Sumamed 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.
Sumamed is a macrolide antibacterial drug indicated for mild to moderate infections caused by designated, susceptible bacteria:
Community-acquired pneumonia in adults (1.1)
Pelvic inflammatory disease (1.2)
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Sumamed and other antibacterial drugs, Sumamed should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. (1.3)
1.1 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.
1.2 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.
Sumamed for injection should be followed by Sumamed by the oral route as required. [see Dosage and Administration ]
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Sumamed (azithromycin) and other antibacterial drugs, Sumamed (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.
2 DOSAGE AND ADMINISTRATION
[see Indications and Usage and Clinical Pharmacology (12.3)]
Community-acquired pneumonia: 500 mg as a single daily dose by the intravenous route for at least two days. (2.1)
Pelvic inflammatory disease in adults: 500 mg as a single daily dose by the intravenous route for one or two days. (2.2)
2.1 Community-Acquired Pneumonia
The recommended dose of Sumamed for injection for the treatment of adult patients with community-acquired pneumonia due to the indicated organisms is 500 mg as a single daily dose by the intravenous route for at least two days. Intravenous therapy should be followed by Sumamed by the oral route at a single, daily dose of 500 mg, administered as two 250 mg tablets to complete a 7- to 10-day course of therapy. The timing of the switch to oral therapy should be done at the discretion of the physician and in accordance with clinical response.
2.2 Pelvic Inflammatory Disease
The recommended dose of Sumamed for injection for the treatment of adult patients with pelvic inflammatory disease due to the indicated organisms is 500 mg as a single daily dose by the intravenous route for one or two days. Intravenous therapy should be followed by Sumamed by the oral route at a single, daily dose of 250 mg to complete a 7-day course of therapy. The timing of the switch to oral therapy should be done at the discretion of the physician and in accordance with clinical response.
2.3 Preparation of the Solution for Intravenous Administration
The infusate concentration and rate of infusion for Sumamed for injection should be either 1 mg/mL over 3 hr or 2 mg/mL over 1 hr. Sumamed for injection should not be given as a bolus or as an intramuscular injection.
Prepare the initial solution of Sumamed for injection by adding 4.8 mL of Sterile Water for Injection to the 500 mg vial, and shaking the vial until all of the drug is dissolved. Since Sumamed for injection is supplied under vacuum, it is recommended that a standard 5 mL (non-automated) syringe be used to ensure that the exact amount of 4.8 mL of Sterile Water is dispensed. Each mL of reconstituted solution contains 100 mg azithromycin. Reconstituted solution is stable for 24 hr when stored below 30°C (86°F).
Parenteral drug products should be inspected visually for particulate matter prior to administration. If particulate matter is evident in reconstituted fluids, the drug solution should be discarded.
Dilute this solution further prior to administration as instructed below.
To provide Sumamed over a concentration range of 1.0–2.0 mg/mL, transfer 5 mL of the 100 mg/mL Sumamed solution into the appropriate amount of any of the diluents listed below:
Normal Saline (0.9% sodium chloride)
1/2 Normal Saline (0.45% sodium chloride)
5% Dextrose in Water
Lactated Ringer's Solution
5% Dextrose in 1/2 Normal Saline (0.45% sodium chloride) with 20 mEq KCl
5% Dextrose in Lactated Ringer's Solution
5% Dextrose in 1/3 Normal Saline (0.3% sodium chloride)
5% Dextrose in 1/2 Normal Saline (0.45% sodium chloride)
Normosol®-M in 5% Dextrose
Normosol®-R in 5% Dextrose
When used with the Vial-Mate® drug reconstitution device, please reference the Vial-Mate® instructions for assembly and reconstitution.
Final Infusion Solution Concentration (mg/mL)
Amount of Diluent (mL)
Other intravenous substances, additives, or medications should not be added to Sumamed for injection, or infused simultaneously through the same intravenous line.
When diluted according to the instructions (1.0 mg/mL to 2.0 mg/mL), Sumamed for injection is stable for 24 hr at or below room temperature 30°C (86°F), or for 7 days if stored under refrigeration 5°C (41°F).
3 DOSAGE FORMS AND STRENGTHS
Sumamed for injection is supplied in lyophilized form in a 10 mL vial equivalent to 500 mg of Sumamed for intravenous administration.
Sumamed (azithromycin) for injection is supplied in lyophilized form in a 10 mL vial equivalent to 500 mg of Sumamed for intravenous administration. (3)
Patients with known hypersensitivity to azithromycin, erythromycin, any macrolide, or ketolide antibacterial drug.
Patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin. (4.2)
Sumamed is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drugs.
4.2 Hepatic Dysfunction
Sumamed is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.
5 WARNINGS AND PRECAUTIONS
Serious allergic reactions and skin reactions. Discontinue Sumamed and initiate appropriate therapy if reaction occurs. (5.1)
Hepatotoxicity: Severe and sometimes fatal, hepatoxicity has been reported. Discontinue Sumamed immediately if signs and symptoms of hepatitis occur. (5.2)
Infantile Hypertrophic Pyloric Stenosis (IHPS): Following the use of Sumamed 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. (5.3)
Prolongation of QT interval and cases of torsades de pointes have been reported. This risk which can be fatal should be considered in patients with certain cardiovascular disorders including known QT prolongation or history torsades de pointes, those with prorrhythmic conditions, and with other drugs that prolong the QT interval.(5.4)
Clostridium difficile-Associated Diarrhea: Evaluate patients if diarrhea occurs. (5.5)
Sumamed may exacerbate muscle weakness in persons with myasthenia gravis. (5.6)
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 Sumamed therapy. [see Contraindications (4.1)]
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 Sumamed exposure. These patients required prolonged periods of observation and symptomatic treatment. The relationship of these episodes to the long tissue half-life of Sumamed 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 the allergic symptoms may reappear after symptomatic therapy has been discontinued.
Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death. Discontinue Sumamed immediately if signs and symptoms of hepatitis occur.
5.3 Infantile Hypertrophic Pyloric Stenosis
Following the use of Sumamed 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.
5.4 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 Sumamed for at-risk groups including:
patients with known prolongation of the QT interval, a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias 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 or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents.
Elderly patients may be more susceptible to drug-associated effects on the QT interval.
5.5 Clostridium difficile-Associated Diarrhea
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Sumamed (azithromycin for injection), 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 antibacterial 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 antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
5.6 Exacerbation of Myasthenia Gravis
Exacerbations of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azitrhromycin therapy.
5 7 Infusion Site Reactions
Sumamed for injection should be reconstituted and diluted as directed and administered as an intravenous infusion over not less than 60 minutes. [see Dosage and Administration ]
Local IV site reactions have been reported with the intravenous administration of azithromycin. The incidence and severity of these reactions were the same when 500 mg Sumamed was given over 1 hour (2 mg/mL as 250 mL infusion) or over 3 hr (1 mg/mL as 500 mL infusion) [see Adverse Reactions (6)]. All volunteers who received infusate concentrations above 2.0 mg/mL experienced local IV site reactions and, therefore, higher concentrations should be avoided.
5.8 Development of Drug-Resistant Bacteria
Prescribing Sumamed 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.
6 ADVERSE REACTIONS
Most common adverse reactions are nausea, diarrhea (4%), abdominal pain (3%), or vomiting (1%). (6)
To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1 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 Sumamed 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 co-morbid diseases and were receiving concomitant medications. Approximately 1.2% of the patients discontinued intravenous Sumamed therapy, and a total of 2.4% discontinued Sumamed 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 Sumamed and 4% who received Sumamed 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.
Overall, the most common adverse reactions associated with treatment in adult patients who received IV/Oral Sumamed in studies of community-acquired pneumonia were related to the gastrointestinal system with diarrhea/loose stools (4.3%), nausea (3.9%), abdominal pain (2.7%), and vomiting (1.4%) being the most frequently reported.
Approximately 12% of patients experienced a side effect related to the intravenous infusion; most common were pain at the injection site (6.5%) and local inflammation (3.1%).
The most common adverse reactions associated with treatment in adult women who received IV/Oral Sumamed in trials of pelvic inflammatory disease were related to the gastrointestinal system. Diarrhea (8.5%) and nausea (6.6%) were most commonly reported, followed by vaginitis (2.8%), abdominal pain (1.9%), anorexia (1.9%), rash and pruritus (1.9%). When Sumamed was co-administered with metronidazole in these trials, a higher proportion of women experienced adverse reactions of nausea (10.3%), abdominal pain (3.7%), vomiting (2.8%), infusion site reaction, stomatitis, dizziness, or dyspnea (all at 1.9%).
Adverse reactions that occurred with a frequency of 1% or less included the following:
Gastrointestinal: Dyspepsia, flatulence, mucositis, oral moniliasis, and gastritis.
