Pediazole is a combination of erythromycin ethylsuccinate, USP, and sulfisoxazole acetyl, USP. When reconstituted with water as directed on the label, the granules form a white, strawberry-banana flavor suspension that provides the equivalent of 200 mg erythromycin activity and the equivalent of 600 mg of sulfisoxazole activity per teaspoonful (5 mL).

Erythromycin is produced by a strain of Saccaropolyspora erythraea and belongs to the macrolide group of antibiotics. It is basic and readily forms salts and esters. Erythromycin ethylsuccinate is the 2'-ethylsuccinyl ester of erythromycin. It is essentially a tasteless form of the antibiotic suitable for oral administration, particularly in suspension dosage forms. The chemical name is erythromycin 2'-(ethyl succinate).

Sulfisoxazole acetyl or N ¹ -acetyl sulfisoxazole is an ester of sulfisoxazole. Chemically, sulfisoxazole is N-(3,4-Dimethyl-5-isoxazolyl)-N-sulfanilylacetamide.

Inactive Ingredients:   Citric acid, magnesium aluminum silicate, poloxamer, sodium carboxymethylcellulose, sodium citrate, sucrose and artificial flavoring.

Last updated on RxList: 12/8/2004

For treatment of ACUTE OTITIS MEDIA in children that is caused by susceptible strains of Haemophilus influenzae.

PEDIAZOLE SHOULD NOT BE ADMINISTERED TO INFANTS UNDER 2 MONTHS OF AGE BECAUSE OF CONTRAINDICATIONS OF SYSTEMIC SULFONAMIDES IN THIS AGE GROUP.

For Acute Otitis Media in Children:   The dose of Pediazole can be calculated based on the erythromycin component (50 mg/kg/day) or the sulfisoxazole component (150 mg/kg/day to a maximum of 6 g/day). The total daily dose of Pediazole should be administered in equally divided doses three or four times a day for 10 days.Pediazole may be administered without regard to meals.

The following approximate dosage schedules are recommended for using Pediazole:

Children: Two months of age or older

FOUR-TIMES-A-DAY SCHEDULE

 

THREE-TIMES-A-DAY SCHEDULE

TO PATIENT: Shake before using. Oversize bottle provides shake space. Keep tightly closed. Store in the refrigerator. Use within 14 days. Unused portion should be discarded after 14 days.

Pediazole Suspension is available for teaspoon dosage in 100-mL ( NDC 0074-8030-13), 150-mL ( NDC 0074-8030-43), 200-mL ( NDC 0074-8030-53) and 250-mL ( NDC 0074-8030-73) bottles, in the form of granules to be reconstituted with water. The suspension provides erythromycin ethylsuccinate equivalent to 200 mg erythromycin activity and sulfisoxazole acetyl equivalent to 600 mg sulfisoxazole per teaspoonful (5 mL).

Before mixing, store below 86°F (30°C).

 

REFERENCES

1. Biovert A, Barbeau G, Belanger PM: Pharmacokinetics of sulfisoxazole in young and elderly subjects. Gerontology 1984;30:125-131.
2. Oie S, Gambertoglio JG, Fleckenstein L: Comparison of the disposition of total and unbound sulfisoxazole after single and multiple dosing. J Pharmacokinet Biopharm 1982;10:157-172.
3. National Committee for Clinical Laboratory Standards: Performance Standards for Antimicrobial Disk Susceptibility Tests, ed. 4. Approved Standard NCCLS Document M2-A4, Vol 10, No. 7. Villanova, Pa: NCCLS, 1990.

July, 1994

Last updated on RxList: 12/8/2004

Erythromycin ethylsuccinate:   The most frequent side effects of oral erythromycin preparations are gastrointestinal and are dose-related. They include nausea, vomiting, abdominal pain, diarrhea and anorexia. Symptoms of hepatic dysfunction and/or abnormal liver-function test results may occur (see WARNINGS section). Pseudomembranous colitis has been rarely reported in association with erythromycin therapy.

Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis have occurred.

There have been isolated reports of reversible hearing loss occurring chiefly in patients with renal insufficiency and in patients receiving high doses of erythromycin.

Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. (See WARNINGS .)

Sulfisoxazole acetyl:   Included in the listing that follows are adverse reactions that have been reported with other sulfonamide products: pharmacologic similarities require that each of the reactions be considered with Pediazole administration.

Allergic/Dermatologic:   Anaphylaxis, erythema multiforme (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, angioedema, arteritis, vasculitis, allergic myocarditis, serum sickness, rash, urticaria, pruritus, photosensitivity, and conjunctival and scleral injection. In addition, periarteritis nodosa and systemic lupus erythematosus have been reported. (See WARNINGS.)

Cardiovascular:   Tachycardia, palpitations, syncope, and cyanosis.

Rarely, erythromycin has been associated with the production of ventricular arrhythmias, including ventricular tachycardia and torsade de pointes, in individuals with prolonged QT intervals.

Endocrine:   The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic agents. Cross-sensitivity may exist with these agents. Developments of goiter, diuresis, and hypoglycemia have occurred rarely in patients receiving sulfonamides.

Gastrointestinal:   Hepatitis, hepatocellular necrosis, jaundice, pseudomembranous colitis, nausea, emesis, anorexia, abdominal pain, diarrhea, gastrointestinal hemorrhage, melena, flatulence, glossitis, stomatitis, salivary gland enlargement, and pancreatitis. Onset of pseudomembranous colitis symptoms may occur during or after treatment with sulfisoxazole, a component of Pediazole. (See WARNINGS.)

The sulfisoxazole acetyl component of Pediazole has been reported to cause increased elevation of liver-associated enzymes in patients with hepatitis.

Genitourinary:   Crystalluria, hematuria, BUN and creatinine elevations, nephritis, and toxic nephrosis with oliguria and anuria. Acute renal failure and urinary retention have also been reported.

The frequency of renal complications, commonly associated with some sulfonamides, is lower in patients receiving the more soluble sulfonamides such as sulfisoxazole.

Hematologic:   Leukopenia, agranulocytosis, aplastic anemia, thrombocytopenia, purpura, hemolytic anemia, anemia, eosinophilia, clotting disorders including hypoprothrombinemia and hypofibrinogenemia, sulfhemoglobinemia, and methemoglobinemia.

Neurologic:   Headache, dizziness, peripheral neuritis, paresthesia, convulsions, tinnitus, vertigo, ataxia, and intracranial hypertension.

Psychiatric:   Psychosis, hallucinations, disorientation, depression, and anxiety.

Respiratory:   Cough, shortness of breath, and pulmonary infiltrates. (See WARNINGS.)

Vascular:   Angioedema, arteritis, and vasculitis.

Miscellaneous:   Edema (including periorbital), pyrexia, drowsiness, weakness, fatigue, lassitude, rigors, flushing, hearing loss, insomnia, and pneumonitis.

 

Drug Interactions:   Erythromycin use in patients who are receiving high doses of theophylline may be associated with an increase in serum theophylline levels and potential theophylline toxicity. In case of theophylline toxicity and/or elevated serum theophylline levels, the dose of theophylline should be reduced while the patient is receiving concomitant erythromycin therapy.

Concomitant administration of erythromycin and digoxin has been reported to result in elevated digoxin serum levels.

There have been reports of increased anticoagulant effects when erythromycin and oral anticoagulants were used concomitantly. Increased anticoagulation effects due to this drug may be more pronounced in the elderly.

Concurrent use of erythromycin and ergotamine or dihydroergotamine has been associated in some patients with acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.

Erythromycin has been reported to decrease the clearance of triazolam and midazolam and thus may increase the pharmacologic effect of these benzodiazepines.

The use of erythromycin in patients concurrently taking drugs metabolized by the cytochrome P450 system may be associated with elevations in serum levels of these other drugs. There have been reports of interactions of erythromycin with carbamazepine, cyclosporine, hexobarbital, phenytoin, alfentanil, diisopyramide, lovastatin, and bromocriptine. Serum concentrations of drugs metabolized by the cytochrome P450 system should be monitored closely in patients concurrently receiving erythromycin.

Erythromycin significantly alters the metabolism of terfenadine when taken concomitantly. Rare cases of serious cardiovascular adverse events, including death, cardiac arrest, torsades de pointes, and other ventricular arrhythmias, have been observed. (See CONTRAINDICATIONS.)

It has been reported that sulfisoxazole may prolong the prothrombin time in patients who are receiving the anticoagulant warfarin. This interaction should be kept in mind when Pediazole is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed.

It has been proposed that sulfisoxazole competes with thiopental for plasma protein binding. In one study involving 48 patients, intravenous sulfisoxazole resulted in a decrease in the amount of thiopental required for anesthesia and in a shortening of the awakening time. It is not known whether chronic oral doses of sulfisoxazole have a similar effect. Until more is known about this interaction, physicians should be aware that patients receiving sulfisoxazole might require less thiopental for anesthesia.

Sulfonamides can displace methotrexate from plasma protein binding sites, thus increasing free methotrexate concentrations. Studies in man have shown sulfisoxazole infusions to decrease plasma protein-bound methotrexate by one fourth.

Sulfisoxazole can also potentiate the blood-sugar-lowering activity of sulfonylureas.

Last updated on RxList: 12/8/2004

FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF SULFONAMIDES, ALTHOUGH RARE, HAVE OCCURRED DUE TO SEVERE REACTIONS INCLUDING STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC ANEMIA, AND OTHER BLOOD DYSCRASIAS.

SULFONAMIDES, INCLUDING SULFONAMIDE-CONTAINING PRODUCTS SUCH AS PEDIAZOLE, SHOULD BE DISCONTINUED AT THE FIRST APPEARANCE OF SKIN RASH OR ANY SIGN OF ADVERSE REACTION. In rare instances, a skin rash may be followed by a more severe reaction, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, and serious blood disorders. (See

PRECAUTIONS

.)

Clinical signs such as sore throat, fever, pallor, rash, purpura, or jaundice may be early indications of serious reactions.

There have been reports of hepatic dysfunction with or without jaundice, occurring in patients receiving oral erythromycin products.

Cough, shortness of breath, and pulmonary infiltrates are hypersensitivity reactions of the respiratory tract that have been reported in association with sulfonamide treatment.

The sulfonamides should not be used for the treatment of group A beta-hemolytic streptococcal infections. In an established infection, they will not eradicate the streptococcus and, therefore, will not prevent sequelae such as rheumatic fever.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including Pediazole, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of "antibiotic-associated colitis."

After diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.

There have been reports suggesting that erythromycin does not reach the fetus in adequate concentration to prevent congenital syphilis. Infants born to women treated during pregnancy with erythromycin for early syphilis should be treated with an appropriate penicillin regimen.

Rhabdomyolysis with or without renal impairment has been reported in seriously ill patients receiving erythromycin concomitantly with lovastatin. Therefore, patients receiving concomitant lovastatin and erythromycin should be carefully monitored for creatine kinase (CK) and serum transaminase levels. (See package insert for lovastatin.)

 

General: Erythromycin is principally excreted by the liver. Caution should be exercised when erythromycin is administered to patients with impaired hepatic function. (See CLINICAL PHARMACOLOGY and WARNING sections.)

Prolonged or repeated use of erythromycin may result in an overgrowth of nonsusceptible bacteria or fungi. If superinfection occurs, erythromycin should be discontinued and appropriate therapy instituted.

There have been reports that erythromycin may aggravate the weakness of patients with myasthenia gravis.

When indicated, incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy.

Sulfonamides should be given with caution to patients with impaired renal or hepatic function and to those with severe allergy or bronchial asthma. In glucose-6-phosphate dehydrogenase-deficient individuals, hemolysis may occur; this reaction is frequently dose-related.

Information for Patients:   Patients should maintain an adequate fluid intake to prevent crystalluria and stone formation.

Laboratory Tests:   Complete blood counts should be done frequently in patients receiving sulfonamides. If a significant reduction in the count of any formed blood element is noted, Pediazole should be discontinued. Urinalysis with careful microscopic examination and renal function tests should be performed during therapy, particularly for those patients with impaired renal function. Blood levels should be measured in patients receiving a sulfonamide for serious infections. (See INDICATIONS AND USAGE.)

Drug/laboratory Test Interactions:   Erythromycin interferes with the fluorometric determination of urinary catecholamines.

 

Drug Interactions:   Erythromycin use in patients who are receiving high doses of theophylline may be associated with an increase in serum theophylline levels and potential theophylline toxicity. In case of theophylline toxicity and/or elevated serum theophylline levels, the dose of theophylline should be reduced while the patient is receiving concomitant erythromycin therapy.

Concomitant administration of erythromycin and digoxin has been reported to result in elevated digoxin serum levels.

There have been reports of increased anticoagulant effects when erythromycin and oral anticoagulants were used concomitantly. Increased anticoagulation effects due to this drug may be more pronounced in the elderly.

Concurrent use of erythromycin and ergotamine or dihydroergotamine has been associated in some patients with acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.

Erythromycin has been reported to decrease the clearance of triazolam and midazolam and thus may increase the pharmacologic effect of these benzodiazepines.

The use of erythromycin in patients concurrently taking drugs metabolized by the cytochrome P450 system may be associated with elevations in serum levels of these other drugs. There have been reports of interactions of erythromycin with carbamazepine, cyclosporine, hexobarbital, phenytoin, alfentanil, diisopyramide, lovastatin, and bromocriptine. Serum concentrations of drugs metabolized by the cytochrome P450 system should be monitored closely in patients concurrently receiving erythromycin.

Erythromycin significantly alters the metabolism of terfenadine when taken concomitantly. Rare cases of serious cardiovascular adverse events, including death, cardiac arrest, torsades de pointes, and other ventricular arrhythmias, have been observed. (See CONTRAINDICATIONS.)

It has been reported that sulfisoxazole may prolong the prothrombin time in patients who are receiving the anticoagulant warfarin. This interaction should be kept in mind when Pediazole is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed.

It has been proposed that sulfisoxazole competes with thiopental for plasma protein binding. In one study involving 48 patients, intravenous sulfisoxazole resulted in a decrease in the amount of thiopental required for anesthesia and in a shortening of the awakening time. It is not known whether chronic oral doses of sulfisoxazole have a similar effect. Until more is known about this interaction, physicians should be aware that patients receiving sulfisoxazole might require less thiopental for anesthesia.

Sulfonamides can displace methotrexate from plasma protein binding sites, thus increasing free methotrexate concentrations. Studies in man have shown sulfisoxazole infusions to decrease plasma protein-bound methotrexate by one fourth.

Sulfisoxazole can also potentiate the blood-sugar-lowering activity of sulfonylureas.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Carcinogenesis:  Pediazole has not undergone adequate trials relating to carcinogenicity; each component, however, has been evaluated separately. Long-term (21 month) oral studies conducted in rats with erythromycin ethylsuccinate did not provide evidence of tumorigenicity. Sulfisoxazole was not carcinogenic in either sex when administered to mice by gavage for 103 weeks at dosages up to approximately 18 times the recommended human dose or to rats at 4 times the human dose. Rats appear to be especially susceptible to the goitrogenic effects of sulfonamides, and long-term administration of sulfonamides has resulted in thyroid malignancies in this species.

Mutagenesis:  There are no studies available that adequately evaluate the mutagenic potential of Pediazole or either of its components. However, sulfisoxazole was not observed to be mutagenic in E. coli  Sd-4-73 when tested in the absence of a metabolic activating system. There was no apparent effect on male or female fertility in rats fed erythromycin (base) at levels up to 0.25% of diet.

Impairment of Fertility:  Pediazole has not undergone adequate trials relating to impairment of fertility. In a reproduction study in rats given 7 times the human dose per day of sulfisoxazole, no effects were observed regarding mating behavior, conception rate or fertility index (percent pregnant).

Pregnancy:   Teratogenic Effects. Pregnancy Category C. At dosages 7 times the human daily dose, sulfisoxazole was not teratogenic in either rats or rabbits. However, in two other teratogenicity studies, cleft palates developed in both rats and mice after administration of 5 to 9 times the human therapeutic dose of sulfisoxazole.

There is no evidence of teratogenicity or any other adverse effect on reproduction in female rats fed erythromycin base (up to 0.25% of diet) prior to and during mating, during gestation, and through weaning of two successive litters. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Erythromycin has been reported to cross the placental barrier in humans, but fetal plasma levels are generally low.

There are no adequate or well-controlled studies of Pediazole in either laboratory animals or in pregnant women. It is not known whether Pediazole can cause fetal harm when administered to a pregnant woman prior to term or can affect reproduction capacity. Pediazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects:  Kernicterus may occur in the newborn as a result of treatment of a pregnant woman at term with sulfonamides. (See CONTRAINDICATIONS.)

Labor and Delivery:   The effects of erythromycin and sulfisoxazole on labor and delivery are unknown.

Nursing Mothers:   Both erythromycin and sulfisoxazole are excreted in human milk. Because of the potential for the development of kernicterus in neonates due to the displacement of bilirubin from plasma proteins by sulfisoxazole, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. (See CONTRAINDICATIONS .)

Pediatric Use:   See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION sections. Not for use in children under 2 months of age. (See CONTRAINDICATIONS.)

 

 

Last updated on RxList: 12/8/2004

No information is available on a specific result of overdose with Pediazole. Overdosage of erythromycin should be handled with the prompt elimination of unabsorbed drug and all other appropriate measures. Erythromycin is not removed by peritoneal dialysis or hemodialysis.

The amount of a single dose of sulfisoxazole that is either associated with symptoms of overdosage or is likely to be life-threatening has not been reported. Signs and symptoms of overdosage reported with sulfonamides include anorexia, colic, nausea, vomiting, dizziness, headache, drowsiness and unconsciousness. Pyrexia, hematuria and crystalluria may be noted. Blood dyscrasias and jaundice are potential late manifestations of overdosage.

General principles of treatment include the immediate discontinuation of the drug, instituting gastric lavage or emesis, forcing oral fluids, and administering intravenous fluids if urine output is low and renal function is normal. The patient should be monitored with blood counts and appropriate blood chemistries, including electrolytes. If the patient becomes cyanotic, the possibility of methemoglobinemia should be considered and, if present, the condition should be treated appropriately with intravenous 1% methylene blue. If a significant blood dyscrasia or jaundice occurs, specific therapy should be instituted for these complications. Peritoneal dialysis is not effective, and hemodialysis is only moderately effective in removing sulfonamides.

The acute toxicity of sulfisoxazole in animals is as follows:

 

Species	LD 50 ± S.E. · (mg/kg)
mouse	5700 ± 235
rats	>10,000
rabbits	>2000

 

Pediazole is contraindicated in the following patient populations:

Patients with a known hypersensitivity to either of its components, children younger than 2 months, pregnant women at term, and mothers nursing infants less than 2 months of age.

Use in pregnant women at term, in children less than 2 months of age, and in mothers nursing infants less than 2 months of age is contraindicated because sulfonamides may promote kernicterus in the newborn by displacing bilirubin from plasma proteins.

Erythromycin is contraindicated in patients taking terfenadine. ( See PRECAUTIONS -- Drug Interactions. )

Last updated on RxList: 12/8/2004

Orally administered erythromycin ethylsuccinate suspensions are readily and reliably absorbed. Erythromycin ethylsuccinate products have demonstrated rapid and consistent absorption in both fasting and nonfasting conditions. However, higher serum concentrations are obtained when these products are given with food. Bioavailability data are available from Ross Products Division. Erythromycin is largely bound to plasma proteins. After absorption, erythromycin diffuses readily into most body fluids. In the absence of meningeal inflammation, low concentrations are normally achieved in the spinal fluid, but the passage of the drug across the blood-brain barrier increases in meningitis. Erythromycin crosses the placental barrier and is excreted in human milk. Erythromycin is not removed by peritoneal dialysis or hemodialysis.

In the presence of normal hepatic function, erythromycin is concentrated in the liver and is excreted in the bile; the effect of hepatic dysfunction on biliary excretion of erythromycin is not known. After oral administration, less than 5% of the administered dose can be recovered in the active form in the urine.

Wide variation in blood levels may result following identical doses of a sulfonamide. Blood levels should be measured in patients receiving these drugs for serious infections. Free sulfonamide blood levels of 50 to 150 mcg/mL may be considered therapeutically effective for most infections, with blood levels of 120 to 150 mcg/mL being optimal for serious infections. The maximum sulfonamide level should be 200 mcg/mL, because adverse reactions occur more frequently above this concentration.

Following oral administration, sulfisoxazole is rapidly and completely absorbed; the small intestine is the major site of absorption, but some of the drug is absorbed from the stomach. Sulfonamides are present in the blood as free, conjugated (acetylated and possibly other forms), and protein-bound forms. The amount present as "free" drug is considered to be the therapeutically active form. Approximately 85% of a dose of sulfisoxazole is bound to plasma proteins, primarily to albumin; 65% to 72% of the unbound portion is in the nonacetylated form.

Maximum plasma concentrations of intact sulfisoxazole following a single 2-g oral dose of sulfisoxazole to healthy adult volunteers ranged from 127 to 211 mcg/mL (mean, 169 mcg/mL), and the time of peak plasma concentration ranged from 1 to 4 hours (mean, 2.5 hours). The elimination half-life of sulfisoxazole ranged from 4.6 to 7.8 hours after oral administration. The elimination of sulfisoxazole has been shown to be slower in elderly subjects (63 to 75 years) with diminished renal function (creatine clearance 37 to 68 mL/min). ¹ After multiple-dose oral administration of 500 mg q.i.d. to healthy volunteers, the average steady-state plasma concentrations of intact sulfisoxazole ranged from 49.9 to 88.8 mcg/mL (mean, 63.4 mcg/mL). ²

Sulfisoxazole and its acetylated metabolites are excreted primarily by the kidneys through glomerular filtration. Concentrations of sulfisoxazole are considerably higher in the urine than in the blood. The mean urinary recovery following oral administration of sulfisoxazole is 97% within 48 hours; 52% of this is intact drug, and the remainder is the N ⁴ -acetylated metabolite.

Sulfisoxazole is distributed only in extracellular body fluids. It is excreted in human milk. It readily crosses the placental barrier. In healthy subjects, cerebrospinal fluid concentrations of sulfisoxazole vary; in patients with meningitis, however, concentrations of free drug in cerebrospinal fluid as high as 94 mcg/mL have been reported.

Microbiology:

Pediazole has been formulated to contain sulfisoxazole for concomitant use with erythromycin.

Erythromycin acts by inhibition of protein synthesis by binding 50 S ribosomal subunits of susceptible organisms. It does not affect nucleic acid synthesis. Antagonism has been demonstrated in vitro between erythromycin and clindamycin, lincomycin, and chloramphenicol.

The sulfonamides are bacteriostatic agents, and the spectrum of activity is similar for all. Sulfonamides inhibit bacterial synthesis of dihydrofolic acid by preventing the condensation of the pteridine with para -aminobenzoic acid through competitive inhibition of the enzyme dihydropteroate synthetase. Resistant strains have altered dihydropteroate synthetase with reduced affinity for sulfonamides or produce increased quantities of para -aminobenzoic acid.

Susceptibility Testing:

Quantitative methods that require measurement of zone diameter give the most precise estimates of the susceptibility of bacteria to antimicrobial agents. One such standardized single-disc procedure ³ has been recommended for use with discs to test susceptibility to erythromycin and sulfisoxazole. Interpretation involves correlation of the zone diameters obtained in the disc test with minimal inhibitory concentration (MIC) values for erythromycin and sulfisoxazole.

If the standardized procedure of disc susceptibility is used, a 15-mcg erythromycin disc should give a zone diameter of at least 18 mm when tested against an erythromycin-susceptible bacterial strain, and a 250-300 mcg sulfisoxazole disc should give a zone diameter of at least 17 mm when tested against a sulfisoxazole-susceptible bacterial strain.

In vitro sulfonamide susceptibility tests are not always reliable because media containing excessive amounts of thymidine are capable of reversing the inhibitory effect of sulfonamides, which may result in false resistant reports. The tests must be carefully coordinated with bacteriological and clinical responses. When the patient is already taking sulfonamides, follow-up cultures should have aminobenzoic acid added to the isolation media but not to subsequent susceptibility test media.

Last updated on RxList: 12/8/2004

Patients should maintain an adequate fluid intake to prevent crystalluria and stone formation.

Laboratory Tests:   Complete blood counts should be done frequently in patients receiving sulfonamides. If a significant reduction in the count of any formed blood element is noted, Pediazole should be discontinued. Urinalysis with careful microscopic examination and renal function tests should be performed during therapy, particularly for those patients with impaired renal function. Blood levels should be measured in patients receiving a sulfonamide for serious infections. (See INDICATIONS AND USAGE .)

Drug/laboratory Test Interactions:   Erythromycin interferes with the fluorometric determination of urinary catecholamines.

Last updated on RxList: 12/8/2004

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

ERYTHROMYCIN/SULFISOXAZOLE SUSPENSION - ORAL

(eh-rith-row-MY-sin/sull-fih-SOX-uh-zole)

COMMON BRAND NAME(S): Eryzole, Pediazole

USES: This medication is used to treat middle ear infections in children. It is a combination of two antibiotics, erythromycin (a macrolide-type) and sulfisoxazole (a sulfa-type). This product works by stopping the growth of bacteria.

This antibiotic combination treats only bacterial infections. It will not work for viral infections (e.g., common cold, flu). Unnecessary use or overuse of any antibiotic can lead to its decreased effectiveness.

This medication should not be used in children younger than 2 months of age due to the risk of serious side effects.

HOW TO USE: Shake the bottle well before each dose. The dose should be measured out carefully with a medication spoon/cup. This medication is taken by mouth usually 3 or 4 times a day or as directed by the doctor. It may be taken with or without food. However, nausea commonly occurs with the use of erythromycin, especially when it is taken on an empty stomach. To reduce this side effect, this medication should be taken with food or milk.

Though this is unlikely, kidney stones may form during treatment with this medication. Drink plenty of fluids to prevent this effect unless the doctor advises you otherwise.

The dosage is based on your child's medical condition, weight, and response to therapy.

Antibiotics work best when the amount of medicine in your body is kept at a constant level. Therefore, this drug should be taken at evenly spaced intervals.

This medication should be taken until the full prescribed amount is finished, even if symptoms disappear after a few days. Stopping the medication too early may allow bacteria to continue to grow, which may result in a relapse of the infection.

Inform the doctor if your child's condition persists or worsens.

SIDE EFFECTS: Nausea, vomiting, diarrhea, stomach pain/cramping, and loss of appetite may occur. Taking this medication with food may lessen these symptoms. Headache and dizziness may also occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: mouth sores, sun sensitivity (sunburn), hearing problems (e.g., hearing loss), joint pain/aches, new lump/growth in the neck (goiter), change in the amount of urine, mental/mood changes (e.g., confusion), numbness or tingling of the hands/feet, muscle weakness.

This medication may rarely cause serious (possibly fatal) allergic reactions and other side effects such as a severe peeling skin rash (e.g., Stevens-Johnson syndrome), blood disorders (e.g., agranulocytosis, aplastic anemia), liver damage, lung injury, or heart problems. Seek immediate medical attention if you notice any of the following symptoms: severe dizziness, fainting, fast/irregular heartbeat, skin rash/blisters, itching, swelling, persistent sore throat/fever, paleness, persistent cough, trouble breathing, easy bleeding/bruising, yellowing eyes/skin, persistent nausea/vomiting, seizures, stomach/abdominal pain, unusual tiredness, dark urine.

This medication may rarely cause a severe intestinal condition (pseudomembranous colitis) due to resistant bacteria. This condition may occur during treatment or weeks to months after treatment has stopped. Do not use anti-diarrhea products or narcotic pain medications if you have the following symptoms because these products may make them worse. Tell your doctor immediately if you develop: persistent diarrhea, abdominal or stomach pain/cramping, blood/mucus in your stool.

Use of this medication for prolonged or repeated periods may result in oral thrush or a new vaginal yeast infection (oral or vaginal fungal infection). Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge or other new symptoms.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking erythromycin with sulfisoxazole, tell your doctor or pharmacist if you are allergic to it; or to other macrolide antibiotics (e.g., azithromycin, clarithromycin) or sulfa medications; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: severe allergies, asthma, blood disorders, decreased bone marrow function (bone marrow suppression), diabetes, a certain genetic condition (glucose-6-phosphate dehydrogenase/G6PD deficiency), certain heart problems (QT prolongation in the EKG, slow heartbeat, heart failure), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death), kidney disease, liver disease, a certain type of muscle disease (myasthenia gravis), low levels of potassium or magnesium in the blood.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

Before having surgery, tell your doctor or dentist that you are taking this medication.

Caution is advised when using this drug in the elderly because they may be more sensitive to its side effects, especially hearing loss and irregular heartbeat.

This medication should not be used in children younger than 2 months of age due to the risk of serious side effects.

Caution is advised when erythromycin is used in infants. Although very unlikely, a stomach problem called IHPS (infantile hypertrophic pyloric stenosis) has sometimes occurred. Contact your child's doctor immediately if your child has persistent vomiting or increased irritability with feeding.

This medication should be used only when clearly needed during pregnancy. This medication should not be used near the time of delivery because of possible harm to the unborn baby. Discuss the risks and benefits with your doctor.

This medication passes into breast milk and may have undesirable effects on a nursing infant. Therefore, breast-feeding while using this medication is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: eletriptan, ergot alkaloids (e.g., ergotamine, dihydroergotamine), methenamine, drugs which may affect the heart rhythm (QT prolonging drugs such as cisapride, pimozide), ivabradine, ranolazine.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting erythromycin with sulfisoxazole.

Other drugs besides erythromycin and those listed above which may affect the heart rhythm (QT prolongation in the EKG) include amiodarone, dofetilide, gatifloxacin, moxifloxacin, procainamide, propafenone, quinidine, sotalol, and thioridazine, among others. Before using this medication, report all medications you are currently using to your doctor or pharmacist. QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (e.g., severe dizziness, fainting) that require immediate medical attention. Ask your doctor or pharmacist for more details and for instructions on how you may reduce the risk of this effect.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: colchicine, certain diabetes medications (sulfonylureas such as glipizide, glyburide, tolbutamide), digoxin, live bacterial vaccines, methotrexate, oral PABA, warfarin, certain "water pills" (potassium-wasting diuretics such as hydrochlorothiazide, furosemide), drugs affecting liver enzymes that remove erythromycin from your body (such as azole antifungals including itraconazole and fluconazole, rifamycins including rifabutin, quinupristin-dalfopristin, calcium channel blockers including diltiazem and verapamil, certain anti-seizure medicines including carbamazepine and phenytoin and valproate).

Erythromycin can slow down the removal of other drugs from your body by affecting certain liver enzymes. Some examples of these affected drugs include alfentanil, bromocriptine, buspirone, certain benzodiazepines (alprazolam, midazolam, triazolam), caffeine-containing drugs, cilostazol, corticosteroids (e.g., prednisone), cyclosporine, eplerenone, certain erectile dysfunction medications (sildenafil, vardenafil), eszopiclone, felodipine, certain "statin" drugs (atorvastatin, lovastatin, simvastatin), quetiapine, tacrolimus, theophylline, tolterodine, vinblastine.

This medication may decrease the effectiveness of combination-type birth control pills. This can result in pregnancy. You may need to use an additional form of reliable birth control while using this medication. Consult your doctor or pharmacist for details.

This drug can affect the results of certain lab tests. Make sure laboratory personnel and your doctors know you are taking this medication.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for another infection unless told to do so by your doctor. A different medication may be necessary in those cases.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store in the refrigerator between 36-46 degrees F (2-8 degrees C). Discard any unused medication after 14 days. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised August 2008 Copyright(c) 2008 First DataBank, Inc.