Zenith Special Precautions

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.
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 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 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.
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).
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; 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 indications mentioned before. 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.