Consumer medicine information

Blooms The Chemist Pregabalin

Pregabalin

BRAND INFORMATION

Brand name

Blooms the Chemist Pregabalin Capsules

Active ingredient

Pregabalin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Blooms The Chemist Pregabalin.

What is in this leaflet

Read this leaflet carefully before taking your medicine.

This leaflet answers some common questions about pregabalin. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the last page. More recent information on this medicine may be available.

Ask your doctor or pharmacist:

  • if there is anything you do not understand in this leaflet,
  • if you are worried about taking your medicine, or
  • to obtain the most up-to-date information.

You can also download the most up to date leaflet from www.apotex.com.au.

All medicines have risks and benefits. Your doctor has weighed the risks of you using this medicine against the benefits they expect it will have for you.

Pharmaceutical companies cannot give you medical advice or an individual diagnosis.

Keep this leaflet with your medicine. You may want to read it again.

What this medicine is used for

The name of your medicine is Blooms The Chemist Pregabalin. It contains the active ingredient pregabalin.

It is used to:

  • treat neuropathic pain, which is pain caused by an abnormality of, or damage to, the nerves
  • control epilepsy. Epilepsy is a condition where you have repeated seizures (fits). There are many different types of seizures, ranging from mild to severe.

Pregabalin may be used alone, or in combination with other medicines, to treat your condition.

Your doctor may prescribe pregabalin in addition to your current therapy when your current treatment is no longer working as well as before.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed this medicine for another reason.

This medicine is available only with a doctor's prescription.

How it works

Pregabalin belongs to a group of medicines called anticonvulsants. These drugs are thought to work by controlling brain chemicals which send signals to nerves so that seizures do not happen.

Pregabalin also has analgesic effects (relieves pain).

Use in children

There is not enough information to recommend the use of this medicine in children under the age of 18 years.

Before you take this medicine

When you must not take it

Do not take this medicine if:

  • You have had an allergic reaction to pregabalin or any of the ingredients listed at the end of this leaflet.
    Symptoms of an allergic reaction may include cough, shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body, rash, itching or hives on the skin; fainting or hay fever-like symptoms.
    If you think you are having an allergic reaction, do not take any more of the medicine and contact your doctor immediately or go to the Accident and Emergency department at the nearest hospital.
  • The expiry date (EXP) printed on the pack has passed.
  • The packaging is torn, shows signs of tampering or it does not look quite right.

Before you start to take it

Before you start taking this medicine, tell your doctor if:

  1. You have allergies to:
  • any other medicines, especially barbiturates or any other anticonvulsant medicines
  • any other substances, such as foods, preservatives or dyes.
  1. You have or have had any medical conditions, especially the following:
  • congestive heart failure
  • hereditary problems with galactose metabolism
  • kidney problems
  • diabetes
  • depression
  • a history of substance abuse.
  1. Tell your doctor if you have a history of substance abuse.

There have been reported cases of misuse and abuse with pregabalin.

  1. You are currently pregnant or you plan to become pregnant.

Pregabalin is not recommended for use during pregnancy. However, if you have epilepsy, it is very important to control your fits while you are pregnant. If it is necessary for you to take pregabalin, your doctor can help you decide whether or not to take it during pregnancy.

  1. You are currently breast-feeding or you plan to breast-feed.

It is recommended that you do not breast-feed while taking pregabalin, as it passes into breast milk and its safety in infants is unknown.

  1. You are planning to have surgery or an anaesthetic.
  2. You are taking or are planning to take any other medicines. This includes vitamins and supplements that are available from your pharmacy, supermarket or health food shop.

Some medicines may interact with pregabalin. These include:

  • oxycodone, morphine or codeine, pain relievers called opioid analgesics
  • lorazepam, a medicine used to treat anxiety
  • medicines used to treat allergies (antihistamines)
  • medicines used to treat certain psychiatric disorders.

Taking these medicines together with pregabalin may increase your chance of experiencing side effects. You may need a different dose or need to take different medicines. Your doctor or pharmacist will advise you.

Other medicines not listed above may also interact with pregabalin.

How to take this medicine

Follow carefully all directions given to you by your doctor. Their instructions may be different to the information in this leaflet.

How much to take

Your doctor will tell you how much of this medicine you should take. This will depend on your age, your condition and whether you are taking any other medicines.

Do not stop taking your medicine or change your dosage without first checking with your doctor.

Your doctor may recommend that you start with a low dose of pregabalin and slowly increase the dose to the lowest amount needed to control your epilepsy/convulsions or neuropathic pain.

The usual dose range is 150 mg per day to 600 mg per day given in two divided doses.

How to take it

Swallow the capsules whole with a full glass of water.

When to take it

Take this medicine at the same time each day. Taking it at the same time each day will have the best effect and will also help you remember when to take it.

It does not matter if you take it before, with or after food.

How long to take it for

Continue taking your medicine for as long as your doctor tells you.

This medicine helps to control your condition, but does not cure it. It is important to keep taking your medicine, even if you feel well.

Do not stop taking pregabalin, or lower the dosage, without checking with your doctor.

