Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.
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.
Prescribing ZITHROMAX 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.
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.
In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Potentially serious adverse reactions of angioedema and cholestatic jaundice were reported.
Approximately 0. Most of the adverse reactions leading to discontinuation were related to the gastrointestinal tract, e. Gastrointestinal: Dyspepsia, flatulence, vomiting, melena, and cholestatic jaundice. Overall, the most common adverse reactions 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. The majority of these complaints were mild in nature.
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. Gastrointestinal: Dyspepsia, constipation, anorexia, enteritis, flatulence, gastritis, jaundice, loose stools, and oral moniliasis. Nervous System: Headache otitis media dosage , hyperkinesia, dizziness, agitation, nervousness, and insomnia.
General: Fever, face edema, fatigue, fungal infection, malaise, and pain. Skin and Appendages: Eczema, fungal dermatitis, pruritus, sweating, urticaria, and vesiculobullous rash. The following adverse reactions have been identified during post-approval use of azithromycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiovascular: Arrhythmias including ventricular tachycardia and hypotension. There have been reports of QT prolongation and torsades de pointes. Genitourinary: Interstitial nephritis and acute renal failure and vaginitis.
The majority of subjects with elevated serum creatinine also had abnormal values at baseline. When follow-up was provided, changes in laboratory tests appeared to be reversible. In multiple-dose clinical trials involving more than patients, four patients discontinued therapy because of treatment-related liver enzyme abnormalities and one because of a renal function abnormality. In multiple-dose clinical trials involving approximately pediatric patients, no patients discontinued therapy because of treatment-related laboratory abnormalities.
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. 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. 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. 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 see Data. 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 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 mg based on body surface area see Data.
The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U. Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes with azithromycin use in pregnant women. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications.
Based on body surface area, this dose is approximately 4 rats and 2 mice times an adult human daily dose of mg. Maternal toxicity reduced food consumption and body weight gain; increased stress at parturition was observed at the higher dose. Azithromycin is present in human milk see Data.
Non-serious adverse reactions have been reported in breastfed infants after maternal administration of azithromycin see Clinical Considerations.
There are no available data on the effects of azithromycin on milk production. Azithromycin breastmilk concentrations were measured in 20 women after receiving a single 2 g oral dose of azithromycin during labor. Breastmilk samples collected on days 3 and 6 postpartum as well as 2 and 4 weeks postpartum revealed the presence of azithromycin in breastmilk up to 4 weeks after dosing.
In another study, a single dose of azithromycin mg was administered intravenously to 8 women prior to incision for cesarean section. Breastmilk colostrum samples obtained between 12 and 48 hours after dosing revealed that azithromycin persisted in breastmilk up to 48 hours.
Safety and effectiveness in the treatment of pediatric patients with acute otitis media, acute bacterial sinusitis and community-acquired pneumonia under 6 months of age have not been established.
Use of ZITHROMAX for the treatment of acute bacterial sinusitis and community-acquired pneumonia in pediatric patients 6 months of age or greater is supported by adequate and well-controlled trials in adults. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Elderly patients may be more susceptible to development of torsades de pointes arrhythmias than younger patients. Adverse reactions experienced at higher than recommended doses were similar to those seen at normal doses particularly nausea, diarrhea, and vomiting.
In the event of overdosage, general symptomatic and supportive measures are indicated as required. ZITHROMAX azithromycin tablets and azithromycin for oral suspension contain the active ingredient azithromycin, a macrolide antibacterial drug, for oral administration. 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 Azithromycin has the following structural formula:. After constitution, each 5 mL of suspension contains mg or mg of azithromycin. Azithromycin is a macrolide antibacterial drug. QTc interval prolongation was studied in a randomized, placebo-controlled parallel trial in healthy subjects who received either chloroquine mg alone or in combination with oral azithromycin mg, mg, and mg once daily.
Co-administration of azithromycin increased the QTc interval in a dose- and concentration- dependent manner. Two azithromycin mg tablets are bioequivalent to a single mg tablet. In a two-way crossover study, 12 adult healthy volunteers 6 males, 6 females received mg of azithromycin administered in single daily doses over either 5 days two mg tablets on day 1, followed by one mg tablet on days 2—5 or 3 days mg per day for days 1—3.
The antibacterial activity of azithromycin is pH related and appears to be reduced with decreasing pH, However, the extensive distribution of drug to tissues may be relevant to clinical activity. Azithromycin has been shown to penetrate into human tissues, including skin, lung, tonsil, and cervix. Extensive tissue distribution was confirmed by examination of additional tissues and fluids bone, ejaculum, prostate, ovary, uterus, salpinx, stomach, liver, and gallbladder.
As there are no data from adequate and well-controlled studies of azithromycin treatment of infections in these additional body sites, the clinical significance of these tissue concentration data is unknown. Following a regimen of mg on the first day and mg daily for 4 days, very low concentrations were noted in cerebrospinal fluid less than 0. In vitro and in vivo studies to assess the metabolism of azithromycin have not been performed.
The prolonged terminal half-life is thought to be due to extensive uptake and subsequent release of drug from tissues. Biliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination. Azithromycin pharmacokinetics was investigated in 42 adults 21 to 85 years of age with varying degrees of renal impairment.
Following the oral administration of a single 1. The pharmacokinetics of azithromycin in subjects with hepatic impairment has not been established. There are no significant differences in the disposition of azithromycin between male and female subjects. No dosage adjustment is recommended based on gender. Pharmacokinetic parameters in older volunteers 65 to 85 years old were similar to those in young adults 18 to 40 years old for the 5-day therapeutic regimen.
