Replica (Capsules) Instructions for Use

Marketing Authorization Holder

ARS, LLC (Russia)

Manufactured By

Scan Biotech LLC (India)

Labeled By

ROZLEKS PHARM, LLC (Russia)

ATC Code

N02BF02 (Pregabalin)

Active Substance

Pregabalin (Rec.INN registered by WHO)

Dosage Forms

	Replica	Capsules 75 mg: 20, 50, or 100 pcs.
		Capsules 150 mg: 20, 50, or 100 pcs.
		Capsules 300 mg: 20, 50, or 100 pcs.

Dosage Form, Packaging, and Composition

Capsules with a transparent colorless body and a pink cap, hard gelatin size No. 3; capsule contents – white or almost white powder or a mixture of white or almost white powder and colorless crystals.

Excipients: lactose monohydrate – 67 mg, corn starch – 20 mg, talc – 3 mg.

Capsule shell:
Capsule body composition: gelatin – 85.5%, methylparaben – 0.18%, propylparaben – 0.02%, sodium lauryl sulfate – 0.1%, water – 14.2%.
Cap composition gelatin – 85.413%, methylparaben – 0.18%, propylparaben – 0.02%, sodium lauryl sulfate – 0.1%, water – 14.2%, azorubine colorant – 0.0875%.

10 pcs. – Al/PVC blisters (2) – cardboard packs.
10 pcs. – Al/PVC blisters (5) – cardboard packs.
10 pcs. – Al/PVC blisters (10) – cardboard packs.

Capsules with a brownish-red body and cap, hard gelatin size No. 1; capsule contents – white or almost white powder or a mixture of white or almost white powder and colorless crystals.

Excipients: lactose monohydrate – 134 mg, corn starch – 40 mg, talc – 6 mg.

Capsule shell:
Capsule body composition: gelatin – 83.3125%, methylparaben – 0.18%, propylparaben – 0.02%, sodium lauryl sulfate – 0.1%, water – 14.2%, Ponceau 4R colorant – 0.1458%, sunset yellow FCF colorant – 0.2917%, azorubine colorant – 0.5833%, titanium dioxide – 1.1667%.
Cap composition gelatin – 83.3125%, methylparaben – 0.18%, propylparaben – 0.02%, sodium lauryl sulfate – 0.1%, water – 14.2%, Ponceau 4R colorant – 0.1458%, sunset yellow FCF colorant – 0.2917%, azorubine colorant – 0.5833%, titanium dioxide – 1.1667%.

10 pcs. – Al/PVC blisters (2) – cardboard packs.
10 pcs. – Al/PVC blisters (5) – cardboard packs.
10 pcs. – Al/PVC blisters (10) – cardboard packs.

Capsules with a white body and a dark red cap, hard gelatin size No. 0; capsule contents – white or almost white powder or a mixture of white or almost white powder and colorless crystals.

Excipients: lactose monohydrate – 194 mg, corn starch – 40 mg, talc – 6 mg.

Capsule shell:
Capsule body composition: gelatin – 82.875%, methylparaben – 0.18%, propylparaben – 0.02%, sodium lauryl sulfate – 0.1%, water – 14.2%, titanium dioxide – 2.625%.
Cap composition gelatin – 84.147%, methylparaben – 0.18%, propylparaben – 0.02%, sodium lauryl sulfate – 0.1%, water – 14.2%, Ponceau 4R colorant – 0.3937%, sunset yellow FCF colorant – 0.07%, azorubine colorant – 0.3062%, titanium dioxide – 0.5833%.

10 pcs. – Al/PVC blisters (2) – cardboard packs.
10 pcs. – Al/PVC blisters (5) – cardboard packs.
10 pcs. – Al/PVC blisters (10) – cardboard packs.

Clinical-Pharmacological Group

Antiepileptic drug

Pharmacotherapeutic Group

Antiepileptic agent

Pharmacological Action

Anticonvulsant with analgesic and anxiolytic action. Pregabalin is a GABA analogue.

It is assumed that the analgesic and anticonvulsant action is due to the binding of pregabalin to the auxiliary subunit (α₂-delta protein) of voltage-gated calcium channels in the CNS, which leads to the irreversible displacement of [3H]-gabapentin.

Pregabalin reduces the clinical manifestations of generalized anxiety disorder.

Pharmacokinetics

After oral administration on an empty stomach, Pregabalin is rapidly absorbed from the gastrointestinal tract. C_max in plasma is reached within 1 hour after both single and repeated administration. The bioavailability of pregabalin after oral administration is ≥ 90% and is independent of the dose. With repeated use, steady state is reached within 24-48 hours. When taken after a meal, C_max is reduced by approximately 25-30%, and the time to reach C_max is increased to approximately 2.5 hours. However, food intake does not have a clinically significant effect on the overall absorption of pregabalin.

The pharmacokinetics of pregabalin in the range of recommended daily doses is linear, with low interindividual variability (<20%).

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

Pregabalin is practically not metabolized. After administration of labeled pregabalin, approximately 98% of the radioactive label was determined in the urine unchanged. The proportion of the N-methylated derivative of pregabalin, which is the main metabolite found in urine, was 0.9% of the dose. No signs of racemization of the S-enantiomer of pregabalin to the R-enantiomer were noted.

Pregabalin is excreted mainly by the kidneys unchanged. The mean T_1/2 is 6.3 hours. Plasma clearance of pregabalin and renal clearance are directly proportional to CrCl.

The pharmacokinetic parameters of pregabalin at steady state in healthy volunteers, in patients with epilepsy receiving antiepileptic therapy, and in patients receiving it for chronic pain syndromes were similar.

In case of impaired renal function, it should be taken into account that the clearance of pregabalin is directly proportional to CrCl. Pregabalin is effectively removed from plasma by hemodialysis (after a 4-hour hemodialysis session, pregabalin plasma concentrations are reduced by approximately 50%).

The pharmacokinetics of pregabalin in patients with impaired liver function has not been specifically studied. Pregabalin is practically not metabolized and is excreted mainly unchanged in the urine, so impaired liver function should not significantly alter the plasma concentrations of the drug.

When prescribing the drug to elderly patients over 65 years of age, it should be taken into account that the clearance of pregabalin tends to decrease with age, which reflects the age-related decrease in CrCl. Elderly people with impaired renal function may require a dose reduction of the drug.

Indications

Treatment of neuropathic pain in adults.

Treatment of fibromyalgia in adults.

Epilepsy: as adjunctive therapy in adults with partial seizures, with or without secondary generalization.

Treatment of generalized anxiety disorder in adults.

ICD codes

Dosage Regimen

Take orally regardless of meals at a daily dose of 150 to 600 mg in 2 or 3 divided doses.

If treatment needs to be discontinued, it is recommended to do so gradually over a minimum of 1 week.

For patients with impaired renal function, the dose should be individually selected taking into account CrCl.

In patients with impaired liver function, no dose adjustment is required.

For elderly patients over 65 years of age, a dose reduction of pregabalin may be required due to decreased renal function.

If a dose of pregabalin is missed, the next dose should be taken as soon as possible, but the missed dose should not be taken if it is almost time for the next dose.

Adverse Reactions

Psychiatric disorders common – euphoria, confusion, decreased libido, irritability, insomnia, disorientation; uncommon – depersonalization, anorgasmia, anxiety, depression, agitation, mood lability, depressed mood, difficulty in word selection, hallucinations, unusual dreams, increased libido, panic attacks, apathy, increased insomnia; rare – disinhibition, elevated mood.

Nervous system disorders very common – dizziness, drowsiness; common – ataxia, attention disturbance, coordination abnormal, memory impairment, tremor, dysarthria, paresthesia, balance disorder, amnesia, sedated state, lethargy; uncommon – cognitive disorder, hypesthesia, nystagmus, speech disorder, myoclonic seizures, hyporeflexia, dyskinesia, psychomotor hyperactivity, postural dizziness, hyperesthesia, taste loss, burning sensation on mucous membranes and skin, intention tremor, stupor, syncope; rare – hypokinesia, parosmia, dysgraphia; frequency unknown – headache.

Eye disorders common – vertigo, blurred vision, diplopia; uncommon – hyperacusis, visual field defect, visual acuity reduced, eye pain, asthenopia, dry eye, eye swelling, lacrimation increased; rare – photopsia, eye irritation, mydriasis, oscillopsia (subjective sensation of oscillation of viewed objects), depth perception visual impaired, peripheral vision loss, strabismus, visual brightness; frequency unknown – keratitis.

Metabolism and nutrition disorders common – increased appetite, weight increased; uncommon – anorexia, hypoglycemia; rare – weight decreased.

Cardiac disorders uncommon – tachycardia, first degree atrioventricular block, flushing, blood pressure decreased, cold extremities, blood pressure increased; rare – sinus tachycardia, sinus arrhythmia, sinus bradycardia; frequency unknown – chronic heart failure, QT interval prolonged.

Respiratory, thoracic and mediastinal disorders uncommon – dyspnea, cough, nasal dryness, nasopharyngitis; rare – nasal congestion, epistaxis, rhinitis, snoring, throat tightness; uncommon – pulmonary edema.

Gastrointestinal disorders common – dry mouth, constipation, vomiting, flatulence, abdominal distension; uncommon – hypersalivation, gastroesophageal reflux disease, oral mucosa hypesthesia; rare – ascites, dysphagia, pancreatitis; frequency unknown – tongue edema, nausea, diarrhea.

Musculoskeletal and connective tissue disorders: uncommon – muscle twitching, joint swelling, muscle spasms, myalgia, arthralgia, back pain, limb pain, muscle stiffness; rare – neck muscle spasms, neck pain, rhabdomyolysis.

Renal and urinary disorders uncommon – dysuria, urinary incontinence; rare – oliguria, renal failure.

Reproductive system and breast disorders: common – erectile dysfunction; uncommon – delayed ejaculation, sexual dysfunction; rare – amenorrhea, breast pain, breast discharge, dysmenorrhea, breast enlargement.

Blood and lymphatic system disorders rare – neutropenia.

Skin and subcutaneous tissue disorders uncommon – skin hyperemia, sweating, papular rash; rare – cold sweat; frequency unknown – pruritus, Stevens-Johnson syndrome.

Immune system disorders rare – urticaria; frequency unknown – angioedema, hypersensitivity.

Investigations uncommon – increased ALT, increased AST, increased CPK, platelet count decreased; rare – blood glucose increased, blood creatinine increased, blood potassium decreased, white blood cell count decreased.

General disorders and administration site conditions common – fatigue, peripheral edema, feeling drunk, gait disturbance; uncommon – asthenia, falls, thirst, chest tightness, generalized edema, chills, pain; rare – hyperthermia.

Contraindications

Children and adolescents up to 17 years of age inclusive, hypersensitivity to pregabalin.

Use in Pregnancy and Lactation

There are no adequate and well-controlled studies on the safety of pregabalin use during pregnancy. Women of reproductive age using pregabalin should use adequate methods of contraception.

It is not known whether Pregabalin is excreted in human breast milk. If it is necessary to use pregabalin during lactation, the issue of discontinuing breastfeeding should be considered.

In experimental studies in animals, Pregabalin had a toxic effect on reproductive function. It has been established that Pregabalin is excreted in the milk of rats.

Special Precautions

Use with caution in renal failure, in heart failure. Due to isolated reports of uncontrolled use of pregabalin, it should be used with caution in patients with a history of drug dependence (during treatment in such cases, strict medical supervision is required).

In patients with diabetes mellitus, if weight gain occurs during treatment with pregabalin, dose adjustment of hypoglycemic drugs may be required.

Pregabalin should be discontinued if symptoms of angioedema (such as facial edema, perioral edema, or swelling of the upper respiratory tract tissues) develop.

Pregabalin, like other anticonvulsants, may increase the risk of suicidal thoughts or behavior. Therefore, during treatment, patients require careful medical supervision for the emergence or worsening of depression, the appearance of suicidal thoughts or behavior.

Treatment with pregabalin is accompanied by dizziness and drowsiness, which increase the risk of accidental injuries (falls) in the elderly. Cases of loss of consciousness, confusion, and cognitive impairment have also been reported during post-marketing use. Therefore, until patients have assessed the possible effects of pregabalin, they should exercise caution.

Data on the possibility of discontinuing other anticonvulsants when seizures are suppressed by pregabalin and the advisability of pregabalin monotherapy are insufficient. There are reports of the development of seizures, including status epilepticus and petit mal seizures, during the use of pregabalin or immediately after the end of therapy.

Cases of renal failure have also been reported; in some cases, renal function recovered after discontinuation of pregabalin.

The following adverse events were observed as a result of pregabalin withdrawal after long-term or short-term therapy: insomnia, headache, nausea, diarrhea, flu-like syndrome, depression, sweating, dizziness, seizures, and anxiety. There is no information on the frequency and severity of pregabalin withdrawal syndrome manifestations depending on the duration of therapy and its dose.

During post-marketing use of pregabalin, the development of chronic heart failure has been reported during pregabalin therapy, mainly in elderly patients with pre-existing heart conditions receiving the drug for neuropathy. Therefore, Pregabalin should be used with caution in this category of patients. After discontinuation of pregabalin, manifestations of such reactions may disappear.

The frequency of adverse reactions from the CNS, especially such as drowsiness, increases when treating central neuropathic pain due to spinal cord injury, which, however, may be a consequence of the summation of the effects of pregabalin and other concomitantly taken drugs (for example, antispastic drugs). This circumstance should be taken into account when prescribing pregabalin for this indication.

There are reports of cases of dependence developing with the use of pregabalin. Patients with a history of drug dependence require careful medical supervision for symptoms of pregabalin dependence.

Cases of encephalopathy have been noted, especially in patients with concomitant conditions that may lead to the development of encephalopathy.

Effect on ability to drive vehicles and operate machinery

Pregabalin may cause dizziness and drowsiness and thus affect the ability to drive vehicles and operate complex machinery. Patients should not drive vehicles, operate complex machinery, or engage in other potentially hazardous activities until their individual response to pregabalin intake has been established.

Drug Interactions

Cases of respiratory depression and coma have been reported with the concomitant use of pregabalin with other CNS depressants.

Negative effects of pregabalin on gastrointestinal function (including the development of intestinal obstruction, paralytic ileus, constipation) have also been reported when used concomitantly with drugs that cause constipation (such as non-narcotic analgesics).

Repeated oral administration of pregabalin with oxycodone, lorazepam, or ethanol did not have a clinically significant effect on respiration. Pregabalin appears to enhance the cognitive and motor function impairments caused by oxycodone. Pregabalin may enhance the effects of ethanol and lorazepam.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.