Retorin Suspension

Erythromycin ethylsuccinate.

Almost pink to pink colour dry powder, forming pink colour suspension on reconstitution with water.
Composition: 125 mg/5 mL: Each 5 ml of the Reconstituted suspension contains: Erythromycin Ethyl Succinate equivalent to Erythromycin 125 mg and preservative Sodium Benzoate 2.08 mg.
200 mg/5 mL: Each 5 ml suspension contains Erythromycin Ethyl Succinate equivalent to 200 mg Erythromycin.
Excipients/Inactive Ingredients: Contains Ponceau 4R as colouring agent, and Vanilla as flavouring agent.

Pharmacotherapeutic group: Macrolides, Lincosamides and Streptogramins, Macrolides.
Pharmacology: Pharmacodynamics: Mechanism of Action: Erythromycin exerts its antimicrobial action by binding to the 50S ribosomal sub-unit of susceptible microorganisms and suppresses protein synthesis.
Erythromycin is usually active against most strains of the following organisms both in vitro and in clinical infections.
Gram positive bacteria - Listeria monocytogenes, Corynebacterium diphtheriae (as an adjunct to antitoxin), Staphylococci spp, Streptococci spp (including Enterococci).
Gram negative bacteria - Haemophilus influenzae, Neisseria meningitidis, Neisseria gonorrhoeae, Legionella pneumophila, Moraxella (Branhamella) catarrhalis, Bordetella pertussis, Campylobacter spp.
Mycoplasma - Mycoplasma pneumoniae, Ureaplasma urealyticum.
Other organisms - Treponema pallidum, Chlamydia spp, Clostridia spp, L-forms, the agents causing trachoma and lymphogranuloma venereum.
Note: The majority of strains of Haemophilus influenzae are susceptible to the concentrations reached after ordinary doses.
Pharmacokinetics: Absorption is facilitated if the stomach is empty.
Peak blood levels normally occur within 1 hour of dosing of erythromycin ethyl succinate granules. The elimination half-life is approximately 2 hours. Doses may be administered 2, 3 or 4 times a day.
Erythromycin ethyl succinate is less susceptible than erythromycin to the adverse effect of gastric acid. It is absorbed from the small intestine. It is widely distributed throughout body tissues. Little metabolism occurs and only about 5% is excreted in the urine. It is excreted principally by the liver.
The drug is not removed by either peritoneal dialysis or haemodialysis. It diffuses readily into intracellular fluids and antibacterial activity can be achieved at essentially all sites.
There is some retention in liver and spleen. Only low concentrations are achieved in cerebrospinal fluid, unless the meninges are inflamed. Diffusion into the aqueous humour, but not the vitreous humour of the eye is good. A significant proportion is bound to serum proteins.

Consideration should be given to the official guidance on the appropriate use of antibacterial agents. Antibiotic for treatment of infections caused by erythromycin sensitive organisms especially gram positive pyogenic cocci and some gram-negative bacteria. It may be used in a wide variety of clinical infections.
Erythromycin is an appropriate alternative to penicillin in hypersensitive patients especially in pre or post-operative patients.
Respiratory Tract Infections: Acute and chronic bronchitis, legionnaires disease, tracheitis, bronchiectasis, pneumonia.
Skin and Soft Tissue Infections: Acute infections of skin and soft tissue which are mild to moderately severe.
Eye/Ear infections: Otitis media and otitis externa mastoiditis, chlamydial conjunctivitis, blepharitis.
Oral infections: Gingivitis, Vincent's angina.
Gastrointestinal Infections: Staphylococcal enterocolitis, cholecystitis, campylobacter infections.
Other infections: Gonorrhoea, syphilis, urethritis, diphtheria, pertussis.

