Neurontin 300, 400 mg

/ Dexcel

For all indications a titration scheme for the initiation of therapy described below, which is recommended for adults and adolescents aged 12 years and above:
1^st day: 300 mg once a day.
2^nd day: 300 mg two times a day.
3^rd day: 300 mg three times a day.
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: Epilepsy typically requires long-term therapy. Dosage is determined by the treating physician according to individual tolerance and efficacy.
Adults and adolescents: In clinical trials, the effective dosing range was 900 to 3600 mg/day. Therapy may be initiated by titrating the dose as described in Table 1 or by administering 300 mg three times a day (TID) on Day 1. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day increments every 2-3 days up to a maximum dose of 3600 mg/day. Slower titration of gabapentin dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks. Dosages up to 4800 mg/day have been well tolerated in long-term open-label clinical studies. The total daily dose should be divided in three single doses, the maximum time interval between the doses should not exceed 12 hours to prevent breakthrough convulsions. 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
Adults: The therapy may be initiated by titrating the dose as described above. Alternatively, the starting dose is 900 mg/day given as three equally divided doses. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day increments every 2-3 days up to a maximum dose of 3600 mg/day. Slower titration of gabapentin dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks. In the treatment of peripheral neuropathic pain such as painful diabetic neuropathy and post-herpetic neuralgia, efficacy and safety have not been examined in clinical studies for treatment periods longer than 5 months. If a patient requires dosing longer than 5 months for the treatment of peripheral neuropathic pain, the treating physician should assess the patient’s clinical status and determine the need for additional therapy.
Instruction for all areas of indication: In patients with poor general health, i.e., low body weight, after organ transplantation etc., the dose should be titrated more slowly, either by using smaller dosage strengths or longer intervals between dosage increases.
Use in elderly patients (over 65 years of age): Elderly patients may require dosage adjustment because of declining renal function with age (see Table 2). Somnolence, peripheral oedema and asthenia may be more frequent in elderly patients.
Use in patients with renal impairment: Dosage adjustment is recommended in patients with compromised renal function as described in Table 2  at the attached doctor’s leaflet and/or those undergoing haemodialysis.
Use in patients undergoing haemodialysis: For anuric patients undergoing haemodialysis who have never received gabapentin, a loading dose of 300 to 400 mg, then 200 to 300 mg of gabapentin following each 4 hours of haemodialysis, is recommended. On dialysis-free days, there should be no treatment with gabapentin. For renally impaired patients undergoing haemodialysis, the maintenance dose of gabapentin: See prescribing information for full details. In addition to the maintenance dose, an additional 200 to 300 mg dose following each 4-hour haemodialysis treatment is recommended.
See prescribing information for full details.
Method of administration: For oral use. Gabapentin can be given with or without food and should be swallowed whole with sufficient fluid-intake (e.g. a glass of water).

Epilepsy: Gabapentin is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in adults and adolescents (age 12 and up) with epilepsy.
Treatment of neuropathic pain: Gabapentin is indicated for the treatment of neuropathic pain in diabetic neuropathy or post-herpetic neuropathy (neuralgia) in adults.

Hypersensitivity to the active substance or to any of the excipients.

