Angioedema: There have been post-marketing reports of angioedema in patients during initial and chronic treatment with pregabalin. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment. Discontinue pregabalin immediately in patients with these symptoms.
Exercise caution when prescribing pregabalin to patients who have had a previous episode of angioedema. In addition, patients who are taking other drugs associated with angioedema [e.g., angiotensin converting enzyme inhibitors (ACE-inhibitors)] may be at increased risk of developing angioedema.
Hypersensitivity reactions: There have been reports in the postmarketing experience of hypersensitivity reactions in patients shortly after initiation of treatment with pregabalin. Adverse reactions included skin redness, blisters, hives, rash, dyspnea and wheezing. Discontinue pregabalin immediately in patients with these symptoms.
Withdrawal of antiepileptic medicinal products (AEDs): As with all AEDs, withdraw pregabalin gradually to minimize the potential of increased seizure frequency in patients with seizure disorders. If pregabalin is discontinued, taper the medicinal product gradually over a minimum of 1 week.
Suicidal behaviour and ideation: AEDs, including pregabalin, increase the risk of suicidal thoughts or behaviour in patients taking these medicinal products for any indication. Monitor patients treated with and AED for any indication for the emergence or worsening of depression, suicidal thoughts or behaviour, and/or unusual changes in mood or behaviour.
The increased risk of suicidal thoughts or behaviour with AEDs was observed as early as one week after starting treatment with AEDs and persisted for the duration of the treatment assessed (risk of suicidal thoughts or behaviour was not assessed beyond 24 weeks of treatment).
The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years).
Anyone considering prescribing pregabalin or any other AED must balance the risk of suicidal thoughts or behaviour with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behaviour. Should suicidal thoughts and behaviour emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patients may be related to the illness being treated.
Inform patients, their caregivers and families that pregabalin and other AEDs increase the risk of suicidal thoughts and behaviour and advise them of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behaviour or the emergence of suicidal thoughts, behaviour or thoughts about self-harm. Report behaviours of concern immediately to the healthcare providers.
Peripheral edema: Pregabalin treatment may cause peripheral edema. Peripheral edema was not associated with laboratory changes suggestive of deterioration in renal or hepatic function nor with cardiovascular complications such as hypertension or congestive heart failure.
Higher frequencies of weight gain and peripheral edema were observed in patients taking both pregabalin and thiazolidinedione antidiabetic agent compared to taking either medicinal product alone. As the thiazolidinedione class of antidiabetic medicinal products can cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, exercise caution when co-administering pregabalin and these agents.
Although there has been no causal relationship identified between exposure to pregabalin and congestive heart failure, there has been post-marketing reports on congestive heart failure in some patients receiving pregabalin. Because there are limited data on congestive heart failure patients with New York Heart Association (NYHA) class III or IV cardiac status, exercise caution when using pregabalin in these patients.
Dizziness, somnolence: Pregabalin may cause dizziness and somnolence. Inform patients that pregabalin-related dizziness and somnolence may impair their ability to perform tasks such as driving or operating machinery and could increase the occurrence of accidental injury (fall) in the elderly population.
Loss of consciousness, confusion and mental impairment have been reported. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication.
Pregabalin in not known to be active at receptor sites associated with drug abuse. Cases of abuse have been reported. As with any CNS active drug, carefully evaluate patients for history of drug abuse and observe them for signs of pregabalin abuse.
Weight gain: Pregabalin treatment may cause weight gain. Pregabalin associated weight gain is related to dose and duration of treatment, but is not associated with baseline BMI, gender or age. Weight gain is also not limited to patients with edema. The long-term cardiovascular effects of pregabalin-associated weight gain are not known. The effects of pregabalin-associated weight gain on glycemic control have not been systematically assessed. Some diabetic patients who gain weight on pregabalin treatment may need to adjust hypoglycemic medications.
Abrupt or rapid discontinuation: After discontinuation of short-term and long-term treatment with pregabalin withdrawal symptoms have been observed in some patients. The following events have been mentioned: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, nervousness, depression, pain, convulsion, hyperhidrosis and dizziness, suggestive of physical dependence. The patient should be informed about this at the start of the treatment.
Convulsions, including status epilepticus and grand mal convulsions, may occur during pregabalin use or shortly after discontinuing pregabalin.
Concerning discontinuation of long-term treatment of pregabalin, there are no data of the incidence and severity of withdrawal symptoms in relation to duration of use and dose of pregabalin.
Ophthalmological effects: A higher proportion of patients treated with pregabalin reported blurred vision which resolved in a majority of cases with continued dosing. Although the clinical significance of the ophthalmologic findings is unknown, inform patients to notify their physician if changes in vision occur. If visual disturbance persist, consider further assessment. Consider more frequent assessment of patients who are already routinely monitored for ocular conditions.
Visual adverse reactions have also been reported, including loss of vision, visual blurring or other changes of visual acuity, many of which were transient. Discontinuation of pregabalin may result in resolution or improvement of these visual symptoms.
Creatine kinase elevations: Pregabalin treatment was associated with creatine kinase elevations. Instruct patients to promptly report unexplained muscle pain, tenderness or weakness particularly if these muscle symptoms are accompanied by malaise or fever. Discontinue treatment with pregabalin if myopathy is diagnosed or suspected or if markedly elevated creatine kinase levels occur.
Decreased platelet count: Pregabalin treatment was associated with a decrease in platelet count.
PR interval prolongation: Pregabalin treatment was associated with PR interval prolongation. In analyses of ECG data the mean PR interval increase was 3-6msec at pregabalin doses ≥300 mg/day. This mean change difference was not associated with an increased risk of PR increase ≥25% from baseline, in increased percentage of subject with on-treatment PR >200 msec, or an increased risk of adverse reactions of second or third degree AV block.
Others: Although the effects of discontinuation on the reversibility of renal failure have not been systematically studied, improved renal failure following discontinuation or dose reduction of pregabalin has been reported.
Abuse potential: Cases of abuse have been reported. Caution should be exercised in patients with history of substance abuse and the patient should be monitored for symptoms of pregabalin abuse.
Encephalopathy: Cases of encephalopathy have been reported, mostly in patients with underlying conditions that may precipitate encephalopathy.
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 medicinal products (e.g. anti-spasticity agents) needed for this condition. This should be considered when prescribing pregabalin in this condition.
Effects on Ability to Drive and Use Machines: Pregabalin may have minor or moderate influence on the ability to drive and use machines.
Pregabalin may cause dizziness and somnolence and therefore may influence the ability to drive or use machines. Patients are advised not to drive, operate complex machinery or engage in other potentially hazardous activities until it is known whether this medicinal product affects their ability to perform these activities.