Prabegin - instructions for use, doses, side effects, contraindications

Composition of hard gelatin capsule (% m / m): gelatin - as much as necessary up to 100%; titanium dioxide (E171) - 2%; ink (shellac, propylene glycol, iron dye red oxide (E172), potassium hydroxide) - traces.

Description:

Capsules 25 mg: White or almost white opaque hard gelatin capsules size 4, with red markings “PR25” on the basis of a capsule and with a red marking “EGIS” on the capsule caps containing a mixture of powders of white or almost white color.

Capsules 50 mg: White or almost white opaque hard gelatin capsules size 3, with red markings “PR50” on the basis of a capsule and with a red marking “EGIS” on the capsule caps containing a mixture of powders of white or almost white color.

Capsules 75 mg: White or almost white opaque hard gelatin capsules size 4, with red markings “PR75” on the basis of a capsule and with a red marking “EGIS” on the capsule caps containing a mixture of powders of white or almost white color.

Capsules 150 mg: White or almost white opaque hard gelatin capsules of size 2, with red markings “PR150” on the basis of a capsule and with a red marking “EGIS” on the capsule caps containing a mixture of powders of white or almost white color.

Capsules 300 mg: White or almost white opaque hard gelatin capsules in size 0, with red markings “PR300” on the basis of a capsule and with a red marking “EGIS” on the capsule caps containing a mixture of powders of white or almost white color.

Pharmacotherapeutic group:antiepileptic agent

ATX: & nbsp

N.03.A.X.16 Pregabalin

Pharmacodynamics:

The active substance is pregabalinum - analogue of gamma-aminobutyric acid (GABA) - (S) -3- (aminomethyl) -5-methylhexanoic acid.

Mechanism of action

It was found that pregabalinum is associated with an additional subunit (α2-delta protein) of potential-dependent calcium channels in the central nervous system (CNS). It is suggested that such binding can promote the manifestation of analgesic and anticonvulsant effects.

Neuropathic pain

The efficacy of pregabalin was noted in patients with diabetic neuropathy and postherpetic neuralgia.

It has been established that when taking pregabalin with courses up to 13 weeks 2 times a day and up to 8 weeks 3 times a day, in general, the risk of side effects and the effectiveness of the drug in the two or three times a day are the same.

When taking a course of up to 13 weeks, the pain decreased during the first week, and the effect persisted until the end of treatment.

The pain index was reduced by 50% in 35% of patients who received pregabalinum, and 18% of patients taking placebo. Among patients who did not experience drowsiness, the effect of this pain reduction was observed in 33% of patients in the pregabalin group and 18% in the placebo group. In 48% of patients who took pregabalinum, and 16% of patients taking a placebo, there was drowsiness.

Fibromyalgia

A marked decrease in pain symptoms associated with fibromyalgia is noted with the use of pregabalin in doses from 300 mg to 600 mg per day. The efficacy of doses of 450 and 600 mg per day is comparable, but tolerability of 600 mg per day is usually worse.

Also, the use of pregabalin is associated with a marked improvement in the functional activity of patients and a decrease in the severity of sleep disorders. The use of pregabalin at a dose of 600 mg per day led to a more pronounced improvement in sleep, compared with a dose of 300-450 mg per day.

Epilepsy

When taking the drug for 12 weeks 2 or 3 times a day, the noted risk of side effects and the effectiveness of the drug under these dosing regimens are the same. The reduction in the frequency of seizures began within the first week.

Generalized anxiety disorder

Reduction of symptoms of generalized anxiety disorder is noted in the first week of treatment. When using the drug for 8 weeks, 52% of patients who received pregabalinum. And in 38% of patients receiving placebo, there was a 50% reduction in symptoms on the Hamilton anxiety scale (NAM-A).

Pharmacokinetics:

Parameters of pharmacokinetics of pregabalin in equilibrium in healthy volunteers, in patients with epilepsy receiving antiepileptic therapy, and in patients receiving it for chronic pain syndromes were similar.

Suction

Pregabalin is rapidly absorbed on an empty stomach. The maximum concentration of the drug in plasma (C_m_Oh) reaches a peak after 1 h as with a single or repeated application. Bioavailability of pregabalin for oral administration is ≥90% and does not depend on the dose. With repeated use, the equilibrium concentration (Css) is reached after 24-48 hours. When using pregabalin after a meal C_m_Oh decreases by about 25-30%, and the time to reach the maximum concentration (TC_m_Oh) increases to about 2.5 hours.However, eating does not have a clinically significant effect on the overall absorption of pregabalin.

