Azenil Suspension

/ Pfizer

Oral azithromycin should be administered as a single daily dose. The period of dosing with regard to infection is given below.
Powder for oral suspension can be taken with or without food.
In Adults: For the treatment of sexually transmitted diseases caused by Chlamydia trachomatis, the dose is 1000 mg as a single oral dose.
ZITHROMAX IV: For the treatment of adult patients with CAP due to the indicated organisms, the recommended dose of intravenous azithromycin is 500 mg as a single daily dose by the IV route for at least two days. Intravenous therapy should be followed by oral azithromycin at a single daily dose of 500 mg to complete a 7 to 10 day 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.
For the treatment of adult patients with PID due to the indicated organisms, the recommended dose of intravenous azithromycin is 500 mg as a single dose by the IV route for one or two days. Intravenous therapy should be followed by azithromycin by the oral route at a single daily dose of 250 mg to complete a 7-day 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. If anaerobic microorganisms are suspected of contributing to the infection, an antimicrobial anaerobic agent may be administered in combination with azithromycin.
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. As an alternative, the same total dose can be given over 5 days with 500 mg given on day 1, then 250 mg daily on days 2 to 5.
Intravenous Administration: After reconstitution and dilution, the recommended route of administration for intravenous azithromycin is by IV infusion only. Do not administer as an intravenous bolus or an intramuscular injection.
The infusate concentration and rate of infusion for azithromycin intravenous (IV) should be either 1 mg/ml over 3 hours or 2 mg/ml over 1 hour. An intravenous dose of 500 mg azithromycin should be infused for a minimum duration of one (1) hour.
In Children: Children over 45kg body weight and adults, including elderly patients: The total dose of azithromycin is 1500mg which should be given over three days (500mg once daily). In uncomplicated genital infections due to Chlamydia trachomatis, the dose is 1000mg as a single oral dose.
In general, the total dose in children is 30 mg/kg. Treatment for pediatric streptococcal pharyngitis should be dosed at a different regimen. The total dose of 30 mg/kg should be given as a single daily dose of 10 mg/kg daily for 3 days, or given over 5 days with a single daily dose of 10 mg/kg on day 1, then 5 mg/kg on days 2-5. As an alternative to the above dosing, treatment for children with acute otitis media can be given as a single dose of 30 mg/kg.
For pediatric streptococcal pharyngitis: azithromycin given as a single dose of 10 mg/kg or 20 mg/kg for 3 days has been shown to be effective; however, a daily dose of 500 mg must not be exceeded. In clinical trials comparing these two dosage regimens, similar clinical efficacy was observed but greater bacteriologic eradication was evident at the 20 mg/kg per day dose. However, penicillin is the usual drug of choice in the treatment of Streptococcus pyogenes pharyngitis, including prophylaxis of rheumatic fever.
For children weighing less than 15 kg, azithromycin suspension should be measured as closely as possible. For children weighing 15 kg or more, azithromycin suspension, should be administered according to the guide provided at the attached doctor’s leaflet.
There is no information on children less than 6 months of age.
Elderly: The same dosage as in adult patients is used in the elderly. Elderly patients may be more susceptible to development of torsades de pointes arrhythmia than younger patients.
Patients with Renal Impairment: No dose adjustment is necessary in patients with mild to moderate renal impairment (GFR 10 – 80 ml/min). Caution should be exercised when azithromycin is administered to patients with severe renal
impairment (GFR < 10 ml/min).
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. Since azithromycin is metabolised in the liver and excreted in the
bile, the drug should not be given to patients suffering from severe liver disease. No studies have been conducted regarding treatment of such patients with azithromycin.

Infections caused by susceptible organism in lower respiratory tract infections including: bronchitis, and pneumonia, skin and soft tissue infections, otitis media; upper respiratory tract infections including sinusitis, pharyngitis/tonsilitis. Also in uncomplicated genital infections due to chlamydia trachmastis.
Limitations of Use: Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for oral therapy because of moderate to severe illness or risk factors such as any of the following:
• patients with cystic fibrosis,
• patients with nosocomial 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).
Usage: To reduce the development of drug-resistant bacteria and maintain the effectiveness of Azenil (azithromycin) and other antibacterial drugs, Azenil (azithromycin) should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and
susceptibility patterns may contribute to the empiric selection of therapy.

