Prigabilon^® (Capsules) Instructions for Use

Marketing Authorization Holder

Pharmaceutical Plant POLPHARMA, JSC (Poland)

ATC Code

N02BF02 (Pregabalin)

Active Substance

Pregabalin (Rec.INN registered by WHO)

Dosage Forms

	Prigabilon®	Capsules 25 mg: 14 or 56 pcs.
		Capsules 50 mg: 14 or 56 pcs.
		Capsules 75 mg: 14 or 56 pcs.
		Capsules 100 mg: 21 or 84 pcs.
		Capsules 150 mg: 14 or 56 pcs.
		Capsules 200 mg: 21 or 84 pcs.
		Capsules 300 mg: 14 or 56 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin No. 4, white in color with the inscription “25” on the body, containing powder or slightly formed agglomerates of white or almost white color.

Excipients: lactose monohydrate – 55 mg, corn starch – 10 mg, talc – 10 mg.

Capsule shell composition:
Capsule cap gelatin – 14.896 mg, titanium dioxide (E171) – 0.304 mg;
capsule body: gelatin – 22.344 mg, titanium dioxide (E171) – 0.456 mg;
composition of the ink used for applying inscriptions on capsules shellac solution in ethanol – 59.42%, iron oxide black dye – 24.65%, butanol – 9.75%, purified water – 3.249%, propylene glycol – 1.3%, ethanol – 1.08%, isopropanol – 0.55%, aqueous ammonia – 0.001%.

14 pcs. – blisters made of PVC/PVDX/aluminum foil (1) – cardboard packs.
14 pcs. – blisters made of PVC/PVDX/aluminum foil (4) – cardboard packs.

Capsules hard gelatin No. 3, white in color with the inscription “50” on the body, containing powder or slightly formed agglomerates of white or almost white color.

Excipients: lactose monohydrate – 18 mg, corn starch – 16 mg, talc – 16 mg.

Capsule shell composition:
Capsule cap gelatin – 18.816 mg, titanium dioxide (E171) – 0.384 mg;
capsule body: gelatin – 28.224 mg, titanium dioxide (E171) – 0.576 mg;
composition of the ink used for applying inscriptions on capsules shellac solution in ethanol – 59.42%, iron oxide black dye – 24.65%, butanol – 9.75%, purified water – 3.249%, propylene glycol – 1.3%, ethanol – 1.08%, isopropanol – 0.55%, aqueous ammonia – 0.001%.

14 pcs. – blisters made of PVC/PVDX/aluminum foil (1) – cardboard packs.
14 pcs. – blisters made of PVC/PVDX/aluminum foil (4) – cardboard packs.

Capsules hard gelatin No. 3, body white in color, cap – red-brown in color, with the inscription “75” on the body, containing powder or slightly formed agglomerates of white or almost white color.

Excipients: lactose monohydrate – 27 mg, corn starch – 24 mg, talc – 24 mg.

Capsule shell composition:
Capsule cap gelatin – 18.7553 mg, iron oxide red dye (E172) – 0.242 mg, iron oxide yellow dye (E172) – 0.1815 mg, titanium dioxide (E171) – 0.0212 mg;
capsule body: gelatin – 28.224 mg, titanium dioxide (E171) – 0.576 mg;
composition of the ink used for applying inscriptions on capsules shellac solution in ethanol – 59.42%, iron oxide black dye – 24.65%, butanol – 9.75%, purified water – 3.249%, propylene glycol – 1.3%, ethanol – 1.08%, isopropanol – 0.55%, aqueous ammonia – 0.001%.

14 pcs. – blisters made of PVC/PVDX/aluminum foil (1) – cardboard packs.
14 pcs. – blisters made of PVC/PVDX/aluminum foil (4) – cardboard packs.

Capsules hard gelatin No. 1, red-brown in color, with the inscription “100” on the body, containing powder or slightly formed agglomerates of white or almost white color.

Excipients: lactose monohydrate – 36 mg, corn starch – 32 mg, talc – 32 mg.

