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Azole Antifungals
July 26, 2009 | Leave a Comment
Type of Drug
Azole Antifungals
Brand Names
Generic Ingredient: Fluconazole 91 Diflucan
Generic Ingredient: Itraconazole Sporanox
Generic Ingredient: Ketoconazole 0
Extina Nizoral
Ketozole Xolegel
Generic Ingredient: Posaconazole Noxafil
Generic Ingredient: Voriconazole Wend
PlIM-fibed For
Fungal infections of the blood, mouth, throat, vagina, or central nervous system.
Fluconazole, posaconazole, and itraconazole can be used to treat opportunistic fungal infections that inflict many people with HIV or cancer whose immune systems have been compromised.
General Information
Azole antifungals are used to treat a variety of fungal organisms, including Candida, aspergillus, cryptococcus, blastomycosis, fusarium, histoplasmosis, and Scedosporium. They work by inhibiting important enzyme systems in the organisms they attack. These drugs are broken down in the liver.
Cautions and Warnings
Do not take azole antifungals if you are allergic or sensitive to any of their ingredients. People who are allergic to similar antifungals may also be allergic to these drugs, but cross-reactions are not common and serious allergic reaction is rare.
Azole antifungals can affect heart rhythm and should be used with caution if you have a history of abnormal heart rhythms.
Rarely, azole antifungals can cause liver damage. The drugs should be used with caution in people with liver disease. At least one in every 10,000 people who take ketOGonazole develop liver inflammation. The inflammation generally subsides when the drug is discontinued.
Voriconazole tablets contain lactose. They should not be taken by patients with rare hereditary problems of galactose intolerance, Lapp-lactase deficiency, or glucose-galactose malabsorption.
Rash may be an important sign of drug toxicity, especially in people with HIV or others with compromised immune function. Report any rashes, especially ones that do not heal readily, to your doctor.
These drugs can have very serious effects if combined with other medicines. See “Drug Interactions” for specific information.
Possible Side Effects
Side effects are generally more common among people with HIV.
Fluconazole
V Most common *wa)jsea, headache, rash, vomiting, ab- dominal pain, and diarrhea.
V Less common: liver toxicity, as measured by increases in specific lab tests. These changes in lab values are more common in people with HIV or cancer, who are more likely to be taking several drugs.
Possible Side Effects (continued)
V Rare: seizures and exfoliative skin disorders. People with
HIV or cancer who take fluconazole for fungal infections
may develop severe liver or skin problems. Contact your
doctor if you experience any side effect not listed above.
Itraconazole
• Most common: nausea, vomiting, and rash.
♦ Less common: diarrhea, abdominal pain, appetite loss, swelling in the legs or feet, fatigue, fever, feeling unwell, itching, headache, dizziness, reduced sex drive, tiredness, high blood pressure, liver or kidney function abnormalities, low blood potassium, and impotence.
♦ Rare: gas, sleeplessness, depression, ringing or buzzing in the ears, bronchitis, chest pain, coughing, and swollen or painful breasts in men or women. Contact your doctor if you experience any side effect not listed above.
Ketoconazole
✓ Common: nausea, vomiting, upset stomach, abdominal pain or discomfort, itching, and swollen breasts in men. Most of these side effects are mild and only a small number of people-1.5%—have to stop taking the drug because of severe side effects.
Posaconazole
✓ Most common: fever, headache, chills, swelling in the legs, appetite loss, dizziness, fluid accumulation, weakness, blood pressure changes, anemia, low white-blood-cell counts with or without fever, vaginal bleeding, diarrhea, nausea, vomiting, abdominal pain, constipation, upset stomach, mucous membrane irritation, rapid heart beat, bacteria in the blood, herpes infection, CMV infection, infection, sore throat, low blood potassium, low blood magnesium, high blood sugar, muscle and joint pain, back pain, low blood-platelet levels, ‘,-A-&ZVanO -blue marks, sleep%’Mess, cough, difficulty breathing, nosebleeds, and rash and itching.
♦ Common: upper respiratory infection, low blood calcium, and anxiety.
✓ Less common: tiredness, weakness, blurred vision, taste changes, and heart rhythm changes.
Drug Interactions
• Do not mix astemizole, cisapride, halofantrine, pimozide. quinidine, or terfenadine with itraconazole, ketoconazole, or posaconazole. Severe cardiac side effects may occur. Similarly, combining fluconazole with cisapride may cause cardiac events. Do not mix these medicines.
• Antacids interfere with the absorption of ketoconazole and itraconazole. Take antacids more than 2 hours after taking these drugs.
• Fluconazole and ketoconazole may increase the amount of the sulfonylurea-type antidiabetes drugs (eg. tolbutamide, glyburide, and glipizide) in the blood, causing low blood sugar. Cyclosporine, phenytoin, theophyiline, warfarin, and zidovudine (an HIV drug—also known as AZT) are similarly affected. Dosage adjustments of these drugs and monitoring may be required.
• Ketoconazole may also increase blood levels of HIV drugs including protease inhibitors and didanosine (ddl).
• Use caution when combining fluconazole with rifabutin, rifampin, tacromilus, and terfenadine. Dose adjustments may be necessary.
• Fluconazole and ketoconazole may interfere with contraceptive drugs. Consider using an alternative form of birth control.
