Pregabalin

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Pregabalin: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Pregabalin

ATX code: N03AX16

Active ingredient: pregabalin (Pregabalin)

Manufacturer: GEROPHARM, LLC (Russia); Izvarino Pharma, LLC (Russia); Dongbang Futures Tech & Life Co. Ltd (Dongbang Future Tech & Life Co., Ltd.) (Korea)

Description and photo update: 19.10.2018

Pregabalin is a drug for systemic use that has anticonvulsant and analgesic effects.

Release form and composition

Dosage form of the drug - capsules: gelatinous, solid, filled with powder or compacted powder mass from almost white to white:

dosage 25 mg - capsules No. 4, the body is white or almost white with a yellowish tinge, the color of the cap is from green to dark green;
dosage 75 mg - capsules No. 4, the body is white or almost white with a yellowish tinge, the color of the cap is blue; body white, cap color from red-brown to dark red-brown;
dosage 100 mg - capsules No. 4, body and lid are white or almost white with a yellowish tinge;
dosage 150 mg - capsules No. 2, body and cap are white or almost white with a yellowish tinge;
dosage 300 mg - capsules No. 0, body and lid are white or almost white with a yellowish tinge; the body is white, the color of the cap is from red-brown to dark red-brown.

Capsules (1)

Composition of Pregabalin:

active substance: pregabalin - 25, 75, 100, 150 or 300 mg;
auxiliary components: colloidal silicon dioxide, calcium carbonate, magnesium stearate, sodium lauryl sulfate, potato starch, talc;
capsule cap: titanium dioxide, gelatin, for a dosage of 25 mg - indigo carmine and an iron oxide yellow dye, for a dosage of 75 mg - indigo carmine;
capsule body: gelatin, titanium dioxide.

Packing: 10 pcs. in contoured cell packs, 30 or 60 pcs. in plastic jars or glass bottles; in a cardboard box 1 bottle / can or 1-6 packs of cell contour.

Capsules (2)

Composition of Pregabalin:

active substance: pregabalin - 75, 150 or 300 mg;
auxiliary components: corn starch, lactose monohydrate, talc;
capsule cap: gelatin; for a dosage of 75 mg and 300 mg - iron dye red dioxide E172; for a dosage of 150 mg - titanium dioxide;
capsule body: gelatin, titanium dioxide.

Packing: 14 pcs. in blister contour packages made of polyvinyl chloride film and aluminum foil; in a cardboard box 1, 2 or 4 packs, cell contour.

Pharmacological properties

Pharmacodynamics

The active ingredient of the drug is pregabalin, an analogue of γ-aminobutyric acid [(S) -3- (aminomethyl) -5-methylhexanoic acid].

It has been proven that pregabalin, irreversibly replacing [3H] -gabapentin, binds to α2-delta-protein, an additional subunit of voltage-gated calcium channels in the CNS (central nervous system). Perhaps this kind of binding contributes to the manifestation of the analgesic and anticonvulsant action of the drug.

The mechanism of action of pregabalin when used according to indications:

neuropathic pain: the effectiveness of therapy in patients with postherpetic neuralgia and diabetic neuropathy is noted; the effect of the drug and the risk of developing adverse reactions do not depend on the frequency of administration and the duration of the course, for example, taking Pregabalin 2 times a day for a course of up to 13 weeks and 3 times a day for up to 8 weeks, in general, are equally effective; during the course of treatment, lasting 13 weeks, during the first week, the pain decreased and this effect persisted until the end of the course; 35% of those receiving pregabalin and 18% of those taking placebo had a 50% decrease in pain index;
fibromyalgia: a pronounced decrease in pain symptoms associated with fibromyalgia is observed with the use of daily doses of pregabalin in the range of 300-600 mg; the clinical efficacy of daily doses of 450 and 600 mg is comparable, but at a dose of 600 mg, the drug is usually worse tolerated; the use of the drug also noticeably improves the functional activity of patients and reduces the severity of sleep disorders, while in a daily dose of 600 mg, the drug improves sleep more pronounced in comparison with a dose of 300-450 mg;
epilepsy: with a course of 12 weeks of therapy, the effect of the drug and the risk of developing adverse reactions do not depend on the frequency of administration (2 or 3 times a day), the frequency of seizures begins to decrease from the first week of administration;
generalized anxiety disorder: the manifestation of symptoms begins to decrease from the first week of therapy; use of the drug for 8 weeks reduced symptoms on the Hamilton Anxiety Scale (HAM-A) by 50% in 52% of patients receiving pregabalin and 38% of those receiving placebo.

Pharmacokinetics

The pharmacokinetic parameters of pregabalin in healthy volunteers, in patients receiving antiepileptic therapy with epilepsy, and in patients receiving it for the relief of chronic pain syndromes, in the equilibrium state were similar.

Characteristics:

absorption: on an empty stomach, pregabalin is absorbed quickly, Cmax (maximum plasma concentration) is achieved after 1 hour, both with a single dose and with repeated administration; the oral bioavailability of the substance does not depend on the dose and is ≥ 90%; in case of repeated use, the level of equilibrium plasma concentration is reached after 24–48 hours. Taking capsules after a meal reduces the Cmax value by 25–30%, and Tmax (time to reach maximum concentration) increases to 2.5 hours, while food intake does not have a clinically significant effect on the total absorption of the substance;
distribution: after oral administration of Pregabalin, its Vp (apparent volume of distribution) is approximately 0.56 l / kg, it does not bind to plasma proteins; studies on animals have shown that in rats, mice and monkeys, pregabalin penetrates the blood-brain barrier, in addition, in experiments with rats, its penetration into the placenta and during lactation into breast milk was revealed;
metabolism: pregabalin practically does not participate in metabolic processes, and up to 98% is determined unchanged in the urine. The main metabolite is an N-methylated derivative, found in urine in an amount of not more than 0.9% of the dose of the active substance; preclinical studies did not reveal signs of racemization of the S-enantiomer of pregabalin to the R-enantiomer;
Excretion: basically, the substance is excreted unchanged by the kidneys, with an average half-life of ~ 6.3 hours; plasma and renal clearance of pregabalin are in direct proportion, therefore, in case of impaired renal function and while on hemodialysis, dose adjustment is required.

In the range of recommended daily doses, the pharmacokinetics of pregabalin reveals a linear character, interindividual variability is insignificant, less than 20%. With repeated use of the drug, its pharmacokinetic characteristics can be calculated on the basis of data after taking a single dose, therefore, there is no need for regular monitoring of the concentration of the substance.

Indications for use

Pregabalin is recommended for use in adult patients of the following diseases:

neuropathic pain;
fibromyalgia;
generalized anxiety disorder;
epilepsy (if additional treatment is necessary for patients with partial seizures, with or without secondary generalization).

Contraindications

Absolute:

galactose intolerance, lactase deficiency, glucose / galactose malabsorption - for capsules (2) containing lactose;
children and adolescents up to 17 years old;
increased individual sensitivity to the active substance or other components of the drug.

Relative contraindications: Pregabalin is prescribed with caution in case of impaired renal function, heart failure, and in patients with a history of drug dependence.

Instructions for the use of Pregabalin: method and dosage

Pregabalin capsules are taken orally, regardless of the diet.

Recommended dosage: 150-600 mg per day, divided into 2-3 doses.

Indication therapy:

neuropathic pain: initial daily dose - 150 mg; after 3-7 days, depending on the tolerance of the drug and the achieved result, the daily dose can be increased to 300 mg, and after another 7 days, if necessary, to the maximum daily dose - 600 mg;
epilepsy: initial daily dose - 150 mg; after 7 days, depending on the tolerance of the drug and the result achieved, the daily dose can be increased to 300 mg, and after another 7 days, if necessary, to the maximum daily dose - 600 mg;
fibromyalgia: initial daily dose - 150 mg is taken 2 times a day, 75 mg; depending on the tolerance of the drug and the result achieved, the daily dose can be increased to 300 mg, taken 2 times a day, 150 mg; in the absence of a positive result, the daily dose is increased to 450 mg, taken 2 times a day at 225 mg, and after another 7 days, if necessary, to a maximum daily dose of 600 mg; the daily dose of 600 mg does not provide additional benefits, but is worse tolerated by patients;
generalized anxiety disorder: initial daily dose - 150 mg; after 7 days, depending on the tolerance of the drug and the result achieved, the daily dose can be increased to 300 mg, after another 7 days, if necessary, increased to 450 mg, and in the absence of a positive therapeutic effect, after 7 days, to the maximum daily - 600 mg.

In the course of treatment, it is necessary to regularly assess the appropriateness of its continuation. If it is necessary to discontinue therapy with Pregabalin, it is recommended to do so gradually, for at least 7 days.

In case of impaired renal function, the dose of Pregabalin is selected individually, taking into account the CC (creatinine clearance), calculated using a special formula: CC (ml / min) = [(140 - age in years) × body weight in kg] / 72 × serum creatinine (mg / dl) (for women × 0.85).

Selection of the pregabalin dose (mg / day) depending on the degree of renal failure:

CC ≥60: starting dose - 150; the maximum dose is 600; frequency of admission - 2-3 times;
CC ≥30, but <60: starting dose - 75; the maximum dose is 300; frequency of admission - 2-3 times;
CC ≥15, but <30: starting dose - 25-50; the maximum dose is 150; frequency of admission - 1-2 times;
CC <15: starting dose - 25; the maximum dose is 75; frequency of admission - 1 time;
additional dose after dialysis: starting dose - 25; the maximum dose is 100; frequency of admission - once.

Having missed the next dose, it must be taken as soon as possible, but not when it is already time for the next dose.

Side effects

The most common adverse reactions due to taking Pregabalin are dizziness and drowsiness, and are usually mild to moderate. Discontinuation of therapy, depending on the subjective tolerance of these effects, was required in 4% of patients with dizziness and in 3% with drowsiness. Other side effects requiring discontinuation of the drug are confusion, ataxia, asthenia, peripheral edema, blurred vision, impaired attention and coordination.

The frequency of occurrence of adverse reactions by system-organ classes, determined by the number of adverse reactions in the array of clinical observations, regardless of the assessment of the causal relationship (scale used: very often -> 0.1; often - ≥ 0.01, but <0, 1; infrequently - ≥0.001, but <0.01; rarely - <0.001):

infections and invasions: often - nasopharyngitis;
blood and lymphatic system: infrequently - neutropenia;
metabolic processes and nutrition: often - increased appetite; infrequently - hypoglycemia, anorexia;
mental disorders: often - confusion, euphoria, irritability, insomnia, depression, decreased libido, apathy, disorientation, panic attack; infrequently - anxiety, hallucinations, agitation, aggression, depressed / elated mood, mood swings, anxious dreams, depersonalization, difficulty finding words, anorgasmia, increased libido, increased insomnia; rarely - disinhibition;
neurological disorders: very often - drowsiness, dizziness, headache; often - memory impairment, amnesia, impaired coordination, ataxia, dysarthria, tremor, impaired attention, hypesthesia, paresthesia, imbalance, sedation, lethargy, ageusia; infrequently - fainting, psychomotor agitation, myoclonus, dyskinesia, intentional tremor, orthostatic dizziness, speech impairment, nystagmus, decreased reflexes, burning sensation on the mucous membranes and on the skin, hyperesthesia, cognitive impairment, loss of consciousness; rarely - pathological numbness, dysgraphia, hypokinesia, convulsions, parosmia;
organ of vision: often - diplopia, blurred vision; infrequently - visual impairment, visual field defect, loss of peripheral vision, eye swelling, eye pain, asthenopia, photopsia, increased tearing, dry eye syndrome, eye irritation; rarely - fluctuation of visible objects (oscillopsia), change in the depth of visual perception, keratitis, strabismus, mydriasis, increased brightness of visual perception, loss of vision;
organ of hearing and vestibular apparatus: often - vertigo; infrequently - hyperacusis;
cardiovascular system: infrequently - tachycardia, sinus bradycardia, atrioventricular block of the 1st degree, chronic heart failure; rarely - sinus arrhythmia, sinus tachycardia, prolongation of the QT interval;
vascular disorders: infrequently - hypertension, hypotension, flushing of the skin, hot flashes, cold extremities;
respiratory system: often - dryness of the nasal mucosa; infrequently - nosebleeds, shortness of breath, cough, rhinitis, nasal congestion, snoring; rarely - a feeling of tightness in the throat, pulmonary edema;
digestive system: often - vomiting, flatulence, constipation, bloating, nausea, dry mouth, diarrhea; infrequently - hypersecretion of the salivary glands, gastroesophageal reflux, decreased susceptibility of the oral mucosa; rarely - pancreatitis, ascites, tongue edema, dysphagia;
skin and subcutaneous tissues: infrequently - urticaria, papular rash, excessive sweating, pruritus, facial edema; rarely - Stevens-Johnson syndrome, cold sweat;
musculoskeletal system: often - muscle spasm in the cervical spine, arthralgia, muscle cramps, back pain, pain in the limbs; infrequently - myalgia, joint swelling, muscle cramps, muscle stiffness, neck pain; rarely - rhabdomyolysis;
urinary system: infrequently - dysuria, urinary incontinence; often - oliguria, renal failure, urinary retention;
reproductive system: often - erectile dysfunction, pain in the area of the mammary glands; infrequently - delayed ejaculation, sexual dysfunction, dysmenorrhea; rarely - amenorrhea, breast enlargement, discharge from the mammary glands, gynecomastia;
general disorders and disorders at the injection site: often - falls, gait disturbance, peripheral edema, drunkenness, feeling unwell, fatigue; infrequently - pain, generalized edema, fever, chest tightness, thirst, general weakness, chills, malaise;
data from laboratory and instrumental studies: often - an increase in body weight, an increase in the concentration of creatinine in the blood; infrequently - an increase in the activity of liver enzymes - KF (creatine phosphokinase), ALT (alanine aminotransferase), ACE (aspartate aminotransferase); changes in blood counts - an increase in glucose concentration, a decrease in the number of platelets and potassium; weight loss; rarely - a decrease in the number of leukocytes in the blood;
immune system: infrequently - hypersensitivity reactions; rarely - angioedema, allergic reactions.

