Active ingredients: Gabapentin
Gabapentin Pfizer 600 mg film-coated tablets
Gabapentin Pfizer 800 mg film-coated tablets
The package inserts of Gabapentin - Generic Drug are available for pack sizes: - Gabapentin Pfizer 600 mg film-coated tablets
Gabapentin Pfizer 800 mg film-coated tablets - Gabapentin Pfizer 100 mg hard capsules, Gabapentin Pfizer 300 mg hard capsules, Gabapentin Pfizer 400 mg hard capsules
Why is Gabapentin - Generic Drug used? What is it for?
Gabapentin Pfizer belongs to a group of medicines used to treat epilepsy and peripheral neuropathic pain (long lasting pain caused by damage to the nerves). The active substance in Gabapentin Pfizer is gabapentin.
Gabapentin Pfizer is used to treat:
- Various forms of epilepsy (seizures initially limited to certain areas of the brain, whether the seizures spread to other parts of the brain or not). Your doctor will prescribe Gabapentin Pfizer to help you treat epilepsy when the treatment you are already taking does not fully control your condition. You should take Gabapentin Pfizer in addition to your current treatment unless you receive other instructions. Gabapentin Pfizer can be also used alone to treat adults and children over 12 years of age.
- Peripheral neuropathic pain (long lasting pain caused by damage to the nerves). A variety of different diseases can cause peripheral neuropathic pain (occurs mainly in the legs and / or arms), such as diabetes or shingles. Pain sensations can be described as heat, burning, throbbing, lightning pain, aches stabbing, sharp pains, cramps, aching, tingling, numbness, stinging pains, etc.
Contraindications When Gabapentin - Generic Drug should not be used
Do not take Gabapentin Pfizer
- if you are allergic (hypersensitive) to gabapentin or any of the other ingredients of this medicine (listed in section 6).
Precautions for use What you need to know before taking Gabapentin - Generic Drug
Talk to your doctor or pharmacist before taking Gabapentin Pfizer:
- if you have kidney problems, your doctor may prescribe a different dosage schedule
- if you are on hemodialysis (to remove waste from kidney failure), tell your doctor if you have muscle pain and / or weakness
- if you develop signs such as persistent stomach pain, nausea and vomiting, contact your doctor immediately as these may be symptoms of acute pancreatitis (an "inflammation of the pancreas)
Cases of abuse and dependence have been reported for gabapentin from post-marketing experience. Tell your doctor if you have a history of abuse or dependence.
A small number of patients being treated with antiepileptic medicines such as gabapentin have developed thoughts of suicide or self harm. If at any time you have such thoughts, contact your doctor immediately.
Important information on potentially serious reactions
A small number of patients being treated with Gabapentin Pfizer have had an allergic reaction or potentially serious skin reaction which, if left untreated, can develop into more serious problems. You need to know the symptoms to be able to recognize them while you are taking Gabapentin Pfizer.
Read the description of these symptoms in section 4 of this leaflet under "Contact your doctor immediately if you notice any of the following symptoms after taking this medicine as they can be serious"
Muscle weakness, aches or pains and particularly if you feel unwell and have a fever at the same time, it can be caused by a muscle breakdown which can be life-threatening and can lead to kidney problems. Urine discoloration and changes in blood tests (in particular increased creatine phosphokinase) may also occur. If you experience any of these signs or symptoms, please contact your doctor immediately.
Interactions Which drugs or foods can modify the effect of Gabapentin - Generic Drug
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Medicines containing opioids such as morphine
If you are taking medicines that contain opioids (such as morphine), tell your doctor or pharmacist because opioids may increase the effect of Gabapentin Pfizer. In addition, the combination of gabapentin with opioids can cause symptoms such as sleepiness and / or decreased blood pressure. breathing.
Antacids for poor digestion
If Gabapentin Pfizer and antacids containing aluminum and magnesium are taken together, the absorption of Gabapentin Pfizer from the stomach may be reduced. It is therefore recommended to take Gabapentin Pfizer no earlier than two hours after taking the antacid.
Gabapentin Pfizer:
- it is not expected to interact with other antiepileptic medicines or the birth control pill.
- it can interfere with some laboratory tests; if you need a urine test, tell your doctor or hospital what you are taking.
Gabapentin Pfizer with food
Gabapentin Pfizer can be taken with or without food.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Gabapentin Pfizer should not be taken during pregnancy unless your doctor has told you otherwise. Women of childbearing age must use an effective method of contraception.
No specific studies have been conducted to evaluate the use of gabapentin in pregnant women, but an increased risk for the development of the child has been reported for other medicines used to treat seizures, particularly when more than one drug is taken at the same time. a medicine for seizures. Therefore, whenever possible, you should try to take only a medicine for epilepsy during pregnancy and only on medical advice.
Contact your doctor immediately if you are pregnant, think you may be pregnant or are planning to become pregnant while taking Gabapentin Pfizer. Do not suddenly stop taking this medicine as this can cause a sudden onset of seizures which can have serious consequences for you and your baby.
