Source: Health Products Regulatory Authority (ZA) Revision Year: 2023 Publisher: Forrester Pharma (Pty) Ltd, 2 Waterford Mews, Waterford Place, Century City, 7441, Cape Town, South Africa
Hypersensitivity to pregabalin or to any of the inactive ingredients of NUBACAP (see sections 2 and 6.1).
There have been post-marketing reports of hypersensitivity reactions, including cases of angioedema and urticaria. NUBACAP 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) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported 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 If signs and symptoms suggestive of these reactions appear, NUBACAP should be withdrawn immediately and an alternative treatment considered (as appropriate).
NUBACAP may increase weight gain. Diabetic patients who gain weight on NUBACAP treatment may need to adjust the dose of hypoglycaemic medicines.
There have been post-marketing reports of congestive heart failure or deterioration of heart failure in some patients receiving NUBACAP. ln short-term trials of patients without clinically significant heart or peripheral vascular disease, there was no apparent association between peripheral oedema and cardiovascular complications such as hypertension or congestive heart failure. NUBACAP should be used with caution in patients with congestive heart failure (see section 4.8).
Although the effects of discontinuation on the reversibility of renal failure have not been systematically studied, improved renal function following discontinuation or dose reduction of NUBACAP has been reported (see section 4.8). Renal failure has occurred.
NUBACAP treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in elderly patients. There have been post-marketing reports of Ioss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of NUBACAP (see section 4.8).
When NUBACAP is used in combination with antidepressants, respiratory failure has occurred.
After discontinuation of short-term and long-term treatment with NUBACAP, withdrawal symptoms have been observed in some patients. The following events have been mentioned: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, nervousness, depression, pain, convulsions, hyperhidrosis and dizziness, suggestive of physical dependence (see section 4.8). Patients should be informed about this at the start of the treatment.
Convulsions, including status epilepticus and grand mal convulsions, may occur during NUBACAP use or shortly after discontinuing NUBACAP.
Concerning discontinuation of long-term treatment of NUBACAP, data suggest that the incidence and severity of withdrawal symptoms may be dose-related.
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 NUBACAP may result in resolution or improvement of these visual symptoms.
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 medicinal products (e.g. anti-spasticity medicines) needed for this condition. This should be considered when prescribing pregabalin in this condition.
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.
There are post-marketing reports of events related to reduced lower gastrointestinal tract function (e.g. intestinal obstruction, paralytic ileus, constipation) when NUBACAP was co-administered with medicines that have the potential to produce constipation, such as opioid analgesics. When NUBACAP and opioids will be used in combination, measures to prevent constipation may be considered (especially in female patients and the elderly).
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 NUBACAP misuse, abuse or dependence (development of tolerance, dose escalation, substance-seeking behaviour have been reported).
Cases of encephalopathy have been reported, mostly in patients with underlying conditions that may precipitate encephalopathy.
There have been reports of severe respiratory depression in relation to NUBACAP 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).
Since NUBACAP is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (<2% of a dose recovered in urine as metabolites), does not inhibit substance metabolism in vitro, and is not bound to plasma proteins, NUBACAP is unlikely to produce, or be subject to, pharmacokinetic interactions.
Accordingly, in vivo studies indicated no clinically relevant pharmacokinetic interactions between NUBACAP and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. In addition, population pharmacokinetic analysis indicated that the 3 commonly used medicine classes, oral antidiabetics, diuretics and insulin, and the commonly used anti-epileptic medicines, phenytoin, carbamazepine, valproic acid, lamotrigine, phenobarbitone, tiagabine, and topiramate had no clinically significant effect on pregabalin clearance. Similarly, these analyses indicated that NUBACAP had no clinically significant effect on the clearance of phenytoin, carbamazepine, valproic acid, lamotrigine, topiramate and phenobarbitone.
Co-administration of NUBACAP with the oral contraceptives norethisterone and/or ethinylestradiol does not influence the steady-state pharmacokinetics of either medicine.
Multiple oral doses of NUBACAP co-administered with oxycodone, lorazepam or ethanol did not result in clinically important effects on respiration. NUBACAP appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone. NUBACAP may potentiate the effects of ethanol and lorazepam. In post-marketing experience, there are reports of respiratory failure and coma in patients taking NUBACAP and other central nervous system (CNS) depressant medicines.
There are no adequate data on the use of NUBACAP in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk to humans is unknown. Therefore, NUBACAP should not be used during pregnancy.
It is not known if NUBACAP is excreted into the breast milk of humans; however, it is present in the milk of rats. Therefore, breastfeeding is not recommended.
NUBACAP frequently causes dizziness and somnolence (see section 4.8).
Caution is advised before driving a vehicle or operating machinery until it is established that the ability to perform such activities is not affected.
| System Organ Class | Frequency | Side effects |
|---|---|---|
| Infections and infestations | Less frequent | Infection, nasopharyngitis. |
| Blood and the lymphatic system disorders | Less frequent | Neutropenia. |
| Immune system disorders | Less frequent | Hypersensitivity reaction, Stevens- Johnson syndrome, angioedema, allergic reaction. |
| Metabolism and nutrition disorders | Frequent | Increased appetite. |
| Less frequent | Anorexia, hypoglycaemia. | |
| Psychiatric disorders | Frequent | Euphoric mood, confusion, irritability, disorientation, insomnia. |
| Less frequent | Depersonalisation, anorgasmia, restlessness, depression, agitation, mood swings, depressed mood, aggression, word finding difficulty, hallucinations, abnormal dreams, panic attack, apathy, disinhibition, elevated mood, nervousness. | |
| Nervous system disorders | Frequent | Dizziness, somnolence, headache, ataxia, attention disorder, abnormal coordination, memory impairment, tremor, dysarthria, paraesthesia, abnormal thinking, amnesia, sedation, balance disorder, lethargy. |
| Less frequent | Cognitive disorder, hypoaesthesia, speech disorder, myoclonus, hyporeflexia, dyskinesia, psychomotor hyperactivity, postural dizziness, hyperaesthesia, ageusia, burning sensation, intention tremor, stupor, syncope, loss of consciousness, mental impairment, reversible paralysis, malaise, convulsions, hypokinesia, parosmia, dysgraphia, myasthenia, neuropathy. | |
| Eye disorders | Frequent | Blurred vision, diplopia. |
| Less frequent | Visual disturbance, dry eye, eye swelling, visual acuity reduced, eye pain, asthenopia, increased lacrimation, photopsia, eye irritation, mydriasis, vision loss, keratitis, oscillopsia, altered visual depth perception, peripheral vision loss, strabismus, visual brightness, visual field defect, nystagmus. | |
| Ear and labyrinth disorders | Frequent | Vertigo. |
| Less frequent | Hyperacusis. | |
| Cardiac disorders | Less frequent | Tachycardia, first degree atrioventricular block, sinus tachycardia, sinus dysrhythmia, sinus bradycardia, congestive heart failure, chest tightness, chest pain, QT prolongation. |
| Vascular disorders | Less frequent | Flushing, hot flushes, hypotension, peripheral coldness, hypertension. |
| Respiratory, thoracic and mediastinal disorders | Less frequent | Dyspnoea, nasal dryness, nasopharyngitis, cough, nasal congestion, epistaxis, rhinitis, snoring, throat tightness, flu symptoms, bronchitis, 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 hypaesthesia, ascites, dysphagia, pancreatitis, swollen tongue. | |
| Hepatobiliary disorders | Less frequent | Elevated liver enzymes, jaundice, hepatic failure, hepatitis. |
| Skin and subcutaneous tissue disorders | Less frequent | Sweating, papular rash, cold sweat, urticaria, hyperhidrosis, pruritus. |
| Musculoskeletal, connective tissue and bone disorders | Less frequent | Muscle twitching, joint swelling, muscle cramp, myalgia, arthralgia, back pain, pain in limb, muscle stiffness, cervical spasm, 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, decreased libido. |
| Less frequent | Delayed ejaculation, sexual dysfunction, increased libido, amenorrhoea, breast pain, breast discharge, dysmenorrhoea, breast hypertrophy, gynaecomastia. | |
| General disorders and administrative site conditions | Frequent | Fatigue, peripheral oedema, facial oedema, oedema, abnormal gait, accidental injury. |
| Less frequent | Asthenia, fall, thirst, exacerbated pain, anasarca, pyrexia, rigors. | |
| 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. |
Reporting of suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the “6.04 Adverse Drug Reactions Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8.
Not applicable.
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