Consumer medicine information

Ausgem

Gemfibrozil

BRAND INFORMATION

Brand name

Ausgem Tablets

Active ingredient

Gemfibrozil

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ausgem.

What is in this leaflet

This leaflet answers some common questions about AUSGEM. It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking gemfibrozil against the benefits this medicine is expected to have for you.

Keep this leaflet with your medicine.

You may need to read it again.

What is AUSGEM used for

The name of your medicine is AUSGEM. It contains the active ingredient, gemfibrozil.

AUSGEM belongs to group of medicines known as fibric acid derivatives. AUSGEM is used to help regulate cholesterol and triglycerides which are fat-like substances in the blood.

Everyone has cholesterol in their blood. It is a type of blood fat needed by the body for many things, such as making bile acids (which help digest food) and some hormones. However, having too much cholesterol in the blood can contribute to the development of heart disease.

Cholesterol is present in many foods and is also made in your body by the liver. If your body does not balance the amount of cholesterol it needs with the amount of cholesterol you obtain from your food, then your cholesterol becomes too high.

High cholesterol is more likely to occur with certain diseases or if you have a family history of high cholesterol.

When you have high levels of cholesterol, this fat may “stick” to the inside of your blood vessels instead of being carried to the parts of the body where it is needed.

Over time, this can form hard areas (called a “plaque”) on the lining of your blood vessels, making it more difficult for the blood to flow. This blocking of your blood vessels can lead to heart disease (such as heart attack and angina), and stroke.

There are different types of cholesterol, called LDL and HDL. LDL cholesterol is the harmful or “bad” cholesterol that can block your blood vessels. HDL cholesterol is the beneficial or “good” cholesterol that is thought to remove the LDL (“bad”) cholesterol from the blood vessels.

High levels of triglycerides may also increase your risk of heart disease, as these fats can be associated with a low level of the beneficial or “good” cholesterol.

In most patients, AUSGEM reduces the bad cholesterol and increases the good cholesterol.

AUSGEM does not reduce the cholesterol that comes from the fat in food.

When you are taking AUSGEM, you also need to follow a low fat diet and other measures, such as exercise and weight control.

In most people, there are no symptoms of high cholesterol. Your doctor can measure your cholesterol with a simple blood test.

The exact way in which AUSGEM works is not known, but it is thought to work by reducing the amount of triglycerides made in the body.

Your doctor will have explained to you why you are being treated with AUSGEM.

Follow all the directions given to you by your doctor carefully.

Your doctor may have prescribed this medicine for another reason.

Ask your doctor if you want more information about why this medicine has been prescribed for you.

There is no evidence that AUSGEM is addictive.

Before you take it

You should not take AUSGEM if:

  • You are allergic to the medicine, “gemfibrozil” or any of the ingredients listed under the “Product description” section.

Some of the symptoms of an allergic reaction may include skin rash, itching or hives; shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body.

  • You have severe liver disease.
  • You have severe kidney disease.
  • You have gall bladder disease.
  • You are pregnant or breast-feeding.
    Your baby may absorb this medicine in the womb or from breast milk and there is a possibility that this may be harmful to the baby.
  • You have a lipid disorder called “type I hyperlipoproteinaemia”.
  • You have had muscle pain, tenderness or weakness from other medicines that treat high cholesterol or triglycerides.
  • You are taking the drug cerivastatin (i.e. ‘Kazak’ or ‘Lipobay’).
  • You are taking the drug repaglinide (i.e. ‘NovoNorm’).

Do not use AUSGEM if the packaging is torn or shows signs of tampering.

Do not use this medicine if the expiry date on the pack has passed.

If you take the medicine after the expiry date has passed, it may make you unwell.

This medicine is not suitable for children.

You should tell your doctor if:

  • You intend to become pregnant or breast-feed during the course of your treatment.
  • You suffer from any other medical condition which your doctor does not know about, including thyroid problems or diabetes.
  • You are on any other medications. If you are taking medicines to “thin” the blood, the dose of these medicines may need to be adjusted. If you are taking another medication to lower the fats in your blood, you should tell your doctor, as AUSGEM may not be suitable with these medicines.