Nervous system: Headache, somnolence.
Special senses: Taste perversion.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of azithromycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Adverse reactions reported with Sumamed during the post-marketing period in adult and/or pediatric patients for which a causal relationship may not be established include:
Allergic: Arthralgia, edema, urticaria and angioedema.
Cardiovascular: Arrhythmias including ventricular tachycardia and hypotension. There have been reports of QT prolongation and torsades de pointes.
Gastrointestinal: Anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea, pseudomembranous colitis, pancreatitis, oral candidiasis, pyloric stenosis, and reports of tongue discoloration.
General: Asthenia, paresthesia, fatigue, malaise and anaphylaxis.
Genitourinary: Interstitial nephritis and acute renal failure and vaginitis.
Liver/biliary: Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure. [see Warnings and Precautions (5.2)]
Special senses: Hearing disturbances including hearing loss, deafness and/or tinnitus and reports of taste/smell perversion and/or loss.
6.3 Laboratory Abnormalities
Significant abnormalities (irrespective of drug relationship) occurring during the clinical trials were reported as follows:
elevated ALT (SGPT), AST (SGOT), creatinine (4 to 6%)
elevated LDH, bilirubin (1 to 3%)
leukopenia, neutropenia, decreased platelet count, and elevated serum alkaline phosphatase (less than 1%)
When follow-up was provided, changes in laboratory tests appeared to be reversible.
In multiple-dose clinical trials involving more than 750 patients treated with Sumamed (IV/Oral), less than 2% of patients discontinued Sumamed therapy because of treatment-related liver enzyme abnormalities.
7 DRUG INTERACTIONS
Nelfinavir: Close monitoring for known adverse reactions of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted.
Warfarin: Use with Sumamed may increase coagulation times; monitor prothrombin time. (7.2)
Co-administration of nelfinavir at steady-state with a single oral dose of Sumamed resulted in increased Sumamed serum concentrations. Although a dose adjustment of Sumamed 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. [see Adverse Reactions (6)]
Spontaneous post-marketing reports suggest that concomitant administration of Sumamed may potentiate the effects of oral anticoagulants such as warfarin, although the prothrombin time was not affected in the dedicated drug interaction study with Sumamed and warfarin. Prothrombin times should be carefully monitored while patients are receiving Sumamed and oral anticoagulants concomitantly.
7.3 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 Sumamed careful monitoring of patients is advised.
8 USE IN SPECIFIC POPULATIONS
Pediatric use: Safety and effectiveness in the treatment of patients under 16 years of age have not been established.
Geriatric use : Elderly patients may be more susceptible to development of torsades de pointes arrhythmias.(8.5)
Teratogenic Effects. Pregnancy Category B: Reproductive and development studies have not been conducted using IV administration of Sumamed to animals. Reproduction studies have been performed in rats and mice using oral administration at doses up to moderately maternally toxic dose concentrations (i.e., 200 mg/kg/day). These daily doses in rats and mice based on body surface area, are estimated to be 4 and 2 times, respectively, an adult daily dose of 500 mg. In the animal studies, no evidence of harm to the fetus due to Sumamed 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, Sumamed should be used during pregnancy only if clearly needed.
8.3 Nursing Mothers
Sumamed has been reported to be excreted in human breast milk in small amounts. Caution should be exercised when Sumamed is administered to a nursing woman.
8.4 Pediatric Use
Safety and effectiveness of Sumamed for injection in children or adolescents under 16 years have not been established. In controlled clinical studies, Sumamed has been administered to pediatric patients by the oral route. For information regarding the use of Sumamed (azithromycin for oral suspension) in the treatment of pediatric patients, [see Indications and Usage (1), and Dosage and Administration (2)] of the prescribing information for Sumamed (azithromycin for oral suspension) 100 mg/5 mL and 200 mg/5 mL bottles.
8.5 Geriatric Use
Pharmacokinetic studies with intravenous Sumamed have not been performed in older volunteers. Pharmacokinetics of Sumamed following oral administration in older volunteers (65–85 years old) were similar to those in younger volunteers (18–40 years old) for the 5-day therapeutic regimen.
In multiple-dose clinical trials of intravenous Sumamed in the treatment of community-acquired pneumonia, 45% of patients (188/414) were at least 65 years of age and 22% of patients (91/414) were at least 75 years of age. No overall differences in safety were observed between these subjects and younger subjects in terms of adverse reactions, laboratory abnormalities, and discontinuations. Similar decreases in clinical response were noted in azithromycin- and comparator-treated patients with increasing age.
