Year : 2021 | Volume
: 10 | Issue : 2 | Page : 69--71
Abametapir: A novel pediculicide with a unique mechanism
Suruchi Aditya1, Aditya Rattan2,
1 Department and Institution-Senior Lecturer, Department of Pharmacology, Dr Harvansh Singh Judge Institute of Dental Sciences, Panjab University, Sector 25, Chandigarh, India
2 Department and Institution-Consultant Cardiologist, Heartline, SCO 60, Sector 6, Panchkula, Haryana, India
Dr. Suruchi Aditya
Department of Pharmacology, Dr Harvansh Singh Judge Institute of Dental Sciences, Panjab University, Sector 25, Chandigarh
Pediculus humanus capitis or head louse, a blood-sucking, wingless arthropod, has been a source of repulsion and embarrassment causing social distress, parental anxiety, and absenteeism. The battle to eradicate this infestation has not been rewarding as the obligate parasite continues to produce resistance to effective first-line pediculicides such as permethrin. Abametapir is a new pediculicide that inhibits the metalloproteinases critical to the hatching process of the eggs. Being an ovicidal drug, it needs a single application. In two large phase 3 studies with 704 subjects aged ≥6 months, abametapir lotion eliminated lice in ≥80% of subjects after a single 10-min application with no nit combing. The common adverse effects observed are erythema, rash, and sensation of skin burning. The Food and Drug Administration approved abametapir lotion, 0.74%, for a one-time topical treatment of head louse infestation for patients aged 6 months and older in July 2020. Good efficacy, safety, and a novel mechanism of action make it a welcome addition to the list of effective lousicidal drugs.
|How to cite this article:|
Aditya S, Rattan A. Abametapir: A novel pediculicide with a unique mechanism.J NTR Univ Health Sci 2021;10:69-71
|How to cite this URL:|
Aditya S, Rattan A. Abametapir: A novel pediculicide with a unique mechanism. J NTR Univ Health Sci [serial online] 2021 [cited 2022 Jan 24 ];10:69-71
Available from: https://www.jdrntruhs.org/text.asp?2021/10/2/69/332849
The head louse (Pediculus humanus capitis), a blood-sucking arthropod of the suborder Anoplura, measures about the size of the sesame seed and can crawl with a speed up to 23 cm/min.
Each female lays 8–10 eggs daily at the skin–hair junction and up to 300 eggs during her lifetime. Egg cases, called nits, shaped like oval capsules and glued to hair by an adhesive produced by the mother's accessory gland, are laid preferentially at the temples, behind the ears, and at the back of the neck. 7–10 days later, hatching results in three nymphal stages that moult on the third, fifth, and tenth days. Empty egg casings are white or clear.
The length of infestation can be assessed by measuring the farthest distance of eggs from the scalp and comparing it to the growth rate of hair; a distance of >1/4 in may indicate an inactive, old infestation.
Prevalence of head louse infestation is estimated to range between 0.7% and 59% in Asian population. Head-to-head contact can transmit the infestation to caregivers and close contacts. It is a common health problem in vulnerable population—school children and lower socioeconomic groups such as homeless people, refugees, and slum dwellers, underlining the role of overcrowding and lack of hygiene. Besides being a stigmatic issue associated with low self-esteem and absenteeism, lice infestation can lead to negative ramifications such as postponement of surgery, quarantine, and overtreatment.
The hallmark symptom—scalp itching—is a delayed hypersensitivity reaction to louse saliva, which may take up to 6 weeks to develop after the first exposure; successive exposures result in pruritus within 1–2 days. Scratching can lead to excoriations at the back of the neck, predisposing the patient to secondary infection with Staphylococcus aureus or streptococci. Impetigo and infection can cause cervical adenopathy.
Since finding only nits on examination does not indicate current infestation, therapy is recommended only when live lice are observed. Traditional methods used to kill head lice are wet combing, manual removal, and shaving. The selection of a therapeutic agent depends on the availability and cost of agents and the age and medical status of the patient. Insecticidal agents that are neurotoxic to lice are permethrin 1% lotion or shampoo, pyrethrins 0.3%/piperonyl butoxide 4% shampoo, malathion 0.5% lotion, spinosad 0.9% suspension, ivermectin 0.5% lotion, and oral ivermectin (off-label use). Topical permethrin 1% is recommended as first-line treatment for head lice. Noninsecticidal agents that act by suffocation or exoskeleton dissolution are dimethicone, isopropyl myristate solutions, and benzyl alcohol 5% lotion.
Malathion, spinosad, and topical ivermectin are ovicidal as they kill both live lice and eggs in single application. Nonovicidal agents (permethrin, pyrethrins, benzyl alcohol, dimethicone, oral ivermectin, and isopropyl myristate) necessitate a repeat application for complete eradication (to kill emerging nymphs).
Failure of first-line treatment leading to reinfestation creates a challenge for both physicians and parents. Resistance to permethrin and pyrethrins reflects the remarkable adaptability of the arthropod. Pseudoresistance may be due to misdiagnosis, poor adherence, incorrect product use (underdosing or not following directions), and reinfestation by close contact. Lack of ovicidal or residual killing properties of the pediculicide can also be the cause of self-reinfestation. Spinosad, benzyl alcohol 5%, or malathion 0.5% may be used in failure to respond to permethrin.,
Abametapir (5,5'-dimethyl-2,2'-bipyridine) is a heterocyclic organic molecule that chelates heavy metal ions—iron(Fe), copper(Cu), zinc (Zn), and thus interacts with a range of targets within the arthropod that need metal cofactors for function, including metalloproteinases, which are critical for hatching process. The mechanism was corroborated by the observation that the inhibitory effects were reversed after the addition of metal ions (Fe, Cu, and Zn).
Abametapir (0.74% in isopropanol) resulted in complete inhibition of hatching (100% ovicidal) in all stages of egg development in the dichlorodiphenyltrichloroethane and permethrin-resistant laboratory-based SF-HL strain of human head louse in an in vitro study.
A double-blind, phase 2 study combined in vivo treatment followed by ex vivo evaluation of eggs and hatch rates. Fifty subjects aged ≥3 years with active head lice infestation (≥3 live head lice and ≥10 unhatched eggs) received a single 10-min application of 0.74% abametapir lotion or vehicle (control). Ovicidal efficacy was assessed by observing the hatch rate of eggs obtained from each subject's clipped hair before and after the medication and incubated for 14 days. 100% eggs treated with abametapir remained unhatched in contrast to 64.0% for vehicle. Moreover, 92.0% patients were louse-free in the abametapir group on day 1 and 88.0% on day 7 in comparison to the vehicle group (64.0% and 32.0% on day 1 and 7, respectively).
In two similar phase 3 clinical trials in 704 subjects, a significantly higher percentage of index patients attained treatment success (absence of live lice) with abametapir lotion than with vehicle in study 1 (81.1% versus 50.9%, P = 0.001) as well as in study 2 (81.8% versus 47.2%, P < 0.001). Through day 14, taking into account nonindex patients (household contacts with >1 live lice), 88.2% of the abametapir group and 62.0% of the vehicle group in study 1, and 81.0% of the abametapir group and 60.5% of the vehicle group in study 2 achieved treatment success (P < 0.001 in both cases).
The most common adverse effects were erythema (4%), rash (3.2%), skin burning sensation (2.6%), contact dermatitis, vomiting, eye irritation, pruritus, and hair color changes. Drugs that are substrates of CYP3A4, CYP2B6, or CYP1A2 should be avoided within 2 weeks after application as it may result in high systemic concentrations of the interacting drugs. This has been attributed to slow clearance of its metabolite abametapir carboxyl, which is inhibitor of these enzyme isoforms. Children aged <6 months should not be administered the lotion as it contains benzyl alcohol, associated with risk of toxicity in neonates.
A novel mechanism of action, remarkable ovicidal action, convenience of use, combined with good efficacy, and safety make this Food and Drug Administration approved drug a welcome addition to the armamentarium of effective and safe pediculicides for head lice in patients aged >6 months.
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Conflicts of interest
There are no conflicts of interest.
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