Permethrin

Class: Scabicides and Pediculicides
VA Class: AP300
Molecular Formula: C₂₁H₂₀Cl₂O₃
CAS Number: 52645-53-1
Brands: Acticin, Elimite, Nix Creme Rinse

Introduction

Pediculicide^{1 4 5 6 7 8 16 17 22 27 28 29 36 44 51 61 62 64 65} and scabicide;^{2 4 6 8 10 11 12 13 14 17 18 21 22 25 26 32 37 38 43 44 45 60 65} synthetic pyrethrin derivative.^{5 8 26 29 31 33 34 35 44 64 65}

Uses for Permethrin

Pediculosis

Topical treatment of pediculosis capitis (head lice infestation) in adults and children ≥2 months of age.^{1 4 6 7 8 17 22 35 36 51 61 62 63 64 65 79 80 82 91}

Considered a pediculicide of choice by AAP and others because of low toxicity potential and good ovicidal activity.^{6 7 17 61 63 64 79 80 82 96} Topical malathion 0.5% is recommended when permethrin resistance is suspected.^{10 17 63 79 80 82 96}

Base selection of a pediculicide on 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

Has been used for prophylaxis of pediculosis capitis during head lice epidemics.^{1 89} Such use should only be considered for individuals exposed to head lice epidemics in which ≥20% of the population at an institution is infested or for immediate household members of infested individuals; casual use strongly discouraged.^{1 89}

Topical treatment of pediculosis corporis† (body lice infestation).^{95 96} 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.^{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}

Topical treatment of pediculosis pubis† (pubic lice infestation; crab lice).^{9 22 62} Considered a pediculicide of choice by CDC and others for treatment of pediculosis pubis, including in HIV-infected patients.^{9 22 62}

Scabies

Topical treatment of scabies in adults and children ≥2 months of age.^{2 4 6 8 9 10 11 13 14 18 21 22 25 26 32 37 38 43 44 45 60 65 90}

Considered the topical scabicide of choice by AAP, CDC, and others because of its safety and efficacy profile relative to other available agents (e.g., lindane).^{4 6 9 10 12 17 21 25 26 36 37 88 94 96}

Recommended for use in institutional outbreaks of scabies.^{42 92} In such situations, the entire population at risk should be treated.^{9 42 54 92} CDC recommends that scabies epidemics in institutional settings (e.g., nursing homes, hospitals, residential facilities and communities) be managed in consultation with an expert.⁹

Has been used to treat Norwegian scabies (crusted scabies).^{42 55 68} Aggressive treatment with sequential use of several different scabicides,^{26 41 55} concomitant use of oral ivermectin and a topical scabicide, or a multiple-dose oral ivermectin regimen may be necessary.^{26 41 55} HIV-infected individuals and other immunocompromised patients are at increased risk of developing Norwegian scabies;^{9 19 26 41} CDC recommends that such patients be managed in consultation with an expert.⁹

HIV-infected individuals with uncomplicated scabies should receive the same treatment regimens as those without HIV infection.⁹

Demodicidosis

Has been used for treatment of Demodex folliculorum†^{48 49 50 52 53 87} infestations in children and adults and D. brevis† infestations in children,⁵⁰ including patients with immunosuppression (e.g., AIDS, acute lymphoblastic leukemia)^{48 50 53 87} .

Permethrin Dosage and Administration

General

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, dry-cleaned, or treated with an appropriate pesticide) or removed from body contact for ≥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.^{2 26} For lice infestation, although it may not be necessary, items that cannot be laundered or dry-cleaned should 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 patients infected with lice may be disinfected by soaking in hot water (temperature >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}

  
  


• 
  

  Furniture and floors of rooms inhabited by patients infested with lice should 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}

  
  


• 
  

  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.^{1 28 47 51 62 64 66 82 83} Some experts do not consider nit removal necessary since only live lice can be transmitted, but recommend it for aesthetic reasons and to decrease diagnostic confusion and unnecessary retreatment.^{6 36 82} Others 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} Although many schools will not allow children with nits to attend, AAP and other experts consider these no-nit policies excessive.^{6 80 82}

