LYRICS

Active material: Pregabalin
When ATH: N03AX16
CCF: Anticonvulsants
ICD-10 codes (testimony): B02.2, G40, G63.2, R52.2
When CSF: 02.05.10
Manufacturer: PFIZER GmbH (Germany)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Capsules with a white body and white cap, on the body in black ink indicated dosage and product code “PGN 25”, on cap label applied “Pfizer”.

Excipients: lactose monohydrate, corn starch, talc.

The composition of the shell capsules: gelatin, water, Titanium dioxide (E171), sodium lauryl, colloidal silicon dioxide.

10 PC. – blisters (10) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (4) – packs cardboard.
21 PC. – blisters (4) – packs cardboard.

Capsules white (with black stripe) body and white cap, on the body in black ink indicated dosage and product code “PGN 50”, on a lid affixed label “Pfizer”.

Excipients: lactose monohydrate, corn starch, talc.

The composition of the shell capsules: gelatin, water, Titanium dioxide (E171), sodium lauryl, colloidal silicon dioxide.

10 PC. – blisters (10) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (4) – packs cardboard.
21 PC. – blisters (4) – packs cardboard.

Capsules with white body and orange cap, on the body in black ink indicated dosage and product code “PGN 75”, on a lid affixed label “Pfizer”.

Excipients: lactose monohydrate, corn starch, talc.

The composition of the shell capsules: gelatin, water, Titanium dioxide (E171), sodium lauryl, colloidal silicon dioxide, iron oxide red (E172).

10 PC. – blisters (10) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (4) – packs cardboard.
21 PC. – blisters (4) – packs cardboard.

Capsules with an orange body and orange cap, on the body in black ink indicated dosage and product code “PGN 100”, on a lid affixed label “Pfizer”.

Excipients: lactose monohydrate, corn starch, talc.

The composition of the shell capsules: gelatin, water, Titanium dioxide (E171), sodium lauryl, colloidal silicon dioxide, iron oxide red (E172).

10 PC. – blisters (10) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (4) – packs cardboard.
21 PC. – blisters (4) – packs cardboard.

Capsules with a white body and white cap, on the body in black ink indicated dosage and product code “PGN 150”, on a lid affixed label “Pfizer”.

Excipients: lactose monohydrate, corn starch, talc.

The composition of the shell capsules: gelatin, water, Titanium dioxide (E171), sodium lauryl, colloidal silicon dioxide.

10 PC. – blisters (10) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (4) – packs cardboard.
21 PC. – blisters (4) – packs cardboard.

Capsules with light orange body and a light-orange lid, on the body in black ink indicated dosage and product code “PGN 200”, on a lid affixed label “Pfizer”.

Excipients: lactose monohydrate, corn starch, talc.

The composition of the shell capsules: gelatin, water, Titanium dioxide (E171), sodium lauryl, colloidal silicon dioxide, iron oxide red (E172).

10 PC. – blisters (10) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (4) – packs cardboard.
21 PC. – blisters (4) – packs cardboard.

Capsules with white body and orange cap, on the body in black ink indicated dosage and product code “PGN 300”, on a lid affixed label “Pfizer”.

Excipients: lactose monohydrate, corn starch, talc.

The composition of the shell capsules: gelatin, water, Titanium dioxide (E171), sodium lauryl, colloidal silicon dioxide, iron oxide red (E172).

10 PC. – blisters (10) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (4) – packs cardboard.
21 PC. – blisters (4) – packs cardboard.

Pharmacological action

The antiepileptic drug, active substance which is an analog of gamma-aminobutyric acid (GABA).

Although the exact mechanism of action of pregabalin is still unclear, It was found, that pregabalin binds with an additional subunit (a₂-Delta protein) voltage-dependent calcium channels in the CNS, It assumed, that such binding can promote expression of its analgesic and anticonvulsant effects.

