GABAPENTIN

Gabapentin

Nopantin^®

Category:

Anticonvulsant; Antineuralgic.

(USP DI)

Chemistry:

1- (Aminomethyl) cyclohexaneacetic acid. C₉H₁₇NO₂= 171.2.

(Martindale)

Mechanism of Action /Pharmacokinetic:

The mechanism by which gabapentin exerts its analgesic action is unknown, but in animal models of analgesia, gabapentin prevents allodynia and hyperalgesia. In particular, gabapentin prevents pain-related responses in several models of neuropathic pain in rats or mice. Gabapentin also decreases pain-related responses after peripheral inflammation. Gabapentin did not alter immediate pain-related behaviors. The mechanism by which gabapentin exerts its anticonvulsant action is unknown, but in animal test systems designed to detect anticonvulsant activity, gabapentin prevents seizures as do other marketed anticonvulsants. Gabapentin is structurally related to the neurotransmitter GABA but it does not modify GABA_A or GABA_B radioligand binding, it is not converted metabolically into GABA or a GABA agonist, and it is not an inhibitor of GABA uptake or degradation. Furthermore, gabapentin did not alter the cellular uptake of dopamine, noradrenalin, or serotonin.

Pharmacokinetic properties

(PDR / USP DI)

Indication:

-Postherpetic neuralgia: For the management of postherpetic neuralgia in adults.

-Epilepsy: As adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients over 12 years of age with epilepsy. Gabapentin is also

indicated as adjunctive therapy in the treatment of partial seizures in pediatric patients age 3 to 12 years.

(Facts)

Contraindications:

Hypersensitivity to the drug or its ingredients.

(Facts)

Warnings & Precautions:

1- Gabapentin use in pediatric patients with epilepsy 3-12 years of age is associated with the occurrence of central nervous system related adverse events. The most significant of these can be classified into the following categories: emotional lability, hostility, thought disorder, including concentration problems and change in school performance, and hyperkinesias. Among the gabapentin treated patients, most of the events were mild to moderate in intensity. 

2- Antiepileptic drugs should not be abruptly discontinued because of the possibility of increasing seizure frequently.

3- Patients should be advised that gabapentin may cause dizziness, somnolence and other symptoms and signs of CNS depression. Accordingly, they should be advised neither to drive

a car nor to operate other complex machinery until they have gained sufficient experience on gabapentin to gauge whether or not it affects their mental and/or motor performance adversely.

(PDR-Facts)

Pregnancy:

FDA Pregnancy Category C.

Gabapentin should be used during pregnancy only if the benefit justifies the potential risk to the fetus. Adequate and well-controlled studies have not been done in humans.

 (USP DI)

Breast-Feeding:

It is not known whether gabapentin is distributed into breast milk.

 (USP DI)

Drug Interactions:

1- The absorption of gabapentin from the gastrointestinal tract is reduced by antacids containing aluminum with magnesium; it is recommended that gabapentin is taken at least 2 hours after the administration of such an antacid.

2- Cimetidine has been reported to reduce the renal clearance of gabapentin but the product information does not consider this to be of clinical importance.

3- Coadministration of gabapentin decreases hydrocodone C_max and AUC values in a dose-dependent manner. Hydrocodone increases gabapentin AUC values by 14%.

4- Coadministration of 60 mg morphine 2 hours prior to administration of 600 mg gabapentin resulted in an increase in gabapentin AUC by 44%. Morphine pharmacokinetic parameter values were not affected by administration of gabapentin 2 hours after morphine.

5- Coadministration of naproxen sodium capsules (250mg) with gabapentin (125mg) appears to increase the amount of gabapentin absorbed by 12% to 15%. Gabapentin had no effect on naproxen pharmacokinetic parameters.

(Facts-PDR)

Adverse Reactions:

Ataxia, nystagmus, neuropsychiatric problems, including emotional lability, hostility, hyperkinesia, and thought disorders, amnesia, depression, irritability, or other mood or mental changes, leucopenia, dizziness, fatigue, myalgia, peripheral edema, somnolence, tremor, vision abnormalities, including blurred vision and diplopia, asthenia, back pain, dryness of mouth or throat, dysarthria, frequent urination, gastrointestinal effects, including constipation, diarrhea, dyspepsia, nausea, and vomiting, headache, hypotension, impotence, insomnia, rhinitis, tinnitus, trouble in thinking, twitching, weight gain.

 (USP DI)

Overdose:

Symptoms: A lethal dose of gabapentin was not identified in mice and rats receiving single oral doses as high as 800 mg/kg. Signs of acute toxicity in animals included ataxia, labored breathing, ptosis, sedation, hypoactivity, or excitation.

Acute oral overdoses of gabapentin up to 49 g have been reported. In these cases, double vision, slurred speech, drowsiness, lethargy and diarrhea were observed. All patients recovered with supportive care.

Treatment: Gabapentin can be removed by hemodialysis. Although hemodialysis has not been performed in the few overdose cases reported, it may be indicated by the patient's clinical state or in patients with significant renal impairment..

(Facts / USP DI)

Dosage & Administration:

Postherpetic neuralgia:

In adults it may be initiated as a single 300 mg dose on day one, 600 mg/day on day 2 (divided twice daily), and 900 mg/day on day 3 (divided 3 times daily). The dose can

subsequently be titrated up as needed for pain relief to a daily dose of 1800 mg (divided 3 times daily).

Epilepsy:

Gabapentin is recommended for add-on therapy in patients 3 years of age and older. Effectiveness in children below the age of 3 years has not been established.

- Patients greater than 12 years of age:.

The effective dose of gabapentin is 900 to 1800 mg/day and given in divided doses (3 times a day). The starting dose is 300 mg 3 times a day.

-Children age 3 to 12 years:

The starting dose should range from 10 to 15 mg/kg/day in 3 divided doses, and the effective dose reached by upward titration over a period of approximately 3 days. The effective dose of

gabapentin in patients 5 years of age and older is 25 to 35 mg/kg/day and given in divided doses (3 times a day). The effective dose in pediatric patients aged 3 and 4 years is 40 mg/kg/day and given in divided doses (3 times a day).

- Renal function impairment:

In patients with renal function impairment, dosage should be adjusted based on creatinine clearance values.

- Elderly:

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.

(Facts)

Storage:

Store below 30^oC, in a dry place and protect from light.

(PDR)

How Supplied:

Gabapentin-Tedapharm 100 and 300 are supplied as pink opaque cap / white opaque body capsules in transparent blisters of 10's in boxes of 30's.

References:

1-      Drug Facts & Comparisons 2008

2-      Martindale (35)  2007

3-      PDR  2008

4-      USP DI  2004

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