Consumer medicine information

Eryc Capsules

Erythromycin

BRAND INFORMATION

Brand name

Eryc Capsules

Active ingredient

Erythromycin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Eryc Capsules.

What is in this leaflet

This leaflet answers some common questions about Eryc® Capsules. 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 Eryc® Capsules against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What Eryc® Capsules are used for

This medicine is an antibiotic used to:

  • treat infections in different parts of the body caused by bacteria
  • prevent infections in patients with a history of rheumatic disease who may be allergic to penicillin.

This medicine is an antibiotic which belongs to a group of medicines called macrolides.

It works by killing or stopping the growth of bacteria which cause infections.

This medicine will not work against viral infections such as colds or flu.

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

Your doctor may have prescribed it for another reason.

This medicine is not addictive.

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

Before you take Eryc® Capsules

When you must not take it

Do not take Eryc® Capsules if you have an allergy to:

  • any medicine containing erythromycin
  • any of the ingredients listed at the end of this leaflet.

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

Do not take this medicine if you have severe liver problems.

Do not take this medicine if you are taking any of the following medications:

  • cisapride, a medicine which helps move food through the digestive system
  • pimozide, a medicine used to treat some psychiatric (mental) conditions
  • ergotamine or dihydroergotamine, medicines used to treat migraine headache

Ask you doctor or pharmacist if you are not sure if you are taking any of these medicines.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • liver problems
  • irregular or very slow heart beat
  • myasthenia gravis, a condition in which the muscles become weak and tire easily.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding.

Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you start taking Eryc® Capsules.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you get without a prescription from a pharmacy, supermarket or health food shop.

Some medicines and Eryc® Capsules may interfere with each other. These include:

  • theophylline, a medicine used to treat asthma
  • methylprednisolone, a corticosteroid
  • some medicines used for epilepsy such as carbamazepine, phenytoin and valproate
  • digoxin, a drug used to treat heart failure or heart disease
  • some medicines used to treat irregular heart beats, such as quinidine, disopyramide, procainamide, amiodarone and sotalol
  • some medicines used to treat high blood pressure or angina such as verapamil, amlodipine and diltiazem
  • alprazolam, triazolam or midazolam, medicines used to produce sleep or drowsiness and to relieve anxiety
  • medicines used to prevent blood clots, such as warfarin
  • medicines used to prevent organ transplant rejection or to treat certain problems with the immune system, such as cyclosporin and tacrolimus
  • medicines used to lower high blood cholesterol, such as lovastatin, simvastatin and atorvastatin
  • the antibiotics clindamycin, lincomycin, penicillin and rifabutin
  • medicines used to treat fungal infections such as ketoconazole, itraconazole and fluconazole
  • colchicine, a medicine used in the treatment of gout
  • some medicines for migraine headache such as ergotamine or dihydroergotamine
  • pimozide, a medicine used to treat some psychiatric (mental) conditions
  • cisapride, a medicine which helps food move through the digestive system
  • bromocriptine, a medicine use to treat Parkinson’s disease
  • sildenafil (Viagra), a medicine used to treat impotence
  • vinblastine, a medicine used in the treatment of some types of cancer
  • cimetidine, a medicine used to treat stomach problems, such as ulcers
  • zopiclone, a medicine used for sleeping problems
  • the contraceptive pill (birth control pill). Eryc® Capsules may decrease the effectiveness of some birth control pills.

Your doctor may advise you to use an additional method of contraception such as a barrier method while taking Eryc® Capsules and for seven days after finishing the course of Eryc® Capsules. Consult your doctor or pharmacist for advice.

These medicines may be affected by Eryc® Capsules or may affect how well it works. You may need different amounts of your medicine or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking Eryc® Capsules.

How to take Eryc® Capsules

Follow all directions given to you by your doctor or pharmacist carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much to take

Your doctor or pharmacist will tell you how many capsules you will need to take each day. This depends on your condition and whether or not you are taking any other medicines.

For treating most infections, the usual adult dose of Eryc® Capsules is one 250 mg capsule four times a day or two 250 mg capsules twice a day.

For the long-term prevention of streptococcal infections in persons with a history of rheumatic heart disease and an allergy to penicillin, the usual dose is one 250 mg capsule twice a day.

Your doctor may ask you to take a different dose, depending on your condition and how you react to the medicine.

How to take it

Swallow the capsules whole with a full glass of water.

Do not chew or crush the capsule.

