Azithral 250

Azithral 250 which contains Azithromycin 250 mg belongs to the therapeutic class of Antibiotics and belonging to pharmacological class of macrolide antibiotics. 

Azithral 250 is a broad-spectrum macrolide antibiotic used to treat a variety of bacterial infections. It is primarily used for the treatment of respiratory, enteric and genitourinary infections and may be used instead of other macrolides for some sexually transmitted and enteric infections.

Rapidly absorbed from the gastrointestinal tract. Bioavailability is Approximately 37%. Time taken to reach peak plasma concentration is approximately 2-3 hours (oral, immediate release). Azithromycin is Extensively distributed in the tissues (skin, lungs, tonsils, cervix) and sputum. Apparent volume of distribution is 31-33 L/kg. It is having Plasma protein-binding of 7-51%. It is Extensively metabolized in liver to inactive metabolites. Biliary excretion of azithromycin, primarily as unchanged drug, is a major route of elimination. 50%, as unchanged drug is excreted via bile and 6-14%, as unchanged drug via urine.

Azithral 250 shows side effects like Nausea, diarrhea, vomiting, stomach pain, headache irregular heartbeat, dizziness, fainting, rash with or without a fever, blisters or peeling, fever and pus-filled, blister-like sores, redness, and swelling of the skin, hives, itching, wheezing or difficulty breathing or swallowing, swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs, hoarseness, vomiting or irritability while feeding (in infants less than 6 weeks old), severe diarrhea, yellowing of the skin or eyes, extreme tiredness, unusual bleeding or bruising, lack of energy, loss of appetite, pain in the upper right part of the stomach, flu-like symptoms, dark-colored urine, unusual muscle weakness or difficulty with muscle control, pink and swollen eyes.

Azithral 250 is available in form of oral tablet.

Azithromycin is available in India, US, UK, Japan, Canada, Europe and Netherlands.

Azithral 250 which contains Azithromycin 250 mg belongs to macrolide class of drug acts as an antibiotic.

Azithromycin Inhibits RNA-dependent protein synthesis at the chain elongation step; binds to the 50S ribosomal subunit resulting in blockage of transpeptidation.

The Onset of action and duration of action is not clinically established.

The Time to peak serum is approximately 2 to 3 hours (oral, immediate release) and 3 to 5 hours (oral, Extended release).

Azithral 250 contains Azithromycin 250 mg is approved for use in the following clinical indications

Adult indication

Babesiosis

Bronchiectasis, prevention of pulmonary exacerbations

Bronchiolitis obliterans

Chronic obstructive pulmonary disease, acute exacerbation

Cystic fibrosis, anti-inflammatory

Pertussis

Streptococcus, group A

Pediatric indication

Babesiosis

Cat scratch disease

Chancroid

Cholera, treatment

Endocarditis; prophylaxis

Lyme disease, erythema migrans

Meningococcal disease, chemoprophylaxis of high-risk contacts

Peritonitis, prophylaxis for patients receiving peritoneal dialysis who require dental procedures

Pertussis

Pneumonia, community-acquired

Rhinosinusitis, bacterial

Streptococcus, group A; pharyngitis/tonsillitis

Typhoid fever, treatment

Adult Dose

• Babesiosis

Mild to moderate disease: Oral: Recommended dose 250 mg once daily in combination with atovaquone.

• Bronchiectasis, prevention of pulmonary exacerbations

Oral: mg once daily. An initial dose of 250 mg 3 times weekly, with subsequent titration according to patient response, may be considered to minimize adverse effects.

• Bronchiolitis obliterans

Oral: 250 mg 3 times weekly; some experts recommend an initial dose of 250 mg daily for the first 5 days. Usually given for a 3-month trial period.

• Chronic obstructive pulmonary disease, acute exacerbation

Oral: Recommended dose 250 mg once daily on days 2 to 5

Cystic fibrosis, anti-inflammatory

Oral: 250 mg (<40 kg) 3 times weekly or 250 mg once daily.

• Pertussis

Oral: Recommended dose- 250 mg once daily on days 2 to 5.

• Streptococcus, group A

Pharyngitis: Oral: Recommended dose- 6 mg/kg (maximum: 250 mg) once daily on days 2 through 5.

Secondary prophylaxis in patients with rheumatic fever (prevention of recurrent attacks) (off-label use): Oral: 250 mg once daily. Duration depends on risk factors, age, and presence of valvular disease.

Pediatric Dose

• Babesiosis

Infants, Children, and Adolescents: Oral: Maintenance dose 5 mg/kg/dose once daily (maximum dose: 250 mg/dose) in combination with atovaquone for a total duration of 7 to 10 days; longer duration may be necessary in some patients with severe or persistent symptoms until parasitemia is cleared.

