Erythromycin Stearate Tablets USP 500mg Taj Pharma

1.NAME OF THE MEDICINAL PRODUCT
a) Erythromycin Stearate Tablets USP 250mg Taj Pharma.
b) Erythromycin Stearate Tablets USP 500mg Taj Pharma.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION
a) Each tablet contains:
Erythromycin stearate USP
equivalent to erythromycin 250mg buffered with sodium citrate.

b) Each tablet contains:
Erythromycin stearate USP
equivalent to erythromycin 500mg buffered with sodium citrate.

3. PHARMACEUTICAL FORM
Film coated tablet

4. CLINICAL PARTICULARS

4.1 Therapeutic indications
For the prophylaxis and treatment of infections caused by erythromycin-sensitive organisms.
Erythromycin is highly effective in the treatment of a great variety of clinical infections such as:

Upper Respiratory Tract infections: tonsillitis, peritonsillar abscess, pharyngitis, laryngitis, sinusitis, secondary infections in influenza and common colds
Lower Respiratory Tract infections: tracheitis, acute and chronic bronchitis, pneumonia (lobar pneumonia, bronchopneumonia, primary atypical pneumonia), bronchiectasis, Legionnaire’s disease
Ear infection: otitis media and otitis externa, mastoiditis
Oral infections: gingivitis, Vincent’s angina
Eye infections: blepharitis
Skin and soft tissue infections: boils and carbuncles, paronychia, abscesses, pustular acne, impetigo, cellulitis, erysipelas
Gastrointestinal infections: cholecystitis, staphylococcal enterocolitis
Prophylaxis: pre- and post- operative trauma, burns, rheumatic fever
Other infections: osteomyelitis, urethritis, gonorrhoea, syphilis, lymphogranuloma venereum, diphtheria, prostatitis, scarlet fever

4.2 Posology and method of administration
For oral administrations.

Adults and children over 8 years: For mild to moderate infections 2g daily in divided doses. Up to 4g daily in severe infections.

Elderly: No special dosage recommendations.

Note: For younger children, infants and babies, Erythroped, erythromycin ethylsuccinate suspensions, are normally recommended. The recommended dose for children age 2-8 years, for mild to moderate infections, is 1 gram daily in divided doses. The recommended dose for infants and babies, for mild to moderate infections, is 500 mg daily in divided doses. For severe infections doses may be doubled.

4.3 Contraindications
Known hypersensitivity to erythromycin.

Erythromycin is contraindicated in patients taking simvastatin, tolterodine, mizolastine, amisulpride, astemizole, terfenadine, domperidone, cisapride or pimozide.

Erythromycin is contraindicated with ergotamine and dihydroergotamine.

4.4 Special Warnings and precautions for use
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 (see section.4.8). 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.

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.

Patients receiving erythromycin concurrently with drugs which can cause prolongation of the QT interval should be carefully monitored. The concomitant use of erythromycin with some of these drugs is contraindicated (See sections 4.3 & 4.5)

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 should be informed to contact their physician if vomiting or irritability with feeding occurs.

4.5 Interaction with other medicinal products and other forms of interaction
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, domperidone, 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 (see sections 4.3 and 4.8).

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) 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 (see section 4.3).

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.

4.6 Fertility, Pregnancy and lactation
There are no adequate and well-controlled studies in pregnant women. However, observational studies in humans have reported cardiovascular malformations 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).

Erythromycin can be excreted into breast-milk. Caution should be exercised when administering erythromycin to lactating mothers due reports of infantile hypertrophic pyloric stenosis in breast-fed infants.

4.7 Effects on ability to drive and use machines
None reported

4.8 Undesirable Effects
Blood and lymphatic system disorders:
Eosinophilia.

Cardiac disorders
QTc interval prolongation, torsades de pointes, palpitations, and cardiac rhythm disorders including ventricular tachyarrhythmias.

