LYRICA. 75 mg. 14 capsules
Lyrica is indicated as adjunctive therapy in adults with partial seizures with or bezvtorichna generalization.
LYRICA. 75 mg. 14 capsules
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 25 mg pregabalin (pregabalin). Lyrica capsules also contain lactose monohydrate.
Hard kapsulaByala marked with "Pfizer" on the cap and "PGN 25" on the body with chernomastilo .
4.1 Therapeutic indications
Lyrica is indicated for the treatment of peripheral and central neuropathic pain in adults.
Lyrica is indicated as adjunctive therapy in adults with partial seizures with or bezvtorichna generalization.
Lyrica is indicated for the treatment of generalized anxiety disorder (GAD ) in adults.
4.2 Posology and method of administration
The dose range is 150 to 600 mg per day , divided into two or three priema.Lyrica can be taken with or without food.
Pregabalin treatment can be started at a dose of 150 mg per day . Depending otindividualniya patient response and tolerability, the dose can badeuvelichena to 300 mg per day, after an interval of 3 to 7 days , and if necessary to maksimalnadoza than 600 mg per day after additional 7-day interval .
Pregabalin treatment can be started at a dose of 150 mg per day . Depending otindividualniya patient response and tolerability, the dose can badeuvelichena to 300 mg per day after 1 week. The maximum dose of 600 mg per day can badedostignata after an additional week. GAD
The dose range is 150 to 600 mg per day , divided into two or three priema.Neobhodimostta treatment should be reassessed redovno.Lechenieto pregabalin may begin with a dose of 150 mg per day . Depending otindividualniya patient response and tolerability, the dose can badeuvelichena to 300 mg per day after 1 week. After an additional week dozirovkatamozhe be increased to 450 mg per day . The maximum dose of 600 mg per day can badedostignata after an additional sedmitsa.Prekratyavane treatment pregabalinV accordance with current clinical practice , if pregabalin should badeprekrateno recommended this should be done gradually over a minimum of 1 sedmitsanezavisimo of reading ( see . 4.8) . Use in patients with hepatic impairment
In patients with hepatic impairment is not required dosage adjustment (see tochka5.2 ) .
Use in children and adolescents
Lyrica is not recommended for use in children under 12 years of age and older (12 - 17godishna age) due to insufficient data on safety and efficacy (see section 5.3 ) . Use in the elderly (over 65 years ) in patients with elderly may be necessary to reduce the dose of pregabalinporadi reduced renal function (see "Patients with impaired renal function " ) .
Hypersensitivity to the active substance or to any of the excipients.
4.4 Special warnings and precautions for use
In accordance with current clinical practice, some patients with diabetes who naddavatna weight on pregabalin treatment may need to adjust hypoglycaemic lechenie.Ot postmarketing experience, there have been reports of hypersensitivity reactions , angioedema vklyuchitelnosluchai . If you experience symptoms of angioedema such as swollen face , okoloustata or upper respiratory tract , pregabalin should be stopped nezabavno.Lechenieto Pregabalin has been associated with dizziness and somnolence, which could dauvelichat occurrence of accidental injury ( fall) in elderly . There ipost - marketing reports of loss of consciousness, confusion and mental uvrezhdane.Sledovatelno , patients should be advised to exercise caution dokatone be familiar with the potential effects of treatment.
In controlled studies, a higher proportion of patients treated with pregabalin sasaobshtili blurred vision, compared with patients treated with placebo , which eotzvuchalo in most cases with continued dosing . In clinical studies where ophthalmologic testing was conducted , the rate of reduction of zritelnataostrota and visual field changes was greater in patients treated with pregabalin than patients treated with placebo , the incidence of fundoscopic changes was greater in patients treated with placebo (see section 5.1). from post-marketing experience are also reported side effects in terms of vision, most of which relate to transient blurred vision or other changes vzritelnata sharpness. Discontinuation of pregabalin may result in resolution or improvment these visual simptomi.Saobshtavat cases of renal failure and discontinuation of pregabalin ubeditelnopokazva reversibility of this adverse reaktsiya.Sashtestvuvat insufficient data on the withdrawal of concomitant antiepileptichnilekarstva after achieving seizure control with pregabalin in the add , set to monotherapy on pregabalin. Observed withdrawal symptoms in some patients after discontinuation of short idalgosrochno treatment with pregabalin. The following events have been mentioned: insomnia , headache , nausea, diarrhea, flu syndrome, nervousness , depression , pain, sweating and dizziness. Patsientitetryabva be informed of this at the start of treatment.
