Rontin

Gabapentin.

Rontin is available in 2 dosage forms.
Capsules: Each capsule contains 300 mg of Gabapentin.
Tablets: Each film coated tablet contains 600 mg of Gabapentin.

Pharmacology: Pharmacodynamics: Gabapentin is structurally related to the neurotransmitter GABA (gamma amino butyric acid) but its mechanism of action is different from that of several other drugs that interact with GABA synapses including valproate, barbiturates, benzodiazepines, GABA transaminase inhibitors, GABA uptake inhibitors, GABA agonists, and GABA prodrugs. In vitro studies with radiolabeled gabapentin have characterized a novel peptide binding site in rat brain tissues including neocortex and hippocampus that may relate to anticonvulsant activity of gabapentin and its structural derivatives. However, the identification and function of the gabapentin binding site remains to be elucidated.
In animals, gabapentin readily enters the brain and prevents seizures from maximal electroshock, from chemical convulsants including inhibitors of GABA synthesis, and in genetic models of seizures.
The mechanism by which gabapentin exerts its analgesic action is unknown.
ln particular, gabapentin presents pain related responses in several models of neuropathic pain in rats or mice.
Gabapentin also decreases pain-related responses after peripheral inflammation. However, the drug has not altered immediate pain-related behaviors. The clinical relevance of these findings is not known.
Pharmacokinetics: Gabapentin bioavailability is not dose-proportional. That is, as the dose is increased, bioavailability decreases. Following oral administration peak plasma gabapentin concentrations are observed with 2 to 3 hours.
Bioavailability of gabapentin is approximately 60%, 47%, 34%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day given in 3 divided doses, respectively. Food has only a slight effect on rate and extent of absorption of gabapentin.
Gabapentin is not bound to plasma proteins and has a volume of distribution equal to 57.7 liters. In patients with epilepsy, gabapentin concentration in CSF are approximately 20% of corresponding steady-state trough plasma concentrations.
Gabapentin is eliminated from the systemic circulation by renal excretion as unchanged drug.
Gabapentin does not induce hepatic mixed function oxidase enzymes responsible for drug metabolism. Gabapentin elimination rate constant, plasma clearance, and renal clearance, are directly proportional to creatinine plasma clearance. In elderly patients, and in patients with impaired renal function, gabapentin plasma clearance is reduced. Dosage adjustment in patients undergoing hemodialysis is necessary and dose should be adjusted based on creatinine clearance values in these patients. Gabapentin can be removed from plasma by hemodialysis.

Epilepsy: Gabapentin is indicated as monotherapy in the treatment of partial seizures with and without secondary generalization in adults and children over 12 years of age.
Gabapentin is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in adults and children age 3 years and above.
Neuropathic pain: Gabapentin is indicated for the treatment of neuropathic pain in adults age 18 years and above.

General: Gabapentin can be given with or without food.
Discontinuation of gabapentin: In accordance with current clinical practice, if gabapentin has to be discontinued it is recommended this should be done gradually over a minimum of 1 week independent of the indication.
Epilepsy: Adults and pediatric patients over 12 years of age: The effective dosage of gabapentin is 900 to 3600 mg daily administered in 3 divided doses. Therapy may be initiated by titrating the dose as described in Table 1 or by administering 300 mg three times a day in Day 1. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day up to a maximum does of 3,600 mg/day. The total daily dose should be divided in three single doses, the maximum time interval between the dose should not exceed 12 hours to prevent breakthrough convulsions. (See Table 1.)

