DRUGS & SUPPLEMENTS
advertisement
What are the side effects you encounter while taking this medicine?

Medication: Sumamed

Rating: 3.65 - 15 review(s)

Sumamed uses

  1. 1 INDICATIONS AND USAGE
  2. 2 DOSAGE AND ADMINISTRATION
  3. 3 DOSAGE FORMS AND STRENGTHS
  4. 4 CONTRAINDICATIONS
  5. 5 WARNINGS AND PRECAUTIONS
  6. 6 ADVERSE REACTIONS
  7. 7 DRUG INTERACTIONS
  8. 8 USE IN SPECIFIC POPULATIONS
  9. 10 OVERDOSAGE
  10. 11 DESCRIPTION
  11. 12 CLINICAL PHARMACOLOGY
  12. 13 NONCLINICAL TOXICOLOGY
  13. 14 CLINICAL STUDIES
  14. 15 REFERENCES
  15. 16 HOW SUPPLIED/STORAGE AND HANDLING
  16. 17 PATIENT COUNSELING INFORMATION
  17. PATIENT INFORMATIONZMAX® (AZITHROMYCIN EXTENDED RELEASE)ORAL SUSPENSION
  18. PRINCIPAL DISPLAY PANEL - 2 G BOTTLE LABEL
  19. PRINCIPAL DISPLAY PANEL - 2 G BOTTLE CARTON

1 INDICATIONS AND USAGE


Zmax is a macrolide antimicrobial drug indicated for mild to moderate infections caused by designated, susceptible bacteria:

  • Acute bacterial sinusitis in adults
  • Community-acquired pneumonia in adults and children 6 months and older
  • Limitation of Use
    Sumamed 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.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Zmax and other antibacterial drugs, Zmax should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.

1.1 Acute Bacterial Sinusitis in Adults and Community-Acquired Pneumonia


Zmax is a macrolide antibacterial drug indicated for the treatment with mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below. [See Clinical Studies (14)]

Acute bacterial sinusitis in adults due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.

Community-acquired pneumonia in adults and pediatric patients six months of age or older due to Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae, in patients appropriate for oral therapy. Pediatric use in this indication is based on extrapolation of adult efficacy. [See Use in Specific Populations (8.4)]

1.2 Limitations of Use


Zmax is not recommended for use 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 nosocomial 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).

1.3 Usage


To reduce the development of drug-resistant bacteria and maintain the effectiveness of Zmax (azithromycin) and other antibacterial drugs, Zmax (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

  • Adults: 2 g as a single dose; consume contents of full bottle.
  • Pediatric: 60 mg/kg as a single dose, up to a maximum of 2 g.

2.1 Adults


Zmax should be taken as a single 2 g dose. Zmax provides a full course of antibacterial therapy in a single oral dose. It is recommended that Zmax be taken on an empty stomach (at least 1 hr before or 2 hr following a meal).

2.2 Pediatric Patients


For pediatric patients 6 months and older, Zmax should be taken as a single dose of 60 mg/kg body weight. The Zmax dose in mL is equivalent to the child's weight in lb (1 mL/lb dose, see Table 1 below), for a body weight of less than 75 lb (34 kg). It is recommended that Zmax be taken on an empty stomach (at least 1 hr before or 2 hrs following a meal).

Pediatric patients weighing 75 lb (34 kg) or more should receive the adult dose (2 g).

Dosing Calculated on 1 mL/lb, Dose 1 mL of Suspension for every 1 lb of Body Weight for Children <75 lb (34 kg)To ensure accurate dosing, a dosing spoon, medicine syringe, or cup is recommended.
Weight 1 mL/lb Dose
Lb Kg Dose Volume
(mg) (mL)
       
10 5 270 10
15 7 405 15
20 9 540 20
25 11 675 25
30 14 810 30
35 16 945 35
40 18 1080 40
45 20 1215 45
50 23 1350 50
55 25 1485 55
60 27 1620 60
65 30 1755 65
70 32 1890 70
≥75 34 2000 Consume entire contents of bottle

2.3 Additional Treatment after Vomiting with Zmax


In the event that a patient vomits within 5 minutes of administration, the health care provider should consider additional antibiotic treatment since there would be minimal absorption of azithromycin. Since insufficient data exist on absorption of Sumamed if a patient vomits between 5 and 60 minutes following administration, alternative therapy should be considered. Neither a second dose of Zmax nor alternative treatment is warranted if vomiting occurs ≥60 minutes following administration, in patients with normal gastric emptying. In patients with delayed gastric emptying, alternative therapy should be considered.

2.4 Instructions for the Pharmacist


Constitute with 60 mL of water and replace cap. Shake bottle well before dispensing. Do not refrigerate. Constituted suspension should be consumed within 12 hr.

For pediatric dosing in patients weighing less than 75 lb (34 kg), use of a dosing device is recommended. The pharmacist should inform the patient's caregiver that any suspension remaining after dosing MUST be discarded.

3 DOSAGE FORMS AND STRENGTHS


Each bottle of Zmax contains Sumamed dihydrate equivalent to 2 g of azithromycin. After constitution with 60 mL of water, each mL of suspension contains 27 mg of azithromycin. The suspension is a white or off-white color and has a cherry/banana flavor.

Bottle containing 2 g Sumamed for constitution with 60 mL of water (final concentration 27 mg/mL).

4 CONTRAINDICATIONS


Hypersensitivity to azithromycin, erythromycin, or any macrolide or ketolide drug.

History of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

4.1 Hypersensitivity Reactions


Zmax is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin or any macrolide or ketolide drug.

