Expiration date: 12/2025
Therapeutic: antiepileptics
The drug forms
Capsules 200 mg: solid, gelatinous, the size ?1, Coni-Snap, with a dark brown cap and yellow body, containing white or almost white crystalline powder.
pharmachologic effect
Mode of action - an anticonvulsant, analgesic.
pharmacodynamics
Active ingredient: pregabalin - analogue ?-aminobutyric acid (5) -3- (aminomethyl) -5-methylhexanoic acid).
Mechanism of action
It is established that is associated with additional pregabalin subunit (?2-delta protein) of voltage-gated calcium channels in the CNS of irreversibly displacing (3H) gabapentin. It is assumed that this binding can promote their analgesic and anticonvulsant effects of pregabalin.
neuropathic pain
Pregabalin is effective in patients with diabetic neuropathy and postherpetic neuralgia.
It is found that when taking pregabalin rates up to 13 weeks to 2 times a day to 8 weeks and 3 times per day, the risk of side effects and efficacy when 2 or 3 times a day the same.
When you receive a rate of up to 13 weeks reduced pain during the 1st week, and the effect persisted throughout the course of therapy.
In 35% of patients during treatment with pregabalin and 18% of patients treated with placebo, there was a decrease of the index of pain by 50%. Among patients treated with pregabalin and not marked drowsiness, decrease in the index of pain by 50% was noted in 33% of cases among patients treated with placebo, the rate was 18%. Drowsiness was observed in 48% of patients treated with pregabalin and 16% of patients receiving placebo.
Fibromyalgia
Marked reduction in pain symptoms of fibromyalgia was observed in patients treated with pregabalin at a dose of 300-600 mg / day. The effectiveness of doses of 450 and 600 mg / day was similar, but the dose of 600 mg / day is usually less tolerated.
In addition, during treatment with pregabalin showed improvement in functional activity of patients, as well as reducing the severity of sleep disorders. Use of pregabalin in the dosage of 600 mg / day resulted in a more pronounced improvement of sleep when compared with a dose of 300-450 mg / day.
Epilepsy
When receiving the drug for 12 weeks 2 or 3 times a day, the risk of undesired reactions and efficacy at these same dosing regimens. Reducing the frequency of seizures has been celebrated during the 1st week of treatment.
Generalized anxiety disorder
Reducing the symptoms of generalized anxiety disorder is celebrated on the 1st week of treatment. After 8 weeks of treatment, 50% reduction in symptoms on the Hamilton Anxiety Scale (HAM-A) was observed in 52% of patients treated with pregabalin and 38% of patients receiving placebo.
Pharmacokinetics
In healthy volunteers, patients with epilepsy receiving antiepileptic therapy, and in patients treated with pregabalin for the relief of chronic pain syndromes, observed similar rates of pregabalin pharmacokinetics at steady state.
Suction
Pregabalin is rapidly absorbed after oral administration on an empty stomach. Plasma Tmax - 1 h, both single and repeated administration. Bioavailability of pregabalin ingestion of> 90% ,, and is independent of dose. With repeated use Cssdostigaetsya 24-48 hours. Food intake reduces Cmax by approximately 25-30%, and Tmaxuvelichivaetsya approximately 2.5 hours. However, the food intake has no clinically significant effect on the total absorption of pregabalin.
Distribution
after receiving pregabalin Visible inside Vd is about 0.56 l / kg. Pregabalin is not bound to plasma proteins.
Metabolism
Pregabalin hardly metabolized. Upon receiving pregabalin labeled about 98% of the radiolabel was determined in the urine in unchanged form. Percentage of N-methylated derivative of pregabalin, which is the major metabolite found in urine was 0.9% of the dose. No signs of marked racemization S-enantiomer of pregabalin in the R-enantiomer.
breeding
Pregabalin is derived mainly kidneys unchanged. The average T1 / 2 is 6.3 hours. Pregabalin clearance from plasma and renal clearance are directly proportional to creatinine clearance (see. Impaired Renal Function). Patients with impaired renal function, and dose adjustment is required in hemodialysis (see. "Dosage and administration" table).
Linearity / non-linearity
Pharmacokinetics of pregabalin when used in a range of recommended daily dose is linear, interindividual variability is low (less than 20%). The pharmacokinetics of pregabalin with repeated use can be predicted on the basis of a single dose. Therefore, the need for regular monitoring of pregabalin plasma concentration absent.
Special patient groups
Impaired renal function. Pregabalin clearance is directly proportional to creatinine clearance. Given that pregabalin is mainly excreted by the kidneys, patients with impaired renal function is recommended to reduce the dose of pregabalin. Furthermore, pregabalin is effectively removed from plasma by hemodialysis (after 4-hour hemodialysis concentration pregabalin plasma decreases by about 50%), after dialysis to assign additional dose (cm. "Dosage and Administration" table).
