PREGABALIN

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

PREGABALIN commonly prescribed for

(Bold for FDA approved)

How PREGABALIN works

• Pregabalin is a leucine analog and is transported both into the blood from the gut and also across the blood–brain barrier into the brain by the system L transport system (a sodium-independent transporter) as well as by additional sodium-dependent amino acid transporter systems

• 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 PREGABALIN works

• Can reduce neuropathic pain and anxiety within a week

• Should reduce seizures by 2 weeks

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

Notable Side Effects

• Sedation, dizziness

• Ataxia, fatigue, tremor, dysarthria, paresthesia, memory impairment, coordination abnormal, impaired attention, confusion, euphoric mood, irritability

• Vomiting, dry mouth, constipation, weight gain, increased appetite, flatulence

• Blurred vision, diplopia

• Peripheral edema

• Libido decreased, erectile dysfunction

Life Threatening Side Effects

• Rare activation of suicidal ideation and behavior (suicidality)

weight gain

not usual

sedation

common

What to do about PREGABALIN 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

• IR: 150–600 mg/day in 2–3 doses

• CR: 330 mg once per day

Dosage Forms

• Capsule 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg

• Oral solution 20 mg/mL

• Extended-release tablet 82.5 mg, 165 mg, 330 mg

long term use

• Safe

habit forming

• No

Renal Impairment

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

• Dosing can be adjusted according to creatinine clearance, such that patients with clearance below 15 mL/minute should receive 25–75 mg/day in one dose, patients with clearance between 15–29 mL/minute should receive 25–150 mg/day in 1–2 doses, and patients with clearance between 30–59 mL/minute should receive 75–300 mg/day in 2–3 doses

• Starting dose should be at the bottom of the range; titrate as usual up to maximum dose

• Can be removed by hemodialysis; patients receiving hemodialysis may require a supplemental dose of pregabalin following hemodialysis (25–100 mg)

Hepatic Impairment

• Dose adjustment not necessary

Cardiac Impairment

• No specific recommendations

Elderly

• Some patients may tolerate lower doses better

• Elderly patients may be more susceptible to adverse effects

Children and Adolescents

• Approved for partial-onset seizures in children ages 1 month and older

• Safety and efficacy have not been established in mental illness indications

• Use should be reserved for the expert

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, developmental toxicity (including fetal structural abnormalities, skeletal malformations, retarded ossification, and decreased fetal body weight) was observed when pregabalin was administered to pregnant animals at doses greater than or equal to 16 times the maximum recommended human dose

• 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

Breast Feeding

• Unknown if pregabalin is secreted in human breast milk, but all psychotropics are assumed to be secreted in 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