Pregabalin Ivax 25/50/75/150 25/50/75/150 mg Capsules

Neuropathic pain:

PREGABALIN IVAX is indicated for the treatment of adult patients with neuropathic pain due to Herpes zoster infections and diabetes.

The recommended starting dose for PREGABALIN IVAX is 75 mg twice daily (150 mg/day), with or without food. Based on individual patient response and tolerability, the dose may be increased to 150 mg twice daily after an interval of 3 to 7 days.

In accordance with current clinical practice, if PREGABALIN IVAX has to be discontinued, it is recommended this should be done gradually over a minimum of 1 week.

Patients with renal impairment:

PREGABALIN IVAX is eliminated unchanged from the systemic circulation primarily by renal excretion. As PREGABALIN IVAX clearance is directly proportional to creatinine clearance (see section 5.2 - Pharmacokinetics in special patient groups u2013 Renal impairment), dosage reduction in patients with compromised renal function must be individualised according to creatinine clearance (CLcr), as indicated in Table 1 determined using the following formula:

CLcr (ml/min) = (140 u2013 age) x weight (kg) u2014u2014u2014u2014u2014u2014u2014u2014u2014u2014u2014u2014u2014u2014 0,82 x Serum creatinine (u03bcmol/l)
*For females multiply the CLcr by 0,85

PREGABALIN IVAX is removed effectively from plasma by haemodialysis (50 % of pregabalin in 4 hours). For patients receiving haemodialysis, the daily dose of PREGABALIN IVAX should be adjusted based on renal function. In addition to the daily dose, a supplementary dose should be given immediately following every 4 hour haemodialysis treatment (refer to Table 1).

TABLE 1: PREGABALIN IVAX DOSAGE ADJUSTMENT BASED ON RENAL FUNCTION:

CREATININE CLEARANCE (Clcr) (ml/min)

TOTAL PREGABALIN IVAX DAILY DOSE*

DOSE REGIMEN

Starting dose (mg/day) Maximum dose (mg/day)

u2265 60 150 300 BD

30 to 60 75 150 OD or BD

15 to 30 25 to 50 75 OD or BD

< 15 25 25 to 50 OD

Supplementary dosage following haemodialysis (mg)

25 50 Single dose + BD = Two divided doses

OD = Once daily

* Total daily dose (mg/day) should be divided as indicated by dose regimen to provide mg/dose + Supplementary dose is a single additional dose

Use in patients with hepatic impairment:

No dosage adjustments are required for patients with hepatic impairment (see section 5.2 - Pharmacokinetics in special patient groups u2013 Hepatic impairment).

Use in children:

The safety and effectiveness of PREGABALIN IVAX in patients below the age of 18 years with neuropathic pain has not been established.

Use in the elderly (over 65 years of age):

No dosage adjustment is necessary for elderly patients unless their renal function is compromised, refer to Table 1.

Method of administration:

PREGABALIN IVAX is given orally with or without food.

PREGABALIN IVAX is contraindicated in patients who are hypersensitive to pregabalin or to any of the excipients.

Hypersensitivity reactions:

There have been reports of hypersensitivity reactions, including cases of angioedema and urticaria. PREGABALIN IVAX should be discontinued immediately if symptoms of angioedema, such as facial, perioral or upper airway swelling occur (see section 4.8).

Severe cutaneous adverse reactions (SCARs):

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported rarely in association with pregabalin treatment. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, PREGABALIN IVAX should be withdrawn immediately and an alternative treatment considered (as appropriate).

Dizziness, somnolence, loss of consciousness, confusion and mental impairment:

Pregabalin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population. There have also been post-marketing reports of loss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of PREGABALIN IVAX (see section 4.8).

Use with anti-depressant medicines:

When PREGABALIN IVAX is used in combination with anti-depressant medicines, respiratory failure has occurred.

Withdrawal symptoms:

After discontinuation of short-term and long-term treatment with PREGABALIN IVAX, withdrawal symptoms have been observed. The following events have been reported: insomnia, headache, nausea, diarrhoea, anxiety, flu syndrome, nervousness, depression, suicidal ideation, pain, convulsion, hyperhidrosis and dizziness. The occurrence of withdrawal symptoms following discontinuation of PREGABALIN IVAX may indicate drug dependence (see section 4.8). The patient should be informed about this at the start of the treatment. If PREGABALIN IVAX should be discontinued, it is recommended this should be done gradually over a minimum of 1 week independent of the indication (see section 4.2).

Convulsions, including status epilepticus and grand mal convulsions, may occur during PREGABALIN IVAX use or shortly after discontinuing PREGABALIN IVAX.

During discontinuation of long-term treatment with PREGABALIN IVAX, the incidence and severity of withdrawal symptoms may be dose-related.

Renal failure:

Renal failure may occur with PREGABALIN IVAX. Improved renal function was reported following dose reduction or discontinuation of PREGABALIN IVAX.

Congestive heart failure:

There have been post-marketing reports of congestive heart failure or deterioration of heart failure in some patients receiving PREGABALIN IVAX. These are mostly seen in elderly cardiovascular compromised patients during PREGABALIN IVAX treatment. Therefore PREGABALIN IVAX should be used with caution in patients with congestive heart failure (see section 4.8). Discontinuation of PREGABALIN IVAX may resolve the reaction.

Diabetic patients:

In accordance with current clinical practice, some diabetic patients who gain weight on PREGABALIN IVAX treatment may need to adjust hypoglycaemic medicines.

Vision-related effects:

There have been post-marketing reports of visual adverse reactions including loss of vision, visual blurring or other changes of visual acuity, many of which were transient. Discontinuation of PREGABALIN IVAX may result in resolution or improvement of these visual symptoms.

Treatment of central neuropathic pain due to spinal cord injury:

In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse reactions in general, central nervous system adverse reactions and especially somnolence was increased. This may be attributed to an additive effect due to concomitant medicines (e.g. anti-spasticity medicines) needed for this condition. This should therefore be considered when prescribing PREGABALIN IVAX in this condition.

Suicidal ideation and behaviour:

Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic medicines in several indications. Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

Reduced lower gastrointestinal tract function:

There are post-marketing reports of events related to reduced lower gastrointestinal tract function (e.g. intestinal obstruction, paralytic ileus, constipation) when pregabalin was co-administered with medicines that have the potential to produce constipation, such as opioid analgesics. When PREGABALIN IVAX and opioids will be used in combination, measures to prevent constipation may be considered (especially in female patients and the elderly).

Concomitant use with opioids:

Caution is advised when prescribing pregabalin as contained in PREGABALIN IVAX concomitantly with opioids due to the risk of CNS depression (see section 4.5). Studies in opioid users found that patients who took pregabalin concomitantly with an opioid had an increased risk for opioid-related death compared to opioid use alone. This increased risk was observed at low doses of pregabalin and there was a greater risk at high doses of pregabalin.

Misuse, abuse potential or dependence:

Cases of misuse, abuse and dependence have been reported. Caution should be exercised in patients with a history of substance abuse and the patient should be monitored for symptoms of pregabalin misuse, abuse or dependence (development of tolerance, dose escalation, drug-seeking behaviour have been reported).

Encephalopathy:

Cases of encephalopathy have been reported, mostly in patients with underlying conditions that may precipitate encephalopathy.

Respiratory depression:

There have been reports of severe respiratory depression in relation to PREGABALIN IVAX use. Patients with compromised respiratory function, respiratory or neurological disease, renal impairment, concomitant use of CNS depressants and the elderly may be at higher risk of experiencing this severe adverse reaction. Dose adjustments may be necessary in these patients (see section 4.2).

Mannitol:

PREGABALIN IVAX contains mannitol and may have a laxative effect.

Since PREGABALIN IVAX is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans, does not inhibit medicine metabolism in vitro and is not bound to plasma proteins, PREGABALIN IVAX is unlikely to produce, or be subject to, pharmacokinetic interactions.

No pharmacokinetic interactions were observed between PREGABALIN IVAX and the following medicines: phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone, ethanol, oral anti-diabetics, diuretics, insulin and anti-epileptic medicines (such as phenytoin, carbamazepine, phenobarbitone, tiagabine and topiramate), oral contraceptives (e.g. norethisterone and/or ethinyl oestradiol).

PREGABALIN IVAX appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone and may potentiate the effects of ethanol and lorazepam.

In patients taking PREGABALIN IVAX and other central nervous system (CNS) depressant medicines, there have been post-marketing reports of respiratory failure and coma.

Pregnancy:

PREGABALIN IVAX should not be used during pregnancy since safety and efficacy has not been established, therefore effective contraception must be used in women of childbearing potential.

Breastfeeding:

PREGABALIN IVAX is excreted in breast milk therefore breastfeeding is not recommended, since the effects on newborns/infants are unknown.

PREGABALIN IVAX frequently causes dizziness and somnolence. Therefore, patients are advised not to drive, operate complex machinery or engage in other potentially hazardous activities until it is known whether PREGABALIN IVAX affects their ability to perform these activities.

The most frequently reported adverse reactions are dizziness and somnolence.