If you stop taking pregabalin suddenly you may worsen your condition or cause unwanted effects such as sleeplessness, headache, nausea (feeling sick), anxiety, excessive sweating or diarrhoea (runny stools). If appropriate, your doctor will slowly reduce your dose before you can stop taking it completely.

Make sure you have enough pregabalin to last over weekends and holidays.

If you forget to take it

If it is almost time to take your next dose (within 4 hours), skip the missed dose and take your next dose at the usual time.

Otherwise take it as soon as you remember and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for missed doses.

This may increase the chance of you experiencing side effects.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints to help you remember.

If you take too much (overdose)

If you think that you or anyone else may have taken too much of this medicine, immediately telephone your doctor or the Poisons Information Centre (Tel: 13 11 26 in Australia) for advice. Alternatively go to the Accident and Emergency Department at your nearest hospital.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose with pregabalin may include mood changes, feeling tired, confusion, depression, agitation and restlessness or seizures.

While you are taking this medicine

Things you must do

Tell your doctor that you are taking this medicine if:

  • you are about to be started on any new medicine
  • you are pregnant or are planning to become pregnant
  • you are breastfeeding or are planning to breast-feed
  • you are about to have any blood tests
  • you are going to have surgery or an anaesthetic or are going into hospital. Pregabalin may affect other medicines used during surgery.
  • you experience any changes in your vision. Pregabalin may cause blurring or other changes in eyesight. Your doctor may ask you to stop taking pregabalin to improve these symptoms.
  • you have any thoughts of suicide or self-harm, any unusual changes in mood or behaviour, or show signs of depression

Some people being treated with anti-epileptics such as pregabalin have had thoughts of harming themselves or taking their life.

Patients and caregivers should be alert and monitor for these effects.

Signs and symptoms of suicidal risk include:
- thoughts or talk of death or suicide
- thoughts or talk of self-harm or harm to others
- any recent attempts of self-harm
- new or an increase in aggressive behaviour, irritability or agitation
- new or worsening depression.

Mention of suicide or violence must be taken seriously.

If you or someone you know is demonstrating these warning signs of suicide while taking pregabalin, contact your doctor or a mental health professional right away.

Tell your doctor if:

  • you feel that pregabalin is not helping your condition. Your doctor may need to change your medicine.
  • you have not taken pregabalin exactly as prescribed. Your doctor otherwise may change your treatment unnecessarily.

If you become pregnant while taking pregabalin, tell your doctor immediately.

Keep all of your doctor's appointments so that your progress can be checked.

Your doctor may occasionally do tests to make sure the medicine is working and to prevent side effects.

Tell any other doctors, dentists and pharmacists who are treating you that you take this medicine.

Things you must not do

Do not:

  • Give this medicine to anyone else, even if their symptoms seem similar to yours
  • Take your medicine to treat any other condition unless your doctor tells you to
  • Stop taking your medicine, or change the dosage, without first checking with your doctor.

Things to be careful of

Be careful when driving or operating machinery until you know how this medicine affects you.

As with other anticonvulsant medicines, pregabalin may cause dizziness and drowsiness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Be careful when drinking alcohol while you are taking this medicine.

If you drink alcohol, symptoms such as dizziness and drowsiness may be worse.

Possible side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking pregabalin or if you have any questions or concerns.

Pregabalin helps most people with neuropathic pain or epilepsy, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious but most of the time they are not.

It can be difficult to tell whether side effects are the result of taking pregabalin, effects of your condition or side effects of other medicines you may be taking. For this reason it is important to tell your doctor of any change in your condition.

If you are over 65 years of age you may have an increased chance of getting side effects.

If you get any side effects, do not stop taking pregabalin without first talking to your doctor.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Tell your doctor if you notice any of the following:

  • dizziness
  • feeling tired or drowsy
  • constipation
  • diarrhoea
  • nausea
  • headache
  • increase in weight
  • unsteadiness when walking, reduced co-ordination, shaking or tremors
  • dry mouth
  • blurred or double vision.

Tell your doctor as soon as possible if you notice any of the following.

These may be serious side effects. You may need medical attention.

  • unusual changes in mood or behaviour
  • signs of new or increasedirritability or agitation
  • signs of depression
  • swelling of the hands, ankles or feet
  • enlargement of breasts
  • unexplained muscle pain, tenderness and weakness
  • passing little to no urine.

If you experience any of the following, stop taking your medicine and contact your doctor immediately or go to the Accident and Emergency department at your nearest hospital.

These are very serious side effects. You may need urgent medical attention or hospitalisation.

  • shortness of breath, swelling of the feet and legs, weight increase due to fluid build-up
  • irritated red eyes that are sensitive to light
  • more frequent or more severe seizures (fits)
  • sudden signs of allergy such as rash, itching or hives, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or difficulty breathing.

Tell your doctor if you notice anything else that is making you feel unwell.

Other side effects not listed above may occur in some patients. Some of these side effects (for example, changes in blood pressure) can only be found when your doctor does tests from time to time to check your progress.

Storage and disposal

Storage

Keep your medicine in its original packaging until it is time to take it.

