Movirica

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MOVIРИCA® (MOVIRIСA®)

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 dosage of 75 mg.

Pharmaceutical form. Hard capsules.

Main physicochemical characteristics:

50 mg or 150 mg capsules: hard capsules with white body and white cap;

75 mg capsules: hard capsules with white body and red cap.

Pharmacotherapeutic group. Antiepileptic agents. Other antiepileptic agents.

ATC code N03AX16.

Pharmacological properties.

Pharmacodynamics.

Pregabalin is a structural analogue of gamma-aminobutyric acid. Its mechanism of action is based on binding 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 associated with diabetic neuropathy, postherpetic neuralgia, and spinal cord injury. In epilepsy, a reduction in seizure frequency was observed during the first week of treatment; safety and efficacy are similar with administration of pregabalin twice or three times daily. In generalized anxiety disorder, a reduction in symptoms measured by the Hamilton Anxiety Rating Scale (HAM-A) was demonstrated as early as the first week of treatment. In fibromyalgia, a reduction in pain measured by the visual analogue scale has been established, as well as improvement in fibromyalgia-related symptoms.

Pharmacokinetics.

Absorption. Rapidly absorbed after oral administration on an empty stomach and reaches maximum plasma concentration within 1 hour after administration. Bioavailability is 90% or higher and is dose-independent. Steady-state concentrations are achieved within 24–48 hours after repeated dosing. Concomitant administration of pregabalin with food does not result in any clinically significant effect on absorption.

Distribution. Crosses the blood-brain barrier, placenta, and is excreted into breast milk. The volume of distribution is approximately 0.56 L/kg. Does not bind to plasma proteins.

Metabolism. Undergoes negligible metabolism; 98% is excreted unchanged in urine.

Elimination. Eliminated primarily by the kidneys, mostly in unchanged form; elimination half-life is 6.3 hours.

Renal impairment. Pregabalin clearance is directly proportional to creatinine clearance. Pregabalin is effectively removed from plasma by hemodialysis. In patients with renal impairment, the dose should be reduced; an additional dose should be administered after hemodialysis.

Hepatic impairment. Hepatic dysfunction is not expected to significantly affect pregabalin plasma concentrations, as pregabalin is primarily excreted unchanged in urine.

Elderly patients. Elderly patients with age-related renal impairment may require dose reduction of pregabalin.

Clinical characteristics.

Indications.

Neuropathic pain

The medicinal product is indicated for the treatment of peripheral or central neuropathic pain in adults.

Epilepsy

The medicinal product is indicated in adults as adjunctive therapy for partial seizures with or without secondary generalization.

Generalized anxiety disorder

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

Fibromyalgia

Contraindications.

Hypersensitivity to the active substance or to any of the excipients.

Interaction with other medicinal products and other forms of interaction.

Pregabalin is predominantly excreted unchanged in urine, undergoes negligible metabolism in humans, does not affect the metabolism of other drugs in vitro, and does not bind to plasma proteins; therefore, pharmacokinetic interactions are unlikely.

In vivo studies and population pharmacokinetic analysis

No clinically significant in vivo pharmacokinetic interactions were observed between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone, or ethanol. Oral antidiabetic agents, diuretics, insulin, phenobarbital, tiagabine, and topiramate have no clinically significant effect on pregabalin clearance.

Oral contraceptives, norethisterone and/or ethinylestradiol

Concomitant administration of pregabalin with oral contraceptives, norethisterone and/or ethinylestradiol does not affect the steady-state pharmacokinetics of either medicinal product.

Medicinal products affecting the CNS

May potentiate the effects of ethanol and lorazepam. Cases of respiratory depression, coma, and fatal outcomes have been reported in patients taking pregabalin concomitantly with opioids and/or other medicinal products that depress CNS function. Pregabalin is likely to enhance the cognitive and basic motor impairment caused by oxycodone.

Interactions in elderly patients

Pharmacodynamic interaction studies involving elderly patients have not been conducted.

Special precautions for use.

Patients with diabetes mellitus

Patients with diabetes mellitus who experience weight gain during pregabalin treatment may require adjustment of their antihyperglycemic medication doses.

