Convalis capsules 300mg, 50pcs

Composition

Active ingredient: gabapentin-300.0 mg;

excipients: lactose monohydrate – 66.0 mg, pregelatinized corn starch-30.0 mg, talc-3.0 mg, magnesium stearate-1.0 mg.

The weight of the capsule contents is 400.0 mg.

Capsule shell composition

Solid gelatin capsules No. 0-96.0 mg.

Body and lid: titanium dioxide (E 171) – 2.0000%, iron oxide yellow dye (E 172) – 0.6286%, gelatin – up to 100%.

The total weight of the capsule with the contents is 496.0 mg

Pharmacological action

Pharmacotherapeutic group: antiepileptic agent.

ATC code: N03AX12.

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics

Chemical structure of gabapentin is similar to the structure of the neurotransmitter GABA (gamma-aminobutyric acid), but its mechanism of action differs from other active substances that interact with GABA synapses, such as the valproata, barbiturates, benzodiazepines, inhibitors of GABA-transaminase, inhibitors of the reuptake of GABA agonists and GABA prodrug of GABA. In vitro studies with radioisotope-labeled gabapentin in rat brains revealed new regions of drug binding to proteins, including in the neocortex and hippocampus, which may be related to the anticonvulsant and analgesic activity of gabapentin and its derivatives. It was found that the binding site of gabapentin is the α-2-δ (alpha-2-delta) subunit of potential-dependent calcium channels.

At clinically significant concentrations, gabapentin does not bind to other common drug receptors and neurotransmitters present in the brain, including GABA_A, GABA_B, benzodiazepine, glutamate, glycine, and N-methyl-D-aspartate receptors.

Gabapentin does not interact with sodium channels in vitro, which distinguishes it from phenytoin and carbamazepine. In a number of in vitro test systems, the use of gabapentin resulted in a partial decrease in the response to the glutamate agonist N-methyl-D-aspartate (NMDA), but only at concentrations exceeding 100 mmol/L, which is unattainable in vivo. In vitro use of gabapentin leads to a slight decrease in the release of monoamine neurotransmitters.

The exact mechanism of action of gabapentin is unknown.

Pharmacokinetics

Suction

After oral use, the maximum concentration of gabapentin in the blood plasma is reached within 2-3 hours. The bioavailability of gabapentin tends to decrease with increasing dose. The absolute bioavailability of 300 mg capsules is approximately 60%. Food, including those with a high fat content, does not have a clinically significant effect on the pharmacokinetics of gabapentin.

The pharmacokinetics of gabapentin do not change with repeated use of the drug.

Distribution

Gabapentin does not bind to plasma proteins, and its volume of distribution is 57.7 liters. In patients with epilepsy, the concentration of gabapentin in the cerebrospinal fluid (CSF) is approximately 20% of the minimum steady-state plasma concentration. Gabapentin is excreted in breast milk.

Biotransformation

There are no data on the metabolism of gabapentin in humans. Gabapentin does not induce non-specific liver oxidases responsible for drug metabolism.

Deduction

Gabapentin is excreted unchanged exclusively by renal excretion. The half-life of gabapentin does not depend on the dose taken and is on average from 5 to 7 hours.

In the elderly and patients with impaired renal function, the clearance of gabapentin from blood plasma decreases. The elimination constant, plasma clearance, and renal clearance of gabapentin are directly proportional to creatinine clearance.

Gabapentin is removed from the blood plasma by hemodialysis. Patients with impaired renal function or undergoing hemodialysis are recommended to adjust the dose of the drug (see the section “Dosage and use”).

Linearity/non-linearity of pharmacokinetic parameters

The bioavailability of gabapentin decreases with increasing dose, which leads to non-linearity of pharmacokinetic parameters that include the bioavailability index (F) in the calculation, for example, Ae%, CL/F, Vd/F. The pharmacokinetics of elimination (parameters that do not include F, such as CLr and T_1/2) are better described by a linear model. Steady-state plasma concentrations of gabapentin are predictable based on data on the kinetics of a single dose.

