Azith

AZITH (250 MG CAPSULE): Each capsule contains Azithromycin dihydrate equivalent to Azithromycin 250 mg.
AZITH (ORAL SUSPENSION 200 MG/5 ML): Each 5 mL (after reconstituted) contains Azithromycin dihydrate equivalent to Azithromycin 200 mg.
Each bottle contains Azithromycin 600 mg/15 mL.

Pharmacology: Pharmacodynamics: Azithromycin is an azalide antibiotic, a subclass of macrolide antibiotics. Azithromycin binds to the bacterial 50S ribosomal subunits. It blocks protein synthesis by inhibiting the transpeptidation step of protein synthesis. It leads to inhibit cell growth. Azithromycin usually is bacteriostatic.
Azithromycin is active in vitro against many gram-positive and gram-negative bacteria.
Gram positive aerobic bacteria: Staphylococcus aureus, Streptococcus pyogenes (group A β-hemolytic streptococci), Streptococcus pneumoniae, α-hemolytic Streptococci and other Streptococci.
Erythromycin gram positive bacteria resistance will also resist to Azithromycin include, Streptococcus faecalis (enterococcus) and methicillin-resistant staphylococci.
Gram negative aerobic bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Legionella pneumophila, Bordetella pertussis, Shigella spp., Vibrio cholerae, Plesiomonas shigelloides, Escherichia coli, Salmonella enteritidis, Salmonella typhi, Aeromonas hydrophila.
Anaerobic bacteria: Bacteroides fragilis, Bacteroides sp., Clostridium perfringens, Peptostreptococcus sp. and Propionibacterium acnes.
Bacterial in sexual transmitted diseases: Chlamydia trachomatis, Treponema pallidum, Neisseria gonorrhoeae and Haemophilus ducreyi.
Opportunistic infections in HIV: Mycobacterium avium-intracellulare complex, Pneumocystis carinii and Toxoplasma gondii.
Other: Borrelia burgdorferi (Lyme disease agent), Chlamydia pneumoniae, Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum, Campylobacter sp. and Listeria monocytogenes.
Pharmacokinetics: Azithromycin given orally is rapidly absorbed and about 40% bioavailable. Absorption from capsules, not including suspensions, is reduced by food. The peak plasma concentrations occur 2 to 3 hours after an oral dose. Azithromycin plasma concentration following IV administration of a single 500-mg dose of the drug are substantially higher than those following oral administration of the same dose. Peak plasma concentrations occur 1 to 2 hours after intravenous administration. Azithromycin is extensively distributed into the tissues, and tissue concentration subsequently remain much higher than those in the blood. High concentrations are taken up into white blood cells. There is little diffusion into the CSF. Azithromycin crosses the placenta. Small amounts of Azithromycin are demethylated in the liver, and it is excreted in bile mainly as unchanged drug. About 6% of an oral dose is excreted in the urine. While approximately 11% of a 500-mg IV dose of Azithromycin appear in urine as unchanged drug over 24 hours on day 1, and 14% of a 500-mg IV dose of Azithromycin appear in urine as unchanged drug over on day 5. The terminal elimination half-life is about 68 hours.

Azithromycin is used in the treatment of bacterial infection caused by susceptible bacteria: Lower respiratory tract infections: bronchitis, pneumonia.
Upper respiratory tract infections: sinusitis, pharyngitis/tonsillitis (Penicillin is the usual drug of choice in the treatment of Streptococcus  pyogenes  pharyngitis including the prophylaxis of rheumatic fever. Azithromycin is generally effective in the eradication of streptococci from the oropharynx, however, data establishing the efficacy of Azithromycin and the subsequent prevention of rheumatic fever are not available at present.).
Odontostomatological infections.
Acute otitis media.
Skin and soft tissue infections.
Sexually transmitted diseases: uncomplicated genital infections due to Chlamydia trachomatis, chancroid due to Haemophilus ducreyi, uncomplicated genital infections due to non-multiresistant Neisseria gonorrhoeae, concurrent infection with Treponema pallidum should be excluded. Moreover, Azithromycin is indicated, either alone or in combination with rifabutin, for prophylaxis against Mycobacterium avium-intracellulare complex (MAC), an opportunistic infection prevalent in patients with advanced human immunodeficiency virus (HIV).
Azithromycin is indicated in combination with ethambutol for the treatment of disseminated MAC (DMAC) infection in patients with advanced HIV infection.
Azithromycin intravenous is indicated for the treatment of community acquired pneumonia (CAP) caused by susceptible organisms, including Legionella pneumophila, in patients who require initial intravenous therapy.
Azithromycin intravenous is indicated for the treatment of pelvic inflammatory diseases (PID) caused by susceptible organisms (Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma hominis), in patients who require initial intravenous therapy.

