RAPTEN 75

INSTRUCTIONS for medical use of the medicinal product MOVIRICA^®(MOVIRICA^®)

Composition

active substance: pregabalin; 1 capsule contains pregabalin 50 mg, 75 mg or 150 mg; excipients: lactose monohydrate; corn starch; talc; capsule shell: gelatin, titanium dioxide (E 171) - for dosages of 50 mg, 75 mg or 150 mg, iron oxide red (E 172), iron oxide yellow (E 172), erythrosine (E 127) - for dosages of 75 mg.

Pharmaceutical form

Hard capsules.

Main physical and chemical properties

Capsules of 50 mg or 150 mg: hard capsules with a white body and a white cap; capsules of 75 mg: hard capsules with a white body and a red cap.

Pharmacotherapeutic group

Antiepileptic drugs. Other antiepileptic drugs.

ATC code N03A X16.

Pharmacological properties

Pharmacodynamics

Pregabalin is an analogue of gamma-aminobutyric acid. The mechanism of action is due to the fact that pregabalin binds to the auxiliary subunit (α2-δ protein) of voltage-dependent calcium channels in the central nervous system (CNS).

Pregabalin is effective in the treatment of neuropathic pain in diabetic neuropathy, postherpetic neuralgia, and spinal cord injury. In epilepsy, a decrease in the frequency of seizure attacks was observed in the first week of use; safety and efficacy are similar when using pregabalin 2 or 3 times a day. In generalized anxiety disorder, a decrease in symptoms according to the Hamilton scale for anxiety assessment (HAM-A) was established already in the first week of use of the drug. In fibromyalgia, a decrease in pain according to the visual analog scale was established, as well as an improvement in the condition regarding the manifestations of fibromyalgia.

Pharmacokinetics

Absorption. It is rapidly absorbed when taken orally on an empty stomach and reaches a maximum concentration in plasma within 1 hour after administration. Bioavailability is 90% or more and does not depend on the dose. After multiple administration, a steady state is reached within 24-48 hours. When pregabalin is taken with food, no significant effect on absorption has been established.

Distribution. It penetrates the blood-brain barrier, placenta, and breast milk. The volume of distribution is approximately 0.56 l/kg. It does not bind to plasma proteins.

Metabolism. It undergoes minimal metabolism, 98% is excreted in the urine unchanged.

Excretion. It is excreted by the kidneys, mainly in an unchanged form, with a half-life of 6.3 hours.

Kidney failure. The clearance of pregabalin is directly proportional to the clearance of creatinine, and it is effectively removed from the plasma by hemodialysis. In kidney failure, the dose of the drug should be reduced; after hemodialysis, an additional dose should be administered.

Liver failure. Liver function disorders cannot significantly affect the concentration of pregabalin in the blood plasma, since pregabalin is excreted in the urine, mainly in an unchanged form.

Elderly patients. Patients with age-related kidney function impairment may require a reduction in the dose of pregabalin.

Clinical characteristics

Indications

Neuropathic pain

The drug is indicated for the treatment of neuropathic pain of peripheral or central origin in adults.

Epilepsy

The drug is indicated for adults as an additional treatment for partial seizure attacks with secondary generalization or without it.

Generalized anxiety disorder

The drug is indicated for the treatment of generalized anxiety disorder in adults.

Fibromyalgia

Contraindications

Hypersensitivity to the active substance or to any excipient.

Interaction with other medicinal products and other types of interactions

Pregabalin is mainly excreted in an unchanged form with urine, undergoes minimal metabolism in the human body, and in vitro does not affect the metabolism of other drugs and does not bind to plasma proteins, so pharmacokinetic interactions are unlikely.

In vivo studies and population pharmacokinetic analysis

No significant clinical pharmacokinetic interaction was observed in vivo between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone, or ethanol. Oral antidiabetic drugs, diuretics, insulin, phenobarbital, tiagabine, and topiramate do not have a clinically significant effect on pregabalin clearance.

Oral contraceptives, norethindrone, and/or ethinyl estradiol

Concomitant use of pregabalin with oral contraceptives, norethindrone, and/or ethinyl estradiol does not affect the pharmacokinetics of these drugs in a steady state.

Drugs that affect the CNS

May potentiate the effect of ethanol and lorazepam. There have been reports of respiratory failure, coma, and fatal outcomes in patients taking pregabalin with opioids and/or other drugs that suppress CNS function. Pregabalin is likely to exacerbate cognitive and motor function disorders caused by oxycodone.

