Ketoconazole Shampoo

Introduction Overview

Generic Name

Brand Name

Nizoral Shampoo, Extina, Ketodan Foam, Xolegel

Dosage Form

Shampoo (2% aqueous suspension)

Drug Class

Topical antifungals

Pharmacokinetics

Absorption:
Ketoconazole shampoo, 2%, is intended solely for topical application to the skin and scalp. Human pharmacokinetic studies demonstrate minimal to no systemic absorption of ketoconazole when used as directed. Plasma concentrations of ketoconazole were not detectable in patients shampooing the product 2 to 10 times weekly for prolonged periods up to 26 months, indicating negligible systemic exposure. The lack of systemic absorption greatly minimizes the risk of systemic toxicity and drug interactions seen with oral formulations.

Distribution:
Due to the negligible systemic absorption from topical application, systemic distribution of ketoconazole from the shampoo is not clinically significant. The drug primarily partitions on the skin surface and hair follicles, targeting the fungi residing on the epidermis. The shampoo’s vehicle facilitates sufficient delivery of ketoconazole to the stratum corneum and hair shafts where pathogenic yeasts and dermatophytes colonize.

Metabolism:
No significant metabolism occurs systemically because ketoconazole from the shampoo is minimally absorbed. When ketoconazole is absorbed systemically via oral administration, it undergoes hepatic metabolism predominantly via cytochrome P450 enzymes (CYP3A4). However, topical use avoids this metabolic pathway due to negligible plasma levels.

Elimination:
Because systemic absorption does not occur with ketoconazole shampoo, renal and hepatic elimination pathways are not clinically relevant. The drug is primarily removed from the skin surface after rinsing. Any minimal absorbed drug, if present, would undergo hepatic metabolism and biliary excretion like oral ketoconazole, but studies confirm systemic levels remain well below limits of quantification with topical use.

Dosage Forms

Available Dosage Forms:
Ketoconazole Shampoo is formulated as a 2% aqueous suspension. The drug is presented as a red-orange colored liquid shampoo intended for topical application to the scalp and affected skin areas.

Dosages for Adults and Adolescents:
The recommended administration involves applying the shampoo to damp skin or scalp of the affected area plus a surrounding margin, thoroughly lathering, leaving it in place for five minutes, then rinsing off. One application is generally sufficient for therapeutic effect in tinea (pityriasis) versicolor. For other indications like dandruff or seborrheic dermatitis, dosing frequency and duration may vary but generally involves 2-3 times per week.

Specific Patient Populations:
Safety and effectiveness in pediatric patients have not been established. Use in pregnancy is categorized as FDA Category C; however, adverse systemic effects are unlikely from topical use due to absence of systemic ketoconazole detection. Nursing mothers should exercise caution. No dose adjustments are necessary for elderly patients or those with hepatic or renal impairment given minimal systemic exposure.

Formulation Details:
The shampoo contains 2% ketoconazole (20 mg/mL), sodium laureth sulfate, disodium laureth sulfosuccinate, cocamide diethanolamide, hydrochloric acid, PEG-120 methyl glucose dioleate, imidurea, sodium chloride, sodium hydroxide, fragrance, FD&C Red No. 40, and purified water. It is supplied as a 120 mL bottle in a non-breakable plastic container.

Mechanism Of Action

Ketoconazole acts as a broad spectrum synthetic antifungal agent by inhibiting the synthesis of ergosterol, a key component of fungal cell membranes essential for maintaining their integrity and function. By disrupting ergosterol biosynthesis, ketoconazole increases fungal cell membrane permeability, leading to leakage of cellular contents and eventual fungal cell death. This molecular action impairs fungal growth and viability.

At the cellular level, ketoconazole targets fungal cytochrome P450-dependent 14-alpha demethylase enzyme, blocking the conversion of lanosterol to ergosterol, resulting in accumulation of toxic sterol precursors and depletion of ergosterol. This biochemical interference inhibits fungal cell replication and growth.

Clinically, ketoconazole shampoo reduces the population of Pityrosporum orbiculare (Malassezia furfur), the yeast responsible for tinea (pityriasis) versicolor, as well as Pityrosporum ovale implicated in dandruff and seborrheic dermatitis. The reduction of these skin commensals restores skin health and alleviates symptoms. Notably, pigment normalization after tinea versicolor treatment may take weeks to months due to skin repair dynamics.

Comparatively, ketoconazole exhibits a broader antifungal spectrum than some other topical agents like selenium sulfide, with demonstrated lower irritancy potential. Clinical studies have shown significantly greater mycological cure rates with ketoconazole shampoo versus placebo, underscoring its effective antifungal mechanism. The lack of resistance development further highlights its robust mechanism of action against pathogenic fungi.

Pharmacological Actions

Broad-spectrum antifungal activity against dermatophytes and yeasts including Trichophyton spp., Microsporum spp., Epidermophyton floccosum, Candida spp., and Malassezia spp.
Disruption of fungal cell membrane ergosterol synthesis leading to increased cell membrane permeability and fungal cell death.
Reduction of fungal colonization on skin and scalp surfaces resulting in resolution of tinea versicolor, dandruff, and seborrheic dermatitis.
Anti-inflammatory properties secondary to reduction of fungal antigen burden, helping relieve pruritus and irritation.
Low irritancy potential compared to other antifungal shampoos such as selenium sulfide formulations.
Minimal systemic absorption when used topically, which reduces systemic adverse effects and drug interactions.
No reported development of fungal resistance with topical therapy indicating sustained efficacy.
Selective action on fungal cytochrome P450 14-alpha demethylase sparing human homolog enzymes significantly.
Effective in both single-dose and multi-dose regimens providing flexible therapeutic options.

Therapeutic Or Clinical Uses

Treatment of tinea (pityriasis) versicolor caused by Pityrosporum orbiculare (Malassezia furfur).
Management of dandruff associated with seborrheic dermatitis due to Malassezia ovale.
Used to reduce scalp flaking, scaling, and pruritus related to fungal colonization.
Topical antifungal therapy for superficial fungal infections of the skin and scalp.
Adjunctive treatment in recurrent tinea versicolor to reduce relapse frequency.
Alternative to systemic antifungals for mild to moderate cutaneous fungal infections when systemic therapy is contraindicated.
Treatment of seborrheic dermatitis presenting with erythema and scaling.
Reduction of fungal load prior to dermatological procedures in susceptible patients.
Relief of symptoms associated with fungal colonization including itching, irritation, and erythema.
Management of fungal scalp infections in immunocompetent adults.
Off-label use in some dermatologic conditions associated with Malassezia species.

Side Or Adverse Effects

Mild scalp irritation including itching and burning sensation.
Contact dermatitis or hypersensitivity reactions including rash and urticaria.
Hair discoloration and abnormal hair texture reported post-therapy.
Removal or alteration of curl pattern in permanently waved hair.
Dryness of the scalp and hair leading to flaking or mild dryness.
Localized application site reactions such as erythema or stinging.
Rare reports of angioedema and severe hypersensitivity reactions.
Increased hair shedding observed in a very small percentage of patients (<1%).
Scalp pustules and mild dermatologic eruptions post-application in isolated cases.
Post-marketing reports of alopecia associated with use.
Transient pruritus during or after shampooing.
No phototoxic or photoallergic reactions demonstrated.
No systemic adverse effects due to minimal absorption.
Rare incidences of hypersensitivity reactions requiring drug discontinuation.
Infrequent reports of dry skin with continued use.

Precautions

Avoid contact with eyes and mucous membranes to prevent irritation.
Discontinue use immediately if signs of hypersensitivity or severe skin reactions occur.
Use with caution in patients with known hypersensitivity to ketoconazole or shampoo excipients.
Inform patients about potential for hair texture changes or hair discoloration.
Not established as safe or effective in pediatric populations; avoid use in children unless prescribed.
Pregnancy Category C; use only if potential benefits justify possible risks and avoid systemic exposure.
Caution advised when used by nursing mothers; minimal systemic absorption but data limited.
Patients should be counseled on proper application and avoidance of prolonged contact.
Monitor for allergic reactions such as urticaria, angioedema, or generalized rash.
Avoid excessive frequency of use beyond prescribed dosing to minimize irritation.
Use cautiously in patients with sensitive skin prone to dermatitis or eczema.
Not intended for oral ingestion; in case of accidental ingestion, seek appropriate care.
Prolonged use beyond recommended duration may increase risk of local adverse effects.
Patients advised to report any unexpected skin changes or symptoms during therapy.
Appropriate storage conditions to maintain product stability should be observed.

Warnings

Do not use in individuals with known hypersensitivity to ketoconazole or any shampoo ingredients.
Severe hypersensitivity reactions including anaphylaxis have been reported post-marketing; discontinue if such reactions occur.
Avoid contact with eyes; if contact occurs, rinse immediately with plenty of water.
Use only as directed; excessive or prolonged use may lead to increased irritation or sensitivity.
Not for oral, ophthalmic, or intravaginal administration; to be used topically only.
Safety and effectiveness in children have not been established; not recommended in pediatric patients.
Use in pregnancy only if clearly needed as systemic absorption is minimal but teratogenicity noted with oral use in animals.
Discontinue use if severe skin irritation, rash, or swelling develop and seek medical advice promptly.
Not to be used concurrently with other topical antiseptics or treatments without physician consultation.
Careful patient counseling is important to minimize inadvertent exposure to sensitive areas.
Avoid applying to open wounds or severely inflamed skin unless advised.
Store out of reach of children to prevent accidental ingestion.
Do not use product if the packaging is damaged or the shampoo appearance has changed.
Patients should be informed that pigment normalization after treatment may take several weeks to months.
In case of overdose or accidental ingestion, supportive measures should be taken; induced emesis is contraindicated due to risk of aspiration.

Contraindication

Known hypersensitivity or allergy to ketoconazole or any components of the shampoo formulation.
Patients who have experienced allergic reactions or severe sensitivity to imidazole antifungals.
Contraindicated for oral or mucosal use; shampoo intended for external topical application only.
Should not be used in patients with damaged skin or open wounds in the affected area without medical supervision.
Contraindicated in individuals with a history of severe anaphylactic reactions to ketoconazole-containing products.
Avoid use if any previous adverse dermatologic reactions to ketoconazole shampoo were documented.
Not recommended in pediatric patients due to lack of established safety data.
Avoid use during pregnancy unless potential benefits outweigh risks due to lack of adequate human studies.
Contraindicated in patients with scalp infections caused by non-susceptible organisms where ketoconazole would be ineffective.
Avoid concurrent use with other topical medications that may cause irritation or allergic reactions without physician guidance.

Drug Interactions

Minimal potential for systemic drug interactions when used topically due to lack of significant systemic absorption.
No clinically relevant interactions with systemic medications reported for ketoconazole shampoo.
Concurrent use with other topical antifungal or antiseptic agents may increase risk of local irritation; clinical monitoring recommended.
No significant interactions with cytochrome P450 enzymes expected from topical application unlike oral ketoconazole.
No documented interactions with systemic drugs including anticoagulants or immunosuppressants.
Caution advised when used with other shampoos containing irritants or allergens to prevent additive scalp sensitivity.
No known interaction with cosmetic hair products, but patients should avoid immediate application of multiple agents.
Patients should inform healthcare providers of all topical and systemic treatments to avoid unexpected skin reactions.
No dose adjustments necessary due to absence of systemic exposure and metabolism.
No data indicating interference with hormonal contraceptives or other common medications.

Preparations Of The Drug

Ketoconazole Shampoo 2% aqueous suspension as a red-orange colored liquid.
Formulated with excipients such as sodium laureth sulfate, disodium laureth sulfosuccinate, cocamide diethanolamide, hydrochloric acid, PEG-120 methyl glucose dioleate, imidurea, sodium chloride, sodium hydroxide, fragrance, FD&C Red No. 40, and purified water.
Packaged in 120 mL non-breakable plastic bottles suitable for patient use.
Stored at controlled room temperature between 20ºC to 25ºC (68ºF to 77ºF) and protected from light to maintain stability.
Not combined with other active drugs; single-agent topical antifungal shampoo preparation.
Contains coloring agents and surfactants to facilitate cleaning, lathering, and delivery of active ingredient.
Labeled for prescription-only use with detailed instructions for topical application.
Supplied with child-resistant caps to minimize accidental ingestion risks.
No oral, ophthalmic, or intravaginal formulations in this preparation; strictly topical.
Manufactured and distributed by Cosette Pharmaceuticals, Inc.
Packaging includes a nationally recognized drug code (NDC 0713-0592-04) for identification.
Product designed to meet USP standards for controlled room temperature storage.