SIDE EFFECTS

TROVAN®/Zithromax® Compliance Pak (trovafloxacin and azithromycin)

Twenty healthy subjects participated in a Phase 1 pharmacokinetic study to assess the safety of the TROVAN®/Zithromax® Compliance Pak (trovafloxacin and azithromycin) .

Treatment-Related Adverse Events (>1%) Associated with TROVAN Use Alone or in Combination with ZITHROMAX

The adverse events listed in the table above were obtained from the experience of the 20 healthy volunteers that participated in the study and were described as mild to moderate in nature.

Trovafloxacin

Over 6000 patients have been treated with TROVAN in multidose clinical efficacy trials worldwide.

In TROVAN studies, the majority of adverse reactions were described as mild in nature (over 90% were described as mild or moderate). TROVAN was discontinued for adverse events thought related to drug in 5% of patients (dizziness 2.4%, nausea 1.9%, headache 1.1%, and vomiting 1.0%).

Dizziness/lightheadedness on TROVAN is generally mild, lasts for a few hours following a dose, and in most cases, resolves with continued dosing. The incidence of dizziness and lightheadedness in TROVAN patients over 65 years is 3.1% and 0.6%, respectively. (See PRECAUTIONS and PATIENT INFORMATION)

TROVAN appears to have a low potential for phototoxicity. In clinical trials with TROVAN, only mild, treatment-related phototoxicity was observed in less than 0.03% (2/7096) of patients.

Additional reported drug-related events in clinical trials (remotely, possibly, probably or unknown) that occurred in <1% of TROVAN-treated patients are:

APPLICATION/INJECTION/INSERTION SITE: Application/injection/insertion site device complications, inflammation, pain, edema

AUTONOMIC NERVOUS: flushing, increased sweating, dry mouth, cold clammy skin, increased saliva

CARDIOVASCULAR: peripheral edema, chest pain, thrombophlebitis, hypotension, palpitation, periorbital edema, hypertension, syncope, tachycardia, angina pectoris, bradycardia, peripheral ischemia, edema, dizziness postural

CENTRAL &PERIPHERAL NERVOUS SYSTEM: confusion, paresthesia, vertigo, hypoesthesia, ataxia, convulsions, dysphonia, hypertonia, migraine, involuntary muscle contractions, speech disorder, encephalopathy, abnormal gait, hyperkinesia, hypokinesia, tongue paralysis, abnormal coordination, tremor, dyskinesia

GASTROINTESTINAL: altered bowel habit, constipation, Clostridium difficile-associated diarrhea, dyspepsia, flatulence, loose stools, gastritis, dysphagia, increased appetite, gastroenteritis, rectal disorder, colitis, pseudomembranous colitis, enteritis, eructation, gastrointestinal disorder, melena, hiccup

ORAL CAVITY: gingivitis, stomatitis, altered saliva, tongue disorder, tongue edema, tooth disorder, chelitis, halitosis

GENERAL/OTHER: fever, fatigue, pain, asthenia, moniliasis, hot flushes, back pain, chills, infection (bacterial, fungal), malaise, sepsis, alcohol intolerance, allergic reaction, anaphylactoid reaction, drug (other) toxicity/reaction, weight increase, weight decrease

HEMATOPOIETIC: anemia, granulocytopenia, hemorrhage unspecified, leukopenia, prothrombin decreased, thrombocythemia, thrombocytopenia

LIVER/BILIARY: increased hepatic enzymes, hepatic function abnormal, bilirubinemia, discolored feces, jaundice

METABOLIC/NUTRITIONAL: hyperglycemia, thirst

MUSCULOSKELETAL: arthralgia, muscle cramps, myalgia, muscle weakness, skeletal pain, tendinitis, arthropathy

PSYCHIATRIC: anxiety, anorexia, agitation, nervousness, somnolence, insomnia, depression, amnesia, concentration impaired, depersonalization, dreaming abnormal, emotional lability, euphoria, hallucination, impotence, libido decreased-male, paroniria, thinking abnormal

