Chemical Name: (3aS,4R,5S,6S,8R,9R,9aR,10R)-6-ethenyldecahydro-5-hydroxy-4,6,9,10-tetramethyl-1-oxo-3a,9-propano-3aH-cyclopentacycloocten-8-yl-[[(3exo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]thio] acetic acid ester
Molecular Formula: C30H47NO4S
CAS Number: 224452-66-8
Antibacterial; pleuromutilin antibiotic.
Uses for Retapamulin
Topical treatment of impetigo caused by Staphylococcus aureus (oxacillin-susceptible [methicillin-susceptible] isolates only) or Streptococcus pyogenes (group A β-hemolytic streptococci; GAS).
Although impetigo may be self-limiting, anti-infective treatment usually indicated to reduce duration of symptoms and prevent recurrence or transmission to others. Empiric treatment with an appropriate narrow-spectrum anti-infective generally used for initial treatment and considered reasonable for typical cases. Some clinicians suggest in vitro testing (i.e., Gram stain and culture of pus or exudates from skin lesions) to identify causative organism and confirm in vitro susceptibility, especially if impetigo is extensive and/or failed to respond to initial empiric treatment.
Nonbullous and bullous impetigo have been treated with topical and/or systemic anti-infective therapy. Although comparative efficacy of various regimens not established in well-controlled clinical trials, topical anti-infectives generally used for less extensive disease and systemic anti-infectives generally recommended if impetigo is severe or involves numerous lesions or if an outbreak is affecting multiple individuals (e.g., family members, childcare groups, athletic teams).
When empiric treatment used, select appropriate narrow-spectrum anti-infective based on local patterns of resistance reported for S. aureus and S. pyogenes.
Retapamulin Dosage and Administration
Apply topically to the skin as a 1% ointment.
Do not apply to eyes or mucous membranes; do not administer orally, intranasally, or intravaginally.
Apply thin layer of ointment to affected area. May be applied to a maximum total treatment area of 100 cm2 in adults or a maximum of 2% of total body surface area (≤100 cm2) in pediatric patients 9 months of age or older.
Treated area may be covered with sterile bandage or gauze dressing, if desired. Such coverings may protect treated area and prevent accidental transfer of ointment to eyes or other areas and may prevent infants and young children from accidentally touching or licking lesion site.
Wash hands after applying the ointment, unless the hands are being treated.
Children ≥9 months of age: Apply thin layer of 1% ointment to affected area twice daily for 5 days.
Apply thin layer of 1% ointment to affected area twice daily for 5 days.
Children ≥9 months: Maximum treatment area is 2% of total body surface area.
Maximum treatment area is 100 cm2.
Cautions for Retapamulin
Manufacturer states no known contraindications.
Local irritation at application site (e.g., pruritus, burning, pain, eczema, erythema) reported following topical application to skin.
Allergic contact dermatitis reported rarely with topical retapamulin; confirmed with patch testing.
Postmarketing reports of hypersensitivity, including angioedema.
If sensitization or severe local irritation occurs, discontinue the drug, wipe off ointment, and institute appropriate alternative anti-infective therapy.
For external use only.
Use only for topical application to skin. Not intended for oral, intranasal, ophthalmic, or intravaginal use.
Safety and efficacy not established for topical use on mucosal surfaces. Epistaxis reported when retapamulin was applied to nasal mucosa.
Use of anti-infectives may promote selection of nonsusceptible organisms.
If superinfection occurs, discontinue the drug and institute appropriate therapy.
Selection and Use of Anti-infectives
To reduce development of drug-resistant bacteria and maintain effectiveness of retapamulin and other anti-infectives, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.
Prescribing topical retapamulin in the absence of a proven or strongly suspected bacterial infection unlikely to provide benefit to the patient and increases risk of development of drug-resistant bacteria.
In the absence of culture and in vitro susceptibility testing, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.
No adequate and well-controlled studies evaluating topical retapamulin in pregnant women. Use topical retapamulin only when potential benefits outweigh potential risks.
In rats, oral retapamulin associated with maternal toxicity (decreased weight gain, decreased food consumption) and developmental toxicity (decreased fetal body weight, delayed skeletal ossification); no treatment-related malformations reported. In rabbits, continuous IV infusion of retapamulin (at 8 times estimated maximum achievable human exposure) associated with maternal toxicity (decreased weight gain, decreased food consumption, abortions); no treatment-related effects on embryofetal development.
Not known whether retapamulin distributed into milk following topical application to skin.
Use with caution in nursing women.
Safety and efficacy not established in infants <9 months of age.
Safety and efficacy for topical treatment of impetigo in pediatric patients ≥9 months of age supported by evidence from adequate and well-controlled studies that included pediatric patients 9 months to 17 years of age. Safety profile in pediatric patients in this age group similar to that reported in adults.
Safety and efficacy in geriatric patients ≥65 years of age similar to younger adults.
Common Adverse Effects
Application site irritation.
Interactions for Retapamulin
Metabolized by CYP3A4.
Possible effects of concurrent topical application of retapamulin and other topical products to the same skin area not studied to date.
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
CYP inhibitors: Dosage adjustments of topical retapamulin not necessary if used concomitantly with CYP3A4 inhibitors in adults and children ≥2 years of age. Do not use topical retapamulin concomitantly with potent CYP3A4 inhibitors in infants <24 months of age; systemic absorption following topical application is higher in this age group. (See Plasma Concentrations under Pharmacokinetics.)