Neuropathic pain

The effectiveness of pregabalin was observed in patients with diabetic neuropathy and postherpetic neuralgia. Effective in other types of neuropathic pain has not been studied.

Established, that when taking pregabalin courses to 13 weeks 2 times / day and up 8 weeks 3 times / day, in general, the risk of side effects and efficacy in methods of 2 or 3 times / day the same.

When you receive a rate of up to 13 weeks the pain decreased during the first week, and the effect was maintained up to the end of treatment.

There was a decrease in the index of pain 50% in 35% patients, receiving pregabalin, and 18% patients, placebo. Among patients, did not experience drowsiness, the effect of such a reduction in pain was observed in 33% patients pregabalin group and 18% patients in the placebo group. Patients, experiencing drowsiness, response rates were 48% in the pregabalin group and 16% placebo.

Epilepsy

When receiving the drug for 12 weeks 2 or 3 times / day marked by the risk of side effects and efficacy in these modes are the same dosing. Reducing the frequency of seizures began during the first week.

Pharmacokinetics

Pharmacokinetics of pregabalin in the range of the recommended daily doses is linear, interindividual variability is low (<20%). The pharmacokinetics of the drug in repeated use can be predicted based on the data reception unit dose. Hence, the need for regular monitoring of the concentration of pregabalin there.

Absorption

Pregabalin is rapidly absorbed after oral administration on an empty stomach. C_max plasma achieved through 1 h both single, and repeated use. Bioavailability pregabalin ingestion of ≥ 90% and does not depend on the dose. Repeated application of the equilibrium state is achieved through the 24-48 no. Absorption of pregabalin is deteriorating under the influence of food. Thus C_max reduced by about 25-30%, and the time to reach C_max increases to approximately 2.5 no. However, food intake has no clinically significant effect on the total absorption of pregabalin.

Distribution

V_d pregabalin after ingestion is approximately 0.56 l / kg. The drug does not bind to plasma proteins.

Metabolism

Pregabalin is hardly metabolized. Then accept mechennogo pregabalin example 98% radiolabel was determined in the urine in unchanged form. Percentage of N-methylated derivative of pregabalin, which is the major metabolite, detectable in the urine, was 0.9% dose. There was no sign of racemization S- enantiomer of pregabalin in the R-enantiomer.

Deduction

Pregabalin is derived mainly kidneys unchanged. Average T_1/2 is 6.3 no. Pregabalin clearance from the plasma and renal clearance are directly proportional to creatinine clearance.

Pharmacokinetics in special clinical situations

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

If the kidney function should be considered, that pregabalin clearance is directly proportional to creatinine clearance. Because, the drug is mainly excreted by the kidneys, with impaired renal function it is advisable to reduce the dose of pregabalin. Besides, pregabalin plasma effectively removed from the hemodialysis (after a 4-hour dialysis session plasma concentrations of pregabalin reduced by approximately 50%), after hemodialysis is necessary to appoint an additional dose of the drug.

Pharmacokinetics of pregabalin in patients with hepatic impairment has not been studied specifically. Pregabalin is hardly metabolized and excreted largely unchanged in the urine, Therefore, liver dysfunction should not significantly alter plasma concentrations.

In appointing the drug elderly patients (senior 65 years) should be considered, that the clearance of pregabalin with age tends to decrease, reflecting the age-related decline QC. Older people with impaired renal function may require a reduction in dose.

Testimony

Neuropathic pain:

- the treatment of neuropathic pain in adults.

Epilepsy:

- as an aid in adults with partial seizures, occur with or without secondary generalization.

Dosage regimen

The drug is taken orally without food in a daily dose of 150 to 600 mg 2 or 3 admission.

Treatment neuropathic pain start with a dose 150 mg / day. Depending on the achieved effect and tolerability through 3-7 days the dose can be increased to 300 mg / day, and later, if necessary 7 days – up to a maximum dose of 600 mg / day.

