Cresemba 200 mg powder for concentrate for infusion solution

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Cresemba 200 mg powder for concentrate for solution for infusion

isavuconazol

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience side effects, consult your doctor, pharmacist or nurse, even if they are possible side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Cresemba is and what it is used for

What Cresemba is

Cresemba is an antifungal medicine that contains the active substance isavuconazol.

How Cresemba works

Isavuconazol works by killing or stopping the growth of the fungus causing the infection.

What Cresemba is used for

Cresemba is used in patients from 1 year of age to treat the following fungal infections:

• invasive aspergillosis, caused by a fungus of the 'Aspergillus' group,
• mucormycosis, caused by a fungus belonging to the 'Mucorales' group, in patients for whom treatment with amphotericin B is not appropriate.

2. What you need to know before using Cresemba

Do not use Cresemba

• if you are allergic to isavuconazole or any of the other ingredients of this medicine (listed in section 6),
• if you have a heart rhythm problem called ‘short QT syndrome’,
• if you are taking any of the following medicines:
  • ketoconazole, used for fungal infections,
  • high-dose ritonavir (more than 200 mg every 12 hours), used for HIV,
  • rifampicin, rifabutin, used for tuberculosis,
  • carbamazepine, used for epilepsy,
  • barbiturates such as phenobarbital, used for epilepsy and sleep disorders,
  • phenytoin, used for epilepsy,
  • St. John’s wort, a herbal medicine used for depression,
  • efavirenz, etravirenine, used for HIV,
  • nafcillin, used for bacterial infections.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using Cresemba:

• if you have previously had an allergic reaction to another antifungal ‘azole’ treatment, such as ketoconazole, fluconazole, itraconazole, voriconazole, or posaconazole,
• if you have severe liver disease. Your doctor should monitor for possible adverse effects.

Monitoring for adverse effects

Stop using Cresemba and call your doctor immediately if you experience any of the following side effects:

• sudden wheezing, difficulty breathing, swelling of the face, lips, mouth, or tongue, severe itching, sweating, dizziness or fainting, rapid heartbeat or palpitations in the chest: these may be signs of a serious allergic reaction (anaphylaxis).

Problems with Cresemba and its intravenous administration (infusion)

Call your doctor immediately if you experience any of the following side effects:

• low blood pressure, difficulty breathing, nausea, dizziness, headache, tingling; your doctor will decide whether to stop the infusion.

Changes in liver function

Cresemba may sometimes affect liver function. Your doctor may perform blood tests while you are taking this medicine.

Skin problems

Call your doctor immediately if you develop severe peeling of the skin, mouth, eyes, or genitals.

Children and adolescents

Do not give Cresemba to children under 1 year of age, as there is no information available on its use in this age group.

Other medicines and Cresemba

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. Some medicines may alter the way Cresemba works, or Cresemba may alter the way other medicines work when taken together.

Specifically, do not take this medicine and inform your doctor or pharmacist if you are taking any of the following medicines:

• ketoconazole, used for fungal infections,
• high-dose ritonavir (more than 200 mg every 12 hours), used for HIV,
• rifampicin, rifabutin, used for tuberculosis,
• carbamazepine, used for epilepsy,
• barbiturates such as phenobarbital, used for epilepsy and sleep disorders,
• phenytoin, used for epilepsy,
• St. John’s wort, a herbal medicine used for depression,
• efavirenz, etravirenine, used for HIV,
• nafcillin, used for bacterial infections.

Unless your doctor tells you otherwise, do not take this medicine and inform your doctor or pharmacist if you are taking any of the following medicines:

• rufinamide or any other medicine that shortens the QT interval on the electrocardiogram (ECG),
• aprepitant, used to prevent nausea and vomiting during cancer treatment,
• prednisone, used for rheumatoid arthritis,
• pioglitazone, used for diabetes.