When to take it

Take your medicine on an empty stomach, for example one hour before food or two hours after food.

Food can interfere with the absorption of this medicine.

How long to take it

Continue taking your medicine until you finish the pack or for as long as your doctor recommends.

For treating infections, this medicine is usually taken for one to two weeks.

However, your doctor may prescribe it for longer periods.

Keep taking this medicine for the full time of treatment, even if you begin to feel better after a few days.

If you do not complete the full course prescribed by your doctor, the infection may not clear up completely or your symptoms may return.

Check with your doctor if you are not sure how long you should be taking Eryc® Capsules.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

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 the dose you have missed.

This may increase the chance of you getting an unwanted side effect.

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.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too many Eryc® Capsules. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention

If you take too many Eryc®Capsules you may feel sick (nauseous) or vomit, experience diarrhoea or hearing problems. Other effects may include those listed in the ‘side effects’ section, but are usually of a more severe nature.

While you are using Eryc® Capsules

Things you must do

If you are taking Eryc® Capsules for an infection and your symptoms do not improve within a few days, or if they become worse, tell your doctor.

If you get severe diarrhoea, tell your doctor immediately. Do this even if it occurs several weeks after Eryc® Capsules have been stopped.

Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care.

Do not take any diarrhoea medicine without first checking with your doctor.

If you get a sore, white mouth or tongue while taking or soon after stopping Eryc® Capsules, tell your doctor. Also tell your doctor if you get vaginal itching or discharge.

This may mean you have a fungal infection called thrush. Sometimes the use of Eryc® Capsules allows fungi to grow and the above symptoms to occur. Eryc® Capsules do not work against fungi.

If you are about to be started on any new medicines, remind your doctor and pharmacist that you are taking Eryc® Capsules.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

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

If you have to have any blood or urine tests, tell your doctor you are taking this medicine.

It may interfere with the results of some tests.

Things you must not do

Do not take Eryc® Capsules to treat any other complaints unless your doctor tells you to.

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

Do not stop taking your medicine or lower the dosage because you are feeling better, unless advised by your doctor.

If you do not complete the full course prescribed by your doctor, all of the bacteria causing your infection may not be killed. These bacteria may continue to grow and multiply so that your infection may not clear completely or it may return.

Things to be careful of

Be careful driving or operating machinery until you know how Eryc® Capsules affects you.

This medicine generally does not cause any problems with your ability to drive a car or operate machinery. However, as with many other medicines, it may cause dizziness in some people. If this occurs do not drive, operate machinery or do anything else that could be dangerous.

Side effects

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

This medicine helps to treat or prevent particular infections in most people, 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 attention if you get some of the side effects.

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

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

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:

  • mild stomach upsets such as feeling sick, diarrhoea, or mild stomach pains
  • vomiting
  • loss of appetite.

The above list includes some of the more common side effects of your medicine. They are usually mild and short-lived.

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

  • yellowing of the skin and eyes, also called jaundice
  • difficulty hearing
  • hallucinations or confusion
  • increasingly poor appetite.

The above list includes serious side effects which may require medical attention. Serious side effects are rare.

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

  • signs of an allergic reaction (for example, rash, itching or hives on the skin; swelling of the face, lips, tongue or other parts of the body; shortness of breath, wheezing or difficulty breathing)
  • chest pain
  • changes in the rhythm or rate of the heart beat
  • convulsions (fits)
  • watery and severe diarrhoea, which may also be bloody
  • severe abdominal cramps, stomach cramps or stomach pain.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

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

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

After finishing Eryc® Capsules

Tell your doctor immediately if you notice any of the following side effects, particularly if they occur several weeks after stopping treatment with Eryc® Capsules:

  • severe abdominal cramps or stomach cramps
  • watery and severe diarrhoea, which may also be bloody
  • fever, in combination with one or both of the above.

These are rare but serious side effects. You may have a serious condition affecting your bowel. Therefore, you may need urgent medical attention. However, these side effects are rare.

Do not take any diarrhoea medicine without first checking with your doctor.

After using Eryc® Capsules

Storage

Keep your capsules in the pack until it is time to take them.

If you take the capsules out of the pack they may not keep well.

Keep your capsules in a cool, dry place where the temperature stays below 25°C.

Do not store Eryc® Capsules 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 it 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 the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Eryc® Capsules 250 mg are transparent red/yellow capsules filled with white coated pellets, marked ERYC in black. It is available in packs of 25 capsules.

