Azithromycin pfizer

Overdose

Adverse events experienced in higher than recommended doses were similar to those seen at normal doses. In the event of overdosage, general symptomatic and supportive measures are indicated as required.

Adverse events experienced in higher than recommended doses were similar to those seen at normal doses. The typical symptoms of an overdose with macrolide antibiotics include reversible loss of hearing, severe nausea, vomiting and diarrhoea. In the event of overdose, the administration of medicinal charcoal and general symptomatic treatment and supportive measures are indicated as required.

Incompatibilities

Not applicable

Not applicable.

Undesirable effects

The table below lists the adverse reactions identified through clinical trial experience and postmarketing surveillance by system organ class and frequency.

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 Pfizer based on clinical trial experience and post-marketing surveillance:

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:

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme (www.mhra.gov.uk/yellowcard) or search for MHRA Yellow Card in the Google Play or Apple App Store.

Azithromycin Pfizer is well tolerated with a low incidence of side effects.

The section below lists the adverse reactions identified through clinical trial experience and postmarketing 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:

Infections and Infestations

Uncommon (>1/1,000 to <1/100)

Candidiasis, oral candidiasis, vaginal infection

Not known (cannot be estimated from available data)

Pseudomembranous colitis

Blood and Lymphatic System Disorders

Uncommon (> 1/1,000 to < 1/100)

Leukopenia, neutropenia

Not known (cannot be estimated from available data)

Thrombocytopenia, haemolytic anaemia

Immune System Disorders

Uncommon (>1/1,000 to <1/100)

Angioedema, hypersensitivity

Not known (cannot be estimated from available data)

Anaphylactic reaction

Metabolism and Nutrition Disorders

Common (> 1/100, < 1/10)

Anorexia

Psychiatric Disorders

Uncommon (>1/1,000 to <1/100)

Nervousness

Rare (> 1/10000, < 1/1000)

Agitation

Not known (cannot be estimated from available data)

Aggression, anxiety

Nervous System Disorders

Common (> 1/100, < 1/10)

Dizziness, headache, paraesthesia, dysgeusia

Uncommon (>1/1,000 to <1/100)

Hypoaesethesia, somnolence, insomnia

Not known (cannot be estimated from available data)

Syncope, convulsion, psychomotor hyperactivity, anosmia, ageusia, parosmia, Myasthenia gravis.

Eye Disorders

Common (> 1/100, < 1/10)

Visual impairment

Ear and Labyrinth Disorders

Common (> 1/100, < 1/10)

Deafness

Uncommon (>1/1,000 to <1/100)

Hearing impaired, tinnitus

Rare (> 1/10000, < 1/1000)

Vertigo

Cardiac Disorders

Uncommon (>1/1,000 to <1/100)

Palpitations

Not known (cannot be estimated from available data)

Torsades de pointes , arrhythmia including ventricular tachycardia

Vascular Disorders

Not known (cannot be estimated from available data)

Hypotension

Gastrointestinal Disorders

Very common (>1/10)

Diarrhoea, abdominal pain, nausea, flatulence

Common (> 1/100, < 1/10)

Vomiting, dyspepsia

Uncommon (> 1/1000, < 1/100)

Gastritis, constipation

Not known (cannot be estimated from available data)

Pancreatitis, tongue discolouration

Hepatobiliary Disorders

Uncommon (> 1/1000, < 1/100)

Hepatitis

Rare (> 1/10000, < 1/1000)

Hepatic function abnormal

Not known (cannot be estimated from available data)

Hepatic failure , which has rarely resulted in death, hepatitis fulminant, hepatic necrosis, jaundice cholestatic

Skin and Subcutaneous Tissue Disorders

Common (> 1/100, < 1/10)

Pruritus and rash

Uncommon (> 1/1000, < 1/100)

SJS, photosensitivity reaction, urticarial

Rare (>1/10,000 to <1/1,000)

