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Pregabalin 

Pregabalin
Chapter:
Pregabalin
Author(s):

Andrea E. Cavanna

DOI:
10.1093/med/9780198791577.003.0011
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Pregabalin is a second-generation antiepileptic drug (AED; (Fig. 11.1) known with the proprietary brand name of Lyrica® (Pfizer, Tadworth) in the UK and USA (Pfizer, New York, NY; Fig. 11.2).

Fig. 11.1 Chronology of the clinical use of pregabalin

Fig. 11.1 Chronology of the clinical use of pregabalin

Fig. 11.2 Chemical structure of pregabalin

Fig. 11.2 Chemical structure of pregabalin

This figure is licensed under the Creative Commons Attribution-Share Alike 4.0 International license, https://creativecommons.org/licenses/by-sa/4.0/deed.en

Preparations

Capsules

  • Pregabalin 25 mg (56-cap pack).

  • Pregabalin 50 mg (84-cap pack).

  • Pregabalin 75 mg (56-cap pack).

  • Pregabalin 100 mg (84-cap pack).

  • Pregabalin 150 mg (56-cap pack).

  • Pregabalin 200 mg (84-cap pack).

  • Pregabalin 225 mg (56-cap pack).

  • Pregabalin 300 mg (56-cap pack).

Oral solution

Pregabalin 20 mg/1 mL (473 mL).

Generic formulation

MHRA/CHM advice to minimize risk when switching patients with epilepsy between different manufacturers’ products (including generic products):

  • Category 3: it is usually unnecessary to ensure that patients are maintained on a specific manufacturer’s product unless there are specific concerns, such as patient anxiety and risk of confusion/dosing error.

Indications

Epilepsy

Adjunctive therapy of focal seizures with and without secondary generalization.

Recommendations summarized from NICE (2012)

  • Seizure types—on referral to tertiary care (focal seizures), contraindicated (generalized tonic-clonic seizures, tonic/atonic seizures, absence seizures, myoclonic seizures).

  • Epilepsy types—on referral to tertiary care (benign epilepsy with centrotemporal spikes, panayiotopoulos syndrome, late-onset childhood occipital epilepsy), contraindicated (absence syndromes, idiopathic generalized epilepsy, juvenile myoclonic epilepsy, Dravet syndrome, Lennox–Gastaut syndrome).

Psychiatry

Generalized anxiety disorder.

Neurology

Peripheral and central neuropathic pain.

Dose titration

  • Epilepsy—adjunctive therapy: 25 mg bd for 7 days, to be increased by 50 mg every 7days; usual maintenance 300 mg daily, divided into 2 or 3 doses (max. 600 mg daily, divided into 2 or 3 doses).

  • Generalized anxiety disorder: 150 mg daily, divided into 2 or 3 doses, for 7 days, to be increased by 150 mg every 7 days (max. 600 mg daily, divided into 2 or 3 doses).

If stopping pregabalin, it is recommended to taper over at least 1 week to avoid abrupt withdrawal.

Plasma levels monitoring

Pregabalin pharmacokinetics are linear over the recommended daily dose range; inter-subject pharmacokinetic variability for pregabalin is low (<20%) and multiple dose pharmacokinetics are predictable from single-dose data. Therefore, there is no need for routine monitoring of plasma concentrations of pregabalin.

Cautions

  • Patients with conditions that may precipitate encephalopathy.

  • Patients with severe congestive heart failure.

Adverse effects

Pregabalin can be associated with adverse effects at the level of the nervous system and other systems (Table 11.1).

Table 11.1 Estimated frequency of adverse effects of pregabalin

Very common (>1 in 10 patients on pregabalin)

Nervous system

  • dizziness

  • drowsiness

  • headache

Other systems

Common (>1 in 100 patients on pregabalin)

Nervous system

  • amnesia

  • ataxia

  • blurred vision, visual field defects, and other visual disturbances

  • confusion

  • diplopia

  • euphoria

  • impaired attention

  • insomnia

  • irritability

  • paraesthesias

  • speech disorder

Other systems

  • appetite changes

  • constipation

  • dry mouth

  • flatulence

  • malaise

  • oedema

  • sexual dysfunction

  • vomiting

  • weight gain

Uncommon (>1 in 1000 patients on pregabalin)

