AZITHROMYCIN

For oral use.

Posology:

Adults, elderly, children and adolescents over 45 kg body weight: Azithromycin tablets should be given as a single daily dose. The duration of treatment in each of the infectious diseases is given below. Method of Administration For oral use.

Tablets should be swallowed whole as a single daily dose and may be taken with or without a meal. Administration immediately before a meal may enhance the gastrointestinal tolerability. The tablets should be taken with ½ glass of water.

g. g. metronidazole)*+ Only as an oral switch after intravenous administration if clinically indicated: 250 mg once daily to complete a 7- day course of treatment Chronic prostatitis caused by Chlamydia trachomatis 500 mg/day on 3 consecutive days per week for 3 weeks (total dose: 4500 mg) Chancroid 1000 mg as a single dose Treatment of disseminated Mycobacterium avium complex (DMAC) infection in people living with advanced HIV infection (in combination with ethambutol) <500 mg> or <600 mg> once daily Prophylaxis of Mycobacterium avium complex (MAC) infections in people living with HIV with inadequate immune restoration <1200 mg> or <1250 mg> once a week * for treatment of adults only # in adults, oral treatment may also follow intravenous treatment, if clinically indicated to complete a 7- to 10-day total course of treatment (for details refer to the Summary of Product Characteristics of azithromycin IV formulations).

+ oral azithromycin should not be used for the initial treatment of pelvic inflammatory disease (for details refer to the Summary of Product Characteristics of azithromycin IV formulations). Consideration should be given to the treatment regimens, doses and duration of treatment as recommended in updated treatment guidelines for each indication.

Missed dose If 12 hours or less have passed since the missed dose, the patient should be advised to take it as soon as possible and then take the next dose at the regularly scheduled time. If more than 12 hours have passed since the time the dose is usually taken, the patient should be advised to wait until the next scheduled dose.

Special Populations Children and adolescents 45 kg and under body weight:

Azithromycin tablets are not suitable for these patients. Other dosage forms are available for this group of patients. g. suspensions may be used.

Elderly patients:

No dose adjustments are required for elderly patients. 4). 4). 2). 2). No data are available in patients with severe hepatic impairment (Child-Pugh Class C). 4). Paediatric population The safety and efficacy of Azithromycin for the treatment of adolescent girls with pelvic inflammatory disease has not been established.

There is no relevant use of Azithromycin for the treatment of acute exacerbations of chronic bronchitis in paediatric patients. The safety and efficacy of Azithromycin in prevention or treatment of Mycobacterium avium complex infections in paediatric patients < 12 years has not been established.

Other pharmaceutical forms are available that may be more appropriate to treat patients unable to swallow capsules as well as paediatric patients weighing less than 45 kg.

Summary of the safety profile The most commonly reported adverse reactions during treatment include diarrhoea, headache, vomiting, abdominal pain, nausea and abnormal laboratory test values. 4). 4). Tabulated list of adverse reactions Adverse reactions identified through clinical trial experience and post marketing surveillance are listed below, by system organ class and frequency.

The table below lists the adverse reactions identified through clinical trial experience and post- marketing surveillance by system organ class and frequency. Adverse reactions identified from post-marketing experience are included in italics.

The frequency grouping is defined using the following convention:

Very common (≥1/10); Common (≥ 1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very Rare (< 1/10,000); and Not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Adverse reactions possibly or probably related to azithromycin based on clinical trial experience and post-marketing surveillance: Table 3: Tabulated list of adverse reactions very common ≥ 1/10 common ≥ 1/100 to < 1/10 uncommon ≥ 1/1,000 to < 1/100 rare ≥ 1/10,000 to <1/1,000 very rare < 1/10,000 not known frequency cannot be estimated from available data Infections and infestations Candidiasis, oral, candidiasis, vaginal infection, pneumonia, fungal infection, bacterial infection, pharyngitis, gastroenteritis, respiratory disorder, rhinitis.

4)*, hepatitis fulminant, hepatic necrosis, Skin and subcutaneous tissue disorders , , urticaria, Dermatitis, dry skin, hyperhidrosis , Rash#2, pruritus#2 Allergic reactions including angioneurotic oedema, photosensitivit y reaction, Acute generalised exanthematous Toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome#3 pustulosis (AGEP) Drug reaction with eosinophilia and systemic symptoms (DRESS) Musculoskeletal and connective tissue disorders Osteoarthritis, Myalgia, back pain, neck pain Arthralgia#2 Renal and urinary disorders Dysuria, renal pain , Blood urea increased Blood creatinine increased Acute kidney injury Tubulointerstitial nephritis Reproductive system and breast disorders Intermenstrual bleeding Testicular Disorder General disorders and administration site conditions Chest pain, face oedema, pyrexia, peripharal pain, oedema malaise , Fatigue#2 asthenia Investigations Blood bicarbonate Decreased blood potassium abnormal, blood alkaline phosphatase increased, chloride increased, glucose increased, platelets increased, hematocrit decreased, bicarbonate increased, abnormal sodium Injury poisoning and procedural complications Post procedural complications * These ADRs were only seen during azithromycin administration for MAC prophylaxis and/or therapy #1 In MAC the frequency of these ADRs was Very Common (>1/10).

#2 In MAC the frequency of these ADRs was Common (>1/100 to <1/10). #3 In MAC the frequency of these ADRs was Uncommon (>1/1 000 to <1/100). Adverse reactions possibly or probably related to Mycobacterium Avium Complex prophylaxis and treatment based on clinical trial experience and post-marketing surveillance.

These adverse reactions differ from those reported with immediate release or the prolonged release formulations, either in kind or in frequency: System Organ Class Adverse reaction Frequency Anorexia CommonMetabolism and Nutrition Disorders Dizziness, headache, paraesthesia, dysgeusia CommonNervous System Disorders Hypoesthesia Uncommon Eye Disorders Visual impairment Common […]

2). Treatment with azithromycin should only be initiated after a careful assessment of the benefit and the risks, considering the local prevalence of resistance, and when preferred treatment regimens are not indicated. 8). At the time of prescription, patients should be advised of the signs and symptoms and monitored closely for skin reactions.

Some of these reactions with azithromycin have resulted in recurrent symptoms and required a longer period of observation and treatment. If an allergic reaction occurs, azithromycin should be discontinued and appropriate therapy should be instituted.

73m2). 2).

Hepatic impairment:

Since liver is the principal route of elimination for azithromycin, the use of azithromycin should be undertaken with caution in patients with significant hepatic disease. 8). Some patients may have had pre- existing hepatic disease or may have been taking other hepatotoxic medicinal products.

In case of signs and symptoms of liver dysfunction, such as rapid developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy, liver function tests/ investigations should be performed immediately.

Azithromycin administration should be stopped if liver dysfunction has emerged.

Ergot alkaloids and azithromycin:

The concurrent use of ergot alkaloids and macrolide antibiotics has been found to accelerate the development of ergotism. The interactions between ergot alkaloids and azithromycin have not been studied. The development of ergotism is however possible, so that azithromycin and ergot alkaloid derivatives should not be administered simultaneously.

In patients receiving ergot derivatives, ergotism has been precipitated by co- administration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergot and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin and ergot derivatives may not be co- administered.

8). Therefore as the following situations may lead to an increased risk for ventricular arrhythmias (including torsade de pointes) which can lead to cardiac arrest, azithromycin should be used with caution in patients with ongoing proarrhythmic conditions (especially women and elderly patients) such as patients: - with congenital or documented acquired QT prolongation.

5). - with electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesaemia - with clinically relevant bradycardia, cardiac arrhythmia or severe cardiac insufficiency. 8). Safety and efficacy for the prevention or treatment of Mycobacterium Avium Complex (MAC) in children have not been established.

Non-susceptible organisms :

As with any antibiotic preparation, observation for signs of superinfection with nonsusceptible organisms, including fungi is recommended. A superinfection may require an interruption of the azithromycin treatment and initiation of adequate measures.

8). CDAD and pseudomembranous colitis must be considered in patients who present with diarrhoea during or subsequent to the administration of azithromycin. 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 antimicrobial […]

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