Cresemba

Package leaflet: Information for the patient

Cresemba 200 mg powder for concentrate for solution for infusion

isavuconazole
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

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

Contents of this leaflet

1. What Cresemba is and what it is used for
2. What you need to know before you use 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 isavuconazolus.
How Cresemba works
Isavuconazolo works by killing the fungus causing the infection or by stopping its growth.
What Cresemba is used for
Cresemba is used in adult patients and patients aged 1 year and older to treat the following fungal infections:

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

2. What you should know before using Cresemba

Do not use Cresemba

• if you are allergic to isavuconazole or to any of the other ingredients of this medicine (listed in section 6),
• if you have a heart rhythm disorder called "familial short QT syndrome",
• if you are taking any of the following medicines:
• ketoconazole, used for fungal infections,
• ritonavir at high doses (more than 200 mg every 12 hours), used for HIV,
• rifampicin, rifabutin, used for tuberculosis,
• carbamazepine, used for epilepsy,
• barbiturate medicines such as phenobarbital, used for epilepsy and sleep disorders,
• phenytoin, used for epilepsy,
• St John’s wort, a herbal medicine used for depression,
• efavirenz, etravirine, 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 other antifungal "azole" treatments such as ketoconazole, fluconazole, itraconazole, voriconazole, or posaconazole,
• if you have severe liver disease. Your doctor will monitor you for possible side effects.

Be alert for possible side effects
Stop taking Cresemba and inform your doctor immediately if you notice 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 sensation of a pounding heart – these may be signs of a serious allergic reaction (anaphylaxis).

Problems that may occur during intravenous infusion of Cresemba
Inform your doctor immediately if you notice any of the following side effects:

• low blood pressure, shortness of breath, nausea, dizziness, headache, tingling; your doctor may decide to stop the infusion.

Changes in liver function
Cresemba may sometimes affect liver function. Your doctor may perform blood tests during treatment with this medicine.
Skin problems
Inform your doctor immediately if severe blisters appear on 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
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine. Some medicines may affect how Cresemba works, or Cresemba may affect how they work, if taken at the same time.
In particular, 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,
• ritonavir at high doses (more than 200 mg every 12 hours), used for HIV,
• rifampicin, rifabutin, used for tuberculosis,
• carbamazepine, used for epilepsy,
• barbiturate medicines such as phenobarbital, used for epilepsy and sleep disorders,
• phenytoin, used for epilepsy,
• St John’s wort, a herbal medicine used for depression,
• efavirenz, etravirine, 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 other medicines that shorten the QT interval on electrocardiogram (ECG),
• aprepitant, used to prevent nausea and vomiting caused by cancer treatments,
• prednisone, used for rheumatoid arthritis,
• pioglitazone, used for diabetes.

Inform your doctor or pharmacist if you are taking any of the following medicines, as dose adjustment or monitoring may be needed to ensure the medicines still have the desired effect:

• ciclosporin, tacrolimus and sirolimus, used to prevent transplant rejection,
• cyclophosphamide, used for cancer,
• digoxin, used to treat heart failure or irregular heartbeat,
• colchicine, used for 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 various types of cancer.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before using this medicine.
Do not take Cresemba if you are pregnant, unless your doctor tells you otherwise, as it is not known whether it could affect or harm the unborn baby.
Do not breastfeed while taking Cresemba.
Driving and using machines
Cresemba may cause confusion, tiredness, or drowsiness. It may also cause fainting.
Therefore, be very careful when driving or operating machinery.

3. How to use Cresemba

Cresemba will be administered to you by a doctor or a nurse.
The recommended dose is as follows:

This dose will be administered to you until your doctor gives you different instructions. The duration of
treatment with Cresemba may be longer than 6 months if your doctor considers it necessary.
The vial will be administered as an intravenous infusion by your doctor or nurse.
If you use more Cresemba than you should
If you think you have been given too much Cresemba, inform your doctor or nurse immediately. You may experience more side effects such as:

• headache, dizziness, restlessness or drowsiness,
• tingling, reduced sense of touch or sensitivity in the mouth,
• difficulty perceiving things, hot flushes, anxiety, joint pain,
• altered taste, dry mouth, diarrhoea, vomiting,
• palpitations, rapid heartbeat, increased sensitivity to light.

If you forget to use Cresemba
Since the medicine will be administered under close medical supervision, it is unlikely that a dose will be missed. However, inform your doctor or nurse if you think a dose has been missed.
If you stop treatment with Cresemba
Treatment with Cresemba will continue for the entire period indicated by your doctor to ensure that the fungal infection is cured.
If you have any doubts about using this medicine, consult your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking Cresemba and contact your doctor immediately if you notice any of the following
side 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 sensation of a pounding heart.
Contact your doctor immediately if you notice any of the following side effects:

• development of severe blisters on the skin, in the mouth, eyes or genital area.

Other side effects
Tell your doctor, pharmacist or nurse if you notice any of the following side effects:
Common: may affect up to 1 in 10 people

• low levels of potassium in the blood,
• reduced appetite,
• confusion (delirium),
• headache,
• drowsiness,
• inflammation of the veins which may lead to blood clots,
• sudden and severe shortness of breath or breathing difficulties,
• nausea, vomiting, diarrhoea, stomach pain,
• abnormal blood test results indicating liver function,
• rash, itching,
• kidney failure (symptoms may include swelling of the legs),
• chest pain, feeling of tiredness or drowsiness,
• problems at the injection site.

Uncommon: may affect up to 1 in 100 people

• reduction in white blood cells: may increase the risk of infections and fever,
• reduction in blood cells called "platelets": may increase the risk of bleeding or bruising,
• reduction in red blood cells: may cause weakness, shortness of breath or pale skin,
• severe reduction in blood cells: may cause weakness, bruising or make infections more likely,
• skin rash, swelling of lips, mouth, tongue or throat with breathing difficulties (hypersensitivity),
• low blood sugar levels,
• low levels of magnesium in the blood,
• low levels of a protein called “albumin” in the blood,
• lack of benefit from nutrition (malnutrition),
• low levels of sodium in the blood (hyponatraemia),
• depression, sleep disturbances,
• seizures, fainting or feeling faint, dizziness,
• sensation of tingling, pricking or burning of the skin (paraesthesia),
• change in mental state (encephalopathy),
• altered taste (dysgeusia),
• sensation of spinning or dizziness (vertigo),
• heart rhythm problems (too fast or irregular or extra heartbeats) evident on electrocardiogram (ECG),
• circulation problems,
• low blood pressure,
• wheezing, very rapid breathing, coughing up blood or blood-stained sputum, nosebleeds,
• indigestion,
• constipation,
• sensation of bloating (abdominal distension),
• enlarged liver,
• inflammation of the liver,
• skin problems, red or purple spots on the skin (petechiae), inflamed skin (dermatitis), hair loss,
• back pain,
• swelling of the limbs,
• feeling of weakness, extreme tiredness, drowsiness or irritability (malaise).

Side effects with unknown frequency:

• anaphylaxis (a severe allergic reaction).

Reporting of side effects
If you get any side effects, including any not listed in this leaflet, talk to your doctor, pharmacist or nurse.
You can also report side effects directly via the national reporting system detailed in Annex V. By reporting
side effects, you can help provide more information on the safety of this medicine.

5. How to store Cresemba

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label after Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C - 8 °C).
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Cresemba contains

• 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.

Description of the appearance of Cresemba and contents of the pack
Cresemba 200 mg is a powder for concentrate for solution for infusion in a single-use glass vial.

Marketing Authorisation 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 further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Pfizer SA/NV Pfizer Luxembourg SARL filialas Lietuvoje
Tel/Tél: +32 (0)2 554 62 11 Tel. +3705 2514000

България Luxembourg/Luxemburg
Пфайзер Люксембург САРЛ, Клон България Pfizer SA/NV
Тел.: +359 2 970 4333 Tél/Tel: +32 (0)2 554 62 11

Česká republika Magyarország
Pfizer s.r.o. Pfizer Kft.
Tel: +420-283-004-111 Tel.: +36 1 488 37 00

Danmark Malta
Unimedic Pharma AB Vivian Corporation Ltd.
Tlf: +46 (0) 10-130 99 50 Tel: +35621 344610

Deutschland Nederland
PFIZER PHARMA GmbH Pfizer bv
Tel: +49 (0)30 550055-51000 Tel: +31 (0)800 63 34 636

Eesti Norge
Pfizer Luxembourg SARL Eesti filiaal Unimedic Pharma AB
Tel: +372 666 7500 Tlf: +46 (0) 10-130 99 50

Ελλάδα Österreich
Pfizer ΕΛΛΑΣ A.E. Pfizer Corporation Austria Ges.m.b.H.
Τηλ: +30 210 67 85 800 Tel: +43 (0)1 521 15-0

España Polska
Pfizer S.L. Pfizer Polska Sp. z o.o.
Tel: +34 91 490 99 00 Tel.: +48 22 335 61 00