Distribution

Apparent volume of distribution (V_d) Pregabalinum after ingestion is approximately 0.56 l / kg. The drug does not bind to plasma proteins.

In preclinical studies it was shown that pregabalinum penetrates the blood-brain barrier in mice, rats and monkeys, and also penetrates the placenta in rats.

Pregabalin is present in the milk of rats during lactation.

Metabolism

Pregabalinum is practically not exposed to a metabolism. After taking labeled pregabalin, approximately 98% of the radioactive label was detected in the urine unchanged. Share of Nmethylated derivative of pregabalin, which is the main metabolite found in urine, was 0.9% of the dose. There were no signs of racemization Senantiomer of pregabalin in R-enantiomer.

Excretion

Pregabalin is excreted mainly by the kidneys in unchanged form.

Average half-life (T_1/2) is 6.3 hours. The clearance of pregabalin from the plasma and the kidney clearance are directly proportional to the clearance of creatinine (CC) (see the paragraph "Violation of kidney function").In patients with impaired renal function and patients on hemodialysis, dose adjustment is necessary (see section "Dosage regimen, route of administration" Table 1).

Linearity/ nonlinearity

The pharmacokinetics of pregabalin in the range of recommended daily doses is linear, interindividual variability is low (<20%). The pharmacokinetics of the drug in repeated application can be predicted on the basis of single dose data. Consequently, there is no need for regular monitoring of pregabalin concentrations.

Farmakokinetics in special groups

Floor the patient has no clinically significant effect on plasma pregabalin concentrations.

Impaired renal function

Clearance of pregabalin is directly proportional to QC. Given that the drug is mainly excreted by the kidneys, in patients with impaired renal function it is recommended to reduce the dose of pregabalin. Besides, pregabalinum is effectively removed from the plasma during hemodialysis (after a 4-hour hemodialysis session, pregabalania concentrations in the plasma are reduced by approximately 50%), after hemodialysis, an additional dose of the drug should be prescribed (see.section "Dosage regimen, mode of administration", tab. 1).

Impaired liver function

The pharmacokinetics of pregabalin in patients with impaired liver function has not been specifically studied. Pregabalin practically does not undergo metabolism and is excreted mainly unchanged in the urine, therefore, the violation of liver function should not significantly change the concentration of the drug in the plasma.

Elderly patients (over 65 years of age)

Clearance of pregabalin with age tends to decrease, which reflects the age-related decrease in QC. Elderly people with impaired renal function may need to reduce the dose of the drug (see the section "Dosage regimen, route of administration," Table 1).

Indications:

Neuropathic pain

Treatment of neuropathic pain in adults.

Epilepsy

As an additional therapy in adults with partial seizures, accompanied or not accompanied by secondary generalization.

Generalized anxiety disorder

Treatment of generalized anxiety disorder in adults.

Fibromyalgia

Treatment of fibromyalgia in adults.

Contraindications:

Hypersensitivity to the active substance or any other component of the drug.

Children and adolescents under 17 years of age (no application data).

Carefully:

Be wary of using the drug for kidney failure (see section "Method of administration and dose") and heart failure (see section "Side effect").

In connection with the registered single cases of uncontrolled use of pregabalin, it must be administered with caution in patients with drug dependence in the history. Such patients need close medical supervision during drug treatment.

Pregnancy and lactation:

Adequate data on the use of pregabalin in pregnant women do not. There are no clinical data on the effect of pregabalin on fertility in women. When used in animals, the drug had a toxic effect on reproductive function. Concerning pregabalinum can be prescribed during pregnancy only if the intended benefit to the mother clearly outweighs the possible risk to the fetus. In the treatment of pregabalin, women of reproductive age should use adequate methods of contraception.

There is no information about the excretion of pregabalin with breast milk in women.In this regard, during treatment with pregabalin is not recommended to breast-feed. A clinical study was conducted to evaluate the effect of pregabalin used at a dose of 600 mg / day on the motility of spermatozoa in healthy men. After three months of using pregabalin, the effect of the drug on sperm motility was not revealed.

Dosing and Administration:

Inside, regardless of food intake.

The drug is used in a daily dose of 150 to 600 mg in 2 or 3 divided doses.

Neuropathic pain

The initial dose is 150 mg / day. Depending on the effect achieved and tolerance in 3-7 days, the dose can be increased to 300 mg / day, and, if necessary, after 7 days - up to a maximum dose of 600 mg / day.

