Permethrin

Permethrin is used for the topical treatment of pediculosis (lice infestation) ^{[1][4][6][7][8][17][22][27][28][29][36][44][51][61][62][64][65]} and scabies (mite infestation).^{[2][4][6][8][10][11][13][14][17][18][21][22][25][26][32][37][38][43][44][45][60][65][90]} Permethrin has been used topically for prophylaxis of pediculosis capitis during head lice epidemics.^[89] In addition, the drug has been used topically for the treatment of other arthropod infestations^† (e.g., demodicidosis^† ).^{[48][49][50][52][53][69][87]}

Pediculosis

Pediculosis Capitis

Permethrin is used for the topical treatment of pediculosis capitis (head lice infestation),^{[1][4][6][7][8][17][22][35][36][51][61][62][63][64][65][79][80][82]} and many clinicians consider it a pediculicide of choice.^{[6][7][17][61][63][64][79][80][82][96]} Permethrin has been used for prophylaxis of pediculosis capitis during head lice epidemics.^[89]

When selecting a pediculicide for the treatment of pediculosis capitis, 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.^[79] Although no pediculicide possesses true ovicidal activity, drugs with residual activity may kill emerging nymphs.^[6] 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.^{[6][17][61][62][79][82]}

Permethrin 1% generally is considered the treatment of choice and malathion 0.5% is recommended when permethrin resistance is suspected.^{[10][17][63][79][80][82]} Permethrin 1% has the advantages of a low potential for toxicity and good ovicidal activity; however, widespread resistance to permethrin has been reported in other countries and the prevalence of resistance to the drug in the US is unclear.^[6][63][80] Malathion 0.5% has the advantages of fast pediculicidal and ovicidal activity, a residual effect, and possible efficacy in lice infestations resistant to other pediculicides; however, safety and efficacy of the drug have not been established in children younger than 6 years of age, the topical preparation commercially available in the US has an alcoholic vehicle that is flammable and may be irritating, and the preparation has a characteristic odor that may impact patient preference.^{[6][9][63][79][80]} Some clinicians consider topical pyrethrins with piperonyl butoxide an alternative rather than a preferred treatment for pediculosis capitis^[17][61][63] 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)^{[6][17][61][63][79][82][84]} and treatment failures have been reported even when dosage and administration recommendations were followed.^[63][79] In the past, lindane was widely recommended for the treatment of pediculosis capitis;^{[22][51][61][63][64][65]} however, the drug is no longer recommend for initial therapy because of reports of resistance and neurotoxicity (e.g., seizures)^{[9][22][29][61][63]} 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.^{[6][9][61][77][78][88]} (See Uses: Pediculosis in Lindane 84:04.12.)

If used correctly, one treatment with permethrin 1% usually is effective in eradicating pediculosis capitis.^{[1][4][6][65][70]} Some clinicians recommend a second treatment 7-10 days later to achieve maximum results, especially if the patient's hair is washed 7 days after initial treatment;^{[6][51][61][62][64][80]} however, the manufacturer recommends a second application only if live lice are observed 7 days or more after the first treatment.^[1] In resistant cases, some clinicians recommend use of permethrin 5% cream^† (left on overnight);^{[61][63][64][68][79]} use of permethrin 1% left on for a longer period of time (e.g., 30-60 minutes); or use of another drug (e.g., topical malathion 0.5%).^[79] (See Pediculosis Capitis under Dosage and Administration: Dosage.) Alternatively, some clinicians recommend that resistant cases of head lice be treated with topical petrolatum (30-40 g left on overnight);^[64][68] however, the efficacy of such therapy with occlusive agents has not been evaluated to date.^[6]

Pediculicides kill lice quickly after application, therefore when living lice are detected during scalp inspection performed at least 24 hours after treatment, it is likely that the pediculicide was not applied correctly or that a very heavy infestation, reinfestation, or resistant infection exists.^[6] After incorrect pediculicide application is ruled out, the AAP recommends that such patients be immediately retreated with a different pediculicide, followed 7-10 days later by a second application.^[6]

Permethrin 1% lotion has been used for prophylaxis of pediculosis capitis during head lice epidemics.^[89] Such prophylactic use of permethrin 1% lotion should only be considered for individuals exposed to head lice epidemics in which at least 20% of the population at an institution is infested or for immediate household members of infested individuals.^[89] The manufacturer states that casual use of the drug is strongly discouraged.^[89]

Clinical Experience

In controlled studies, a single application of permethrin 1% lotion (cream rinse) generally has been at least as effective or more effective than lindane 1% shampoo or pyrethrins with piperonyl butoxide for the treatment of pediculosis capitis.^{[4][7][27][28][31][35][47]} However, comparative efficacy of pediculicides is difficult to evaluate because of factors related to the study populations and concerns that adherence to treatment regimens and reinfestation may impact clinical outcome.^[79][80] Most comparative clinical studies published to date have involved patients in other countries where resistance to other pediculicides may be widespread or in developing countries among patients with no previous exposure to pediculicides.^[79][80] It is unclear whether results of these studies are applicable to the US population.^[79][80]

In studies comparing permethrin 1% cream rinse and lindane 1% shampoo applied to adults and children with pediculosis capitis, cure (absence of live adult lice or nymphs during a 5-minute examination of the hair and scalp) was attained in over 97% of those treated with permethrin and in 67-85% of those treated with lindane within 14 days.^[16][31][35] When permethrin 1% was compared with pyrethrins with piperonyl butoxide, results of clinical studies have varied;^[27][28][47] some studies have shown that the treatments are both highly effective,^[28][47] while the results of another study indicated that permethrin was more effective (96% cured) than pyrethrins with piperonyl butoxide (62% cured).^[27] This difference may be due to study design differences; in one study where nits in the hair were not combed out and pyrethrins with piperonyl butoxide was applied only once (rather than the recommended 2 applications), its efficacy at 14 days was 62%.^[27] In studies where combing of nits was performed by evaluators, the efficacy of pyrethrins with piperonyl butoxide as either a single application or repeated in 7 days was similar or equal to that of permethrin.^[28][47]

Pediculosis Pubis

Although there are few well-controlled, clinical studies of topical permethrin for 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 the treatment of pediculosis pubis.^[9][22][62] Alternatives recommended by the CDC and others are topical malathion 0.5% or oral ivermectin.^[9][17][63] Topical malathion 0.5% may be effective for pediculosis pubis resistant to other pediculicides, but the drug is commercially available in an alcohol vehicle that is flammable and irritating and patients may find the drug's odor and longer duration of application objectionable.^[9] 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)^{[22][29][61][63]} and is now considered a second-line agent that should be used for the treatment pediculosis only in patients who have not responded to or who cannot tolerate other recommended therapies.^{[6][9][61][77][78]} (See Uses: Pediculosis in Lindane 84:04.12.)