Recommended dose: Dosing of therapy depends on the severity of the infection, patient's condition and susceptibility of organisms or to be used as directed by the physician.
The drug should be taken in complete treatment course or as directed by the physician.
Oral Azithromycin should be administered as a single daily dose. Each dose should be taken at least 1 hour before meal or 2 hours after meal.
In adults: For the treatment of adult patients with CAP due to the indicated organisms, the recommended dose of IV Azithromycin is 500 mg as a single daily dose for at least 2 days. IV therapy should be followed by AZITH (250 MG CAPSULE) at a single daily dose of 500 mg to complete a 7- to 10-day course of therapy. The timing of the conversion to oral therapy should be done at the discretion of the physician and in accordance with clinical response.
For the treatment of adult patients with PID due to the indicated organisms, the recommended dose of IV Azithromycin is 500 mg as a single daily dose by the IV route for 1 or 2 days. IV therapy should be followed by AZITH (250 MG CAPSULE) at a single daily dose of 250 mg to complete a 7-day course of therapy. The timing of the conversion to oral therapy should be done at the discretion of the physician and in accordance with clinical response. If anaerobic microorganisms are suspected of contributing to the infection, an antimicrobial agent with anaerobic activity may be administered in combination with Azithromycin.
For the treatment of sexually transmitted diseases caused by Chlamydia trachomatis and Haemophilus ducreyi, the dose is 1000 mg as a single oral dose. For susceptible Neisseria gonorrhoeae, the recommended dose is 1000 mg or 2000 mg of Azithromycin orally in combination with 250 mg or 500 mg of Ceftriaxone according to local clinical treatment guidelines. For patients who are allergic to penicillin and/or cephalosporins, prescribers should consult local treatment guidelines.
For prophylaxis against MAC infections in patients infected with the HIV, the dose is 1200 mg orally once per week.
For the treatment of DMAC infections in patients with advanced HIV infection, the recommended dose is 600 mg orally once a day. Azithromycin should be administered in combination with ethambutol at the approved dose.
For all other indications in which the oral formulation is administered, the total dosage of 1500 mg should be given as 500 mg daily for 3 days. As an alternative, the same total dose can be given over 5 days with 500 mg given on day 1, then 250 mg daily on days 2 to 5.
Mode of administration: Administration of AZITH (ORAL SUSPENSION 200 MG/5 ML): Tap the bottle to loosen the powder. Pull the measuring cup out to measure the volume of 9 mL as specified. Then open the bottle cap to fill water in a bottle containing medicinal powder. Close the bottle cap, shake to wet and disperse the powder. Finally, AZITH (ORAL SUSPENSION 200 MG/5 ML) (1 teaspoon) will be obtained as directed in the label.
Shake well before used. Shake prior to use everytime.
For children weighing less than 15 kg, the suspension should be measured as closely as possible. For children weighing 15 kg or more, the suspension should be administered using an appropriate measuring spoon.
The reconstituted product can be kept for 10 days below 30°C.
In Children: AZITH (250 MG CAPSULE) should be only administered to children weighing more than 45 kg.
The maximum recommended total dose for any treatment is 1500 mg for children.
Total dose of 30 mg/kg should be given as a single daily dose of 10 mg/kg daily for 3 days, or given over 5days with a single daily dose of 10 mg/kg on Day 1, then 5 mg/kg on Days 2-5.
AZITH (ORAL SUSPENSION 200 MG/5 ML) should be administered orally according to the guide provided as follows: See table.

Click on icon to see table/diagram/image

For pediatric streptococcal pharyngitis (only in patients who are contraindicated with penicillin, which is the first choice treatment), Azithromycin given as a single dose of 10 mg/kg or 20 mg/kg orally for 3 days has been shown to be effective. However, a daily dose of 500 mg must not be exceeded.
Treatment for children with acute otitis media, can be given as a single recommended dose of 30 mg/kg orally.
The safety and efficacy of IV Azithromycin for the treatment of infections in children have not been established.
In the elderly: The same dosage as in adult patients is used in the elderly.
In patients with renal impairment: No dosage adjustment is necessary in patients with mild to moderate renal impairment (GFR 10-80 mL/min). Caution should be exercised when Azithromycin is administered to patients with severe renal impairment (GFR < 10 mL/min).
In patients with hepatic impairment: The same dosage as in patients with normal hepatic function may be used in patients with mild to moderate hepatic impairment.

