CRESEMBA: Uses, Dosage & Side Effects
A triazole antifungal agent for the treatment of invasive aspergillosis and mucormycosis in adults and children from 6 years of age
CRESEMBA (isavuconazole) is a broad-spectrum triazole antifungal medication used in adults and children from 6 years of age for the treatment of life-threatening invasive fungal infections, specifically invasive aspergillosis and mucormycosis. It is administered as isavuconazonium sulfate, a water-soluble prodrug that is rapidly converted to the active moiety isavuconazole after administration. CRESEMBA works by inhibiting the synthesis of ergosterol, a vital component of the fungal cell membrane, thereby killing or preventing the growth of the fungus. It is available as hard capsules for oral use and requires a prescription from a specialist physician experienced in the management of invasive fungal infections.
Quick Facts: CRESEMBA
Key Takeaways
- CRESEMBA (isavuconazole) is a triazole antifungal used to treat invasive aspergillosis and mucormycosis, two serious and potentially fatal fungal infections that primarily affect immunocompromised patients such as those undergoing chemotherapy, organ transplant recipients, or people with severe immune deficiency.
- The drug works by blocking the enzyme lanosterol 14-alpha-demethylase (CYP51), which fungi need to produce ergosterol for their cell membranes. Without ergosterol, fungal cells cannot maintain membrane integrity and die.
- Treatment begins with a loading dose of 200 mg (two 100 mg capsules) every 8 hours for the first two days (6 doses total), followed by a maintenance dose of 200 mg once daily. Capsules can be taken with or without food.
- CRESEMBA must not be used in patients with familial short QT syndrome or together with strong CYP3A4 inhibitors (ketoconazole) or inducers (rifampicin, carbamazepine, phenytoin, St. John’s wort). It has significant drug interactions requiring careful medication review.
- Common side effects include low potassium levels, decreased appetite, confusion, headache, nausea, vomiting, diarrhea, abnormal liver function tests, and rash. Liver function should be monitored throughout treatment. Do not take during pregnancy unless specifically advised by your doctor.
What Is CRESEMBA and What Is It Used For?
CRESEMBA contains the active substance isavuconazole, which belongs to the triazole class of antifungal agents. Triazole antifungals are a cornerstone of modern antifungal therapy and are considered first-line treatment for many invasive fungal infections. CRESEMBA is administered as isavuconazonium sulfate, a water-soluble prodrug that is rapidly cleaved by plasma esterases in the bloodstream to release the active moiety isavuconazole and an inactive cleavage product. This prodrug design allows for both oral and intravenous formulations, providing flexibility in clinical management.
Isavuconazole works by inhibiting the fungal enzyme lanosterol 14-alpha-demethylase, also known as CYP51. This enzyme is essential for the biosynthesis of ergosterol, a sterol that serves a similar structural role in fungal cell membranes as cholesterol does in human cell membranes. Ergosterol is vital for maintaining the integrity, fluidity, and function of the fungal cell membrane. When isavuconazole blocks CYP51, the fungal cell can no longer produce adequate ergosterol. Instead, toxic methylated sterol precursors accumulate, disrupting the membrane structure and leading to increased membrane permeability. This ultimately results in leakage of cellular contents and either inhibition of fungal growth (fungistatic effect) or fungal cell death (fungicidal effect), depending on the concentration achieved and the fungal species involved.
CRESEMBA demonstrates a broad spectrum of antifungal activity. In vitro, isavuconazole is active against Aspergillus species (including A. fumigatus, A. flavus, A. niger, and A. terreus), several species within the order Mucorales (including Rhizopus, Mucor, and Lichtheimia species), as well as various Candida species and other clinically relevant moulds. This broad-spectrum activity distinguishes isavuconazole from earlier triazoles such as voriconazole, which lacks reliable activity against the Mucorales.