Capsule shell composition:
Capsule cap gelatin – 29.6959 mg, iron oxide red dye (E172) – 0.3832 mg, iron oxide yellow dye (E172) – 0.2874 mg, titanium dioxide (E171) – 0.0335 mg;
capsule body: gelatin – 44.5438 mg, iron oxide red dye (E172) – 0.5748 mg, iron oxide yellow dye (E172) – 0.4311 mg, titanium dioxide (E171) – 0.0503 mg;
composition of the ink used for applying inscriptions on capsules shellac solution in ethanol – 59.42%, iron oxide black dye – 24.65%, butanol – 9.75%, purified water – 3.249%, propylene glycol – 1.3%, ethanol – 1.08%, isopropanol – 0.55%, aqueous ammonia – 0.001%.

7 pcs. – blisters made of PVC/PVDX/aluminum foil (3) – cardboard packs.
7 pcs. – blisters made of PVC/PVDX/aluminum foil (12) – cardboard packs.

Capsules hard gelatin No. 1, white in color, with the inscription “150” on the body, containing powder or slightly formed agglomerates of white or almost white color.

Excipients: lactose monohydrate – 54 mg, corn starch – 48 mg, talc – 48 mg.

Capsule shell composition:
Capsule cap gelatin – 29.792 mg, titanium dioxide (E171) – 0.608 mg;
capsule body: gelatin – 44.688 mg, titanium dioxide (E171) – 0.912 mg;
composition of the ink used for applying inscriptions on capsules shellac solution in ethanol – 59.42%, iron oxide black dye – 24.65%, butanol – 9.75%, purified water – 3.249%, propylene glycol – 1.3%, ethanol – 1.08%, isopropanol – 0.55%, aqueous ammonia – 0.001%.

7 pcs. – blisters made of PVC/PVDX/aluminum foil (2) – cardboard packs.
7 pcs. – blisters made of PVC/PVDX/aluminum foil (8) – cardboard packs.

Capsules hard gelatin No. 0, light brown in color, with the inscription “200” on the body, containing powder or slightly formed agglomerates of white or almost white color.

Excipients: lactose monohydrate – 72 mg, corn starch – 64 mg, talc – 64 mg.

Capsule shell composition:
Capsule cap gelatin – 37.5881 mg, iron oxide red dye (E172) – 0.0424 mg, iron oxide yellow dye (E172) – 0.1273 mg, iron oxide black dye (E172) – 0.0424 mg, titanium dioxide (E171) – 0.5998 mg;
capsule body: gelatin – 56.3821 mg, iron oxide red dye (E172) – 0.0636 mg, iron oxide yellow dye (E172) – 0.1909 mg, iron oxide black dye (E172) – 0.0636 mg, titanium dioxide (E171) – 0.8998 mg;
composition of the ink used for applying inscriptions on capsules shellac solution in ethanol – 59.42%, iron oxide black dye – 24.65%, butanol – 9.75%, purified water – 3.249%, propylene glycol – 1.3%, ethanol – 1.08%, isopropanol – 0.55%, aqueous ammonia – 0.001%.

7 pcs. – blisters made of PVC/PVDX/aluminum foil (3) – cardboard packs.
7 pcs. – blisters made of PVC/PVDX/aluminum foil (12) – cardboard packs.

Capsules hard gelatin No. 0, body white in color, cap – red-brown in color, with the inscription “300” on the body, containing powder or slightly formed agglomerates of white or almost white color.

Excipients: lactose monohydrate – 108 mg, corn starch – 96 mg, talc – 96 mg.

Capsule shell composition:
Capsule cap gelatin – 37.5106 mg, iron oxide red dye (E172) – 0.484 mg, iron oxide yellow dye (E172) – 0.363 mg, titanium dioxide (E171) – 0.0424 mg;
capsule body: gelatin – 56.448 mg, titanium dioxide (E171) – 1.152 mg;
composition of the ink used for applying inscriptions on capsules shellac solution in ethanol – 59.42%, iron oxide black dye – 24.65%, butanol – 9.75%, purified water – 3.249%, propylene glycol – 1.3%, ethanol – 1.08%, isopropanol – 0.55%, aqueous ammonia – 0.001%.

