Pregabalin


Article Author:
Aaron Cross


Article Editor:
Andrew Sherman


Editors In Chief:
Jeff Thompson


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
5/10/2019 8:22:33 PM

Indications

Pregabalin is approved by the United States Food and Drug Administration (FDA) for the treatment of neuropathic pain associated with diabetic peripheral neuropathy, spinal cord injury and postherpetic neuralgia. Pregabalin is FDA-approved for the treatment of fibromyalgia. Pregabalin is also FDA approved as an adjunctive therapy for partial onset seizures in adults with epilepsy. Off-label uses include generalized anxiety disorder, social anxiety disorder, bipolar disorder, insomnia and chronic pain conditions not otherwise approved by the FDA. There is significant disagreement regarding the effectiveness of pregabalin for the psychiatric disorders listed above.[1][2][3][4]

Mechanism of Action

Pregabalin is structurally similar to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). It has been modified to be a lipophilic analog to enhance diffusion across the blood-brain barrier. However, pregabalin does not directly bind to GABA-A or GABA-B receptors. In addition, it is not metabolized to a GABA receptor agonist. In animal models, pregabalin binds to presynaptic voltage-gated calcium channels at the alpha-2-delta subunit in central nervous system tissues. Binding of the alpha-2-delta subunit decreases the depolarization-induced influx of calcium into neurons and thus reduces the release of excitatory neurotransmitters. This action may account for the anticonvulsant and analgesic effects of pregabalin. Pregabalin has no known activity at sodium channels, dopamine receptors, serotonin receptors, opiate receptors and does not modify the activity of cyclooxygenase.

Administration

Pregabalin is administered orally and is available in capsules or oral solution. Following oral administration, pregabalin reaches peak plasma concentrations within 1.5 hours and achieves steady state within 24 to 48 hours. The absorption of pregabalin is independent of the dose. Pregabalin readily crosses the blood-brain barrier. Humans cannot significantly metabolize pregabalin. It is primarily eliminated as an unchanged drug (less than 2% metabolized) by renal excretion. In patients with normal renal function, the mean elimination half-life is 6.3 hours. Pregabalin has been studied at dosages up to 600 mg/day. However, 600 mg/day was not found to provide significant additional benefit and was less well tolerated due to side effects.

When discontinuing pregabalin, it is recommended to gradually taper the drug over one week. In patients with seizure disorders, withdraw pregabalin gradually to minimize the risk of increased seizure.

  • Management of Neuropathic Pain Associated with Diabetic Peripheral Neuropathy: The recommended maximum therapeutic dose is 300 mg/day. The suggested starting dose is 50 mg three times per day. The dose can be increased up to 300 mg/day within 1 week of starting treatment.
  • Management of Neuropathic Pain Associated with Spinal Cord Injury: The recommended therapeutic dose is 150 mg to 600 mg per day. The recommended starting dose is 75 mg twice per day. The dose may be increased to 150 mg twice per day within 1 week of initiating treatment. Patients with suboptimal pain relief following 2 to 3 weeks of treatment with 150 mg twice a day may be increased up to 300 mg twice per day. In spinal cord injury, improvement in pain can be seen as early as 1 week after initiating treatment. However, to evaluate the efficacy of pregabalin, it is recommended to try the medication for 4 to 6 weeks, if tolerated by the patient.
  • Management of Postherpetic Neuralgia: The recommended therapeutic dose is 150 mg to 300 mg per day, divided into twice per day or three times per dosing. The recommended starting dose is 75 mg two times per day or 50 mg three times per day. The dose can be increased up to 300 mg per day within 1 week of starting treatment. Patients with suboptimal pain relief after 2 to 4 weeks of treatment with 300 mg per day can be increased to 600 mg per day divided into twice per day or three times per dosing.  
  • Management of Fibromyalgia: The recommended therapeutic dose is 300 mg to 450 mg per day. The recommended starting dose is 150 mg/day divided into twice per day dosing. The dose can be increased to 300 mg per day within one week of starting treatment. Patients with suboptimal pain relief on 300 mg per day may be further increased to 450 mg per day divided into twice per day dosing.
  • Adjunctive Therapy for Adults with Partial Onset Seizures: Pregabalin is FDA-approved only as an adjunctive for the treatment of partial-onset seizures. The effective dose is 150 mg to 600 mg per day, divided into twice per day or three times per dosing. The suggested starting dose is no greater than 150 mg per day. The total dose can be increased to a maximum of 600 mg per day.  
  • Dosing Modifications: Pregabalin is eliminated primarily by renal excretion. Adjust the dose in patients with impaired renal function. Refer to prescription drug manufacturer information for further recommendations on dose reductions for patients with reduced creatinine clearance and those undergoing hemodialysis (http://labeling.pfizer.com/ShowLabeling.aspx?id=561). Although not specifically studied, because pregabalin is not protein bound, it is unlikely that patients with hepatic impairment require dosing modifications.

