GABAPENTIN

brands

Class

• Neuroscience-based Nomenclature: glutamate, voltage-gated calcium channel blocker (Glu-CB)
• Anticonvulsant, antineuralgic for chronic pain, alpha 2 delta ligand at voltage- sensitive calcium channels

GABAPENTIN commonly prescribed for

(Bold for FDA approved)

How GABAPENTIN works

• Gabapentin is a leucine analog and is transported both into the blood from the gut and also across the blood–brain barrier into the brain from the blood by the system L transport system

• Binds to the alpha 2 delta subunit of voltage-sensitive calcium channels

• This closes N and P/Q presynaptic calcium channels, diminishing excessive neuronal activity and neurotransmitter release

• Although structurally related to gamma- aminobutyric acid (GABA), no known direct actions on GABA or its receptors

How long until GABAPENTIN works

• Should reduce seizures by 2 weeks

• Should also reduce pain in postherpetic neuralgia by 2 weeks; some patients respond earlier

• May reduce pain in other neuropathic pain syndromes within a few weeks

• If it is not reducing pain within 6–8 weeks, it may require a dosage increase or it may not work at all

• May reduce anxiety in a variety of disorders within a few weeks

• Not yet clear if it has mood-stabilizing effects in bipolar disorder or antineuralgic actions in chronic neuropathic pain, but some patients may respond and if so, would be expected to show clinical effects starting by 2 weeks although it may take several weeks to months to optimize

Notable Side Effects

• Sedation (dose-dependent), dizziness

• Ataxia (dose-dependent), fatigue, nystagmus, tremor

• Peripheral edema

• Blurred vision

• Vomiting, dyspepsia, diarrhea, dry mouth, constipation, weight gain

• Additional effects in children under age 12: hostility, emotional lability, hyperkinesia, thought disorder, weight gain

Life Threatening Side Effects

• Anaphylaxis and angioedema

• Sudden unexplained deaths have occurred in epilepsy (unknown if related to gabapentin use)

• Rare activation of suicidal ideation and behavior (suicidality)

weight gain

not usual

sedation

common

What to do about GABAPENTIN side effects

• Wait

• Wait

• Wait

• Take more of the dose at night to reduce daytime sedation

• Lower the dose

• Switch to another agent

usual dosage range

• 900–1800 mg/day in 3 divided doses (immediate-release)

Dosage Forms

• Capsule 100 mg, 300 mg, 400 mg

• Tablet 100 mg, 300 mg, 400 mg, 600 mg, 800 mg

• Tablet extended-release 300 mg, 600 mg

• Liquid 250 mg/5 mL – 470 mL bottle

long term use

• Safe

habit forming

• No

Renal Impairment

• Gabapentin is renally excreted, so the dose may need to be lowered

• Can be removed by hemodialysis; patients receiving hemodialysis may require supplemental doses of gabapentin

• Use in renal impairment has not been studied in children under age 12

Hepatic Impairment

• No available data but not metabolized by the liver and clinical experience suggests normal dosing

Cardiac Impairment

• No specific recommendations

Elderly

• Some patients may tolerate lower doses better

• Elderly patients may be more susceptible to adverse effects, including peripheral edema and ataxia

Children and Adolescents

• Approved for use starting at age 3 as adjunct treatment for partial seizures

• Ages 5–12: initial 10–15 mg/kg per day in 3 doses; titrate over 3 days to 25–35 mg/kg per day given in 3 doses; maximum dose generally 50 mg/kg per day; time between any 2 doses should usually not exceed 12 hours

• Ages 3–4: initial 10–15 mg/kg per day in 3 doses; titrate over 3 days to 40 mg/kg per day; maximum dose generally 50 mg/kg per day; time between any 2 doses should usually not exceed 12 hours

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• In animal studies, gabapentin was developmentally toxic (increased fetal skeletal and visceral abnormalities, and increased embryofetal mortality) when administered to pregnant animals at doses similar to or lower than those used clinically

• Use in women of childbearing potential requires weighing potential benefits to the mother against the risks to the fetus

• Taper drug if discontinuing

• Seizures, even mild seizures, may cause harm to the embryo/fetus

• Lack of convincing efficacy for treatment of bipolar disorder or psychosis suggests risk/benefit ratio is in favor of discontinuing gabapentin during pregnancy for these indications

• For bipolar patients, given the risk of relapse in the postpartum period, moodstabilizer treatment, especially with agents with better evidence of efficacy than gabapentin, should generally be restarted immediately after delivery if patient is unmedicated during pregnancy

• Atypical antipsychotics may be preferable to gabapentin if treatment of bipolar disorder is required during pregnancy

• Bipolar symptoms may recur or worsen during pregnancy and some form of treatment may be necessary

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended either to discontinue drug or bottle feed

• If drug is continued while breast feeding, infant should be monitored for possible adverse effects

• If infant becomes irritable or sedated, breast feeding or drug may need to be discontinued

• Bipolar disorder may recur during the postpartum period, particularly if there is a history of prior postpartum episodes of either depression or psychosis

• Relapse rates may be lower in women who receive prophylactic treatment for postpartum episodes of bipolar disorder

• Atypical antipsychotics and anticonvulsants such as valproate may be safer and more effective than gabapentin during the postpartum period when treating a nursing mother with bipolar disorder