Feeding time
Gabapentin, the active substance in Gabapentin Pfizer, passes into breast milk. As the effect on the baby is not known, it is recommended that you do not breastfeed during treatment with Gabapentin Pfizer.
Fertility
Animal studies have shown no effect on fertility.
Driving and using machines
Gabapentin Pfizer can cause dizziness, sleepiness and tiredness. You should not drive vehicles, operate complex machinery or engage in other potentially dangerous activities until you understand whether this medicine may affect your ability to perform these activities.
Dose, Method and Time of Administration How to use Gabapentin - Generic Drug: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If you are unsure, consult your doctor or pharmacist.
Your doctor will work out the right dose for you.
Epilepsy, the recommended dose is:
Adults and adolescents:
Take the number of tablets your doctor has prescribed for you. Your doctor will usually increase the dose gradually. The starting dose will generally be between 300 mg and 900 mg per day. Subsequently, the dose may be increased, on the doctor's recommendation, up to a maximum of 3600 mg per day and your doctor will tell you to take this dose in 3 separate doses, i.e. once in the morning, once in the afternoon and once in the evening.
Children aged 6 and over:
The dose to be given to the child will be determined by the doctor because it is calculated based on the weight of the child. Treatment is started with a low starting dose which is gradually increased over approximately 3 days. The usual dose for controlling epilepsy is 25-35 mg / kg per day. It is usually given in 3 divided doses, taking the tablet (s) each day, usually once in the morning, once in the afternoon and once in the evening.
The use of Gabapentin Pfizer is not recommended in children under 6 years of age.
Peripheral neuropathic pain, the recommended dose is:
Adults:
Take the number of tablets according to your doctor's instructions. Your doctor will usually increase the dose gradually. The starting dose will generally be between 300 mg and 900 mg per day. Subsequently, the dose may be increased on the doctor's recommendation up to a maximum of 3600 mg per day and your doctor will tell you to take the medicine in 3 divided doses, i.e. once in the morning, once in the afternoon and once in the evening.
If you have kidney problems or are on hemodialysis: If you have kidney problems or are on hemodialysis, your doctor may prescribe a different schedule for taking this medicine and / or a different dose.
If you are an elderly patient (over 65 years of age), you should take your normal dose of Gabapentin Pfizer, unless you have kidney problems. If you have kidney problems, your doctor may prescribe a different schedule of taking the medicine and / or a different dose.
If you have the impression that the effect of Gabapentin Pfizer is too strong or too weak, please tell your doctor or pharmacist as soon as possible.
Method of administration:
Oral use.
Always swallow the tablets with a large amount of water. The tablet can be divided into equal halves.
Continue treatment with Gabapentin Pfizer until your doctor tells you to stop
Overdose What to do if you have taken an overdose of Gabapentin - Generic Drug
If you take more Gabapentin Pfizer than you should
A higher dose than recommended may lead to increased side effects including loss of consciousness, dizziness, double vision, difficulty in speaking, sleepiness and diarrhea.
Contact your doctor immediately or go to the nearest emergency department if you take more Gabapentin Pfizer than prescribed by your doctor. Take the tablets you did not take with you together with the pack and the package leaflet so that the hospital can easily understand how much medicine you have taken.
If you forget to take Gabapentin Pfizer
If you forget to take a dose, take it as soon as you remember, unless it is time for your next dose. Do not take a double dose to make up for a forgotten dose.
If you stop taking Gabapentin Pfizer
Do not stop taking Gabapentin Pfizer unless your doctor tells you to. Withdrawal of treatment should be done gradually over a period of at least 1 week. If you suddenly stop taking Gabapentin Pfizer or before your doctor prescribes it, the risk of seizures increases.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Gabapentin - Generic Drug
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately if you notice any of the following symptoms after taking this medicine as they can be serious:
- severe skin reactions requiring immediate attention, swelling of the lips and face, rash and redness of the skin, and / or hair loss (these may be symptoms of a severe allergic reaction).
- persistent stomach pain, nausea and vomiting as these may be symptoms of acute pancreatitis (an 'inflammation of the pancreas).
- Gabapentin Pfizer can cause severe or life-threatening allergic reactions, these can affect your skin or other parts of the body such as the liver or blood cells. There is "the possibility or not that a" rash will occur when this type of reaction occurs. This may lead to hospitalization or discontinuation of treatment with Gabapentin Pfizer. Contact your doctor immediately if you have any of the following symptoms:
- rash
- urticaria
- fever
- enlarged glands that persist or swelling of the lips and tongue
- yellowing of the skin or whites of the eyes
- unusual bleeding
- bruising
- severe fatigue or weakness
- unexpected muscle pain
- frequent infections
These symptoms can be the first signs of a serious reaction. Your doctor should examine you to decide whether you should continue treatment with Gabapentin Pfizer.
If you are on hemodialysis, tell your doctor if you experience muscle pain and / or weakness.
