Lyrica (pregabalin)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Pregabalin is an anticonvulsant structurally related to the inhibitory CNS neurotransmitter gamma-aminobutyric acid (GABA); the drug also possesses analgesic activity.
Pregabalin is an anticonvulsant that is structurally related to the inhibitory CNS neurotransmitter gamma-aminobutyric acid (GABA). Pregabalin also has demonstrated analgesic activity. Although pregabalin was developed as a structural analog of GABA, the drug does not bind directly to GABAA, GABAB, or benzodiazepine receptors; does not augment GABAA responses in cultured neurons; and does not alter brain concentrations of GABA in rats or affect GABA uptake or degradation.
However, in cultured neurons, prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport.
Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in CNS tissues. Although the exact mechanism of action of pregabalin has not been elucidated, binding to the alpha2-delta subunit may be involved in pregabalin's analgesic and anticonvulsant effects. In vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, including glutamate, norepinephrine, calcitonin gene-related peptide, and substance P, possibly by modulation of calcium channel function.
Pregabalin is well absorbed following oral administration and exhibits linear pharmacokinetics; peak plasma concentrations are attained within 1.5 or 12 hours with conventional or extended-release preparations, respectively. Steady-state concentrations are achieved within 24-48 hours following repeated administration of conventional pregabalin and within 48-72 hours following repeated administration of the extended-release tablets. In pediatric patients receiving conventional pregabalin, peak plasma concentrations of the drug are achieved within 0.5-2 hours in the fasted state.
The oral bioavailability of pregabalin (administered as the conventional preparation) is at least 90% and is independent of dose. Bioavailability of the extended-release tablets administered once daily following an evening meal is equivalent to that of comparable doses of the conventional preparation administered without food twice daily. Administration of conventional preparations of pregabalin with food has been shown to delay the time to peak concentration and decrease peak plasma concentrations of the drug by approximately 25-30%, but does not affect the extent of absorption.
Administration of the extended-release tablets in the fasted state reduces systemic exposure of pregabalin by approximately 30% compared with administration following an evening meal. Pregabalin is not appreciably metabolized. Following administration of a single radiolabeled dose of pregabalin, approximately 90% of the administered dose was recovered in urine as unchanged drug.
Clearance of pregabalin is nearly proportional to creatinine clearance in both adults and pediatric patients. In pediatric patients, the weight-normalized clearance of pregabalin is approximately 40% higher in those weighing less than 30 kg. (See Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions.) The mean elimination half-life of pregabalin is 6.3 hours in adults with normal renal function, 3-4 hours in children up to 6 years of age, and 4-6 hours in children 7 years of age or older.
USES: This medication is used to treat pain caused by nerve damage due to diabetes, shingles (herpes zoster) infection, or spinal cord injury. This medication is also used to treat pain in people with fibromyalgia. Pregabalin is also used to treat certain types of seizures (focal seizures).
Generic name: pregabalin
Pronunciation: (pree-GAH-ba-lin)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Lyrica
Indications
The following indications are listed for Lyrica:
- Diabetic Peripheral Neuropathy
- Fibromyalgia
- Neuropathic Pain Associated With Spinal Cord Injury
- Partial Epilepsy Treatment Adjunct
- Postherpetic Neuralgia
Also known as: Diabetic Neuropathy, Fibromyalgia Syndrome, Partial Onset Seizures Treatment Adjunct, Partial Seizures Treatment Adjunct, Post Herpetic Neuralgia, Postherpetic Neurodynia, Spinal Cord Injury Related Neuropathic Pain.
Dosing
No dosing information is available for this tab.
Pregabalin is administered orally as conventional (immediate-release) capsules or oral solution. The drug also is available as extended-release tablets for the treatment of postherpetic neuralgia (PHN) or diabetic peripheral neuropathy (DPN) in adults; efficacy of this preparation has not been established for other indications. Pregabalin capsules and oral solution are administered orally without regard to food; the extended-release tablets should be administered once daily after the evening meal. The extended-release tablets should be swallowed whole and not split, crushed, or chewed.
When switching from conventional preparations of pregabalin to the extended-release tablets, patients should take their usual morning dose of conventional capsules or oral solution, and initiate therapy with the extended-release tablets after the evening meal. The appropriate dose conversion should be performed according to the table below (see Table 1).
Table 1. Dose Conversion from Conventional to Extended-release Pregabalin
Conventional Pregabalin Total Daily Extended-release Pregabalin Dose Dose 75 mg daily (given 2 or 3 times 82.5 mg once daily daily) 150 mg daily (given 2 or 3 times 165 mg once daily daily) 225 mg daily (given 2 or 3 times 247.5 mg once daily daily) 300 mg daily (given 2 or 3 times 330 mg once daily daily) 450 mg daily (given 2 or 3 times 495 mg once daily daily) 600 mg daily (given 2 or 3 times 660 mg once daily daily)
When discontinuing therapy, pregabalin should be withdrawn gradually by tapering the dosage over at least 1 week. (See Discontinuance of Therapy under Cautions: Warnings/Precautions.)
