Erythromycin and benzoyl peroxide

Uses

Topical therapy for the treatment of acne vulgaris.

Erythromycin tablet is highly effective in the treatment of a wide variety of clinical infections, such as

• Upper respiratory tract infections: Tonsillitis, peritonsillar abscess, pharyngitis, laryngitis, sinusitis, and secondary infections in cold and influenza.
• Lower respiratory tract infections: Tracheitis, acute and chronic bronchitis. Mycoplasma pneumoniae (lobar pneumonia, broncho pneumonia, primary atypical pneumoniae), bronchiectasis.
• Skin and soft tissue infections: Boils and carbuncles, paronychia, abscesses, pustular acne, impetigo, cellulitis, furuncolosis, erythrasma.
• Veneral infections: Non-specific urethritis, syphilis (if the patient is allergic to penicillin).
• Gastro-intestinal infections: Cholecystitis, Staphylococcal enterocolitis, infectious diarrhoea, & cholera.
• Ear and oral infections: 0titis media and otitis externa, gingivitis, dental abscesses.
• Prophylaxis: Pre-operative and post-operative, trauma, burns, rheumatic fever.
• Other infections: Diphtheria, whooping cough.

For topical treatment of acne, pimples & bacterial skin infections susceptible to Erythromycin

Erythromycin and benzoyl peroxide is also used to associated treatment for these conditions: Acne, Acne Vulgaris, Inflammatory Acne VulgarisAcne, Acne Vulgaris, Acute Otitis Media caused by Haemophilus Influenzae, Acute pelvic inflammatory disease caused by Neisseria Gonorrheae Infection, Bacterial Infections, Chancroid, Chlamydia Trachomatis, Chlamydial ophthalmia neonatorum, Community Acquired Pneumonia (CAP), Diphtheria, Erythrasma, Gastroparesis, Granuloma Inguinale, Intestinal amebiasis caused by entamoeba histolytica, Legionella Pneumophila Infections, Listeria infection, Lower Respiratory Tract Infection (LRTI), Lymphogranuloma Venereum, Nongonococcal urethritis, Ophthalmia neonatorum (gonococcal), Pertussis, Postoperative Infections, Primary Syphilis, Respiratory Tract Infections (RTI), Staphylococcal Skin Infections, Syphilis, Upper Respiratory Tract Infection, Ureaplasma urethritis, Whooping Cough, Inflammatory papular lesions, Mild Acne vulgaris, Moderate Acne vulgaris, Predominant skin comedones, papules and pustules, Prophylaxis of Rheumatic fever, Pustular lesions, Skin and skin-structure infections, Skin and subcutaneous tissue bacterial infections caused by streptococcus pyogenes, Superficial ocular infections

How Erythromycin and benzoyl peroxide works

Acne vulgaris is caused by inflammation in the pilosebaceous gland. Acne is generally caused by increased excretion of sebum from pilosebaceous glands, endocrine factors such as androgenic hormones, keratin developing around follicles, bacterial growth, and inflammation. These factors contribute to the formation of comedones (whiteheads and blackheads).

The peroxide bond of benzoyl peroxide is cleaved to form 2 benzoyloxy radicals. These radicals interact nonspecifically with bacterial proteins, interfering with their function, and survival of the bacteria. Over time, free radical interactions with bacterial proteins lead to decreased keratin and sebum around follicles.

Benzoyl peroxide can also increase the turnover rate of epithelial cells, leading to skin peeling, and breaking down comedones.

In order to replicate, bacteria require a specific process of protein synthesis, enabled by ribosomal proteins. Erythromycin acts by inhibition of protein synthesis by binding to the 23S ribosomal RNA molecule in the 50S subunit of ribosomes in susceptible bacterial organisms. It stops bacterial protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit. This results in the control of various bacterial infections. The strong affinity of macrolides, including erythromycin, for bacterial ribosomes, supports their broad‐spectrum antibacterial activities.

Dosage

Erythromycin and benzoyl peroxide dosage

Adult: As 2.5-10% preparation: Apply 1-2 times daily after cleansing, may gradually increase to tid if needed. Start with lower strength preparations.

As cleanser: Wash 1-2 times daily.

Child: ≥12 yr Same as adult dose.

Adult and Child over 8 years: 250-500 mg every 6 hours or 0.5-1 gm every 12 hours. This may be increased up to 4 gm daily according to severity of infections.

Child of 2-8 years: 250 mg every 6 hours, doses doubled for severe infections.

Child up to 2 years: 125 mg every 6 hours.

Neonates: 30 to 45 mg/kg daily in 3 divided doses.

Elderly: Same as for adults.If administration on a twice daily schedule is desirable, one half of the total daily dose may be given every 12 hours, one hour before meal.

Amoebic dysentery:

• Adult: 250 - 500 mg four times daily for 10 - 14 days.
• Children: 30 - 50 mg/kg/day in divided doses for 10 - 14 days.

Pertussis: 30 - 50 mg/kg/day in divided doses for 5-14 days depending upon eradication of a positive culture.Streptococcal infections: In the treatment of group A beta haemolytic streptococcal infections, therapeutic dosage of Erythromycin should be administered for at least 10 days.

Acne: The usual dosage regimen of erythromycin in the treatment of acne is 500 mg twice daily for 3 months. Then the dose is to be reduced to 250 mg twice daily for another 3 months.

Early Syphilis: 500 mg 4 times daily for 14 days.Uncomplicated genital Chlamydia nongonococcal Urethritis: 500 mg twice daily for 14 days.

Prophylaxis: In continuous prophylaxis of streptococcal infections in person with a rheumatic heart disease, the dosage is 250 mg twice daily.

When Erythromycin is used prior to surgery to prevent endocarditis caused by alpha haemolytic streptococci, a recommended schedule:

• For children: 20 mg/Kg 1.5 - 2 hours pre-operatively and 10 mg/kg every 6 hours for 8 doses post-operatively.
• For adults:The dose is 1 g, 1.5 - 2 hours pre-operatively and 500 mg every 6 hours for 8 doses post-operatively.

Topical: Apply to the affected areas in the morning and evening. Before applying thoroughly wash with warm water and soap, rinse and pat dry all areas to be treated. Apply with applicator. Wash hands after use.

Direction for reconstitution of suspension: Shake the bottle to loosen powder. Add 60 ml (12 measuring spoonful) of boiled and cooled water to the dry powder of the bottle. For ease of preparation, add water to the bottle in two proportions. Shake well after each addition until all the powder is in suspension.

Note: Shake the suspension well before each use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool and dry place, preferably in refrigerator and unused portion should be discarded after 7 days.

Side Effects

The major adverse reaction reported to date with Benzoyl Peroxide cutaneous therapy is irritation of the skin including erythema, burning, peeling, dryness, itching, stinging, feeling of skin tension locally at the site of application. This is reversible when treatment is reduced in frequency or discontinued. Allergic contact dermatitis, including face oedema, may occur.

Generally erythromycin is well tolerated and serious adverse effects are rare. Side-effects are gastrointestinal and are dose-related. They include nausea, vomiting, abdominal pain, diarrhea and anorexia. Mild allergic reactions, such as urticaria and skin rashes have occurred. Serious allergic reactions, including anaphylaxis may occur.

Toxicity

Data regarding overdoses of benzoyl peroxide are not readily available. During an overdose patients may experience and increased risk or severity of adverse effects such as skin itching, burning, peeling, inflammation, and erythema.

The oral LD₅₀ in rats is 490 mg/kg.

LD50

The oral LD50 of erythromycin in rats is 9272 mg/kg.

Overdose information

Symptoms of overdose may include diarrhea, nausea, stomach cramps, and vomiting. Erythromycin should immediately be discontinued in cases of overdose. Rapid elimination of unabsorbed drug should be attempted. Supportive measures should be initiated. Erythromycin is not adequately removed by peritoneal dialysis or hemodialysis.

Precaution

Children, Pregnancy and lactation.

Lotion/Cream: For external use only. Keep away from eyes, nose, mouth and other mucous membrane.

Use of antibiotics (especially prolonged or repeated therapy) may result in bacterial or fungal overgrowth of non-susceptible organisms. Such overgrowth may lead to a secondary infection. Take appropriate measures if superinfections occur.

Tablet: Since Erythromycin is metabolized principally by the liver, caution should be exercised when erythromycin is administered to patients with impaired hepatic function. There have been reports of hepatic dysfunction with or without jaundice occurring in patients taking oral Erythromycin.

Interaction

There is no known interaction with other medications which might be used cutaneously and concurrently with Benzoyl Peroxide; however, drugs with desquamative, irritant and drying effects should not be used concurrently with Benzoyl Peroxide gel.

Theophylline: The use of Erythromycin in patients who are receiving concomitant high doses of theophylline may be associated with an increase in serum theophylline and potential theophylline toxicity. If symptoms of toxicity develop, the dose of theophylline should be reduced.

Digoxin: Concomitant administration of Erythromycin and Digoxin has been reported to result in elevated digoxin serum levels.

Clindamycin interacts with Erythromycin

Volume of Distribution

Erythromycin is found in most body fluids and accumulates in leucocytes and inflammatory liquid. Spinal fluid concentrations of erythromycin are low, however, the diffusion of erythromycin through the blood-brain barrier increases in meningitis, likely due to the presence of inflamed tissues which are easily penetrated. Erythromycin crosses the placenta.

Elimination Route

In a sample of excised skin, 1.9% of a radiolabelled topical dose fully penetrates the skin, and 2.6% remains in the skin. The radiolabelled dose that fully penetrates the skin is recovered as benzoic acid, while the dose in the skin is approximately half benzoic acid and half benzoyl peroxide. 95.5% of a radiolabelled dose is not absorbed or metabolized after 8 hours.

Orally administered erythromycin is readily absorbed. Food intake does not appear to exert effects on serum concentrations of erythromycin. Some interindividual variation exists in terms of erythromycin absorption, which may impact absorption to varying degrees. The Cmax of erythromycin is 1.8 mcg/L and the Tmax is 1.2 hours. The serum AUC of erythromycin after the administration of a 500mg oral dose was 7.3±3.9 mg.h/l in one pharmacokinetic study. Erythromycin is well known for a bioavailability that is variable (18-45%) after oral administration and its susceptibility to broken down under acidic conditions.

Half Life

The elimination half-life of oral erythromycin was 3.5 hours according to one study and ranged between 2.4-3.1 hours in another study. Repetitive dosing of erythromycin leads to increased elimination half-life.

Clearance

The clearance of erythromycin in healthy subjects was 0.53 ± 0.13 l/h/kg after a 125mg intravenous dose. In a clinical study of healthy patients and patients with liver cirrhosis, clearance of erythromycin was significantly reduced in those with severe liver cirrhosis. The clearance in cirrhotic patients was 42.2 ± 10.1 l h–1 versus 113.2 ± 44.2 l h-1 in healthy patients.

Elimination Route

Benzoyl peroxide's metabolite benzoic acid, is eliminated in the urine. Data regarding fecal elimination is not readily available.

In patients with normal liver function, erythromycin concentrates in the liver and is then excreted in the bile.Under 5% of the orally administered dose of erythromycin is found excreted in the urine. A high percentage of absorbed erythromycin is not accounted for, but is likely metabolized.

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Safety for use during pregnancy has not been established. Use only when the potential benefits outweigh potential hazards to the fetus.

Erythromycin is excreted in breast milk. Exercise caution when administering to a nursing mother.

Contraindication

Benzoyl Peroxide gel is contra-indicated in patients with known hypersensitivity to Benzoyl Peroxide.

Erythomycin is contraindicated in patients with a known hypersensitivity to this drug.

Special Warning

Safety and effectiveness in children less than 12 years have not been established.

Acute Overdose

Benzoyl Peroxide gel is a preparation indicated for topical treatment only. If the medication is applied excessively, no more rapid or better results will be obtained and severe irritation might develop. In this event, treatment must be discontinued and appropriate symptomatic therapy should be instituted.

In case of overdosage, Erythromycin should be discontinued. Overdosage should be handled with the prompt elimination of unabsorbed drug and all other appropriate measures should be instituted. Erythromycin is not removed by peritoneal dialysis or haemodialysis.

Storage Condition

Store in a cool and dry place, protected from light.

Keep at room temperature and away from light.

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