ZITHROMAX®

(azithromycin) Tablets and for Oral Suspension

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 or prevent infections that are proven or strongly suspected
to be caused by bacteria.
INDICATIONS
ZITHROMAX (azithromycin) is indicated for the treatment of patients with mild to moderate infections (pneumonia: see WARNINGS)
caused by susceptible strains of the designated microorganisms in the specific conditions listed below. As recommended dosages,
durations of therapy and applicable patient populations vary among these infections, please see DOSAGE AND ADMINISTRATION
for specific dosing recommendations.
Adults
Acute bacterial exacerbations of chronic obstructive pulmonary disease due to Haemophilus influenzae, Moraxella catarrhalis or
Streptococcus pneumoniae.
Acute bacterial sinusitis due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.
Community-acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus
pneumoniae in patients appropriate for oral therapy.
NOTE: Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for oral therapy
because of moderate to severe illness or risk factors such as any of the following:
patients with cystic fibrosis,
patients with nosocomially acquired infections,
patients with known or suspected bacteremia,
patients requiring hospitalization,
elderly or debilitated patients, or
patients with significant underlying health problems that may compromise their ability to respond to their illness (including
immunodeficiency or functional asplenia).
Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line
therapy.
NOTE:Penicillin by the intramuscular route is the usual drug of choice in the treatment of Streptococcus pyogenes infection and the
prophylaxis of rheumatic fever. ZITHROMAX is often effective in the eradication of susceptible strains of Streptococcus pyogenes from
the nasopharynx. Because some strains are resistant to ZITHROMAX, susceptibility tests should be performed when patients are treated
with ZITHROMAX. Data establishing efficacy of azithromycin in subsequent prevention of rheumatic fever are not available.
Uncomplicated skin and skin structure infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae.
Abscesses usually require surgical drainage.
Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae.
Genital ulcer disease in men due to Haemophilus ducreyi (chancroid). Due to the small number of women included in clinical trials, the
efficacy of azithromycin in the treatment of chancroid in women has not been established.
ZITHROMAX, at the recommended dose, should not be relied upon to treat syphilis. Antimicrobial agents used in high doses for short
periods of time 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 cultures for gonorrhea performed at the time of
diagnosis. Appropriate antimicrobial therapy and follow-up tests for these diseases should be initiated if infection is confirmed.
Appropriate culture and susceptibility tests should be performed before treatment to determine the causative organism and its
susceptibility to azithromycin. Therapy with ZITHROMAX may be initiated before results of these tests are known; once the results
become available, antimicrobial therapy should be adjusted accordingly.
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 or prevent 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.
Pediatric Patients: (See PRECAUTIONS—Pediatric Use and Clinical Studies In Pediatric Patients.)
Acute otitis media caused by Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae. (For specific dosage
recommendation, see DOSAGE AND ADMINISTRATION.)
Community-acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus
pneumoniae in patients appropriate for oral therapy. (For specific dosage recommendation, see DOSAGE AND ADMINISTRATION.)
NOTE: Azithromycin should not be used in pediatric patients with pneumonia who are judged to be inappropriate for oral
therapy because of moderate to severe illness or risk factors such as any of the following:
patients with cystic fibrosis,
patients with nosocomially acquired infections,
patients with known or suspected bacteremia,
patients requiring hospitalization, or
patients with significant underlying health problems that may compromise their ability to respond to their illness (including
immunodeficiency or functional asplenia).
Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line
therapy. (For specific dosage recommendation, see DOSAGE AND ADMINISTRATION.)
NOTE: Penicillin by the intramuscular route is the usual drug of choice in the treatment of Streptococcus pyogenes infection and the
prophylaxis of rheumatic fever. ZITHROMAX is often effective in the eradication of susceptible strains of Streptococcus pyogenes from
the nasopharynx. Because some strains are resistant to ZITHROMAX, susceptibility tests should be performed when patients are treated
with ZITHROMAX. Data establishing efficacy of azithromycin in subsequent prevention of rheumatic fever are not available.
Appropriate culture and susceptibility tests should be performed before treatment to determine the causative organism and its
susceptibility to azithromycin. Therapy with ZITHROMAX may be initiated before results of these tests are known; once the results
become available, antimicrobial therapy should be adjusted accordingly.
