Vfend

Mechanism of Action

Triazole antifungal agent: Acts by inhibition of fungal cytochrome P-450 and sterol C-14 alpha-demethylation; decreases ergosterol synthesis and inhibits fungal cell membrane formation

Pharmacokinetics

Half-Life: Variable, dose-dependent due to non-linear kinetics

Peak Plasma Time: 1-2 hr

Vd: 4.6 L/Kg

Protein binding: 58%

Metabolism: Via hepatic CYP2C19, CYP2C9, CYP3A4

Bioavailability: 96%

Excretion: urine (80%)

Before taking voriconazole,

• tell your doctor and pharmacist if you are allergic to voriconazole; other antifungal medications such as fluconazole (Diflucan), itraconazole (Onmel, Sporanox), or ketoconazole (Nizoral);any other medications, or any of the ingredients in voriconazole tablets and suspension. Ask your pharmacist for a list of the ingredients in voriconazole tablets and suspension.
• do not take voriconazole if you are taking any of the following medications: astemizole (Hismanal) (not available in the United States); carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, Teril); cisapride (Propulsid); efavirenz (Sustiva, in Atripla); ergot-type medications such as dihydroergotamine (D.H.E. 45, Migranal), ergoloid mesylates (Hydergine), ergotamine (Ergomar, in Cafergot, in Migergot), and methylergonovine (Methergine); phenobarbital; pimozide (Orap); quinidine (Quinidex, in Nuedexta); rifabutin (Mycobutin); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); ritonavir (Norvir, in Kaletra); sirolimus (Rapamune); St. John's wort; and terfenadine (Seldane) (not available in the United States).
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking. Be sure to mention any of the following: ; anticoagulants ('blood thinners') such as warfarin (Coumadin, Jantoven); benzodiazepines such as alprazolam (Niravam, Xanax), midazolam, and triazolam (Halcion); calcium channel blockers such as amlodipine (Norvasc, in Amturnide, in Tekamlo), felodipine (Plendil), isradipine, nicardipine (Cardene), nifedipine (Adalat, Afeditab, Procardia), nimodipine (Nymalize), and nisoldipine (Sular); cholesterol-lowering medications (statins) such as atorvastatin (Lipitor, in Caduet, in Liptruzet), fluvastatin (Lescol), lovastatin (Altoprev, in Advicor), pravastatin (Pravachol), and simvastatin (Zocor, in Simcor, in Vytorin); cyclosporine (Gengraf, Neoral, Sandimmune); everolimus (Afinitor, Zortress); fentanyl (Abstral, Actiq, Fentora, Lazanda, Subsys); medications for diabetes such as glipizide (Glucotrol), glyburide (Diabeta, Glynase, , in Glucovance), and tolbutamide; medications for HIV such as delavirdine (Rescriptor), nelfinavir (Viracept), nevirapine (Viramune), and saquinavir (Invirase); methadone (Dolophine, Methadose); nonsteroidal anti-inflammatory drugs (diclofenac, ibuprofen), oral contraceptives; oxycodone (Oxecta, Oxycontin, in Oxycet, in Percocet, in Percodan, in Roxicet, in Xartemis); phenytoin (Dilantin, Phenytek); proton-pump inhibitors such as esomeprazole (Nexium, in Vimovo), lansoprazole (Prevacid), omeprazole (Prilosec, in Prevpac), pantoprazole (Protonix), and rabeprazole (AcipHex); tacrolimus (Astagraf, Prograf); vinblastine; and vincristine. Many other medications may also interact with voriconazole, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have ever been treated with chemotherapy medications for cancer, and if you have or have ever had a prolonged QT interval (a rare heart problem that may cause irregular heartbeat, fainting, or sudden death), or if you have or ever had a slow or irregular heartbeat, low blood levels of potassium, magnesium, or calcium, cardiomyopathy (enlarged or thickened heart muscle that stops the heart from pumping blood normally), cancer of the blood cells, any condition that makes it difficult for you to digest sucrose or lactose, or liver or kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking voriconazole, call your doctor immediately.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking voriconazole.
• you should know that voriconazole may cause blurred vision or other problems with your eyesight and may make your eyes sensitive to bright light. Do not drive a car at night while taking voriconazole. Do not drive a car during the day or operate machinery if you have any problems with your vision while you are taking this medication.
• plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Voriconazole may make your skin sensitive to sunlight.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Do not refrigerate or freeze the medication. Dispose of any unused suspension after 14 days.