7 pcs. – blisters made of PVC/PVDX/aluminum foil (2) – cardboard packs.
7 pcs. – blisters made of PVC/PVDX/aluminum foil (8) – 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 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 after 1 hour both after single and repeated administration. The bioavailability of pregabalin when taken orally is ≥ 90% and does not depend on the dose. With repeated use, the equilibrium state is reached within 24-48 hours. When used after a meal, C_max decreases by approximately 25-30%, and the time to reach C_max increases 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, and interindividual variability is low (<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. The plasma clearance of pregabalin and renal clearance are directly proportional to CCr.

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 CCr. Pregabalin is effectively removed from plasma by hemodialysis (after a 4-hour hemodialysis session, plasma concentrations of pregabalin decrease 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 change 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 CCr. Elderly people with impaired renal function may require a reduction in the dose of the drug.

Indications

Treatment of neuropathic pain in adults.

Treatment of fibromyalgia in adults.

Epilepsy: as an 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 in 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 selected individually taking into account CCr.

In patients with impaired liver function, dose adjustment is not required.

Elderly patients over 65 years of age may require a reduction in the dose of pregabalin 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 already 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 disorders, hypesthesia, nystagmus, speech disorder, myoclonic seizures, hyporeflexia, dyskinesia, psychomotor hyperactivity, postural dizziness, hyperesthesia, loss of taste sensation, burning sensation on mucous membranes and skin, intention tremor, stupor, syncope; rare – hypokinesia, parosmia, dysgraphia; frequency unknown – headache.

Sensory organ disorders common – dizziness, 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 impaired, peripheral vision loss, strabismus, visual brightness enhancement; 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 prolongation.

Respiratory, thoracic and mediastinal disorders uncommon – dyspnea, cough, dry nasal mucosa, 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, pain in extremity, 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, galactorrhea, 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

Adequate and well-controlled studies on the safety of pregabalin use during pregnancy have not been conducted. 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 reported isolated cases 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 body weight increases during treatment with pregabalin, dose adjustment of hypoglycemic drugs may be required.

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

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

Treatment with pregabalin has been associated with dizziness and somnolence, which increase the risk of accidental injury (falls) in elderly patients. Cases of loss of consciousness, confusion, and cognitive impairment have also been reported during post-marketing use. Therefore, until patients experience the effects of pregabalin, they should exercise caution.

Data on the possibility of discontinuing other antiepileptic drugs upon seizure suppression with pregabalin and the advisability of pregabalin monotherapy are insufficient. There are reports of seizures, including status epilepticus and petit mal seizures, developing during the use of pregabalin or immediately after discontinuation 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 following the withdrawal of pregabalin after long-term or short-term therapy: insomnia, headache, nausea, diarrhea, flu-like syndrome, depression, hyperhidrosis, dizziness, convulsions, and anxiety. Information on the frequency and severity of pregabalin withdrawal symptoms depending on the duration of therapy and its dose is not available.

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 cardiac impairment who were taking the drug for neuropathy. Therefore, Pregabalin should be used with caution in this patient category. Manifestations of such reactions may resolve after discontinuation of pregabalin.

The frequency of central nervous system adverse reactions, particularly such as somnolence, increases when treating central neuropathic pain due to spinal cord injury, which, however, may be a consequence of the additive effects of pregabalin and other concurrently administered drugs (e.g., antispastic agents). 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 monitoring for symptoms of pregabalin dependence.

Cases of encephalopathy have been reported, especially in patients with comorbid conditions that may lead to encephalopathy.

Effect on the Ability to Drive and Use Machines

Pregabalin may cause dizziness and somnolence and thereby affect the ability to drive and use complex machinery. Patients should not drive, operate complex machinery, or engage in other potentially hazardous activities until their individual response to pregabalin intake is established.

Drug Interactions

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

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

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