Composition, form of production and packaging
Hard gelatin capsules, в„–4, with a lid and a white body, the dosage and product code "PGN 25", on the lid - "Pfizer" are indicated on the body with black ink; the contents of the capsules are white or almost white powder.
1 caps.
pregabalin 25 mg
Excipients: lactose monohydrate - 35 mg, corn starch - 20 mg, talc - 20 mg.
The composition of the capsule body: titanium dioxide - 2.4423%, gelatin - up to 100%.
Composition of capsule capsule: titanium dioxide - 2.4423%, gelatin - up to 100%.
The composition of ink: shellac - 24-27%, ethanol - 23-26%, isopropanol - 0.5-3%, butanol - 0.5-3%, propylene glycol - 3-7%, ammonia solution concentrated - 1-2%, potassium hydroxide - 0.05-0.1%, purified water - 15-18%, ferric oxide black oxide - 24-28%.
14 pcs. - blisters (1) - packs of cardboard.
Capsules hard gelatinous, в„–4, with a lid from red-brown to dark-red-brown color * and white body; on the body black ink indicates the dosage and product code "PGN 75", on the lid - "Pfizer"; the contents of the capsules are white or almost white powder.
1 caps.
pregabalin 75 mg
Excipients: lactose monohydrate - 8.25 mg, corn starch - 8.375 mg, talc - 8.375 mg.
The composition of the capsule body: titanium dioxide - 2.4423%, gelatin - up to 100%.
Composition of capsule cap: iron oxide red oxide - 1.7361%, titanium dioxide - 0.409%, gelatin - up to 100%.
The composition of ink: shellac - 24-27%, ethanol - 23-26%, isopropanol - 0.5-3%, butanol - 0.5-3%, propylene glycol - 3-7%, ammonia solution concentrated - 1-2%, potassium hydroxide - 0.05-0.1%, purified water - 15-18%, ferric oxide black oxide - 24-28%.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
Capsules hard gelatinous, в„–2, with a lid and a body of white color; on the body black ink indicates the dosage and product code "PGN 150", on the lid - "Pfizer"; the contents of the capsules are white or almost white powder.
1 caps.
pregabalin 150 mg
Excipients: lactose monohydrate - 16.5 mg, corn starch - 16.75 mg, talcum - 16.75 mg.
The composition of the capsule body: titanium dioxide - 2.4423%, gelatin - up to 100%.
Composition of capsule capsule: titanium dioxide - 2.4423%, gelatin - up to 100%.
The composition of ink: shellac - 24-27%, ethanol - 23-26%, isopropanol - 0.5-3%, butanol - 0.5-3%, propylene glycol - 3-7%, ammonia solution concentrated - 1-2%, potassium hydroxide - 0.05-0.1%, purified water - 15-18%, ferric oxide black oxide - 24-28%.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
Hard gelatin capsules, в„–0, with a lid of red-brown to dark-red-brown color * and white body, the dosage and product code "PGN 300" is indicated on the body with black ink, the inscription "Pfizer" is inscribed on the lid; the contents of the capsules are white or almost white powder.
1 caps.
pregabalin 300 mg
Excipients: lactose monohydrate - 33 mg, corn starch - 33.5 mg, talcum - 33.5 mg.
The composition of the capsule body: titanium dioxide - 2.4423%, gelatin - up to 100%.
The composition of the capsule cap: iron oxide red oxide - 0.7361%, titanium dioxide - 0.409%, gelatin - up to 100%.
Ink composition: shellac - 24-27%, ethanol 23-26%, isopropanol 0.5-3%, butanol 0.5-3%, propylene glycol 3-7%, concentrated ammonium solution 1-2%, potassium hydroxide - 0.05-0.1%, purified water - 15-18%, ferric oxide black oxide - 24-28%.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
* in the original manufacturer's certificates, these colors are described as: "from reddish-brown to dark-reddish-brown" - "orange", from light reddish brown to reddish brown "-" light orange ", which corresponds to the color of pontoons Comparison used in the European Union in carrying out this type of analysis.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
An antiepileptic drug whose active substance is an analogue of gamma-aminobutyric (gamma-aminobutyric acid) (GABA).