4.2 Cholestatic Jaundice/Hepatic Dysfunction


Zmax is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

5 WARNINGS AND PRECAUTIONS

  • Allergic and Skin Reactions : Discontinue Zmax if reaction occurs.
  • Hepatotoxicity: severe, and sometimes fatal, hepatotoxicity has been reported. Discontinue immediately if signs and symptoms of hepatitis occur.
  • 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.
  • Prolongation of the 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 of torsades de pointes, those with proarrhythmic conditions, and with other drugs that prolong the QT interval.
  • Clostridium difficile-Associated Diarrhea: Evaluate patients if diarrhea occurs.
  • Zmax may exacerbate muscle weakness in persons with myasthenia gravis.
  • Gastrointestinal Disturbances: higher incidence in patients with GFR<10 mL/min.

5.1 Allergic and Skin Reactions


Serious allergic reactions, including angioedema, anaphylaxis, Acute Generalized Exanthematous Pustulosis (AGEP), Stevens Johnson syndrome, and toxic epidermal necrolysis have been reported in patients on Sumamed therapy using other formulations. 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 exposure to antigen has not been determined.

If an allergic reaction occurs, appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.

5.2 Hepatotoxicity


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 in 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 (CDAD)


Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Zmax, 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.

5.6 Exacerbation of Myasthenia Gravis


Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving Sumamed therapy.

5.7 Gastrointestinal Disturbances


A higher incidence of gastrointestinal adverse events was observed when Zmax was administered to a limited number of subjects with GFR<10 mL/min. [See Use in Specific Populations (8.6)]

5.8 Development of Drug Resistant Bacteria


Prescribing Zmax 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 diarrhea/loose stools, nausea, abdominal pain, headache, and vomiting.



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.

Adults:

The data described below reflect exposure to Zmax in 728 adult patients. All patients received a single 2 g oral dose of Zmax. The population studied had community-acquired pneumonia and acute bacterial sinusitis.

In controlled clinical trials with Zmax, the majority of the reported treatment-related adverse reactions were gastrointestinal in nature and mild to moderate in severity.

Overall, the most common treatment-related adverse reactions in adult patients receiving a single 2 g dose of Zmax were diarrhea/loose stools (12%), nausea (4%), abdominal pain (3%), headache (1%), and vomiting (1%). The incidence of treatment-related gastrointestinal adverse reactions was 17% for Zmax and 10% for pooled comparators.

Treatment-related adverse reactions following Zmax treatment that occurred with a frequency of <1% included the following:

Cardiovascular: Palpitations, chest pain

Gastrointestinal: Constipation, dyspepsia, flatulence, gastritis, oral moniliasis

Genitourinary: Vaginitis

Nervous system: Dizziness, vertigo

General: Asthenia

Allergic: Rash, pruritus, urticaria

Special senses: Taste perversion

Pediatric Patients:

The data described below reflect exposure to Zmax in 907 pediatric patients. The population was 3 months to 12 years of age. All patients received a single 60 mg/kg oral dose of Zmax.

As in adults, the most common treatment-related adverse reactions in pediatric subjects were gastrointestinal in nature. The pediatric subjects all received a single 60 mg/kg dose (equivalent to 27 mg/lb) of Zmax.

In a trial with 450 pediatric subjects (ages 3 months to 48 months), vomiting (11%), diarrhea (10%) loose stools (9%), and abdominal pain (2%) were the most frequently reported treatment-related gastrointestinal adverse reactions. Many treatment related gastrointestinal adverse reactions with an incidence greater than 1% began on the day of dosing in these subjects [43% (68/160)] and most [53% (84/160)] resolved within 48 hr of onset. Treatment-related adverse events that were not gastrointestinal, occurring with a frequency ≥ 1% were: rash (5%), anorexia (2%), fever (2%), and dermatitis (2%).

In a second trial of 337 pediatric subjects, ages 2 years to 12 years, the most frequently reported treatment-related adverse reactions also included vomiting (14%), diarrhea (7%), loose stools (2%), nausea (4%) and abdominal pain (4%).

A third trial investigated the tolerability of two different concentrations of Sumamed oral suspension in 120 pediatric subjects (ages 3 months to 48 months), all of whom were treated with azithromycin. The study evaluated the hypothesis that a more dilute, less viscous formulation (the recommended 27 mg/mL concentration of Zmax) is less likely to induce vomiting in young children than a more concentrated suspension used in other pediatric studies. The vomiting rate for subjects taking the dilute concentration Sumamed was 3% (2/61). The rate was numerically lower but not statistically different from the vomiting for the more concentrated suspension Across both treatment arms, the only treatment-related adverse events with a frequency of ≥ 1% were vomiting (6%, 7/120) and diarrhea (2%, 2/120).

Treatment-related adverse reactions with a frequency of < 1% following Zmax treatment in all 907 pediatric subjects in the Phase 3 studies were:

Body as a whole: Chills, fever, flu syndrome, headache;

Digestive: Abnormal stools, constipation, dyspepsia, flatulence, gastritis, gastrointestinal disorder, hepatitis;

Hematologic and lymphatic: Leukopenia;

Nervous system: Agitation, emotional liability, hostility, hyperkinesia, insomnia, irritability, paresthesia, Somnolence;

Respiratory: Asthma, bronchitis, cough, dyspnea, pharyngitis, rhinitis;

Skin and appendages: Dermatitis, fungal dermatitis, maculopapular rash, pruritus, urticaria;

Special senses: Otitis media, taste perversion;

Urogenital: Dysuria.

6.2 Postmarketing Experience with Other Sumamed Products


Because these reactions are reported voluntarily from a population of uncertain size, reliably estimating their frequency or establishing a causal relationship to drug exposure is not always possible.

Adverse events reported with Sumamed immediate release formulations during the postmarketing period for which a causal relationship may not be established include:

Allergic: Arthralgia, edema, urticaria and angioedema

Cardiovascular: Palpitations and 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 rare reports of tongue discoloration

General: Asthenia, paresthesia, fatigue, malaise and anaphylaxis

Genitourinary: Interstitial nephritis, acute renal failure and vaginitis

Hematopoietic: Thrombocytopenia, mild neutropenia

Liver/biliary: Adverse reactions related to hepatic dysfunction have been reported in postmarketing experience with azithromycin. [See Warnings and Precautions ]

Nervous system: Convulsions, dizziness/vertigo, headache, somnolence, hyperactivity, nervousness, agitation and syncope

Psychiatric: Aggressive reaction and anxiety

Skin/appendages: Pruritus, rash, photosensitivity, serious skin reactions including erythema multiforme, AGEP, Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS.