CRESEMBA is approved by the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and regulatory authorities in numerous other countries for the following indications:
- Invasive aspergillosis: This is a severe fungal infection caused by Aspergillus species, most commonly Aspergillus fumigatus. Invasive aspergillosis primarily affects the lungs but can disseminate to other organs including the brain, skin, and sinuses. It occurs predominantly in severely immunocompromised patients, such as those receiving chemotherapy for hematological malignancies, solid organ or hematopoietic stem cell transplant recipients, and patients on prolonged high-dose corticosteroid therapy. The pivotal SECURE trial demonstrated that isavuconazole was non-inferior to voriconazole for the primary treatment of invasive aspergillosis, with a favorable safety profile including fewer hepatobiliary, skin, and eye-related adverse events.
- Mucormycosis (zygomycosis): This is a rare but highly aggressive and often rapidly fatal fungal infection caused by fungi of the order Mucorales, including Rhizopus, Mucor, Rhizomucor, and Lichtheimia species. Mucormycosis can present as rhinocerebral (sinus and brain), pulmonary (lung), cutaneous (skin), gastrointestinal, or disseminated disease. CRESEMBA is approved for the treatment of mucormycosis in patients for whom amphotericin B therapy is not appropriate. The approval was based on the VITAL study, an open-label, single-arm trial in patients with invasive fungal disease caused by rare fungi, including Mucorales.
Invasive fungal infections remain a major cause of morbidity and mortality in immunocompromised patients worldwide. The incidence of invasive aspergillosis in high-risk hematology patients ranges from 5% to 25%, with mortality rates of 30% to 95% depending on the patient population and timing of treatment initiation. Mucormycosis, though less common, carries an even higher mortality rate of 40% to 80%, and its incidence has been rising globally, partly driven by the increasing number of immunocompromised patients and, more recently, the global COVID-19 pandemic which was associated with a surge in mucormycosis cases, particularly in regions with high diabetes prevalence.
CRESEMBA represents an important advance in antifungal therapy because it offers activity against both Aspergillus and Mucorales species, has predictable pharmacokinetics without the need for therapeutic drug monitoring in most patients, can be given orally or intravenously (allowing seamless step-down therapy), and has a more favorable side effect profile compared with some other antifungal agents. Its long half-life of approximately 130 hours supports convenient once-daily dosing after the initial loading period.
What Should You Know Before Taking CRESEMBA?
Contraindications
There are specific situations in which CRESEMBA must not be used. Understanding these absolute contraindications is essential before treatment begins. Your doctor will review these carefully before prescribing.
- Hypersensitivity: Do not take CRESEMBA if you are allergic to isavuconazole or any of the other ingredients in the capsules, including magnesium citrate, microcrystalline cellulose, talc, colloidal anhydrous silica, stearic acid, hypromellose, iron oxide (E172), or titanium dioxide (E171).
- Familial short QT syndrome: CRESEMBA must not be used in patients with a hereditary heart rhythm condition known as familial short QT syndrome. Unlike most other azole antifungals, which tend to prolong the QT interval, isavuconazole has been shown to shorten the QT interval in a dose-dependent manner. In patients with already shortened QT intervals, this effect could potentially precipitate dangerous cardiac arrhythmias.
- Concurrent use with strong CYP3A4 inhibitors or inducers: CRESEMBA must not be taken together with ketoconazole (a strong CYP3A4 inhibitor), high-dose ritonavir (more than 200 mg every 12 hours), rifampicin, rifabutin, carbamazepine, barbiturates (such as phenobarbital), phenytoin, St. John’s wort, efavirenz, etravirine, or nafcillin. These medications can either dangerously increase or decrease the blood levels of isavuconazole.
Warnings and Precautions
Stop taking CRESEMBA and seek immediate medical attention if you experience sudden wheezing, difficulty breathing, swelling of the face, lips, mouth or tongue, severe itching, sweating, dizziness or fainting, rapid heartbeat, or pounding in the chest. These may be signs of a serious allergic reaction (anaphylaxis).
Talk to your doctor, pharmacist, or nurse before taking CRESEMBA in the following situations:
- Previous allergic reaction to azole antifungals: If you have previously had an allergic reaction to other azole antifungal agents such as ketoconazole, fluconazole, itraconazole, voriconazole, or posaconazole, inform your doctor. Cross-sensitivity between azole antifungals is possible, and your doctor will weigh the risks and benefits of prescribing CRESEMBA.
