ERYC®

Erythromycin

Presentation

Eryc 250 mg capsules contain erythromycin base presented as orange and white enteric coated pellets in size 0 capsules with an opaque orange cap and a natural transparent body. The capsule has two black imprints; ERYC and P-D 696 parallel to the long axis of the capsule.

Dimensions of capsule: Outside diameter of body approximately 7.4 mm.

Outside diameter of cap approximately 7.7 mm.

Fully closed length of full capsule approximately 21.4 mm.

Uses

Actions

Erythromycin belongs to the macrolide group of antibiotics and acts by inhibition of protein synthesis by binding 50 S ribosomal subunits of susceptible organisms. It does not affect nucleic acid synthesis. Antagonism has been demonstrated in vitro between erythromycin, clindamycin, lincomycin and chloramphenicol.

Erythromycin is usually active against the following organisms in vitro and in clinical infections:

• Streptococcus pyogenes
• α haemolytic streptococci (viridans group)
• Staphylococcus aureus (resistant organisms may emerge during treatment)
• Streptococcus pneumoniae
• Mycoplasma pneumoniae (Eaton's agent)
• Haemophilus influenzae (many strains are resistant to erythromycin alone, but are susceptible to erythromycin and sulphonamides together)
• Treponema pallidum
• Corynebacterium diphtheriae
• Corynebacterium minutissiumum
• Entamoeba histolytica (in intestinal amoebiasis only)
• Listeria monocytogenes
• Neisseria gonorrhoeae
• Bordetella pertussis
• Legionella pneumophila (agent of Legionnaires' Disease)
• Chlamydia trachomatis
• Campylobacter jejuni

Resistance to erythromycin by some strains of Haemophilus influenzae and staphylococci has been demonstrated. Specimens should be obtained for culture and susceptibility testing.

Pharmacokinetics

Orally administered erythromycin base and its salts are 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. After administration of a single dose of a 250 mg ERYC capsule, peak serum levels in the range of 1.13 to 1.68 microgram/mL are attained in approximately 3 hours and with a t_½ of 2 hours, declining to 0.30 to 0.42 microgram/mL in 6 hours.

Erythromycin is largely bound to plasma proteins, and the freely dissociating bound fraction after administration of erythromycin base represents 90% of the total erythromycin absorbed. After absorption, erythromycin diffuses readily into most body fluids. In the absence of meningeal inflammation, low concentrations are normally achieved in the spinal fluid but the passage of the medicine across the blood-brain barrier increases in meningitis. Erythromycin is excreted in breast milk. The medicine crosses the placental barrier but foetal plasma levels are low. Erythromycin is not removed by peritoneal dialysis or haemodialysis.

In the presence of normal hepatic function, erythromycin is concentrated in the liver and excreted in its active form in the bile. After oral administration less than 5% of the administered dose can be recovered in the active form in the urine. The effect of hepatic dysfunction on biliary excretion of erythromycin is not known, therefore caution should be exercised when administered to patients with impaired hepatic function.

The enteric coating of the pellets in ERYC capsules protects the erythromycin base from inactivation by gastric acidity. Because of their small size and enteric coating, the pellets readily pass intact from the stomach to the small intestine where they dissolve efficiently and reliably to allow absorption of erythromycin in a uniform manner. The most reliable serum levels of solid dose erythromycin are achieved when ERYC capsules are taken one hour before meals or in the fasting state.

Indications

ERYC is indicated in children and adults for the treatment of the following conditions:

• Upper respiratory tract infections: tonsillitis, pharyngitis, laryngitis, sinusitis, acute otitis media.
• Lower respiratory tract infections: acute and chronic bronchitis and bronchiectasis, pneumonia (including primary atypical, Legionnaires' disease).
• Skin and soft tissue infections: boils, carbuncles, impetigo, abscesses, acne.
• Other infections: gonorrhoea and syphilis (in cases of penicillin allergy), diphtheria (prophylaxis), prophylaxis of rheumatic fever and bacterial endocarditis (where penicillin allergy exists), amoebic dysentery (intestinal infection only).

Reports also indicate that erythromycin may be useful in the treatment of Campylobacter enteritis (severe or protracted cases only) and Chlamydial infections.