France Portugal
Pfizer Laboratoires Pfizer, Lda.
Tél: +33 (0)1 58 07 34 40 Tel: +351 21 423 5500

Hrvatska România
Pfizer Croatia d.o.o. Pfizer România S.R.L.
Tel: +385 1 3908 777 Tel: +40 (0) 21 20 728 00

Ireland Slovenija
Pfizer Healthcare Ireland Unlimited Company Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja
Tel: +1800 633 363 (toll free) farmacevtske dejavnosti, Ljubljana
+44 (0)1304 616161 Tel: +386 (0)1 52 11 400

Ísland Slovenská republika
Unimedic Pharma AB Pfizer Luxembourg SARL, organizačná zložka
Sími: +46 (0) 10-130 99 50 Tel: +421-2-3355 5500

Italia Suomi/Finland
Pfizer S.r.l. Unimedic Pharma AB
Tel: +39 06 33 18 21 Puh/Tel: +46 (0) 10-130 99 50

Κύπρος Sverige
Pfizer ΕΛΛΑΣ Α.Ε. (CYPRUS BRANCH) Unimedic Pharma AB
Τηλ: +357 22 817690 Tel: +46 (0) 10-130 99 50

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel: +371 670 35 775

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/. Additionally, links to other websites on rare diseases and their therapeutic treatments are provided.

The following information is intended exclusively for healthcare professionals:

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

Reconstitution
A vial of powder for concentrate for solution for infusion must be reconstituted by adding 5 mL of water for injections. The reconstituted concentrate contains 40 mg of isavuconazole per mL. The vial must be shaken to completely dissolve the powder. The reconstituted solution must be visually inspected for the presence of particulate matter or discoloration. The reconstituted concentrate must be clear and free from visible particulates. It must be further diluted prior to administration.

Dilution
Adults and pediatric patients with body weight of 37 kg or more:
After reconstitution, the entire content of the reconstituted concentrate must be withdrawn from the vial and added to an infusion bag containing 250 mL of either 9 mg/mL (0.9%) sodium chloride injection solution or 50 mg/mL (5%) dextrose solution. The infusion solution contains approximately 0.8 mg of isavuconazole per mL.

Pediatric patients with body weight below 37 kg:
The final concentration of the infusion solution must be between 0.4 and 0.8 mg of isavuconazole per mL. Higher concentrations should be avoided as they may cause local irritation at the infusion site.
To achieve the final concentration, the appropriate volume of reconstituted concentrate according to pediatric dosing recommendations (see section 3) must be withdrawn from the vial and added to an infusion bag containing the appropriate amount of diluent. The appropriate volume of the infusion bag is calculated as follows:
[Required dose (mg) / final concentration (mg/mL)] – Volume of concentrate (mL)
The concentrate may be diluted with either 9 mg/mL (0.9%) sodium chloride injection solution or 50 mg/mL (5%) dextrose solution.

Administration
After further dilution of the reconstituted concentrate, the diluted solution may contain fine white to translucent particles of isavuconazole that do not settle (but will be removed by in-line filtration). The diluted solution must be gently mixed or the infusion bag rotated to minimize particulate formation. Unnecessary agitation or vigorous shaking of the solution must be avoided. The infusion solution must be administered through an infusion set equipped with an in-line filter (pore size 0.2 μm to 1.2 μm) made of polyethersulfone (PES). Infusion pumps may be used and must be placed before the infusion set. Regardless of the size of the infusion container used, the entire volume of the container must be administered to ensure complete delivery of the dose.

Isavuconazole must not be infused simultaneously with other intravenous products in the same line or cannula.

Chemical and physical in-use stability after reconstitution and dilution has been demonstrated for 24 hours at 2–8 °C or for 6 hours at room temperature.

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

Whenever possible, intravenous administration of isavuconazole should be completed within 6 hours after reconstitution and dilution at room temperature. If this is not possible, the infusion solution must be stored in a refrigerator immediately after dilution, and the infusion must be completed within 24 hours.

If an existing intravenous line is used, it must be flushed with 9 mg/mL (0.9%) sodium chloride injection solution or 50 mg/mL (5%) dextrose solution.

The medicinal product is for single use only. Partially used vials must be discarded.