Severe cutaneous adverse reactions (SCARs): Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and Drug rash with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported in association with gabapentin treatment. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, gabapentin should be withdrawn immediately and an alternative treatment considered (as appropriate).
If the patient has developed a serious reaction such as SJS, TEN or DRESS with the use of gabapentin, treatment with gabapentin must not be restarted in this patient at any time.
Anaphylaxis: Gabapentin can cause anaphylaxis. Signs and symptoms in reported cases have included difficulty breathing, swelling of the lips, throat, and tongue, and hypotension requiring emergency treatment. Patients should be instructed to discontinue gabapentin and seek immediate medical care should they experience signs or symptoms of anaphylaxis.
Suicidal ideation and behaviour: Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known. Cases of suicidal ideation and behaviour have been observed in patients treated with gabapentin in the post-marketing experience.
Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. Patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Discontinuation of gabapentin treatment should be considered in case of suicidal ideation and behaviour.
Acute pancreatitis: If a patient develops acute pancreatitis under treatment with gabapentin, discontinuation of gabapentin should be considered.
Seizures: Although there is no evidence of rebound seizures with gabapentin, abrupt withdrawal of anticonvulsants in epileptic patients may precipitate status epilepticus. As with other antiepileptic medicinal products, some patients may experience an increase in seizure frequency or the onset of new types of seizures with gabapentin.
As with other anti-epileptics, attempts to withdraw concomitant anti-epileptics in treatment refractive patients on more than one anti-epileptic, in order to reach gabapentin monotherapy have a low success rate.
Gabapentin is not considered effective against primary generalized seizures such as absences and may aggravate these seizures in some patients. Therefore, gabapentin should be used with caution in patients with mixed seizures including absences.
Gabapentin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall). There have also been post-marketing reports of confusion, loss of consciousness and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication.
Concomitant use with opioids and other CNS depressants: Patients who require concomitant treatment with opioids should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence, sedation and respiratory depression. Patients who use gabapentin and morphine concomitantly may experience increases in gabapentin concentrations. The dose of gabapentin or opioids should be reduced appropriately.
Respiratory depression: Gabapentin has been associated with severe respiratory depression. Patients with compromised respiratory function, respiratory or neurological disease, renal impairment, concomitant use of CNS depressants and the elderly might be at higher risk of experiencing this severe adverse reaction. Dose adjustments might be necessary in these patients.
Elderly (over 65 years of age): No systematic studies in patients 65 years or older have been conducted with gabapentin. In one double blind study in patients with neuropathic pain, somnolence, peripheral oedema and asthenia occurred in a somewhat higher percentage in patients aged 65 years or above, than in younger patients. Apart from these findings, clinical investigations in this age group do not indicate an adverse event profile different from that observed in younger patients.
Paediatric population: The effects of long-term (greater than 36 weeks) gabapentin therapy on learning, intelligence, and development in children and adolescents have not been adequately studied. The benefits of prolonged therapy must therefore be weighed against the potential risks of such therapy.
Misuse, abuse potential and dependence: Gabapentin can cause drug dependence, which may occur at therapeutic doses. Cases of abuse and misuse have been reported. Patients with a history of substance abuse may be at higher risk for gabapentin misuse, abuse and dependence, and gabapentin should be used with caution in such patients. Before prescribing gabapentin, the patient’s risk of misuse, abuse or dependence should be carefully evaluated.
Patients treated with gabapentin should be monitored for signs and symptoms of gabapentin misuse, abuse or dependence, such as development of tolerance, dose escalation and drug-seeking behaviour.
Withdrawal symptoms: After discontinuation of short-term and long-term treatment with gabapentin, withdrawal symptoms have been observed.
Withdrawal symptoms may occur shortly after discontinuation, usually within 48 hours. Most frequently reported symptoms include anxiety, insomnia, nausea, pains, sweating, tremor, headache, depression, feeling abnormal, dizziness, and malaise. The occurrence of withdrawal symptoms following discontinuation of gabapentin may indicate drug dependence. The patient should be informed about this at the start of the treatment. If gabapentin should be discontinued, it is recommended this should be done gradually over a minimum of 1 week independent of the indication.
Laboratory tests: False positive readings may be obtained in the semi-quantitative determination of total urine protein by dipstick tests. It is therefore recommended to verify such a positive dipstick test result by methods based on a different analytical principle such as the Biuret method, turbidimetric or dye-binding methods, or to use these alternative methods from the beginning.
Neurontin capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Very Common: Viral infection, somnolence, dizziness, ataxia, fatigue, fever.
Common: Convulsions, hyperkinesias, dysarthria, amnesia, tremor, insomnia, headache, sensations such as paresthesia, hypaesthesia, coordination abnormal, nystagmus, increased, decreased, or absent reflexes, pneumonia, respiratory infection, urinary tract infection, infection, otitis media, leucopenia , anorexia, increased appetite,  hostility, confusion and emotional lability, depression, anxiety, nervousness, thinking abnormal, visual disturbances such as amblyopia, diplopia, vertigo, hypertension, vasodilatation, dyspnoea, bronchitis, pharyngitis, cough, rhinitis, vomiting, nausea, dental abnormalities, gingivitis, diarrhoea, abdominal pain, dyspepsia, constipation, dry mouth or throat, flatulence, facial oedema, purpura most often described as bruises resulting from physical trauma, rash, pruritus, acne, arthralgia, myalgia, back pain, twitching, impotence, WBC (white blood cell count) decreased, weight gain, accidental injury, fracture, abrasion.
See prescribing information for full details.