Adverse events experienced in higher than recommended doses were similar to those seen at normal doses. In the event of overdosage, general symptomatic and supportive measures are indicated as required.

The drug is contraindicated in patients with a hypersensitivity to Azithromycin, erythromycin, any macrolide or ketolide antibiotic.

1. Azithromycin is contraindicated in patients with known hypersensitivity to this drug.
2. The drug may be harmful to the liver.

If an allergic reaction occurs, the drug should be discontinued and consult a physician immediately.
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. Discontinue Azithromycin immediately if signs and symptoms of hepatitis occur.
In patients receiving ergot derivatives, ergotism has been precipitated by co-administration of some macrolide antibiotics. Azithromycin and ergot derivatives should not be co-administered.
As with other anti-infective agents, use of Azithromycin may result in an overgrowth of non-susceptible bacteria or fungi. If superinfection occurs, appropriate therapy should be instituted.
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Azithromycin and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile. C. difficile produces toxin which contribute to the development of CDAD.
In patients with severe renal impairment (GFR < 10 mL/min) a 33% increase in systemic exposure to Azithromycin was observed. Azithromycin should be used with caution in patients with severe renal impairment.
Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with macrolides, including Azithromycin. Prescribers should consider the risk of QT prolongation which can be fatal when weighing the risks and benefits of Azithromycin for at-risk groups including: Patients with congenital or documented QT prolongation; Patients currently receiving treatment with other active substances known to prolong QT interval such as antiarrhythmics of Classes IA and III, antipsychotic agents, antidepressants and fluoroquinolones; Patients with electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesemia; Patients with clinically relevant bradycardia, cardiac arrhythmia or cardiac insufficiency.
Exacerbation of the symptoms of myasthenia gravis have been reported in patients receiving Azithromycin therapy.
Azithromycin for injection should be reconstituted and diluted as directed and administered as an IV infusion over not less than 60 minutes. Do not administer as an IV bolus or an intramuscular injection.
Use in Children: The use of Azithromycin in neonates may cause infantile hypertrophic pyloric stenosis (IHPS). Parents should be informed to contact the physician if vomiting or irritability with feeding occurs.
Use in the Elderly: Elderly patients may be more susceptible to drug-associated effects on the QT interval.

As Azithromycin crosses the placenta and there are no adequate and controlled studies to date using Azithromycin in pregnant women, and the drug should be used during pregnancy only when clearly needed. Azithromycin is excreted in breast milk then the drug should be used with caution in nursing women.

Undesirable effects in association with DMAC prophylaxis and treatment: The most frequent (> 5% in any treatment group) advance reactions in HIV-infected patients receiving Azithromycin for prophylaxis for DMAC were diarrhea, abdominal pain, nausea, loose stools, flatulence, vomiting, dyspepsia, rash, pruritus, headache and arthralgia.
When 600 mg Azithromycin is given daily for the treatment of DMAC infection for prolonged periods, the most frequently reported treatment-related side effects are abdominal pain, nausea, vomiting, diarrhea, flatulence, headache, abnormal vision and hearing impairment.
Undesirable effects: Infections and Infestations: moniliasis and vaginitis.
Blood and Lymphatic System Disorders: thrombocytopenia, transient episodes of mild neutropenia have occasionally been observed.
Immune System Disorders: anaphylaxis (rarely fatal).
Metabolism and Nutrition Disorders: anorexia.
Psychiatric Disorders: aggressive reaction, nervousness, agitation and anxiety.
Nervous System Disorders: dizziness, convulsions, headache, hyperactivity, hypoesthesia, paresthesia, somnolence and syncope. There have been rare reports of taste/smell perversion and/or loss.
Ear and Labyrinth Disorders: deafness, tinnitus, hearing impaired, vertigo.
Hearing impairment (including hearing loss, deafness and/or tinnitus) has been reported in some patients receiving Azithromycin. Many of these have been associated with prolonged use of high doses in investigational studies. In those cases where follow-up information was available, the majority of these events were reversible.
Cardiac Disorders: palpitations and arrhythmias including ventricular tachycardia have been reported. There have been rare reports of QT prolongations and torsades de pointes.
Vascular Disorders: hypotension.
Gastrointestinal Disorders: vomiting/diarrhea (rarely resulting in dehydration), dyspepsia, constipation, pseudomembranous colitis, pancreatitis and rare reports of tongue discoloration, nausea, loose stools, abdominal discomfort (pain/cramps) and flatulence.
Hepatobiliary Disorders: abnormal liver function. Hepatitis and cholestatic jaundice have been reported, as well as rare case of hepatic necrosis and hepatic failure, which have resulted in death.
Skin and Subcutaneous Tissue Disorders: allergic reactions including pruritus, rash, photosensitivity, edema, urticaria and angioedema. Rarely, serious cutaneous adverse reactions including erythema multiforme, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms have been reported.
Musculoskeletal and Connective Tissue Disorders: arthralgia.
Renal and Urinary Disorders: interstitial nephritis and acute renal failure.
General Disorders and Administration Site Conditions: Local pain and inflammation at the site of infusion, asthenia, fatigue and malaise.