DOSAGE AND ADMINISTRATION
(See INDICATIONS and CLINICAL PHARMACOLOGY.)
Adults
Recommended Dose/Duration of
Infection*
Therapy
Community-aquired pneumonia (mild severity) 500 mg as a single dose on Day 1,
Pharyngitis/tonsillitis (second line therapy) Skin/skin followed by 250 mg once daily on
structure (uncomplicated) Days 2 through 5.
500 mg QD x 3 days
OR
Acute bacterial exacerbations of chronic obstructive
500 mg as a single dose on Day 1,
pulmonary disease (mild to moderate)
followed by 250 mg once daily on
Days 2 through 5.
Acute bacterial sinusitis 500 mg QD x 3 days
Genital ulcer disease (chancroid) One single 1 gram dose
Non-gonoccocal urethritis and cervicitis One single 1 gram dose
Gonococcal urethritis and cervicitis One single 2 gram dose
*DUE TO THE INDICATED ORGANISMS (See INDICATIONS.)
ZITHROMAX tablets can be taken with or without food.
Renal Insufficiency
No dosage adjustment is recommended for subjects with renal impairment (GFR ≤ 80 mL/min). The mean AUC 0-120 was similar in
subjects with GFR 10-80 mL/min compared to subjects with normal renal function, whereas it increased 35% in subjects with GFR < 10
mL/min compared to subjects with normal renal function. Caution should be exercised when azithromycin is administered to subjects
with severe renal impairment. (See CLINICAL PHARMACOLOGY, Special Populations, Renal Insufficiency.)
Hepatic Insufficiency
The pharmacokinetics of azithromycin in subjects with hepatic impairment have not been established. No dose adjustment
recommendations can be made in patients with impaired hepatic function (See CLINICAL PHARMACOLOGY, Special Populations,
Hepatic Insufficiency.)
No dosage adjustment is recommended based on age or gender. (See CLINICAL PHARMACOLOGY, Special Populations.)
Pediatric Patients
ZITHROMAX for oral suspension can be taken with or without food.
Acute Otitis Media: The recommended dose of ZITHROMAX for oral suspension for the treatment of pediatric patients with acute otitis
media is 30 mg/kg given as a single dose or 10 mg/kg once daily for 3 days or 10 mg/kg as a single dose on the first day followed by 5
mg/kg/day on Days 2 through 5. (See chart below.)
Acute Bacterial Sinusitis: The recommended dose of ZITHROMAX for oral suspension for the treatment of pediatric patients with
acute bacterial sinusitis is 10 mg/kg once daily for 3 days. (See chart below.)
Community-Acquired Pneumonia: The recommended dose of ZITHROMAX for oral suspension for the treatment of pediatric patients
with community-acquired pneumonia is 10 mg/kg as a single dose on the first day followed by 5 mg/kg on Days 2 through 5. (See chart
below.)
SIDE EFFECTS
In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug.
Potentially serious side effects of angioedema and cholestatic jaundice were reported rarely. Approximately 0.7% of the patients (adults
and pediatric patients) from the 5-day multiple-dose clinical trials discontinued ZITHROMAX (azithromycin) therapy because of
treatment-related side effects. In adults given 500 mg/day for 3 days, the discontinuation rate due to treatment-related side effects was
0.6%. In clinical trials in pediatric patients given 30 mg/kg, either as a single dose or over 3 days, discontinuation from the trials due to
treatment-related side effects was approximately 1%. (See DOSAGE AND ADMINISTRATION.) Most of the side effects leading to
discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. (See Clinical Studies In
Pediatric Patients.)
Clinical
Adults
Multiple-dose regimens: Overall, the most common treatment-related side effects in adult patients receiving multiple-dose regimens of
ZITHROMAX were related to the gastrointestinal system with diarrhea/loose stools (4-5%), nausea (3%) and abdominal pain (2-3%)
being the most frequently reported.
No other treatment-related side effects occurred in patients on the multiple-dose regimens of ZITHROMAX with a frequency greater than
1%. Side effects that occurred with a frequency of 1% or less included the following:
Cardiovascular: Palpitations, chest pain.
Gastrointestinal: Dyspepsia, flatulence, vomiting, melena and cholestatic jaundice.
