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  • CLASSES

    Topical Antibacterial Agents, Other

    DEA CLASS

    Rx

    DESCRIPTION

    Topical pleuromutilin antibiotic
    Used for treatment of impetigo due to methicillin-susceptible S. aureus and S. pyogenes
    Safety in patients younger than 9 months not established

    COMMON BRAND NAMES

    ALTABAX

    HOW SUPPLIED

    ALTABAX Topical Ointment: 1%

    DOSAGE & INDICATIONS

    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

    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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment needed.

    Renal Impairment

    No dosage adjustment needed.

    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.[33239]

    STORAGE

    ALTABAX:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Ophthalmic administration, vaginal administration

    Retapamulin is not for ophthalmic administration or intranasal, oral, or vaginal administration.[33239]

    Pregnancy

    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.[33239]

    Breast-feeding

    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.[33239] 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.[48357] 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.[33239]

    ADVERSE REACTIONS

    Severe

    eczema vaccinatum / Delayed / 1.0-1.0

    Moderate

    erythema / Early / 0-1.0
    contact dermatitis / Delayed / 0-1.0

    Mild

    headache / Early / 1.2-2.0
    pruritus / Rapid / 1.5-1.9
    diarrhea / Early / 1.4-1.7
    skin irritation / Early / 1.4-1.6
    pharyngitis / Delayed / 1.2-1.5
    nausea / Early / 1.2-1.2
    fever / Early / 1.2-1.2

    DRUG INTERACTIONS

    Amoxicillin; Clarithromycin; Lansoprazole: (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.
    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.
    Conivaptan: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as conivaptan, in patients younger than 24 months is not recommended. Wait at least 1 week after infusion of conivaptan to begin retapamulin treatment. 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.
    Dasabuvir; Ombitasvir; Paritaprevir; 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.
    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.
    Lopinavir; Ritonavir: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as lopinavir; 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 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.
    Ombitasvir; Paritaprevir; 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.
    Telithromycin: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as telithromycin, 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.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    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.[33239]

    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.[33239] 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.[48357] 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.[33239]

    MECHANISM OF ACTION

    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.[33239]
     
    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.[33239]

    PHARMACOKINETICS

    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.[33239]
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
    CYP3A4 is the major enzyme responsible for the metabolism of retapamulin.[33239]

    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.[33239]