Overdose

In case of an overdose of Pregabalin (up to 15 g), only the adverse reactions listed in the "Side effects" chapter were recorded. Most often during post-registration use were observed: drowsiness, depression, affective disorders, confusion, anxiety, agitation; in rare cases - coma.

Overdose treatment: gastric lavage, supportive therapy, if necessary - hemodialysis.

special instructions

Patients with diabetes mellitus with weight gain during therapy with pregabalin may require dose adjustment of hypoglycemic drugs.

With the development of symptoms of angioedema (edema of the face, edema of the tissues of the upper respiratory tract, perioral edema), the drug must be canceled.

Antiepileptic drugs, including Pregabalin, may increase the risk of suicidal thoughts or behavior. In this connection, patients receiving these drugs should be closely monitored for the occurrence or aggravation of depression, suicidal thoughts and suicidal behavior.

Concomitant use of pregabalin with opioids can cause constipation, especially in elderly patients, therefore it is recommended to take preventive measures to prevent them.

With the suppression of seizure activity, data on the advisability of monotherapy with pregabalin with the possibility of canceling other anticonvulsants are insufficient. Cases of the development of seizures, including status epilepticus, as well as minor epileptic seizures, were recorded during therapy with Pregabalin or immediately after its termination.

In clinical trials, blurred vision was reported more frequently in patients treated with Pregabalin than with placebo. As the therapy continued, vision returned to normal. At the same time, the frequency of changes in the fundus in patients receiving placebo was higher. Any changes on the part of the organ of vision should be immediately reported to the doctor, especially to patients already under the control of an ophthalmologist. Cancellation of the drug can lead to the disappearance of such undesirable reactions as blurred or loss of vision and other disorders of the organ of vision.

The development of renal failure was noted as a result of taking Pregabalin, in some cases, after its cancellation, renal function was restored.

After discontinuation of Pregabalin, the following adverse reactions are possible: headache, insomnia, hyperexcitability, anxiety, flu-like syndrome, pain, convulsions, depression, hyperhidrosis, nausea, diarrhea. Due to adverse reactions, the withdrawal rates for placebo and pregabalin were 7% and 14%, respectively. Based on the available data, it can be concluded that the frequency and severity of the withdrawal syndrome may depend on the dose received.

In the course of post-marketing studies, cases of abuse of pregabalin have been reported, as with the use of any drugs that affect the central nervous system. In this connection, a careful assessment of the patient's history for drug abuse is necessary, as well as monitoring him to assess the possibility of dosing violations and the appearance of drug dependence (for example, the development of resistance to pregabalin, an unreasonable increase in its dose, additive behavior of the patient).

There was no obvious relationship between Pregabalin therapy and the development of heart failure. Despite this, in the course of post-marketing studies, cases of the development of chronic heart failure were recorded in some patients. In the absence of clinically pronounced signs of heart or vascular disease, there was no association between peripheral edema and cardiovascular complications such as increased blood pressure or chronic heart failure. Such reactions were mainly observed in elderly patients with impaired cardiac function who received drug therapy for neuropathy. Therefore, patients in this category should take Pregabalin with caution. After canceling it, such reactions can go away on their own.

In the treatment of central neuropathic pain associated with spinal cord injury, an overall increase in the frequency of side effects is recorded, as well as an increase in the number of side effects from the central nervous system, especially drowsiness. However, such reactions may be a consequence of the effect of the summation of the action of Pregabalin and other drugs taken in parallel (for example, antispastic). These circumstances must be taken into account when prescribing a drug for this indication.

There have been cases of encephalopathy, mainly in patients with concomitant diseases that can lead to the development of this condition.

