Zenith Suspension/Zenith OD Suspension

Zenith Suspension: Powder for oral suspension.
White or off-white crystalline powder.
Each 5 mL powder for oral suspension contains: Azithromycin (as monohydrate) 200 mg.
Zenith OD Suspension: Azithromycin dihydrate (Zenith OD) 200 mg/5 mL Powder for Oral Suspension is a white to off-white free-flowing granular powder, after reconstitution it gives white to off-white suspension with banana flavor.
Each 5 mL suspension contains Azithromycin (as dihydrate) 200 mg.

Pharmacotherapeutic group: Azithromycin is a semi-synthetic azalide derivative with a 15-membered lactone ring. Azalides belong to the macrolide antibiotics. ATC code: J01FA10.
Pharmacology: Pharmacotherapeutic group: Azithromycin is a semi-synthetic azalide derivative with a 15-membered lactone ring. Azalides belong to the macrolide antibiotics. ATC code: J01FA10.
Pharmacodynamics: Zenith Suspension: Mode of action: By binding to the 50S-ribosomal subunit, azithromycin avoids the translocation of peptide chains from one side of the ribosome to the other. Azithromycin acts as a bacteriostatic.
PK/PD relationship: The efficacy of azithromycin is best described by the relationship AUC/MIC, where AUC describes the area under the curve and MIC represents the mean inhibitory concentration of the microbe concerned.
Following assessment of studies in children, the use of azithromycin is not recommended for the treatment of malaria, neither as monotherapy nor combined with chloroquine or artemisinin-based drugs, as non-inferiority to anti-malarial drugs recommended in the treatment of uncomplicated malaria was not established.
Mechanism of resistance: Resistance to azithromycin may be natural or acquired. There are 3 main mechanisms of resistance affecting azithromycin: Efflux: Resistance may be due to an increase in the number of efflux pumps on the cell membrane.
In particular, 14- and 15-link macrolides are affected (M-phenotype).
Alterations of the cell structure: methylation of the 23s rRNA may reduce the affinity of the ribosomal binding sites, which can result in microbial resistance to macrolides, lincosamides and group B streptogramins (SB) (so-called MLSB-phenotype).
Enzymatic deactivation of macrolides is only of limited clinical significance.
In the presence of the M-phenotype, complete cross-resistance exists between azithromycin and clarithomycin, erythromycin and roxithromycin. With the MLSB-phenotype, additional cross-resistance exists with clindamycin and streptogramin B. A partial cross-resistance exists with spiramycin.
Breakpoints: Testing of azithromycin is done by using the usual dilution series. The following minimum inhibitory concentrations for susceptible and resistant germs were determined: See Table 1.

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Prevalence of acquired resistance in Germany: 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.
Microbiological diagnosis with detection of the pathogen and its susceptibility to azithromycin should be attempted, particularly in the case of serious infections or treatment failures. (See Table 2.)

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Zenith OD Suspension: Azithromycin is a semi-synthetic azalide antibiotic, a subclass of macrolide antibiotics, with a broader spectrum of activity than erythromycin or clarithromycin. Azithromycin exerts its antibacterial action by binding to the 23S rRNA of the 50S ribosomal subunit of susceptible bacteria. It blocks protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal unit.
Antimicrobial Spectrum of Activity: Azithromycin is active in vitro and in clinical infections against most isolates of the following microorganisms: See Table 3.

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Azithromycin has demonstrated in vitro activity against strains of the following microorganisms; however, clinical significance is unknown. (See Tables 4 and 5.)

