Erythromycin and Sulfisoxazole (Oral)

Used primarily to treat a variety of ear infections in children, the combination antibiotic erythromycin and sulfisoxazole has been available since the 1970s, and has proven an effective and relatively safe medication for the general population.

Overview

Erythromycin and sulfisoxazole was originally approved as a combination drug in 1979 for the treatment of bacterial infection. Its primary use is in the treatment of otitis media, or infection of the middle ear in children. However, it does have other applications including treatment in adults and in fighting chest and sinus infections as well. It was originally marketed under several brand names, including Pediazole, Eryzole, and Ilosone. However, these brand names have been discontinued and this medication is now available as a generic antibiotic.

The combination of erythromycin, which is a member of the class of antimicrobials called macrolides, and sulfisoxazole, a member of the sulfanomide family, are both effective agents in disrupting the life cycle of the bacterial cells that cause infection. This combination drug is a common first line treatment because it is readily available, relatively inexpensive and generally well tolerated. Most patients who take this medication experience few side effects. The most common side effects experienced are digestive in nature from stomach ache to diarrhea, as both of these medicines alter the natural flora in the stomach and gut. It may also lead to yeast infection. However, there is a risk of allergic reaction to this medication that can be quite serious. Erythromycin/sulfisoxazole also interacts with a wide variety of other medications that can impact the efficacy of the antibiotic, but also the medication it interacts with. Patients with certain medical conditions including hepatic impairment, certain anemias and diseases of the blood or renal dysfunction may be better served to take another class of antibiotics in the treatment of infection.

Erythromycin and sulfisoxazole is considered a class C drug with regard to pregnant women. Data is not clear on the risks this medication presents to the fetus, but pregnant women and their physicians should proceed with caution when administering this antibiotic during pregnancy. It is not recommended for women in the final month of pregnancy. It is also contraindicated for infants under the age of two months.

Erythromycin and sulfisoxazole is delivered as a suspension, usually cherry flavored. The typical dosage schedule is three or four times daily for a period of ten days. Prolonged use of this medication is not recommended as side effects may become worse or symptoms of other conditions may be exacerbated over extended periods. It is very important that the patient follow dosing instructions exactly and take the medication for the entire dosing period. Failure to do so will decrease the effectiveness of the antibiotic in treating this particular infection, but may also decrease the efficacy of this medication for this patient in the future. Also, over-prescription of antibiotics and incorrect usage has led to a rise in antibiotic resistant strains of bacteria that are increasingly difficult to treat.

Conditions Treated

  • Infections of the middle ear
  • Infections of the sinus and respiratory tract
  • Nasal congestion
  • Chest congestion
  • Ear infections caused by the H. Influenzae Bacteria

Type Of Medication

  • Combination antibiotic

Side Effects

Erythromycin and sulfisoxazole is a powerful combination antibiotic, which makes it very effective in fighting bacterial infection, but also means it can cause multiple side effects in patients taking this medication. Some of the most common side effects are inconvenient or uncomfortable, but do not require medical attention or discontinuation of use. Other reactions can be much more dangerous and require immediate medical intervention or advice from a doctor. Some of the less serious and more common side effects include:

  • Decreased appetite
  • Cramping of the stomach or abdominal area
  • Vomiting
  • Diarrhea
  • Headache
  • Feeling nauseous
  • Vaginal itching and discharge

The following side effects can be dangerous or indicate an allergic reaction and require immediate medical attention. It may require immediate discontinuation of medication.

  • Aching joints
  • Itching
  • Unusually pale skin
  • Severe nausea and vomiting
  • Rash or hives
  • Sore muscles
  • Skin blistering or peeling
  • Difficulty swallowing
  • Yellowing of skin or eyes
  • Bruising easily
  • Excessive fatigue
  • Severe or significant stomach pain or cramping
  • Fever
  • Feeling weak or difficulty in moving
  • Unusual bleeding
  • Sore throat
  • Bloody urine
  • Heart arrhythmia
  • Pain in the lower back
  • Darker colored urine
  • Painful urination
  • Syncope or sudden fainting
  • Sore mouth
  • Pale colored stools
  • Sudden loss of hearing (may occur in patients with kidney disease)
  • Swelling in the neck
  • Increased sun sensitivity
  • Sore or swollen tongue
  • Difficulty breathing
  • Black or tarry stool

Dosage

Erythromycin/sulfisoxazole (Pediazole or generic), is delivered as a suspension. It is not recommended for any infant under two months of age. It is also not recommended for women in the ninth month of pregnancy.