You should also tell your doctor about any other medicines that you have bought without a prescription from either your pharmacy, the supermarket or health food shop.

How to use it

How much to take

The usual dose of AUSGEM to regulate the fats in your blood is ONE tablet twice a day.

The tablet should be taken with a glass of water half an hour before breakfast and half an hour before the evening meal.

If you forget to take it

If you miss a dose, take it when you remember. However, if it is nearly time for your next dose, you can skip the missed dose and continue to take your next tablet at the usual time.

Do not take a double dose of AUSGEM to make up for the dose that you missed.

AUSGEM helps lower your cholesterol and triglyceride levels. It does not cure your condition. You must continue to take this medicine for as long as your doctor recommends.

If you stop taking your medication before your doctor tells you to, your cholesterol and triglyceride levels may rise again. Some people need to take medicines to lower their fat levels for the rest of their lives.

If you take too much (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26), or go to casualty at your nearest hospital, if you think that you or anyone else may have taken too much AUSGEM. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention. Keep telephone numbers of these places handy.

If you take too much AUSGEM you may have the following symptoms: abdominal cramps, nausea, vomiting and diarrhoea.

While you are taking it

Your doctor will ask you to have blood tests while you are taking AUSGEM. This is to check on a number of conditions including your fat levels. This is the way your doctor will know if the medicine is working for you.

The blood tests will also tell your doctor if AUSGEM is affecting your blood or liver. In some patients, this medication can affect your blood cells which may cause anaemia or make you more prone to infection. This medicine may also affect your liver.

Although these unwanted effects only occur in some patients and are generally temporary, it is important that you help your doctor check on your health by keeping these appointments.

If you become pregnant while you are taking AUSGEM, contact your doctor immediately.

Do not give AUSGEM to anyone else, even if they have the same condition as you.

Do not use it to treat any other complaints unless your doctor tells you to.

Avoid drinking large quantities of alcohol.

Drinking large quantities of alcohol may increase the chance of AUSGEM causing you liver problems.

Be careful driving or operating machinery until you know how AUSGEM affects you.

This medicine generally does not cause any problems with your ability to drive a car or operate machinery. However, as with any medicine, it may cause dizziness in some people.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking AUSGEM.

This medicine helps most people with high levels of cholesterol and triglycerides, but it may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • weakness
  • confusion
  • feeling depressed or sad
  • dizziness
  • sleepiness
  • aching muscles, muscle tenderness or weakness, not caused by exercise
  • painful, swollen joints
  • tiredness
  • headache
  • skin rash
  • change in taste
  • nausea and/or vomiting
  • heartburn
  • stomach pains
  • diarrhoea
  • constipation
  • blurred vision or eyesight
  • increase in the number of infections such as colds or bladder infections
  • decreased interest in sex or inability to have sexual intercourse
  • swelling with fluid in tissues
  • swelling around the neck

Tell your doctor immediately if you notice any of the following:

  • increased feeling or sensitivity, especially on the skin
  • pinkish, itchy swellings on the skin, also called hives or nettle rash
  • yellowing of the skin and/or eyes (this may be related to jaundice)
  • tingling or numbness in the hands or feet, also known as ‘pins and needles’
  • spinning sensation (vertigo)
  • sudden onset of severe stomach pain in the lower right hand side of the stomach with tenderness or muscle tightness
  • signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers

If any of the following happen, tell your doctor immediately or go to casualty at your nearest hospital:

  • signs of anaemia, such as tiredness, being short of breath, dizziness and looking pale
  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in breathing
  • sudden signs of allergy such as rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing

Other side effects not listed above may also occur in some patients.

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

After using it

Storage

Keep your tablets in the bottle until it is time to take them.

If you take the tablets out of the bottle they may not keep as well.

Keep your tablets in a cool dry place where the temperature stays below 30ºC.

Do not store AUSGEM or any other medicine in the bathroom or near a sink.

Do not leave it in the car or on windowsills.

Heat and dampness can destroy some medicines.

Keep it where young 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 the tablets or the tablets have passed their expiry date, ask your pharmacist what to do with any medicine that is left over.

This is not all the information that is available on AUSGEM. If you have any more questions or are not sure about anything, ask your doctor or pharmacist.

Product description

AUSGEM is presented as a white, film-coated, oval, film coated, biconvex tablet with a scoreline on one side and plain on the other.

In addition to the active ingredient “gemfibrozil”, the tablets also contain:

  • povidone
  • polysorbate 80
  • crospovidone
  • pregelatinised maize starch
  • microcrystalline cellulose
  • colloidal anhydrous silica
  • croscarmellose sodium
  • magnesium stearate
  • sodium lauryl sulfate

The tablet coating contains:

  • polydextrose
  • hypromellose
  • titanium dioxide
  • triacetin
  • polyethylene glycol

AUSGEM does not contain any gluten, lactose, sucrose, tartrazine or other azo dyes.

Supplier

Arrow Pharma Pty Ltd
15 – 17 Chapel Street
Cremorne VIC 3121

The registration number for AUSGEM tablets is AUST R 62099.

This leaflet was revised in April 2017

BRAND INFORMATION

Brand name

Ausgem Tablets

Active ingredient

Gemfibrozil

Schedule

S4

 

Name of the medicine

Gemfibrozil.

Excipients.

Povidone, polysorbate 80, crospovidone, pregelatinised maize starch, microcrystalline cellulose, anhydrous colloidal silica, croscarmellose sodium, magnesium stearate and sodium lauryl sulfate. The tablet coating contains polydextrose, hydroxypropyl methylcellulose, titanium dioxide, triacetin and polyethylene glycol.

Description

Chemical name: 5-(2,5-dimethylphenoxy)- 2,2-dimethylpentanoic acid. Molecular formula: C15H22O3. MW: 250.35. CAS: 25812-30-0. Gemfibrozil is a nonhalogenated phenoxypentanoic acid. It is a white, waxy powder with a melting point of 58°C to 61°C. The solubility in water and acid is 0.0019% (w/v). The solubility in dilute base is over 1%.
Ausgem tablets contain gemfibrozil 600 mg and the excipients; povidone, polysorbate 80, crospovidone, pregelatinised maize starch, microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, magnesium stearate and sodium lauryl sulphate.
The tablet coating contains polydextrose, hydroxypropyl methylcellulose, titanium dioxide, triacetin and polyethylene glycol.

Pharmacology

Pharmacodynamics.