Genitourinary: Monilia, vaginitis and nephritis.
Nervous System: Dizziness, headache, vertigo and somnolence.
General: Fatigue.
Allergic: Rash, pruritus, photosensitivity and angioedema.
Single 1-gram dose regimen: Overall, the most common side effects in patients receiving a single-dose regimen of 1 gram of
ZITHROMAX were related to the gastrointestinal system and were more frequently reported than in patients receiving the multiple-dose
regimen.
Side effects that occurred in patients on the single one-gram dosing regimen of ZITHROMAX with a frequency of 1% or greater
included diarrhea/loose stools (7%), nausea (5%), abdominal pain (5%), vomiting (2%), dyspepsia (1%) and vaginitis (1%).
Single 2-gram dose regimen: Overall, the most common side effects in patients receiving a single 2-gram dose of ZITHROMAX were
related to the gastrointestinal system. Side effects that occurred in patients in this study with a frequency of 1% or greater included
nausea (18%), diarrhea/loose stools (14%), vomiting (7%), abdominal pain (7%), vaginitis (2%), dyspepsia (1%) and dizziness (1%). The
majority of these complaints were mild in nature.
WARNINGS
Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Stevens Johnson Syndrome and
toxic epidermal necrolysis have been reported rarely in patients on azithromycin therapy. Although rare, fatalities have been reported.
(See CONTRAINDICATIONS.) 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.
If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware
that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.
In the treatment of pneumonia, azithromycin has only been shown to be safe and effective in the treatment of community-
acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus
pneumoniae in patients appropriate for oral therapy. Azithromycin should not be used in patients with pneumonia who are
judged to be inappropriate for oral therapy because of moderate to severe illness or risk factors such as any of the following:
patients with cystic fibrosis, patients with nosocomially acquired infections, patients with known or suspected bacteremia,
patients requiring hospitalization, elderly or debilitated patients, or patients with significant underlying health problems that
may compromise their ability to respond to their illness (including immunodeficiency or functional asplenia).
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ZITHROMAX,
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 antimicrobial 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.
PRECAUTIONS
General
Because azithromycin is principally eliminated via the liver, caution should be exercised when azithromycin is administered to patients
with impaired hepatic function. Due to the limited data in subjects with GFR < 10 mL/min, caution should be exercised when prescribing
azithromycin in these patients. (See CLINICAL PHARMACOLOGY - Special Populations -Renal Insufficiency.)
Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been
seen in treatment with other macrolides. A similar effect with azithromycin cannot be completely ruled out in patients at increased risk
for prolonged cardiac repolarization.
Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving
azithromycin therapy.
Prescribing ZITHROMAX (azithromycin) in the absence of a proven or strongly suspected bacterial infection or a prophylactic
indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate carcinogenic potential. Azithromycin has shown no mutagenic
potential in standard laboratory tests: mouse lymphoma assay, human lymphocyte clastogenic assay, and mouse bone marrow clastogenic
assay. No evidence of impaired fertility due to azithromycin was found.
Pregnancy
Teratogenic Effects. Pregnancy Category B: Reproduction studies have been performed in rats and mice at doses up to moderately
maternally toxic dose concentrations (i.e., 200 mg/kg/day). These doses, based on a mg/m 2 basis, are estimated to be 4 and 2 times,
respectively, the human daily dose of 500 mg. In the animal studies, no evidence of harm to the fetus due to azithromycin was found.
There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always
predictive of human response, azithromycin should be used during pregnancy only if clearly needed.
Nursing Mothers
It is not known whether azithromycin is excreted in human milk. Because many drugs are excreted in human milk, caution should be
exercised when azithromycin is administered to a nursing woman.
Pediatric Use
(See CLINICAL PHARMACOLOGY, INDICATIONS, and DOSAGE AND ADMINISTRATION.)
Acute Otitis Media (total dosage regimen: 30 mg/kg, see DOSAGE AND ADMINISTRATION): Safety and effectiveness in the
treatment of pediatric patients with otitis media under 6 months of age have not been established.
