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RESIDENTS CORNER
Year : 2020  |  Volume : 21  |  Issue : 3  |  Page : 235-240

Use of antifungals in pediatric superficial dermatophytosis


1 Department of Dermatology, The Children's Hospital, Mumbai, Maharashtra, India
2 Department of Pediatric Dermatology, BJ Wadia Hospital for Children, Parel, Mumbai, Maharashtra, India

Date of Submission27-Feb-2020
Date of Decision29-Feb-2020
Date of Acceptance03-Mar-2020
Date of Web Publication30-Jun-2020

Correspondence Address:
Dr. Resham J Vasani
Bhojani Clinic, Ground Floor, Earth Classic, Babasaheb Ambedkar Road, Matunga, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_33_20

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  Abstract 


There has been a rise in the incidence of dermatophytic infections in children in the last decade. Additionally, there has been a sea change in the clinical presentation, treatment practices and course of the condition seen in practice. This article summarises information on the available topical and oral antifungal agents in question and asnwer format for better understanding.

Keywords: Dermatophytoses, fluconazole, griseofulvin, itraconazole, terbinafine


How to cite this article:
Gandhi GR, Vasani RJ. Use of antifungals in pediatric superficial dermatophytosis. Indian J Paediatr Dermatol 2020;21:235-40

How to cite this URL:
Gandhi GR, Vasani RJ. Use of antifungals in pediatric superficial dermatophytosis. Indian J Paediatr Dermatol [serial online] 2020 [cited 2020 Aug 9];21:235-40. Available from: http://www.ijpd.in/text.asp?2020/21/3/235/288500




  Introduction Top


Dermatophytosis in the pediatric age group is a common presentation in the current scenario.[1] Unlike tinea capitis, which was the most common presentation before the onslaught of the epidemic of chronic recalcitrant dermatophytosis through out the country, tinea corporis et cruris is now the most common presentation encountered.[2],[3]

The factors responsible for the increase in the incidence in this age group are untreated contacts with superficial dermatophytosis, inappropriate treatment with incorrectly prescribed or over-the-counter steroid-containing triple/quadruple combination creams, and inadequate dosing and duration of antifungal treatment.[2],[4] Clinical presentation with large patches and extensive body surface area involvement accompanying changes of steroid abuse is common.[5]

With the emergence of antifungal resistance,[6] and the change in the causative organism to Trichophyton mentagrophytes,[7] conventional topical antifungals such as clotrimazole or ketoconazole are being replaced with off-label use of newer topical antifungals such as luliconazole, sertaconazole, eberconazole, and amorolfine as the first-line treatment of tinea cruris, corporis, and faciei.[8] Systemic antifungal therapy which was usually reserved for the treatment of superficial dermatophytosis of the scalp, nails, palms and soles, now, needs to be administered more often in nonresponsive cases of tinea cruris/corporis/faciei.

Hence, it is imperative to have a solid understanding of the differences in the pharmacokinetics of antifungals in the pediatric age versus that in an adult. Most of the data on use of antifungals in pediatric age group has been extrapolated from adult data on account of lack of sufficient studies in children.[5] For the ease of understanding, the topic is covered in a question–answer format.


  Why are Topical Antifungals Preferred in the Treatment of Superficial Dermatophytosis in the Pediatric Age Group? Top


Topical antifungals are preferred in the pediatric age group as they have a thin skin which enables better penetration of the topically applied creams and the high turnover rate which allows rapid elimination of the fungus.[9],[8],[10] [Table 1] gives an overview of the topical agents available currently in India.
Table 1: Topical antifungal agents in superficial dermatophytosis

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  What are the Indications of Systemic Antifungals in the Pediatric Age? Top


In certain cases where the lesions are inflammatory, extensive, or relapsing, especially in the background of steroid abuse, the use of oral antifungals becomes necessary.[9]

The commonly used oral antifungals are listed in [Box 1].




  Terbinafine Top


Is the drug approved for the treatment of tinea corporis and cruris?

