Faculty of Pharmacy
Zithromax Tablet
Prepared by
Rawan Amr Abd Elaal Mohammed
Group C2 - 1190180
3rd grade
Supervised by
Prof. Ramadan Abdullah Hemeida
Dr. Remon Roshdy
Dr. Mahmoud Nabil
2020/2021
DESCRIPTION
ZITHROMAX (azithromycin tablets and oral suspension) contains the
active ingredient azithromycin, a macrolide antibacterial drug , for oral
administration. Azithromycin has the chemical name
(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-
3-O-methyl-α-L-ribo-hexopyranosyl)oxy]-2-ethyl- 3,4,10-trihydroxy-
3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6- trideoxy-3-(dimethylamino)-β-
D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one.
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 C 38H72N2O12,
and its molecular weight is 749.0. Azithromycin has the following
structural formula:
Azithromycin, as the dihydrate, is a white crystalline powder with a
molecular formula of C38H72N2O12•2H2O and a molecular weight of 785.0.
ZITHROMAX tablets contain azithromycin dihydrate equivalent to 600
mg azithromycin. They also contain the following inactive ingredients:
dibasic calcium phosphate anhydrous, pregelatinized starch, sodium
croscarmellose, magnesium stearate, sodium lauryl sulfate, and an aqueous
film coat consisting of hypromellose, titanium dioxide, lactose, and
triacetin.
ZITHROMAX for oral suspension is supplied in a single-dose packet
containing azithromycin dihydrate equivalent to 1 g azithromycin. It also
contains the following inactive ingredients: colloidal silicon dioxide,
sodium phosphate tribasic, anhydrous; spray dried artificial banana flavor,
spray dried artificial cherry flavor, and sucrose.
INDICATIONS
ZITHROMAX (azithromycin) for injection is a macrolide antibacterial
drug indicated for the treatment of patients with infections caused by
susceptible strains of the designated microorganisms in the conditions
listed below.
Community-Acquired Pneumonia
due to Chlamydophila pneumoniae, Haemophilus influenzae, Legionella
pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae,
Staphylococcus aureus, or Streptococcus pneumoniae in patients who
require initial intravenous therapy.
Pelvic Inflammatory Disease
due to Chlamydia trachomatis, Neisseria gonorrhoeae, or Mycoplasma
hominis in patients who require initial intravenous therapy. If anaerobic
microorganisms are suspected of contributing to the infection, an
antimicrobial agent with anaerobic activity should be administered in
combination with ZITHROMAX.
ZITHROMAX for injection should be followed by ZITHROMAX by the
oral route as required.
USAGE
To reduce the development of drug-resistant bacteria and maintain the
effectiveness of ZITHROMAX (azithromycin) and other antibacterial
drugs, ZITHROMAX (azithromycin) should be used only to treat
infections that are proven or strongly suspected to be caused by susceptible
bacteria. When culture and susceptibility information are available, they
should be considered in selecting or modifying antibacterial therapy. In the
absence of such data, local epidemiology and susceptibility patterns may
contribute to the empiric selection of therapy.
SIDE EFFECTS
Clinical Trials Experience
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 of intravenous azithromycin for community-acquired
pneumonia, in which 2 to 5 IV doses were given, the reported adverse
reactions were mild to moderate in severity and were reversible upon
discontinuation of the drug. The majority of patients in these trials had one
or more comorbid diseases and were receiving concomitant medications.
Approximately 1.2% of the patients discontinued intravenous
ZITHROMAX therapy, and a total of 2.4% discontinued azithromycin
therapy by either the intravenous or oral route because of clinical or
laboratory side effects.
In clinical trials conducted in patients with pelvic inflammatory disease, in
which 1 to 2 IV doses were given, 2% of women who received
monotherapy with azithromycin and 4% who received azithromycin plus
metronidazole discontinued therapy due to clinical side effects.
Clinical adverse reactions leading to discontinuations from these studies
were gastrointestinal (abdominal pain, nausea, vomiting, diarrhea), and
rashes; laboratory side effects leading to discontinuation were increases in
transaminase levels and/or alkaline phosphatase levels.
DRUG INTERACTIONS
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 the following drugs listed below have not been reported
in clinical trials with azithromycin; however, 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 or phenytoin are used with azithromycin careful monitoring of
patients is advised.
PRECAUTIONS
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 unknown at
present.
OVERDOSE
Adverse reactions experienced in 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.
CONTRAINDICATIONS
Hypersensitivity
ZITHROMAX is contraindicated in patients with known hypersensitivity
to azithromycin, erythromycin, any macrolide or ketolide drugs.
Hepatic Dysfunction
ZITHROMAX is contraindicated in patients with a history of cholestatic
jaundice/hepatic dysfunction associated with prior use of azithromycin.
CLINICAL PHARMACOLOGY
Mechanism Of Action
Azithromycin is a macrolide antibacterial drug [see Microbiology]
Pharmacodynamics
Based on animal models of infection, the antibacterial activity of
azithromycin appears to correlate with the ratio of area under the
concentration-time curve to minimum inhibitory concentration
(AUC/MIC) for certain pathogens (S. pneumoniae and S. aureus). The
principal pharmacokinetic/pharmacodynamic parameter best associated
with clinical and microbiological cure has not been elucidated in clinical
trials with azithromycin.
Cardiac Electrophysiology
QTc interval prolongation was studied in a randomized, placebo-controlled
parallel trial in 116 healthy subjects who received either chloroquine (1000
mg) alone or in combination with oral azithromycin (500 mg, 1000 mg,
and 1500 mg once daily). Co- administration of azithromycin increased the
QTc interval in a dose- and concentration- dependent manner. In
comparison to chloroquine alone, the maximum mean (95% upper
confidence bound) increases in QTcF were 5 (10) ms, 7 (12) ms and 9 (14)
ms with the co-administration of 500 mg, 1000 mg and 1500 mg
azithromycin, respectively.
Since the mean Cmax of azithromycin following a 500 mg IV dose given
over 1 hr is higher than the mean Cmax of azithromycin following the
administration of a 1500 mg oral dose, it is possible that QTc may be
prolonged to a greater extent with IV azithromycin at close proximity to a
one hour infusion of 500 mg.