Hypersensitivity: AZENIL is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drug, or to any of the excipients.
Hepatic Dysfunction: AZENIL is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

Hypersensitivity: Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported in patients on azithromycin therapy.
Fatalities have been reported. Cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have also been reported. 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 azithromycin exposure. These patients required prolonged periods of observation and symptomatic treatment. The relationship of these episodes to the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen is presently unknown.
If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that allergic symptoms may reappear when symptomatic therapy has been discontinued.
Hepatotoxicity: 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), IHPS has been reported. Direct parents and caregivers to contact their physician if vomiting or irritability with feeding occurs.
QT Prolongation: Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen with treatment with macrolides, including azithromycin. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving azithromycin. Providers should consider the risk of QT prolongation which can be fatal when weighing the risks and benefits of azithromycin for at-risk groups including:
• 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.
Elderly patients may be more susceptible to drug-associated effects on the QT interval.
Clostridium difficile-associated diarrhea: 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 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 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 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.
Exacerbation of Myasthenia Gravis: Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients
receiving azithromycin therapy.
Use in Sexually Transmitted Infections: Azenil, at the recommended dose, should not be relied upon to treat syphilis. Antibacterial agents used to treat non-gonococcal urethritis may mask or delay the symptoms of incubating syphilis. All patients with sexually transmitted urethritis or cervicitis should have a serologic test for syphilis and appropriate testing for gonorrhea performed at the time of diagnosis. Appropriate antibacterial therapy and follow-up tests for these diseases should be initiated if infection is confirmed.
Development of Drug-Resistant Bacteria: Prescribing AZENIL in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Excipients: Patients with rare hereditary problems of galactose intolerance, fructose intolerance total lactase deficiency, glucosegalactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Adults: Multiple-dose regimens: Overall, the most common treatment-related adverse reactions in adult patients receiving multiple-dose regimens of AZENIL were related to the gastrointestinal system with diarrhea/loose stools (4 to 5%), nausea (3%), and abdominal pain (2 to 3%) being the most frequently reported.
Single 1-gram dose regimen: Overall, the most common adverse reactions in patients receiving a single-dose regimen of 1 gram of AZENIL were related to the gastrointestinal system and were more frequently reported than in patients receiving the multiple-dose regimen.
Pediatric Patients: Single and Multiple-dose regimens: The types of adverse reactions in pediatric patients were comparable to those seen in adults, with different incidence rates for the dosage regimens recommended in pediatric patients.
Acute Otitis Media: For the recommended total dosage regimen of 30 mg/kg, the most frequent adverse reactions (≥1%) attributed to treatment were diarrhea, abdominal pain, vomiting, nausea, and rash.
See prescribing information for full details.

Nelfinavir: Co-administration of nelfinavir at steady-state with a single oral dose of azithromycin resulted in increased azithromycin serum concentrations. Although a dose adjustment of azithromycin is not recommended when administered in combination with nelfinavir, close monitoring for known adverse reactions of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted.
Warfarin: Spontaneous postmarketing reports suggest that concomitant administration of azithromycin may potentiate the effects of oral anticoagulants such as warfarin, although the prothrombin time was not affected in the dedicated drug interaction study with azithromycin and warfarin. Prothrombin times should be carefully monitored while patients are receiving azithromycin and oral anticoagulants concomitantly.
Potential Drug-Drug Interaction with Macrolides: Interactions with digoxin, colchicine or phenytoin have not been reported in clinical trials with azithromycin. No specific drug interaction studies have been performed to evaluate potential drug-drug interaction. However, drug interactions have been observed with other macrolide products. Until further data are developed regarding drug interactions when digoxin, colchicine or phenytoin are used with azithromycin careful monitoring of patients is advised.

Pregnancy: Available data from published literature and postmarketing experience over several decades with azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Developmental toxicity studies with azithromycin in rats, mice, and rabbits showed no drug-induced fetal malformations at doses up to 4, 2, and 2 times, respectively, an adult human daily dose of 500 mg based on body surface area. Decreased viability and delayed development were observed in the offspring of pregnant rats administered azithromycin from day 6 of pregnancy through weaning at a dose equivalent to 4 times an adult human daily dose of 500 mg based on body surface area.
Lactation: Azithromycin is present in human milk. Non-serious adverse reactions have been reported in breastfed infants after maternal administration of azithromycin. There are no available data on the effects of azithromycin on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AZENIL and any potential adverse effects on the breastfed infant from AZENIL or from the underlying maternal condition.
Advise women to monitor the breastfed infant for diarrhea, vomiting, or rash.
See prescribing information for full details.

Adverse events experienced in higher than recommended doses were similar to those seen at normal doses. The typical symptoms of an overdose with macrolide antibiotics include reversible loss of hearing, severe nausea, vomiting and diarrhoea. In the event of overdose, the administration of medicinal charcoal and general symptomatic and supportive measures are indicated as required.

Shelf-life: The expiry date of the product is indicated on the packaging materials. After reconstitution of the powder, the product should be used within 5 days.