If you take your medicine out of its original packaging it may not keep well.

Keep your medicine in a cool dry place where the temperature will stay below 25°C.

Do not store your medicine, or any other medicine, in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep this medicine where children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or they have passed their expiry date, your pharmacist can dispose of the remaining medicine safely.

Product description

What Blooms The Chemist Pregabalin looks like

25 mg capsules: white body/white cap, imprinted with "APO" and "P25" in black ink.

50 mg capsules: white body/white cap, imprinted with "APO" and "P50" in black ink.

75 mg capsules: white body/orange cap, imprinted with "APO" and "P75" in black ink.

100 mg capsules: orange body/orange cap, imprinted with "APO" and "P100" in black ink.

150 mg capsules: white body/white cap, imprinted with "APO" and "P150" in black ink.

200 mg capsules: light orange body/light orange cap, imprinted with "APO" and "P200" in black ink.

225 mg capsules: white body/light orange cap, imprinted with "APO" and "P225" in black ink.

300 mg capsules: white body/orange cap, imprinted with "APO" and "P300" in black ink.

Also available in bottles of 14, 20, 56 and 60 tablets.

Not all strengths, pack types and/or pack sizes may be available.

Ingredients

Each capsule contains 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg or 300 mg of pregabalin as the active ingredient.

It also contains the following inactive ingredients:

  • lactose monohydrate
  • purified talc
  • maize starch
  • gelatin
  • purified water
  • titanium dioxide
  • sodium lauryl sulfate
  • TekPrint SW-9008 black ink
  • iron oxide red (75 mg, 100 mg, 200 mg, 225 mg or 300 mg strengths only).

This medicine is gluten-free, sucrose-free, tartrazine-free and free of other azo dyes.

Australian Registration Numbers

Blooms The Chemist Pregabalin
25 mg capsules (blister pack):
AUST R 193298

Blooms The Chemist Pregabalin
50 mg capsules (blister pack):
AUST R 193299

Blooms The Chemist Pregabalin
75 mg capsules (blister pack):
AUST R 193300

Blooms The Chemist Pregabalin
100 mg capsules (blister pack):
AUST R 193301

Blooms The Chemist Pregabalin
150 mg capsules (blister pack):
AUST R 193302

Blooms The Chemist Pregabalin
200 mg capsules (blister pack):
AUST R 193303

Blooms The Chemist Pregabalin
225 mg capsules (blister pack):
AUST R 193304

Blooms The Chemist Pregabalin
300 mg capsules (blister pack):
AUST R 193305

Sponsor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park, NSW 2113

This leaflet was prepared in May 2017.

BRAND INFORMATION

Brand name

Blooms the Chemist Pregabalin Capsules

Active ingredient

Pregabalin

Schedule

S4

 

Name of the medicine

Pregabalin.

Excipients.

Lactose monohydrate, maize starch, purified talc, gelatin, purified water, titanium dioxide, sodium lauryl sulfate and TekPrint SW 9008 black ink. The 75 mg, 100 mg, 200 mg, 225 mg and 300 mg capsules also contain iron oxide red.

Description

Chemical name:(S)-3-(aminomethyl)-5-methylhexanoic acid. Molecular formula: C8H17NO2. Molecular weight: 159.23. CAS registry number: 148553-50-8.
Pregabalin is an analogue of the neurotransmitter gamma-aminobutyric acid (GABA). It has analgesic and anticonvulsant activity. Pregabalin is a white to off-white solid. It is freely soluble in water and basic and acidic aqueous solutions.
Each capsule contains 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg or 300 mg of pregabalin, as the active ingredient.
In addition, each capsule contains the following inactive ingredients: lactose monohydrate, maize starch, purified talc, gelatin, purified water, titanium dioxide, sodium lauryl sulfate and TekPrint SW 9008 black ink. The 75 mg, 100 mg, 200 mg, 225 mg and 300 mg capsules also contain iron oxide red.

Pharmacology

Pharmacological actions.

In vitro studies show that pregabalin binds to an auxiliary subunit (α2 delta 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 delta site is required for analgesic and anticonvulsant 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 delta 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 show affinity for receptor sites or alter responses associated with the action of several common drugs for treating seizures or pain. 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 acute GABA uptake or degradation.
Pregabalin prevents pain-related behaviours in animal models of neuropathic and post-surgical pain, including hyperalgesia and allodynia.
Pregabalin also shows efficacy in animal models of seizures including: maximal electroshock tonic extensor seizures in mice or rats; threshold clonic seizures from pentylenetetrazol, behavioural and electrographic seizures in hippocampal kindled rats; and tonic and clonic seizures in DBA/2 audiogenic mice. Pregabalin does not reduce the incidence of spontaneous absence seizures in Genetic Absence Epilepsy in Rats from Strasbourg (GAERS).

Pharmacokinetics.

Pregabalin steady-state pharmacokinetics are similar in healthy volunteers, patients with epilepsy receiving anti-epileptic drugs and patients with chronic pain.

Absorption.

Pregabalin is rapidly absorbed when administered in the fasted state, with peak plasma concentrations occurring within 1 hour following both single and multiple dose administration. Pregabalin oral bioavailability is estimated to be ≥ 90% and is independent of dose. Following repeated administration, steady state is achieved within 24 - 48 hours. The rate of pregabalin absorption is decreased when given with food resulting in a decrease in Cmax by approximately 25 - 30% and a delay in Tmax to approximately 2.5 hours. However, administration of pregabalin with food has no clinically significant effect on the extent of pregabalin bioavailability.

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 is not bound to plasma proteins. At clinical doses of 150 and 600 mg/day, the average steady-state plasma pregabalin concentrations were approximately 1.5 and 6.0 microgram/mL, respectively.

Metabolism.

Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabelled pregabalin, approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The N-methylated derivative of pregabalin, the major metabolite of pregabalin found in urine, accounted for 0.9% of the dose. In preclinical studies, there was no indication of racemisation of pregabalin S-enantiomer to the R-enantiomer.

Excretion/ elimination.

Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. Renal clearance (CrCl) derived from Phase I studies was 73 mL/min.
Pregabalin mean elimination half-life is 6.3 hours. Pregabalin plasma clearance and renal clearance are directly proportional to creatinine clearance (see Special populations, Renal impairment).
Pregabalin clearance is reduced in patients with impaired renal function (see Dosage and Administration, Use in renal impairment, Table 7).

Linearity/ non-linearity.

Pregabalin pharmacokinetics are linear over the recommended daily dose range. Inter-subject pharmacokinetic variability for pregabalin is low (< 20%). Multiple dose pharmacokinetics are predictable from single-dose data.

Special populations.

Race.

Population pharmacokinetic analyses of the Phase 2/3 studies in patients with chronic pain, general anxiety disorder (GAD) or partial seizures showed that the relationship between daily dose and pregabalin exposure is similar among Caucasians, Blacks and Hispanics.

Gender.

Population pharmacokinetic analyses of the Phase 2/3 studies in patients with chronic pain, GAD or partial seizures showed that the relationship between daily dose and pregabalin drug exposure is similar between genders when adjusted for gender-related differences in CrCl.

Renal impairment.

Pregabalin clearance is directly proportional to creatinine clearance. In addition, pregabalin is effectively removed from plasma by haemodialysis (following a 4-hour haemodialysis treatment, plasma pregabalin concentrations are reduced by approximately 50%). Since renal elimination is the major elimination pathway, dosage reduction in patients with renal impairment and dosage supplementation following haemodialysis is necessary (see Dosage and Administration, Use in renal impairment, Table 7).

Hepatic impairment.

No specific pharmacokinetic studies were carried out in patients with impaired liver function. Since pregabalin does not undergo significant metabolism and is excreted predominantly as unchanged drug in the urine, impaired liver function would not be expected to significantly alter pregabalin plasma concentrations.

Elderly (> 65 years).

Pregabalin clearance tends to decrease with increasing age. This decrease in pregabalin oral clearance is consistent with decreases in creatinine clearance associated with increasing age. Reduction of pregabalin dose may be required in patients who have age related compromised renal function (see Dosage and Administration, Use in renal impairment, Table 7).

Paediatrics (< 18 years).

No specific pharmacokinetic studies have been undertaken in patients < 18 years of age.

Breastfeeding women.

The pharmacokinetics of 150 mg pregabalin given every 12 hours (300 mg daily dose) was evaluated in 10 lactating women who were at least 12 weeks postpartum. Lactation had little to no influence on pregabalin pharmacokinetics. Pregabalin was excreted into breast milk with average steady-state concentrations approximately 76% of those in maternal plasma. The estimated average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 mL/kg/day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose (see Precautions, Use in lactation).

Clinical Trials

Neuropathic pain.

The effectiveness of pregabalin for the management of neuropathic pain was investigated in 11 double-blind, placebo-controlled, multi-centre studies with either twice a day (BID) or three times a day (TID) dosing.
The analysis of the primary efficacy variable is provided below for each study within the diabetic peripheral neuropathy and post-herpetic neuralgia population.
The overall picture of the primary efficacy variable across populations is confirmed by the responder rates. The response rates for a 30% reduction in pain score showed that the proportion of patients responding increased with increasing doses, from 34 - 49% at 150 mg/day to 54 - 65% at 600 mg/day, compared with 19 - 45% for placebo. The response rates for a 50% reduction in pain score showed that the proportion of patients responding increased with increasing doses, from 19 - 34% at 150 mg/day to 39 - 50% at 600 mg/day, compared with 8 - 30% for placebo.
Up to 88% of patients treated with 300 or 600 mg/day pregabalin reported benefit, compared with 26 - 66% for placebo, as measured by an improvement in the Patient Global Impressions of Change (PGIC) score. The PGIC is a patient-rated instrument that measures change in a patient's overall status on a scale ranging from 1 (very much improved) to 7 (very much worse).
A significant reduction in pain was seen by Week 1 and maintained relative to placebo throughout the treatment. Significant reductions in sleep interference were seen, when patients were treated with pregabalin for neuropathic pain, by Week 1 and maintained throughout the treatment.

