Kovalis - instructions for use, dose, side effects, contraindications

Gabapentin is structurally similar to the neurotransmitter gamma-aminobutyric acid (GABA), but its mechanism of action differs from that of some other drugs that interact with the GABA - receptor, including valproate, barbiturates, benzodiazepines, GABA transaminase inhibitors; inhibitors of GABA uptake, GABA agonists and prodrug forms of GABA: it does not possess GABA-ergic properties and does not affect GABA capture and metabolism.

Preliminary studies indicate that gabapentin communicates with α2-δ-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, suppression of the release of neurotransmitters of the monoamine group. Gabapentin in clinically significant concentrations does not bind to other receptors, including GABA, GABA, benzodiazepine, glutamate,glycine or N-methyl-d-aspartate. 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 in vitro tests, but only at a concentration of more than 100 μmol / L, which is not achieved in vivo. Gabapentin slightly reduces the release of monoamine neurotransmitters in vitro.

Pharmacokinetics:

The bioavailability of gabapentin is not proportional to the dose: thus, as the dose is increased, it decreases. After oral administration, the maximum concentration (Cmax) gabapentin in plasma is achieved after 2-3 hours. Absolute bioavailability of gabapentin in capsules is about 60%. Food, including those with a high fat content, does not affect the pharmacokinetics. Half-life (T1/2) from the plasma does not depend on the dose and averages 5-7 hours. Pharmacokinetics does not change with repeated application; equilibrium concentrations 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 volume distribution of 57.7 liters. 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 people and in patients with impaired renal function. The rate of elimination constant, clearance from plasma and renal clearance are directly proportional to the creatinine clearance. Gabapentin is removed from the plasma during hemodialysis. In patients with impaired renal function and patients on hemodialysis, dose adjustment is recommended (see Dosage and Administration).

Indications:Epilepsy: in adults and children over 12 years of age - in the form of monotherapy or as part of a combination therapy for the treatment of partial epileptic seizures, including those occurring with secondary generalization.

For the treatment of neuropathic pain in adults.

Contraindications:

Sensitive sensitivity to the drug and / or its components, age up to 12 years. Acute pancreatitis. Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Carefully:Renal failure (see "Method of administration and dose").

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.

Dosing and Administration:

Inside, regardless of food intake, without chewing and washing down with the necessary amount of liquid.

Monotherapy and the use of Kovalis as an adjuvant for the treatment of partial epileptic seizures in children over 12 years of age and adults.

Treatment begins with a dose of 300 mg orally once a day and gradually increases to 900 mg / day (the first day - 300 mg orally once a day, three times - 300 mg twice a day, the third - 300 mg three times a day ) Subsequently, the dose may be increased. Usually the dose Convalisa is 900-1200 mg per day. The maximum dose is 3600 mg / day, divided into three equal doses after 8 hours.The maximum interval between taking doses of the drug should not exceed 12 hours in order to avoid the resumption of seizures.

Neuropathic pain in adults.

Treatment begins with a dose of 300 mg on the first day, 600 mg (300 mg twice) on the second day, 900 mg (300 mg 3 times) on the third day. In the presence of intense pain Convalis can be appointed from the first day to 300 mg three times a day. Depending on the effect, the dose can be gradually increased, but not more than 3600 mg / day.

In patients with impaired renal function, the daily dose of the drug is: for creatinine clearance of 50-79 ml / min - 600-1800 mg / day, Z0-49 ml / min - 300-900 mg / day, 15-29 ml / min - 300 -600 mg / day, less than 15 ml / min - 300 mg every other day or every day.

In patients on hemodialysis, the initial dose Convalisa is 300 mg. The additional postgemodialysis dose is 300 mg after each 4-hour hemodialysis session. On days when dialysis is not performed, Convalis do not apply.

Side effects:

In the treatment of neuropathic pain

Gastrointestinal tract: constipation, diarrhea, dry mouth, indigestion, flatulence, nausea, vomiting, abdominal pain.