Interactions in elderly patients

No pharmacodynamic interaction studies have been conducted in elderly patients.

Special warnings and precautions for use

Patients with diabetes

Patients with diabetes who have gained weight during treatment with pregabalin may need to adjust the dose of hypoglycemic drugs.

Hypersensitivity reactions

If symptoms of angioedema (facial swelling, perioral swelling, and swelling of the upper respiratory tract) occur, pregabalin should be discontinued immediately.

Severe skin reactions

Rarely, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported, which can be life-threatening or fatal, when using pregabalin. Patients should be informed about the signs and symptoms and closely monitored for skin reactions when prescribing the drug. If signs and symptoms of these reactions occur, pregabalin should be discontinued immediately and alternative treatment should be considered (if necessary).

Dizziness, drowsiness, loss of consciousness, confusion, and mental disorders

The use of pregabalin has been associated with dizziness and drowsiness, which can increase the risk of traumatic events (falls) in elderly patients. There have been reports of loss of consciousness, confusion, mental disorders, so patients should be careful until they know the possible effects of pregabalin.

Visual disturbances

Temporary blurred vision has been reported when using pregabalin, which disappeared in most cases with continued therapy. Adverse reactions from the organs of vision, including loss of vision, blurred vision, or other changes in visual acuity, have been reported, most of which were temporary; these symptoms disappeared or decreased when pregabalin was discontinued.

Kidney failure

There have been reports of kidney failure. Sometimes this effect was reversible after discontinuation of pregabalin.

Withdrawal of concomitant antiepileptic drugs

There is insufficient data on the withdrawal of concomitant antiepileptic drugs after achieving control over seizures when adding pregabalin to existing treatment to switch to monotherapy with pregabalin.

Withdrawal symptoms

In some patients, withdrawal symptoms were observed after stopping short-term or long-term treatment with pregabalin. Insomnia, headache, nausea, anxiety, diarrhea, flu-like syndrome, nervousness, depression, suicidal thoughts, pain, seizures, hyperhidrosis, and dizziness have been reported, indicating physical dependence. The appearance of withdrawal symptoms after stopping pregabalin may indicate dependence on the drug. This information should be communicated to the patient before starting treatment. If pregabalin needs to be discontinued, it is recommended to do so gradually, over at least 1 week, regardless of the indication.

Seizures, including epileptic status and grand mal seizures

May occur during treatment with pregabalin or soon after its discontinuation. Data on the withdrawal of pregabalin after long-term use indicate that the frequency and severity of withdrawal symptoms may depend on the dose.

Heart failure

There have been reports of heart failure in some patients taking pregabalin, mostly during the treatment of neuropathic pain in elderly patients with cardiovascular disorders. Pregabalin should be used with caution in such patients. When pregabalin is discontinued, this phenomenon may disappear.

Treatment of neuropathic pain of central origin due to spinal cord injury

During the treatment of neuropathic pain of central origin due to spinal cord injury, the frequency of adverse reactions in general and from the central nervous system, especially drowsiness, was increased. This may be associated with the additive effect of concomitant medications (e.g., antispastic agents) necessary for the treatment of this condition, which should be taken into account when prescribing pregabalin to such patients.

Respiratory depression

There have been reports of severe respiratory depression when using pregabalin. Patients with impaired respiratory function, respiratory or neurological diseases, kidney failure, concomitant use of CNS depressants, and elderly patients may have a higher risk of this severe adverse reaction. For such patients, dose adjustment may be necessary.

Suicidal thoughts and behavior

There have been reports of suicidal thoughts and behavior in patients receiving antiepileptic treatment. A meta-analysis of clinical trials of antiepileptic drugs showed a slight increase in the risk of such thoughts and behavior. The mechanism of the occurrence of this risk is unknown. Cases of suicidal thoughts and behavior have been observed in patients receiving pregabalin. According to the study, an increased risk of such behavior and suicide was found in patients receiving pregabalin. Patients and those caring for them should be warned to seek medical attention if signs of suicidal thoughts or behavior are detected. Monitoring of the patient's condition for the appearance of such signs is recommended, and if they occur, discontinuation of pregabalin and appointment of appropriate treatment are recommended.

Worsening of lower gastrointestinal tract function

There have been reports of worsening of lower gastrointestinal tract function (intestinal obstruction, paralytic ileus, constipation) when taking pregabalin with drugs that can cause constipation, such as opioid analgesics. When combining pregabalin with opioids, measures should be taken to prevent constipation (especially in women and elderly patients).

Concomitant use with opioids

Caution should be exercised when prescribing pregabalin concomitantly with opioids due to the risk of CNS depression and increased risk of mortality when used concomitantly compared to opioid monotherapy.

Incorrect use, abuse, or dependence

There have been reports of incorrect use, abuse, and dependence on the drug. Caution should be exercised when prescribing pregabalin to patients with a history of substance abuse; the patient should be monitored for signs of incorrect use, abuse, or dependence on pregabalin (development of tolerance, exceeding the prescribed dose, behavior aimed at obtaining the drug).

Encephalopathy

Encephalopathy occurred mainly in patients with concomitant diseases that can cause encephalopathy.

Use during pregnancy or breastfeeding

Women of childbearing potential/contraception

Women of childbearing potential should use effective contraception.

Pregnancy

The use of pregabalin during the first trimester of pregnancy may lead to serious fetal malformations. The drug penetrates the placenta. It should not be used during pregnancy, except in cases where the benefit to the pregnant woman outweighs the potential risk to the fetus.

Breastfeeding

Pregabalin penetrates breast milk, so breastfeeding is not recommended when using pregabalin.

Fertility

Data on the effect of pregabalin on female fertility are not available. It does not affect sperm motility (according to a study during 3 months of use of pregabalin at a dose of 600 mg/day).

Ability to influence the reaction rate when driving vehicles or operating other mechanisms

Pregabalin may cause dizziness and drowsiness and have a minor or moderate effect on the ability to drive vehicles or operate mechanisms. Patients should refrain from driving vehicles, working with complex equipment, and other potentially hazardous activities until they know the effect of pregabalin on their ability to perform such activities.

Method of administration and dosage

The drug should be taken orally, regardless of food intake. The daily dose of 150-600 mg should be divided into 2-3 doses.

Neuropathic pain

Therapy should be started with a dose of 150 mg/day, divided into 2-3 doses. Depending on the individual response and tolerability, the dose can be increased to 300 mg/day after 3-7 days; if necessary, up to a maximum dose of 600 mg/day after another 7 days.

Epilepsy

Therapy should be started with a dose of 150 mg/day, divided into 2-3 doses. Depending on the individual response and tolerability, the dose can be increased to 300 mg/day after the first week of treatment; if necessary, up to a maximum dose of 600 mg/day after another 7 days.

Generalized anxiety disorder

Therapy should be started with a dose of 150 mg/day, divided into 2-3 doses.

The need for continued therapy should be periodically reviewed. Depending on the individual response and tolerability, the dose can be increased to 300 mg/day after the first week of treatment and to 450 mg/day after another week of treatment; if necessary, up to a maximum dose of 600 mg/day after another 7 days.

Fibromyalgia

The recommended daily dose is 300-450 mg/day. Treatment should be started with a dose of 75 mg twice a day (150 mg/day). Depending on efficacy and tolerability, the dose can be increased to 150 mg twice a day (300 mg/day) within one week. For patients for whom a dose of 300 mg/day is not effective enough, the dose can be increased to 225 mg twice a day (450 mg/day).

No additional benefit has been established for a dose of 600 mg/day; worse tolerability of such a dose has been found. Since adverse reactions are dose-dependent, the use of doses above 450 mg/day is not recommended.

Withdrawal of pregabalin

Treatment should be discontinued gradually, over at least one week, regardless of the indication.

Kidney dysfunction

Pregabalin is excreted from the systemic circulation in an unchanged form, mainly by the kidneys, so the dose of the drug should be adjusted in patients with kidney dysfunction.

The dose should be reduced in patients with kidney dysfunction individually, as specified in the table below, according to the creatinine clearance (CLcr), which is determined by the formula:

* The total daily dose (mg/day) should be divided into several doses according to the dosing regimen to obtain the dose for a single dose (mg/dose).

+

Additional dose - this is an additional single dose.

Liver failure

For patients with liver dysfunction, there is no need to adjust the dose.

Elderly patients

For elderly patients, due to decreased kidney function, a reduction in the dose of pregabalin may be necessary.

Children

The safety and efficacy of the drug in children under 18 years of age have not been established.

