Thu 20 Aug 2009
For a lingering suspected infection in my lungs, the doctor from Hospice Care Association had prescribed ZMAX, a single-dosed Antibiotic from Pfizer. It cost a whopping 50 Sing dollars. The following drug information was extracted from Pfizer’s website.
INTRODUCTION
Zmax is indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below.
Adults
Acute bacterial sinusitis due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.
Community-acquired pneumonia due to Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae, in patients appropriate for oral therapy.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Zmax and other antibacterial drugs, Zmax 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.
Appropriate culture and susceptibility tests should be performed before treatment to determine the causative organism and its susceptibility to Zmax. Therapy with Zmax may be initiated before results of these tests are known; once the results become available, antimicrobial therapy should be adjusted accordingly.
Please see below for a list of professional tools, programs, and slides designed to keep you up-to-date on Pfizer medicines and the conditions they treat.
A 12-page brochure for health care professionals that provides a brief overview of the use of single dose Zmax as a treatment for community-acquired pneumonia and acute bacterial sinusitis, including a profile of efficacy, safety, tolerability, and pharmacokinetics.
Please see below for links to access downloadable materials, such as diagnostic screeners and patient support and adherence programs.
Treat sinusitis and pneumonia with a single-dose antibiotic (PDF)
This 10-page brochure answers common patient questions about single-dose Zmax, such as what sinusitis and pneumonia are, what makes Zmax different and when to expect to feel better. It also includes a valuable coupon.
Please see below for a complete description(s) of the condition(s) for which this medicine is indicated.
Zmax is indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below.
Adults
Acute bacterial sinusitis due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.
Community-acquired pneumonia due to Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae, in patients appropriate for oral therapy.
For a complete listing of the conditions indicated for treatment by this medicine, click on the Indication tab above.
Please see below for detailed information on product features and benefits when used to treat the indicated conditions.
Paediatric One-Dose Treatment for CAP
One-dose treatment of Zmax for paediatric community-acquired pneumonia is safe and effective.
A single dose of Zmax is effective against key pathogens in CAP and ABS.
Zmax Concentrations Peak Early and Remain High
Zmax concentrations remain high for at least 10 days.
Early Targeted Delivery to the Site of Infection
Zmax quickly targets areas of inflammation.
Overall clinical cure rates and bacterial eradication rates for Zmax vs. 7-day Levaquin and 7-day Biaxin XL.
Overall clinical cure rates and clinical cure by ABS pathogen for Zmax vs. Levaquin.
The most common treatment-related adverse events and comparison of days of therapy vs. Biaxin XL, Levaquin, and Avelox.
Zmax is Different From Zithromax
Different delivery and bioavailability from other azithromycin formulations.
Lowest Cost of Treatment vs. Competitors
Zmax is cost-effective, single-dose therapy.
Zmax Challenge: Zmax for $20 or less
Take the Zmax Challenge and give your patients the power of Zmax for no more than $20.
Never Pay More Than $20 for Zmax
The Zmax Challenge saves patients money.
Zmax Safety Information
Important Safety Information
Zmax is indicated for mild to moderate Acute Bacterial Sinusitis in adults due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae, and is also indicated for community-acquired pneumonia due to Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, or Streptococcus pneumoniae in adults and paediatrics aged 6 months and over deemed appropriate for oral therapy.
Zmax is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, or any macrolide or ketolide antibiotic. If an allergic reaction occurs, appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.
In the 27 mg/mL currently approved oral suspension (n=61), the most common side effects of Zmax are vomiting (3.3%), diarrhea (1.6%), abdominal pain (1.6%), rash (1.6%), dermatitis (1.6%), fungal rash (1.6%), and constipation (1.6%).
In clinical trials using the 60 mg/mL premarketing oral concentration (n=846), the most common side effects of Zmax are vomiting (11.9%), diarrhea (8%), loose stools (5.6%), abdominal pain (3%), rash (2.8%), nausea (1.7%), and anorexia (1.2%).
