Abametapir

Abametapir Uses, Dosage, Side Effects, Food Interaction and all others data.

Abametapir is a novel pediculicidal metalloproteinase inhibitor used to treat infestations of head lice. The life cycle of head lice (Pediculus capitis) is approximately 30 days, seven to twelve of which are spent as eggs laid on hair shafts near the scalp. Topical pediculicides generally lack adequate ovicidal activity, including standard-of-care treatments such as permethrin, and many require a second administration 7-10 days following the first to kill newly hatched lice that resisted the initial treatment. The necessity for follow-up treatment may lead to challenges with patient adherence, and resistance to agents like permethrin and pyrethrins/piperonyl butoxide may be significant in some areas.

Investigations into novel ovicidal treatments revealed that several metalloproteinase enzymes were critical to the egg hatching and survival of head lice, and these enzymes were therefore identified as a potential therapeutic target. Abemetapir is an inhibitor of these metalloproteinase enzymes, and the first topical pediculicide to take advantage of this novel target. The improved ovicidal activity (90-100% in vitro) of abemetapir allows for a single administration, in contrast to many other topical treatments, and its novel and relatively non-specific mechanism may help to curb the development of resistance to this agent.

Abametapir was first approved for use in the United States under the brand name Xeglyze on July 27, 2020.

Abametapir
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Abametapir
Generic	Abametapir
Abametapir Other Names	Abametapir
Type	Topical application
Formula	C₁₂H₁₂N₂
Weight	Average: 184.242 Monoisotopic: 184.100048394
Protein binding	Both abametapir and abametapir carboxyl are high protein-bound in plasma, although the specific proteins to which they bind are unclear. Following topical administration, abametapir is 91.3-92.3% protein-bound and abametapir carboxyl is 96.0-97.5% protein-bound.
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Abametapir is a pediculicide metalloproteinase used topically in the treatment of head lice infection.

Abametapir is indicated, in the context of an overall lice management program, for the topical treatment of head lice infestation in patients 6 months of age and older.

Abametapir is also used to associated treatment for these conditions: Head Lice Infestation

How Abametapir works

There are several metalloproteinases (enzymes requiring metal co-factors to function) involved in the process of louse egg hatching and survival. In vitro studies have demonstrated that metal-chelating agents can inhibit the activity of these proteins, and may therefore be valuable pediculicidal agents.

Abametapir is a metalloproteinase inhibitor that targets louse metalloproteinases which are critical to their development and hatching.

Toxicity

The intraperitoneal LD₅₀ of abametapir in mice is 225 mg/kg. Topical formulations of abametapir contain benzyl alcohol, which has been associated with fatal reactions including "gasping syndrome" following systemic exposure in neonates and low birth weight infants. The use of benzyl alcohol-containing abametapir formulations should be avoided in patients 4 As benzyl alcohol toxicity may also occur in pediatric patients following accidental oral ingestion, the manufacturer recommends that it be administered to pediatric patients only under the direct supervision of adult. Symptoms of benzyl alcohol toxicity may include significant gastrointestinal and central nervous system adverse effects, with severe cases leading to respiratory depression and death. If toxicity is expected, patients should be advised to contact their nearest poison control center.

The minimal amount of benzyl alcohol at which toxicity might occur is unclear. Toxicity is more likely in premature infants, low birth weight infants, and those receiving high doses.

Food Interaction

No interactions found.

Volume of Distribution

Data regarding the volume of distribution of abametapir are not available.

Elimination Route

In a pharmacokinetic trial with both adult and pediatric patients, the C_max and AUC_0-8h in the adult group were 41 ng/mL and 121 ng.h/mL and the C_max and AUC_0-8h in the pediatric group were 73 ng/mL and 264 ng.h/mL. In general, systemic exposure to abametapir appears to decrease with increasing age. The median T_max of abemetapir is 0.57 - 1.54 hours.

Following topical administration, benzyl alcohol was found in detectable quantities in the serum of 7 out of 39 pediatric patients. The C_max of benzyl alcohol in these subjects ranged from 0.52 to 3.57 μg/mL.

The predominant circulating metabolite of abemetapir (abemtapir carboxylate) is eliminated slowly from the circulation and is therefore found at higher serum concentrations than its parent drug - based on data collected for 72 hours post-administration, the ratios of serum C_max and AUC_0-72h between abametapir and abametapir carboxylate were approximately 30 and 250, respectively.

Half Life

The elimination half-lives of abametapir and its metabolites have not been well-characterized, but the estimated half-life of abametapir carboxyl is 71 ± 40 hours (or longer) in adults.