Acute Generalized Exanthematous Pustulosis (AGEP)*§

Very Rare (< 1/10,000)

DRESS

Not known (cannot be estimated from available data)

TEN, erythema multiforme

Musculoskeletal, Connective Tissue Disorders

Common (> 1/100, < 1/10)

Arthralgia

Renal and Urinary Disorders

Not known (cannot be estimated from available data)

Renal failure acute, nephritis interstitial

General disorders and Administration Site Conditions

Common (> 1/100, < 1/10)

Fatigue

Uncommon (> 1/1000, < 1/100)

Chest pain, oedema, malaise, asthenia

Investigations

Common (> 1/100, < 1/10)

Lymphocyte count decreased, eosinophil count increased, blood bicarbonate decreased

Uncommon (> 1/1000, < 1/100)

Aspartate aminotransferase increased, alanine aminotransferase increased, blood bilirubin increased, blood urea increased, blood creatinine increased, blood potassium abnormal

Not known (cannot be estimated from available data)

Electrocardiogram QT prolonged

*ADR identified post-marketing

§ADR frequency represented by the estimated upper limit of the 95% confidence interval calculated using the “Rule of 3”.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

Preclinical safety data

In animal tests in which the dosages used amounted to 40 times the clinical therapeutic dosages, Azithromycin Pfizer was found to have caused reversible phospholipidosis, but as a rule, no true toxicological consequences were observed which were associated with this. The relevance of this finding to humans receiving Azithromycin Pfizer in accordance with the recommendations is unknown.

Carcinogenic potential:

Long-term studies in animals have not been performed to evaluate carcinogenic potential as the drug is indicated for short-term treatment only, and there were no signs indicative of carcinogenic activity.

Mutagenic potential:

There was no evidence of a potential for genetic and chromosome mutations in in-vivo and in-vitro test models.

Reproductive toxicity:

In animal studies of the embryotoxic effects of the substance, no teratogenic effect was observed in mice and rats. In rats, Azithromycin Pfizer dosages of 100 and 200 mg/kg bodyweight/day led to mild retardations in foetal ossification and in maternal weight gain. In peri- and postnatal studies in rats, mild retardation in physical development and delay in reflex development following treatment with 50 mg/kg/day Azithromycin Pfizer and above were observed.

Phospholipidosis (intracellular phospholipid accumulation) has been observed in several tissues (e.g. eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and/or pancreas) of mice, rats, and dogs given multiple doses of azithromycin. Phospholipidosis has been observed to a similar extent in the tissues of neonatal rats and dogs. The effect has been shown to be reversible after cessation of azithromycin treatment. The significance of the finding for animals and humans is unknown.

Carcinogenic potential:

Long-term studies in animals have not been performed to evaluate carcinogenic potential as the drug is indicated for short-term treatment only and there were no signs indicative of carcinogenic activity.

Mutagenic potential:

There was no evidence of a potential for genetic and chromosome mutations in in-vivo and in-vitro test models.

Reproductive toxicity:

In animal studies for embryotoxic effects of the substance, no teratogenic effect was observed in mice and rats. In rats, azithromycin doses of 100 and 200 mg/kg bodyweight/day led to mild retardation of foetal ossification and in maternal weight gain. In peri- and postnatal studies in rats, mild retardation following treatment with 50 mg/kg/day azithromycin and above was observed.

Azithromycin Pfizer price

Pharmacotherapeutic group

Pharmacodynamic properties

General properties

Pharmacotherapeutic group: antibacterials for systemic use, macrolides, Azithromycin Pfizer,

ATC code: J01FA10

Mode of action

The mechanism of action of Azithromycin Pfizer is based on the suppression of bacterial protein synthesis, that is to say that it binds to the ribosomal 50s sub-unit and inhibits the translocation of peptides. Azithromycin Pfizer acts bacteriostatic.

PK/PD Relationship

The efficacy of Azithromycin Pfizer is best described by the relationship AUC/MIC, where AUC describes the area under the curve and MIC represents the mean inhibitory concentration of the microbe concerned.

