Pediazole

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 (erythromycin and sulfisoxazole) 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.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

This medicine has been tested in children over the age of 2 months and has not been shown to cause different side effects or problems than it does in adults. This medicine should not be given to infants under 2 months of age unless directed by the child's doctor, because it may cause unwanted effects.

Geriatric

This medicine is intended for use in children and is not generally used in adult patients.

Pregnancy

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Astemizole
• Bepridil
• Cisapride
• Colchicine
• Dihydroergotamine
• Dronedarone
• Ergoloid Mesylates
• Ergonovine
• Ergotamine
• Flibanserin
• Fluconazole
• Grepafloxacin
• Levomethadyl
• Lomitapide
• Lovastatin
• Mesoridazine
• Methenamine
• Methylergonovine
• Methysergide
• Pimozide
• Piperaquine
• Posaconazole
• Saquinavir
• Simvastatin
• Sparfloxacin
• Terfenadine
• Thioridazine
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acecainide
• Afatinib
• Ajmaline
• Amiodarone
• Amitriptyline
• Amoxapine
• Anagrelide
• Apixaban
• Apomorphine
• Aprepitant
• Aprindine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Atorvastatin
• Azimilide
• Azithromycin
• Bedaquiline
• Bosutinib
• Bretylium
• Brexpiprazole
• Buserelin
• Carbamazepine
• Ceritinib
• Cerivastatin
• Chloral Hydrate
• Chloroquine
• Chlorpromazine
• Cholera Vaccine, Live
• Cilostazol
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clindamycin
• Clomipramine
• Clozapine
• Cobicistat
• Cobimetinib
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Darunavir
• Dasatinib
• Deflazacort
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Deutetrabenazine
• Dibenzepin
• Digoxin
• Diltiazem
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Droperidol
• Efavirenz
• Eliglustat
• Encainide
• Enflurane
• Eplerenone
• Escitalopram
• Fingolimod
• Flecainide
• Fluoxetine
• Fosaprepitant
• Foscarnet
• Gatifloxacin
• Gemifloxacin
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Halothane
• Histrelin
• Hydrocodone
• Hydroquinidine
• Hydroxychloroquine
• Hydroxyzine
• Ibrutinib
• Ibutilide
• Idelalisib
• Ifosfamide
• Iloperidone
• Imipramine
• Isoflurane
• Isradipine
• Ivabradine
• Ivacaftor
• Ketoconazole
• Lapatinib
• Leuprolide
• Levofloxacin
• Lidoflazine
• Lopinavir
• Lorcainide
• Lumacaftor
• Lumefantrine
• Lurasidone
• Mefloquine
• Methadone
• Methotrexate
• Metronidazole
• Mifepristone
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nafarelin
• Naloxegol
• Netupitant
• Nilotinib
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Olaparib
• Ondansetron
• Oxycodone
• Paliperidone
• Panobinostat
• Pasireotide
• Pazopanib
• Pentamidine
• Pimavanserin
• Pirmenol
• Pitavastatin
• Pitolisant
• Pixantrone
• Prajmaline
• Probucol
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Ranolazine
• Ribociclib
• Risperidone
• Sematilide
• Sertindole
• Sevoflurane
• Simeprevir
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sonidegib
• Sorafenib
• Sotalol
• Spiramycin
• Sulfamethoxazole
• Sulpiride
• Sultopride
• Sunitinib
• Tacrolimus
• Tadalafil
• Tedisamil
• Telaprevir
• Telavancin
• Telithromycin
• Tetrabenazine
• Theophylline
• Tizanidine
• Tolvaptan
• Topotecan
• Toremifene
• Trazodone
• Trifluoperazine
• Trimethoprim
• Trimipramine
• Triptorelin
• Troleandomycin
• Vandetanib
• Vardenafil
• Vasopressin
• Vemurafenib
• Venetoclax
• Verapamil
• Vinblastine
• Vincristine
• Vincristine Sulfate Liposome
• Vinflunine
• Voriconazole
• Warfarin
• Zolmitriptan
• Zotepine
• Zuclopenthixol

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acetohexamide
• Alfentanil
• Alprazolam
• Aminolevulinic Acid
• Anisindione
• Avanafil
• Bexarotene
• Budesonide
• Buspirone
• Cyclosporine
• Diazepam
• Dicumarol
• Methylprednisolone
• Midazolam
• Phenprocoumon
• Roflumilast
• Salmeterol
• Sildenafil
• Sirolimus
• Suvorexant
• Tolterodine
• Triazolam
• Trimetrexate
• Valproic Acid
• Zafirlukast

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or other blood problems or
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency—Erythromycin and sulfisoxazole may increase the chance of blood problems

• Heart disease—High doses of erythromycin and sulfisoxazole may increase the chance of side effects in patients with a history of an irregular heartbeat

• Kidney disease or
• Liver disease—Patients with liver or kidney disease may have an increased chance of side effects

• Loss of hearing—High doses of erythromycin and sulfisoxazole may increase the chance for hearing loss in some patients

• Porphyria—Erythromycin and sulfisoxazole may increase the chance of a porphyria attack

It is very important that your doctor check you at regular visits for any blood problems that may be caused by this medicine, especially if you will be taking this medicine for a long time.

If your symptoms do not improve within a few days, or if they become worse, check with your doctor.

Erythromycin and sulfisoxazole may cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness or other discoloration of the skin, or a severe sunburn. When you begin taking this medicine:

• Stay out of direct sunlight, especially between the hours of 10:00 a.m. and 3:00 p.m., if possible.
• Wear protective clothing, including a hat. Also, wear sunglasses.
• Apply a sun block product that has a skin protection factor (SPF) of at least 15. Some patients may require a product with a higher SPF number, especially if they have a fair complexion. If you have any questions about this, check with your health care professional.
• Apply a sun block lipstick that has an SPF of at least 15 to protect your lips.
• Do not use a sunlamp or tanning bed or booth.

If you have a severe reaction from the sun, check with your doctor.

Erythromycin and sulfisoxazole combination may cause blood problems. These problems may result in a greater chance of infection, slow healing, and bleeding of the gums. Therefore, you should be careful when using regular toothbrushes, dental floss, and toothpicks. Dental work should be delayed until your blood counts have returned to normal. Check with your medical doctor or dentist if you have any questions about proper oral hygiene (mouth care) during treatment.