For infestation of the eyelashes with pubic lice, the CDC recommends treatment with an occlusive ophthalmic ointment (e.g., petrolatum) 2-4 times daily for 8-10 days;^{[6][9][17][36][51][62]} nits should be removed from the eyelashes manually.^[6][36] In addition to the pubic area and the eyelashes, pubic lice also may be found on other hairy areas of the body, including the eyebrows, mustache, beard, axilla, coarse hair of the back and trunk, perianal area, and, rarely, the scalp.^{[6][29][51][56][62]}

If used correctly, one treatment with permethrin 1% usually is effective in eradicating pediculosis pubis.^[68] Some clinicians suggest use of permethrin 5% for the treatment of pediculosis pubis.^[17] The CDC recommends reevaluating the patient 1 week after treatment if symptoms persist.^[9] The CDC recommends retreatment with an alternative regimen in patients who fail to respond to the initial regimen.^[9] However, some clinicians recommend routine retreatment of patients with pediculosis pubis using the same regimen 7-10 days after initial treatment.^[6][29][68]

Pediculosis pubis usually is transmitted by sexual contact.^[9] Presumptive concurrent treatment of sexual contacts to whom lice might have been spread within the last month is recommended.^[6][9][62] Patients should avoid sexual contact with their sexual partner(s) until patients and partners have been treated and reevaluated to rule out persistent disease.^[9] Presumptive concurrent treatment also has been recommended for other close contacts of the patient.^[8][36]

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.^[9]

In a controlled study comparing single applications of permethrin 1% cream rinse or lindane 1% shampoo, followed by nit combing, in otherwise healthy adults, cure (absence of viable nymphs or adult lice) was obtained in 57% of those who received permethrin or 60% of those who received lindane.^[29] It was noted that the study population was predominantly male and homosexual, and reinfestation could not be excluded;^[29] other clinicians have confirmed the difficulty of successfully treating sexually active male homosexuals and their sexual contacts.^[8]

Pediculosis Corporis

Permethrin 1% is used for the topical treatment of pediculosis corporis^† (body lice infestation).^[95][96] In some cases, body louse infestations may be treated by improving hygiene and by decontaminating clothes and bedding by washing at temperatures that kill lice.^[6][96] If the infestation is severe, a pediculicide should also be used (e.g., topical permethrin, topical pyrethrins with piperonyl butoxide, topical malathion, oral ivermectin).^[95][96]

Scabies

Permethrin is used for the topical treatment of scabies.^{[2][4][6][8][9][10][11][13][14][18][21][22][25][26][32][37][38][43][44][45][60][65][90][92][93]} The American Academy of Pediatrics (AAP), CDC, and other clinicians consider topical permethrin 5% the scabicide of choice because of its safety and efficacy profile relative to other available agents;^{[4][6][9][10][12][17][21][25][26][36][37][93][94][96]} the CDC also recommends oral ivermectin as a scabicide of choice in adults.^[9] Recommendations for alternative therapy differ among various clinicians.^{[6][9][17][25][26]} The AAP and some clinicians recommend topical crotamiton 10% or oral ivermectin as preferred alternatives.^{[6][17][25][75][76]} Other clinicians recommend use of topical sulfur in infants younger than 2 months of age and in pregnant or lactating women,^{[11][24][25][26][37][38][68]} although it is less convenient since it must be applied on 2-3 consecutive days and some patients object to the drug because it is messy, malodorous, and tends to stain.^{[11][12][25][26][37][38][68]} Topical lindane 1% (not recommended in pregnant or lactating women, children younger than 2 years of age, or individuals with extensive dermatitis) is considered a second-line agent and should be used for the treatment of scabies only in patients who have not responded to or who cannot tolerate other recommended therapies.^{[6][9][61][77][78][88]} (See Uses: Scabies in Lindane 84:04.12.)

If used correctly, one treatment with permethrin 5% usually is effective in eradicating scabies.^{[2][10][13][14][21][24][25][26][90]} Experts disagree on the need for retreatment;^[9] some experts recommend retreatment if symptoms persist after 1-2 weeks, while others recommend retreatment only if live mites are observed.^[9] Still others recommend routine retreatment (i.e., 2 courses), particularly in severe cases with diffuse cutaneous findings.^{[11][24][37][51][68]} The CDC recommends retreating patients who do not respond to permethrin with an alternative regimen.^[9] Pruritus associated with scabies usually is not considered an indication for retreatment;^{[2][9][13][21]} such pruritus results from a hypersensitivity reaction of the host to the mite^{[6][9][11][24][36][37]} and may persist for several weeks despite successful treatment.^{[6][10][18][21][24][26][37]} Oral antihistamines and topical corticosteroids may be used to help relieve symptoms.^{[6][11][24][26][37][41][93]} Many clinicians recommend follow-up examinations of patients 2 and 4 weeks after treatment.^{[14][18][24][26]} If the patient is not clear of new lesions at either examination, it should be considered a treatment failure;^{[14][18][24][26]} such treatment failures may be secondary to failure to treat all exposed individuals or failure to apply the drug properly.^{[14][24][25][37]} If the patient is clear of new lesions when examined at 2 weeks, but has new lesions at 4 weeks, it should be considered a reinfestation rather than a treatment failure.^[24][26]