Ingredients

Eryc® Capsules 250 mg contains 250 mg of erythromycin as the active ingredient. It also contains:

  • lactose
  • povidone
  • cellacephate
  • diethyl phthalate
  • gelatin
  • shellac
  • potassium phosphate
  • erythrosine
  • indigo carmine (132)
  • sunset yellow (110)
  • carbon black (153).

This medicine does not contain sucrose or gluten.

NAME AND ADDRESS OF THE SPONSOR

Mayne Pharma International Pty Ltd
ABN 88 007 870 984
1538 Main North Road
Salisbury South, SA 5106
AUSTRALIA

Eryc® is a registered trademark of Mayne Pharma International Pty Ltd

This leaflet was prepared in October 2012.

Eryc® 250 mg:
Blister pack AUST R 63156
Bottle AUST R 63154

BRAND INFORMATION

Brand name

Eryc Capsules

Active ingredient

Erythromycin

Schedule

S4

 

1 Name of Medicine

Erythromycin.

6.7 Physicochemical Properties

Chemical structure.

The chemical structure of erythromycin is shown below.

CAS number.

114-07-8.

2 Qualitative and Quantitative Composition

Erythromycin is produced by a strain of Streptomyces erythreus and belongs to the macrolide group of antibiotics. It is basic and readily forms salts with acids.
Each Eryc capsule contains 250 mg erythromycin, comprising of enteric coated pellets of erythromycin for oral administration. The enteric coating on the pellets covers the bitter tasting erythromycin as well as protects the erythromycin from gastric acid destruction during the passage through the stomach.
Eryc contains lactose. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Eryc Capsules are transparent red/yellow capsules imprinted with ‘Eryc’, containing white enteric coated pellets.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Erythromycin acts by inhibition of protein synthesis; it binds to the 50S ribosomal subunits of susceptible organisms. Erythromycin is bacteriostatic at low concentrations and bactericidal at high concentrations.

Microbiology.

Erythromycin is active against a number of pathogenic microorganisms, in particular Gram positive cocci and bacilli. Erythromycin is usually active against the following organisms in vitro and in clinical infections.
Streptococcus pyogenes, α-haemolytic Streptococci (viridans group), Staphylococcus aureus, Streptococcus pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae (some strains are resistant), Legionella pneumophila, Treponema pallidum, Neisseria gonorrhoeae, Corynebacterium diphtheriae (as an adjunct to antitoxin), Corynebacterium minutissimum, Listeria monocytogenes, Clostridium tetani, Bordetella pertussis, Campylobacter jejuni (in severe or prolonged cases), Chlamydia trachomatis, Ureaplasma urealyticum.
Not all strains of the organisms listed above are sensitive and culture and susceptibility testing should be done. Several strains of Haemophilus influenzae and Staphylococci have been found to be resistant to erythromycin. Staphylococcal resistance to erythromycin may emerge during a course of therapy. If the Kirby-Bauer method of disc susceptibility is used, an erythromycin 15 microgram disc should give a zone diameter of at least 18 mm when tested against erythromycin susceptible organisms. Antagonism has been demonstrated in vitro between erythromycin and clindamycin, lincomycin and chloramphenicol.

Susceptibility testing.

Quantitative methods that require measurement of zone diameters give the most precise estimates of antibiotic susceptibility. One such standardised single disc procedure has been recommended for use with discs to test susceptibility to erythromycin. Interpretation involves correlation of the zone diameters obtained in the disc test with minimal inhibitory concentration (MIC) values for erythromycin.
Reports from the laboratory giving results of the standardised single disc susceptibility test using an erythromycin 15 microgram disc should be interpreted according to the following criteria. Susceptible organisms produce zones of 18 mm or greater, indicating that the tested organism is likely to respond to therapy.
Resistant organisms produce zones of 13 mm or less, indicating that other therapy should be selected.
Organisms of intermediate susceptibility produce zones of 14 to 17 mm. The ‘intermediate’ category provides a ‘barrier zone’ which should prevent small uncontrolled technical factors from causing major discrepancies in interpretations, thus, when a zone diameter falls within the ‘intermediate’ range, the results may be considered equivocal. If alternative drugs are not available, confirmation by dilution test may be indicated.
Standardised procedures require the use of control organisms. The erythromycin 15 microgram disc should give zone diameters between 22 and 30 mm for the Staphylococcus aureus ATCC 25923 control strain.
A bacterial isolate may be considered susceptible if the MIC value for erythromycin is not more than 2 microgram/mL. Organisms are considered resistant if the MIC is 8 microgram/mL or higher. The MIC of erythromycin for Staphylococcus aureus ATCC 29213 control strain should be between 0.12 and 0.5 microgram/mL.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Orally administered erythromycin is readily absorbed in the microbiologically active form. Interindividual variations in the absorption of erythromycin are, however, observed and some patients do not achieve acceptable serum levels. Absorption may be interfered with by the presence of food in the stomach. Optimal conditions for stability in the presence of gastric secretion and for complete absorption are attained when Eryc Capsules are taken on an empty stomach.

Distribution.

After administration of the third dose of two Eryc 175 mg capsules to adults, a mean peak serum level of 2.01 ± 0.69 microgram/mL was attained in approximately two to four hours. This is comparable to peak serum levels achieved with two 250 mg of other formulations of erythromycin. Erythromycin is bound to plasma proteins to the extent of approximately 75%. It diffuses readily into most body fluids with the exception of cerebrospinal fluid, synovial fluid and vitreous humour.
Erythromycin appears in breast milk at levels which are approximately 50% of the plasma concentration. It crosses the placenta and fetal plasma levels are usually 5 to 20% of the maternal plasma concentration.

Metabolism and excretion.

In the presence of normal hepatic function, erythromycin is concentrated in the liver; this results in high concentrations in the bile. However, approximately 1.5% of the absorbed erythromycin can be recovered unchanged in bile over a period of eight hours.
Substantial quantities appear in the faeces and probably represent the unabsorbed drug plus the drug excreted via the bile. Approximately 5% of an orally administered dose appears in the urine. A large proportion of the absorbed drug remains unaccounted for and is presumably metabolised, probably in the liver.
In the presence of normal renal function, the plasma half-life is approximately 1.4 hours; this may increase to six hours in anuric patients but does not usually require dosage adjustment. Erythromycin is not removed by dialysis.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Eryc Capsules are indicated in children and adults for the treatment of the following conditions.
Upper respiratory tract infections of mild to moderate degree caused by Streptococcus pyogenes (group A β-haemolytic Streptococci), Streptococcus pneumoniae (Diplococcus pneumoniae).
Lower respiratory tract infections of mild to moderate severity caused by Streptococcus pyogenes (group A β-haemolytic Streptococci), Streptococcus pneumoniae (Diplococcus pneumoniae), acute and chronic bronchitis, pneumonia.
Sinusitis caused by Streptococcus pneumoniae, Streptococcus pyogenes.
Otitis media due to Streptococcus pneumoniae, Streptococcus pyogenes.
Respiratory tract infections due to Mycoplasma pneumoniae (Eaton agent).
Skin and skin structure infections of mild to moderate severity caused by Streptococcus pyogenes and Staphylococcus aureus (resistant Staphylococci may emerge during treatment).
Bordetella pertussis. Erythromycin produces early elimination of the causative organism from the nasopharynx although the clinical course of the disease is not altered; therapeutic doses should be continued for at least ten days.
Diphtheria. As an adjunct to antitoxin infections due to Corynebacterium diphtheriae, to prevent establishment of carriers and to eradicate the organism in carriers.
Erythrasma. In the treatment of infections due to Corynebacterium minutissimum.
Infections due to Listeria monocytogenes.
Nongonococcal urethritis. Chlamydia trachomatis and Ureaplasma urealyticum have been shown to be sensitive to erythromycin and clinical studies have demonstrated its efficacy in urethritis due to these organisms. A minimum of ten days therapy appears to be required.
Chlamydia trachomatis infection (excluding nongonococcal urethritis). Erythromycin has been shown to be effective in the treatment of trachoma or inclusion body conjunctivitis and pneumonia in infants caused by Chlamydia trachomatis.
Campylobacter fetus (subspecies) jejuni. Infections due to this organism when antibiotic therapy is indicated.
Primary syphilis caused by Treponema pallidum. Erythromycin (oral forms only) is an alternative choice of treatment for primary syphilis in patients allergic to the penicillins. In the treatment of primary syphilis, spinal fluid should be examined before treatment and as part of the follow-up after therapy.
Legionnaires' disease caused by Legionella pneumophila. Although no controlled clinical efficacy studies have been conducted, in vitro and limited preliminary clinical data suggest that erythromycin may be effective in treating Legionnaires' disease.
Prevention of initial attacks of rheumatic fever. Penicillin is considered by the American Heart Association to be the drug of choice in the prevention of initial attacks of rheumatic fever (treatment of group A β-haemolytic streptococcal infections of the upper respiratory tract, e.g. tonsillitis or pharyngitis). Erythromycin is indicated for the treatment of penicillin allergic patients. A therapeutic dose should be administered for ten days.
Prevention of recurrent attacks of rheumatic fever. Penicillin or sulfonamides are considered by the American Heart Association to be the drugs of choice in the prevention of recurrent attacks of rheumatic fever.
In patients who are allergic to penicillin and sulfonamides, oral erythromycin is recommended by the American Heart Association in the long-term prophylaxis of streptococcal pharyngitis (for the prevention of recurrent attacks of rheumatic fever).
Prevention of bacterial endocarditis. Although no controlled clinical efficacy trials have been conducted, oral erythromycin has been suggested by the American Heart Association and the American Dental Association in a regimen for prophylaxis against bacterial endocarditis in patients sensitive to penicillin who have congenital heart disease, or rheumatic or other acquired valvular heart disease, when they undergo dental or surgical procedures of the upper respiratory tract.
Erythromycin is not suitable prior to genitourinary or gastrointestinal tract surgery.

