Drugs List

Therapeutic Indications

Uses

Epilepsy-partial seizures (adjunctive treatment)
Neuropathic pain
Treatment of generalised anxiety disorder (GAD)

Contraindications

Children under 18 years

Precautions and Warnings

Constipation
Elderly
Females of childbearing potential
Suicidal ideation
Breastfeeding
Cardiac disorder in the elderly
Diabetes mellitus
Galactosaemia
Glucose-galactose malabsorption syndrome
Haemodialysis
History of drug misuse
Lactose intolerance
Neurological disorder
Paralytic ileus
Pregnancy
Renal impairment - creatinine clearance below 60ml/minute
Respiratory impairment

Consider antidiabetic drug dosage in diabetic patients who gain weight
Reduce dose in patients with creatinine clearance below 60ml/min
Advise ability to drive/operate machinery may be affected by side effects
Folic acid 5mg daily required pre-conception to end of 1st trimester
Oral liquid contains hydroxybenzoate: caution in hypersensitivity
Some formulations contain lactose
Monitor for constipation; give laxatives as required
Monitor for depressive disorders/suicidal ideation-consider discontinuation
Monitor for signs of tolerance and dependence
Potential for drug abuse
Refer women considering pregnancy for specialist advice and monitoring
Advise patient of potential side effects and risks associated with therapy
Consider discontinuing if visual function deteriorates unexpectedly
May cause convulsions
May cause dependence
Patient should be made aware of possible adverse effects on mood/behaviour
Potential for withdrawal symptoms
To discontinue, reduce dose gradually over at least 1-2 weeks
Advise patient to seek advice at first indications of pregnancy
Discontinue if angioedema occurs
Discontinue if renal failure develops
Reduce dose in elderly
Advise patient not to take St John's wort concurrently
Advise that effects are potentiated by CNS depressants (including alcohol)
Female: Ensure adequate contraception during treatment
Advise patient of increased risk of falls
Advise patient/carers to report signs of suicide ideation or behaviour

Antiepileptic treatment is associated with a small increased risk of suicidal thoughts and behaviour; available data suggest that the increased risk applies to all antiepileptics and is seen as early as 1 week after staring treatment. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for pregabalin.

The available evidence does not define whether the risk of suicidal thoughts and behaviour differs between antiepileptics. Patients should not stop or switch treatment on the basis of this information and without speaking to a healthcare professional.

There have been post-marketing reports of congestive heart failure in some patients receiving pregabalin. These reactions are mostly seen in elderly cardiovascular compromised patients during pregabalin treatment for a neuropathic indication. Pregabalin should be used with caution in these patients, and discontinuation may resolve the reaction.

There are post-marketing reports of events related to reduced lower gastrointestinal tract function (e.g., intestinal obstruction, paralytic ileus, constipation) when pregabalin was co-administered with medications that have the potential to produce constipation, such as opioid analgesics. When pregabalin and opioids are used in combination, measures to prevent constipation may be considered (especially in female patients and elderly).

Visual disturbances may occur with pregabalin, which should resolve or improve upon discontinuation. These may include: visual blurring, visual acuity reduction, visual field changes, fundoscopic changes or loss of vision.

Discontinuation of concurrent antiepileptic medicinal products, once seizure control with pregabalin in the add-on situation has been reached, is not recommended due to insufficient data. There is no experience of monotherapy with pregabalin.

Concerning discontinuation of short or long term treatment, there is no data on the incidence and severity of withdrawal symptoms in relation to duration of use or dosage of pregabalin.

The incidence of general adverse effects, central nervous system adverse reactions and especially somnolence, may be increased in patients with spinal cord injury being treated for central neuropathic pain. This may be attributed to an additive effect due to concomitant medicinal products needed for this condition. This should be considered when prescribing pregabalin in this condition.