Tell your doctor or pharmacist if you are taking any of the following medicines, as dose adjustment or monitoring may be needed to ensure these medicines remain effective:

• ciclosporin, tacrolimus, and sirolimus, used to prevent organ transplant rejection,
• cyclophosphamide, used for cancer,
• digoxin, used to treat heart failure or irregular heartbeat,
• colchicine, used to treat gout attacks,
• dabigatran etexilate, used to prevent blood clots after hip or knee replacement surgery,
• clarithromycin, used for bacterial infections,
• saquinavir, fosamprenavir, indinavir, nevirapine, lopinavir/ritonavir combination, used for HIV,
• alfentanil, fentanyl, used for severe pain,
• vincristine, vinblastine, used for cancer,
• mycophenolate mofetil (MMF), used in transplant patients,
• midazolam, used for severe insomnia and stress,
• bupropion, used for depression,
• metformin, used for diabetes,
• daunorubicin, doxorubicin, imatinib, irinotecan, lapatinib, mitoxantrone, topotecan, used for different types of cancer.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Do not take Cresemba if you are pregnant, unless your doctor tells you otherwise. It is unknown whether it may affect or harm the fetus.

Cresemba must not be used during breastfeeding.

Driving and using machines

Cresemba may make you feel confused, tired, or drowsy. It may also cause fainting. Therefore, be very careful when driving or operating machinery.

3. How to use Cresemba

Cresemba will be administered under the supervision of a doctor or nurse.

The recommended dose is as follows:

This dose should be administered until your doctor advises otherwise. The duration of treatment with Cresemba may be longer than 6 months, if your doctor considers it necessary.

Your doctor or nurse will administer the vial as an intravenous infusion.

If you use more Cresemba than you should

If you think you have been given too much Cresemba, contact your doctor or nurse immediately. This may cause more adverse effects such as:

• headache, dizziness, restlessness, or drowsiness,
• tingling, reduced sensitivity, or impaired tactile sensation,
• difficulty concentrating, hot flashes, anxiety, joint pain,
• altered taste, dry mouth, diarrhea, vomiting,
• palpitations, increased heart rate, increased sensitivity to light.

If you forget to take Cresemba

Since this medicine will be administered under close medical supervision, it is unlikely that you will miss a dose. However, inform your doctor or nurse if you think you have missed a dose.

If you stop treatment with Cresemba

Treatment with Cresemba will continue for as long as your doctor indicates. This is to ensure that the fungal infection has been completely eliminated.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Stop using Cresemba and contact your doctor immediately if you notice any of the following adverse effects:

• a severe allergic reaction (anaphylaxis), such as sudden wheezing, difficulty breathing, swelling of the face, lips, mouth or tongue, severe itching, sweating, dizziness or fainting, rapid heartbeat or palpitations in the chest.

Contact your doctor immediately if you notice any of the following adverse effects:

• severe blistering of the skin, mouth, eyes or genitals.

Other adverse effects

Contact your doctor, pharmacist or nurse if you notice any of the following adverse effects:

Common: may affect up to 1 in 10 people

• reduced potassium levels in the blood,
• decreased appetite,
• confusion (delirium),
• headache,
• drowsiness,
• inflamed veins that may lead to blood clots,
• sudden and severe shortness of breath or breathing problems,
• nausea, vomiting, diarrhoea and stomach pain,
• changes in blood tests indicating liver function abnormalities,
• skin rash, itching,
• kidney failure (symptoms may include swelling of the legs),
• chest pain, feeling tired or drowsy,
• injection site reactions.

Uncommon: may affect up to 1 in 100 people

• reduced white blood cell count, which may increase the risk of infection and fever,
• reduced number of blood cells called 'platelets', which may increase the risk of bleeding or bruising,
• reduced red blood cell count, which may make you feel weak, short of breath or pale,
• severe reduction in blood cell counts, which may cause weakness, bruising or increased risk of infections,
• skin rash, swelling of the lips, mouth, tongue or throat with difficulty breathing (hypersensitivity),
• low blood sugar levels,
• low magnesium levels in blood,
• low levels of a protein called 'albumin' in blood,
• poor absorption of nutrients from food (malnutrition),
• low sodium levels in blood (hyponatremia),
• depression, difficulty sleeping,
• stroke, collapse or feeling faint, dizziness,
• tingling, prickling or pins and needles sensation on the skin (paraesthesia),
• changes in mental state (encephalopathy),
• altered taste (dysgeusia),
• spinning sensation or dizziness (vertigo),
• heart rhythm problems, which may be too fast, irregular, or extra heartbeats, which may appear on your electrocardiogram or ECG,
• circulatory problems,
• low blood pressure,
• wheezing, very rapid breathing, coughing up blood or blood-stained sputum, nosebleeds,
• indigestion,
• constipation,
• abdominal swelling (abdominal distension),
• enlarged liver,
• liver inflammation,
• skin problems, red or purple spots on the skin (petechiae), skin inflammation, hair loss,
• back pain,
• swelling of the limbs,
• feeling of weakness, extreme tiredness, drowsiness, feeling unwell (malaise).

