Drugs List

Therapeutic Indications

Uses

Anxiety state (severe) - short term relief
Depressive illness with anxiety

Short term symptomatic treatment of anxiety

Anxiety associated with depression

It is only indicated when the disorder is severe, disabling or subjecting the individual to unacceptable distress

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Myasthenia gravis
Severe hepatic impairment
Severe respiratory impairment
Sleep apnoea

Precautions and Warnings

Debilitation
Elderly
Females of childbearing potential
Suicidal ideation
Depression
Glucose-galactose malabsorption syndrome
History of alcohol abuse
History of drug misuse
Lactose intolerance
Mild hepatic impairment
Muscle weakness
Personality disorder
Pregnancy
Renal impairment
Respiratory impairment

Consider dose modification in patients with respiratory depression
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise impaired alertness may affect ability to drive or operate machinery
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 may be subject to driving restrictions
Not suitable as sole treatment of depression or anxiety with depression
Contains lactose
Monitor patients with a history of alcoholism and drug abuse
Neonate exposed in utero: Monitor neonate for adverse effects
Potential for drug abuse
Refer women considering pregnancy for specialist advice and monitoring
Review therapy after 4 weeks
Tolerance and dependence may occur
Advise patient to report any new or worsening depression/suicidal ideation
Advise patients/carers to seek medical advice if suicidal intent develops
Amnesia may occur
Discontinue if psychiatric disturbances develop
Elderly: More susceptible to musculoskeletal weakness & sedation
Potential for withdrawal symptoms
Psychological adjustment may be impaired in loss or bereavement
Avoid abrupt withdrawal
To discontinue, reduce dose gradually
Discontinue if paradoxical reactions occur
Limit prescribing quantity due to suicide risk
Maintain treatment at the lowest effective dose
Reduce dose in debilitated patients
Reduce dose in elderly
Only recommended for short term use
Advise patient to avoid alcohol during treatment
Advise patient of increased risk of falls
Advise patient on possible rebound phenomena on withdrawal

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, in order to minimise the anxiety this may provoke.

Use with caution in elderly, due to the risk of sedation and/or musculoskeletal weakness that can increase chances of falls, often with serious consequences in this population.

Pregnancy and Lactation

Pregnancy

Caution is advised in the use of alprazolam during pregnancy. The manufacturer recommends that alprazolam should not be used unless the clinical condition of the mother requires treatment. The patient should be advised of the potential hazard to the foetus if it is used.

Data on teratogenicity and postnatal development and behaviour following benzodiazepine treatment are inconsistent; some indicate that first trimester exposure is not associated with an increased risk of major malformation but others have found a twofold increased risk of oral clefts. The long-term effects of in utero exposure on neurobehaviour, especially when the exposure occurs in the latter half of pregnancy, have not been studied and are of concern.

Benzodiazepine treatment at high dose during the second and/or third trimesters has revealed a decrease in foetal active movements and variability of foetal cardiac rhythm. When administered during the last part of pregnancy, even at low doses, floppy infant syndrome has been observed. This is reversible but may last from 1 to 3 weeks, according to the half life of the product. At high doses, it may produce neonatal respiratory depression, apnoea or hypothermia. Neonatal withdrawal symptoms may be observed a few days after birth, even if no floppy infant syndrome is observed, and depend again on the half life of the substance. If alprazolam treatment is necessary, avoid high doses and monitor the neonate for withdrawal symptoms and/or floppy infant syndrome.

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

Contraindicated in breastfeeding.

Alprazolam is excreted in breast milk at a low level, probably too low to induce a clinical effect. However, due to the nature of the substance and the potential for neonatal withdrawal symptoms, it should not be used by breastfeeding mothers. A single dose does not require any limitation of breastfeeding however, a shorter-acting benzodiazepine without active metabolites is preferred.

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

Abdominal cramps
Abnormal thoughts
Aggression
Agitation
Alteration of autonomic nervous system
Amnesia
Anger
Angioedema
Anterograde amnesia
Anxiety
Ataxia
Attention disturbances
Behavioural disturbances
Blurred vision
Changes in hepatic function
Confusion
Constipation
Convulsions
Decreased appetite
Delusions
Dependence
Depression
Dermatitis
Disorientation
Dizziness
Dry mouth
Dysarthria
Dysphoria
Dystonia
Fatigue
Gastrointestinal disorder
Hallucinations
Headache
Hepatitis
Hostility
Hyperprolactinaemia
Hypersomnia
Hypomania
Impaired memory
Inco-ordination
Incontinence
Increased intra-ocular pressure
Insomnia
Irregular menstruation
Irritability
Jaundice
Lethargy
Loss of balance
Mania
Muscle cramps
Muscle weakness
Nausea
Nervousness
Nightmares
Peripheral oedema
Pre-existing depression may be unmasked
Psychomotor hyperactivity
Psychosis
Rages
Reduced libido
Restlessness
Sedation
Seizures
Sexual dysfunction
Somnolence
Sweating
Tremor
Urinary retention
Vomiting
Weight changes

Presentation

Tablets containing alprazolam

Drugs List

Therapeutic Indications

Uses

Anxiety state (severe) - short term relief
Depressive illness with anxiety

Short term symptomatic treatment of anxiety

Anxiety associated with depression

It is only indicated when the disorder is severe, disabling or subjecting the individual to unacceptable distress

Dosage

The overall duration of treatment should not be more than 8 to 12 weeks, including the tapering off process.

Treatment should be reviewed at least 4 weekly. If extension beyond the maximum treatment period is necessary, it should not take place without re-evaluation of the patient's status with special expertise.

When higher dosage is required, the evening dose should be increased before the daytime dose.

Treatment should be taper off gradually by no more than 0.5 mg every three days. Some patients may require an even slower dosage reduction.

Adults

Elderly

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Myasthenia gravis
Severe hepatic impairment
Severe respiratory impairment
Sleep apnoea

Precautions and Warnings

Debilitation
Elderly
Females of childbearing potential
Suicidal ideation
Depression
Glucose-galactose malabsorption syndrome
History of alcohol abuse
History of drug misuse
Lactose intolerance
Mild hepatic impairment
Muscle weakness
Personality disorder
Pregnancy
Renal impairment
Respiratory impairment

Consider dose modification in patients with respiratory depression
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise impaired alertness may affect ability to drive or operate machinery
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 may be subject to driving restrictions
Not suitable as sole treatment of depression or anxiety with depression
Contains lactose
Monitor patients with a history of alcoholism and drug abuse
Neonate exposed in utero: Monitor neonate for adverse effects
Potential for drug abuse
Refer women considering pregnancy for specialist advice and monitoring
Review therapy after 4 weeks
Tolerance and dependence may occur
Advise patient to report any new or worsening depression/suicidal ideation
Advise patients/carers to seek medical advice if suicidal intent develops
Amnesia may occur
Discontinue if psychiatric disturbances develop
Elderly: More susceptible to musculoskeletal weakness & sedation
Potential for withdrawal symptoms
Psychological adjustment may be impaired in loss or bereavement
Avoid abrupt withdrawal
To discontinue, reduce dose gradually
Discontinue if paradoxical reactions occur
Limit prescribing quantity due to suicide risk
Maintain treatment at the lowest effective dose
Reduce dose in debilitated patients
Reduce dose in elderly
Only recommended for short term use
Advise patient to avoid alcohol during treatment
Advise patient of increased risk of falls
Advise patient on possible rebound phenomena on withdrawal

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, in order to minimise the anxiety this may provoke.

Use with caution in elderly, due to the risk of sedation and/or musculoskeletal weakness that can increase chances of falls, often with serious consequences in this population.

Pregnancy and Lactation

Pregnancy

Caution is advised in the use of alprazolam during pregnancy. The manufacturer recommends that alprazolam should not be used unless the clinical condition of the mother requires treatment. The patient should be advised of the potential hazard to the foetus if it is used.

Data on teratogenicity and postnatal development and behaviour following benzodiazepine treatment are inconsistent; some indicate that first trimester exposure is not associated with an increased risk of major malformation but others have found a twofold increased risk of oral clefts. The long-term effects of in utero exposure on neurobehaviour, especially when the exposure occurs in the latter half of pregnancy, have not been studied and are of concern.

Benzodiazepine treatment at high dose during the second and/or third trimesters has revealed a decrease in foetal active movements and variability of foetal cardiac rhythm. When administered during the last part of pregnancy, even at low doses, floppy infant syndrome has been observed. This is reversible but may last from 1 to 3 weeks, according to the half life of the product. At high doses, it may produce neonatal respiratory depression, apnoea or hypothermia. Neonatal withdrawal symptoms may be observed a few days after birth, even if no floppy infant syndrome is observed, and depend again on the half life of the substance. If alprazolam treatment is necessary, avoid high doses and monitor the neonate for withdrawal symptoms and/or floppy infant syndrome.

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

Contraindicated in breastfeeding.

Alprazolam is excreted in breast milk at a low level, probably too low to induce a clinical effect. However, due to the nature of the substance and the potential for neonatal withdrawal symptoms, it should not be used by breastfeeding mothers. A single dose does not require any limitation of breastfeeding however, a shorter-acting benzodiazepine without active metabolites is preferred.

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). 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.

Counselling

Advise the patient or carer regarding the short term nature of the treatment, how it will be tapered off and how rebound phenomenon may occur, in order to minimise the anxiety this may provoke.

Alcohol should be avoided during treatment.

Insufficient sleep may also increase the likelihood of impaired alertness.

Drowsiness, amnesia, impaired concentration and muscle function may adversely affect the ability to drive or use machinery.

Advise elderly patients of increased risk of falls due to the risk of sedation and/or musculoskeletal weakness.

Side Effects

Abdominal cramps
Abnormal thoughts
Aggression
Agitation
Alteration of autonomic nervous system
Amnesia
Anger
Angioedema
Anterograde amnesia
Anxiety
Ataxia
Attention disturbances
Behavioural disturbances
Blurred vision
Changes in hepatic function
Confusion
Constipation
Convulsions
Decreased appetite
Delusions
Dependence
Depression
Dermatitis
Disorientation
Dizziness
Dry mouth
Dysarthria
Dysphoria
Dystonia
Fatigue
Gastrointestinal disorder
Hallucinations
Headache
Hepatitis
Hostility
Hyperprolactinaemia
Hypersomnia
Hypomania
Impaired memory
Inco-ordination
Incontinence
Increased intra-ocular pressure
Insomnia
Irregular menstruation
Irritability
Jaundice
Lethargy
Loss of balance
Mania
Muscle cramps
Muscle weakness
Nausea
Nervousness
Nightmares
Peripheral oedema
Pre-existing depression may be unmasked
Psychomotor hyperactivity
Psychosis
Rages
Reduced libido
Restlessness
Sedation
Seizures
Sexual dysfunction
Somnolence
Sweating
Tremor
Urinary retention
Vomiting
Weight changes

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 ).

Further Information

Last Full Review Date: March 2013

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.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 03 June 2016.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Xanax tablets 250 and 500 micrograms. Pharmacia Limited. Revised April 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
Record 335 - Alprazolam
Last revised: August 31, 2012
Last accessed: March 7, 2013

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 New drug driving offence implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 6 January 2015