Composition, form of production and packaging
Capsules size no. 0, yellow; the contents of the capsules are a crystalline powder of white or white with a slightly yellowish hue of color.
1 caps.
gabapentin 300 mg
Excipients: lactose monohydrate - 0.066 g, corn pregelatinized corn starch - 0.03 g, talc 0.003 g, magnesium stearate - 0.001 g.
The composition of hard gelatin capsules: titanium dioxide - 2%, iron oxide oxide yellow - 0.6286%, gelatin - up to 100%.
10 pieces. - packings cellular planimetric (5) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Gabapentin is structurally similar to the GABA neurotransmitter, however its mechanism of action differs from that of some other drugs interacting with GABA receptors, including valproic acid, barbiturates, benzodiazepines, GABA transaminase inhibitors, GABA capture inhibitors, GABA agonists and prodrugs of GABA: it is not has GABA-ergic properties and does not affect the capture and metabolism of GABA.
Preliminary studies suggest that gabapentin binds to? 2 -? - subunit of potential-dependent calcium channels and suppresses the flow of calcium ions, which plays an important role in the occurrence of neuropathic pain. Other mechanisms involved in the action of gabapentin in neuropathic pain are: reduction of glutamate-dependent neuronal death, an increase in GABA synthesis, inhibition of the release of neurotransmitters of the monoamine group. Gabapentin does not bind to other receptors at clinically significant concentrations, including the GABA A , GABA B , benzodiazepine, glutamate, glycine, or N-methyl-d-acanthate receptors. Unlike phenytoin and carbamazepine, gabapentin does not interact with sodium channels in vitro. Gabapentin partially attenuated the effects of the glutamate receptor agonist N-methyl-d-aspartate in some tests in vitro, but only at a concentration of more than 100 Ојmol / L, which is not achieved in vivo. Gabapentin somewhat reduces the release of monoamine neurotransmitters in vitro.
PHARMACOKINETICS
Suction and distribution
After oral administration of C max, gabapentin in plasma is achieved after 2-3 hours. Absolute bioavailability of gabapentin in capsules is about 60%. Bioavailability is not proportional to the dose; When the dose is increased, it decreases. Food, incl. with a high fat content, does not affect the pharmacokinetics.
Pharmacokinetics does not change with repeated application. C ss in plasma can be predicted based on the results of a single dose of the drug. Gabapentin practically does not bind to plasma proteins (<3%) and has a V d of 57.7 l.
Metabolism and excretion
T 1/2 from the plasma is dose independent and averages 5-7 hours. It is excreted exclusively by the kidneys in unchanged form, it is not metabolized. The drug does not induce oxidative liver enzymes with a mixed function involved in the metabolism of drugs.
The clearance of gabapentin from plasma decreases in elderly patients and patients with impaired renal function. The rate of elimination constant, clearance from plasma and renal clearance are directly proportional to QC. Gabapentin is removed from the plasma during hemodialysis. In patients with impaired renal function and patients on hemodialysis, dose adjustment is recommended.
INDICATIONS
- epilepsy: in adults and children older than 12 years - as a monotherapy or as part of a combination therapy for the treatment of partial epileptic seizures, incl.proceeding with secondary generalization;
- for the treatment of neuropathic pain in adults.
DOSING MODE
The drug is taken orally, regardless of food intake, without chewing and washing down with the necessary amount of liquid.
Monotherapy and the use of Kovalis as an adjunct for the treatment of partial epileptic seizures in children over 12 years of age and adults
Treatment begins with a dose of 300 mg 1 time / day and gradually increases to 900 mg / day (the first day - 300 mg 1 time / day, the second - 300 mg 2 times / day, the third - 300 mg 3 times / day). In the future, the dose may be increased. Usually the dose of Convalis is 900-1200 mg / day. The maximum dose is 3600 mg / day, divided into three equal doses in 8 hours. The maximum interval between taking the doses of the drug should not exceed 12 hours in order to avoid the resumption of seizures.
Neuropathic pain in adults
Treatment starts with a dose of 300 mg on the first day, then: 600 mg (300 mg 2 times) on the second day, 900 mg (300 mg 3 times) on the third day. With intense pain, Convalis В® can be used from the first day to 300 mg 3 times / day. Depending on the effect, the dose can be gradually increased, but not more than 3600 mg / day.
In patients with impaired renal function ( with KK 50-79 ml / min), the daily dose of the drug is 600-1800 mg / day, with QC 30-49 ml / min - 300-900 mg / day,with KK 15-29 ml / min - 300-600 mg / day, with QC less than 15 ml / min - 300 mg every other day or every day.
In patients on hemodialysis , the initial dose of Convalis is 300 mg. The additional postgemodialysis dose is 300 mg after each 4-hour hemodialysis session. In days when dialysis is not performed, Convalis В® is not used.
SIDE EFFECT
In the treatment of neuropathic pain
From the digestive system: constipation, diarrhea, dry mouth, dyspepsia, flatulence, nausea, vomiting, abdominal pain.
From the side of the central nervous system: gait disturbance, amnesia, ataxia, confusion, dizziness, hypoesthesia, drowsiness, impaired thinking, tremor.
From the respiratory system: shortness of breath, pharyngitis.
From the skin: skin rash.
From the sense organs: amblyopia.
Other: asthenic syndrome, flu-like syndrome, headache, infectious diseases, pain of different localization, peripheral edema, weight gain.
When treating partial seizures
From the cardiovascular system: symptoms of vasodilation, increase or decrease in blood pressure.
From the digestive system: flatulence, anorexia, gingivitis, abdominal pain, constipation, dental disease, diarrhea, dyspepsia, increased appetite, dry mouth or throat, nausea, vomiting.
On the part of the blood system: purpura (most often it was described as bruising arising from physical trauma), leukopenia.