Hypersensitivity reactions

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

Severe skin reactions

Rare cases of severe cutaneous adverse reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), which may be life-threatening or fatal, have been reported with pregabalin use. Patients should be informed about signs and symptoms of these reactions, and skin reactions should be closely monitored. If signs or symptoms suggestive of these reactions occur, pregabalin should be discontinued immediately and alternative therapy considered (if necessary).

Dizziness, somnolence, loss of consciousness, confusion, and psychiatric disturbances

Pregabalin use has been associated with dizziness and somnolence, which may increase the risk of traumatic events (e.g., falls) in elderly patients. Cases of loss of consciousness, confusion, and psychiatric disturbances have been reported; therefore, patients should exercise caution until they are aware of the potential effects of pregabalin.

Visual disturbances

Transient blurred vision has been reported during pregabalin therapy, which resolved in most cases with continued treatment. Adverse effects related to vision, including vision loss, blurred vision, or other changes in visual acuity, have been reported, most of which were temporary; such symptoms resolved or diminished upon discontinuation of pregabalin.

Renal impairment

Cases of renal failure have been reported. In some instances, this effect was reversible after discontinuation of pregabalin.

Discontinuation of concomitant antiepileptic drugs

There is insufficient data on discontinuing concomitant antiepileptic drugs after seizure control is achieved when pregabalin is added to ongoing therapy, with the aim of switching to pregabalin monotherapy.

Withdrawal symptoms

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

Seizures, including status epilepticus and generalized tonic-clonic seizures, may occur during pregabalin treatment or shortly after discontinuation. Data on withdrawal after prolonged use suggest that the frequency and severity of withdrawal symptoms may depend on the dose.

Congestive heart failure

Congestive heart failure has been reported in some patients taking pregabalin, mostly during treatment of neuropathic pain in elderly patients with cardiovascular disorders. Pregabalin should be used with caution in such patients. This condition may resolve upon discontinuation of pregabalin.

Treatment of central neuropathic pain due to spinal cord injury

During treatment of central neuropathic pain due to spinal cord injury, the incidence of adverse reactions in general and those affecting the central nervous system, particularly somnolence, was increased. This may be related to the additive effect of concomitant medications (e.g., antispastic agents) required for managing this condition, which should be considered when prescribing pregabalin to these patients.

Respiratory depression

Cases of severe respiratory depression have been reported with pregabalin use. Patients with impaired respiratory function, respiratory or neurological disorders, renal impairment, those receiving concomitant CNS depressants, and elderly patients may be at higher risk of this serious adverse reaction. Dose adjustments may be required for such patients.

Suicidal thoughts and behavior

Cases of suicidal thoughts and behavior have been reported in patients receiving antiepileptic drugs. A meta-analysis of clinical trials of antiepileptic drugs showed a small increased risk of such thoughts and behaviors. Suicidal thoughts and behavior have occurred in patients receiving pregabalin. Clinical studies have shown an increased risk of such behavior and suicide in patients treated with pregabalin. Patients and caregivers should be warned to seek medical help if signs of suicidal thoughts or behavior are observed. Patients should be monitored for emergence of such signs, and discontinuation of pregabalin and initiation of appropriate treatment are recommended if such signs occur.

Worsening of lower gastrointestinal tract function

Worsening of lower gastrointestinal tract function (intestinal obstruction, paralytic ileus, constipation) has been reported with pregabalin use, particularly when co-administered with drugs that may cause constipation, such as opioid analgesics. When pregabalin is used concomitantly with opioids, preventive measures for constipation should be taken (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 mortality risk compared to opioid monotherapy.

Misuse, abuse, or dependence

Cases of misuse, abuse, and dependence on pregabalin have been reported. Use with caution in patients with a history of substance abuse; patients should be monitored for signs of misuse, abuse, or dependence on pregabalin (development of tolerance, dose escalation, drug-seeking behavior).

Encephalopathy

Encephalopathy has occurred predominantly in patients with concomitant conditions that may predispose to encephalopathy.

Pregnancy/women of childbearing potential

Pregabalin use during the first trimester of pregnancy may result in serious fetal developmental abnormalities. It should not be used during pregnancy except when the benefit to the pregnant woman outweighs the potential risk to the fetus. Women of childbearing potential should use effective contraception.

Lactose intolerance

If a patient has known intolerance to certain sugars, they should consult a physician before taking this medicinal product.

Use during pregnancy or breastfeeding.

