ZITHROMAX Azithromycin Dihydrate 200mg / 5mL Powder for Oral Suspension 22.5mL

Azithromycin is indicated for infections caused by susceptible organisms; in lower respiratory tract infections including bronchitis and pneumonia, in skin and soft tissue infections, in acute otitis media and in upper respiratory tract infections including sinusitis and 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.)
In sexually transmitted diseases in men and women, azithromycin is indicated for the treatment of uncomplicated genital infections due to Chlamydia trachomatis. It is also indicated for the treatment of chancroid due to Hemophilus ducreyi and uncomplicated genital infections due to non-multiresistant Neisseria gonorrhoeae; concurrent infection with Treponema pallidum should be excluded.
Azithromycin is indicated, either alone or in combination with rifabutin, for prophylaxis against Mycobacterium avium-intracellulare complex (MAC) infection, 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 IV is indicated for the treatment of community-acquired pneumonia (CAP) caused by susceptible organisms, including Legionella pneumophila, in patients who require initial IV therapy.
Azithromycin IV is indicated for the treatment of pelvic inflammatory diseases (PID) caused by susceptible organisms (Chlamydia trachomatis, Neisseria gonorrhoea, Mycoplasma hominis) in patients who require initial IV therapy.

 

Oral azithromycin should be administered as a single daily dose. The period of dosing with regard to infection is given as follows.
Azithromycin tablets, powder for oral suspension can be taken with or without food.
In adults: For the treatment of sexually transmitted diseases caused by Chlamydia trachomatis and Hemophilus 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 in combination with 250 mg or 500 mg 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 once per week.
For the treatment of DMAC infections in patients with advanced HIV infection, the recommended dose is 600 mg once a day. Azithromycin should be administered in combination with other antimycobacterial agents that have shown in vitro activity against MAC, such as ethambutol, at the approved dose.
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 by the IV route for at least 2 days. IV therapy should be followed by oral azithromycin 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 dose by the IV route for 1 or 2 days. IV therapy should be followed by oral azithromycin 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 anaerobic agent may be administered in combination with azithromycin.
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.
Intravenous Administration: After reconstitution and dilution, the recommended route of administration for IV azithromycin is by IV infusion only. Do not administer as an IV bolus or an intramuscular injection (see section Precautions and Special Precautions for Disposal and Other Handling under Cautions for Usage).
The infusate concentration and rate of infusion for azithromycin IV should be either 1 mg/mL over 3 hours or 2 mg/mL over 1 hour. An IV dose of 500 mg azithromycin should be infused for a minimum duration of 1 hour.
In children: The maximum recommended total dose for any treatment is 1500 mg for children.
In general, the total dose in children is 30 mg/kg. Treatment for pediatric streptococcal pharyngitis should be dosed at a different regimen (see as follows).
The 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 5 days with a single daily dose of 10 mg/kg on Day 1, then 5 mg/kg on Days 2-5. As an alternative to the previously mentioned dosing, treatment for children with acute otitis media can be given as a single dose of 30 mg/kg.
For pediatric streptococcal pharyngitis, azithromycin given as a single dose of 10 mg/kg or 20 mg/kg for 3 days has been shown to be effective; however, a daily dose of 500 mg must not be exceeded. In clinical trials comparing these two dosage regimens, similar clinical efficacy was observed but greater bacteriologic eradication was evident at the 20 mg/kg/day dose. However, penicillin is the usual drug of choice for the treatment of Streptococcus pyogenes pharyngitis, including prophylaxis of rheumatic fever.
For children weighing less than 15 kg, azithromycin suspension should be measured as closely as possible. For children weighing 15 kg or more, azithromycin suspension should be administered according to the guide provided as follows: See Table 5.

Azithromycin tablets should only be administered to children weighing more than 45 kg.
The safety and efficacy of IV azithromycin for the treatment of infections in children have not been established.
Safety and efficacy for the prevention or treatment of MAC in children have not been established. Based on pediatric pharmacokinetic data, a dose of 20 mg/kg would be similar to the adult dose of 1200 mg but with a higher C_max.
Special populations: In the Elderly: The same dosage as in adult patients is used in the elderly. Elderly patients may be more susceptible to the development of torsades de pointes arrhythmia than younger patients (see Precautions).
In Patients with Renal Impairment: No dose 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) (see Precautions and Pharmacology: Pharmacokinetics under Actions).
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 (see Precautions).

 

Overdosage

May be taken with or without food: May be taken w/ meals to reduce GI discomfort.

The use of this product is contraindicated in patients with a hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic, or to any excipient listed in Description.