Dosage and Administration

Adults

The usual dose is 250 mg every six hours, taken one hour before meals. If twice-a-day dosage is desired, the recommended dose is 500 mg every 12 hours. Dosage may be increased up to 4 g per day, according to the severity of infection. Twice-a-day dosing is not recommended when doses larger than 1 g daily are administered.

Children

Age, weight and severity of infection are important factors in determining the proper dosage. The usual dosage is 30 to 50 mg/kg/day in divided doses. For the treatment of more severe infections, this dose may be doubled. Subdividing the contents of a capsule is not recommended.

Streptococcal infections

A therapeutic dosage of oral erythromycin should be administered for at least 10 days. For long term prophylaxis against recurrences of streptococcal infections in persons with a history of rheumatic heart disease who are allergic to penicillin the dose is 250 mg twice-a-day. For prevention of bacterial endocarditis in penicillin-allergic patients with valvular heart disease who are to undergo dental procedures or surgical procedures of the upper respiratory tract, the adult dose is 1.0 g orally (20 mg/kg for children) 1˝ to 2 hours prior to the procedure and then 500 mg (10 mg/kg for children) orally 6 hours later (see Uses).

Primary Syphilis

3 to 4g given in divided doses over a period of 10 to 15 days.

Intestinal Amoebiasis

250 mg 4 times daily for 10 to 14 days for adults; 30 to 50 mg/kg/day in divided doses for 10 to 14 days for children.

Legionnaires' Disease

Although optimal doses have not been established, doses utilised in reported clinical data were those recommended above (1 to 4 g daily in divided doses).

Pertussis

Although optimum dosage and duration of therapy have not been established, doses of erythromycin utilised in reported clinical studies were 4 to 50 mg/kg/day, given in divided doses for 5 to 14 days.

Contraindications

ERYC is contraindicated in patients taking terfenadine, astemizole or cisapride and in patients with known hypersensitivity to erythromycin, or any of the product's components.

Warnings and Precautions

There have been a few reports of hepatic dysfunction, with or without jaundice, occurring in patients receiving erythromycin ethylsuccinate, base and stearate products. Caution should be exercised when erythromycin is administered to patients with impaired hepatic function. If findings suggestive of significant hepatic dysfunction occur, therapy should be discontinued.

Pseudomonas colitis has been occasionally reported to occur in association with erythromycin therapy. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during treatment with erythromycin. Mild cases of colitis may respond to drug discontinuation alone. Moderate to severe cases should be managed with fluid, electrolyte and protein supplementation as indicated. If the colitis is not relieved by discontinuation of erythromycin administration or when it is severe, consideration should be given to the administration of vancomycin or other suitable therapy. Other possible causes of the colitis should also be considered.

If an allergic reaction to erythromycin occurs, administration of the drug should be discontinued. Serious hypersensitivity reactions may require epinephrine, antihistamines or corticosteroids.

Reports have suggested that ototoxicity may occur in patients with renal dysfunction following daily doses in excess of 2 g of oral erythromycin.

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

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

Laboratory tests

Erythromycin interferes with the fluorometric determination of urinary catecholamines.

Carcinogenicity, Mutagenicity and Impairment of Fertility

Long-term (20-month) oral studies conducted in rats with erythromycin base did not provide evidence of tumorigenicity. Mutagenicity studies have not been conducted. There was no apparent effect on male or female fertility in rats fed erythromycin (base) at levels up to 0.25% of diet.

Use in Pregnancy

Reproduction studies have been performed in rats, mice and rabbits, using erythromycin and its various salts and esters, at doses which were several times multiples of the human dose. No evidence of impaired fertility or harm to the foetus that appeared related to erythromycin was reported in these studies. There are, however, no adequate and well controlled studies with pregnant women. Nevertheless, a large number of pregnant women have taken erythromycin without any harmful effects on the foetus being observed.

This medicine should be used during pregnancy only if clearly needed. Erythromycin crosses the placental barrier.

Use during Labour and Delivery

The effect of ERYC on labour and delivery is unknown.

Use in Nursing Mothers

There are insufficient adequate and well-controlled studies in nursing women. Caution should also be exercised when administering erythromycin to nursing mothers as it has been found to be excreted in breast milk.

Paediatric Use

See Uses and Dosage and Administration

Adverse 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. Pseudomembranous colitis has been occasionally reported to occur in association with erythromycin therapy (see Warnings and Precautions).

Symptoms of hepatic dysfunction with or without jaundice and/or abnormal liver function test results may occur (see Warnings and Precautions).

