ADVERSE REACTIONS
Clinical studies experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adults:
The data described below reflect exposure to Zmax in 728 adult patients. All patients received a single 2 g oral dose of Zmax. The population studied had community-acquired pneumonia and acute bacterial sinusitis.
In controlled 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 patients receiving a single 2 g dose of Zmax were diarrhea/loose stools (12%), nausea (4%), abdominal pain (3%), headache (1%), and vomiting (1%). The incidence of treatment-related gastrointestinal adverse reactions was 17% for Zmax and 10% for pooled comparators.
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
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.
Pediatric Patients:
The data described below reflect exposure to Zmax in 907 pediatric patients. The population was 3 months to 12 years of age. All patients received a single 60 mg/kg oral dose of Zmax.
As in adults, the most common treatment-related adverse reactions in pediatric subjects were gastrointestinal in nature. The pediatric subjects all received a single 60 mg/kg dose (equivalent to 27 mg/lb) of Zmax.
In a study with 450 pediatric subjects (ages 3 months to 48 months), vomiting (11%), diarrhea (10%) loose stools (9%), and abdominal pain (2%) were the most frequently reported treatment-related gastrointestinal adverse reactions. Many treatment related gastrointestinal adverse reactions with an incidence greater than 1% began on the day of dosing in these subjects [43% (68/160)] and most [53% (84/160)] resolved within 48 hours of onset. Treatment-related adverse events that were not gastrointestinal, occurring with a frequency ≥ 1% were: rash (5%), anorexia (2%), fever (2%), and dermatitis (2%).
In a second study of 337 pediatric subjects, ages 2 years to 12 years, the most frequently reported treatment-related adverse reactions also included vomiting (14%), diarrhea (7%), loose stools (2%), nausea (4%) and abdominal pain (4%).
A third study investigated the tolerability of two different concentrations of azithromycin oral suspension in 120 pediatric subjects (ages 3 months to 48 months), all of whom were treated with azithromycin. The study evaluated the hypothesis that a more dilute, less viscous formulation (the recommended 27 mg/mL concentration of Zmax) is less likely to induce vomiting in young children than a more concentrated suspension used in other pediatric studies. The vomiting rate for subjects taking the dilute concentration azithromycin was 3% (2/61). The rate was numerically lower but not statistically different from the vomiting for the more concentrated suspension Across both treatment arms, the only treatment-related adverse events with a frequency of ≥ 1% were vomiting (6%, 7/120) and diarrhea (2%, 2/120).
Treatment-related adverse reactions with a frequency of < 1% following Zmax treatment in all 907 pediatric subjects in the Phase 3 studies were:
Body as a whole: chills, fever, flu syndrome, headache;
Digestive: abnormal stools, constipation, dyspepsia, flatulence, gastritis, gastrointestinal disorder, hepatitis;
Hemic and Lymphatic : leukopenia;
Nervous System : agitation, emotional liability, hostility, hyperkinesia, insomnia, irritability, parasthesia, somnolence;
Respiratory: asthma, bronchitis, cough increased, dyspnea, pharyngitis, rhinitis;
Skin and Appendages: dermatitis, fungal dermatitis, maculopapular rash, pruritus, urticaria;
Special Senses: otitis media, taste perversion;
Urogenital: dysuria.
Laboratory Abnormalities
In subjects with normal baseline values, the following clinically significant laboratory abnormalities (irrespective of drug relationship) were reported in Zmax pediatric clinical trials:
- -with an incidence of greater than or equal to 1%: elevated eosinophils, BUN, and potassium; decreased lymphocytes; and alterations in neutrophils;
- -with an incidence of less than 1%: elevated SGOT, SGPT and creatinine; decreased potassium; and alterations in sodium and glucose.
Postmarketing experience with other azithromycin products
Because these reactions are reported voluntarily from a population of uncertain size, reliably estimating their frequency or establishing a causal relationship to drug exposure is not always possible.
Adverse events reported with azithromycin immediate release formulations during the postmarketing 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/smell perversion and/or loss
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REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO ZMAX
Below is a sample of reports where side effects / adverse reactions may be related to Zmax. The information is not vetted and should not be cosidered as verified clinical evidence.
Possible Zmax side effects / adverse reactions in 58 year old female
Reported by a consumer/non-health professional from United States on 2007-01-12
Patient: 58 year old female
Reactions: Weight Decreased, Diarrhoea, Nausea, Pain, Stomach Discomfort, Discomfort
Adverse event resulted in: disablity
Suspect drug(s):
Zmax
Possible Zmax side effects / adverse reactions in 21 year old female
Reported by a physician from United States on 2007-07-05
Patient: 21 year old female weighing 73.5 kg (161.7 pounds)
Reactions: Hypersensitivity, Vomiting, Nausea, Hypotension, Abdominal Pain Upper, Diarrhoea, Palpitations, Heart Rate Increased
Adverse event resulted in: hospitalization
Suspect drug(s):
Zmax
Dosage: (2 gram, 1 in 1 d), oral
Administration route: Oral
Indication: Sinusitis
Start date: 2007-03-23
End date: 2007-03-23
Zmax
Dosage: (2 gram, 1 in 1 d), oral
Administration route: Oral
Indication: Tonsillitis
Start date: 2007-03-23
End date: 2007-03-23
Other drugs received by patient: Yasmin
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