Acute Bacterial Sinusitis (dosage regimen: 10 mg/kg on Days 1-3): Safety and effectiveness in the treatment of pediatric patients with
acute bacterial sinusitis under 6 months of age have not been established. Use of Zithromax for the treatment of acute bacterial sinusitis
in pediatric patients (6 months of age or greater) is supported by adequate and well-controlled studies in adults, similar pathophysiology
of acute sinusitis in adults and pediatric patients, and studies of acute otitis media in pediatric patients.
Community-Acquired Pneumonia (dosage regimen: 10 mg/kg on Day 1 followed by 5 mg/kg on Days 2-5): Safety and effectiveness
in the treatment of pediatric patients with community-acquired pneumonia under 6 months of age have not been established. Safety and
effectiveness for pneumonia due to Chlamydia pneumoniae and Mycoplasma pneumoniae were documented in pediatric clinical trials.
Safety and effectiveness for pneumonia due to Haemophilus influenzae and Streptococcus pneumoniae were not documented
bacteriologically in the pediatric clinical trial due to difficulty in obtaining specimens. Use of azithromycin for these two microorganisms
is supported, however, by evidence from adequate and well-controlled studies in adults.
Pharyngitis/Tonsillitis (dosage regimen: 12 mg/kg on Days 1-5): Safety and effectiveness in the treatment of pediatric patients with
pharyngitis/tonsillitis under 2 years of age have not been established.
Studies evaluating the use of repeated courses of therapy have not been conducted. (See CLINICAL PHARMACOLOGY and
Animal Toxicology.)
Geriatric Use
Pharmacokinetic parameters in older volunteers (65-85 years old) were similar to those in younger volunteers (18-40 years old) for the 5-
day therapeutic regimen. Dosage adjustment does not appear to be necessary for older patients with normal renal and hepatic function
receiving treatment with this dosage regimen. (See CLINICAL PHARMACOLOGY.)
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.
ZITHROMAX 250 mg tablets contain 0.9 mg of sodium per tablet.
ZITHROMAX 500 mg tablets contain 1.8 mg of sodium per tablet.
ZITHROMAX for oral suspension 100 mg/5 mL contains 3.7 mg of sodium per 5 mL of constituted solution.
ZITHROMAX for oral suspension 200 mg/5 mL contains 7.4 mg of sodium per 5 mL of constituted solution.

OVERDOSE
No information provided.
CONTRAINDICATIONS
ZITHROMAX is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide
antibiotic.
Zantac Drug Description

ZANTAC® 150
(ranitidine hydrochloride) Tablets, USP
ZANTAC® 300
(ranitidine hydrochloride) Tablets, USP
ZANTAC® 25
(ranitidine hydrochloride effervescent) EFFERdose® Tablets
ZANTAC®
(ranitidine hydrochloride) Syrup, USP
INDICATIONS
ZANTAC is indicated in:
1. Short-term treatment of active duodenal ulcer. Most patients heal within 4 weeks. Studies available to date have not assessed
the safety of ranitidine in uncomplicated duodenal ulcer for periods of more than 8 weeks.
2. Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of acute ulcers. No placebo-controlled
comparative studies have been carried out for periods of longer than 1 year.
3. The treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome and systemic mastocytosis).
4. Short-term treatment of active, benign gastric ulcer. Most patients heal within 6 weeks and the usefulness of further treatment
has not been demonstrated. Studies available to date have not assessed the safety of ranitidine in uncomplicated, benign gastric
ulcer for periods of more than 6 weeks.
5. Maintenance therapy for gastric ulcer patients at reduced dosage after healing of acute ulcers. Placebo-controlled studies have
been carried out for 1 year.
6. Treatment of GERD. Symptomatic relief commonly occurs within 24 hours after starting therapy with ZANTAC 150 mg b.i.d.
 7. Treatment of endoscopically diagnosed erosive esophagitis. Symptomatic relief of heartburn commonly occurs within 24 hours
of therapy initiation with ZANTAC 150 mg q.i.d.
8. Maintenance of healing of erosive esophagitis. Placebo-controlled trials have been carried out for 48 weeks.
Concomitant antacids should be given as needed for pain relief to patients with active duodenal ulcer; active, benign gastric ulcer;
hypersecretory states; GERD; and erosive esophagitis.
