Torgabaline 150

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TORGABALIN 75 TORGABALIN 150

Composition:

Active substance: pregabalin;

1 hard capsule contains pregabalin 75 mg or 150 mg;

Excipients of 75 mg capsule: STARCAP 1500® mixture (corn starch and pregelatinized starch), talc, hard gelatin capsule No. 4*;

*Composition of hard gelatin capsule No. 4: gelatin, sodium lauryl sulfate, iron oxide red (E 172), titanium dioxide (E 171);

Excipients of 150 mg capsule: STARCAP 1500® mixture (corn starch and pregelatinized starch), talc, hard gelatin capsule No. 1*;

*Composition of hard gelatin capsule No. 1: gelatin, sodium lauryl sulfate, titanium dioxide (E 171).

Pharmaceutical form. Hard capsules.

Main physicochemical properties:

75 mg capsules: hard gelatin capsules No. 4 with an opaque orange cap and white body, marked "1360" on the cap and "75" on the body, containing white to almost white powder;

150 mg capsules: hard gelatin capsules No. 1 with opaque white cap and body, marked "1362" on the cap and "150" on the body, containing white to almost white powder.

Pharmacotherapeutic group.

Antiepileptic drugs. ATC code N03A X16.

Pharmacological Properties

Pharmacodynamics

The active substance, pregabalin, is a structural analogue of gamma-aminobutyric acid ((S)-3-(aminomethyl)-5-methylhexanoic acid).

Pregabalin binds to the auxiliary subunit (α2-δ protein) of voltage-dependent calcium channels in the central nervous system (CNS), potently displacing [3H]-gabapentin in experimental settings.

Neuropathic Pain

The efficacy of the drug has been demonstrated in clinical studies on diabetic neuropathy and postherpetic neuralgia. Efficacy in other types of neuropathic pain has not been studied.

The safety and efficacy profiles were similar for dosing regimens administered twice daily and three times daily.

Pain reduction was observed during the first week of treatment and was maintained throughout the treatment period.

Pharmacokinetics

Pharmacokinetic parameters of pregabalin were similar in healthy volunteers, patients with epilepsy taking antiepileptic drugs, and patients with chronic pain.

Absorption. Pregabalin is rapidly absorbed after oral administration on an empty stomach, reaching peak plasma concentration within 1 hour after single and multiple doses. The estimated oral bioavailability of pregabalin is 90% or greater and is dose-independent. Steady-state concentrations are achieved within 24–48 hours after repeated administration. The extent of pregabalin absorption is reduced when administered with food, resulting in a decrease of approximately 25–30% in maximum concentration (Cmax) and an increase of about 2.5 hours in time to reach peak concentration (tmax). However, administration of pregabalin with food does not have a clinically significant effect on the overall extent of absorption.

Distribution. The apparent volume of distribution of pregabalin after oral administration is approximately 0.56 L/kg. Pregabalin does not bind to plasma proteins.

Metabolism. Pregabalin undergoes minimal metabolism. After administration of a radiolabeled dose of pregabalin, approximately 98% of the radioactivity is excreted in urine as unchanged drug. The N-methylated derivative of pregabalin (the main metabolite detected in urine) accounts for 0.9% of the administered dose. Studies have demonstrated the absence of racemization of the S-enantiomer to the R-enantiomer.

Elimination. Pregabalin is eliminated from systemic circulation primarily by renal excretion as unchanged drug. The mean elimination half-life of pregabalin is 6.3 hours. Plasma and renal clearance of pregabalin are directly proportional to creatinine clearance. Dose adjustment is required for patients with renal impairment or those undergoing hemodialysis.

Linearity/Non-linearity. The pharmacokinetics of pregabalin are linear across the entire recommended dose range. Inter-subject pharmacokinetic variability for pregabalin is low (less than 20%). Multiple-dose pharmacokinetics are predictable based on single-dose data. Therefore, routine monitoring of plasma pregabalin concentrations is not necessary.

Pharmacokinetics in Specific Patient Populations

Gender. There is no clinically significant effect of gender on pregabalin plasma concentrations.

Renal Impairment. Pregabalin clearance is directly proportional to creatinine clearance. In addition, pregabalin is effectively removed from plasma by hemodialysis (after 4 hours of hemodialysis, plasma pregabalin concentration decreases by approximately 50%). Since renal excretion is the primary route of elimination, dosage reduction is required for patients with renal impairment, and an additional dose should be administered after hemodialysis.

Hepatic Impairment. Specific pharmacokinetic studies in patients with hepatic impairment have not been conducted. Since pregabalin undergoes negligible metabolism and is primarily excreted unchanged in urine, it is unlikely that hepatic impairment would significantly affect pregabalin plasma concentrations.

Elderly Patients (aged 65 years and older). Pregabalin clearance tends to decrease with age. This age-related reduction in oral pregabalin clearance is consistent with the decline in creatinine clearance associated with aging. Dose reduction of pregabalin may be required for elderly patients with age-related renal impairment.

Clinical characteristics.

Indications.

Neuropathic pain

Treatment of neuropathic pain in adults associated with peripheral and central nervous system injury.

Epilepsy

Adjunctive therapy for partial seizures with or without secondary generalization in adults.

Generalized anxiety disorder

Treatment of generalized anxiety disorder in adults.

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

Since pregabalin is predominantly excreted unchanged in urine, undergoes minimal metabolism in humans (less than 2% of the dose is excreted in urine as metabolites), does not inhibit *in vitro* metabolism of other drugs, and does not bind to plasma proteins, it is unlikely that pregabalin would cause pharmacokinetic interactions or be subject to such interactions.

*In vivo* studies and population pharmacokinetic analysis

In *in vivo* studies, no clinically significant pharmacokinetic interactions were observed between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone, or ethanol. Population pharmacokinetic analysis showed that 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 agent.

Medicinal products affecting the CNS

Pregabalin may enhance the effects of ethanol and lorazepam. During post-marketing surveillance, cases of respiratory depression and coma have been reported in patients taking pregabalin together with other medicinal products that depress central nervous system (CNS) function. Pregabalin may likely enhance cognitive and gross motor function impairment caused by oxycodone.

Interaction in elderly patients

Specific pharmacodynamic interaction studies involving elderly volunteers have not been conducted. Interaction studies have been performed only in younger adults.

Special precautions for use.

Patients with diabetes

According to current clinical practice, some patients with diabetes whose body weight has increased during pregabalin treatment may require adjustment of doses of antihyperglycemic medicinal products.

Hypersensitivity reactions

Hypersensitivity reactions, including angioedema, have been reported. If symptoms of angioedema such as facial swelling, perioral swelling, or swelling of the upper airways occur, pregabalin should be discontinued immediately.

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

Pregabalin has been associated with dizziness and somnolence, which may increase the risk of traumatic events (falls) in elderly patients. Loss of consciousness, confusion, and psychiatric disturbances have been reported. Therefore, patients should be advised to exercise caution until they are aware of the potential effects of the medicinal product.

Visual disturbances

During clinical trials, blurred vision was reported more frequently in patients receiving pregabalin compared to those receiving placebo. In most cases, this phenomenon resolved with continued use of the drug. In studies involving ophthalmological examinations, the frequency of decreased visual acuity and visual field changes was higher in patients receiving pregabalin compared to placebo group patients; the frequency of ocular fundus changes was higher in the placebo group.

Adverse reactions related to the eye, including vision loss, blurred vision, or other changes in visual acuity, have been reported, many of which were transient. Symptoms related to the eye may decrease or resolve after discontinuation of pregabalin.

Renal impairment

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

Discontinuation of concomitant antiepileptic drugs

There is insufficient data regarding discontinuation of concomitant antiepileptic drugs after seizure control has been achieved by adding pregabalin to the treatment regimen to allow transition to pregabalin monotherapy.

Withdrawal symptoms

Withdrawal symptoms have been observed in some patients after discontinuation of short-term or long-term pregabalin therapy. Reported events include insomnia, headache, nausea, anxiety, diarrhea, flu-like symptoms, restlessness, depression, suicidal ideation, pain, seizures, hyperhidrosis, and dizziness, indicating physical dependence. This information should be communicated to patients prior to initiating treatment. Seizures, including status epilepticus and generalized tonic-clonic seizures, may occur during treatment with pregabalin or shortly after discontinuation. Data on withdrawal after long-term use suggest that the frequency and severity of withdrawal symptoms may depend on the dose.

Heart failure

Cases of congestive heart failure have been reported in some patients taking pregabalin. This reaction was mostly observed during treatment of neuropathic pain in elderly patients with cardiovascular disorders. Pregabalin should be used with caution in such patients. This phenomenon may resolve after 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 overall frequency of adverse reactions, particularly CNS-related adverse reactions such as somnolence, was increased. This may be related to additive effects of concomitant medications (e.g., antispastic agents) required for treatment of this condition. This should be taken into account when prescribing pregabalin to such patients.

Respiratory depression

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

Suicidal thoughts and behavior

Cases of suicidal thoughts and behavior have been reported in patients treated with antiepileptic drugs for various indications. A meta-analysis of randomized, placebo-controlled trials of antiepileptic drugs also showed a small increased risk of suicidal thoughts and behavior. The mechanism of this risk is unknown. Post-marketing reports have described cases of suicidal thoughts and behavior in patients receiving pregabalin (see section "Adverse reactions"). An epidemiological study using a self-controlled design (comparing treatment periods with non-treatment periods in individual patients) demonstrated an increased risk of new-onset suicidal behavior and fatal outcomes due to suicide in patients receiving pregabalin.

Patients and caregivers should seek medical help if signs of suicidal thoughts or behavior occur. Patients should be monitored for signs of suicidal thoughts and behavior, and appropriate treatment should be considered. If suicidal thoughts or behavior occur, discontinuation of pregabalin therapy should be considered.

Worsening of lower gastrointestinal tract function

Events related to worsening of lower gastrointestinal tract function (intestinal obstruction, paralytic ileus, constipation) have been reported with pregabalin use, particularly when used concomitantly with medications that may cause constipation, such as opioid analgesics. When pregabalin is used in combination with opioids, preventive measures for constipation should be implemented (especially in women and elderly patients).

Concomitant use with opioids

Caution is recommended when prescribing pregabalin concomitantly with opioids due to the risk of CNS depression (see section "Interaction with other medicinal products and other forms of interaction"). In a case-control study of individuals using opioids, an increased risk of opioid-related mortality was observed in patients using pregabalin concomitantly with an opioid compared to those using opioids alone (adjusted odds ratio [aOR], 1.68 [95% CI, 1.19–2.36]). This increased risk was observed at low doses of pregabalin (≤ 300 mg, aOR 1.52 [95% CI, 1.04–2.22]) with a trend toward increased risk at higher doses of pregabalin (> 300 mg, aOR 2.55 [95% CI, 1.24–5.06]).

Improper use, abuse, or dependence

Cases of improper use, abuse, and dependence have been reported. The drug should be used with caution in patients with a history of substance abuse; patients should be monitored for symptoms of improper use, abuse, or dependence on pregabalin (cases of tolerance development, dose escalation, and drug-seeking behavior have been reported).

Encephalopathy

Cases of encephalopathy occurred predominantly in patients with comorbid conditions that may cause encephalopathy.

Severe skin adverse reactions (SSARs)

Severe skin adverse reactions (SSARs), including Stevens-Johnson syndrome and toxic epidermal necrolysis, which may be life-threatening or fatal, have been rarely reported in association with pregabalin treatment. Patients should be informed about the signs and symptoms of such reactions, and skin reactions should be closely monitored during treatment. If signs or symptoms suggestive of these reactions occur, pregabalin should be discontinued immediately and alternative treatment considered (if necessary).

Women of childbearing potential/contraception

Use of pregabalin during the first trimester of pregnancy may cause serious congenital malformations (CM) in the unborn child. The drug should not be used during pregnancy except in cases where the expected benefit to the mother clearly outweighs the potential risk to the fetus. Women of childbearing potential should use effective contraception during treatment with pregabalin (see section "Use during pregnancy or lactation").

Use during pregnancy or lactation.

Women of childbearing potential/contraceptive methods for women and men

Since the potential risk to humans is unknown, women of childbearing potential should use effective contraceptive methods.

Pregnancy

Animal studies have demonstrated reproductive toxicity. Pregabalin has been shown to cross the placenta in rats. Pregabalin may cross the human placenta. The drug should not be used during pregnancy except in exceptional cases where the expected benefit to the pregnant woman clearly outweighs the potential risk to the fetus.

Serious congenital malformations (CM)

Data from an observational study involving over 2700 pregnant women exposed to pregabalin during the first trimester showed a higher prevalence of serious CMs among children (live or stillborn) exposed to pregabalin in utero compared to children not exposed (5.9% vs. 4.1%).

The risk of serious CMs in children exposed to pregabalin in utero during the first trimester of pregnancy was slightly higher compared to children not exposed (adjusted prevalence ratio and 95% confidence interval: 1.14 (0.96–1.35)) and compared to the population exposed to lamotrigine (1.29 (1.01–1.65)) or duloxetine (1.39 (1.07–1.82)).

Analysis of specific CMs showed a higher risk of orofacial clefts and defects of the eye, nervous, or genitourinary system, but the numbers were small and estimates imprecise.

Therefore, the drug should not be used during pregnancy unless clearly necessary (used only when the expected benefit to the mother clearly outweighs the potential risk to the fetus).

Lactation

Pregabalin passes into human breast milk. The effect of pregabalin on newborns/infants is unknown. A decision should be made whether to discontinue breastfeeding or to discontinue pregabalin therapy, taking into account the benefits of breastfeeding for the child and the benefits of treatment for the woman.

Fertility

There are no clinical data on the effect of pregabalin on female fertility.

In a clinical study assessing the effect of pregabalin on sperm motility in healthy male volunteers, a dose of 600 mg per day was administered. After 3 months of treatment, no effect on sperm motility was observed.

In fertility studies in female rats, an adverse effect on reproductive function was observed. Similarly, in fertility studies in male rats, an adverse effect on reproductive function and development was observed. The clinical significance of these findings is unknown.

Ability to affect reaction speed when driving vehicles or operating machinery.

The medicinal product may have a minor or moderate influence on the ability to drive vehicles or operate machinery. The drug may cause dizziness and somnolence and may affect the ability to drive vehicles or operate machinery. Therefore, patients should be advised to refrain from driving vehicles or operating complex machinery or engaging in other potentially hazardous activities until it is known whether this medicinal product affects their ability to perform such activities.

Dosage and Administration

For oral use.

The dosage range may vary from 150 to 600 mg per day. The daily dose should be divided into 2 or 3 doses.

Neuropathic pain

Treatment with pregabalin may be initiated at a dose of 150 mg per day, divided into 2 or 3 doses. Depending on efficacy and tolerability in individual patients, the dose may be increased to 300 mg per day after an interval of 3 to 7 days, and if necessary, to the maximum dose of 600 mg per day after an additional 7-day interval.

Epilepsy

Treatment with pregabalin may be initiated at a dose of 150 mg per day, divided into 2 or 3 doses. Depending on efficacy and tolerability in individual patients, the dose may be increased to 300 mg per day after the first week of treatment. After another week, the dose may be increased to the maximum of 600 mg per day.

Generalized anxiety disorder

The daily dose, divided into 2 or 3 doses, may range from 150 to 600 mg per day. The need for continued treatment should be periodically reassessed.

Treatment with pregabalin may be initiated at a dose of 150 mg per day. Depending on efficacy and tolerability in individual patients, the dose may be increased to 300 mg per day after the first week of treatment. After another week of treatment, the dose may be increased to 450 mg per day. Following an additional week, the dose may be increased to the maximum of 600 mg per day.

Discontinuation of pregabalin therapy

According to current clinical practice, if discontinuation of pregabalin therapy is necessary, it is recommended to taper the dose gradually over a period of at least one week, regardless of the indication.

Patients with renal impairment

Pregabalin is eliminated from systemic circulation in unchanged form primarily by renal excretion. Since pregabalin clearance is directly proportional to creatinine clearance (CrCl), dosage reduction in patients with impaired renal function should be individualized according to creatinine clearance (CrCl), as indicated in the table below and calculated using the following formula:

CrCl (mL/min) =

Pregabalin is effectively removed from plasma by hemodialysis (approximately 50% of the drug is eliminated 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, an extra dose of the drug should be administered immediately after each 4-hour hemodialysis session (see table).

Dosage adjustment of pregabalin according to renal function

Creatinine clearance (CLcr), (mL/min)	Total daily dose of pregabalin *		Dosing regimen
	Initial dose (mg/day)	Maximum dose (mg/day)
≥ 60	150	600	2–3 times daily
≥ 30–< 60	75	300	2–3 times daily
≥ 15–< 30	25–50	150	1–2 times daily
< 15	25	75	Once daily
Additional dose after hemodialysis (mg)
	25	100	Single dose

*The total daily dose (mg/day) should be divided by the number of doses according to the dosing regimen to obtain the single dose (mg/dose).

Patients with 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 (see section "Pharmacological properties").

The drug is taken independently of food intake.

Children.

Safety and efficacy of pregabalin in children (under 18 years of age) have not been established. No data are available.

Overdose.

The most commonly reported adverse reactions in cases of pregabalin overdose were somnolence, confusion, agitation, and restlessness.

Cases of coma have been reported rarely.

Treatment of pregabalin overdose consists of general supportive measures and, if necessary, may include hemodialysis.

Side effects.

The most commonly reported side effects were dizziness and somnolence. Side effects were generally mild or moderate in severity.

Adverse reactions are listed by system organ class and frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); frequency not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are listed in order of decreasing severity.

The adverse reactions listed may also be related to the underlying disease and/or concomitant use of other medicinal products.

During treatment of central neuropathic pain due to spinal cord injury, the overall frequency of adverse reactions increased, as did the frequency of CNS-related adverse reactions, particularly somnolence (see section "Special warnings and precautions for use").

Infections and infestations

Common: nasopharyngitis.

Blood and lymphatic system disorders

Uncommon: neutropenia.

Immune system disorders

Uncommon: hypersensitivity.

Rare: angioedema, allergic reactions, 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 behaviour, suicidal ideation.

Nervous system disorders

Very common: dizziness, somnolence, headache.

Common: ataxia, coordination impairment, 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 impairment, mental impairment, speech disorder, hyporeflexia, hyperesthesia, burning sensation, ageusia, malaise, perioral paresthesia, myoclonus.

Rare: convulsions, parosmia, hypokinesia, dysphagia, parkinsonism, hypoalgesia, dependence, cerebellar syndrome, cogwheel syndrome, coma, delirium, encephalopathy, extrapyramidal syndrome, 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 defect, reduced visual acuity, eye pain, asthenopia, photopsia, dry eyes, increased lacrimation, eye irritation, blepharitis, accommodation disorder, subconjunctival haemorrhage, photophobia, retinal edema.

Rare: vision loss, keratitis, oscillopsia, altered depth perception, mydriasis, strabismus, visual brightness, anisocoria, corneal ulcer, exophthalmos, oculomotor nerve 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, arterial hypertension, flushing, hyperemia, cold sensation in extremities.

Rare: QT interval prolongation, 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, excessive salivation, oral hypesthesia, cholecystitis, cholelithiasis, colitis, gastrointestinal hemorrhage, melena, tongue swelling, rectal bleeding.

Rare: ascites, tongue swelling, 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

Common: pressure ulcers.

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

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

Musculoskeletal and connective tissue disorders

Common: muscle spasms, arthralgia, back pain, limb pain, neck spasm.

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

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 swelling, gynecomastia, cervicitis, balanitis, epididymitis.

General disorders and administration site conditions

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

Uncommon: generalized edema, facial swelling, chest tightness, pain, increased body temperature, thirst, chills, malaise, abscess, cellulitis, photosensitivity reactions.

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

Investigations

Common: weight increased.

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

Rare: decreased blood leukocyte count.

*Elevated alanine aminotransferase, elevated aspartate aminotransferase.

Symptoms of withdrawal have been observed in some patients following discontinuation of short- or long-term pregabalin treatment. Reported events include: insomnia, headache, nausea, anxiety, diarrhea, influenza-like symptoms, convulsions, restlessness, depression, suicidal thoughts, pain, hyperhidrosis, and dizziness. This information should be communicated to the patient prior to initiating treatment.

Data on withdrawal following prolonged pregabalin use suggest that the frequency and severity of withdrawal symptoms may be dose-dependent.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals, as well as patients or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua/.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 30 °C.

Keep out of reach and sight of children.

Packaging.

75 mg: 10 capsules in a blister; 3 blisters in a cardboard pack.

150 mg: 4 capsules in a blister; 3 blisters in a cardboard pack; 10 capsules in a blister; 3 blisters in a cardboard pack.

Prescription category. Prescription only.

Manufacturer.

Torrent Pharmaceuticals Ltd.

Manufacturer's address and location of operations.

Indrad Plant, Vill. Indrad, Taluka Kadi, Dist. Mehsana, Gujarat 382721, India.