Method of Administration: Oral.
125 mg/5mL: Posology: Adults and Children over 8 Years: For mild to moderate infections 2 g daily in divided doses up to 4 g daily in severe infections; 250-500 mg every 6 hours or 0.5-1 g every 12 hours.
For acne vulgaris the usual dose is 250 mg three times daily before meals for one to four weeks and then reduced to twice daily until improvement occurs.
Children Aged 2 to 8 Years: For mild to moderate infections 1 g daily in divided doses; 250 mg every 6 hours; 30 mg/kg/day in divided doses. For severe infections up to 50 mg/kg/day in divided doses.
Infants and Babies up to 2 Years: For mild to moderate infections 500 mg daily in divided doses; 125 mg every 6 hours; 30 mg/kg/day in divided doses.
For severe infections up to 50 mg/kg/day in divided doses.
Elderly: No special dosage recommendations.
Renal Impairment: If impairment is severe (GFR <10 ml/min), the daily dose should not exceed 1.5 g due to risk of ototoxicity.
For severe infections dosage may be doubled. Duration of dosage regimen is dependent on the nature of the infection and is at the discretion of the physician.
200 mg/5 mL: Usual adult dose: Antibacterial; the equivalent of erythromycin 400 mg every six hours.
Note: Gonorrhoea (disseminated): the equivalent of erythromycin: 800 mg every six hours for seven days.
Legionnaires disease: The equivalent of erythromycin 800 mg to 1.6 grams every six hours.
Streptococcal prophylaxis continuous prophylaxis of streptococcal infections in patients with a history of rheumatic heart disease and/or chorea: Oral, the equivalent of erythromycin 400 mg every twelve hours.
Syphilis: the equivalent of erythromycin 800 mg every six hours for fifteen days (early syphilis) or thirty days (late syphilis).
Usual adult prescribing limits: Antibacterial, the equivalent of erythromycin: Up to 4 grams daily.
Note: Doses up to the equivalent of 8 grams of erythromycin daily are apparently well tolerated.
Usual paediatric dose: Antibacterial, the equivalent of erythromycin: 7.5 to 12.5 mg per kg of body weight every six hours; or 15 to 25 mg per kg of body weight every twelve hours.

Symptoms: hearing loss, severe nausea, vomiting and diarrhoea.
Treatment: Gastric lavage and general supportive measures.
Erythromycin is not dialyzable.

Hypersensitivity to the active substance or to any of the excipients.
Erythromycin is contraindicated in patients taking simvastatin, tolterodine, mizolastine, amisulpride, astemizole, terfenadine, domperidone, cisapride or pimozide.
Erythromycin is contraindicated with ergotamine and dihydroergotamine.
Erythromycin should not be given to patients with a history of QT prolongation (congenital or documented acquired QT prolongation) or ventricular cardiac arrhythmia, including torsades de pointes.
Erythromycin should not be given to patients with electrolyte disturbances (hypokalaemia, hypomagnesaemia due to the risk of prolongation of QT interval).

As with other macrolides, rare serious allergic reactions, including acute generalised exanthematous pustulosis (AGEP) have been reported. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.
Erythromycin is excreted principally by the liver, so caution should be exercised in administering the antibiotic to patients with impaired hepatic function or concomitantly receiving potentially hepatotoxic agents. Hepatic dysfunction including increased liver enzymes and/or cholestatic hepatitis, with or without jaundice, has been infrequently reported with erythromycin.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including macrolides, and may range in severity from mild to life-threatening Clostridium difficile-associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents including erythromycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, which may lead to overgrowth of C. difficile. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
Cardiovascular Events: Prolongation of the QT interval, reflecting effects on cardiac repolarisation imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in patients treated with macrolides including erythromycin. Fatalities have been reported.
Erythromycin should be used with caution in the following: Patients with coronary artery disease, severe cardiac insufficiency, conduction disturbances or clinically relevant bradycardia; Patients concomitantly taking other medicinal products associated with QT prolongation; Elderly patients may be more susceptible to drug-associated effects on the QT interval.
Epidemiological studies investigating the risk of adverse cardiovascular outcomes with macrolides have shown variable results. Some observational studies have identified a rare short term risk of arrhythmia, myocardial infarction and cardiovascular mortality associated with macrolides including erythromycin. Consideration of these findings should be balanced with treatment benefits when prescribing erythromycin.
There have been reports suggesting erythromycin does not reach the foetus in adequate concentrations 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.
There have been reports that erythromycin may aggravate the weakness of patients with myasthenia gravis.
Erythromycin interferes with the fluorometric determination of urinary catecholamines.
Rhabdomyolysis with or without renal impairment has been reported in seriously ill patients receiving erythromycin concomitantly with statins.
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 non-bilious vomiting or irritability with feeding and were subsequently diagnosed as having IHPS requiring surgical pyloromyotomy. Since erythromycin may be used in the treatment of conditions in infants which are associated with significant mortality or morbidity (such as pertussis or chlamydia), the benefit of erythromycin therapy needs to be weighed against the potential risk of developing IHPS.
Parents and caregivers should be informed to contact their physician if vomiting and/or irritability with feeding occurs.
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
This medicine contains 7.4 mg/5 ml sodium. To be taken into consideration by patients on a controlled sodium diet.
In the event of severe acute hypersensitivity reactions, such as anaphylaxis, severe cutaneous adverse reactions (SCARs) [e.g. Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) & acute generalised exanthematous pustulosis (AGEP)], Retorin Powder for Suspension should be discontinued immediately and appropriate treatment should be urgently initiated.
Sodium benzoate may increase jaundice (yellowing of the skin and eyes) in newborn babies (up to 4 weeks old). Sodium benzoate may cause local irritation. Sodium benzoate may increase jaundice (yellowing of the skin and eyes) in newborn babies (up to 4 weeks old).

