Drugs List

Therapeutic Indications

Uses

Acute alcohol withdrawal
Anxiety state (severe) - short term relief
Child night terrors and somnambulism
Control of muscle spasm in tetanus
Epilepsy (adjunctive treatment)
Muscle spasms
Muscular spasm in spastic conditions
Obsessive-compulsive disorders
Premedication - sedative

Administration

For oral administration

Nasoduodenal tube (Muscle spasm in tetanus)

Shake syrup well before use.

Contraindications

Acute respiratory impairment
Breastfeeding
Chronic psychosis
Myasthenia gravis
Respiratory depression
Severe hepatic impairment
Severe respiratory impairment
Sleep apnoea

Precautions and Warnings

Children under 18 years
Debilitation
Elderly
Hypoalbuminaemia
Suicidal ideation
Cardiorespiratory insufficiency
Cerebral arteriosclerosis
Chronic respiratory impairment
Coma
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary fructose intolerance
History of alcohol abuse
History of drug misuse
Lactose intolerance
Muscle weakness
Organic brain syndrome
Personality disorder
Pregnancy
Renal impairment

May exacerbate myasthenia gravis
Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine is subject to driving restrictions
Not suitable as sole treatment of depression or anxiety with depression
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain lactose
Some formulations contain sucrose
Monitor patients with a history of alcoholism and drug abuse
Monitor patients with marked personality disorders
Reassess need for continued treatment at regular intervals
Refer women considering pregnancy for specialist advice and monitoring
Tolerance and dependence may occur
Amnesia may occur
Discontinue if psychiatric disturbances develop
Potential for withdrawal symptoms
Psychological adjustment may be impaired in loss or bereavement
Withdraw gradually after long-term use
Discontinue if paradoxical reactions occur
Limit prescribing quantity due to suicide risk
Reduce dose in debilitated patients
Reduce dose in elderly
Not recommended for use longer than 4 weeks
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient grapefruit products may increase plasma level
Advise patient on possible rebound phenomena on withdrawal

The lowest dose and shortest duration possible should be used.

There is a risk of both physical and psychic dependence to diazepam which increases with dose and duration. A maximum of 2 to 4 weeks treatment is recommended (including tapering off period) due to the risk of dependence.

The efficacy to the hypnotic effects of diazepam may lessen after repeated use for a few weeks.

It may be useful to specifically discuss the short term nature of the treatment, how it will be tapered off and how rebound phenomenon may occur to minimise the anxiety this may provoke.

Diazepam is considered unsuitable for the short term management of mild anxiety

Elderly and debilitated patients may be more prone to adverse effects such as sedation, drowsiness and confusion and so lower dosages should be used. However, if these symptoms occur in any patient , which might be expected to be more likely during the first week of treatment or with high doses, it may be suitable for half the total daily dose to be given at night with the remaining dose given in divided doses during the day.

Use with caution in patients with organic brain disease, particularly arteriosclerosis as the limits of tolerance may be very wide in this patient group and dosage adjustment should be considered.

Diazepam may induce anterograde amnesia which occurs most frequently several hours after a dose. To reduce the risk patients should ideally ensure they can have uninterrupted sleep for 7 to 8 hours after a dose.

Use with caution in patients with cardiorespiratory insufficiency, as the limits of tolerance may be very wide in this patient group and dosage adjustment should be considered.

Chronic mild to moderate pulmonary insufficiency - reduce dose

Pregnancy and Lactation

Pregnancy

Use diazepam with caution in pregnancy.

Women of child bearing potential should be advised to discuss withdrawal of diazepam if they should wish to become, or discover they are, pregnant.

There may be a small increased risk of congenital malformation (such as oral cleft) if benzodiazepines are used during the first trimester of pregnancy.

If, for compelling reasons, diazepam 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 drug.

Moreover, infants born to mothers who took benzodiazepines chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Diazepam is contraindicated in breastfeeding.

Benzodiazepines are found in breast milk and so should not be used by breast feeding mothers.

Reports have shown milk plasma concentration ratios vary. Therefore there is a risk of accumulation in the breastfeeding child. LactMed suggest in a single dose of diazepam in sedation before a procedure, there would be no need to wait before the patient resumes breastfeeding unless it was a newborn or preterm infant where caution is advised and a wait of 6 to 8 hours before the mother resumes breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Aggressive reaction
Agitation
Allergic skin reactions
Anterograde amnesia
Anxiety
Apnoea
Ataxia
Behavioural disturbances
Blood dyscrasias
Blurred vision
Bradycardia
Cardiac arrest
Cardiac failure
Changes in libido
Confusion
Constipation
Decreased appetite
Delirium
Delusions
Dependence
Depression (with risk of suicide)
Dizziness
Drowsiness
Dysarthria
Dystonia
Epileptic seizures
Erythema
Excitement
Fatigue
Gastric upset
Gynaecomastia
Hallucinations
Headache
Hypersensitivity reactions including anaphylaxis
Hyperuricaemia
Hypotension
Impaired co-ordination
Impaired concentration
Impotence
Incontinence
Increase in alkaline phosphatase
Increase in serum ALT/AST
Increase in serum transaminases
Increased appetite
Increased bronchial secretions
Irritability
Itching
Jaundice
Light-headedness
Loss of balance
Muscle spasm
Muscle weakness
Myasthenia
Nightmares
Numbed emotions
Nystagmus
Palpitations
Panic attack
Paranoid delusions
Pruritus
Psychosis
Rages
Rash
Respiratory arrest
Respiratory depression
Restlessness
Salivation changes
Sedation
Sensory disturbances
Slurred speech
Sweating
Syncope
Tremor
Unsteady gait
Urinary retention
Vertigo
Visual disturbances
Withdrawal symptoms