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Some side effects may occur during the injection. Tell your caregiver right away if you feel dizzy, nauseated, light-headed, itchy, sweaty, or have chest tightness or trouble breathing.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• changes in your color vision;
• headache with chest pain and severe dizziness, fainting, fast or pounding heartbeats;
• slow heart rate, weak pulse, fainting, slow breathing;
• bone pain;
• severe pain in your upper stomach spreading to your back, vomiting;
• kidney problems--little or no urinating; painful or difficult urination; swelling in your feet or ankles; feeling tired or short of breath;
• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
• severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

• blurred vision, eyes being more sensitive to light;
• rash;
• headache, hallucinations;
• fast heart rate;
• nausea, vomiting; or
• abnormal liver function tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Voriconazole may cause vision changes such as blurred vision and sensitivity to light. Wear sunglasses during the day to protect your eyes from bright light. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

Avoid exposure to sunlight or tanning beds. Voriconazole can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Many drugs can interact with voriconazole, and some drugs should not be used together. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with voriconazole. Give a list of all your medicines to any healthcare provider who treats you.

Included as part of the "PRECAUTIONS" Section

• Cardinal Health, Inc.

• Roerig

Tell your healthcare provider if you are pregnant or plan to become pregnant. Vfend can harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant. Women who can become pregnant should use effective birth control while taking Vfend.

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if Vfend passes into breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Vfend.

If you take too much Vfend, call your healthcare provider or go to the nearest hospital emergency room.

You should not take voriconazole if you are allergic to it.

Some medicines can cause unwanted or dangerous effects when used with voriconazole. Your doctor may need to change your treatment plan if you use any of the following drugs:

• carbamazepine;

• cisapride;

• efavirenz;

• pimozide;

• quinidine;

• rifabutin, rifampin;

• ritonavir;

• sirolimus;

• St. John's wort;

• certain barbiturates (mephobarbital, phenobarbital); or

• "ergot" migraine headache medicines (dihydroergotamine, ergotamine, ergonovine, methylergonovine).

To make sure voriconazole is safe for you, tell your doctor if you have ever had:

• heart disease;

• a heart rhythm disorder such as long QT syndrome;

• high or low levels of calcium, potassium, or magnesium in your blood;

• liver or kidney disease; or

• trouble digesting sugar or dairy products (voriconazole tablets contain lactose, voriconazole liquid contains sucrose).

Do not use voriconazole if you are pregnant. It could harm the unborn baby. Use effective birth control to prevent pregnancy while you are using this medicine>

It is not known whether voriconazole passes into breast milk or if it could affect the nursing baby. Tell your doctor if you are breast-feeding.

Voriconazole is not approved for use by anyone younger than 12 years old.

You should not take Vfend if you are allergic to voriconazole.

Some medicines can cause unwanted or dangerous effects when used with Vfend. Your doctor may need to change your treatment plan if you use any of the following drugs:

• carbamazepine;

• cisapride;

• efavirenz;

• pimozide;

• quinidine;

• rifabutin, rifampin;

• ritonavir;

• sirolimus;

• St. John's wort;

• certain barbiturates (mephobarbital, phenobarbital); or

• "ergot" migraine headache medicines (dihydroergotamine, ergotamine, ergonovine, methylergonovine).

To make sure Vfend is safe for you, tell your doctor if you have ever had:

• heart disease;

• a heart rhythm disorder such as long QT syndrome;

• high or low levels of calcium, potassium, or magnesium in your blood;

• liver or kidney disease; or

• trouble digesting sugar or dairy products (the tablets contain lactose, liquid contains sucrose).

Do not use Vfend if you are pregnant. It could harm the unborn baby. Use effective birth control to prevent pregnancy while you are using this medicine>

It is not known whether voriconazole passes into breast milk or if it could affect the nursing baby. Tell your doctor if you are breast-feeding.

Vfend is not approved for use by anyone younger than 12 years old.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Call your doctor for instructions if you miss a dose of injectable Vfend.

Many drugs can interact with voriconazole, and some drugs should not be used together. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all your current medicines and any medicine you start or stop using.

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother; breastfeeding must be stopped on initiation of therapy. Excreted into human milk: Unknown Excreted into animal milk: Unknown