Lyrica

Lyrica Capsule, Capsule*, Oral Capsule, Oral Solution, Oral Tablet, Extended Release

Lyrica binds presynaptically to the alpha-2-delta subunit of the voltage-gated calcium channels in central nervous system tissues located in the brain and spinal cord. The mechanism of action has not been fully elucidated but studies suggest that pregabalin produces a disruption of calcium channel traficking or a reduction of calcium currents. The inhibition of subunits of voltage-gated calcium channels reduces calcium release which in order inhibits the release of several neurotransmitters. Studies also suggest that the descending noradrenergic and serotonergic pathways originating from the brainstem may be involved with the mechanism of pregabalin. Interestingly, although pregabalin is a structural derivative of inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors.

Although the structure of pregabalin is similar to gamma-aminobutyric acid (GABA), it does not bind to GABA receptors. Instead, it binds the alpha2-delta subunit of presynaptic voltage-gated calcium channels in the central nervous system. Lyrica does not modulate dopamine receptors, serotonin receptors, opiate receptors, sodium channels or cyclooxygenase activity.

Although the structure of pregabalin is similar to gamma-aminobutyric acid (GABA), it does not bind to GABA receptors. Instead, it binds the alpha2-delta subunit of presynaptic voltage-gated calcium channels in the central nervous system. Lyrica does not modulate dopamine receptors, serotonin receptors, opiate receptors, sodium channels or cyclooxygenase activity.

Uses

Lyrica is used for the management of neuropathic pain associated with diabetic peripheral neuropathy and management of post-herpetic neuralgia. It is also used for the adjunctive therapy for adult patients with partial onset seizures. It can be used for the management of fibromyalgia and neuropathic pain associated with spinal cord injury.

Lyrica is also used to associated treatment for these conditions: Diabetic Peripheral Neuropathic Pain (DPN), Epilepsies, Fibromyalgia, Generalized Anxiety Disorder (GAD), Neuropathic Pain, Partial-Onset Seizures, Peripheral Neuropathic Pain, Peripheral neuropathy, Postherpetic Neuralgia

How Lyrica works

Although the mechanism of action has not been fully elucidated, studies involving structurally related drugs suggest that presynaptic binding of pregabalin to voltage-gated calcium channels is key to the antiseizure and antinociceptive effects observed in animal models.

By binding presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system, pregabalin modulates the release of several excitatory neurotransmitters including glutamate, substance-P, norepinephrine, and calcitonin gene related peptide. In addition, pregabalin prevents the alpha2-delta subunit from being trafficked from the dorsal root ganglia to the spinal dorsal horn, which may also contribute to the mechanism of action.

Although pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors.

Lyrica

Trade Name Lyrica
Availability Prescription only
Generic Pregabalin
Pregabalin Other Names 3-Isobutyl GABA, Pregabalin, Pregabalina
Related Drugs gabapentin, prednisone, duloxetine, clonazepam, amitriptyline, lamotrigine, Cymbalta, Lyrica, topiramate, methylprednisolone
Weight 75mg, 150mg, 300mg, , 25mg, 50mg, 100mg, 200mg, 225mg, 20mg/ml, 165mg, 330mg, 82.5mg
Type Capsule, Capsule*, Oral Capsule, Oral Solution, Oral Tablet, Extended Release
Formula C8H17NO2
Weight Average: 159.2261
Monoisotopic: 159.125928793
Protein binding

Pregabalin is not plasma protein bound.

Groups Approved, Investigational
Therapeutic Class Adjunct anti-epileptic drugs
Manufacturer Pfizer Ltd, Pfizer Laboratories Ltd, , Upjohn Uk Limited, Pfizer Saudi Limited, Pfzer Indonesia, Pfizer Manufacturing Deutschland Gmbh
Available Country India, Pakistan, United Kingdom, Canada, Australia, Saudi Arabia, United States, Italy, Netherlands, Portugal, Spain, Switzerland, Indonesia, Germany, Nigeria,
Last Updated: June 7, 2022 at 8:52 pm

Structure

Lyrica
Pregabalin Structure

Dosage

Lyrica dosage

Neuropathic pain associated with diabetic peripheral neuropathy: The maximum recommended dose of Lyrica is 100 mg three times a day (300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Dosing should begin at 50 mg three times a day (150 mg/day) and may be increased to 300 mg/day within 1 week based on efficacy and tolerability.

Post-herpetic neuralgia: The recommended dose of Lyrica is 75 to 150 mg two times a day, or 50 to 100 mg three times a day (150 to 300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Dosing should begin at 75 mg two times a day, or 50 mg three times a day (150 mg/day) and may be increased to 300 mg/day within 1 week based on efficacy and tolerability.

Adjunctive therapy for adult patients with partial onset seizures: Lyrica at doses of 150 to 600 mg/day has been shown to be effective as adjunctive therapy in the treatment of partial onset seizures in adults. The total daily doseshould be divided and given either two or three times daily. In general, it is recommended that patients be started on a total daily dose no greater than 150 mg/day (75 mg two times a day, or 50 mg three times a day). Based on individual patient response and tolerability, the dose may be increased to a maximum dose of 600 mg/day.

Management of Fibromyalgia: The recommended dose of Lyrica for fibromyalgia is 300 to 450 mg/day. Dosing should begin at 75 mg two times a day (150 mg/day) and may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient benefit with 300 mg/day may be further increased to 225 mg two times a day (450 mg/day). 

Neuropathic pain associated with spinal cord injury: The recommended dose range is 150 to 600 mg/day. The recommended starting dose is 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability.

.Patients who do not experience sufficient pain relief after treatment with 300 mg/day and who tolerate pregabalin may be treated with up to 300 mg two times a day. Neurolin® capsules can be taken without regards to meals.

Side Effects

The most common side effects include dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and abnormal thinking.

Toxicity

In a systematic review that included 38 randomized controlled trials, there were 20 identified adverse effects that were significantly associated with pregabalin, most of which involve the central nervous system and cognition. The identified adverse effects include vertigo, dizziness, balance disorder, incoordination, ataxia, blurred vision, diplopia, amblyopia, somnolence, confusional state, tremor, disturbance in attention, abnormal thinking, asthenia, fatigue, euphoria, edema, peripheral edema, dry mouth, and constipation .

The most common symptoms of pregabalin toxicity (dose range includes 800 mg/day and single doses up to 11,500 mg) include somnolence, confusion, restlessness, agitation, depression, affective disorder and seizures.

Since there is no antidote for pregabalin overdose, patients should receive general supportive care. If appropriate, gastric lavage or emesis may help eliminate unabsorbed pregabalin (healthcare providers should take standard precautions to maintain the airway).

Lyrica pharmacokinetic properties suggest that extra-corporeal elimination methods including haemodialysis, may be useful in situations of severe toxicity. However, there are cases where patients have presented with very high serum levels of pregabalin and have been successfully managed with supportive care alone.

Precaution

Discontinuation of Lyrica without tapering may produce insomnia, nausea, headache and diarrhea. So it should be tapered gradually over a minimum of 1 week rather than discontinued abruptly. Creatinine kinase may be elevated if treated with Lyrica. It should be discontinued rapidly if myopathy is diagnosed or suspected or if creatinine kinase is elevated markedly.

Food Interaction

  • Avoid alcohol. Alcohol may increase CNS effects.
  • Take with or without food. Food alters drug absorption, but not to a clinically significant extent.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Lyrica Drug Interaction

Major: acetaminophen / hydrocodone

Moderate: diphenhydramine, duloxetine, alprazolam, cetirizine

Unknown: aspirin, aspirin, celecoxib, apixaban, omega-3 polyunsaturated fatty acids, metoprolol, metoprolol, acetaminophen, budesonide / formoterol, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, ergocalciferol, cholecalciferol

Lyrica Disease Interaction

Major: drug dependence

Moderate: suicidal tendency, angioedema, creatine kinase elevations, peripheral edema, PR interval prolongation

Volume of Distribution

After oral administration of pregabalin, the reported apparent volume of distribution is roughly 0.5 L/kg.

Although pregabalin is not very lipophilic, it is able to cross the blood brain barrier(BBB). System L transporters facilitate the transport of large amino acids across the BBB and it has been confirmed that pregabalin is a substrate. This information suggests that system L transporters are responsible for pregabalin uptake into the BBB.

In rat models, pregabalin has been shown to cross the placenta.

Elimination Route

After oral dosing administered in the fasted state, pregabalin absorption is rapid, and extensive. Lyrica oral bioavailability is reported to be ≥90% regardless of the dose. Cmax is attained within 1.5 hours after single or multiple doses, and steady state is attained within 24-48 hours with repeated administration. Both Cmax and AUC appear to be dose proportional.

Food decreases the rate of pregabalin absorption and as a result, lowers the Cmax by an estimated 25-30% and increases the Tmax to approximately 3 hours. However, the effect of food does not appear to impact the total absorption of pregabalin in a way that is clinically relevant. As a result, pregabalin can be administered with or without food.

Half Life

The elimination half life of pregabalin is 6.3 hours.

Clearance

In young healthy subjects the mean renal clearance is estimated to be 67.0 to 80.9 mL mL/min. Given pregabalin's lack of plasma protein binding, this clearance rate suggests that renal tubular reabsorption is involved.

Elimination Route

Lyrica is almost exclusively eliminated in the urine.

Further, based on preclinical studies, pregabalin does not appear to undergo racemization to the R enantiomer in the body.

Pregnancy & Breastfeeding use

Pregnancy category C. So it should only used if potential benefit justifies the potential risks to the fetus.

Nursing mother: It is not known if pregabalin is excreted in human milk; it is, however, present in the milk of rats. So it should be used in nursing mother only if there is a clear benefit over the risk.