Influence on the ability to drive vehicles and complex mechanisms

According to the instructions, Pregabalin can cause dizziness and drowsiness, conditions that affect the performance of potentially hazardous types of work, requiring an increased speed of psychomotor reactions and increased concentration. Until the extent of such an effect on patients is ascertained, they should not use complex equipment, drive a car or engage in other similar activities.

Application during pregnancy and lactation

There are no adequate data on the use of Pregabalin by pregnant women. In animal studies, the toxic effect of the drug on reproductive function was revealed. Therefore, during pregnancy, Pregabalin can be used only if the benefits to the mother are significantly higher than the possible risks to the fetus. During treatment, women of reproductive age should use reliable methods of contraception.

Since Pregabalin is excreted in breast milk, and the safety of its use in newborns is unknown, breastfeeding is not recommended during drug therapy. Breastfeeding should be discontinued or discontinued with pregabalin.

Pediatric use

The use of Pregabalin in children and adolescents under 17 years of age is not recommended due to the fact that the efficacy and safety of the drug for this age group have not been established.

With impaired renal function

Since the clearance of Pregabalin is directly proportional to the clearance of creatinine, since the substance is predominantly excreted by the kidneys, it is recommended to reduce its dose in patients with renal insufficiency. Given the effective removal of the substance from the plasma during hemodialysis (a 4-hour hemodialysis session reduces the concentration of pregabalin in plasma by ~ 50%), an additional dose of the drug is required after the procedure.

For violations of liver function

Pregabalin is practically not subject to metabolism, it is excreted mainly in the urine unchanged, therefore, special studies of the pharmacokinetics of the drug in liver failure have not been conducted. It is assumed that the state of hepatic function does not significantly affect the concentration of a substance in plasma. No dose adjustment of Pregabalin is required for patients with liver disease.

Use in the elderly

Due to the age-related decrease in CC, the clearance of Pregabalin decreases accordingly, therefore, the elderly, especially with impaired renal function, may need to reduce the dose.

Treatment side effects such as drowsiness and dizziness increase the risk of accidental injury in older patients. According to post-marketing use data, loss / confusion and impairment of cognitive functions were also noted. In this connection, in old age, special caution is required during therapy with Pregabalin until a comprehensive assessment of possible side effects.

Drug interactions

The pharmacokinetic interaction of Pregabalin with other drugs / substances is unlikely, since it is mainly excreted by the kidneys unchanged, it undergoes minimal metabolism (less than 2% of the dose is excreted by the kidneys as metabolites), does not inhibit the metabolism of other drugs in vitro, does not bind to plasma proteins …

Established interaction:

carbamazepine, phenytoin, valproic acid, gabapentin, lamotrigine, lorazepam, oxycodone, ethanol: no signs of clinically significant pharmacokinetic interaction with Pregabalin are detected;
oral hypoglycemic substances, insulin, diuretics, phenobarbital, tiagabine, topiramate: they do not have a clinically significant effect on the clearance of Pregabalin;
oral contraceptives (norethisterone / ethinyl estradiol): the equilibrium pharmacokinetics of both drugs does not change;
other drugs that depress the central nervous system: respiratory failure is possible, up to the onset of coma;
oxycodone, lorazepam or ethanol (with repeated use): no clinically significant effect on respiration; it is possible that Pregabalin enhances the cognitive and motor impairments caused by oxycodone and exacerbates the effects of ethanol and lorazepam.

Analogs

Analogues of Pregabalin are: Algerika, Prabegin, Lyrica, Prigabilon, Replica, Pregabalin Zentiva, Pregabalin-SZ, etc.

Terms and conditions of storage

Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Pregabalin

Reviews of Pregabalin are mostly positive; at the beginning of therapy, the drug effectively eliminates the symptoms of diseases. But many patients note that with prolonged use, its effect gradually decreases. The main side effects accompanying therapy - drowsiness and lethargy in most patients are transient. It is noted that in each case the drug acts individually, therefore, only the attending physician should give all recommendations for its use.

Price for Pregabalin in pharmacies

Pregabalin is included in the list of drugs that can be prescribed to patients for free.

Price for Pregabalin in pharmacies:

capsules at a dosage of 75 mg: 14 pcs. in the package - from 251 rubles; 56 pcs. in the package - from 773 rubles;
capsules at a dosage of 150 mg: 14 pcs. in the package - from 265 rubles; 56 pcs. in the package - from 1150 rubles;
capsules at a dosage of 300 mg: 14 pcs. in the package - from 300 rubles; 56 pcs. in the package - from 1646 rubles.

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!