COMPOSITION:
Each film coated tablet contains: Azithromycin Dihydrate equivalent to Azithromycin ………………. 250/500 mg
DESCRIPTION:
For Ziomycin 250 mg Tablet: Yellow colored, film-coated capsule shaped tablets with engraving “A250” on one side and plain on other side.
For Ziomycin 500 mg Tablet: Yellow colored, film-coated capsule shaped tablets with engraving “A500” on one side and plain on other side.

INDICATIONS:
Azithromycin tablets can be applied in situations where micro-organisms sensitive to azithromycin have caused:
− upper respiratory tract infections: sinusitis, pharyngitis, tonsillitis
− acute otitis media
− lower respiratory tract infections: acute bronchitis and mild to moderately severe community acquired pneumonia
− skin and soft tissue infections
− uncomplicated Chlamydia trachomatis urethritis and cervicitis
Considerations should be given to official guidance on the appropriate use of antibacterial agents.
RECOMMENDED DOSE & MODE OF ADMINISTRATION:
Azithromycin tablets should be given as a single daily dose. The tablets may be taken with food.
Adults
In uncomplicated Chlamydia trachomatis urethritis and cervicitis the dosage is 1000 mg as a single oral dose. For all other indications the dose is 1500 mg, to be administered as 500 mg per day for three consecutive days. As an alternative the same total dose (1500 mg) can also be administered over a period of five days with 500 mg on the first day and 250 mg on the second to the fifth day.
Elderly patients
The same dose range as in younger patients may be used in the elderly.
Children
Azithromycin tablets should only be administered to children weighing more than 45 kg when normal adult dose should be used. For children under 45 kg other pharmaceutical forms of Azithromycin, e.g. suspensions, may be used.
In patients with renal impairment:
No dose adjustment is necessary in patients with mild to moderate renal impairment (GFR 10-80 ml/min)
In patients with hepatic impairment:
A dose adjustment is not necessary for patients with mild to moderately impaired liver function.

UNDESIRABLE EFFECTS:
The table below lists the adverse reactions identified through clinical experience and post-marketing surveillance by system organ class and frequency. Adverse The frequency grouping is defined using the following convention: Very common ( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to < 1/100); rare ( 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). Within each frequency group, undesirable effects are listed in order of decreasing seriousness.
Adverse reactions possibly or probably related to azithromycin based on clinical trial experience and post-marketing surveillance.
Infections and infestations:
Uncommon:
Candidiasis, oral candidiasis, vaginal infection
Blood and lymphatic system disorders:
Common:
Lymphocyte count decreased, eosinophil count increased Uncommon:
Leukopenia, neutropenia
Rare:
Thrombocytopenia, haemolytic anaemia
Immune system disorders:
Uncommon:
Angioedema, hypersensitivity
Metabolism and nutrition disorders:
Common:
Anorexia
Psychiatric disorders:
Uncommon:
Nervousness
Rare:
Agitation, depersonalization
Nervous system disorders:
Common:
Dizziness, headache, paraesthesia, dysgeusia
Uncommon: Hypoaesthesia, somnolence, insomnia
Eye disorders:
Common:
Visual impairment
Ear and labyrinth disorders:
Common:
Deafness
Uncommon:
Hearing impaired, tinnitus Rare:
Vertigo
Cardiac disorders:
Uncommon:
Palpitations
Gastrointestinal disorders:
Very common:
Diarrhoea, abdominal pain, nausea, flatulence Common: Vomiting, dyspepsia
Uncommon:
Gastritis, constipation
Hepatobiliary disorders:
Uncommon:
Hepatitis, aspartate aminotransferase increased, alanine aminotransferase increased, blood bilirubine increased Rare: Hepatic function abnormal
Skin and subcutaneous tissue disorders:
Common:
Rash, pruritus
Uncommon:
Steven-Johnson syndrome, photosensitivity reaction, urticaria
Musculoskeletal and connective tissue disorders:
Common:
Arthralgia
Renal and urinary disorders:
Uncommon:
Blood urea increased
Rare:
Renal failure acute, nephritis interstitial
General disorders and administration site conditions:
Common:
Fatigue
Uncommon:
Chest pain, oedema, malaise, asthenia
Investigations:
Common:
Blood bicarbonate decreased Uncommon: Blood potassium abnormal

INTERACTION WITH OTHER MEDICINAL PRODUCTS :
Effects of other medicinal products on azithromycin:
Antacids
In a pharmacokinetic study investigating the effects of simultaneous administration of antacids and azithromycin, no effect on the total bio-availability was seen,

SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
As with erythromycin and other macrolides, rare serious allergic reactions including angioneurotic oedema and anaphylaxis (rarely fatal), have been reported. Some of these reactions with azithromycin have resulted in recurrent symptoms and required a longer period of observation and treatment. Azithromycin tablets contains soya lecithin which might be a source of soya protein and should therefore not be taken in patients allergic to soya or peanut due to the risk of hypersensitivity reactions.
Since liver is the principal route of elimination for azithromycin, the use of azithromycin should be undertaken with caution in patients with significant hepatic disease. Cases of fulminant hepatitis potentially leading to life-threatening liver failure have been reported with Azithromycin. Liver function tests/investigations should be performed in cases where signs and symptoms of liver dysfunction occur such as rapid developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy.
In patients receiving ergotamine derivatives, ergotism has been precipitated by coadministration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergotamine derivatives and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin and ergot derivatives should not be co-administered. Prolonged cardiac repolarisation and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with other macrolides. A similar effect with azithromycin cannot be completely ruled out in patients at increased risk for prolonged cardiac repolarisation.
Therefore caution is required when treating patients:
– with congenital or documented acquired QT prolongation.
– currently receiving treatment with other active substances known to prolong QT interval such as antiarrhythmics of classes IA and III, cisapride and terfenadine.
– with electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesaemia
– with clinically relevant bradycardia, cardiac arrhythmia or severe cardiac insufficiency.
Clostridium difficile associated diarrhoea (CDAD) has been reported with the use of nearly all antibacterial agents, including azithromycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. 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 antimicrobial agents. In case of CDAD anti-peristaltics are contraindicated. Exacerbations of the symptoms of myasthenia gravis and new onset of myasthenia syndrome have been reported in patients receiving azithromycin therapy. Safety and efficacy for the prevention or treatment of MAC in children have not been established.
The following should be considered before prescribing azithromycin: Azithromycin tablets are not suitable for treatment of severe infections where a high concentration of the antibiotic in the blood is rapidly needed. In areas with a high incidence of erythromycin a resistance, it is especially important to take into consideration the evolution of the pattern of susceptibility to azithromycin and other antibiotics. As for other macrolides, high resistance rates of Streptococcus pneumoniae (> 30%) have been reported for azithromycin in some European countries. This should be taken into account when treating infections caused by
Streptococcus pneumoniae.
Pharyngitis/ tonsillitis
Azithromycin is not the substance of first choice for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes. For this and for the prophylaxis of acute rheumatic fever, penicillin is the treatment of first choice.
Sinusitis
Often, azithromycin is not the substance of first choice for the treatment of sinusitis.
Acute otitis media
Often, azithromycin is not the substance of first choice for the treatment of acute otitis media.
Skin and soft tissue infections
The main causative agent of soft tissue infections, Staphylococcus aureus, is frequently resistant to azithromycin. Therefore, susceptibility testing is considered a precondition for treatment of soft tissue infections with azithromycin.
Infected burn wounds
Azithromycin is not indicated for the treatment of infected burn wounds.
Sexually transmitted disease
In case of sexually transmitted diseases a concomitant infection by T. pallidum should be excluded.
Neurological or psychiatric diseases
Azithromycin should be used with caution in patients with neurological or psychiatric disorders. As with any antibiotic preparation, observation for signs of superinfection with non-susceptible organisms, including fungi is recommended. In patients with severe renal impairment (GFR < 10 ml/min) a 33% increase in systemic exposure to azithromycin was observed.
PREGNANCY & LACTATION:
There are no adequate data from the use of Azithromycin tablets in pregnant women. In reproduction toxicity studies in animals azithromycin was shown to pass the placenta, but no teratogenic effects were observed. The safety of azithromycin has not been confirmed with regard to the use of the active substance during pregnancy. Therefore Azithromycin tablets should only be used during pregnancy if definitely indicated.
Azithromycin passes into breast milk. Because it is not known whether azithromycin may have adverse effects on the breast-fed infant, nursing should be discontinued during treatment with Azithromycin tablets. Among other things diarrhoea, fungus infection of the mucous membrane as well as sensitisation is possible in the nursed infant. It is recommended to discard the milk during treatment and up until 2 days after discontinuation of treatment. Nursing may be resumed thereafter.

OVERDOSE:
Adverse events experienced in higher than recommended doses were similar to those seen at normal doses. In the event of overdosage general symptomatic and general supportive measures are indicated as required.
CONTRAINDICATIONS:
The use of azithromycin is contraindicated in patients with hypersensitivity to azithromycin, erythromycin, any macrolide or ketolideantibiotic, or to any of the excipients.

PHARMACODYNAMICS:
Pharmacotherapeutic group: Systematic antibacterial agent
ATC Code: J01FA10
Mode of action
Azithromycin is an azalide, a sub-class of the macrolide antibiotics. By binding to the 50S-ribosomal sub-unit, azithromycin avoids the translocation of peptide chains from one side of the ribosome to the other. As a consequence of this, RNA-dependent protein synthesis in sensitive organisms is prevented.
PK/PD relationship
For azithromycin the AUC/MIC is the major PK/PD parameter correlating best with the efficacy of azithromycin.
Mechanism of resistance
Resistance to azithromycin may be inherent or acquired. There are three main mechanisms of resistance in bacteria: target site alteration, alteration in antibiotic transport and modification of the antibiotic. Complete cross resistance exists among Streptococcus pneumoniae, betahaemolytic streptococcus of group A, Enterococcus faecalis and Staphylococcus aureus, including methicillin resistant S. aureus (MRSA) to erythromycin, azithromycin, other macrolides and lincosamides.
Breakpoints
EUCAST (European Committee on Antimicrobial Susceptibility Testing)

