Konvalis

Excipients: lactose monohydrate, starch corn prezhelatinizirovanny, talc, magnesium stearate, gelatinous solid capsules: (titanium dioxide, gelatin, yellow oxide of iron).

 

Pharmacodynamics. Gabapentin on a structure is similar to the neurotransmitter piperidic acid (GAMK), however the mechanism of its action differs from that some other drugs interacting with GAMK-receptors including Valproatum, barbiturates, benzodiazepines, GAMK-transaminase inhibitors; inhibitors of capture of GAMK, agonists of GAMK and pro-dosage forms of GAMK: it has no GABA-ergic properties and does not influence for capture and metabolism of GAMK. Preliminary researches demonstrate to what габапентин communicates with _{α2-δ-субъединицей} a voltage - dependent calcium channels and suppresses the flow of calcium ions playing an important role in developing of neyropatichesky pain. Other mechanisms participating in operation a gabapentina at neyropatichesky pain are: reduction a glutamate - dependent death of neurons, increase in synthesis of GAMK, suppression of release of neurotransmitters of monoamine group. Gabapentin in clinically significant concentration does not contact receptors of other widespread drugs or neurotransmitters, including receptors _{of GAMKA, GAMKV}, benzodiazepine, a glutamate, glycine or N-methyl-d-aspartate. Unlike Phenytoinum and carbamazepine габапентин does not interact with natrium channels of in vitro. Gabapentin partially weakened effects of an agonist of glyutamatny receptors of N-methyl-d-aspartate in some in vitro tests, but only in concentration more than 100 µmol which is not reached in vivo. Gabapentin reduces emission of monoamine in vitro neurotransmitters a little.  

Pharmacokinetics. Bioavailability of a gabapentin is not proportional to a dose: so, at increase in a dose it decreases. After intake the maximum concentration (Cmax) of a gabapentin in plasma is reached in 2-3 h. Absolute bioavailability of a gabapentin in capsules makes about 60%. Food, including with high content of fats, does not exert impact on pharmacokinetics. The elimination half-life _(T1/2) from plasma does not depend on a dose and averages 5-7 h. The pharmacokinetics does not change at repeated use; equilibrium concentration in plasma can be predicted on the basis of results of a single dose of drug. Gabapentin practically does not contact proteins of plasma (<3 %) and has the volume of distribution of 57,7 l. It is removed only by kidneys in not changed look, is not exposed to metabolism. Drug does not induce the oxidizing enzymes of a liver with the mixed function participating in metabolism of medicines. The clearance of a gabapentin from plasma decreases at elderly people and patients with an impaired renal function. The removal speed constant, clearance from plasma and renal clearance are directly proportional to clearance of creatinine. Gabapentin leaves from plasma at a hemodialysis. At patients with an impaired renal function and the patients who are on a hemodialysis dose adjustment is recommended (see the Route of administration and doses).

Monotherapy and Konvalis's use as supportive application at children are more senior than 12 years and adults.

Treatment begin with a dose 300 mg once a day and gradually increase to
900 mg/days (the first day – 300 mg once a day, the second - 300 mg two times a day, the third – 300 mg three times a day). In the subsequent the dose can be increased. Usually Konvalis's dose makes 900-1200 mg a day. The maximum dose - 3600 mg/days (in three equal receptions in 8 h).

Neyropatichesky pain at adults.

Treatment there begin with a dose 300 mg in the first day, 600 mg (on 300 mg two times) – for the second day, 900 mg (on 300 mg 3 times) – for the third day. In the presence of a megalgia Konvalis can be appointed from the first day on 300 mg three times a day. Depending on effect, the dose can be gradually increased, but no more than 3600 mg/days.

At patients with an impaired renal function the daily dose of drug makes: at clearance of creatinine of 50-79 ml/min. – 600-1800 mg/days, 30-49 ml/min. – 300-900 mg/days, 15-29 ml/min. – 300-600 mg/days, less than 15 ml/min. – 300 mg every other day or daily.

At the patients who are on a hemodialysis, the initial dose of Konvalis makes 300 mg. The additional post-hemodialysis dose makes 300 mg after each 4-hour session of a hemodialysis. In days when dialysis is not carried out, Konvalis do not appoint.