  
  

Administration

Topical Administration

Apply topically to hair and scalp as 1% lotion (cream rinse) or apply topically to skin as 5% cream.^{1 2 13 89 90}

For external use only; do not administer orally.^{1 2 13 89}

Avoid contact with eyes;^{1 2 13 89 90} avoid contact with mucous membranes (e.g., inside the nose, mouth, or vagina).^{1 69 89}

Shake 1% cream rinse before using.¹

Pediculosis

For treatment of pediculosis capitis (head lice infestation), wash the hair with regular shampoo, rinse with water, and towel dry before applying permethrin cream rinse.¹ Shampoos that contain a conditioner or a separate post-shampoo conditioner should not be used since they may decrease the drug’s pediculocidal effect.¹ After the recommended period (usually no longer than 10 minutes), rinse with water.¹

During application, protect children’s eyes with a washcloth, towel, or other suitable method.¹

Following proper pediculicide application, lice die quickly; therefore, living lice detected during scalp inspection ≥24 hours after treatment probably indicates a very heavy infestation, reinfestation, or resistant infection.⁶ After ruling out improper application in such patients, AAP recommends immediate retreatment with a different pediculicide followed 7–10 days later by a second application.⁶

Other family members and close contacts of the individual with pediculosis capitis 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}

Since pediculosis pubis (pubic lice infestation) 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} Presumptive concurrent treatment also has been recommended for other close contacts of the patient.^{8 36}

Patients with pediculosis pubis should avoid sexual contact with their sexual partner(s) until patients and partners have been treated and reevaluated to rule out persistent disease.⁹

Scabies

For treatment of scabies, the 5% cream is applied and massaged into the skin over the entire body, from the head to the soles of the feet.^{2 8 9 11 13 90} After the recommended period (usually 8–14 hours), the cream is removed by bathing or showering.^{2 8 9 11 13}

The patient or caregiver should be careful to apply the 5% 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}

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, 5% cream should be applied to the entire head and neck, including the scalp, temples, and forehead of such patients.^{2 6 12 13 37 90}

Sexual contacts of patients receiving treatment for scabies and other individuals (household, family) who have had close personal contact with the patient within the previous month should be examined and treated.^{6 8 9 11 14 18 21 24 25 26 37 41}

If 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

In patients with Norwegian scabies, the entire surface of the body, including areas under the nails, should be treated.^{19 26 55} Multiple treatments, including sequential use of multiple scabicides may be necessary.^{26 41 51 55} Some clinicians recommend pretreatment with a keratolytic agent before using a topical scabicide;^{26 41} others recommend concomitant use of oral ivermectin in conjunction with a topical scabicide or multiple doses of oral ivermectin.⁹

The CDC recommends that patients with HIV infection who have uncomplicated scabies 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

Dosage

Pediatric Patients

Pediculosis

Pediculosis Capitis (Head Lice Infestation)

Topical

1% Lotion (cream rinse): apply a sufficient amount (30–60 mL) to washed and towel-dried hair to thoroughly saturate the hair and the scalp (including the areas behind the ears and the nape of the neck).^{1 89} After 10 minutes, rinse with water.^{1 89}

One treatment usually is successful;^{1 6 65} treatment may be repeated with 1% permethrin cream rinse (especially if hair is shampooed 7 days after initial treatment or live lice are observed ≥7 days after initial treatment) 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.^{6 51 61 62 64 80 82} During pediculosis epidemics, the manufacturer recommends a second treatment 2 weeks after the first, since the head louse life cycle is approximately 4 weeks.⁸⁹

In resistant cases of pediculosis capitis, some clinicians recommend leaving the cream rinse on for a longer period of time (e.g., 30–60 minutes)† or, alternatively, applying the 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 79}

Scabies

Topical

5% Cream: apply a thin, uniform layer and massage 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} Wash off (by showering or bathing) after 8–14 hours.^{2 6 8 9 11 12 13 24 26 37 42 90}

One treatment usually is successful in eradicating scabies.^{2 11 13 21 32 37 90}