Other side effects include:
Very common (may affect more than 1 in 10 people):
- Viral infections
- Feeling sleepy, dizzy, lack of coordination
- Feeling tired, fever
Common (may affect up to 1 in 10 people):
- Pneumonia, respiratory infections, urinary tract infections, ear inflammation or other infections
- Low white blood cell count
- Anorexia, increased appetite
- Anger towards other people, confusion, mood changes, depression, anxiety, nervousness, difficulty thinking
- Convulsions, jerking movements, difficulty speaking, memory loss, tremors, sleep disturbances, headaches, skin sensitivity, decreased sensation (numbness), difficulty in coordination, abnormal eye movement, increase, decrease or absence of reflexes
- Blurred vision, double vision
- Dizziness
- High blood pressure, flushing of the face or dilation of blood vessels
- Difficulty in breathing, bronchitis, sore throat, cough, dry nose
- Vomiting, nausea, dental problems, sore gums, diarrhea, stomach pain, indigestion, constipation, dry mouth or throat, flatulence
- Facial swelling, bruising, rash, itching, acne
- Joint pain, muscle pain, back pain, muscle twitching
- Erection problems (impotence)
- Swelling of the legs and arms, difficulty walking, weakness, pain, feeling unwell, flu-like symptoms
- Reduction in white blood cells, weight gain
- Accidental wounds, fractures, abrasions In addition, aggressive behavior and jerking movements were commonly reported in clinical trials in children.
Uncommon (may affect up to 1 in 100 people):
- Allergic reaction such as urticaria
- Movement reduction
- Increased heart rate
- Swelling which may affect the face, trunk and limbs
- Abnormal blood test values that suggest liver problems
- Mental impairment
- Falls
- Increase in blood glucose levels (seen more often in patients with diabetes)
Rare (may affect up to 1 in 1,000 people):
- Loss of consciousness
- Decrease in blood glucose levels (observed more often in patients with diabetes)
The following undesirable effects have been reported since the post-marketing phase of Gabapentin Pfizer:
- Reduction in platelets (cells that clot the blood)
- Hallucinations
- Problems with abnormal movements such as convulsive shaking, jerking movements and stiffness
- I tinkled in my ear
- Some side effects, including swollen lymph nodes (small isolated lumps under the skin), fever, rash, and inflammation of the liver can occur simultaneously
- Yellowing of the skin and eyes (jaundice). Inflammation of the liver.
- Acute renal failure, incontinence.
- Breast tissue enlargement, breast enlargement.
- Adverse events occurring after abrupt withdrawal of gabapentin (anxiety, sleep disturbances, feeling sick, pain, sweating), chest pain.
- Injury to muscle fibers (rhabdomyolysis).
- Abnormalities in blood tests (increased creatine phosphokinase).
- Problems with sexual function including inability to reach orgasm, delayed ejaculation.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Undesirable effects can also be reported directly through the national reporting system at the address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The expiry date refers to the last day of that month.
Do not store above 25 ° C.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Gabapentin Pfizer contains
The active ingredient is gabapentin. Each film-coated tablet contains 600 mg or 800 mg of gabapentin.
The other ingredients of Gabapentin Pfizer film-coated tablets are:
poloxamer 407 (ethylene oxide and propylene oxide)
copovidone
cornstarch
magnesium stearate
Coating film:
opadry white YS-1-18111
hydroxypropylcellulose talc
What Gabapentin Pfizer looks like and contents of the pack
Film-coated tablets
The 600 mg tablets are white, oval, film-coated tablets with a bisector line on both sides and debossed with "NT" and "16" on one side.
The 800 mg tablets are white, oval, film-coated tablets with a bisector line on both sides and debossed with "NT" and "26" on one side.
The tablet can be divided into equal halves.
PVC / PE / PVDC / aluminum blisters or PVC / PVDC / aluminum blisters of 20, 30, 45, 50, 60, 84, 90, 100, 200, 500 tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
GABAPENTIN PFIZER
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 600 mg of gabapentin.
Each film-coated tablet contains 800 mg of gabapentin.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablet
Gabapentin Pfizer 600 mg film-coated tablets, are white, oval film-coated tablets (length and width: 8.96 x 17.27 mm, thickness: 6.48 mm) with a bisector line on both sides and imprinted with " NT "and" 16 "on the one hand.
Gabapentin Pfizer 800 mg film-coated tablets, are white, oval film-coated tablets (length and width: 9.87 x 19.01 mm; thickness: 7.24 mm) with a bisector line on both sides and imprinted with " NT "and" 26 "on the one hand.
The tablet can be divided into equal halves.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Epilepsy:
Gabapentin is indicated as adjunct therapy in the treatment of partial seizures with or without secondary generalization in adults and children aged 6 years and above (see section 5.1).
Gabapentin is indicated as monotherapy for the treatment of partial seizures in the presence or absence of secondary generalization in adults and adolescents 12 years of age and older.
Treatment of peripheral neuropathic pain:
Gabapentin is indicated in adults for the treatment of peripheral neuropathic pain, such as painful diabetic neuropathy and post-herpetic neuralgia.
04.2 Posology and method of administration
Table 1 describes the titration scheme to initiate treatment for all indications; This dosing regimen is recommended in both adults and adolescents aged 12 years and over. Dosage instructions for use in children below 12 years of age are provided in a separate sub-chapter later in this section.
Table 1 DOSAGE SCHEME - INITIAL TITRATION
Gabapentin discontinuation:
In accordance with current clinical practice, if gabapentin treatment is to be discontinued it is recommended that this be done gradually at least over a week regardless of the indication being treated.
Epilepsy:
Epilepsy generally requires long-term treatments. The dosage is established by the treating physician on the basis of tolerability and efficacy for the individual patient.
Adults and adolescents:
In clinical trials, the effective dose range was 900 to 3600 mg / day. Treatment can be initiated with a dose titration as described in Table 1 or by administering 300 mg three times a day (TID) on the first day. Thereafter, based on individual patient response and tolerability, the dose may be further increased by 300 mg / day step by step every 2-3 days up to a maximum of 3600 mg / day. In some patients it may be appropriate a slower dose titration of gabapentin. The minimum time to reach the dose of 1800 mg / day is one week, for the 2400 mg / day dose it is 2 weeks, and for 3600 mg / day it is 3 weeks. up to 4800 mg / day have been well tolerated in long-term open-label clinical trials. The total daily dose should be divided into three single administrations and, to prevent sudden onset of seizures, the maximum time interval between doses should not exceed 12 hours.
Children aged 6 years or older:
The starting dose should vary between 10 and 15 mg / kg / day and the effective dose is achieved by increasing the titration over a period of approximately three days. The effective dose of gabapentin in children 6 years of age and older is 25 to 35 mg / kg / day. Doses up to 50 mg / kg / day have been well tolerated in a long-term clinical study. The total daily dose should be divided into three single administrations and the maximum time interval between doses should not exceed 12 hours. .
It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin therapy. Furthermore, gabapentin can be used in combination with other antiepileptic medicinal products without the risk of altering the plasma concentrations of gabapentin or the serum concentrations of other antiepileptic medicinal products.
Peripheral neuropathic pain
Adults:
Therapy can be initiated with dose titration as described in Table 1. Alternatively, the starting dose is 900 mg / day divided into three equal administrations. Thereafter, based on individual patient response and tolerability, the dose may be further increased by 300 mg / day at a time every 2-3 days up to a maximum of 3600 mg / day. Slower titration of gabapentin dosage may be appropriate in some patients. The minimum time to reach the 1800 mg / day dose is one week, for the 2400 mg / day dose it is 2 weeks and for 3600 mg / day it is 3 weeks.
In the treatment of peripheral neuropathic pain, such as painful diabetic neuropathy and post-herpetic neuralgia, efficacy and safety have not been investigated in clinical trials for treatment periods longer than 5 months. If a patient requires treatment longer than 5 months. 5 months for peripheral neuropathic pain, the treating physician should evaluate the patient's clinical condition and determine the need for prolongation of treatment.
Instructions for all indications:
In patients with poor general health conditions, eg patients with low body weight, organ transplant recipients, etc., dose titration should be done more slowly, using lower dosages or longer time intervals. between dose increments.
Use in elderly patients (over 65 years of age):
Dosage adjustment may be required in elderly patients due to age-related decreased renal function (see Table 2). Somnolence, peripheral edema and asthenia may be more frequent in elderly patients.
Use in patients with renal impairment:
In patients with impaired renal function and / or in those undergoing hemodialysis, dose adjustment is recommended as described in Table 2. 100 mg gabapentin capsules can be used to follow the dosing recommendations in patients with renal insufficiency.
Table 2 DOSE OF Gabapentin IN ADULTS BASED ON KIDNEY FUNCTIONALITY
a The total daily dose should be administered in three divided doses. For patients with renal impairment (creatinine clearance
b To be administered at a dose of 300 mg every other day.
c For patients with creatinine clearance
Use in patients undergoing hemodialysis:
In hemodialysis patients with anuria who have never been treated with gabapentin, a loading dose of 300 to 400 mg is recommended, followed by a dose of 200 to 300 mg of gabapentin after each 4-hour hemodialysis session. On hemodialysis free days, gabapentin treatment should not be given.
In patients with renal impairment undergoing hemodialysis, the maintenance dose of gabapentin should be based on the dosing recommendations given in Table 2. In addition to the maintenance dose, an additional "200-300 mg dose is recommended after each hemodialysis session. 4 hours.
Method of administration:
Oral use.
Gabapentin can be taken with or without food and should be swallowed whole with a sufficient amount of fluid (eg a glass of water).
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
04.4 Special warnings and appropriate precautions for use
Cases of suicidal ideation and behavior have been reported in patients receiving antiepileptic drugs in their various indications. A meta-analysis of randomized, placebo-controlled clinical trials of anti-epileptic drugs also found a small increased risk of suicidal ideation and behavior.
The mechanism of this risk is unknown and the available data do not exclude the possibility of an increased risk with gabapentin.
Therefore, patients should be monitored for signs of suicidal ideation and behavior and appropriate treatment considered. Patients (and caregivers) should be advised to seek medical attention if signs of suicidal ideation or behavior emerge.
If a patient develops acute pancreatitis during gabapentin treatment, discontinuation of gabapentin treatment should be considered (see section 4.8).
Although there is no evidence of rebound seizures with gabapentin, abrupt discontinuation of anticonvulsants in epileptic patients may worsen status epilepticus (see section 4.2).
With gabapentin, as with other antiepileptic medicines, some patients may experience an increased frequency of seizures or the onset of new types of seizures.
As with other antiepileptics, attempts to withdraw concomitant antiepileptics with gabapentin in patients refractory to treatment with more than one antiepileptic drug in order to achieve gabapentin monotherapy have a low success rate.
Gabapentin is not considered effective in treating attacks of primary generalized epilepsy, such as absences and, in some patients, may aggravate these seizures. Therefore, gabapentin should be used with caution in patients with mixed seizures, including absences.
No systematic studies have been conducted with gabapentin in patients 65 years of age or older. In a double-blind study in patients with neuropathic pain, somnolence, peripheral edema and asthenia occurred in a slightly higher percentage in patients 65 years of age and older than in younger patients. In addition to these data, clinical evaluations in this age group do not indicate a different adverse event profile from that observed in younger patients.
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.
Drug Rash with Eosinophilia and Systemic Symptoms (DRESS):
Serious and life-threatening systemic hypersensitivity reactions, such as drug rash with eosinophilia and systemic symptoms (DRESS), have been reported in patients taking antiepileptic drugs, including gabapentin (see section 4.8).
It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may occur even if a rash is not evident. If such signs or symptoms occur, the patient should be examined immediately. Treatment with gabapentin should be discontinued if not. it is possible to establish an "alternative etiology for these signs or symptoms.
Laboratory tests:
In the semi-quantitative determination of total proteinuria with the dipstick test false positive results can be obtained. It is therefore recommended to verify a positive result obtained with the dipstick test using methods based on a different analytical principle, such as the Biuret method, turbidimetric or colorimetric binding methods, or to use these alternative methods from the start.
04.5 Interactions with other medicinal products and other forms of interaction
In a study in healthy volunteers (N = 12), when a 60 mg controlled-release morphine capsule was administered 2 hours prior to a 600 mg gabapentin capsule, the mean gabapentin AUC increased by 44%. compared to when gabapentin was administered without morphine Therefore, patients should be carefully observed for any signs of CNS depression, such as somnolence, and the dose of gabapentin or morphine should be reduced appropriately.
No interactions were observed between gabapentin and phenobarbital, phenytoin, valproic acid or carbamazepine.
Steady state pharmacokinetics of gabapentin are similar in healthy subjects and in patients with epilepsy treated with these antiepileptic agents.
Concomitant administration of gabapentin and oral contraceptives containing norethindrone and / or ethinylestradiol does not affect the steady-state pharmacokinetics of either component.
Concomitant administration of gabapentin and antacids containing aluminum and magnesium reduces the bioavailability of gabapentin by up to 24%. It is recommended that gabapentin be taken no earlier than two hours after administration of the antacids.
Renal excretion of gabapentin is not affected by probenecid.
The slight reduction in renal excretion of gabapentin observed when co-administered with cimetidine is not expected to be of clinical importance.
04.6 Pregnancy and lactation
Risk related to epilepsy and antiepileptic drugs in general:
The risk of birth defects increases 2-3 times in the offspring of women treated with an antiepileptic medicine. The most frequently reported defects are cleft lip, cardiovascular malformations and neural tube defects. Multiple antiepileptic drug therapy may be associated with a greater risk of congenital malformations than monotherapy, so it is important to use monotherapy whenever possible. Women who are likely to become pregnant or who are of childbearing age should be given specialist advice and the need for antiepileptic treatment should be reassessed when a woman is planning to become pregnant. Antiepileptic therapy should not be stopped suddenly as this can cause seizures which can have serious consequences for both mother and baby. Developmental delay in children born to epileptic women has rarely been observed. It is not possible to distinguish whether the developmental delay is caused by genetic or social factors, by the mother's epilepsy or by antiepileptic treatment.
Risk related to Gabapentin:
There are no adequate data from the use of gabapentin in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Gabapentin should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the potential risk to the fetus.
It is not possible to draw definitive conclusions regarding the possible association between gabapentin and an increased risk of congenital malformations when the drug is taken during pregnancy, due to the epilepsy itself and the presence of antiepileptic drugs used concomitantly in the course of individual pregnancies examined.
Gabapentin is excreted in breast milk. Because the effects on the baby during breastfeeding are not known, caution should be exercised when gabapentin is administered to breastfeeding women. Gabapentin should only be used in breastfeeding mothers if the benefits clearly outweigh the risks.
04.7 Effects on ability to drive and use machines
Gabapentin may have "mild or moderate influence on the ability to drive and use machines. Gabapentin acts on the central nervous system and may cause sleepiness, dizziness or other related symptoms. Even if they have been mild or moderate in severity, these side effects may also occur. be potentially dangerous in patients who drive or use machines. This is especially true at the start of treatment and after a dose increase.