It was established that pregabalin binds to the additional subunit (? 2- delta-protein) of the potential-dependent calcium channels in the CNS, irreversibly replacing [3H] -gabapentin. It is suggested that such binding can contribute to the manifestation of its 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 / day and up to 8 weeks 3 times / day, in general, the risk of side effects and the effectiveness of the drug when applied 2 or 3 times / 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.
A 50% reduction in pain index was noted in 35% of patients treated with pregabalin and 18% in patients taking placebo. Among patients who did not experience drowsiness, the effect of this pain reduction was noted in 33% of patients in the pregabalin group and 18% in the placebo group. 48% of patients taking pregabalin and 16% of patients receiving placebo had drowsiness.
Fibromyalgia
The 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 mg and 600 mg per day is comparable, but the tolerability of the dose of 600 mg / 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 in a dose of 600 mg / day led to a more pronounced improvement in sleep, compared with a dose of 300-450 mg / day.
Epilepsy
When using the drug for 12 weeks 2 or 3 times / day, the noted risk of side effects and the effectiveness of the drug at these dosing regimes 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 the drug was used for 8 weeks, 52% of patients receiving pregabalin and 38% of patients receiving placebo had a 50% reduction in the Hamilton anxiety symptom score (NAM-A).
PHARMACOKINETICS
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.
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 after ingestion on an empty stomach. C max in plasma is achieved after 1 hour as with a single or repeated application. Bioavailability of pregabalinum at intake makes? 90% and does not depend on the dose. With repeated use, the equilibrium state is reached after 24-48 hours. When the drug is administered after meals, Cmax decreases by about 25-30%, and the time to reach Cmax increases to about 2.5 hours. However, eating does not have a clinically significant effect on total absorption pregabalin.
Distribution
The apparent V d of pregabalin after oral administration is approximately 0.56 l / kg. The drug does not bind to plasma proteins.
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. The proportion of the N-methylated derivative of pregabalin, which is the main metabolite found in the urine, was 0.9% of the dose. There were no signs of racemization of the S-enantiomer of pregabalin into the R-enantiomer.
Excretion
Pregabalin is excreted mainly by the kidneys in unchanged form. The mean T 1/2 is 6.3 h. The clearance of pregabalin from the plasma and the kidney clearance are directly proportional to the CK.
Pharmacokinetics in special clinical cases
The sex of the patient does not have a clinically significant effect on the concentration of pregabalin in plasma.
If the kidney function is disturbed, it should be borne in mind that pregabalin clearance is directly proportional to QC. Due to the fact that the drug is mainly excreted by the kidneys, it is recommended that the dose of pregabalin be reduced if the renal function is impaired. In addition, pregabalin is effectively removed from the plasma during hemodialysis (after a 4-hour hemodialysis session, pregabalin plasma concentrations are reduced by approximately 50%), after hemodialysis, an additional dose of the drug should be prescribed.
The pharmacokinetics of pregabalin in patients with impaired liver function has not been specifically studied. Pregabalinum is practically not exposed to a metabolism and deduced basically in the unchanged kind with urine, therefore infringement of function of a liver should not essentially change concentration of a preparation in a plasma.
When prescribing the drug, patients older than 65 years should take into account that the clearance of pregabalin with age tends to decrease, which reflects the age-related decrease in QC. Older patients with impaired renal function may need to reduce the dose of the drug.
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.
DOSING MODE
The drug is taken orally regardless of food intake in a daily dose of 150 to 600 mg in 2 or 3 divided doses.
With neuropathic pain, treatment starts with a dose of 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.
With epilepsy, treatment starts with a dose of 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.
With fibromyalgia, treatment starts with a dose of 75 mg 2 times / 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.
With a generalized anxiety disorder, treatment starts with a dose of 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.