Special senses: Hearing disturbances including hearing loss, deafness and/or tinnitus and reports of taste/smell perversion and/or loss

6.3 Laboratory Abnormalities


In subjects with normal baseline values, the following clinically significant laboratory abnormalities (irrespective of drug relationship) were reported in Zmax clinical trials in adults and pediatric patients:

Adults:

Laboratory abnormalities with an incidence of greater than or equal to 1%: reduced lymphocytes and increased eosinophils; reduced bicarbonate. Laboratory abnormalities with an incidence of less than 1%: leukopenia, neutropenia, elevated bilirubin, AST, ALT, BUN, creatinine, alterations in potassium. Where follow-up was provided, changes in laboratory tests appeared to be reversible.

Pediatric Patients:

Laboratory abnormalities with an incidence of greater than or equal to 1%: elevated eosinophils, BUN, and potassium; decreased lymphocytes; and alterations in neutrophils; with an incidence of less than 1%: elevated SGOT, SGPT and creatinine; decreased potassium; and alterations in sodium and glucose.

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.

7.1 Nelfinavir


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 ]

7.2 Warfarin


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 Interactions with Macrolides


Interactions with digoxin or phenytoin have not been reported in clinical trials with azithromycin; however, no specific drug interaction studies have been performed to evaluate potential drug-drug interactions. However, drug interactions have been observed with other macrolide products. Until further data are developed regarding drug interactions when digoxin or phenytoin are used concomitantly with Sumamed careful monitoring of patients is advised.

8 USE IN SPECIFIC POPULATIONS

  • Pediatric use: Safety and efficacy in the treatment of patients under 6 months of age have not been established.
  • Geriatric use: Elderly patients may be more susceptible to development of torsades de pointes arrhythmias.

8.1 Pregnancy


Teratogenic Effects. Pregnancy Category B: Reproduction studies have been performed in rats and mice at doses up to moderately maternally toxic dose concentrations. These daily doses in rats and mice, based on body surface area, are estimated to be approximately equivalent to one or one-half of, respectively, the single adult oral dose of 2 g. 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 in the treatment of pediatric patients under 6 months of age have not been established.

Community-Acquired Pneumonia: The safety and effectiveness of Zmax have been established in pediatric patients 6 months of age or older with community-acquired pneumonia due to Chlamydophila pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae or Streptococcus pneumoniae. Use of Zmax for these patients is supported by evidence from adequate and well-controlled studies of Zmax in adults with additional safety and pharmacokinetic data in pediatric patients. [See Dosage and Administration , Adverse reactions (6), Clinical Pharmacology (12.3)]

Acute bacterial sinusitis: Safety and effectiveness in the treatment of pediatric patients with acute bacterial sinusitis have not been established.

8.5 Geriatric Use


Data collected from the Sumamed capsule and tablet formulations indicate that a dosage adjustment does not appear to be necessary for older patients with normal renal function (for their age) and hepatic function receiving treatment with Zmax.

In clinical trials of Zmax, 17% of subjects were at least 65 years of age (214/1292) and 5% of subjects (59/1292) were at least 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Elderly patients may be more susceptible to development of torsades de pointes arrhythmia than younger patients. [See Warnings and Precautions (5.4)]

8.6 Renal Impairment


No dosage adjustment is recommended for patients GFR >10 mL/min. Caution should be exercised when Zmax is administered to patients with GFR <10 mL/min, due to a higher incidence of gastrointestinal adverse events observed in a limited number of subjects with GFR <10 mL/min. [See Clinical Pharmacology (12)]

8.7 Gender


The impact of gender on the pharmacokinetics of Sumamed has not been evaluated for Zmax. However, previous studies have demonstrated no significant differences in the disposition of Sumamed between male and female subjects. No dosage adjustment of Zmax is recommended based on gender.

10 OVERDOSAGE


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

11 DESCRIPTION


Zmax (azithromycin extended-release) for oral suspension contains the active ingredient Sumamed (as Sumamed dihydrate), an azalide, a subclass of macrolide antibacterial drug. 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-heptamethyl-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 749.0. 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.

Zmax is a single-dose, extended-release formulation of microspheres for oral suspension containing Sumamed (as Sumamed dihydrate) and the following excipients: glyceryl behenate, poloxamer 407, sucrose, sodium phosphate tribasic anhydrous, magnesium hydroxide, hydroxypropyl cellulose, xanthan gum, colloidal silicon dioxide, titanium dioxide, artificial cherry flavor, and artificial banana flavor.

Note: Each bottle of Zmax 2 g for oral suspension contains approximately 148 mg of sodium and 19 g of sucrose. Constituted Zmax oral suspension contains approximately 2 mg/mL of sodium and 0.26 g/mL of sucrose.

Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action


Sumamed is a macrolide antibacterial drug. [See Clinical Pharmacology ]

12.2 Pharmacodynamics


Cardiac Electrophysiology

QTc interval prolongation was studied in a randomized, placebo-controlled parallel trial in 116 healthy subjects who received either chloroquine (1000 mg) alone or in combination with 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.

12.3 Pharmacokinetics


Zmax is an extended-release microsphere formulation. Based on data obtained from studies evaluating the pharmacokinetics of Sumamed in healthy adult subjects a higher peak serum concentration and greater systemic exposure (AUC 0–24) of Sumamed are achieved on the day of dosing following a single 2 g dose of Zmax versus 1.5 g of Sumamed tablets administered over 3 days (500 mg/day) or 5 days (500 mg on day 1, 250 mg/day on days 2–5) [Table 2]. Consequently, due to these different pharmacokinetic profiles, Zmax is not interchangeable with Sumamed tablet 3-day and 5-day dosing regimens.

Pharmacokinetic ParameterZmax, 3-day and 5-day regimen parameters obtained from separate pharmacokinetic studies Sumamed Regimen
Zmax
[N=41]N = 21 for AUC0–∞ and t1/2
3-day Cmax, Tmax and AUC0–24 values for Day 1 only
[N=12]
5-day
[N=12]
¶ Total AUC for the 1-day, 3-day and 5-day regimens
SD = standard deviation
Cmax = maximum serum concentration
Tmax = time to Cmax
AUC = area under concentration vs. time curve
t1/2 = terminal serum half-life
Cmax (mcg/mL) 0.821
(0.281)
0.441
(0.223)
0.434
(0.202)
Tmax Median (range) (hr) 5.0
(2.0–8.0)
2.5
(1.0–4.0)
2.5
(1.0–6.0)
AUC0–24
(mcg∙hr/mL)
8.62
(2.34)
2.58
(0.84)
2.60
(0.71)
AUC0–∞
(mcg∙hr/mL)
20.0
(6.66)
17.4
(6.2)
14.9
(3.1)
t1/2 (hr) 58.8
(6.91)
71.8
(14.7)
68.9
(13.8)

Absorption

The bioavailability of Zmax relative to Sumamed immediate release (IR) (powder for oral suspension) was 83%. On average, peak serum concentrations were achieved approximately 2.5 hr later following Zmax administration and were lower by 57%, compared to 2 g Sumamed IR. Thus, single 2 g doses of Zmax and Sumamed IR are not bioequivalent and are not interchangeable.

Effect of food on absorption: A high-fat meal increased the rate and extent of absorption of a 2 g dose of Zmax (115% increase in Cmax, and 23% increase in AUC0–72) compared to the fasted state. A standard meal also increased the rate of absorption (119% increase in Cmax) and with less effect on the extent of absorption (12% increase in AUC0–72) compared to administration of a 2 g Zmax dose in the fasted state.

Effect of antacids: Following the administration of Zmax with an aluminum and magnesium hydroxide antacid, the rate and extent of Sumamed absorption were not altered.

Distribution

The serum protein binding of Sumamed is concentration dependent, decreasing from 51% at 0.02 mcg/mL to 7% at 2 mcg/mL. Following oral administration, Sumamed is widely distributed throughout the body with an apparent steady-state volume of distribution of 31.1 L/kg.

Sumamed concentrates in fibroblasts, epithelial cells, macrophages, and circulating neutrophils and monocytes. Higher Sumamed concentrations in tissues than in plasma or serum have been observed. White blood cell and lung exposure data in humans following a single 2 g dose of Zmax in adults are shown in Table 3. Following a 2 g single dose of Zmax, Sumamed achieved higher exposure (AUC0–120) in mononuclear leukocytes (MNL) and polymorphonuclear leukocytes (PMNL) than in serum. The Sumamed exposure (AUC0–72) in lung tissue and alveolar cells (AC) was approximately 100 times that in serum; and the exposure in epithelial lining fluid (ELF) was also higher (approximately 2–3 times) than in serum. The clinical significance of this distribution data is unknown.

A single 2 g dose of Zmax
Abbreviation: WBC: white blood cells; MNL: mononuclear leukocytes; PMNL: polymorphonuclear leukocytes; ELF: Epithelial lining fluid
WBC Cmax (mcg/mL) AUC0–24 (mcg∙hr/mL) AUC0–120 (mcg∙hr/mL) Ct=120 Sumamed concentration at 120 hr after the start of dosing (mcg/mL)
MNLData are presented as mean (standard deviation) 116 (40.2) 1790 (540) 4710 (1100) 16.2 (5.51)
PMNL 146 (66.0) 2080 (650) 10000 (2690) 81.7 (23.3)
         
LUNG Cmax (mcg/mL) AUC0–24 (mcg∙hr/mL) AUC0–72 (mcg∙hr/mL)
ALVEOLAR CELLCmax and AUC were calculated based on composite profile (n = 4 subjects/time point/formulation). 669 7028 20403 -
ELF 3.2 17.6 131 -
         
Cmax (mcg/g) AUC0–24 (mcg∙hr/g) AUC0–72 (mcg∙hr/g)
LUNG TISSUE 37.9 505 1693 -

Following a regimen of 500 mg of Sumamed tablets on the first day and 250 mg daily for 4 days, only very low concentrations were noted in cerebrospinal fluid (less than 0.01 mcg/mL) in the presence of non-inflamed meninges.

Metabolism

In vitro and in vivo studies to assess the metabolism of Sumamed have not been performed.

Excretion

Serum Sumamed concentrations following a single 2 g dose of Zmax declined in a polyphasic pattern with a terminal elimination half-life of 59 hr. The prolonged terminal half-life is thought to be due to a large apparent volume of distribution.

Biliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination. Over the course of a week, approximately 6% of the administered dose appears as unchanged drug in urine.

Specific Populations

Renal Insufficiency

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 1.0 g dose of Sumamed (4 × 250 mg capsules), the mean Cmax and AUC0–120 were 5.1% and 4.2% higher, respectively in subjects with GFR 10 to 80 mL/min compared to subjects with normal renal function (GFR >80 mL/min). The mean Cmax and AUC0–120 were 61% and 35% higher, respectively in subjects with GFR <10 mL/min compared to subjects with normal renal function. [See Use in Specific Populations Renal Impairment (8.6)]

Hepatic Insufficiency

The pharmacokinetics of Sumamed in subjects with hepatic impairment has not been established.

Pediatric Patients

The pharmacokinetics of Sumamed were characterized following a single 60 mg/kg dose of Zmax in pediatric patients aged 3 months to 16 years. Although there was high inter-patient variability in systemic exposure (AUC and Cmax) across the age groups studied, individual Sumamed AUC and Cmax values in pediatric patients were comparable to or higher than those following administration of 2 g Zmax in adults (Table 4). [See Use in Specific Populations (8.4)]

Treatment Group Pharmacokinetic Parameters
Cmax
(mcg/mL)
Tmax Median (range) presented only for Tmax
(hr)
AUC(0–24)
(mcg∙hr/mL)
AUC(0–∞)
(mcg∙hr/mL)
Empty stomach = dosed with Zmax at least 1 hr before or 2 hr after a meal (Groups I–VI)
Fed = dosed with Zmax within 5 minutes of consuming an age-appropriate high-fat breakfast (Group VII)
Group 1 (N = 6)
[3 to 18 months]
0.74 (0.20) 3 (3–3) 6.29 (1.17) 14.1 (2.16)
(n = 3)
Group 2High mean values were driven by 2 subjects with high exposure (N = 6)
[>18 to 36 months]
1.88 (0.50) 3 (3–3) 19.7 (5.35) 37.3 (12.9)
(n = 5)
Group 3 (N = 6)
[>36 to 48 months]
1.23 (0.42) 3 (3–6) 12.9 (3.79) 22.4 (5.96)
Group 4 (N = 6)
[>48 months to 8 years]
1.13 (0.34) 3 (3–6) 13.0 (4.21) 22.2 (6.89)
Group 5 (N = 6)
[>8 to 12 years]
1.65 (0.38) 3 (3–6) 16.0 (4.99) 30.1 (10.7)
Group 6 (N = 6)
[>12 to 16 years]
0.98 (0.35) 3 (3–6) 11.0 (4.78) 21.3 (9.37)
Pooled 1–6 (N = 36)
[On an empty stomach]
1.27 (0.53) 3 (3–6) 13.1 (5.78) 25.2 (10.7)
(n = 32)
Group 7One subject vomited immediately after dosing and discontinued from the study (N = 7)
[Fed; 18 months to 8 years]
1.41 (0.62) 3 (1.5–3.1) 7.43 (3.00) 18.9 (3.57)
(n = 3)

Gender

The impact of gender on the pharmacokinetics of Sumamed has not been evaluated for Zmax. However, previous studies have demonstrated no significant differences in the disposition of Sumamed between male and female subjects.

Pharmacokinetic Interaction Studies

A drug interaction study was performed with Zmax and antacids. All other drug interaction studies were performed with Sumamed immediate release (IR) formulations (capsules and tablets, doses ranging from 500 to 1200 mg) 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 5 and the effects of other drugs on the pharmacokinetics of Sumamed are shown in Table 6.

When used at therapeutic doses, Sumamed IR had a minimal effect on the pharmacokinetics of atorvastatin, carbamazepine, cetirizine, didanosine, efavirenz, fluconazole, indinavir, midazolam, nelfinavir, sildenafil, theophylline (intravenous and oral), triazolam, trimethoprim/sulfamethoxazole or zidovudine (Table 5). Although the drug interaction studies were not conducted with Zmax, similar modest effect as observed with IR formulation are expected since the total exposure to Sumamed is comparable for Zmax and other Sumamed IR regimens. Therefore, no dosage adjustment of drugs listed in Table 5 is recommended when co-administered with Zmax.

Nelfinavir significantly increased the Cmax and AUC of Sumamed following co-administration with Sumamed IR 1200 mg (Table 6). However, no dose adjustment of Sumamed is recommended when Zmax is co-administered with nelfinavir.

Pharmacokinetic and/or pharmacodynamic interactions with the 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. Nonetheless, pharmacokinetic and/or pharmacodynamic interactions with these drugs have been observed with other macrolide products. Until further data are developed, careful monitoring of patients is advised when Sumamed and these drugs are used concomitantly: digoxin, ergotamine or dihydroergotamine, cyclosporine, hexobarbital and phenytoin.

Co-administered Drug Dose of Co-administered Drug Dose of AzithromycinRefers to Sumamed capsules and tablets unless specified n Ratio (with/without Azithromycin) of Co-administered Drug Pharmacokinetic Parameters (90% CI); No Effect = 1.00
Mean Cmax Mean AUC
Atorvastatin 10 mg/day for 8 days 500 mg/day orally on days 6–8 12 0.83
(0.63 to 1.08)
1.01
(0.81 to 1.25)
Carbamazepine 200 mg/day for 2 days, then 200 mg twice a day for 18 days 500 mg/day orally for days 16–18 7 0.97
(0.88 to 1.06)
0.96
(0.88 to 1.06)
Cetirizine 20 mg/day for 11 days 500 mg orally on day 7, then 250 mg/day on days 8–11 14 1.03
(0.93 to 1.14)
1.02
(0.92 to 1.13)
Didanosine 200 mg orally twice a day for 21 days 1,200 mg/day orally on days 8–21 6 1.44
(0.85 to 2.43)
1.14
(0.83 to 1.57)
Efavirenz 400 mg/day for 7 days 600 mg orally on day 7 14 1.0490% confidence interval not reported 0.95
Fluconazole 200 mg orally single dose 1,200 mg orally single dose 18 1.04
(0.98 to 1.11)
1.01
(0.97 to 1.05)
Indinavir 800 mg three times a day for 5 days 1,200 mg orally on day 5 18 0.96
(0.86 to 1.08)
0.90
(0.81 to 1.00)
Midazolam 15 mg orally on day 3 500 mg/day orally for 3 days 12 1.27
(0.89 to 1.81)
1.26
(1.01 to 1.56)
Nelfinavir 750 mg three times a day for 11 days 1,200 mg orally on day 9 14 0.90
(0.81 to 1.01)
0.85
(0.78 to 0.93)
Sildenafil 100 mg on days 1 and 4 500 mg/day orally for 3 days 12 1.16
(0.86 to 1.57)
0.92
(0.75 to 1.12)
Theophylline 4 mg/kg IV on days 1, 11, 25 500 mg orally on day 7, then 250 mg/day on days 8–11 10 1.19
(1.02 to 1.40)
1.02
(0.86 to 1.22)
Theophylline 300 mg orally twice a day for 15 days 500 mg orally on day 6, then 250 mg/day on days 7–10 8 1.09
(0.92 to 1.29)
1.08
(0.89 to 1.31)
Triazolam 0.125 mg on day 2 500 mg orally on day 1, then 250 mg/day on day 2 12 1.06 1.02
Trimethoprim/
Sulfamethoxazole
160 mg/800 mg/day orally for 7 days 1,200 mg orally on day 7 12 0.85
(0.75 to 0.97)/
0.90
(0.78 to 1.03)
0.87
(0.80 to 0.95)/
0.96
(0.88 to 1.03)
Zidovudine 500 mg/day orally for 21 days 600 mg/day oraly for 14 days 5 1.12
(0.42 to 3.02)
0.94
(0.52 to 1.70)
Zidovudine 500 mg/day orally for 21 days 1,200 mg/day orally for 14 days 4 1.31
(0.43 to 3.97)
1.30
(0.69 to 2.43)
Co-administered Drug Dose of Co-administered Drug Dose of AzithromycinRefers to Sumamed capsules and tablets unless specified n Ratio (with/without co-administered drug) of Sumamed Pharmacokinetic Parameters (90% CI); No Effect = 1.00
Mean Cmax Mean AUC
Efavirenz 400 mg/day for 7 days 600 mg orally on day 7 14 1.22
(1.04 to 1.42)
0.9290% confidence interval not reported
Fluconazole 200 mg orally single dose 1,200 mg orally single dose 18 0.82
(0.66 to 1.02)
1.07
(0.94 to 1.22)
Nelfinavir 750 mg three times a day 11 days 1,200 mg orally on day 9 14 2.36
(1.77 to 3.15)
2.12
(1.80 to 2.50)
Aluminum and Magnesium hydroxide 20 mL regular strength, single dose 2 g Zmax, single dose 39 0.99
(0.93 to 1.06)
0.99
(0.92 to 1.08)

12.4 Microbiology


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.

Resistance

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)].

Gram-Positive Bacteria

  • Streptococcus pneumoniae

Gram-Negative Bacteria

  • Haemophilus influenzae
  • Moraxella catarrhalis

"Other" Bacteria

  • Chlamydophila pneumoniae
  • Mycoplasma pneumoniae

Susceptibility Testing Methods

When available, the clinical microbiology laboratory should provide cumulative reports of in vitro susceptibility test results for antimicrobial products 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.

Dilution Techniques

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 7.

Diffusion Techniques

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 a standardized method 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 7.

Pathogen Minimum Inhibitory Concentrations (mcg/mL) Disk Diffusion
(zone diameter in mm)
S I R S I R
Haemophilus influenzae Insufficient information is available to determine Intermediate or Resistant interpretive criteria ≤4 - - ≥12 - -
Moraxella catarrhalis ≤0.25 - - ≥26 - -
Streptococcus pneumoniae ≤0.5 1 ≥2 ≥18 14–17 ≤13

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.

Quality Control

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 1,2,3,4. Standard Sumamed powder should provide the following range of MIC values provided in Table 8. For the diffusion technique using the 15-mcg Sumamed disk the criteria provided in Table 8 should be achieved.

Quality Control Organism Minimum Inhibitory Concentrations (mcg/mL) Disk Diffusion
(zone diameters in mm)
Haemophilus Influenzae
ATCCATCC = American Type Culture Collection 49247 1–4 13–21
Staphylococcus aureus
ATCC 25923 Not Applicable 21–26
Staphylococcus aureus
ATCC 29213 0.5–2 Not Applicable
Streptococcus pneumoniae
ATCC 49619 0.06–0.25 19–25
Neisseria gonorrhoeae
ATCC 49226 0.25–1 Not Applicable

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 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 treated with Sumamed at doses which, expressed on the basis of mg/m2, are approximately one-sixth the recommended adult dose, and in rats treated at doses approximately one-fourth the recommended adult 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/kgbased on the 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 finding for animals and for humans is unknown.

14 CLINICAL STUDIES

14.1 Acute Bacterial Maxillary Sinusitis


Adult subjects with a diagnosis of acute bacterial maxillary sinusitis were evaluated in a randomized, double-blind, multicenter study; a maxillary sinus tap was performed on all subjects at baseline. Clinical evaluations were conducted for all subjects at the TOC visit, 7 to 14 days post-treatment. Two hundred seventy subjects were treated with a single 2 g oral dose of Zmax and 268 subjects were treated with levofloxacin, 500 mg orally once daily for 10 days. A subject was considered a cure if signs and symptoms related to the acute infection had resolved, or if clinical improvement was such that no additional antibiotics were deemed necessary. The clinical response for the primary population, Clinical Per Protocol Subjects, is presented below.

ZMAX LEVOFLOXACIN
RESPONSE AT TOC N = 255 N = 254
  CURE 241 (94.5%) 236 (92.9%)
  FAILURE 14 (5.5%) 18 (7.1%)

Clinical response by pathogen in the Bacteriologic Per Protocol population is presented below.

Zmax Levofloxacin
Pathogen N Cure N Cure
S. pneumoniae 37 36 (97.3%) 39 36 (92.3%)
H. influenzae 27 26 (96.3%) 30 30 (100.0%)
M. catarrhalis 8 8 (100.0%) 11 10 (90.9%)

14.2 Community-Acquired Pneumonia


Adult subjects with a diagnosis of mild-to-moderate community-acquired pneumonia were evaluated in two, randomized, double-blind, multicenter studies. In both studies, clinical and microbiologic evaluations were conducted for all subjects at the Test of Cure (TOC) visit, 7 to 14 days post-treatment. In Trial 1, 247 subjects were treated with a single 2 g oral dose of Zmax and 252 subjects were treated with clarithromycin extended-release, 1 g orally once daily for 7 days. In Trial 2, 211 subjects were treated with a single 2.0 g oral dose of Zmax and 212 subjects were treated with levofloxacin, 500 mg orally once daily for 7 days. A patient was considered a cure if signs and symptoms related to the acute infection had resolved, or if clinical improvement was such that no additional antibiotics were deemed necessary; in addition, the chest x-ray performed at the TOC visit was to be either improved or stable. The clinical response at TOC for the primary population, Clinical Per Protocol Subjects, is presented in the table below.

Zmax Comparator
Zmax vs. Clarithromycin extended-release N=202 N=209
  Cure 187 (92.6%) 198 (94.7%)
  Failure 15 (7.4%) 11 (5.3%)
Zmax vs. Levofloxacin N=174 N=189
  Cure 156 (89.7%) 177 (93.7%)
  Failure 18 (10.3%) 12 (6.3%)

Clinical response by pathogen in the Bacteriologic Per Protocol population, across both studies, is presented below:

Pathogen Zmax Comparators
N Cure N Cure
S. pneumoniae 33 28 (84.8%) 39 35 (89.7%)
H. influenzae 30 28 (93.3%) 34 31 (91.2%)
C. pneumoniae 40 37 (92.5%) 53 50 (94.3%)
M. pneumoniae 33 30 (90.9%) 39 38 (97.4%)

15 REFERENCES

  • 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, 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


NDC 0069-4170-34 for combined adult and pediatric use is supplied in bottles containing 2 g of Sumamed and should be constituted with 60 mL of water.

Storage

Before constitution, store dry powder at or below 30°C (86°F).

After constitution, store suspension at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) . Do not refrigerate or freeze.

Constituted suspension should be consumed within 12 hr. For adult patients, the entire bottle should be consumed. For pediatric patients, any suspension remaining after dosing MUST be discarded.

17 PATIENT COUNSELING INFORMATION


General Patient Counseling

  • Patients should be instructed to take Zmax on an empty stomach (at least 1 hr before or 2 hr following a meal).
  • To ensure accurate dosing for children, use of a dosing spoon, medicine syringe, or cup is recommended.
  • Patients should be told that Zmax needs time to work, so the patient may not feel better right away. If the patient's symptoms do not improve in a few days, the patient or their guardian should call their doctor.
  • Patients should be instructed to immediately contact a physician if any signs of an allergic reaction occur.
  • Direct parents or caregivers to contact their physician if vomiting and irritability with feeding occurs in the infant.
  • Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, 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 antibiotic. If this occurs, patients should contact their physician as soon as possible.
  • Patients who vomit within the first hr should contact their health care provider about further treatment.
  • Keep bottle tightly closed. Store at room temperature. Use within 12 hr of constitution. Shake bottle well before use. Adult patients should consume the entire contents of the bottle; pediatric patients should take the recommended dose and MUST discard any unused portion.
  • Patients should be advised that Zmax may be taken without regard to antacids containing magnesium hydroxide and/or aluminum hydroxide.

Patients should be counseled that antibacterial drugs including Zmax should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). Not taking the complete prescribed dose may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Zmax or other antibacterial drugs in the future.

See FDA-approved Patient Labeling

Rx only

This product's label may have been updated. For current full prescribing information, please visit www.pfizer.com

LAB-0384-12.0

Logo

Patient Information
Zmax®
Oral suspension


Read the Patient Information that comes with Zmax® carefully before you or your child take it. This leaflet does not take the place of talking with your doctor about you or your child's medical condition or treatment. Only your doctor can decide if Zmax is right for you or your child.

What is Zmax?

Zmax is an antibiotic that kills certain bacteria. Zmax is dosed differently from other antibiotics.

You take just one dose, one time.

  • Day 1: Take Zmax in one dose. Zmax starts working.
  • Days 2 – 3: As with most antibiotics, you may not feel better right away.
  • After Day 3: Zmax continues to work over time. If your symptoms are not better, call your doctor.

Zmax is used in adults and in children over the age of 6 months against bacteria to treat certain kinds of pneumonia (lung infections)

Zmax is used in adults against bacteria to treat sinus infections.

Zmax only works against bacteria. It does not work against viruses, like the common cold or flu.

Zmax has not been studied in children under 6 months of age.

Who should not take Zmax?

  • You or your child should not take Zmax if allergic to:
    • anything in Zmax. See the end of this leaflet for a complete list of ingredients in Zmax.
    • antibiotics like erythromycin or telithromycin (Ketek®).

Talk with your doctor or pharmacist if you have questions about your medicine allergies.

Before you start Zmax

Tell your doctor about all your or your child's medical problems including if you or your

Child:

  • have liver problems.
  • have kidney problems.
  • have myasthenia gravis.
  • are pregnant, or might be pregnant. It is not known if Zmax could harm your baby.
  • are breast-feeding.

Contact your healthcare provider immediately if you are giving Zmax to a young child (less than 6 weeks of age) and he or she vomits or becomes irritable when fed.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Especially tell your doctor if you or your child are taking warfarin (Coumadin®, Jantoven)

Know the medicines you take. Keep a list of your medicines and show it to your doctor or pharmacist when you get a new prescription.

Do I need to prepare Zmax?

  • If you get Zmax in liquid form, it is ready to take.
  • If you get Zmax as dry powder, you must add water to the bottle
  • before you take it. To prepare Zmax:
    • Open the bottle: To open the bottle, press down on the cap and twist.
    • Use a measuring cup to add 60 mL (1/4 cup) water to the Zmax bottle.
    • Tightly close the bottle and shake to mix it.

How do I take Zmax?