Severe respiratory depression has been reported with the use of pregabalin. Dose adjustment may be necessary in patients at higher risk of developing severe respiratory depression including patients with respiratory impairment, respiratory disorder, neurological disorder, renal impairment, elderly patients and concomitant use with CNS depressants.

Pregnancy and Lactation

Pregnancy

Use pregabalin with caution during pregnancy.

The manufacturer does not recommend using pregabalin during pregnancy. Pregabalin should only be used if the benefit to the mother clearly outweighs the potential risk to the foetus. There is no adequate data on the use of pregabalin in human pregnancy. It is not known whether it crosses the placenta, but the low molecular weight, minimal metabolism, lack of protein binding and moderately long elimination half life are consistent with embryo/foetal transfer (Briggs 2015). Some studies have shown a higher risk for major congenital malformations in the first trimester among the paediatric population compared to the unexposed population.

Animal studies have shown some reproductive toxicity, mainly skeletal abnormalities and neural tube defects. Reproduction studies in rats found developmental toxicity (growth retardation, behavioural defects, death) at doses from 10 times the human exposure at the maximum recommended dose, and pregabalin was found to be carcinogenic in mice.

Schaefer (2015) concludes that there is insufficient experience to allow for an accurate risk assessment. Exposure does not require termination, but a detailed ultrasound diagnosis should be conducted in the second trimester as an additional preventative measure. Briggs agrees that since the available data suggest a potential for toxicity, the best course is to avoid use until more experience is available.

However, adjusting or stopping any anti-epileptic medication during pregnancy should not be done without specialist advice, and the relative benefits and risks should be discussed carefully first. The risk of inadequate seizure control may be more detrimental to the foetus than the use of antiepileptic drugs. Pregnancy in epileptic women is associated with a higher risk of congenital abnormalities, which are mainly associated with the use of anti-epileptic drugs rather than the disease itself. This risk is increased when multiple drugs are used. Routine monitoring of antiepileptic drugs is not recommended, but may be useful in cases where seizures have increased or are likely to, in order to plan the extent of dose adjustment needed. The Clinical Knowledge Summaries recommend that folic acid 5 mg daily should be prescribed to all women with epilepsy who are taking antiepileptic drugs, prior to conception and continued until the 12th week of pregnancy.

Lactation

Use pregabalin with caution during breastfeeding.

The manufacturers suggest that pregabalin can be used in breastfeeding if the benefit to the mother or infant is deemed acceptable versus the lack of data. Pregabalin is excreted into human milk but the effects of exposure on the nursing infant are unknown. LactMed also says that very limited data indicate that amounts of pregabalin in breast milk are low. If pregabalin is required by the mother of an older infant, it is not a reason to discontinue breastfeeding, but until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Though Briggs (2015) concludes that it should not be used during breastfeeding as it has been found to be carcinogenic in long-term studies in mice, which, coupled with the lack of excretion data and potential for serious toxicity.

Side Effects

Ageusia
Aggression
Agitation
Alanine aminotransferase increased
Allergic reaction
Anxiety
Arrhythmias
Aspartate aminotransferase increased
Ataxia
Attention disturbances
Blood dyscrasias
Blood glucose disturbances
Blurred vision
Bradycardia
Breast changes
Burning sensation
Cervical muscle spasm
Changes in blood chemistry
Changes in libido
Chest tightness
Chills
Cognitive impairment
Confusion
Congestive cardiac failure
Convulsions
Cough
Creatine phosphokinase increased
Depersonalisation
Depression
Diarrhoea
Disorientation
Disturbances of appetite
Dizziness
Dream abnormalities
Dysgraphia
Dyskinesia
Dyspnoea
Encephalopathy
Epistaxis
Eye disorder
Falls
Fatigue
First degree AV block
Gait abnormality
Gastroesophageal reflux
Gastrointestinal disorder
Hallucinations
Headache
Hot flushes
Hyperacusis
Hyperaesthesia
Hypersensitivity reactions
Hypertension
Hypoaesthesia
Hypokinesia
Hyporeflexia
Hypotension
Impaired co-ordination
Impaired memory
Impairment of mental skills
Influenza-like syndrome
Insomnia
Joint swelling
Loss of consciousness (transient)
Menstrual disturbances
Mood changes
Muscle cramps
Muscle disorders
Nasal congestion
Nasal dryness
Nasopharyngitis
Nausea
Oedema
Pain
Pancreatitis
Paraesthesia
Parosmia
Prolongation of QT interval
Pruritus
Psychomotor hyperactivity
Pyrexia
Rash
Renal failure
Rhabdomyolysis
Rhinitis
Sexual dysfunction
Snoring
Somnolence
Speech disturbances
Stevens-Johnson syndrome
Suicidal tendencies
Sweating
Syncope
Tachycardia
Throat tightness
Tremor
Urinary abnormalities
Vertigo
Visual disturbances
Weight changes

