EMESSA LABS

NOROGAB 100

Each capsule contains Gabapentin 100 mg

Powder

Box of 20 capsules

 160 sp

 132 sp

Miscellaneous

The mechanism by which gabapentin exerts its analgesic action is unknown,but in animal models of
analgesia , gabapentin prevents allodynia (pain -related behavior in response to a normally innocuous
stimulus) and hyperalgesia, in particular, gabapentin prevents pain-related responses in several models of neuropathic pain (e.g. spinal nerve ligation models, steptozocin - induced diabetes model, spinal cord injury model, acute herpes zoster infection model).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 gabapentin exhibits antiseizure activity in both the maximal electroshock and pentylenetetrazole seizure models and other preclinical models.
Gabapentin is structurally related to the neurotransmitter NOROGAB (gamma-aminobutyric acid) but it does not converted metabolically into NOROGAB or NOROGAB agonist, and it is not an inhibitor of GABA uptake or degradation.
Gabapentin did not exhibit affinity for a number of other common receptor sites, including benzodiazepine, glutamate, N-methyl-D-aspartate, (NMDA), alpha 1, alpha 2, or beta adrenergic,
dopamine D1 or D2, histamine H1, serotonin S1, S2, voltage - sensitive calcium channel sites.
Furthermore, gabapentin did not alter the uptake of dopamine,noradrenaline,or serotonin.

1- postherpatic Neuralgia:
NOROGAB (gabapentin) is indicated for the management of postherpetic neuralgia in adults.
2-Peripheral Neuropathic Pain.
3- Epilepsy:
NOROGAB (gabapentin) is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients over 12 years of age with epilepsy.NOROGAB is indicated also as adjunctive therapy in the treatment of partial seizures in pediatric patients age 3 – 12 years.

NOROGAB is contraidicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.