Nervous system: gait disturbance, amnesia, ataxia, confusion, dizziness, hypoesthesia, drowsiness, impaired thinking, tremor. Respiratory system: shortness of breath, pharyngitis.

Skin: skin rash.

Sense organs: amblyopia.

Other: asthenic syndrome, flu-like syndrome; headache, infectious diseases, pain of different localization, peripheral edema, weight gain.

When treating partial seizures

The cardiovascular system: symptoms of vasodilation, increased blood pressure, increased or decreased blood pressure.

Gastrointestinal tract: flatulence, anorexia, gingivitis; abdominal pain, constipation, dental disease, diarrhea, dyspepsia, increased appetite, dry mouth or throat; nausea, vomiting.

System of blood, lymphatic system: purpura (most often it was described as bruising that occurs with physical trauma), and leukopenia.

Musculoskeletal system: arthralgia, back pain, increased brittle bones, myalgia.

Nervous system: dizziness, hyperkinesis; strengthening, weakening or lack of tendon reflexes, paresthesia, anxiety, hostility, amnesia, ataxia, confusion, impaired coordination of movements, depression, dysarthria, emotional lability, insomnia, nystagmus,drowsiness; disturbance of thinking, tremor, fibrillation of muscles.

Respiratory system: pneumonia, cough, pharyngitis, rhinitis.

Skin: abrasions, acne, skin itching, skin rash.

Genitourinary system: urinary tract infection, impotence.

Sense organs: impaired vision, amblyopia; diplopia.

Other: asthenic syndrome, face swelling, fatigue, fever, headache, viral infection, peripheral edema, weight gain.

When comparing the tolerability of the drug - in doses of 300 and 3600 mg / day, the dose-dependence of such phenomena as dizziness, ataxia, drowsiness, paresthesia and nystagmus was noted.

Post-registration experience of application.

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 the ears, urination disorders.

After the abrupt withdrawal of gabapentin therapy, the most common side effects were: anxiety, insomnia, nausea; pain of different localization and sweating.

If any of the side effects listed in the instructions are aggravated, or you notice any other side effects not listed in the instructions, report this to the doctor.

Overdose:

With a single administration of 49 g of gabapentin, dizziness, diplopia, speech impairment, drowsiness, dysarthria, and diarrhea were observed, which completely disappeared during symptomatic therapy.

Patients with severe renal insufficiency can be shown hemodialysis.

The lethal dose of gabapentin when ingested was 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.

Interaction:

With the joint administration of gabapentin and morphine, when morphine was taken 2 hours prior to gabapentin, an increase in the mean area under the pharmacokinetic concentration-time curve (AUC) of gabapentin by 44% compared with gabapentin alone was associated with an increase in the pain threshold (cold pressor test).The clinical significance of this change has 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. not noted. 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 ethinyl estradiol, 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. Cimetidine slightly reduces renal excretion of gabapentin. Alcohol and drugs acting on the central nervous system can increase the side effects of gabapentin from the side of the central nervous system.

When co-administration of naproxen with gabapentin increases absorption of the latter, while gabapentin does not affect the pharmacokinetic parameters of naproxen.

The joint administration of gabapentin with hydrocodone leads to a decrease in pharmacokinetic parameters Cmax and AUC of hydrocodone and an increase in AUC

gabapentin.

Special instructions:

When analyzing urine for total protein using the Ames N-Multistix SG® 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 convulsions (see Dosage and Administration).

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.

Effect on the ability to drive transp.cf. and fur:

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.

Form release / dosage:Capsules.

Packaging:

For 10 capsules in a planar cell packaging made of polyvinylchloride film and aluminum foil printed lacquered.

3 or 5 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001576

Date of registration:13.05.2011 / 01.12.2014

Expiration Date:Unlimited

The owner of the registration certificate:LEKKO, ZAO LEKKO, ZAO Russia

Manufacturer: & nbsp

LEKKO, ZAO Russia

Information update date: & nbsp01.12.2014

Illustrated instructions

Instructions

Convalis (Convalis)