Itraconazole Oral Solution

Itraconazole is an antifungal medication.

Itraconazole is used to treat infections caused by fungus, which can invade any part of the body including the lungs, mouth or throat, toenails, or fingernails.

Itraconazole may also be used for purposes not listed in this medication guide.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• To gain the most benefit, do not miss doses.
• Keep taking itraconazole oral solution as you have been told by your doctor or other health care provider, even if you feel well.
• Take this medicine at the same time of day.
• Take itraconazole oral solution without food.
• Measure liquid doses carefully. Use the measuring device that comes with this medicine. If there is none, ask the pharmacist for a device to measure itraconazole oral solution.
• For yeast infections in the mouth, throat, or swallowing tube (esophagus): Swish in your mouth for a few seconds and swallow.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of low potassium levels like muscle pain or weakness, muscle cramps, or a heartbeat that does not feel normal.
• Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
• A burning, numbness, or tingling feeling that is not normal.
• Not able to pass urine or change in how much urine is passed.
• Pain when passing urine.
• Chest pain or pressure or a fast heartbeat.
• Change in sex ability.
• Low mood (depression).
• Very bad dizziness or passing out.
• Fever or chills.
• Hair loss.
• Joint pain.
• Ringing in ears.
• Any unexplained bruising or bleeding.
• Change in eyesight.
• Feeling very tired or weak.
• Hearing loss has happened with this medicine. Many times this has happened when itraconazole oral solution was taken along with quinidine. This will most often go away after this medicine is stopped but may last for a long time in some people. Talk with your doctor.
• Very bad and sometimes deadly liver problems have rarely happened with itraconazole oral solution. Sometimes this happened within 7 days of starting this drug. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Belly pain.
• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Dizziness.
• Gas.
• Runny nose.
• Bad taste in your mouth.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Itraconazole, USP is an azole antifungal agent. Itraconazole, USP is a 1:1:1:1 racemic mixture of four diastereomers (two enantiomeric pairs), each possessing three chiral centers. It may be represented by the following structural formula and nomenclature:

(±)-1-[(R*)-sec-butyl]-4-[p-[4-[p-[[(2R*,4S*)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-Δ2-1,2,4-triazolin-5-one mixture with (±)-1-[(R*)-sec-butyl]-4-[p-[4-[p-[[(2S*,4R*)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-Δ2-1,2,4-triazolin-5-one

or

(±)-1-[(RS)-sec-butyl]-4-[p-[4-[p-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-Δ2-1,2,4-triazolin-5-one.

Itraconazole, USP has a molecular formula of C35H38Cl2N8O4 and a molecular weight of 705.64. It is a white to slightly yellowish powder. It is insoluble in water, very slightly soluble in alcohols, and freely soluble in dichloromethane. It has a pKa of 3.70 (based on extrapolation of values obtained from methanolic solutions) and a log (n-octanol/water) partition coefficient of 5.66 at pH 8.1.

Itraconazole Oral Solution contains 10 mg of itraconazole, USP per mL, solubilized by hydroxypropyl-β-cyclodextrin (400 mg/mL) as a molecular inclusion complex. Itraconazole Oral Solution is clear and yellowish in color with a target pH of 2. Other ingredients are caramel flavor, cherry flavor, hydrochloric acid, propylene glycol, purified water, sodium hydroxide, sodium saccharin, and sorbitol. Hydrochloric acid solution or sodium hydroxide solution may be added for adjustment of pH.

Oropharyngeal Candidiasis:

Two randomized, controlled studies for the treatment of oropharyngeal candidiasis have been conducted (total n=344). In one trial, clinical response to either 7 or 14 days of Itraconazole Oral Solution, 200 mg/day, was similar to fluconazole tablets and averaged 84% across all arms. Clinical response in this study was defined as cured or improved (only minimal signs and symptoms with no visible lesions). Approximately 5% of subjects were lost to follow-up before any evaluations could be performed. Response to 14 days therapy of Itraconazole Oral Solution was associated with a lower relapse rate than 7 days of itraconazole therapy. In another trial, the clinical response rate (defined as cured or improved) for Itraconazole Oral Solution was similar to clotrimazole troches and averaged approximately 71% across both arms, with approximately 3% of subjects lost to follow-up before any evaluations could be performed. Ninety-two percent of the patients in these studies were HIV seropositive.

In an uncontrolled, open-label study of selected patients clinically unresponsive to fluconazole tablets (n=74, all patients HIV seropositive), patients were treated with Itraconazole Oral Solution 100 mg b.i.d. (Clinically unresponsive to fluconazole in this study was defined as having received a dose of fluconazole tablets at least 200 mg/day for a minimum of 14 days.) Treatment duration was 14 to 28 days based on response. Approximately 55% of patients had complete resolution of oral lesions. Of patients who responded and then entered a follow-up phase (n=22), all relapsed within 1 month (median 14 days) when treatment was discontinued. Although baseline endoscopies had not been performed, several patients in this study developed symptoms of esophageal candidiasis while receiving therapy with Itraconazole Oral Solution. Itraconazole Oral Solution has not been directly compared to other agents in a controlled trial of similar patients.