Pregnancy: There are no adequate and well-controlled studies in pregnant women. However, observational studies in humans have reported cardiovascular malformation after exposure to medicinal products containing erythromycin during early pregnancy.
Erythromycin has been reported to cross the placental barrier in humans, but foetal plasma levels are generally low.
There have been reports that maternal macrolide antibiotics exposure within 7 weeks of delivery may be associated with a higher risk of infantile hypertrophic pyloric stenosis (IHPS).
Therefore, erythromycin should only be used during pregnancy if clinically needed and the benefit of treatment is expected to outweigh any small increased risks which may exist. The risk-benefit balance should be considered for each individual patient before prescribing erythromycin during pregnancy.
Breast-feeding: Erythromycins can be excreted into breast-milk. Caution should be exercised when administering erythromycin to lactating mothers due to reports of infantile hypertrophic pyloris stenosis in breast-fed infants.

Blood and lymphatic system disorders: Eosinophilia.
Immune system disorders: Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis have occurred.
Psychiatric disorders: Hallucinations.
Nervous system disorders: There have been isolated reports of transient central nervous system side effects including confusion, seizures and vertigo; however, a cause and effect relationship has not been established.
Eye disorders: Mitochondrial Optic Neuropathy.
Ear and labyrinth disorders: Deafness, tinnitus.
There have been isolated reports of reversible hearing loss occurring chiefly in patients with renal insufficiency or taking high doses.
Cardiac disorders: QTc interval prolongation, torsades de pointes, palpitations, and cardiac rhythm disorders including ventricular tachyarrhythmias.
Cardiac arrest, ventricular fibrillation (frequency not known).
Vascular disorders: Hypotension.
Gastrointestinal disorders: The most frequent side effects of oral erythromycin preparations are gastrointestinal and are dose-related. The following have been reported: upper abdominal discomfort, nausea, vomiting, diarrhoea, pancreatitis, anorexia, infantile hypertrophic pyloric stenosis.
Pseudomembranous colitis has been rarely reported in association with erythromycin therapy.
Hepatobiliary disorders: Cholestatic hepatitis, jaundice, hepatic dysfunction, hepatomegaly, hepatic failure, hepatocellular hepatitis.
Skin and subcutaneous tissue disorders: Skin eruptions, pruritus, urticaria, exanthema, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.
Not known: acute generalised exanthematous pustulosis (AGEP).
Frequency not known: severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) & acute generalised exanthematous pustulosis (AGEP).
Renal and urinary disorders: Interstitial nephritis.
General disorders and administration site conditions: Chest pain, fever, malaise.
Investigations: Increased liver enzyme values.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Postmarketing Experience: Gastrointestinal Disorders: infantile hypertrophic pyloric stenosis.

