Pregabalin

In this article, we will discuss about Pregabalin (LYRICA). So, let’s get started.

Pregabalin is described chemically as (S)-3-(aminomethyl)-5-methylhexanoic acid. The molecular formula is CH, NO, and the molecular weight is 159.23. Pregabalin is a white to off-white, crystalline solid with a pKa1 of 4.2 and a pKa2 of 10.6. It is
freely soluble in water and both basic and acidic aqueous solutions. The log of the partition coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is – 1.35.

Mechanism of Action

Pregabalin (LYRICA) binds with high affinity to the alpha2 -delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin has not been fully elucidated, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in pregabalin’s anti-nociceptive and antiseizure effects in animals. In animal models of nerve damage, pregabalin has been shown to reduce calcium-dependent release of pro-nociceptive neurotransmitters in the spinal cord, possibly by disrupting alpha2-delta containing-calcium channel trafficking and/or reducing calcium currents. Evidence from other animal models of nerve damage and persistent pain suggest the anti-nociceptive activities of pregabalin may also be mediated through interactions with descending noradrenergic and serotonergic pathways originating from the brainstem that modulate pain transmission in the
spinal cord.

While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-
aminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA, responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on 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 does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.

Indications

Pregabalin (LYRICA) is indicated for:
• Management of neuropathic pain associated with diabetic peripheral
neuropathy
• Management of postherpetic neuralgia
• Adjunctive therapy for the treatment of partial onset seizures in patients 4 years of age and older
• Management of fibromyalgia
• Management of neuropathic pain associated with spinal cord Injury

Dosage

Pregabalin can be taken with or without food.

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

• Solution, Oral:
• 20 mg/mL (473 mL)

• Tablet Extended Release 24 Hour, Oral:
• 825 mg, 165 mg, 330 mg

Diabetic Neuropathy

-Initial dose 50 mg orally 3 times a day
-Titration: The dose may be increased to 100 mg orally 3 times a day within 1 week based on efficacy and tolerability
-Maximum dose: 300 mg/day

Postherpetic Neuralgia

-Initial 150-300 mg/day PO divided q8-12hr
-Maintenance: May increase to 300 mg/day divided q8-12hr after 1 week, as needed.

Partial Seizure

-Initial: 150 mg/day PO divided q8-12hr
-Maintenance: Based on clinical response and tolerability, may increase dose in weekly increments, not to exceed 600 mg/day

Fibromyalgia

-Initial: 150 mg/day PO divided q12hr
-Maintenance: May increase to 300-450 mg/day divided q12hr after 1 week, as needed

Neuropathic Pain

-Initial 150 mg/day PO divided q12hr, may increase within 1 week to 300 mg/day PO divided q12hr.
-If there is insufficient pain relief after 2-3 weeks and 300 mg/day dose is tolerated, may increase dose again up to 600 mg/day PO divided q12hr

Contraindications

Known hypersensitivity to pregabalin or any of its components.

Warnings

• Angioedema (e.g., swelling of the throat, head and neck) can occur, and may be associated with life-threatening respiratory compromise requiring emergency treatment. Discontinue LYRICA inmediately in these cases.
• Hypersensitivity reactions (e.g., hives, dyspnea, and wheezing) can occur. Discontinue Pregabalin (LYRICA) inmediately in these patients.
• Increased seizure frequency or other adverse reactions may occur if Pregabalin (LYRICA) is rapidly discontinued. Withdraw Pregabalin (LYRICA) gradually over a
minimum of 1 week.
• Antiepileptic drugs, including Pregabalin (LYRICA), increase the risk of suicidal thoughts or behavior.
• Pregabalin (LYRICA) may cause peripheral edema. Exercise caution when co-administering Pregabalin (LYRICA) and thiazolidinedione antidiabetic agents.
• Pregabalin (LYRICA) may cause dizziness and somnolence and impair patients ability to drive or operate machinery.

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