At epilepsy treatment is initiated with dosages 150 mg / day. Taking into account the achieved effect and tolerability through 1 week the dose may be increased to 300 mg / day, and a week later – up to a maximum dose of 600 mg / day.

If treatment with Lyrics^® Patients with neuropathic pain or epilepsy should stop, It encouraged to do so gradually over a minimum 1 of the week.

Patients with impaired renal function Dose picked individually, taking into account QC (Table. 1), which is calculated by the following formula:

To Men with a body weight >60 kg:

CC (ml / min)= (weight in kg) x (140 – age in years) /72 x creatinine sыvorotochnыy (mg / dL)

To Women:

CC (ml / min)= Value QC Men's 0.85

Patients, receiving hemodialysis, pregabalin daily dose is selected taking into account the function of kidneys. Immediately following each 4-hour hemodialysis administered an additional dose of (Table. 1).

Table 1. Selection dose of pregabalin with the renal function

In patients with impaired liver function dose adjustment is required.

Elderly patients (senior 65 years) It may need to reduce the dose of pregabalin due to decreased kidney function.

Side effect

According to the existing experience of the clinical use of pregabalin in more than 9000 patients, the most common adverse events were dizziness and somnolence. The observed effects were usually mild or moderate. The frequency cancellation pregabalin and placebo due to adverse reactions was 13% and 7% respectively. The main adverse effects, demanding the cessation of treatment, were dizziness and somnolence.

These side reactions frequency greater than that in the placebo group (observed in more than 1 man) and they could be related to the underlying disease and / or concomitant therapy. Determination of the frequency of adverse reactions: Often (>1/10), often (>1/100, <1/10), less frequently (>1/1000, <1/100), rarely (<1/1000).

From the hematopoietic system: rarely – neutropenia.

Metabolism: often – increased appetite, weight gain; less frequently – anorexia; rarely – gipoglikemiâ, weight loss.

On the part of the psyche: often – euphoria, confusion, decreased libido, irritability; less frequently – depersonalization, anorgazmija, anxiety, depression, ažitaciâ, mood lability, strengthening of insomnia, dejection, difficulties in finding words, hallucinations, unusual dreams, increased libido, panic attacks, apathy; rarely – disinhibition, high spirits.

From the central and peripheral nervous system: Often – dizziness, drowsiness; often – ataxia, impaired attention, incoordination, memory impairment, tremor, dysarthria, paresthesia; less frequently – cognitive abnormality, gipesteziya, defects in visual fields, nistagmo, speech disorder, myoclonic seizures, weakening of reflexes, dyskinesia, psychomotor hyperactivity, dizziness upright, gipersteziya, loss of taste, burning sensation on the skin and mucous membranes, intention tremor, stupor, fainting; rarely – gipokinez, parosmija, chirospasm.

On the part of the organ of vision: often – mist, diplopia; less frequently – reduced visual acuity, sore eyes, asthenopia, as well as dry eyes, eye puffiness, increased lacrimation; rarely – flickering sparks before the eyes, eye irritation, midriaz, oscillopsia (subjective feeling vibrations considered subjects), violation of depth perception, the loss of peripheral vision, kosoglazie, Brightness enhancement of visual perception.

On the part of the organ of hearing and vestibular: often – dizziness; rarely – hyperacusis.

Cardio-vascular system: less frequently – tachycardia, tides; rarely – decrease in blood pressure, cold extremities, increased blood pressure, AV block I degrees, sinus tachycardia, sinus arrhythmia, sinusovaya bradycardia.

The respiratory system: less frequently – breathlessness, xeromycteria; rarely – nazofaringit, cough, nasal congestion, nosebleed, rhinitis, snoring, tightness in the throat.

From the digestive system: often – dry mouth, constipation, vomiting, flatulence; less frequently – increased salivation, hastroэzofahealnыy reflux, sensation of reducing sensitivity in the oral cavity; rarely – ascites, dysphagia, pancreatitis.