Epilepsy

The initial dose is 150 mg / day. Taking into account the achieved effect and tolerability after 1 week, the dose can be increased to 300 mg / day, and in a week - up to a maximum dose of 600 mg / day.

Fibromyalgia

The initial dose is 75 mg twice a day (150 mg / day). Depending on the effect achieved and the tolerance in 3-7 days, the dose can be increased to 300 mg / day. In the absence of a positive effect, the dose is increased to 450 mg / day, and if necessary, after 7 days - up to a maximum dose of 600 mg / day.

Generalized anxiety disorder

The initial dose is 150 mg / day.Depending on the effect achieved and the tolerability after 7 days, the dose can be increased to 300 mg / day. In the absence of a positive effect, the dose is increased to 450 mg / day, and if necessary, after 7 days - up to a maximum dose of 600 mg / day.

Canceling pregabalinum

If treatment with pregabalin patients should be stopped, it is recommended to do this gradually for at least 1 week.

Patients with impaired renal function

For patients with impaired renal function, the dose is individually adjusted for KK (Table 1), which is calculated using the following formula:

CK (ml / min) = [140-yr (years) x body weight (kg)] / 72 x CS, where CS is serum creatinine (mg / dL)

QC for women can be calculated using the following formula:

CK (ml / min) = [140th age (years) x body weight (kg) x 0.85] / 72 x CS

In patients receiving hemodialysis treatment, the daily dose of pregabalin is selected taking into account the function of the kidneys. Immediately after each 4-hour session of hemodialysis an additional dose is prescribed (Table 1).

Table 1. Selection of a dose of pregabalin with account of kidney function

Clearance creatinine, ml / min	Daily dose of pregabalinum		Multiplicity of reception per day
	Starting dose, mg / day	The maximum dose, mg / day
>60	150	600	2-3
≥30-<60	75	300	2-3
≥15-<30	25-50	150	1-2
<15	25	75	1
Beforethe full dose after dialysis, mg
	25	100	Once

Use in patients with impaired liver function

In patients with impaired liver function, dose adjustment is not required (see the section "Pharmacokinetics").

Use in children under 12 years of age and adolescents (12-17 years of age)

Safety and efficacy of pregabalin in children under 12 years of age and adolescents 12-17 years old have not been established. The use of the drug in children is not recommended.

Application in the elderly (over 65 years)

Older patients (over 65 years of age) may need to reduce the dose of pregabalin due to a decrease in kidney function.

In the case of missing a dose of pregabalin, the next dose should be taken as soon as possible, however, do not take the missed dose if the next time is appropriate.

Side effects:

According to the experience of clinical use of pregabalin in more than 12000 patients, the most common adverse events were dizziness and drowsiness. The observed phenomena were usually mild or moderate. The frequency of cancellation of pregabalin and placebo because of adverse reactions was 14 and 7%, respectively.The main undesirable effects that required cessation of treatment were dizziness (4%) and drowsiness (3%), depending on their subjective tolerance. Other side effects that also lead to drug cancellation: ataxia, confusion, asthenia, impaired attention, blurred vision, impaired coordination, peripheral edema.

Below are listed all the undesirable events, the frequency of which exceeded that in the placebo group (observed in more than 1 person). They are distributed according to system-organ classes and frequency (very frequent (> 1/10), frequent (> 1/100, <1/10), infrequent (> 1/1000, <1/100), rare (<1 / 1000)). The listed undesirable phenomena could be associated with the underlying disease and / or concomitant therapy.

Infections and invasions: infrequent - nasopharyngitis.

On the part of the blood and lymphatic system: rare - neutropenia.

Metabolic and nutritional disorders: frequent - increased appetite; infrequent - anorexia, hypoglycemia.

Mental disorders: frequent - euphoria, confusion, decreased libido, irritability, insomnia, disorientation; infrequent - depersonalization, anorgasmia, anxiety, depression,agitation, lability of mood, depressed mood, difficulty in word selection, hallucinations, unusual dreams, increased libido, panic attacks, apathy, increased insomnia; rare - disinhibition, high spirits.

Neurological disorders: very frequent - dizziness, drowsiness; frequent - ataxia, impaired attention, impaired coordination, memory impairment, tremor, dysarthria, paresthesia, imbalance, amnesia, sedation, lethargy; infrequent - cognitive disorders, hypoesthesia, nystagmus, speech disorders, myoclonic cramps, weakening of reflexes, dyskinesia, psychomotor agitation, postural dizziness, hyperesthesia, loss of taste sensations, burning sensation on mucous membranes and skin, intentional tremor, stupor, fainting; rare - hypokinesia, parosmia, dysgraphy.

