Gabapentin; Uses, Dosage, Side Effects, Interactions, Pregnan

Gabapentin

Gabapentin is a unique anticonvulsant that is used as adjunctive therapy in the management of epilepsy and for neuropathic pain syndromes. Therapy with gabapentin is not associated with serum aminotransferase elevations, but several cases of clinically apparent liver injury from gabapentin have been reported. Gabapentin is an Anti-epileptic Agent. The physiologic effect of gabapentin is by means of Decreased Central Nervous System Disorganized Electrical Activity.

Gabapentin is a synthetic analog of the neurotransmitter gamma-aminobutyric acid with anticonvulsant activity. Although its exact mechanism of action is unknown, gabapentin appears to inhibit excitatory neuron activity. This agent also exhibits analgesic properties. Gabapentin is an anti-epileptic medication, also called an anticonvulsant. It affects chemicals and nerves in the body that are involved in the cause of seizures and some types of pain.

Mechanism of Action of Gabapentin

Gabapentin interacts with cortical neurons at auxiliary subunits of voltage-sensitive calcium channels. Gabapentin increases the synaptic concentration of GABA, enhances GABA responses at non-synaptic sites in neuronal tissues, and reduces the release of monoamine neurotransmitters. One of the mechanisms implicated in this effect of gabapentin is the reduction of the axon excitability measured as an amplitude change of the presynaptic fibre volley (FV) in the CA1 area of the hippocampus. This is mediated through its binding to presynaptic NMDA receptors. Other studies have shown that the antihyperalgesic and antiallodynic effects of gabapentin are mediated by the descending noradrenergic system, resulting in the activation of spinal alpha2-adrenergic receptors. Gabapentin has also been shown to bind and activate the adenosine A1 receptor.
Gabapentin is an anticonvulsant agent structurally related to the inhibitory CNS neurotransmitter gamma-aminobutyric acid (GABA). Gabapentin enacarbil is a prodrug of gabapentin that is rapidly converted to gabapentin following oral administration; the therapeutic effects of gabapentin enacarbil are attributed to gabapentin. Although gabapentin was developed as a structural analog of GABA that would penetrate the blood-brain barrier (unlike GABA) and mimic the action of GABA at inhibitory neuronal synapses, the drug has no direct GABA-mimetic action and its precise mechanism of action has not been elucidated.
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Results of some studies in animals indicate that gabapentin protects against seizure and/or tonic extensions induced by the GABA antagonists picrotoxin and bicuculline or by GABA synthesis inhibitors (e.g., 3-mercaptopropionic acid, isonicotinic acid, semicarbazide). However, gabapentin does not appear to bind to GABA receptors nor affect GABA reuptake or metabolism and does not act as a precursor of GABA or of other substances active at GABA receptors. Gabapentin also has no affinity for binding sites on common neuroreceptors (e.g., benzodiazepine; glutamate; quisqualate; kainate; strychnine-insensitive or -sensitive glycine; alpha1-, alpha2-, or beta-adrenergic; adenosine A1 or A2; cholinergic [muscarinic or nicotinic]; dopamine D1 or D2; histamine H1; type 1 or 2 serotonergic [5-HT1 or 5-HT2]; opiate mc, delta, or k) or ion channels (e.g., voltage-sensitive calcium channel sites labeled with nitrendipine or diltiazem, voltage-sensitive sodium channel sites labeled with batrachotoxinin A 20alpha-benzoate). Conflicting results have been reported in studies of gabapentin affinity for and activity at N-methyl-d-aspartic acid (NMDA) receptors.