Dosage adjustment does not appear to be necessary for older patients with normal renal and hepatic function receiving treatment with this dosage regimen. In this study, azithromycin concentrations were determined over a 24 hr period following the last daily dose. Patients weighing above Seventeen patients weighing Drug interaction studies were performed with azithromycin and other drugs likely to be co-administered.
The effects of co-administration of azithromycin on the pharmacokinetics of other drugs are shown in Table 1 and the effects of other drugs on the pharmacokinetics of azithromycin are shown in Table 2.
Co-administration of azithromycin at therapeutic doses had a modest effect on the pharmacokinetics of the drugs listed in Table 1. No dosage adjustment of drugs listed in Table 1 is recommended when co-administered with azithromycin. Co-administration of azithromycin with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin.
Nelfinavir significantly increased the C max and AUC of azithromycin. No dosage adjustment of azithromycin is recommended when administered with drugs listed in Table 2.
Azithromycin acts by binding to the 23S rRNA of the 50S ribosomal subunit of susceptible microorganisms inhibiting bacterial protein synthesis and impeding the assembly of the 50S ribosomal subunit. Azithromycin demonstrates cross resistance with erythromycin. The most frequently encountered mechanism of resistance to azithromycin is modification of the 23S rRNA target, most often by methylation. Ribosomal modifications can determine cross resistance to other macrolides, lincosamides, and streptogramin B MLS B phenotype.
Azithromycin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections.
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration MIC less than or equal to the susceptible breakpoint for azithromycin against isolates of similar genus or organism group.
However, the efficacy of azithromycin in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials. 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. The relevance of these findings to patients being treated with azithromycin at the doses and durations recommended in the prescribing information is uncertain.
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. This effect has been shown to be reversible after cessation of azithromycin treatment. The significance of these findings for animals and for humans is unknown. Acute Bacterial Exacerbations of Chronic Bronchitis. In a randomized, double-blind controlled clinical trial of acute exacerbation of chronic bronchitis AECB , azithromycin mg once daily for 3 days was compared with clarithromycin mg twice daily for 10 days.
The primary endpoint of this trial was the clinical cure rate at Days 21— The following outcomes were the clinical cure rates at the Days 21—24 visit for the bacteriologically evaluable patients by pathogen:. Clinical response assessments were made at Day 10 and Day The primary endpoint of this trial was prospectively defined as the clinical cure rate at Day For the patients analyzed in the modified intent to treat analysis at the Day 28 visit, the clinical cure rate for 3 days of azithromycin was In an open label, non-comparative study requiring baseline transantral sinus punctures, the following outcomes were the clinical success rates at the Day 7 and Day 28 visits for the modified intent to treat patients administered mg of azithromycin once daily for 3 days with the following pathogens:.
From the perspective of evaluating pediatric clinical trials, Days 11—14 were considered on-therapy evaluations because of the extended half-life of azithromycin. Days 11—14 data are provided for clinical guidance. Days 24—32 evaluations were considered the primary test of cure endpoint. Azithromycin was clinically and microbiologically statistically superior to penicillin at Day 14 and Day 30 with the following clinical success i.
For the patients who were evaluated for clinical efficacy, the clinical success rate i. The combined clinical success rate i. Microbiologic determinations were made at the pre-treatment visit. Microbiology was not reassessed at later visits.
The following clinical success rates were obtained from the evaluable group:. For this reason, Protocol 3 was not considered to be an independent study. Ninety-two 92 patients were evaluable for clinical and microbiologic efficacy. At the Day 11 and Day 30 visits, the following clinical success rates were obtained from the evaluable group:. Each patient received active drug and placebo matched for the comparator. For the patients who were evaluated for clinical efficacy at the Day 12 visit, the clinical success rate i.
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule.
Do not take a double dose to make up for a missed one. Azithromycin may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store azithromycin tablets, suspension, and extended-release suspension at room temperature and away from excess heat and moisture not in the bathroom.
Do not refrigerate or freeze the extended-release suspension. Discard any azithromycin suspension that is left over after 10 days or no longer needed. Discard any unused extended-release azithromycin suspension after dosing is complete or 12 hours after preparation. Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet.
Instead, the best way to dispose of your medication is through a medicine take-back program. It is important to keep all medication out of sight and reach of children as many containers such as weekly pill minders and those for eye drops, creams, patches, and inhalers are not child-resistant and young children can open them easily.
To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location — one that is up and away and out of their sight and reach. In case of overdose, call the poison control helpline at If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at Keep all appointments with your doctor and the laboratory.
Your doctor may order certain lab tests to check your body's response to azithromycin. Do not let anyone else take your medication. Your prescription is probably not refillable. If you still have symptoms of infection after you finish the azithromycin, call your doctor. It is important for you to keep a written list of all of the prescription and nonprescription over-the-counter medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements.
You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies. Azithromycin pronounced as az ith roe mye' sin. Why is this medication prescribed? How should this medicine be used? Other uses for this medicine What special precautions should I follow?
What special dietary instructions should I follow? What should I do if I forget a dose? What side effects can this medication cause? What should I know about storage and disposal of this medication? Brand names. Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.
Other uses for this medicine. What special precautions should I follow? Before taking azithromycin, tell your doctor and pharmacist if you are allergic to azithromycin, clarithromycin Biaxin, in Prevpac , dirithromycin not available in the U. Ask your pharmacist for a list of the ingredients. Be sure to mention any of the following: anticoagulants 'blood thinners' such as warfarin Coumadin, Jantoven ; colchicine Colcrys, Gloperba ; cyclosporine Neoral, Sandimmune ; digoxin Lanoxin ; dihydroergotamine D.
Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Ask your doctor or pharmacist how many hours before or after you take azithromycin you may take these medications. The extended-release suspension may be taken at any time with antacids.
Your doctor will probably tell you not to take azithromycin.
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