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. 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, and appropriate management and treatment of C. difficile should be instituted as clinically indicated.
Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Zmax and other antibacterial drugs, Zmax should be used only to treat infections that are proven or strongly suspected to be caused by bacteria.
Zmax (azithromycin extended release) for oral suspension contains the active ingredient azithromycin (as azithromycin dihydrate), an azalide, a subclass of macrolide antibiotics. Azithromycin has the chemical name (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-Dideoxy-3-C-methyl-3- O-methyl-a-L-ribo-hexopyranosyl(oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[3,4,6-trideoxy-3-(dimethylamino)-ß- D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring. Its molecular formula is C38H72N2O12, and its molecular weight is 749.0.
Azithromycin has the following structural formula:
Azithromycin, as the dihydrate, is a white crystalline powder with a molecular formula of C38H72N2O12·2H2O and a molecular weight of 785.0.
Zmax is a single-dose, extended release formulation of microspheres for oral suspension containing azithromycin (as azithromycin dihydrate) and the following excipients: glyceryl behenate, poloxamer 407, sucrose, sodium phosphate tribasic anhydrous, magnesium hydroxide, hydroxypropyl cellulose, xanthan gum, colloidal silicon dioxide, titanium dioxide, artificial cherry flavour, and artificial banana flavour.
Each bottle contains azithromycin dihydrate equivalent to 2.0 g of azithromycin. It is constituted with 60 mL of water and the entire contents are administered orally as a single dose.
Zmax is indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below.
Adults
Acute bacterial sinusitis due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.
Community-acquired pneumonia due to Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae, in patients appropriate for oral therapy.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Zmax and other antibacterial drugs, Zmax 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.
Appropriate culture and susceptibility tests should be performed before treatment to determine the causative organism and its susceptibility to Zmax. Therapy with Zmax may be initiated before results of these tests are known; once the results become available, antimicrobial therapy should be adjusted accordingly.
CONTRAINDICATION
Zmax is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin or any macrolide or ketolide antibiotic.
Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported rarely in patients on azithromycin therapy using other formulations. Although rare, fatalities have been reported. (See CONTRAINDICATIONS.) 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 exposure to antigen has not been determined.
If an allergic reaction occurs, appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.
Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of “antibiotic-associated colitis.”
After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.
In controlled Phase 3 clinical trials with Zmax, the majority of the reported treatment-related adverse reactions were gastrointestinal in nature and mild to moderate in severity.
Overall, the most common treatment-related adverse reactions in adult subjects receiving a single 2.0 dose of Zmax were diarrhea/loose stools (11.6%), nausea (3.9%), abdominal pain (2.7%), headache (1.3%), and vomiting (1.1%). The incidence of treatment-related gastrointestinal adverse reactions was 17.2% for Zmax and 9.7% for pooled comparators.
No other treatment-related adverse events occurred in subjects on Zmax with a frequency of =1%.
Treatment-related adverse reactions following Zmax treatment that occurred with a frequency of <1% included the following:
Cardiovascular: palpitations, chest pain
Gastrointestinal: constipation, dyspepsia, flatulence, gastritis, oral moniliasis, loose stools
Genitourinary: vaginitis
Nervous System: dizziness, vertigo
General: asthenia
Allergic: rash, pruritus, urticaria
Special Senses: taste perversion
Laboratory Abnormalities
In subjects with normal baseline values, the following clinically significant laboratory abnormalities (irrespective of drug relationship) were reported in Zmax clinical trials:
- with an incidence of greater than or equal to 1%: reduced lymphocytes and increased eosinophils; reduced bicarbonate;
- with an incidence of less than 1%: leukopenia, neutropenia, elevated bilirubin, AST, ALT, BUN, creatinine, alterations in potassium.
Where follow-up was provided, changes in laboratory tests appeared to be reversible.
