GABAPENTIN NOUMED

Posology:

For all indications a titration scheme for the initiation of therapy is described in Table 1, which is recommended for adults and adolescents aged 12 years and above. Dosing instructions for children under 12 years of age are provided under a separate sub- heading later in this section.

4). Treatment should be given for the shortest possible duration. If this medicine is being used for the treatment of epilepsy this medicine should be used for as long as the prescriber considers it necessary 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.

Children aged 6 years and above:

The starting dose should range from 10 to 15 mg/kg/day and the effective dose is reached by upward titration over a period of approximately three days. The effective dose of gabapentin in children aged 6 years and older is 25 to 35 mg/kg/day.

Dosages up to 50 mg/kg/day have been well tolerated in a long-term clinical study. The total daily dose should be divided in three single doses, the maximum time interval between doses should not exceed 12 hours. 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.

Peripheral neuropathic pain Adults The therapy may be initiated by titrating the dose as described in Table 1. 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.

, the dose should be titrated more slowly, either by using smaller dosage strengths or longer intervals between dosage increases. Elderly (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. Renal impairment Dosage adjustment is recommended in patients with compromised renal function as described in Table 2 and/or those undergoing haemodialysis.

Gabapentin 100 mg capsules can be used to follow dosing recommendations for patients with renal insufficiency. Table 2 DOSAGE OF GABAPENTIN IN ADULTS BASED ON RENAL FUNCTION Creatinine Clearance (mL/min) Total Daily Dosea (mg/day) ≥80 900-3600 50-79 600-1800 30-49 300-900 15-29 150b-600 <15c 150b-300 a Total daily dose should be administered as three divided doses.

Reduced dosages are for patients with renal impairment (creatinine clearance < 79 mL/min). b The 150 mg daily dose to be administered as 300 mg every other day. 5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).

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 should be based on the dosing recommendations found in Table 2. In addition to the maintenance dose, an additional 200 to […]

The adverse reactions observed during clinical studies conducted in epilepsy (adjunctive and monotherapy) and neuropathic pain have been provided in a single list below by class and frequency (very common (1/10); common (1/100 to < 1/10); uncommon (1/1000 to < 1/100); rare (1/10000 to < 1/1000); very rare (< 1/10000).

Where an adverse reaction was seen at different frequencies in clinical studies, it was assigned to the highest frequency reported. Additional reactions reported from post-marketing experience are included as frequency Not known (cannot be estimated from the available data) in italics in the list below.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. g. g. 4) Musculoskeletal and connective tissue disorders Common arthralgia, myalgia, back pain, twitching Not known rhabdomyolysis, myoclonus Renal and urinary disorder Not known acute renal failure, incontinence Reproductive system and breast disorders Common impotence Not known breast hypertrophy, gynaecomastia, sexual dysfunction (including changes in libido, ejaculation disorders and anorgasmia) General disorders and administration site conditions Very Common fatigue, fever Common peripheral oedema, abnormal gait, asthenia, pain, malaise, flu syndrome Uncommon generalized oedema Not known Withdrawal reactions (mostly anxiety, insomnia, nausea, pains, sweating), *chest pain.

Sudden unexplained deaths have been reported where a causal relationship to treatment with gabapentin has not been established. Investigations Common WBC (white blood cell count) decreased, weight gain Uncommon elevated liver function tests SGOT (AST), SGPT (ALT) and bilirubin Not known blood glucose fluctuations in patients with diabetes, blood creatine phosphokinase increased Injury, poisoning and procedural complications Common accidental injury, fracture, abrasion Uncommon fall *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. 4). 8). The patient should be informed about this at the start of the treatment. Concerning discontinuation of long-term treatment of Gabapentin, data suggest that the incidence and severity of withdrawal symptoms may be dose-related.

4). Under treatment with gabapentin cases of acute pancreatitis were reported. 4). In patients on haemodialysis due to end-stage renal failure, myopathy with elevated creatine kinase levels has been reported. Respiratory tract infections, otitis media, convulsions and bronchitis were reported only in clinical studies in children.

Additionally, in clinical studies in children, aggressive behaviour and hyperkinesias were reported commonly. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal […]

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.

8).

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 and the available data do not exclude the possibility of an increased risk for gabapentin. 8). Therefore, patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered.

Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. Discontinuation of gabapentin treatment should be considered in case of suicidal ideation and behaviour.

8). 2). 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 in the treatment of primary generalised seizures such as absence seizures and may aggravate these seizures in some patients. Therefore, gabapentin should be used with caution in patients with mixed seizures including absences.

Concomitant use with opioids and other CNS depressants Patients who require concomitant treatment with central nervous system (CNS) depressants, including 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. 5). Caution is advised when prescribing gabapentin concomitantly with opioids due to risk of CNS depression. 001]). 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. Dizziness, somnolence, loss of consciousness, confusion, and mental impairment Gabapentin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population.

There have also been post-marketing reports of loss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicinal product 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 […]

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