In less than 10% of patients with scabies, nodular scabies may develop, which is characterized by intensely pruritic nodules that persist for months after effective scabies therapy;^{[6][26][30][37]} mites seldom are identified in these nodules.^[30] Scabicide therapy usually is ineffective in nodular scabies since mites are not typically present.^[26][30][37] Topical or intralesional corticosteroids may be useful to treat the pruritus associated with nodular scabies.^{[26][30][37][93]}

Mild infections secondary to scabies usually remit, but concurrent systemic anti-infective therapy may be necessary for severe secondary infections.^{[6][14][24][26][37][41]}

Sexual contacts and other individuals (household, family) who have had close personal contact with a patients with scabies within the previous month should be examined and treated.^{[6][8][9][11][14][18][21][24][25][26][37][41]} Manifestations of scabies (e.g., pruritus, erythema, skin lesions) are the result of hypersensitivity to the mite and its eggs and waste products, and manifestations usually are not evident until 1-2 months after infestation in individuals without previous exposure.^{[6][9][11][24][36][37][42][51][68]} Therefore, the absence of symptoms in individuals in close contact with a patient with scabies should not be interpreted as an absence of infection; failure to treat such individuals may result in reinfestation of the patient.^{[6][11][24][25][26][37][51][54][68]}

The CDC recommends that scabies epidemics in institutional settings (e.g., nursing homes, hospitals, residential facilities, communities) be managed in consultation with an expert.^[9] Control of such epidemics requires treatment of the entire population at risk.^{[9][42][54][92]} Permethrin has been recommended as a scabicide of choice in institutional outbreaks.^[42][92] Oral ivermectin may be useful in this setting, especially if treatment with topical scabicides fails.^[9][92] In one study, topical permethrin 5% cream produced an overall cure rate of 98% in the residents, staff, and frequent visitors of 3 nursing homes with scabies epidemics that had not responded to other topical scabicides (e.g., lindane, crotamiton, benzyl benzoate, precipitated sulfur), although some patients required 3 or more treatments.^[45]

Norwegian Scabies

Norwegian scabies (crusted scabies) is a particularly severe and highly infectious form of scabies that presents as crusted, hyperkeratotic, scaling plaques, which may be generalized or localized to the hands and feet.^{[6][21][24][37][41][54][55]} In this condition, the patient is infested with large numbers (thousands to millions) of Sarcoptes mites.^{[19][21][24][41][54][55]} Norwegian scabies is highly contagious and, because the infestation may have an atypical presentation, months to years may pass before the condition is diagnosed, and transmission of scabies to personal contacts may occur before symptoms of scabies develop in the index patient.^{[6][36][37][41][42][51][54][55][68]}

Patients with Norwegian scabies often require multiple treatments with scabicides,^[26][41][55] and it is important that the total body, including areas under the nails, be treated when topical therapy is used.^[19][26][55] Permethrin has been used to treat Norwegian scabies with good results.^[42][55][68] However, sequential use of several different scabicides may be necessary.^[26][41][55] Some clinicians pretreat patients with a keratolytic agent before using a topical scabicide.^[26][41] Other clinicians recommend therapy with a topical scabicide in conjunction with oral ivermectin or multiple doses of oral ivermectin.^[9] Some clinicians consider oral ivermectin the therapy of choice for patients whose infection is refractory to topical therapy;^[6] however, the comparative efficacy of ivermectin and standard scabies therapies remains to be established.^[9] Norwegian scabies results in extensive skin excoriation and requires heavy topical scabicide application, therefore lindane 1% is not recommended because of the increased risk of toxicity.^[9]

HIV-infected Individuals

The CDC states that patients with HIV infection who have uncomplicated scabies should receive the same treatment as those without HIV infection.^[9] Other clinicians recommend that 2 courses (1 week apart) of permethrin 5% routinely be used for treating scabies in patients with HIV infections.^[19] Alternatively, weekly treatment until symptoms and lesions clear has been recommended.^[19] Treatment with lindane 1% or sulfur 5% ointment also has been recommended for the treatment of scabies in patients with HIV infection.^[19][26]

HIV-infected individuals and other immunocompromised patients are at increased risk of developing Norwegian scabies,^{[9][19][26][41]} and the CDC recommends that such patients be managed in consultation with an expert.^[9] Some clinicians recommend oral ivermectin for immunocompromised patients whose scabies is refractory to topical therapy.^[6][19]

Clinical Experience

Results of several controlled studies in otherwise healthy adults and children with scabies indicate that topical permethrin 5% cream is as effective as, or in some cases, more effective than topical lindane 1% lotion.^{[10][18][32][43]} However, in some cases the lower efficacy of lindane may be related to resistance secondary to widespread use of the drug in the treatment of scabies and pediculosis.^[18][32][69] Cure (healing of old lesions and an absence of new lesions) was attained 3-4 weeks after treatment in 91-100% of patients who received permethrin 5% and in 65-92% of those who received lindane 1%.^{[10][18][32][43]} In a controlled study in a community in which scabies had been endemic for over 10 years, single application of permethrin 5% cream or lindane 1% lotion to otherwise healthy children and adults cured 91% of patients who received permethrin and 65% of those who received lindane.^[18] In this study, 9 patients judged as treatment failures (8 of whom had received lindane) were retreated with permethrin and were cured in 2-3 weeks.^[18] However, the low efficacy of lindane in this study may have been related to widespread use of the drug in the area resulting in increased resistance, since cure of scabies after lindane treatment was achieved in 90% of patients in nearby communities not previously exposed to lindane.^[18][69]

In a comparative study evaluating topical permethrin 5% cream and topical crotamiton 10% cream administered once daily on 2 successive nights in children and adults, 98% of patients who received permethrin and 88% of those who received crotamiton were cured (no new lesions and healing of all original lesions) 4 weeks after treatment.^[43] In a double-blind, randomized study comparing single applications of topical permethrin 5% cream and crotamiton 10% cream in children 2 months to 5 years of age, 89% of patients who received permethrin and 60% of those who received crotamiton were cured (no new lesions and healing of all original lesions).^[14] In an open study comparing a single topical application of permethrin 5% (2.5% for children younger than 5 years of age) cream with topical benzyl benzoate 20% (10% for children younger than 5 years of age) applied on 3 successive nights, all patients in both groups were cured.^[32]