  • Keep Zmax at room temperature between 59°F to 86°F (15° to 30°C).
  • Shake the bottle well before using.
  • Take Zmax or give it to your child within 12 hr after it has been prepared by the pharmacy or you add water to the powder.
  • Take Zmax or give it to your child exactly how your doctor prescribes it. This will help to treat you or your child's infection and decrease the chance that Zmax or other antibiotics will not work to treat infections in the future.
  • Adults: take all the medicine in the bottle.
  • Children: give your child the amount of Zmax prescribed by your doctor and throw away the rest of the medicine.
  • To be sure that you give your child the right dose of Zmax, use a dosing spoon, medicine syringe, or cup.
  • Take Zmax on an empty stomach (at least 1 hr before eating or 2 hr after eating).
  • You can take antacids with Zmax.
  • If you or your child throws up (vomits) within one hr of taking Zmax, call your doctor right away to see if more medicine is needed. Do not give your child more Zmax unless your doctor tells you to.
  • If your child takes too much Zmax, call your doctor right away or go to the nearest hospital emergency room.

How will I know Zmax is working?

Zmax needs time to work, so you or your child may not feel better right away. If you or your child's symptoms do not get better in a few days, call your doctor.

What are the possible side effects of Zmax?

Zmax may cause serious side effects. These happened in a small number of patients. Call your doctor right away or get emergency treatment if you or your child have any of the following:

  • Serious allergic reaction or serious skin reaction: Get emergency help right away if you or your child has:
    • Skin rash (hives), sores in your mouth, or your skin blisters and peels
    • Trouble swallowing,
    • Swelling of your face, eyes, lips, tongue or throat
    • Wheezing or trouble breathing
    • New onset of fever and swollen lymph nodes

These symptoms could go away and then come back.

  • Diarrhea: Call your doctor right away if you have diarrhea that does not go away, is severe, watery, or has blood in it. Diarrhea can occur as late as two or more months after you take an antibiotic such as Zmax.
  • Abnormal heart rhythm. Tell your doctor right away if you or your child feel your heart beating in your chest or an abnormal heart beat, get dizzy or faint. This has been seen with other antibiotics like Zmax.

The most common side effects in adults are:

  • Diarrhea/loose stools
  • Nausea
  • Stomach pain
  • Headache
  • Vomiting

The most common side effects in children are:

  • Vomiting
  • Diarrhea/loose stools
  • Nausea
  • Stomach pain

Tell your doctor if you have any side effects that bother your or your child, or that does not go away.

These are not all of the possible side effects with Zmax. For a list of all reported side effects, ask your doctor or pharmacist.

General information about Zmax

Doctors sometimes prescribe medicines for conditions that are not in the patient leaflets. Do not use Zmax for anything other than what your doctor prescribed. Do not give it to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information leaflet is a summary of the most important information about Zmax. For more information, talk with your doctor. You can ask your doctor or pharmacist for information about Zmax that is written for healthcare professionals. For more information, go to our website at www.zmaxinfo.com or call 1-800-438-1985.

What is in Zmax?

Active ingredient: Sumamed dihydrate

Inactive ingredients: glyceryl behenate, poloxamer 407, sucrose, sodium phosphate tribasic anhydrous, magnesium hydroxide, hydroxypropyl cellulose, xanthan gum, colloidal silicon dioxide, titanium dioxide, artificial cherry flavor, and artificial banana flavor

Brand names are registered trademarks of their respective owners.

Coumadin® is a registered trademark of Bristol-Myers Squibb, Inc.

Ketek® is a registered trademark of Aventis Pharmaceuticals Inc.

This product's label may have been updated. For current full prescribing information, please visit www.pfizer.com

This Patient Information has been approved by the U.S. Food and Drug Administration.

LAB-0606-5.0

February 2017

PRINCIPAL DISPLAY PANEL - 2 g Bottle Label


Rx only
NDC 0069-4170-34

Zmax ®
(azithromycin
extended release)
for oral suspension

2 g

Cherry-Banana Flavored

Pfizer

Distributed by
Pfizer Labs
Division of Pfizer Inc, NY, NY 10017

PRINCIPAL DISPLAY PANEL - 2 g Bottle Label

PRINCIPAL DISPLAY PANEL - 2 g Bottle Carton


single use 2g bottle
NDC 0069-4170-34

Rx only

Zmax ®
(azithromycin
extended release)
for oral suspension

2 g

Cherry-Banana Flavored

FOR ORAL USE ONLY

PRINCIPAL DISPLAY PANEL - 2 g Bottle Carton

advertisement

Sumamed pharmaceutical active ingredients containing related brand and generic drugs, medications or other health care products:

infoActive 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.


Sumamed available forms, composition, doses:

infoForm 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.


Sumamed destination | category:

infoDestination 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.


advertisement

Sumamed indications and usages, anatomical therapeutic chemical and diseases classification codes:

infoA 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:

infoPharmaceutical 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.


advertisement

References

  1. Dailymed."AZITHROMYCIN- azithromycin tablet, film coated". https://dailymed.nlm.nih.gov/dailymed/dr... (accessed September 18, 2017).

Sumamed - Frequently asked Questions

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.

Review

Medicatione.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.

Visitor reports

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 Medicatione.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.
Visitors%
Useful5
100.0%


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 Medicatione.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.
Visitors%
It has side effects4
66.7%
No side effects2
33.3%


Four 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 Medicatione.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.
Visitors%
Not expensive4
100.0%


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 Medicatione.com website users about the frequency of taking the drug Sumamed is mentioned below.
Visitors%
Once in a day4
100.0%


Three visitors reported doses

What is the dose of Sumamed drug you are taking?
According to the survey conducted among Medicatione.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.
Visitors%
201-500mg3
100.0%


Four 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 Medicatione.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.
Visitors%
3 days4
100.0%


Three 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.
Visitors%
Before food2
66.7%
Empty stomach1
33.3%


Four visitors reported age

Visitors%
46-603
75.0%
< 11
25.0%


Visitor reviews


There are no reviews yet. Be the first to write one!


Your name: 
Email: 
Spam protection:  <= Write 18 here

Information checked by Dr. Arunabha Ray, MD Pharmacology

  |  About  |  Privacy Policy

© 2002 - 2017 "Medicatione.com". All Rights Reserved
0.197