Azee 1000

Azee 1000 which contains Azithromycin 1000 mg belongs to the therapeutic class of Antibiotics and belongs to the pharmacological class of macrolide antibiotics.

Azee 1000 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.

Azee 1000 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.

Azee 1000 is available in form of oral tablet.

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

Azee 1000 which contains Azithromycin 1g 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).

Azee 1000 contains Azithromycin 1 g is approved for use in the following clinical indications

Adult indication

Babesiosis

Diarrhea, infectious

Sexually transmitted infections

Typhoid and paratyphoid fever

Pediatric indication

Babesiosis

Cervicitis or urethritis, empiric treatment

Chancroid

Chlamydia trachomatis infection

Cholera, treatment

Gonococcal infection

Sexual victimization, prophylaxis

Streptococcus, group A; pharyngitis/tonsillitis

Typhoid fever, treatment

Adult Dose

• Babesiosis

Mild to moderate disease: Oral: higher doses of azithromycin (up to 1 g daily) may be used in highly immunocompromised patients.

• Diarrhea, infectious

Oral: 1 g as a single dose

• Sexually transmitted infections

Cervical infection, empiric therapy for cervicitis or pathogen-directed therapy for Chlamydia trachomatis (alternative agent):

Oral: 1 g as a single dose, preferably under direct observation; give in combination with ceftriaxone if the patient is at high risk for gonorrhea, if follow-up is a concern, or if the local prevalence of gonorrhea is high (eg, >5%).

Chancroid (due to Haemophilus ducreyi):

Oral: 1 g as a single dose.

Gonococcal infection, uncomplicated (infection of the cervix, rectum [off-label use], or urethra ) (alternative agent):

Oral: 2 g as a single dose in combination with IM gentamicin (preferred) or oral gemifloxacin. When treatment failure is suspected (eg, detection of N. gonorrhoeae after treatment without additional sexual exposure), consult an infectious diseases specialist. Report failures to the CDC through state and local health departments.

• Typhoid and paratyphoid fever

Oral: 1 g once daily or 1 g once on day 1, followed by 500 mg once daily; total duration: 5 to 7 days.

Pediatric Dose

• Babesiosis

Infants, Children, and Adolescents: Oral: longer duration may be necessary in some patients with severe or persistent symptoms until parasitemia is cleared; in immunocompromised patients, higher doses (eg, adults: 600 to 1,000 mg daily) have been used.

• Cervicitis or urethritis, empiric treatment

Infants and Children <45 kg: Optimal dose uncertain: Oral: 60 mg/kg as a single dose in combination with ceftriaxone; maximum dose: 1,000 mg/dose.

Children ≥45 kg and Adolescents: Oral: 1,000 mg as a single dose in combination with ceftriaxone

• Chancroid

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

Children ≥45 kg and Adolescents: Oral: 1,000 mg as a single dose.

• Chlamydia trachomatis infection

Urogenital/anogenital tract or oropharyngeal infection (eg, cervicitis, urethritis): Children <8 years weighing ≥45 kg or Children ≥8 years and Adolescents: Oral: 1,000 mg as a single dose.

• Cholera, treatment

Infants, Children, and Adolescents: Oral: 20 mg/kg as a single dose in combination with hydration; maximum dose: 1,000 mg/dose.

• Gonococcal infection

Uncomplicated gonococcal infections of the cervix, urethra, or rectum (alternative agent in severe cephalosporin allergy): Children >45 kg and Adolescents: Oral: 2,000 mg as a single dose in combination with IM gentamicin.

Disseminated gonococcal infection (arthritis, arthritis-dermatitis, meningitis, endocarditis): Children >45 kg and Adolescents: Oral: 1,000 mg as a single dose in combination with daily ceftriaxone.

Gonococcal conjunctivitis: Children >45 kg and Adolescents: Oral: 1,000 mg as a single dose in combination with ceftriaxone

• Sexual victimization, prophylaxis

Adolescents: Oral: 1,000 mg as a single dose in combination with ceftriaxone and either metronidazole or tinidazole.

• Streptococcus, group A; pharyngitis/tonsillitis

Three-day regimen: Children and Adolescents: Oral: 20 mg/kg/dose once daily for 3 days; maximum dose: 1,000 mg/dose

• Typhoid fever, treatment

Children and Adolescents: Oral: 1 20 mg/kg/dose (maximum dose: 1,000 mg/dose) once daily for 5 to 7 days.

Azee 1000 is available in the strength of 1g.

Azee 1000 is available in the form of Oral Tablet.

Azee 1000 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.

Azee 1000 containing Azithromycin 1g 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.

Azee 1000 contains Azithromycin 1g. 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.

Azee 1000 contains Azithromycin 1g. 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 Azee 1000 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 Azee 1000 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 Azee 1000 which contains amlodipine 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.

Azee 1000 contains Azithromycin 1g.

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 Azee 1000

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

Management: Initiate symptomatic and supportive measures as necessary.

Azee 1000 contains Azithromycin 1g

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.