Sumamed (azithromycin for injection) contains 114 mg (4.96 mEq) of sodium per vial. At the usual recommended doses, patients would receive 114 mg (4.96 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. The total sodium content from dietary and non-dietary sources may be clinically important with regard to such diseases as congestive heart failure.
Elderly patients may be more susceptible to development of torsades de pointes arrhythmias than younger patients. [see Warnings and Precautions (5.4)]
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.
Sumamed for injection contains the active ingredient azithromycin, an azalide, a subclass of macrolide antibacterial drug, for intravenous injection. Sumamed 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-hepta-methyl- 11- [[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa- 6-azacyclopentadecan-15-one. Sumamed 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 C38H72N2O12, and its molecular weight is 749.00. Sumamed has the following structural formula:
Sumamed, as the dihydrate, is a white crystalline powder with a molecular formula of C38H72N2O12∙ 2H2O and a molecular weight of 785.0.
Sumamed for injection consists of Sumamed dihydrate and the following inactive ingredients: citric acid and sodium hydroxide. Sumamed for injection is supplied in lyophilized form in a 10 mL vial equivalent to 500 mg of Sumamed for intravenous administration. Reconstitution, according to label directions, results in approximately 5 mL of Sumamed for intravenous injection with each mL containing Sumamed dihydrate equivalent to 100 mg of azithromycin.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Sumamed is a macrolide antibacterial drug [see Microbiology ]
Based on animal models of infection, the antibacterial activity of Sumamed 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.
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 Sumamed (500 mg, 1000 mg, and 1500 mg once daily). Co- administration of Sumamed 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 Sumamed following a 500 mg IV dose given over 1 hr is higher than the mean Cmax of Sumamed following the administration of a 1500 mg oral dose, it is possible that QTc may be prolonged to a greater extent with IV Sumamed at close proximity to a one hour infusion of 500 mg.
In patients hospitalized with community-acquired pneumonia receiving single daily one-hour intravenous infusions for 2 to 5 days of 500 mg Sumamed at a concentration of 2 mg/mL, the mean Cmax ± S.D. achieved was 3.63 ± 1.60 mcg/mL, while the 24-hour trough level was 0.20 ± 0.15 mcg/mL, and the AUC24 was 9.60 ± 4.80 mcg∙hr/mL.
The mean Cmax, 24-hour trough and AUC24 values were 1.14 ± 0.14 mcg/mL, 0.18 ± 0.02 mcg/mL, and 8.03 ±0.86 mcg∙hr/mL, respectively, in normal volunteers receiving a 3-hour intravenous infusion of 500 mg Sumamed at a concentration of 1 mg/mL. Similar pharmacokinetic values were obtained in patients hospitalized with community-acquired pneumonia who received the same 3-hour dosage regimen for 2–5 days.
Infusion Concentration, Duration
Time after starting the infusion
2 mg/mL, 1 hr500 mg (2 mg/mL) for 2–5 days in community-acquired pneumonia patients.
1 mg/mL, 3 hr500 mg (1 mg/mL) for 5 days in healthy subjects.
Comparison of the plasma pharmacokinetic parameters following the 1st and 5th daily doses of 500 mg intravenous Sumamed showed only an 8% increase in Cmax but a 61% increase in AUC24 reflecting a threefold rise in C24 trough levels.
Following single-oral doses of 500 mg Sumamed (two 250 mg capsules) to 12 healthy volunteers, Cmax, trough level, and AUC24 were reported to be 0.41 mcg/mL, 0.05 mcg/mL, and 2.6 mcg∙hr/mL, respectively. These oral values are approximately 38%, 83%, and 52% of the values observed following a single 500-mg I.V. 3-hour infusion (Cmax: 1.08 mcg/mL, trough: 0.06 mcg/mL, and AUC24: 5.0 mcg∙hr/mL). Thus, plasma concentrations are higher following the intravenous regimen throughout the 24-hour interval.
The serum protein binding of Sumamed is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 mcg/mL to 7% at 2 mcg/mL.