Gemfibrozil is a lipid regulating agent which decreases serum triglycerides and total cholesterol and very low density lipoprotein cholesterol (VLDL), and increases high density lipoprotein cholesterol (HDL cholesterol). The lipid lowering changes occur primarily in the very low density lipoprotein (VLDL) fraction rich in triglycerides and to a lesser extent in the low density lipoprotein (LDL) fraction rich in cholesterol. Ausgem treatment of patients with elevated triglycerides due to type IV hyperlipoproteinaemia may cause a rise in LDL cholesterol.
Gemfibrozil increases the HDL cholesterol subfractions, HDL2 and HDL3, as well as apolipoproteins AI and AII.
Gemfibrozil's exact mechanism of action is still unknown. In humans, gemfibrozil inhibits peripheral lipolysis and decreases the hepatic extraction of free fatty acids, thus reducing hepatic triglyceride production. Gemfibrozil also inhibits synthesis and increases clearance of apolipoprotein B, which is a carrier of VLDL, leading to a decrease in VLDL production.
While modest decreases in total and LDL cholesterol may be observed with gemfibrozil therapy, treatment of patients with elevated triglycerides due to type IV hyperlipoproteinaemia often results in a rise in LDL cholesterol. LDL cholesterol levels in type IIb patients with elevations of both serum LDL cholesterol and triglycerides are, in general, minimally affected by gemfibrozil treatment; however, gemfibrozil usually raises HDL cholesterol significantly in this group. Gemfibrozil increases levels of HDL subfractions HDL2 and HDL3 as well as apolipoproteins AI and AII. Epidemiological studies have shown that both low HDL cholesterol and high LDL cholesterol are independent risk factors for coronary heart disease.
In the Helsinki Heart Study, a large randomised double blind, placebo controlled, primary prevention trial in 4,081 male patients between the ages of 40 and 55, gemfibrozil therapy was associated with significant reductions in total plasma triglycerides and a significant increase in high density lipoprotein cholesterol. Moderate reductions in total plasma cholesterol and low density lipoprotein cholesterol were observed for the gemfibrozil treatment group as a whole, but the lipid response was heterogeneous, especially among different Fredrickson types. The study involved subjects with serum non-HDL cholesterol of over 5.2 mmol/L and no previous history of coronary heart disease. Over the five year study period, the gemfibrozil group experienced a 34% reduction in serious coronary events (sudden cardiac deaths plus fatal and nonfatal myocardial infarctions) compared to placebo. There was a 37% reduction in nonfatal myocardial infarction. There was no significant difference in death rate due to all causes between the gemfibrozil group and the placebo group. (See Table 1.)
The greatest reduction in the incidence of serious coronary events occurred in type IIb patients who had elevations of both LDL cholesterol and total plasma triglycerides. This subgroup of type IIb gemfibrozil group patients had a lower mean HDL cholesterol level at baseline than the type IIa subgroup that had elevations of LDL cholesterol and normal plasma triglycerides. The mean increase in HDL cholesterol in this study was 12.6% compared to placebo. It is not clear to what extent the findings of the Helsinki Heart Study can be extrapolated to other segments of the dyslipidaemic population not studied or to other lipid altering drugs. (See Table 2.)

Pharmacokinetics.

Following oral administration gemfibrozil is well absorbed with peak plasma levels being attained within 1 to 2 hours. The biological half-life of gemfibrozil is 1.5 hours and 1.3 hours following ingestion of single and multiple doses respectively. Plasma levels appear proportional to dose and do not demonstrate accumulation across time following multiple dosing.
Gemfibrozil mainly undergoes oxidation of a ring methyl group to successively form a hydroxymethyl and carboxyl metabolite. Approximately 70% of the administered dose is excreted in the urine (mostly as the glucuronide conjugate) with less than 2% excreted as unchanged gemfibrozil and 6% of the dose excreted in the faeces.

Indications

Ausgem is indicated as an adjunct to diet and other therapeutic measures for the following conditions.
Severe hypertriglyceridaemia (types IV and V) in those who present a risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them.
Dyslipidaemia associated with diabetes.
Reduction of risk of coronary heart disease in patients with type IIa and IIb hypercholesterolaemia.
Because of potential toxicity such as malignancy, gall bladder disease, abdominal pain leading to appendectomy and other abdominal surgeries, an increased incidence in noncoronary mortality and the 29% increase in all cause mortality seen with the chemically and pharmacologically related drug clofibrate, the potential benefits of gemfibrozil in treating type IIa patients with elevations of LDL cholesterol only is not likely to outweigh the risks. In a subgroup analysis of patients in the Helsinki Heart Study with above median HDL cholesterol values at baseline (> 1.2 mmol/L), both gemfibrozil and placebo subgroups had similar incidences of serious coronary events.

Note.

Ausgem is indicated when exercise, weight loss and specific dietary or other nondrug measures such as limiting alcohol intake have failed. Other medical disorders such as hypothyroidism and diabetes should be controlled as much as possible.
Periodic determinations of serum lipids should be obtained during treatment with Ausgem. The drug should be withdrawn or additional therapy instituted if the lipid response is deemed inadequate after 3 months.