Contraindication

Lyrica is contraindicated in patients with known hypersensitivity to Lyrica or any of its components.

Special Warning

Use in children & adolescents: The safety and effectiveness of Lyrica have not been established in patients below the age of 18 years. 

Use in elderly (Over 65 years of age): No dosage adjustment is necessary in elderly patients. Overdose: In overdoses up to 15 g, no unexpected adverse effects were reported.

Paediatric use: The safety and efficacy of pregabalin in paediatric patients have not been established.

Storage Condition

Store at a cool & dry place, protected from light and moisture. Keep out of reach of the children.

Innovators Monograph

Lyrica contains Pregabalin see full prescribing information from innovator Lyrica Monograph, Lyrica MSDS, Lyrica FDA label

FAQ

What is Lyrica used for?

Lyrica is used to treat epilepsy and anxiety. It's also taken to treat nerve pain. Lyrica is an anticonvulsant and anxiolytic medication used to treat epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, and generalized anxiety disorder.

How safe is Lyrica?

Lyrica oral capsule is used for long-term treatment. It comes with serious risks if you don't take it as prescribed.

How does Lyrica work?

Lyrica works by decreasing the number of pain signals that are sent out by damaged nerves in the body.

What are the common side effects of Lyrica?

Common side effects of Lyrica are include:

  • dizziness
  • blurry vision
  • headache
  • nausea
  • weight gain
  • sleepiness
  • trouble concentrating
  • swelling of hands and feet
  • dry mouth

Can I take Lyrica while pregnant?

Lyrica is not generally recommended in pregnancy. There's no firm evidence that it's harmful to an unborn baby, but for safety pregnant women are usually advised to take it only if the benefits of the medicine outweigh the potential harm.

Is Lyrica safe during breastfeeding?

No adverse effects have been attributed to infant exposure to Lyrica through the breast milk. If Lyrica is used by a breastfeeding mother, monitor the infant for gastrointestinal adverse effects, appetite changes, adequate weight gain, drowsiness and normal developmental milestones.

Can I drink alcohol with Lyrica?

This study provides initial evidence that the anticonvulsant Lyrica is safe if used in conjunction with alcohol consumption in alcoholic individuals.

How quickly does Lyrica work for anxiety?

It can take a little time for Lyrica to start helping with anxiety. In most clinical trials, researchers saw people getting relief from the symptoms of anxiety by week four of taking Lyrica.

How should I take Lyrica?

Take the medicine at the same time each day, with or without food.Swallow an extended-release tablet whole and do not crush, chew, or break it.

What happen If I stop taking Lyrica?

Do not stop using Lyrica suddenly, even if you feel fine. Stopping suddenly may cause increased seizures or unpleasant withdrawal symptoms. Follow your doctor's instructions about tapering your dose for at least 1 week before stopping completely.

How good is Lyrica for nerve pain?

Lyrica has an average rating of 5.9 out of 10 from a total of 286 ratings for the treatment of Neuropathic Pain. 45% of reviewers reported a positive effect, while 34% reported a negative effect.

How long does it take for Lyrica to kick in?

Peak concentrations of Lyrica occur within 2 to 3 hours. Although Lyrica may improve sleep problems due to nerve pain within a week, it may take up to two weeks for symptom relief from nerve pain to occur.

Can I take Lyrica long term?

Lyrica oral capsule is used for long-term treatment. It comes with serious risks if you don't take it as prescribed. If you stop taking the drug suddenly or don't take it at all: Your pain or seizures won't go away or may get worse.

How long should I take Lyrica for nerve pain?

Although you may experience some pain relief within the first few weeks of treatment the full benefit takes longer as the dose is increased to effective levels and may take up to 1 month.

Does Lyrica affect sleep?

Polysomnographic data reveal that Lyrica primarily affects sleep maintenance.

Can Lyrica cause memory loss?

Combination with gabapentin and Lyrica can cause memory impairment because of their additive effects in combination therapy on inhibition of excitatory neurotransmitters and hippocampal-memory network.

Can Lyrica be taken without food?

Lyrica capsule or oral liquid may be taken with or without food.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

Is Lyrica used for sciatica?

The nerve pain drug Lyrica is not an effective treatment for sciatica and is associated with a significant number of side effects, researchers have concluded.

Is Lyrica good for lower back pain?

Lyrica is known to have a considerable impact on neuropathic lower back pain.

Does Lyrica cause liver damage?

Since its approval and more wide scale use, however, Lyrica has been linked to rare instances of clinically apparent liver injury.

Can Lyrica affect my kidneys?

Lyrica  does not directly influence or damage the kidney. You should check with your physician about the dose of Lyrica that you are taking.

Can Lyrica affects my heart ?

Although evidence suggests Lyrica can cause edema and heart failure, its cardiac safety profile in clinical practice is unknown. We sought to examine the risk of heart failure among older patients receiving pregabalin compared to those receiving Lyrica.