Demodicidosis

Topical permethrin has been used to treat infestations with Demodex folliculorum^{† [48][49][50][52][53][87]} in children and adults and D. brevis^† in children,^[50] including patients with immunosuppression (e.g., acquired immunodeficiency syndrome, acute lymphoblastic leukemia).^{[48][50][53][87]} The role of Demodex as a pathogen in human disease is controversial,^{[48][49][50][68]} and some clinicians consider Demodex a normal inhabitant of the skin that generally does not cause clinical disease in humans since the mite has been found in normal biopsies without any inflammation or evidence of disease.^[48][49][68] Other clinicians suggest that alterations in the immune system may allow the mite to proliferate to the extent that clinically evident disease occurs.^[48][50] Topical treatment with permethrin 1% or permethrin 5% have been used successfully for the treatment of demodicidosis,^{† [48][49][50][87]} although failures also have been reported.^[52] Some clinicians note that it is not certain how much permethrin penetrates into the follicle and what effect, if any, the drug has on D. follicularis or D. brevis.^[68] Additional study and experience are needed to evaluate fully the efficacy of permethrin and the optimum regimen, if any, for the treatment of demodicidosis.^[52]

Administration

Permethrin 5% cream or 1% lotion (cream rinse) is applied topically.^{[1][2][13][89][90]}

The drug is for external use only and should not be administered orally.^{[1][2][13][89]}

Contact with the eyes should be avoided during application of permethrin 5% cream or permethrin 1% lotion (cream rinse) since ocular irritation may occur.^{[1][2][13][89][90]} Patients using permethrin also should be advised to avoid contact with mucous membranes such as inside the nose, mouth, or vagina.^[1][69][89]

The cream rinse should be shaken before using.^[1]

Measures to Avoid Reinfestation and Transmission

To avoid reinfestation or transmission of pediculosis or scabies, most experts recommend that clothing and bed linen that may have been contaminated by the infested individual during the 2 days prior to treatment should 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.^{[1][6][9][82][83][89]} It is not necessary to launder clean clothes or heavy winter jackets and sweaters belonging to patients with scabies.^[26] For lice infestation, although it may not be necessary, items that cannot be laundered or dry-cleaned be removed from contact and sealed in a plastic bag for 10-14 days.^{[1][6][82][83][89]} Alternatively, such items may be sprayed with a pesticide designed for this purpose.^[89] Combs and brushes used by the infected patient may be disinfected by soaking in hot water (temperature exceeding 54°C) for 5-10 minutes;^{[1][6][64][83][89]} alternatively, they can be soaked in alcohol or a pediculicide for 1 hour.^[51][62][64] It also is recommended that furniture and floors of rooms inhabited by patients infested with lice be thoroughly vacuumed.^{[6][61][82][83][89]} Many experts recommend particular attention to thorough cleaning of areas inhabited by patients with Norwegian scabies because of the large numbers of mites infesting these patients.^[6][54][68] Thorough cleaning of patients rooms also is recommended in institutional outbreaks of scabies,^{[42][45][54][92]} where warmer temperatures and higher humidity levels maintained for patient comfort may allow scabies mites to survive for several days without a host.^[68] Fumigation of living areas is not necessary and is not recommended.^{[6][9][82][83][92]}

Other family members and close contacts of the individual with pediculosis capitis (head lice infestation) should be evaluated by a clinician and treated if lice infestation is present.^{[6][80][82][83]} 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.^[6][82]

In the treatment of pediculosis capitis, a fine-toothed comb often is recommended to remove any remaining nits (eggs) or nit shells.^{[1][28][47][51][62][64][66][82][83]} Nit removal is not necessary to prevent transmission 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.^{[6][47][66][68][82]} Nits also may be removed for aesthetic reasons, to decrease diagnostic confusion and unnecessary retreatment, and to decrease the risk of self-reinfestation.^[6][36][82] 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;^[66][71] combing is necessary to slide the nit attachment structure off the hair.^[66] Many solutions (e.g., vinegar mixtures, formic acid solutions) traditionally have been recommended to aid in nit removal,^{[6][61][62][64][66][79][80][82]} but no clinical benefit has been demonstrated^[61][80][82] 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.^[66] 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.^[68] Although many schools will not allow children with nits to attend, the American Academy of Pediatrics (AAP) and other experts consider these no-nit policies excessive.^[6][80][82]

Dosage

Pediculosis Capitis

For the topical treatment of pediculosis capitis (head lice infestation), about 30-60 mL of permethrin 1% lotion (cream rinse) is applied to washed and towel-dried hair and allowed to remain for 10 minutes, then rinsed with water.^[1][89] Shampoos that contain a conditioner or a separate post-shampoo conditioner should not be used since they may decrease the pediculocidal effect of permethrin.^[1] The amount of permethrin 1% lotion (cream rinse) used should be sufficient to thoroughly saturate the hair and the scalp, including the areas behind the ears and the nape of the neck.^[1][89]

Although one treatment with permethrin usually is successful,^[1][65][89] treatment may be repeated with permethrin or an alternative pediculicide after 7-10 days if lice or nits are detected at the hair-skin junction.^[1][9] Some clinicians recommend a second treatment routinely 1 week later to achieve maximum results (especially if the patient's hair was washed within 7 days after initial treatment).^{[6][51][61][62][64][80][82]} When 1% permethrin lotion is used during pediculosis epidemics, the manufacturer recommends a second treatment 2 weeks after the first, since the life cycle of the head louse is approximately 4 weeks.^[89]

Application of topical pediculicides, including permethrin, may result in skin inflammation and resultant pruritus or mild burning of the scalp that may persist for several days after lice are killed; such an inflammatory response is not an indication for retreatment and a topical corticosteroid and/or an oral antihistamine may provide relief in patients who develop these manifestations.^[6] In resistant cases of pediculosis capitis, some clinicians recommend application of permethrin 5% cream^† to the hair, covering it with a shower cap, and leaving it on overnight to overcome the ectoparasite's resistance to lower concentrations of the drug^{[61][63][64][68]} or leaving the permethrin 1% preparation on for a longer period of time (e.g., 30-60 minutes)^† .^[79]