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Resistance to azithromycin may be inherent or acquired. Azithromycin demonstrates cross-resistance with erythromycin-resistant Gram-positive strains. Most strains of Enterococcus faecalis, Bacteroides fragilis and methicillin-resistant staphylococci are resistant to azithromycin.
Pharmacokinetics: Zenith Suspension: Absorption: After oral administration, peak plasma levels are reached after 2 to 3 hours; plasma terminal elimination half-life closely reflects the tissue depletion half-life of 2 to 4 days. After a 5-day treatment slightly higher AUC values were seen in the elderly patients (>65 years of age) compared to the younger patients (<40 years of age). However, these differences are not regarded as clinically relevant; therefore, a dose adjustment is not recommended.
In animal tests, high concentrations of azithromycin have been found in phagocytes. It has also been established that during active phagocytosis higher concentrations of azithromycin are released from inactive phagocytes. In animal models this results in high concentrations of azithromycin being delivered to the site of infection.
Non-linearity: Study data suggest non-linear pharmacokinetics of azithromycin in the therapeutic range.
Distribution: It has been demonstrated that the concentrations of azithromycin measured in tissues are noticeably higher (as much as 50 times) than those measured in plasma, which indicates that the agent strongly binds to tissues. Concentrations in target tissues such as lung, tonsil, and prostate exceed the MIC90 for likely pathogens after a single dose of 500 mg.
Binding to serum proteins varies according to plasma concentration and ranges from 12% at 0.5 μg/mL up to 52% at 0.05 μg azithromycin/mL serum. The mean volume of distribution at steady state (VV_ss) has been calculated to be 31.1 L/kg.
Elimination: About 12% of an intravenously administered dose is excreted unchanged within 3 days; the majority is excreted in the first 24 hours. Particularly high concentrations of unchanged azithromycin have been found in human bile. Also in bile, 10 metabolites were detected, which were formed through N- and O-demethylation, hydroxylation of desosamine and aglycone rings and cleavage of cladinose conjugate. Corresponding studies indicate that the metabolites of azithromycin are not microbiologically active.
Following a single oral dose of azithromycin 1 g, pharmacokinetics were unchanged in subjects with a glomerular filtration rate 10-80 mL/min. At a glomerular filtration rate <10 mL/min, there were statistically significant differences compared with subjects with normal renal function in AUC_0-120 (8.8 μg x h/mL vs. 11.7 μg x h/mL), C_max (1.0 μg/mL vs. 1.6 μg/mL) and CLr (2.3 mL/min/kg vs. 0.2 mL/min/kg).
In patients with mild (class A) to moderate (class B) hepatic impairment, there is no evidence of a marked change in serum pharmacokinetics of azithromycin compared to patients with normal hepatic function. In these patients, urinary recovery of azithromycin appears to increase perhaps to compensate for reduced hepatic clearance.
The mean bioavailability of azithromycin after oral administration is approximately 37%.
Zenith OD Suspension: Azithromycin is rapidly but incompletely absorbed from the gastrointestinal tract after oral administration; its absorption, however, exceeds that of erythromycin. Peak plasma levels are achieved 2-3 hours after oral administration with absolute bioavailability of about 37%.
After administration of azithromycin oral suspension (10 mg/kg as a single dose on Day 1 followed by 5 mg/kg daily on Days 2 to 5) in fasting children 1 to 5 years old, mean peak plasma concentration (C_max) on Day 5 was 0.216 mcg/mL at 1.9 hours with an area under the curve (AUC_0-24) of 1.822 mcg·hr/mL. When the same dosage regimen was administered in fasting children 5 to 15 years old, mean C_max on Day 5 was 0.383 mcg/mL at 2.4 hours with an AUC of 3.109 mcg·hr/mL.
Pharmacokinetics in children given a total dose of 30 mg/kg delivered as a single dose have not been studied.
When azithromycin oral suspension (at a total dose of 60 mg/kg in divided doses given as 20 mg/kg/day for 3 days or 12 mg/kg/day over 5 days with a maximum daily dose of 500 mg) was given to children 3 to 16 years old with pharyngitis/tonsillitis, C_max was 1.05 ± 0.44 mcg/mL at 3 ± 2 hours with an AUC_0-24 of 7.92 ± 2.87 mcg·hr/mL for the 3-day regimen; C_max was 0.534 ± 0.361 mcg/mL at 2.2 ± 0.8 hours with an AUC_0-24 of 3.94 ± 1.9 mcg·hr/mL for the 5 day regimen.
Food does not have a substantial effect on the extent of absorption (AUC) of azithromycin oral suspension, although the absorption rate may be increased. Compared with fasting administration, a single 500 mg dose of azithromycin oral suspension with food was associated with a 56% increase in peak plasma drug concentration but no change in AUC.
Azithromycin is widely distributed into most body fluids and tissues. High concentrations are found in the pulmonary tissue, tonsillar tissue, gastric mucosa, liver, prostate, and gynecological tissues, even 4 to 5 days after a single dose. These sustained tissue concentrations are significantly above the minimum inhibitory concentration (MIC₉₀) values for most common pathogens. Lower concentrations are found in fat, muscle and bone samples.
Serum concentrations decline polyphasically. The initial decline in plasma levels is caused by the rapid and extensive distribution of the drug into tissues. Azithromycin concentration in most tissues generally exceeds that in serum by 10- to 100-fold.
Only very low concentrations of azithromycin (less than 0.01 mcg/mL) have been detected in cerebrospinal fluid (CSF) in the presence of noninflamed meninges. Concentrations in peritoneal fluid are also very low.
Azithromycin crosses the placenta and is distributed into cord blood and amniotic fluid. The drug is distributed into milk.
Azithromycin's serum protein binding decreases with increasing drug concentration (from 12% at 0.5 mcg/mL to 52% at 0.05 mcg/mL).
Azithromycin undergoes metabolism primarily via N-demethylation of the desosamine sugar or at the 9a position on the macrolide ring. Other metabolic pathways include O-demethylation and hydrolysis and/or hydroxylation of the cladinose and desosamine sugar moieties and the macrolide ring. Up to 10 metabolites have been identified, and all are not microbiologically active.
The terminal elimination phase of azithromycin from the serum is via hepatic metabolism, biliary excretion and transintestinal passage. Although high azithromycin concentrations in the bile relative to serum concentrations suggest biliary excretion as an important route of elimination, transintestinal excretion may be the principal route of excretion for unchanged drug. The half-life (t_1/2) of the drug in peripheral leukocytes ranges from 34 to 57 hours. The average tissue t_1/2 is about 1 to 4 days. Only a small portion (6%) of a 500 mg oral dose of azithromycin appears in urine as unchanged drug over a one-week period.
An elimination t_1/2 of 54.5 hours has been reported in children 4 months to 15 years old given a single or multiple doses of azithromycin.
In patients with severe renal impairment [glomerular filtration rate (GFR) <10 mL/min], the C_max and AUC were increased by 61% and 35%, respectively, after administration of a single 1 g dose of azithromycin.
Toxicology: Preclinical safety data: Zenith Suspension: Phospholipidosis (intracellular phospholipid accumulation) has been observed in several tissues (e.g. eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and/or pancreas) of mice, rats, and dogs given high doses of azithromycin. Phospholipidosis has been observed to a similar extent in the tissues of neonatal rats and dogs. The effect has been shown to be reversible after cessation of azithromycin treatment. The significance of the finding in a clinical context is unknown.
Electrophysiological studies have shown that azithromycin prolongs the QT interval.
There was no evidence of a potential for genetic and chromosome mutations in in vivo and in vitro test models.
Long-term studies in animals have not been performed to evaluate carcinogenic potential as the medicinal product is indicated for short-term treatment only and there were no signs indicative of carcinogenic activity.
No teratogenic effects were observed in animal studies of embryotoxicity in mice and rats. In rats, azithromycin doses of 100 and 200 mg/kg bodyweight/day led to mild retardations in foetal ossification and in maternal weight gain. In peri-/postnatal studies in rats, mild retardations following treatment with 50 mg/kg/day azithromycin and above were observed (retardation in physical development and reflex behaviour).
In neonatal studies, rats and dogs did not show higher sensitivity to azithromycin than adult animals of the respective species.