Diabetic peripheral neuropathy.

The effectiveness of pregabalin for the management of neuropathic pain was investigated in 6 double-blind, placebo-controlled, multi-centre studies with either twice a day (BID) or three times a day (TID) dosing. A total of 1525 patients were enrolled in the 6 studies. To enter the study patients had to have moderate to severe pain. The mean age of patients in these studies was 59 years (range 21 to 85 years), 89% of patients had Type II diabetes mellitus with an average HbA1c of 8.9%.
In the 5 completed studies, the average age was 59 years, the duration of diabetes was 11 years and the average baseline pain score was 6.5. The use of concurrent medication that may affect the assessments was prohibited. Antidiabetic medication was required to be stable and constant during the study. See Table 1.

Post-herpetic neuralgia.

The effectiveness of pregabalin for the management of neuropathic pain was investigated in 5 double-blind, placebo-controlled, multi-centre studies with either BID or TID dosing. A total of 1250 patients were enrolled in the 5 studies. To enter the study patients had to have moderate to severe pain for ≥ 3 months (or ≥ 6 months in one study). The mean duration of post-herpetic neuralgia for patients in these studies was 3 years (range < 1 to 22 years).
In the 4 completed studies, the average age was 71 years, the average duration of post-herpetic neuralgia was 38 months and the average baseline pain score was 6.6. Concomitant use of analgesics and antidepressants was allowed, provided the regimen was stable and in place at the time of randomisation. See Table 2.

Epilepsy.

The efficacy of pregabalin as adjunctive therapy was investigated in three 12-week, randomised, double-blind, placebo-controlled, multi-centre studies involving 1052 patients, with BID and/or TID dosing. Patients had refractory partial seizures with or without secondary generalisation and had mean baseline seizure rates of 21 to 22 and median baseline seizure rates of 10 to 12 seizures per 28 days.
The primary efficacy measure in all studies was based on seizure reduction as analysed by response ratio (RRatio), a measure of change defined as [(T - B)/(T + B)] x 100, where B is the patient's baseline seizure frequency and T is the patient's seizure frequency during treatment. The RRatio is distributed within the range -100 to +100. A zero value indicates no change and a complete elimination of seizures would give a value of -100. Responder rate was defined as the proportion of patients who have a ≥ 50% reduction in partial seizure frequency during treatment as compared to baseline. See Table 3.
A significant reduction in seizure frequency was observed by Week 1. Overall, there was a significant reduction in seizure frequency over the 12-week treatment period.
Long-term efficacy data in support of the chronic use of pregabalin for the treatment of patients with partial seizures were provided by four open label extension studies. These studies permitted pregabalin as adjunctive therapy with marketed antiepileptic drugs (AEDs). Data from the long-term studies support the long-term use of pregabalin for the treatment of patients with partial seizures, as well as demonstrating the maintenance of effect over the long term.

Indications

Pregabalin is indicated for the treatment of neuropathic pain in adults.
Pregabalin is indicated as adjunctive therapy in adults with partial seizures with or without secondary generalisation.

Contraindications

Pregabalin is contraindicated in patients who have demonstrated hypersensitivity to pregabalin or to any of the excipients.

Precautions

Hereditary problems of galactose metabolism.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Weight gain.

In the controlled studies, weight gain occurred more frequently in patients treated with pregabalin than in patients treated with placebo. Pregabalin-associated weight gain was related to dose and length of exposure, but did not appear to be associated with baseline BMI, gender or age.
In accordance with current clinical practice, some diabetic patients who gain weight on pregabalin treatment may need to adjust hypoglycaemic medications.

Hypersensitivity reactions.

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

Dizziness and somnolence.

Pregabalin causes dizziness and somnolence (see Adverse Effects). In the controlled studies, dizziness and somnolence generally began shortly after initiation of pregabalin and occurred more frequently at higher doses. Dizziness and somnolence were the adverse events most frequently leading to withdrawal (4% each) from controlled studies. In pregabalin-treated patients reporting these adverse events in short-term controlled studies, dizziness persisted until the last dose in 31% and somnolence persisted until the last dose in 46%.
There have also been reports of loss of consciousness, confusion and mental impairment.

Suicidal behaviour and ideation.

Antiepileptic drugs (AEDs), including pregabalin, increase the risk of suicidal thoughts or behaviour in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behaviour and/or any unusual changes in mood or behaviour.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomised to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behaviour compared to patients randomised to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behaviour or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behaviour for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behaviour with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behaviour beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behaviour was generally consistent among drugs in the data analysed. 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 to 100 years) in the clinical trials analysed. Table 4 shows absolute and relative risk by indication for all evaluated AEDs.
The relative risk for suicidal thoughts or behaviour was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing pregabalin or any other AED must balance this risk 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 patient may be related to the illness being treated.
Patients, their caregivers and families should be informed that AEDs increase the risk of suicidal thoughts and behaviour and should be advised 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. Behaviours of concern should be reported immediately to the treating doctor.

Monotherapy for seizure control.