- Liver disease: If you have any liver condition, your doctor should monitor you for potential adverse effects on the liver. CRESEMBA can occasionally affect liver function, and liver function blood tests should be performed before starting treatment and regularly throughout therapy. Cases of severe hepatic reactions, including hepatitis and liver failure, have been reported with azole antifungals as a class.
CRESEMBA can sometimes affect liver function. Your doctor may order blood tests before and during your treatment to monitor your liver enzymes. If you notice yellowing of your skin or eyes, dark urine, pale stools, persistent nausea, or unusual fatigue, contact your doctor immediately as these may be signs of liver problems.
Additionally, tell your doctor immediately if you develop severe blistering of the skin, mouth, eyes, or genital area during treatment with CRESEMBA. These may be signs of a serious skin reaction that requires prompt medical attention.
Use in Children and Adolescents
CRESEMBA 40 mg capsules are not suitable for children between 1 and 6 years of age, as this formulation has not been studied in this age group. For children from 6 years of age and adolescents weighing at least 32 kg, the doctor may prescribe CRESEMBA 100 mg capsules. Other formulations of isavuconazole may be available for children who cannot swallow capsules. The dosing in pediatric patients is weight-based and differs from adult dosing. Always follow the specific dosing instructions provided by the treating physician.
Pregnancy and Breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking CRESEMBA. The effects of isavuconazole on the unborn baby are not fully known. As with other azole antifungals, there is a theoretical risk of harm to the developing fetus based on the mechanism of action (interference with sterol synthesis) and findings in animal studies with related compounds. Therefore, CRESEMBA should not be used during pregnancy unless your doctor specifically determines that the potential benefit to you outweighs the potential risk to the unborn child.
Do not breastfeed while taking CRESEMBA. It is not known whether isavuconazole or its metabolites are excreted in human breast milk, and a risk to the breastfed infant cannot be excluded. Your doctor will discuss alternative feeding options with you if you need treatment with CRESEMBA while you have a nursing infant.
Driving and Operating Machinery
CRESEMBA may cause side effects such as confusion, drowsiness, sleepiness, and fainting. These effects can impair your ability to drive safely or operate machinery. If you experience any of these symptoms, you should exercise extreme caution and avoid driving or using machines until the symptoms have fully resolved. Discuss with your doctor if you have any concerns about these potential effects on your daily activities.
How Does CRESEMBA Interact with Other Drugs?
Drug interactions with CRESEMBA are clinically important because isavuconazole is primarily metabolized by the CYP3A4 and CYP3A5 enzymes and also acts as an inhibitor of CYP3A4. This means that medications which strongly inhibit or induce CYP3A4 can significantly alter isavuconazole blood levels, while isavuconazole itself can increase the levels of other drugs that are metabolized by CYP3A4. Additionally, isavuconazole is a mild inhibitor of P-glycoprotein (P-gp) and organic cation transporter 2 (OCT2), which can affect the levels of certain other medications. It is essential to inform your doctor about all medications, herbal products, and dietary supplements you are currently taking or have recently taken.