DOSAGE AND ADMINISTRATION
Active Duodenal Ulcer: The current recommended adult oral dosage of ZANTAC for duodenal ulcer is 150 mg or 10 mL of syrup (2
teaspoonfuls of syrup equivalent to 150 mg of ranitidine) twice daily. An alternative dosage of 300 mg or 20 mL of syrup (4 teaspoonfuls
of syrup equivalent to 300 mg of ranitidine) once daily after the evening meal or at bedtime can be used for patients in whom dosing
convenience is important. The advantages of one treatment regimen compared to the other in a particular patient population have yet to
be demonstrated (see CLINICAL TRIALS: Active Duodenal Ulcer). Smaller doses have been shown to be equally effective in
inhibiting gastric acid secretion in US studies, and several foreign trials have shown that 100 mg twice daily is as effective as the 150-mg
dose.
Antacid should be given as needed for relief of pain (see CLINICAL PHARMACOLOGY: Pharmacokinetics).
Maintenance of Healing of Duodenal Ulcers: The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2 teaspoonfuls
of syrup equivalent to 150 mg of ranitidine) at bedtime.
Pathological Hypersecretory Conditions (such as Zollinger-Ellison syndrome):
The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to 150 mg of ranitidine)
twice a day. In some patients it may be necessary to administer ZANTAC 150-mg doses more frequently. Dosages should be adjusted to
individual patient needs, and should continue as long as clinically indicated. Dosages up to 6 g/day have been employed in patients with
severe disease.
Benign Gastric Ulcer: The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to
150 mg of ranitidine) twice a day.
Maintenance of Healing of Gastric Ulcers: The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2 teaspoonfuls of
syrup equivalent to 150 mg of ranitidine) at bedtime.
GERD: The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to 150 mg of
ranitidine) twice a day.
Erosive Esophagitis: The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to
150 mg of ranitidine) 4 times a day.
Maintenance of Healing of Erosive Esophagitis: The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2
teaspoonfuls of syrup equivalent to 150 mg of ranitidine) twice a day.
Pediatric Use: The safety and effectiveness of ZANTAC have been established in the age-group of 1 month to 16 years. There is
insufficient information about the pharmacokinetics of ZANTAC in neonatal patients (less than 1 month of age) to make dosing
recommendations.
The following 3 subsections provide dosing information for each of the pediatric indications. Also, see the subsection on Preparation of
ZANTAC 25 EFFERdose Tablets, below.
Treatment of Duodenal and Gastric Ulcers: The recommended oral dose for the treatment of active duodenal and gastric ulcers is 2 to
4 mg/kg twice daily to a maximum of 300 mg/day. This recommendation is derived from adult clinical studies and pharmacokinetic data
in pediatric patients.
Maintenance of Healing of Duodenal and Gastric Ulcers: The recommended oral dose for the maintenance of healing of duodenal and
gastric ulcers is 2 to 4 mg/kg once daily to a maximum of 150 mg/day. This recommendation is derived from adult clinical studies and
pharmacokinetic data in pediatric patients.
Treatment of GERD and Erosive Esophagitis: Although limited data exist for these conditions in pediatric patients, published
literature supports a dosage of 5 to 10 mg/kg per day, usually given as 2 divided doses.
Dosage Adjustment for Patients With Impaired Renal Function: On the basis of experience with a group of subjects with severely
impaired renal function treated with ZANTAC, the recommended dosage in patients with a creatinine clearance <50 mL/min is 150 mg
or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to 150 mg of ranitidine) every 24 hours. Should the patient's condition require, the
frequency of dosing may be increased to every 12 hours or even further with caution. Hemodialysis reduces the level of circulating
ranitidine. Ideally, the dosing schedule should be adjusted so that the timing of a scheduled dose coincides with the end of hemodialysis.
Elderly patients are more likely to have decreased renal function, therefore caution should be exercised in dose selection, and it may be
useful to monitor renal function (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Geriatrics and PRECAUTIONS: Geriatric
Use). Preparation of ZANTAC 25 EFFERdose Tablets: Tablets should not be chewed, swallowed whole, or dissolved on the tongue.
Dissolve 1 tablet in no less than 5 mL (1 teaspoonful) of water in an appropriate measuring cup. Wait until the tablet is completely
dissolved before administering the solution to the infant/child. The solution may be administered by medicine dropper or oral syringe for
infants.