Presentation

Oral formulations containing diazepam.

Drugs List

Therapeutic Indications

Uses

Acute alcohol withdrawal
Anxiety state (severe) - short term relief
Child night terrors and somnambulism
Control of muscle spasm in tetanus
Epilepsy (adjunctive treatment)
Muscle spasms
Muscular spasm in spastic conditions
Obsessive-compulsive disorders
Premedication - sedative

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Administration

For oral administration

Nasoduodenal tube (Muscle spasm in tetanus)

Shake syrup well before use.

Contraindications

Acute respiratory impairment
Breastfeeding
Chronic psychosis
Myasthenia gravis
Respiratory depression
Severe hepatic impairment
Severe respiratory impairment
Sleep apnoea

Precautions and Warnings

Children under 18 years
Debilitation
Elderly
Hypoalbuminaemia
Suicidal ideation
Cardiorespiratory insufficiency
Cerebral arteriosclerosis
Chronic respiratory impairment
Coma
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary fructose intolerance
History of alcohol abuse
History of drug misuse
Lactose intolerance
Muscle weakness
Organic brain syndrome
Personality disorder
Pregnancy
Renal impairment

May exacerbate myasthenia gravis
Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine is subject to driving restrictions
Not suitable as sole treatment of depression or anxiety with depression
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain lactose
Some formulations contain sucrose
Monitor patients with a history of alcoholism and drug abuse
Monitor patients with marked personality disorders
Reassess need for continued treatment at regular intervals
Refer women considering pregnancy for specialist advice and monitoring
Tolerance and dependence may occur
Amnesia may occur
Discontinue if psychiatric disturbances develop
Potential for withdrawal symptoms
Psychological adjustment may be impaired in loss or bereavement
Withdraw gradually after long-term use
Discontinue if paradoxical reactions occur
Limit prescribing quantity due to suicide risk
Reduce dose in debilitated patients
Reduce dose in elderly
Not recommended for use longer than 4 weeks
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient grapefruit products may increase plasma level
Advise patient on possible rebound phenomena on withdrawal

The lowest dose and shortest duration possible should be used.

There is a risk of both physical and psychic dependence to diazepam which increases with dose and duration. A maximum of 2 to 4 weeks treatment is recommended (including tapering off period) due to the risk of dependence.

The efficacy to the hypnotic effects of diazepam may lessen after repeated use for a few weeks.

It may be useful to specifically discuss the short term nature of the treatment, how it will be tapered off and how rebound phenomenon may occur to minimise the anxiety this may provoke.

Diazepam is considered unsuitable for the short term management of mild anxiety

Elderly and debilitated patients may be more prone to adverse effects such as sedation, drowsiness and confusion and so lower dosages should be used. However, if these symptoms occur in any patient , which might be expected to be more likely during the first week of treatment or with high doses, it may be suitable for half the total daily dose to be given at night with the remaining dose given in divided doses during the day.

Use with caution in patients with organic brain disease, particularly arteriosclerosis as the limits of tolerance may be very wide in this patient group and dosage adjustment should be considered.

Diazepam may induce anterograde amnesia which occurs most frequently several hours after a dose. To reduce the risk patients should ideally ensure they can have uninterrupted sleep for 7 to 8 hours after a dose.

Use with caution in patients with cardiorespiratory insufficiency, as the limits of tolerance may be very wide in this patient group and dosage adjustment should be considered.

Chronic mild to moderate pulmonary insufficiency - reduce dose

Pregnancy and Lactation

Pregnancy

Use diazepam with caution in pregnancy.

Women of child bearing potential should be advised to discuss withdrawal of diazepam if they should wish to become, or discover they are, pregnant.

There may be a small increased risk of congenital malformation (such as oral cleft) if benzodiazepines are used during the first trimester of pregnancy.

If, for compelling reasons, diazepam 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 drug.

Moreover, infants born to mothers who took benzodiazepines chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Diazepam is contraindicated in breastfeeding.

Benzodiazepines are found in breast milk and so should not be used by breast feeding mothers.

Reports have shown milk plasma concentration ratios vary. Therefore there is a risk of accumulation in the breastfeeding child. LactMed suggest in a single dose of diazepam in sedation before a procedure, there would be no need to wait before the patient resumes breastfeeding unless it was a newborn or preterm infant where caution is advised and a wait of 6 to 8 hours before the mother resumes breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). This medicine may be subject to police testing and has specified maximum blood levels for driving. When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them. It is an offence to drive while under the influence of this medicine. However, a patient is not committing an offence (called 'statutory defence') if: 1.The medicine has been prescribed to treat a medical or dental problem and 2.The medicine has been taken according to the instructions given by the prescriber and/or in the information provided with the medicine and 3.The medicine was not affecting the ability to drive safely. For further guidance see https://www.gov.uk

Side Effects

Aggressive reaction
Agitation
Allergic skin reactions
Anterograde amnesia
Anxiety
Apnoea
Ataxia
Behavioural disturbances
Blood dyscrasias
Blurred vision
Bradycardia
Cardiac arrest
Cardiac failure
Changes in libido
Confusion
Constipation
Decreased appetite
Delirium
Delusions
Dependence
Depression (with risk of suicide)
Dizziness
Drowsiness
Dysarthria
Dystonia
Epileptic seizures
Erythema
Excitement
Fatigue
Gastric upset
Gynaecomastia
Hallucinations
Headache
Hypersensitivity reactions including anaphylaxis
Hyperuricaemia
Hypotension
Impaired co-ordination
Impaired concentration
Impotence
Incontinence
Increase in alkaline phosphatase
Increase in serum ALT/AST
Increase in serum transaminases
Increased appetite
Increased bronchial secretions
Irritability
Itching
Jaundice
Light-headedness
Loss of balance
Muscle spasm
Muscle weakness
Myasthenia
Nightmares
Numbed emotions
Nystagmus
Palpitations
Panic attack
Paranoid delusions
Pruritus
Psychosis
Rages
Rash
Respiratory arrest
Respiratory depression
Restlessness
Salivation changes
Sedation
Sensory disturbances
Slurred speech
Sweating
Syncope
Tremor
Unsteady gait
Urinary retention
Vertigo
Visual disturbances
Withdrawal symptoms

Withdrawal Symptoms and Signs

Abrupt withdrawal of diazepam may result in symptoms such as headache, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability, sleep disturbance, diarrhoea and mood changes. In severe cases the following may occur: a feeling of unreality or of being separated from the body, depersonalisation, confusional states, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, psychotic manifestations including hallucinations or epileptic seizures.

Withdrawal symptoms will be worse in patients with epilepsy, patients who have been dependent on alcohol or other narcotic drugs in the past, but can occur following abrupt cessation of treatment in patients receiving normal therapeutic doses for a short period of time.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Signs and Symptoms

Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. Coma, hypotension and respiratory depression occasionally occur but are seldom serious if these drugs are taken alone. Coma usually lasts only a few hours but in elderly people it may be more protracted and cyclical. Benzodiazepine respiratory depressant effects are more serious in patients with severe chronic respiratory disease.

Benzodiazepines potentiate the effects of other central nervous system depressants, including alcohol.

Treatment

Consider activated charcoal in adults or children who have taken more than 1 mg/kg within 1 hour, provided they are not too drowsy. Gastric lavage is unnecessary if these drugs have been taken alone. Patients who are asymptomatic at four hours are unlikely to develop symptoms. Institute supportive measures as indicated by the patient's clinical state.

If CNS depression is severe consider the use of flumazenil (Anexate), a benzodiazepine antagonist. This should rarely be required. It has a short half-life (about an hour) and should NOT TO BE USED IN MIXED OVERDOSE OR AS A "DIAGNOSTIC" TEST. It is contraindicated in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants).

Further Information

Last Full Review Date: May 2016

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference. 39th Edition. London: Brayfield A (ed). Pharmaceutical Press; 2017.

Summary of Product Characteristics: Diazepam Tablets 2mg. Actavis. Revised December 2014.
Summary of Product Characteristics: Diazepam Tablets 5mg. Actavis. Revised December 2014.
Summary of Product Characteristics: Diazepam Tablets 10mg. Actavis. Revised December 2014.
Summary of Product Characteristics: Diazepam Oral solution 2mg/5ml sugar free. Accord. Revised August 2018.
Summary of Product Characteristics: Diazepam 2mg/5ml oral suspension. Sandoz Ltd. Revised September 2018.
Summary of Product Characteristics: Diazepam Forte Syrup 5mg/5ml. Sandoz. Revised July 2005.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

diazepam/temazepam
MHRA 22nd January 2007
Available at: https://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/Genericoverdosesections/index.htm
Last accessed: 19 May 2016

NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 27 June 2017.

The Norwegian Porphyria Centre (NAPOS).
Available at: https://www.drugs-porphyria.org
Last revised: 21 March 2013
Last accessed: 19 May 2016

The Welsh Medicines Information Centre (WMIC) - Porphyria Information Service.
Available at: https://www.wmic.wales.nhs.uk/porphyria_info.php
Last revised: 01 May 2016
Last accessed: 19 May 2016

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Diazepam Last revised: 07 September 2013
Last accessed: 19 May 2016

Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk Last accessed: 6 January 2015