REPRODUCTIVE: Female: leukorrhea, menstrual disorder; Male: balanoposthitis

RESPIRATORY: dyspnea, rhinitis, sinusitis, bronchospasm, coughing, epistaxis, respiratory insufficiency, upper respiratory tract infection, respiratory disorder, asthma, hemoptysis, hypoxia, stridor

SKIN/APPENDAGES: pruritus ani, skin disorder, skin ulceration, angioedema, dermatitis, dermatitis fungal, photosensitivity skin reaction, seborrhea, skin exfoliation, urticaria

SPECIAL SENSES:taste perversion, eye pain, abnormal vision, conjunctivitis, photophobia, conjuctival hemorrhage, hyperacusis, scotoma, tinnitus, visual field defect, diplopia, xerophthalmia

URINARY SYSTEM: dysuria, face edema, micturition frequency, interstitial nephritis, renal failure acute, renal function abnormal, urinary incontinence

Azithromycin

In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Approximately 0.7% of the patients from the multiple-dose clinical trials discontinued ZITHROMAX® (azithromycin) therapy because of treatment-related side effects. Most of the side effects leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. Rarely but potentially serious side effects were angioedema and cholestatic jaundice.

Single 1-gram dose regimen: Overall, the most common side effects in patients receiving a single-dose regimen of 1 gram of ZITHROMAX® were related to the gastrointestinal system and were more frequently reported than in patients receiving the multiple-dose regimen.

Side effects that occurred in patients on the single one-gram dosing regimen of ZITHROMAX® with a frequency of 1% or greater included diarrhea/loose stools (7%), nausea (5%), abdominal pain (5%), vomiting (2%), dyspepsia (1%), and vaginitis (1%).

LABORATORY CHANGES - Trovafloxacin: Changes in laboratory parameters, without regard to drug relationship, occurring in ≥ 1% of TROVAN-treated patients were: decreased hemoglobin and hematocrit; increased platelets; decreased and increased WBC; eosinophilia; increased ALT (SGPT), AST (SGOT), and alkaline phosphatase; decreased protein and albumin; increased BUN and creatinine; decreased sodium; and bicarbonate. It is not known whether these abnormalities were caused by the drug or the underlying condition being treated.

The incidence and magnitude of liver function abnormalities with TROVAN were the same as comparator agents except in the only study in which oral TROVAN was administered for 28 days. In this study (chronic bacterial prostatitis) nine percent (13/140) of TROVAN-treated patients experienced elevations of serum transaminases (AST and/or ALT) of ≥ 3 times the upper limit of normal. These liver function test abnormalities generally developed at the end of, or following completion of, the planned 28-day course of therapy, but were not associated with concurrent elevations of related laboratory measures of hepatic function (such as serum bilirubin, alkaline phosphatase, or lactate dehydrogenase). Patients were asymptomatic with these abnormalities, which generally returned to normal within 1-2 months after discontinuation of therapy. (See ADVERSE REACTIONS: Post-Marketing Experience subsection.)

TROVAN Post-Marketing Experience

Adverse reactions reported with TROVAN during the post-marketing period include: anaphylaxis, symptomatic hepatitis (some patients experienced an associated peripheral eosinophilia), liver failure (including acute hepatic necrosis with eosinophilic infiltration), Stevens-Johnson Syndrome, and symptomatic pancreatitis.

During the post-marketing period, TROVAN-associated liver enzyme abnormalities and/or symptomatic hepatitis have occurred during short-term or long-term therapy. (See PRECAUTIONS.)

LABORATORY CHANGES - Azithromycin: Significant abnormalities (irrespective of drug relationship) occurring during the clinical trials were reported as follows:

With an incidence of 1-2%, elevated serum creatine phosphokinase, potassium, ALT (SGPT), GGT, and AST (SGOT).

With an incidence of less than 1%, leukopenia, neutropenia, decreased platelet count, elevated serum alkaline phosphatase, bilirubin, BUN, creatinine, blood glucose, LDH, and phosphate.

When follow-up was provided, changes in laboratory tests appeared to be reversible.

In multiple-dose clinical trials involving more than 3000 patients, 3 patients discontinued therapy because of treatment-related liver enzyme abnormalities and one because of a renal function abnormality.

Read the entire FDA prescribing information for Trovan-Zithromax (Trovafloxacin and Azithromycin) »