Pediculosis Pubis

For the topical treatment of pediculosis pubis^† (pubic lice infestation), a sufficient amount of permethrin 1% cream rinse should be applied to thoroughly saturate the pubic and other affected areas.^[9] Alternatively, some clinicians recommend use of permethrin 5% cream.^[17] Permethrin should be allowed to remain for 10 minutes and should then be rinsed off with water.^[9]

Routine retreatment of patients with pediculosis pubis 7-10 days after initial treatment is recommended by some clinicians.^[6] For infestation of the eyelashes with pubic lice, the CDC and some clinicians recommend treatment with an occlusive ophthalmic ointment (e.g., petrolatum) 2-4 times daily for 8-10 days;^{[6][9][17][36][51][62]} topical pediculicides should not be used for such infestations.^[6][9] Nits should be manually removed from the eyelashes.^[6]

Scabies

For the treatment of scabies, a thin layer of permethrin 5% cream should be applied uniformly and massaged gently and thoroughly into all skin surfaces (entire trunk and extremities) from the neck to the toes (including the soles of the feet).^{[2][8][9][11][13][90]} Scabies rarely infest the scalp of adults, but the hairline, neck, temples, and forehead may be infested in infants and geriatric patients,^[2][13][90] and therefore, permethrin should be applied to the entire head and neck, including the scalp, temples, and forehead of such patients.^{[2][6][12][13][37][90]} The patient or caregiver should be careful to apply the cream in all skin folds (e.g., between the toes and fingers, the cleft of the buttocks, in the folds of the waist or wrist).^{[2][8][18][26][37]} The cream also should be brushed under the fingernails and toenails.^[8][26] If the cream is removed before the end of the treatment period (e.g., handwashing, diapering of infants), additional cream should be applied to the area.^{[8][18][26][51]} The cream should be washed off (by showering or bathing) after 8-14 hours.^{[2][6][8][9][11][12][13][24][26][37][42]} Usually, 30 g of cream is sufficient to treat an average adult.^{[2][12][13][26][42][90]}

One application of permethrin 5% cream usually is successful in eradicating scabies.^{[2][11][13][21][32][37][90]} Even though persistent pruritus may occur after treatment, this usually is not a sign of treatment failure and is not a cause for retreatment.^{[2][13][21][90]} Oral antihistamines and/or topical corticosteroids may be used to help relieve pruritus.^{[6][11][24][26][37][41]} Experts disagree on the need for retreatment;^[9] some experts recommend retreatment in 1 week,^{[9][37][51][68]} while others recommend retreatment only if live mites are observed.^[9][11] Many clinicians recommend follow-up examinations of patients 2 and 4 weeks after treatment.^{[14][18][24][26]} If the patient is not clear of new lesions at either examination, it should be considered a treatment failure;^{[14][18][24][26]} such treatment failures may be secondary to failure to treat all exposed individuals or failure to apply the drug properly.^{[14][24][25][37]} If the patient is clear of new lesions when examined at 2 weeks, but has new lesions at 4 weeks, it should be considered a reinfestation rather than a treatment failure.^[24][26] Patients who experience treatment failure should be retreated with an alternative scabicide.^[9]

If permethrin is used during institutional outbreaks of scabies, the entire population at risk should be treated.^{[9][42][54][92]} Multiple treatments (e.g., once-weekly for 2-3 weeks) have been recommended.^[92]

Patients with Norwegian scabies often require multiple treatments with scabicides,^[26][41][55] and it is important that the total body, including areas under the nails, be treated when topical therapy is used.^[19][26][55] Patients may be pretreated with a keratolytic agent before topical scabicide treatment is initiated.^[26][41] Sequential use of several different scabicides^{[26][41][51][55]} or concomitant therapy with a topical scabicide and oral ivermectin may be necessary.^[9] (See Norwegian Scabies under Uses: Scabies.)

Demodicidosis

Although permethrin 1% and permethrin 5% have been used topically to treat infestations with Demodex folliculorum^{† [48][49][50][52][53][87]} in children and adults and D. brevis^† in children,^[50] an effective dosage regimen has not been established for these infestations.^[68][69]

Adverse Effects

When used topically in appropriate concentrations and dosages, topically applied permethrin appears to have a low order of toxicity in mammals.^{[4][5][6][8][9][10][11][12][14][16][18][21][22][23][24][25][26][27][28][29][31][32][35][39][41][43][44][46][47][51][54][61][63][69][90]} Permethrin has less potential for toxicity than lindane;^{[9][12][44][51]} studies in mice and rats indicate that permethrin is about 36 times less toxic than lindane on a mg/kg basis.^{[8][18][24][26][32][43]} In addition, based on in vitro absorption studies on guinea pig and human cadaver skin and an in vivo study in guinea pigs under conditions simulating overuse of permethrin 5% cream and lindane 1% lotion, some clinicians have predicted that the risk for adverse systemic effects secondary to topical permethrin may be 40-400 times lower than for topical lindane.^[44]

Mild and transient burning and stinging are the most common adverse effects reported following topical application of permethrin.^{[2][6][10][12][13][26][27][29][32][90]} These effects have been reported in 10% of patients using permethrin 5% cream for the treatment of scabies and generally were associated with the severity of infestation with the scabies mite.^[2][13] Pruritus also is a frequently reported adverse effect with topical permethrin.^{[2][8][10][12][13][90]} In 7% of patients, pruritus was reported at various times after topical application of permethrin 5% cream for scabies treatment.^{[2][10][13][90]} However, pruritus commonly is associated with lice infestation^{[6][8][9][20][27][29][31][35][36][37][47][61][62]} and scabies^{[2][6][8][9][10][11][13][14][24][37][45]} as a result of a hypersensitivity reaction of the host to the ectoparasite.^{[6][9][13][24][29][37][61]} Such pruritus may persist despite successful treatment,^{[6][8][10][11][18][24][26][37][45]} and it is difficult to distinguish between pruritus caused by permethrin and pruritus associated with the infestation.^{[20][31][35][39][45]} Such an inflammatory response is not an indication for retreatment; oral antihistamines and/or topical corticosteroids may be used to help relieve pruritus.^{[6][24][26][37][41]} Erythema, numbness, tingling, and rash have been reported in 1-2% of patients.^{[2][13][29][31][39][90]}

