Neurontin, capsules 300 mg 50 pcs

Gabapentin is structurally similar to GABA, but its mechanism of action differs from some other similar drugs that interact with GABA receptors, including valproate, barbiturates, benzodiazepines, GABA transaminase inhibitors, GABA capture inhibitors, GABA agonists and GABA prodrug forms: it has no GABAergic properties and does not affect GABA capture or metabolism. Preliminary studies suggest that gabapentin binds to the α2-δ-subunit of voltage-dependent calcium channels and suppresses calcium ion flux, which plays an important role in the onset of neuropathic pain.

Other mechanisms involved in the action of gabapentin in neuropathic pain are: reduction of glutamate-dependent neuronal death, increase in GABA synthesis, inhibition of monoamine group neurotransmitter release. Gabapentin in clinically relevant concentrations does not bind to receptors of other common drugs or neurotransmitters, including GABAA, GABABAB, benzodiazepine, glutamate, glycine or N-methyl-d-aspartate (NMDA) receptors.

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

A rat trial showed that administration of gabapentin resulted in increased GABA metabolism in some brain sites; this effect was similar to that of sodium valproate, although observed in other brain sites. The significance of these effects of gabapentin for its anticonvulsant activity has not been established. In animals gabapentin has also been shown to readily penetrate brain tissue and prevent seizures induced by maximal electroshock, chemicals including GABA synthesis inhibitors, and genetic factors.

Pharmacokinetics

Intake

After oral administration, Cmax of gabapentin in plasma is reached after 2-3 hours. The bioavailability of gabapentin is not proportional to the dose; thus, it decreases with increasing dose. Absolute bioavailability of gabapentin in capsules is about 60%. Food, including those with high fat content, has no effect on pharmacokinetics.

The plasma excretion of gabapentin is linear.

Metabolism

There is no evidence of metabolism in humans, The drug does not induce oxidative liver enzymes with mixed function involved in drug metabolism.

Distribution

The pharmacokinetics do not change with repeated administration; equilibrium plasma concentrations can be predicted from a single drug administration. Gabapentin is practically not bound to plasma proteins (less than 3%); Vd is approximately 57.7 L.

The T1/2 from plasma is independent of the dose and averages 5-7 hours.

Extracted exclusively by the kidneys in unchanged form.

Pharmacokinetics in special clinical cases

The clearance of gabapentin from plasma is decreased in elderly people and patients with impaired renal function.

The elimination rate constant, plasma clearance and renal clearance are directly proportional to CK. Gabapentin is eliminated from plasma by hemodialysis.

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

Plasma concentrations of gabapentin in children aged 4 to 12 years have been found to be generally similar to those in adults.

Indications

Active ingredient

Composition

1 capsulabapentin 300 mg

Ancillary substances:

Lactose monohydrate – 42.75 mg,

Corn starch – 30 mg,

Talc – 30 mg.

Capsule shell composition:

Gelatin – 64.07 mg, titanium dioxide (E171) – 0.76 mg, iron oxide yellow dye (E172) – 0.15 mg, sodium lauryl sulfate – less than 0.15 mg.

Ink composition:

Shellac – 0.075 mg, titanium dioxide (E171) – 0.027 mg, indigo carmine – 0.021 mg.

How to take, the dosage

Neurontin is given orally with or without food. If it is necessary to reduce the dose, cancel the drug or replace it with an alternative remedy, this should be done gradually over at least one week.

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

In partial seizures for adults and children over 12 years of age, the effective dose is 900 mg to 3.6 g/day. Therapy may be started with a dose of 300 mg 3 times daily on the first day or increased gradually to 900 mg according to the scheme described above. Subsequently, the dose may be increased to a maximum of 3.6 g/day (divided into 3 equal doses). Good tolerability at doses up to 4.8 g/day has been observed. The maximum interval between doses in triple dosing should not exceed 12 hours in order to avoid recurrence of seizures.

In children aged 3-12 years: the initial dose of the drug varies from 10 to 15 mg/kg/day, the frequency of administration is 3 times/day in equal doses, the increase to the effective dose is carried out within about 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 doses. Effective dose of Neurontin in children aged 3 to 5 years is 40 mg/kg/day in equal doses in 3 intakes. There is good tolerability of the drug in doses up to 50 mg/kg/day in long-term use. The maximum interval between doses of the drug should not exceed 12 hours in order to avoid recurrence of seizures.

It is not necessary to monitor the plasma concentration of gabapentin. Neurontin may be used in combination with other anticonvulsants without regard to changes in its plasma concentrations or serum concentrations of other anticonvulsants.

Patients with renal impairment 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

*Daily dose should be administered in three doses.

**Prescribe 300 mg every other day.

Patients on hemodialysis who have not previously taken Neurontin are advised to prescribe a saturation dose of 300-400 mg and then use 200-300 mg every 4 hours of hemodialysis.

Interaction

Concomitant administration of Neurontin and morphine (when morphine was taken 2 h before Neurontin administration) resulted in a 44% increase in the mean AUC of gabapentin compared to Neurontin monotherapy, which was accompanied by an increase in pain threshold (cold pressor test). The clinical significance of this change has not been established, and the pharmacokinetic characteristics of morphine were not altered. Side effects of morphine co-administration with Neurontin did not differ from those of morphine co-administration with placebo.

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

The equilibrium pharmacokinetics of gabapentin are similar in healthy subjects and patients receiving other anticonvulsants.

The concomitant use of Neurontin with oral contraceptives containing norethindrone and/or ethinylestradiol was not accompanied by changes in the pharmacokinetics of both components.

The concomitant use of Neurontin with antacids containing aluminum and magnesium is accompanied by a decrease in the bioavailability of gabapentin by approximately 20%. It is recommended to take gabapentin about 2 hours after taking an antacid. Probenecid has no effect on renal excretion of gabapentin.

The slight decrease in renal excretion of gabapentin with concomitant administration of cimetidine is probably not clinically relevant.

Special Instructions

While Neurontin has not resulted in seizure withdrawal, abrupt discontinuation of anticonvulsant therapy in patients with partial seizures may induce seizures.

Neurontin in general is not considered an effective treatment for absences epilepsy.

When co-therapy with morphine may require increasing the concentration of gabapentin. Patients should be closely monitored for signs of CNS depression such as drowsiness. In this case, the dose of Neurontin or morphine should be adequately reduced.

When Neurontin is added to other anticonvulsants, false-positive results have been reported with the Ames N-Multistix SG urine protein test strips. The more specific sulfosalicylic acid precipitation method is recommended for determining protein in urine.

Pediatric use

The efficacy and safety of the drug in the treatment of neuropathic pain in children and adolescents under the age of 18 years has 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 adjunctive agent in the treatment of partial seizures with secondary generalization, the safety and efficacy of the drug in children under 3 years of age have not been established.

Impact on driving and operating machinery

Patients should not drive or operate moving machinery until an individual response to the use of the drug has been determined.

Contraindications

The drug should be used with caution in renal failure.

Performance with renal impairment

The drug should be used with caution in patients with renal impairment. In patients with renal insufficiency, it is recommended to reduce the dose of Neurontin.

Side effects

In treatment of neuropathic pain

Injuries to the body in general: not less than 1% – accidental injury, asthenia, back pain, flu-like syndrome, headache, infection, pain of different localization, peripheral edema, weight gain.

Digestive system disorders: at least 1% – constipation, diarrhea, dry mouth, dyspepsia, flatulence, nausea, vomiting, abdominal pain.

CNS and peripheral nervous system disorders: not less than 1% – gait disturbance, amnesia, ataxia, confusion, dizziness, hypoesthesia, somnolence, thought disorder, tremor.

Respiratory system: at least 1% – dyspnea, pharyngitis;

Dermatological reactions: at least 1% – skin rash.

Sensory system disorders: 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 the side effects (if any).

In general body: at least 1% – asthenia, general malaise, facial edema, fatigue, fever, headache, viral infection, peripheral edema, weight gain.

Cardiovascular system disorders: at least 1% – symptoms of vasodilation or arterial hypertension.

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

Hematopoietic system: at least 1% – purpura (most commonly described as bruising that occurred with physical trauma), leukopenia.

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

CNS and peripheral nervous system disorders: at least 1% – dizziness, hyperkinesias, increased, decreased or absent reflexes, paresthesias, restlessness, hostility, amnesia, ataxia, confusion, coordination disorders, depression, dysarthria, emotional lability, insomnia, nervousness, nystagmus, drowsiness, thinking disorders, tremor, muscle twitching.

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

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

Urinary system disorders: at least 1% – urinary tract infection, impotence.

Sensory system disorders: at least 1% – visual impairment, amblyopia, diplopia.

The indicated side effects were mild to moderate.

There were no new or unexpected side effects with monotherapy. In comparisons of tolerability of 300 mg/day and 3.6 g/day doses, there was a dose-dependence of dizziness, ataxia, somnolence, paresthesia and nystagmus.

The following are the side effects seen in children with adjunctive therapy with an incidence of about 2% or higher compared to placebo.

Body side effects in general: viral infection, fever, weight gain, fatigue.

In the digestive system: nausea and/or vomiting.

CNS and peripheral nervous system disorders: drowsiness, hostility, emotional lability, dizziness, hyperkinesia.

Respiratory system disorders: bronchitis, respiratory infection.

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

The side effects that most often required withdrawal of the drug used as adjuvant therapy were drowsiness, ataxia, dizziness, fatigue, nausea and/or vomiting; as monotherapy, dizziness, nervousness, weight gain, nausea and/or vomiting and drowsiness.

The undesirable phenomena that most often led to withdrawal of the drug in children were somnolence, hyperkinesia, and hostility.

Post-registration experience of use

There have been reported cases of sudden unexplained death, the association of which with treatment with gabapentin has not been established. Other adverse events – acute renal failure, allergic reactions (including urticaria, angioneurotic edema), alopecia, blood glucose fluctuations in diabetic patients, chest pain, increased liver enzyme activity, erythema multiforme exudative (including erythema multiforme).including Stevens-Johnson syndrome), hallucinations, motor disorders (choreoathetosis, dyskinesia and dystonia), palpitations, pancreatitis, thrombocytopenia, tinnitus, urinary incontinence, hepatitis and jaundice.

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

Overdose

A single administration of Neurontin at a dose of 49 g resulted in the following symptoms: dizziness, double vision, speech impairment, somnolence, lethargy, and mild diarrhea.

In experimental studies, lethal doses of gabapentin when ingested have not been established in mice and rats receiving the drug in doses up to 8000 mg/kg. Signs of acute toxicity in animals included ataxia, difficulty breathing, ptosis, hypoactivity or agitation.

Treatment: administration of symptomatic therapy. Patients with severe renal failure may be indicated for hemodialysis.

Pregnancy use

There are no data on safety and efficacy of the drug in pregnancy; therefore, the use in pregnancy is possible only if the estimated benefit to the mother justifies the possible risk to the fetus.

Gabapentin is excreted with the breast milk. The effect of Neurontin on the infant is unknown, so the drug should only be prescribed during lactation if the expected benefit to the mother outweighs the potential risk to the infant

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