Terbinafine is FDA approved for age ≥4 years as the first-line treatment of tinea capitis.[5],[11]

Which scalp infections is terbinafine more effective in?

There is evidence in literature that suggests that terbinafine is more effective than griseofulvin in children with Trichophyton tonsurans infection. Terbinafine is less efficacious for ectothrix scalp infections in children due to a lack of penetration into eccrine sweat and low levels of sebum before puberty.[9],[12] However, in children with Microsporum infections, the evidence suggests that griseofulvin works better than terbinafine.[4]

What are the contraindications of terbinafine?

Absolute: Allergy or hypersensitivity reaction to terbinafine.[5]

Relative: Terbinafine is not indicated in cases of active or chronic liver disease and renal impairment.[5] Terbinafine clearance is reduced by 50% in case of renal or hepatic impairment.[13],[14] The use of terbinafine has not been adequately studied and requires dose adjustments in patients with creatinine clearance ≤50 mL/min.[15] The dose should be reduced by 50% when creatinine clearance ≤50 ml/min.

What are the oral formulations available for the pediatric age?

It is available as oral scored tablets of 125, 250, and 500 mg.[5],[8],[10] Dispersible tablets are available which make it suitable for pediatric use (oral absorption is not affected by food).

What is the dosing regimen?

Dosage is according to the weight: 1/4th tablet (62.5 mg) for children weighing<20 kg, ½ tablet (125 mg) for patients weighing 20–40 kg, and 1 full tablet (250 mg) for patients >40 kg.

Daily dose is 3–6 mg/kg/d.[5],[11],[12],[16]

What is the duration of treatment?

Duration of treatment depends on the type of tinea infection

  • 2–4 weeks for tinea corporis/cruris and pedis. In the current scenario, it is recommended to continue the oral antifungal till the patient achieves clinical cure and at least 2 weeks beyond the clinical resolution[17]
  • 4 weeks for tinea capitis[5],[14],[18]
  • 6 weeks for fingernail onychomycosis[5],[14],[18] and
  • 12 weeks for toenail onychomycosis (250 mg daily for 12 weeks, FDA approved).[10]


What are the possible side effects?

Terbinafine has good safety profile in children, most common side effects being gastrointestinal and skin reactions (rash and urticaria), followed by, rarely, hepatic enzyme abnormalities and hematologic parameter abnormalities.[13],[14],[19]

What are the differences in pharmacokinetics of terbinafine in children and adults?

Terbinafine has a 40% higher clearance rate in children compared to adults; consequently, children require a dose that is approximately double the median dose which would result in a systemic exposure that is comparable to the standard adult dose of 250 mg/day.[20],[21]

Does terbinafine require monitoring in the pediatric age group?

Course duration more than 6 weeks requires laboratory monitoring. It is recommended to do baseline liver function tests (LFTs) and complete blood count (CBC).[19]

Is doubling the dose of terbinafine safe in the pediatric age group?

There is evidence that terbinafine has been safely administered in double the recommended dose (for e.g., 125 mg/day for children of 10–15 kg body weight, 187.5 mg/day for children of 16–25 kg, and 250 mg/day for children >25 kg) for the treatment of Microsporum infections.[16],[22],[23] Increasing the duration of treatment in Microsporum infections (to 6 weeks) is found to have similar efficacy as a higher dose. On account of increasing resistance to terbinafine, higher doses of terbinafine for longer durations are increasingly being used in the treatment of tinea infections.[16],[17],[24]


  Griseofulvin Top


What is the Food and Drug Administration-approved indication of griseofulvin in dermatophytosis?

Griseofulvin is FDA approved for children aged 2 years and older for the treatment of tinea capitis.[5]

However, it is used off-label for the treatment of other superficial dermatophytosis such as tinea cruris, corporis and faciei.

Above what age is it Food and Drug Administration approved?

It is approved for children ≥2 years, but it is used off label above the age of 1 month (10 mg/kg/day).[5]

What are the contraindications?

It is absolutely contraindicated in patients with porphyria, hepatocellular failure, and hypersensitivity to giseofulvin.[5],[25]

What are the formulations available?