Dosage is typically divided into three times daily or four times daily, and is usually prescribed for a period of ten days. Dosage levels are assigned based on the weight of the patient.

When prescribed for four times per day, the medication should be taken every six hours as follows:

  • Less than 18 pounds adjust based on weight and age
  • 18-35 pounds take 2.5 mL
  • 35-53 pounds take 5 mL
  • 53-70 pounds take 7.5 mL
  • Over 70 pounds take 10 mL

When assigned a schedule to take the medication three times a day, it should be taken every eight hours as follows:

  • Less than 13 pounds adjust based on weight and age of patient
  • 13-26 pounds take 2.5 mL
  • 26-40 pounds take 5 mL
  • 40-53 pounds take 7.5 mL
  • 53-66 pounds take 10 mL
  • Over 66 pounds take 12.5 mL

This medication does not have to be taken with food, but may be taken at mealtimes. In some cases, for maximum efficacy, erythromycin/sulfisoxazole should be taken between half an hour to two hours prior to mealtimes.

Interactions

Erythromycin/sulfisoxazole interact with a variety of other medications, diseases and medicines used to treat them and food. Key characteristics of erythromycin/sulfizoxazole that contribute to its interactions include:

  • Increased photo-sensitivity
  • Impacted by delayed gastric emptying
  • GI flora is altered
  • Moderate CYP2C9 inhibitor
  • Methemoglobinemia
  • Moderate P-gp inhibitor
  • Moderate CYP3A4 inhibitor
  • Can prolong QT interval
  • Moderate OATP1B1 inhibitor

Given these characteristics, this combination medication interacts with 13 diseases, 2 dietary and over 750 medications.

Erythromycin/sulfisoxazole is contraindicated for use with the following medications and should not be prescribed if patients are taking one or more of the following:

  • Ergotamine
  • BCG live intravesical
  • Eliglustat
  • Cisapride
  • Flibanserin
  • Dihydroergotamine
  • Grazoprevir
  • Dronedarone
  • Lomitapide
  • Fluconazole
  • Methenamine
  • Lovastatin
  • Methylergonovine
  • Thioridazine
  • Simvastatin
  • Pimozide
  • Saquinavir
  • Toremifene

Erythromycin/sulfisoxazole has major interaction with these medications and an alternative medication should be used if at all possible for patients taking one or more of the following:

  • Amiodarone
  • Alfentanil
  • Aminophylline
  • Aprepitant
  • Aminolevulinic acid topical
  • Anagrelide
  • Amitriptyline
  • Arsenic trioxide
  • Amoxapine
  • Asenapine
  • Artemether/lumefantrine
  • Bosutinib
  • Buprenorphine
  • Atazanavir
  • Bupivacaine
  • Bedaquiline
  • Cabozantinib
  • Ciprofloxacin
  • Cholera vaccine, live
  • Carbamazepine
  • Chloroquine
  • Ceritinib
  • Cobicistat
  • Chloroprocaine
  • Codeine
  • Clofazimine
  • Citalopram
  • Cocaine, topical
  • Colchicine
  • Clarithromycin
  • Conivaptan
  • Cobimetinib
  • Danazol
  • Darunavir
  • Crizotinib
  • Degarelix
  • Dihydrocodeine
  • Cyclosporine
  • Dasatinib
  • Dofetilide
  • Diltiazem
  • Delavirdine
  • Dolasetron
  • Disopryamide
  • Desflurane
  • Enflurane
  • Desipramine
  • Ephedra
  • Fentanyl
  • Droperidol
  • Eribulin
  • Efavirenz
  • Ezogabine
  • Flecainide
  • Ephedrine
  • Fluoxetine
  • Fosfomycin
  • Epirubicin
  • Fluvoxamine
  • Fosaprepitant
  • Goserelin
  • Fluphenazine
  • Haloperidol
  • Fosamprenavir
  • Hydroxychloroquine
  • Histrelin
  • Ibutilide
  • Indinavir
  • Hydrocodone
  • Imatinib
  • Idelalisib
  • Ivabradine
  • Iloperidone
  • Isavucuonazonium sulfate
  • Imipramine
  • ixabepilone
  • Inotuzumab ozogamicin
  • Ketoconazole
  • Isoflurane
  • Lidocaine
  • Leuprolide
  • Lopinavir/ritonavir
  • Levofloxacin
  • Mepivacaine
  • Loperamide
  • Meperidine
  • Mifepristone
  • Methadone
  • Moxifloxacin
  • Methotrexate
  • Naloxegol
  • Neratinib
  • Nilotinib
  • Nefazodone
  • Nortriptyline
  • Nelfinavir
  • Netupitant
  • Oxycodone
  • Olaparib
  • Palonosetron
  • Osimertinib
  • Palbociclib
  • Pimavanserin
  • Panobinostat
  • Paliperidone
  • Pentamidine
  • Pirfenidone
  • Pasireotide
  • Pramlintide
  • Procainamide
  • Posaconazole
  • Prochlorperazine
  • Protriptyline
  • Quinine
  • Promethazine
  • Quetiapine
  • Quinupristin/dalfopristin
  • Quinidine (antiarrhythmic)
  • Rifabutin
  • Rivaroxaban
  • Ribociclib
  • Ritonavir
  • Romidepsin
  • Rilpivirine
  • Ropivacaine
  • Sevoflurane
  • Rucaparib
  • Sildenafil
  • Sonidegib
  • Sirolimus
  • Sotalol
  • Simeprevir
  • Sodium phosphate (bowel prep)
  • Sunitinib
  • Sodium phosphate rectal
  • Tacrolimus
  • Theophylline
  • Telbivudine
  • Tramdol
  • Telavancin
  • Tolvaptan
  • Temsirolimus
  • Tipranavir
  • Tetrabenazine
  • Trazodone
  • Triptorelin
  • Trifluoperazine
  • Triazolam
  • Trifluridine
  • Vardenafil
  • Voxilaprevir
  • Vemurafenib
  • Vandetanib
  • Voriconazole
  • Verapamil
  • Venetoclax
  • Ziprasidone

The following medications may be taken in conjunction with erythromycin/sulfisoxazole, but the patient should be closely monitored during the course of the antibiotic prescription:

  • Acetazolamide
  • Albuterol
  • Abemaciclib
  • Afatinib
  • Albuterol (inhaled)
  • Acalabrutinib
  • Apixaban
  • Atovastatin
  • Alfuzosin
  • Aripiprazole
  • Alprazolam
  • Apomorphine
  • Amlodipine
  • Arformoterol inhaled
  • Axitinib
  • Avanafil
  • Butorphanol
  • Buspirone
  • Brexpiprazole
  • Bumetanide
  • Chlorpromazine
  • Carboplatin
  • Cilostazol
  • Chlorothiazide
  • Cisplatin
  • Chlorthalidone
  • Clozapine
  • Chlorpropamide
  • Corticotropin
  • Diclofenac
  • Deflazacort
  • Dinutuximab
  • Deutetrabenazine
  • Docetaxel
  • Digoxin
  • Eplerenone
  • Everolimus
  • Edoxaban
  • Ethacrynic acid
  • Exenatide
  • Escitalopram
  • Ethosuximide
  • Fosphenytoin
  • Fingolimod
  • Formoterol (inhaled)
  • Felodipine
  • Furosemide
  • Glimepiride
  • Guanfacine
  • Gemifloxacin
  • Glyburide
  • Gemtuzumab ozogamicin
  • Granisetron
  • Glipizide
  • Ibrutinib
  • Hydroxyzine
  • Indacaterol (inhaled)
  • Hydrochlorothiazide
  • Isoproterenol
  • Ivacaftor
  • Itraconazole
  • Lixisenatide
  • Lapatinib
  • Levalbuterol (inhaled)
  • Lurasidone
  • Lenvatinib
  • Mefloquine
  • Metolazone
  • Magnesium citrate
  • Metaproterenol
  • Morphine
  • Methyclothiazide
  • Midostaurin
  • Methazolamide
  • Nevirapine
  • Nimodipine
  • Nicardipine
  • Nisodipine
  • Nifedipine
  • Oxaliplatin
  • Ofloxacin
  • Phenytoin
  • Pazopanib
  • Ondansetron
  • Primaquine
  • Pitavastatin
  • Quinidine
  • Prednisone
  • Repaglinide
  • Ranolazine
  • Suvorexant
  • Solifenacin
  • Terbutaline
  • Sorafenib
  • Tofacitinib
  • Torsemide
  • Tolterodine
  • Tolazamide
  • Valbenzine
  • Vilazodone
  • Tolbutamide
  • Valproic acid

The following list of medications are generally regarded as relatively safe to be used concomitantly with erythromycin/sulfisoxazole, but patients are advised to do so with caution as there is some minor interaction.