Mechanism of resistance

Resistance to Azithromycin Pfizer may be natural or acquired. There are 3 main mechanisms of resistance affecting Azithromycin Pfizer:

- Efflux: resistance may be due to an increase in the number of efflux pumps on the cell membrane. In particular, 14- and 15-link macrolides are affected. (M-phenotype)

- Alterations of the cell structure: methylisation of the 23s rRNS may reduce the affinity of the ribosomal binding sites, which can result in microbial resistance to macrolides, lincosamides and group B streptogramins (SB) (MLSB-phenotype).

- Enzymatic deactivation of macrolides is only of limited clinical significance.

In the presence of the M-phenotype, complete cross resistance exists between Azithromycin Pfizer and clarithomycin, erythromycin and roxithromycin. With the MLSB-phenotype, additional cross resistance exists with clindamycin and streptogramin B. A partial cross resistance exists with spiramycin.

Breakpoints

According to EUCAST (European Committee on Antimicrobial Susceptibility Testing) the following breakpoints have been defined for Azithromycin Pfizer (2009-06-01):

Susceptibility

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Pathogens for which resistance may be a problem: prevalence of resistance is equal to or greater than 10% in at least one country in the European Union.

Table of Susceptibility

* Clinical effectiveness is demonstrated by sensitive isolated organisms for approved clinical indication.

General properties

Pharmacotherapeutic group: Antibacterials for systemic use. ATC code: J01FA10

Mode of action:

Azithromycin Pfizer is a macrolide antibiotic belonging to the azalide group. The molecule is constructed by adding a nitrogen atom to the lactone ring of erythromycin A. The chemical name of azithromycin is 9-deoxy-9a-aza-9a-methyl-9a-homoerythromycin A. The molecular weight is 749.0. The mechanism of action of azithromycin is based upon the suppression of bacterial protein synthesis by means of binding to the ribosomal 50S sub-unit and inhibition of peptide translocation.

Mechanism of resistance:

Resistance to azithromycin may be inherent or acquired. There are three main mechanisms of resistance in bacteria: target site alteration, alteration in antibiotic transport and modification of the antibiotic.

Azithromycin demonstrates cross resistance with erythromycin resistant gram positive isolates. A decrease in macrolide susceptibility over time has been noted particularly in Streptococcus pneumoniae and Staphylococcus aureus. Similarly, decreased susceptibility has been observed among Streptococcus viridans and Streptococcus agalactiae (Group B) streptococcus against other macrolides and lincosamides.

Breakpoints

Azithromycin susceptibility breakpoints for typical bacterial pathogens, as published by EUCAST are:

Susceptibility

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Table: Antibacterial spectrum of Azithromycin

* Methycillin-resistant staphylococci have a very high prevalence of acquired resistance to macrolides and have been placed here because they are rarely susceptible to azithromycin.

Pharmacokinetic properties

Absorption

Bioavailability after oral administration is approximately 37%. Peak concentrations in the plasma are attained 2-3 hours after taking the medicinal product.

Distribution

Orally administered Azithromycin Pfizer is widely distributed throughout the body.

In pharmacokinetic studies it has been demonstrated that the concentrations of Azithromycin Pfizer measured in tissues are noticeably higher (as much as 50 times) than those measured in plasma.

Concentrations in the infected tissues, such as lungs, tonsil and prostate are higher than the MRC90 of the most frequently occurring pathogens after a single dose of 500 mg.

Binding to serum proteins varies in dependence on exposure in concentration range from 12% in 0.5 microgram/ml up to 52% in 0.05 microgram Azithromycin Pfizer/ml serum. The mean volume of distribution at steady state (VVss) has been calculated to be 31.1 l/kg.

Elimination

Terminal plasma elimination half-life closely reflects the elimination half-life from tissues of 2-4 days.

