LYRICA is indicated for the treatment of adult patients with neuropathic pain due to Herpes zoster infections and diabetes.
Hypersensitivity to the active substance or to any of the excipients.
Warnings and Special Precautions
Effects on ability to drive and use machines:
LYRICA 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 this medication affects their ability to perform these activities.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose- galactose malabsorption should not take this medicine.
There have been reports in the post-marketing experience of hypersensitivity reactions, including cases of angioedema and urticaria. LYRICA should be discontinued immediately if symptoms of angioedema, such as facial, perioral or upper airway swelling occur (see SIDE EFFECTS).
LYRICA treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population. There have 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 the medication (see SIDE EFFECTS).
When LYRICA is used in combination with antidepressants, respiratory failure has occurred.
After discontinuation of short-term and long-term treatment with LYRICA, withdrawal symptoms have been observed in some patients. The following events have been reported: insomnia, headache, nausea and diarrhoea (see SIDE EFFECTS).
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 LYRICA has been reported (see SIDE EFFECTS). Renal failure has occurred.
There have been post-marketing reports of congestive heart failure or deterioration of heart failure in some patients receiving LYRICA. In 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. LYRICA should be used with caution in patients with congestive heart failure (see SIDE EFFECTS).
The LYRICA clinical programme involved over 9 000 patients who were exposed to LYRICA, of whom over 5 000 were in double-blind placebo-controlled trials. The most commonly reported adverse reactions were dizziness and somnolence which were dose-related. Adverse reactions were usually mild to moderate in intensity. In all controlled studies, the discontinuation rate due to adverse events was 13 % for patients receiving LYRICA and 7 % for patients receiving placebo. The adverse reactions resulting in discontinuation from LYRICA treatment groups were dizziness and somnolence.
In the table below all adverse reactions, which occurred at an incidence greater than placebo and in more than one patient, are listed by class and frequency: Very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1 000, <1/100) and rare (< 1/1 000).
The adverse reactions listed may also be associated with the underlying disease and concomitant medications.
|Body system||Adverse drug reactions|
|Blood and lymphatic system disorders|
|Metabolism and Nutrition Disorders|
|Common||Euphoric mood, confusion, libido decreased,|
|Uncommon||Depersonalisation, anorgasmia, restlessness,|
depression, agitation, mood swings, insomnia
exacerbated, depressed mood, word finding
difficulty, hallucination, abnormal dreams, libido
increased, panic attack, apathy
|Rare||Disinhibition, elevated mood|
|Nervous System Disorders|
|Very Common||Dizziness, somnolence|
|Common||Ataxia, disturbance in attention, coordination|
abnormal, memory impairment, tremor, dysarthria,
|Uncommon||Cognitive disorder, hypoaesthesia, visual field|
defect, nystagmus, speech disorder, myoclonus,
hyporeflexia, dyskinesia, psychomotor
hyperactivity, dizziness postural, hyperaesthesia,
ageusia, burning sensation, intention tremor,
|Rare||Hypokinesia, parosmia, dysgraphia|
|Common||Vision blurred, diplopia|
|Uncommon||Visual disturbance, dry eye, eye swelling, visual|
acuity reduced, eye pain, asthenopia, lacrimation
|Rare||Photopsia, eye irritation, mydriasis, oscillopsia,|
altered visual depth perception, peripheral vision
loss, strabismus, visual brightness
|Ear and labyrinth disorders|
|Rare||Atrioventricular block first degree, sinus|
tachycardia, sinus arrhythmia,
|Uncommon||Flushing, hot flushes|
|Rare||Hypotension, peripheral coldness, hypertension|
|Respiratory, thoracic and mediastinal disorders|
|Uncommon||Dyspnoea, nasal dryness|
|Rare||Nasopharyngitis, cough, nasal congestion,|
epistaxis, rhinitis, snoring, throat tightness
|Common||Dry mouth, constipation, vomiting, flatulence|
|Uncommon||Abdominal distension, salivary hypersecretion,|
gastroesophageal reflux disease, hypoaesthesia oral
|Rare||Ascites, dysphagia, pancreatitis|
|Skin and subcutaneous tissue disorders|
