OGB

 

Capsule

Composition:
Each GABAPENTIN capsule contains:
Gabapentin 300 mg

Pharmacology:
All pharmacological actions following gabapentin administration are due to the activity of the parent compound; gabapentin is not appreciably metabolized in humans; does not bind to plasma protein; does not induce hepatic enzyme activity; and does not appear to alter the pharmacokinetics of commonly used anticonvulsant drugs (e.g., carbamazepine, phenytoin, valproate, phenobarbital, diazepam) or oral contraceptive. In addition, the pharmacokinetics of gabapentin are not altered substantially by concomitant administration of other anticonvulsant drugs.

Pharmacodynamic:
Gabapentin is structurally related to the neurotransmitter γ-aminobutyric acid (GABA) but its mechanism of action is different from that of several other medications that interact with GABA synapses. The identification and function of the gabapentin binding site remains to be elucidated and the relevance of these various actions to the anticonvulsant effects remains to be established.

Pharmacokinetics:
Absorption
The mean peak plasma concentration (Cmax) occurs approximately 3 hours after single oral dose regardless of the size of the dose formulations. Tmax after multiple doses, approximately 1 hour shorter than Tmax in a single dose. Gabapentin bioavailability is not dose proportional, as dose is increased, bioavailability decreases. However, the difference of bioavailability is not significant. Bioavailability of gabapentin is approximately 60%. Food has only a slight effect on the rate and extent of absorption of gabapentin (14% increase in AUC and Cmax)

Distribution
Gabapentin circulates largely unbound (<3%) to plasma proteins. The apparent volume of distribution of gabapentin after 150 mg IV administration is 58±6 l (mean ±SD). In patients with epilepsy, steady-state (Cmin) concentrations of gabapentin in cerebrospinal fluid were approximately 20% of the corresponding plasma concentrations. After multiple dose administration, steady state is reached within 1 to 2 days after initiating the multiple doses and is maintained throughout the regimen dose.

Metabolism
Gabapentin is not metabolized in humans and does not induces oxidation system hepatic enzymes.

Elimination
Gabapentin is eliminated from the systemic circulation by renal excretion as unchanged drug. Gabapentin elimination half-life is 5 to 7 hours and is unaltered by dose or following multiple dosing. Gabapentin elimination rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance. Renal clearance was the sole elimination pathway for gabapentin.

Special population:
Renal impairment
In patients with impaired renal function, gabapentin plasma clearance is reduced. Dosage adjustment in patients with impaired renal function is recommended. Pediatric patients with renal insufficiency have not been studied.

Hemodialysis
Gabapentin can be removed from plasma by hemodialysis. In a study in anuric adult subjects, the apparent elimination half-life of gabapentin on nondialysis days was about 132 hours; during dialysis three times a weeks (duration 4 hours), the apparent half-life of gabapentin was reduced approximately 60% from 132 hours to 51 hours. Hemodialysis thus has a significant effect on gabapentin elimination in anuric subjects.

Impaired hepatic function
No study was performed in patients with hepatic impairment, because gabapentin is not metabolized.

Age
The effect of age was studied in subjects 20–80 years of age. Apparent oral clearance of gabapentin decreased as age increased, from about 225 ml/minutes in those less than 30 years of age to about 125 ml/minutes in those over 70 years of age. Renal clearance adjusted for body surface area also declined with age. However, the decline in the renal clearance of gabapentin with age can largely be explained by the decline in renal function. Reduction of gabapentin dose may be required in patients who have age related compromised renal function.

Children
In general, pediatric subjects between 1 month and less than 5 years of age achieved approximately 30% lower exposure (AUC) than that observed in those 5 years of age and older. Accordingly, oral clearance normalized per body weight was higher in the younger children. Apparent oral clearance of gabapentin was directly proportional to creatinine clearance. Gabapentin elimination half-life averaged 4.7 hours and was similar across the age groups studied. The normalized clearance values observed in pediatric patients 5 years of age and older were consistent with values observed in adults after a single dose. The oral volume of distribution normalized per body weight was constant across the age range.

Gender
The pharmacokinetic parameters for males and females are no significant differences.

Ethnic
Although no formal studies have been conducted, ethnic-based differences in pharmacokinetics are not expected.