4.3 Contraindications

Eryc Capsules are contraindicated in patients with known hypersensitivity to erythromycin and in patients with severely impaired hepatic function.
Concomitant administration of erythromycin and cisapride is contraindicated. The concurrent administration of cisapride and drugs that inhibit its cytochrome P450 metabolism, including erythromycin, has been associated with increased blood levels of cisapride and an increased risk of life threatening cardiac arrhythmias. These may include torsades de pointes, prolongation of the QT interval, ventricular tachycardia and fibrillation.
Concomitant administration of erythromycin and pimozide is contraindicated. Ventricular arrhythmias and prolongation of the QT interval have been associated with the concurrent use of macrolide antibiotics and pimozide. Specifically, two sudden deaths have been reported when clarithromycin was added to ongoing pimozide therapy.
Concomitant administration of erythromycin with ergotamine or dihydroergotamine is contraindicated (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Erythromycin is contraindicated in patients taking terfenadine or astemizole (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Do not use erythromycin concomitantly with HMG CoA reductase inhibitors (statins) that are extensively metabolized by CYP 3A4 (lovastatin or simvastatin), due to the increased risk of myopathy, including rhabdomyolysis (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

QT prolongation.

Erythromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving erythromycin. Fatalities have been reported. Erythromycin should be avoided in patients with known prolongation of the QT interval, patients with ongoing proarrhythmic conditions such as uncorrected hypokalaemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug associated effects on the QT interval.

Antibiotic associated pseudomembranous colitis.

Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including erythromycin. A toxin produced with Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases, appropriate therapy with a suitable oral antibacterial agent effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated. Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine (e.g. Lomotil), may prolong and/or worsen the condition and should not be used.

Prolonged or repeated use.

Prolonged or repeated use of erythromycin may result in overgrowth of nonsusceptible bacteria or fungi. If superinfection occurs, erythromycin should be discontinued and appropriate therapy instituted.

Surgical procedures.

When indicated, incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy.

Syphilis in pregnancy.

There have been reports suggesting that erythromycin does not reach the foetus in adequate concentration to prevent congenital syphilis. Infants born to women treated during pregnancy with oral erythromycin for early syphilis should be treated with an appropriate penicillin regimen.

Myasthenia gravis.

Erythromycin may aggravate the weakness of patients with myasthenia gravis.

Use in hepatic impairment.

There have been reports of hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, occurring in patients receiving oral erythromycin products. Since erythromycin is principally excreted by the liver, caution should be exercised when erythromycin is administered to patients with impaired hepatic function (see Section 5.2 Pharmacokinetic Properties, Excretion).

Use in the elderly.

See Section 4.4 Special Warnings and Precautions for Use, QT prolongation.

Paediatric use.

There have been reports of infantile hypertrophic pyloric stenosis (IHPS) occurring in infants following erythromycin therapy. In one cohort of 157 newborns who were given erythromycin for pertussis prophylaxis, seven neonates (5%) developed symptoms of nonbilious vomiting or irritability with feeding and were subsequently diagnosed as having IHPS requiring surgical pyloromyotomy. A possible dose response effect was described with an absolute risk of IHPS of 5.1% for infants who took erythromycin for 8 to 14 days and 10% for infants who took erythromycin for 15 to 21 days. Since erythromycin may be used in the treatment of conditions in infants which are associated with significant mortality or morbidity (e.g. pertussis or neonatal Chlamydia trachomatis infections), the benefit of erythromycin therapy needs to be weighed against the potential risk of developing IHPS. Parents should be informed to contact their physician if vomiting or irritability with feeding occurs.

