Neurontin capsules 300mg N100
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Active ingredients
Gabapentin
Release form
Capsules
Composition
Active ingredient: gabapentin Concentration of active ingredient (mg): 300 mg
Pharmacological effect
Anticonvulsant drug. According to the structure gabapentin similar to the neurotransmitter gamma-aminobutyric acid (GABA), but its mechanism of action differs from that of some other drugs that interact with GABA receptors, including valproate, barbiturates, benzodiazepines, inhibitors of GABA-transaminase reuptake inhibitors GABA agonists, GABA and prodrugs of GABA: it does not possess GABA-ergic properties and does not affect the uptake and metabolism of GABA. It is assumed that gabapentin binds to the α2-δ-subunit of voltage-dependent calcium channels and inhibits the flow of calcium ions, which plays an important role in the occurrence of neuropathic pain. Gabapentin does not affect the reuptake of dopamine, norepinephrine and serotonin. Gabapentin in clinically significant concentrations does not bind to the receptor drugs or neurotransmitters, including GABAA, GABAH, benzodiazepine, glutamate, glycine or N-methyl-d-aspartate receptors. Unlike phenytoin and carbamazepine, gabapentin does not interact with sodium channels in vitro. Gabapentin partially attenuates the effects of the N-methyl-d-aspartate glutamate receptor agonist in some in vitro tests, but only at a concentration of more than 100 mcmol / l, which is not achieved in vivo. Gabapentin somewhat reduces the release of monoamine neurotransmitters in vitro. The use of gabapentin in rats led to an increase in the exchange of GABA in some areas of the brain; this effect was similar to that of valproic acid, although it was observed in other parts of the brain. The significance of these effects of gabapentin for its anticonvulsant activity has not been established. In animals, gabapentin easily penetrates into the brain tissue and prevents seizures caused by maximum electroshock, chemicals, including inhibitors of GABA synthesis, as well as due to genetic factors.
Pharmacokinetics
All the pharmacological effects of gabapentin are related to the activity of the unchanged compound. In humans, the body is practically not metabolized. Absorption The bioavailability of gabapentin is not proportional to the dose; so, with an increase in the dose, it decreases and amounts to 60, 47, 34, 33 and 27% at the intake of 900, 1200, 2400, 3600 and 4800 mg / day, divided into 3 doses, respectively.Meal has little effect on the rate and extent of absorption of gabapentin (there is an increase in the maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 14%). Distribution Vd 57.7 l. Metabolism and elimination. Excreted from the systemic blood flow by the kidneys in unchanged form. In humans, almost not metabolized. The half-life (T1 / 2) of blood plasma does not depend on the dose and averages 5-7 hours. The rate of excretion is constant, plasma and renal clearance is directly proportional to creatinine clearance (CK). In patients with renal impairment, plasma clearance of gabapentin decreases . It is removed from plasma using hemodialysis. Patients with impaired renal function or on hemodialysis are recommended to adjust the dose. Pharmacokinetics in special groups of patients Renal failure Patients (n = 60) with renal insufficiency (average CC 13-114 ml / min) took 400 mg gabapentin . The average T1 / 2 ranged from 6.5 h (CC more than 60 ml / min) to 52 h (CC less than 30 ml / min), and renal clearance of gabapentin from 90 ml / min (CC more than 60 ml / min) to 10 ml / min (CC less than 30 ml / min). The mean plasma clearance (C1 / F) decreased from 190 ml / min to 20 ml / min. In adult patients with renal insufficiency, dose adjustment is necessary. Children with renal failure have not been studied. The clearance of gabapentin from plasma decreases in the elderly and patients with impaired renal function. HemodialysisGabapentin is removed from plasma during hemodialysis. In patients with anuria, hemodialysis has a significant effect on the elimination of gabapentin. Hepatic insufficiency. gabapentin is not metabolized in the liver, its use in patients with impaired liver function has not been studied. The age of the clearance of gabapentin decreases with increasing age. Patients under the age of 30 years, the clearance of gabapentin is 225 ml / min, and in patients at the age of 70 years - 125 ml / min. Renal clearance and clearance per unit of the body surface of the subject also decreases with age. Reduction of renal clearance with age may be explained by a decrease in renal function. Children It has been established that plasma concentrations of gabapentin in children aged 1 month to 12 years are generally similar.Cmax reached after 2-3 hours. In children aged 1 month to 5 years, AUC gabapentin was 30% lower than in children aged 5 years and older. Clearance in terms of body weight in children of the younger group is higher. The apparent clearance of gabapentin is proportional to QC. The average T1 / 2 is about 4.7 hours and is similar between the indicated age groups. According to pharmacokinetic data, the effective daily dose in children with epilepsy at the age of 3–4 years is 40 mg / kg / day, while plasma concentrations are similar to plasma concentrations in children aged 5 years and older when they are last treated with a dose of 30 mg / kg / day. Despite the fact that the comparison of gabapentin pharmacokinetics in men and women has not been carried out, it is assumed that their pharmacokinetic parameters do not differ significantly. Rasovyjastiya gabapentin pharmacokinetic differences among representatives of different their races have not been investigated. Since gabapentin is mainly excreted by the kidneys, and there are no differences in renal function in patients of different races, then no differences in pharmacokinetic parameters are expected.
Indications
Treatment of neuropathic pain in adults aged 18 years and older. Efficacy and safety in patients under the age of 18 years have not been established. Monotherapy of partial seizures with secondary generalization and without it in adults and children over the age of 12 years. The efficacy and safety of monotherapy in children under the age of 12 years have not been established. As an additional agent in the treatment of partial seizures with secondary generalization and without it in adults and children aged 3 years and older. The safety and efficacy of additional gabapentin therapy in children less than 3 years old has not been established.
Contraindications
Hypersensitivity to gabapentin or auxiliary components of the drug. These dosage forms are not intended for use in children under 3 years of age.
Precautionary measures
Do not exceed the recommended dose. With caution, you should prescribe the drug for renal failure.
Use during pregnancy and lactation
There are no data on the use of the drug in pregnant women, so gabapentin should be used during pregnancy only if the intended benefit to the mother justifies the possible risk to the fetus. Gabapentin is excreted with breast milk, its effect on the fed infant is unknown, therefore during breastfeeding Neurontin should be prescribed only if the benefit to the mother clearly outweighs the risk to the infant.
Dosage and administration
Neurontin is administered internally, regardless of the meal or with food. If it is necessary to reduce the dose, discontinue the drug or replace it with an alternative means, this should be done gradually over at least one week. Neuropathic pain in adults. The initial dose is 900 mg / day in three doses in equal doses; If necessary, depending on the effect, the dose is gradually increased to the maximum - 3600 mg / day. Treatment can be started immediately with a dose of 900 mg / day (300 mg 3 times a day) or during the first 3 days the dose can be increased gradually to 900 mg per day according to the following scheme: Day 1: 300 mg of the drug 1 time per day 2nd day: 300 mg 2 times a day 3rd day: 300 mg 3 times a day Partial seizures Adults and children over 12 years of age: The effective dose is from 900 to 3600 mg / day. Therapy can be started with a dose of 300 mg 3 times a day on the first day or increased gradually to 900 mg according to the scheme described above (see the section “Neuropathic pain in adults”). Subsequently, the dose can be increased to a maximum of 3,600 mg / day (divided into 3 equal doses). There was a good tolerability of the drug in doses up to 4800 mg / day. The maximum interval between doses when taking the drug three times should not exceed 12 hours in order to avoid the resumption of seizures. Children aged 3-12 years: The initial dose of the drug varies from 10 to 15 mg / kg / day, which is prescribed in equal doses 3 times a day and increased to an effective amount in about 3 days. The effective dose of gabapentin in children aged 5 years and older is 25-35 mg / kg / day in equal doses in 3 doses. The effective dose of gabapentin in children aged 3 to 5 years is 40 mg / kg / day in equal doses in 3 doses. There was a good tolerability of the drug in doses up to 50 mg / kg / day with prolonged use. The maximum interval between doses of the drug should not exceed 12 hours in order to avoid the resumption of seizures. There is no need to control the concentration of gabapentin in plasma. It can be used in combination with other anticonvulsants without taking into account changes in its plasma concentration or concentration of other anticonvulsant drugs in serum. Selection of doses for renal failure. Patients with renal insufficiency are recommended to reduce the dose of gabapentin according to Table 1: Creatinine clearance (ml / min) Daily dose (mg / day) A≥80 900-360050-79 600-180030-49 300-90015-29 150B-600miner15 150B-300A The daily dose should be prescribed in three doses; B. Assign 300 mg every other day. Recommendations for patientson hemodialysis. For patients on hemodialysis who have not previously taken gabapentin, it is recommended to administer the drug in a saturating dose of 300-400 mg, and then apply it to 200-300 mg every 4 hours of hemodialysis.
Side effects
In the treatment of neuropathic pain The main side effects that occurred during treatment were no less than in 1% of patients: The body as a whole: accidental injuries, asthenia, back pain, flu-like syndrome, infection, pain of different localization, peripheral edema, weight gain ; Digestive tract: constipation, diarrhea, dry mouth, dyspepsia, flatulence, nausea, vomiting, abdominal pain; Nervous system: gait disturbance, amnesia, ataxia, confusion, headache, dizziness, hypesthesia, drowsiness, impaired thinking, tremor; Respiratory system: shortness of breath, pharyngitis; Skin and Subcutaneous Tissue: skin rash; Sense organs: amblyopia. In the treatment of partial seizures, safety of gabalentine as an additional agent has been studied in more than 2,000 patients; its portability was good. Gabapentin is most often used in combination with other anticonvulsants, therefore, it was impossible to establish which drug (s) caused the side effects (if such a connection existed at all). The main side effects that occurred during treatment were no less than in 1% of patients: The body as a whole: back pain, fatigue, fever, viral infection, peripheral edema, weight gain, asthenia, general malaise, swelling of the face; Cardiovascular system: increase or decrease in blood pressure; Digestive tract: constipation, dental disease, diarrhea, dyspepsia, increased appetite, dry mouth or throat, nausea and / or vomiting, abdominal pain, flatulence, anorexia, gingivitis; Blood system, lymphatic system: leukopenia; Musculoskeletal system: fractures, myalgia, arthralgia; Nervous system: amnesia, ataxia, confusion, incoordination, depression, dysarthria, emotional lability, insomnia, nervousness, nystagmus, drowsiness, impaired thinking, tremor, muscle twitching, headache, dizziness, hyperkinesis; strengthening, weakening or lack of reflexes, paresthesia, anxiety, hostility; Respiratory system: cough, pharyngitis, rhinitis,pneumonia; Skin and subcutaneous tissues: abrasions, acne, itchy skin, skin rash, purpura (most often it was described as bruises that occurred during a physical injury); Sense organs: amblyopia, diplopia, visual disturbances; Urogenital system: urinary tract infection, impotence; These side effects were mild or moderate. The side effects observed in older patients did not differ from those in younger people. Against the background of monotherapy, no new or unexpected side effects were noted. When comparing the tolerability of the drug in doses of 300 and 3600 mg / day, a dependence on the dose of such phenomena as dizziness, ataxia, drowsiness, paresthesia and nystagmus was observed. Children The following are the side effects observed when prescribing the drug as part of combination therapy in children 3-12 years old with a frequency of about 2% and higher than with placebo. The body as a whole: viral infection, fever, weight gain, fatigue; Digestive system: nausea and / or vomiting; Nervous system: drowsiness, hostility, emotional lability, dizziness, hyperkinesis; Respiratory system: bronchitis, respiratory infection. Other adverse events observed in more than 2% of children whose frequency in the placebo group was similar or higher: pharyngitis, upper respiratory tract infections, headache, rhinitis, seizures, diarrhea, anorexia, cough and otitis media. Termination of treatment due to adverse events Side effects that most often led to the abolition of the drug as adjuvant therapy: drowsiness, ataxia, dizziness, fatigue, nausea and / or vomiting; in monotherapy: dizziness, nervousness, weight gain, nausea and / or vomiting and drowsiness. Adverse events that most often led to the abolition of the drug in children: drowsiness, hyperkinesis and hostility. Post-registration experience of use There have been cases of sudden unexplained death, whose connection with gabapentin treatment has not been established. Other adverse events reported during the post-registration use of the drug included acute renal failure; allergic reactions, including urticaria, erythema multiforme exudative (including Stevens-Johnson syndrome); hypersensitivityincluding systemic reactions; alopecia; angioedema; generalized edema; fluctuations in blood glucose concentration in patients with diabetes mellitus; chest pain; an increase in the volume of the mammary glands; gynecomastia; increase in liver function ;. hallucinations; movement disorders such as choreoathetosis; myoclonus, dyskinesia and paging; heartbeat; pancreatitis; thrombocytopenia; noise in ears; urinary incontinence. After abrupt discontinuation of gabapentin therapy, the following side effects were most frequently noted: anxiety, insomnia, nausea, pain of various locations and sweating.
Overdose
With a single dose of gabapentin in a dose of 49 g, the following symptoms were observed: dizziness, double vision, impaired speech, drowsiness, lethargy and mild diarrhea. Treatment: symptomatic therapy; Hemodialysis may be indicated in patients with severe renal failure.
Interaction with other drugs
When using 600 mg of gabapentin 2 hours after taking morphine in the form of 60 mg prolonged-release capsules, an increase in the average AUC value of gabapentin is noted by 44% compared with gabapentin monotherapy, which is associated with an increase in the pain threshold (cold pressor test). The clinical significance of this change has not been established, and the pharmacokinetic characteristics of morphine did not change. The side effects of morphine when taken together with gabapentin did not differ from those of taking morphine together with placebo. The degree of interaction of these drugs in other doses is unknown. The interaction between gabapentin and phenobarbital, phenytoin, valproic acid and carbamazepine is not marked. The pharmacokinetics of gabapentin in the equilibrium state are the same in healthy people and patients receiving other anticonvulsants. Simultaneous use of gabapentin with oral contraceptives containing norethisterone and / or ethinylestradiol is not accompanied by changes in the pharmacokinetics of both components. Simultaneous use of gabapentin with antacids, with a glutandin, with an antacid, with a gluten, antacids with antacids will not be accompanied by changes in the pharmacokinetics of both components. gabapentin bioavailability of approximately 20% (seesection Specific Instructions). Probenecid does not affect renal excretion of gabapentin. A slight decrease (14%) of renal excretion of gabapentin while taking cimetidine is probably not of clinical significance. With simultaneous use of naproxen (250 mg) and gabapentin (125 mg), there was an increase gabapentin absorption from 12% to 15%. Gabapentin does not affect the pharmacokinetic parameters of naproxen. The indicated doses of drugs are less than the minimum therapeutic. The simultaneous use of these drugs in high doses has not been studied. With the simultaneous use of gabapentin and hydrocodone, a dose-dependent decrease in C max and AUC of hydrocodone is observed compared with hydrocodone monotherapy.
special instructions
Antiepileptic drugs, including gabapentin, may increase the risk of suicidal thoughts or behavior. Therefore, patients receiving these drugs should be carefully monitored for the occurrence or worsening of depression, the appearance of suicidal thoughts or behavior, and also for any changes in behavior. In the case of acute pancreatitis with gabapentin, the possibility of drug withdrawal should be evaluated. cancellation, accompanied by the development of seizures, with treatment with gabapentin is not marked, abrupt cessation of therapy with anticonvulsant drugs in patients with epilepsy may provoke the development of epilepsy status (see the section on the route of administration and dosage). Gabapentin is not considered an effective treatment for the absence of epilepsy. An increase in the concentration of gabapentin in the blood plasma can be observed when used simultaneously with morphine. In this regard, the patient needs to be carefully monitored for the development of signs of depression of the central nervous system (CNS), such as drowsiness. The dose of gabapentin or morphine should be adequately reduced (see the section on Interaction with Other Drugs). On the background of taking antiepileptic drugs, incl. gabapentin, cases of severe life-threatening hypersensitivity reactions, such as a drug rash with concomitant eosinophilia and systemic symptoms, have been reported. It must be remembered that early signs of a hypersensitivity reaction, such as an increase in body temperature, lymphadenopathy, can develop even in the absence of a skin rash. In the event of these symptoms, an immediate examination of the patient is necessary.If no other reasons, except for the use of gabapentin, have been found, the use of the drug should be discontinued. It is recommended to take gabapentin approximately 2 hours after taking the antacid. The effect of long-term therapy (more than 36 weeks) with gabapentin on the ability to learn, the intelligence and development of the child has not been sufficiently studied. It is necessary to evaluate the ratio of the possible risk and benefit when prescribing long-term therapy. As with other anti-epileptic drugs, an increase in the frequency of seizures or the appearance of another type of seizures can be observed while using gabapentin. in the urine using test strips Ames N-Multistix SG. To determine protein in urine, it is recommended to use a more specific method of precipitation with sulfosalicylic acid. Effect on the ability to drive vehicles and control mechanisms. While taking the drug, patients are not recommended to drive or use potentially dangerous equipment until there is no negative effect of the drug on these functions.