Zistic® Powder for Infusion 0.5 g, each vial contains : Azithromycin dihydrate sterile buffered sodium citrate lyophilized equivalent to Azithromycin 0.5 g.
Zistic® with Azithromycin dihydrate (equivalent with Azithromycin) as active ingredient is available in film coated caplet 500 mg, dry syrup 200 mg/5 ml and powder for infusion 0.5 g.
Azithromycin IV is indicated for the treatment of Community Acquired Pneumonia (CAP) caused by susceptible organisms, including Legionella pneumophila, in patients who required initial IV therapy.
In combination with Metronidazole, Azithromycin IV is indicated for the treatment of Pelvic Inflammatory Disease (PID) caused by susceptible organisms, in patients who require initial IV therapy.
DOSAGE AND ADMINISTRATIONS :
Treatment of CAP due to the indicated organisms :
Recommended dose : 500 mg IV as a single daily dose for at least 2 days. Intravenous therapy should be followed by oral Azithromycin at a single daily dose of 500 mg to complete a 7 to 10 days course of therapy. The timing of the conversion to oral therapy should be done at the discretion of the physician and in accordance with clinical response.
Treatment of PID due to the indicated organisms :
Recommended dose : 500 mg IV as a single dose for 1 or 2 days. Intravenous therapy should be followed by Azithromycin by the oral route at a single daily dose of 250 mg to complete a 7 days course of therapy. The time of the conversion to oral therapy should be done at the discretion of the physician and in accordance with clinical response. If anaerobic microorganisms are suspected of contributing to the infection, an antimicrobial anaerobic agent may be administered in combination with Azithromycin.
Preparation of the solution for intravenous administration :
Prepare the initial solution of Azithromycin by adding 4.8 ml of Sterile Water For Injection to the 500 mg vial and shaking the vial until all of the drug is dissolved. Since Azithromycin is supplied under vacuum, it is recommended that a standard 5 ml (non-automated) syringe be used to ensure that the exact amount of 4.8 ml of Sterile Water For Injection is dispensed. Each ml of reconstituted solution contains 100 mg Azithromycin.
Chemical and physical in-use stability of the reconstituted product has been demonstrated for 24 hours below 30°C. When diluted according to the instructions, the diluted solution is chemically and physically stable for 24 hours or below 30°C or for 7 days if stored under refrigeration (2 – 8)°C.
To provide Azithromycin over a concentration range of 1.0 – 2.0 mg/ml, transfer 5 ml of the 100 mg/ml Azithromycin solution into the appropriate amount of any of the diluents listed below :
|Final infusion solution concentration (mg/ml)
|Amount of diluent (ml)
The reconstituted solution can be diluted with :
- Sodium chloride 0.9%
- 5% Dextrose in water
Parenteral drug products should be inspected visually for particulate matter prior to administration. If particulate matter is evident in reconstituted fluids, the drug solution should be discarded.
Intravenous administration :
Zistic® Powder for Infusion should be reconstituted and diluted as directed and administered as an intravenous infusion over not less than 60 minutes. Do not administer as an intravenous bolus or an intramuscular injection.
Adverse events experienced in higher than recommended doses were similar to those seen at normal doses. In the event of overdosage, general symptomatic and supportive measures are indicated as required.
Patients with hypersensitivity to Azithromycin, Erythromycin or any macrolide antibiotics.
WARNINGS AND PRECAUTIONS :
As with Erythromycin and other macrolides, rare serious allergic reactions, including angioedema and anaphylaxis (rarely fatal), and dermatologic reactions including Stevens-Johnson Syndrome and toxic epidermal necrolysis (rarely fatal), have been reported. Some of these reactions with Azithromycin have resulted in recurrent symptom and required a longer period of observation and treatment.
If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physician should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.
Since liver is the principal route of elimination for Azithromycin, the use of Azithromycin should be undertaken with caution in patients with significant hepatic disease.
Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis and hepatic failure have been reported, some of which have resulted in death. Discontinue Azithromycin immediately if signs and symptoms of hepatitis occur.
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 those with normal hepatic function. In these patients urinary recovery of Azithromycin appears to increase, perhaps to compensate for reduced hepatic clearance. Hence no dose adjustment is recommended for patients mild to moderate hepatic impairment.
In patients receiving ergot derivatives, ergotism has been precipitated by co-administration of some macrolide antibiotic. 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.
As with any antibiotic preparation, observation for signs of superinfection with non-susceptible organisms, including fungi is recommended.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Azithromycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of Clostridium difficile.
Clostridium difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of Clostridium difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against Clostridium difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of Clostridium difficile and surgical evaluation should be instituted as clinically indicated.
Penicillin is the usual drug of choice in the treatment of Streptococcus pyogenes infections and the prophylaxis of rheumatic fever. Azithromycin is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx. Because some strains are resistant to Azithromycin, susceptible test should be performed when patients are treated with Azithromycin. Data establishing efficacy of Azitromycin in subsequent prevention of rheumatic fever are not available. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physician should aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.
Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for outpatient oral therapy because of moderate to severe illness or risk factors such as any of the following :
- Patients with nosocomially acquired infections.
- Patients with known or suspected bacteremia.
- Patients requiring hospitalization.
- Elderly or debilitated patients, or
- Patients with significant underlying health problems that may compromise their ability to respond to their illness (including immunodeficiency or functional asplenia).
In patients with severe renal impairment (GFR < 10 ml/minute) a 33% increase in systemic exposure to Azithromycin was observed.
Due to the sucrose content, this medicinal product is not indicated for persons with fructose intolerance (hereditary fructose intolerance), glucose-galactose malabsorption or saccharase-isomaltase deficiency.
No dose adjustment is needed in patients with mild renal impairment (creatinine clearance > 40 mg/minute) but there are no data regarding Azithromycin usage in patients with more severe renal impairment.
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 caution is required when treating :
- Patients with congenital or documented QT prolongation.
- Patients currently receiving treatment with other active substance known to prolong QT interval such as antiarrhytmics of classes IA and III, antipsychotic agents, antidepressants and Fluoroquinolones.
- Patients with electrolyte disturbance, particularly in cases of hypokalemia and hypomagnesemia.
- Patients with clinically relevant bradycardia, cardiac arrhythmia or cardiac insufficiency.
- Elderly patients may be more susceptible to drug-associated effects on the QT interval.
Pregnancy and lactation :
Animal reproduction studies have been performed at doses up to moderately maternally toxic dose concentration. 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 woman. Because animal reproduction studies are not always predictive of human response, Azithromycin should be used during pregnancy only if clearly needed.
Azithromycin has been reported to be excreted into human breast milk but there are no adequate and well controlled clinical studies in nursing women that have characterized the pharmacokinetics of Azithromycin excretion into human breast milk.
In fertility studies conducted in rat, reduced pregnancy rates were noted following administration of Azithromycin. The relevance of this finding to human is unknown.
Effect 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.
Zistic® Powder for Infusion 0.5 g Box, 1 vial @ 0.5 g
Reg. No. DKL1302347480A1
STORE BELOW 30ºC
Stable reconstitution solution within 24 hours when stored below 30°C. When reconstituted as directed, chemical and physical solubility stable for 24 hours under the temperature of 30°C or for 7 days if stored at refrigerator temperature (2 – 8)°C.
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
Sidoarjo – Indonesia