Preparation of ZANTAC 150 EFFERdose Tablets: Tablets should not be chewed, swallowed whole, or dissolved on the tongue.
Dissolve each dose in approximately 6 to 8 oz of water before drinking.
SIDE EFFECTS
The following have been reported as events in clinical trials or in the routine management of patients treated with ZANTAC. The
relationship to therapy with ZANTAC has been unclear in many cases. Headache, sometimes severe, seems to be related to
administration of ZANTAC.
Central Nervous System: Rarely, malaise, dizziness, somnolence, insomnia, and vertigo. Rare cases of reversible mental confusion,
agitation, depression, and hallucinations have been reported, predominantly in severely ill elderly patients. Rare cases of reversible
blurred vision suggestive of a change in accommodation have been reported. Rare reports of reversible involuntary motor disturbances
have been received.
Cardiovascular: As with other H2-blockers, rare reports of arrhythmias such as tachycardia, bradycardia, atrioventricular block, and
premature ventricular beats.
Gastrointestinal: Constipation, diarrhea, nausea/vomiting, abdominal discomfort/pain, and rare reports of pancreatitis.
Hepatic: There have been occasional reports of hepatocellular, cholestatic, or mixed hepatitis, with or without jaundice. In such
circumstances, ranitidine should be immediately discontinued. These events are usually reversible, but in rare circumstances death has
occurred. Rare cases of hepatic failure have also been reported. In normal volunteers, SGPT values were increased to at least twice the
pretreatment levels in 6 of 12 subjects receiving 100 mg intravenously 4 times daily for 7 days, and in 4 of 24 subjects receiving 50 mg
intravenously 4 times daily for 5 days.
Musculoskeletal: Rare reports of arthralgias and myalgias.
Hematologic: Blood count changes (leukopenia, granulocytopenia, and thrombocytopenia) have occurred in a few patients. These were
usually reversible. Rare cases of agranulocytosis, pancytopenia, sometimes with marrow hypoplasia, and aplastic anemia and exceedingly
rare cases of acquired immune hemolytic anemia have been reported.
Endocrine: Controlled studies in animals and man have shown no stimulation of any pituitary hormone by ZANTAC and no
antiandrogenic activity, and cimetidine-induced gynecomastia and impotence in hypersecretory patients have resolved when ZANTAC
has been substituted. However, occasional cases of gynecomastia, impotence, and loss of libido have been reported in male patients
receiving ZANTAC, but the incidence did not differ from that in the general population.
Integumentary: Rash, including rare cases of erythema multiforme. Rare cases of alopecia and vasculitis.
Respiratory: A large epidemiological study suggested an increased risk of developing pneumonia in current users of histamine-2-
receptor antagonists (H2RAs) compared to patients who had stopped H2RA treatment, with an observed adjusted relative risk of 1.63
(95% CI, 1.072.48). However, a causal relationship between use of H2RAs and pneumonia has not been established.
Other: Rare cases of hypersensitivity reactions (e.g., bronchospasm, fever, rash, eosinophilia), anaphylaxis, angioneurotic edema, acute
interstitial nephritis, and small increases in serum creatinine.
PRECAUTIONS
General:
1. Symptomatic response to therapy with ZANTAC does not preclude the presence of gastric malignancy.
2. Since ZANTAC is excreted primarily by the kidney, dosage should be adjusted in patients with impaired renal function (see
DOSAGE AND ADMINISTRATION). Caution should be observed in patients with hepatic dysfunction since ZANTAC is
metabolized in the liver.
3. Rare reports suggest that ZANTAC may precipitate acute porphyric attacks in patients with acute porphyria. ZANTAC should
therefore be avoided in patients with a history of acute porphyria.
Laboratory Tests: False-positive tests for urine protein with MULTISTIX® may occur during ZANTAC therapy, and therefore testing
with sulfosalicylic acid is recommended.
Carcinogenesis, Mutagenesis, Impairment of Fertility: There was no indication of tumorigenic or carcinogenic effects in life-span
studies in mice and rats at dosages up to 2,000 mg/kg per day.