No consensus on the need for retreatment;⁹ some experts recommend retreatment if symptoms persist after 1 week, 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}

CDC recommends retreating patients who do not respond to permethrin with an alternative regimen.⁹

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, treatment should be considered a 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, the case should be considered a reinfestation rather than a treatment failure.^{24 26} Patients who experience actual treatment failure should be retreated with an alternative scabicide.⁹

Demodicidosis†

D. folliculorum or D. brevis Infestations†

Topical

Permethrin 1% or 5% has been used;^{48 49 50 52 53 87} effective dosage regimen not established.^{68 69}

Adults

Pediculosis

Pediculosis Capitis (Head Lice Infestation)

Topical

1% Lotion (cream rinse): apply a sufficient amount (30–60 mL) to washed and towel-dried hair to thoroughly saturate the hair and the scalp (including the areas behind the ears and the nape of the neck).^{1 89} After 10 minutes, rinse with water.^{1 89}

One treatment usually is successful;^{1 65} treatment may be repeated with 1% permethrin cream (especially if hair is shampooed 7 days after initial treatment or live lice are observed ≥7 days after initial treatment) 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.^{6 51 61 62 64 80 82} During pediculosis epidemics, the manufacturer recommends a second treatment 2 weeks after the first, since the head louse life cycle is approximately 4 weeks.⁸⁹

In resistant cases of pediculosis capitis, some clinicians recommend leaving the cream rinse on for a longer period of time (e.g., 30–60 minutes)† or, alternatively, applying the 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 79}

Pediculosis Pubis (Pubic Lice Infestation)

Topical

1% Lotion (cream rinse): Apply to the pubic and other affected areas; allow to remain for 10 minutes and then rinse off with water.⁹ Alternatively, some clinicians recommend use of permethrin 5% cream.¹⁷

CDC recommends reevaluating the patient 1 week after treatment if symptoms persist;⁹ retreatment may be necessary if lice are found or eggs are observed.⁹ If retreatment in necessary, CDC recommends use of an alternative regimen.⁹

Routine retreatment 7–10 days after initial treatment is recommended by some clinicians,^{6 29 68} but if used correctly, one treatment usually is effective.⁹

Scabies

Topical

5% Cream: apply a thin layer uniformly and massage 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} Usual dosage to treat an average adult is 30 g of 5% cream.^{2 12 13 26 42 90} Wash off (by showering or bathing) after 8–14 hours.^{2 6 8 9 11 12 13 24 26 37 42 90}

One treatment usually is successful in eradicating scabies.^{2 10 11 13 14 21 24 25 26 32 37 90}

No consensus on the need for retreatment;⁹ some experts recommend retreatment if symptoms persist after 1 week, 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}

CDC recommends retreating patients who do not respond to permethrin with an alternative regimen.⁹

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, treatment should be considered a 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, the case should be considered a reinfestation rather than a treatment failure.^{24 26} Patients who experience actual treatment failure should be retreated with an alternative scabicide.⁹

Demodicidosis†

D. folliculorum or D. brevis Infestations†

Topical

Permethrin 1% and permethrin 5% have been used;^{48 49 50 52 53 87} effective dosage regimen not established.^{68 69}

Cautions for Permethrin

Contraindications

• 
  

  Known hypersensitivity to permethrin, any synthetic pyrethroid or pyrethrin, or any component in the formulation.^{2 13 20 90}

  
  

Warnings/Precautions

Sensitivity Reactions

Asthmatic Episodes

May cause breathing difficulty or an asthmatic episode in susceptible individuals.^{1 46 89}

Discontinue use and contact a clinician if breathing difficulties occur.^{1 46 89}

Contact Dermatitis

5% cream contains formaldehyde 0.1% as a preservative,^{2 13 37 39 90} which may cause contact dermatitis.^{26 37 39 69 70}

Photosensitivity

Photosensitization or phototoxicity reactions not reported to date.^{20 69}

Cross-sensitization

Theoretical cross-sensitivity between permethrin and ragweed or chrysanthemums; appears unlikely.^{20 51 55 69}