Indications

Treatment of neuropathic pain in adults aged 18 years and older. Efficacy and safety in patients under 18 years of age have not been established. Monotherapy of partial seizures with and without secondary generalization in adults and children aged 12 years and older. The efficacy and safety of monotherapy in children under 12 years of age have not been established.

Use during pregnancy and lactation

Overall risk due to epilepsy and antiepileptic drugs

The risk of having children with congenital abnormalities in mothers who are treated with anticonvulsants increases by 2-3 times. Most often, there is a cleft upper lip and palate, malformations of the cardiovascular system and neural tube defects. At the same time, taking several anticonvulsant medications may be associated with a greater risk of developing malformations than in the case of monotherapy. Therefore, if possible, one of the anticonvulsant medications should be used. Women of childbearing age, as well as all women who may become pregnant, should consult a qualified specialist. If a woman is planning to become pregnant, the need for continuing anticonvulsant therapy should be re-evaluated. At the same time, anticonvulsants should not be abruptly discontinued, as this may lead to a resumption of seizures with severe consequences for the mother and child. In rare cases, children whose mothers suffer from epilepsy have experienced developmental delays. However, it is not possible to determine whether the developmental delay is due to genetic or social factors, maternal illness, or anticonvulsant therapy.

Gabapentin-related risk

There are no data on the use of the drug in pregnant women. In animal experiments, the toxicity of the drug to the fetus was shown. People don’t have any data on the possible risk. Therefore, gabapentin should only be used during pregnancy if the intended benefit to the mother justifies the possible risk to the fetus.

In reported cases, it is not possible to say with certainty whether or not the use of gabapentin during pregnancy is accompanied by an increased risk of malformations, firstly, due to the presence of epilepsy itself, and secondly, due to the use of other anticonvulsants.

Breast-feeding

Gabapentin is excreted in breast milk, its effect on the breastfed child is unknown, so during breast-feeding Convalis® should be prescribed only if the benefit to the mother clearly outweighs the risk to the infant.

No effect of gabapentin on fertility has been observed in animal studies.

Contraindications

• Hypersensitivity to gabapentin or auxiliary components of the drug.
• Epilepsy: use as monotherapy for partial seizures with and without secondary generalization in children under 12 years of age.
• Neuropathic pain: for the treatment of neuropathic pain in children and adolescents under 18 years of age.
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

WITH CAUTION

Renal failure (see “Dosage and use”).

Side effects

Side effects observed in clinical trials of patients with epilepsy (when using gabapentin as monotherapy or in combination with other anticonvulsants) or neuropathic pain are presented below and distributed by organ system and frequency.

The frequency category was defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare ( If the frequency category was different in different studies, then the side effect was assigned a higher category.

Side effects that were reported during the use of the drug after registration were assigned the frequency category “unknown” (the frequency cannot be calculated based on available data).

In each frequency section, side effects are presented in order of decreasing severity.

Infectious and parasitic diseases: very often – viral infections; often-pneumonia, respiratory tract infection, urinary tract infection, other types of infection, otitis media.

Disorders of the blood and lymphatic system: often-leukopenia; unknown-thrombocytopenia.

Immune system disorders: infrequently-allergic reactions, including urticaria; unknown-hypersensitivity, including systemic reactions, such as fever, rashes, hepatitis, lymphadenopathy, eosinophilia and others.

Metabolic and nutritionaldisorders: common– anorexia, increased appetite.

Mental disorders: often-hostility, confusion, depression, anxiety, nervousness, impaired thinking, emotional lability; infrequently-mental deterioration; unknown-hallucinations.

Violations of the nervous system: very often – drowsiness, dizziness, ataxia; often – convulsions, hyperkinesis, dysarthria, amnesia, tremor, insomnia, headache, sensitivity (e. g., paresthesia, hypoesthesia), loss of coordination, nystagmus, strengthening, weakening or absence of reflexes; rarely – hypokinesia; rarely – loss of consciousness; unknown – other disorders of movement (e. g., choreoathetosis, dyskinesia and dystonia).

Visual disturbances: often – visual impairment (such as amblyopia, diplopia).