Ranitidine was not mutagenic in standard bacterial tests (Salmonella, Escherichia coli) for mutagenicity at concentrations up to the
maximum recommended for these assays.
In a dominant lethal assay, a single oral dose of 1,000 mg/kg to male rats was without effect on the outcome of 2 matings per week for
the next 9 weeks.
Pregnancy: Teratogenic Effects: Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at doses up to
160 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to ZANTAC. There are, however,
no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human
response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers: ZANTAC is secreted in human milk. Caution should be exercised when ZANTAC is administered to a nursing
mother.
Pediatric Use: The safety and effectiveness of ZANTAC have been established in the age-group of 1 month to 16 years for the treatment
of duodenal and gastric ulcers, gastroesophageal reflux disease and erosive esophagitis, and the maintenance of healed duodenal and
gastric ulcer. Use of ZANTAC in this age-group is supported by adequate and well-controlled studies in adults, as well as additional
pharmacokinetic data in pediatric patients and an analysis of the published literature (see CLINICAL PHARMACOLOGY: Pediatrics
and DOSAGE AND ADMINISTRATION: Pediatric Use).
Safety and effectiveness in pediatric patients for the treatment of pathological hypersecretory conditions or the maintenance of healing of
erosive esophagitis have not been established.
Safety and effectiveness in neonates (less than 1 month of age) have not been established (see CLINICAL PHARMACOLOGY:
Pediatrics).
Geriatric Use: Of the total number of subjects enrolled in US and foreign controlled clinical trials of oral formulations of ZANTAC, for
which there were subgroup analyses, 4,197 were 65 and over, while 899 were 75 and over. 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 responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with
impaired renal function. Because elderly patients are more likely to have decreased renal function, caution should be exercised in dose
selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Geriatrics and
DOSAGE AND ADMINISTRATION: Dosage Adjustment for Patients With Impaired Renal Function).
PRECAUTIONS
General:
1. Symptomatic response to therapy with ZANTAC does not preclude the presence of gastric malignancy.
2. Since ZANTAC is excreted primarily by the kidney, dosage should be adjusted in patients with impaired renal function (see
DOSAGE AND ADMINISTRATION). Caution should be observed in patients with hepatic dysfunction since ZANTAC is
metabolized in the liver.
3. Rare reports suggest that ZANTAC may precipitate acute porphyric attacks in patients with acute porphyria. ZANTAC should
therefore be avoided in patients with a history of acute porphyria.
Laboratory Tests: False-positive tests for urine protein with MULTISTIX® may occur during ZANTAC therapy, and therefore testing
with sulfosalicylic acid is recommended.
Carcinogenesis, Mutagenesis, Impairment of Fertility: There was no indication of tumorigenic or carcinogenic effects in life-span
studies in mice and rats at dosages up to 2,000 mg/kg per day.
Ranitidine was not mutagenic in standard bacterial tests (Salmonella, Escherichia coli) for mutagenicity at concentrations up to the
maximum recommended for these assays.
In a dominant lethal assay, a single oral dose of 1,000 mg/kg to male rats was without effect on the outcome of 2 matings per week for
the next 9 weeks.
Pregnancy: Teratogenic Effects: Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at doses up to
160 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to ZANTAC. There are, however,
no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human
response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers: ZANTAC is secreted in human milk. Caution should be exercised when ZANTAC is administered to a nursing
mother.
Pediatric Use: The safety and effectiveness of ZANTAC have been established in the age-group of 1 month to 16 years for the treatment
of duodenal and gastric ulcers, gastroesophageal reflux disease and erosive esophagitis, and the maintenance of healed duodenal and
gastric ulcer. Use of ZANTAC in this age-group is supported by adequate and well-controlled studies in adults, as well as additional
pharmacokinetic data in pediatric patients and an analysis of the published literature (see CLINICAL PHARMACOLOGY: Pediatrics
and DOSAGE AND ADMINISTRATION: Pediatric Use).
Safety and effectiveness in pediatric patients for the treatment of pathological hypersecretory conditions or the maintenance of healing of
erosive esophagitis have not been established.
Safety and effectiveness in neonates (less than 1 month of age) have not been established (see CLINICAL PHARMACOLOGY:
Pediatrics).
