ATC Class:P03BA
VA Class:AP300
Pyrethrins with piperonyl butoxide is a fixed-combination preparation containing 0.17-0.33% pyrethrins (pyrethrum extract), which is a pediculicide, and 2-4% piperonyl butoxide, which has little or no insecticidal activity but potentiates that of pyrethrins.
Pyrethrins with piperonyl butoxide is used for the topical treatment of pediculosis capitis (head lice infestation), pediculosis pubis (pubic lice infestation), and pediculosis corporis (body lice infestation).103, 104, 107, 112, 117, 120, 121, 122, 123, 124 Pyrethrins with piperonyl butoxide is not effective for the treatment of scabies (mite infestation).
When selecting a pediculicide for the treatment of pediculosis capitis (head lice infestation), clinicians should consider efficacy (including both pediculicidal and ovicidal activity), safety, cost, availability, ease of application, age of patient, presence of other scalp infections, patient preference, severity of the infestation, potential for transmission, number of recurrences, and the pattern of resistance in the geographic region.113 Although no pediculicide possesses true ovicidal activity, drugs with residual activity may kill emerging nymphs.103 The American Academy of Pediatrics (AAP) and others currently recommend use of topical permethrin 1%, topical malathion 0.5%, topical pyrethrins with piperonyl butoxide, topical crotamiton 10%, or oral ivermectin for the treatment of head lice infestations in the US.113, 107, 111, 113, 116, 117
Permethrin 1% generally is considered the treatment of choice and malathion 0.5% is recommended when permethrin resistance is suspected.103, 107, 108, 113, 114, 116, 117, 125 Some clinicians consider topical pyrethrins with piperonyl butoxide an alternative rather than a preferred treatment for pediculosis capitis107, 108 since the drug has low ovicidal activity without residual activity (a second treatment 7-10 days after the first treatment usually is necessary to kill newly hatched lice)103, 107, 108, 112, 113, 116, 117 and treatment failures have been reported even when dosage and administration recommendations were followed.108, 113 In the past, lindane was widely recommended for the treatment of pediculosis capitis;101, 108 however, the drug is no longer recommend for initial therapy because of reports of resistance and neurotoxicity (e.g., seizures)101, 103, 108 and is now considered a second-line agent that should be used for the treatment of pediculosis only in patients who have not responded to or who cannot tolerate other recommended therapies.110 (See Uses: Pediculosis in Lindane 84:04.12.)
Although there are few well-controlled, clinical studies of the treatment of pediculosis pubis (pubic lice infestation), the US Centers for Disease Control and Prevention (CDC) and others consider topical permethrin 1% or topical pyrethrins with piperonyl butoxide to be the pediculicides of choice for treatment of pediculosis pubis.101, 104, 112, 115 Alternatives recommended by the CDC and others are topical malathion 0.5% or oral ivermectin.104, 107, 108 Although topical lindane 1% also has been recommended for the treatment of pubic lice, the drug is no longer recommended as initial therapy because of reports of resistance and neurotoxicity (e.g., seizures)108 and is now considered a second-line agent that should be used for the treatment of pediculosis only in patients who have not responded to or who cannot tolerate other recommended therapies.110 (See Uses: Pediculosis in Lindane 84:04.12.)
For infestation of the eyelashes with pubic lice, the CDC and others recommend treatment with an occlusive ophthalmic ointment (e.g., petrolatum) 2-4 times daily for 8-10 days;103, 104, 107, 105 nits should be removed from the eyelashes manually.103, 105
The CDC recommends reevaluating the patient 1 week after treatment if symptoms persist.104 Retreatment may be necessary if lice are found or eggs are observed 1 week after treatment.104 The CDC recommends retreatment with an alternative regimen in patients who fail to respond to the initial regimen.104 However, some clinicians recommend routine retreatment of patients with pediculosis pubis using the same regimen 7-10 days after initial treatment.103
Pediculosis pubis usually is transmitted by sexual contact.104 Presumptive concurrent treatment of sexual contacts to whom lice might have been spread within the last month is recommended.103, 104 Patients should avoid sexual contact with their sexual partner(s) until patients and partners have been treated and reevaluated to rule out persistent disease.104 Presumptive concurrent treatment also has been recommended for other close contacts of the patient.105
The CDC states that patients with human immunodeficiency virus (HIV) infection who have pediculosis pubis should receive the same treatment as those without HIV infection.104
Pyrethrins with piperonyl butoxide is used for the topical treatment of pediculosis corporis (body lice infestation).120, 121, 122, 123, 124, 125 In some cases, body louse infestations may be treated by improved hygiene and by decontaminating clothes and bedding by washing at temperatures that kill lice.103, 125 If the infestation is severe, a pediculicide also should be used (e.g., topical permethrin, topical pyrethrins with piperonyl butoxide, topical malathion, oral ivermectin).124, 125
Topical pyrethrins with piperonyl butoxide has been recommended as one option for the treatment of pediculosis corporis in the adjunctive treatment of epidemic (louseborn) typhus.103 The causative agent of epidemic typhus ( Rickettsia prowazekii ) is transmitted person-to-person by Pediculus humanus var. corporis and adjunctive use of a topical cream or gel pediculicide (e.g., pyrethrins with piperonyl butoxide, crotamiton, lindane) may help prevent transmission of louseborn typhus.103 Thorough delousing (especially among exposed contacts of individuals with typhus) is recommended in epidemic situations.103
Pyrethrins with piperonyl butoxide is applied topically, usually as a shampoo containing 0.33% pyrethrins and 4% piperonyl butoxide.120, 121, 122, 123
Pyrethrins with piperonyl butoxide is for external use only.120, 121, 122, 123 The drug should not be administered orally and should not be applied to mucous membranes such as inside the nose, mouth, or vagina.120, 121, 122, 123
Preparations containing pyrethrins with piperonyl butoxide should not be applied to eyebrows or eyelashes and contact with the eyes should be avoided.120, 121, 122, 123 The eyes should be closed tightly and covered with a soft towel or washcloth while the shampoo is applied to scalp hair or washed off.120, 121, 122, 123 If contact with the eye(s) occurs, the affected eye should be rinsed thoroughly with water.120, 121, 122, 123
Pyrethrins with piperonyl butoxide should be applied to dry hair.120, 121, 122, 123
Containers of pyrethrins with piperonyl butoxide shampoo should be shaken before using.120, 123
Measures to Avoid Reinfestation and Transmission
To avoid reinfestation or transmission of lice, most experts recommend that clothing and bed linen that may have been contaminated by the infested individual during the 2 days prior to treatment be decontaminated (machine-washed in hot water and dried in a hot dryer or dry-cleaned) or removed from body contact for at least 72 hours.103, 104, 106, 113 Although it may not be necessary, items that cannot be laundered or dry-cleaned can be removed from contact and sealed in a plastic bag for 10-14 days.103, 106, 116 Combs and brushes used by the infected patient can be disinfected by soaking in hot water (temperature exceeding 53.5°C) for 5-10 minutes;103, 106 alternatively, they can be soaked in alcohol or a pediculicide for 1 hour.106, 112 It also is recommended that furniture and floors of rooms inhabited by patients infested with lice should be thoroughly vacuumed.103, 106, 116 Fumigation of living areas is not necessary and is not recommended.103, 106, 114, 116
Other family members and close contacts of the individual with pediculosis should be evaluated by a clinician and treated if lice infestation is present.103, 106, 113, 116 Some clinicians suggest that it is prudent to treat family members who share a bed with the infested individual, even if no live lice are found on this family member.103, 116
In the treatment of pediculosis capitis (head lice infestation), a fine-toothed comb often is recommended to remove any remaining nits (eggs) or nit shells.103, 106, 112, 113, 116, 117, 118 Nit removal is not necessary since only live lice can be transmitted; however, some clinicians strongly recommend removal of nits (especially those within 1 cm of the scalp) since no pediculicide is 100% ovicidal and potentially viable nits may remain on the hair after pediculicide treatment.103, 116, 117, 118 Nits also may be removed for aesthetic reasons, to decrease diagnostic confusion and unnecessary retreatment, and to decrease the risk of self-reinfestation.103, 116 Nits are attached to hair shafts by a cylindrical sheath that apparently is composed principally of amino acid derivatives and fatty acids, with an overall composition similar to hair;118 combing is necessary to slide the nit attachment structure off the hair.119 Many solutions (e.g., vinegar mixtures, formic acid solutions) traditionally have been recommended to aid in nit removal,103, 113, 114, 116, 117, 118 but no clinical benefit has been demonstrated114, 116, 117 and a recent in vitro study showed that none of these commonly used solutions was more than mildly useful in detaching the nits from hair shafts.118 In addition, since the sheath composition is similar to that of hair, any solution that would effectively facilitate nit removal would likely damage the hair.119 Although many schools will not allow children with nits to attend, the American Academy of Pediatrics and other experts consider these no-nit policies excessive.103, 114, 116
For the topical treatment of pediculosis capitis (head lice infestation), pediculosis pubis (pubic lice infestation), or pediculosis corporis (body lice infestation), pyrethrins with piperonyl butoxide shampoo is applied in an amount sufficient to thoroughly wet the affected hair or other areas.120, 121, 122, 123 When treating head lice, the shampoo should first be applied behind the ears and to the back of neck.120, 121 After 10 minutes, warm water should be added to form a good lather, and the hair and affected areas washed and thoroughly rinsed with water until all lather is gone.120, 121, 122, 123 The hair should then be dried with a clean towel and combed with a fine tooth comb to remove any remaining nit shells.120, 121, 122, 123 (See Measure to Avoid Reinfestation and Transmission under Dosage and Administration: Administration.)
