Retapamulin is a topical pleuromutilin antibiotic indicated for the treatment of impetigo due to Staphylococcus aureus (methicillin-susceptible isolates only) and Streptococcus pyogenes. It is a semisynthetic derivative of the compound pleuromutilin, which is isolated through fermentation from Clitopilus passeckerianus. Retapamulin ointment application twice daily for 5 days was shown to be at least as effective as 10 days of twice-daily oral cephalexin for the treatment of secondarily infected traumatic skin lesions. Absorption in pediatric patients may be greater than adult patients. Safety in patients younger than 9 months has not been established.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
-Apply a thin layer to affected area.
-Treated area may be covered with sterile gauze dressing if desired.
-Do not apply to the eye, or in the nose, mouth, or vagina.
-Wash hands after application if the hands are not the area for treatment.
Less than 1% of adult patients treated with topical retapamulin experienced an increase in creatinine phosphokinase.
The most frequently reported dermatologic adverse reaction with the use of topical retapamulin is skin irritation (1.4% to 1.6%) at the site of application. Pruritus (1.5%), application site pruritus (1.9%), eczema (1%), application site pain (less than 1%), erythema (less than 1%), and contact dermatitis (less than 1%) were reported in pediatric patients after topical application. Discontinue use and wipe off the ointment if the patient experiences sensitization or severe local irritation.
Headache was among the most commonly reported adverse events with topical retapamulin use in adults (2%) and was also reported in pediatric patients (1.2%).
Diarrhea (1.4%) and nausea (1.2%) were among the most commonly reported adverse events with topical retapamulin use in adults. Diarrhea (1.7%) was also reported in pediatric patients.
Naso-pharyngitis (1.2%) was among the most commonly reported adverse events with topical retapamulin use in adults. Naso-pharyngitis (1.5%) and fever (1.2%) were also reported in pediatric patients.
Retapamulin is not for ophthalmic administration or intranasal, oral, or vaginal administration.
There are no available data on retapamulin use in pregnant women to inform any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Retapamulin is negligibly absorbed systemically after topical administration, and maternal use during pregnancy is not expected to result in fetal exposure.
There are no data available on the presence of retapamulin in human milk, its effects on the breast-fed infant, or its effects on milk production. However, breast-feeding is not expected to result in exposure of the child to retapamulin due to the negligible systemic absorption in humans after topical administration. Due to minimal systemic absorption, risk to the breast-feeding infant would be minimal. Only apply water-miscible cream products to the breast because ointments may expose the infant to high concentrations of mineral paraffins. Consider the benefits of breast-feeding along with the mother's clinical need for retapamulin and any potential adverse effects on the breast-fed infant from retapamulin or the underlying maternal condition.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Staphylococcus aureus (MSSA), Streptococcus pyogenes (group A beta-hemolytic streptococci)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of impetigo:
Topical dosage:
Adults: Apply a thin layer to the affected area up to 100 cm2 in total area twice daily for 5 days.
Infants 9 months and older, Children, Adolescents: Apply a thin layer to the affected area up to 2% total body surface area twice daily for 5 days.
Maximum Dosage Limits:
-Adults
Do not apply to more than 100 cm2 in total area.
-Geriatric
Do not apply to more than 100 cm2 in total area.
-Adolescents
Do not apply to more than 2% total body surface area.
-Children
Do not apply to more than 2% total body surface area.
-Infants
9 to 11 months: Do not apply to more than 2% total body surface area.
1 to 9 months: Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustment needed.
Patients with Renal Impairment Dosing
No dosage adjustment needed.
*non-FDA-approved indication
Adagrasib: (Moderate) Coadministration of retapamulin with strong CYP3A inhibitors, such as adagrasib, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A substrate.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as clarithromycin, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Atazanavir: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as atazanavir boosted with ritonavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Atazanavir; Cobicistat: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as atazanavir boosted with ritonavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate. (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as cobicistat, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Ceritinib: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as ceritinib, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Chloramphenicol: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as chloramphenicol, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Clarithromycin: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as clarithromycin, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Cobicistat: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as cobicistat, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Darunavir: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as darunavir boosted with ritonavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Darunavir; Cobicistat: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as cobicistat, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate. (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as darunavir boosted with ritonavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as cobicistat, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate. (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as darunavir boosted with ritonavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Delavirdine: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as delavirdine, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as cobicistat, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as cobicistat, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Fosamprenavir: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as fosamprenavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Grapefruit juice: (Moderate) Advise parents that children younger than 24 months should not eat or drink grapefruit or grapefruit juice while using retapamulin due to potential for increased systemic retapamulin exposure. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate. Grapefruit is a strong CYP3A4 inhibitor.
Idelalisib: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as idelalisib, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Indinavir: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as indinavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Itraconazole: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as itraconazole, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Ketoconazole: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as ketoconazole, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as clarithromycin, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Levoketoconazole: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as ketoconazole, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Lonafarnib: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as lonafarnib, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Lopinavir; Ritonavir: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as ritonavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Mifepristone: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as chronic mifepristone therapy, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Nefazodone: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as nefazodone, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Nelfinavir: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as nelfinavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Nirmatrelvir; Ritonavir: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as ritonavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Posaconazole: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as posaconazole, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Ribociclib: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as ribociclib, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Ribociclib; Letrozole: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as ribociclib, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Ritonavir: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as ritonavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Saquinavir: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as saquinavir boosted with ritonavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Tipranavir: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as tipranavir boosted with ritonavir, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Tucatinib: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as tucatinib, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as clarithromycin, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Voriconazole: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as voriconazole, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Retapamulin is a semisynthetic derivative of the compound pleuromutilin. Retapamulin selectively inhibits bacterial protein synthesis by interacting at a site on the 50S subunit of the bacterial ribosome through an interaction that is different from that of other antibiotics. This binding site is in the region of the ribosomal P site and peptidyl transferase center and involves ribosomal protein L3. By binding to this site, retapamulin inhibits peptidyl transfer, blocks P-site interactions, and prevents the normal formation of active 50S ribosomal subunits. Retapamulin is bacteriostatic generally but is bactericidal at concentrations 1,000 times the in vitro MIC.
Resistance is caused by mutations in the ribosomal protein LC, the presence of Cfr rRNA methyltransferase, or the presence of an efflux mechanism. Although cross-resistance between retapamulin and other antibacterial classes (such as clindamycin and oxazolidones) exist, isolates resistant to these classes may be susceptible to retapamulin.
Retapamulin is administered topically to the skin. It is approximately 94% bound to human plasma proteins with protein binding independent of concentration. The apparent volume of distribution has not been determined in humans. In vitro studies have shown that retapamulin is extensively metabolized via mono-oxygenation and N-demethylation to numerous metabolites. Due to the low systemic absorption after topical application, retapamulin elimination has not been investigated in humans.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
CYP3A4 is the major enzyme responsible for the metabolism of retapamulin.
-Route-Specific Pharmacokinetics
Topical Route
There is little systemic absorption of retapamulin after topical administration to intact and abraded skin. In a trial of healthy patients, retapamulin 1% was applied once daily to intact skin (800 cm2 surface area) and to abraded skin (200 cm2 surface area) under occlusion for up to 7 days. Retapamulin concentrations (more than 0.5 ng/mL) were measurable in 3% of blood samples obtained on day 1 and 82% of blood samples obtained on day 7 after topical application to intact skin. In patients with abraded skin, 97% of blood samples obtained on day 1 and 100% of blood samples obtained on day 7 had measurable retapamulin concentrations. The median Cmax value in plasma after application to intact skin was 3.5 ng/mL on day 7. The median Cmax values in plasma after application to abraded skin were 11.7 ng/mL on day 1 and 9 ng/mL on day 7. In a study that included 380 adult patients receiving topical treatment with retapamulin twice daily, 11% had measurable retapamulin concentrations with a median concentration 0.8 ng/mL. The maximum measured retapamulin concentration was 10.7 ng/mL.
-Special Populations
Pediatrics
In a study that included 136 pediatric patients aged 2 to 17 years receiving topical treatment with retapamulin twice daily, 11% had measurable retapamulin concentrations (more than 0.5 ng/mL) with a median concentration 0.8 ng/mL. The maximum measured retapamulin concentration was 18.5 ng/mL. A single plasma sample was obtained from 79 pediatric patients, aged 2 to 24 months, who were receiving topical retapamulin twice daily. Retapamulin concentrations were measurable in 46% of patients aged 2 to 24 months compared to 7% of patients aged 2 to 17 years. A higher proportion (69%) of pediatric patients aged 2 to 9 months had measurable concentrations compared with patients aged 9 to 24 months (32%). Among pediatric patients aged 2 to 9 months (n = 29), 4 patients had retapamulin concentrations that were higher (26.9 ng/mL or more) than the maximum concentration observed in pediatric patients aged 2 to 17 years (18.5 ng/mL). Among pediatric patients aged 9 to 24 months (n = 50), 1 patient had a retapamulin concentration that was higher (95.1 ng/mL) than the maximum concentration observed in pediatric patients aged 2 to 17 years.