Contraindications

Hepatic or severe renal dysfunction, including primary biliary cirrhosis.
Pre-existing gall bladder disease (see Precautions).
Hypersensitivity to Ausgem.
Pregnant or lactating women.
Type I hyperlipoproteinaemia.
Concurrent use of cerivastatin, due to a risk of myopathy and rhabdomyolysis (see Precautions and Interactions with Other Medicines).
Concurrent use of repaglinide, due to a potentially serious pharmacokinetic interaction between repaglinide and gemfibrozil.

Precautions

Because of chemical, pharmacological and clinical similarities between gemfibrozil and clofibrate the adverse findings seen with clofibrate in two large clinical studies may also apply to gemfibrozil. The physician should be aware that in one of these studies, the Coronary Drug Project, 1000 subjects with previous myocardial infarction were treated for 5 years with clofibrate, there was no difference in mortality between the clofibrate-treated subjects and 3000 placebo-treated subjects. However, twice as many clofibrate-treated patients developed cholelithiasis and cholecystitis requiring surgery than the placebo patients. In the other study, conducted by the World Health Organization (WHO), 5000 subjects without known coronary heart disease were treated with clofibrate for 5 years and followed one year on. There was a statistically significant (29%) higher total mortality in the clofibrate-treated patients than in a comparable placebo treated control group.
This excess mortality was due to a 33% increase in non-cardiovascular causes, including malignancy, post-cholecystectomy complications, and pancreatitis. The higher risk of clofibrate-treated subjects for gall bladder disease was confirmed in this study.
During the Helsinki Heart Study and in the one and a half years follow-up period since the trial was completed, mortality from any cause was 59 (2.9%) in the gemfibrozil group and 55 (2.7%) in the placebo group. Mortality from any cause during the double-blind portion of the study was 44 deaths in the gemfibrozil group and 43 in the placebo group. Because of the more limited size of the Helsinki Heart Study, this result is not statistically significantly different from the 29% excess mortality seen in the clofibrate group in the separate WHO study. Non-coronary heart disease related mortality showed a 58% greater trend in the gemfibrozil group (43 vs 27 patients in the placebo group, p = 0.056).
In the Helsinki Heart Study, the incidence of total malignancies discovered during the trial and in the one and a half years since the trial was completed was 39 in the gemfibrozil group and 29 in the placebo group (difference not statistically significant). This includes 5 basal cell carcinomas in the gemfibrozil group and none in the placebo group (p = 0.06); historical data predicted an expected 4.7 cases in the placebo group. GI malignancies and deaths from malignancies were not statistically different between gemfibrozil and placebo subgroups. Follow-up of the Helsinki Heart Study participants will provide further information on cause-specific mortality and cancer morbidity.
A gallstone prevalence substudy of 450 Helsinki Heart Study participants showed a trend towards a greater prevalence of gallstones during the study within the gemfibrozil-treatment group (7.5% versus 4.9% for the placebo group, a 55% excess for the gemfibrozil group). A trend toward a greater incidence of gall bladder surgery was observed for the gemfibrozil group (17 versus 11 subjects, a 54% excess). This result did not differ statistically from the increased incidence of cholecystectomy observed in the WHO study in the group treated with clofibrate. Both clofibrate and gemfibrozil may increase cholesterol excretion into the bile leading to cholelithiasis. If cholelithiasis is suspected, gall bladder studies are indicated. Ausgem therapy should be discontinued if gallstones are found.
Since reduction of mortality from coronary artery disease has not been demonstrated and because hepatic and interstitial cell testicular tumours were shown to increase in rat studies, Ausgem should only be administered to those patients described in the Indications section. If a significant serum response is not obtained, Ausgem should be discontinued.

Concomitant anticoagulants.

Caution should be exercised when anticoagulants are administered concomitantly with Ausgem. The anticoagulant dosage should be reduced to maintain the prothrombin time at the level which prevents bleeding complications. Frequent prothrombin determinations are advisable until it has been definitely determined that the prothrombin time has stabilised.

Concomitant HMG-CoA reductase inhibitors.

There have been reports of severe myositis with markedly elevated creatine kinase and myoglobinuria (rhabdomyolysis) when gemfibrozil and HMG-CoA reductase inhibitors were used concomitantly. This may be seen as early as 3 weeks after initiation of combined therapy, or after several months. In most subjects who have had an unsatisfactory lipid response to either drug alone, the possible benefit of combined therapy with HMG-CoA reductase inhibitors and gemfibrozil does not outweigh the risks of severe myopathy, rhabdomyolysis, and acute renal failure (see Interactions with Other Medicines). Periodic monitoring of creatine kinase provides no assurance that the occurrence of severe myopathy and kidney damage will be prevented. The use of fibrates alone, including Ausgem, may occasionally be associated with myositis. Patients receiving Ausgem and complaining of muscle pain, tenderness or weakness should have prompt medical evaluation for myositis, including serum creatinine kinase level determination. If myositis is suspected or diagnosed, Ausgem therapy should be withdrawn.

Carcinogenesis, mutagenesis, impairment of fertility.

Long-term studies have been conducted in rats and mice at doses of 30 and 300 mg/kg/day. The incidence of benign hepatic nodules and hepatic carcinomas was significantly increased in high dose male rats. The incidence of hepatic carcinomas also increased in low dose males, but this increase was not statistically significant (p = 0.1). In high dose female rats, there was a significant increase in the combined incidence of benign and malignant hepatic neoplasms. In male and female mice, there were no statistically significant differences from controls in the incidence of hepatic tumours, but the doses tested were lower than those shown to be carcinogenic with other fibrates.
Male rats had a dose related and statistically significant increase of benign Leydig cell tumours at 1 and 10 times the human dose.
Administration of approximately 2 times the human dose (based on surface area) to male rats for 10 weeks resulted in a dose related decrease of fertility. Subsequent studies demonstrated that this effect was reversed after a drug free period of about eight weeks and it was not transmitted to the offspring. Minor fetotoxicity was manifested by reduced birthrates observed at the high dose levels.
Electron microscopy studies have demonstrated a florid hepatic peroxisome proliferation following Ausgem administration to the male rat. An adequate study to test for peroxisome proliferation has not been done in humans; but changes in peroxisome morphology have been observed.

Cataracts.

Subcapsular bilateral cataracts occurred in 10%, and unilateral in 6.3% of male rats treated with gemfibrozil at 10 times the human dose.

Impairment of fertility.

Gemfibrozil was administered in oral doses of approximately 95 and 325 mg/kg/day to male and female rats for 61 and 15 days respectively before mating. Dosing was continued through pregnancy and weaning of offspring. Gemfibrozil produced a dose related suppression of fertility but had no effect on length of gestation, duration of parturition, litter size, or embryonic or foetal wastage. Treated males were responsible for the reduced fertility rate, probably because of the marked suppression of weight gain they experienced.

Initial therapy.

Before starting therapy with Ausgem, attempts should be made to control serum lipids with appropriate diet, exercise, weight loss in obese patients, and control of any of the causes of secondary hyperlipidaemia such as diabetes mellitus or hypothyroidism.

Long-term therapy.

Since long-term administration of Ausgem is recommended, pretreatment clinical chemistry studies should be performed to ensure that the patient has elevated serum lipid or low HDL cholesterol levels. Periodic determinations of serum lipids and lipoproteins should be done during Ausgem administration, including measurement of LDL cholesterol/ HDL cholesterol ratio, particularly in type IV hyperlipoproteinaemic patients.

Continued therapy.

Periodic determination of serum lipids should be obtained and the drug withdrawn if lipid response is inadequate after 3 months of therapy.

Cholelithiasis.