• Cat scratch disease

Infants, Children, and Adolescents weighing ≤45 kg: Oral: Recommended dose-5 mg/kg/dose once daily for 4 additional days (maximum dose: 250 mg/dose).

Children and Adolescents weighing >45 kg: Oral: Recommended dose- 250 mg once daily for 4 additional days.

• Chancroid

Infants and Children <45 kg: Oral: 20 mg/kg as a single dose; Recommended dose: 1,000 mg/dose.

Pneumonia, congenital: Infants: Oral, IV: 20 mg/kg/dose once daily for 3 days

• Cholera, treatment

Infants, Children, and Adolescents: Oral: 20 mg/kg as a single dose in combination with hydration; recommended dose: 250 mg/dose.

• Endocarditis; prophylaxis

Infants, Children, and Adolescents: Oral: 15 mg/kg/dose 30 to 60 minutes before procedure; recommended dose:  mg/dose.

• Lyme disease, erythema migrans

Infants, Children, and Adolescents: Oral: 10 mg/kg/dose once daily for 7 days; Recommended dose: 250 mg/dose.

• Meningococcal disease, chemoprophylaxis of high-risk contacts

Infants, Children, and Adolescents: Oral: 10 mg/kg as a single dose; Recommended dose: 250 mg/dose.

• Peritonitis, prophylaxis for patients receiving peritoneal dialysis who require dental procedures

Infants, Children, and Adolescents: Oral: 15 mg/kg administered 30 to 60 minutes before dental procedure; Recommended dose: 250 mg/dose.

• Pertussis

Infants 1 to 5 months: 10 mg/kg/dose once daily for 5 days.

Infants ≥6 months, Children, and Adolescents: 10 mg/kg once on day 1 (Recommended dose: 250 mg/dose), followed by 5 mg/kg once daily on days 2 to 5 (maximum dose: 250 mg/dose).

• Pneumonia, community-acquired

Mild infection or step-down therapy: Infants >3 months, Children, and Adolescents: Oral: 10 mg/kg once on day 1 (Recommended dose: 250 mg/dose), followed by 5 mg/kg/dose (maximum dose: 250 mg/dose) once daily on days 2 to 5.

Severe infection: Infants >3 months, Children, and Adolescents: IV: 10 mg/kg/dose once daily for at least 2 days (Recommended dose: 250 mg/dose); when able transition to the oral route with a single daily dose of 5 mg/kg/dose (maximum dose: 250 mg/dose) to complete a 5-day course of therapy.

• Rhinosinusitis, bacterial

Infants ≥6 months, Children, and Adolescents: Oral: 10 mg/kg/dose once daily for 3 days; Recommended dose: 250 mg/dose.

• Streptococcus, group A; pharyngitis/tonsillitis

Five-day regimen: Children and Adolescents: Oral: 12 mg/kg/dose once daily for 5 days; Recommended dose: 250 mg/dose.

Three-day regimen: Children and Adolescents: Oral: 20 mg/kg/dose once daily for 3 days; Recommended dose: 250 mg/dose

• Typhoid fever, treatment

Children and Adolescents: Oral: 10 mg/kg/dose (Recommended dose: 250 mg/dose) once daily for 7 days or 20 mg/kg/dose (Recommended dose: 250 mg/dose) once daily for 5 to 7 days.

Azithral 250 is available in the strength of 250 mg.

Azithral 250 is available in the form of Oral Tablet.

Azithral 250 which contains Azithromycin is contraindicated in patients with

Hypersensitivity

Azithromycin is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drug.

Hepatic Dysfunction

Azithromycin is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

Azithral 250 containing Azithromycin 250 mg should be used with certain warnings and precautions

The treating physician must closely monitor the patient and keep pharmacovigilance as follows

Hypersensitivity

Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported in patients on azithromycin therapy. Fatalities have been reported. Cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have also been reported. 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 prolonged exposure to antigen is presently unknown. If an allergic reaction occurs, the drug should be discontinued, and appropriate therapy should be instituted. Physicians should be aware that allergic symptoms may reappear when symptomatic therapy has been discontinued.

Hepatotoxicity

Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.

Infantile Hypertrophic Pyloric Stenosis (IHPS)

Following the use of azithromycin in neonates (treatment up to 42 days of life), IHPS has been reported. Direct parents and caregivers to contact their physician if vomiting or irritability with feeding occurs.

QT Prolongation

Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen with treatment with macrolides, including azithromycin. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving azithromycin. Providers should consider the risk of QT prolongation which can be fatal when weighing the risks and benefits of azithromycin for at-risk groups including:

Patients with known prolongation of the QT interval, a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmia or uncompensated heart failure

Patients on drugs known to prolong the QT interval.

Patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval.

Exacerbation of Myasthenia Gravis

Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.

Use in Sexually Transmitted Infections

azithromycin, at the recommended dose, should not be relied upon to treat syphilis. 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.

Development of Drug-Resistant Bacteria

Prescribing azithromycin 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.

Clostridium difficile-Associated Diarrhea (CDAD)

Clostridium difficile-associated diarrhea has been reported with use of nearly all antibacterial agents, including azithromycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. 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. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Azithral 250 contains Azithromycin 250 mg. Azithromycin is present in human milk. Non-serious adverse reactions have been reported in breastfed infants after maternal administration of azithromycin. There are no available data on the effects of azithromycin on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for azithromycin and any potential adverse effects on the breastfed infant from azithromycin or from the underlying maternal condition.

Azithral 250 contains Azithromycin 250 mg. Azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. 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 500 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 500 mg based on body surface area. 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.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

The adverse reactions related to Azithral 250 can be categorized as

Common

Myasthenia gravis, Deafness, Pruritus, burning, stinging of the eye or ocular discomfort, sticky eye sensation, foreign body sensation (ophthalmic), Diarrhea, vomiting, abdominal pain, nausea, flatulence, dyspepsia, dysgeusia, Injection site pain, fatigue, Decreased lymphocyte count and blood bicarbonate; increased eosinophil count, basophils, monocytes and neutrophils, Anorexia. Arthralgia, Headache, dizziness, paresthesia, Pruritus, rash.

Rare

Serious hypersensitivity reactions (e.g. anaphylaxis, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis drug reaction with eosinophilia and systemic symptoms), fulminant hepatitis leading to liver failure, prolonged cardiac repolarization and QT interval, cardiac arrhythmia, torsades de pointes, Clostridium difficile associated diarrhea (CDAD).

The clinically relevant drug interactions of Azithral 250 is briefly summarized here

Nelfinavir

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.

Warfarin

Spontaneous post marketing 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.

Potential Drug-Drug Interaction with Macrolides

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.

The common side effects of Azithral 250 which contains Azithromycin includes the following

Common side effects

Nausea, diarrhea, vomiting, stomach pain, headache.

Rare side effects

Fast, pounding, or irregular heartbeat, dizziness, fainting, rash with or without a fever, blisters or peeling, fever and pus-filled, blister-like sores, redness, and swelling of the skin, hives, itching, wheezing or difficulty breathing or swallowing, swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs, hoarseness, vomiting or irritability while feeding (in infants less than 6 weeks old), severe diarrhea (watery or bloody stools) that may occur with or without fever and stomach cramps (may occur up to 2 months or more after your treatment), yellowing of the skin or eyes, extreme tiredness, unusual bleeding or bruising, lack of energy, loss of appetite, pain in the upper right part of the stomach, flu-like symptoms, dark-colored urine, unusual muscle weakness or difficulty with muscle control, pink and swollen eyes.

Azithral 250 contains Azithromycin 250 mg.

Pregnancy

Pregnancy Category B

Azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. 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 500 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 500 mg based on body surface area. 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.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Nursing Mothers

Azithromycin is present in human milk. Non-serious adverse reactions have been reported in breastfed infants after maternal administration of azithromycin. There are no available data on the effects of azithromycin on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for azithromycin and any potential adverse effects on the breastfed infant from azithromycin or from the underlying maternal condition.

Pediatric Use

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 azithromycin 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.

Geriatric Use

In multiple-dose clinical trials of oral azithromycin, 9% of patients were at least 65 years of age (458/4949) and 3% of patients (144/4949) were at least 75 years of age. 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.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Azithral 250

Symptoms: Diarrhea, reversible hearing loss, severe nausea, and vomiting.

Management: Initiate symptomatic and supportive measures as necessary.

Azithral 250 contains Azithromycin 250 mg

Pharmacodynamic

Macrolides stop bacterial growth by inhibiting protein synthesis and translation, treating bacterial infections. Azithromycin has additional immunomodulatory effects and has been used in chronic respiratory inflammatory diseases for this purpose.

Pharmacokinetics

Absorption

Rapidly absorbed from the gastrointestinal tract. The bioavailability is approximately 37%. Time taken to reach peak plasma concentration is approximately 2-3 hours (oral, immediate release).

Distribution

Azithromycin is extensively distributed in the tissues (skin, lungs, tonsils, cervix) and sputum. The apparent volume of distribution is 31-33 L/kg. It is having Plasma protein-binding of 7-51%.

Metabolism and Excretion

Azithromycin is extensively metabolized in liver to inactive metabolites. Biliary excretion of azithromycin, primarily as unchanged drug, is a major route of elimination. About 50%, as unchanged drug is excreted via bile and 6-14%, as unchanged drug via urine.