Altabax

Altabax information, interactions and side effects, ALTABAX contains retapamulin, a semisynthetic pleuromutilin antibiotic. The chemical name of retapamulin is acetic acid, [[(3-exo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]thio]-, (3aS,4R,5S,6S,8R,9R,9aR,10R)-6-ethenyldecahydro-5-hydroxy-4,6,9,10-tetramethyl-1-oxo-3a,9-propano-3a#-cyclopentacycloocten-8-yl ester. Retapamulin, a white to pale-yellow crystalline solid, has a molecular formula of C30H47NO4S, and a molecular weight of 517.78. The chemical structure is:

altabax

Each gram of ointment for dermatological use contains 10 mg of retapamulin in white petrolatum.

INDICATIONS

ALTABAX® is indicated for use in adults and pediatric patients aged 9 months and older for the topical treatment of impetigo (up to 100 cm² in total area in adults or 2% total body surface area in pediatric patients aged 9 months or older) due to Staphylococcus aureus (methicillin-susceptible isolates only) or Streptococcus pyogenes. Safety in patients younger than 9 months has not been established.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ALTABAX and other antibacterial drugs, ALTABAX should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

DOSAGE AND ADMINISTRATION

A thin layer of ALTABAX should be applied to the affected area (up to 100 cm² in total area in adults or 2% total body surface area in pediatric patients aged 9 months or older) twice daily for 5 days. The treated area may be covered with a sterile bandage or gauze dressing if desired.

HOW SUPPLIED

Dosage Forms And Strengths

10 mg retapamulin/lg of ointment in 15- and 30-gram tubes

Storage And Handling

ALTABAX is supplied in 15-gram and 30-gram tubes.

NDC 0007-5180-22 (15-gram tube)
NDC 0007-5180-25 (30-gram tube)

Store at 25°C (77°F) with excursions permitted to 15°-30°C (59°-86°F).

SIDE EFFECTS

Clinical Studies Experience

Because clinical studies are conducted under varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The adverse reaction information from the clinical studies does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

The safety profile of ALTABAX was assessed in 2,115 adult and pediatric patients > 9 months who used at least one dose from a 5-day, twice a day regimen of retapamulin ointment. Control groups included 819 adult and pediatric patients who used at least one dose of the active control (oral cephalexin), 172 patients who used an active topical comparator (not available in the US), and 71 patients who used placebo.

Adverse events rated by investigators as drug-related occurred in 5.5% (116/2,115) of patients treated with retapamulin ointment, 6.6% (54/819) of patients receiving cephalexin, and 2.8% (2/71) of patients receiving placebo. The most common drug-related adverse events ( ≥ 1% of patients) were application site irritation (1.4%) in the retapamulin group, diarrhea (1.7%) in the cephalexin group, and application site pruritus (1.4%) and application site paresthesia (1.4%) in the placebo group.

Adults

The adverse events, regardless of attribution, reported in at least 1% of adults (18 years of age and older) who received ALTABAX or comparator are presented in Table 1.

Table 1: Adverse Events Reported by ≥ 1% of Adult Patients Treated With ALTABAX or Comparator in Phase 3 Clinical Studies

 

Adverse Event ALTABAX
N = 1,527
%
Cephalexin
N = 698
%
Headache 2.0 2.0
Application site irritation 1.6 < 1.0
Diarrhea 1.4 2.3
Nausea 1.2 1.9
Nasopharyngitis 1.2 < 1.0
Creatinine phosphokinase increased < 1.0 1.0

 

Pediatrics

The adverse events, regardless of attribution, reported in at least 1% of pediatric patients aged 9 months to 17 years who received ALTABAX are presented in Table 2.

Table 2: Adverse Events Reported by ≥ 1% in Pediatric Patients Aged 9 Months to 17 Years Treated With ALTABAX in Phase 3 Clinical Studies

 

Adverse Event ALTABAX
N = 588
%
Cephalexin
N = 121
%
Placebo
N = 64
%
Application site pruritus 1.9 0 0
Diarrhea 1.7 5.0 0
Nasopharyngitis 1.5 1.7 0
Pruritus 1.5 1.0 1.6
Eczema 1.0 0 0
Headache 1.2 1.7 0
Pyrexia 1.2 < 1.0 1.6

 

Other Adverse Events

Application site pain, erythema, and contact dermatitis were reported in less than 1% of patients in clinical studies.

Postmarketing Experience

In addition to reports in clinical trials, the following events have been identified during postmarketing use of ALTABAX. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

General Disorders and Administration Site Conditions

Application site burning.

Immune System Disorders

Hypersensitivity including angioedema.

DRUG INTERACTIONS

Coadministration of oral ketoconazole 200 mg twice daily increased retapamulin geometric mean AUC(0-24) and Cmax by 81% after topical application of retapamulin ointment, 1% on the abraded skin of healthy adult males. Due to low systemic exposure to retapamulin following topical application in adults and pediatric patients 2 years of age and older, dosage adjustments for retapamulin are unnecessary in these patients when coadministered with CYP3A4 inhibitors, such as ketoconazole. Based on in vitro P450 inhibition studies and the low systemic exposure observed following topical application of ALTABAX, retapamulin is unlikely to affect the metabolism of other P450 substrates.

Concomitant administration of retapamulin and CYP3A4 inhibitors, such as ketoconazole, has not been studied in pediatric patients. In pediatric patients 2 to 24 months of age, systemic exposure of retapamulin was higher compared with patients > 2 years of age after topical application. Based on the higher exposure of retapamulin, it is not recommended to coadminister ALTABAX with strong CYP3A4 inhibitors in patients younger than 24 months of age.

The effect of concurrent application of ALTABAX and other topical products to the same area of skin has not been studied.

PRECAUTIONS

Local Irritation

In the event of sensitization or severe local irritation from ALTABAX, usage should be discontinued, the ointment wiped off, and appropriate alternative therapy for the infection instituted.

Not for Systemic or Mucosal Use

ALTABAX is not intended for ingestion or for oral, intranasal, ophthalmic, or intravaginal use. The efficacy and safety of ALTABAX on mucosal surfaces have not been established. Epistaxis has been reported with the use of ALTABAX on nasal mucosa.

Potential for Microbial Overgrowth

The use of antibiotics may promote the selection of nonsusceptible organisms. Should superinfection occur during therapy, appropriate measures should be taken.

Prescribing ALTABAX in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to evaluate carcinogenic potential have not been conducted with retapamulin.

Retapamulin showed no genotoxicity when evaluated in vitro for gene mutation and/or chromosomal effects in the mouse lymphoma cell assay, in cultured human peripheral blood lymphocytes, or when evaluated in vivo in a rat micronucleus test.

No evidence of impaired fertility was found in male or female rats given retapamulin 50, 150, or 450 mg/kg/day orally.

Use In Specific Populations

Pregnancy

Pregnancy Category B

Effects on embryo-fetal development were assessed in pregnant rats given 50, 150, or 450 mg/kg/day by oral gavage on days 6 to 17 postcoitus. Maternal toxicity (decreased body weight gain and food consumption) and developmental toxicity (decreased fetal body weight and delayed skeletal ossification) were evident at doses ≥ 150 mg/kg/day. There were no treatmentrelated malformations observed in fetal rats.

Retapamulin was given as a continuous intravenous infusion to pregnant rabbits at dosages of 2.4, 7.2, or 24 mg/kg/day from day 7 to 19 of gestation. Maternal toxicity (decreased body weight gain, food consumption, and abortions) was demonstrated at dosages ≥ 7.2 mg/kg/day (8-fold the estimated maximum achievable human exposure, based on AUC, at 7.2 mg/kg/day). There was no treatment-related effect on embryo-fetal development.

There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ALTABAX should be used in pregnancy only when the potential benefits outweigh the potential risk.

Nursing Mothers

It is not known whether retapamulin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ALTABAX is administered to a nursing woman. The safe use of retapamulin during breast-feeding has not been established.

Pediatric Use

The safety and effectiveness of ALTABAX in the treatment of impetigo have been established in pediatric patients 9 months to 17 years of age. Use of ALTABAX in pediatric patients (9 months to 17 years of age) is supported by evidence from adequate and wellcontrolled studies of ALTABAX in which 588 pediatric patients received at least one dose of retapamulin ointment, 1%. The magnitude of efficacy and the safety profile of ALTABAX in pediatric patients 9 months and older were similar to those in adults.

The safety and effectiveness of ALTABAX in pediatric patients younger than 9 months of age have not been established. An open-label clinical study of topical treatment with ALTABAX (twice daily for 5 days) was conducted in patients 2 to 24 months of age. Plasma samples were obtained from 79 patients. In these pediatric patients, systemic exposure of retapamulin was higher compared with patients 2 to 17 years of age. Furthermore, a higher proportion of pediatric patients 2 to 9 months of age had measurable concentrations ( > 0.5 ng/mL) of retapamulin compared with patients 9 to 24 months of age. The highest levels were seen in patients 2 to 6 months of age. The use of retapamulin is not indicated in pediatric patients younger than 9 months of age.

Geriatric Use

Of the total number of patients in the adequate and well-controlled studies of ALTABAX, 234 patients were 65 years of age and older, of whom 114 patients were 75 years of age and older. No overall differences in effectiveness or safety were observed between these patients and younger adult patients.

OVERDOSE

Overdosage with ALTABAX has not been reported. Any signs or symptoms of overdose, either topically or by accidental ingestion, should be treated symptomatically consistent with good clinical practice.

There is no known antidote for overdoses of ALTABAX.

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