General Precautions

Administration Precautions

Avoid contact with eyes since ocular irritation may occur.^{1 2 13 90} Do not use for treatment of pediculosis of the eyebrows or eyelashes.^{6 9} If accidental contact with the eyes occurs, the affected eye(s) should be flushed thoroughly with water.^{1 2 13 90}

Avoid contact with mucous membranes (e.g., inside the nose, mouth, or vagina).^{1 69}

Exacerbation of Symptoms or Secondary Infection in Scabies

Manifestations of scabies (e.g., pruritus, erythema, edema, skin lesions) are the result of hypersensitivity to the mite and its eggs and waste products.^{6 9 11 24 36 37 42 51 68} Treatment with permethrin may temporarily exacerbate these symptoms.^{2 6 11 90} Persistent skin inflammation (e.g., pruritus, mild burning of the scalp) may occur after treatment and usually is not a sign of treatment failure and is not a cause for retreatment.^{2 6 13 21} Oral antihistamines and/or topical corticosteroids may be used to help relieve pruritus.^{6 11 24 26 37 41}

Mild secondary bacterial infections in patients with scabies usually resolve; concurrent systemic anti-infective therapy may be necessary for severe secondary infections.^{6 14 24 26 37 41}

Specific Populations

Pregnancy

Category B.^{1 2 13 90}

CDC and some clinicians consider permethrin the pediculicide or scabicide of choice when treatment is considered necessary in a pregnant woman.^{6 9 17 93}

Lactation

Not known whether distributed into milk.^{2 13 90} Discontinue nursing or the drug.^{2 13 90}

CDC and some clinicians consider permethrin the pediculicide or scabicide of choice when treatment is considered necessary in a lactating woman.^{6 9}

Pediatric Use

Safety and efficacy of 1% lotion (cream rinse) or 5% cream not established in children <2 months of age.^{1 2 13 89 90 91} Has been used effectively without unusual adverse effects in this age group.^{38 68}

Geriatric Use

Insufficient experience in controlled clinical studies in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^{2 13 90} Other clinical experience has not revealed age-related differences in response.^{2 13 90}

Renal Impairment

When used as directed, 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.)

Common Adverse Effects

Mild and transient burning and stinging^{2 10 12 13 26 27 29 32 90} and pruritus;^{6 8 9 10 12 13 20 27 29 31 35 36 37 47 61 62} may be the result hypersensitivity reaction to the ectoparasite.^{6 9 13 24 29 37 61} Erythema, numbness, tingling, and rash reported less frequently.^{2 13 29 31 39 90}

Permethrin Pharmacokinetics

Absorption

Bioavailability

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}

Following topical application of 5% cream to patients with moderate to severe scabies, ≤2% of the amount applied is absorbed systemically.^{2 8 13 39 61 90} Similar results reported with topical application of 1% cream rinse in healthy adults.²⁰

Distribution

Extent

Information on distribution into human body tissues and fluids following topical application to skin is not available.^{68 69 70}

Not known whether permethrin crosses the placenta following topical application to the skin.^{13 69 70}

Not known whether permethrin is distributed into human milk,^{2 3 69 70 90} but distributed into milk in small amounts in animals.⁷⁰

Elimination

Metabolism

Rapidly metabolized by ester hydrolysis to inactive metabolites.^{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% lotion (cream rinse) are not detectable.⁸

Elimination Route

Inactive metabolites of permethrin are eliminated rapidly in the urine.^{2 8 12 13 14 18 23 31 39 67 90}

Stability

Storage

Topical

Cream

15–25°C.^{2 13 90} Viscosity decreases at higher temperatures and product separation may occur.^{69 2 13}

Lotion (Cream Rinse)

15–25°C⁸⁹ or 20–25°C,¹ depending on the manufacturer.

Actions and SpectrumActions

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  A synthetic pyrethrin derivative;^{3 4 5 8 10 12 14 16 18 21 25 26 29 31 33 34 35 44 64 65} like natural pyrethrins, acts as a neurotoxin by depolarizing the nerve cell membrane.