Zenith Suspension: For the treatment of the following infections caused by microorganisms sensitive to azithromycin (see Precautions and Pharmacology: Pharmacodynamics under Actions): Upper respiratory tract infections, including sinusitis, pharyngitis, tonsillitis; Lower respiratory tract infections, including bronchitis and pneumonia; Acute otitis media; Skin and soft tissue infections; Uncomplicated genital infections caused by Chlamydia trachomatis or Neisseria gonorrhoeae (non-multi-resistant strains).
Considerations should be given to official guidance on the appropriate use of antibacterial agents.
Zenith OD Suspension: For the treatment of the following mild to moderate infections caused by susceptible microorganisms: Lower respiratory tract infections: Acute bacterial bronchitis UK; Community-acquired pneumonia (CAP) in patients suitable for outpatient oral treatment. [Note: Azithromycin should not be administered to patients with moderate to severe pneumonia or when there are risk factors that make oral therapy inappropriate (see Precautions)].
Upper respiratory tract infections: Acute bacterial sinusitis; Acute otitis media; Acute streptococcal pharyngitis or tonsillitis (as second-line treatment).
Note: Penicillin is usually the drug of choice for the treatment of streptococcal pharyngitis/tonsillitis and also for prophylaxis of acute rheumatic fever. Azithromycin appears to be as effective as penicillin against streptococcus in the oropharynx, however, the efficacy of azithromycin in the subsequent prevention of rheumatic fever has not been established.
Uncomplicated skin and skin structure infections.
Chlamydia trachomatis conjunctivitis and trachoma.

Zenith Suspension: Azithromycin differs from other antibiotics by its high tissue affinity. Azithromycin reaches levels up to 50 times higher in tissue than in plasma and tissue elimination half-life ranges between 2 to 4 days.
Thus, azithromycin dose regimen differs from that of other antibiotics.
Dosage: Children and adolescents up to 45 kg body weight: The dosage in children and adolescents up to 45 kg body weight (KG) is based on the body weight (BW), taking either 10 mg once a day for 3 days in a 3-day regimen.
Azithromycin per kg BW or alternatively in a 5-day therapy schedule on the first day 10 mg/kg BW and 5 mg/kg BW on days 2 to 5 (exception: see Streptococcal pharyngitis as follows).
Depending on the body weight, dosing is carried out using the examples in the following tables. (See Tables 6 and 7.)

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Acute otitis media: In acute otitis media, the total dose is also 30 mg/kg BW azithromycin. This total dose can be administered as a single dose, 3-day therapy or 5-day therapy (according to the above dosing schedule).
Streptococcal pharyngitis: For streptococcal pharyngitis, 10 mg/kg BW or 20 mg/kg BW azithromycin should be administered daily for 3 days. However, the daily dose must not exceed 500 mg. In clinical trials, both doses showed comparable clinical efficacy. With 20 mg/kg BW, however, a higher bacteriological eradication rate can be achieved. Nevertheless, penicillin remains the first choice of treatment for pharyngitis caused by Streptococcus pyogenes. This also applies to the prevention of rheumatic fever.
A maximum total dose in children corresponds to the usual adult dose of 1,500 mg azithromycin in all indications.
Adults and adolescents over 45 kg body weight: Adults and adolescents over 45 kg body weight (KG) usually receive a total dose of 1,500 mg azithromycin, which can be taken either according to the 3-day therapy schedule or the 5-day therapy schedule: 3-day therapy schedule: 500 mg azithromycin once daily for 3 days, corresponding to 12.5 mL of the prepared suspension once daily.
5-day therapy schedule: Alternatively, a 5-day therapy can be carried out: Day 1: 500 mg azithromycin (corresponding to 12.5 mL suspension) all at once and Days 2 to 5: 250 mg azithromycin each day (corresponding to 6.25 mL suspension).
Uncomplicated genital infections from Chlamydia trachomatis or sensitive Neisseria gonorrhoeae: Deviating from the above-mentioned dosages, a simple dose of 1000 mg azithromycin, corresponding to 25 mL of the prepared suspension, is taken for uncomplicated genital infections from Chlamydia trachomatis or sensitive Neisseria gonorrhoeae.
For adults and adolescents over 45 kg body weight, other suitable dosage forms such as film-coated tablets are also available.
A 5-day treatment regimen of azithromycin was shown to have sufficient efficacy in the treatment of pneumonia. In most cases, use of a 3-day treatment regimen also seems to be sufficient.
Older people: The same dose as in adult patients is used in older people. Since older patients can be patients with ongoing proarrhythmic conditions a particular caution is recommended due to the risk of developing cardiac arrhythmia and torsades de pointes (see Precautions).
In patients with renal impairment: No dose adjustment is necessary in patients with mild to moderate renal impairment with (Glomerular Filtration Rate [GFR] of 10-80 mL/min) (see Precautions and Pharmacology: Pharmacokinetics under Actions).
In patients with hepatic impairment: A dose adjustment is not necessary for patients with mild to moderately impaired liver function (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Method of administration: For oral use after preparation of the suspension (see Preparation of the suspension under Cautions for Usage). Preparation yields a white to off-white or slightly yellowish, homogeneous suspension.
Azithromycin can be taken with meals. The bottle must be shaken vigorously before each use.
The daily dose can be measured as described as follows using the included 10 mL dosing syringe with millilitre scale: Place the dosing syringe in the stopper on the bottle.
Rotate the bottle with the dosing syringe in place.
Withdraw the appropriate number of milliliters of the prescribed daily dose into the syringe.
Stand the bottle upright again before removing the dosing syringe.
The measured amount of the suspension can be emptied directly into the child's mouth - as slowly as possible against the inside of the cheek so that the child does not choke - or first put on a spoon.
After each dose, the bottle should be closed well and the dosing syringe cleaned with water.
Zenith OD Suspension: General Dosing Recommendations: Azithromycin suspension may be taken with or without food.
Azithromycin suspension should be administered using the measuring cup provided.
Usual Oral Pediatric Dose: Total dosage of 30 mg/kg body weight given as: 10 mg/kg body weight once a day for 3 days OR;
10 mg/kg body weight on Day 1 followed by 5 mg/kg body weight once a day for Days 2 to 5. (See Table 8.)