Hypersensitivity: As with erythromycin and other macrolides, rare serious allergic reactions, including angioedema and anaphylaxis (rarely fatal), Dermatologic reactions including Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) (rarely fatal), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have been reported. Some of these reactions with azithromycin have resulted in recurrent symptoms and required a longer period of observation and treatment.
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.
Hepatotoxicity: 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.
Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.
Infantile hypertrophic pyloric stenosis (IHPS): Following the use of azithromycin in neonates (treatment up to 42 days of life), infantile hypertrophic pyloric stenosis (IHPS) has been reported. Parents and caregivers should be informed to contact their physician if vomiting or irritability with feeding occurs.
Ergot derivatives: In patients receiving ergot derivatives, ergotism has been precipitated by co-administration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergot and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin and ergot derivatives should not be co-administered.
Superinfection: As with any antibiotic preparation, observation for signs of superinfection with non-susceptible organisms, including fungi is recommended.
Clostridium difficile-associated diarrhea: Clostridium difficile-associated diarrhea (CDAD) has been reported with the 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 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 diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.
Renal impairment: In patients with severe renal impairment (GFR <10 mL/min), a 33% increase in systemic exposure to azithromycin was observed (see Pharmacology: Pharmacokinetics under Actions).
Diabetes: Azithromycin 40 mg/mL Powder for Oral Suspension: Caution in diabetic patients: 5 mL of reconstituted suspension contains 3.87 g of sucrose.
Due to the sucrose content (3.87 g/5 mL of reconstituted suspension), this medicinal product is not indicated for persons with fructose intolerance (hereditary fructose intolerance), glucose-galactose malabsorption or saccharase-isomaltase deficiency.
Prolongation of the QT interval: 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 (see Adverse Reactions). 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 hypokalemia and hypomagnesemia.
Patients with clinically relevant bradycardia, cardiac arrhythmia or cardiac insufficiency.
Elderly patients: elderly patients may be more susceptible to drug-associated effects on the QT interval.
Myasthenia gravis: Exacerbations of the symptoms of myasthenia gravis have been reported in patients receiving azithromycin therapy.
Intravenous administration: 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 (see Dosage & Administration and Special Precautions for Disposal and Other Handling under Cautions for Usage).
Effects on Ability to Drive and Use Machines: There is no evidence to suggest that azithromycin may have an effect on a patient's ability to drive or operate machinery.

 

Use In Pregnancy & Lactation

Azithromycin is well tolerated with a low incidence of side effects.
In clinical trials, the following undesirable effects have been reported: Blood and Lymphatic System Disorders: Transient episodes of mild neutropenia have occasionally been observed in clinical trials.
Ear and Labyrinth Disorders: 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.
Gastrointestinal Disorders: Nausea, vomiting, diarrhea, loose stools, abdominal discomfort (pain/cramps), and flatulence.
Hepatobiliary Disorders: Abnormal liver function.
Skin and Subcutaneous Tissue Disorders: Allergic reactions including rash and angioedema.
General Disorders and Administration Site Conditions: Local pain and inflammation at the site of infusion.
The following undesirable effects have been reported in association with DMAC prophylaxis and treatment clinical trials: The most frequent (>5% in any treatment group) adverse 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.
In post-marketing experience, the following additional undesirable effects have been reported: Infections and Infestations: Moniliasis and vaginitis.
Blood and Lymphatic System Disorders: Thrombocytopenia.
Immune System Disorders: Anaphylaxis (rarely fatal) (see Precautions).
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, and vertigo.
Cardiac Disorders: Palpitations and arrhythmias including ventricular tachycardia have been reported. There have been rare reports of QT prolongation and torsades de pointes. (see Precautions).
Vascular Disorders: Hypotension.
Gastrointestinal Disorders: Vomiting/diarrhea (rarely resulting in dehydration), dyspepsia, constipation, pseudomembranous colitis, pancreatitis, and rare reports of tongue discoloration.
Hepatobiliary Disorders: Hepatitis and cholestatic jaundice have been reported, as well as rare cases of hepatic necrosis and hepatic failure, which have resulted in death. (see Precautions).
Skin and Subcutaneous Tissue Disorders: Allergic reactions including pruritus, rash, photosensitivity, edema, urticaria, and angioedema. Rarely, serious cutaneous adverse reactions including erythema multiforme, AGEP, SJS, TEN, and DRESS 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: Asthenia, fatigue, and malaise.

 

Antacids: In a pharmacokinetic study investigating the effects of simultaneous administration of antacid with azithromycin, no effect on overall bioavailability was seen, although peak serum concentrations were reduced by approximately 24%. In patients receiving both azithromycin and antacids, the drugs should not be taken simultaneously.
Cetirizine: In healthy volunteers, co-administration of a 5-day regimen of azithromycin with 20 mg cetirizine at steady-state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.
Didanosine (Dideoxyinosine): Co-administration of 1200 mg/day azithromycin with 400 mg/day didanosine in six HIV-positive subjects did not appear to affect the steady-state pharmacokinetics of didanosine as compared to placebo.
Digoxin and colchicine: Concomitant administration of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates such as digoxin and colchicine, has been reported to result in increased serum levels of the P-glycoprotein substrate. 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: There is a theoretical possibility of interaction between azithromycin and ergot derivatives (see Precautions).
Zidovudine: Single 1000 mg doses and multiple 1200 mg or 600 mg doses of azithromycin had little effect on the plasma pharmacokinetics 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.
Pharmacokinetic studies have been conducted between azithromycin and the following drugs known to undergo significant cytochrome P450-mediated metabolism.
Atorvastatin: Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) 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.
Carbamazepine: In a pharmacokinetic interaction study in healthy volunteers, no significant effect was observed on the plasma levels of carbamazepine or its active metabolite in patients receiving concomitant azithromycin.
Cimetidine: In a pharmacokinetic study investigating the effects of a single dose of cimetidine, given 2 hours before azithromycin, on the pharmacokinetics of azithromycin, no alteration of azithromycin pharmacokinetics was seen.
Coumarin-type oral anticoagulants: In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single dose of 15 mg 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.
Cyclosporin: In a pharmacokinetic study with healthy volunteers who were administered a 500 mg/day oral dose of azithromycin for 3 days and were then administered a single 10 mg/kg oral dose of cyclosporin, the resulting cyclosporin C_max and AUC_0-5 were found to be significantly elevated. Consequently, caution should be exercised before considering concurrent administration of these drugs. If co-administration of these drugs is necessary, cyclosporin levels should be monitored and the dose adjusted accordingly.
Efavirenz: Co-administration of a single dose of 600 mg azithromycin and 400 mg efavirenz daily for 7 days did not result in any clinically significant pharmacokinetic interactions.
Fluconazole: Co-administration of a single dose of 1200 mg azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole. Total exposure and half-life of azithromycin were unchanged by the co-administration of fluconazole; however, a clinically insignificant decrease in C_max (18%) of azithromycin was observed.
Indinavir: Co-administration of a single dose of 1200 mg azithromycin had no statistically significant effect on the pharmacokinetics of indinavir administered as 800 mg three times daily for 5 days.
Methylprednisolone: In a pharmacokinetic interaction study in healthy volunteers, azithromycin had no significant effect on the pharmacokinetics of methylprednisolone.
Midazolam: In healthy volunteers, co-administration of 500 mg/day azithromycin for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single dose of 15 mg midazolam.
Nelfinavir: Co-administration of azithromycin (1200 mg) and nelfinavir at steady-state (750 mg three times daily) resulted in increased azithromycin concentrations. No clinically significant adverse effects were observed and no dose adjustment was required.
Rifabutin: Co-administration of azithromycin and rifabutin did not affect the serum concentrations of either drug.
Neutropenia: was observed in subjects receiving concomitant treatment of azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship to combination with azithromycin has not been established (see Adverse Reactions).
Sildenafil: In normal healthy male volunteers, there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC and C_max of sildenafil or its major circulating metabolite.
Terfenadine: Pharmacokinetic studies have reported no evidence of an interaction between azithromycin and terfenadine. There have been rare cases reported where the possibility of such an interaction could not be entirely excluded; however, there was no specific evidence that such an interaction had occurred.
Theophylline: There is no evidence of a clinically significant pharmacokinetic interaction when azithromycin and theophylline are co-administered to healthy volunteers.
Triazolam: In 14 healthy volunteers, co-administration of 500 mg azithromycin on Day 1 and 250 mg on Day 2 with 0.125 mg triazolam on Day 2 had no significant effect on any of the pharmacokinetic variables for triazolam compared to triazolam and placebo.
Trimethoprim/sulfamethoxazole: Co-administration of trimethoprim/sulfamethoxazole DS (160 mg/800 mg) for 7 days with 1200 mg azithromycin on Day 7 had no significant effect on peak concentrations, total exposure or urinary excretion of either trimethoprim or sulfamethoxazole. Azithromycin serum concentrations were similar to those seen in other studies.

 

Caution For Usage

Storage

Action

Macrolides