Torgabalin 75

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, gelatin capsule size #4*;

*Composition of gelatin capsule size #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, gelatin capsule size #1*;

*Composition of gelatin capsule size #1: gelatin, sodium lauryl sulfate, titanium dioxide (E 171).

Pharmaceutical form. Hard capsules.

Main physicochemical properties:

75 mg capsules: hard gelatin capsules size #4 with an opaque orange cap and a white body, marked "1360" on the cap and "75" on the body, containing a white to almost white powder;

150 mg capsules: hard gelatin capsules size #1 with an opaque white cap and body, marked "1362" on the cap and "150" on the body, containing a 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 maximum 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 approximately a 25–30% decrease in maximum concentration (Cmax) and an increase in time to maximum concentration (tmax) by about 2.5 hours. However, administration of pregabalin with food did 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 radioactivity is excreted in urine as unchanged drug. The N-methylated derivative of pregabalin (the main metabolite detected in urine) accounted 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 removed 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 plasma concentrations of pregabalin.

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, dose reduction is required in 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 plasma concentrations of pregabalin.

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

Clinical characteristics.

Indications.

Neuropathic pain

Treatment of neuropathic pain in adults due to damage of the peripheral and central nervous system.

Epilepsy

As 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 may cause or be subject to pharmacokinetic 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 do not have a 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. In the post-marketing surveillance period, cases of respiratory depression and coma have been reported in patients taking pregabalin together with other medicinal products that depress CNS function. Pregabalin may likely enhance cognitive and motor 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 their antihyperglycemic medication dosage.

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 accidental injury (falls) in elderly patients. Cases of 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 disorders

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

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

Renal impairment

Cases of renal impairment have been reported. This effect was sometimes reversible after discontinuation of pregabalin.

Discontinuation of concomitant antiepileptic drugs

There is insufficient data on discontinuation of concomitant antiepileptic drugs after seizure control has been achieved with the addition of pregabalin to support switching to pregabalin monotherapy.

Withdrawal symptoms

Withdrawal symptoms have been observed in some patients after discontinuation of short-term or long-term pregabalin therapy. Reported symptoms 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 epileptic status and generalized seizures, may occur during pregabalin treatment or shortly after discontinuation. Data on withdrawal after prolonged pregabalin use suggest that the frequency and severity of withdrawal symptoms may be dose-dependent.

Heart failure

Cases of congestive heart failure have been reported in some patients taking pregabalin. This reaction was mostly observed during pregabalin treatment for neuropathic pain in elderly patients with cardiovascular disorders. Pregabalin should be used with caution in such patients. This effect 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 overall incidence 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 the management of this condition. This factor should be taken into account when prescribing pregabalin to such patients.

Respiratory depression

Cases of severe respiratory depression have been reported in association with pregabalin use. 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 adjustment may be required for these patients.

Suicidal ideation and behavior

Cases of suicidal ideation 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 ideation 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 within 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 ideation or behavior occur. Patients should be monitored for emergence of suicidal thoughts and behavior, and appropriate treatment should be considered. If suicidal ideation or behavior occurs, 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 co-administered with medications that may cause constipation, such as opioid analgesics. When pregabalin is used concomitantly 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 who used 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 pregabalin doses (≤ 300 mg, aOR 1.52 [95% CI, 1.04–2.22]) with a trend toward increased risk at higher pregabalin doses (> 300 mg, aOR 2.55 [95% CI 1.24–5.06]).

Abuse, misuse, or dependence

Cases of abuse, misuse, 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 inappropriate use, abuse, or dependence on pregabalin (cases of tolerance development, dose escalation, and drug-seeking behavior have been reported).

Encephalopathy

Cases of encephalopathy have occurred predominantly in patients with comorbid conditions that may predispose to encephalopathy.

Severe skin reactions (SSRs)

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

Women of childbearing potential/contraception

Pregabalin use during the first trimester of pregnancy may cause serious congenital malformations (CMs) 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 breastfeeding").

Use during pregnancy or breastfeeding.

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 contraception.

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 (CMs)

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 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 populations exposed to lamotrigine (1.29 (1.01–1.65)) or duloxetine (1.39 (1.07–1.82)).

Analysis of specific CMs showed higher risks for orofacial clefts and eye, nervous, or urogenital system defects, although the numbers were small and estimates imprecise.

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

Breastfeeding period

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 benefit of breastfeeding for the child and the benefit of treatment for the woman.

Fertility

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

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

In fertility studies in female rats, adverse effects on reproductive function were observed. Similarly, in fertility studies in male rats, adverse effects on reproductive function and development were observed. The clinical relevance of these findings is unknown.

Effect on ability to drive and use machines.

The medicinal product may have a minor or moderate influence on the ability to drive and use machines. 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 or operating complex machinery or engaging in other potentially hazardous activities until they know how 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 individual patient tolerance, 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 individual patient tolerance, 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 dose, divided into 2 or 3 administrations, may range from 150 to 600 mg per day. The need for continued treatment should be periodically re-evaluated.

Treatment with pregabalin may be initiated at a dose of 150 mg per day. Depending on efficacy and individual patient tolerance, 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 treatment

According to current clinical practice, if discontinuation of pregabalin treatment 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, 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 removed 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 supplemental dose 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 a day
≥ 30–< 60	75	300	2-3 times a day
≥ 15–< 30	25-50	150	1-2 times a day
< 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 in order to obtain the dose per administration (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 medication should be 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.

Coma has been reported rarely.

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

Adverse Reactions

The most commonly reported adverse reactions were dizziness and somnolence. Adverse reactions 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 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 incidence of adverse reactions increased, as did the incidence 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 changes, depersonalization, difficulty in word finding, abnormal dreams, increased libido, anorgasmia, apathy.

Rare: disinhibition, suicidal behaviour, suicidal ideation.

Nervous system disorders

Very common: dizziness, somnolence, headache.

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

Rare: convulsions, parosmia, hypokinesia, dysphagia, parkinsonism, hypalgesia, 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 hemorrhage, 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 abscesses.

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 cramps, 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 enlargement, gynecomastia, cervicitis, balanitis, epididymitis.

General disorders and administration site conditions

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

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

Rare: granuloma, self-injury, 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.

*Elevated alanine aminotransferase, elevated aspartate aminotransferase.

Withdrawal symptoms have been observed in some patients following discontinuation of short- or long-term pregabalin treatment. Reported events include: insomnia, headache, nausea, anxiety, diarrhea, flu-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 pregabalin discontinuation after prolonged use suggest that the frequency and severity of withdrawal symptoms may be dose-dependent.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients 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 status. Prescription only.

Manufacturer.

Torrent Pharmaceuticals Ltd.

Manufacturer's address and site of operation.

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