Presentation

Oral formulations containing pregabalin.

Drugs List

Therapeutic Indications

Uses

Epilepsy-partial seizures (adjunctive treatment)
Neuropathic pain
Treatment of generalised anxiety disorder (GAD)

Dosage

Adults

Patients with Renal Impairment

Contraindications

Children under 18 years

Precautions and Warnings

Constipation
Elderly
Females of childbearing potential
Suicidal ideation
Breastfeeding
Cardiac disorder in the elderly
Diabetes mellitus
Galactosaemia
Glucose-galactose malabsorption syndrome
Haemodialysis
History of drug misuse
Lactose intolerance
Neurological disorder
Paralytic ileus
Pregnancy
Renal impairment - creatinine clearance below 60ml/minute
Respiratory impairment

Consider antidiabetic drug dosage in diabetic patients who gain weight
Reduce dose in patients with creatinine clearance below 60ml/min
Advise ability to drive/operate machinery may be affected by side effects
Folic acid 5mg daily required pre-conception to end of 1st trimester
Oral liquid contains hydroxybenzoate: caution in hypersensitivity
Some formulations contain lactose
Monitor for constipation; give laxatives as required
Monitor for depressive disorders/suicidal ideation-consider discontinuation
Monitor for signs of tolerance and dependence
Potential for drug abuse
Refer women considering pregnancy for specialist advice and monitoring
Advise patient of potential side effects and risks associated with therapy
Consider discontinuing if visual function deteriorates unexpectedly
May cause convulsions
May cause dependence
Patient should be made aware of possible adverse effects on mood/behaviour
Potential for withdrawal symptoms
To discontinue, reduce dose gradually over at least 1-2 weeks
Advise patient to seek advice at first indications of pregnancy
Discontinue if angioedema occurs
Discontinue if renal failure develops
Reduce dose in elderly
Advise patient not to take St John's wort concurrently
Advise that effects are potentiated by CNS depressants (including alcohol)
Female: Ensure adequate contraception during treatment
Advise patient of increased risk of falls
Advise patient/carers to report signs of suicide ideation or behaviour

Antiepileptic treatment is associated with a small increased risk of suicidal thoughts and behaviour; available data suggest that the increased risk applies to all antiepileptics and is seen as early as 1 week after staring treatment. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for pregabalin.

The available evidence does not define whether the risk of suicidal thoughts and behaviour differs between antiepileptics. Patients should not stop or switch treatment on the basis of this information and without speaking to a healthcare professional.

There have been post-marketing reports of congestive heart failure in some patients receiving pregabalin. These reactions are mostly seen in elderly cardiovascular compromised patients during pregabalin treatment for a neuropathic indication. Pregabalin should be used with caution in these patients, and discontinuation may resolve the reaction.

There are post-marketing reports of events related to reduced lower gastrointestinal tract function (e.g., intestinal obstruction, paralytic ileus, constipation) when pregabalin was co-administered with medications that have the potential to produce constipation, such as opioid analgesics. When pregabalin and opioids are used in combination, measures to prevent constipation may be considered (especially in female patients and elderly).