Ear and labyrinth disorders
Deafness, tinnitus
There have been isolated reports of reversible hearing loss occurring chiefly in patients with renal insufficiency or high doses.

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 (see section 4.4).

General disorders and administration site conditions
Chest pain, fever, malaise.

Hepatobiliary disorders
Cholestatic hepatitis, jaundice, hepatic disfunction, hepatomegaly, hepatic failure, hepatocellular hepatitis (see section 4.4).

Immune system disorders
Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis have occurred.

Investigations
Increased liver enzyme values.

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.

Psychiatric disorders
Hallucinations

Eye disorders
Mitochondrial Optic Neuropathy

Renal and urinary disorders
Interstitial nephritis

Skin and subcutaneous tissue disorders
Skin eruptions, prurituls, urticaria, exanthema, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.

Not known: acute generalised exanthematous pustulosis (AGEP).

Vascular disorders
Hypotension.

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.

4.9 Overdose
Symptoms: hearing loss, severe nausea, vomiting and diarrhoea.
Treatment: gastric lavage, general supportive measures.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties
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.

5.2 Pharmacokinetic properties
Peak blood levels normally occur within one hour of dosing of erythromycin ethylsuccinate granules. The elimination half life is approximately two hours. Doses may be administered two, three or four times a day.

Erythromycin ethylsuccinate 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.

5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients
Povidone
Maize starch
Magnesium hydroxide
Polacrilin potassium
Polyethylene glycol 8000
Polyethylene glycol 400
Hydroxypropyl methyl cellulose
Sorbic acid.

6.2 Incompatibilities
None stated.

6.3 Shelf life
60 months.

6.4 Special precautions for storage
None stated.

6.5 Nature and contents of container
High density Polyethylene bottle with urea cap with 100 tablets, securitainer or snap-secure container with 50, 100 or 1000 tablets. Blister packs containing 10, 14, 15, 28 or 56 tablets: PVC, heat sealed with 20 micron hard tamper aluminium foil.

6.6 Special precautions for disposal and other handling
Not applicable.

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Erythromycin Stearate Tablets USP 250mg Taj Pharma

Package leaflet: Information for the patient

a) Erythromycin Stearate Tablets USP 250mg Taj Pharma.
b) Erythromycin Stearate Tablets USP 500mg Taj Pharma.

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.
– Keep this leaflet. You may need to read it again.
– If you have any further questions, ask your doctor or pharmacist.
– This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
– If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

What is in this leaflet
1. What Erythromycin is and what it is used for
2. Before you are given Erythromycin
3. How you will be given Erythromycin
4. Possible side effects
5. How Erythromycin is stored
6. Further Information

1. What Erythromycin is and what it is used for
The name of your medicine is Erythromycin Tablets. Erythromycin contains the active ingredient erythromycin which belongs to a group of medicines called macrolide antibiotics. Erythromycin Tablets are used to prevent and treat infections such as:
• Throat and sinus infections
• Chest infections, such as bronchitis and pneumonia
• Ear infections
• Mouth and dental infections
• Eye infections
• Skin and tissue infections, such as acne
• Stomach and intestinal infections
• Prevention of infection following burns, operations or dental procedures
• Other infections, such as sexually transmitted diseases, bone infections or scarlet fever