Griseofulvin is poorly absorbed after an oral dosage. Microsized and ultramicrosized preparations are used to enhance absorption.[14] It is available in a tablet formulation in India.

Available strengths are as follows:

  • 125 mg and 250 mg (available as ultramicrosized)[25]
  • 375 mg and 500 mg (available as micronized strength)[25]
  • It is recommended to administer it after a meal high in fat content or with a glass of milk to increase the absorption.[9],[11]


What is the dosing regimen of griseofulvin?

The dose recommended in the pediatric age group was 10 mg/kg/day (micronized) in two divided doses, but in the current scenario, there is a preference to use a higher dose of 20–25 mg/kg/day.[9],[19]

Recommended dosing schedule according to the weight of the child is as follows:[9],[19]

  • 10–20 kg: 125 mg/day once daily
  • 20–40 kg: 250 mg/day once daily
  • >40 kg: 500 mg/day once daily.


What is the treatment duration?

  • 2–4 weeks for tinea cruris, tinea corporis, and tinea faciei[12],[19]
  • 6–12 weeks for tinea capitis (The 2009 AAP Red Book and ECTODERM guidelines recommend that treatment should be continued for 2 additional weeks beyond clinical resolution)[12],[19],[26]
  • 6–8 weeks for tinea pedis and manuum[12]
  • 6 months for fingernail infection[12]
  • 6–12 months for toenails.[12]


How is it administered to the child?

Tablet can be crushed and added to soft food without chewing.[25],[27]

What are the possible side effects?

Griseofulvin has long-standing history of safety in children. Infrequent side effects noted are headache, photosensitive rash, urticaria, nausea, vomiting, diarrhea, fatigue, proteinuria, and leukopenia.[9],[16],[19]

How does one monitor a child on griseofulvin?

Laboratory monitoring is not required in healthy children treated with durations of 8 weeks or less. Periodic monitoring of CBC and liver and renal function tests recommended if therapy is continued for ≥8 weeks.[9],[19]

How does the pharmacokinetics of griseofulvin differ in a child versus in an adult?

There is no statistically significant difference in pharmacokinetic observations of griseofulvin in adults and children. Accordingly, administering the drug along with whole milk is said to increase the bioavailability in pediatric age group similar to adults.[28]


  Fluconazole Top


Is the drug approved for the treatment of tinea corporis and cruris?

Its FDA approved for the treatment of cryptococcosis and oropharyngeal candidiasis in children aged 6 months and above, not yet for tinea infections.[10],[19],[29]

What is the youngest age at which fluconazole has been used for superficial fungal infections?

There is evidence that fluconazole has been used safely for the treatment of tinea capitis in a neonate aged 3 weeks.[30]

What are the contraindications?

It is contraindicated in hepatic and renal impairment.[5] It is recommended in patients with an estimated creatinine clearance of 10–50 ml/min, a standard initial dose may be given, but subsequent doses should be reduced by 50%.[24]

What are the formulations available?

Fluconazole is available in India as oral dispersible tablets (50 mg/150 mg/200 mg/400 mg), suspension (50 mg/ml) for children, and injection for intravenous use.[31]

What is the recommended dosing regimen?

  • 3–5 mg/kg/day once a week for 8 weeks for tinea capitis[12]
  • 3–6 mg/kg once weekly for 12–16 weeks for fingernail infection and 18–26 weeks for toenail onychomycosis.[12]


The safety of fluconazole in the pediatric age group is evident from various studies, and hence, it is increasingly being used off label in the treatment of tinea corporis and cruris in the dose of 6 mg per kg every other day for at least 2 weeks beyond clinical cure.

How is it administered to the child?

  • Dispersible tablets and oral suspension (50 mg/ml)[5],[19]
  • Absorption is not affected by meals or gastric pH.[32]


What are the possible side effects?

Fluconazole has excellent safety profile in children similar to adults. Most common side effects include gastrointestinal toxicity (vomiting, nausea, and diarrhea). Hepatotoxicity (elevated transaminases), rash, and renal dysfunction have been reported rarely. A baseline CBC and LFT is recommended.[5],[29],[31]

How does the pharmacokinetics of fluconazole differ in the pediatric age group?

The pharmacokinetics of fluconazole is different between adults and children. Children have a higher and more rapid clearance and a larger volume of distribution (neonates especially); hence, the daily dose needs to be doubled to 6–12 mg/kg/day to match adult exposures (children >3 months).[29],[31]


  Itraconazole Top


Is the drug approved for the treatment of tinea corporis cruris in the pediatric age group?

Itraconazole received approval in 1990 for use in adult patients. Since then, it has been used in pediatric age group for both superficial and deep fungal infections, although it has not been approved by the US FDA for use in tinea infections in this age group.[17]

What is the youngest age at which itraconazole has been used for superficial dermatophytosis in literature till date?

There is evidence in literature that itraconazole has been safely used in infants as early as 3 weeks with complete clinical and mycological cure. The study quoted included children between the age group of 3 and 46 weeks and treatment duration ranging from 3 to 6 weeks. The drug was administered as 5 mg/kg in capsule or solution form.[33]

What are the indications of itraconazole in pediatric dermatology?

Itraconazole is not yet FDA approved in the pediatric age group, but it has been used (off label) safely and effectively in superficial fungal infections such as tinea corporis, cruris, capitis, pedis, and mannum and onychomycosis.[17],[34]

Itraconazole has a wide spectrum of activity, including dermatophytes (Trichophyton, Microsporum, and Epidermophyton) and Candida species, and has been used effectively and safely in children and infants.[10],[34],[35]

What are the contraindications?

Itraconazole is not indicated in the setting of liver disease.[14] It is contraindicated in the setting of congestive cardiac failure and QT prolongation (data extrapolated from adult literature).

What are the formulations available?

It is available as capsules and tablets (100 mg, 200 mg, and 400 mg) and oral solution (10 mg/ml).[5],[17],[34]

What is the recommended dosing regimen?

  • 50–100 mg/day for 4 weeks or 5 mg/kg/day for 2–4 weeks for tinea capitis[5]
  • Pulse therapy (5 mg/kg/day for 1 week every month), two pulses for fingernail and three pulses for toenail onychomycosis (off-label use)[5]
  • Oral solution, having better bioavailability compared to capsules, is given in the dose of 3–5 mg/kg/day[11]
  • Children weighing >50 kg are given an adult dose of 200 mg/day.[17]


How is it administered to the children?

The capsules can be opened or chewed. Absorption of the capsule formulation is affected by gastric pH; acid-suppressant medications such as H2 receptor antagonists may decrease the absorption, whereas food and acidic beverages such as colas or cranberry juice may enhance absorption.[9],[19] It is recommended to consume oral preparation on a full stomach. Absorption of oral suspension is not affected by gastric pH and is better absorbed on an empty stomach.[9]

What are the side effects of oral itraconazole?

The reported adverse effects include fatigue, gastritis, headache, sleepiness, dizziness, fever, rash, and LFT abnormalities. It is usually advisable to monitor LFT in case of continuous dosing of itraconazole for more than 4 weeks and when used concomitantly with other hepatotoxic drugs.[5],[17],[34],[35]

The nature of adverse reactions in pediatric patients was similar to that observed in adult patients, but the incidence is reported higher in pediatric patients according to the literature.[36]


  Conclusion Top


In the absence of guidelines and the current off-label use of antifungals, thorough knowledge of dosing, side effects, and monitoring of antifungals is imperative, especially before administration in the pediatric age group. The dose and duration of the antifungals may need to be increased depending upon the clinical response considering the recalcitrant and recurrent nature of the dermatophytic infections in the current scenario.[37] Fluconazole is the systemic antifungal of choice in neonates and infants. Itraconazole is the second-line systemic agent in infants 1 month and above.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Abstract
Introduction
Why are Topical ...
What are the Ind...
Terbinafine
Griseofulvin
Fluconazole
Itraconazole
Conclusion
References
Article Tables

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