Abametapir: A New Solution to an Age Old Problem

ABSTRACT

Abametapir is a new metalloproteinase inhibitor that received Food and Drug Administration approval in July 2020 as a topical pediculocide. The uniqueness of this new drug is that it targets metalloproteinase needed for hatching the eggs as well as killing adults. Herein we discuss this new drug, its history of development, its modality of use and its adverse drug reactions. It is hoped it will make Dermatologists aware of this new development.

INTRODUCTION

Abametapir is a new pediculocide that belongs to the subclass of metalloproteinase inhibitors which received Food and Drug Administration (FDA) approval on July 27, 2020.

HISTORY

The search for developing an effective ovicide began in 1999 when resistance to multiple agents became widespread. In the USA, apart from embarrassment and unnecessary absenteism from schools, a total of 1 billion Dollars was spent on lice treatment.[1] Such estimates as well as comprehensive studies measuring the disease burden are unfortunately lacking from India.

In this background, Spinosad 0.9% was FDA approved in 2011. However Professor Vern Bowell of the University of Melbourne observed that metalloproteinase was a key enzyme in the process of egg hatching. Inhibition of metalloproteinase les to high in vitro mortality in lice eggs.

This led to the development of an ovicidal cum adult pediculocidal compound.[2]

Chemical structure

The chemical has 12 carbons with a bipyridine structure.[3]

MODE OF APPLICATION

It is applied for 10 min on dry scalp followed by washing the hair to remove any residual drug. Repeat application is not indicated.

PHARMACOKINETIC DATA

A small part is systemically absorbed following topical application. It is 91.3%–92.3% plasma protein bound.[3]

METABOLISM

The drug is principally metabolized by Cytochrome P1A2 (CYP1A2) enzyme into a monohydroxylated compound, abametapir hydroxylate.[3] It is further metabolized into Carboxyl compound, which has significantly higher half life than its parent compound abametapir.

Studies also suggest potential of inhibition of CYP 1A2, CYP 3A4 and CYP 2B6 with the carboxylated compound. Hence application of abametapir in patients taking concomitant cytochrome inhibitors might lead to drug interactions.

MECHANISM OF ACTION

Abametapir is a metalloproteinase inhibitor. Metalloproteinases play a vital role in development of a lice from egg till adulthood. Interference with metalloproteinase functioning is believed to kill the lice and their eggs.

FORMULATIONS

Abametapir is available at 0.74% solution. No systemic formulations are available. The lotion is an off white colored lotion. Excipients include benzyl alcohol, butylated hydroxytoluene, carbomer 980, light mineral oil, polysorbate 20, trolamine and water.

METHOD OF USAGE

The solution should be applied on dry scalp. Hair should not be wet.[3] The amount should be sufficient to coat the entire hair and scalp. Upto one bottle may be used.

The solution may be left for upto 10 min, following which the scalp should be thoroughly washed with soap and water. This should be followed by wet combing to remove dead lice and nits.

It is important to stress the treatment of family members and close contacts simultaneously. Repeat application is not needed. General hygienic practices such as.

It is equally important to stress the need for general anti pediculosis measures such as ironing of clothes, washing of hats, head gears clothes etc., to prevent re infection.

EFFICACY

The efficacy as judged by complete freedom from live lice and nits from day 1 through day 14 is 81.1%–81.8%.[2]

The direct ovicidal effect was 100% with no reports of resistance emerging so far.[4]

TARGET PATIENT GROUP

The drug is FDA approved for children 6 months of age and older. The drug should not be used below this age group.

Animal studies have found it devoid of teratogenecity but its safety in lactation is not known.

ADVERSE DRUG REACTIONS

Scalp erythema and rash occurred at approximately 4% and 3.2% of the population. Contact sensitization occurred at 1.7% while scalp irritation has also been reported.[3] In addition, vomiting, eye irritation and hair color changes have also been observed.[2]

The most serious adverse reaction might be the Gasping Syndrome, which is a potentially fatal syndrome characterized by gasping respiration, nausea vomiting and metabolic acidosis. It is related to systemic exposure to benzyl alcohol. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. It can occur in the event of accidental ingestion. The potential of gasping syndrome from systemic absorption remains a possibility especially for neonates and premature babies and hence the drug is better avoided in these cases.

CONCLUDING THOUGHTS

While a successful treatment of pediculosis has been complicated by the rapid development of resistance as seen in many parts of the USA, the unique modality of action of abametapir preventing the hatching of eggs will probably preclude early development of resistance. With its promise of a single application, only time will tell if humanity has come close to the development of an ideal pediculocide.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.