|Uncommon||Sweating, rash papular|
|Rare||Cold sweat, urticaria|
|Musculoskeletal and connective tissue disorders|
|Uncommon||Muscle twitching, joint swelling, muscle cramp,|
myalgia, arthralgia, back pain, pain in limb, muscle
|Rare||Cervical spasm, neck pain, rhabdomyolysis|
|Renal and urinary disorders|
|Uncommon||Dysuria, urinary incontinence|
|Rare||Oliguria, renal failure|
|Reproductive system and breast disorders|
|Uncommon||Ejaculation delayed, sexual dysfunction|
|Rare||Amenorrhoea, breast pain, breast discharge,|
dysmenorrhoea, hypertrophy breast
|General disorders and administration site conditions|
|Common||Fatigue, oedema peripheral, feeling drunk, oedema,|
|Uncommon||Asthenia, fall, thirst, chest tightness|
|Rare||Pain exacerbated, anasarca, pyrexia, rigors|
|Uncommon||Alanine aminotransferase increased, blood|
creatine phosphokinase increased, aspartate
aminotransferase increased, platelet count
|Rare||Blood glucose increased, blood creatinine|
increased, blood potassium decreased, weight
decreased, white blood cell count decreased
Elderly (over 65 years of age):
In a total of 998 elderly patients, no overall differences in safety were observed compared with patients less than 65 years of age.
Post-marketing: (see WARNINGS AND SPECIAL PRECAUTIONS)
Immune system disorder:
Angioedema, allergic reaction, hypersensitivity.
Rare cases of swollen tongue have been reported, diarrhoea, nausea.
Congestive heart failure.
Skin and subcutaneous tissue disorders:
Rare cases of face swelling have been reported, pruritus.
Nervous system disorders:
Headache, loss of consciousness, mental impairment, reversible paralysis.
Renal and urinary disorders:
Since LYRICA is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (< 2 % of a dose recovered in urine as metabolites), does not inhibit drug metabolism in vitro, and is not bound to plasma proteins, LYRICA is unlikely to produce, or be subject to, pharmacokinetic interactions.
Accordingly, in in vivo studies no clinically relevant pharmacokinetic interactions were observed between LYRICA and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. In addition, population pharmacokinetic analysis indicated that the 3 commonly used drug classes, oral antidiabetics, diuretics and insulin, and the commonly used anti-epileptic drugs, phenytoin, carbamazepine, valproic acid, lamotrigine, phenobarbital, tiagabine, and topiramate, had no clinically significant effect on pregabalin clearance. Similarly, these analyses indicated that LYRICA had no clinically significant effect on the clearance of phenytoin, carbamazepine, valproic acid, lamotrigine, topiramate and phenobarbital.
Co-administration of LYRICA with the oral contraceptives norethisterone and/or ethinyl oestradiol does not influence the steady-state pharmacokinetics of either agent. Multiple oral doses of LYRICA co-administered with oxycodone, lorazepam, or ethanol did not result in clinically important effects on respiration. LYRICA appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone. LYRICA may potentiate the effects of ethanol and lorazepam.
In post-marketing experience, there are reports of respiratory failure and coma in patients taking LYRICA and other CNS depressant medications.
Dosage and Directions for Use
LYRICA is given orally with or without food. The recommended starting dose for LYRICA 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 LYRICA has to be discontinued, it is recommended this should be done gradually over a minimum of 1 week.
Patients with renal impairment:
LYRICA is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. As LYRICA clearance is directly proportional to creatinine clearance (see Pharmacokinetics in special patient groups – 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 – age) x Wt (kg)
0,82 x Serum creatinine (µmol/l)
*For females multiply the CLcr by 0,85
LYRICA is removed effectively from plasma by haemodialysis (50 % of drug in 4 hours). For patients receiving haemodialysis, the LYRICA daily dose 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 (see Table 1).
|Total LYRICA daily dose*||Dose regimen|
|30-60||75||150||OD or BD|
|15-30||25-50||75||OD or BD|
|Supplementary dosage following haemodialysis|
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 adjustment is required for patients with hepatic impairment (see Pharmacokinetics in special patient groups – Hepatic impairment).