Hearing disorders and labyrinthine disorders: often-vertigo; unknown-tinnitus.

Cardiac disorders: infrequently-palpitation sensation.

Vascular disorders: often-symptoms of vasodilation or arterial hypertension.

Respiratory, thoracic and mediastinaldisorders: often-shortness of breath, bronchitis, pharyngitis, cough, rhinitis.

Gastrointestinal disorders: often-constipation, diarrhea, dryness of the oral or pharyngeal mucosa, dyspepsia, flatulence, nausea, vomiting, abdominal pain, dental diseases, gingivitis; unknown-pancreatitis.

Liver and biliary tractdisorders: unknown-hepatitis, jaundice.

Violations of the skin and subcutaneous tissues: often – swelling of the face, purpura (often described as bruises that occurred when physical injury), skin rashes, acne, itching of the skin; unknown – the Stevens-Johnson syndrome, angioedema, erythema multiforme, alopecia, drug skin rash, including eosinophilia and systemic reactions (see section “Special instructions”).

Musculoskeletal and connective tissuedisorders: common – myalgia, arthralgia, back pain, muscle twitching; unknown-rhabdomyolysis, myoclonus.

Kidney and urinary tract disorders: unknown – urinary incontinence, acute renal failure.

Genital and breast disorders: common-impotence; unknown-breast enlargement, gynecomastia, sexual dysfunction (including changes in libido, ejaculation disorders and anorgasmia).

General disorders and disorders at the injection site: very often – fatigue, fever; often – peripheral edema, gait disturbance, asthenia, pain of various localization, General malaise, flu-like symptoms; rarely generalized edema; unknown – syndrome (the most commonly noted side effects: anxiety, insomnia, nausea, pain of various localization, and increased sweating), chest pain. Cases of sudden unexplained death have been reported that are not related to gabapentin treatment.

Laboratory and instrumental data: often-a decrease in the concentration of white blood cells, an increase in body weight; infrequently-an increase in the activity of alanine aminotransferase, aspartate aminotransferase and bilirubin concentration in blood plasma, hyperglycemia; rarely-hypoglycemia (mainly in patients with diabetes mellitus); unknown – hyponatremia, an increase in creatine phosphokinase activity.

Injuries, intoxications, and manipulation complications: often – injuries, fractures, abrasions associated with falls.

Acute pancreatitis has been reported with gabapentin therapy. The causal relationship with gabapentin remains unclear (see section “Special instructions”).

Cases of myopathy with increased creatine kinase activity have been reported in patients with end-stage renal failure undergoing hemodialysis.

Cases of respiratory tract infection, otitis media, bronchitis, and seizures were reported only in clinical trials. In addition, cases of aggressive behavior and hyperkinesis in children have been reported in clinical studies.

If any of the side effects listed in the instructions get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Interaction

Spontaneous cases have been reported, as well as possible respiratory depression and/or sedation symptoms associated with gabapentin and opioid analgesics, according to literature sources. In some of these cases, the authors associated these symptoms with the concomitant use of gabapentin and opioids, especially in elderly patients.

When using 600 mg of gabapentin 2 hours after taking morphine in the form of 60 mg long-release capsules, there is an increase in the average gabapentin AUC by 44% compared to 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 co-administered with gabapentin did not differ from those of morphine co-administered with placebo. The degree of interaction of these drugs in other doses is unknown.

Interactions between gabapentin and phenobarbital, phenytoin, valproic acid, and carbamazepine were not observed. The pharmacokinetics of gabapentin at steady state are similar in healthy individuals and patients receiving other anticonvulsants.

Concomitant use of gabapentin with oral contraceptives containing norethisterone and / or ethinyl estradiol is not accompanied by changes in the pharmacokinetics of both components.

Concomitant use of gabapentin with antacids containing aluminum and magnesium is associated with a decrease in the bioavailability of gabapentin by approximately 24% (see the section “Special instructions”).

Probenecid does not affect the renal excretion of gabapentin.

A slight decrease (14%) in the renal excretion of gabapentin with concomitant use of cimetidine is probably not clinically relevant.

With the simultaneous use of naproxen (250 mg) and gabapentin (125 mg), gabapentin absorption increased from 12% to 15%. Gabapentin does not affect the pharmacokinetic parameters of naproxen. The indicated doses of drugs are less than the minimum therapeutic ones. Concomitant use of these drugs in large doses has not been studied.

How to take, course of use and dosage

Convalis® is administered orally regardless of food intake. If it is necessary to reduce the dose, discontinue the drug or replace it with an alternative remedy, this should be done gradually for at least one week.

Neuropathic pain in adults

The initial dose is 900 mg / day in three equal doses; if necessary, depending on the effect, the dose is gradually increased to a maximum of 3600 mg/day. Treatment can be started immediately with a dose of 900 mg / day (300 mg 3 times a day) or you can increase the dose gradually to 900 mg / day for the first 3 days according to the following scheme:

Day 1: 300 mg of the drug once a day;

day 2: 300 mg of the drug twice a day;

day 3: 300 mg of the drug 3 times a day.

Partial seizures

Epilepsy usually requires long-term treatment. The dose of the drug is determined by the attending physician, depending on the individual tolerance and effectiveness of the drug.

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 gradually increased to 900 mg according to the scheme described above (see the subsection “Neuropathic pain in adults”). Subsequently, the dose can be increased to a maximum of 3600 mg / day (divided into 3 equal doses). Good tolerability of the drug in doses up to 4800 mg / day was noted. The maximum interval between doses when taking the drug three times should not exceed 12 hours to avoid the resumption of seizures.

Patients in serious condition

In patients in a serious condition, for example, in the case of low body weight, after organ transplantation, etc., the dose should be increased more slowly, either using smaller doses or taking longer intervals before increasing the dose.

Use in elderly patients (over 65 years of age)

Due to age-related decline in renal function, elderly patients may need to adjust the dose (for more information, see table 1). Drowsiness, peripheral edema, and asthenia may occur more frequently in elderly patients.

Recommendations for patients undergoing hemodialysis

Patients on hemodialysis who have not previously taken gabapentin are recommended to take the drug in a saturating dose of 300 mg, and then apply it 300 mg after every 4 hours of hemodialysis.

For patients with reduced renal function undergoing dialysis, the maintenance dose of gabapentin should be selected in accordance with the recommendations presented in table 1. In addition to maintenance therapy,300 mg of gabapentin is recommended after each 4-hour hemodialysis procedure.

Overdose

With a single dose of 49 g of gabapentin, the following symptoms were observed: dizziness, double vision, speech disorders, drowsiness, loss of consciousness, lethargy and mild diarrhea, which completely disappeared with symptomatic therapy. It should be borne in mind that after taking high doses of gabapentin, its absorption in the intestine decreases. Overdose with gabapentin may lead to coma, especially with the simultaneous use of other drugs that suppress the central nervous system. Despite the fact that gabapentin can be eliminated by hemodialysis, experience shows that this is usually not necessary. Hemodialysis may be indicated for patients with severe renal insufficiency.

Description

Capsules No. 0 are yellow in color. The contents of the capsules are white or yellowish crystalline powder.

Special instructions

Antiepileptic drugs, including gabapentin, may increase the risk of suicidal thoughts or behavior. A meta-analysis of randomized placebo-controlled trials of antiepileptic drugs showed a small increase in the risk of suicidal thoughts and behavior. The mechanism of increased risk of suicidal ideation is unknown, but it cannot be ruled out for gabapentin.

Therefore, patients receiving these medications should be carefully monitored for the onset or worsening of depression, suicidal thoughts or behaviors, and any changes in behavior. If signs of suicidal thoughts or behavior appear, patients or their caregivers should consult a doctor.

Acute pancreatitis

If acute pancreatitis develops while taking gabapentin, the possibility of discontinuing the drug should be evaluated.

Seizures (withdrawal syndrome)

Although withdrawal symptoms associated with seizures have not been reported during gabapentin treatment, abrupt discontinuation of anticonvulsant therapy in patients with epilepsy may provoke the development of status epilepticus.