In the analysis on crude protein in urine by means of a litmus paper the false positive result is possible. It is necessary to confirm the received result by means of other method of the analysis. Patients with a diabetes mellitus sometimes have a need for change of a dose of antidiabetic drugs. At emergence of symptoms of acute pancreatitis treatment by drug needs to be stopped. It is necessary to cancel drug or to replace it with alternative means gradually, at least within a week.

 

DRIVING OF THE CAR AND USE OF THE EQUIPMENT.

During treatment it is necessary to abstain from driving of transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

At treatment of neyropatichesky pain

Digestive tract: a lock, diarrhea, dryness in a mouth, dyspepsia, a meteorism, nausea, vomiting, an abdominal pain.

Nervous system: gait disturbance, amnesia, ataxy, confusion of consciousness, dizziness, hypesthesia, drowsiness, disturbance of thinking, tremor.

Respiratory system: short wind, pharyngitis.

Integuments: skin rash.

Sense bodys: amblyopia.

Others: asthenic syndrome, grippopodobny syndrome, headache, infectious diseases, pain of various localization, peripheral hypostases, increase in body weight.

At treatment of partial spasms

Cardiovascular system: vazodilatation symptoms, arterial hypertension.

increase or decrease in the ABP.

Digestive tract: a meteorism, anorexia, an ulitis, an abdominal pain, a lock, a disease of teeth, diarrhea, dyspepsia, increase in appetite, dryness in a mouth or a throat, nausea, vomiting.

System of blood, lymphatic system: a purpura (most often it was described as the bruises arising at a physical injury, a leukopenia.

Musculoskeletal system: an arthralgia, a dorsodynia, the increased fragility of bones, a mialgiya.

Nervous system: dizziness, hyperkinesias; strengthening, easing or lack of tendon jerks, paresthesia, concern, hostility, amnesia, ataxy, confusion of consciousness, lack of coordination of movements, depression, dysarthtia, emotional lability, sleeplessness, nystagmus, drowsiness, disturbance of thinking, tremor, fibrillations of muscles.

Respiratory system: pneumonia, cough, pharyngitis, rhinitis.

Integuments: grazes, acne, skin itch, skin rash.

Urinogenital system: infection of uric ways, impotence.

Sense bodys: vision disorder, amblyopia, diplopia.

Others: asthenic syndrome, face edema, exhaustion, fever, headache, viral infection, peripheral hypostases, increase in body weight.

When comparing portability of drug in doses of 300 and 3600 mg/days dozo-dependence of such phenomena as dizziness, an ataxy, drowsiness, paresthesia and a nystagmus is noted.

At joint reception of a gabapentin and morphine when morphine was accepted in 2 hours prior to reception of a gabapentin, increase in average value of the area under a pharmacokinetic curve "concentration - time" (AUC) of a gabapentin for 44% in comparison with monotherapy gabapentiny was observed that was associated with increase in a pain threshold (the holodovy pressor test). Clinical value of this change is not established, pharmacokinetic characteristics of morphine at the same time did not change. Side effects of morphine at joint reception with gabapentiny did not differ from those at reception of morphine together with placebo.

Interaction between gabapentiny and phenobarbital, Phenytoinum, valproic acid and carbamazepine is noted. The pharmacokinetics of a gabapentin in an equilibrium state is identical at the healthy people and patients receiving other anticonvulsants.

Simultaneous use of a gabapentin with the oral contraceptives containing norethindrone and/or ethinylestradiol was not followed by changes of pharmacokinetics of both components.

The antiacid drugs containing aluminum or magnesium reduce bioavailability of a gabapentin approximately by 20%. In this regard drug should be accepted not earlier than in 2 h after reception of antacids. Cimetidinum slightly reduces renal excretion of a gabapentin. The alcohol and means operating on TsNS can strengthen side effects of a gabapentin from TsNS.

Symptoms: dizziness, diplopia, drowsiness, dysarthtia, diarrhea.

List B. In the dry, protected from light place at a temperature not above 25 °C.

To store in the places unavailable to children.