Pharmacologic classification:1-amino-methyl cyclohexoneaceticacid

Therapeutic classification: anticonvulsant

Pregnancy risk : category C

Tablet:600 mg,800 mg

Capsule:100mg,300mg,400mg

Oral solution 250 mg per 5 mL

-Gabapentin was initially synthesized to mimic the chemical structure of the neurotransmitter gamma-aminobutyric acid (GABA), but is not believed to act on the same brain receptors.Its exact mechanism of action is unknown, but its therapeutic action on neuropathic pain is thought to involve voltage-gated N-type calcium ion channels. It is thought to bind to the α2δ subunit of the voltage-dependent calcium channel in the CNS ,modulate calcium influx in hyperexcited neuron ,reduce neurotransmitter

release…

Adjunctive therapy in treatment of partial seizures with or without secondary generalization in patients older than 12 yr of age with epilepsy; adjunctive therapy for partial seizures in children 3 to 12 yr of age; management of postherpetic neuralgia in adults.

Unlabeled UsesAgitation in dementia; alcohol withdrawal; bipolar disorder; cocaine withdrawal; diabetic neuropathy; fibromyalgia; headaches; hiccups (singultus); hot flashes (cancer- and/or postmenopausal-related); hyperhidrosis; nausea (cancer-related); neuralgia/neuropathy/chronic pain; prevention of migraine; pruritus (brachioradial/cholestatic/uremic); rectal administration; restless leg syndrome; tremors in multiple sclerosis.

Children 2–12 yr: 15–35 mg/kg/24 hr in 3 divided doses (max: 50 mg/kg/24 hr).

Children >12 yr and adults: Start 300 mg daily, then daily increase by 300 mg to 900–

3,600 mg/24 hr in 3 divided doses.

If Cr Cl is more than 60ml/minute give 400mg P.O t.i.d.daily

If Cr Cl is 15 to 30ml/minute give 300mgP.O.t.i.d daily

If Cr Cl is less than 15ml/minute give 300mg P.O other day.

Patients on haemodialysis should receive a loading dose of 300mg-400mgP.O,then 200mg to 300mg P.O. after q4 h of haemodialysis

Absorption: Gabapenten bioavailability is not dose proportional. A400mg dose, for example is about 25% less bioavailable than 100mg dose. Over the recommended dose range of 300 to 600mg t.i.d, however differences in bioavailability are not large and bioavailability is about 60%.Food has not effect on the rate or extent of absorption..

Distribution: Gabapentin circulate largely unbound (less than3%) to plasma protein.Cross BBB with approximately 20% of the corresponding plasma conc. Found in CSF.

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Metabolism: is not appreciably metabolized in human.

Excretion :is eliminated from the systemic circulation by renal excretion as unchanged drug, it elimination t1/2is5-7hr,gabapentin can removed from plasma by haemodialysis

Contraindication: contraindicate in patients hypersensitive to the drug

Interaction: Antacid decreases the absorption of gabapentin .Administration of the two drugs

should be separate by at least 2 hr .Laboratory Test InteractionsFalse-positive readings for Ames N-Multistix SG dipstick test when gabapentin is added to other antiepileptic drugs. Sulfosalicylic acid precipitation procedure is recommended

to determine the presence of urine protein.

CNS: fatigue, somnolence ,dizziness ,ataxia ,nystagmus, tremor ,nervousness ,dysarthria ,amnesia , depression , abnormal thinking ,twitching , incordorationCV: peripheral odema , vasodilation.

EENT: diplopia, rhinitis, phyringitis, dry throat ,coughing ,amblyopia.GU: impotence.

Haematologic: leukopenia ,decrease WBC countSkin: pruritis ,abrasionOther: dental abnormalities , increased appetite ,

weight gain , back pain , myalgia, fracture

Acute over dose of gabapentin may cause double vision, slurred speech , drowsiness ,lethargy and diarrhea.

Supportive care is recommended. In addition gabapentin can removed by haemodialysis and may be indicated by the patient’s clinical state or in plasma with significant renal impairment.

If gabapentin therapy is discontented or alternative medication is substituted ,do so gradually over at least 1 week to minimize the risk of precipitating seizure. Do not suddenly withdraw other anticonvulsant drugs in patients starting gabapentin therapy

Breast feedingIt is not known if gabapentin excreted in human milk. Because many drug are excreted in human milk. Gabapentin should be used in breast feeding patient only if the benefit clearly out-weight the risks.

*Warn patient to avoid driving or operating heavy machinery until adverse CNS effects of the drug are known.

*Instruct patient to take first dose at bed time to minimize drowsiness , dizziness, fatigue , and ataxia.

*Inform patient that he can take gabapentin without regard to meal

Pregablin (lyrica)

Clinical studyObjective: To compare the dose-response (seizure frequency) relationship of pregabalin and gabapentin add-on treatment in patients with refractory partial epilepsy.Background: Pregabalin (Lyrica®) and gabapentin (Neurontin®) are antiepileptic drugs that appear to have a similar mechanism of action through binding to the α2-δ subunit of voltage-gated calcium channels. Preclinical studies with pregabalin and gabapentin indicate similar anticonvulsant pharmacological profiles; however, pregabalin shows 3- to 6-fold greater potency. Pregabalin, unlike gabapentin, exhibits linear absorption , increasing proportionally with dose. In contrast, the extent of gabapentin absorption decreases with increasing dose. 

Results: Pregabalin (50–600 mg/d) and gabapentin (600–1800 mg/d) showed an asymptotic dose-related decrease in seizure frequency. Both pregabalin- and gabapentin-treated patients demonstrated a dose-response relationship; however, the maximal decrease in seizure frequency from baseline with pregabalin was 100%, while the maximal decrease with gabapentin therapy was 24.5%. Based on this information, pregabalin was estimated to be 4 times more effective than gabapentin in patients who responded to treatment. Pregabalin was also 2.5 times more potent than gabapentin in responding patients, as measured by the dose that reduced seizure frequency by 50%.Conclusions: The observed improvement in potency and effectiveness combined with the pharmacokinetic-pharmacodynamic properties of pregabalin relative to gabapentin offer distinct advantages over standard gabapentin therapy for the treatment of refractory partial seizures .