Dermatological reactions: less frequently – Sweating, papulleznaya rash; rarely – cold sweat, hives.

On the part of the musculoskeletal system: less frequently – muscle twitching, swelling of joints, muscle cramps, myalgia, arthralgia, backache, pain in the extremities, stiffness in muscles; rarely – trachelism, pain in the neck, raʙdomioliz.

From the urinary system: less frequently – dizurija, urinary incontinence; rarely – oligurija, renal failure.

Reproductive system: often – erectile dysfunction; less frequently – delayed ejaculation, sexual dysfunction; rarely – amenorrhea, pain in the breasts, discharge from the breast, dysmenorrhoea, hypertrophy breast.

From the body as a whole: often – fatiguability, peripheral edema, generalized edema, feeling of intoxication, gait disturbance; less frequently – asthenia, drop, thirst, chest tightness; rarely – increased pain when Anasarca, fever, chills.

From the laboratory parameters: less frequently – increased ALT, CPK, IS, reduction in the number of platelets; rarely – elevated blood glucose levels, creatinine, lowering blood levels of potassium, reduction in the number of leukocytes in blood.

Side effects, marked with the post-marketing surveillance

CNS: headache.

From the digestive system: rarely – swelling of the tongue, nausea.

Other: rarely – swelling of the face.

Contraindications

- Childhood and adolescence up 17 years inclusive (no data on the use of);

- increased sensitivity to the active ingredient or any other component of the preparation.

FROM caution should be prescribed in patients with renal insufficiency, in the presence of rare hereditary diseases.

Pregnancy and lactation

There are no adequate data on the use of pregabalin in pregnancy is not.

IN experimental studies animal drug has toxic effects on the reproductive function.

In this regard, the preparation Lyrics^® It can be administered during pregnancy only if, if the expected benefit to the mother clearly outweighs the potential risk to the fetus.

In applying the drug Lyric^® women of reproductive age You should use adequate contraception methods.

Information about the excretion of pregabalin with the breast milk of women there.

But in experimental studies found, it is excreted in the breast milk of rats.

Therefore, during treatment with Lyrics^® Breastfeeding should stop.

Cautions

The drug should not be administered to patients with hereditary galactose intolerance, lapp lactase deficiency (lactase deficiency, some people of the North), malabsorption of glucose / galactose.

In some patients with diabetes in the case of weight gain during treatment with a drug Lyrics^® may require correction doses hypoglycemic drugs.

Treatment with Lyrics^® accompanied by dizziness and drowsiness, which increase the risk of accidental injury (downs) elderly. Until, while patients do not appreciate the possible effects of the drug, they must be careful.

Information about the possibility of cancellation of other anticonvulsant drugs in suppressing seizures, pregabalin and feasibility of monotherapy with this drug are insufficient.

Use in Pediatrics

The safety and efficacy of the drug in children aged 12 years and adolescents 12-17 years not set.

Effects on ability to drive vehicles and management mechanisms

preparation Lyrics^® may cause dizziness and somnolence and, respectively, affect the ability to drive and use sophisticated technology. Patients should not drive a car, use complex machinery or perform other potentially dangerous activities, until it is determined by the individual patient's response to the drug.

Overdose

If overdose (to 15 g) any of the above-described no adverse reactions were not reported.

Treatment: conduct gastric lavage, supportive therapy, and if necessary – hemodialysis.

Drug Interactions

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

No indication of clinically significant pharmacokinetic interactions with phenytoin, pregabalin, karʙamazepinom, valproic acid, lamotriginom, Gabapentin, lorazepam, oxycodone or ethanol. Established, that oral hypoglycemic agents, Diuretic, insulin, phenobarbital, tiagabine and topiramate does not have a clinically significant effect on pregabalin clearance.

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

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

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored in a dry, inaccessible to children at temperature not exceeding 25 ° C. Shelf life – 3 year. Do not take medicine after the expiration date.