There are spontaneous and literature case reports of respiratory depression and/or sedation associated with gabapentin and opioid use. In some of these reports, the authors considered this a particular concern with the combination of gabapentin and opioids, especially in elderly patients.
In a study involving healthy volunteers (N=12), when a 60 mg controlled-release morphine capsule was administered 2 hours prior to a 600 mg gabapentin capsule, mean gabapentin AUC increased by 44% compared to gabapentin administered without morphine. Therefore, patients who require concomitant treatment with opioids should be carefully observed for signs of CNS depression, such as somnolence, sedation and respiratory depression and the dose of gabapentin or opioid should be reduced appropriately.
No interaction between gabapentin and phenobarbital, phenytoin, valproic acid or carbamazepine has been observed.
Gabapentin steady-state pharmacokinetics are similar for healthy subjects and patients with epilepsy receiving these antiepileptic agents.
Co-administration of gabapentin with oral contraceptives containing norethindrone and/or ethinyl estradiol, does not influence the steady-state pharmacokinetics of either component.
Co-administration of gabapentin with antacids containing aluminium and magnesium, reduces gabapentin bioavailability up to 24%. It is recommended that gabapentin be taken at the earliest two hours following antacid administration.
Renal excretion of gabapentin is unaltered by probenecid.
A slight decrease in renal excretion of gabapentin that is observed when it is coadministered with cimetidine is not expected to be of clinical importance.     

Pregnancy:
Risk related to epilepsy and antiepileptic drugs (AEDs) in general:  Specialist advice regarding the potential risk to a foetus caused by both seizures and antiepileptic treatment should be given to women of childbearing potential, and especially to women planning for pregnancy and women who are pregnant. The need for antiepileptic treatment should be reviewed when a woman is planning to become pregnant. In women being treated for epilepsy, no sudden discontinuation of antiepileptic therapy should be undertaken as this may lead to breakthrough seizures, which could have serious consequences for both mother and child. Monotherapy should be preferred whenever possible because therapy with multiple AEDs could be associated with a higher risk of congenital malformations than monotherapy, depending on the antiepileptics used.
Risk related to gabapentin: Gabapentin crosses the human placenta.
Data from a Nordic observational study of more than 1700 pregnancies exposed to gabapentin in the first trimester showed no higher risk of major congenital malformations among the children exposed to gabapentin compared to the unexposed children and compared to the children exposed to pregabalin, lamotrigine and pregabalin or lamotrigine. Likewise, no increased risk of neurodevelopmental disorders was observed in children exposed to gabapentin during pregnancy.
There was limited evidence of a higher risk of low birth weight and preterm birth but not of stillbirth, small for gestational age, low Apgar score at 5 minutes and microcephaly in newborns of women exposed to gabapentin.
Studies in animals have shown reproductive toxicity.
Gabapentin can be used during the first trimester of pregnancy if clinically needed.
Neonatal withdrawal syndrome has been reported in newborns exposed in utero to gabapentin. Co-exposure to gabapentin and opioids during pregnancy may increase the risk of neonatal withdrawal syndrome. Newborns should be monitored carefully.
Lactation:
Gabapentin is excreted in human milk. Because the effect on the breast-fed infant is unknown, caution should be exercised when gabapentin is administered to a breast-feeding mother. Gabapentin should be used in breast-feeding mothers only if the benefits clearly outweigh the risks.

Acute, life-threatening toxicity has not been observed with gabapentin overdoses of up to 49 g. Symptoms of the overdoses included dizziness, double vision, slurred speech, drowsiness, loss of consciousness, lethargy and mild diarrhoea. All patients recovered fully with supportive care. Reduced absorption of gabapentin at higher doses may limit drug absorption at the time of overdosing and, hence, minimize toxicity from overdoses.
Overdoses of gabapentin, particularly in combination with other CNS depressant medications, may result in coma.
Although gabapentin can be removed by haemodialysis, based on prior experience it is usually not required. However, in patients with severe renal impairment, haemodialysis may be indicated.
An oral lethal dose of gabapentin was not identified in mice and rats given doses as high as 8000 mg/kg. Signs of acute toxicity in animals included ataxia, laboured breathing, ptosis, hypoactivity, or excitation.

Storage: Store in a dry place below 25°C.