Infections and infestations:

Frequent: Nasopharyngitis

Immune system disorders:

Frequency unknown: Hypersensitivity reactions, angioedema, allergic reaction

Blood and lymphatic system disorders:

Less frequent: Neutropenia

Metabolism and nutrition disorders:

Frequent: Increased appetite

Less frequent: Anorexia, hypoglycaemia

Psychiatric disorders:

Frequent: Euphoric mood, confusion, decreased libido, irritability, disorientation, insomnia

Less frequent: Depersonalisation, anorgasmia, restlessness, depression, agitation, mood swings, insomnia exacerbated, depressed mood, word finding difficulty, hallucination, abnormal dreams, libido increased, panic attack, apathy, disinhibition, elevated mood, aggression

Nervous system disorders:

Frequent: Dizziness, somnolence, ataxia, disturbance in attention, abnormal co-ordination, memory impairment, tremor, dysarthria, paraesthesia, headache, amnesia, hypoaesthesia, balance disorder, lethargy

Less frequent: Cognitive disorder, visual field defect, nystagmus, speech disorder, myoclonus, hyporeflexia, dyskinesia, psychomotor hyperactivity, postural dizziness, hyperaesthesia, ageusia, burning sensation, intention tremor, stupor, syncope, hypokinesia, parosmia, dysgraphia, loss of consciousness, nystagmus, mental impairment, malaise, convulsions, parkinsonism

Frequency unknown: Reversible paralysis

Eye disorders:

Frequent: Vision blurred, diplopia

Less frequent: Visual disturbance, dry eye, eye swelling, reduced visual acuity, eye pain, asthenopia, increased lacrimation, photopsia, eye irritation, mydriasis, oscillopsia, altered visual depth perception, peripheral vision loss, strabismus, visual brightness, keratitis

Ear and labyrinth disorders:

Frequent: Vertigo

Less frequent: Hyperacusis

Cardiac disorders:

Less frequent: Tachycardia, atrioventricular block first degree, sinus tachycardia, sinus dysrhythmia, sinus bradycardia, congestive heart failure, QT prolongation

Vascular disorders:

Less frequent: Flushing, hot flushes, hypotension, peripheral coldness, hypertension

Respiratory, thoracic and mediastinal disorders:

Less frequent: Dyspnoea, nasal dryness, cough, nasal congestion, epistaxis, rhinitis, snoring, throat tightness, pulmonary oedema

Frequency unknown: Respiratory depression

Gastrointestinal disorders:

Frequent: Dry mouth, constipation, vomiting, flatulence, nausea, diarrhoea, abdominal distension

Less frequent: Salivary hypersecretion, gastro-oesophageal reflux disease, oral hypoaesthesia, ascites, dysphagia, pancreatitis, swollen tongue

Hepatobiliary disorders:

Less frequent: Elevated liver enzymes, jaundice, hepatic failure, hepatitis

Skin and subcutaneous tissue disorders:

Less frequent: Sweating, rash papular, cold sweat, urticaria, face swelling, Stevens-Johnson syndrome, pruritus, toxic epidermal necrolysis

Musculoskeletal and connective tissue disorders:

Frequent: Muscle cramp, arthralgia, back pain, pain in limb, cervical spasm

Less frequent: Muscle twitching, joint swelling, myalgia, muscle stiffness, neck pain, rhabdomyolysis

Renal and urinary disorders:

Less frequent: Dysuria, urinary incontinence, oliguria, renal failure, urinary retention

Reproductive system and breast disorders:

Frequent: Erectile dysfunction

Less frequent: Ejaculation delayed, sexual dysfunction, amenorrhoea, breast pain, breast discharge, dysmenorrhoea, breast hypertrophy, gynaecomastia

General disorders and administration site conditions:

Frequent: Fatigue, peripheral oedema, feeling drunk, oedema, abnormal gait, fall, feeling abnormal

Less frequent: Asthenia, thirst, chest tightness, exacerbated pain, anasarca, pyrexia, rigors, face oedema, chills, generalised oedema

Investigations:

Frequent: Increased weight

Less frequent: Increased alanine aminotransferase, increased blood creatine phosphokinase, increased aspartate aminotransferase, decreased platelet count, increased blood glucose, increased blood creatinine, decreased blood potassium, decreased weight, decreased white blood cell count

Description of selected adverse reactions:

After discontinuation of short-term and long-term treatment with PREGABALIN IVAX, withdrawal symptoms have been observed. The following reactions have been reported: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, convulsions, nervousness, depression, suicidal ideation, pain, hyperhidrosis and dizziness. These symptoms may indicate drug dependence. The patient should be informed about this at the start of the treatment. Concerning discontinuation of long-term treatment of PREGABALIN IVAX, data suggests that the incidence and severity of withdrawal symptoms may be dose-related (see sections 4.2 and 4.4).

Reporting of suspected adverse reactions:

Reporting suspected adverse reactions after registration of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the 6.04 Adverse Drug Reactions Reporting Form, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Post-marketing reports of pregabalin overdose included affective disorder, somnolence, confusional state, depression, agitation, restlessness, seizures and coma.

Treatment of PREGABALIN IVAX overdose should include general supportive measures and may include haemodialysis if necessary (see section 4.2).