Overdose

The most common adverse reactions to overdose with pregabalin were drowsiness, confusion, agitation, and restlessness. There have been reports of seizures and, rarely, coma. Treatment of overdose consists of general supportive measures and may include hemodialysis (see "Method of administration and dosage", Table 1).

Adverse reactions

Adverse reactions identified during clinical trials were mild or moderate, the most common were dizziness and drowsiness.

Adverse reactions are presented by classes of organ systems and frequency of occurrence (very often (≥ 1/10); often (from ≥ 1/100 to < 1/10); uncommon (from ≥ 1/1000 to < 1/100); rare (from ≥ 1/10000 to < 1/1000); very rare (< 1/10000), frequency unknown (cannot be estimated from available data).

Adverse reactions may also be associated with the course of the underlying disease and/or concomitant use of other medicinal products. During the treatment of neuropathic pain of central origin due to spinal cord injury, the frequency of adverse reactions in general and from the CNS, especially drowsiness, was increased.

Adverse reactions reported after the drug was released on the market are listed below and marked in italics.

Infections and invasions

Often: nasopharyngitis.

Blood and lymphatic system disorders

Uncommon: neutropenia.

Immune system disorders

Uncommon: hypersensitivity.

Rare: angioedema, allergic reaction, anaphylactoid reactions.

Metabolism and nutrition disorders

Often: increased appetite.

Uncommon: decreased appetite, hypoglycemia.

Pсихічні розлади

Часто: ейфоричний настрій, сплутаність свідомості, дратівливість, дезорієнтація, безсоння, зниження лібідо.

Нечасто: галюцинації, панічні атаки, неспокій, збудження, депресія, пригнічений настрій, піднесений настрій, агресія, зміни настрою, деперсоналізація, утруднений добір слів, патологічні сновидіння, посилення лібідо, аноргазмія, апатія.

Рідко: розгальмовування, суїцидальні думки та поведінка.

Частота невідома: медикаментозна залежність.

Nervous system disorders

Very often: dizziness, drowsiness, headache.

Often: ataxia, coordination disorders, tremor, dysarthria, amnesia, memory impairment, attention disorders, paresthesia, hypesthesia, sedation, balance disorders, lethargy.

Uncommon: syncope, stupor, myoclonus, loss of consciousness, psychomotor hyperactivity, dyskinesia, postural dizziness, intention tremor, nystagmus, cognitive function disorders, mental disorders, speech disorders, hyporeflexia, hyperesthesia, burning sensation, ageusia, general malaise, perioral paresthesia.

Rare: convulsions, parosmia, hypokinesia, dysgraphia, parkinsonism, hypalgesia, dependence, cerebellar syndrome, wheel spinning syndrome, coma, delirium, encephalopathy, extrapyramidal syndrome, Guillain-Barré syndrome, intracranial hypertension, manic reactions, paranoid reactions, sleep disorders.

Eye disorders

Often: blurred vision, diplopia, conjunctivitis.

Uncommon: peripheral vision loss, vision disorders, eye swelling, visual field defects, decreased visual acuity, eye pain, asthenopia, photopsia, dry eyes, increased lacrimation, eye irritation, blepharitis, accommodation disorders, eye hemorrhage, photophobia, anisocoria, corneal ulcers, exophthalmos, oculomotor palsy, uveitis.

Rare: vision loss, keratitis, oscillopsia, change in depth perception, mydriasis, strabismus, visual brightness, anisocoria, corneal ulcers, eyelid edema, paralytic oculomotor palsy, iritis, keratoconjunctivitis, miosis, night blindness, ophthalmoplegia, optic nerve atrophy, optic disc edema, ptosis, uveitis.

Ear and labyrinth disorders

Often: vertigo.

Uncommon: hyperacusis.

Cardiovascular disorders

Uncommon: tachycardia, first-degree atrioventricular block, sinus bradycardia, congestive heart failure, arterial hypotension/hypertension, flushing, hyperemia, feeling of cold in the limbs.

Rare: QT interval prolongation, sinus tachycardia, sinus arrhythmia.

Respiratory, thoracic, and mediastinal disorders

Often: pharyngolaryngeal pain.

Uncommon: dyspnea, nasal bleeding, cough, nasal congestion, rhinitis, snoring, dryness of the nasal mucosa.

Rare: pulmonary edema, throat tightness, laryngospasm, apnea, atelectasis, bronchiolitis, hiccups, fibrosis of the lungs, yawning.

Frequency unknown: respiratory depression.

Gastrointestinal disorders

Often: vomiting, nausea, constipation, diarrhea, flatulence, abdominal distension, dry mouth, gastroenteritis.

Uncommon: gastroesophageal reflux disease, hypersalivation, oral hypogeusia, cholecystitis, cholelithiasis, colitis, gastrointestinal bleeding, melena, rectal bleeding.

Rare: ascites, pancreatitis, dysphagia, aphthous stomatitis, esophageal ulcer, periodontal abscess.

Hepatobiliary disorders

Uncommon: increased liver enzymes*.

Rare: jaundice.

Very rare: liver failure, hepatitis.

Skin and subcutaneous tissue disorders

Often: pruritus.

Uncommon: papular rash, urticaria, hyperhidrosis, itching, alopecia, dry skin, eczema, hirsutism, skin ulcers, vesiculobullous rash.

Rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, cold sweat, exfoliative dermatitis, lichenoid dermatitis, melanosis, nail disorders, petechial rash, purpura, pustular rash, skin atrophy, skin necrosis, subcutaneous nodules.

Musculoskeletal and connective tissue disorders

Often: muscle spasms, arthralgia, back pain, limb pain, neck muscle spasms.

Uncommon: joint swelling, myalgia, muscle twitching, neck pain, muscle stiffness.

Rare: rhabdomyolysis.

Renal and urinary disorders

Uncommon: urinary incontinence, dysuria, albuminuria, hematuria, kidney stone formation, nephritis.

Rare: kidney failure, oliguria, urinary retention, acute kidney failure, glomerulonephritis, pyelonephritis.

Reproductive system and breast disorders

Often: erectile dysfunction, impotence.

Uncommon: sexual dysfunction, ejaculation delay, dysmenorrhea, breast pain, leucorrhea, menorrhagia.

Rare: amenorrhea, breast discharge, breast enlargement, gynecomastia, cervicitis, balanitis, epididymitis.

General disorders

Often: peripheral edema, edema, gait disturbance, falls, feeling of intoxication, unusual sensations, increased fatigue.

Uncommon: generalized edema, facial edema, chest tightness, pain, fever, thirst, chills, asthenia, malaise, abscess, inflammation of fatty tissue, photosensitivity reactions.

Rare: granuloma, self-inflicted injury, retroperitoneal fibrosis, shock.

Laboratory and other tests

Often: weight gain.

Uncommon: increased creatine phosphokinase level in blood, increased glucose level in blood, decreased platelet count, increased creatinine level in blood, decreased potassium level in blood, weight loss.

Rare: decreased white blood cell count in blood.

* Increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels

In some patients, after stopping short-term or long-term treatment with pregabalin, the following withdrawal symptoms were observed: insomnia, headache, nausea, anxiety, diarrhea, flu-like syndrome, nervousness, depression, suicidal thoughts, pain, seizures, hyperhidrosis, and dizziness, indicating physical dependence. This information should be communicated to the patient before starting treatment. Data on the withdrawal of pregabalin after long-term use indicate that the frequency and severity of withdrawal symptoms may be dose-dependent.

Children

The safety profile of pregabalin in children in clinical trials is similar to that in adult patients with epilepsy. The most common adverse reactions were drowsiness, pyrexia, upper respiratory tract infections, increased appetite, weight gain, and nasopharyngitis.

Reporting suspected adverse reactions

Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring the ratio of benefits and risks when using this medicinal product. Medical and pharmaceutical workers, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product through the Automated Information System for Pharmacovigilance at: https://aisf.dec.gov.ua.

Shelf life

3 years.

Storage conditions

For a dosage of 50 mg

Store in a place inaccessible to children in the original packaging at a temperature not exceeding 30°C.

For dosages of 75 mg and 150 mg

Store in a place inaccessible to children in the original packaging. No special storage conditions are required.

Packaging

7 capsules in a blister pack; 2 blister packs in a cardboard box.

Release category

By prescription.

Manufacturer

Atlantic Pharma Productos Farmacéuticos S.A.

Location of the manufacturer and address of the place of its activities.

Rua de Tapada Grande 2, Abrunheira, Sintra, 2710-228, Portugal.

Applicant

LLC "Movi Health).

Location of the applicant.

08140, Ukraine, Kyiv region, Kyiv-Sviatoshyn district, village of Shevchenkove, Shevchenko street, 162-A.