There are no data on the incidence and severity of withdrawal symptoms depending otprodalzhitelnostta of use and dosage of pregabalin in termination nadalgosrochno treatment with pregabalin.
There have been post -marketing reports of congestive heart failure in nyakoipatsienti receiving pregabalin . These occurred primarily in patients vstarcheska age with cardiovascular damage during treatment of neuropathy spregabalin . Pregabalin should be used with caution in these ????????.????????????????? of pregabalin may resolve the reaktsiyata.Patsienti with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this treatment lekarstvo.Pri central neuropathic pain due to spinal cord injury bilauvelichena frequency of adverse events in general , adverse events of CNS iosobeno sleepiness. This can be attributed to an additive effect due to sapatstvashtotolechenie (e.g., anti- spasticity agents ) needed for this state . This should be imapredvid when prescribing pregabalin in this condition.
4.5 Interaction with other medicinal products and other forms of interaction
Since pregabalin is predominantly excreted unchanged in the urine seprenebrezhimo metabolism in humans (<2% of the dose was recovered in the urine in the form nametaboliti ) , does not inhibit drug metabolism in vitro and is not associated with plazmenitebeltatsi , it is unlikely to cause or contribute to the ?????????????????????????????? .
Accordingly, in in vivo studies no clinically significant ?????????????????????????????? between pregabalin and phenytoin , carbamazepine, valproic acid , lamotrigine, gabapentin, lorazepam, or ethanol oskikodon . Farmakokinetichenanaliz population indicated that oral antidiabetics, diuretics , insulin, phenobarbital , tiagabine and topiramate had no clinically significant effect on the clearance of pregabalin.Ednovremennoto administration of pregabalin oral contraceptives sredstvanoretisteron and / or ethinyl estradiol pharmacokinetics in statsionarnosastoyanie any of these veshtestva.Pregabalin may potentiate the effects of ethanol and lorazepam . In controlled klinichniprouchvaniya multiple oral doses of pregabalin co-administered with oxycodone, lorazepam, or ethanol did not result in clinically important effects on respiration . In post - marketing experience respiratory failure and coma in patients taking pregabalin and other CNS depressant drug . Pregabalin appears to be aditivnodeystvie the impairment of cognitive and gross motor function caused otoksikodon.Ne have been no specific pharmacodynamic interaction studies pridobrovoltsi elderly . Interaction studies have only been performed privazrastni .
4.6 Pregnancy and lactation
There are no adequate data from the use of pregabalin in bremenni.Prouchvaniyata in animals have shown reproductive toxicity ( see section 5.3 ) Potentsialniyatrisk in humans is unknown. Lyrica should not be used during pregnancy unless the is not necessary (if the benefit to the mother clearly outweighs the potential risk to the fetus) . Prizheni childbearing age should be given effective kontratseptsiya.Ne known if pregabalin is excreted in human milk , however, it seustanovyava in the milk of rats . Therefore , during the treatment with pregabalin recommended lactation .
4.7 Effects on ability to drive and use machines
Lyrica may have minor or moderate influence on the ability to drive and use of machinery . Lyrica may cause dizziness and somnolence and therefore can povliyaesposobnostta to drive or operate machinery. Patients are advised not to drive, being down complex machinery or engage in other potentially hazardous activities until serazbere whether treatment affects their ability to perform these activities.
4.8 Undesirable effects
Pregabalin clinical program involved over 9000 patients who izpolzvalipregabalin , over 5,000 of whom participated in a double- blind placebo - kontroliraniprouchvaniya . The most frequently reported adverse events were dizziness and sanlivost.Nezhelanite reactions were generally mild to moderate in intensity . The incidence of discontinuation due to adverse reactions nalechenieto all controlled studies was 13% of patients who achieved remission receiving pregabalin and 7% for patients receiving placebo. Most chestitenezhelani events leading to discontinuation in the group treated with pregabalin bilizamayanost and drowsiness.
In the table below are listed by class and frequency (very common (> 1/10 ), common (> 1/100 , <1 /10) , uncommon (> 1/1000 , <1 /100) and rare (<1 / 1000 ) ) all adverse reactions that occurred with an incidence greater than placebo and in more than one patient . In vsyakogrupirane frequency undesirable effects are presented in order otnoshenieserioznostta .
These side effects could be associated with the underlying disease and / ilisapatstvashto treatment.
In the treatment of central neuropathic pain due to spinal cord injury bilauvelichena frequency of adverse events in general , adverse events of CNS iosobeno sleepiness (see section 4.4).
Additional reactions reported from post- marketing experience are included as " Sneizvestna frequency" in Italic below. Body System
Immune system disorders
Hypersensitivity , angioedema, allergic reaction
Blood and lymphatic system
Metabolism and nutrition
Euphoric mood , confusion , irritability , decreased libido
Hallucinations, panic attacks , anxiety , agitation , depression, depressed mood , changes vnastroenieto , depersonalization , increased insomnia , difficulty finding words , patologichnisanishta , increased libido , anorgasmia , apathy
Disinhibition , elation
Nervous System Disorders
Ataxia, incoordination , tremors, dysarthria , memory impairment , impaired attention , paraesthesia
Syncope , stupor , myoclonus , increased psychomotor activity , ageusia , dyskinesia, orthostatic dizziness , intention tremor, nystagmus, cognitive disorder, speech disorder , hyporeflexia , hypoesthesia , amnesia, hyperaesthesia , burning
Hypokinesia , parosmia , dysgraphia
Loss of consciousness, mental impairment , headache
Blurred vision, diplopiyaNechesti
Visual disturbance , eye swelling , visual field defect , decreased visual acuity , eye pain , asthenopia , dry eyes , increased lakrimatsiyaRedkiS unknown chestotaZaguba of peripheral vision , ostsilopsiya , narushenozritelno depth perception , photopsia, vochite irritation , mydriasis , strabismus , increased brightness ?????????????????????????? ear and ????????????????????????????????????????????????? ????????????????????????????????????????????????? block first degree , sinus tachycardia, sinus bradycardia , sinus aritmiyaS unknown chestotaZastoyna heart nedostatachnostSadovi ???????????????????????????????? , hot valniHipotoniya , hypertension , peripheral coldness Respiratory, thoracic and mediastinal disorders
Dyspnea, nasal dryness
Epistaxis, throat tightness, nasopharyngitis , cough , nasal congestion , rhinitis , snoring
Vomiting , dry mouth , constipation , flatulence
Bloating, gastroesophageal reflux , increased salivation, hypoaesthesia ustnatakuhina
Ascites, pancreatitis , dysphagia, nausea
Swollen tongue, diarrhea , nausea
Skin and subcutaneous tissue disorders
Papular rash , sweating
Urticaria, cold sweat
Syndrome Stevens Johnson, Itching
Disorders of the musculoskeletal system and connective tissue
Muscle twitching , joint swelling , muscle cramps, myalgia , arthralgia , back pain , pain in limb , muscle stiffness
RedkiRabdomioliza , cervical spasm , neck pain
Renal and urinary patishtNechesti
Urinary incontinence , dysuria
Renal failure , oliguria
Reproductive system and breast disorders
Delayed ejaculation, sexual dysfunction
Amenorrhea , breast discharge , breast pain , dysmenorrhea, breast hypertrophy
General disorders and administration site conditions
Abnormal gait, feeling drunk , fatigue , peripheral edema, edema
Fall , chest tightness , asthenia , thirst
Anasarca , pyrexia , chills , increased pain
Swelling of the face
Increases in creatinine phosphokinase , increased alanine aminotransferase , aspartate aminotransferase increased , decreased platelet count
RedkiPovishenie blood sugar , decrease in blood potassium , reduction in the number of leukocytes , increased blood creatinine , weight loss
In some patients, symptoms of withdrawal after stopping short idalgosrochno pregabalin treatment . The following events have been mentioned: insomnia , headache , nausea, diarrhea, flu syndrome, nervousness , depression , pain, sweating and dizziness. Patsientitetryabva be informed of this at the start of lechenieto.Lipsvat data on the incidence and severity of withdrawal symptoms depending otprodalzhitelnostta of use and dosage of pregabalin in termination of dalgosrochnolechenie pregabalin .
In overdoses up to 15 g no reported unexpected adverse reaktsii.Nay frequently reported adverse reactions from post- marketing experience observed of pregabalin overdose included somnolence , confusional state , agitation and bezpokoystvo.Lechenieto of pregabalin overdose should include general supportive measures ieventualno hemodialysis if necessary ( see section 4.2 Table 1). Pharmacological SVOYSTVA5.1 Pharmacodynamic ??????????????????????????? group: antiepileptics, ATC code: N03AH16Aktivnoto substance Pregabalin is an analogue of gamma-aminobutyric acid ((S) -3 - ( aminomethyl) -5- methylhexanoic acid). Mechanism deystviePregabalin binds to an auxiliary subunit (? 2 -? protein) of voltage - zavisimitekaltsievi channels in the central nervous system , potently displacing [3 H]- gabapentin.Klinichen experience
Efficacy has been shown in studies in diabetic neuropathy, post-herpetic neuralgia igrabnachnomozachna trauma. Effectiveness have not been studied in other models of nevropatichnabolka .
Pregabalin has been studied in 10 controlled clinical trials up to 13 weeks with twice-daily dosing (BID) and up to 8 weeks with three times daily (TID) dosing . Overall, the safety and effectiveness of dosing regimens BID and TID were shodni.V clinical studies up to 12 weeks for both peripheral and zatsentralna neuropathic pain, a reduction in pain was seen by parvatasedmitsa and was maintained throughout the treatment period.
In controlled clinical trials in peripheral neuropathic pain 35% of patients treated with pregabalin and 18% of patients on placebo had a 50% improvement natochkoviya score for pain assessment . Among patients not experiencing somnolence takovapodobrenie was observed in 33% of patients treated with pregabalin and 18 % of placebo patsientitena . In patients with somnolence the responder rates were 48 % in the spregabalin and 16% in the placebo group .
In a controlled clinical trial in central neuropathic pain 22 % of patients treated with pregabalin and 7% of patients on placebo had a 50% improvement of tochkoviyarezultat assessment of pain. EpilepsiyaPregabalin has been studied in 3 controlled clinical studies of 12 sedmitsipri twice ( BID) or three times ( TID ) daily intake. Overall, the safety iefektivnostta dosing regimens BID and TID were shodni.Namalenie of seizure frequency was observed by the end of the first week .
Pregabalin has been studied in 6 controlled clinical trials lasting 4-6 weeks , a study in elderly patients with a duration of 8 weeks ednodalgosrochno study for prevention of recurrence of double-blind phase of prevention retsidivas duration of 6 months.
Relief of symptoms of GAD as measured by the Hamilton scale assessment natrevozhnostta (HAM-A), was observed by the end of the first sedmitsa.V controlled clinical trials ( 4-8 weeks duration) 52% of patients treated with pregabalin and 38 % of patients on placebo had at least a 50% improvement in obshtiyarezultat HAM-A from baseline to endpoint.
In controlled studies, a higher proportion of patients treated with pregabalin sasaobshtili blurred vision than did patients treated with placebo , which eotzvuchalo in most cases with continued dosing . Studies were oftalmologichniizsledvaniya (including testing of visual acuity testing nazritelnoto field testing and dilated funduscopic examination ) in more than 3600 patients WITHIN controlled clinical trials. In these patients, visual acuity was reduced pri6 , 5% of patients treated with pregabalin and 4.8% of patients treated with platsebo.Promeni visual field were detected in 12.4 % of patients treated with pregabalin and 11.7% otlekuvanite placebo patients. Funduscopic changes were observed in 1.7% otlekuvanite pregabalin and 2.1% of placebo-treated patients.
5.2 Pharmacokinetic properties
Steady state pharmacokinetics of pregabalin are similar in healthy volunteers, patients with epilepsy receiving antiepileptic drugs and patients with chronic pain.
Pregabalin is rapidly absorbed under fasting conditions , with peak plasma concentrations occurring within one hour after administration as a single dose and namnogokratni doses. Oral bioavailability of pregabalin is expected to be ? 90% and enezavisima dose . After repeated administration , steady state is achieved within 48 hours 24do . The rate of pregabalin absorption is decreased when given with food, resulting doponizhenie C max by approximately 25-30 % and delayed t max to approximately 2.5 hours . Napregabalin food intake , however , no clinically significant effect on the extent of absorption napregabalin .
Preclinical studies indicate that pregabalin crosses the blood -brain barrier in mice, rats and monkeys. It has been shown that pregabalin crosses the placenta priplahove and is found in the milk of lactating rats. In humans, the volume of distribution napregabalin following oral administration is approximately 0,56 l / kg. Pregabalin is not bound splazmenite proteins.
Metabolism of pregabalin in humans is negligible . Following administration of radiolabelled pregabalin dozaradioaktivno approximately 98% of the radioactivity vurinata was unchanged pregabalin. N- methylated derivative of pregabalin osnovniyatmetabolit pregabalin found in urine , accounted for 0.9 % of the dose . In predklinichniprouchvaniya no evidence of racemization of the S- enantiomer of pregabalin to negoviyaR - enantiomer.
Pregabalin is eliminated from the systemic circulation primarily by renal excretion vnepromenen form. Mean half-life of pregabalin is 6.3 hours . Ibabrechniyat plasma clearance of pregabalin are directly proportional to creatinine clearance ( see section 5.2 Renal impairment) .