As with other antiepileptic drugs, gabapentin may cause an increase in the frequency of seizures or a different type of seizure.

As with other anticonvulsants, attempts to cancel all concomitant antiepileptic drugs in order to start monotherapy with gabapentin in case of treatment refractoriness in patients taking several anticonvulsants are generally unsuccessful.

Gabapentin is considered ineffective in primary generalized seizures, such as absences, and may even increase such seizures in some patients. Therefore, gabapentin should be used with caution in patients with mixed seizures, including absences.

Elderly patients

Systematic studies of patients aged 65 years and older taking gabapentin have not been conducted. In a double-blind study using gabapentin for neuropathic pain, patients aged 65 years and older had a higher incidence of drowsiness, peripheral edema, and asthenia compared to patients under 65 years of age. With the exception of these results, a clinical examination of this group of patients showed that their side effect profile did not differ from the rest.

Children

The effect of long-term gabapentin therapy (more than 36 weeks) on the child’s learning ability, intelligence, and development is not well understood. It is necessary to evaluate the ratio of possible risk and benefit when prescribing long-term therapy.

Abuse and addiction

The database of post-marketing observations contains reports of cases of drug abuse and dependence. As with any drug that affects the central nervous system, doctors should carefully examine patients ‘ medical history for drug abuse and monitor them for possible signs of gabapentin abuse (for example, unwarranted desire to receive the drug, development of resistance to gabapentin therapy, unjustified increase in the dose of the drug).

DRESS-syndrome

Severe life-threatening hypersensitivity reactions, such as drug-induced rash with concomitant eosinophilia and systemic symptoms, have been reported while taking antiepileptic drugs, including gabapentin. It should be remembered that early signs of a hypersensitivity reaction, such as fever, lymphadenopathy, can develop even in the absence of a skin rash. If such symptoms occur, the patient should be examined immediately. If no other reason is found other than the use of gabapentin, the drug should be discontinued.

Anaphylaxis

Taking gabapentin can lead to the development of anaphylaxis. The following symptoms and signs were noted in cases of anaphylaxis while taking gabapentin: difficulty breathing, swelling of the lips, throat and tongue, and a pronounced decrease in blood pressure requiring urgent medical intervention. Patients should be warned that if signs or symptoms of anaphylaxis develop, they should stop taking the drug and seek medical attention.

Laboratory tests

When gabapentin and other anticonvulsants were co-administered, false positive results were reported when determining protein in the urine using Ames N-Multistix SG®test strips. To determine protein in the urine, it is recommended to use a more specific method of precipitation with sulfosalicylic acid.

Impact on the central nervous system

During treatment with gabapentin, dizziness and drowsiness have been reported, which may increase the likelihood of accidental injury (in a fall). In the post-marketing period, cases of confusion, loss of consciousness and impaired mental activity were also reported. Therefore, patients should be advised to exercise caution until they become aware of the possible effects of this medication.

When used concomitantly with opioid analgesics, an increase in the concentration of gabapentin in blood plasma may occur. In this regard, the patient should be closely monitored for signs of CNS depression, such as drowsiness, sedation, and respiratory depression. Doses of gabapentin or opioid analgesics should be reduced.

Combined use with antacids

Gabapentin is recommended to be taken approximately 2 hours after taking the antacid.

INFLUENCE ON THE ABILITY TO DRIVE VEHICLES AND MECHANISMS

While taking the drug, patients are not recommended to drive vehicles or use potentially dangerous equipment until it is confirmed that the drug does not negatively affect the performance of these functions.

Gabapentin affects the central nervous system and can cause dizziness, drowsiness, confusion, loss of consciousness, or other CNS symptoms. Even if mild or moderate, these undesirable effects can be dangerous for patients driving vehicles or other machinery. This is especially likely at the beginning of treatment or after increasing the dose of gabapentin.

Form of production

Capsules,300 mg. 10 capsules in a contour cell package made of polyvinyl chloride film and aluminum foil printed varnished. 3 or 5 contour cell packs together with instructions for use in a cardboard pack.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 C. Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Gabapentin

Conditions of release from pharmacies

By prescription

Dosage form

Capsules