Patients currently receiving or beginning therapy with pregabalin and/or any other anticonvulsant for any indication should be closely monitored for the emergence or worsening of depression, suicidal thoughts or behavior (suicidality), and/or any unusual changes in mood or behavior. (See Suicidality Risk under Cautions: Warnings/Precautions.)
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Specific drug interaction studies conducted with pregabalin extended-release tablets are limited; the information presented below is derived principally from studies with conventional preparations of pregabalin. Similar pharmacokinetic interactions are expected with the various preparations of pregabalin.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Known hypersensitivity to pregabalin or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects in adults receiving conventional pregabalin preparations across indications in clinical trials (occurring in 5% or more of patients and more frequently than placebo) include dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and abnormal thinking (primarily difficulty with concentration/attention). The most common adverse effects in pediatric patients receiving conventional pregabalin for the treatment of partial seizures (occurring in 5% or more of patients and more frequently than placebo) include somnolence, weight gain, and increased appetite.
The most common adverse effects in adults receiving extended-release pregabalin in clinical studies include dizziness, somnolence, headache, fatigue, peripheral edema, nausea, blurred vision, dry mouth, and weight gain.
Other adverse effects commonly reported in adults receiving conventional pregabalin in combination with other anticonvulsant agents in the management of partial seizures include ataxia, tremor, amnesia, speech disorder, increased appetite, peripheral edema, diplopia, and accidental injury.
Other adverse effects commonly reported in adults receiving conventional pregabalin for the management of PHN include headache, ataxia, constipation, peripheral edema, infection, and pain.
Other adverse effects commonly reported in adults receiving conventional pregabalin for the management of DPN include asthenia and peripheral edema.
Other adverse effects commonly reported in adults receiving conventional pregabalin for the management of fibromyalgia include headache, euphoric mood, attention disturbance, balance disorder, constipation, fatigue, peripheral edema, increased appetite, and sinusitis.
Other adverse effects commonly reported in adults receiving conventional pregabalin for the management of neuropathic pain associated with spinal cord injury include fatigue, peripheral edema, constipation, nasopharyngitis, and muscle weakness.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of pregabalin conventional preparations for adjunctive treatment of partial seizures have not been established in children younger than 1 month of age. Use of conventional pregabalin in older children is supported by evidence from 2 randomized placebo-controlled studies. (See Uses: Seizure Disorders.) Although the youngest patient evaluated in these studies was 3 months of age, use of pregabalin in infants 1-3 months of age can be supported by additional pharmacokinetic data.
Clearance of pregabalin (normalized for body weight) is approximately 40% higher in patients weighing less than 30 kg. For children weighing less than 30 kg, a dosage increase is required to achieve comparable exposure to those weighing 30 kg or more.
Safety and efficacy of pregabalin for the treatment of fibromyalgia, diabetic peripheral neuropathy (DPN), postherpetic neuralgia (PHN), or neuropathic pain associated with spinal cord injury have not been established in pediatric patients.
Safety and efficacy of pregabalin extended-release tablets have not been established in pediatric patients.
Women who are pregnant while receiving pregabalin should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry at 888-233-2334 (for patients); registry information also is available on the website https://www.aedpregnancyregistry.org/.
There are no adequate and well-controlled studies of pregabalin in pregnant women; however, based on animal studies, pregabalin may cause fetal harm. In animal reproductive studies, pregabalin produced developmental toxicity (e.g., fetal structural abnormalities, skeletal malformations, retarded ossification, decreased fetal body weight) when administered orally to pregnant animals during the period of organogenesis at exposure levels 16 times higher than those associated with the maximum recommended human dosage of 600 mg daily. When pregabalin was administered to female rats throughout the period of gestation and lactation, growth retardation, impairment to the nervous and reproductive systems, and decreased survival were observed in the offspring.
Pregabalin is distributed into human milk at steady-state concentrations approximately 76% of those in maternal plasma. Following administration of maternal dosages of 300 mg daily, the estimated average infant dose of pregabalin from breast milk is 0.31 mg/kg daily (approximately 7% of the maternal dose). Because of the potential for tumorigenicity (see Carcinogenicity under Cautions: Warnings/Precautions), breastfeeding is not recommended during pregabalin therapy.
The manufacturer states that no substantial differences in safety and efficacy have been observed in geriatric patients relative to younger adults; however, increased sensitivity to pregabalin in certain individuals cannot be ruled out. In controlled clinical studies of patients with fibromyalgia, neurological adverse reactions including dizziness, blurred vision, balance disorder, tremor, confusional state, abnormal coordination, and lethargy occurred more frequently in patients 65 years of age and older than in younger adults. In addition, FDA warns that geriatric patients receiving gabapentinoids are at increased risk of potentially serious, life-threatening, or fatal respiratory depression; pregabalin therapy should be initiated at the lowest dosage and titrated carefully with close monitoring in such patients.
It should be considered that pregabalin is substantially excreted by the kidneys, and the risk of adverse reactions to the drug may be increased in patients with impaired renal function. The dosage should be adjusted for geriatric patients with renal impairment. Monitoring renal function in geriatric patients may be helpful. (See Dosage and Administration: Special Populations.)
ICD codes
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Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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