Itraconazole 10 mg/ml Concentrate and Solvent for Solution for Infusion

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Itraconazole is and what it is used for
2. What you need to know before you are given Itraconazole
3. How Itraconazole is given
4. Possible side effects
5. How to store Itraconazole
6. Contents of the pack and other information

• if you are allergic to itraconazole or any of the other ingredients of this medicine (listed in section 6)
• if you are pregnant, think you might be pregnant or are trying to become pregnant, (see the section on “Pregnancy”)
• if you have seriously reduced kidney function
• if you cannot have sodium chloride by injection
• if you are taking any of the following medicines:
  • terfenadine or mizolastine (antihistamines for allergies)
  • bepridil, ivabradine or ranolazine - used to treat angina (crushing chest pain)
  • nisoldipine, lercanidipine or eplerenone (used for high blood pressure)
  • cisapride (used for stomach upsets)
  • domperidone (for nausea and vomiting)
  • midazolam by mouth or triazolam (used to help you sleep or for anxiety)
  • lovastatin or simvastatin (used to lower cholesterol)
  • lurasidone, pimozide or sertindole (for conditions affecting thoughts, feelings and/or behaviour)
  • dihydroergotamine or ergotamine (for migraine headaches)
  • ergometrine (ergonovine) or methylergometrine (methylergonovine) used after giving birth
  • disopyramide, dronedarone, quinidine or dofetilide (for irregular heart beat rhythms)
  • telithromycin (for pneumonia) when used in patients with severe kidney or liver problems
  • colchicine (for gout) when used in patients with kidney or liver problems
  • halofantrine (for malaria)
  • irinotecan (for cancer)
  • dabigatran (for blood thinning)
  • ticagrelor (for blood clots)
  • quetiapine (for psychosis)
  • aliskiren (for hypertension)
  • darifenacin (for urinary incontinence)
  • fesoterodine (for irritated urinary bladder) when used in patients with certain kidney or liver problems
  • sildenafil when used to treat pulmonary hypertension (increased blood pressure in the blood vessels in the lungs)
  • solifenacin (for irritated urinary bladder) when used in patients with certain kidney or liver problems
  • vardenafil (for erectile dysfunction) when used in men older than 75 years of age.

Also, upon completing your course of Itraconazole, do not take any of the medicines listed above for 2 weeks.

Tell your doctor immediately if you:

• have any unusual feelings of tingling, numbness or weakness in your hands or feet whilst taking Itraconazole
• experience any hearing loss symptoms. In very rare cases patients taking Itraconazole have reported temporary or permanent hearing loss.

Talk to your doctor or nurse before you are given Itraconazole

You must tell your doctor before you are given Itraconazole if you suffer from or have suffered in the past from any of the following:

• any liver problems or jaundice (yellowing of the skin). If your doctor decides to give you Itraconazole the dose may have to be changed. Your doctor may give you instructions on symptoms to watch out for and ask you to have your blood checked. In addition, there may be specific medication you may not be able to take.
• an allergic reaction to any other antifungal medicine.
• heart problems, including heart failure (also called congestive heart failure or CHF), Itraconazole could make it worse. If your doctor decides to give you Itraconazole you should be told about the symptoms listed below to watch out for. If you get any of the following stop taking Itraconazole and tell your doctor straight away. These may be signs of heart failure:
  • shortness of breath
  • unexpected weight gain
  • swelling of your legs or stomach
  • feel unusually tired
  • wake up short of breath at night.
• are on a low salt diet.
• a kidney disorder, you may be monitored more closely or your dose of Itraconazole may have to be changed. In addition, there may be specific medication you may not be able to take.

Itraconazole is not normally given to children and adolescents. Your doctor may prescribe it in special cases.

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines.

There are some medicines that you must not take whilst being given Itraconazole. These are listed above under the heading “You must not be given Itraconazole:”.

Tell your doctor if you are using the following as they may stop Itraconazole from working properly:

• rifampicin, rifabutin or isoniazid (antibiotics used to treat tuberculosis)
• phenytoin, carbamazepine or phenobarbital (anti-epileptics)
• efavirenz or nevirapine (medicines used for HIV/AIDS)
• St John’s Wort (a herbal medicine).

You must not be given Itraconazole within 2 weeks of taking these medicines.

Tell your doctor if you are using the following medicines as they are not recommended with Itraconazole unless your doctor feels it is necessary:

• medicines for cancer (namely axitinib, dabrafenib, dasatinib, ibrutinib, lapatinib, nilotinib, sunitinib or trabectedin)
• simeprevir (for Hepatitis C)
• riociguat, when used to treat pulmonary hypertension (increased blood pressure in the blood vessels in the lungs)
• rifabutin (for tuberculosis)
• carbamazepine (for epilepsy)
• colchicine (for gout)
• everolimus or temsirolimus (given after an organ transplant)
• fentanyl (for pain)
• apixaban (for blood clots)
• rivaroxaban (for blood clots)
• salmeterol (for breathing problems)
• tamsulosin (for male urinary incontinence)
• vardenafil (for erectile dysfunction) when used in men 75 years of age and younger
• atorvastatin (for lowering levels of cholesterol)
• ciclesonide (for inflammation, asthma and allergies)
• ebastine (for allergies)
• eletriptan (for migraine headaches)
• tolterodine (for irritated urinary bladder)
• felodipine (for the heart or blood vessels).

Also, upon completing your course of Itraconazole, do not take any of the medicines listed above for 2 weeks.

Tell your doctor before taking any of the following medicines as the dose of Itraconazole or other treatments may need to be altered:

• ciprofloxacin, clarithromycin or erythromycin (anitibiotics for infections)
• medicines that act on the heart or blood vessels (bosentan, digoxin, nadolol, calcium channel blockers such as, dihydropyridines, verapamil)
• telithromycin (for pneumonia)
• medicines that slow down blood clotting or thin the blood, such as the coumarins (e.g. warfarin) or cilostazol
• methylprednisolone, budesonide, fluticasone or dexamethasone, medicines given by mouth and injection for inflammation, asthma and allergies
• ciclosporin, tacrolimus or rapamycin (also known as sirolimus), which are usually given after an organ transplant
• medicines used in HIV-infected patients, such as maraviroc, ritonavir, ritonavir-boosted darunavir, ritonavir-boosted fosamprenavir, indinavir or saquinavir
• telaprevir (used in the treatment of Hepatitis C virus)
• medicines for cancer (such as bortezomib, busulphan, docetaxel, erlotinib, gefitinib, imatinib, ixabepilone, ponatinib, trimetrexate or a group of medicines known as vinca alkaloids)
• alfentanil, buprenorphine, oxycodone or sufentanil (for pain)
• methadone for treatment of drug abuse (opioid-dependency)
• buspirone, alprazolam, brotizolam, perospirone or midazolam when given by injection into a vein (for anxiety or to help you sleep)
• reboxetine (for depression)
• repaglinide or saxagliptin (for diabetes)
• aripiprazole, haloperidol or risperidone (for psychosis)
• aprepitant (for nausea and vomiting)
• fesoterodine, oxybutynin or solifenacin (for irritated urinary bladder)
• sildenafil or tadalafil (for erectile dysfunction)
• praziquantel (for fluke and tapeworms)
• bilastine (for allergies)
• meloxicam (for joint inflammation and pain)
• cinacalcet (for an over active parathyroid)
• tolvaptan (to treat low blood sodium or some kidney problems)
• alitretinoin (oral) (for eczema)

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

You must not be given Itraconazole if you are pregnant, unless your doctor has told you to. If you are of childbearing age and could become pregnant, you should use contraceptives to make sure that you do not become pregnant while you are receiving your medicine. As Itraconazole remains in the body for some time after you stop receiving it, you should continue to use some form of contraception until your next period after your treatment with Itraconazole has finished.

If you do find that you are pregnant after receiving a course of Itraconazole, tell your doctor straight away.

Before taking any medicine - always tell your doctor if you are pregnant, think you might be pregnant or are trying to become pregnant.

You must stop breast-feeding before you are given Itraconazole, as small amounts of the medicine could be present in your breast milk.

Itraconazole can sometimes cause dizziness, blurred/double vision or hearing loss. If you have these symptoms, do not drive or use machines.

This medicine contains approximately 177 mg sodium (main component of cooking/table salt) in each dose. This is equivalent to 9 % of the recommended maximum daily dietary intake of sodium for an adult.

This medicine contains 26 mg propylene glycol per 10 mg/ml of Itraconazole Concentrate for Solution for Infusion.

If you are pregnant or breast-feeding, do not take this medicine unless recommended by your doctor. Your doctor may carry out extra checks while you are taking this medicine.

If you suffer from a liver or kidney disease, do not take this medicine unless recommended by your doctor. Your doctor may carry out extra checks while you are taking this medicine.

Propylene glycol in this medicine can have the same effects as drinking alcohol and increase the likelihood of side effects.

Do not use this medicine in children less than 5 years old.

Use this medicine only if recommended by a doctor. Your doctor may carry out extra checks while you are taking this medicine.

The recommended dosage is as follows:

Adults

Day 1 and Day 2 of the treatment: Two 1-hour infusions of 200 mg itraconazole will be given each day as a 60 ml infusion.

From Day 3 onwards: One 1-hour infusion of 200 mg itraconazole will be given each day as a 60 ml infusion.

Elderly

Itraconazole is not normally given to the elderly. Your doctor may prescribe it in special cases.

Since this medicine will be given to you by a doctor or nurse, it is unlikely that you will be given too much or that a dose will be missed. However, if you are worried, tell your doctor or nurse.

• any sudden wheeziness, difficulty in breathing, swelling of the face, rash, itching (especially affecting the whole body) or a severe skin disorder (widespread rashes with peeling skin and blisters in the mouth, eyes and genitals, or rashes with small pustules or blisters)
• severe lack of appetite, feeling sick, being sick, unusual tiredness, abdominal (stomach) pain, unusually dark urine, or pale stools. These may be symptoms of severe liver problems.

• Symptoms that resemble heart failure such as shortness of breath, unexpected weight gain, swelling of the legs, unusual fatigue (tiredness), repeated waking at night
• A tingling sensation, sensitivity to light, numbness or weakness in the limbs
• Blurred vision/double vision, ringing in your ears, lose the ability to control your urine or increased need to urinate (pass water)
• If you experience any symptoms of hearing loss
• Severe upper stomach pain, often with nausea and vomiting due to inflammation of the pancreas (pancreatitis).

Very common side effects (may affect more than 1 in 10 people):

• feeling sick (nausea)
• being sick (vomiting)
• diarrhoea
• cough
• rash
• general swelling.

Common side effects (may affect up to 1 in 10 people):

• headache, dizziness
• stomach ache, constipation
• increases in specific liver function tests (hepatic enzyme increased), inflammation of the liver (hepatitis), yellowing of the skin (jaundice)
• itching, hives
• fever or high temperature
• shortness of breath
• certain blood disorder which may increase the risk of infections (possible symptom of low levels of granulocytes)
• high blood sugar levels
• muscle cramps or irregular heart beat (possible symptoms of low blood levels of magnesium)
• confusion
• sleepiness
• tremors
• increase in heart rate
• high blood pressure
• low blood pressure
• fluid in the lungs
• indigestion
• hair loss
• excess sweating
• muscle pain
• kidney problems
• chest pain
• pain
• chills
• fatigue
• increase in blood urea levels
• abnormal urine findings
• injection site swelling.

Uncommon side effects (may affect up to 1 in 100 people):

• unpleasant taste
• muscle cramps or irregular heart beat (possible symptoms of high blood levels of potassium)
• certain blood disorder which may increase the risk of bleeding or bruising (possible symptoms of low levels of platelets)
• difficulty speaking
• decreased feeling or sensitivity, especially in the skin
• increase in blood creatine phosphokinase levels.

The following side effect has been reported in patients being given itraconazole with an unknown frequency:

• excess of triglycerides (fats) in the blood.

The following side effects have been reported in patients taking other formulations of itraconazole:

• infection of the upper respiratory tract
• inflammation of the nose
• inflammation of the sinuses
• certain blood disorder which may increase the risk of infections (possible symptom of low levels of white blood cells)
• muscle cramps or irregular heart beat (possible symptoms of low blood levels of potassium)
• excess gas in the intestinal tract
• painful joints
• excessive urine production
• abnormal menstrual bleeding
• erectile dysfunction.

Not known: frequency cannot be estimated from the available data.

• Pseudoaldosteronism, which results in high blood pressure with a low potassium level (shown in blood tests).

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for ‘MHRA Yellow Card’ in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is itraconazole (10 mg of itraconazole per ml).
• The other ingredients are hydroxypropyl-β-cyclodextrin, propylene glycol, hydrochloric acid, sodium hydroxide and water for injections.

• sodium chloride and water for injections.

Also see section 2 “Itraconazole contains sodium”.

It is a kit containing a clear, colourless or faintly yellow coloured concentrated solution for intravenous (IV) infusion, which means the solution needs to be diluted before use.

Itraconazole concentrate comes in a 25 millilitre (ml) ampoule, together with a bag containing a clear, colourless Sodium Chloride solution and an extension line. These two solutions will be mixed together to give a clear, colourless solution before they are given directly into your veins.

One ml of Itraconazole concentrate contains 10 milligrams (mg) of itraconazole. When the Itraconazole concentrate is added to the bag containing sodium chloride solution, each ml of the mixed solution contains 3.33 mg itraconazole.

The Sodium Chloride bag is a plastic polypropylene infusion bag, which contains 50 ml of Sodium Chloride solution. One ml of solution contains 9 mg sodium chloride. It is used to dilute the Itraconazole concentrate making it easier to be given.