Visual disturbances may occur with pregabalin, which should resolve or improve upon discontinuation. These may include: visual blurring, visual acuity reduction, visual field changes, fundoscopic changes or loss of vision.

Discontinuation of concurrent antiepileptic medicinal products, once seizure control with pregabalin in the add-on situation has been reached, is not recommended due to insufficient data. There is no experience of monotherapy with pregabalin.

Concerning discontinuation of short or long term treatment, there is no data on the incidence and severity of withdrawal symptoms in relation to duration of use or dosage of pregabalin.

The incidence of general adverse effects, central nervous system adverse reactions and especially somnolence, may be increased in patients with spinal cord injury being treated for central neuropathic pain. This may be attributed to an additive effect due to concomitant medicinal products needed for this condition. This should be considered when prescribing pregabalin in this condition.

Severe respiratory depression has been reported with the use of pregabalin. Dose adjustment may be necessary in patients at higher risk of developing severe respiratory depression including patients with respiratory impairment, respiratory disorder, neurological disorder, renal impairment, elderly patients and concomitant use with CNS depressants.

Pregnancy and Lactation

Pregnancy

Use pregabalin with caution during pregnancy.

The manufacturer does not recommend using pregabalin during pregnancy. Pregabalin should only be used if the benefit to the mother clearly outweighs the potential risk to the foetus. There is no adequate data on the use of pregabalin in human pregnancy. It is not known whether it crosses the placenta, but the low molecular weight, minimal metabolism, lack of protein binding and moderately long elimination half life are consistent with embryo/foetal transfer (Briggs 2015). Some studies have shown a higher risk for major congenital malformations in the first trimester among the paediatric population compared to the unexposed population.

Animal studies have shown some reproductive toxicity, mainly skeletal abnormalities and neural tube defects. Reproduction studies in rats found developmental toxicity (growth retardation, behavioural defects, death) at doses from 10 times the human exposure at the maximum recommended dose, and pregabalin was found to be carcinogenic in mice.

Schaefer (2015) concludes that there is insufficient experience to allow for an accurate risk assessment. Exposure does not require termination, but a detailed ultrasound diagnosis should be conducted in the second trimester as an additional preventative measure. Briggs agrees that since the available data suggest a potential for toxicity, the best course is to avoid use until more experience is available.

However, adjusting or stopping any anti-epileptic medication during pregnancy should not be done without specialist advice, and the relative benefits and risks should be discussed carefully first. The risk of inadequate seizure control may be more detrimental to the foetus than the use of antiepileptic drugs. Pregnancy in epileptic women is associated with a higher risk of congenital abnormalities, which are mainly associated with the use of anti-epileptic drugs rather than the disease itself. This risk is increased when multiple drugs are used. Routine monitoring of antiepileptic drugs is not recommended, but may be useful in cases where seizures have increased or are likely to, in order to plan the extent of dose adjustment needed. The Clinical Knowledge Summaries recommend that folic acid 5 mg daily should be prescribed to all women with epilepsy who are taking antiepileptic drugs, prior to conception and continued until the 12th week of pregnancy.

Lactation

Use pregabalin with caution during breastfeeding.

The manufacturers suggest that pregabalin can be used in breastfeeding if the benefit to the mother or infant is deemed acceptable versus the lack of data. Pregabalin is excreted into human milk but the effects of exposure on the nursing infant are unknown. LactMed also says that very limited data indicate that amounts of pregabalin in breast milk are low. If pregabalin is required by the mother of an older infant, it is not a reason to discontinue breastfeeding, but until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Though Briggs (2015) concludes that it should not be used during breastfeeding as it has been found to be carcinogenic in long-term studies in mice, which, coupled with the lack of excretion data and potential for serious toxicity.

Counselling

Advise patients not to use products containing St John's Wort with pregabalin.