Esophageal Candidiasis:

A double-blind randomized study (n=119, 111 of whom were HIV seropositive) compared Itraconazole Oral Solution (100 mg/day) to fluconazole tablets (100 mg/day). The dose of each was increased to 200 mg/day for patients not responding initially. Treatment continued for 2 weeks following resolution of symptoms, for a total duration of treatment of 3 to 8 weeks. Clinical response (a global assessment of cured or improved) was not significantly different between the two study arms, and averaged approximately 86% with 8% lost to follow-up. Six of 53 (11%) itraconazole-treated patients and 12/57 (21%) fluconazole-treated patients were escalated to the 200 mg dose in this trial. Of the subgroup of patients who responded and entered a follow-up phase (n=88), approximately 23% relapsed across both arms within 4 weeks.

Congestive Heart Failure:

Itraconazole Oral Solution should not be administered to patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF except for the treatment of life-threatening or other serious infections. (See BOXED WARNING,WARNINGS, PRECAUTIONS: Drug Interactions-Calcium Channel Blockers, ADVERSE REACTIONS: Post-marketing Experience and CLINICAL PHARMACOLOGY: Special Populations.)

Drug Interactions

Co-administration of a number of CYP3A4 substrates are contraindicated with itraconazole, USP. Plasma concentrations increase for the following drugs: methadone, disopyramide, dofetilide, dronedarone, quinidine, ergot alkaloids (such as dihydroergotamine, ergometrine (ergonovine), ergotamine, methylergometrine (methylergonovine)), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ranolazine, eplerenone, cisapride, lovastatin, simvastatin, ticagrelor and, in subjects with varying degrees of renal or hepatic impairment, colchicine, fesoterodine, telithromycin and solifenacin. (See PRECAUTIONS: Drug Interactions Section for specific examples.) This increase in drug concentrations caused by co-administration with itraconazole, USP may increase or prolong both the pharmacologic effects and/or adverse reactions to these drugs. For example, increased plasma concentrations of some of these drugs can lead to QT prolongation and ventricular tachyarrhythmias including occurrences of torsade de pointes, a potentially fatal arrhythmia. Specific examples are listed in PRECAUTIONS: Drug Interactions.

Itraconazole Oral Solution is contraindicated for patients who have shown hypersensitivity to itraconazole, USP. There is limited information regarding cross-hypersensitivity between itraconazole, USP and other azole antifungal agents. Caution should be used when prescribing itraconazole, USP to patients with hypersensitivity to other azoles.

Treatment of Oropharyngeal and Esophageal Candidiasis:

The solution should be vigorously swished in the mouth (10 mL at a time) for several seconds and swallowed.

The recommended dosage of Itraconazole Oral Solution for oropharyngeal candidiasis is 200 mg (20 mL) daily for 1 to 2 weeks. Clinical signs and symptoms of oropharyngeal candidiasis generally resolve within several days.

For patients with oropharyngeal candidiasis unresponsive/refractory to treatment with fluconazole tablets, the recommended dose is 100 mg (10 mL) b.i.d. For patients responding to therapy, clinical response will be seen in 2 to 4 weeks. Patients may be expected to relapse shortly after discontinuing therapy. Limited data on the safety of long-term use (>6 months) of Itraconazole Oral Solution are available at this time.

The recommended dosage of Itraconazole Oral Solution for esophageal candidiasis is 100 mg (10 mL) daily for a minimum treatment of three weeks. Treatment should continue for 2 weeks following resolution of symptoms. Doses up to 200 mg (20 mL) per day may be used based on medical judgment of the patient’s response to therapy.

Itraconazole Oral Solution and itraconazole capsules should not be used interchangeably. Patients should be instructed to take Itraconazole Oral Solution without food, if possible. Only Itraconazole Oral Solution has been demonstrated effective for oral and/or esophageal candidiasis.

Use in Patients with Renal Impairment:

Limited data are available on the use of oral itraconazole, USP in patients with renal impairment. Caution should be exercised when this drug is administered in this patient population. (See CLINICAL PHARMACOLOGY: Special Populations and PRECAUTIONS.)

Use in Patients with Hepatic Impairment:

Limited data are available on the use of oral itraconazole, USP in patients with hepatic impairment. Caution should be exercised when this drug is administered in this patient population. (See CLINICAL PHARMACOLOGY: Special Populations, WARNINGS, and PRECAUTIONS.)

Itraconazole Oral Solution, 10 mg/mL, is available in 150 mL amber glass bottles (NDC 65162-087-74) containing 10 mg of itraconazole, USP per mL.

Store at or below 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Do not freeze.

Keep out of reach of children.

ITRACONAZOLE (i tra KO na zole) is an antifungal medicine. It is used to treat certain kinds of fungal or yeast infections.

This drug also comes in other forms, including Oral capsule, Injectable solution, Oral tablet

This drug can cause serious side effects. See which side effects you should report to your doctor right away.

Know how to use your medication, and learn what might happen if you miss a dose.

Talk to your healthcare provider if you have any of these conditions.

Know what to watch for and get tips for reducing your risks while taking this drug.