Post-Marketing Experience with Azithromycin Immediate Release
Adverse events reported with azithromycin during the post-marketing period for which a causal relationship may not be established include:
Allergic: arthralgia, edema, urticaria and angioedema
Cardiovascular: palpitations and arrhythmias including ventricular tachycardia and hypotension. There have been rare reports of QT prolongation and torsades de pointes.
Gastrointestinal: anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea rarely resulting in dehydration, pseudomembranous colitis, pancreatitis, oral candidiasis and rare reports of tongue discoloration
General: asthenia, paresthesia, fatigue, malaise and anaphylaxis (rarely fatal)
Genitourinary: interstitial nephritis, acute renal failure, moniliasis and vaginitis
Hematopoietic: thrombocytopenia, mild neutropenia
Liver/Biliary: abnormal liver function including hepatitis and cholestatic jaundice, as well as rare cases of hepatic necrosis and hepatic failure, some of which have resulted in death
Nervous System: convulsions, dizziness/vertigo, headache, somnolence, hyperactivity, nervousness, agitation and syncope
Psychiatric: aggressive reaction and anxiety
Skin/Appendages: pruritus, rash, photosensitivity, rarely serious skin reactions including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis
Special Senses: hearing disturbances including hearing loss, deafness and/or tinnitus and rare reports of taste perversion and/or loss
General
Because azithromycin is principally excreted via the liver, caution should be exercised when azithromycin is administered to patients with impaired hepatic function. Due to the limited data in subjects with GFR <10 mL/min, caution should be exercised when prescribing azithromycin in these patients. (See CLINICAL PHARMACOLOGY – Special Populations – Renal Insufficiency.)
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. A similar effect with azithromycin cannot be completely ruled out in patients at increased risk for prolonged cardiac repolarization.
Prescribing Zmax 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.
Information for Patients
Patients should be instructed to take Zmax on an empty stomach (at least 1 hour before or 2 hours following a meal).
Patients should be instructed to immediately contact a physician if any signs of an allergic reaction occur.
Patients who vomit within the first hour should contact their health care provider about further treatment.
Keep bottle tightly closed. Store at room temperature. Use within 12 hours of constitution. Shake bottle well before use. The entire contents of the bottle should be consumed.
Patients should be advised that Zmax may be taken without regard to antacids containing magnesium hydroxide and/or aluminium hydroxide.
Patients should be counselled that antibacterial drugs including Zmax should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). Not taking the complete prescribed dose may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Zmax or other antibacterial drugs in the future.
Drug Interactions
Co-administration of nelfinavir at steady-state with a single dose of azithromycin (2 × 600 mg tablets) results in increased azithromycin serum concentrations. Although a dose adjustment of azithromycin is not recommended when administered in combination with nelfinavir, close monitoring for known side effects of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted. (See ADVERSE REACTIONS.)
Azithromycin did not affect the prothrombin time response to a single dose of warfarin. However, prudent medical practice dictates careful monitoring of prothrombin time in all patients treated with azithromycin and warfarin concomitantly. Concurrent use of macrolides and warfarin in clinical practice has been associated with increased anticoagulant effects.
Drug interaction studies were performed with azithromycin and other drugs likely to be co-administered. (See CLINICAL PHARMACOLOGY – Drug-Drug Interactions.) When used in therapeutic doses, azithromycin had a modest effect on the pharmacokinetics of atorvastatin, carbamazepine, cetirizine, didanosine, efavirenz, fluconazole, indinavir, midazolam, rifabutin, sildenafil, theophylline (intravenous and oral), triazolam, trimethoprim/sulfamethoxazole or zidovudine. Co-administration with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin. No dosage adjustment of either drug is recommended when azithromycin is co-administered with any of the above agents.
Interactions with the drugs listed below have not been reported in clinical trials with azithromycin; however, no specific drug interaction studies have been performed to evaluate potential drug-drug interaction. Nonetheless, they have been observed with macrolide products. Until further data are developed regarding drug interactions when azithromycin and these drugs are used concomitantly, careful monitoring of patients is advised:
Digoxin–elevated digoxin concentrations.