Susceptibility:
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
Pathogens for which resistance may be a problem: prevalence of resistance is equal to or greater than 10% in at least one country in the European Union. Commonly susceptible species
Aerobic Gram-negative microorganisms:
Haemophilus influenzae*; Moraxella catarrhalis*
Other microorganisms:
Chlamydophila pneumoniae; Chlamydia trachomatis; Legionella pneumophila; Mycobacterium avium; Mycoplasma pneumonia*
Species for which acquired resistance may be a problem
Aerobic Gram-positive microorganisms:
Staphylococcus aureus *; Streptococcus agalactiae; Streptococcus pneumoniae*; Streptococcus pyogenes*
Other microorganisms:
Ureaplasma urealyticum
Inherently resistant organisms
Staphylococcus aureus (methicillin resistant and erythromycin resistant strains); Streptococcus pneumoniae (penicillin resistant strains); Pseudomonas aeruginosa; Klebsiella spp.
*Clinical effectiveness is demonstrated by sensitive isolated organisms for approved clinical indications.
PHARMACOKINETICS:
Absorption
After oral administration the bioavailability of azithromycin is approximately 37%. Peak plasma levels are reached after 2-3 hours (Cmax after a single dose of 500 mg orally was approximately 0.4 mg/l).
Distribution
Kinetic studies have shown markedly higher azithromycin levels in tissue than in plasma (up to 50 times the maximum observed concentration in plasma) indicating that the active substance is heavily tissue bound (steady state distribution volume of approximately 31 l/kg). Concentrations in target tissues such as lung, tonsil, and prostate exceed the MIC90 for likely pathogens after a single dose of 500 mg. In experimental in vitro and in vivo studies azithromycin accumulates in the phagocytes, freeing is stimulated by active phagocytosis. In animal studies this process appeared to contribute to the accumulation of azithromycin in the tissue.
In serum the protein binding of azithromycin is variable and depending on the serum concentration varies from 50% in 0.05 mg/l to 12% in 0.5 mg/l.
Excretion
Plasma terminal elimination half-life closely reflects the tissue depletion half-life of 2 to 4 days. About 12% of an intravenously administered dose is excreted in the urine unchanged over a period of 3 days; the majority in the first 24 hours. Biliary excretion of azithromycin, predominantly in unchanged form, is a major route of elimination. The identified metabolites (formed by N- and O- demethylising, by hydroxylising of the desosamine and aglycone rings, and by the splitting of the cladinose conjugate) are microbiologically inactive.
After a 5 day treatment slightly higher (29%) AUC values were seen in the elderly volunteers (>65 years of age) compared to the younger volunteers (< 45 years of age). Pharmacokinetics in special populations
Renal insufficiency
Following a single oral dose of azithromycin 1 g, mean Cmax and AUC0-120 increased by 5.1% and 4.2% respectively, in subjects with mild to moderate renal impairment (glomerular filtration rate of 10-80 ml/min) compared with normal renal function (GFR> 80 ml/min). In subjects with severe renal impairment, the mean Cmax and AUC0-120 increased 61% and 33% respectively compared to normal.
Hepatic insufficiency
In patients with mild to moderate hepatic impairment, there is no evidence of a marked change in serum pharmacokinetics of azithromycin compared to normal hepatic function. In these patients, urinary recovery of azithromycin appears to increase perhaps to compensate for reduced hepatic clearance.
Elderly
The pharmacokinetics of azithromycin in elderly men was similar to that of young adults; however, in elderly women, although higher peak concentrations (increased by 30-50%) were observed, no significant accumulation occurred.
Infants, toddlers, children and adolescents
Pharmacokinetics have been studied in children aged 4 months 15 years taking capsules, granules or suspension.. At 10 mg/kg on day 1 followed by 5 mg/kg on days 2-5, the Cmax achieved is slightly lower than adults with 224 ug/l in children aged 0.6-5 years and after 3 days dosing and 383 ug/l in those aged 6-15 years. The t1/2 of 36 h in the older children was within the expected range for adults.
STORAGE CONDITIONS:
Store below 30°C in dry place .
Keep all medicines out of reach of children.
SHELF-LIFE:
36 months
DOSAGE FORM AND PACKAGING AVAILABLE:
250 mg: 6 tablets are in a PVC/PVDC blister; 1 or 10 blisters are in a carton box.
500 mg: 3 tablets are in a PVC/PVDC blister; 1 or 10 blisters are in a carton box.
NAME AND ADDRESS OF MANUFACTURER:
Kusum Healthcare Pvt. Ltd.
DATE OF REVISION OF PACKAGE INSERT:
Not Applicable
put this address under Name and address of manufacturer

Ziomycin 250 mg- MM Reg. No.: 1709AA 4704 A
Ziomycin 500 mg- MM Reg. No.: 1709AA 4705