Mild allergic reactions such as rashes, with or without pruritis, urticaria, bullous fixed eruptions and eczema have been reported with erythromycin. Serious allergic reactions, including anaphylaxis have been reported.

A few cases of transient deafness have been reported with high doses of erythromycin. There have also been isolated reports of transient central nervous system side effects including confusion, hallucinations, seizures and vertigo; however, a cause and effect relationship has not been established.

Interactions

The use of erythromycin in patients taking concurrent medicines which are metabolised by the cytochrome P450 system may be associated with elevations in serum levels of these other medicines. In addition to the interactions listed below, there have been reports of interactions of erythromycin with tacrolimus, hexobarbital and phenytoin. Serum concentrations of drugs metabolised by the cytochrome P450 system should be monitored closely in patients concurrently receiving erythromycin.

Alfentanil

The concomitant use of erythromycin with alfentanil can significantly inhibit the clearance of alfentanil and may increase the risk of prolonged or delayed respiratory depression.

Anticoagulants

Erythromycin has been reported to prolong prothrombin time in patients receiving anticoagulant therapy. If an alternative antibiotic is not appropriate, prothrombin activity should be monitored when initiating and discontinuing ERYC in oral anticoagulant patients.

Carbamazepine

Erythromycin administration in patients receiving carbamazepine has been reported to cause increased serum levels of carbamazepine with subsequent development of signs of carbamazepine toxicity.

Cisapride

Rare cases of serious cardiovascular adverse events, including death, cardiac arrest, torsades de pointes and other ventricular arrhythmias have been observed in some patients taking cisapride concomitantly with macrolide antibiotics, including erythromycin (see Contraindications).

Clindamycin / Lincomycin / Chloramphenicol

Antagonism has been demonstrated between clindamycin and erythromycin. Erythromycin should be used with caution if administered concomitantly with lincomycin, clindamycin or chloramphenicol. In vitro experiments have demonstrated that binding sites for erythromycin, lincomycin, clindamycin and chloramphenicol overlap and competitive inhibition may occur.

Cyclosporin

Erythromycin has been reported to increase the plasma levels of cyclosporin. If co-administration is necessary, plasma levels of cyclosporin should be monitored and the dosage adjusted accordingly.

Digoxin

Concomitant administration of erythromycin and digoxin has been reported to result in elevated serum levels of cardiac glycosides, leading to toxicity in some patients.

Ergotamine

There are reports that ischaemic reactions may occur when erythromycin is given concurrently with ergotamine-containing medicines.

Lovastatin

Patients receiving concomitant lovastatin and erythromycin should be carefully monitored; cases of rhabdomyolysis have been reported in seriously ill patients.

Terfenadine / Astemizole

Erythromycin significantly alters the metabolism of terfenadine and astemizole when taken concomitantly. Rare cases of serious cardiovascular adverse events, including death, cardiac arrest, torsades de pointes and other ventricular arrhythmias have been reported (see Contraindications).

Theophylline

Erythromycin use in patients who are receiving high doses of theophylline may be associated with an increase in serum theophylline levels and potential theophylline toxicity. In 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

Erythromycin has been reported to decrease the clearance of triazolam and midazolam and thus may increase the pharmacologic effect of these medicines.

Overdosage

With dosages of over 2 g per day, abdominal discomfort, nausea, vomiting or diarrhoea may occur. There has been a report of a case of erythromycin-induced pancreatitis following erythromycin overdosage. There is no specific treatment for accidental overdosage. Erythromycin should be discontinued and gastric lavage should be considered; otherwise treatment should be symptomatic. Erythromycin is not removed by peritoneal dialysis or haemodialysis.

Pharmaceutical Precautions

Store below 30°C. Protect from moisture and light.

Package Quantities

ERYC capsules are supplied in bottles of 100s

Further Information

Erythromycin capsules contain enteric-coated pellets of erythromycin base for oral administration. The capsule also contains lactose, povidone, FD&C Yellow number 6 and is gluten, paraben, sodium, sulfite and tartrazine free. 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 but it is the base which is microbiologically active. Erythromycin base is 3R*, 4S*, 5S*, 6R*, 7R*, 9R*, 11R*, 12R*, 13S*, 14R*-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-3-(dimethyl-amino)- β-D-xylo-hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione.