Zenith Suspension/Zenith OD Suspension Special Precautions

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).