Patient Information Leaflet

CRESEMBA 40 mg hard capsules, 100 mg hard capsules

isavuconazole
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

1. What Cresemba is and what it is used for
2. What you need to know before taking Cresemba
3. How to take 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 isavuconazolo.
How Cresemba works
Isavuconazolo works by killing the fungus causing the infection or by stopping its growth.
What Cresemba is used for
Cresemba is used in adults and pediatric patients aged 6 years and older to treat the following fungal infections:

• Invasive aspergillosis, caused by a fungus of the genus Aspergillus;
• Mucormycosis, caused by a fungus belonging to the order Mucorales, in patients for whom treatment with amphotericin B is not appropriate.

2. What you should know before taking Cresemba

Do not take Cresemba

• if you are allergic to isavuconazole or to any of the other ingredients of this medicine (listed in section 6),
• if you have a heart rhythm disorder called "familial 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,
• barbiturate medicines such as phenobarbital, used for epilepsy and sleep disorders,
• phenytoin, used for epilepsy,
• St. John’s wort, a herbal medicine used for depression,
• efavirenz, etravirine, used for HIV,
• nafcillin, used for bacterial infections.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Cresemba:

• if you have previously had an allergic reaction to other "azole" antifungal treatments such as ketoconazole, fluconazole, itraconazole, voriconazole, or posaconazole,
• if you have severe liver disease. Your doctor will monitor you for possible side effects.

Be aware of possible side effects
Stop taking Cresemba and contact your doctor immediately if you notice 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 sensation of a pounding heart; these may be signs of a serious allergic reaction (anaphylaxis).

Liver function changes
Cresemba may sometimes affect liver function. Your doctor may carry out blood tests during treatment with this medicine.
Skin problems
Contact your doctor immediately if severe blisters appear on the skin, mouth, eyes, or genitals.
Children and adolescents
Do not give Cresemba capsules to children aged between 1 and 6 years, as this formulation has not been tested in this age group. For children over 6 years of age and adolescents weighing at least 32 kg, your doctor may prescribe Cresemba 100 mg capsules. Other formulations of this medicine may be more suitable for children or adolescents unable to swallow capsules; please consult your doctor or pharmacist.
Other medicines and Cresemba
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Some medicines may affect how Cresemba works, or Cresemba may affect how other medicines work, if taken at the same time.
In particular, 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,
• barbiturate medicines such as phenobarbital, used for epilepsy and sleep disorders,
• phenytoin, used for epilepsy,
• St. John’s wort, a herbal medicine used for depression,
• efavirenz, etravirine, 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 other medicines that shorten the QT interval on electrocardiogram (ECG),
• aprepitant, used to prevent nausea and vomiting caused by cancer treatments,
• prednisone, used for rheumatoid arthritis,
• pioglitazone, used for diabetes.

Inform 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 still have the intended effect:

• ciclosporin, tacrolimus, and sirolimus, used to prevent rejection of a transplant,
• cyclophosphamide, used for cancer,
• digoxin, used to treat heart failure or irregular heartbeat,
• colchicine, used for 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 various types of cancer.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before using this medicine.
Do not take Cresemba during pregnancy unless your doctor tells you otherwise, as it is not known whether it could affect or harm the unborn baby.
Do not breastfeed while taking Cresemba.
Driving and using machines
Cresemba may cause confusion, fatigue, or drowsiness. It may also cause fainting.
Therefore, exercise great caution when driving or operating machinery.

3. How to take Cresemba

Take this medicine exactly as instructed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
The recommended dose is as follows:

Use in children and adolescents
The use of Cresemba 100 mg capsules in children and adolescents has not been studied. The doctor may prescribe Cresemba 100 mg capsules to children and adolescents weighing at least 32 kg.
Other forms of this medicine are suitable for children and adolescents who cannot swallow capsules; please consult your doctor or pharmacist.
You should take this dose until your doctor gives you other instructions. The duration of treatment with Cresemba may exceed 6 months if your doctor considers it necessary.
The capsules can be taken with or without food. Swallow the capsules whole. Do not chew, crush, dissolve, or open the capsules.

If you take more Cresemba than you should
If you take more Cresemba than you should, contact a doctor or go to a hospital immediately.
Take the medicine package with you so that the doctor knows what you have taken.
You may experience more side effects such as:

• headache, dizziness, restlessness, or drowsiness,
• tingling, reduced sense of touch or sensitivity in the mouth,
• difficulty perceiving things, hot flushes, anxiety, joint pain,
• changes in taste, dry mouth, diarrhoea, vomiting,
• palpitations, rapid heartbeat, increased sensitivity to light.

If you forget to take Cresemba
Take the capsules as soon as you remember. However, if it is almost time for the next dose, skip the missed dose.
Do not take a double dose to make up for the forgotten dose.