Adverse effects with frequency not known:

• anaphylaxis (severe allergic reaction).

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Cresemba

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label after EXP. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C).

Medicines should not be disposed of via wastewater. Ask your pharmacist how to properly dispose of any unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Cresemba

• The active substance is isavuconazole. Each vial contains 372.6 mg of isavuconazonium sulfate, equivalent to 200 mg of isavuconazole.
• The other components (excipients) are: mannitol (E421) and sulfuric acid.

Appearance of Cresemba and contents of the pack

Cresemba 200 mg is presented in a single-use glass vial as a powder for concentrate for solution for infusion.

Marketing Authorization Holder:

Basilea Pharmaceutica Deutschland GmbH
Marie-Curie-Strasse 8
79539 Lörrach
Germany

Manufacturer:

Almac Pharma Services (Ireland) Limited
Finnabair Industrial Estate
Dundalk, Co. Louth
A91 P9KD
Ireland

Almac Pharma Services Limited
Seagoe Industrial Estate
Craigavon, Co. Armagh
BT63 5UA
United Kingdom (Northern Ireland)

For more information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this summary:

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu. Links to other websites on rare diseases and orphan medicinal products are also available.

This information is intended for healthcare professionals only:

Cresemba 200 mg powder for concentrate for solution for infusion must be reconstituted and diluted before infusion.

Reconstitution

To reconstitute one vial of powder for concentrate for solution for infusion, add 5 ml of water for injections to the vial. The reconstituted concentrate contains 40 mg of isavuconazole per ml. The vial should be shaken until the powder is completely dissolved. The reconstituted solution should be inspected visually for particles and discoloration. The reconstituted concentrate should be clear and free of visible particles. It must be diluted before administration.

Dilution

Adults and pediatric patients weighing more than 37 kg:

After reconstitution, the entire contents of the vial of reconstituted concentrate should be withdrawn and added to an infusion bag containing 250 ml of 0.9% sodium chloride injection (9 mg/ml) or 5% dextrose solution (50 mg/ml). The infusion solution contains approximately 0.8 mg of isavuconazole per ml.

Pediatric patients weighing less than 37 kg:

The final concentration of the infusion solution should be within the range of 0.4 to 0.8 mg/ml of isavuconazole. Concentrations higher than this range should be avoided, as they may cause infusion site irritation.

To achieve the final concentration, the appropriate volume of reconstituted concentrate should be withdrawn from the vial according to the recommended pediatric dosing (see section 3) and added to an infusion bag containing the appropriate amount of diluent. The appropriate infusion bag volume should be calculated as follows:

[Dose required (mg) / final concentration (mg/ml)] – Volume of concentrate (ml)

The concentrate may be diluted with 0.9% sodium chloride injection (9 mg/ml) or 5% dextrose solution (50 mg/ml).

Administration

After further dilution of the reconstituted concentrate, the diluted solution may show fine white to translucent particles of isavuconazole that do not sediment (but will be removed by in-line filtration). The diluted solution should be gently mixed, or the bag may be gently rolled to minimize particle formation. Avoid vigorous shaking or agitation of the solution. The infusion solution should be administered using an infusion set with an in-line filter (pore size 0.2 μm to 1.2 μm) made of polyether sulfone (PES). Infusion pumps may be used and should be placed before the infusion set. Regardless of the size of the infusion container used, the entire volume of the container should be administered to ensure delivery of the complete dose.

Isavuconazole must not be administered by infusion through the same line or cannula as other intravenous products.

Chemical and physical stability has been demonstrated for 24 hours at 2°C to 8°C, or 6 hours at room temperature, after reconstitution and dilution.

From a microbiological standpoint, the medicine should be used immediately. If not used immediately, the in-use storage time and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C to 8°C, unless reconstitution and dilution were carried out under validated and controlled aseptic conditions.

If possible, intravenous administration of isavuconazole should be performed within 6 hours after reconstitution and dilution at room temperature. If this is not possible, the infusion solution should be refrigerated immediately after dilution, and the infusion should be administered within 24 hours.

An existing intravenous line should be flushed with 0.9% sodium chloride injection (9 mg/ml) or 5% dextrose solution (50 mg/ml).

This medicinal product is for single use only. Discard partially used vials.