COMPOSITIONS :
Zistic® Film coated caplet 500 mg, each film coated caplet contains : Azithromycin dihydrate equivalent with Azithromycin 500 mg.
DESCRIPTIONS :
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.
INDICATIONS :
Zistic® is indicated for the treatment of patients with mild to moderate infections (i.e., pneumonia,) caused by susceptible strains of the designated microorganisms in the spesific conditions listed as follow :
- Lower respiratory tract : Acute bacterial exacerbations of chronic obstructive pulmonary disease due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae. Community-acquired pneumonia of mild severity due to Streptoccocus pneumoniae or Haemophilus influenzae in patients appropriate for outpatient oral therapy.
- Upper respiratory tract : Streptococcal pharyngitis/tonsillitis : As an alternative to first-line therapy of acute pharyngitis/tonsillitis due to Streptoccocus pyogenes occuring in individuals who cannot use the 1st-line therapy.
- Skin and skin structure : Uncomplicated skin and skin structure infections due to Staphylococus aureus, Streptococcus pyogenes or Streptococcus agalactiae. Abscesses usually required surgical
- Sexually transmitted diseases : Non-gonococcal urethritis and cervicitis due to Chlamydia trachomatis.
Azithromycin, at the recommended dose, should not be relied upon to treat gonorrhea or syphilis. Antimicrobial agents used in high doses for short periods of time to treat non-gonococcal urethritis may mask or delay the symptoms of incubating gonorrhea or syphilis. All patients with sexually-transmitted urethritis or cervicitis should have a serologic test for syphilis and appropriate cultures for gonorrhea performed at the time of diagnosis. Appropriate antimicrobial therapy and follow-up tests for these disease should be initiated if infection is confirmed.
Appropriate culture and susceptibility tests should be performed before treatment to determine the causative organism and its susceptibility to Azithromycin. Therapy with Azithromycin may be initiated before results of these tests are known; the results become available, antimicrobial therapy should be adjusted accordingly.
DOSAGE AND ADMINISTRATIONS :
Zistic® should be administered as a single daily dose. The period of dosing with regard to infection is given below.
Adults (including elderly) :
- For the treatment of sexually transmitted diseases caused by Chlamydia trachomatis, Haemophilus ducreyi or susceptible Neisseria gonorrhoeae the dose is 1000 mg as a single oral dose.
- For all other indications in which the oral formulation is administered, the total dosage of 1500 mg should be given as 500 mg daily for 3 days.
- Elderly patients may be more susceptible to development of torsades de pointes arrhythmia than younger patients (see WARNINGS AND PRECAUTIONS).
Children :
There is no information on children less than 6 months.
The total dose of 30 mg/kg should be given as a single daily dose of 10 mg/kg or as an alternative, given over 5 days with single daily dose of 10 mg/kg dose on day 1, then 5 mg/kg on days 2 – 5.
Patients with renal impairment :
No dose adjustment is necessary in patients with mild to moderate renal impairment (GFR 10 – 80 ml/minute). Caution should be exercised when Azithromycin is administered to patients with severe renal impairment (GFR < 10 ml/minute).
Patients with hepatic impairment :
The same dosage as in patients with normal hepatic function may be used in patients with mild to moderate hepatic impairment.
OVERDOSAGE :
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.
CONTRAINDICATIONS :
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.
PRESENTATIONS :
Zistic® Film coated caplet 500 mg Box, 1 strip @ 10 film coated caplets
Reg. No. DKL9502321309A1
STORAGE :
Zistic® Film coated caplet :
STORE BELOW 30ºC
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
PT. BERNOFARM
Sidoarjo – Indonesia
