Sudorega

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT SUDOREGA (SUDOREGA)

Composition:

Active substance: pregabalin;

1 capsule contains 75 mg or 150 mg of pregabalin;

Excipients: lactose monohydrate; corn starch; talc;

capsule shell: gelatin, titanium dioxide (E 171), sodium lauryl sulfate, iron oxide red (E 172) – for the 75 mg dosage; gelatin, titanium dioxide (E 171), sodium lauryl sulfate – for the 150 mg dosage.

Pharmaceutical form. Hard capsules.

Main physicochemical properties:

75 mg capsules: white to almost white powder in a solid, opaque gelatin capsule of size "4" with a red cap and a white body, marked with black characters "RDY" on the cap and "293" on the body;

150 mg capsules: white to almost white powder in a solid, opaque gelatin capsule of size "2" with a white cap and a white body, marked with black characters "RDY" on the cap and "295" on the body.

Pharmacotherapeutic group. Antiepileptic drugs. Other antiepileptics. ATC code N03AX16.

Pharmacological properties.

Pharmacodynamics.

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

Mechanism of action

Pregabalin binds to the auxiliary subunit (α2-δ protein) of voltage-dependent calcium channels in the central nervous system (CNS).

Clinical efficacy and safety

Neuropathic pain

Clinical studies with pregabalin have demonstrated efficacy in the treatment of diabetic neuropathy, postherpetic neuralgia, and spinal cord injury. The efficacy of the drug in other types of neuropathic pain has not been studied.

Epilepsy

In three controlled clinical trials of 12 weeks' duration with dosing regimens of 2 or 3 times daily, pregabalin (as adjunctive therapy) reduced seizure frequency as early as the first week of treatment.

Generalized anxiety disorder

In controlled clinical trials (lasting 4–8 weeks), improvement in symptoms of generalized anxiety disorder was reported according to the Hamilton Anxiety Rating Scale (HAM-A), which was observed during the first week of treatment with pregabalin.

Fibromyalgia

Pregabalin studies included patients diagnosed with fibromyalgia based on American College of Rheumatology criteria (widespread pain lasting at least 3 months and pain present in 11 or more of 18 specific tender points). The studies demonstrated a reduction in pain measured by the visual analog scale. Additional improvement was demonstrated by patient global assessment and fibromyalgia impact questionnaire.

Pharmacokinetics.

Pharmacokinetic parameters of pregabalin at steady state 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 and reaches maximum plasma concentration (Cmax) within 1 hour after single or multiple doses. The calculated oral bioavailability of pregabalin is 90% or more and is dose-independent. Steady-state concentrations are achieved within 24–48 hours after multiple dosing. The rate of pregabalin absorption is reduced when administered with food, resulting in approximately a 25–30% decrease in Cmax and a prolongation of time to reach maximum concentration (tmax) by about 2.5 hours. However, co-administration with food did not have a clinically significant effect on the extent of absorption.

Distribution

Pregabalin crosses the blood-brain barrier. It also crosses the placenta in animals and is excreted into milk during lactation. In humans, the apparent volume of distribution of pregabalin after oral administration is approximately 0.56 L/kg. Pregabalin does not bind to plasma proteins.

Metabolism

In humans, pregabalin undergoes minimal metabolism. After administration of radiolabeled pregabalin, approximately 98% of the radioactivity is excreted in urine as unchanged pregabalin. The N-methylated derivative of pregabalin is the main metabolite detected in urine, accounting for 0.9% of the administered dose. Racemization of the S-enantiomer of pregabalin to the R-enantiomer did not occur during preclinical studies.

Excretion

Pregabalin is eliminated from systemic circulation unchanged, primarily via renal excretion. The mean elimination half-life of pregabalin is 6.3 hours. Plasma and renal clearance of pregabalin are directly proportional to creatinine clearance (see section "Pharmacokinetics" ("Renal impairment")).

Dosage adjustment is required for patients with renal impairment or patients undergoing hemodialysis (see section "Dosage and administration", Table 1).

Linearity/non-linearity

The pharmacokinetics of pregabalin are linear over the entire recommended dose range. The variability in pregabalin pharmacokinetics among patients 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.

Gender

Clinical study results indicate no clinically significant effect of gender on plasma pregabalin 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 the drug is primarily eliminated by the kidneys, dosage reduction is required in patients with renal impairment, and an additional dose should be administered after hemodialysis (see section "Dosage and administration", Table 1).

Hepatic impairment

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

Geriatric patients

Pregabalin clearance tends to decrease with age. This age-related reduction in pregabalin clearance after oral administration is consistent with the age-related decline in creatinine clearance. Dose reduction of pregabalin may be required in patients with age-related renal impairment (see section "Dosage and administration", Table 1).