Nervous system

  • abnormal dreams

  • agitation

  • cognitive impairment

  • depersonalization

  • depression

  • hallucinations

  • hyperacusis

  • panic attacks

  • stupor

  • syncope

  • taste disturbance

Other systems

  • abdominal distension

  • arthralgia

  • chills

  • dry eye

  • dyspnoea

  • dysuria

  • first-degree atrio-ventricular block

  • flushing

  • gastro-oesophageal reflux disease

  • hypersalivation

  • hypertension

  • hypotension

  • lacrimation

  • myalgia

  • nasal dryness

  • nasopharingitis

  • rash

  • sweating

  • tachycardia

  • thirst

  • thrombocytopenia

  • urinary incontinence

Rare (>1 in 10,000 patients on pregabalin)

Nervous system

  • dysphagia

  • parosmia

Other systems

  • arrhythmia

  • ascites

  • bradycardia

  • breast pain, hypertrophy, and discharge

  • cold extremities

  • cough

  • epistaxis

  • hyperglycaemia

  • hypokalaemia

  • leucopenia and neutropenia

  • menstrual disturbances

  • oliguria

  • pancreatitis

  • renal failure

  • rhabdomylisis

  • rhinitis

  • urticaria

  • weight loss

Very rare (<1 in 10,000 patients on pregabalin)

Nervous system

Other systems

Interactions

  • Since pregabalin is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans, does not inhibit drug metabolism in vitro, and is not bound to plasma proteins, it is unlikely to produce or be subject to pharmacokinetic interactions.

  • Pregabalin may potentiate the effects of lorazepam.

  • In the post-marketing experience, there are reports of respiratory failure and coma in patients taking pregabalin and other central nervous system depressant medicinal products. Pregabalin appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone.

With alcohol/food

  • There are no specific foods that must be excluded from diet when taking pregabalin.

  • Pregabalin may potentiate the effects of alcohol.

Special populations

Hepatic impairment

No dose adjustment is required for patients with hepatic impairment.

Renal impairment

Reduce maintenance dose according to degree of reduction in creatinine clearance.

Pregnancy

  • There is no adequate data from the use of pregabalin in pregnant women. The potential risk for reproductive toxicity in humans is unknown. Pregabalin should not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus.

  • Pregabalin is excreted into human milk. The effect of pregabalin on newborns/infants is unknown. A case-by-case decision must be made whether to discontinue breast-feeding or to discontinue pregabalin therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Behavioural and cognitive effects in patients with epilepsy

Pregalin is characterized by a good behavioural profile. This AED does not appear to have significant negative effects on mood or behaviour in patients with epilepsy, although depression has been reported in some patients (dose-dependent effects of mild-to-moderate intensity). A potential abuse or misuse of pregabalin has also been reported, with implications in terms of dependence and withdrawal. Pregabalin is also associated with limited negative cognitive effects, mainly related to sedation, decreased arousal, decreased attention and concentration (dose-dependent effects of mild-to-moderate intensity).

Psychiatric use

Pregabalin has an approved indication and is widely used for the treatment of generalized anxiety disorder. Several randomized, double-blind, placebo-controlled trials found that pregabalin is an effective treatment for patients with generalized anxiety disorder and social anxiety disorder. Possible implications in the treatment of mood disorders and benzodiazepines dependence are emerging. Moreover, pregabalin may be a therapeutic agent for the treatment of alcohol abuse, in both withdrawal phase and relapse prevention (Fig. 11.3).

Fig. 11.3 Level of evidence supporting the psychiatric use of pregabalin in patients with behavioural symptoms

Fig. 11.3 Level of evidence supporting the psychiatric use of pregabalin in patients with behavioural symptoms

Overall rating

Pregabalin is characterized by few antiepileptic indications, with a very good interaction profile in polytherapy; it has a very good behavioural tolerability profile and a wide range of psychiatric uses (Table 11.2).

Table 11.2 Overall rating of pregabalin

Antiepileptic indications

Interactions in polytherapy

☺☺☺

Behavioural tolerability

☺☺☺

Psychiatric use

☺☺☺

Key: ☺☺☺ = very good; ☺☺ = good; ☺ = acceptable.