Indications of Gabapentin

Therapeutic Indications of Gabapentin

  • Neurontin is indicated for: Management of postherpetic neuralgia in adults.
  • Neurontin is indicated for: Adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and pediatric patients 3 years and older with epilepsy.
  • Gabapentin enacarbil Extended-Release Tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS) in adults.
  • Gabapentin enacarbil Extended-Release Tablets are indicated for the management of postherpetic neuralgia (PHN) in adults.
  • Gabapentin also has been used with some evidence of benefit for the relief of chronic neurogenic pain in a variety of conditions including trigeminal neuralgia, pain, and control of paroxysmal symptoms of multiple sclerosis, complex regional pain syndromes, HIV-related peripheral neuropathy, and neuropathic pain associated with cancer.
  • Gabapentin is used for the treatment of pain associated with diabetic neuropathy.
  • Gabapentin has been used for the management of vasomotor symptoms in women with breast cancer and in postmenopausal women.
  • Therapy with the drug has improved both the frequency and severity of vasomotor symptoms (e.g., hot flushes or flashes) in these women.
  • The possible role of gabapentin in the management of vasomotor symptoms associated with antiandrogenic therapy in men with prostate cancer remains to be established. Current evidence of efficacy is limited; well-designed, controlled studies are underway in this population.

Contra-Indications of Gabapentin

Dosage of Gabapentin 

Strengths: 100 mg, 300 mg, 400 mg, 600 mg, 800 mg

Epilepsy

  • Initial dose: 300 mg orally on day one, 300 mg orally 2 times a day on day two, then 300 mg orally 3 times a day on day three
  • Maintenance dose: 300 to 600 mg orally 3 times a day
  • Maximum dose: 3600 mg orally daily (in 3 divided doses)
  • Maximum time between doses in the 3 times a day schedule should not exceed 12 hours

Postherpetic Neuralgia

  • Initial dose: 300 mg orally on day one, 300 mg orally 2 times the day on day two, then 300 mg orally 3 times a day on day three
  • Titrate up as needed for pain relief
  • Maximum dose: 1800 mg per day (600 mg orally 3 times a day)

Recommended titration schedule

  • Day 1: 300 mg orally with the evening meal
  • Day 2: 600 mg orally with the evening meal
  • Days 3 through 6: 900 mg orally with the evening meal
  • Days 7 through 10: 1200 mg orally with the evening meal
  • Days 11 through 14: 1500 mg orally with the evening meal
  • Day 15: 1800 mg orally with the evening meal

Gabapentin enacarbil extended-release tablets 

  • The recommended dosage is 600 mg orally 2 times a day. Therapy should be initiated at a dose of 600 mg orally in the morning for 3 days of therapy, then increased to 600 mg 2 times a day (1200 mg/day) on day four.

Pediatric Epilepsy

Less than 3 years: Not recommended

Greater than or equal to 3 and less than 12 years

  • Starting Dose: Ranges from 10 to 15 mg/kg/day in 3 divided doses
  • Effective Dose: Reached by upward titration over a period of approximately 3 days; the effective dose in patients 5 years of age and older is 25 to 35 mg/kg/day in divided doses (3 times a day).
  • The effective dose in pediatric patients ages 3 and 4 years is 40 mg/kg/day and given in divided doses (3 times a day). Gabapentin may be administered as the oral solution, capsule, or tablet, or using combinations of these formulations. Dosages up to 50 mg/kg/day have been well tolerated in a long-term clinical study. The maximum time interval between doses should not exceed 12 hours.

Greater than 12 years

  • Initial dose: 300 mg orally on day one, 300 mg orally 2 times a day on day two, then 300 mg orally 3 times a day on day three
  • Maintenance dose: 900 to 1800 mg orally in 3 divided doses; the dose may be increased up to 1800 mg/day.
  • Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies.
  • Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. The maximum time between doses in the three times a day schedule should not exceed 12 hours.

Side Effects of Gabapentin

Common

Common

Rare

Drug Interactions of Gabapentin

Gabapentin may interact with the following drugs, supplements, & may change the efficacy of drugs

Pregnancy& Lactation

 Pregnancy Category C 

Pregnancy

This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately. Talk to your doctor if you’re pregnant or planning to become pregnant. This drug should only be used if the potential benefit justifies the potential risk to the fetus. Call your doctor if you become pregnant while taking this drug.

Lactation

Gabapentin may pass into breast milk and cause serious side effects in a breastfeeding child. Tell your doctor if you are breastfeeding. You should decide together if you should stop taking this drug or stop breastfeeding.

For children

Gabapentin has not been studied in children for the management of postherpetic neuralgia or restless legs syndrome. It should not be used in people younger than 18 years. This drug should not be used to treat partial seizures in children younger than 3 years.

References

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