Active ingredients: Pregablin
Lyrica 25 mg hard capsules Lyrica 50 mg hard capsules Lyrica 75mg hard capsules Lyrica 100 mg hard capsules Lyrica 150 mg hard capsules Lyrica 200 mg hard capsules Lyrica 225 mg hard capsules Lyrica 300 mg hard capsules
Why is Lyrica used? What is it for?
Lyrica belongs to a group of medicines used to treat epilepsy, neuropathic pain and Generalized Anxiety Disorder (GAD) in adults.
Peripheral and central neuropathic pain: Lyrica is used to treat chronic pain caused by damage to the nervous system. Various diseases can cause peripheral neuropathic pain, such as diabetes or shingles. Pain sensations can be described as heat, burning, throbbing, lightning pain, shooting pains, sharp pains, cramping pains, aching, tingling, numbness, stinging pains. Peripheral and central neuropathic pain can also be associated with mood changes, sleep disturbances and fatigue (tiredness) and can impact physical and social activity and overall quality of life.
Epilepsy: Lyrica is used to treat some forms of epilepsy in adults (partial seizures with or without secondary generalization). Your doctor will prescribe Lyrica to help you treat epilepsy when ongoing treatment does not control the situation. You will need to take Lyrica in addition to the treatment you are already under. Lyrica is not used on its own, but should always be combined with other treatments antiepileptics.
Generalized Anxiety Disorder: Lyrica is used for the treatment of Generalized Anxiety Disorder (GAD). Symptoms of Generalized Anxiety Disorder are characterized by excessive and prolonged anxiety and worry that are difficult to control. Generalized Anxiety Disorder can also cause restlessness or a feeling of tension or nerves on the skin, easy fatigue, difficulty concentrating or memory lapses, irritability, muscle tension or sleep disturbances. These conditions are different from stress and strains of everyday life.
Precautions for use What you need to know before taking Lyrica
Do not take Lyrica
if you are allergic to pregabalin or any of the other ingredients of this medicine (listed in section 6).
Warnings and Precautions
- Symptoms suggestive of allergic reactions have been reported in some patients taking Lyrica. These symptoms include swelling of the face, lips, tongue and throat, as well as a widespread rash. If any of these reactions occur you should contact your doctor immediately.
- Lyrica has been associated with dizziness and somnolence which may increase the incidence of accidental injury (falls) in the elderly. Therefore, you should be careful until you are familiar with the effects the medicine may have.
- Lyrica can cause blurring or loss of vision or other changes in vision, many of which are temporary. If any vision changes occur you should contact your doctor immediately.
- Some diabetes patients who gain weight during pregabalin treatment may need to change their diabetes medicines.
- Some side effects, such as sleepiness, may be more common because patients with spinal cord injury may be being treated with other medicines to treat, for example, pain or spasticity, which have side effects similar to those of Pregabalin and severity of these effects may increase when these medicines are taken together.
- There have been reports of heart failure in some patients taking Lyrica; these patients were mostly elderly with cardiovascular disease. If you have a history of cardiovascular disease you should inform your doctor before starting treatment with this medicine.
- There have been reports of renal failure in some patients taking Lyrica. If during treatment with Lyrica you notice a decrease in urinating, you should inform your doctor as stopping the use of this medicine may improve this condition.
- A small number of patients being treated with antiepileptic medicines such as Lyrica have had thoughts of killing and harming (harming themselves). If you have any such thoughts, please contact your doctor immediately.
- When Lyrica is used together with other medicines that can cause constipation (such as some types of pain relievers), gastrointestinal problems (eg, constipation, blocked or paralyzed bowel) may occur. Tell your doctor if you have constipation, especially if you have this problem.
- Before taking this medicine tell your doctor if you have a history of alcohol dependence or any drug abuse or dependence. Do not take more medicine than prescribed.
- There have been reports of seizures when taking Lyrica or soon after stopping it. If you experience seizures, contact your doctor immediately.
- There have been cases of decreased brain function (encephalopathy) in some patients who take LYRICA when they have other conditions. Tell your doctor if you have a history of any other serious medical conditions, including liver or kidney disease.
Children and adolescents
The safety and efficacy of pregabalin in children and adolescents (less than 18 years of age) have not been established and therefore pregabalin should not be used in this age group.
Interactions Which drugs or foods may change the effect of Lyrica
Other medicines and Lyrica
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Lyrica and other medicines may affect each other (interaction). When Lyrica is taken together with other medicines it may potentiate the side effects seen with these medicines, including respiratory failure and coma. The intensity of dizziness, sleepiness and decreased concentration may be increased if Lyrica is taken together with other medicines containing: Oxycodone - (used as an analgesic) Lorazepam - (used to treat anxiety) Alcohol Lyrica can be taken at the same time as oral contraceptives.
Lyrica with food and drink
Lyrica capsules can be taken with or without food. It is advisable not to drink alcohol while taking Lyrica.
Pregnancy and breastfeeding
Lyrica should not be taken during pregnancy unless your doctor has told you otherwise. Women of childbearing age must use an effective method of contraception. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. It is recommended that you do not breastfeed while taking Lyrica as it is not known whether Lyrica can pass into breast milk. Ask your doctor or pharmacist for advice before taking any medicine while breastfeeding.
Driving and using machines
Lyrica can cause dizziness, sleepiness and decreased concentration. You should not drive, operate complex machinery or engage in potentially hazardous activities until you are satisfied that this medicine affects your ability to perform these activities.
Lyrica contains lactose monohydrate
If you have been told by your doctor that you have an "intolerance to some sugars, contact your doctor before taking this medicinal product.
Contents of the pack and other information What Lyrica contains
The active ingredient is pregabalin. Each hard capsule contains 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg or 300 mg of pregabalin.
The other ingredients are: lactose monohydrate, corn starch, talc, gelatin, titanium dioxide (E171), sodium lauryl sulfate, colloidal anhydrous silica, black ink (contains shellac, black iron oxide (E172)), propylene glycol, potassium hydroxide) and purified water.
The 75 mg, 100 mg, 200 mg, 225 mg and 300 mg capsules also contain red iron oxide (E172).
Lyrica is available in eight PVC packs with an aluminum coated side: a pack of 14 capsules containing 1 blister, a pack of 21 capsules containing 1 blister, a pack of 56 capsules containing 4 blisters, a pack of 70 capsules containing 5 blisters , a pack of 84 capsules containing 4 blisters, a pack of 100 capsules containing 10 blisters, a pack of 112 (2 x 56) capsules and a pack of 100 capsules x 1 in the form of perforated unit dose blisters.
Lyrica is also available in HDPE bottle containing 200 capsules for 75, 150 and 300 mg strengths.
Not all pack sizes may be marketed.
Dose, Method and Time of Administration How to use Lyrica: Posology
Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist. Your doctor will work out the right dose for you. Lyrica is for oral use only.
Peripheral and central neuropathic pain, epilepsy or Generalized Anxiety Disorder:
- Take the number of capsules prescribed by your doctor.
- The right dose for you and your condition generally varies between 150 mg and 600 mg per day.
- Your doctor will tell you to take Lyrica two or three times a day. If you take this medicine twice a day take Lyrica once in the morning and once in the evening, always at about the same time. If you take this medicine three times a day take Lyrica once in the morning, once in the afternoon and once in the evening, always around the same time.
If you have the impression that the effect of Lyrica is too strong or too weak, talk to your doctor or pharmacist. If you are elderly (over 65 years of age), you will need to take Lyrica normally except if you have kidney problems. Your doctor may prescribe a different strength and / or a different dose if you have kidney problems. Swallow the capsule whole with the water. Continue taking Lyrica until your doctor tells you to stop.
Overdose What to do if you have taken too much Lyrica
If you take more Lyrica than you should
Contact your doctor immediately or go to the nearest hospital immediately. Take the pack of Lyrica capsules with you. You may feel sleepy, confused, agitated and restless, as you have taken more LYRICA than you should.
If you forget to take Lyrica
It is important that you take your Lyrica capsules regularly at the same time every day. If you forget to take a dose, take it as soon as you remember that you have not taken it unless it is time for your next dose. In this case, just take the next dose as planned. Do not take a double dose to make up for any forgotten doses.
If you stop taking Lyrica
Do not stop taking Lyrica unless your doctor tells you to. If treatment is stopped, it should be withdrawn gradually over at least 1 week. You should be aware that some side effects may occur after stopping Lyrica long and short term treatment. These include, sleep disturbances, headaches, nausea, anxiety, diarrhea, flu symptoms, seizures, nervousness, depression, pain, sweating and dizziness. These symptoms may occur more frequently or severely if you have been taking Lyrica for a longer period of time. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Lyrica
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Very common side effects that may affect more than 1 in 10 people:
- Dizziness, sleepiness, headache
Common side effects that may affect more than 1 in 100 people:
- Increased appetite
- Feeling aroused, confused, disoriented, decreased sexual interest,
- irritability
- Disturbance in attention, clumsiness, memory impairment, memory loss,
- tremor, difficulty speaking, tingling sensation, numbness, sedation, lethargy,
- insomnia, exhaustion feeling strange,
- Blurred vision, double vision
- Vertigo, balance disturbances, falls
- Dry mouth, constipation, vomiting, flatulence, diarrhea, nausea and bloating,
- Difficulty in erection
- Swelling of the body, including hands and feet
- Feeling of intoxication, abnormal gait
- Weight gain
- Muscle cramps, joint pain, back pain, pain in the limbs
- Sore throat
Uncommon side effects which may affect more than 1 in 1,000 people:
- Loss of appetite, weight loss, low blood sugar, high blood sugar
- Altered perception of self, restlessness, depression, agitation, mood swings, difficulty finding words, hallucinations, altered dreams, panic attacks, apathy, aggression, euphoric mood, mental impairment, difficulty thinking, increased "sexual interest, problems with sexuality, including inability to reach orgasm, delayed ejaculation"
- Vision changes, eye movement abnormalities, vision changes including tubular vision, flashes of light, jerking movements, reduced reflexes, increased activity, dizziness on standing, skin sensitivity, loss of taste, burning sensation, tremor during movement, decreased consciousness, loss of consciousness, fainting, increased sensitivity to noise, feeling unwell
- Dry eyes, eye swelling, eye pain, eye weakness, watery eyes, eye irritation
- Heart rhythm disturbances, increased heart rate, low blood pressure, high blood pressure, changes in heart beat, heart failure,
- Vasomotor disorders (redness), hot flashes
- Difficulty in breathing, nasal dryness, nasal congestion,
- Increased saliva production, heartburn, numbness around the mouth
- Sweating, rash, chills, fever. Muscle twitching, joint swelling, muscle stiffness, pain including muscle pain, neck pain
- Breast pain
- Difficult or painful urinating, incontinence
- Weakness, thirst, chest tightness. Changes in blood test results and liver function tests (blood creatine phosphokinase increased, alanine aminotransferase increased, aspartate aminotransferase increased, platelet count decreased, neutropenia, blood creatine increased, blood potassium decreased.
- Hypersensitivity, facial swelling, itching, hives, runny nose, nosebleed, cough, snoring,
- Painful menstrual cycles
- Cold hands and feet
Rare side effects which may affect less than 1 in 1,000 people:
- Altered sense of smell, sensation of oscillation of the visual field, altered perception of depth, visual brilliance, loss of vision
- Dilated pupils, strabismus,
- Cold sweats, throat tightness, swelling of the tongue
- Inflammation of the pancreas
- Difficulty swallowing
- Slowed or reduced body movement
- Difficulty writing properly
- Increased fluid in the abdomen
- Presence of fluid in the lungs
- Convulsions
- Changes in the electrocardiogram (ECG) that correspond to heart rhythm disturbances
- Muscle damage
- Breast discharge, abnormal breast growth, breast growth in men
- Interrupted menstrual cycles
- Renal failure, decreased urine volume, urinary retention,
- Reduction in white blood cell count
- Inappropriate behavior
- Allergic reactions (which may include difficulty in breathing, inflammation of the eyes (keratitis), and a severe skin reaction characterized by rash, blisters, peeling of the skin and pain
If you experience swelling of the face or tongue or if the skin turns red and blisters begin to form or peeling of the skin you should contact your doctor immediately.
Some side effects, such as sleepiness, may be more common because patients with spinal cord injury may be being treated with other medicines to treat, for example, pain or spasticity, which have side effects similar to those of Pregabalin and severity of these effects may increase when these medicines are taken together.
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton or bottle. The expiry date refers to the last day of the month.
This medicinal product does not require any special storage conditions.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
LYRICA 100 mg HARD CAPSULES
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each hard capsule contains 100 mg of pregabalin.
Excipients
Each hard capsule also contains 11 mg of lactose monohydrate.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Hard capsule.
Capsule marked with black ink "Pfizer" on the cap and "PGN 100" on the body.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Neuropathic pain
Lyrica is indicated for the treatment of peripheral and central neuropathic pain in adults.
Epilepsy
Lyrica is indicated as add-on therapy in adults with partial seizures with or without secondary generalization.
Generalized Anxiety Disorder
Lyrica is indicated for the treatment of Generalized Anxiety Disorder (GAD) in adults.
04.2 Posology and method of administration
The dose varies from 150 to 600 mg per day, divided into two or three administrations.
Neuropathic pain
Pregabalin treatment can be started at a dose of 150 mg per day in two or three divided doses. Based on individual patient response and tolerability, the dose can be increased to 300 mg per day after an interval of 3 to 7 days and, if necessary, to a maximum dose of 600 mg per day after an additional interval. 7 days.
Epilepsy
Pregabalin treatment can be started at a dose of 150 mg per day in two or three divided doses. Based on individual patient response and tolerability, the dose can be increased to 300 mg per day after 1 week. The maximum dose of 600 mg per day can be reached after an additional week.
Generalized Anxiety Disorder
The dose is 150-600 mg per day to be administered in two or three doses. The need for treatment should be reassessed on a regular basis.
Pregabalin treatment can be started at a dose of 150 mg per day. Based on individual patient response and tolerability, the dose can be increased to 300 mg per day after 1 week. After an additional week the dose can be increased to 450 mg per day.
The maximum dose of 600 mg per day can be reached after an additional week.
Discontinuation of pregabalin treatment
In accordance with current clinical practice, if pregabalin has to be discontinued, regardless of the indication, it is recommended that treatment be withdrawn gradually over at least 1 week (see sections 4.4 and 4.8).
Special population
Patients with renal impairment
Pregabalin is eliminated from the systemic circulation mainly by renal excretion in the form of unchanged drug. Since pregabalin clearance is directly proportional to creatinine clearance (see section 5.2), the dose reduction of pregabalin in patients with renal impairment should be individualized based on creatinine clearance (CLcr), as indicated in Table 1 by applying the following formula:
Pregabalin is effectively eliminated from plasma by hemodialysis (50% of the drug in 4 hours). For patients undergoing hemodialysis, the pregabalin daily dosage should be adjusted based on renal function. In addition to the daily dose, an additional dose of pregabalin should be administered immediately after each 4-hour dialysis session (see Table 1).
Table 1. Pregabalin dose adjustment based on renal function
TID = Three administrations
BID = Two administrations
* The total daily dose (mg / day) should be split as directed by the dosing regimen to obtain the intended single dose in mg
+ The supplemental dose is a single additional dose
Use in patients with hepatic impairment
No dosage adjustment is necessary in patients with hepatic impairment (see section 5.2).
Pediatric population
The safety and efficacy in children under 12 years of age and adolescents (12-17 years) has not yet been established. No data are yet available.
Use in the elderly (over 65 years)
A dose reduction of pregabalin may be required in elderly patients due to decreased renal function (see patients with renal impairment).
Method of administration
Lyrica can be taken with or without food.
LYRICA is for oral use only.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
04.4 Special warnings and appropriate precautions for use
Diabetic patients
According to current clinical practice, in some diabetic patients who gain weight during treatment with pregabalin the dosage of hypoglycaemic medicinal products may need to be adjusted.
Hypersensitivity reactions
Hypersensitivity reactions, including cases of angioedema, have been reported post-marketing. Pregabalin treatment should be stopped immediately in the presence of symptoms of angioedema such as swelling of the face, perioral swelling or swelling of the upper respiratory tract.
Dizziness, sleepiness, loss of consciousness, confusion and mental impairment
Pregabalin treatment has been associated with dizziness and somnolence which may increase the risk of accidental injury (falls) in elderly patients. Cases of unconsciousness, confusion and mental impairment have also been reported. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of this medicine.
Effects related to sight
In the unchecked trials, blurred vision was reported in a higher proportion of pregabalin-treated patients than placebo-treated patients and resolved in the majority of cases with continued treatment. In clinical trials in which an ophthalmological test was performed, the incidence of decreased visual acuity and visual field changes was higher in pregabalin-treated patients than in placebo-treated patients; on the other hand, the incidence of alterations detected on the fundoscopic examination was higher in patients treated with placebo (see section 5.1).
Visual adverse reactions, including loss of vision, blurred vision or other alterations in visual acuity, many of them transient, have also been reported in the post-marketing setting. Stopping pregabalin treatment may lead to a resolution or improvement of these vision symptoms.
Kidney failure
Cases of renal failure have been reported and in some cases discontinuation of pregabalin has shown that this adverse reaction is reversible.
Discontinuation of treatment with other antiepileptic medicinal products
There are insufficient data that once control of seizures has been achieved with pregabalin add-on therapy, concomitant treatment with other antiepileptic medicinal products can be discontinued and pregabalin monotherapy maintained.
Withdrawal symptoms
In some patients, withdrawal symptoms have been observed following discontinuation of short- and long-term treatment with pregabalin. The following events have been reported: insomnia, headache, nausea, anxiety, diarrhea, flu syndrome, nervousness, depression, pain, convulsions, hyperhydrosis and dizziness. Patients should be informed of this occurrence before starting treatment.
Convulsions, including status epilepticus and grand mal seizures, may occur during treatment with pregabalin or soon after treatment is stopped.
Regarding the discontinuation of long-term treatment with pregabalin, there are no data on the incidence and severity of withdrawal symptoms in relation to the duration of treatment and the dose of pregabalin.
Congestive heart failure
There have been post-marketing reports of congestive heart failure in some patients taking pregabalin. These reactions are mainly seen in elderly patients with cardiovascular disease being treated with pregabalin for neuropathic pain. Pregabalin should be used with caution in these patients. Stopping pregabalin treatment can resolve this condition.
Treatment of central neuropathic pain due to a spinal 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 somnolence in particular is increased. This may be attributed to an additional effect caused by concomitant medications. (eg anti-spastic agents) required for this condition This should be taken into consideration when pregabalin is prescribed in this condition.
Suididary conception and behavior
Cases of suicidal ideation and behavior have been reported in patients receiving antiepileptic medicinal products in their various indications. A meta-analysis of randomized, placebo-controlled trials with antiepileptic drugs also found a small increased risk of suicidal ideation and behavior. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk during treatment with pregabalin.
Therefore, patients should be monitored for signs of suicidal ideation and behavior and appropriate treatment should be considered. Patients (and caregivers) should be advised to consult their physician if signs of suicidal ideation or behavior emerge.
Reduced function of the lower gastrointestinal tract
Events related to decreased lower gastrointestinal function (eg intestinal obstruction, paralytic ileus, constipation) have been reported when pregabalin was co-administered with medicinal products that can cause constipation, such as opioid analgesics. When pregabalin and opioids are used in combination, preventive measures for constipation (particularly in women and elderly people) may be considered.
Cases of abuse
Cases of abuse have been reported. Caution should be exercised in patients with a history of abuse and in these cases the patient should be monitored for possible onset of pregabalin abuse symptoms,
Encephalopathy
Cases of encephalopathy have been reported, mostly in patients with underlying conditions that can precipitate an "encephalopathy."
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 medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Since pregabalin is mainly excreted unchanged in the urine, it undergoes negligible metabolism in humans (in vitro and does not bind to plasma proteins, it is unlikely to cause or undergo pharmacokinetic interactions.
Education in vivo and population pharmacokinetic analysis
As a result, in the studies in vivo no clinically relevant pharmacokinetic interactions were observed between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. The population pharmacokinetic analysis indicated that oral antidiabetics, diuretics, insulin, phenobarbital, tiagabine and topiramate did not have a clinically significant effect on pregabalin clearance.
Oral contraceptives norethisterone and / or ethinyl estradiol
Concomitant administration of pregabalin with the oral contraceptives norethisterone and / or ethinylestradiol does not affect the pharmacokinetics of the two substances. steady-state.
Ethanol, lorazepam and oxycodone
Pregabalin can potentiate the effects of ethanol and lorazepam. In controlled clinical trials, multiple oral doses of pregabalin administered with oxycodone, lorazepam or ethanol had no clinically important effect on respiration. There have been post-marketing reports of respiratory failure and coma in patients taking pregabalin and other CNS depressant medicines. Pregabalin appears to have an additive effect on impaired cognitive function and motor function caused by 'oxycodone.
Interactions in elderly patients
No specific pharmacodynamic interaction studies have been conducted in healthy elderly volunteers. Interaction studies have only been conducted in adults.
04.6 Pregnancy and lactation
Women of childbearing age / Contraception in men and women
As a potential risk in men is not yet known, women of childbearing age should use an effective method of contraception.
Pregnancy
There are no adequate data on the use of pregabalin in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk to humans is unknown. Lyrica should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the fetus).
Feeding time
It is not known whether pregabalin is excreted in human milk; however, it is present in the milk of rats. Therefore, it is recommended not to breastfeed during pregabalin treatment.
Fertility
There are no clinical data on the effects of pregabalin on women of childbearing age.
In a clinical study to evaluate the effect of pregabalin on sperm motility, healthy male patients were exposed to a pregabalin dose of 600 mg / day. After 3 months of treatment there was no evidence of effects on sperm motility.
A fertility study in female rats has shown adverse reproductive reactions.
The fertility study in male rats showed adverse reproductive and developmental reactions. The clinical relevance of these diseases is unknown. (see paragraph 5.3)
04.7 Effects on ability to drive and use machines
Lyrica may have minimal or moderate influence on the ability to drive and use machines. Lyrica may cause dizziness and somnolence and therefore may affect the ability to drive or use machines. Patients should be advised not to drive, operate complex machinery or engage in other potentially dangerous activities until it is known whether this medicine affects the ability to perform these activities.
04.8 Undesirable effects
The pregabalin clinical program involved over 8900 patients treated with pregabalin; over 5,600 of these patients were enrolled in double-blind placebo-controlled clinical trials. The most commonly reported adverse reactions were dizziness and somnolence. Adverse reactions were usually mild to moderate in intensity. In all controlled studies, the discontinuation rate for adverse reactions was 12% for pregabalin-treated patients and 5% for placebo-treated patients. The most common adverse reactions leading to discontinuation of pregabalin were dizziness and somnolence.
The table below lists all adverse reactions that occurred at an "incidence greater than placebo and in more than one patient and are classified by system organ class and frequency (very common (≥ 1/10), common (≥ 1 / 100,
The listed adverse reactions may also be associated with the underlying disease and / or the use of concomitant medications.
In the treatment of central neuropathic pain due to spinal cord injury, the incidence of adverse reactions in general, CNS reactions and in particular somnolence is increased (see section 4.4).
Other reactions reported from post-marketing experience are included with a Frequency Not Known in italics in the list below.
In some patients, withdrawal symptoms have been observed following discontinuation of short- and long-term treatment with pregabalin. The following reactions have been reported: insomnia, headache, nausea, anxiety, diarrhea, flu syndrome, convulsions, nervousness, depression, pain, hyperhidrosis and dizziness. Patients should be informed of this occurrence before starting treatment.
Regarding the discontinuation of long-term treatment with pregabalin, there are no data on the incidence and severity of withdrawal symptoms in relation to the duration of treatment and the dose of pregabalin.
04.9 Overdose
With overdoses up to 15 g, no unexpected adverse reactions have been reported.
During the post-marketing period, the most commonly observed adverse reactions when pregabalin was taken at higher than recommended doses included somnolence, confusion, agitation and restlessness.
Treatment of pregabalin overdose should include general supportive measures and, if necessary, may include hemodialysis (see section 4.2 Table 1).
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antiepileptics, other antiepileptics.
ATC code: N03AX16
The active substance, pregabalin, is an analog ((S-3- (aminomethyl) -5-methylhexanoic acid) of gamma-aminobutyric acid.
Mechanism of action
Pregabalin binds to the accessory subunit (α2-δ protein) of voltage-gated calcium channels in the central nervous system.
Clinical experience
Neuropathic pain
Efficacy has been demonstrated in trials in diabetic neuropathy, post-herpetic neuralgia and spinal cord injury. Efficacy has not been studied in other neuropathic pain models.
Pregabalin has been studied in 10 controlled clinical trials, in which it was administered twice daily (BID) for up to 13 weeks and 3 times daily (TID) for up to 8 weeks. Overall, the safety and efficacy profiles for the BID and TID dosing regimens were similar.
In clinical trials of up to 12 weeks in both peripheral and central neuropathic pain a reduction in pain was observed after one week of treatment and this reduction was maintained throughout the duration of treatment.
In controlled clinical trials in peripheral neuropathic pain, 35% of pregabalin-treated patients and 18% of placebo-treated patients reported a 50% improvement in pain score. In patients who did not report somnolence, this improvement was seen in 33% of pregabalin-treated patients and 18% of placebo-treated patients. The response rate for patients who reported somnolence was 48% for pregabalin-treated patients and 16% for placebo-treated patients.
In the controlled clinical trial in central neuropathic pain, 22% of patients treated with Pregabalin and 7% of those taking placebo reported a 50% improvement in pain score.
Epilepsy
Additional treatment
Pregabalin has been studied in 3 12-week controlled clinical trials with both two (BID) and three (TID) daily administrations. Overall, the safety and efficacy profiles for the BID or TID dosing regimens were similar.
A reduction in the frequency of seizures was observed within one week of treatment.
Monotherapy (Newly diagnosed patients)
Pregabalin was studied in 1 controlled clinical trial lasting 56 weeks with two daily doses (BID). Pregabalin did not show non-inferiority to lamotrigine and considered as an endpoint a period of 6 months without seizures. Pregabalin and lamotrigine were similarly safe and well tolerated.
Generalized Anxiety Disorder
Pregabalin was studied in 6 controlled clinical trials lasting 4-6 weeks, an 8-week study in elderly subjects and a long-term, 6-month double-blind phase of relapse prevention.
A "relief of symptoms of Generalized Anxiety Disorder" on the Hamilton Anxiety Scale (HAM-A) was observed within one week of treatment.
In controlled clinical trials (duration 4-8 weeks), 52% of patients treated with pregabalin and 38% of those in the placebo group reported an improvement of at least 50% in HAM-A total score from baseline to end. of study.
In controlled trials, blurred vision was reported in a higher proportion of pregabalin-treated patients than placebo-treated patients and resolved in the majority of cases with continued treatment. An ophthalmological test (including visual acuity test, formal visual field examination and dilated pupil fundoscopic examination) was performed in over 3600 patients enrolled in controlled clinical trials. In these patients, visual acuity was reduced by 6.5% in pregabalin-treated patients and 4.8% in placebo-treated patients. Visual field changes were observed in 12.4% of patients taking pregabalin and 11.7% of those taking placebo. pregabalin and in 2.1% of those treated with placebo.
05.2 Pharmacokinetic properties
The steady-state pharmacokinetics of pregabalin are similar in healthy volunteers, epileptic patients receiving antiepileptic medicinal products and patients with chronic pain.
Absorption
Pregabalin is rapidly absorbed when administered in the fasted state, with peak plasma concentrations reached within 1 hour of single or multiple dose administration. The oral bioavailability of pregabalin is ≥ 90% and is independent of dose. Following repeated administration, steady-state is achieved within 24-48 hours. The absorption rate of pregabalin decreases when administered with food, with a reduction in C of approximately 25-30% and a delay in t of approximately 2.5 hours. However, administration of pregabalin with food has no clinically significant effect on the absorption of pregabalin.
Distribution
In preclinical studies, pregabalin has been shown to cross the blood brain barrier in mice, rats and monkeys. Pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats. In humans, the apparent volume of distribution of pregabalin following oral administration is approximately 0.56 L / kg. Pregabalin does not bind to plasma proteins.
Biotransformation
Pregabalin is metabolised negligibly in humans. Following administration of a dose of radiolabelled pregabalin, approximately 98% of the radioactivity found in the urine was present as unchanged drug. The N-methylated derivative of pregabalin, the major metabolite of pregabalin found in urine corresponds to 0.9% of the dose. In preclinical studies, there was no indication of racemization of pregabalin S-enantiomer to R-enantiomer.
Elimination
Pregabalin is eliminated from the circulation mainly by renal excretion in the form of unchanged drug. The mean elimination half-life of pregabalin is 6.3 hours. Plasma clearance and renal clearance are directly proportional to creatinine clearance (see section 4.2 Renal impairment).
Dosage adjustment is required in patients with impaired renal function or undergoing hemodialysis (see section 4.2 Table 1).
Linearity / non-linearity
Pregabalin pharmacokinetics are linear over the recommended daily dose range. Inter-subject variability in pharmacokinetics is low (
Pharmacokinetics in particular groups of patients
Sex
Clinical studies indicate that gender does not significantly affect the plasma concentrations of pregabalin.
Renal impairment
Pregabalin clearance is directly proportional to creatinine clearance. In addition, pregabalin is effectively removed from plasma by hemodialysis (after a 4-hour hemodialysis session, pregabalin plasma concentrations are reduced by approximately 50%). Since renal elimination is the major route of elimination, a dose reduction is required in patients with renal impairment and an additional dose is required following a hemodyliasis session (see section 4.2 Table 1).
Hepatic impairment
No specific pharmacokinetic studies have been conducted in patients with hepatic impairment. Since pregabalin is not significantly metabolised and is mainly excreted as unchanged drug in the urine, hepatic impairment is not expected to significantly alter the plasma concentrations of pregabalin.
Elderly (over 65 years of age)
Pregabalin clearance tends to decrease with increasing age. This reduction in clearance of orally administered pregabalin is consistent with the reductions in creatinine clearance associated with increasing age. A dose reduction of pregabalin may be required in patients with age-related renal impairment (see section 4.2 Table 1).
05.3 Preclinical safety data
Based on conventional animal safety pharmacology studies, pregabalin was well tolerated at clinically significant doses. In repeat dose toxicity studies in rats and monkeys, CNS effects including hypoactivity, hyperactivity and ataxia were observed. An increased incidence of retinal atrophy was commonly observed in the elderly albino rat following long-term exposure to pregabalin with exposure ≥ 5 times the mean human exposure at maximum recommended clinical doses.
Pregabalin was not teratogenic in mice, rats or rabbits. Fetal toxicity occurred in rats and rabbits only at exposures sufficiently in excess of human exposure. In prenatal / postnatal toxicity studies, pregabalin induced developmental toxicity in rats at exposure> 2 times the recommended maximum human exposure.
Adverse effects on fertility in male and female rats were observed only at exposures sufficiently in excess of the therapeutic exposure. Adverse effects in reproductive organs and sperm parameters of male rats are reversible and only occur at one time. exposure above the therapeutic one or are associated with a spontaneous degenerative process of the reproductive organ of the male rat. However, the effects are considered minor or in any case not of clinical relevance.
Pregabalin was not shown to be genotoxic based on the results of a series of tests in vitro and in vivo.
Two-year carcinogenicity studies were conducted with pregabalin in rats and mice. No tumor formation was observed in rats exposed to doses up to 24 times the mean human exposure at the maximum recommended clinical dose of 600mg / day. In mice, no increased incidence of tumors was observed with exposures similar to the average human exposure, but an increased incidence of haemangiosarcoma was observed with higher exposures. The non-genotoxic mechanism of pregabalin-induced tumor formation in mice causes platelet changes and associated endothelial cell proliferation. These platelet changes have not been found in rats or humans based on limited short- and long-term clinical data. . There is no evidence to suggest an associated risk in humans.
In juvenile rats the types of toxicity did not differ qualitatively from those observed in adult rats. However, young rats are more sensitive. At therapeutic exposures, there were CNS clinical signs of hyperactivity and bruxism and some changes in growth (transient reduction in weight gain). Effects on the menstrual cycle were observed with 5 times the therapeutic exposure in "Human. A reduction in response to acoustic stimuli was observed in juvenile rats 1-2 weeks after" exposure 2 times greater than the human therapeutic exposure. Nine weeks after exposure, this effect was no longer observed.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Capsule contents:
Lactose monohydrate
Cornstarch
Talc
Capsule operculum:
Jelly
Titanium dioxide (E171)
Sodium lauryl sulfate
Anhydrous colloidal silica
Purified water
Red iron oxide (E172)
Ink:
Shellac
Black iron oxide (E172)
Propylene glycol
Potassium hydroxide
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
PVC / Aluminum blisters containing 21, 84 or 100 hard capsules.
100 x 1 hard capsules in PVC / Aluminum perforated unit dose blisters.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions for disposal.
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Limited,
Ramsgate Road,
Sandwich,
Kent - CT13 9NJ
UK
08.0 MARKETING AUTHORIZATION NUMBER
EU / 1/04/279/014 - AIC n. 036476149
EU / 1/04/279/015 - AIC n. 036476152
EU / 1/04/279/016 - AIC n. 036476164
EU / 1/04/279/39
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 06 July 2004
Date of last renewal: 06 July 2009
10.0 DATE OF REVISION OF THE TEXT
11/2011
