vesicular rash
Azithromycin (Zithromax) Adverse Reactions
During clinical trials of azithromycin, adverse reactions were mild to moderate in severity and were reversible upon discontinuation of the drug. The most common adverse reactions in adults receiving multiple-dose regimens of azithromycin were diarrhea/loose stools (4 - 5%), nausea/vomiting (3%/<1%), and abdominal pain (2 - 3%). No other treatment-related adverse reactions were reported on the multiple-dose regimens with a frequency greater than 1%. Adverse GI and genitourinary effects occurring in <= 1% of patients receiving multiple-dose azithromycin included dyspepsia, flatulence, melena, nephritis, vaginal candidiasis, and vaginitis. The most common adverse reactions associated with single-dose regimens of azithromycin were gastrointestinal and were more frequently reported than in multiple-dose regimens. Adverse GI and genitourinary effects associated with single 1-gram azithromycin doses included diarrhea/loose stools (7%), nausea/vomiting (5%/2%), abdominal pain (5%), dyspepsia (1%), and vaginitis (1%). Adverse GI and genitourinary effects associated with single 2-gram azithromycin doses were included nausea/vomiting (18%/7%), diarrhea/loose stools (14%), abdominal pain (7%), vaginitis (2%), dyspepsia (1%), and dizziness (1%). The types of adverse reactions for single and multiple-dose regimens in children were comparable to those seen in adults, with different incidence rates for the dosage regimens recommended in children. The most common (> 1% of patients) adverse reactions in children were abdominal pain, diarrhea, headache, nausea/vomiting, and rash. No other treatment-related adverse reactions were reported in children with a frequency greater than 1%. Adverse GI effects occurring in <= 1% of children receiving azithromycin included anorexia, constipation, dyspepsia, enteritis, flatulence, gastritis, jaundice, and oral candidiasis. Approximately 0.7% of patients (adults and children) from the 5-day multiple-dose clinical trials discontinued azithromycin therapy because of treatment-related adverse reactions. In clinical trials in children receiving 30 mg/kg PO, either as a single dose or over 3 days, discontinuation due to treatment-related adverse reactions was about 1%. Most adverse reactions leading to discontinuation of oral azithromycin were gastrointestinal and included abdominal pain, diarrhea, and nausea/vomiting. Diarrhea (8.5%), nausea (6.6%, vaginitis (2.8%), abdominal pain (1.9%), anorexia (1.9%) are the most frequently reported GI adverse effects associated with intravenous azithromycin. Post-marketing adverse GI and genitourinary reactions have also included acute renal failure (unspecified), interstitial nephritis, pancreatitis and rare reports of tongue discoloration.
Post marketing reports indicate that azithromycin has been associated with abnormal liver function including hepatitis and cholestasis with jaundice. Also, rare cases of hepatic necrosis and hepatic failure, some of which have resulted in death, have been reported.
Azithromycin can disturb the normal bacterial flora, causing an overgrowth of Candida. Candidiasis and vaginitis have been reported for both oral and intravenous dosage forms. Antibiotic interference with the normal flora of the colon may allow an overgrowth of clostridia. It has been established that a toxin produced by Clostridium difficile is a primary cause of ‘antibiotic-associated colitis.’ The possibility of pseudomembranous colitis should be considered in patients presenting with a severe watery diarrhea. Pseudomembranous colitis has occurred rarely with azithromycin.
Hematologic adverse reactions have been reported with azithromycin. In children, anemia and leukopenia have occurred in less than 1% of patients. Thrombocytopenia has been reported during post marketing surveillance.
Respiratory adverse reactions have been reported in less than 1% of children receiving azithromycin. These adverse reactions have included cough, pharyngitis, pleural effusion, and rhinitis.
Injection site reactions are associated with intravenous azithromycin. The most frequent types of injection site reaction are erythema, pain, rash, redness, and tenderness.
Fatigue, facial edema, fever, malaise, pain (unspecified) have been reported in less than 1% of patients receiving azithromycin. Other post-marketing general adverse reactions include asthenia and paresthesias.
Central nervous system adverse reactions occurred in less than 1% of patients receiving azithromycin. These CNS adverse reactions include agitation, dizziness, headache, hyperkinesis, insomnia, nervousness, seizures, somnolence (drowsiness), and vertigo. Post-marketing CNS effects have also included hyperactivity and syncope. Post-marketing psychiatric adverse reactions include aggression and anxiety.
Cardiovascular adverse reactions associated with azithromycin have been reported in less than 1% of patients. These adverse reactions include chest pain (unspecified), palpitations, and arrhythmias including ventricular tachycardia and hypotension. Although uncommon, these are potentially serious adverse reactions.
Adverse reactions affecting the special senses were reported in less than 1% of patients receiving azithromycin and include conjunctivitis, hearing disturbances including hearing loss, deafness and/or tinnitus, and rare reports of dysgeusia.
Dermatological adverse reactions occur in less than 1% of patients receiving oral azithromycin and are usually mild. The most frequently reported dermatological adverse reactions include diaphoresis, eczema, fungal dermatitis, pruritus, urticaria, and vesicular rash. Rash (unspecified) and pruritus occurred in 1.9% of patients receiving intravenous azithromycin. Rare serious skin reactions including erythema multiforme, Steven Johnson Syndrome, and toxic epidermal necrolysis have been reported. Azithromycin therapy should be withdrawn if there are signs and symptoms of an allergic reaction such as angioedema, arthralgia, edema, photosensitivity, pruritus, rash, urticaria. Angioedema indicates a severe hypersensitivity reaction. Some patients have a recurrence of allergic symptoms once symptomatic treatment is withdrawn, even though azithromycin therapy is not reinstated. Correlation between the long tissue half-life of azithromycin and duration of allergic symptoms has not yet been determined. Anaphylaxis has been rarely reported.
Azithromycin has been associated with acute generalized exanthematous pustulosis (AGEP). The nonfollicular, pustular, erythematous rash starts suddenly, is associated with fever above 38 degrees C, and is distinct from pustular psoriasis, although biopsy results in each reveal spongiform subcorneal pustules. Drugs are the main cause of AGEP. A period of 2 - 3 weeks after an inciting drug exposure appears necessary for a first episode of AGEP. Unintentional reexposure may cause a second episode within 2 days. Clinical presentation is diverse with cutaneous lesions beyond erythema and pustules present in half of the cases. For example, bullous lesions, edema, purpura, pruritus, and mucosal erosions are possible. The mean duration of the pustules is 9.7 days followed by an annular desquamation, as long as the causative drug or factor is discontinued. The physiopathological mechanisms of AGEP have not been determined but the pathological criteria of edema, leukocytoclastic vasculitis, eosinophil exocytosis, and keratinocyte focal necrosis are distinctive. Pustule confluence or very small pustules may lead a clinician to make an incorrect diagnosis of TEN, of drug-induced erythroderma, or of staphylococcal scalded skin syndrome.
[ Last revised: 8/10/2004 12:35:00 PM ]
References
. Beylot C, Doutre M, Beylot-Barry M. Acute generalized exanthematous pustulosis. Semin Cutan Med Surg 1996;15:244 - 9.
Related entries
Monthly Archives
Syndicate
Allergies