In patients with reduced renal function or undergoing hemodialysis is necessary nadozata (see section 4.2, Table 1).
Linearity / non-linearity:
Pregabalin pharmacokinetics are linear over the dose range preporachitelniyadneven . The variability of the pharmacokinetics of pregabalin mezhduindividite is low (< 20%). Multiple-dose pharmacokinetics can badepredskazana from single-dose data . Therefore , it is not necessary rutinnomonitorirane plasma concentrations of pregabalin.
Pharmacokinetics in special patient groups
Clinical trials indicate that gender does not have a clinically significant impact varhuplazmenite pregabalin concentrations .
Pregabalin clearance is proportional to creatinine clearance. Furthermore tovapregabalin is effectively removed from plasma by hemodialysis ( after 4 chasovohemodializno treatment plasma pregabalin concentrations are reduced by priblizitelno50 %). Because renal elimination is the major route of elimination in patients snarushena renal function is necessary to reduce the dosage following hemodialysis eneobhodim supplementation (see section 4.2 Table 1).
No specific pharmacokinetic studies conducted in patients with narushenachernodrobna function. Since pregabalin does not undergo significant metabolism and ekskretirapredimno unchanged in the urine, impaired liver function should dapromenya significant plasma concentrations of pregabalin.
Elderly (over 65 years)
There is a tendency to reduce the clearance of pregabalin with increasing vazrastta.Tova decrease in pregabalin oral clearance is consistent with decreases in creatinine clearance associated with increasing age. In patients with age obuslovenonarushenie of renal function may be necessary to reduce the dose of pregabalin (see section 4.2 Table 1).
5.3 Preclinical safety data
In conventional safety pharmacology studies in animals, pregabalin epokazal well tolerated at doses clinically relevant . In studies zatoksichnost repeated dose performed in rats and monkeys were nablyudavaniefekti CNS , including hypoactivity, hyperactivity and ataxia . Sledprodalzhitelna exposure to pregabalin at exposures ? 5 times the midst of human exposure at the maximum recommended clinical dose nablyudavapovishena incidence of retinal atrophy commonly observed in albino rats vnaprednala age.
Pregabalin was not teratogenic in mice, rats or rabbits. Fetal toxicity in the rats rabbits occurred only at exposures sufficiently above people. Vprenatalni / postnatal toxicity studies, pregabalin has led to the emergence of toksichniefekti on offspring development in rats at exposures > 2 times larger otmaksimalnata recommended human exposure .
Pregabalin is not genotoxic based on results from a series of in vitro and in vivo prouchvaniya.Pri rats and mice were conducted biennial surveys pregabalin zakartsinogennost . In rats, no tumors were observed at exposures up to 24 times the average golemiot human exposure at the maximum recommended clinical dose of 600 mg / den.Pri mice, no increased incidence of tumors at exposures similar midst of human exposure , but higher exposures was observed povishenachestota of hemangiosarcoma . The non-genotoxic mechanism pregabalinobrazuvane induced tumors in mice involves platelet changes and proliferation naendotelni cells. These platelet changes were not present in rats or prihora based on short term and limited long-term clinical data. Lipsvatdokazatelstva suggesting risk in humans.
In young rats the types of toxicity do not differ qualitatively from those observed Prizren rats. Young rats, however , are more sensitive . At therapeutic exposures Sabina established clinical manifestations of CNS hyperactivity and bruxism and izvestnipromeni growth (transient suppression of body weight gain ) . Effects on cycle narazgonvane were observed at exposures exceeding 5-fold hora.Redutsiran response to acoustic startle was observed in juvenile rats 1-2 sedmitsisled exposure > 2 times greater than the human therapeutic exposure . Nine sedmitsisled exposure, this effect was not observed.
6.1 List of excipients
Titanium dioxide (E171)
sodium lauryl sulfate
Silica colloidal anhydrous
Black iron oxide (E172)
Not applicable .
6.3 Shelf life
Three years .
6.4 Special precautions for storage
This medicinal product does not require any special sahranenie.6.5 data opakovkataPVC / aluminum blister packs containing 14 , 21, 56, 84 or 112 (2 x 56) hard kapsuli.100 x 1 capsules in PVC / Aluminium perforated unit dose blisteri.100 capsules in PVC / aluminum blisters ( slotted ) . not all pack sizes may be marketed prodazhba.6.6 special precautions for disposal and rabotaNyama special requirements.