Azythrex

Azithromycin dihydrate.

Each 5 mL contains: Azithromycin (as Dihydrate) 200 mg.

Pharmacotherapeutic Group: Antibacterials for systemic use.
Pharmacology: Pharmacodynamics: Mode of Action: Azithromycin is a macrolide antibiotic belonging to the azalide group. The molecule is constructed by adding a nitrogen atom to the lactone ring of erythromycin A. The chemical name of Azithromycin is 9-deoxy-9a-aza-a-methyl-9a-homoerythromycin A. The molecular weight is 749.0. The mechanism of action of Azithromycin is based upon the suppression of bacterial protein synthesis by means of binding to the ribosomal 50S sub-unit and inhibition of peptide translocation.
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. Azithromycin demonstrates cross resistance with erythromycin resistant gram positive isolates. A decrease in macrolide susceptibility over time has been noted particularly in Streptococcus pneumoniae and Staphylococcus aureus. Similarly, decreased susceptibility has been observed among Streptococcus viridans and Streptococcus agalactiae (Group B) streptococcus against other macrolides and lincosamides.
Pharmacokinetics: Peak plasma concentrations are extensively distributed to the tissues, and tissue concentration are achieved 2 to 3 hours after a dose, but Azithromycin is extensively distributed to the tissues, and tissues concentrations subsequently remain much higher than those in the blood; in contrast to most other antibacterials, plasma concentrations are therefore of little value as a guide to efficacy. High concentrations are taken up into white blood cells. There is little diffusions into the CSF when the meninges are not inflamed. Small amount of Azithromycin (Azythrex) are demethylated in the liver, and it is excreted in bile as unchanged drug and metabolites. About 6% of an oral dose (representing about 20% of the amount in the systemic circulation) is excreted in the urine. The terminal elimination half life is probably in excess of 40 hours.

Infections for respiratory pathogens (e.g. S. pyogenes, S. pneumoniae, M. catarrhalis, C. trachomatis, Legionella sp., Mycoplasma pneumoniae, S. aerus, and H. influenzae); C. pneumoniae and M. avium infection; uncomplicated chlamydial urethritis, cervicitis or pharyngitis; alternative drug for multi-drug resistant Salmonella typhi infection outside the Central Nervous System (CNS).

10 mg/kg/day orally for 3 days or alternatively, given for 5 days with a single 10 mg/kg dose on day 1, then 5 mg/kg on days 2-5. Or as prescribed by the physician.

Azithromycin is contraindicated in patients with a known hypersensitivity to Azithromycin, Erythromycin, any Macrolide or Ketolide antibiotic, or to any of the excipients.

This product contains FD & C yellow No. 5 (Tartrazine) which may cause allergic type reactions (including bronchial asthma) in certain susceptible persons.

Should not be given to patients with hepatic impairment.

Pregnancy: Animal reproduction studies have been performed at doses up to moderately maternally toxic dose concentrations. In these studies, no evidence of harm to the fetus due to Azithromycin was found. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Azithromycin should be used during pregnancy only if clearly needed.
Breast-feeding: There are no data on secretion in breast milk. As many drugs are excreted in human milk, Azithromycin should not be used in the treatment of a lactating woman unless the physician feels that the potential benefits justify the potential risks to the infant.

Anaphylactic Reaction; Metabolism and Nutrition Disorders: Common (>1/100 <1/10).
Nervous System Disorders: Common (>1/100 <1/10).
Eye Disorders: Common (>1/100 <1/10).
Visual Impairment; Ear and Labyrinth Disorders: Common (>1/100 <1/10).
Gastrointestinal Disorders: Very Common (≥1/10).
Diarrhoea, Abdominal Pain, Nausea, Flatulence: Common (>1/100 <1/10).
Skin and Subcutaneous Tissue Disorders: Common (>1/100 <1/10).
Musculoskeletal, Connective Tissue Disorders: Common (>1/100 <1/10).
General Disorders and Administration Site Conditions: Common (>1/100 <1/10).

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: Some of the macrolide antibiotics have been reported to impair the microbial metabolism of digoxin in the gut in some patients. In patients receiving concomitant Azithromycin, a related azalide antibiotic, and digoxin the possibility of raised digoxin levels should be borne in mind.
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.
Ergot derivatives: Due to the theoretical possibility of ergotism, the concurrent use of Azithromycin with ergot derivatives is not recommended. 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).
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.
Ciclosporin: 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 ciclosporin, the resulting ciclosporin Cmax and AUC0-5 were found to be significantly elevated (by 24% and 21% respectively), however no significant changes were seen in AUC0-∞. Consequently, caution should be exercised before considering concurrent administration of these drugs. If co-administration of these drugs is necessary, Ciclosporin levels should be monitored and the dose adjusted accordingly.
Efavirenz: Co-administration of a single dose of 600mg 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 Cmax (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.
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 Cmax, 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 500mg 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.

Direction for Reconstitution: Tap the bottle to loosen powder contents prior to reconstitution. Add 9 mL previously boiled and cool water for reconstitution and shake it for at least 2 minutes. Shake well before withdrawing each dose. Reconstituted solution should be used within 5 days of preparation.

Store at temperatures not exceeding 30°C.

Macrolides

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

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