Pregabalin

When ATH: N03AX16

Pharmacological action

Antiepileptics; subunit binds to more (a2-delta protein) voltage-dependent Ca2 -channels in the central nervous system, which contributes to the manifestation of analgesic and anticonvulsant action. Reducing the frequency of seizures started in the first week.

Pharmacokinetics

Absorption of fasting – fast, decreases in food intake. Bioavailability – about 90%, not dose. TCMax – 1 no (the single and repeated administration). TCSS (with repeated use) – 24-48 no. Food intake reduces Cmax by 25-30%, and increases to TCmax 2.5 no. The volume of distribution – 0.56 l / kg. The pharmacokinetics in the range of the recommended daily dose is linear; interindividual variability less 20%; with repeated use pharmacokinetics predictable on the basis of a single dose of. It binds to plasma proteins, hardly metabolized (the major metabolite – N-methylated derivative of pregabalin). There was no sign of racemization S-enantiomer of pregabalin the R-enantiomer. The plasma and renal clearance are directly proportional to creatinine clearance. After a 4-hour hemodialysis drug concentration in the plasma is reduced by 50%. The clearance of the drug in patients over 65 declining years, reflecting the age-related decline in creatinine clearance. T1/2 – 6.3 no. Excreted by the kidneys in unchanged form (98%) and an N-methylated derivative of pregabalin (0.9%).

Testimony

Neuropathic pain, epilepsy (in polytherapy), generalized anxiety disorder, fibromyalgia.

Contraindications

Hypersensitivity, childhood (to 17 years), lactation; dosage forms, containing lactose – galactose intolerance, lactase deficiency Lapa, malabsorption of glucose / galactose.

C care

Renal failure, diabetes, pregnancy.

Dosage regimen

Inside, regardless of the meal, daily dose – 150-600 mg, razdelennaya of 2-3 admission. Neuropathic pain: the initial dose – 150 mg / day; depending on the achieved effect and tolerability through 3-7 days to increase the dose 300 mg / day, if necessary, even through 7 days – up to a maximum dose of 600 mg / day. In epilepsy: the initial dose – 150 mg / day; depending on the achieved effect and tolerability through 7 days to increase the dose 300 mg / day, through 7 days – up to a maximum dose of 600 mg / day. In renal insufficiency, the daily dose is chosen based on creatinine clearance: creatinine clearance 60 ml / min or more initial dose – 150 mg / day, maximum – 600 mg / day, the multiplicity of reception – 2-3 times; creatinine clearance 30-60 ml / min, initial dose – 75 mg / day, maximum – 300 mg / day, the multiplicity of reception 2-3 times; creatinine clearance 15-30 ml / min, initial dose – 25-50 mg / day, maximum – 150 mg / day, the multiplicity of reception 1-2 times; creatinine clearance less than 15 ml / min, initial dose - 25 mg / day, the maximum dose – 75 mg / day, the multiplicity of reception – 1 time. With hemodialysis, after each 4-hour session, assign additional starting dose – 25 mg / day, maximally – 100 mg / day one. Patients over 65 s may require dose reduction due to the decrease in renal function. Treatment stopped gradually for at least 1 of the week. When fibromyalgia daily dose is 300 to 600 mg.

Side effects

Frequency: very frequent (more 1/10), frequent (more 1/100 less 1/10), infrequent (more 1/1 000 less 1/100), few (less 1/1000).

From the nervous system: very frequent – dizziness, drowsiness; frequent – ataxia, impaired concentration, coordination, memory impairment, tremor, dysarthria, paraesthesia, euphoria, confusion, decreased libido, irritability; infrequent – cognitive abnormality, gipesteziya, violation of the visual fields, nistagmo, dysarthria, 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, depersonalization, anorgazmija, anxiety, depression, ažitaciâ, mood lability, strengthening of insomnia, dejection, difficulties in finding words, hallucinations, unusual dreams, increased libido, panic attacks, apathy; rarely – gipokinez, parosmija, chirospasm, disinhibition, high spirits.

From the senses: frequent - blurred vision, diplopia; infrequent – reduced visual acuity, sore eyes, asthenopia, dryness of mucous membranes of the eyes, eye puffiness, increased lacrimation; few – 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, hyperacusis.

Cardio-vascular system: infrequent – tachycardia, "Tides"; few – AV blockade of the 1st century., sinus tachycardia, sinus arrhythmia, sinusovaya bradycardia, decrease or increase in blood pressure, cold extremities.

The respiratory system: infrequent – breathlessness, dryness of the nasal mucosa; few – nazofaringit, cough, nasal congestion, nose bleed, rhinitis, snoring, a sense of "tightness" in the throat.

From the digestive system: frequent – dry mouth, increased appetite, vomiting, constipation, flatulence; infrequent – hyperptyalism, hastroэzofahealnыy reflux, desensitization in the oral cavity, anorexia; few – ascites, dysphagia, pancreatitis.

From the side of hematopoiesis: few – neutropenia.

With the genitourinary system: frequent – erectile dysfunction; infrequent – dizurija, urinary incontinence, delayed ejaculation, sexual dysfunction; few – oligurija, renal failure, menorrhea, breast pain, discharge from the breast, dysmenorrhoea, hypertrophy breast.

On the part of the musculoskeletal system: infrequent – muscle twitching, swelling of joints, constraint, muscle cramps, myalgia, arthralgia, backache, pain in the extremities; few – trachelism, neck pain, raʙdomioliz.

Other: frequent – fatiguability, peripheral and generalized edema, feeling "intoxicated", gait disturbance; infrequent – asthenia, thirst, chest tightness, increase or reduction of body weight, Sweating, papulleznaya rash; few – cold sweat, hives, increased pain when Anasarca, fever, chills.

Laboratory findings: infrequent – increased activity of alanine aminotransferase, aspartate aminotransferase, creatine, thrombocytopenia; few – giperglikemiâ, gipoglikemiâ, giperkreatininemiя, kaliopenia, leukopenia.

Side effects with postmarketing surveillance: the nervous system – headache. From the digestive system: rarely – swelling of the tongue, nausea. For the skin: rarely – swelling of the face.

Overdose

Treatment: gastric lavage, simptomaticheskaya therapy, hemodialysis.

Cautions

In diabetes (in the case of weight gain on a background of pregabalin) a correction dose hypoglycemic drugs. Treatment may be accompanied by dizziness, sleepiness, that increase the risk of injuries in the elderly. Information about the possible cancellation of others. anticonvulsant drugs and feasibility alone is not enough pregabalin. When pregnancy is used only in the event, if the expected benefit to the mother outweighs the risk to the fetus. During treatment, women of childbearing age should use reliable methods of contraception. During the period of treatment should refrain from driving vehicles and Occupation potentially hazardous activities, require high concentration and speed of psychomotor reactions.

Drug Interactions

There were no pharmacokinetic interaction with phenytoin, karʙamazepinom, valproic acid, lamotrigine, Gabapentin, lorazepam, oxycodone, ethanol. Oral hypoglycemic drugs, Diuretic, insulin, phenobarbital, tiagaʙin, Topiramate did not affect the clearance of pregabalin. When using oral contraceptives, containing norethisterone and / or ethinyl estradiol, simultaneously with pregabalin pharmacokinetics of both drugs remained unchanged. Reapply with oxycodone, lorazepam, ethanol has no clinically significant effect on respiration. Pregabalin, probably, enhances cognitive disorders and motor functions, caused by oxycodone. Pregabalin may potentiate the effects of ethanol and lorazepam.