Adverse Effects

The majority of reported adverse effects caused by pregabalin were of mild to moderate intensity, dose-dependent, and occurred within the first 2 weeks of initiating treatment. The most common adverse events were those affecting the central nervous system (CNS). Somnolence and dizziness occurred most frequently and were the most common adverse reactions that lead to discontinuation of pregabalin. The most common adverse reactions reported across all patient populations in premarketing controlled trials which occurred in greater than or equal to 5% of patients taking pregabalin and twice the rate reported by patients taking placebo were: somnolence, dizziness, blurred vision, difficulty with concentration/attention, dry mouth, edema and weight gain.[5][6][7]

Weight gain associated with pregabalin is dose-dependent and occurred in up to 14% of patients receiving 600 mg per day.

Following rapid or abrupt discontinuation of pregabalin, some patients reported symptoms including insomnia, nausea, headache, anxiety, nervousness, irritability, hyperhidrosis, and diarrhea.

Contraindications

Pregabalin is contraindicated in patients who have a known hypersensitivity to pregabalin. Hypersensitivity reactions have occurred in patients receiving pregabalin, including angioedema. There are no adequate studies with pregabalin in pregnant women. Pregabalin may cause fetal harm. Advise patients there is a potential risk to the fetus.

Pregabalin has been detected in the milk of lactating women thus breastfeeding is not recommended.

Monitoring

Antiepileptic drugs such as pregabalin may increase the risk of suicidal thoughts or behavior. Monitor patients being treated with pregabalin for symptoms of new or worsening depression, suicidal ideation or behavior, and other changes in behavior or mood.

Toxicity

There is limited information regarding overdose with pregabalin. The highest known accidental overdose of pregabalin during clinical development was 8000 mg, and this was without significant clinical consequences. There is no specific antidote for overdose with pregabalin.

Enhancing Healthcare Team Outcomes

Pregabalin is a widely used medication for the management of seizures and pain disorders. While the drug is relatively safe, the priamry care provider, pharmacist, nurse practitoner and internist must monitor the patient regularly. The drug is known to cause depression and suicidal thoughts, so a mental assessment is recommended at each visit. Patients should be educated about the other side effects and told not to drive when taking the drug or combine it with other anti-seizure medications or alcohol. The neurologist should be consulted before making a change in the dose.[8] (level II)


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Pregabalin - Questions

Take a quiz of the questions on this article.

Take Quiz
Pregabalin has demonstrated efficacy in the treatment of which of the following disorders?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient who is on pregabalin is least likely to experience which of the following?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
For which of the following is pregabalin effective but not approved by the FDA?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is an antidote for overdose with pregabalin?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Pregabalin - References

References

Abou-Khalil BW, Update on Antiepileptic Drugs 2019. Continuum (Minneapolis, Minn.). 2019 Apr;     [PubMed]
Goodman CW,Brett AS, A Clinical Overview of Off-label Use of Gabapentinoid Drugs. JAMA internal medicine. 2019 Mar 25;     [PubMed]
Parikh SK,Silberstein SD, Current Status of Antiepileptic Drugs as Preventive Migraine Therapy. Current treatment options in neurology. 2019 Mar 18;     [PubMed]
Bendtsen L,Zakrzewska JM,Abbott J,Braschinsky M,Di Stefano G,Donnet A,Eide PK,Leal PRL,Maarbjerg S,May A,Nurmikko T,Obermann M,Jensen TS,Cruccu G, European Academy of Neurology guideline on trigeminal neuralgia. European journal of neurology. 2019 Mar 12;     [PubMed]
Preuss CV,Kalava A,King KC, Prescription of Controlled Substances: Benefits and Risks 2019 Jan;     [PubMed]
Derry S,Bell RF,Straube S,Wiffen PJ,Aldington D,Moore RA, Pregabalin for neuropathic pain in adults. The Cochrane database of systematic reviews. 2019 Jan 23;     [PubMed]
Drugs for chronic insomnia. The Medical letter on drugs and therapeutics. 2018 Dec 17;     [PubMed]
Bidari A,Moazen-Zadeh E,Ghavidel-Parsa B,Rahmani S,Hosseini S,Hassankhani A, Comparing duloxetine and pregabalin for treatment of pain and depression in women with fibromyalgia: an open-label randomized clinical trial. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences. 2019 Mar 14;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of PA-Psychiatry. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for PA-Psychiatry, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in PA-Psychiatry, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of PA-Psychiatry. When it is time for the PA-Psychiatry board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study PA-Psychiatry.