Tissue concentrations have not been obtained following intravenous infusions of azithromycin, but following oral administration in humans Sumamed has been shown to penetrate into tissues, including skin, lung, tonsil, and cervix. Tissue levels were determined following a single oral dose of 500 mg Sumamed in 7 gynecological patients. Approximately 17 hr after dosing, Sumamed concentrations were 2.7 mcg/g in ovarian tissue, 3.5 mcg/g in uterine tissue, and 3.3 mcg/g in salpinx. Following a regimen of 500 mg on the first day followed by 250 mg daily for 4 days, concentrations in the cerebrospinal fluid were less than 0.01 mcg/mL in the presence of non-inflamed meninges.
In vitro and in vivo studies to assess the metabolism of Sumamed have not been performed.
Plasma concentrations of Sumamed following single 500 mg oral and IV doses declined in a polyphasic pattern with a mean apparent plasma clearance of 630 mL/min and terminal elimination half-life of 68 hr. The prolonged terminal half-life is thought to be due to extensive uptake and subsequent release of drug from tissues.
In a multiple-dose study in 12 normal volunteers utilizing a 500 mg (1 mg/mL) one-hour intravenous-dosage regimen for five days, the amount of administered Sumamed dose excreted in urine in 24 hr was about 11% after the 1st dose and 14% after the 5th dose. These values are greater than the reported 6% excreted unchanged in urine after oral administration of azithromycin. Biliary excretion is a major route of elimination for unchanged drug, following oral administration.
Sumamed pharmacokinetics were investigated in 42 adults (21 to 85 years of age) with varying degrees of renal impairment. Following the oral administration of a single 1,000 mg dose of azithromycin, mean Cmax and AUC0–120 increased by 5.1% and 4.2%, respectively in subjects with mild to moderate renal impairment (GFR 10 to 80 mL/min) compared to subjects with normal renal function (GFR >80 mL/min). The mean Cmax and AUC0–120 increased 61% and 35%, respectively in subjects with severe renal impairment (GFR <10 mL/min) compared to subjects with normal renal function (GFR >80 mL/min).
The pharmacokinetics of Sumamed in subjects with hepatic impairment has not been established.
There are no significant differences in the disposition of Sumamed between male and female subjects. No dosage adjustment is recommended based on gender.
Pharmacokinetic studies with intravenous Sumamed have not been performed in older volunteers. Pharmacokinetics of Sumamed following oral administration in older volunteers (65–85 years old) were similar to those in younger volunteers (18–40 years old) for the 5-day therapeutic regimen. [see Geriatric Use 8.5)].
Pharmacokinetic studies with intravenous Sumamed have not been performed in children.
Drug interaction studies were performed with oral Sumamed and other drugs likely to be co-administered. The effects of co-administration of Sumamed on the pharmacokinetics of other drugs are shown in Table 1 and the effects of other drugs on the pharmacokinetics of Sumamed are shown in Table 2.
Co-administration of Sumamed at therapeutic doses had a modest effect on the pharmacokinetics of the drugs listed in Table 1. No dosage adjustment of drugs listed in Table 1 is recommended when co-administered with azithromycin.
Co-administration of Sumamed with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin. Nelfinavir significantly increased the Cmax and AUC of azithromycin. No dosage adjustment of Sumamed is recommended when administered with drugs listed in Table 2 [see Drug Interactions (7.3)].
Dose of Co-administered Drug
Dose of Azithromycin
Ratio (with/without azithromycin) of Co-administered Drug Pharmacokinetic Parameters (90% CI); No Effect = 1.00
10 mg/day for 8 days
500 mg/day orally on days 6–8
(0.63 to 1.08)
(0.81 to 1.25)
200 mg/day for 2 days, then 200 mg twice a day for 18 days
500 mg/day orally for days 16–18
(0.88 to 1.06)
(0.88 to 1.06)
20 mg/day for 11 days
500 mg orally on day 7, then 250 mg/day on days 8–11
(0.93 to 1.14)
(0.92 to 1.13)
200 mg orally twice a day for 21 days
1,200 mg/day orally on days 8–21
(0.85 to 2.43)
(0.83 to 1.57)
400 mg/day for 7 days
600 mg orally on day 7
1.04- 90% Confidence interval not reported
200 mg orally single dose
1,200 mg orally single dose
(0.98 to 1.11)
(0.97 to 1.05)
800 mg three times a day for 5 days
1,200 mg orally on day 5
(0.86 to 1.08)