- Due to postherpatic Neuralgia Treatment:
Dizziness, somnolence, and peripheral edema were observed, and were not seen among placebo- treated patients.
The adverse events that most frequently led to withdrawal in gabapentin –treated patients were dizziness, somnolence, and nausea.
Adverse events were usually mild to moderate intensity, other adverse events were reported in a trial on the treatment of postherpatic neuralgia, the incidence of these adverse events was about 1% of gabapentin –treated patients as compared with placebo group:
-Body as a whole: Asthenia, infection, headache, accidental injury, abdominal pain.
-Digestive disorders: diarrhea, dry mouth, constipation, nausea, vomiting, flatulence.
-Metabolic and nutritional disorders: peripheral edema, weight gain,hyperglycemia.
-Nervous system: dizziness, somnolence, ataxia, thiking abnormal, abnormal gait, incoordination, amnesia, hypesthesia.
-Respiratory system: pharyngitis.
-Skin & Appendages: rash.
-Special senses: amblyopia, conjunctivitis , diplopia, otitis media.
- Due To Epilepsy Treatment:
The most commonly observed adverse events associated with the use of gabapentin in combination with other antiepileptic drugs in patients >12 years of age, not seen at an equivalent frequency among placebo-treated paients,were somnolence, dizziness, ataxia, fatigue, and nystagmus. In pediatric patients 3 to 12 years of age, viral infection, fever, nausea, and / or vomiting, somnolence,
and hostility, and 7% of 2074 patients > 12 years of age, and 7% of 449 pediatric patients 3 to 12 years of age who received gabapentin discontinue treatment because of an adverse events.
The adverse events associated with withdrawl of gabapentin from the therapeutic regimen in patients >12 year of age were somnolence, ataxia, fatigue, nausea or vomiting and dizziness, the adverse events most commonly associated with withdrawal of gabapentin from the combination therapy in pediatric patients were emotional lability, hostility and hyperkinesia.
The following adverse events in patients >12 years of age were more frequent than in the placebo group:
- Body as a whole : fatigue, weight increase, back pain, peripheral edema.
- Cardiovasculare: vasodilation.
- Digestive system: dyspepsia, mouth or throat dry , constipation, dental abnormalities, increased appetite.
- Hematologic and lymphatic systems: lenkopenia.
- Musculoskeletal system: maylgia, fructure.
- Nervous system: somnolence, dizziness, ataxia, nystagmus, tremor, nervousness, dysarthria, amnesia, depression, thinking abnormal, twitching, corrdination abnormal.
- Respiratory system : rhinitis, pharyngitis, coughing.
- Skin and appendages: abrasion, pruritus.
- Urogenital system: impotence.
- Special senses: diplopia, amblyopia.
Adverse events that were reported in pediatric patients aged between 3 to 12 years and
incidence were at least 2%:
Viral infections, fever, weight increase, fatigue, nausea and vomiting, somnolence, hostility, emotional lability, dizziness, hyperkinesias, bronchitis, respiratory infection.
Other adverse events observed during all clinical trials in adults and adolescents with epilepsy, when gabapentin has been used as adjunctive therapy in epilepsy treatment in clinical trials, the incidence of occuring of these adverse events were fewer than 1/1000 patients.
- Body as a whole: asthenia, malaise, face edema, allergy, generalized edema.
- Cardiovascular system: hypertension,hypotension (in frequent), angina pectoris, palpitation, tachycardia, migraine, murmur , heart failure.
- Digestive system : anorexia, flatulence, gingivitis.
- Endocrine system: hyperthyroid, hypothyroid, goiter, swollen testicle.
- Hematologic and lymphatic system: purpura, anemia, thrombocytopenia.
- Musculoskeletal system: arthralgia, tendinitis, joint stiffness, joint swelling.
- Nervous system: vertigo, hyperkinesia, decreased or absent reflexes, increased reflexes, anxiety, hostility.
- Respiratory system: pneumonia, dyspnea, apnea.
- Dermatological: alopecia, eczema, seborrhea, photosensetive reaction.
- Urogential system: hematoria, dysuria, urination frequency, cyctitis.
- Special senses: abnormal vision, conjunctivitis, eyes dry, eye pain.
Adverse events occuring during the treatment of epilepsy with gabapentin in pediatric patients 3 to 12 years
- Body as a whole : dehydration, infectious mononucleosis.
- Digestive system: hepatitis.
- Hemic and lymphatic system: coagulation defect.
- Nervous system: aura disappeared, occipital neuralgia.
- Psychobiological function: sleepwalking.
- Respiratory system: pseudocroup, hoarseness.
Adverse events which obtained from clinical trials in adults with neuropathic pain of various etiologies:
- Body as a whole: chest pain, cellulites, malaise, neck pain.
- Cardiovascular system: hypertension, syncope, hypotension, peripheral vascular disorders.
- Digestive system: gastroenteritis, increased appetite, thirst, liver function tests abnormal.
- Edocrine system: infrequent: diabets mellitus.
- Hemic and lymphatic system: ecchymosis, anemia, rare: prothrombin decreased.
- Metabolic and nutritional: gout, hypoglycemia, weight loss.
- Musculoskeletal: arthralgia, myalgia, infrequent arthrosis.
- Nervous system: confusion, depression, infrequent: vertigo, nervousness, abnormal dreams, nystagmus.
- Respiratory system: cough, rhinitis, asthma, pneumonia, all these adverse events are classified between infrequent to rare.
- Special senses: abnormal vision, ear pain, eye disorders, taste perversion, deafness, rare: retinal, vein thrombosis.
- Urogential system: urinary tract infection, dysuria, impotence, urinary incontinence, breast pain, menstrual disorder, polyuria.