Geriatric Use: Of the total number of subjects enrolled in US and foreign controlled clinical trials of oral formulations of ZANTAC, for
which there were subgroup analyses, 4,197 were 65 and over, while 899 were 75 and over. 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 responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with
impaired renal function. Because elderly patients are more likely to have decreased renal function, caution should be exercised in dose
selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Geriatrics and
DOSAGE AND ADMINISTRATION: Dosage Adjustment for Patients With Impaired Renal Function).
Contents
Metoprolol tartrate
Indications
HTN & chronic angina pectoris.
Dosage
Adult Initially 100 mg daily. May increase at wkly intervals to max: 400 mg/day. Maintenance: 100-400 mg/day.
Overdosage
View Neobloc overdosage for action to be taken in the event of an overdose.
Administration
May be taken with or without food
Contraindications
Heart block >1st degree, AV block II & III, cardiogenic shock, overt cardiac failure, sinus bradycardia, bronchospastic disease.
Warnings
For additional cautionary notes to warn of the potential risk of using the medicine... click to view
Special Precautions
Avoid abrupt w/drawal. Diabetes, anesth, 1st trimester of pregnancy.
Adverse Drug Reactions
Gl & sleep pattern disturbances, headache, dizziness & weakness.
View ADR Monitoring Website
Side Effects
View Neobloc side effects
Drug Interactions
Increased risk of myocardial depression w/ verapamil, diltiazem & Class I antiarrhythmics.
View more drug interactions with Neobloc
Pregnancy Category (US FDA)

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no
controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit
justifies the potential risk to the foetus.
in 2nd & 3rd trimesters.

Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the
risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are
ineffective).

Storage
View Neobloc storage conditions for details to ensure optimal shelf-life.
Description
View Neobloc description for details of the chemical structure and excipients (inactive components).
Mechanism of Action
View Neobloc mechanism of action for pharmacodynamics and pharmacokinetics details.
MIMS Class
Beta-Blockers
ATC Classification
C07AB02 - Metoprolol ; Belongs to the class of selective beta-blocking agents. Used in the treatment of cardiovascular diseases.
Poison Schedule
Rx

Acute gastroenteritis is usually caused by bacteria and protozoan. In the Philippines, one of the most
common causes of acute gastroenteritis is E. histolytica. The pathologic process starts with ingestion of fecally
contaminated food and water. The organism affects the body through direct invasion and by endotoxin being
released by the organism. Through these two processes the bowel mucosal lining is stimulated and destroyed the
eventually lead to attempted defecation or tenesmus as the body tries to get rid of the foreign organism in the
stomach.
The client with acute gastroenteritis may also report excessive gas formation that may leads to
abdominal distention and passing of flatus due to digestive and absorptive malfunction in the system. Feeling of
fullness and the increase motility of the gastrointestinal tract may progress to nausea and vomiting and
increasing frequency of defecation. Abdominal pain and feeling of fullness maybe relieved only when the
patient is able to pass a flatus.
As the destruction of the bowel continues the mucosal lining erodes due to toxin, direct invasion of the
organism and the action of the hydrochloric acid of the stomach. As the protective coating of the stomach erodes
the digestive capabilities of the acid helps in destroying the stomach lining. Pain or tenderness of the abdomen
is then felt by the patient. When the burrows or ulceration reaches the blood vessels in the stomach bleeding
will be induced. Dysentery may be characterized by melena or hematochezia depending on the site and quantity
of bleeding that may ensue. Signs of bleeding may be observed also through hematemesis.
As the bowel is stimulated by the organism and its toxin, the intestinal tract secretes water and
electrolytes in the intestinal lumen. The body secretes and therefore lost Chloride and bicarbonate ions in the
bowel as the body try to get rid of the organism by increasing peristalsis and number of defecation. Sodium and
water reabsorption in the bowel is inhibited with the lost of the two electrolytes.
Mild diarrhea is characterized by 2-3 stool, borborygmi (hyperactive bowel sound),fluid and electrolyte imbalance and
hypernatremia. When the condition continue to progress, protein in the body is excreted to the lumen that further decreases the
reabsorption and the body become overwhelmed that leads to intense diarrhea with more than 10 watery stool. Serious fluid volume
deficit may lead to hypovolemic shock and eventually death.