Abolition of LYRICA В® : if treatment should be stopped, it is recommended to do this gradually for at least 1 week.
For patients with impaired renal function, the dose is selected individually, taking into account KK (table), which is calculated by the following formula:
For men :
CK (ml / min) = (body weight in kg) x (140 - age in years) / 72 x serum creatinine (mg / dl)
For women :
CK (ml / min) = value of the CK for men x 0.85
In patients on hemodialysis, the daily dose of pregabalin is selected taking into account the function of the kidneys. Immediately after each 4-hour hemodialysis session, an additional dose is prescribed (table).
Selection of a dose of pregabalin with account of kidney function.
KK (ml / min) Daily dose of pregabalin Multiplicity of admission per day
Starting dose (mg / day) 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
Additional dose after dialysis
25 mg 100 mg Once
In patients with impaired liver function, dose adjustment is not required.
Patients older than 65 years 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 EFFECT
According to the experience of clinical use of pregabalin in more than 12 000 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 due to 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 led to the withdrawal of the drug: ataxia, confusion, asthenia, attention disturbance, blurred vision, impaired coordination, peripheral edema.
The listed adverse reactions in frequency exceeded that in the placebo group (observed in more than 1 person) and could be associated with the underlying disease and / or concomitant therapy. Determination of the frequency of adverse reactions: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (<1/1000).
Infections and infestations:
infrequently nasopharyngitis
On the part of the hematopoiesis system:
rarely neutropenia
From the side of metabolism:
often increased appetite, weight gain
infrequently anorexia, hypoglycemia
rarely weight loss
From the side of the psyche:
often euphoria, confusion, decreased libido, irritability, insomnia, disorientation
infrequent depersonalization, anorgasmia, anxiety, depression, agitation, mood lability, depressed mood, difficulty in word selection, hallucinations, unusual dreams, increased libido, panic attacks, apathy, increased insomnia
rarely disinhibition, high spirits
From the nervous system:
very often dizziness, drowsiness
often ataxia, impaired attention, impaired coordination, memory impairment, tremor, dysarthria, paresthesia, imbalance, amnesia, sedation, lethargy
infrequently cognitive disorders, hypoesthesia, nystagmus, speech disorders, myoclonic cramps, weakened reflexes, dyskinesia, psychomotor agitation, postural dizziness, hyperesthesia, loss of taste sensations, burning sensation on mucous membranes and skin, intentional tremor, stupor, fainting
rarely hypokinesia, parosmia, dysgraphia
From the side of the organ of vision:
often blurred vision, diplopia
infrequent narrowing of the visual fields, reduced visual acuity, eye pain, asthenopia, dry eyes, puffiness of the eyes, increased lacrimation
rarely flashing sparks before the eyes, eye irritation, mydriasis, oscilloscopy (subjective sensation of fluctuations in the subjects under consideration), impaired perception of the depth of vision, loss of peripheral vision, strabismus, increased brightness of visual perception
From the organ of hearing and the vestibular apparatus:
often dizzy
infrequently hyperacusis
From the cardiovascular system:
infrequently tachycardia, AV-blockade of I degree, hot flashes, lowering of blood pressure, cold extremities, increased blood pressure
rarely sinus tachycardia, sinus arrhythmia, sinus bradycardia
From the respiratory system:
infrequently shortness of breath, cough, dryness of the nasal mucosa
rarely stuffy nose, nosebleed, rhinitis, snoring, feeling tight in the throat
From the digestive system:
often dry mouth, constipation, vomiting, flatulence, bloating
infrequently increased salivation, gastroesophageal reflux, hypoesthesia of the oral mucosa
rarely ascites, dysphagia, pancreatitis
Dermatological reactions:
infrequent skin hyperemia, sweating, papular rash
rarely cold sweat, hives
From the musculoskeletal system:
infrequent muscle twitches, swelling of the joints, muscle spasms, myalgia, arthralgia, back pain, pain in the limbs, stiffness in the muscles
rarely spasm of the neck muscles, neck pain, rhabdomyolysis
From the urinary system:
infrequent dysuria, incontinence
rarely oliguria, renal insufficiency
On the part of the reproductive system:
often erectile dysfunction
infrequently delayed ejaculation, sexual dysfunction
rarely amenorrhea, pain in the mammary glands, discharge from the mammary glands, dysmenorrhea, enlargement of mammary glands in the volume
From the laboratory indicators:
infrequently increased activity of ALT, AST, CKK, decrease in the number of platelets
rarely an increase in glucose and creatinine in the blood, a decrease in the level of potassium in the blood, a decrease in the number of leukocytes in the blood
Other:
often fatigue, peripheral edema, feeling of intoxication, gait disturbance
infrequent asthenia, falls, thirst, a feeling of restraint in the chest, generalized edema, chills, pain
rarely hyperthermia
Side effects noted during post-marketing surveillance (frequency unknown):
From the nervous system: headache, loss of consciousness, cognitive impairment, convulsions.
From the digestive system: rarely - swelling of the tongue, nausea, diarrhea.
From the side of the organ of vision: keratitis, loss of vision.
Dermatological reactions: rarely - skin itching, Stevens-Johnson syndrome.
Allergic reactions: rarely - angioneurotic reactions (including facial edema), hypersensitivity.
From the side of the cardiovascular system: chronic heart failure, prolongation of the QT interval.
From the urinary system: urinary retention.
From the respiratory system: pulmonary edema.
On the part of the reproductive system: gynecomastia.
Other: increased fatigue.
CONTRAINDICATIONS
- children and adolescents under 17 years of age (no application data);
- rare hereditary diseases, incl. intolerance to galactose, lactase deficiency and impaired absorption of glucose / galactose;
- Hypersensitivity to the components of the drug.
With caution should prescribe the drug for kidney failure, with heart failure. In connection with the registered isolated cases of uncontrolled use of pregabalin, it should be used with caution in patients with a history of drug dependence (such patients require close medical supervision during treatment with).
PREGNANCY AND LACTATION
There are no adequate data on the use of pregabalin in pregnancy is not.
In experimental studies on animals the drug has toxic effects on reproductive function.
In connection with this drug Lyric В® can be prescribed during pregnancy only if the expected benefit to the mother clearly outweighs the potential risk to the fetus.
In applying the drug Lyric В® women of childbearing age should use adequate contraception methods.
Information about the excretion of pregabalin with the breast milk of women there. However, experimental studiesIt found that it is excreted in breast milk in rats.Therefore, during treatment with Lyric В® breastfeeding should stop.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution should prescribe the drug for kidney failure. Patients with impaired renal function dose picked individually, taking into account the spacecraft.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In patients with impaired hepatic function dose adjustment is required.
APPLICATION FOR CHILDREN
Contraindications: childhood and adolescence to 17 years inclusive (no data on the use).
APPLICATION IN ELDERLY PATIENTS
Elderly patients (over 65 years) may require dose reduction of pregabalin due to declining renal function.
SPECIAL INSTRUCTIONS
In some patients with diabetes mellitus in the case of increase in body weight during treatment with pregabalin may require correction doses hypoglycemic agents.
Pregabalin is necessary to cancel in the case of angioedema symptoms (such as swelling of the face, perioral edema or swelling of the upper airway tissue).
Antiepileptic drugs, including pregabalin, may increase the risk of suicidal thoughts or behavior. Therefore, patients receiving these drugs should be closely monitored for the emergence or worsening of depression, the emergence of suicidal thoughts or behavior.
Pregabalin treatment was accompanied by dizziness and drowsiness, which increase the risk of accidental injury (fall) in the elderly. During post-marketing use of the drug were also reported cases of loss of consciousness, confusion and impaired cognitive function. Therefore, as long as patients do not appreciate the possible effects of the drug, they should 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. There have been reports of seizures development, including status epilepticus and small seizures during treatment with pregabalin or immediately after the end of therapy.
