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Spinosad Topical Suspension (Natroba)

National Drug Monograph

November 2011

VA Pharmacy Benefits Management Services,

Medical Advisory Panel, and VISN Pharmacist Executives

The purpose of VA PBM Services drug monographs is to provide a comprehensive drug review for making formulary decisions. These documents will be updated when new clinical data warrant additional formulary discussion. Documents will be placed in the Archive section when the information is deemed to be no longer current.

Executive Summary

Spinosad topical suspension that received FDA approval for the topical treatment of head lice infestation (Pediculosis capitis) in patients 4 years of age and older. The regimen includes a 10 minute application of spinosad topical suspension and may be repeated 7 days later if live lice are still seen.1

Spinosad topical suspension is neurotoxic to lice but is not absorbed systemically by humans, resulting in minimal human toxicity.

• Two pivotal, Phase III clinical trials were conducted to evaluate the efficacy and safety of the home use of spinosad topical suspension in the treatment of head lice. In these trials, spinosad topical suspension demonstrated superiority over permethrin 1% crème rinse in the proportion of patients who were lice free 14 days after last day of treatment (primary efficacy endpoint).2

Most common adverse effects reported include application site erythema, ocular erythema, and application site irritation.

Introduction

The purposes of this monograph are to (1) evaluate the available evidence of safety, tolerability, efficacy, cost, and other pharmaceutical issues that would be relevant to evaluating spinosad topical suspension for possible addition to the VA National Formulary; (2) define its role in therapy; and (3) identify parameters for its rational use in the VA.

Pharmacology/Pharmacokinetics

Mechanism of Action: Spinosad causes neuronal excitation in insects. After periods of hyperexcitation, the lice become paralyzed and die. Spinosad is both pediculicidal and ovicidal.3

The bioavailability of spinosad topical suspension following a single 10-minute application was evaluated in a pharmacokinetic study. The plasma concentrations of spinosad for all patients were below the lower limit of quantitation. The bioavailability of benzyl alcohol from spinosad topical suspension is unknown as plasma concentrations of benzyl alcohol were not determined in the subjects included in the pharmacokinetic study.

Microbiology

In vitro activity

Resistance to older head lice treatments has been reported in the published literature starting in the 1990s. One group found permethrin resistance rates to be greater than 80% at two different school districts in the United Kingdom. The same study found malathion in vitro resistance rates to be 44%-96% depending on the concentration of the drug; the corresponding treatment failure rate was 64%. Currently, no susceptibility studies for spinosad have been published.

FDA Approved Indication(s)

Spinosad topical suspension is FDA approved for the topical treatment of head lice infestation (P. capitis) in patients four years of age and older.3

Current VA National Formulary Alternatives

Permethrin lotion 1%

Dosage and Administration

1. Shake bottle well.

2. Apply sufficient amount of spinosad topical suspension on dry scalp then cover remainder of hair.

3. Leave on for 10 minutes.

4. Thoroughly rinse off with water.

5. If live lice are seen after one week, repeat treatment.

Refer to patient counseling section of package information for more specific details of administration.3

Efficacy

Two pivotal, Phase III clinical trials were conducted to evaluate the efficacy and safety of the home use of spinosad topical suspension in the treatment of head lice. The study designs of these two clinical trials were identical and designed to establish superiority of spinosad topical suspension compared to permethrin 1% crème rinse. The results of these trials were published together in one article in the peer-reviewed literature.2

Efficacy Measures

The primary efficacy endpoint in the pivotal clinical trials was treatment effectiveness. Treatment effectiveness was defined as the proportion of primary participants in the enrolled households in the intent-to-treat (ITT) population who were lice free 14 days after last day of treatment in the spinosad-without-nit-combing group compared with the permethrin-with-combing group. Because spinosad is ovicidal, the investigators did not require nit combing, while nit combing was required for the permethrin group because of its lack of ovicidal activity and its inclusion in the package directions.7 The primary participants were the youngest members of the household who had at least 3 live lice at baseline. Intent-to-treat population defined as all enrolled subjects who were randomly assigned to treatment. All participants in the same household received the same treatment. “Lice free” was defined as no live lice, adults or nymphs, present as determined by a trained evaluator. Last day of treatment for subjects treated once was day 14; last day of treatment for subjects treated twice was day 21.

Summary of efficacy findings

Significantly more primary study participants in the enrolled households in both the ITT population and PP population who received spinosad were lice free 14 days after last day of treatment compared with the permethrin group. (Study 1 ITT population: 84.6% spinosad, 44.9% permethrin, p 6 members with infestation or > 1 infected household member would not enroll in |

| |study or use rescue treatment |

| |Use of excluded medication or systemic antibiotic |

| |Pregnant or breastfeeding |

| |Drug abuse within last 12 months |

| |Participation in clinical study in last 30 days |

|Results |Study 1 |

| | |

| |Demographics |

| | |

| |Spinosad without comb |

| |Permethrin with comb |

| |Spinosad with comb |

| | |

| |Randomly assigned patients, n |

| |243 |

| |256 |

| |59 |

| | |

| |Households, n |

| |91 |

| |89 |

| |23 |

| | |

| |Completed patients, n |

| |227 |

| |230 |

| |54 |

| | |

| |Mean age, years |

| |16 |

| |17 |

| |19 |

| | |

| |Age range, years |

| |0.5-66.0 |

| |0.5-84.0 |

| |1.0-64.0 |

| | |

| |Girls or women, % |

| |82.3 |

| |82.0 |

| |79.7 |

| | |

| |White race, % |

| |53.5 |

| |56.6 |

| |54.2 |

| | |

| |Hispanic race, % |

| |43.2 |

| |39.8 |

| |37.3 |

| | |

| | |

| |Efficacy Results |

| | |

| |Spinosad Topical Suspension Without Comb |

| |Number (%) |

| |Permethrin Crème Rinse With Comb |

| |Number (%) |

| |P Value |

| | |

| |Subjects (ITT primary participants) |

| |91 |

| |89 |

| | |

| | |

| |Lice Free 14 days after application for primary participant |

| |(primary efficacy endpoint) |

| |77 |

| |(84.6%) |

| |40 |

| |(44.9%) |

| | ................
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