Abnormal liver function. Specific pharmacokinetic studies in patients with hepatic impairment have not been conducted. Since pregabalin is practically not metabolized and excreted mainly kidneys unchanged, impaired liver function should not significantly affect the concentration of pregabalin in blood plasma.
Elderly patients (over 65 years). Pregabalin clearance with age tends to decrease, reflecting the age-related decline in creatinine clearance. Older patients with impaired renal function may require a reduction in dose (see. "Dosing and administration" table).
Sex patient has no clinically significant impact on the concentration in the blood plasma of pregabalin.
Indications of the drug Pregabalin
- neuropathic pain,
- epilepsy (as adjunctive therapy in patients with partial seizures, accompanied or not by secondary generalization)
- generalized anxiety disorder,
- fibromyalgia.
Contraindications
Hypersensitivity to the active substance or to any other component of the drug,
rare hereditary diseases, including galactose intolerance, lactase deficiency or glucose-galactose malabsorption,
childhood and adolescence to 17 years inclusive (due to lack of data).
Precautions: renal (. See "Dosage and administration") and heart failure (see "Side Effects."), In patients with a history of drug addiction. These patients require close medical supervision during treatment with the drug.
Pregnancy and breast-feeding
Data on the use of pregabalin in pregnant women is not enough.
In studies using animal signs of reproductive toxicity of the drug have been reported. Therefore, pregabalin can be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. In applying the drug women of childbearing age should use adequate contraception methods.
Data on the penetration of pregabalin in the breast milk of women do not have, but noted that in lactating rats, it is excreted in the milk. In this regard, pregabalin breast-feeding is not recommended during treatment.
Side effects
According to the experience of the clinical use of the drug in more than 12,000 patients, the most common adverse events were dizziness and somnolence. Generally, adverse events were mild or moderate. Frequency cancellation pregabalin and placebo due to adverse events was 14 and 7% respectively. The main adverse events demanding the cessation of treatment were dizziness (4%), and somnolence (3%), depending on their individual tolerance. Other side effects that lead to drug discontinuation were ataxia, confusion, fatigue, impaired attention, blurred vision, incoordination, peripheral edema.
Adverse events were classified by system-organ class and frequency: very common - ?1 / 10, often - ?1 / 100, <1 ,, 10 = "" 1 = "" 1000 = "" 100 = "" p = "" > ,,
These adverse events may be related to underlying disease and / or concomitant therapy.
Infections and infestations: Infrequent - nasopharyngitis.
From the blood and lymphatic system: rarely - neutropenia.
Eating disorders and metabolism: often - increased appetite, rarely - anorexia, hypoglycemia.
Psychiatric disorders: often - euphoria, confusion, decreased libido, insomnia, irritability, disorientation, infrequently - depersonalization, anorgasmia, restlessness, depression, agitation, mood lability, depressed mood, difficulty finding words, hallucinations, abnormal dreams, libido increased, panic attacks, apathy, increased insomnia, rarely - disinhibition, elation.
From the nervous system: very often - dizziness, drowsiness, often - ataxia, impaired attention, impaired coordination, memory impairment, tremor, dysarthria, paresthesia, impaired balance, amnesia, sedation, lethargy, infrequently - cognitive disorders, hypoesthesia, nystagmus, disturbance speech, myoclonic seizures, hyporeflexia, dyskinesia, psychomotor agitation, postural dizziness, hypersensitivity, loss of taste, burning sensation in the mucous membranes and skin, intention tremor, stupor, syncope, rarely - hypokinesia, parosmiya, dysgraphia, the frequency is unknown - headache, loss of consciousness, cognitive disorders, seizures.
From a sight organ: often - blurred vision, diplopia, rarely - visual field loss, blurred vision, eye pain, asthenopia, dry eyes, swelling of the eye, excessive tearing, rarely - flickering sparks before the eyes, eye irritation, mydriasis, oscillopsia (subjective feeling vibrations considered subjects), impaired perception of visual depth, loss of peripheral vision, strabismus, increasing the brightness of visual perception, the frequency is unknown - keratitis, vision loss.
On the part of the organ of hearing and the labyrinth: often - vertigo, rarely - hyperacusis.
From the CCC: rarely - tachycardia, AV block I degree, hot flashes, decrease in blood pressure, cold extremities, increased blood pressure, flushing of the skin, rarely - sinus tachycardia, sinus arrhythmia, sinus bradycardia, the frequency is unknown - Chronic heart failure, prolongation of the interval QT.
The respiratory system, organs, thoracic and mediastinal disorders: rarely - shortness of breath, cough, dry nasal mucosa, rarely - nasal congestion, nosebleeds, rhinitis, snoring, feeling of tightness in the throat, the frequency is unknown - pulmonary edema.
From the digestive system: often - dry mouth, constipation, vomiting, flatulence, abdominal distension, not often - increased salivation, gastroesophageal reflux disease, hypoesthesia oral mucosa, rarely - ascites, dysphagia, pancreatitis, frequency is unknown - swelling of the tongue, nausea, diarrhea.