Effects on laboratory tests.

Erythromycin interferes with the fluorometric determination of urinary catecholamines. Erythromycin may falsely elevate levels of 17-hydroxycorticosteroids, 17-ketosteroids, serum alanine and aspartate aminotransferase levels. Unidentified metabolites of erythromycin may interfere with colorimetric determinations resulting in falsely elevated AST levels. There may be a decrease in serum folate assay results due to inhibition of Lactobacillus casei growth but results appear to be unaffected if Landon's chromatographic procedure is used. Erythromycin in the blood may also interfere with the diagnosis of Mycoplasma pneumoniae by masking a rise in the titre of the tetrazolium reduction inhibition neutralising antibody to this organism. Erythromycin may interfere with tests for serum aspartate aminotransferase (AST), which may make diagnosis of hepatotoxicity more difficult.

4.5 Interactions with Other Medicines and Other Forms of Interactions

CYP3A.

Erythromycin is a substrate and inhibitor of the 3A isoform subfamily of the cytochrome P450 enzyme system (CYP3A). Coadministration of erythromycin and a drug primarily metabolised by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both the therapeutic and adverse effects of the concomitant drug. Dosage adjustments may be considered and, when possible, serum concentrations of drugs primarily metabolised by CYP3A should be monitored closely in patients concurrently receiving erythromycin.
Clinically significant CYP3A based drug interactions reported with erythromycin include ergotamine/ dihydroergotamine, triazolobenzodiazepines (such as triazolam and alprazolam) and related benzodiazepines, HMG-CoA reductase inhibitors (such as lovastatin, simvastatin and atorvastatin), calcium channel blockers metabolised by CYP3A4 (such as verapamil, amlodipine, diltiazem) and sildenafil (Viagra).
There have been spontaneous or published reports of CYP3A based interactions of erythromycin with cyclosporin, carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine, methylprednisolone, vinblastine and bromocriptine.
In one published study patients who used both oral erythromycin and strong CYP3A inhibitors (azole antifungal drugs (ketoconazole, itraconazole and fluconazole, all administered systemically), diltiazem, verapamil, troleandomycin, mibefradil, nefazodone) had a risk of sudden death from cardiac causes that was five times as great as that among patients who had not used these drugs. Many of the drugs that are known to block CYP3A4 also have direct effects on repolarisation which may cause a dramatic lengthening of the QT interval. Given that there are alternatives to erythromycin and these listed CYP3A inhibitors, the use of these combinations should be avoided.

QT prolongation.

Patients with uncorrected electrolyte disorders, particularly hypokalaemia, known prolongation of the QTc interval, or those concurrently receiving drugs that prolong the QTc interval, in particular class 1A (e.g. quinidine, procainamide) or class III (amiodarone, sotalol) antiarrhythmics, are at increased risk for ventricular arrhythmias. As these predisposing conditions may increase the risk for ventricular arrhythmias, erythromycin should not be used in patients with ongoing proarrhythmic conditions.

Carbamazepine.

Isolated cases of interaction between carbamazepine and erythromycin have been reported with elevated serum carbamazepine levels resulting in toxicity. Patients receiving carbamazepine and erythromycin should be monitored and erythromycin therapy stopped or carbamazepine dosage reduced if carbamazepine toxicity occurs.

Cimetidine.

Cimetidine may increase the risk of erythromycin toxicity, particularly hepatotoxicity and ototoxicity.

Cisapride.

Concurrent administration of erythromycin and cisapride is contraindicated (see Section 4.3 Contraindications).

Colchicine.

There have been postmarketing reports of colchicine toxicity with concomitant use of erythromycin and colchicine. This interaction is potentially life threatening and may occur while using both drugs at their recommended doses. If coadministration of colchicine and erythromycin is necessary, the starting dose of colchicine may need to be reduced, and the maximum colchicine dose should be lowered. Patients should be monitored for clinical symptoms of colchicine toxicity.

Cyclosporin.

Study reports and isolated cases indicate that erythromycin causes an increase in the plasma concentration of cyclosporin. It is recommended that erythromycin should be avoided whenever possible when patients are receiving cyclosporin. When the use of erythromycin with cyclosporin is unavoidable careful monitoring of plasma cyclosporin concentrations and appropriate modification of cyclosporin dose are essential.