Antacids: Oral Azithromycin preparations should not be administered simultaneously with aluminum-or magnesium-containing antacids. Administration of oral Azithromycin with an aluminum- and magnesium hydroxide-containing antacid resulted in a decreased rate of absorption of Azithromycin. In patients receiving both Azithromycin and antacids, the drugs should not be taken simultaneously.
Cyclosporine: Coadministration of Azithromycin with cyclosporine will significantly increase plasma concentration of cyclosporine. Consequently, caution should be exercised before considering concurrent administration of these drugs. If co-administration of these drugs is necessary, cyclosporine levels should be monitored and the dose adjusted accordingly.
Digoxin: Concomitant administration of macrolide antibiotics, including Azithromycin with P-glycoprotein substrates, such as digoxin, has been reported to result in increased serum levels of the P-glycoprotein substrates. Therefore, if Azithromycin and P-glycoprotein substrates, such as digoxin are administered concomitantly, the possibility of elevated serum digoxin concentrations should be considered. Clinical monitoring, and possibly serum digoxin levels, during treatment with Azithromycin and after its discontinuation are necessary.
Ergot: In patients receiving ergot derivatives, ergotism has been precipitated by co-administration of some macrolide antibiotics. Azithromycin and ergot derivatives should not be co-administered.
Atorvastatin: Coadministration of atorvastatin and Azithromycin did not alter the plasma concentrations of atorvastatin (based on a HMG CoA-reductase inhibition assay). However, post-marketing cases of rhabdomyolysis in patients receiving Azithromycin with statins have been reported.
Pimozide: Prolongation of QT interval and, rarely, serious cardiovascular effects, including ventricular arrhythmias and death, have been reported in patients receiving drugs that inhibit the cytochrome P-450 isoenzyme concomitantly with pimozide. Macrolide antibiotics may inhibit metabolism of pimozide, resulting in increased plasma concentrations of unchanged drug. Because such alterations in pharmacokinetics of pimozide may be associated with prolongation of the QT and QT_c interval. Consequently concomitant administration of pimozide and Azithromycin is contraindicated.
Coumarin-type oral anticoagulants: In a study, Azithromycin did not alter the anticoagulant effect of a single dose of warfarin administered to healthy volunteers. There have been reports received in the post-marketing period of potentiated anticoagulation subsequent to co-administration of Azithromycin and coumarin-type oral anticoagulants. Although a causal relationship has not been established, consideration should be given to the frequency of monitoring prothrombin time when Azithromycin is used in patients receiving coumarin-type oral anticoagulants.
Zidovudine: Coadministration of Azithromycin with zidovudine results in the zidovudine plasma level or urinary excretion of zidovudine or its glucuronide metabolite. However, administration of Azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this finding is unclear, but it may be of benefit to patients.
Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is not believed to undergo the pharmacokinetic drug interactions as seen with erythromycin and other macrolides. Hepatic cytochrome P450 induction or inactivation via cytochrome-metabolite complex does not occur with Azithromycin.

AZITH (250 MG CAPSULE): Store below 30°C.
AZITH (ORAL SUSPENSION 200 MG/5 ML): Store below 30°C.
The reconstituted product can be kept for 10 days at 30°C.

Macrolides

J01FA10 - azithromycin ; Belongs to the class of macrolides. Used in the systemic treatment of infections.

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