There are insufficient data on seizure control when pregabalin is used as monotherapy once concomitant antiepileptic medical products have been withdrawn in patients where pregabalin was used as add-on therapy.

Substance misuse, abuse and dependence.

There have been post-marketing reports of substance misuse and abuse with pregabalin. As with any CNS drug, patients should be carefully evaluated for a history of substance abuse and observed for signs of pregabalin misuse or abuse (e.g. development of tolerance, increase in dose, drug-seeking behaviour).

Renal failure.

Renal failure is a rare adverse reaction to pregabalin. Although the effects of discontinuation on the reversibility of renal failure have not been systematically studied, cases of renal failure have been reported and in some cases discontinuation of pregabalin did show reversibility of this adverse reaction.

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, hyperhidrosis and diarrhoea.

Blurred vision.

In controlled studies, a higher proportion of patients treated with pregabalin reported blurred vision than did patients treated with placebo (see Adverse Effects). In the majority of cases, blurred vision resolved with continued dosing. If blurred vision persists, further assessment should be considered.
Post marketing experience with pregabalin has reported transient visual blurring and other changes in visual acuity. Discontinuation of pregabalin may result in resolution or improvement of these visual symptoms.

Congestive heart failure.

There have been post-marketing reports of congestive heart failure in some patients receiving pregabalin. Pregabalin should be used with caution in these patients.

Peripheral oedema.

In controlled studies, peripheral oedema occurred more frequently in patients treated with pregabalin than in patients treated with placebo (see Adverse Effects). Peripheral oedema was not associated with laboratory changes suggestive of deterioration in renal or hepatic function. There are limited data on the use of pregabalin in patients with congestive heart failure and pregabalin should be used with caution in these patients.

Creatine kinase elevations.

Treatment with pregabalin was associated with creatine kinase elevations. Mean changes in creatine kinase from baseline to the maximum value were 60 U/L for pregabalin treated patients and 28 U/L for the placebo patients. In all controlled trials across multiple patient populations, 2% of patients on pregabalin and 1% of placebo patients had a value of creatine kinase at least three times the upper limit of normal. Three pregabalin treated subjects had events reported as rhabdomyolysis in premarketing clinical trials. The relationship between these myopathy events and pregabalin is not completely understood because the cases had documented factors that may have caused or contributed to these events. Pregabalin should be discontinued if myopathy is diagnosed or suspected or if markedly elevated creatine kinase levels occur.

Effects on fertility.

Preclinical data.

In male rats, oral administration of high doses of pregabalin resulted in reversible decreased sperm motility and fertility. These were not observed at exposures (plasma AUC) up to 11 times the expected human exposure at the maximum recommended clinical dose of 600 mg/day. There were also no drug-related effects on sperm parameters in a long-term monkey study with exposures up to 8 times the expected maximum human exposure. In female rats, oestrus cycles were prolonged by high oral doses of pregabalin, but fertility was unaffected and an increase in post-implantation loss also occurred. No adverse effects were seen at an exposure approximately 50 times the expected maximum human exposure.

Human data.

In a double-blind, placebo-controlled clinical trial to assess the effect of pregabalin on sperm motility, 30 of 46 healthy male subjects were exposed to pregabalin at 600 mg/day for 3 months. Pregabalin did not exhibit detrimental effects on the reproductive function of healthy male subjects, as measured by semen analysis.

Use in pregnancy.

(Category B3)
Pregabalin has not been studied in pregnant women and it should not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus. In a pre- and post-natal study in rats, pregabalin treatment resulted in offspring developmental toxicity at exposures (plasma AUC) ≥ 5 times the expected human exposure at the maximum recommended clinical dose of 600 mg/day. Offspring development was unaffected at 2 times the expected maximum human exposure.

Labour and delivery.

The effects of pregabalin on labour and delivery in pregnant women are unknown. In a pre- and post-natal development study in rats, pregabalin prolonged gestation and induced dystocia at exposures (plasma AUC) approximately 50 times the expected human exposure at the maximum recommended clinical dose of 600 mg/day. These effects were not observed at an exposure that was approximately 12 times the expected human exposure.

Teratogenicity.

Pregabalin was not teratogenic in mice, rats or rabbits. Foetal developmental toxicity was not observed after treatment of pregnant mice and rabbits with oral doses that resulted in respective pregabalin exposures that were 30 times and 17 times the expected human exposure at the maximum recommended clinical dose of 600 mg/day. Increased foetal skeletal variations were seen in rats at oral doses resulting in exposures > 17 times the expected maximum human exposure, but lower doses were not tested in a full study.

Use in lactation.

Pregabalin is excreted in the milk of lactating women (see Pharmacology, Pharmacokinetics, Breastfeeding women). As the safety of pregabalin in infants is not known, breastfeeding is not recommended in women taking pregabalin. A decision must be made whether to discontinue breastfeeding or to discontinue pregabalin therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Use in the elderly (> 65 years).

Pregabalin treatment has been associated with dizziness and somnolence, which may increase the occurrence of accidental injury (falls) in the elderly population.

Genotoxicity.