If you stop taking Cresemba
Do not stop treatment with Cresemba unless your doctor has told you to do so. It is important that you continue taking the medicine for the full period prescribed by your doctor to ensure that the fungal infection is properly treated.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking Cresemba and inform your doctor immediately if you notice any of the following side effects:

• a severe allergic reaction (anaphylaxis), such as sudden wheezing, breathing difficulties, swelling of the face, lips, mouth or severe itching, sweating, dizziness or fainting, rapid heartbeat or sensation of a pounding heart.

Inform your doctor immediately if you notice any of the following side effects:

• development of severe blisters on the skin, mouth, eyes or genitals.

Other side effects
Inform your doctor, pharmacist or nurse if you notice any of the following side effects:
Common: may affect up to 1 in 10 people

• low levels of potassium in the blood,
• reduced appetite,
• confusion (delirium),
• headache,
• drowsiness,
• inflammation of the veins which may lead to blood clots,
• sudden and severe shortness of breath or breathing difficulties,
• nausea, vomiting, diarrhoea, stomach pain,
• abnormal results in blood tests of liver function,
• rash, itching,
• kidney failure (symptoms may include swelling of the legs),
• chest pain, feeling of tiredness or drowsiness.

Uncommon: may affect up to 1 in 100 people

• reduction in white blood cells: may increase the risk of infections and fever,
• reduction in blood cells called “platelets”: may increase the risk of bleeding or bruising,
• reduction in red blood cells: may cause weakness, shortness of breath or pale skin,
• severe reduction in blood cells: may cause weakness, bruising or make infections more likely,
• skin rash, swelling of lips, mouth, tongue or throat with breathing difficulties (hypersensitivity),
• low blood sugar levels,
• low magnesium levels in the blood,
• low levels of a protein called “albumin” in the blood,
• lack of benefit from nutrition (malnutrition),
• low sodium levels in the blood (hyponatremia),
• depression, sleep disorders,
• seizures, fainting or feeling faint, dizziness,
• tingling, prickling or stinging sensation of the skin (paraesthesia),
• altered mental state (encephalopathy),
• changes in taste (dysgeusia),
• sensation of spinning or dizziness (vertigo),
• heart rhythm problems (too fast or irregular, or extra heartbeats) visible on electrocardiogram (ECG),
• circulation problems,
• low blood pressure,
• wheezing, very rapid breathing, coughing up blood or blood-stained sputum, nosebleeds,
• indigestion,
• constipation,
• sensation of bloating (abdominal distension),
• enlarged liver,
• inflammation of the liver,
• skin problems, red or purple spots on the skin (petechiae), inflamed skin (dermatitis), hair loss,
• back pain,
• swelling of the limbs,
• feeling of weakness, extreme tiredness, drowsiness or irritability (malaise).

Side effects with unknown frequency:

• anaphylaxis (a severe allergic reaction).

Reporting of side effects
If you get any side effects, including any not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cresemba

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label after "Exp.".
The expiry date refers to the last day of that month.
Do not store above 30°C.
Keep in the original packaging to protect the medicine from moisture.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Cresemba contains

• The active substance is isavuconazole. Each capsule contains 74.5 mg of isavuconazonium sulfate, corresponding to 40 mg of isavuconazole (for Cresemba 40 mg hard capsules) or 186.3 mg of isavuconazonium sulfate, corresponding to 100 mg of isavuconazole (for Cresemba 100 mg hard capsules).
• The other components are:
• Capsule contents: magnesium citrate (anhydrous), microcrystalline cellulose (E460), talc (E553b), colloidal anhydrous silica, stearic acid.
• Capsule shell of Cresemba 40 mg hard capsules: hypromellose, red iron oxide (E172), titanium dioxide (E171).
• Capsule shell of Cresemba 100 mg hard capsules: hypromellose, red iron oxide (E172) (capsule body only), titanium dioxide (E171), gellan gum, potassium acetate, disodium edetate, sodium lauryl sulfate.
• Printing ink: shellac (E904), propylene glycol (E1520), potassium hydroxide, black iron oxide (E172).

Description of the appearance of Cresemba and contents of the pack
Cresemba 40 mg hard capsules are reddish-brown capsules with the imprint “CR40” in black ink on the cap.
Cresemba 100 mg hard capsules are reddish-brown capsule bodies with the imprint “100” in black ink and white caps with the imprint “C” in black ink.
Cresemba 40 mg hard capsules are available in boxes containing 35 capsules. Each box contains seven aluminium blisters with 5 capsules each.
Cresemba 100 mg hard capsules are available in boxes containing 14 capsules. Each box contains two aluminium blisters with 7 capsules each.
Each capsule cavity is connected to a cavity containing a “desiccant” to protect the capsules from moisture.
Do not pierce the blister containing the desiccant.
Do not ingest or use the desiccant.