Skin and subcutaneous tissue: rare - sweating, papular rash, rarely - a cold sweat, urticaria, frequency is unknown - facial swelling, pruritus, Stevens-Johnson syndrome.
On the part of the musculoskeletal system and connective tissue disorders: rarely - muscle twitching, joint swelling, muscle cramps, myalgia, arthralgia, back pain, pain in limbs, muscle stiffness, rarely - a spasm of the neck muscles, neck pain, rhabdomyolysis.
On the part of the kidney and urinary tract: rarely - dysuria, urinary incontinence, rarely - oliguria, renal failure, the frequency is unknown - urinary retention.
On the part of the immune system: the frequency is unknown - angioneurotic edema, allergic reactions, hypersensitivity.
Reproductive system and breast: often - erectile dysfunction, rarely - delayed ejaculation, sexual dysfunction, rarely - amenorrhea, pain in the breasts, discharge from the breast, dysmenorrhea, breast enlargement in volume, frequency is unknown - gynecomastia.
Other: often - fatigue, edema (including peripheral), feeling of intoxication, gait disturbance, weight gain, rarely - fatigue, fall, thirst, chest tightness, generalized edema, chills, pain, abnormal sensation, rarely - pyrexia, weight loss.
Effect on results of laboratory tests: rarely - increase of alanine aminotransferase activity, CK, aspartate aminotransferase, decreased platelet count, rarely - increased concentrations of glucose and creatinine, decreased potassium content, the number of leukocytes in the blood.
Interaction
Since pregabalin is mainly excreted by the kidneys in an unmodified form, undergoes minimal metabolism in humans (in the form of metabolites kidneys displayed less than 2% of the dose), does not inhibit the metabolism of other in vitro drug and does not bind to plasma proteins, it is unlikely to join the pharmacokinetic interaction.
No evidence of a clinically significant pharmacokinetic interaction of pregabalin with 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.
The use of oral contraceptives containing norethisterone and / or ethinyl, simultaneously with pregabalin equilibrium has no effect on the pharmacokinetics of drugs.
In patients treated with pregabalin and drugs that suppress the central nervous system, there have been cases of respiratory failure and coma.
Reported cases of negative influence of pregabalin on gastrointestinal function (including the development of intestinal obstruction, paralytic ileus, constipation), while the use of drugs that cause constipation (such as opioids).
Repeated use of pregabalin inside with oxycodone, lorazepam, or ethanol did not have a clinically significant effect on respiration. It is assumed that pregabalin increases the violations of cognitive and motor function caused by oxycodone. Pregabalin can enhance the effects of ethanol and lorazepam.
Dosing and Administration
Inside, regardless of meals. At a dose of 150 to 600 mg / day in 2 or 3 divided doses.
neuropathic pain
The initial dose of pregabalin is 150 mg / day. Depending on tolerability and the effect achieved through 3-7 days the dose can be increased to 300 mg / day, and if necessary, even after 7 days - up to a maximum dose of 600 mg / day.
Epilepsy
The initial dose of pregabalin is 150 mg / day. Taking into account the achieved effect and tolerability after 1 week the dose may be increased to 300 mg / day, and a week later - up to a maximum dose of 600 mg / day.
Fibromyalgia
The initial dose of pregabalin 75 mg twice a day (150 mg / day). Depending on tolerability and the effect achieved through 3-7 days the dose can be increased to 300 mg / day. If there is no positive effect dose increased to 450 mg / day, and if necessary, even after 7 days - up to a maximum dose of 600 mg / day.
Generalized anxiety disorder
The initial dose of pregabalin is 150 mg / day. Depending on tolerability and the effect attained after 7 days, the dose can be increased to 300 mg / day. If there is no positive effect dose increased to 450 mg / day, and if necessary, even after 7 days - up to a maximum dose of 600 mg / day.
Cancel pregabalin
If pregabalin treatment should be discontinued, it is recommended to do so gradually over a minimum of 1 week.
Patients with impaired renal function
Dose picked individually for creatinine clearance (see table.), Which is calculated by the following formula:
Cl creatinine (ml / min) = (140-age in years) × body weight (kg) / 72 × serum creatinine (mg / dl) (× 0.85 for women)
Patients undergoing hemodialysis, the pregabalin daily dose is chosen based on renal function. Immediately following each 4-hour hemodialysis administered an additional dose (see. Table).
Table
| Cl creatinine, ml / min | The daily dose of pregabalin | Multiplicity reception per day | |
| The initial dose, mg / day | The maximum dose in mg / day | ||
| ?60 | 150 | 600 | 2–3 |
| ?30–<,,60 td="">,, | 75 | 300 | 2–3 |
| ?15–<,,30 td="">,, | 25–50 | 150 | 1–2 |
| <,,15 td="">,, | 25 | 75 | 1 |
Additional dose after hemodialysis mg | |||
| — | 25 | 100 | once |