Disorders from the side of the organ of vision: frequent - blurred vision, diplopia; infrequent - visual impairment: narrowing of the visual fields, reduced visual acuity, eye pain, asthenopia, dry eyes, puffiness of the eyes, increased lacrimation; rare - flashing of "sparks" before the eyes, eye irritation, mydriasis,Oscilloscopy (subjective sensation of fluctuations in the subjects under consideration), impaired perception of visual depth, loss of peripheral vision, strabismus, increased brightness of visual perception.

Violations of the hearing and vestibular organs: frequent - vertigo; infrequent - hyperacusis.

Disorders from the cardiovascular system (CVS): infrequent - tachycardia, atrioventricular (AV) blockade I degree, lowering blood pressure (BP), cooling of limbs, increased blood pressure, skin hyperemia; rare - sinus tachycardia, sinus arrhythmia, sinus bradycardia.

Disturbances from the respiratory system: infrequent - shortness of breath, cough, dryness of the nasal mucosa; rare - nasal congestion, nosebleed, rhinitis, snoring, a feeling of "embarrassment" in the throat.

Disorders from the digestive system: frequent - dry mouth, constipation, vomiting, flatulence, bloating; infrequent - increased salivation, gastroesophageal reflux, hypoesthesia of the oral mucosa; rare - ascites, dysphagia, pancreatitis.

Diseases from the skin: infrequent - sweating, papular rash; rare - cold sweat, hives.

Disorders from the musculoskeletal system: infrequent - muscle twitching, swelling of the joints, muscle spasms, myalgia, arthralgia, back pain, pain in the limbs, stiffness of the muscles; rare - spasm of the neck muscles, pain in the neck, rhabdomyolysis.

Disorders from the urinary system: infrequent - dysuria, urinary incontinence; rare - oliguria, renal insufficiency.

Disorders from the reproductive system: frequent - erectile dysfunction; infrequent - delay in ejaculation, sexual dysfunction; rare - amenorrhea, pain in the mammary glands, discharge from the mammary glands, dysmenorrhea, enlargement of mammary glands in the volume.

Other: frequent - fatigue, swelling, incl. peripheral, a sense of "intoxication," a violation of gait; infrequent - asthenia, falls, thirst, feeling chest tightness, generalized edema, chills, pain, pathological sensations; rare - hyperthermia.

Laboratory and instrumental data: frequent - weight gain; infrequent - increased activity of alanine aminotransferase (ALT), creatine phosphokinase, aspartate aminotransferase (ACT), a decrease in the number of platelets; rare - an increase in the concentration of glucose and creatinine, a decrease in the concentration of potassium blood, a decrease in body weight, a decrease in the number of leukocytes in the blood.

Effects observed in post-marketing surveillance of patients taking pregabalinum (frequency unknown)

Neurological disorders: headache, loss of consciousness, cognitive impairment, convulsions.

Disorders from the digestive system: rare cases of edema of the tongue, nausea, diarrhea.

Diseases from the skin: rare cases of edema of the face, itching, Stevens-Johnson syndrome.

Disorders from the side of the organ of vision: keratitis, loss of vision.

Immune system disorders: angioedema, allergic reactions, hypersensitivity.

Violations by the CAS: chronic heart failure, lengthening of the interval QT.

Disorders from the urinary system: retention of urine.

Disturbances from the respiratory system: pulmonary edema.

Disorders from the reproductive system: gynecomastia.

Other: increased fatigue.

Overdose:

In case of an overdose of the drug (up to 15 g), none of the unwanted adverse reactions described above was recorded. In rare cases, there is a coma. In the course of postmarketing use, the most frequent adverse events,developed with an overdose of pregabalin, were: affective disorders, drowsiness, confusion, depression, agitation and anxiety.

Treatment: carry out gastric lavage, maintenance therapy and, if necessary, hemodialysis (see section "Method of administration and dose" Table. 1).

Interaction:

Pregabalin is excreted in the urine mostly unchanged, undergoes minimal metabolism in humans (in the form of metabolites, less than 2% of the dose is excreted by the kidneys), does not inhibit the metabolism of other drugs in vitro and does not bind to plasma proteins, so it is unlikely to enter into a pharmacokinetic interaction.

There were no signs of clinically significant pharmacokinetic interaction of pregabalin with phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone and ethanol. It has been established that oral hypoglycemic drugs, diuretics, insulin, phenobarbital, tiagabine and topiramate have no clinically significant effect on the clearance of pregabalin.