Patients should be advised to consult their physician if they are planning a pregnancy, and consider taking folic acid 5mg daily before conception.

Patients and caregivers should be aware of the need to monitor for the emergence of suicidal thoughts and behaviour, and the need to seek medical advice immediately if they present.

Pregabalin may cause dizziness and somnolence and therefore may influence the ability to drive or operate machinery. Patients should be advised to refrain from hazardous activities until their susceptibility is known.

Advise patients that withdrawal symptoms such as insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, nervousness, depression, pain, convulsion, sweating and dizziness have been reported after discontinuation of pregabalin treatment.

Side Effects

Ageusia
Aggression
Agitation
Alanine aminotransferase increased
Allergic reaction
Anxiety
Arrhythmias
Aspartate aminotransferase increased
Ataxia
Attention disturbances
Blood dyscrasias
Blood glucose disturbances
Blurred vision
Bradycardia
Breast changes
Burning sensation
Cervical muscle spasm
Changes in blood chemistry
Changes in libido
Chest tightness
Chills
Cognitive impairment
Confusion
Congestive cardiac failure
Convulsions
Cough
Creatine phosphokinase increased
Depersonalisation
Depression
Diarrhoea
Disorientation
Disturbances of appetite
Dizziness
Dream abnormalities
Dysgraphia
Dyskinesia
Dyspnoea
Encephalopathy
Epistaxis
Eye disorder
Falls
Fatigue
First degree AV block
Gait abnormality
Gastroesophageal reflux
Gastrointestinal disorder
Hallucinations
Headache
Hot flushes
Hyperacusis
Hyperaesthesia
Hypersensitivity reactions
Hypertension
Hypoaesthesia
Hypokinesia
Hyporeflexia
Hypotension
Impaired co-ordination
Impaired memory
Impairment of mental skills
Influenza-like syndrome
Insomnia
Joint swelling
Loss of consciousness (transient)
Menstrual disturbances
Mood changes
Muscle cramps
Muscle disorders
Nasal congestion
Nasal dryness
Nasopharyngitis
Nausea
Oedema
Pain
Pancreatitis
Paraesthesia
Parosmia
Prolongation of QT interval
Pruritus
Psychomotor hyperactivity
Pyrexia
Rash
Renal failure
Rhabdomyolysis
Rhinitis
Sexual dysfunction
Snoring
Somnolence
Speech disturbances
Stevens-Johnson syndrome
Suicidal tendencies
Sweating
Syncope
Tachycardia
Throat tightness
Tremor
Urinary abnormalities
Vertigo
Visual disturbances
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: January 2017

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

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

Summary of Product Characteristics: Axalid capsules. Kent Pharmaceuticals Limited. Revised October 2016.
Summary of Product Characteristics: Lyrica capsules. Pfizer Ltd. Revised November 2022.
Summary of Product Characteristics: Lyrica oral solution. Pfizer Ltd. Revised March 2021.
Summary of Product Characteristics: Pregabalin capsules. Consilient Health Limited. Revised December 2014.
Summary of Product Characteristics: Pregabalin tablets. Neuraxpharm Arzneimittel GmbH. Revised January 2019.

Clinical Knowledge Summaries - Epilepsy
Available at: https://cks.nice.org.uk/epilepsy
Last accessed: 20 January 2017

MHRA Drug Safety Update April 2019
Available at: https://www.mhra.gov.uk
Last accessed: 03 May 2019

MHRA Drug Safety Update Vol 2, Issue 1, August 2008
Antiepileptics: risk of suicidal thoughts and behaviour
Available at: https://webarchive.nationalarchives.gov.uk/20141205150130/https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON023078
Last accessed: 20 January 2017

NICE clinical guideline - The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care
Available at: https://www.nice.org.uk/guidance/cg137
Last accessed: 20 January 2017

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
Pregabalin Last revised: 11 October 2016
Last accessed: 20 January 2017

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 23 January 2020