Marketing Authorisation 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 further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Pfizer SA/NV Pfizer Luxembourg SARL filialas Lietuvoje
Tel/Tél: +32 (0)2 554 62 11 Tel. +3705 2514000

България Luxembourg/Luxemburg
Пфайзер Люксембург САРЛ, Клон България Pfizer SA/NV
Тел.: +359 2 970 4333 Tél/Tel: +32 (0)2 554 62 11

Česká republika Magyarország
Pfizer s.r.o. Pfizer Kft.
Tel: +420-283-004-111 Tel.: + 36 1 488 37 00

Danmark Malta
Unimedic Pharma AB Vivian Corporation Ltd.
Tlf: +46 (0) 10-130 99 50 Tel: +35621 344610

Deutschland Nederland
PFIZER PHARMA GmbH Pfizer bv
Tel: +49 (0)30 550055-51000 Tel: +31 (0)800 63 34 636

Eesti Norge
Pfizer Luxembourg SARL Eesti filiaal Unimedic Pharma AB
Tel: +372 666 7500 Tlf: +46 (0) 10-130 99 50

Ελλάδα Österreich
Pfizer ΕΛΛΑΣ A.E. Pfizer Corporation Austria Ges.m.b.H.
Τηλ: +30 210 67 85 800 Tel: +43 (0)1 521 15-0

España Polska
Pfizer S.L. Pfizer Polska Sp. z o.o.
Tel: +34 91 490 99 00 Tel.: +48 22 335 61 00

France Portugal
Pfizer Laboratórios Pfizer, Lda.
Tél: +33 (0)1 58 07 34 40 Tel: +351 21 423 5500

Hrvatska România
Pfizer Croatia d.o.o. Pfizer România S.R.L.
Tel: +385 1 3908 777 Tel: +40 (0) 21 20 728 00

Ireland Slovenija
Pfizer Healthcare Ireland Unlimited Company Pfizer Luxembourg SARL
Tel: +1800 633 363 (toll free) Pfizer, podružnica za svetovanje s področja
+44 (0)1304 616161 farmacevtske dejavnosti, Ljubljana
Tel: + 386 (0) 1 52 11 400

Ísland Slovenská republika
Unimedic Pharma AB Pfizer Luxembourg SARL, organizačná zložka
Sími: +46 (0) 10-130 99 50 Tel: +421-2-3355 5500

Italia Suomi/Finland
Pfizer S.r.l. Unimedic Pharma AB
Tel: +39 06 33 18 21 Puh/Tel: +46 (0) 10-130 99 50

Κύπρος Sverige
Pfizer ΕΛΛΑΣ Α.Ε. (CYPRUS BRANCH) Unimedic Pharma AB
Τηλ: +357 22 817690 Tel: +46 (0) 10-130 99 50

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel: +371 670 35 775

Other sources of information
More detailed information about this medicine is available on the website of the European Medicines Agency, https://www.ema.europa.eu/. In addition, links to other websites on rare diseases and related therapeutic treatments are provided.

Annex IV
Scientific conclusions and grounds for the variation of the terms of the marketing authorisation(s)

Scientific conclusions
Taking into account the evaluation by the Pharmacovigilance Risk Assessment Committee (PRAC) of the Periodic Safety Update Report(s) (PSUR) for isavuconazole, the PRAC's scientific conclusions are as follows:
In light of available data on hyponatremia from clinical studies, literature, and spontaneous reports—including 23 cases with a close temporal relationship, 11 cases with a positive de-challenge, and 1 case with a positive re-challenge—the PRAC considers that a causal relationship between isavuconazole and hyponatremia is at least a reasonable possibility. The PRAC concluded that the product information for medicinal products containing isavuconazole should therefore be updated accordingly.
Having reviewed the PRAC's recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the general conclusions and the rationale of the recommendation.

Grounds for the variation of the terms of the marketing authorisation(s)
Based on the scientific conclusions regarding isavuconazole, the CHMP considers that the benefit-risk balance of the medicinal product(s) containing isavuconazole remains favourable, subject to the proposed changes to the product information.
The CHMP recommends a variation to the terms of the marketing authorisation(s).