(0.81 to 1.00)
15 mg orally on day 3
500 mg/day orally for 3 days
(0.89 to 1.81)
(1.01 to 1.56)
750 mg three times a day for 11 days
1,200 mg orally on day 9
(0.81 to 1.01)
(0.78 to 0.93)
100 mg on days 1 and 4
500 mg/day orally for 3 days
(0.86 to 1.57)
(0.75 to 1.12)
4 mg/kg IV on days 1, 11, 25
500 mg orally on day 7, 250 mg/day on days 8–11
(1.02 to 1.40)
(0.86 to 1.22)
300 mg orally BID ×15 days
500 mg orally on day 6, then 250 mg/day on days 7–10
(0.92 to 1.29)
(0.89 to 1.31)
0.125 mg on day 2
500 mg orally on day 1, then 250 mg/day on day 2
160 mg/800 mg/day orally for 7 days
1,200 mg orally on day 7
(0.75 to 0.97)/
(0.78 to 1.03)
(0.80 to 0.95/
(0.88 to 1.03)
500 mg/day orally for 21 days
600 mg/day orally for 14 days
(0.42 to 3.02)
(0.52 to 1.70)
500 mg/day orally for 21 days
1,200 mg/day orally for 14 days
(0.43 to 3.97)
(0.69 to 2.43)
Dose of Co-administered Drug
Dose of Azithromycin
Ratio (with/without co-administered drug) of Sumamed Pharmacokinetic Parameters (90% CI); No Effect = 1.00
400 mg/day for 7 days
600 mg orally on day 7
(1.04 to 1.42)
0.92- 90% Confidence interval not reported
200 mg orally single dose
1,200 mg orally single dose
(0.66 to 1.02)
(0.94 to 1.22)
750 mg three times a day for 11 days
1,200 mg orally on day 9
(1.77 to 3.15)
(1.80 to 2.50)
Mechanism of Action
Sumamed acts by binding to the 23S rRNA of the 50S ribosomal subunit of susceptible microorganisms inhibiting bacterial protein synthesis and impeding the assembly of the 50S ribosomal subunit.
Sumamed demonstrates cross-resistance with erythromycin. The most frequently encountered mechanism of resistance to Sumamed is modification of the 23S rRNA target, most often by methylation. Ribosomal modifications can determine cross resistance to other macrolides, lincosamides and streptogramin B (MLSB phenotype).
Sumamed has been shown to be active against the following microorganisms, both in vitro and in clinical infections. [see Indications and Usage (1)]
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for Sumamed against isolates of similar genus or organism group. However, the efficacy of Sumamed in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials.
Aerobic Gram-Positive Bacteria
Streptococci (Groups C, F, G)
Viridans group streptococci
Susceptibility Testing Methods
When available, the clinical microbiology laboratory should provide cumulative reports of in vitro susceptibility test results for antibacterial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug for treatment.
Quantitative methods are used to determine antimicrobial MICs. These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method 1,2,3,4 (broth, and/or agar). The MIC values should be interpreted according to criteria provided in Table 3.
Quantitative methods that require measurement of zone diameters can provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using standardized methods 2,3,4. This procedure uses paper disk impregnated with 15 mcg Sumamed to test the susceptibility of bacteria to azithromycin. The disk diffusion breakpoints are provided in Table 3.
Minimum Inhibitory Concentrations ( mcg/mL)
(zone diameters in mm)
Haemophilus influenzae.Insufficient information is available to determine Intermediate or Resistant interpretive criteria
Streptococci including S. pneumoniae
A report of Susceptible (S) indicates that the antimicrobial drug is likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the site of infection. A report of Intermediate (I) indicates that the result should be considered equivocal and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of the drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant (R) indicates that the antimicrobial drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentrations usually achievable at the infection site; other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test 1,2,3. Standard Sumamed powder should provide the following range of MIC values provided in Table 4. For the diffusion technique using the 15-mcg Sumamed disk the criteria provided in Table 4 should be achieved.
Quality Control Organism
Minimum Inhibitory Concentrations
Disk Diffusion (zone diameters in mm)
ATCCATCC = American Type Culture Collection 25923
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate carcinogenic potential. Sumamed 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 Sumamed was found in rats given daily doses up to 10 mg/kg.
