Pregabalin (Lyrica) is a medicine that is used to treat a variety of conditions listed below. Mostly, it is used in the management of neuropathic pains (pains arising from nerves) and epilepsy.

• Fibromyalgia (immediate release only):

  • It is used in the management of fibromyalgia

• Neuropathic pain associated with diabetic peripheral neuropathy (immediate-release and extended-release):

  • It is used in the management of neuropathic pain associated with diabetic peripheral neuropathy

• Neuropathic pain associated with spinal cord injury (immediate release only):

  • It is used in the management of neuropathic pain associated with spinal cord injury

• Postherpetic neuralgia (immediate-release and extended-release):

  • It is used in the management of postherpetic neuralgia

• Seizures, focal (partial) onset (immediate release only):

  • It is used as adjunctive therapy in patients ≥4 years of age with focal onset (partial-onset) seizures

• Off Label Usage of Pregabalin in Adults:

  • Chronic refractory cough;
  • Generalized anxiety disorder;
  • Postoperative pain
  • Pruritus, neuropathic or malignancy-related;
  • Pruritus, uremic;
  • Restless legs syndrome;
  • Social anxiety disorder;
  • Vasomotor symptoms  with menopause

Pregabalin Dose in Adults

•  When discontinuing, taper off slowly over at least 7 days.

Off label dose as an alternative agent in the treatment of Cough, chronic refractory :

• Immediate release:

  • Initially 75 mg orally once daily is given
  • It can be increased gradually over the first week in increments of 75 mg/day based on response and tolerability up to a maximum dose of 300 mg/day in 3 divided doses

Dosage as an alternative agent in the treatment of Fibromyalgia:

• Immediate release:

  • Initially 75 mg orally twice daily is given
  • It may be increased to 150 mg twice daily within 1 week based on response and tolerability
  • The maximum dose is 450 mg/day

Dosage as an alternative agent in the treatment of Generalized anxiety disorder (Off label):

• It is used as Monotherapy or adjunctive therapy for patients who do not tolerate or respond to preferred agents.

• Immediate release:

  • Initially, 150 mg/day orally in 2 to 3 divided doses is given
  • It may be increased based on response and tolerability at weekly intervals in increments of 150 mg/day up to a usual dose of 300 mg/day.
  • It can be further increased up to 600 mg/day

Dose in the treatment of Neuropathic pain:

• Immediate release:

  • Initially 25 to 150 mg/day orally once daily is given or in 2 divided doses
  • It may be increased in increments of 25 to 150 mg/day at intervals more than 1 week based on response and tolerability up to a usual dose of 300 to 600 mg/day in 2 divided doses

Dose in the treatment of diabetic neuropathy:

• Immediate release:

  • Initially 25 to 75 mg/day orally once daily is given or in 2 to 3 divided doses
  • It may be increased within 7 days based on response and tolerability up to a maximum dose of 300 to 450 mg/day .
  • Higher doses may be associated with greater adverse effects without additional benefits

• Extended-release:

  • Initially 165 mg orally once daily is given
  • It may be increased within 1 week based on response and tolerability up to a maximum dose of 330 mg once daily.

Dosage in the treatment of Postherpetic neuralgia:

• Immediate release:

  • Initially, 150 mg/day orally is given in divided doses (75 mg twice daily or 50 mg 3 times daily)
  • It may be increased to 300 mg/day within 7 days based on response and tolerability
  • It can b increased after 2 to 4 weeks, up to the maximum dose of 600 mg/day.

• Extended-release:

  • Initially 165 mg orally once daily is given
  • It may be increased to 330 mg once daily within 1 week based on response and tolerability
  • It can b increased after 2 to 4 weeks, up to the maximum dose of 660 mg/day

Dose in the treatment of Spinal cord injury-associated neuropathic pain:

• Immediate release:

  • Initially, 75 mg twice daily is given
  • It may b increased within 1 week based on response and tolerability to 150 mg twice daily
  • after 2 to 3 weeks, can further be increased up to a maximum of 600 mg/day.