From the musculoskeletal system: arthralgia, pain in the back, increased brittle bones, myalgia.
From the side of the central nervous system: dizziness, hyperkinesia; strengthening, weakening or lack of tendon reflexes, paresthesia, anxiety, hostility, amnesia, ataxia, confusion, impaired coordination of movements, depression, dysarthria, emotional lability, insomnia, nystagmus, drowsiness, thinking disorder, tremor, fibrillation of muscles.
On the part of the respiratory system: pneumonia, cough, pharyngitis, rhinitis.
From the skin: abrasions, acne, skin itching, skin rash.
From the urinary system: infection of the urinary tract.
On the part of the reproductive system: impotence.
From the sense organs: visual impairment, amblyopia, diplopia.
Other: asthenic syndrome, face swelling, fatigue, fever, headache, viral infection, peripheral edema, weight gain.
When comparing the tolerability of the drug at doses of 300 and 3600 mg / day, the dose-dependence of such phenomena as dizziness, ataxia, drowsiness, paresthesia and nystagmus was noted.
Post-registration application experience
Possible cases of sudden unexplained death are not associated with treatment with gabapentin. In the course of treatment with gabapentin, the following adverse events can occur: various allergic reactions, acute renal failure, impaired liver function, pancreas, increased volume of mammary glands, gynecomastia, hallucinations, motor disorders (myoclonus, discenosis, dystonia), palpitation, thrombocytopenia, noise in ears, urination disorders.
After abrupt abolition of gabapentin therapy, the most common side effects were anxiety, insomnia, nausea, pain of varying localization and sweating.
If any of the side effects listed in the manual are aggravated or other side effects not indicated in the instructions are noted, you should notify the doctor.
CONTRAINDICATIONS
acute pancreatitis;
- children's age till 12 years;
- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
- Hypersensitivity to the drug and / or its components.
Caution should be given in case of kidney failure.
PREGNANCY AND LACTATION
There is insufficient data on the use of gabapentin in pregnant women. Do not use the drug during pregnancy, if the potential benefit to the mother does not exceed the possible risk to the fetus.
The drug penetrates into breast milk, the effect on children during breastfeeding is unknown, so during breastfeeding, the drug should be used only if the potential benefit to the mother from taking the drug clearly exceeds the potential risk for the baby.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution should prescribe the drug for kidney failure.
In patients with impaired renal function ( with KK 50-79 ml / min), the daily dose of the drug is 600-1800 mg / day, with QC 30-49 ml / min - 300-900 mg / day,with KK 15-29 ml / min - 300-600 mg / day, with QC less than 15 ml / min - 300 mg every other day or every day.
In patients on hemodialysis , the initial dose of Convalis is 300 mg. The additional postgemodialysis dose is 300 mg after each 4-hour hemodialysis session. In days when dialysis is not carried out, Kovalis is not used.
APPLICATION FOR CHILDREN
The use of the drug is contraindicated in children under 12 years of age.
SPECIAL INSTRUCTIONS
When analyzing urine for total protein using the Ames N-Multistix SG В® test system, a false positive result is possible. You must confirm the result with another method of analysis.
Patients with diabetes sometimes need a change in the dose of hypoglycemic drugs.
When there are signs of acute pancreatitis, drug treatment should be stopped.
Abolish the drug or replace it with an alternative drug should be gradually, at least within a week. A sharp cessation of therapy with anticonvulsants in patients with partial seizures can provoke the development of seizures.
There is an increased risk of suicide and suicidal thoughts. With the purpose of early detection of behavioral disorders, which may be harbingers of suicidal thoughts and actions, it is recommended to monitor the mental state of patients.
Impact on the ability to drive vehicles and manage mechanisms
During the period of treatment, it is necessary to refrain from driving and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: with a single admission 49 g gabapentin observed dizziness, diplopia, speech disturbance, drowsiness, dysarthria, diarrhea. The lethal dose of gabapentin when ingested is established in mice and rats treated with the drug at doses of 8000 mg / kg. Signs of acute toxicity in animals included ataxia, shortness of breath, ptosis, hypoactivity or agitation.
Treatment: symptomatic therapy. Patients with severe renal insufficiency can be shown hemodialysis.
DRUG INTERACTION
With the simultaneous administration of gabapentin and morphine, when morphine was taken 2 hours before taking gabapeptin, an increase in the mean AUB of gabapentin by 44% was observed compared to gabapentin alone, which was associated with an increase in the pain threshold (a cold pressor test). The clinical significance of this change has not been established, the pharmacokinetic characteristics of morphine remain unchanged. The side effects of morphine when taken together with gabapentin did not differ from those when taking morphine together with placebo.
Interactions between gabapentin and phenobarbital, phenytoin, valproic acid and carbamazepine have not been observed. The pharmacokinetics of gabapentin in the equilibrium state is the same in healthy people and patients receiving other anticonvulsants.
The simultaneous use of gabapentin with oral contraceptives containing norethisterone and / or ethinylestradiol was not accompanied by changes in the pharmacokinetics of both components.
Antacid preparations containing aluminum or magnesium reduce the bioavailability of gabapentin by about 20%. In this regard, the drug should be taken no earlier than 2 hours after taking antacids.
Pimetidine slightly reduces renal excretion of gabapentin.
Ethanol and drugs acting on the central nervous system can increase the side effects of gabapentin from the side of the central nervous system.
With the simultaneous administration of naproxen with gabapentin, the absorption of the latter increases, while gabapentin does not affect the pharmacokinetic parameters of naproxen.
The simultaneous use of gabapentin with hydrocodone leads to a decrease in pharmacokinetic parameters (C max and AUC) of hydrocodone and an increase in gabapentin AUC.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a dry, protected from light and out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 3 years.