Ergotamine or dihydroergotamine–acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
Cyclosporine, hexobarbital and phenytoin concentrations.
Laboratory Test Interactions
There are no reported laboratory test interactions.
Repeat Treatment
Studies evaluating the use of repeated courses of Zmax have not been conducted.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate carcinogenic potential. Azithromycin has shown no mutagenic potential in standard laboratory tests: mouse lymphoma assay, human lymphocyte clastogenic assay, and mouse bone marrow clastogenic assay. No evidence of impaired fertility due to azithromycin was found in rats given daily doses up to 10 mg/kg (approximately 0.05 times the single 2.0 g oral adult human dose on a mg/m2 basis).
Pregnancy
Teratogenic Effects. Pregnancy Category B: Reproduction studies have been performed in rats and mice at doses up to moderately maternally toxic dose concentrations (i.e., 200 mg/kg/day). These daily doses in rats and mice, based on mg/m2, are estimated to be approximately equivalent to one or one-half of, respectively, the single adult oral dose of 2.0 g. In the animal studies, no evidence of harm to the foetus due to azithromycin was found. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, azithromycin should be used during pregnancy only if clearly needed.
Nursing Mothers
It is not known whether azithromycin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when azithromycin is administered to a nursing woman.
Geriatric Use
Data collected from the azithromycin capsule and tablet formulations indicate that a dosage adjustment does not appear to be necessary for older patients with normal renal function (for their age) and hepatic function receiving treatment with Zmax.
In clinical trials of Zmax, 16.6% of subjects were at least 65 years of age (214/1292) and 4.6% of subjects (59/1292) were at least 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.
Zmax 2.0 g oral suspension contains 148 mg of sodium.
Animal Toxicology
Phospholipidosis (intracellular phospholipid accumulation) has been observed in some tissues of mice, rats, and dogs given multiple doses of azithromycin. It has been demonstrated in numerous organ systems (e.g., eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and/or pancreas) in dogs treated with azithromycin at doses which, expressed on the basis of mg/m2, are approximately one-sixth the recommended adult dose, and in rats treated at doses approximately one-fourth the recommended adult dose. This effect has been shown to be reversible after cessation of azithromycin treatment. Based on the pharmacokinetic data, phospholipidosis has been seen in the rat (50 mg/kg/day dose) at the observed maximal plasma concentration of 1.3 µg/mL (1.6 times the observed Cmax of 0.821 µg/mL at the adult dose of 2.0 g). Similarly, it has been shown in the dog (10 mg/kg/day dose) at the observed maximal serum concentration of 1.0 µg/mL (1.2 times the observed Cmax of 0.821 µg/mL at the adult dose of 2.0 g. The significance of the finding for animals and for humans is unknown.
DOSAGE & PREPARATION
Zmax should be taken as a single 2.0 g dose. Zmax provides a full course of antibacterial therapy in a single oral dose. It is recommended that Zmax be taken on an empty stomach (at least 1 hour before or 2 hours following a meal).
In the Phase 3 program, no patient vomited within 5 minutes of dosing Zmax. In the event that a patient vomits within 5 minutes of administration, the health care provider should consider additional antibiotic treatment since there would be minimal absorption of azithromycin. Since insufficient data exist on absorption of azithromycin if a patient vomits between 5 and 60 minutes following administration, alternative therapy should be considered. Neither a second dose of Zmax nor alternative treatment is warranted if vomiting occurs =60 minutes following administration, in patients with normal gastric emptying.
Instructions for Pharmacist
Constitute with 60 mL of water and replace cap. Shake bottle well before dispensing.
Special Populations
Renal Insufficiency:
No dosage adjustment is recommended for patients with renal impairment (GFR 10-80 mL/min). Caution should be exercised when Zmax is administered to patients with end-stage renal disease (GFR <10 mL/min). (See CLINICAL PHARMACOLOGY – Special Populations – Renal Insufficiency.)