CYP substrates: Based on in vitro CYP isoenzyme inhibition studies and low retapamulin systemic exposure following topical application to skin, topical retapamulin unlikely to affect metabolism of other CYP substrates.
Retapamulin AUC and peak plasma concentrations increased 81% when topical retapamulin used concomitantly with oral ketoconazole
Adults and children ≥2 years of age: Dosage adjustments not needed if topical retapamulin used concomitantly with oral ketoconazole
Infants <24 months of age: Do not use topical retapamulin concomitantly with ketoconazole
Systemic exposure is low following topical application of retapamulin to intact or abraded skin. Systemic absorption is enhanced if semi-occlusive or occlusive dressings used at site of application.
Healthy adults: Once-daily topical application of 1% ointment to 800 cm2 of occluded intact skin for up to 7 days resulted in median peak plasma concentrations of 3.5 ng/mL (range: 1.2–7.8 ng/mL) on day 7; plasma concentrations generally undetectable on day 1 (lower limit of detection 0.5 ng/mL). On day 7, 82% had measurable retapamulin plasma concentrations.
Healthy adults: Once-daily topical application of 1% ointment to 200 cm2 of occluded abraded skin for up to 7 days resulted in median peak plasma concentrations of 11.7 ng/mL (range: 5.6–22.1 ng/mL) on day 1 and 9 ng/mL (range: 6.7–12.8 ng/mL) on day 7. On day 7, 100% had measurable retapamulin plasma concentrations.
Adults and children 2–17 years of age: Following twice-daily topical application of 1% ointment, 11% had measurable plasma concentrations (median 0.8 ng/mL); maximum plasma concentrations in these adults or children were 10.7 or 18.5 ng/mL, respectively.
Infants 2–24 months of age: Following twice-daily topical application of 1% ointment for 5 days, 69% of those 2–9 months of age† and 32% of those 9–24 months of age had measurable plasma concentrations (>0.5 ng/mL). Among the 29 infants 2–9 months of age, 4 had plasma concentrations ≥26.9 ng/mL and these concentrations exceeded maximum plasma concentrations reported in children 2–17 years of age. Among the 50 infants 9–24 months of age, 1 infant had plasma concentration of 95.1 ng/mL.
Not known whether distributed into milk following topical application to skin.
Plasma Protein Binding
In vitro studies with human hepatocytes indicate the main routes of metabolism are monooxygenation and dioxygenation; in vitro studies with human liver microsomes indicate the main routes of metabolism are monooxygenation and N-demethylation with extensive metabolism to numerous metabolites.
Metabolized by CYP3A4.
Not investigated due to low systemic exposure after topical application to skin.
25°C (may be exposed to 15–30°C).
Actions and Spectrum
Semisynthetic pleuromutilin antibiotic.
Usually bacteriostatic in vitro against susceptible S. aureus and S. pyogenes (group A β-hemolytic streptococci; GAS); may be bactericidal at high concentrations (MBC is 1000 times higher than MIC).
Selectively inhibits bacterial protein synthesis by binding to a distinct site on the 50S subunit of the bacterial ribosome, inhibiting peptidyl transfer, blocking P-site interactions, and preventing normal formation of active 50S ribosomal subunits.
Gram-positive bacteria: Active in vitro and in clinical infections against S. aureus (methicillin-susceptible [oxacillin-susceptible] isolates only) and S. pyogenes. Although clinical importance unclear, also has in vitro activity against S. epidermidis (including methicillin-resistant S. epidermidis), S. agalactiae (group B streptococci; GBS), groups C and G β-hemolytic streptococci, and viridans group streptococci.
Many strains of methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA) are susceptible to retapamulin in vitro; however, this does not correlate with clinical efficacy for treatment of MRSA infections (e.g., secondarily infected traumatic skin lesions). Treatment failure when used in MRSA infections may be related to virulence factors.
Active in vitro against some strains of S. aureus resistant to mupirocin, fusidic acid, and/or erythromycin. Also active in vitro against clinical isolates of S. pyogenes resistant to bacitracin, fusidic acid, macrolides, quinolones, or tetracycline.
S. aureus, including MRSA, with decreased susceptibility to retapamulin produced in vitro. In addition, clinical isolates of S. aureus, including MRSA, with decreased susceptibility or resistance to retapamulin reported.
Reduced susceptibility or resistance to retapamulin may be the result of mutations in ribosomal protein L3 and 23S rRNA, presence of cfr rRNA methyltransferase, and/or presence of vgaA/vgaAv genes affecting efflux pumps.
Cross-resistance between retapamulin and other classes of anti-infectives (e.g., lincosamides, oxazolidinones, streptogramins) can occur.
Advice to Patients
Importance of applying retapamulin 1% ointment to affected area of skin as directed.
Advise patients that retapamulin ointment is for external use only and should not be swallowed or used in eyes or nose, on mouth or lips, or inside female genital tract.
Inform patients that treated area may be covered with a sterile bandage or gauze dressing, if desired. Such coverings may protect treated area and prevent accidental transfer of ointment to eyes or other areas and may prevent infants and young children from accidentally touching or licking lesion site.
Advise patients to wash hands after applying the ointment, unless the hands are being treated.
Importance of completing full course of treatment, even if symptoms improve.
Importance of notifying clinician if symptoms do not improve within 3–4 days after starting treatment.
Advise patients that topical retapamulin may cause reactions at the site of application. Importance of discontinuing use and contacting clinician if application site worsens in irritation, redness, itching, burning, swelling, blistering, or oozing.
Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
AHFS DI Essentials™. © Copyright 2021, Selected Revisions May 6, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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