Digoxin.

There have been reports of increased digoxin levels during concomitant use of erythromycin.

Ergotamine/ dihydroergotamine.

Concurrent use of erythromycin and ergotamine or dihydroergotamine has been associated in some patients with acute ergot toxicity. This is manifested as ischaemic reactions, characterised by vasospasm and ischaemia of the extremities and other tissues including the central nervous system. Concomitant administration of erythromycin with ergotamine or dihydroergotamine is contraindicated (see Section 4.3 Contraindications).

HMG-CoA reductase inhibitors.

Erythromycin has been reported to increase concentrations of HMG-CoA reductase inhibitors (such as lovastatin, simvastatin, atorvastatin). Rare reports of rhabdomyolysis have been reported in patients taking these drugs concomitantly (see Section 4.3 Contraindications).

Lincomycin/ clindamycin.

Antagonism of bactericidal activity has been observed between erythromycin and clindamycin or lincomycin in vitro. Because of possible clinical significance, these drugs should not be administered concurrently.

Oral anticoagulants.

There have been reports of increased anticoagulant effects when erythromycin and oral anticoagulants were used concomitantly. Isolated cases suggest that erythromycin can potentiate warfarin induced hypoprothrombinaemia, possibly by slowing warfarin clearance. If such an interaction occurs, alternative antibiotic therapy should be initiated or the response monitored and the dosage of warfarin adjusted accordingly.

Non-sedating antihistamines.

Erythromycin has been reported to significantly alter the metabolism of the non-sedating antihistamines terfenadine and astemizole when taken concomitantly. Rare cases of serious cardiovascular adverse events, including electrocardiographic QT/QTc interval prolongation, cardiac arrest, torsades de pointes, and other ventricular arrhythmias, have been observed (see Section 4.3 Contraindications). In addition, deaths have been reported rarely with concomitant administration of terfenadine and erythromycin.

Oral contraceptives.

Concurrent use of erythromycin may render oral contraceptives less effective and breakthrough bleeding may occur. Unplanned pregnancy may occur with this combination. A barrier method of contraception should be used while taking Eryc Capsules and for seven days following completion of the course of Eryc Capsules.

Penicillin.

Erythromycin, in low bacteriostatic concentrations, may inhibit the actions of bactericidal drugs, e.g. penicillin.

Phenytoin/ hexobarbitone/ valproate.

There have been reports of rises in plasma levels of drugs not thought to be metabolised by CYP3A including phenytoin, hexobarbitone and valproate during concomitant administration of erythromycin.

Pimozide.

Concurrent administration of erythromycin and pimozide is contraindicated (see Section 4.3 Contraindications).

Quinidine.

There has been an isolated report of a drug interaction occurring with the concomitant administration of oral erythromycin and oral quinidine, resulting in QT prolongation, torsades de pointes and cardiac arrest. Caution and close monitoring is recommended when the drugs are administered concomitantly.

Sildenafil (Viagra).

Erythromycin has been reported to increase the systemic exposure (AUC) of sildenafil. Reduction of sildenafil dosage should be considered.

Theophylline.

Erythromycin use in patients who are receiving high doses of theophylline has been reported in isolated cases as being associated with an increase in serum theophylline levels and potential theophylline toxicity. In the case of theophylline toxicity and/or elevated serum theophylline levels, the dose of theophylline should be reduced while the patient is receiving concomitant erythromycin therapy.

Triazolam/ midazolam/ alprazolam.

Erythromycin has been reported to decrease the clearance of triazolam and midazolam and, thus, may increase the pharmacological effect of triazolam and midazolam. Triazolam plasma concentrations may approximately double when erythromycin is coadministered, due to a reduction in clearance and increase in elimination half-life, but drug accumulation has not been observed with repeated dosing. Therefore, consideration of dose reduction may be appropriate in patients treated concurrently with triazolam and erythromycin. Potentially, this interaction may occur with other benzodiazepines which are metabolised by similar pathways in the liver.

Vinblastine.

A possible interaction between erythromycin and vinblastine has been reported in which patients receiving the two agents concurrently may experience myalgia, neutropenia and fever. Concurrent administration of erythromycin and vinblastine is, therefore, not recommended.

Zopiclone.