  • Aliskiren
  • Armodafinil
  • Amantadine
  • Atropine
  • Bexarotene
  • Benzocaine topical
  • Black cohosh
  • Benztropine
  • Brigatinib
  • Budesonide
  • Bosentan
  • Bromocriptine
  • Cevimeline
  • Copanlisib
  • Celecoxib
  • Clidinium
  • Dapsone
  • Dicyclomine
  • Desgestrel (contraceptive)
  • Dapsone topical
  • Dienogest (contraceptive)
  • Darifenacin
  • Dexamethasone
  • Diphenoxylate
  • Difenoxin
  • Drospirenone (contraceptive)
  • Eluxadoline
  • Eletriptan
  • Erlotinib
  • Entacapone
  • Estrogens (hormone replacement)
  • Estradiol (contraceptive)
  • Ethinyl estradiol (contraceptive)
  • Ethynodiol (contraceptive)
  • Ethinyl etradiol (hormone replacement)
  • Etravirine
  • Flavoxate
  • Estropipate (hormone replacement)
  • Etonogestrel (contraceptive)
  • Fexofenadine
  • Gefitinib
  • Grapefruit
  • Glycopyrrolate
  • Glecaprevir
  • Griseofulvin
  • Ifosfamide
  • Isoniazid
  • Hyoscyamine
  • Irinotecan
  • Lesinurad
  • Kava
  • Levonorgestrel (contraceptive)
  • Lumacaftor
  • Lidocaine topical
  • Maraviroc
  • Methylprednisolone
  • Methoxsalen
  • Mestranol (contraceptive)
  • Methoxsalen topical
  • Mitotane
  • Mirtazapine
  • Methscopolamine
  • Modafinil
  • Mycophenolic acid
  • Nitrite
  • Mycophenolate mofetil
  • Naldemedine
  • Nitroprusside
  • Norgestimate (contraceptive)
  • Norethindrone (contraceptive)
  • Norelgestromin (contraceptive)
  • Norgestrel (contraceptive)
  • Pibrentasvir
  • Oxcarbazepine
  • Phenobarbital
  • Ponatinib
  • Probenecid
  • Pravastatin
  • Propantheline
  • Porfimer
  • Rifapentine
  • Red yeast
  • Roflumilast
  • Rifampin
  • Ruxolitinib
  • Sildosin
  • Scopolamine
  • Sertraline
  • St. John's wort
  • Saxagliptin
  • Sodium picosulfate
  • Tamsulosin
  • Tadalafil
  • Teniposide
  • Tamoxifen
  • Tretinoin
  • Ticagrelor
  • Topotecan
  • Trospium
  • Tetracaine
  • Trihexyphenidyl
  • Verteporfin
  • Vincristine
  • Vinorelbine
  • Vinblastine
  • Zileuton

It is recommended patients taking erythromycin and sulfisoxazole avoid alcohol intake as its consumption may reduce the efficacy of the antibiotic. Patients should also avoid eating grapefruit or drinking grapefruit juice as the grapefruit may increase the strength of the antibiotic.

Patients who suffer from hepatic impairment should use erythromycin/sulfisoxazole with caution as it can cause further liver dysfunction.

Patients with some sort of cardiac arrhythmia that is treated with macrolides should only take erythromycin/sulfisoxasole if no other acceptable alternative is available, as this medication has been linked to increased episodes of arrhythmia.

Erythromycin/sulfisoxazole is not recommended for patients suffering from glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, as its use, particularly over prolonged periods has been linked to certain forms of anemia and other conditions linked to bone marrow depression.

The sulfanomides contained in the combination drug erythromycin/sulfisoxazole can cause severe reactions in patients with hypersensitivity to sulfa drugs. These reactions can be dangerous, even fatal, and are especially serious in patients with other compromising conditions such as severe allergies, AIDS or asthma. These patients should be monitored very carefully while using this medicine.

The benzyl alcohol that is often used in the packaging of erythromycin/sulfisoxazole is dangerous for newborn babies and should not be used in their treatment.

This medication should not be prescribed for any patient suffering from porphyria.

Erythromycin/sulfisoxazole is primarily metabolized through the kidneys and so for patients with renal impairment, use of this medication should be judicious as it can further impact kidney function.

Because this antibiotic can significantly alter the bacteria in the stomach, patients who suffer from colitis and other gastric conditions may experience more severe gastric and digestive side effects.

Use of this antibiotic has been linked to worsening symptoms for patients with Myasthenia Gravis and should be administered to them with caution and monitoring.

Warnings

As erythromycin and solfisoxazole is an antibiotic, it is critical for the patient to follow the dosing instructions very carefully and not miss a dose. If a dose is missed for whatever reason, the patient should take the missed dose as soon as possible. However, if it is nearer to the next dosing time, the patient should wait and make the dose up at the end of the prescribed dosing period. It is very important that the patient continue to take this medication through to the end of the prescribed period (usually 10-14 days), even if he or she is feeling better. Failure to finish the prescribed dose can lead to a rise in antibiotic resistance in both the patient and the strains of bacteria that cause infection.

It is possible to overdose on this medication. If overdose is suspected, call poison control and seek medical assistance as soon as possible.

Patients who are pregnant or become pregnant while taking erythromycin and sulfisoxazole should inform their doctor immediately.

Patients should inform their physician of any other health conditions they may have before this medication is prescribed, including liver disease, kidney and renal disease, diabetes, cardiovascular disease or cancer, as this antibiotic may exacerbate their condition or interact with medication they take to treat any of those conditions.

Allergic reaction and anaphylaxis can happen with erythromycin and sulfisoxazole. Patients who have shown hypersensitivity to other macrolides or sulfanilomides should not be prescribed this particular antibiotic as it is more likely to cause an allergic reaction.

Patients who require surgery of any kind while taking erythromycin/sulfisoxazole should inform their surgeon that they are taking this medication.

For maximum effectiveness, this medicine should not be taken with carbonated beverages or fruit juice. Grapefruit juice should be avoided during the entire length of the prescription as it interacts negatively with erythromycin/sulfisoxazole.

This medication may be taken with or without food, but should be taken with a full glass of water.

Storage

Erythromycin/sulfisoxazole is delivered to medical facilities and health care providers in a powder form to be reconstituted into a suspension for administration to patients. This powder substance should be stored at room temperature, always below 86 degrees Fahrenheit. It should not be allowed to freeze. Once the powder has been reconstituted into liquid form, it should be stored in the refrigerator.

Most prescriptions call for the medication to be taken over a period of ten days. The solution should be kept tightly sealed and in the refrigerator. It must be discarded after fourteen days.

It is possible to overdose on this medication, and the suspension is usually flavored to make it easier for children to take. It should be kept safely and securely stored out of the reach of children and pets. When discarding unused medication, it should not be flushed down the toilet or disposed of in regular household trash. Consult a pharmacist or healthcare provider for instructions and options for safe disposal.

Summary

While used primarily in the treatment of ear infections in pediatric patients, erythromycin and sulfisoxazole may be used in the treatment of other bacterial infections, particularly related to sinus or chest congestion. This combination antibiotic has been available for decades and is now usually prescribed in its generic form. The medication is delivered as a liquid suspension for easier administration. This suspension should be refrigerated once it has been reconstituted. All unused liquid should be disposed of after fourteen days.

This medication is generally well-tolerated, but does carry the risk of some side effects. For most patients, the side effects will be mild enough that they can take the entire dose of erythromycin/sulfisoxazole without disruption or further medical care. The most common of these side effects are headache, stomach ache, diarrhea and nausea. It is important to note, however, that this medication is contraindicated for patients who have shown hypersensitivity to either macrolide or sulfanomide based antibiotics. Allergic reaction to this medication can be severe and potentially fatal.

Patients with other medical conditions may need to be prescribed a different antibiotic from another family of medications as erythromycin/sulfisoxazole is known to interact negatively with liver disease, kidney disease, irregular heartbeat and other diseases of the blood.