Indications:
Gabapentin is indicated as an adjunctive therapy to standard antiepileptic drugs in patients who cannot be controlled with antiepileptic drugs either single or in combination, or in patients who are intolerant to doses of these drugs. Gabapentin as add-on therapy is indicated for treatment of simple and complex partial seizures and secondarily generalized tonic-clonic seizures

Contraindication:
Gabapentin is contraindicated in patients with known hypersensitivity to the drug.

Dosage and administration:
General

  • Administration: Gabapentin can be given orally with or without food.
  • Dosage: The effective dose for adults and children >12 years was 900 to 1,800 mg/day given in divided doses (three times a day). Titration to an effective dose can take place rapidly, over a few days, by giving 300 mg gabapentin on the first day, 300 mg gabapentin twice a day on the second day, and 300 mg gabapentin three times a day on the third day. Further, dose may be given 1,200 mg/day in divided doses (three times a day) and if necessary, the dose may be increased using 300 mg tablets three times a day up to maximum 2,400 mg/day and the maximum time between doses in the three times a day schedule should not exceed 12 hours.

Adverse effects:

  • Nervous system: drowsiness, dizziness or ataxia, fatigue, nystagmus, tremor, nervousness, dysarthria, amnesia, depression, twitching, abnormal coordination, headache, confusion, insomnia, abnormal thinking, and emotional lability.
  • Gastrointestinal: dyspepsia, dry mouth or throat, constipation, dental abnormalities, increased appetite, nausea, vomiting, abdominal pain, diarrhea, and anorexia.
  • Cardiovascular: peripheral edema, vasodilatation, hypertension, hypotension, angina pectoris, peripheral vascular disorder, palpitation, tachycardia, heart murmur, and generalized edema.
  • Respiratory: rhinitis, pharyngitis, coughing, pneumonia, epistaxis, and dyspnea.
  • Musculoskeletal: myalgia, arthralgia, back pain and fracture.
  • Dermatology and sensitivity reactions: pruritus or abrasion, rash or acne.
  • Hematologic: leukopenia, purpura, anemia, and thrombocytopenia.
  • Ocular and otic: diplopia and amblyopia.

 

Warnings and precautions:

  • Instruct patients to take gabapentin only as prescribed.
  • Gabapentin should not be stopped suddenly but withdrawn gradually over a minimum period of at least 1 week because of the possibility of increased seizure frequency.
  • Patients should be advised not to drive a motor vehicle, or operate machinery as gabapentin may cause drowsiness and other symptoms and signs of central nervous system suppression.
  • Effect of gabapentin in the incidence of new tumors in humans or worsening or recurrence of tumor at diagnosis of the tumor that was not previously known.
  • Safety and efficacy of gabapentin in geriatric patients have not been evaluated systematically, and clinical trials did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently than younger patients.
  • Gabapentin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus because there are no adequate and well-controlled studies in pregnant women.
  • There is no information on whether gabapentin is excreted in human breast milk. Because of the potential for serious adverse reactions in nursing infants from gabapentin, a decision should be made whether to discontinue nursing or to discontinue the medication, taking into account the importance of the drug to the mother.

 

Drugs interactions:

  • Gabapentin is not appreciably metabolized nor does it interfere with the metabolism of commonly coadministered antiepileptic drugs.
  • Antacids, especially those containing,alumunium and magnesium, reduced gabapentin bioavailability up to 24%. It is recommended that gabapentin be taken at least 2 hours following antacids administration.
  • Food has no effect on the pharmacokinetics of gabapentin.
  • Oral contraceptive containing norethisterone and ethinyl estradiol did not influence the pharmacokinetics of gabapentin when administered concomitantly with gabapentin.
  • Renal excretion of gabapentin was unaltered by probenecid.
  • When gabapentin was added to other antiepileptic drugs, the more specific sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine protein. False positive readings were reported with the Ames N-Multistix SG dipstick test for urinary protein.

 

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

Presentation and registration number:
Box, 3 blisters @ 10 capsules;

ON MEDICAL PRESCRIPTION ONLY

STORE AT TEMPERATURE BELOW 30ºC, PROTECT FROM LIGHT

Manufactured by:
PT Dexa Medica