about 12 hours and there is minimal risk of excessive accumulation. 3 Preclinical safety data Oesophageal dilation occurred in rats treated with lorazepam for more than one year at 6 mg/kg/day.

Non-clinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development. However, behavioural disturbances were noted in offspring following longer benzodiazepine exposure of the dams.

4 Special precautions for storage Store below 25°C. 5 Nature and contents of container Aluminium/Aluminium blister packs of 10, 14, 15, 20, 25, 28, 30, 50, 56, 60 and 100 tablets. Not all pack sizes may be marketed. 6 Special precautions for disposal No special requirements.

7 MARKETING AUTHORISATION HOLDER MedRx Licences Limited 9 St George’s Yard Castle Street Farnham Surrey GU9 7LW 8 MARKETING AUTHORISATION NUMBER(S) PL 46055/0004 9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 04/02/2022 10 DATE OF REVISION OF THE TEXT 16/01/2026

6)) • Myasthenia gravis • Benzodiazepines should not be used alone in depression or anxiety with depression (may precipitate suicide). 4 Special warnings and precautions for use Drug dependence, tolerance and potential for abuse Drug addiction comprises behavioural, cognitive and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use and possible tolerance or physical dependence.

Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, which manifests as withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.

Addiction and dependence are related but distinct presentations and in discussing these themes, terminology that apportion blame to the individual should be avoided. For all patients, prolonged use of this product may lead to drug dependence and addiction but can occur with short-term use at recommended therapeutic doses.

, major depression). Additional support and monitoring may be necessary when prescribing for patients at risk of drug misuse. A comprehensive patient history should be taken to document concomitant medications, including over-the-counter medicines and medicines obtained on-line, and past and present medical and psychiatric conditions.

Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of symptom control as initially experienced. Patients may also supplement their treatment with additional medications to achieve the same effect.

These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient. Overuse or misuse may result in overdose and/or death. It is important that patients only use medicines that are prescribed for them at the dose they have been prescribed and do not give this medicine to anyone else.

Patients should be closely monitored for signs of misuse, abuse, or addiction. The clinical need for treatment with Lorazepam should be reviewed regularly, with frequent assessments of patients being undertaken during the course of their treatment.

Drug withdrawal syndrome Prior to starting treatment with Lorazepam, a discussion should be held with patients to explain the risk of dependence, addiction, and drug withdrawal syndrome. A withdrawal strategy for ending treatment with Lorazepam should also be put in place with the patient before starting treatment (there may be exceptions to this in specific clinical situations such as symptom management in end of life palliative care, and for use in epilepsy).

Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction. When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take in excess of weeks or months.

Patients should be informed of this when the medication is first prescribed. The reduction schedule for a patient should be tailored to the individual and should be modified to allow intolerable withdrawal symptoms to improve before making the next reduction.

If using a published withdrawal schedule, apply it flexibly to accommodate the person’s preferences, changes to their circumstances and the response to dose reductions. Suggest a slow stepwise rate of reduction proportionate to the existing dose, so that decrements become smaller as the dose is lowered, unless clinical risk is such that rapid withdrawal is needed.

If a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level. If women take this drug during pregnancy, there is a risk that their newborn infants will experience neonatal withdrawal syndrome.

Patients should be advised that since their tolerance for alcohol and other CNS depressants will be diminished in the presence of lorazepam, these substances should either be avoided or taken in reduced dosage. Lorazepam is not intended for the primary treatment of psychotic illness or depressive disorders and should not be used alone to treat depressed patients.

The use of benzodiazepines may have a disinhibiting effect and may release suicidal tendencies in depressed patients. Therefore, large quantities of lorazepam should not be prescribed to these patients. Pre-existing depression may emerge during benzodiazepine use.

The use of benzodiazepines may lead to physical and psychological dependence. The risk of dependence on lorazepam is low when used at the recommended dose and duration, but increases with higher doses and longer-term use. The risk of dependence is further increased in patients with a history of alcoholism or drug abuse, or in patients with significant personality disorders.

Therefore, use in individuals with a history of alcoholism or drug abuse should be avoided. 8). Therefore, the drug should always be discontinued gradually. Typical taper schedules are to reduce dosage by 25% every 2 weeks. 25 […]