Contraindicated Combinations (Do Not Use Together)
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Ketoconazole | Strong CYP3A4 inhibitor – markedly increases isavuconazole levels | Contraindicated – risk of severe toxicity |
| High-dose ritonavir (>200 mg every 12 hours) | Strong CYP3A4 inhibitor – significantly increases isavuconazole exposure | Contraindicated – risk of increased toxicity |
| Rifampicin, rifabutin | Strong CYP3A4 inducers – dramatically reduce isavuconazole levels | Contraindicated – loss of antifungal efficacy |
| Carbamazepine | Strong CYP3A4 inducer – substantially reduces isavuconazole levels | Contraindicated – inadequate antifungal exposure |
| Phenytoin, phenobarbital (barbiturates) | Strong CYP3A4 inducers – greatly reduce isavuconazole exposure | Contraindicated – treatment failure likely |
| St. John’s wort (Hypericum perforatum) | Potent CYP3A4 inducer – substantially reduces isavuconazole levels | Contraindicated – efficacy compromised |
| Efavirenz, etravirine | CYP3A4 inducers – reduce isavuconazole exposure | Contraindicated – subtherapeutic antifungal levels |
| Nafcillin | CYP3A4 inducer – reduces isavuconazole levels | Contraindicated – may lead to treatment failure |
Medications Requiring Caution or Dose Adjustment
| Interacting Drug | Effect | Recommendation |
|---|---|---|
| Cyclosporine | Isavuconazole increases cyclosporine levels (CYP3A4 substrate) | Monitor cyclosporine levels and adjust dose accordingly |
| Tacrolimus | Isavuconazole increases tacrolimus levels (CYP3A4 substrate) | Monitor tacrolimus levels closely; dose reduction likely needed |
| Sirolimus | Isavuconazole increases sirolimus levels (CYP3A4 substrate) | Monitor sirolimus levels and adjust dose as needed |
| Digoxin | Isavuconazole may increase digoxin levels (P-gp substrate) | Monitor digoxin levels; watch for toxicity signs |
| Midazolam | Isavuconazole increases midazolam levels (CYP3A4 substrate) | Use with caution; consider dose reduction of midazolam |
| Mycophenolate mofetil (MMF) | Potential alteration of MMF exposure | Monitor for MMF-related adverse effects |
| Metformin | Isavuconazole may increase metformin levels (OCT2 inhibition) | Monitor blood glucose; adjust metformin dose if needed |
| Dabigatran | Isavuconazole may increase dabigatran levels (P-gp substrate) | Monitor for signs of bleeding; dose adjustment may be needed |
| Fentanyl, alfentanil | Isavuconazole may increase opioid levels (CYP3A4 substrates) | Monitor for respiratory depression and excessive sedation |
| Vincristine, vinblastine | Increased levels of vinca alkaloids (CYP3A4 substrates) | Monitor for neurotoxicity and other chemotherapy side effects |
Certain other medications may also interact with CRESEMBA. Rufinamid and other drugs that shorten the QT interval on an ECG should only be used with CRESEMBA under careful medical supervision. Aprepitant (used to prevent chemotherapy-induced nausea), prednisone (corticosteroid), and pioglitazone (antidiabetic) may have their levels altered by isavuconazole, though these interactions are generally less severe. Always provide your doctor with a complete list of all your medications, including over-the-counter products and herbal supplements.
What Is the Correct Dosage of CRESEMBA?
Always take CRESEMBA exactly as your doctor or pharmacist has instructed. Do not change the dose or stop taking the medicine without consulting your doctor first, even if you feel better. It is crucial to complete the full course of treatment as prescribed to ensure the fungal infection is fully eradicated.
Adults
Loading Dose (Days 1–2)
Dose: 200 mg (two 100 mg capsules) every 8 hours
Duration: 6 doses total over the first two days
Note: This intensive initial dosing regimen rapidly achieves therapeutic blood levels of isavuconazole, which is critical in the context of life-threatening invasive fungal infections where delays in achieving adequate drug exposure can worsen outcomes.
Maintenance Dose (Day 3 Onwards)
Dose: 200 mg (two 100 mg capsules) once daily
Start: 12 to 24 hours after the last loading dose
Duration: Continue until your doctor advises otherwise. If your doctor considers it necessary, treatment may continue for longer than 6 months.
Children (6 to 17 Years)
For children from 6 years of age, the dose is determined by body weight. The same loading and maintenance schedule applies (every 8 hours on days 1–2, then once daily), but the amount taken depends on the child’s weight:
| Body Weight | Each Loading Dose (every 8 hours, Days 1–2) | Total Daily Loading Dose (Days 1–2) | Maintenance Dose (once daily) |
|---|---|---|---|
| 16 kg to <18 kg | 80 mg (two 40 mg capsules) | 240 mg (six 40 mg capsules) | 80 mg (two 40 mg capsules) |
| 18 kg to <25 kg | 120 mg (three 40 mg capsules) | 360 mg (nine 40 mg capsules) | 120 mg (three 40 mg capsules) |
| 25 kg to <32 kg | 160 mg (four 40 mg capsules) | 480 mg (twelve 40 mg capsules) | 160 mg (four 40 mg capsules) |
| 32 kg to <37 kg | 180 mg (one 100 mg + two 40 mg capsules) | 540 mg | 180 mg (one 100 mg + two 40 mg capsules) |
| ≥37 kg | 200 mg (two 100 mg capsules) | 600 mg (six 100 mg capsules) | 200 mg (two 100 mg capsules) |
Children under 6 years of age or those who cannot swallow capsules may require alternative formulations. Consult your doctor or pharmacist for appropriate options.
How to Take CRESEMBA Capsules
- The capsules can be taken with or without food.
- Swallow the capsules whole. Do not chew, crush, dissolve, or open them.
- Each blister pocket is connected to a pocket containing a desiccant to protect the capsule from moisture. Do not puncture the blister containing the desiccant, and do not swallow or use the desiccant.
Missed Dose
If you miss a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and take the next dose at the normal time. Do not take a double dose to make up for a forgotten one. Maintaining a consistent dosing schedule is important for keeping isavuconazole levels in the therapeutic range.
Overdose
If you have taken more CRESEMBA than prescribed, seek medical attention immediately or go to the nearest hospital emergency department. Take the medicine packaging with you so the doctor knows what you have taken. Overdose symptoms may include headache, dizziness, restlessness, drowsiness, tingling sensations, reduced sensation of touch or feeling in the mouth, difficulty concentrating, hot flushes, anxiety, joint pain, altered taste, dry mouth, diarrhea, vomiting, palpitations, increased heart rate, and increased sensitivity to light.
Stopping Treatment
Do not stop taking CRESEMBA unless your doctor tells you to. It is important to continue taking the medicine for as long as your doctor prescribes to ensure the fungal infection is fully cleared. Stopping treatment prematurely can lead to the infection returning or becoming resistant to treatment.
What Are the Side Effects of CRESEMBA?
Like all medicines, CRESEMBA can cause side effects, although not everyone experiences them. The frequency and severity of side effects vary between individuals and may depend on factors such as the underlying disease, concurrent medications, and overall health status. Your medical team will monitor you regularly and manage side effects as they occur.
Stop taking CRESEMBA and tell your doctor straight away if you notice any of the following: sudden wheezing, difficulty breathing, swelling of the face, lips, mouth or tongue, severe itching, sweating, dizziness or fainting, rapid heartbeat or pounding in the chest. These may be signs of a severe allergic reaction (anaphylaxis). Also tell your doctor immediately if you develop severe blistering of the skin, mouth, eyes, or genital area.
Side Effects by Frequency
Common
May affect up to 1 in 10 people
- Low potassium in the blood (hypokalemia)
- Decreased appetite
- Confusion (delirium)
- Headache
- Drowsiness or sleepiness
- Inflamed veins that may cause blood clots (thrombophlebitis)
- Shortness of breath or sudden severe difficulty breathing
- Nausea, vomiting, diarrhea, abdominal pain
- Abnormal liver function test results
- Skin rash, itching (pruritus)
- Kidney impairment (symptoms may include swollen legs)
- Chest pain
- Fatigue, drowsiness, or feeling generally unwell
Uncommon
May affect up to 1 in 100 people
- Decreased white blood cells (neutropenia) – may increase risk of infections and fever
- Decreased platelets (thrombocytopenia) – may increase risk of bleeding or bruising
- Decreased red blood cells (anemia) – may cause weakness, breathlessness, or pale skin
- Severely decreased blood cell counts (pancytopenia)
- Hypersensitivity reactions – rash, swelling of lips, mouth, tongue or throat with difficulty breathing