Hepatic Insufficiency:
The pharmacokinetics of azithromycin in patients with hepatic impairment have not been established. No dose adjustment recommendations can be made in patients with impaired hepatic function. (See CLINICAL PHARMACOLOGY – Special Populations – Hepatic Insufficiency.)
Zmax is supplied in bottles (NDC 0069-4170-21) containing 2.0 g of azithromycin and should be constituted with 60 mL of water.
See DOSAGE AND ADMINISTRATION for constitution instructions.
Storage
Before constitution, store dry powder at or below 30°C (86°F).
After constitution, store suspension at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Do not refrigerate or freeze.
Constituted suspension should be consumed within 12 hours.
Please note that Pfizer Inc lists active and most inactive ingredients in the package inserts or on the product containers. Inactive ingredients present in trace amounts (e.g., imprint ink) may not be listed. The accuracy of our statements is based upon the final product composition formula only and cannot guarantee that minute amounts of substances are not contained in raw materials obtained from various suppliers for our manufacturing process.
Gluten is a mixture of two proteins, gliadin and glutenin, that are present in wheat flour and to a lesser extent in barley, oats, and rye.1
The pharmacokinetic profile of a novel oral, extended-release, microsphere formulation of azithromycin (AZSR) was compared with that of the commercially available immediate-release azithromycin formulation (AZM) in an open-label, crossover, single-dose study (Study A), and their gastrointestinal tolerability profiles were compared in an observer-blind, parallel group, single-dose study (Study B).
An open-label, randomized, parallel-group study of 24 healthy adult subjects comparing the pharmacokinetic profiles of azithromycin given as a single-dose regimen with those of a 3-day regimen.
An international, multicenter, randomized, double-blind, double-dummy trial to compare the efficacy and safety of a single 2.0-g dose of a novel azithromycin microsphere formulation with that of 10 days of levofloxacin, 500 mg/d, when used to treat adults with uncomplicated acute bacterial maxillary sinusitis.
Non-compliance with antibiotic therapy for acute community infections: a global survey
A global patient survey of non-compliance with antibiotic therapy for acute community infections included 4514 adult respondents (aged 18-99 years) in 11 countries.
A randomized, double-blind, noninferiority study comparing single 2.0-g oral dose of a novel microsphere formulation of azithromycin to 7 days of levofloxacin, 500 mg/day, in the treatment of adult patients with mild to moderate community-acquired pneumonia.
A study comparing the pharmacokinetics of azithromycin in plasma, lung tissue, and bronchial washing after oral administration of 500 mg versus 1000 mg daily for 3 days.
Practice Guidelines in the Diagnosis and Treatment of Community-Acquired Pneumonia
Part of the series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of this guideline is to provide assistance to clinicians in the diagnosis and treatment of community-acquired pneumonia. The targeted groups are immunocompetent adult patients.
A phase III, multinational, multicenter, randomized, double-blind, double-dummy study, comparing single-dose azithromycin microspheres to extended-release clarithromycin, both administered orally.
Important Safety Information For Adults
Zmax fights bacteria that cause infections. These include sinusitis and pneumonia. Like other antibiotics, Zmax takes time to work.
Do not take Zmax if you have a known allergy or hypersensitivity to azithromycin, erythromycin, or any antibiotic.
Call your doctor right away if you have hives, you have trouble swallowing, your face or throat swells, or you have wheezing or trouble breathing after taking Zmax.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes, however, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after taking their last dose of the antibiotic. If this occurs, you should contact your doctor as soon as possible.
The most common side effects in adults taking Zmax are diarrhea/loose stools, nausea, and stomach pain. Others include headache and vomiting. For patients who took Zmax and got diarrhea, most symptoms went away by day 2. Call your doctor if you vomit within one hour of taking Zmax.