Approximately 12% of an intravenously administered dose of Azithromycin Pfizer is excreted unchanged in urine within the following three days. Particularly high concentrations of unchanged Azithromycin Pfizer have been found in human bile. In the same source, 10 metabolites were also detected, which were formed through N- and O-demethylation, hydroxylation of desosamine- and aglycone rings and degradation of cladinose conjugate. Comparison of the results of liquid chromatography and microbiological analyses has shown that the metabolites of Azithromycin Pfizer are not microbiologically active.

In animal tests, high concentrations of Azithromycin Pfizer have been found in phagocytes. It has also been established that during active phagocytosis higher concentrations of Azithromycin Pfizer are released than are released from inactive phagocytes. In animal models the Azithromycin Pfizer concentrations measured in inflammation foci were high.

Pharmacokinetics in Special Populations

Renal insufficiency

Following a single oral dose of Azithromycin Pfizer 1 g, mean Cmax and AUC0-120 increased by 5.1% and 4.2% respectively, in subjects with mild to moderate renal impairment (glomerular filtration rate of 10-80 ml/min) compared with normal renal function (GFR > 80 ml/min). In subjects with severe renal impairment, the mean Cmax and AUC0-120 increased 61% and 33% respectively compared to normal.

Hepatic insufficiency

In patients with mild to moderate hepatic impairment, there is no evidence of a marked change in serum pharmacokinetics of Azithromycin Pfizer compared to normal hepatic function. In these patients, urinary recovery of Azithromycin Pfizer appears to increase perhaps to compensate for reduced hepatic clearance.

Elderly

The pharmacokinetics of Azithromycin Pfizer in elderly men was similar to that of young adults; however, in elderly women, although higher peak concentrations (increased by 30-50%) were observed, no significant accumulation occurred.

Infants, toddlers, children and adolescents

Pharmacokinetics have been studied in children aged 4 months - 15 years taking capsules, granules or suspension. At 10 mg/kg on day 1 followed by 5 mg/kg on days 2-5, the Cmax achieved is slightly lower than adults with 224 ug/l in children aged 0.6-5 years and after 3 days dosing and 383 ug/l in those aged 6-15 years. The t1/2 of 36 h in the older children was within the expected range for adults.

Absorption

Bioavailability after oral administration is approximately 37%. Peak plasma concentrations are attained 2 to 3 hours after taking the medicinal product.

Distribution

Orally administered azithromycin is widely distributed throughout the body. In pharmacokinetic studies it has been demonstrated that the concentrations of azithromycin measured in tissues are noticeably higher (as much as 50 times) than those measured in plasma, which indicates that the agent strongly binds to tissues.

Binding to serum proteins varies according to plasma concentration and ranges from 12% at 0.5 microgram/ml up to 52% at 0.05 microgram azithromycin/ml serum. The mean volume of distribution at steady state (VVss) has been calculated to be 31.1 l/kg.

Elimination

The terminal plasma elimination half-life closely reflects the elimination half-life from tissues of 2-4 days.

Approximately 12% of an intravenously administered dose of azithromycin is excreted unchanged in urine within the following three days. Particularly high concentrations of unchanged azithromycin have been found in human bile. Also in bile, ten metabolites were detected, which were formed through N- and O- demethylation, hydroxylation of desosamine and aglycone rings and cleavage of cladinose conjugate. Comparison of the results of liquid chromatography and microbiological analyses has shown that the metabolites of azithromycin are not microbiologically active.

In animal tests, high concentrations of azithromycin have been found in phagocytes. It has also been established that during active phagocytosis higher concentrations of azithromycin are released from inactive phagocytes. In animal models this results in high concentrations of azithromycin being delivered to the site of infection.

Effects on ability to drive and use machines

There is no evidence to suggest that Azithromycin Pfizer may have an effect on a patient's ability to drive or operate machinery.

There is no evidence to suggest that Azithromycin Pfizer may have an effect on a patient's ability to drive or operate machinery.

Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

No special requirements

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.