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Pediatric patient age 3 - 12 years: The starting dose should range from 10 to 15 mg/kg/day in 3 divided dose, and the effective dose reached by upward titration over a period of approximately three days. The effective does of gabapentin in children age 5 years and older is 25 to 35 mg/kg/day. The effective dose in pediatric patients ages 3 to less than 5 years is 40 mg/kg/day. The total daily dose should be divided in three single dose the maximum time interval between doses should not exceed 12 hours to prevent breakthrough convulsion.
It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin therapy. Further, gabapentin may be used in combination with other antiepileptic medicinal products without concern for alteration of the plasma concentrations of gabapentin or serum concentrations of other antiepileptic medicinal products.
Neuropathic pain in adults: The therapy may be initiated by titrating the dose as described in Table 1, or by administering 300 mg three times a day. Thereafter, based on individual patient response and tolerability, the dose can be increased up to a maximum dose of 3600 mg/day.
Use in patients with renal impairment: The following dosages are recommended in patients with compromised renal function and/or those undergoing haemodialysis. (See Table 2.)

Click on icon to see table/diagram/image

Use in patients undergoing haemodialysis: For patients undergoing haemodialysis who have never received gabapentin, a loading dose of 300 to 400 mg is recommended, then 200 mg to 300 mg of gabapentin following each 4 hours of haemodialysis.

Symptoms: Acute, life-threatening toxicity has not been observed in human with gabapentin overdose of up to 49 grams. In these cases, double vision, slurred speech, drowsiness, lethargy and diarrhea were observed. All patients recovered with supportive case.
Treatment: Reduced absorption of gabapentin at higher doses may limit drug absorption at the time of overdosing and, hence, minimise toxicity from overdoses.
Gabapentin can be removed by haemodialysis. Although haemodialysis has not been performed in the few overdose cases reported, it may be indicated in patients with significant renal impairment.

Gabapentin is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation.

Because of the possibility of increased seizure frequency, anticonvulsant drugs, including gabapentin, should not be discontinued suddenly.
Gabapentin is not generally considered effective in the treatment of absence seizures. In combination treatment with morphine, these patients should be carefully observed for signs of CNS depression, such as somnolence, and the dose of gabapentin or morphine should be reduced appropriately.
Effects on ability to drive and use machines: Gabapentin can produce drowsiness and dizziness, and patients should be cautioned that the drug may impair their ability to perform activities such as operating machinery or operating a motor vehicle.

Pregnancy: There are no adequate data from the use of gabapentin in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit to the patient justifies the potential risk to the fetus.
Lactation: Gabapentin is excreted in human milk. Because the effect on the nursing infant is unknown, use gabapentin in nursing mother only if the benefits clearly outweigh the risk.

Body as a Whole: abdominal pain, back pain, fatigue, fever, headache, viral infection, asthenia malaise, facial edema.
Cardiovascular: vasodilation, hypertension.
Digestive System: constipation, dental abnormalities, diarrhea, dyspepsia, increased appetite, mouth or throat dry, nausea, vomiting, flatulence, anorexia, gingivitis.
Haematologic and Lymphatic: leukopenia, WBC decreased, purpura.
Metabolic and Nutritional: peripheral edema, weight increase.
Musculoskeletal System: fracture, myalgia, arthralgia.
Nervous System: amnesia, ataxia, confusion, coordination abnormal, depression, dizziness, dysarthria, emotional lability, insomnia, nervousness, nystagmus, somnolence, thinking abnormal, tremor, twitching, vertigo, hyperkinesia, increased/decreased or absent reflexes, paresthesia, anxiety, hostility.
Respiratory System: coughing, pharyngitis, rhinitis, pneumonia.
Skin and Appendages: abrasion, acne, pruritus, rash.
Special Senses: amblyopic, diplopia, abnormal vision.
Urogenital System: impotence, urinary tract infection.

Antacids: Coadministration of gabapentin with antacid reduced gabapentin bioavailability by about 20%.
It is recommended that gabapentin be taken at least 2 hours following antacid administration.
Cimetidine: Cimetidine alters the renal excretion of gabapentin. This small decrease in gabapentin excretion is not expected to be of clinical importance.

Capsules (300 mg): Store at temperature not exceeding 25°C.
Tablets (600 mg): Store at temperature not exceeding 30°C.

Anticonvulsants / Drugs for Neuropathic Pain

N02BF01 - gabapentin ; Belongs to the class of gabapentinoids. Used to relieve pain and other conditions.

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