Although the first treatment with pyrethrins and piperonyl butoxide may be successful, treatment should be repeated after 7-10 days to kill any newly hatched lice since the drug is not completely ovicidal and has no residual activity.103, 107, 113, 116, 117, 121, 122, 123 Pyrethrins and piperonyl butoxide should not be used more than twice in 24 hours.123
When used in appropriate dosages, topically applied combinations of pyrethrins with piperonyl butoxide appear to have a low order of toxicity. (See Acute Toxicity.) Local irritation including erythema, pruritus, urticaria, edema, eczema, and slight corneal erosion and stromal edema may occur and, therefore, contact with the face, eyes, mucous membranes, and urethral meatus should be avoided. If accidental contact with the eyes occurs, the eyes should be flushed thoroughly with water. Pyrethrins with piperonyl butoxide should not be applied to acutely inflamed skin or raw, weeping surfaces.
Although pyrethrins are reported to be contact allergens, occasional incidents of sensitization characterized by dermatitis were probably due to impurities from the pyrethrum flowers. Commercially available preparations of pyrethrins are refined, however, and usually only very mild skin sensitization occurs.
Precautions and Contraindications
Individuals sensitive to ragweed have shown cross-sensitivity to unrefined but not to refined pyrethrins. Pyrethrins with piperonyl butoxide should be used with caution in individuals allergic to ragweed.120, 121, 122, 123
If primary irritation or hypersensitivity occurs in patients using pyrethrins with piperonyl butoxide, treatment should be discontinued, the drug washed off, and a physician consulted.123
Pyrethrins with piperonyl butoxide should not be used in children younger than 2 years of age unless directed by a clinician.120, 121
The CDC considers pyrethrins with piperonyl butoxide a pediculicide of choice for the treatment of pediculosis in pregnant or lactating women.104 It is not known whether pyrethrins with piperonyl butoxide is distributed into human milk. Pregnant or lactating women should be advised to consult their clinician before self-medicating with pyrethrins with piperonyl butoxide.120, 121, 122
Death occurred in a 2-year-old child following ingestion of approximately 14 g of pyrethrum powder (1-3% pyrethrins). Ingestion of 5-50 mg of pyrethrins reportedly produces no toxic effects. In animals, large oral, inhaled, or topical doses of pyrethrins have produced CNS excitation, incoordination, tremors, seizures, and death. Piperonyl butoxide reportedly produces nausea, vomiting, diarrhea, CNS depression, and hemorrhagic enteritis when large amounts are ingested. To minimize absorption of pyrethrins and piperonyl butoxide following ingestion, gastric lavage should be performed immediately and saline cathartics administered. Treatment of overdosage mainly involves symptomatic and supportive care.
Following absorption through the chitinous exoskeleton of arthropods, pyrethrins stimulate the nervous system, apparently by competitively interfering with cationic conductances in the lipid layer of nerve cells, thereby blocking nerve impulse transmissions. Paralysis and death follow. Piperonyl butoxide has little or no insecticidal activity but potentiates that of pyrethrins by inhibiting the hydrolytic enzymes responsible for pyrethrins' metabolism in arthropods. When piperonyl butoxide is combined with pyrethrins, the insecticidal activity of the latter drug is increased 2-12 times.
In one in vitro study using live lice and viable nits (eggs) obtained from healthy lice-infested children in Panama, exposure to a commercially available preparation of pyrethrins with piperonyl butoxide (A-200®) killed 43% of the lice within 5 minutes, 86% within 10 minutes, and 99% within 1 hour; 83% of the nits were killed within 10 minutes.112 However, when a different commercially available preparation was used (RID®), only 16% of the lice were killed within 5 minutes; although 75% appeared dead after 30 minutes, this percentage decreased to 50% by 1 hour of exposure and 41% by 2 hours.112 In addition, only 69% of nits were killed within 10 minutes.112 The reason for this difference in pediculicidal activity of these formulations is unclear.112
Pyrethrins are active against Pediculus humanus var. capitis (head louse), P. humanus var. corporis (body louse), and Phthirus pubis (crab louse), and may have some activity against their nits (eggs). Pyrethrins also are toxic to houseflies, fleas, chiggers, and mosquitoes.
Therapeutic failure and resistance to pyrethrins has been reported in Pediculus humanus .107, 116 Although resistance to pyrethrins with piperonyl butoxide has been reported in other countries,103, 113 the prevalence of resistance in the US is unclear.103, 116 Drug resistance assays for P. humanus have not been standardized and are difficult to interpret.108 In addition, treatment failures do not necessarily mean resistance is present since failures can also be related to misdiagnosis, noncompliance with the treatment regimen, and reinfestation.108, 116
Some lice resistant to chlorophenothane (DDT) have been reported to be cross-resistant to pyrethrins.
Pyrethrins are absorbed through intact skin when applied topically. Piperonyl butoxide reportedly is poorly absorbed through intact skin when applied topically. When administered orally to animals, only small amounts of piperonyl butoxide are absorbed.
When animals were exposed to aerosols of pyrethrins with piperonyl butoxide being released into the air, little or none of the combination was systemically absorbed.
Information on the systemic distribution and elimination of pyrethrins and piperonyl butoxide in humans following topical application is not available. Pyrethrins are reportedly inactivated in the GI tract following ingestion. In animals, pyrethrins are rapidly metabolized to water soluble, inactive compounds. When piperonyl butoxide is administered orally to animals, most of the dose is excreted unchanged in feces.
Pyrethrins with piperonyl butoxide is a fixed-combination preparation containing 0.17-0.33% pyrethrins (pyrethrum extract) and 2-4% piperonyl butoxide with petroleum distillate.
Pyrethrins is a collective term for a complex of substances that includes the alcohols and esters of pyrethrolone and cinerolone, the alcohol of chrysanthemic acid, and the ester of pyrethric acid. Pyrethrins are the purified derivatives of pyrethrum flowers ( Chrysanthemum cinerariaefolium ) and collectively occur as a viscous, brown, liquid oleoresin that is soluble in alcohol and practically insoluble in water.
Piperonyl butoxide is a synthetic piperic acid derivative. The drug occurs as a pale, yellow, practically odorless, oily liquid having a faintly bitter taste and is soluble in alcohol and practically insoluble in water. Commercial preparations of the drug contain not more than 20% of related by-products from piperonyl butoxide synthesis.
Pyrethrins are oxidized and inactivated by light and air. Pyrethrins with piperonyl butoxide topical preparations usually should be stored in well-closed containers at a temperature less than 40°C, preferably between 15-30°C.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Topical | Shampoo | Pyrethrins 0.33% with Piperonyl Butoxide 4% | A200® Lice Killing Shampoo (with benzyl alcohol and isopropyl alcohol) | Hogil |
A200® Lice Treatment Kit (with benzyl alcohol and isopropyl alcohol; with comb and lice control spray) | Del | |||
Licide® (with benzyl alcohol 2.4% and petroleum distillate 1.2%) | Reese | |||
Pronto® Plus Lice Killing Mousse Shampoo Plus Vitamin E (with benzyl alcohol and isopropyl alcohol) | Del | |||
Pronto® Plus Lice Killing Shampoo (with benzyl alcohol and isopropyl alcohol) | Del | |||
RID® Maximum Strength Lice Killing Shampoo (with isopropyl alcohol) | Bayer |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions October 1, 2007. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
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104. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2006. MMWR Recomm Rep . 2006; 55(RR-11):1-94. [Fulltext MMWR]
105. Wilson DC, Leyva WH, King LE. Arthropod bites and stings. In: Fitzpatrick TB, Eisen AZ, Wolff K et al, eds. Dermatology in general medicine. 4th ed. New York: McGraw Hill Inc. 1993:2810-26.
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119. Reviewers' comments (personal observations) on Permethrin 84:04.12.
120. Del Pharmaceuticals. Pronto® maximum strength lice killing shampoo (pyrethrins with piperonyl butoxide) product information. Farmington, NY; 2002.
121. Bayer Healthcare. Rid® (pyrethrins with piperonyl butoxide) product information. Morristown, NJ.
122. Hogli Pharmaceutical Corp. A200 lice killing shampoo (pyrethrins with piperonyl butoxide) product information.
123. Del Pharmaceuticals. Pronto® plus lice killing mousse shampoo kit (pyrethrins with piperonyl butoxide) product information. Farmington, NY; 2007.
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