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For pharyngitis/tonsillitis: 12 mg/kg body weight once a day for 5 days.
For conjunctivitis and trachoma in children 12 months or older: 20 mg/kg body weight either as a single dose or once a week for up to 3 weeks;
Or, as prescribed by a physician.
Dosage in Special Populations: Renal Impairment: Dosage adjustment is not necessary in patients with mild to moderate renal impairment (GFR ≤80 mL/min). However, data are limited on the use of azithromycin in patients with severe renal impairment (GFR <10 mL/min).
Hepatic Impairment: Dosage adjustment is not necessary in patients with mild to moderate hepatic impairment. However, since azithromycin is metabolized in the liver and excreted in the bile, the drug is not recommended in patients with significant hepatic disease.
Directions for Reconstitution: For 15 mL bottle: 1. Tap the bottle to loosen the powder.
2. Add 10 mL of water in the bottle.
3. Shake vigorously to mix medicine properly.
4. Shake well before each dose.
5. The reconstituted suspension should be stored at 5°C to 30°C and used within 7 days.
Do not freeze.
For 30 mL bottle: 1. Tap the bottle to loosen the powder.
2. Slowly add water up to the ring mark on bottle.
3. Shake vigorously to mix medicine properly.
4. Add water if necessary to adjust the volume up to the ring mark.
5. Shake well before each dose.
6. The reconstituted suspension should be stored at 5°C to 30°C and used within 7 days.
Do not freeze.

Zenith Suspension: Adverse events experienced in higher than recommended doses were similar to those seen at normal doses.
Symptoms: The typical symptoms of an overdose with macrolide antibiotics include reversible loss of hearing, severe nausea, vomiting and diarrhoea.
Treatment: In the event of overdose, the administration of medicinal charcoal and general symptomatic treatment and supportive measures are indicated as required.
Zenith OD Suspension: Adverse events experienced in higher than recommended doses were similar in nature but may be more frequent than those seen at usual doses. Clinical features of an overdose with macrolides may include reversible hearing loss, severe nausea, vomiting and diarrhea. In case of an overdose, the administration of medicinal charcoal, general symptomatic measures are indicated as required.
Multiple doses of azithromycin, as with cationic amphiphilic drugs, have been shown to induce phospholipidosis (intracellular phospholipid accumulation) in some tissues of mice, rats and dogs. This has been demonstrated in dogs at doses 2 to 3 times greater than the recommended human dose, and in rats at doses comparable to human dose. The effect is reversible upon discontinuation of azithromycin treatment. The clinical significance of these findings in humans is not known.

Zenith Suspension: Hypersensitivity to the active substance, erythromycin, any macrolide or ketolide antibiotic, or to any of the excipients.
Zenith OD Suspension: Hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic, or to any component of the product.
Patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

Zenith Suspension: Hypersensitivity: As with erythromycin and other macrolides, rare serious allergic reactions, including angioneurotic oedema and anaphylaxis (rarely fatal), and dermatologic reactions including acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson syndrome, 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 medicinal product 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 the 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 (see Adverse Reactions). Some patients may have had pre-existing hepatic disease or may have been taking other hepatotoxic medicinal products.
In case of signs and symptoms of liver dysfunction, such as rapid developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy, liver function tests/investigations should be performed immediately. Azithromycin administration should be stopped if liver dysfunction has emerged.
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.
Pseudomembranous colitis: Pseudomembranous colitis has been reported with the use of macrolide antibiotics. This diagnosis should therefore be considered in patients who get diarrhoea after starting treatment with azithromycin.
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 (see Interactions).
Superinfection: As with any antibiotic preparation, observation for signs of superinfection with non-susceptible organisms, including fungi is recommended.
Cross-resistance: Because of existing cross-resistance with erythromycin-resistant gram-positive strains and most strains of methicillin resistant staphylococci, use of azithromycin is not recommended.
Local epidemiology and susceptibility patterns should be taken into consideration.
Serious infections: Azithromycin is not intended to treat suitable severe infections, where fast high blood concentrations of antibiotic have to be achieved.
Clostridium difficile-associated diarrhoea: Clostridium difficile-associated diarrhoea (CDAD) has been reported with 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 causes 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 antibacterial agents.
Cardiovascular events: Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with other macrolides including azithromycin (see Adverse Reactions). Therefore, as the following situations may lead to an increased risk for ventricular arrhythmias (including torsades de pointes) which can lead to cardiac arrest, azithromycin should be used with caution in patients with ongoing proarrhythmic conditions (especially women and elderly patients) such as patients: With congenital or documented QT prolongation.
Currently receiving treatment with other active substances that prolong QT interval such as antiarrhythmics of classes IA (quinidine and procainamide) and class III (dofetilide, amiodarone and sotalol), cisapride and terfenadine (see Interactions); antipsychotic agents such as pimozide; antidepressants such as citalopram; and fluoroquinolones such as moxifloxacin and levofloxacin.
With electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesaemia.
With clinically relevant bradycardia, cardiac arrhythmia or severe cardiac insufficiency.
Epidemiological studies investigating the risk of adverse cardiovascular outcomes with macrolides have shown variable results. Some observational studies have identified a rare short-term risk of arrhythmia, myocardial infarction and cardiovascular mortality associated with macrolides including azithromycin. Consideration of these findings should be balanced with treatment benefits when prescribing azithromycin.
Myasthenia gravis: Exacerbations of the symptoms of myasthenia gravis and new onset of myasthenia syndrome have been reported in patients receiving azithromycin therapy (see Adverse Reactions).
Long-term use: There is no experience on safety and effectiveness of long-term use of azithromycin in the indications mentioned previously. At fast recurrent infections, treatment with other antibiotics should be considered.
Neurological and psychiatric disorders: Azithromycin should be used with caution in patients with neurological and psychiatric disorders.
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.
However, certain adverse reactions, visual impairment and vision blurred may have an effect on a patient's ability to drive or operate machinery (see Adverse Reactions).
Use in Children: Safety and efficacy for the prevention or treatment of Mycobacterium avium complex in children have not been established.
Zenith OD Suspension: Hypersensitivity Reactions: Azithromycin therapy has been associated rarely with serious allergic reactions, including angioedema, anaphylaxis (rarely fatal), and dermatologic reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome, toxic epidermal necrolysis and Drug Reaction/Rash with Eosinophilia and Systemic symptoms (DRESS). Despite initially successful symptomatic treatment of the allergic symptoms when symptomatic therapy was discontinued, the allergic symptoms recurred soon thereafter in some patients without further exposure to azithromycin. Prolonged observation and symptomatic treatment should be given to these patients. The relationship of these episodes to the long tissue t_1/2 of azithromycin and subsequent prolonged exposure to antigen has not been established.
In case of an allergic reaction, azithromycin should be discontinued and appropriate therapy be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.
Hepatotoxicity: Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic liver failure have been reported, some of which have resulted in death.
Liver function tests/investigations should be performed immediately in cases where signs and symptoms of liver impairment occur such as rapid developing asthenia associated with jaundice, dark urine, bleeding tendency, or hepatic encephalopathy. Azithromycin should be discontinued if signs and symptoms of hepatitis occur.
Infantile hypertrophic pyloric stenosis (IHPS): Following the use of azithromycin, infantile hypertropic pyloric stenosis (IHPS) has been reported in neonates (treatment up to 42 days of life). Parents and caregivers should be informed to contact their physician if vomiting or irritability with feeding occurs.
Treatment of Pneumonia: The safety and efficacy of azithromycin in the treatment of pneumonia has only been shown in the treatment of CAP due to Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, or Streptococcus pneumoniae in patients suitable for oral treatment. Azithromycin should not be given to patients with pneumonia who are judged to be inappropriate for oral treatment due to moderate to severe illness or risk factors including patients with the following conditions: cystic fibrosis, nosocomial infection, known or suspected bacteremia, illness requiring hospitalization, elderly or debilitated status, or other significant underlying health problems that may compromise their ability to respond to their illness (including immunodeficiency or functional asplenia).
Clostridium difficile-associated disease (CDAD): This has been reported with the use of nearly all antibacterial agents, including azithromycin, and may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea, or symptoms of colitis, pseudomembranous colitis, toxic megacolon, or perforation of colon subsequent to the administration of any antibacterial agents. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
QT Prolongation: 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. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving azithromycin. Physicians should consider the risk of QT prolongation which can be fatal when weighing the risks and benefits of azithromycin for the following patient groups: Patients with known prolongation of the QT interval, a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure; Patients on drugs known to prolong the QT interval; Patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents, cisapride and terfenadine; antipsychotic agents such as pimozide; antidepressants such as citalopram; and fluoroquinolones such as moxifloxacin and levofloxacin; Patients with electrolyte disturbance, particularly in cases of hypokalemia and hypomagnesemia; Exposed to higher plasma levels of azithromycin (e.g. receiving intravenous azithromycin, hepatobiliary impaired); Elderly patients may be more susceptible to drug-associated effects on the QT interval.
Myasthenia gravis: Exacerbations of the symptoms of myasthenia gravis and new onset of myasthenia syndrome have been reported in patients receiving azithromycin.
Hematologic: Severe neutropenia (WBC <1,000/mm³) may adversely affect the distribution of azithromycin and its transport to the site of infection. Antibacterials with proven efficacy in this population should be used. Efficacy and safety of azithromycin have not been studied in patients with severe neutropenia.
Renal Impairment: In patients with severe renal impairment (GFR <10 mL/min), a 33% increase in systemic exposure to azithromycin was observed.
Ergot Derivatives: Ergotism has been precipitated by coadministration of some macrolide antibiotics in patient receiving ergot derivatives. There are no data concerning the possibility of an interaction between ergot and azithromycin. However, due to the theoretical possibility of ergotism, azithromycin and ergot derivatives should not be coadministered (see Interactions).
Superinfection: As with any antibiotic preparation/antibacterial drugs, observation for signs of superinfection with non-susceptible organisms, including fungi is recommended.
Other Precautions: Use in caution in patients with severe renal impairment and/or significant liver disease.
Azithromycin tablet is not suitable for treatment of severe infections where a high concentration of the antibiotic in the blood is rapidly needed.
Azithromycin is not indicated for the treatment of infected burn wounds.
Used with caution in patients with neurological or psychiatric disorders.
Patients should have a serologic test for syphilis performed at the time of diagnosis.
Appropriate antimicrobial therapy and follow-up tests for this disease should be initiated if infection is confirmed.
Since there is no data on the metabolism and pharmacokinetics of azithromycin in patients with lysosomal lipid storage diseases (e.g., Tay-Sachs disease, Nieman-Pick disease), the use of the drug in such patients is not recommended.
Caution in diabetic patients: Azithromycin suspension contains sucrose.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Prescribing azithromycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to be beneficial to the patient and increases the risk of the development of drug-resistant microorganisms.
Effects on Ability to Drive and Use Machines: Azithromycin may cause dizziness or fatigue. Patients should be advised to avoid performing tasks which require complete mental alertness such as driving and operating machinery.
Use in Children: The safety and efficacy of oral azithromycin for the treatment of CAP, acute otitis media or acute bacterial sinusitis in children younger than 6 months old, or for the treatment of pharyngitis and tonsillitis in children younger than 2 years old have not been established. The safety and efficacy of oral azithromycin for the prevention of MAC infection in children have not been established.
Use in the Elderly: No dose adjustment is necessary in elderly patients with normal renal and hepatic function. Elderly patients may be more susceptible to development of torsades de pointes arrhythmias than younger patients (see QT prolongation as previously mentioned).

Zenith Suspension: Pregnancy: There are no adequate data from the use of azithromycin in pregnant women. In reproduction toxicity studies in animals, azithromycin was shown to pass the placenta, but no teratogenic effects were observed (see Pharmacology: Toxicology: Preclinical safety data under Actions). The safety of azithromycin has not been confirmed with regard to the use of the active substance during pregnancy. Therefore, azithromycin should only be used during pregnancy if the benefit outweighs the risk.
Breastfeeding: Azithromycin has been reported to be secreted into human breast milk, but there are no adequate and well-controlled clinical studies in breastfeeding women that have characterised the pharmacokinetics of azithromycin excretion into human breast milk.
Serious adverse effects of azithromycin on breast-fed infants have not been observed. A decision needs to be made as to whether breastfeeding should be interrupted or whether the azithromycin therapy should be dispensed with or the treatment interrupted. In this context, both the benefits of breastfeeding for the child and the therapeutic benefits for the woman should be taken into account.
Zenith OD Suspension: Pregnancy: Pregnancy Category B.
Reproduction studies have been performed in rats and mice at doses up to moderately maternally toxic levels (200 mg/kg/day). These doses, based on a mg/m² basis, are estimated to be 4 and 2 times, respectively, the human daily dose of 500 mg. No evidence of harm to the fetus has been observed in these animal studies.
However, there are no adequate and controlled studies using azithromycin in pregnant women. Since animal studies are not always predictive of human response, azithromycin should be used in pregnancy only when the potential benefit justifies the potential risk to the fetus.
Lactation: Azithromycin is distributed in human milk and may cause diarrhea, fungal infection of the mucous membrane and sensitization in the breastfed infant. It is recommended to discard the milk during treatment and up to 2 days after discontinuation of treatment. Breastfeeding may be resumed thereafter.

Zenith Suspension: The adverse reactions identified through clinical trial experience and post-marketing surveillance by system organ class and frequency are listed as follows.
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 grouping, undesirable effects are presented in order of decreasing seriousness.
Approximately 13% of the patients in clinical trials reported adverse events, wherein gastrointestinal disorders were the most common.
Adverse reactions possibly or probably related to azithromycin based on clinical trial experience and post-marketing surveillance: Infections and infestations: Uncommon: Candidiasis, vaginal infection, pneumonia, fungal infections, bacterial infection, pharyngitis, gastroenteritis, respiratory disorder, rhinitis, oral candidiasis.
Not known: Pseudomembranous colitis (see Precautions).
Blood and the lymphatic system disorders: Uncommon: Leukopenia, neutropenia, eosinophilia.
Not known: Thrombocytopenia, haemolytic anaemia.
Immune system disorders: Uncommon: Angioedema, hypersensitivity reaction.
Not known: Severe (partly fatal) anaphylactic reaction e.g. anaphylactic shock (see Precautions).
Metabolism and nutrition disorders: Uncommon: Anorexia.
Psychiatric disorders: Uncommon: Nervousness, insomnia.
Rare: Agitation.
Not known: Aggression, anxiety, delirium, hallucination.
Nervous system disorders: Common: Headache.
Uncommon: Dizziness, somnolence, dysgeusia, paraesthesia.
Not known: Syncope, convulsion, hypoesthesia, psychomotor hyperactivity, anosmia, ageusia, parosmia, myasthenia gravis (see Precautions).
Eye disorders: Uncommon: Visual impairment.
Not known: Blurred vision.
Ear and labyrinth disorders: Uncommon: Ear disorder, vertigo.
Not known: Hearing impairment including deafness and/or tinnitus.
Cardiac disorders: Uncommon: Palpitations.
Not known: Torsades de pointes (see Precautions), arrhythmia (see Precautions) including ventricular tachycardia, electrocardiogram QT prolonged (see Precautions).
Vascular disorders: Uncommon: Hot flush.
Not known: Hypotension.
Respiratory, thoracic and mediastinal disorders: Uncommon: Dyspnoea, epistaxis.
Gastrointestinal disorders: Very common: Diarrhoea.
Common: Vomiting, abdominal pain, nausea.
Uncommon: Constipation, flatulence, dyspepsia, gastritis, dysphagia, abdominal distension, dry mouth, eructation, mouth ulceration, salivary hypersecretion.
Not known: Pancreatitis, tongue discoloration.
Hepatobiliary disorders: Rare: Hepatic function abnormal, jaundice cholestatic.
Not known: Hepatic failure (which has rarely resulted in death) (see Precautions), hepatitis fulminant, hepatic necrosis.
Skin and subcutaneous tissue disorders: Uncommon: Rash, pruritus, urticaria, dermatitis, dry skin, hyperhidrosis.
Rare: Photosensitivity reaction, acute generalised exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS)*.
Not known: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.
*Frequency estimated with the "rule of three".
Musculoskeletal and connective tissue disorders: Uncommon: Osteoarthritis, myalgia, back pain, neck pain.
Not known: Arthralgia.
Renal and urinary disorders: Uncommon: Dysuria, renal pain.
Not known: Renal failure acute, nephritis interstitial.
Reproductive system and breast disorders: Uncommon: Metrorrhagia, testicular disorder.
General disorders and administration site conditions: Uncommon: Oedema, asthenia, malaise, fatigue, face oedema, chest pain, pyrexia, pain, peripheral oedema.
Investigations: Common: Lymphocyte count decreased, eosinophil count increased, blood bicarbonate decreased, basophils increased, monocytes increased, neutrophils increased.
Uncommon: Aspartate aminotransferase increased, alanine aminotransferase increased, blood bilirubin increased, blood urea increased, blood creatinine increased, blood potassium abnormal, blood alkaline phosphatase increased, chloride increased, glucose increased, platelets increased, haematocrit decreased, bicarbonate increased, abnormal sodium.
Injury and poisoning: Uncommon: Post procedural complication.
Adverse reactions possibly or probably related to Mycobacterium avium complex prophylaxis and treatment based on clinical trial experience and post-marketing surveillance. These adverse reactions differ from those reported with immediate release or the prolonged release formulations, either in kind or in frequency: Metabolism and nutrition disorders: Common: Anorexia.
Nervous system disorders: Common: Dizziness, headache, paraesthesia, dysgeusia.
Rare: Hypoesthesia.
Eye disorders: Common: Visual impairment.
Ear and labyrinth disorders: Common: Deafness.
Rare: Hearing impaired, tinnitus.
Cardiac disorders: Rare: Palpitations.
Gastrointestinal disorders: Very common: Diarrhoea, abdominal pain, nausea, flatulence, abdominal discomfort, loose stools.
Hepatobiliary disorders: Rare: Hepatitis.
Skin and subcutaneous tissue disorders: Common: Rash, pruritus.
Rare: Stevens-Johnson syndrome, photosensitivity reaction.
Musculoskeletal and connective tissue disorders: Common: Arthralgia.
General disorders and administration site conditions: Common: Fatigue.
Rare: Asthenia, malaise.
Zenith OD Suspension: The most frequently reported adverse effects reported with azithromycin include nausea, vomiting, diarrhea/loose stools, abdominal discomfort (pain, cramps), headache, and rash.
Infections and infestations: Candidiasis/oral candidiasis, fungal/bacterial infection, moniliasis, pseudomembranous colitis.
Blood and lymphatic system disorders: Anemia, eosinophilia, hemolytic anemia, leukocytosis, leukopenia, neutropenia, neutrophilia, thrombocytopenia.
Immune system disorders: Hypersensitivity reactions, anaphylactic reactions, anaphylaxis, angioedema, myasthenia gravis, serum sickness.
Endocrine disorders: Syndrome of inappropriate antidiuretic hormone (SIADH) secretion.
Metabolism and nutrition disorders: Anorexia.
Psychiatric disorders: Aggression/aggressive reaction, agitation, anxiety, delirium, depersonalization, hallucination, insomnia.
Nervous system disorders: Ageusia, anosmia, convulsion, dizziness, dysgeusia, hypoesthesia, hyperkinesia, nervousness, paresthesia, parosmia, psychomotor hyperactivity, restlessness, somnolence, syncope.
Eye disorders: Blurred vision, conjunctivitis, visual impairment.
Ear and labyrinth disorders: Hearing impairment/disturbances including decreased hearing, deafness and/or tinnitus; vertigo.
Cardiac disorders: Arrhythmia, palpitation, torsades de pointes, ventricular tachycardia.
Vascular disorders: Hypotension, hot flush.
Respiratory, thoracic and mediastinal disorders: Bronchospasm, cough increased, dyspnea, epistaxis, pneumonia, pharyngitis, pleural effusion, respiratory disorder, rhinitis.
Gastrointestinal disorders: Abdominal distention, constipation, Clostridium difficile-associated diarrhea and colitis, dry mouth, dysphagia, dyspepsia, enteritis, eructation, esophagitis, flatulence, gastritis, gastroenteritis, melena, mouth ulceration, mucositis, pancreatitis, pseudomembranous colitis, rectal hemorrhage, salivary hypersecretion, stomatitis, tongue/tooth discoloration.
Hepatobiliary disorders: Abnormal liver/hepatic function, hepatitis/drug-induced hepatitis/fulminant hepatitis, cholestatic jaundice, hepatic failure, hepatic necrosis.
Skin and subcutaneous tissue disorders: Acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), dermatitis, dry skin, eczema, erythema multiforme, exfoliative dermatitis, hyperhidrosis, photosensitivity reaction, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), sweating, urticaria.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, osteoarthritis, pain (back, neck).
Renal and urinary disorders: Acute renal failure, dysuria, nephritis/interstitial nephritis, renal pain, urinary frequency.
Reproductive system and breast disorders: Menorrhagia, metrorrhagia, testicular disorder, vaginitis.
General disorders and administration site conditions: Asthenia, chest pain, edema/peripheral edema, facial edema, fatigue, hypothermia, malaise, pyrexia.
Investigations: Increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase, alkaline phosphatase, lactic dehydrogenase (LDH), blood bilirubin, blood creatinine, blood urea, blood potassium, blood alkaline phosphatase, eosinophil count, basophils, monocytes, neutrophils, chloride, glucose, platelet, bicarbonate; decreases in blood bicarbonate, lymphocyte count, hematocrit; abnormal blood potassium, abnormal sodium, prolonged electrocardiogram QT.