Dose in the treatment of Postoperative pain (off-label):

• Immediate-release:
  • 75 to 300 mg is given orally as a single dose
  • 1 to 2 hours before surgery as part of a multimodal analgesia regimen.

Dose as an alternative agent in the treatment of chronic Pruritus (off-label):

• For patients with pruritus resistant to preferred therapies.

Dosage in the treatment of Neuropathic (eg, brachioradial pruritus, notalgia paresthetica) or malignancy-related: 

• Immediate release:
  • The initial dose is  75 mg orally twice daily
  • It may be increased based on response and tolerability up to 150 to 300 mg/day in 2 to 3 divided doses
  • Higher doses (up to 600 mg/day) have been used in oncology populations

Dose in the treatment of Uremic:

• Immediate release:
  • 50 mg orally given every other day given after dialysis on hemodialysis days
  •                                              or
  • 25 mg daily given, each increased based on response and tolerability to 50 or 75 mg daily
  •                                              or
  • 75 mg twice weekly given after dialysis on hemodialysis days also appears effective.

Dose in the treatment of Restless legs syndrome (off-label):

• Immediate release:
  • The initial dose is  50 to 75 mg orally once daily
  • It is given 1 to 3 hours before bedtime
  • It gradually increases (eg, in increments of 75 to 150 mg) every 5 to 7 days according to response and tolerability to a usual effective dose of 150 to 450 mg/day.

Dose in the treatment of Seizures, focal (partial) onset (adjunctive therapy with other anticonvulsants):

• Immediate release:
  • The initial dose is 150 mg/day orally in 2 or 3 divided doses
  • It may be increase based on response and tolerability at weekly intervals up to a maximum dose of 600 mg/day.

Dosage as an alternative agent in the treatment of Social anxiety disorder (off-label):

• For patients who do not tolerate or respond to preferred agents, monotherapy or adjunctive therapy may be used.

• Immediate-release:

  • The initial dose is 100 mg orally 3 times daily
  • It may be increased over 1 week in increments of 150 mg/day based on response and tolerability up to 600 mg/day

Off-label dosage in the treatment of Vasomotor symptoms associated with menopause (alternative agent):

• It is used as a nonhormonal alternative in patients unable or unwilling to take preferred agents

• Immediate-release:

  • The initial dose is  50 mg orally once daily at bedtime
  • It may be increased at weekly intervals based on response and tolerability to 50 mg twice daily, and then up to 75 mg twice daily
  • It may further increase up to 150 mg twice daily.

• Dosing conversion from immediate-release oral formulations to the extended-release oral formulation:

• Give morning dose of the immediate-release product as prescribed, and initiate extended-release therapy after the evening meal on the day of the switch.

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  • The immediate-release total daily dose of 75 mg is equal to the extended-release dose of 82.5 mg once daily.

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  • The immediate-release total daily dose of 150 mg is equal to the extended-release dose of 165 mg once daily.

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  • The immediate-release total daily dose of 225 mg is equal to the extended-release dose of 247.5 mg once daily.

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  • The immediate-release total daily dose of 300 mg is equal to the extended-release dose of 330 mg once daily.

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  • The immediate-release total daily dose of 450 mg is equal to the extended-release dose of 495 mg once daily.

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  • The immediate-release total daily dose of 600 mg is equal to the extended-release dose of 660 mg once daily.

• Discontinuation of therapy:

  • Unless safety concerns require a more rapid withdrawal, pregabalin should be withdrawn gradually over more than 1 week to lessen the potential of increased seizure frequency (in patients with epilepsy) or other withdrawal symptoms (eg, agitation, confusion, delirium, delusions, GI symptoms, mood changes, sweating, withdrawal seizures).

Pregabalin Dose in Children

• When discontinuing, taper off slowly over at least 1 week.

Dose in the treatment of partial-onset Seizures as adjunctive therapy:

• Immediate release:

  • Children ≥4 years and Adolescents <17 years:

  • 11 to <30 kg:

    • The initial dose is 3.5 mg/kg/day orally in 2 or 3 divided doses
    • It may be increased weekly based on clinical response and tolerability
    • maximum daily dose: 14 mg/kg/day

  • ≥30 kg:

    • The initial dose is  2.5 mg/kg/day orally in 2 or 3 divided doses
    • The dose may be increased weekly based on clinical response and tolerability
    • The maximum daily dose is 10 mg/kg/day not to exceed 600 mg/day

  • Adolescents ≥17 years:

    • The initial dose is 150 mg orally daily in 2 or 3 divided doses
    • It may be increased weekly based on tolerability and effect
    • The maximum daily dose is 600 mg/day

Pregnancy Risk factor: C

• Pregabalin can cross the placenta
• Data collection to monitor pregnancy and infant outcomes following exposure to pregabalin is underway.

Pregabalin use during breastfeeding:

• Pregabalin is usually present in breast milk.
• The relative infant dose (RID) of pregabalin is ~7% when calculated by an average breast milk concentration compared to a weight-adjusted maternal dose of 300 mg/day.
• In general, breastfeeding acceptable when the RID of medication is <10%.
• Breastfeeding is not advised by the manufacturer.

Pregabalin dose in Renal Disease:

Immediate-release:

• The Cockcroft-Gault formula can be used to estimate renal function.
• Calculate the recommended dosage regimen using the indicated-specific daily dose for normal kidney function (CrCl>=60 mL/minute).

Pregabalin Renal Impairment Dosing - Immediate Release Pregabalin

Extended-release

• The Cockcroft-Gault formula can be used to evaluate renal function.
• Calculate the recommended dosage regimen using the indicated total daily dose for normal kidney function (CrCl >=60mL/minute).

Extended-Release Pregabalin dosage in Renal Impairment

Pregabalin Dose in Liver Disease:

• There are no dosage adjustments given in the manufacturer's labeling.

Common Side Effects of Pregabalin (Lyrica) Include:

• Cardiovascular:

  • Peripheral Edema

• Central Nervous System:

  • Dizziness
  • Drowsiness
  • Headache
  • Fatigue

• Endocrine & Metabolic:

  • Weight Gain

• Gastrointestinal:

  • Xerostomia

• Ophthalmic:

  • Visual Field Loss
  • Blurred Vision

Less Common Side Effects of Pregabalin (Lyrica) Include:

• Cardiovascular:

  • Edema
  • Facial Edema
  • Chest Pain
  • Hypertension
  • Hypotension

• Central Nervous System:

  • Ataxia
  • Equilibrium Disturbance
  • Abnormal gait
  • Euphoria
  • Confusion
  • Disturbance In Attention
  • Abnormality In Thinking
  • Neuropathy
  • Pain
  • Myasthenia
  • Insomnia
  • Amnesia
  • Memory Impairment
  • Vertigo
  • Hypoesthesia
  • Feeling Abnormal
  • Speech Disturbance
  • Anxiety
  • Paresthesia
  • Disorientation
  • Intoxicated Feeling
  • Lethargy
  • Anorgasmia
  • Depersonalization
  • Hypertonia
  • Sedation
  • Stupor
  • Twitching
  • Nervousness

• Dermatologic:

  • Pressure Ulcer
  • Ecchymoses
  • Pruritus
  • Contact Dermatitis

• Endocrine & Metabolic:

  • Fluid Retention
  • Hypoglycemia
  • Decreased Libido

• Gastrointestinal:

  • Constipation
  • Increased Appetite
  • Nausea
  • Sialorrhea
  • Flatulence
  • Vomiting
  • Abdominal Distension
  • Abdominal Pain
  • Gastroenteritis
  • Diarrhea
  • Viral Gastroenteritis

• Genitourinary:

  • Urinary Incontinence
  • Impotence
  • Urinary Frequency
  • Erectile Dysfunction
  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Thrombocytopenia

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase

• Hypersensitivity:

  • Hypersensitivity Reaction

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Asthenia
  • Arthralgia
  • Muscle Spasm
  • Back Pain
  • Limb Pain
  • Neck Pain
  • Increased Creatine Phosphokinase
  • Tremor
  • Joint Swelling
  • Lower Limb Cramp
  • Myalgia

• Ophthalmic:

  • Decreased Visual Acuity
  • Visual Disturbance
  • Diplopia
  • Eye Disease
  • Conjunctivitis
  • Nystagmus

• Otic:

  • Otitis Media
  • Tinnitus

• Respiratory:

  • Nasopharyngitis
  • Sinusitis
  • Bronchitis
  • Pharyngolaryngeal Pain
  • Dyspnea
  • Flu-Like Symptoms
  • Cough
  • Respiratory Tract Infection

• Miscellaneous:

  • Accidental Injury
  • Fever

Very rare side effects of Pregabalin:

• Cardiovascular:

  • Prolongation P-R interval on ECG is seen

Contraindication to Pregabalin Include:

• Hypersensitivity to pregabalin (or any part thereof) can result in angioedema.

Warnings and precautions

• Angioedema

  • Angioedema can be seen in both chronic and initial treatment. It may even prove to be life-threatening.
  • The most common symptoms include swelling of the neck, throat, larynx, and tongue (tongue and lips), as well as the mouth (tongue and lips) and facial areas.
  • Patients with angioedema episodes should be cautious.
  • Combining angioedema-causing drugs (eg, ACE inhibitors), could increase the risk.
  • If angioedema develops, stop treatment immediately.

• CNS effects

  • Common symptoms include dizziness and somnolence
  • Most effects occur within a few hours of initiation. They also occur more often at higher doses.
  • It is important to inform patients about tasks that require mental alertness, such as driving or operating machinery.

• Hematologic effects

  • It could decrease platelet count.
  • Extremely rare is severe thrombocytopenia.

• Hypersensitivity

  • After treatment began, hypersensitivity reactions such as skin reddening, blistering, hives and dyspnea were seen quickly.
  • If hypersensitivity develops, stop the treatment.

• Peripheral edema

  • Peripheral edema could result from prolonged use
  • Due to the limited data available, patients with heart failure (NYHA Class IV or III) should be used with caution.
  • Additionally, the effect of the Thiazolidinedione class antidiabetic drugs may be additive; caution is advised when administering these agents together, especially in patients with previous cardiovascular disease.

• PR interval:

  • It can cause mild prolongation in the PR interval.
  • It is not known if clinical significance exists.

• Rhabdomyolysis

  • It has been linked to increases in creatine Kinase, and rare cases of Rhabdomyolysis.
  • Patients should be directed to inform their doctor if they experience any muscle pain, tenderness or weakness.
  • If myopathy is suspected, diagnosed, or if creatine kinase levels are elevated, stop treatment.

• Suicidal thoughts:

  • All patients should be evaluated for any changes in behavior that could indicate suicidal thoughts and/or depression.
  • If you experience symptoms, immediately notify your doctor.

• Visual disturbances

  • Therapy has been shown to reduce blurred vision, visual field changes, and decreased acuity.
  • Patients should be told to inform their doctor if they notice any of these symptoms.

• Weight loss

  • Weight gain could result from using
  • Weight gain is usually associated with dosage and duration

• Cardiovascular disease

  • Patients with severe cardiovascular disease (including heart failure) should be cautious. Weight gain and/or peripheral swelling may also occur.
  • Pregabalin was also found to be an agent that can exacerbate myocardial dysfunction.

• Renal impairment

  • Patients with impaired renal function should be cautious
  • Adjustment of dosage is necessary.

• Substance abuse

  • Patients with a history or substance abuse should be cautious
  • This population is susceptible to behavioral dependence

Pregabalin: Drug Interaction

Monitor:

• Measuring efficacy (pain intensity/seizure frequency).
• Graduation of sedation
• Myopathy symptoms
• Creatine kinase (as indicated clinically)
• Ocular disturbances can be symptomatic
• Weight gain/edema
• Skin integrity in patients with diabetes
• Suicidality signs and symptoms (eg suicidal thoughts or behavior changes, anxiety, depression, and/or suicidal thoughts)
• Platelet count (as indicated by clinical evidence)

How to take Pregabalin (Lyrica)?

Instant-release

• You can take it with or without food.

Extended-release

• After an evening meal, give once daily
• Take whole. Do not chew, split, crush or chew.
• After eating a snack, a missed dose should not be taken before bedtime.
• Do not eat if you are late for bed.
• If you miss your morning dose, wait until dinner to get the next one.

Mechanism of action of Pregabalin (Lyrica):

• It binds with the alpha-2 delta subunit of voltage-gated Calcium channels in the CNS and modifies calcium influx at nerve terminals.
• This inhibits excitatory neurotransmitter releases including glutamate (noradrenaline), dopamine, substance, and calcitonin-related peptide.
• It is structurally similar to GABA but does not bind to GABA and benzodiazepine receptors.
• It has antinociceptive, anticonvulsant and other activities.
• It could also affect the descending serotonergic and noradrenergic pain transmission pathways, which run from the brainstem down to the spinal cord.

The beginning of actionPain management:

• You may notice its effects as soon as the first week of therapy.

AbsorptionExtended-release:

• Fasting results in a 30% reduction in AUC

Distribution: V

• 0.5 L/kg

Protein binding:

• 0%

Metabolism:

• Negligible

Bioavailability:

• >=90%

Eliminating half-life:

• Children aged 4-6 years: 3-4 hours
• Children >=7 Years and Adolescents >17 years: 4-6 hours
• Adults can stay for 6.3 hours

Plasma peak time:

• Extended-release: Median 8 hours with food (range 5-12 hours).
• Instant release: Adolescents >=17 years, Children >=4 Years: 0.5 to 2 Hours fasting
• Median: 0.7 Hours fasting (range: 0.0.7 to 1.5 hours), 3 Hours with food

Excretion:

• Via Urine (90% unchanged drug; minor metabolites) 

International Brands of Pregabalin:

• ACT Pregabalin
• AG-Pregabalin
• APO-Pregabalin
• Auro-Pregabalin
• DOM-Pregabalin
• GD-Pregabalin
• JAMP-Pregabalin
• Lyrica
• M-Pregabalin
• Mar-Pregabalin
• MINT-Pregabalin
• MYL-Pregabalin
• MYLAN-Pregabalin
• NRA-Pregabalin
• PMS-Pregabalin
• Pregabalin-150
• Pregabalin-25
• Pregabalin-50
• Pregabalin-75
• RAN-Pregabalin
• RIVA-Pregabalin
• SANDOZ Pregabalin
• TEVA-Pregabalin
• Algecia
• Andogablin
• Aprion
• Axual
• Balinozar
• Brieka
• Egzsta
• Erclany
• Funxion
• Gabarol
• Gabi
• Gabica
• Gabrika
• Galica
• Gavin
• Gloryca
• Innikra
• Kemirica
• Lecaent
• Leptica
• Ligaba
• Linefor
• Lingabat
• Lipapyn
• Lybalin
• Lyrica
• Lyrigab
• Martesia
• Neo Gaba
• Neogabin
• Nervax
• Nervica
• Neugalin
• Neurocover-PG
• Neurovan
• Neurum
• PGB
• Plenica
• Prebarin
• Prebicta
• Prega 150
• Pregabadin
• Pregadex
• Pregalex
• Pregalin
• Pregasafe-150
• Pregax
• Pregeb
• Prelyx
• Preneurin
• Prex
• Provelyn
• Regab
• Rewisca
• Silica
• Toprelin
• Vexer
• Xablin
• Zeegap
• Zyzyx

Pregabalin brands in Pakistan: