Ketoconazole

The selected tablet label covers blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis and paracoccidioidomycosis after failure or intolerance of other therapies. Use only when effective alternatives are unavailable or not tolerated and benefits outweigh risks. Confirm the infection clinically and in the laboratory. Oral tablets are not indicated for onychomycosis, cutaneous dermatophyte or Candida infections, and are unsuitable for fungal meningitis because CSF penetration is poor. Oral ketoconazole is not a first-line antifungal.

The selected 2% cream treats labeled susceptible tinea corporis, cruris and pedis, pityriasis versicolor, cutaneous candidiasis and seborrheic dermatitis. The selected prescription 2% shampoo is labeled for pityriasis versicolor due to Malassezia; dandruff or seborrheic dermatitis shampoo use should not be described as this product’s approved indication merely because its label discusses trials.

Nizoral 1% shampoo controls dandruff-associated flaking, scaling and itching. Its Drug Facts permits self-use from age 12; younger children need a doctor. Foam, gel, veterinary combinations, compounded products and endocrine or prostate-cancer oral regimens are outside this review. The selected tablet label does not approve ketoconazole for Cushing syndrome or prostate cancer.

Adults start 200 mg orally once daily; if the expected clinical response is inadequate, the label permits 400 mg once daily. Do not exceed 400 mg/day. Take with a meal for maximal absorption. The label describes a usual systemic treatment duration of 6 months, continuing until active infection subsides; the infection specialist determines whether this restricted agent is appropriate and the actual course.

The oral label reports 3.3–6.6 mg/kg once daily in small numbers of children over 2 years, not a well-established pediatric protocol; it has not been systematically studied at any pediatric age and has no adequate information below 2 years. Use only if benefit outweighs risk. Acute or chronic liver disease contraindicates tablets. No numerical renal adjustment table is provided; renal PK observations do not remove toxicity or interacting-drug restrictions.

For labeled pityriasis versicolor, apply to damp affected skin and a wide surrounding margin, lather, leave for 5 minutes and rinse with water. The selected label says one application should suffice. This is distinct from a recurring dandruff regimen. Pigment recovery may take months despite successful treatment.

For adults and children 12 or older: wet hair thoroughly, generously lather and rinse; repeat. Use every 3–4 days for up to 8 weeks or as a doctor directs, then only as needed for dandruff. Under 12: ask a doctor. Stop and ask a doctor if a rash develops or the condition worsens or fails to improve within 2–4 weeks.

Tablets: hypersensitivity to ketoconazole, acute or chronic liver disease, and specified interacting drugs. Prohibited combinations include dofetilide, quinidine, pimozide, cisapride, methadone, disopyramide, dronedarone, ranolazine, lurasidone, selected ergot alkaloids, irinotecan, oral midazolam, alprazolam, triazolam, felodipine, nisoldipine, tolvaptan, eplerenone, lovastatin and simvastatin. Colchicine requires special care: the contraindication text lists it, while the interaction table distinguishes contraindicated use with renal or hepatic impairment; do not prescribe that combination without resolving both current product labels.

Cream and 2% shampoo are contraindicated for hypersensitivity to their active or excipient ingredients. OTC shampoo says not to use with ingredient allergy or a broken/inflamed scalp. These topical labels do not carry the oral liver-disease contraindication.

The selected oral tablet box emphasizes restricted use, potentially fatal hepatotoxicity and QT-related interactions. The reviewed cream and shampoos have no boxed warning. Oral risk is not a reason to replace route-specific topical precautions with tablet monitoring requirements.

Oral reports include nausea, vomiting, abdominal symptoms, headache, dizziness, rash, liver injury, adrenal insufficiency and endocrine effects such as gynecomastia or erectile dysfunction; severe allergy is possible. Cream can cause burning, stinging, itching, irritation or contact dermatitis. Shampoo can cause irritation, dryness, itching, hair texture/color changes, alopecia or allergic reactions. Postmarketing reports do not establish a reliable frequency.

Oral ketoconazole can markedly increase exposure to CYP3A4 or P-glycoprotein substrates. Beyond prohibited combinations, opioids, immunosuppressants, anticoagulants, atorvastatin, some antipsychotics, inhaled/systemic corticosteroids and other medicines may need avoidance, dose changes or monitoring. Fentanyl exposure can increase enough to cause fatal respiratory depression; coumarin anticoagulation needs closer monitoring. The selected interaction table extends its contraindicated or not-recommended combination advice through 1 week after oral treatment ends. This is not a universal washout for every medicine.

PPIs, H2 blockers and antacids reduce tablet absorption. The selected label advises an acidic beverage with acid-reducing treatment and antacids at least 1 hour before or 2 hours after tablets; a clinician must manage efficacy and gastric-acidity changes. Potent CYP3A4 inducers such as rifampicin, carbamazepine or phenytoin may reduce efficacy; the label advises avoiding them from 2 weeks before and during therapy unless benefits outweigh risks. Potent inhibitors can raise ketoconazole exposure. Do not self-increase beyond the 400 mg/day limit.

The reviewed topical labels do not supply a systemic drug-interaction dosing table, and studied cream or scalp-shampoo use produced undetectable plasma levels at the stated assay limits. This cannot establish zero exposure for all application sites, damaged skin or other formulations. Do not automatically apply oral interaction dose algorithms to topical use, or assume that an interacting medicine is safe with tablets because shampoo was tolerated.

Oral human pregnancy studies are inadequate and animal developmental harm is described; tablets should be used only when potential benefit justifies fetal risk. The tablet label says treated mothers should not breastfeed. Cream and 2% shampoo also lack adequate pregnancy studies; assess benefit and risk. For cream, the label calls for a nursing-versus-drug decision; for 2% shampoo it advises caution despite undetectable plasma levels in scalp studies. OTC shampoo says ask a doctor before use during pregnancy or breastfeeding.

The limited oral pediatric dose experience is not an established regimen for infants or routine skin disease. Pediatric safety/effectiveness are not established for the reviewed prescription cream or 2% shampoo; OTC 1% shampoo permits age-12-plus directions and refers younger children to a doctor. No separate validated geriatric oral dosing algorithm is given; assess liver disease, polypharmacy and physiologic vulnerability.

Oral liver disease is a contraindication even though the PK text reports no significant overall difference in studied impairment. No specific renal dose adjustment is supplied, but renal impairment can change the safety of coadministered drugs, especially colchicine. Adrenal disease or prolonged stress requires adrenal-function monitoring. Topical labels do not provide renal/hepatic dose tables; select the actual product and avoid inferring oral-dose rules.

Ketoconazole inhibits fungal lanosterol 14-alpha-demethylase, reducing ergosterol and altering fungal membrane structure/function. Oral inhibition of mammalian steroid synthesis explains adrenal and testosterone effects; CYP3A4 and transporter inhibition explains many interactions. It is not a selective fungal effect at all systemic exposures.

Acid-dependent oral absorption is greatest with food; peak levels follow in roughly 1–2 hours. Protein binding is about 99%, CSF penetration poor and hepatic CYP3A4 metabolism produces inactive metabolites. Elimination is biphasic, approximately 2 hours initially and 8 hours later; bile/feces are the main elimination pathway. These observations do not justify liver-disease use.

A cream study on normal volunteers found no detectable blood level at a 5 ng/mL assay limit over 72 hours after one application. Scalp studies of 2% shampoo likewise found no detectable plasma ketoconazole. These are studied-use findings, not a guarantee for every site or patient. Versicolor pigment changes can outlast fungal clearance, and recurrence may occur because Malassezia is part of normal skin flora.

Before tablets document infection, evaluate liver disease, obtain ALT, AST, alkaline phosphatase, bilirubin, GGT, PT/INR and viral-hepatitis assessment as appropriate. Arrange weekly ALT and the interruption thresholds described under Safety; reassess all medicines and clinical response. Monitor adrenal function when indicated. QT, electrolytes and interacting-drug monitoring depend on the patient and combination; no universal ECG schedule is supplied.

With tablets, promptly report jaundice, dark urine, pale stool, unusual fatigue, anorexia, nausea/vomiting or abdominal pain; avoid alcohol and discuss all new medicines. Obtain emergency care for fainting/palpitations with severe symptoms or trouble breathing/swelling. For topicals, avoid eyes, stop for allergy/irritation and follow the exact course. Reconsider the cream diagnosis if the labeled course gives no improvement; OTC shampoo requires review if not improved in 2–4 weeks.

Seek urgent medical or Poison Control advice after an oral overdose or swallowed topical product; emergency symptoms require emergency care. The tablet label describes supportive care and clinician-administered charcoal early after overdose. The 2% shampoo label advises supportive treatment without induced vomiting or gastric lavage because of aspiration risk. Do not attempt home decontamination.

Product

Strides ketoconazole USP 200 mg tablet

Route

Oral; prescription only

Appearance

White to off-white round, scored; S / 500 on scored side

Example package

100 tablets · NDC 64380-827-06

Reviewed products: Strides 200 mg tablets; Fougera cream 2% in 15, 30 and 60 g tubes (15 g NDC 0168-0099-15); Padagis 2% red-orange shampoo in a 120 mL bottle (NDC 45802-465-64); Nizoral 1% OTC shampoo. Shampoo percentages are weight concentrations, not an oral dose. Foam, gel and other manufacturers require their own labeling.

Tablets: 20–25°C (68–77°F), protected from moisture. Selected cream: below 25°C (77°F). Prescription 2% shampoo: 20–25°C, protected from light. OTC 1% shampoo: 20–25°C; check the package expiration. Keep all products out of children’s reach. Do not invent one opened-container discard interval for these different products.