DIAZEPAM

4). Treatment should be given for the shortest possible duration. If this medicine is being used for the treatment of epilepsy this medicine should be used for as long as the prescriber considers it necessary. Posology As an anxiolytic, the lowest effective dose should be employed; dosage regimes should not exceed beyond 14 days, including tapering off.

Patients who have received benzodiazepines for a long time may require an extended withdrawal period. Long-term chronic use is not recommended.

Adults:

Anxiety states, obsessive-compulsive neuroses, and other psychiatric disorders: 2-30mg daily in divided doses. Insomnia associated with anxiety: 5mg to 15mg before retiring. Management of cerebral palsy spasticity in selected cases: 2mg to 60mg daily in divided doses.

Muscle spasm of varied aetiology, fibrositis, cervical spondylosis: 2mg to 15mg daily in divided doses. In the control of muscle spasms as in tetanus: 3mg to 10mg/kg body weight daily. The selected dose should relate to the severity of the case and in extremely severe cases higher doses have been used.

Intravenous diazepam is recommended initially (see separate prescribing information). Adjunct to the management of some types of epilepsy: 2mg to 60mg daily in divided doses. Symptomatic treatment of acute alcohol withdrawal: 5mg to 20mg, repeated if necessary in 2 to 4 hours.

Premedication: 5mg to 20mg.

Paediatric population:

Night terrors and somnambulism: 1mg to 5mg daily before retiring. In the control of muscle spasms as in tetanus: 3mg to 10mg/kg body weight daily. Management of spasticity in cerebral palsy in selected cases: 2mg to 40mg daily in divided doses.

Premedication: 2mg to 10mg.

Elderly and debilitated patients:

Doses should not exceed half the above recommended adult doses. Hepatic impairment Patients with impaired hepatic function should be given a reduced dose. Renal impairment Patients with impaired renal function should be given a reduced dose.

Duration Treatment should be as brief as possible. The indication should be reassessed regularly especially in the absence of symptoms. 4). The patient must be evaluated after a period of no more than 4 weeks and then regularly thereafter in order to assess the need for continued treatment, especially if the patient is free of symptoms.

Treatment should always be tapered off gradually. In some cases, it may be necessary to extend treatment beyond the recommended periods. This requires accurate and repeated assessments of the patient's condition. Prevention and treatment of delirium tremens and other manifestations of alcohol withdrawal: short-term treatment in the range of 8 to 10 days.

Method of administration For oral administration.

Drowsiness, numbed emotions, reduced alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia or double vision predominantly occur at the start of therapy but usually disappear with repeated administration. Among elderly patients there may be confusion conditions at high dose levels.

There is an increased risk of falls and associated fractures in elderly patients using benzodiazepines. Increased salivary and bronchial secretion has been reported, in particular in children. Amnesia Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages.

4). 4). Abuse of benzodiazepines has been reported.

The frequencies of adverse events are ranked according to the following:

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). System Organ Class Frequency Undesirable effects Rare Blood dyscrasiasBlood and lymphatic system disorders Very rare Leukopenia Immune system disorders Very rare Anaphylaxis.

4). a Very common Drowsiness. Common Ataxia, impaired motor ability, tremor. b Concentration difficulties, balance disorders, dizziness, headache, slurred speech. Nervous system disorders Rare Unconsciousness, insomnia, dysarthria. Eye disorders Not known Reversible disorders of vision: blurred vision, diplopia, nystagmus.

Cardiac disorders Rare Bradycardia, heart failure including cardiac arrest. Vascular disorders Rare Hypotension, syncope. Respiratory, thoracic and Uncommon Respiratory depression. Rare Respiratory arrest, increased bronchial secretion.

mediastinal disorders Not Known Apnoea Gastrointestinal disorders Uncommon Gastrointestinal disorders (nausea, vomiting, constipation, diarrhoea), increased salivary secretion. Rare Dry mouth, increased appetite. Hepatobiliary disorders Rare Jaundice, changes of hepatic parameters (elevation of ALT, AST, alkaline phosphatase).

Skin and subcutaneous tissue disorders Uncommon Allergic skin reactions (itching, erythema, rash). Musculoskeletal and connective tissue disorders Uncommon Myasthenia. Renal and urinary disorders Rare Urinary retention, incontinence.

Reproductive system and breast disorders Rare Gynaecomastia, impotence, increased or reduced libido. c General disorders and administration site conditions Investigations Very rare Elevation of transaminases. a Pre-existing depression may be unmasked during benzodiazepine use.

b May occur using therapeutic dosages, the risk increasing at higher dosages. 4). 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. 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.

Warnings Benzodiazepines are not recommended for the main treatment of psychosis. Risk from concomitant use of opioids Concomitant use of diazepam 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 diazepam with opioids should be reserved for patients for whom alternative treatment options are not possible.

2). The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5). Concurrent alcohol use/CNS depressant agents The concomitant use of diazepam and alcohol (ethanol) (alcoholic beverage or alcohol- containing medication) and/or central nervous system depressants should be avoided.

5). Seizures In patients presenting with drowsiness or hypotonia after diazepam, an infection affecting the nervous system should be excluded before attributing symptoms to diazepam. Starting an anti-epileptic medication can be followed by an increase in seizures or the onset of a new type of seizure in the patient.

This is independent of the natural fluctuations to be expected in certain types of epilepsy. Possible causes for seizures after diazepam include: epileptic syndrome of the patient, a concurrent modification of the anti-epileptic treatment, a pharmacokinetic interaction with another medicine, toxicity or overdose.

Otherwise, it may be that there is no explanation other than a paradoxical reaction. Pharmacological tolerance Some loss of efficacy of diazepam may develop after repeated use for a few weeks. Limits of tolerance in patients with organic cerebral changes (particularly arteriosclerosis) or cardiorespiratory insufficiency may be very wide; care must be taken in adapting the dosage with such patients.

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. Routine repeat prescriptions should be avoided and treatment should be withdrawn gradually. 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 diazepam should be reviewed regularly, with frequent assessments of patients being undertaken during the course of their treatment.

As sudden discontinuation of benzodiazepines may result in convulsions, particular care should be taken in patients with epilepsy, other patients who have had a history of seizures or in alcohol or drug dependants. Discontinuation should be gradual in order to minimise the risk of withdrawal symptoms.

Drug withdrawal syndrome Prior to starting treatment with diazepam, 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 diazepam 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 […]

1. • Phobic or obsessional states; chronic psychosis, hyperkinesis (paradoxical reactions may occur). • Acute pulmonary insufficiency; respiratory depression, acute or chronic severe respiratory insufficiency (ventilatory failure may be exacerbated).

• Myasthenia gravis (condition may be exacerbated). • Sleep apnoea (condition may be exacerbated). • Severe hepatic insufficiency (elimination half-life of diazepam may be prolonged). • Acute porphyria. • Diazepam should not be used as monotherapy in patients with depression or those with anxiety and depression as suicide may be precipitated in such patients.

6). 6).