When using oral contraceptives containing norethisterone and / or ethinyl estradiol, simultaneously with pregabalin, the equilibrium pharmacokinetics of both drugs did not change.

There were reports of violations of breathing and the onset of coma with the simultaneous use of pregabalin with other drugs that depress the central nervous system. Also reported was the negative effect of pregabalin on the activity of the gastrointestinal tract (including the development of intestinal obstruction, paralytic ileus, constipation) with simultaneous use with drugs that cause constipation (such as non-narcotic analgesics).

Repeated oral administration of pregabalin with oxycodone, lorazepam or ethanol did not have a clinically significant effect on respiration. Pregabalin, apparently, enhances the violations of cognitive and motor functions caused by oxycodone. Pregabalin can enhance the effects of ethanol and lorazepam.

Special instructions:

Part of patients with diabetes mellitus in case of weight gain on the background of treatment with pregabalin may require correction of doses of hypoglycemic agents.

Pregabalinum should be canceled in case of development of symptoms of angioedema (such as facial edema, perioral edema or swelling of the tissues of the upper respiratory tract).

Antiepileptic drugs, including pregabalinum, may increase the risk of suicidal thoughts or behavior. Therefore, patients receiving these drugs should be carefully monitored for the appearance or deterioration of depression, the appearance of suicidal thoughts or behavior.

Treatment with pregabalin was accompanied by dizziness and drowsiness, which increases the risk of accidental injuries (falls) in the elderly. During the postmarketing use of the drug, there were also cases of loss of consciousness, confusion, and cognitive impairment. Therefore, until patients do not evaluate the possible effects of the drug, they must be careful.

Information on the possibility of canceling other anticonvulsants with suppression of seizures with pregabalin and the advisability of monotherapy with this drug are insufficient.

There are reports of seizures, including epileptic status and minor seizures, with pregabalin or immediately after therapy.

If such undesirable reactions as blurred vision or other abnormalities on the part of the visual organ appear in response to the use of pregabalin, the discontinuation of the drug may lead to the disappearance of these symptoms.

There were also cases of development of renal failure, in some cases after the abolition of pregabalin kidney function was restored.

As a result of cancellation of pregabalin after prolonged or short-term therapy, the following undesirable phenomena were observed: insomnia, headache, nausea, diarrhea, flu-like syndrome, depression, sweating, dizziness, convulsions and anxiety.

Information on the frequency and severity of manifestations of the syndrome of "cancellation" of pregabalin, depending on the duration of therapy by the latter and its dose is not available.

During the post-marketing application of the drug, chronic heart failure was reported against the background of pregabalin therapy in some patients. These reactions were predominantly observed in elderly patients who had cardiac impairment and received a drug for neuropathy. therefore pregabalinum this category of patients should be used with caution. After the abolition of pregabalin, the disappearance of manifestations of such reactions is possible.

The incidence of adverse events on the part of the central nervous system, especially such as drowsiness, increases in the treatment of central neuropathic pain,caused by spinal cord injury, which, however, may be a consequence of the summation of the effects of pregabalin and other concurrently taken drugs (eg, antispastic). This circumstance should be taken into account when presgabalin is prescribed for this indication.

There are reports of cases of development of dependence when using pregabalin. Patients with drug dependence in a history need careful medical observation for symptoms of dependence on pregabalin.

There have been cases of encephalopathy, especially in patients with concomitant diseases, which can lead to the development of encephalopathy.

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

Pregabalin may cause dizziness and drowsiness and, accordingly, affect the ability to drive and use complex techniques. Patients should not drive a car, use complicated equipment or perform other potentially dangerous activities until the patient's individual response to the drug is determined and the patients' ability to perform such tasks is estimated.

Form release / dosage:

Capsules, 25 mg, 50 mg, 75 mg, 150 mg, 300 mg.

Packaging:

For 14 capsules in a blister of the combined film (PVC / PE / PVDC) // aluminum foil.

1, 2 or 4 blisters in a cardboard box together with instructions for use.

Storage conditions:

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:LP-002586

Date of registration:19.08.2014

The owner of the registration certificate:Egis Pharmaceutical Plant OJSCEgis Pharmaceutical Plant OJSC Hungary

Manufacturer: & nbsp

NOBELPHARMA ILAC SANAYII VE TICARET, A.S. Turkey

Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Information update date: & nbsp27.08.2015

Illustrated instructions

Instructions

Prabegin® (Prabegin®)