- Low blood sugar (hypoglycemia)
- Low magnesium in the blood (hypomagnesemia)
- Low albumin in the blood
- Low sodium in the blood (hyponatremia)
- Malnutrition
- Depression, difficulty sleeping (insomnia)
- Seizures, fainting or feeling faint, dizziness
- Tingling and numbness in the skin (paresthesia)
- Altered mental state (encephalopathy)
- Altered taste (dysgeusia), vertigo
- Heart rhythm problems – too fast, irregular, or extra heartbeats (visible on ECG)
- Circulatory problems, low blood pressure
- Wheezing, very fast breathing, coughing up blood, nosebleeds
- Indigestion (dyspepsia), constipation, abdominal bloating
- Enlarged liver (hepatomegaly), liver inflammation (hepatitis)
- Skin problems, red or purple spots on the skin (petechiae), skin inflammation (dermatitis), hair loss
- Back pain, swollen arms and legs (peripheral edema)
- Feeling weak, very tired, or generally unwell (malaise)
Not Known
Frequency cannot be estimated from available data
- Anaphylaxis (a severe, potentially life-threatening allergic reaction)
Changes in Liver Function
CRESEMBA can sometimes affect liver function. Your doctor will monitor your liver function through blood tests during treatment. Symptoms that may suggest liver problems include yellowing of the skin or whites of the eyes (jaundice), unusually dark urine, pale stools, persistent nausea or vomiting, loss of appetite, or unusual tiredness. If you notice any of these symptoms, contact your doctor promptly.
Reporting Side Effects
If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed above. You can also report side effects directly to your national pharmacovigilance authority. By reporting side effects, you help provide more information on the safety of this medicine and contribute to the ongoing monitoring of its benefit-risk balance.
How Should You Store CRESEMBA?
Proper storage of CRESEMBA is important to ensure the medication remains effective and safe throughout its shelf life. Follow these storage guidelines carefully:
- Temperature: Store at or below 30°C (86°F). Do not freeze.
- Packaging: Keep the capsules in their original blister packaging to protect them from moisture. Each blister pocket is connected to a pocket containing a desiccant. Do not puncture the desiccant pocket, and do not swallow or use the desiccant material.
- Child safety: Keep this medicine out of the sight and reach of children at all times.
- Expiry date: Do not use CRESEMBA after the expiry date stated on the packaging after “EXP.” The expiry date refers to the last day of that month.
- Disposal: Do not dispose of medicines by flushing them down the toilet or throwing them in household waste. Ask your pharmacist about proper disposal methods. These measures help protect the environment.
What Does CRESEMBA Contain?
Active Ingredient
The active substance in CRESEMBA is isavuconazole, which is administered in the form of isavuconazonium sulfate, a water-soluble prodrug. The prodrug is rapidly converted to isavuconazole (the active moiety) and an inactive cleavage product by plasma esterases after absorption.
- CRESEMBA 40 mg hard capsules: Each capsule contains 74.5 mg isavuconazonium sulfate, equivalent to 40 mg isavuconazole.
- CRESEMBA 100 mg hard capsules: Each capsule contains 186.3 mg isavuconazonium sulfate, equivalent to 100 mg isavuconazole.
Inactive Ingredients (Excipients)
The other ingredients in CRESEMBA capsules include:
- Capsule contents: Magnesium citrate (anhydrous), microcrystalline cellulose (E460), talc (E553b), colloidal anhydrous silica, stearic acid.
- 40 mg capsule shell: Hypromellos, red iron oxide (E172), titanium dioxide (E171).
- 100 mg capsule shell: Hypromellos, red iron oxide (E172) (lower part 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).
Appearance and Packaging
CRESEMBA 40 mg hard capsules are reddish-brown capsules with the cap printed with “CR40” in black ink. They are available in cartons containing 35 capsules (seven aluminum blisters with 5 capsules each).
CRESEMBA 100 mg hard capsules have a reddish-brown lower part printed with “100” in black ink and a white upper part printed with “C” in black ink. They are available in cartons containing 14 capsules (two aluminum blisters with 7 capsules each).
Each capsule pocket is connected to a desiccant pocket to protect the capsule from moisture. Do not puncture the desiccant pocket, and do not swallow or use the desiccant material.