In a postmarketing surveillance study, adverse effects occurred in 0.22% of permethrin 1% cream rinse treatments compared with a frequency of 0.34 or 0.15% of treatments with lindane or various other nonprescription pediculicides, respectively.^[46] The most important adverse effect was difficulty in breathing, which was reported after permethrin use in 2 patients, both of whom had histories of other allergies.^[46] No serious or unexpected adverse effects related to permethrin use were detected.^[46]

Permethrin has not been associated with phototoxic or photosensitization reactions.^[20][69]

Precautions and Contraindications

Permethrin is contraindicated in patients with a history of hypersensitivity to the drug or any components in the respective formulation, or to any synthetic pyrethroid or pyrethrins.^{[2][13][20][90]}

Because permethrin is a synthetic pyrethrin derivative (pyrethroid)^{[3][4][5][8][23][25][33][44][62][64][65][67][69]} and because pyrethrins are the active insecticidal components of pyrethrum extract, which is derived from the flowers of the plant Chrysanthemum cinerariaefolium,^{[4][8][58][62][63][69]} it was previously thought that there may be a risk of cross-sensitivity between permethrin and ragweed or chrysanthemums.^[51][55][69] However, recent evidence indicates that such cross-sensitivity is unlikely.^[51][55][69] Cross-sensitivity between pyrethrum extract, chrysanthemums, and ragweed has been reported.^[20][61][69] However, immunogenicity of the pyrethrum extract apparently is related to sesquiterpene lactones with an α-methylene group exocyclic to the γ-lactone.^[69] Pyrethrins and synthetic pyrethroids (e.g., permethrin) lacking this structure also appear to lack immunogenicity.^[69] Results of patch tests in patients previously exposed to pyrethroids indicate that no cross-sensitization occurs between natural pyrethrins and permethrin 1%.^[69] In addition, cross-sensitization between permethrin and ragweed or chrysanthemums has not been reported in postmarketing surveillance.^[20][69]

Permethrin 5% cream contains formaldehyde 0.1% as a preservative,^{[2][13][37][39][90]} and this ingredient could potentially cause contact dermatitis.^[26][37][39] However, despite widespread use of permethrin 1 and 5% preparations, very few reports of sensitivity reactions have been confirmed.^[39][69][70]

The manufacturers of permethrin 1% lotion (creme rinse) recommend that patients with a history of asthma be advised that using permethrin may cause breathing difficulty or an asthmatic episode in susceptible patients.^[1][89]

Patients receiving permethrin 5% cream for the treatment of scabies should be advised that pruritus, mild burning, and/or stinging may occur after application of the cream.^[2][13][90] Approximately 75% of patients who continued to experience pruritus 2 weeks after treatment in clinical studies experienced resolution of symptoms by 4 weeks.^[2][13][90] Patients using permethrin should be advised that pruritus, erythema, or swelling of the scalp may occur.^[1] Patients should be instructed to discontinue using permethrin and consult their clinician if irritation persists or infection develops.^{[1][2][13][89][90]} (See Cautions: Adverse Effects.)

Contact with the eyes should be avoided during application of permethrin 5% cream or permethrin 1% lotion (cream rinse) since ocular irritation may occur.^{[1][2][13][89][90]} If accidental contact with the eyes occurs, the affected eye(s) should be flushed thoroughly with water.^{[1][2][13][89][90]} Patients should be instructed to consult their clinician if lice infestation of the eyebrows or eyelashes occurs.^[89] Patients using permethrin 1% lotion (cream rinse) also should be advised to avoid contact with mucous membranes, such as inside the nose, mouth, or vagina.^[1][69][89]

Pediatric Precautions

Safety and efficacy of permethrin 1% lotion (cream rinse) and 5% cream in children younger than 2 months of age have not been established.^{[1][2][13][89][90][91]} However, the drug has been used effectively without unusual adverse effect in this age group.^[38][68]

Geriatric Precautions

Clinical studies of topical permethrin did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients..^[2][13][90] Other clinical experience has not revealed age-related differences in response.^[2][13][90]

When topical permethrin is used as directed, an increased risk of toxicity in patients with impaired renal function is unlikely since the drug is metabolized in the liver and eliminated in urine as inactive metabolites.^[2][13][90] (See Pharmacokinetics.)

Mutagenicity and Carcinogenicity

Permethrin did not exhibit carcinogenic effects in studies with rats.^{[2][13][33][90]} However, in carcinogenicity studies in mice, there were species-specific increases in pulmonary adenomas, a common benign tumor in mice with a high spontaneous incidence.^{[2][13][33][90]} In one study in mice, there was an increased incidence of pulmonary alveolar cell carcinoma and benign liver adenomas, which occurred only in female mice when they were fed permethrin at a concentration of 5000 ppm.^[2][13][90] Permethrin did not exhibit mutagenic potential in several in vitro and in vivo genetic toxicity studies.^{[2][13][40][90]}

Pregnancy, Fertility, and Lactation

Pregnancy

Reproduction studies in mice, rats, and rabbits using oral permethrin dosages of 200-400 mg/kg daily did not impair fertility or cause harm to the fetus.^{[2][13][65][90]} There are no adequate and controlled studies to date using topical permethrin in pregnant women, and the drug should be used during pregnancy only when clearly needed.^[2][13][90] The CDC and some clinicians consider permethrin 5% a drug of choice for the treatment pediculosis or scabies in pregnant or lactating women.^[6][9][93] Pregnant women should be advised to consult their clinician before self-medicating with topical permethrin.^[1][89]

Fertility

Reproduction studies in 3 generations of rats using permethrin dosages of 180 mg/kg daily orally have not revealed evidence of impaired fertility.^[2][13]