The safety and effectiveness of LYRICA 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, see Table 1.
Known Symptoms of Overdosage and Particulars of its Treatment
In overdoses up to 15 g, no unexpected adverse reactions were reported. In post-marketing experience, the most commonly reported adverse events observed when LYRICA was taken in overdose included affective disorder, somnolence, confusional state, depression, agitation and restlessness.
Treatment of LYRICA overdose should include general supportive measures and may include haemodialysis if necessary (see DOSAGE AND DIRECTIONS FOR USE – Patients with renal impairment).
The active substance, pregabalin, is a gamma-aminobutyric acid (GABA) analogue ((S)-3- (aminomethyl)-5-methylhexanoic acid).
Mechanism of action:
In vitro studies show that pregabalin binds to an auxiliary subunit (α2-δ protein) of voltage-gated calcium channels in the central nervous system, potently displacing [3H]-gabapentin. Two lines of evidence indicate that binding of pregabalin to the α2-δ site is required for analgesic activity in animal models: (1) Studies with the inactive R-enantiomer and other structural derivatives of pregabalin and(2) Studies of pregabalin in mutant mice with defective drug binding to the α2-δ protein. In addition, pregabalin reduces the release of several neurotransmitters, including glutamate, noradrenaline, and substance P. The significance of these effects for the clinical pharmacology of pregabalin is not known.
Pregabalin does not interact with either GABAA or GABAB receptors; it is not converted metabolically into GABA or a GABA agonist; it is not an inhibitor of GABA uptake or degradation. Pregabalin prevents pain-related behaviours in animal models of neuropathic and post-surgical pain, including hyperalgesia and allodynia.
The effectiveness of pregabalin for the management of neuropathic pain was investigated in 10 double blind, placebo-controlled, multicentre studies with either twice a day (BD) or three times a day (TDS) dosing. A total of 2 099 patients were enrolled in the 10 studies. To enter the study, patients had to have moderate to severe pain caused by diabetic peripheral neuropathy or pain due to post-Herpes zoster infection.
Store at or below 25
ºC, in a dry place. STORE ALL MEDICINES OUT OF REACH OF CHILDREN.
STORE ALL MEDICINES OUT OF REACH OF CHILDREN.
Proprietary Name and Dosage Form
LYRICA® 25 mg capsule
LYRICA® 50 mg capsule
LYRICA® 75 mg capsule
LYRICA® 100 mg capsule
LYRICA® 150 mg capsule
Pregnancy and Lactation
There are no adequate data on the use of LYRICA in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk to humans is unknown. Therefore, LYRICA should not be used during pregnancy. It is not known if LYRICA is excreted in the breast milk of humans; however, it is present in the milk of rats. Therefore, breastfeeding is not recommended.
Identification and Presentation
LYRICA 25 mg: White, opaque, hard gelatine capsule, marked “Pfizer” on the cap and “PGN 25” on the body with black ink.
LYRICA 50 mg: White, opaque, hard gelatine capsule, marked “Pfizer” on the cap and “PGN 50” on the body with black ink. The body is also marked with a black band.
LYRICA 75 mg: White (body) and orange (cap), opaque, hard gelatine capsule, marked “Pfizer” on the cap and “PGN 75” on the body with black ink.
LYRICA 100 mg: Orange, opaque, hard gelatine capsule, marked “Pfizer” on the cap and “PGN 100” on the body with black ink.
LYRICA 150 mg: White, opaque, hard gelatine capsule, marked “Pfizer” on the cap and “PGN 150” on the body with black ink.
Clear PVC/Aluminium blisters containing 14, 56 or 100 hard capsules.
LYRICA® 25mg, 50mg, 75mg, 100mg, 150 mg capsule package insert - effective date 15 May 2015
** Not all strengths may be available in all markets; i.e. Lyrica 50mg and 100mg are not marketed in South Africa.
NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION:
Pfizer Laboratories (Pty) Ltd
85 Bute Lane
Contact Pfizer Medical Information