04.8 Undesirable effects
Adverse reactions observed in clinical trials in epilepsy (add-on and monotherapy) and neuropathic pain are listed below, by class and by frequency: very common (> 1/10); common (> 1/100, >1/1.000, > 1/10.000,
Other reactions reported during post-marketing experience are included as a frequency "Not Known" (frequency cannot be estimated from the available data) in italics in the list below.
Within each frequency group, undesirable effects are reported in order of decreasing severity.
Cases of acute pancreatitis have been reported during treatment with gabapentin. The causal relationship with gabapentin is unclear (see section 4.4).
Myopathy and elevated creatine kinase levels have been reported in patients undergoing hemodialysis due to end stage renal failure.
Respiratory tract infections, otitis media, seizures and bronchitis have only been reported in clinical trials in children. In addition, aggressive behavior and hyperkinesis were commonly reported in clinical trials in children.
04.9 Overdose
No life-threatening acute toxicity episodes have been observed with gabapentin overdoses up to doses of 49 g. Symptoms of overdose included dizziness, double vision, speech disturbances, somnolence, lethargy and mild diarrhea. All patients made a full recovery with supportive care. Reduced absorption of gabapentin at higher dosages may limit drug absorption at the time of overdose and therefore may minimize toxicity resulting from overdoses.
Overdoses of gabapentin, particularly when associated with the use of other CNS depressant drugs, can lead to coma.
Although gabapentin can be eliminated by hemodialysis, it has been found that this is not necessary based on previous experience. However, hemodialysis may be indicated in patients with severe renal impairment.
A lethal oral dose of gabapentin was not identified in mice and rats treated with doses up to 8000 mg / kg. Signs of acute toxicity in animals included ataxia, labored breathing, ptosis, hypoactivity or excitation.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antiepileptics; other antiepileptics. ATC code: N03AX12.
The exact mechanism of action of gabapentin is not known.
Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid), but its mechanism of action differs from that of numerous other active ingredients that interact with GABAergic synapses such as valproate, barbiturates, benzodiazepines, GABA-transaminase inhibitors, inhibitors of GABA uptake, GABA agonists, and GABA prodrugs. Education in vitro performed with radiolabelled gabapentin identified a novel peptide binding site in rat brain tissues, including neocortex and hippocampus, which may be related to the anticonvulsant and analgesic activity of gabapentin and its structural derivatives. The gabapentin binding site was identified. as the alpha2-delta subunit of voltage-gated calcium channels.
Gabapentin at clinically relevant concentrations does not bind to other common drugs or neurotransmitter receptors in the brain, including GABAA, GABAB, benzodiazepine, glutamate, glycine, or N-methyl-d-aspartate receptors.
Gabapentin does not interact in vitro with sodium channels thus differentiating from phenytoin and carbamazepine. Gabapentin partially reduces responses to the glutamate agonist N-methyl-d-aspartate (NMDA) in some systems in vitro, but only at concentrations above 100 mM which are not achievable in vivo. Gabapentin reduces slightly in vitro the release of monoamine neurotransmitters. Administration of gabapentin to rats increases GABA turnover in numerous brain regions in a similar manner to sodium valproate, albeit in different brain regions. The relevance of these different gabapentin activities to anticonvulsant effects has yet to be defined. In animals, gabapentin easily penetrates the brain and prevents seizures from maximal electroshock, from seizure substances, including inhibitors of GABA synthesis, and in genetic models of seizures.
A clinical study on adjunctive therapy in the treatment of partial seizures in pediatric patients aged 3 to 12 years showed a numerical, but not statistically significant, difference in the 50% response rate in favor of the gabapentin group. compared to the placebo group Further analysis post-hoc response rates calculated on the basis of age did not reveal a statistically significant effect of age, either as a continuous variable or as a dichotomous variable (age groups 3-5 years and 6-12 years). The data of this further analysis post-hoc are summarized in the following table:
* The population intent-to-treat modified was defined as all patients randomized to study drug who also had evaluable epileptic seizure annotations for 28 days during both baseline and double-blind phases.
05.2 "Pharmacokinetic properties
Absorption:
After oral administration, maximum plasma gabapentin concentrations are observed within 2-3 hours. The bioavailability of gabapentin (fraction of the absorbed dose) tends to decrease with increasing dose. The absolute bioavailability of a 300 mg capsule is approximately 60%. Food, including a high-fat diet, does not have a clinically significant effect on gabapentin pharmacokinetics.
The pharmacokinetics of gabapentin are not affected by repeated administration. Although plasma concentrations of gabapentin generally ranged from 2 mg / mL to 20 mg / mL in clinical studies, these concentrations were not indicative of safety or efficacy. Pharmacokinetic parameters are shown in Table 3.
Table 3 - Summary of the pharmacokinetic parameters of the mean (% CV) concentrations of gabapentin at steady state after dosing every 8 hours.
Cmax = Maximum plasma concentration at steady state
tmax = Time to Cmax
T½ = Elimination half-life
AUC (0-8) = Area under the curve at steady state 0 to 8 hours after administration
Ae% = Percentage of drug dose that is excreted unchanged in the urine 0 to 8 hours after administration
NA = Not available
Distribution:
Gabapentin is not bound to plasma proteins and has a volume of distribution of 57.7 liters. In epileptic patients, the concentrations of gabapentin in the cerebrospinal fluid (CSF) are approximately 20% of the corresponding steady-state plasma concentrations. Gabapentin is present in the breast milk of lactating women.
Biotransformation:
There is no evidence of gabapentin metabolism in humans. Gabapentin does not induce mixed function oxidizing liver enzymes responsible for metabolism of the substance.
Elimination:
Gabapentin is eliminated unchanged by the kidney only. The elimination half-life of gabapentin is dose independent and averages 5-7 hours.
In elderly patients and in patients with renal impairment, the plasma clearance of gabapentin is reduced. The elimination constant, plasma clearance and renal clearance of gabapentin are directly proportional to creatinine clearance.
Gabapentin is removed from the plasma by hemodialysis. Dosage adjustments are recommended in patients with impaired renal function or in patients on hemodialysis (see section 4.2).
The pharmacokinetics of gabapentin in children were determined in 50 healthy subjects aged 1 month to 12 years. In general, plasma gabapentin concentrations in children> 5 years of age were comparable to those found in adults when the drug was administered in mg / kg. In a pharmacokinetic study conducted in 24 healthy pediatric patients aged 1 to 48 months, an approximately 30% reduction in AUC, a reduction in Cmax and an increase in clearance based on weight were observed. body, when compared to available data reported for children over 5 years of age.
Linearity / Non-linearity:
The bioavailability of gabapentin (fraction of the absorbed dose) decreases with increasing dose and this confers non-linearity to the pharmacokinetic parameters, including the bioavailability parameter (F), eg Ae%, CL / F, Vd / F. Elimination pharmacokinetics (pharmacokinetic parameters that do not include bioavailability parameters such as CLr and T1 / 2) are best described by linear pharmacokinetics.Steady-state plasma gabapentin concentrations are predictable from single dose data.
05.3 Preclinical safety data
Carcinogenesis:
Gabapentin was administered in the diet, to mice at doses of 200, 600, 2000 mg / kg / day and to rats at doses of 250, 1000, 2000 mg / kg / day for two years. A statistically significant increase in the incidence of pancreatic acinar cell tumors was found only in male rats at the highest dose. The maximum plasma drug concentration in rats, at a dose of 2000 mg / kg / day, was 10 times higher. elevated plasma concentration in humans at a dose of 3600 mg / day. Pancreatic acinar cell tumors in male rats have a low degree of malignancy, did not affect survival, did not result in metastasis or invasion of surrounding tissues and were similar to those observed in control animals. The relationship between these pancreatic acinar cell tumors in male rats and the cancer risk in humans is unclear.
Mutagenesis:
Gabapentin has no genotoxic potential. It was not mutagenic in standard tests in vitro conducted with bacterial or mammalian cells. Gabapentin did not induce chromosomal structural aberrations in mammalian cells in vitro or in vivo and did not induce micronucleus formation in hamster bone marrow cells.
Impaired fertility:
No adverse effects on fertility or reproduction were observed in rats at doses up to 2000 mg / kg (approximately five times the maximum human daily dose in mg / m2 of body surface area).
Teratogenesis:
Gabapentin did not increase the incidence of malformations, compared to controls, in the offspring of mice, rats or rabbits with doses respectively up to 50, 30 and 25 times the daily human dose of 3600 mg (respectively four, five or eight times the daily dose used in humans in mg / m2).
Gabapentin caused a delay in the ossification process of the skull, vertebrae, forelimbs and lower limbs in rodents and this is indicative of a delay in fetal growth. These effects occurred in pregnant female mice treated with oral doses of 1000 or 3000 mg / kg / day during organogenesis and in rats treated with doses of 500, 1000 or 2000 mg / kg before and during mating and during gestation. These doses are approximately 1-5 times the human dose of 3600 mg on a mg / m2 basis.
No effects were observed in pregnant female mice treated with 500 mg / kg / day (approximately ½ of the human dose in mg / m2).
An increase in the incidence of hydroureter and / or hydronephrosis was observed in rats treated with 2000 mg / kg / day in a fertility and general reproduction study, with 1500 mg / kg / day in a teratology study and respectively. 500, 1000 and 2000 mg / kg / day in a perinatal and postnatal study. The significance of these data is unknown, but they have been associated with developmental delay. These doses are approximately 1-5 times the dose used in the "man equal to 3600 mg on a mg / m2 basis.
In a teratology study conducted in rabbits, there was an increase in the incidence of post-implantation fetal losses with doses of 60, 300 and 1500 mg / kg / day during organogenesis. These doses are approximately ¼ to 8 times the daily human dose of 3600 mg on a mg / m2 basis.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Core of the tablet:
Poloxamer 407 (ethylene oxide and propylene oxide);
copovidone;
cornstarch;
magnesium stearate.
Coating film:
opadry white YS-1-18111;
hydroxypropylcellulose;
talc.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
2 years
06.4 Special precautions for storage
Do not store above 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
PVC / PE / PVDC / aluminum blister or PVC / PVDC / aluminum blister
Packs of 20, 30, 45, 50, 60, 84, 90, 100, 200, 500 tablets.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Italia S.r.l. - Via Isonzo, 71 - 04100 Latina
08.0 MARKETING AUTHORIZATION NUMBER
"600 mg film-coated tablets" 20 tablets in PVC / PE / PVDC / AL blister - AIC: 040150346 / M
"600 mg film-coated tablets" 30 tablets in PVC / PE / PVDC / AL blister - AIC: 040150359 / M
"600 mg film-coated tablets" 45 tablets in PVC / PE / PVDC / AL blister - AIC: 040150361 / M
"600 mg film-coated tablets" 50 tablets in PVC / PE / PVDC / AL blister - AIC: 040150373 / M
"600 mg film-coated tablets" 60 tablets in PVC / PE / PVDC / AL blister - AIC: 040150385 / M
"600 mg film-coated tablets" 84 tablets in PVC / PE / PVDC / AL blister - AIC: 040150397 / M
"600 mg film-coated tablets" 90 tablets in PVC / PE / PVDC / AL blister - AIC: 040150409 / M
"600 mg film-coated tablets" 100 tablets in PVC / PE / PVDC / AL blister - AIC: 040150411 / M
"600 mg film-coated tablets" 200 tablets in blister PVC / PE / PVDC / AL - AIC: 040150423 / M
"600 mg film-coated tablets" 500 tablets in PVC / PE / PVDC / AL blister - AIC: 040150435 / M
"600 mg film-coated tablets" 20 tablets in PVC / PVDC / AL blister - AIC: 040150447 / M
"600 mg film-coated tablets" 30 tablets in PVC / PVDC / AL blister - AIC: 040150450 / M
"600 mg film-coated tablets" 45 tablets in PVC / PVDC / AL blister - AIC: 040150462 / M
"600 mg film-coated tablets" 50 tablets in PVC / PVDC / AL blister - AIC: 040150474 / M
"600 mg film-coated tablets" 60 tablets in PVC / PVDC / AL blister - AIC: 040150486 / M
"600 mg film-coated tablets" 84 tablets in PVC / PVDC / AL blister - AIC: 040150498 / M
"600 mg film-coated tablets" 90 tablets in PVC / PVDC / AL blister - AIC: 040150500 / M
"600 mg film-coated tablets" 100 tablets in PVC / PVDC / AL blister - AIC: 040150512 / M
"600 mg film-coated tablets" 200 tablets in PVC / PVDC / AL blister - AIC: 040150524 / M
"600 mg film-coated tablets" 500 tablets in PVC / PVDC / AL blister - AIC: 040150536 / M
"800 mg film-coated tablets" 20 tablets in PVC / PE / PVDC / AL blister - AIC: 040150548 / M
"800 mg film-coated tablets" 30 tablets in PVC / PE / PVDC / AL blister - AIC: 040150551 / M
"800 mg film-coated tablets" 45 tablets in PVC / PE / PVDC / AL blister - AIC: 040150563 / M
"800 mg film-coated tablets" 50 tablets in PVC / PE / PVDC / AL blister - AIC: 040150575 / M
"800 mg film-coated tablets" 60 tablets in PVC / PE / PVDC / AL blister - AIC: 040150587 / M
"800 mg film-coated tablets" 84 tablets in PVC / PE / PVDC / AL blister - AIC: 040150599 / M
"800 mg film-coated tablets" 90 tablets in PVC / PE / PVDC / AL blister - AIC: 040150601 / M
"800 mg film-coated tablets" 100 tablets in blister PVC / PE / PVDC / AL - AIC: 040150613 / M
"800 mg film-coated tablets" 200 tablets in blister PVC / PE / PVDC / AL - AIC: 040150625 / M
"800 mg film-coated tablets" 500 tablets in PVC / PE / PVDC / AL blister - AIC: 040150637 / M
"800 mg film-coated tablets" 20 tablets in PVC / PVDC / AL blister - AIC: 040150649 / M
"800 mg film-coated tablets" 30 tablets in PVC / PVDC / AL blister - AIC: 040150652 / M
"800 mg film-coated tablets" 45 tablets in PVC / PVDC / AL blister - AIC: 040150664 / M
"800 mg film-coated tablets" 50 tablets in PVC / PVDC / AL blister - AIC: 040150676 / M
"800 mg film-coated tablets" 60 tablets in PVC / PVDC / AL blister - AIC: 040150688 / M
"800 mg film-coated tablets" 84 tablets in PVC / PVDC / AL blister - AIC: 040150690 / M
"800 mg film-coated tablets" 90 tablets in PVC / PVDC / AL blister - AIC: 040150702 / M
"800 mg film-coated tablets" 100 tablets in PVC / PVDC / AL blister - AIC: 040150714 / M
"800 mg film-coated tablets" 200 tablets in PVC / PVDC / AL blister - AIC: 040150726 / M
"800 mg film-coated tablets" 500 tablets in PVC / PVDC / AL blister - AIC: 040150738 / M
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 02/03/2012
10.0 DATE OF REVISION OF THE TEXT
AIFA determination of 10/06/2013
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