When during treatment pregabalin undesirable reactions such as blurred vision, or other violations of the organ of vision, removal of the drug can lead to the disappearance of the symptoms.
There were also cases of renal failure, in some cases after discontinuation of pregabalin kidney function was restored.
As a result of the abolition of pregabalin after a long or short-term treatment were observed following adverse effects: insomnia, headache, nausea, diarrhea, flu-like symptoms, depression, sweating, dizziness, convulsions and anxiety. Information about the frequency and severity of the syndrome manifestations cancellation pregabalin, depending on the duration of treatment and the last dose is not available.
There is no evidence that pregabalin is active against the receptors associated with the development of drug abuse patients. During post-marketing studies have been cases of abuse of pregabalin. As with any drug that affects the central nervous system, it is necessary to carefully assess the patient's medical history for existing cases of abuse of drugs, as well as to observe the patient in connection with the possibility of pregabalin abuse.
There are reported cases of dependence in the application of pregabalin. Patients with a history of drug dependence need careful medical supervision for symptoms depending on pregabalin.
During post-marketing use of drugs has been reported about the development of congestive heart failure during therapy with pregabalin, some patients. These reactions are mostly seen in elderly patients suffering from impaired function of the heart and receiving the drug over neuropathy. Therefore, pregabalin in these patients should be used with caution. After the cancellation of pregabalin may disappearance manifestations such reactions.
The incidence of adverse events associated with the central nervous system, especially such as drowsiness, increased in the treatment of central neuropathic pain due to spinal cord lesions which, however, may be the result of summation of the effects of pregabalin and other parallel receiving means (e.g., antispastic). This fact should be taken into account in the appointment of pregabalin for this indication.
Cases of encephalopathy, particularly in patients with underlying medical conditions that may lead to the development of encephalopathy.
Use in Pediatrics
The safety and effectiveness of pregabalin in children under the age of 12 years and adolescents under the age of 17 years have not been established, so the drug should not be administered in these patients.
Impact on the ability to drive vehicles and manage mechanisms
Pregabalin may cause dizziness and somnolence and therefore affect the ability to drive vehicles and use of sophisticated technology. Patients should not drive vehicles, using sophisticated technology, or to perform other potentially hazardous activities until it becomes clear whether the effect of this drug on the performance of such tasks.
OVERDOSE
Symptoms: an overdose of the drug (15 g) any of the above-described no adverse reactions were not registered. During post-marketing use of the most commonly observed affective disorders, drowsiness, confusion, depression, agitation and anxiety.
Treatment: conduct gastric lavage, supportive therapy, and if necessary - hemodialysis.
DRUG INTERACTION
Pregabalin is excreted in the urine largely as unchanged, undergoes minimal metabolism in man (as a metabolite in the urine output of less than 2% of the dose) did not inhibit metabolism of other in vitro drug substances not bound to plasma proteins, therefore it is unlikely to enter into pharmacokinetic interactions.
No indication of clinically significant pharmacokinetic interactions with pregabalin, phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone and ethanol. It was found that oral hypoglycemic agents, diuretics, insulin, phenobarbital, tiagabine and topiramate does not have a clinically significant effect on pregabalin clearance.
When the use of oral contraceptives containing norethisterone and / or ethinyl, simultaneously with pregabalin equilibrium pharmacokinetics of both drugs remained unchanged.
Reported cases of respiratory failure and coma, while the use of pregabalin with other drugs depressing the central nervous system.
Also it reported negative effect of pregabalin on gastrointestinal activity (including the development of ileus, paralytic ileus, constipation), while the use of drugs causing constipation (such as non-narcotic analgesics).
Repeated oral administration of pregabalin with oxycodone, lorazepam or ethanol had no clinically significant effect on respiration. Pregabalin, apparently, enhances cognitive impairment and motor function caused by oxycodone. Pregabalin can enhance the effects of ethanol and lorazepam.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be kept out of the reach of children, dry place at a temperature not higher than 25 В° C. Shelf life - 3 years.