Gemfibrozil may increase cholesterol excretion into the bile leading to cholelithiasis. However, in the Helsinki Heart Study the use of gemfibrozil did not significantly increase the need for cholecystectomy compared to placebo. If cholelithiasis is suspected, gall bladder studies are indicated. Ausgem therapy should be discontinued if gallstones are found.

Haematological changes.

Mild haemoglobin, haematocrit and white cell decreases have been observed occasionally on initiating Ausgem therapy. However, these levels stabilise during long-term administration. Rarely, severe anaemia, leucopoenia, thrombocytopenia and bone marrow hypoplasia have been reported. Therefore, periodic blood counts are recommended during the first 12 months of Ausgem administration.

Liver function.

Abnormal liver function tests have been observed occasionally during gemfibrozil administration, including elevations of AST (SGOT), ALT (SGPT), LDH, and alkaline phosphatase. These are usually reversible when the gemfibrozil is discontinued. Therefore, periodic liver function studies are recommended and Ausgem therapy should be terminated if abnormalities persist.

Hepatobiliary disease.

Ausgem should be used with caution in patients with a past history of jaundice or hepatic disorder.

Cardiac arrhythmias.

Although no clinically significant abnormalities attributed to Ausgem have occurred, the physician should be aware of the possibility of such events occurring.

Use in pregnancy.

(Category B3)
Reproduction studies have been performed in rats at doses of 81 and 281 mg/kg/day and rabbits at 60 and 300 mg/kg/day. These studies have revealed no evidence of impaired fertility in females or harm to the foetus due to gemfibrozil. Minor fetotoxicity was manifested by reduced birth rates observed at the high dose levels. No significant malformations were found among almost 400 offspring from 36 litters of rats and 100 foetuses from 22 litters of rabbits.
There are no studies in pregnant women. In view of the fact that gemfibrozil is tumourigenic in male and female rats, the use of Ausgem in pregnancy should be reserved for those patients where the benefit clearly outweighs the possible risk to the patient or foetus (see Contraindications).

Use in lactation.

The safety of Ausgem in nursing mothers has not been established. It is not known whether gemfibrozil or its metabolites are excreted in human milk. Ausgem is not recommended in lactating women (see Contraindications).

Use in children.

The safety and efficacy of gemfibrozil in children have not been established. Therefore, Ausgem is not recommended in this patient population.

Interactions

Caution should be exercised when anticoagulants are given in conjunction with Ausgem. The dosage of the anticoagulant should be reduced to maintain the prothrombin time at the desired level to prevent bleeding complications. Frequent prothrombin determinations are advisable until it has been definitely determined that the prothrombin level had stabilised (see Precautions).
There have been reports of severe myositis and myoglobinuria (rhabdomyolysis) when gemfibrozil and HMG-CoA reductase inhibitors were used concomitantly. It may be seen as early as three weeks after the initiation of combined therapy or after several months. In most subjects who have had an unsatisfactory lipid response to either drug alone, the possible benefit of combined therapy with HMG-CoA reductase inhibitors and gemfibrozil does not outweigh the risks of severe myopathy, rhabdomyolysis and acute renal failure. There is no assurance that periodic monitoring of creatinine kinase will prevent the occurrence of severe myopathy and kidney damage (see Precautions).
The risk of serious toxicity is increased if gemfibrozil is used concomitantly with other fibrates. Such combination therapy should be used with caution only in patients with severe combined dyslipidaemia who have high cardiovascular risk and no history of muscular disease. Patients should be monitored closely for signs of muscle toxicity, although toxicity may occur even in the presence of such monitoring.
Reduced bioavailability of gemfibrozil may result when given simultaneously with colestipol. Administration of the drugs two hours or more apart is recommended.

Adverse Effects

In the double blind controlled phase of the Helsinki Heart Study, during which 2,046 patients received gemfibrozil for up to five years, the following adverse reactions were statistically more frequent in the gemfibrozil treated patients, expressed as (% gemfibrozil/ % placebo).