Erythromycin has been reported to decrease the clearance of zopiclone and, thus, may increase the pharmacodynamic effects of this drug.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category A)
Erythromycin has been taken by a large number of pregnant women and women of childbearing age without an increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed. Erythromycin should be used during pregnancy only if clearly needed.
Australian categorisation definition of Category A: Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed.

Labour and delivery.

The effect of erythromycin on labour and delivery is unknown.
See Section 4.4 Special Warnings and Precautions for Use, Syphilis in pregnancy.
Erythromycin is excreted in breast milk in low concentrations.

4.8 Adverse Effects (Undesirable Effects)

The most frequent side effects of oral erythromycin preparations are gastrointestinal and are dose related. They include nausea, vomiting, abdominal pain, diarrhoea and anorexia.
There have been rare reports of pancreatitis and convulsions.
There have been reports of hepatic dysfunction, with or without jaundice, occurring in patients receiving erythromycin products. Symptoms of hepatitis, hepatic dysfunction and/or abnormal liver function test results may occur.
There have been reports of interstitial nephritis coincident with erythromycin use.
Mild allergic reactions, e.g. rashes with or without pruritus, urticaria, bullous fixed eruptions and eczema, have been reported with erythromycin. Serious allergic reactions, including anaphylaxis, have been reported.
There have been isolated reports of reversible hearing loss occurring chiefly in patients with renal insufficiency and in patients receiving high doses of erythromycin.
Erythromycin has been associated with QT prolongation and ventricular arrhythmias, including ventricular tachycardia and torsades de pointes (see Section 4.4 Special Warnings and Precautions for Use). Occasional case reports of cardiac arrhythmias, e.g. ventricular tachycardia, have been documented in patients receiving erythromycin. There have been isolated reports of other cardiovascular symptoms, e.g. chest pain, dizziness and palpitations; however, a causal relationship has not been established.
Central nervous system side effects, including hallucinations, confusion and vertigo, have been reported in occasional patients, however, a cause and effect relationship has not been established.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Dosage.

Adults.

250 mg capsules.

The usual dose is 1 g/day administered as 250 mg every six hours or 500 mg every 12 hours.
Some clinicians believe that twice daily dosing is inadequate for all but minor infections caused by highly susceptible organisms. Twice daily dosing should not be employed when more than 1 g/day is required.

Method.

Optimum blood levels of erythromycin are achieved when Eryc Capsules are administered in the fasting state, one hour before food.

Dosage adjustment.

Geriatric.

See Section 4.4 Special Warnings and Precautions for Use, QT prolongation.

Children.

Age, weight and severity of infection are important factors in determining dosage for children. The usual dosage is 30 to 50 mg/kg/day in two to four divided doses.

Streptococcal infections.

In penicillin allergic patients a therapeutic dosage of oral erythromycin should be administered for at least ten days. For continuous prophylaxis against recurrences of streptococcal infections in persons with a history of rheumatic heart disease, the dose is 250 mg twice a day.

For prophylaxis against bacterial endocarditis in patients allergic to penicillin or patients receiving long-term penicillin who have congenital and/or rheumatic or other acquired valvular heart disease undergoing dental procedures or surgical procedures of the upper respiratory tract.

The adult dose is 1 g (20 mg/kg for children) 1.5 to 2 hours prior to the procedure and then 500 mg (10 mg/kg for children) every six hours for eight doses.

Chlamydial infections.

The usual dose is 500 mg every eight hours for at least ten days.

Primary syphilis.

30 to 40 g given in divided doses over a period of 10 to 15 days.

Legionnaires' disease.

Optimal doses have not been established but doses of erythromycin utilised and reported in clinical studies were those recommended above (1 to 4 g daily in divided doses).

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person’s ability to drive and use machines were not assessed as part of its registration.

4.9 Overdose

Reports indicate that the ingestion of large amounts of erythromycin can be expected to produce gastrointestinal distress, hearing problems and other adverse effects (see Section 4.8 Adverse Effects (Undesirable Effects)). Allergic reactions accompanying overdosage should be treated by the prompt elimination of unabsorbed drug and supportive measures. Erythromycin serum levels are not appreciably altered by haemodialysis or peritoneal dialysis.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Eryc capsules also contain the following inactive ingredients: lactose, potassium phosphate monobasic, povidone, water-purified, cellacefate, diethyl phthalate, gelatine, shellac, erythrosine, indigo carmine (132), sunset yellow (110), carbon black (153).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Eryc capsules are available in bottles of 25 capsules.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes