Dosing and uses of Sporanox, Onmel (itraconazole)
Adult dosage forms and strengths
capsule
- 100mg
oral solution
- 10mg/mL
tablet
- 200mg
Life-Threatening Infections
200 mg PO q8hr initially for 3-4 days, then 200-400 mg/day for at least 3 months
Blastomycosis
Immunocompromised and non-immunocompromised patients: 200 mg PO q8hr for 3 days, then 200 mg PO q12hr for 6-12 months; initiate therapy with aproximately 2 weeks of amphotericin B if infection is moderately severe to severe
Aspergillosis
Immunocompromised and non-immunocompromised patients: 200-400 mg/day PO; may be used in combination with corticosteroids
Life-threatening infection: Administer a loading dose of 200 mg PO TID for first 3 days of therapy; continue treatment for at least 3 months and until clinical and laboratory evidence suggest that infection has resolved; current dose on candidiasis is for esophageal candidiasis
Histoplasmosis
Immunocompromised and non-immunocompromised patients: 200 mg/day PO; may be increased by 100 mg/day increments; not to exceed 400 mg/day
Onychomycosis in Non-immunocompromised Patients
Fingernails: 2 treatment pulses, each consisting of 200 mg q12hr for 1 week
Toenails, with or without fingernail involvement: 200 mg/day PO for 12 weeks
Oral Candidiasis
Oral solution: 100-200 mg/day for at least 3 weeks; continued for 2 weeks after symptom resolution
Refractory to fluconazole: 100 mg PO q12hr for 2-4 weeks
Swish in mouth 10 mL at a time for several seconds, then swallow; take without food if possible
Oropharyngeal candidiasis in patients unresponsive to fluconazole: 200 mg PO qDay for 1-2 weeks
Otomycosis (Orphan)
Suspension: Topical treatment of fungal otitis externa (otomycosis)
Orphan indication sponsor
- Fairfield Clinical Trials, LLC; 200 Steep Hill Road; Weston, CT 06883
Pediatric dosage forms and strengths
capsule
- 100mg
oral solution
- 10mg/mL
Systemic Fungal Infections (Off-label)
<3 years: Safety and efficacy not established
≥3 years: 3-5 mg/kg/day PO initially (limited data)
Candidiasis (Off-label)
HIV exposed or positive
Infants and children
- Oropharyngeal: 2.5 mg/kg/dose oral solution BID; not to exceed 200 mg/day for 7-14 days; 400 mg qDay if fluconazole refractory
- Esophageal: 5 mg/kg/day oral solution qDay or divided BID for 14-21 days
Adolescents
- Oropharyngeal: 200 mg oral solution qDay for 7-14 days
- Esophageal: 200 mg oral solution qDay for 14-21 days
Histoplasmosis (Off-label)
HIV exposed or positive
Infants and children
- Mild disseminated disease: 2-5 mg/kg/dose TID for 3 days; followed by twice daily for 12 months; not to exceed 200 mg/dose
- Relapse prevention: Oral solution: 5 mg/kg/dose BID; not to exceed 400 mg/day
Adolescents
- 200 mg PO TID for 3 days; then 200 mg BID for at least 12 months
Cystic Fibrosis (Orphan)
Orphan designation for inhaled itraconazole using iSPERSE technology dry powder delivery platform to improve therapeutic delivery to the lungs by maximizing local concentrations and reducing systemic side effects
Sponsor
- Pulmatrix, Inc; 99 Hayden Avenue; Lexington, Massachusetts 02421
Sporanox, Onmel (itraconazole) adverse (side) effects
>10%
Nausea (11%)
1-10%
Rash (9%)
Vomiting (5%)
Edema (4%)
Headache (4%)
Abnormal liver function test results (3%)
Diarrhea (3%)
Fever (3%)
Hypertension (3%)
Pruritus (3%)
Fatigue (2-3%)
Abdominal pain (2%)
Dizziness (2%)
Hypertriglyceridemia (2%)
Hypokalemia (2%)
Albuminuria (1%)
Anorexia (1%)
Decreased libido (1%)
Hepatitis (1%)
Malaise (1%)
Postmarketing Reports
Blood and Lymphatic System Disorders: Leukopenia, neutropenia, thrombocytopenia
Immune System Disorders: Anaphylaxis; anaphylactic, anaphylactoid and allergic reactions; serum sickness; angioneurotic edema
Nervous System Disorders: Peripheral neuropathy, paresthesia, hypoesthesia, tremor
Eye Disorders: Visual disturbances, including vision blurred and diplopia
Ear and Labyrinth Disorders: Transient or permanent hearing loss
Cardiac Disorders: Congestive heart failure
Respiratory, Thoracic and Mediastinal Disorders: Pulmonary edema, dyspnea
Gastrointestinal Disorders: Pancreatitis, dysgeusia
Hepatobiliary Disorders: Serious hepatotoxicity (including some cases of fatal acute liver failure), hepatitis
Skin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, erythema multiforme, exfoliative dermatitis, leukocytoclastic vasculitis, alopecia, photosensitivity, urticaria
Musculoskeletal and Connective Tissue Disorders: Arthralgia
Renal and Urinary Disorders: Urinary incontinence, pollakiuria
Reproductive System and Breast Disorders: Erectile dysfunction
General Disorders and Administration Site: Peripheral edema
Warnings
Black box warnings
Congestive heart failure
- Do not use for the treatment of onychomycosis in patients with ventricular dysfunction (eg, history of CHF)
- If signs or symptoms of CHF occur during itraconazole therapy, discontinue administration
Contraindicated drug interactions
- Itraconazole is potent CYP4503A4 inhibitor
- Coadministration of the following drugs are contraindicated with itraconazole: methadone, disopyramide, dofetilide, dronedarone, quinidine, ergot alkaloids (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ranolazine, eplerenone, cisapride, lovastatin, simvastatin, ticagrelor, and, in patients with varying degrees of renal or hepatic impairment, colchicine, fesoterodine, telithromycin, and solifenacin
- Coadministration with itraconazole can cause elevated plasma concentrations of these drugs and may increase or prolong both the pharmacologic effects and/or adverse reactions to these drugs (eg, increased plasma concentrations of some of these drugs can lead to QT prolongation and ventricular tachyarrhythmias including occurrences of torsades de pointes)
Contraindications
Onychomycosis treatment in pregnancy or contemplated pregnancy
Hypersensitivity
Contraindicated with certain CYP3A4 substrate drugs (see Black box warnings)
Renal or hepatic impairment
Treatment of onychomycosis in women who are pregnant or plan to become pregnant
Ventricular dysfunction (eg, current or previous CHF), except for treatment of life-threatening or other serious infections
Cautions
Discontinue if liver disease develops, and perform liver function tests; readministration discouraged
Prolongs QT interval; caution with concurrent QT-prolonging drugs or congenital long QT (see Black box warnings for drugs contraindicated for use with itraconazole)
Not for the treatment of other indications in patients with evidence of ventricular dysfunction unless benefit clearly outweighs risks; practitioners should carefully review risks and benefits; risk factors include cardiac disease such as ischemic and valvular disease; significant pulmonary disease such as chronic obstructive pulmonary disease; and renal failure and other edematous disorders; inform patients of signs and symptoms of CHF, and treat with caution; monitor for signs and symptoms of CHF during treatment; if signs or symptoms of CHF appear during therapy, discontinue treatment
Oral capsule and oral solution are not bioequivalent; do not use interchangeably
Parenteral form is incompatible with most aqueous solutions; use dedicated line, and do not mix with other drugs in any way
If neuropathy occurs that may be attributable to itraconazole, discontinue treatment
If cystic fibrosis patient does not respond to itraconazole, consider switching to alternative therapy; large differences in itraconazole pharmacokinetic parameters observed in cystic fibrosis patients
Transient or permanent hearing loss reported in patients receiving treatment with itraconazole; several reports included concurrent administration of quinidine, which is contraindicated; the hearing loss usually resolves when treatment is stopped, but can persist in some patients
May cause CNS depression, which may impair physical or mental abilities; caution when operating heavy machinery or performing tasks that require mental alertness
Rare cases of serious hepatotoxicity reported in patients without preexisting liver disease or risk factors; use caution in patients with preexisting hepatic impairment; monitor liver function closely and adjust dose as necessary; not recommended for use in patients with elevated liver enzymes, active liver disease, or prior hepatotoxic reactions to other drugs unless the expected benefit exceeds the risk of hepatotoxicity
Use with caution in patients with renal impairment; not studied
Absorption of itraconazole capsules is reduced when gastric acidity reduced; administer capsules with acidic beverage in patients with reduced gastric acidity and do not administer concomitantly with acid suppressive therapy; monitor for response
Only oral solution shown to be effective in oral/esophageal candidiasis; oral solution not recommended in patients at immediate risk for systemic candidiasis
Itraconazole should not be used to treat voriconazole-refractory aspergillosis; both agents may share resistance mechanisms
Pregnancy and lactation
Pregnancy category: C
Lactation: Drug enters breast milk; weigh risk against benefit
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Sporanox, Onmel (itraconazole)
Mechanism of action
Triazole antifungal agent; inhibits cytochrome P450-dependent synthesis of ergosterol, which in turn inhibits cell-membrane formation
Absorption
Peak plasma time: Oral solution with fasting, 2.2 hr; capsule with food, 5 hr
Peak plasma concentration: Oral solution with fasting, 544 ng/mL; capsule with food, 302 ng/mL
Distribution
Protein bound: 99.8%
Vd: 796 L or 10 L/kg
Metabolism
Metabolized by hepatic enzyme CYP3A4
Enzymes inhibited: CYP3A4
Elimination
Half-life: 64±32 hr
Excretion: Urine, feces
Administration
Oral Administration
Capsule: Take with food if possible
Oral solution: Swish in mouth 10 mL at a time for several seconds, then swallow; take without food if possible
IV Preparation
Precise dilution (3.33 mg/mL) is required to maintain stability and avoid precipitate formation
Dilute with NS only; do not use dextrose or lactated Ringer solution
Add 25 mL (1 ampule = 250 mg) to 50 mL Ns
Mix and withdraw 15 mL of solution before infusing
IV Administration
Using flow-control device, infuse 60 mL of diluted solution (200 mg itraconazole; pH 4.8) over 60 minutes, using extension line and infusion set provided
After administration, flush infusion set with 15-20 mL NS over 30 seconds to 15 minutes via 2-way stopcock; do not use bacteriostatic Ns
Discard entire infusion set