Gastrointestinal reactions (34.2%/23.8%).

Dyspepsia (19.6%/11.9%), abdominal pain (9.8%/5.6%), acute appendicitis (histologically confirmed in most cases where data were available, 1.2%/0.6%).

Cardiovascular.

Atrial fibrillation (0.7%/0.1%).
The following adverse events were reported in more than 1% of subjects, but without a significant difference between the gemfibrozil and placebo groups: diarrhoea (7.2%/6.5%), fatigue (3.8%/3.5%), nausea and/or vomiting (2.5%/2.1%), eczema (1.9%/1.2%), rash (1.7%/1.3%), vertigo (1.5%/1.3%), constipation (1.4%/1.3%) and headache (1.2%/1.1%).
Gall bladder surgery was performed in 0.9% of gemfibrozil and 0.5% of placebo subjects, a 64% excess, which is not statistically different from the excess of gall bladder surgery observed in the clofibrate compared to the placebo group in the WHO study.
Nervous system and special senses adverse reactions were more common in the gemfibrozil group. These included hypoaesthesia, paraesthesia, and taste perversion. Other adverse reactions that were more common among the gemfibrozil treated subjects, but where a causal relationship was not established, included cataracts, peripheral vascular disease, and intracerebral haemorrhage.
From other studies it seems probable that gemfibrozil is causally related to the occurrence of musculoskeletal symptoms and to abnormal hepatic function tests and haematological changes (see Precautions).
Reports of viral and bacterial infections (common cold, cough, urinary tract infections) were more common in gemfibrozil treated patients in other controlled clinical trials.
Additional adverse reactions that have been reported for gemfibrozil are listed below by system according to whether the relationship to gemfibrozil is probable or not established.

Probable.

Gastrointestinal.

Cholestatic jaundice, cholelithiasis.

Central nervous system.

Dizziness, somnolence, paraesthesia, peripheral neuritis, decreased libido, depression, headache.

Ocular.

Blurred vision.

Genitourinary.

Impotence.

Musculoskeletal.

Myopathy, myasthenia, myalgia, painful extremities, arthralgia, synovitis, rhabdomyolysis (see Precautions and Interactions with Other Medicines).

Clinical laboratory.

Increased creatine phosphokinase, increased bilirubin, increased liver transaminase (AST, ALT), increased alkaline phosphatase.

Haematological.

Anaemia, leucopoenia.

Immunological.

Angioedema, laryngeal oedema, urticaria.

Dermatological.

Exfoliative dermatitis, rash, dermatitis, pruritus.

Not established.

General.

Weight loss.

Cardiovascular.

Extrasystoles.

Gastrointestinal.

Pancreatitis, hepatoma, colitis.

Central nervous system.

Confusion, convulsions, syncope.

Ocular.

Retinal oedema.

Genitourinary.

Decreased male fertility.

Clinical laboratory.

Positive antinuclear antibody.

Haematological.

Thrombocytopenia.

Immunological.

Anaphylaxis, lupus-like syndrome, vasculitis.

Dermatological.

Alopecia.

Dosage and Administration

The recommended dose for adults is 600 mg twice daily (total daily dose 1200 mg) administered half an hour before the morning and evening meals. The tablets should be taken whole without halving.
For patients who cannot tolerate gemfibrozil when given half an hour before food, Ausgem may be taken with food. The bioavailability of gemfibrozil is higher when administered half an hour before food.

Overdosage

Overdosage has been reported with gemfibrozil. Symptoms reported with overdosage were abdominal cramps, abnormal LFTs, diarrhoea, increased CPK, joint and muscle pain, nausea and vomiting. The patients fully recovered.
Symptomatic supportive measures should be provided should overdosage occur.

Presentation

Ausgem film coated tablets 600 mg are available in bottles (HDPE) of 60’s. It is a white, oval, biconvex, film coated tablet with a scoreline on one side and plain on the other.

Storage

Store below 30°C.

Poison Schedule

S4.