2. Before you are given Erythromycin
You should not receive Erythromycin Tablets if you:
• have been told that you are allergic to erythromycin or other macrolide antibiotics such as clarithromycin or azithromycin or any of the other ingredients in these tablets;
• are currently taking a medicine called – are taking ergotamine or dihydroergotamine (used to treat migraines) while taking erythromycin as this may cause serious side effects;
– are taking terfenadine or astemizole or mizolastine (widely taken for hayfever and allergies), domperidone (for nausea (feeling sick) and vomiting (being sick)), cisapride (for stomach disorders) or pimozide or amisulpride (for psychiatric conditions) while receiving erythromycin, as combining these drugs can sometimes cause serious
disturbances in heart rhythm. Consult your doctor for advice on alternative medicines you can take instead;
– simvastatin (used to lower cholesterol and triglycerides (types of fat) in the blood);
– tolterodine (used for treating overactive bladder with symptoms of urinary frequency, urgency, and leakage);
• are taking colchicine (used for treatment of gout and arthritis) whilst taking erythromycin as this may cause serious side effects;
• have any liver problems or have been told that any drugs you are taking can cause liver problems;
• have previously experienced diarrhoea following the use of antibiotics;
• are pregnant and have been told that you have a sexually transmitted disease called syphilis. In this case erythromycin may not be effective for preventing the transfer of this infection to your baby. Consult your doctor before receiving erythromycin. Alternatively if you were treated for early stages of syphilis during your pregnancy, and your child is under 1 year and is prescribed erythromycin, consult your doctor before giving erythromycin to your child;
• are treating a young child with antibiotics and they are irritable or vomit when fed, you should contact your physician immediately;
• suffer from a condition called myasthenia gravis, which causes muscle weakness, consult your doctor before receiving erythromycin;
• are taking erythromycin with ‘statins’ such as simvastatin or lovastatin (used to lower cholesterol) as serious side effects can occur.

If any of these apply to you, or if you are not sure, tell your doctor.

Taking other medicines
Please tell your doctor if you are taking, or have recently taken any other medicines, including any medicines obtained without a prescription.

This is especially important if you are taking medicines from the following families:
• astemizole, terfenadine or mizolastine (used to treat allergies such as hayfever);
• domperidone (used to treat nausea (feeling sick) and vomiting (being sick));
• pimozide (used to treat mental problems);
• ergotamine or dihydroergotamine (used to relieve migraine);
• cisapride (used to treat stomach disorders);
• statins (used to help lower cholesterol levels e.g. lovastatin and simvastatin);
• protease inhibitors (used to treat viral infections e.g. saquinavir);
• oral contraceptives.

This is also important if you are taking medicines called:
• colchicine (used to treat gout and arthritis);
• cimetidine and omeprazole (used to treat acid reflux and other related conditions);
• clarithromycin, rifabutin, or rifampicin (medicines used to treat different types of bacterial infection);
• fluconazole, ketoconazole and itraconazole (medicines used to treat fungal infections);
• digoxin, quinidine or disopyramide (used to treat heart problems);
• cilostazol (a medicine used to treat peripheral circulation problems);
• hexobarbitone, phenobarbital or midazolam (used as sedatives);
• warfarin and acenocoumarol (used to help thin the blood);
• valproate, carbamazepine or phenytoin (used to control epilepsy);
• theophylline (used to treat asthma and other breathing problems);
• ciclosporin or tacrolimus (used following organ transplants);
• bromocriptine (used to treat Parkinson’s disease);
• zopiclone or triazolam/alprazolam (used to help you sleep or relieve states of anxiety);
• alfentanil (a medicine used to provide pain relief);
• methylprednisolone (used to help suppress the body’s immune system – this is useful in treating a wide range of conditions);
• St John’s Wort (a herbal medicine used to treat depression);
• verapamil (used to treat high blood pressure and chest pain);
• vinblastine (used to treat certain types of cancer);
• sildenafil (used to treat erectile dysfunction).

If you or your child goes for any medical tests, tell your doctor that you are taking Erythromycin, as this may interfere with some test results.

Pregnancy and breast-feeding
Erythromycin should be used by women during pregnancy only if clearly needed.
If you are pregnant or think you may be pregnant, or if you are breast-feeding, please consult your doctor before taking this medicine.

3. How you will be given Erythromycin
Always take Erythromycin Tablets exactly as your doctor has told you. You should check with your doctor if you are not sure. The usual dose of Erythromycin Tablets for adults and children over 8 years is:

1-2 g daily in divided doses i.e. four to eight 250 mg tablets daily or two to four 500 mg tablets daily, taken just before or with meals or food. If you have a bad infection you may be told to take up to 4 g daily.

Continue to take this medicine until the course is completed or until your doctor tells you to stop; do not stop taking your medicine, even if you feel better. If you stop the treatment too early your problem could come back.

If you take more Erythromycin than you should
If you accidentally take more medicine in one day than your doctor has told you to, or if a child has taken some of the medicine by mistake, contact your doctor or go to your nearest hospital emergency department immediately. An overdose of Erythromycin® could cause temporary hearing loss, nausea, vomiting and diarrhoea.

If you forget to take Erythromycin
If you forget to take a dose of your medicine, take it as soon as you remember. Do not take more medicine in one day than your doctor tells you to.

If you have any further questions on the use of this product ask your doctor or pharmacist.

4. Possible Side Effects
Like all medicines, Erythromycin Tablets can cause side effects, although not everybody gets them.

If you notice any of the following, contact your doctor immediately:
• difficulty breathing;
• fainting;
• swelling of the face, lips or throat;
• skin rashes;
• severe skin reactions including large fluid-filled blisters, sores and ulcers;
• ulcers in the mouth and throat, as these may be signs of an allergic reaction.

Contact a doctor immediately if you experience a serious skin reaction: a red, scaly rash with bumps under the skin and blisters (exanthematous pustulosis). The frequency of this side effect is not known (cannot be estimated from the available data).

Other side effects of Erythromycin include:
• diarrhoea which may be severe or prolonged and may contain blood or mucus;
• feeling sick or being sick;
• increase in a particular type of white blood cells (eosinophilia);
• stomach pains; these may be a symptom of an inflamed pancreas (pancreatitis);
• ringing in the ears (tinnitus);
• reversible loss of hearing (usually associated with high doses or in patients with kidney problems);
• various liver or gall-bladder problems, which can cause yellowing of the skin and/or eyes (jaundice) or pale stools with dark urine;
• chest pains;
• abnormal heart rhythms (including palpitations);
• fever;
• anorexia;
• confusion;
• fits (seizures);
• vertigo (problems with balance that can result in feelings of dizziness or sickness – particularly on standing);
• hallucinations (seeing or hearing things that aren’t there);
• feeling generally unwell (malaise);
• inflammation of the kidneys (a condition known as interstitial nephritis);
• low blood pressure;
• serious skin rashes that may involve blistering and can cover large areas of the torso, face and limbs (conditions known as Stevens Johnson syndrome, toxic epidermal necrolysis and erythema multiforme);
• vomiting and irritability in young children between the age of 1 month and 12 months;
• visual impairment/blurred vision (Mitochondrial optic neuropathy).

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

By reporting side effects you can help provide more information on the safety of this medicine.

5. How Erythromycin is stored
Do not store above 25°C. Store in the original package.
Do not use these tablets after the expiry date shown on the blister/label.
The expiry date refers to the last day of that month.
KEEP OUT OF THE REACH AND SIGHT OF CHILDREN
Medicines should not be disposed of via waste water or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Further information

What Erythromycin contains
The tablet contains the active ingredient erythromycin stearate.
a) Each tablet contains:
Erythromycin stearate USP
equivalent to erythromycin 250mg buffered with sodium citrate.

b) Each tablet contains:
Erythromycin stearate USP
equivalent to erythromycin 500mg buffered with sodium citrate.
The other ingredients are: hydroxypropyl methyl cellulose, maize starch, povidone, magnesium hydroxide, sorbic acid, polyethylene glycol and polacrilin potassium.

What Erythromycin looks like and contents of the pack
Erythromycin tablets are white.
The Erythromycin tablets are available in containers of 50, 100 or 1000 tablets, or blister packs of 10, 14, 15, 28 or 56 tablets.
Not all pack size are available.