Lactation

It is not known whether permethrin is distributed into human milk.^{[2][13][69][70][90]} Because many drugs are distributed in milk and because of the tumorigenic potential of permethrin in animal studies, a decision should be made whether to discontinue nursing temporarily or to withhold the drug while the mother is nursing, taking into account the importance of the drug to the woman.^[2][13][90] Nursing mothers should be advised to consult their clinician before self-medicating with topical permethrin.^[1][89]

Limited information is available on the acute toxicity of permethrin.^[68][70] The toxicity of topically applied permethrin generally is very low, probably because the drug is hydrolyzed rapidly by esterases present in the skin, blood, and other tissues.^[4][8][69] (See Pharmacokinetics.) Since the drug is metabolized and excreted as inactive metabolites more rapidly than it can be absorbed through the skin, it is not retained or stored in tissues.^[8][69] In acute dermal toxicity studies in rats, the LD₅₀ was 5-15 g/kg (e.g., relatively nontoxic), and the oral LD₅₀ of permethrin 1% cream rinse exceeded 5 g/kg.^[20][69]

Accidental ingestion of permethrin 1% cream rinse or 5% cream has not been reported to date.^[2][13][90] If ingested, gastric lavage and supportive and symptomatic treatment should be initiated and a poison control center consulted.^{[1][2][13][89][90]}

In a patient who ingested about 600 mL of a 20% commercially available permethrin insecticide emulsion (a total dosage of 143 g of permethrin) with a cis:trans ratio of about 43:57, vomiting, diarrhea, loss of consciousness, and metabolic acidosis occurred.^[60] The patient was treated with gastric lavage, activated charcoal, magnesium citrate, and fluid replacement therapy and recovered without severe complications.^[60] Apart from initially impaired consciousness, no signs of neurotoxicity (e.g., tremor, seizures, paralysis) were observed.^[60] It was noted that the ingested insecticide also contained xylene 70%, which may have been responsible for some of the symptoms; vomiting and diarrhea decreased the amount of permethrin absorbed and may have lessened the toxic effects of the insecticide.^[60]

Like natural pyrethrins, permethrin acts as a neurotoxin by depolarizing nerve cell membranes of parasites.^[2][13][65] The drug disrupts the sodium channel current by which membrane repolarization is regulated.^[2][12][13] Delayed repolarization results in paralysis of the nerves in the exoskeletal respiratory muscles of the parasite leading to death. At a concentration of 1%, permethrin is pediculicidal; concentrations of 5% also are scabicidal.^{[2][13][61][68][69][70]}

Permethrin exerts ovicidal effects against lice,^{[6][8][16][31][34][61][64]} and some activity may result from residues that remain on the hair for 2 weeks or longer that kill nymphs as they emerge from eggs.^{[6][16][31][34][61][64]} In one in vitro study using live lice and viable nits obtained from healthy lice-infested children in Panama, exposure to permethrin 1% cream rinse (Nix^®) killed 30% of the lice within 5 minutes, 53% within 10 minutes, and 100% within 1 hour; 89% of the nits were killed within 10 minutes.^[84] However, when permethrin 1% was diluted 10:1 in water to approximate the dilution that occurs when the drug is applied to wet hair, 11% of the lice were killed within 5 minutes, 44% within 10 minutes, and 94% within 1 hour; 81% of the nits were killed within 10 minutes when exposed to the diluted solution.^[84]

Permethrin is active against Pediculus humanus var. capitis (the head louse) and its nits (eggs),^[1][34] Phthirus pubis (the pubic or crab louse) and its nits,^{[9][17][29][56][62]} and Sarcoptes scabiei, the causative parasite of scabies.^{[2][8][9][13][17]} The drug also is active against ticks, fleas, and other arthropods.^{[2][13][61][65]}

Drug resistance assays for Pediculus humanus and Sarcoptes scabiei have not been standardized and are difficult to interpret.^{[8][63][68][86]}

Decreased susceptibility to permethrin has been reported in some strains of P. humanus var. capitis (head louse) in various parts of the world, indicating the emergence of resistance as use of the drug has become more widespread.^{[4][59][63][72][73][74][79][80]} However, the clinical importance of these reports as it relates to treatment of lice infestations in the US is unclear since the prevalence of permethrin resistance in the US remains to be elucidated.^[80] Some reported treatment failures may actually be secondary to reinfestation or failure to apply the permethrin correctly rather than the result of resistance in the lice.^{[8][56][59][63][64][69][85][86]}

No confirmed cases of resistance to permethrin in S. scabiei have been reported to date,^[4][57] and treatment failures appear to be related to reinfestation or failure to apply permethrin correctly.^[4]

Absorption

Small amounts of permethrin are absorbed systemically following topical application to the skin.^{[2][8][12][13][14][18][20][39][61][64][67][90]} In clinical trials, the drug was undetectable in plasma following topical application of permethrin 5% cream^[8][39] or 1% cream rinse.^[20] In an unpublished study in patients with moderate to severe scabies, 2% or less of a mean 23.6-g/m² dose of radiolabeled permethrin 5% cream was absorbed systemically following topical application to the entire body; the cream was allowed to remain on the skin for 14 hours before washing.^{[2][13][69][90]} Similar results were found in absorption studies in healthy adults following application of permethrin 1% cream rinse.^[20]

Permethrin absorption was measured indirectly by measuring excretion of conjugated and unconjugated permethrin metabolites in a study in 10 patients with scabies who applied a mean of 1.25 g of permethrin (25 g of permethrin 5% cream); the mean calculated absorption of permethrin was 0.5% (6 mg) of the total applied dosage.^[67] In this study, metabolite excretion indicated increased absorption (approximately 11 mg) in an alcoholic patient who had abnormal liver function test results prior to permethrin treatment.^[67]

In vitro studies using human cadaver skin under conditions simulating overuse of permethrin 5% cream or lindane 1% lotion also indicate little percutaneous absorption of permethrin.^[44] In human cadaver skin, measurable percutaneous absorption of permethrin was not observed until 10-20 hours after application, while lindane was absorbed much faster, reaching a steady-state rate of absorption within 5 hours after application.^[44] Permethrin was absorbed percutaneously through human skin approximately 20 times less extensively than lindane.^[44] The total amount of permethrin absorbed was approximately 0.7% of the dose applied.^[44] In an in vitro study using guinea pig skin, percutaneous absorption of lindane and permethrin was similar.^[44] However, when permethrin 5% cream or lindane 1% lotion were applied to guinea pigs once daily for 3 days without washing to simulate overuse, lindane was detected in plasma and brain tissue at concentrations that were fourfold greater than those for permethrin.^[44]

