Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use
Diabetic patients
In accordance with current clinical practice, some diabetic patients who gain weight on pregabalin treatment may need to adjust hypoglycaemic medicinal products.

Hypersensitivity reactions
There have been reports in the postmarketing experience of hypersensitivity reactions, including cases of angioedema.
Pregabalin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur.

Severe cutaneous adverse reactions (SCARs)
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 If signs and symptoms suggestive of these reactions appear, pregabalin should be withdrawn immediately and an alternative treatment considered (as appropriate).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 postmarketing 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 the medicinal product.

Vision-related effects
In controlled trials, a higher proportion of patients treated with pregabalin reported blurred vision than did patients treated with placebo which resolved in a majority of cases with continued dosing. In the clinical studies where ophthalmologic testing was conducted, the incidence of visual acuity reduction and visual field changes was greater in pregabalin-treated patients than in placebo-treated patients; the incidence of fundoscopic changes was greater in placebo-treated patients (see section 5.1).

In the postmarketing experience, 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.

Renal failure
Cases of renal failure have been reported and in some cases discontinuation of pregabalin did show reversibility of this adverse reaction.

Withdrawal of concomitant anti-epileptic medicinal products
There are insufficient data for the withdrawal of concomitant anti-epileptic medicinal products, once seizure control with pregabalin in the add-on situation has been reached, in order to reach monotherapy on pregabalin.

Congestive heart failure
There have been postmarketing reports of congestive heart failure in some patients receiving pregabalin. These reactions are mostly seen in elderly cardiovascular compromised patients during pregabalin treatment for a neuropathic indication.
Pregabalin should be used with caution in these patients. Discontinuation of pregabalin may resolve the reaction.

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.
Respiratory depression
There have been reports of severe respiratory depression in relation to pregabalin 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).

Suicidal ideation and behaviour
Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled studies of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known.
Cases of suicidal ideation and behaviour have been observed in patients treated with pregabalin in the postmarketing experience (see section 4.8). An epidemiological study using a self-controlled study design (comparing treatment periods with non-treatment periods within an individual) showed evidence of an increased risk of new onset of suicidal behaviour and death by suicide in patients treated with pregabalin.

Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. Patients should be monitored for signs of suicidal ideation and behaviour and appropriate treatment should be considered. Discontinuation of pregabalin treatment should be considered in case of suicidal ideation and behaviour.

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




Concomitant use with opioids
Caution is advised when prescribing pregabalin concomitantly with opioids due to risk of CNS depression (see section 4.5).
In a case-control study of opioid users, those patients who took pregabalin concomitantly with an opioid had an increased risk for opioid-related death compared to opioid use alone (adjusted odds ratio [aOR], 1.68 [95% CI, 1.19 – 2.36]). This increased risk was observed at low doses of pregabalin (≤ 300 mg, aOR 1.52 [95% CI, 1.04 – 2.22]) and there was a trend for a greater risk at high doses of pregabalin (> 300 mg, aOR 2.51 [95% CI 1.24 – 5.06]).

Misuse, abuse potential or dependence
Pregabalin can cause drug dependence, which may occur at therapeutic doses. Cases of abuse and misuse have been reported.
Patients with a history of substance abuse may be at higher risk for pregabalin misuse, abuse and dependence, and pregabalin should be used with caution in such patients. Before prescribing pregabalin, the patient’s risk of misuse, abuse or dependence should be carefully evaluated.

Patients treated with pregabalin should be monitored for symptoms of pregabalin misuse, abuse or dependence, such as development of tolerance, dose escalation and drug-seeking behaviour.

Withdrawal symptoms
After discontinuation of short-term and long-term treatment with pregabalin, withdrawal symptoms have been observed. The following symptoms have been reported: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, nervousness, depression, suicidal ideation, pain, convulsion, hyperhidrosis and dizziness. The occurrence of withdrawal symptoms following discontinuation of pregabalin may indicate drug dependence (see section 4.8). The patient should be informed about this at the start of the treatment. If pregabalin 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 use or shortly after discontinuing pregabalin.

Concerning discontinuation of long-term treatment of pregabalin, data suggest that the incidence and severity of withdrawal symptoms may be dose-related.

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

Women of childbearing potential/Contraception
Lyrica use in the first-trimester of pregnancy may cause major birth defects in the unborn child. Pregabalin should not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus. Women of childbearing potential have to use effective contraception during treatment (see section 4.6).


Lactose intolerance
Lyrica contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Sodium content
Pregabalin Pfizer contains less than 1 mmol sodium (23 mg) per hard capsule. Patients on low sodium diets can be informed that this medicinal product is essentially ‘sodium-free’.

Effects on Driving

4.7    Effects on ability to drive and use machines
Lyrica may have minor or moderate influence on the ability to drive and use machines.
Lyrica 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.