Neuropsychiatric adverse events in pediatric patients 3 to 12 years of age: the use of gabapentin in pediatric patients 3 - 12 years of age with epilepsy is associated with the occurence of
1)primarily behavioral problems, 2) hostility including aggressive behaviors 3)thought disorder including concentration problems and change in school performance, and 4)hyperkinesia (primarily restlessness and hyperactivity).But most of the events were mild to moderate in intensity.
- withdrawal precipitated seizure, status epilepticus:
Antieplieptic drugs should not be abruptly discontinued because of the possibility of
increasing seizure frequency.
- Tumorigenic potential:
Clinical experience during gabapentin therpay assess its potential for inducing new tumors in (10) patients from 2085 patients, and preexisting tumors worsened in (11) patients, during or up to 2 years follwing discontinuation of gabapentin therapy.
- pancreatitis:
Hemorrhagic pancreatitis has been reported, therefore treatment should be discontinued immediately when the first sign of pancreatitis appear (continued abdominal pain, nausea, reapeted votiming) in addition, clinically and laboratory testes should be done to assure the early diagnosis of this condition .
- Sudden and unexplained death in patients with epilepsy:
Some of these could represent seizure-related death in which the seizure was not observed e.g. at night, this represents an incidence of 0.0038 death per patient-year.
Patients sould be instructed to take NOROGAB only as prescribed and patients sould be advised that NOROGAB 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.
Patients who require concomitant treatment with morphine may experience increase in gabapentin concentrations. Patients should be carefully observed for sign of CNS depression and the dose of gabapentin or morphine should be reduced appropriately to avoid CNS or somnolence.
NOROGAB may be used in combination with other antiepileptic drugs without concern for the alteration of the blood concentration of gabapentin or of other antiepileptic drugs.

- Postherpatric Neuralgia:
In adults with postherpatic neuralgia, NOROGAB therapy may be initiated as a single 300-mg dose on day 1, 600mg/day on day 2 (divided BID), AND 900mg/day on day 3 (divided TID). The dose can subsequently be titrated up as needed for pain relief to a daily dose of 1800mg (divided TID).
In clinical studies, efficacy was demonstrated over a range of doses from 1800mg/day to 3600mg/day with comparable effects across the dose range.
Additional benefit of using doses greater than 1800/day was not demonstrated
-Peripheral Neuropathic Pain:
Initially 300 mg once daily on day 1, then 300 mg twice in day 2, then 300 mg 3 times on day 3, then increased up to 3.6 g daily.
- Epilepsy:
NOROGAB is recommended for add-on therapy in patients 3 years of age and older.
• Patients > 12 years of age:
The effective dose of NOROGAB is 900 to 1800mg / day and given in divided doses (three times a day) using 300mg or 400mg capsules or 600 or 800mg tablets.
If necessary the dose may be increased using 300 or 400 capsules or 600 or 800mg tablets, three times a day up to 1800mg/day.
Dosages up to 2400mg/ day have been well tolerated, doses of 3600mg /day have also been administered for a short duration and have been well tolerated.
The maximum time between doses in the three times a day schedule should not exceed 12 hours.
• Pediatric patients age 3-12 years :
The starting dose should range from 10 –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 for patients 5 years of age and older is 25 – 35mg/ kg/ day and given in divided doses (three times a day).
Dosages up to 50mg/ kg/ day have been well-tolerated and the maximum time interval between doses should not exceed 12 hours.
If GABAN is discontinued and / or an alternate anticonvulsants medication is added to the therapy, this should be done gradually over a minimum of 1 week.
• Dosage in renal impairment:
In patients with stable renal function creatinine can be reasonably well estimated.
Dosage adjustment in patients ≥ 12 years of age with compromised renal functions or undergoing hemodialysis is recommended as follows in Table (1):
Table (1)
- Renal Function Creatinine Clearance(mL/min): ≥60
Total dialy dosemg/Day: 900-3600.
Dose Rgimen(mg):
300 TID - 400 TID - 600 TID - 800 TID - 1200 TID

- Renal Function Creatinine Clearance(mL/min): >30-59
Total dialy dosemg/Day: 400-1400.
Dose Rgimen(mg):
200 BID - 300 BID - 400 BID - 500 BID - 700 BID

- Renal Function Creatinine Clearance(mL/min): >15-29
Total dialy dosemg/Day: 200-700.
Dose Rgimen(mg):
200 QD - 300 QD - 400 QD - 500 QD - 700 QD

For patients with creatinine clearance < 15mL/min, reduce daily dose in proportion to creatinine clearance (e.g.., patients with creatinine clearance of 7.5mL/min should receive one – half the daily dose that patients with a creatinine clearance of 15mL/min receive.
Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the table (1) and supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the table (2):
Table (2):
-Kidney Function: Hemodialysis.
- Post-Hemodialysis supplemental Dose(mg):
125 - 150 - 200 - 250 - 350
Dosage in Eldery:
Because eldery patients are more likely to have decreased renal function, care should be taken in dose selection, and should be adjusted based on creatinine clearance values in these patients.