Marketing Authorization Holder
CRESEMBA is manufactured by Basilea Pharmaceutica Deutschland GmbH, with production facilities operated by Almac Pharma Services in Ireland and the United Kingdom (Northern Ireland). The product is distributed globally through various regional partners.
Frequently Asked Questions About CRESEMBA
CRESEMBA (isavuconazole) is a prescription antifungal medicine used to treat two types of serious invasive fungal infections in adults and children from 6 years of age: invasive aspergillosis (caused by Aspergillus fungi) and mucormycosis (caused by fungi of the order Mucorales) in patients for whom amphotericin B is not appropriate. These are life-threatening infections that primarily affect people with severely weakened immune systems, such as patients undergoing chemotherapy, organ transplant recipients, or those with HIV/AIDS.
The duration of CRESEMBA treatment depends on the type and severity of the infection and your clinical response. Treatment starts with a loading regimen over 2 days (6 doses given every 8 hours) followed by once-daily maintenance dosing. Your doctor will determine when it is safe to stop treatment. In many cases, treatment continues for several weeks to months. If necessary, treatment can last longer than 6 months. Do not stop taking CRESEMBA without your doctor’s approval, as stopping too early may allow the infection to return.
Yes, CRESEMBA capsules can be taken with or without food. This flexibility is a practical advantage for patients who may have reduced appetite or nausea due to their underlying condition or other medications. The capsules should be swallowed whole and must not be chewed, crushed, dissolved, or opened. Each blister pocket includes a desiccant packet for moisture protection – do not puncture or swallow the desiccant.
In the pivotal SECURE trial, isavuconazole was shown to be non-inferior to voriconazole for the primary treatment of invasive aspergillosis, with comparable overall mortality rates at day 42. CRESEMBA demonstrated a favorable safety profile compared with voriconazole, with significantly fewer hepatobiliary adverse events, skin and subcutaneous tissue disorders, and eye disorders. Unlike voriconazole, isavuconazole does not require therapeutic drug monitoring in most patients, shortens (rather than prolongs) the QT interval, and offers convenient once-daily dosing after the loading period. Additionally, CRESEMBA has activity against Mucorales species, which voriconazole does not.
Yes, but in an unusual way compared to most other azole antifungals. CRESEMBA shortens the QT interval on an electrocardiogram (ECG) in a dose-dependent manner, whereas most other azoles prolong it. This QT-shortening effect means CRESEMBA is contraindicated in patients with familial short QT syndrome, a rare inherited heart condition. For most patients, this QT-shortening effect is not clinically significant, but your doctor should be aware of all heart conditions you may have before starting treatment.
All information in this article is based on the officially approved prescribing information from the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), international clinical guidelines from IDSA/ATS, ECIL, and ESCMID/ECMM, the pivotal SECURE and VITAL clinical trials, WHO recommendations, and peer-reviewed medical literature. All medical claims follow the GRADE evidence framework and represent the highest available level of clinical evidence.
References
- European Medicines Agency (EMA). CRESEMBA – Summary of Product Characteristics. Last updated 2025. Available at: ema.europa.eu/cresemba
- U.S. Food and Drug Administration (FDA). CRESEMBA – Prescribing Information. Approved 2015, last revised 2024. Available at: fda.gov/cresemba
- Maertens JA, Raad II, Marr KA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet. 2016;387(10020):760-769. doi:10.1016/S0140-6736(15)01159-9
- Marty FM, Ostrosky-Zeichner L, Cornely OA, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis (VITAL study). Lancet Infect Dis. 2016;16(7):828-837. doi:10.1016/S1473-3099(16)00071-2
- Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America (IDSA). Clin Infect Dis. 2016;63(4):e1-e60. doi:10.1093/cid/ciw326
- Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. 2019;19(12):e405-e421. doi:10.1016/S1473-3099(19)30312-3
- Tissot F, Agrawal S, Pagano L, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017;102(3):433-444. doi:10.3324/haematol.2016.152900
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: WHO; 2023.
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