Lactation period

The pharmacokinetics of pregabalin administered at a dose of 150 mg every 12 hours (daily dose of 300 mg) were evaluated in 10 breastfeeding women at least 12 weeks postpartum. Breastfeeding did not affect or had only a minimal effect on pregabalin pharmacokinetics. Pregabalin was excreted into breast milk, with its average steady-state concentration being approximately 76% of the maternal plasma concentration. The calculated infant dose received via breast milk (assuming average milk intake of 150 mL/kg/day) from a woman taking pregabalin at a daily dose of 300 mg or the maximum daily dose of 600 mg was 0.31 or 0.62 mg/kg/day, respectively. These calculated doses represent approximately 7% of the mother's total daily dose normalized to mg/kg.

Clinical Characteristics.

Indications.

Neuropathic pain.

Treatment of neuropathic pain in adults with peripheral or central nervous system involvement.

Epilepsy.

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

Generalized anxiety disorder.

Treatment of generalized anxiety disorder in adults.

Fibromyalgia.

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 negligible 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 medicinal product.

Medicinal products affecting the CNS

Pregabalin may enhance the effects of ethanol and lorazepam. In controlled clinical trials, concomitant administration of multiple oral doses of pregabalin with oxycodone, lorazepam, or ethanol did not result in clinically significant effects on respiratory function. In the post-marketing surveillance period, cases of respiratory depression, coma, and fatal outcomes have been reported in patients who took pregabalin together with opioids and/or other medicinal products that suppress CNS function, particularly in patients who abused these substances. Pregabalin is likely to potentiate cognitive and motor impairment caused by oxycodone.

Interactions in elderly patients

No specific pharmacodynamic interaction studies were conducted in elderly volunteers. Drug interaction studies were performed only in adult patients.

Special precautions for use.

Patients with diabetes mellitus

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

Hypersensitivity reactions

Post-marketing reports have described hypersensitivity reactions, including angioedema. If symptoms of angioedema such as facial swelling, perioral swelling, or swelling of the upper airways occur, pregabalin should be discontinued immediately.

Severe skin adverse reactions

Rare cases of severe skin adverse reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, which may be life-threatening or fatal, have been reported during treatment with pregabalin. Patients should be informed about the signs and symptoms of skin reactions, and closely monitored for their occurrence. If signs or symptoms suggestive of these reactions appear, 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 (falls) in elderly patients. Post-marketing reports have described cases of loss of consciousness, confusion, and psychiatric disturbances. Therefore, patients should be advised to exercise caution until they are aware of the potential effects of this medicinal product.

Visual disorders

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

Post-marketing reports have also described ocular adverse reactions, including vision loss, blurred vision, or other changes in visual acuity, many of which were transient. Discontinuation of pregabalin may help reduce or eliminate these ocular symptoms.

Renal impairment

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

Discontinuation of concomitant antiepileptic medicinal products

There is insufficient data on whether concomitant antiepileptic drugs can be discontinued after seizure control has been achieved with the addition of pregabalin to allow transition to pregabalin monotherapy.

Withdrawal symptoms

In some patients, withdrawal symptoms have been observed after discontinuation of short-term or long-term pregabalin therapy. Reported events include insomnia, headache, nausea, anxiety, diarrhea, flu-like symptoms, restlessness, depression, pain, seizures, hyperhidrosis, and dizziness, suggesting physical dependence. This information should be communicated to the patient prior to initiating treatment.

Seizures, including epileptic status and generalized tonic-clonic seizures, may occur during treatment with pregabalin or shortly after discontinuation.

Data on pregabalin discontinuation after long-term use indicate that the frequency and severity of withdrawal symptoms may be dose-dependent.

Heart failure

Post-marketing reports have described cases of heart failure in some patients taking pregabalin. This reaction has mostly been observed during treatment of neuropathic pain in elderly patients with pre-existing cardiovascular disorders. Pregabalin should be used with caution in such patients. This condition 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 incidence of adverse reactions, particularly those affecting the CNS such as somnolence, increased. This may be related to additive effects of concomitant medicinal products (e.g., antispastic agents) required for treatment of this condition. This should be taken into account when prescribing pregabalin for this indication.

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 greater risk of this serious adverse reaction. Dose adjustment may be required for such patients.

Suicidal ideation and behavior

Cases of suicidal ideation and behavior have been reported in patients treated with antiepileptic medicinal products for various indications. A meta-analysis of data from 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 taking pregabalin.

Therefore, patients should be closely monitored for signs of suicidal thoughts and behavior, and appropriate treatment considered. Consideration should be given to discontinuing pregabalin therapy if suicidal thoughts or behaviors occur. Patients (and caregivers) should seek immediate medical help if signs of suicidal ideation or behavior emerge.

Lower gastrointestinal tract dysfunction

Post-marketing reports have described events related to lower gastrointestinal tract dysfunction (such as intestinal obstruction, paralytic ileus, constipation) following pregabalin use in combination with medicinal products that may cause constipation, such as opioid analgesics. Preventive measures for constipation should be taken when pregabalin is used concomitantly with opioids (especially in elderly patients and younger women).

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 opioid users, an increased risk of opioid-related mortality was observed in patients receiving pregabalin together with an opioid compared to those receiving opioids alone (adjusted odds ratio [aOR], 1.68 [95% CI, 1.19–2.36]). This increased risk was observed with low-dose pregabalin (≤ 300 mg, aOR 1.52 [95% CI, 1.04–2.22]) and tended to increase with higher doses (> 300 mg, aOR 2.55 [95% CI, 1.24–5.06]).

Misuse, abuse, or dependence

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

Encephalopathy

Cases of encephalopathy have been reported, occurring primarily in patients with concomitant conditions that may predispose to encephalopathy.

Lactose intolerance

Sudorega contains lactose monohydrate. Patients with intolerance to certain sugars should consult their physician before taking this medicinal product.

Special precautions

Keep out of reach and sight of children.

Use during pregnancy or breastfeeding.

Women of reproductive potential/contraception in women and men

Since the potential risk to humans is unknown, women of reproductive potential should use effective contraception.

Pregnancy

Adequate data on the use of pregabalin in pregnant women are lacking.

Animal studies have shown reproductive toxicity. The potential risk to humans is unknown.

Sudorega 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

A small amount of pregabalin has been detected in human breast milk. Women who are breastfeeding should be advised that breastfeeding is not recommended during treatment with pregabalin.

Fertility

Clinical data on the effect of pregabalin on female fertility are lacking.

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

In fertility studies in rats, adverse effects on reproductive function were observed in both females and males, as well as developmental effects in males. The clinical relevance of these findings is unknown.

Ability to influence driving and use of machines.

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

Method of administration and dosage.

Method of administration

Sudorega should be taken independently of food intake.

Sudorega is intended exclusively for oral administration.

Dosage

The dosage range may vary between 150–600 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 individual response and tolerability, the dose may be increased to 300 mg per day after 3–7 days, and if necessary, to the maximum dose of 600 mg per day after another 7 days.

Epilepsy

Treatment with pregabalin may be initiated at a dose of 150 mg per day, divided into 2 or 3 doses. Depending on individual response and tolerability, 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.

Fibromyalgia

The recommended dose of the drug for the treatment of fibromyalgia ranges from 300 to 450 mg per day. Treatment should be initiated at a dose of 75 mg twice daily (150 mg per day). Depending on efficacy and tolerability, the dose may be increased to 150 mg twice daily (300 mg per day) within one week. For patients in whom a dose of 300 mg per day is insufficiently effective, the dose may be increased to 225 mg twice daily (450 mg per day). Although a study has evaluated a dose of 600 mg per day, there is no evidence that this dose provides additional benefit; moreover, this dose was associated with poorer tolerability. Considering dose-dependent adverse reactions, doses exceeding 450 mg per day are not recommended. Since pregabalin is primarily eliminated via the kidneys, dosage adjustment is necessary in patients with renal impairment.

Generalized anxiety disorder

The daily dose, divided into 2 or 3 doses, may range from 150–600 mg per day. The necessity of continued treatment should be periodically reviewed.

Treatment with pregabalin may be initiated at a dose of 150 mg per day. Depending on individual response and tolerability, 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 450 mg per day. After an additional week, the dose may be increased to the maximum of 600 mg per day.

Discontinuation of pregabalin

According to current clinical practice, pregabalin treatment should be discontinued gradually over a minimum of one week, regardless of the indication (see sections "Special precautions" and "Adverse reactions").

Renal impairment

Pregabalin is eliminated from systemic circulation unchanged, primarily via renal excretion. Since pregabalin clearance is directly proportional to creatinine clearance (see section "Pharmacokinetics"), dosage should be individually adjusted in patients with renal impairment according to creatinine clearance (CLcr), as indicated in Table 1. Creatinine clearance should be calculated using the following formula:

Pregabalin is effectively removed from plasma by hemodialysis (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 should be administered immediately after each 4-hour hemodialysis session (see Table 1).

Table 1

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
Supplemental dose after hemodialysis (mg)
	25	100	Single dose+

*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 (see section "Pharmacokinetics").

Elderly patients (aged 65 years and older)

For elderly patients, dose reduction of pregabalin may be required due to impaired renal function (see section "Pharmacokinetics").

Children.

The safety and efficacy of Sudorega in pediatric patients (under 18 years of age) have not been established; therefore, the use of this medicinal product in this patient population is not recommended.

Overdose.

Since the marketing of the medicinal product, the most commonly reported adverse reactions in cases of pregabalin overdose have been somnolence, confusion, agitation, and restlessness. Seizures have also been reported. Coma has been reported rarely.

Management of pregabalin overdose consists of general supportive measures and, if necessary, may include hemodialysis (see section "Posology and method of administration", Table 1).

Adverse reactions

In the clinical development program for pregabalin, over 8,900 patients received the drug, of whom 5,600 were participants in double-blind, placebo-controlled trials. The most commonly reported adverse reactions were dizziness and somnolence. Adverse reactions were generally of mild or moderate severity. In all controlled trials, the discontinuation rate due to adverse reactions was 12% among patients receiving pregabalin and 5% among those receiving placebo. The most common adverse reactions leading to withdrawal from the pregabalin treatment group were dizziness and somnolence.

Table 2 lists all adverse reactions that occurred more frequently than with placebo and in more than one patient. These adverse reactions are categorized by system organ class and frequency as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated from the available data).

Within each frequency category, adverse reactions are listed in order of decreasing severity.

The listed 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 frequency of adverse reactions increased, particularly CNS-related adverse reactions such as somnolence (see section "Special warnings and precautions for use").

Additional adverse reactions reported after marketing authorization are listed below and are indicated in italics.

Table 2

System organ class	Adverse reactions to the drug
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 swings, depersonalization, word-finding difficulty, pathological dreams, increased libido, anorgasmia, apathy
Rare	Disinhibition, suicidal behavior, suicidal thoughts
Not known	Drug dependence
Nervous system disorders
Very common	Dizziness, somnolence, headache
Common	Ataxia, coordination disorder, tremor, dysarthria, amnesia, memory impairment, attention disturbance, paresthesia, hypoesthesia, sedative effect, balance disorder, lethargy
Uncommon	Syncope, stupor, myoclonus, loss of consciousness, psychomotor hyperactivity, dyskinesia, postural dizziness, intention tremor, nystagmus, cognitive impairment, mental disorder, speech disorders, hyporeflexia, hyperesthesia, burning sensation, ageusia, malaise, apathy, perioral paresthesia, myoclonus
Rare	Seizures, parosmia, hypokinesia, dysphagia, hypalgesia, dependence, cerebellar syndrome, cogwheel syndrome, coma, delirium, encephalopathy, extrapyramidal syndrome, Guillain–Barré syndrome, intracranial hypertension, manic reactions, paranoid reactions, sleep disorders, parkinsonism
Eye disorders
Common	Blurred vision, diplopia, conjunctivitis
Uncommon	Peripheral vision loss, visual disturbance, eye swelling, visual field defects, decreased visual acuity, eye pain, asthenopia, photopsia, dry eyes, increased lacrimation, eye irritation, blepharitis, accommodation disorder, eye hemorrhage, photophobia, retinal edema
Rare	Loss of vision, keratitis, oscillopsia, altered depth perception, mydriasis, strabismus, visual brightness, anisocoria, corneal ulcer, exophthalmos, oculomotor 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
Rare	QT interval prolongation, sinus tachycardia, sinus arrhythmia
Vascular disorders
Uncommon	Arterial hypotension, arterial hypertension, flushing, hyperemia, cold sensation in extremities
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
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, tongue swelling, dysphagia, aphthous stomatitis, esophageal ulcer, periodontal abscess
Hepatobiliary disorders
Uncommon	Elevated 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, toxic epidermal necrolysis, 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 delayed, dysmenorrhea, breast pain, leukorrhea, menorrhagia, metrorrhagia
Rare	Amenorrhea, breast discharge, 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, warmth, thirst, chills, generalized weakness, malaise, abscess, fat tissue inflammation, photosensitivity reactions
Rare	Granuloma, self-harm, 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

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

In some patients, withdrawal symptoms have been observed after discontinuation of short-term or long-term pregabalin therapy. Reported reactions include insomnia, headache, nausea, anxiety, diarrhea, flu-like syndrome, seizures, restlessness, depression, suicidal thoughts, pain, hyperhidrosis, and dizziness, suggesting physical dependence. This information should be communicated to the patient prior to initiating therapy.

Data on pregabalin discontinuation after long-term use indicate that the frequency and severity of withdrawal symptoms may be dose-dependent.

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C.

Packaging. 14 capsules in a blister, 2 blisters per carton.

Prescription status. Prescription only.

Manufacturer. Dr. Reddy’s Laboratories Ltd, FTO – II.

Manufacturer's address and location of business operations.
Survey Nos. 42R, 43, 44R, 45R, 46R, 53, 54, 83, Bachupally Village, Bachupally Mandal, Medchal Malkajgiri District – 500090, Telangana State, India.

Adverse reactions or lack of efficacy during drug use can be reported by calling:
+380 44 207 51 97 or +380 50 414 39 39, or via email: [email protected] (available 24/7).