Pregabalin is not genotoxic based on results of in vitro and in vivo tests. It was not mutagenic in bacteria or in mammalian cells in vitro, not clastogenic in mammalian systems in vitro and in vivo and did not induce unscheduled DNA synthesis in mouse or rat hepatocytes.

Carcinogenicity.

Two-year carcinogenicity studies with pregabalin were conducted in rats and mice. No increased incidence of tumours was observed in rats at exposures (plasma AUC) up to 25 times the expected human exposure at the maximum recommended clinical dose of 600 mg/day. In mice, no increased incidence of tumours was found at exposures similar to the expected maximum human exposure, but an increased incidence of haemangiosarcoma was observed at exposures 6 - 33 times the expected maximum human exposure. The precise non-genotoxic mechanism of pregabalin-induced tumour formation is not fully characterised. However, available data show that platelet changes associated with the formation of this tumour in mice are not seen in rats, monkeys or humans. Although long-term data in humans are limited, these findings in mice are thought not to pose a risk to humans.

Effect on laboratory tests.

Pregabalin is not known to interfere with any laboratory tests. Some changes in clinical laboratory tests have been noted in patients taking pregabalin (see Adverse Effects, Table 6 - Body system: Investigations).

Effects on ability to drive and use machines.

Pregabalin may cause dizziness and somnolence and therefore may have an influence on 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 medication affects their ability to perform these activities.

Interactions

Since pregabalin 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, pregabalin is unlikely to produce, or be subject to, pharmacokinetic interactions.
Accordingly, in in vivo studies, no clinically relevant pharmacokinetic interactions were observed between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. In addition, population pharmacokinetic analysis indicated that the three commonly used drug classes, oral antidiabetics, diuretics and insulin, and the commonly used antiepileptic drugs phenytoin, carbamazepine, valproic acid, lamotrigine, phenobarbital, tiagabine and topiramate, had no clinically significant effect on pregabalin clearance. Similarly, these analyses indicated that pregabalin had no clinically significant effect on the clearance of phenytoin, carbamazepine, valproic acid, lamotrigine, topiramate and phenobarbital.
Co-administration of pregabalin with the oral contraceptives norethisterone and/or ethinyl oestradiol did not influence the steady-state pharmacokinetics of either agent.
Pregabalin may potentiate the effects of ethanol and lorazepam. In controlled clinical trials, multiple oral doses of pregabalin co-administered with oxycodone, lorazepam or ethanol did not result in clinically important effects on respiration. Pregabalin appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone. In post-marketing experience, there are reports of respiratory failure and coma in patients taking pregabalin and other CNS depressant medications.
There are post-marketing 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.
No specific pharmacodynamic interaction studies were conducted in elderly volunteers.

Adverse Effects

The pregabalin clinical programme involved over 9000 patients who were exposed to pregabalin, of whom over 5000 were in double-blind, placebo-controlled trials. The clinical efficacy program included patients treated for a maximum of 12 weeks duration.
The most commonly reported adverse effects were dizziness and somnolence. Adverse effects were usually mild to moderate in intensity. In all controlled studies, the discontinuation rate due to adverse events was 13% for patients receiving pregabalin and 7% for patients receiving placebo.
The most common adverse effects resulting in discontinuation from pregabalin treatment groups were dizziness and somnolence.
The adverse effects listed may also be associated with the underlying disease and concomitant medications. See Table 5.
Additional adverse effects, reported in a pooled analysis of all pregabalin clinical trials, are listed in Table 6 by System Organ Class (SOC). The frequency of these terms have been based on all-causality adverse drug reactions in the clinical trial data set (very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100) and rare (< 1/1000)).

Post-marketing experience.

The following adverse events were reported during post-marketing surveillance:

Immune system disorders.

Uncommon: Hypersensitivity.
Rare: Angioedema, allergic reaction.

Nervous system disorders.

Very common: Headache.
Uncommon: Loss of consciousness, mental impairment.

Cardiac disorders.

Rare: Congestive heart failure.

Eye disorders.

Rare: Keratitis.

Gastrointestinal disorders.

Common: Nausea, diarrhoea.
Rare: Swollen tongue.

General disorders and administration site conditions.

Uncommon: Malaise.

Skin and subcutaneous tissue disorders.

Uncommon: Face swelling, pruritus, alopecia.

Renal and urinary disorders.

Rare: Urinary retention.

Reproductive system and breast disorders.

Rare: Gynaecomastia.

Respiratory, thoracic and mediastinal disorders.

Rare: Pulmonary oedema.

Vital signs.

No consistent changes in vital signs have been seen in patients taking pregabalin. Changes in vital signs reported in controlled clinical trials are shown in Table 6.

Elderly (> 65 years).

In a total of 998 elderly patients, no overall differences in safety were observed compared with patients less than 65 years of age.

Dosage and Administration

The dose range is 150 to 600 mg per day given in two divided doses.
Pregabalin may be taken with or without food.

Neuropathic pain.

Pregabalin treatment can be started at a dose of 150 mg per day, given as two divided doses. Based on individual patient response and tolerability, the dosage may be increased to 300 mg/day, given as two divided doses, after an interval of 3 to 7 days, and if needed, to a maximum dose of 600 mg/day after an additional 7-day interval.
Since diabetes is frequently complicated by renal disease, patients with diabetic neuropathy, in accordance with current clinical practice, should be assessed for renal impairment prior to commencing pregabalin and dosage adjusted appropriately.
The effectiveness of pregabalin in the treatment of neuropathic pain has not been assessed in controlled clinical trials for treatment periods longer than 12 weeks (see Clinical Trials). The risks and benefits of treatment to an individual patient should be assessed before extending therapy for longer than 12 weeks.

Epilepsy.

Pregabalin treatment can be started with a dose of 150 mg/day given as two divided doses. Based on individual patient response and tolerability, the dosage may be increased to 300 mg/day given as two divided doses after 1 week. The maximum dosage of 600 mg/day given as two divided doses may be achieved after an additional week.
It is not necessary to monitor plasma pregabalin concentrations to optimise pregabalin therapy. Pregabalin does not alter the plasma concentrations of other commonly used antiepileptic drugs (AEDs). Similarly, commonly used AEDs do not alter plasma concentrations of pregabalin (see Interactions with Other Medicines).

Discontinuation of pregabalin.

In accordance with current clinical practice, if pregabalin has to be discontinued, it is recommended this should be done gradually over a minimum of one week.

Use in renal impairment.

Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. As pregabalin clearance is directly proportional to creatinine clearance (see Pharmacokinetics, Excretion/ elimination), dosage reduction in patients with compromised renal function must be individualised according to creatinine clearance (CrCl), as indicated in Table 7 determined using the following formula:
Pregabalin is removed effectively from plasma by haemodialysis (50% of drug in 4 hours). For patients receiving haemodialysis, the pregabalin 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 7).

Use in hepatic impairment.

No dosage adjustment is required for patients with hepatic impairment (see Pharmacokinetics, Hepatic impairment).

Paediatric use (< 18 years).

The safety and effectiveness of pregabalin has not been established in patients below the age of 18 years, with either epilepsy or neuropathic pain.

Use in the elderly (> 65 years).

No dosage adjustment is necessary for elderly patients unless their renal function is compromised (see Table 7).

Overdosage

Symptoms.

In overdoses up to 15 g, no unexpected adverse effects were reported.
In post-marketing experience, the most commonly reported adverse events observed when pregabalin was taken in overdose included affective disorder, somnolence, confusional state, depression, agitation and restlessness. Seizures were also reported.

Management.

There is no specific antidote for pregabalin. Treatment of pregabalin overdose should be symptomatic and supportive.
Consider administration of activated charcoal in the event of a potentially toxic ingestion. Activated charcoal is most effective when administered within one hour of ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube once the airway is protected.
Haemodialysis may be useful in patients with severe toxicity or those with significant renal impairment (see Dosage and Administration, Use in renal impairment). Standard haemodialysis procedures result in significant clearance of pregabalin (approximately 50% in 4 hours). Emesis is not recommended because of the potential for CNS depression and seizures.
For information on the management of overdose, contact the Poisons Information Centre on 131 126 (Australia).

Presentation

Blooms the Chemist Pregabalin capsules are intended for oral administration.
Each capsule contains 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg or 300 mg of pregabalin, as the active ingredient.

25 mg capsules.

Capsules with a white body/white cap; imprinted with "APO" and "P25" in black ink.
Blister packs (PVC/Al) of 14, 20, 56, 60 capsules (AUST R 193298).

50 mg capsules.

Capsules with a white body/white cap; imprinted with "APO" and "P50" in black ink.
Blister packs (PVC/Al) of 14, 20, 56, 60 capsules (AUST R 193299).

75 mg capsules.

Capsules with a white body/orange cap; imprinted with "APO" and "P75" in black ink.
Blister packs (PVC/Al) of 14, 20, 56, 60 capsules (AUST R 193300).

100 mg capsules.

Capsules with an orange body/orange cap; imprinted with "APO" and "P100" in black ink.
Blister packs (PVC/Al) of 14, 20, 56, 60 capsules (AUST R 193301).

150 mg capsules.

Capsules with a white body/white cap; imprinted with "APO" and "P150" in black ink.
Blister packs (PVC/Al) of 14, 20, 56, 60 capsules (AUST R 193302).

200 mg capsules.

Capsules with a light orange body/light orange cap; imprinted with "APO" and "P200" in black ink.
Blister packs (PVC/Al) of 14, 20, 56, 60 capsules (AUST R 193303).

225 mg capsules.

Capsules with a white body/light orange cap; imprinted with "APO" and "P225" in black ink.
Blister packs (PVC/Al) of 14, 20, 56, 60 capsules (AUST R 193304).

300 mg capsules.

Capsules with a white body/orange cap; imprinted with "APO" and "P300" in black ink.
Blister packs (PVC/Al) of 14, 20, 56, 60 capsules (AUST R 193305).
*Not all strengths and/or pack sizes may be available.

Storage

Store below 25°C.

Poison Schedule

S4.