Women of childbearing potential/contraception

Women of childbearing potential should use effective contraception.

Pregnancy

Pregabalin use during the first trimester of pregnancy may lead to serious fetal developmental abnormalities. The drug crosses the placenta. It should not be used during pregnancy except when the benefit to the pregnant woman outweighs the potential risk to the fetus.

Breastfeeding

Pregabalin passes into breast milk; therefore, breastfeeding is not recommended during pregabalin treatment.

Fertility

Data on the effect of pregabalin on female fertility are lacking. It does not affect sperm motility (based on a 3-month study with 600 mg/day pregabalin).

Ability to affect reaction speed when driving or operating machinery.

Pregabalin may cause dizziness and somnolence and may have a minor or moderate influence on the ability to drive or operate machinery. Patients should refrain from driving, operating complex machinery, or engaging in other potentially hazardous activities until they know how pregabalin affects their ability to perform such tasks.

Method of administration and dosage.

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

Neuropathic pain

Initiate therapy with a dose of 150 mg/day, divided into 2–3 doses. Depending on individual response and tolerability, the dose may be increased to 300 mg/day after 3–7 days; if necessary, to the maximum dose of 600 mg/day after another 7 days.

Epilepsy

Initiate therapy with a dose of 150 mg/day, divided into 2–3 doses. Depending on individual response and tolerability, the dose may be increased to 300 mg/day after the first week of treatment; if necessary, to the maximum dose of 600 mg/day after another 7 days.

Generalized anxiety disorder

Initiate therapy with a dose of 150 mg/day, divided into 2–3 doses.

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

Fibromyalgia

The recommended daily dose is 300–450 mg/day. Treatment should be initiated at a dose of 75 mg twice daily (150 mg/day). Depending on efficacy and tolerability, the dose may be increased to 150 mg twice daily (300 mg/day) within one week. For patients in whom a dose of 300 mg/day is insufficiently effective, the dose may be increased to 225 mg twice daily (450 mg/day).

No additional benefit has been demonstrated with the use of a 600 mg/day dose; worse tolerability has been observed with this dose. Since adverse reactions are dose-dependent, doses above 450 mg/day are not recommended.

Discontinuation of pregabalin

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

Renal impairment

Pregabalin is eliminated from systemic circulation in unchanged form, primarily via the kidneys; therefore, dosage adjustment is required in patients with impaired renal function.

Dosage should be reduced individually in patients with impaired renal function according to creatinine clearance (CLcr), as indicated in the table below.

Pregabalin is effectively removed from plasma by hemodialysis (approximately 50% of the drug within 4 hours). For patients undergoing hemodialysis, the daily dose of pregabalin should be adjusted according to renal function. In addition to the daily dose, a supplemental dose of the drug should be administered immediately after each 4-hour hemodialysis session (see Table 1).

Table 1. Dosage adjustment of pregabalin according to renal function

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

• Additional dose means an extra single dose.

Hepatic impairment

Dose adjustment is not required for patients with hepatic impairment.

Elderly patients

In elderly patients, dose reduction of pregabalin may be necessary due to impaired renal function.

Children

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

Overdose

The most commonly reported adverse reactions in pregabalin overdose were somnolence, confusion, agitation, and restlessness. Seizures have been reported, and coma has been reported rarely. Management of overdose consists of general supportive measures and may include hemodialysis (see "Administration and dosage", Table 1).

Adverse reactions

Adverse reactions identified during clinical trials were mild or moderate in severity; the most common were dizziness and somnolence.

Adverse reactions are listed below by system organ class and frequency of occurrence (very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated from the available data)).

Adverse reactions may also be related to the course of the underlying disease and/or concomitant use of other medicinal products. During treatment of central neuropathic pain due to spinal cord injury, the overall incidence of adverse reactions and those affecting the CNS, particularly somnolence, was increased.

Adverse reactions reported after marketing of the medicinal product are listed below and indicated in italics.

Infections and infestations

Common: nasopharyngitis.

Blood and lymphatic system disorders

Uncommon: neutropenia.

Immune system disorders

Uncommon: hypersensitivity.

Rare: angioedema, allergic reaction, anaphylactoid reactions.

Metabolism and nutrition disorders

Common: increased appetite.

Uncommon: loss of appetite, hypoglycemia.

Psychiatric disorders

Common: euphoric mood, confusion, irritability, disorientation, insomnia, decreased libido.

Uncommon: hallucinations, panic attacks, restlessness, agitation, depression, depressed mood, elevated mood, aggression, mood alterations, depersonalization, word-finding difficulty, pathological dreams, increased libido, anorgasmia, apathy.

Rare: disinhibition, suicidal thoughts and behavior.

Frequency not known: drug dependence.

Nervous system disorders

Very common: dizziness, somnolence, headache.

Common: ataxia, coordination disturbance, tremor, dysarthria, amnesia, memory impairment, attention disturbance, paresthesia, hypesthesia, sedation, balance disorder, lethargy.

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

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

Eye disorders

Common: blurred vision, diplopia, conjunctivitis.

Uncommon: peripheral vision loss, visual disturbance, eye swelling, visual field defects, reduced visual acuity, eye pain, asthenopia, photopsia, dry eyes, increased lacrimation, eye irritation, blepharitis, accommodation disorder, eye hemorrhage, photophobia, retinal edema.

Rare: vision loss, keratitis, oscillopsia, altered depth perception, mydriasis, strabismus, brightness of vision, anisocoria, corneal ulcer, exophthalmos, extraocular muscle paralysis, iritis, keratoconjunctivitis, miosis, night blindness, ophthalmoplegia, optic nerve atrophy, optic disc edema, ptosis, uveitis.

Ear and labyrinth disorders

Common: vertigo.

Uncommon: hyperacusis.

Cardiac disorders

Uncommon: tachycardia, first-degree atrioventricular block, sinus bradycardia, congestive heart failure, arterial hypotension/hypertension, flushing, hyperemia, cold extremities.

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

Respiratory, thoracic and mediastinal disorders

Common: pharyngolaryngeal pain.

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

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

Frequency not known: respiratory depression.

Gastrointestinal disorders

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

Uncommon: gastroesophageal reflux disease, hypersalivation, hypoaesthesia of oral cavity, cholecystitis, cholelithiasis, colitis, gastrointestinal hemorrhage, melena, tongue swelling, rectal bleeding.

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

Hepatobiliary disorders

Uncommon: increased levels of liver enzymes*.

Rare: jaundice.

Very rare: hepatic failure, hepatitis.

Skin and subcutaneous tissue disorders

Common: pressure ulcers.

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, skin and subcutaneous nodules.

Musculoskeletal and connective tissue disorders

Common: 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: renal failure, oliguria, urinary retention, acute renal failure, glomerulonephritis, pyelonephritis.

Reproductive system and breast disorders

Common: erectile dysfunction, impotence.

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

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

General disorders and administration site conditions

Common: peripheral edema, edema, gait disturbance, falls, feeling drunk, unusual sensations, increased fatigue.

Uncommon: generalized edema, facial swelling, chest tightness, pain, hot flushes, thirst, chills, asthenia, malaise, abscess, lipodermatitis, photosensitivity reactions.

Rare: granuloma, self-harm, retroperitoneal fibrosis, shock.

Investigations

Common: weight gain.

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

Rare: decreased blood leukocyte count.

* Increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

In some patients, withdrawal symptoms such as insomnia, headache, nausea, anxiety, diarrhea, flu-like symptoms, seizures, nervousness, depression, suicidal thoughts, pain, hyperhidrosis, and dizziness have been observed after discontinuation of short- or long-term pregabalin treatment, indicating physical dependence. This information should be communicated to the patient prior to initiating treatment. Data on discontinuation of pregabalin after long-term use suggest 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 commonly reported adverse reactions were somnolence, pyrexia, upper respiratory tract infections, increased appetite, weight gain, and nasopharyngitis.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicinal product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients or their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

For 50 mg dosage

Store out of reach of children in the original packaging at a temperature not exceeding 30 °C.

For 75 mg and 150 mg dosages

Store out of reach of children in the original packaging. No special storage conditions required.

Packaging.

7 capsules in a blister; 2 blisters in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Atlantik Pharma Productos Farmaceuticos S.A.

Manufacturer's address.

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

Marketing Authorization Holder. MOVI Health LLC.

Address of Marketing Authorization Holder.

162 A, Shevchenka Street, Shevchenkove, Kyiv-Sviatoshynskyi district, Kyiv Oblast, 08140, Ukraine.