Neurontin capsules 300mg, 50pcs

Composition

of 1 capsule of gabapentin 300 mg

Auxiliary substances:

lactose monohydrate – 42.75 mg,

corn starch-30 mg,

talc-30 mg.

Capsule shell composition:

gelatin-64.07 mg, titanium dioxide (E 171) – 0.76 mg, iron oxide yellow dye (E 172) – 0.15 mg, sodium lauryl sulfate-less than 0.15 mg.

Ink composition:

shellac – 0.075 mg, titanium dioxide (E 171) – 0.027 mg, indigo carmine-0.021 mg

Pharmacological action

Gabapentin is similar in structure to GABA, but the mechanism of action differs from that of some other similar drugs that interact with GABA receptors, including valproate, barbiturates, benzodiazepines, GABA transaminase inhibitors, GABA uptake inhibitors, GABA agonists and prodrug forms of GABA: it does not have GABA-ergic properties and does not affect the uptake and metabolism of GABA. The results of preliminary studies indicate that gabapentin binds to the a2-δ subunit of voltage-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: a decrease in glutamate-dependent neuronal death, an increase in GABA synthesis, and suppression of the release of monoamine group neurotransmitters. Gabapentin in clinically significant concentrations does not bind to the receptors of other common drugs or neurotransmitters, including GABAA, GABAB, benzodiazepine, glutamate, glycine or N-methyl-d-aspartate (NMDA) receptors.

The effect of gabapentin differs from phenytoin and carbamazepine: it does not interact with sodium channels in vitro. Gabapentin partially attenuated the effects of the NMDA glutamate receptor agonist in some in vitro tests, but only at concentrations greater than 100 mmol, which is not achieved in vivo. Gabapentin slightly reduces the release of monoamine neutrotransmitters in vitro.

A rat trial showed that gabapentin use resulted in increased GABA metabolism in some areas of the brain; this effect was similar to that of sodium valproate, although it was observed in other areas of the brain. The significance of these effects of gabapentin for its anticonvulsant activity has not been established. It has also been proven that gabapentin easily penetrates the brain tissue in animals and prevents seizures caused by maximum electric shock, chemical preparations, including GABA synthesis inhibitors, as well as due to genetic factors.

Pharmacokinetics

 Suction

After oral use, the Cmax of gabapentin in plasma is reached in 2-3 hours. The bioavailability of gabapentin is not proportional to the dose; thus, when the dose is increased, it decreases. The absolute bioavailability of gabapentin in capsules is about 60%. Food, including those with a high fat content, does not affect the pharmacokinetics.

The elimination of gabapentin from plasma is linear.

Metabolism

There were no signs of metabolism in humans, and the drug does not induce oxidative liver enzymes with mixed functions involved in drug metabolism.

The distribution

of pharmacokinetics does not change with repeated use; steady-state plasma concentrations can be predicted based on the results of a single dose of the drug. Gabapentin practically does not bind to plasma proteins (less than 3%), Vd is about 57.7 l.

The elimination

of T1 / 2 from plasma does not depend on the dose and averages 5-7 hours.

It is excreted exclusively by the kidneys in unchanged form.

Pharmacokinetics in special clinical cases

The clearance of gabapentin from plasma decreases in the elderly and patients with impaired renal function.

The elimination rate constant, plasma clearance, and renal clearance are directly proportional to CC. Gabapentin is removed from the plasma by hemodialysis.

In patients with impaired renal function and patients receiving hemodialysis treatment, dose adjustment is recommended.

It was found that the plasma concentrations of gabapentin in children aged 4-12 years are generally similar to those in adults.

Indications

• treatment of neuropathic pain in adults aged 18 years and older;
• monotherapy of partial seizures with and without secondary generalization in adults and children over the age of 12 years;
• as an adjunct in the treatment of partial seizures with and without secondary generalization in adults and children aged 3 years and older.

Use during pregnancy and lactation

Data on the safety and efficacy of the drug during pregnancy are not available, so use during pregnancy is possible only if the intended benefit to the mother justifies the possible risk to the fetus.

Gabapentin is excreted in breast milk. The effect of Neurontin on an children is unknown, so during lactation, the drug should be prescribed only if the expected benefit of therapy for the mother exceeds the potential risk for the infant

Contraindications

• children under 3 years of age;
• hypersensitivity to gabapentin and other components of the drug.

The drug should be used with caution in patients with renal insufficiency.

Use in patients with impaired renal function

The drug should be used with caution in patients with renal insufficiency. Patients with renal insufficiency are recommended to reduce the dose of Neurontin.

Side effects

In the treatment of neuropathic pain

From the body as a whole:  at least 1% – accidental injuries, asthenia, back pain, flu-like syndrome, headache, infection, pain of various localization, peripheral edema, weight gain.

From the digestive system:  at least 1% – constipation, diarrhea, dry mouth, dyspepsia, flatulence, nausea, vomiting, abdominal pain.

From the central nervous system and peripheral nervous system:  at least 1% – gait disorders, amnesia, ataxia, confusion, dizziness, hypesthesia, drowsiness, impaired thinking, tremor.

Respiratory system disorders:  at least 1% – shortness of breath, pharyngitis;

Dermatological reactions:  at least 1% – skin rash.

From the side of the senses:  at least 1% – amblyopia.

In the treatment of partial seizures

Neurontin is most often used in combination with other anticonvulsants, so it was impossible to determine which drug caused side effects (if any).

From the body as a whole:  at least 1% – asthenia, general malaise, facial edema, fatigue, fever, headache, viral infection, peripheral edema, weight gain.

From the cardiovascular system:  at least 1% – symptoms of vasodilation or arterial hypertension.

From the digestive system:  at least 1% – flatulence, anorexia, gingivitis, abdominal pain, constipation, dental diseases, diarrhea, dyspepsia, increased appetite, dry mouth or throat, nausea and / or vomiting.

From the hematopoietic system:  at least 1% – purpura (most often described as bruising caused by physical trauma), leukopenia.

Musculoskeletal disorders:  at least 1% – arthralgia, back pain, fractures, myalgia.

From the central nervous system and peripheral nervous system:  at least 1% – dizziness, hyperkinesis, increased, weakened or no reflexes, paresthesia, anxiety, hostility, amnesia, ataxia, confusion, impaired coordination, depression, dysarthria, emotional lability, insomnia, nervousness, nystagmus, drowsiness, impaired thinking, tremor, muscle twitching.

Respiratory system disorders:  at least 1% – pneumonia, cough, pharyngitis, rhinitis.

Dermatological reactions:  at least 1% – abrasions, acne, itchy skin, skin rash.

From the urinary system:  at least 1% – urinary tract infection, impotence.

From the side of the senses:  at least 1% – visual impairment, amblyopia, diplopia.

These side effects were mild to moderate.

No new or unexpected side effects were observed during monotherapy. When comparing the tolerability of the drug at doses of 300 mg/day and 3.6 g/day, dose-dependent phenomena such as dizziness, ataxia, drowsiness, paresthesia and nystagmus were noted.

The following side effects were observed in children with additional therapy with a frequency of about 2% or higher, compared with placebo.

From the body as a whole:  viral infection, fever, weight gain, fatigue.

From the digestive system:  nausea and / or vomiting.

From the central nervous system and peripheral nervous system:  drowsiness, hostility, emotional lability, dizziness, hyperkinesia.

Respiratory system disorders:  bronchitis, a respiratory infection.

Other services:  more than 2% of children (the frequency in the placebo group was similar or higher) – included pharyngitis, upper respiratory tract infections, headache, rhinitis, seizures, diarrhea, anorexia, cough, and otitis media.

Side effects that most often required discontinuation of the drug used as adjunctive therapy – drowsiness, ataxia, dizziness, fatigue, nausea and/or vomiting; as monotherapy – dizziness, nervousness, weight gain, nausea and/or vomiting and drowsiness.

Adverse events that most often led to drug withdrawal in children were drowsiness, hyperkinesia, and hostility.

Post-registration application experience

Cases of sudden unexplained death have been reported that are not related to gabapentin treatment. Other adverse events include acute renal failure, allergic reactions (including urticaria, angioedema), alopecia, fluctuations in blood glucose in diabetic patients, chest pain, increased liver enzyme activity, erythema multiforme (including Stevens – Johnson syndrome), hallucinations, movement disorders (choreoathetosis, dyskinesia and dystonia), palpitations, pancreatitis, thrombocytopenia, tinnitus, urinary incontinence, hepatitis and jaundice.

After abrupt discontinuation of Neurontin therapy, the most common symptoms are anxiety, insomnia, nausea, pain of various localization, and sweating.

Interaction

When Neurontin and morphine were co-administered (when morphine was taken 2 hours before Neurontin), the mean gabapentin AUC increased by 44% compared to Neurontin monotherapy, which was accompanied by 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 Neurontin did not differ from those of morphine co-administered with placebo.

There were no interactions between Neurontin and phenobarbital, phenytoin, valproic acid, and carbamazepine.

The pharmacokinetics of gabapentin at steady state are similar in healthy individuals and patients receiving other anticonvulsants.

Concomitant use of Neurontin with oral contraceptives containing norethindrone and / or ethinyl estradiol was not accompanied by changes in the pharmacokinetics of both components.

Concomitant use of Neurontin with antacids containing aluminum and magnesium is associated with a decrease in the bioavailability of gabapentin by about 20%. Gabapentin is recommended to be taken approximately 2 hours after taking the antacid. Probenecid does not affect the renal excretion of gabapentin.

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

How to take, course of use and dosage

Neurontin is prescribed orally regardless of food intake or together with food. 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.

With neuropathic pain, adults are prescribed an initial dose of 900 mg / day in 3 divided doses; if necessary, depending on the effect, the dose is gradually increased to a maximum of 3.6 g/day. Treatment can be started immediately with a dose of 900 mg/day (300 mg 3 / day) or during the first 3 days, the dose can be increased gradually to 900 mg/day according to the following scheme: 1 day-300 mg of the drug 1 time/day; 2 day-300 mg 2 times/day; 3 day-300 mg 3 times/day.

For partial seizures in adults and children over 12 years of age, the effective dose is from 900 mg to 3.6 g / 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. Subsequently, the dose can be increased to a maximum of 3.6 g / day (divided into 3 equal doses). The drug was well tolerated in doses up to 4.8 g / day. The maximum interval between doses when taking the drug three times should not exceed 12 hours to avoid the resumption of seizures.

For children aged 3-12 years: the initial dose of the drug varies from 10 to 15 mg / kg / day, the frequency of use is 3 times/day in equal doses, the increase to the effective dose is carried out for approximately 3 days. The effective dose of Neurontin in children aged 5 years and older is 25-35 mg / kg / day in equal doses in 3 divided doses. The effective dose of Neurontin in children aged 3 to 5 years is 40 mg / kg / day in equal doses in 3 divided doses. Good tolerability of the drug in doses up to 50 mg / kg / day with long-term use was noted. The maximum interval between doses of the drug should not exceed 12 hours to avoid the recurrence of seizures.

There is no need to monitor the concentration of gabapentin in plasma. Neurontin can be used in combination with other anticonvulsants without taking into account changes in its plasma concentration or the concentration of other anticonvulsants in serum.

Patients with renal insufficiency are recommended to reduce the dose of Neurontin according to the table.

Creatinine clearance (ml / min)Daily dose (mg/day)*≥ 80900-360050-79600-180030-49300-90015-29150**-600150**-300

*The daily dose should be administered in three divided doses.

**Assign 300 mg every other day.

Patients on hemodialysis who have not previously taken Neurontin are recommended to take the drug in a saturating dose of 300-400 mg, and then apply it 200-300 mg every 4 hours of hemodialysis.

Overdose

With a single dose of Neurontin 49 g, the following symptoms were observed: dizziness, double vision, speech disorders, drowsiness, lethargy, and mild diarrhea.

In experimental studies, the lethal dose of gabapentin when taken orally was not established in mice and rats treated with the drug in doses up to 8000 mg / kg. Signs of acute toxicity in animals included ataxia, difficulty breathing, ptosis, hypoactivity, or agitation.

Treatment: conducting symptomatic therapy. Hemodialysis may be indicated for patients with severe renal insufficiency.

Special instructions

Although Neurontin does not cause withdrawal symptoms with seizures, abrupt discontinuation of anticonvulsant therapy in patients with partial seizures may lead to seizures.

Neurontin is generally not considered an effective treatment for absence epilepsy.

When combined with morphine, an increase in the concentration of gabapentin may be required. At the same time, it is necessary to ensure careful monitoring of patients for the development of such a sign of CNS depression as drowsiness. In this case, the dose of Neurontin or morphine should be adequately reduced.

When Neurontin was added to other anticonvulsants, false positive results were recorded in the determination of protein in 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.

Use in pediatrics

In the treatment of neuropathic pain, the efficacy and safety of the drug in children and adolescents under 18 years of age have not been established.

In monotherapy of partial seizures with and without secondary generalization, the efficacy and safety of the drug in children under 12 years of age have not been established.

When used as an adjunct in the treatment of partial seizures with secondary generalization, the safety and efficacy of udetey in children under 3 years of age have not been established.

Influence on the ability to drive motor vehicles and manage mechanisms

Patients should not drive a car or work with moving machinery until an individual response to the drug is determined.

Form of production

Capsules

Storage conditions

The drug should be stored out of the reach of children, at a temperature not exceeding 25°C

Shelf life

3 years

Active ingredient

Gabapentin

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

Children as prescribed by a doctor, Adults as prescribed by a doctor, Children over 3 years of age

Indications

Epilepsy