Increases in serum concentrations of the following drugs metabolised by the cytochrome P450 system may occur when administered concurrently with erythromycin: acenocoumarol, alfentanil, astemizole, bromocriptine, carbamazepine, cilostazol, cyclosporin, digoxin, dihydroergotamine, disopyramide, ergotamine, hexobarbitone, methylprednisolone, midazolam, omeprazole, phenytoin, quinidine, rifabutin, sildenafil, tacrolimus, terfenadine, theophylline, triazolam, valproate, vinblastine, and antifungals e.g. fluconazole, ketoconazole and itraconazole. Appropriate monitoring should be undertaken and dosage should be adjusted as necessary. Particular care should be taken with medications known to prolong the QTc interval of the electrocardiogram.
Drugs that induce CYP3A4 (such as rifampicin, phenytoin, carbamazepine, phenobarbital, St John's Wort) may induce the metabolism of erythromycin. This may lead to sub-therapeutic levels of erythromycin and a decreased effect. The induction decreases gradually during two weeks after discontinued treatment with CYP3A4 inducers. Erythromycin should not be used during and two weeks after treatment with CYP3A4 inducers.
HMG-CoA Reductase Inhibitors: erythromycin has been reported to increase concentrations of HMG-CoA reductase inhibitors (e.g. lovastatin and simvastatin). Rare reports of rhabdomyolysis have been reported in patients taking these drugs concomitantly.
Contraceptives: some antibiotics may in rare cases decrease the effect of contraceptive pills by interfering with the bacterial hydrolysis of steroid conjugates in the intestine and thereby reabsorption of unconjugated steroid. As a result of this plasma levels of active steroid may decrease.
Antihistamine H1 antagonists: care should be taken in the coadministration of erythromycin with H1 antagonists such as terfenadine, astemizole and mizolastine due to the alteration of their metabolism by erythromycin. Erythromycin significantly alters the metabolism of terfenadine, astemizole and pimozide when taken concomitantly. Rare cases of serious, potentially fatal, cardiovascular events including cardiac arrest, torsade de pointes and other ventricular arrhythmias have been observed.
Anti-bacterial agents: an in vitro antagonism exists between erythromycin and the bactericidal beta-lactam antibiotics (e.g. penicillin, cephalosporin). Erythromycin antagonises the action of clindamycin, lincomycin and chloramphenicol. The same applies for streptomycin, tetracyclines and colistin.
Protease inhibitors: in concomitant administration of erythromycin and protease inhibitors, an inhibition of the decomposition of erythromycin has been observed.
Oral anticoagulants: there have been reports of increased anticoagulant effects when erythromycin and oral anticoagulants (e.g. warfarin, rivaroxaban) are used concomitantly.
Triazolobenzodiazepines (such as triazolam and alprazolam) and related benzodiazepines: erythromycin has been reported to decrease the clearance of triazolam, midazolam, and related benzodiazepines, and thus may increase the pharmacological effect of these benzodiazepines.
Post-marketing reports indicate that co-administration of erythromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterised by vasospasm and ischaemia of the central nervous system, extremities and other tissues.
Elevated cisapride levels have been reported in patients receiving erythromycin and cisapride concomitantly. This may result in QTc prolongation and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and torsades de pointes. Similar effects have been observed with concomitant administration of pimozide and clarithromycin, another macrolide antibiotic.
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. There have been published reports suggesting when oral erythromycin is given concurrently with theophylline there is a significant decrease in erythromycin serum concentrations. This decrease could result in sub-therapeutic concentrations of erythromycin.
There have been post-marketing reports of colchicine toxicity with concomitant use of erythromycin and colchicine.
Hypotension, bradyarrhythmias and lactic acidosis have been observed in patients receiving concurrent verapamil, a calcium channel blocker.
Cimetidine may inhibit the metabolism of erythromycin which may lead to an increased plasma concentration.
Erythromycin has been reported to decrease the clearance of zopiclone and thus may increase the pharmacodynamic effects of this drug.

User instructions: Continue the treatment as prescribed by the physician.

Before Reconstitution: Store in a cool place, below 30°C in a well closed container protected from heat and light.
After Reconstitution: The suspension should be stored at 2-8°C. Once reconstituted, reconstituted suspension should be used within 7 days. Discard the reconstituted suspension if more than 7 days.
Complete the treatment as prescribed by the physician. Not to be used in patient with known hypersensitivity to this drug.
Shake the bottle to loosen powder.
Reconstitute the powder with water to 100 ml graduation mark. White color HDPE 120 ml round bottle, contains 20 graduation marks up to 100 ml, each marking represents 5 ml; with cap (PP) and insert/stopper (LDPE).
Shake well to mix uniformly.
Shake well before taking each dose.
Shelf Life: 2 years.

Macrolides

J01FA01 - erythromycin ; Belongs to the class of macrolides. Used in the systemic treatment of infections.

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