13.2 Animal Toxicology and/or Pharmacology
Phospholipidosis (intracellular phospholipid accumulation) has been observed in some tissues of mice, rats, and dogs given multiple oral doses of azithromycin. It has been demonstrated in numerous organ systems (e.g., eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and/or pancreas) in dogs and rats treated with Sumamed at doses which, expressed on the basis of body surface area, are similar to or less than the highest recommended adult human dose. This effect has been shown to be reversible after cessation of Sumamed treatment. Based on the pharmacokinetic data, phospholipidosis has been seen in the rat (50 mg/kg/day dose) at the observed maximal plasma concentration of 1.3 mcg/mL (1.6 times the observed Cmax of 0.821 mcg /mL at the adult dose of 2 g.) Similarly, it has been shown in the dog (10 mg/kg/day dose) at the observed maximal serum concentration of 1 mcg /mL (1.2 times the observed Cmax of 0.821 mcg /mL at the adult dose of 2 g).
Phospholipidosis was also observed in neonatal rats dosed for 18 days at 30 mg/kg/day, which is less than the pediatric dose of 60 mg/kg based on body surface area. It was not observed in neonatal rats treated for 10 days at 40 mg/kg/day with mean maximal serum concentrations of 1.86 mcg /ml, approximately 1.5 times the Cmax of 1.27 mcg/ml at the pediatric dose. Phospholipidosis has been observed in neonatal dogs (10 mg/kg/day) at maximum mean whole blood concentrations of 3.54 mcg /ml, approximately 3 times the pediatric dose Cmax. The significance of the findings for animals and for humans is unknown.
14 CLINICAL STUDIES
14.1 Community-Acquired Pneumonia
In a controlled trial of community-acquired pneumonia performed in the U.S., Sumamed (500 mg as a single daily dose by the intravenous route for 2 to 5 days, followed by 500 mg/day by the oral route to complete 7 to 10 days therapy) was compared to cefuroxime (2250 mg/day in three divided doses by the intravenous route for 2 to 5 days followed by 1000 mg/day in two divided doses by the oral route to complete 7 to 10 days therapy), with or without erythromycin. For the 291 patients who were evaluable for clinical efficacy, the clinical outcome rates, i.e., cure, improved, and success (cure + improved) among the 277 patients seen at 10 to 14 days post-therapy were as follows:
Success (Cure + Improved)
In a separate, uncontrolled clinical and microbiological trial performed in the U.S., 94 patients with community-acquired pneumonia who received Sumamed in the same regimen were evaluable for clinical efficacy. The clinical outcome rates, i.e., cure, improved, and success (cure + improved) among the 84 patients seen at 10 to 14 days post-therapy were as follows:
Success (Cure + Improved)
Microbiological determinations in both trials were made at the pre-treatment visit and, where applicable, were reassessed at later visits. Serological testing was done on baseline and final visit specimens. The following combined presumptive bacteriological eradication rates were obtained from the evaluable groups:
Combined Bacteriological Eradication Rates for Azithromycin:
(at last completed visit)
64/67 (96%)Nineteen of twenty-four patients (79%) with positive blood cultures for S. pneumoniae were cured (intent-to-treat analysis) with eradication of the pathogen.
The presumed bacteriological outcomes at 10 to 14 days post-therapy for patients treated with Sumamed with evidence (serology and/or culture) of atypical pathogens for both trials were as follows:
Evidence of Infection
Cure + Improved
Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - tenth Edition. CLSI document M07-A10, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-sixth Informational Supplement, CLSI document M100-S26. CLSI document M100-S26, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2016.
Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – twelfth Edition CLSI document M02-A12, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Dilution and Disk Susceptibility Testing for Infrequently Isolated or Fastidious Bacteria: Approved Guidelines—Third Edition CLSI document M45-A3, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2016.
16 HOW SUPPLIED/STORAGE AND HANDLING
Sumamed is supplied in lyophilized form under a vacuum in a 10 mL vial equivalent to 500 mg of Sumamed for intravenous administration. Each vial also contains sodium hydroxide and 413.6 mg citric acid.
These are packaged as follows:
10 vials of 500 mg
10 vials of 500 mg with 1 Vial-Mate® Adaptor each
17 PATIENT COUNSELING INFORMATION
Patients should be informed of the following serious and potentially serious adverse reactions that have been associated with ZITHROMAX®
Diarrhea: Inform patients that diarrhea is a common problem caused by antibacterial drugs which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial. If this occurs, patients should notify their physician as soon as possible.
Licensed from Pliva
Vial-Mate is a registered trademark of Baxter International Inc., Reg. U.S. Pat and TM Off.