Zenith Suspension: 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 medicinal products should not be taken simultaneously, but with an interval of about 2 hours.
Cetirizine: In healthy volunteers, co-administration of a 5-day regimen of azithromycin with cetirizine 20 mg at steady-state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.
Didanosine: (dideoxyinosine): Co-administration of 1,200 mg/day azithromycin with 400 mg/day didanosine in 6 HIV-positive subjects did not appear to affect the steady-state pharmacokinetics of didanosine as compared with placebo.
Digoxin and colchicine (P-gp substrates): 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-gp substrates such as digoxin are administered concomitantly, the possibility of elevated serum concentrations of the substrate should be considered.
It is necessary to perform clinical checks during the azithromycin treatment and possibly to measure serum digoxin levels.
Ergot derivatives: Due to the theoretical possibility of ergotism, the concurrent use of azithromycin with ergot derivatives is not recommended (see Precautions).
Zidovudine: Single 1,000 mg doses and multiple 1,200 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 medicinal products 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 an 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 15 mg 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.
Ciclosporin: In a pharmacokinetic study with healthy volunteers that 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 C_max and AUC_0-5 were found to be significantly elevated. Consequently, caution should be exercised before considering concurrent administration of these medicinal products. If co-administration of these medicinal products is necessary, ciclosporin levels should be monitored and the dose adjusted accordingly.
Efavirenz: Co-administration of a 600 mg single dose of 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 1,200 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 1,200 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 azithromycin 500 mg/day for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single 15 mg dose of midazolam.
Nelfinavir: Co-administration of azithromycin (1,200 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 is required.
Rifabutin: Co-administration of azithromycin and rifabutin did not affect the serum concentrations of either medicinal product.
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 azithromycin 500 mg 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 variable for triazolam compared to triazolam and placebo.
Trimethoprim/sulfamethoxazole: Co-administration of trimethoprim/sulfamethoxazole (160 mg/800 mg) for 7 days with azithromycin 1,200 mg 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.
Other antibiotics: On a possible co-resistance between macrolide antibiotics and azithromycin (e.g. erythromycin) as well as lincomycin and clindamycin is to look at. Concomitant use of several medicinal products from the same group of substances is not recommended.
Medicinal products known to prolong the QT interval: Azithromycin should not be co-administered with other medicinal products, known to prolong the QT interval (see Precautions).
Zenith OD Suspension: See Table 9.

Click on icon to see table/diagram/image

Zenith Suspension: Incompatibilities: Not applicable.
Preparation of the suspension: Shake the dry powder loose. Add the amount of water described as follows to the powder.
Azithromycin monohydrate 200 mg/5 mL: For 20 mL (800 mg) bottle: Add 10.5 mL water.
Shake well until a homogenous suspension is achieved. For administration, the syringe adapter should be placed in the neck of the bottle and the stopper should be opened.

Store at temperatures not exceeding 30°C.
Zenith Suspension: Reconstituted suspension: Do not store above 25°C.
Do not refrigerate or freeze. The ready-to-use suspension is stable for 5 days.

Macrolides

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

Rx