• Hydrochlorothiazide may increase blood levels of fluconazole up to 40%.
• Do not mix ketoconazole with triazolam.
• Ketoconazole increases the effects of benzodiazepk”-_ se0atives, buspirone, carbamaze, ime. corticosteroids, digoxin, do(I8ptl15, Wodipine, nisoldipine, tacrolimus, tricyclic antidepressants, vinca-type alkaloids, and zolpidem. Dosage adjustments may be required.
• Do not mix itraconazole with dofetilide, ergot alkaloids, midazolam, or triazolam.
• Use caution when combining itraconazole with alfentanil, aripiprazole, buspirone, calcium channel blockers,
Possible Side Effects (continued) Voriconazole
✓ Most common: visual disturbances.
♦ Common: fever, rash, nausea, in blood infections, swelling the arms or legs, and
respiratory disorder.
carbamazepine, cilostazol, clarithromycin, corticosteroids, digoxin, erythromycin, halofantrine, haloperidol, sirolimus, tacrolimus, verapamil, vinca-type alkaloids, warfarin, and zolpidem. Dose adjustments may be necessary.
• Rarely, people who combine itraconazole or posaconazole with a statin-type blood-fat lowering drug experience muscle pain and destruction. The statin drug dose should be reduced. Some people who have experienced this interaction were also taking cyclosporine. cyclosporine dosages should be lowered when combined with itraconazole and a statin drug. Do not combine itraconazole with lovastatin or simvastin.
• Cimetidine, didanosine, famotidine, isoniazid, nizatidine, phenytoin, protease inhibitors, ranitidine, rifabutin, rifampin, and rifapentine may interfere with the effectiveness of itraconazole and posaconazole.
• Voriconazole should not be combined with astemizole, barbiturates, carbamazepine, cisapride, efavirenz, ergot drugs for migraines, pirnozide, quinidine, rifabutin, rifampin, sirolimus, and terfenadine.
• Serious increases in levels of cyclosporine and tacrolimus have been reported when mixed with posaconazole. Dosage adjustments are required.
• Posaconazole and an ergot drug should not be mixed.
• Voriconazole and posaconazole should be used with caution with benzodiazepine sedatives, calcium channel blockers, cyclosporine, methadone, statin-type drugs, sulfonylureatype antidiabetes drugs, tacrolimus, vinca-type anti-cancer drugs, and warfarin. Dosage adjustments of these drugs may be needed to avoid side effects.
• Combining voriconazole and contraceptive drugs, omeprazole, phenytoin, or a protease inhibitor (excluding indinavir) may require dose adjustments and frequent monitoring for drug toxicity.
• Combining voriconazole with an NNRTI for HIV can either increase or decrease blood levels of voriconazole and increase blood levels Qt the NNM~.Drug side effects may occur.
Food Interactions
Take voriconazole at least 1 hour before or 2 hours after a meal. Take ketoconazole and itraconazole with food or meals. Posaconazole must be taken with food or a nutritional supplement. Another treatment should be considered if this requirement cannot be met.
Usual Dose
6uconazole
Adult and Child (age 14 and over): 100-400 mg once a day. Child: 1.3-5.5 mg per lb. of body weight once a day; no more
than 400 mg a day.
Itraconazole
Adult: 200-600 mg once a day.
Child (age 3-16): 100 mg a day has been prescribed, but the long-term effects of itraconazole in children are not known.
Ketoconazole
Oral
Adult: 200-400 mg once a day. Treatment may continue for several months, depending on the type of infection being treated.
Child (age 2 and over): 1.5-3 mg per lb. of body weight once a day.
Child (under age 2): not recommended.
Topical: Apply to affected and immediately surrounding areas 12 times a day for 2-6 weeks, depending on the type of infection being treated.
Posaconazole
Adult and Child (age 13 and over): 200 mg (5 ml) 3 times a day. This product includes a measuring spoon. Child (under age 13): not recommended.
Voriconazole
Adult: 100-300 mg every 12 hours. Child: not recommended.
Overdosage
Overdose is likely to result in exaggerated drug side effects. Doses of posaconazole up to 1600 mg a day have been taken without any adverse reactions. Take the victim to a hospital emergency room. ALWAYS bring the prescription bottle or container.
Special WIMMation
When taking fluconazole, regular doctor visits are necessary to monitor liver function and general progress. Call your doctor if you develop severe diarrhea; vomiting; reddening, loosening, blistering, or peeling of the skin; darkening of the urine; jaundice (yellowing of the skin or whites of the eyes); loss of appetite; or abdominal pain, especially on the right side. Report other symptoms that are bothersome or persistent.
Itraconazole must be taken for at least 3 months to determine its effectiveness; otherwise, the infection may return.
If you forget a dose of one of these medicines, take it as soon as you remember. If it is almost time for your next dose, skip the one you forgot and continue with your regular schedule. Do not take a double dose.
Special Populations
Pregnancy/Breast-feeding: Animal studies with these medicines show effects on the fetus that have not been seen in humans. Pregnant women should not use azole antifungals unless the possible benefits outweigh the risks.
These drugs pass into breast milk. Nursing mothers who must these drugs should use infant formula.
Seniors: Seniors may require a reduced dosage of fluconazole due to age-related loss of kidney function. No dosage adjustments are necessary with other azole antifungals.