This product's label may have been updated. For current full prescribing information, please visit www.pfizer.com
PRINCIPAL DISPLAY PANEL - 500 mg Vial Label
(azithromycin for injection)
For I.V. infusion only
equivalent to 500 mg of azithromycin
No Latex No Preservative
PRINCIPAL DISPLAY PANEL - 500 mg Vial Label
PRINCIPAL DISPLAY PANEL - 10 Vials Carton
Contains 10 of NDC 0069-3150-84
(azithromycin for injection)
For I.V. infusion only
Equivalent to 500 mg/vial of azithromycin
To yield 100 mg/mL* of solution when reconstituted as directed
PRINCIPAL DISPLAY PANEL - 10 Vials Carton
Sumamed pharmaceutical active ingredients containing related brand and generic drugs, medications or other health care products:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug. The below information contains the active ingredients of Sumamed.
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results. Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable. Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease. The below information contains the forms, composition, doses of Sumamed.
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination. Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so. The below information contains the destination, category of Sumamed.
Sumamed indications and usages, anatomical therapeutic chemical and diseases classification codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code. The below information contains the Indications and usages, anatomical therapeutic chemical and diseases classification codes of Sumamed.
Sumamed pharmaceutical companies, researchers, developers, manufacturers, distributors and suppliers:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug. Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug. The below information contains the information about Pharmaceutical companies and Researchers involved in the development of Sumamed.
Can i drive or operate heavy machine after consuming Sumamed?
Depending on the reaction of the Sumamed after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Sumamed not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Sumamed addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
sDrugs.com conducted a study on Sumamed, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Sumamed consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
Five visitors reported useful
How is the drug Sumamed useful in reducing or relieving the symptoms? How useful is it? According to the survey conducted by the website sDrugs.com, there are variable results and below are the percentages of the users that say the medicine is useful to them and that say it is not helping them much. It is not ideal to continue taking the medication if you feel it is not helping you much. Contact your healthcare provider to check if there is a need to change the medicine or if there is a need to re-evaluate your condition. The usefulness of the medicine may vary from patient to patient, depending on the other diseases he is suffering from and slightly depends on the brand name.
Six visitors reported side effects
Did you get side effects while taking the Sumamed drug, or were there no side effects? According to the survey conducted by website sDrugs.com users, the below-mentioned percentages indicate the number of people experiencing the side effects and the number of people not experiencing the side effects when taking Sumamed medicine. Every drug produces minimal side effects, and they are negligible most times, when compared to the desired effect [use] of the medicine. Side effects depend on the dose you are taking, any drug interactions that happen when you are on other medications, if the patient is sensitive, and other associated conditions. If you cannot tolerate the side effects, consult your doctor immediately, so he can either adjust the dose or change the medication.
It has side effects
No side effects
Five visitors reported price estimates
What is your opinion about drug cost? Did you feel the cost is apt, or did you feel it is expensive? The report given by the sDrugs.com website users shows the following figures about several people who felt the medicine Sumamed is expensive, and the medicine is not expensive. The results are mixed. The perception of the cost of the medicine to be expensive or not depends on the brand name of the medicine, country, and place where it is sold, and the affordability of the patient. You can choose a generic drug in the place of the branded drug to save the cost. The efficiency of the medicine will not vary if it is generic or a branded one.
Four visitors reported frequency of use
How often in a day do you take the medicine? Are you taking the Sumamed drug as prescribed by the doctor? Few medications can be taken Once in a day more than prescribed when the doctor's advice mentions the medicine can be taken according to frequency or severity of symptoms. Most times, be very careful and clear about the number of times you are taking the medication. The report of sDrugs.com website users about the frequency of taking the drug Sumamed is mentioned below.
Once in a day
Five visitors reported doses
What is the dose of Sumamed drug you are taking? According to the survey conducted among sDrugs.com website users, the maximum number of people are using the following dose 201-500mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
Five visitors reported time for results
What is the time duration Sumamed drug must be taken for it to be effective or for it to reduce the symptoms? Most chronic conditions need at least some time so the dose and the drug action gets adjusted to the body to get the desired effect. The stastistics say sDrugs.com website users needed 3 days to notice the result from using Sumamed drug. The time needed to show improvement in health condition after using the medicine Sumamed need not be same for all the users. It varies based on other factors.
Four visitors reported administration
The drugs are administered in various routes, like oral or injection form. They are administered before food or after food. How are you taking Sumamed drug, before food or after food? Click here to find out how other users of our website are taking it. For any doubts or queries on how and when the medicine is administered, contact your health care provider immediately.
Four visitors reported age
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The information was verified by Dr. Arunabha Ray, MD Pharmacology