Distribution

Information on distribution of permethrin into human body tissues and fluids following topical application to the skin is not available.^[68][69][70] In a study in guinea pigs under conditions simulating cutaneous topical overdosage of permethrin 5% cream, permethrin concentrations in brain and plasma (0.62 mcg/g and 0.11 mcg/mL, respectively) were much lower than those in the dermis and epidermis (41 and 966 mcg/g, respectively)^[44] and were lower than those of lindane after topical application to the skin.^[44] In this study in guinea pigs, the ratio of cis:trans isomers of permethrin varied in different tissues after topical application of permethrin 5% cream.^[44] The ratio in the dermis and epidermis was 2.8, approximately the same as the ratio of isomers in the cream formulation itself; however, the concentrations of isomers in brain and plasma were nearly equal, yielding ratios of 1.3 and 0.7, respectively.^[44] These data suggest stereoselective distribution and/or elimination of permethrin isomers.^[44] Studies in rats indicate that permethrin is widely distributed into most body tissues and fluids following oral or IV administration;^[23] peak concentrations of the drug in the brain and sciatic nerve region are substantially higher than corresponding peak plasma concentrations, indicating an accumulation of the drug in the brain.^[23]

It is not known whether permethrin crosses the placenta following topical application to the skin.^[13][69][70] It also is not known whether permethrin is distributed into human milk,^{[2][3][69][70][90]} but very small amounts are distributed into milk in animals.^[70]

Elimination

Permethrin is rapidly metabolized by ester hydrolysis to inactive metabolites, which are eliminated rapidly in the urine.^{[2][8][12][13][14][18][23][31][39][67][90]} Since the rate of metabolism of permethrin exceeds the rate of percutaneous absorption, plasma permethrin concentrations following topical application of a 5% cream or 1% cream rinse are not detectable.^[8] (See Pharmacokinetics: Absorption.)

Permethrin occurs as a mixture of the cis and trans isomers.^{[2][3][4][5][8][13][39][90]} Because the trans isomer of permethrin is more rapidly metabolized and therefore less toxic to mammals than the cis isomer,^{[4][8][16][18][60]} the cis:trans ratio is 25:75 in permethrin preparations for human use,^{[2][4][8][13][16][18][27][29][31][39][90]} while higher ratios (40:60 or 50:50) are found in agricultural products.^[8][18][60] Animal studies indicate possible stereoselective distribution and/or elimination of permethrin isomers.^[44] (See Pharmacokinetics: Distribution.) Following oral administration, approximately one-third of permethrin is metabolized to cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acids, which are excreted in conjugated and unconjugated forms in the urine.^[67]

In a patient who ingested about 600 mL of a 20% commercially available permethrin insecticide emulsion (a total dosage of 143 g of permethrin) with a cis:trans ratio of about 43:57, the trans isomer was rapidly cleared from blood and was undetectable within about 1 day; the cis isomer was still detected in blood 10 days later.^[60] (See Acute Toxicity.)

Chemistry

Permethrin is a synthetic pyrethrin derivative^{[3][4][5][8][10][12][14][16][18][21][23][25][26][29][31][33][34][35][44][64][65]} that is used as a pediculicide^{[1][4][5][6][7][8][9][16][17][22][27][28][29][36][44][51][61][62][64][65]} and a scabicide.^{[2][4][6][8][9][10][11][12][13][14][17][18][21][22][25][26][32][37][38][43][44][45][60][65]} Pyrethrins are the active insecticidal components of the flowers of the plant Chrysanthemum cinerariaefolium.^{[4][8][16][35][58]}

Permethrin occurs as a mixture of the cis and trans isomers of the drug.^{[2][3][4][5][8][13][39][44][90]} Because the trans isomer of permethrin is more rapidly metabolized and therefore less toxic to mammals than the cis isomer,^{[4][8][16][18][60]} the cis:trans ratio of permethrin in human preparations is 25:75^{[2][4][8][13][16][18][27][29][31][39][90]} while ratios of 40:60 and 50:50 are found in agricultural preparations.^[8][18][60] (See Pharmacokinetics: Elimination.)

Permethrin occurs as a yellow to light orange-brown, low-melting solid or viscous liquid.^{[2][3][5][13]} Permethrin is practically insoluble in water^{[3][4][5][26][70]} and soluble in alcohol^[70] and nonpolar organic solvents.^[3][70]

For the topical treatment of head lice, permethrin is commercially available in a 1% lotion (cream rinse) formulation containing isopropyl alcohol 20% with methylparaben and propylparaben.^[1][16][89] Each 28 mL of commercially available permethrin 1% lotion (cream rinse) contains 280 mg of the drug.^[1][89] For the topical treatment of scabies, permethrin is commercially available as a 5% cream in an off-white^[2][13][90] vanishing base^{[2][13][18][90]} containing butylated hydroxytoluene, carbomer 934P, fractionated coconut oil, glycerin, glyceryl monostearate, isopropyl myristate, mineral oil, lanolin alcohols, polyoxyethylene cetyl ethers, purified water, sodium hydroxide, and formaldehyde as a preservative.^[2][13] Each gram of commercially available permethrin 5% cream contains 50 mg of the drug.^[2][13][90] Permethrin 5% cream does not stain and is odorless.^[18]

Stability

Permethrin 5% cream should be stored at 15-25°C.^[2][13][90] Viscosity of the cream formulation is temperature-dependent; viscosity decreases as temperature increases and the probability of phase separation also increases.^[69]

Permethrin 1% lotion (cream rinse) should be stored at 15-25°C or 20-25°C, depending on the manufacturer.^[1][89]

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.

\* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

†Use is not currently included in the labeling approved by the US Food and Drug Administration.

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