Cresemba 186mg Capsules
It is used to treat fungal infections.
Drug Class
Antifungal
Pharmacologic Class
Triazole Antifungal
Pregnancy Category
Not assigned (Risk Summary available)
FDA Approved
Mar 2015
DEA Schedule
Not Controlled
Overview
What is this medicine?
Cresemba is an antifungal medication used to treat serious and life-threatening fungal infections, such as invasive aspergillosis and invasive mucormycosis. It works by stopping the growth of the fungus.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take the medication with or without food, and swallow the capsule whole - do not chew, crush, open, or dissolve it. Only remove the medication from the blister pack when you are ready to take it, and take it immediately after opening. Do not store the removed medication for later use.
When handling the medication, be sure to only open the capsule pocket, leaving the desiccant pocket (which protects the capsule from moisture) closed. Continue taking the medication as directed, even if your symptoms improve.
Important Administration Note
Do not administer this medication through a feeding tube.
Storing and Disposing of Your Medication
Store the medication in its original container at room temperature, in a dry location, and away from bathrooms. Keep all medications in a safe place, out of the reach of children and pets.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take the medication with or without food, and swallow the capsule whole - do not chew, crush, open, or dissolve it. Only remove the medication from the blister pack when you are ready to take it, and take it immediately after opening. Do not store the removed medication for later use.
When handling the medication, be sure to only open the capsule pocket, leaving the desiccant pocket (which protects the capsule from moisture) closed. Continue taking the medication as directed, even if your symptoms improve.
Important Administration Note
Do not administer this medication through a feeding tube.
Storing and Disposing of Your Medication
Store the medication in its original container at room temperature, in a dry location, and away from bathrooms. Keep all medications in a safe place, out of the reach of children and pets.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Take Cresemba capsules with or without food.
- Swallow capsules whole; do not chew, crush, dissolve, or open them.
- Avoid strong sun exposure and use sunscreen, as this medication may increase sensitivity to sunlight.
- Inform your doctor about all other medications you are taking, including over-the-counter drugs, herbal supplements, and vitamins, as many drugs can interact with Cresemba.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Loading: 2 capsules (372 mg isavuconazonium sulfate, equivalent to 200 mg isavuconazole) orally every 8 hours for 6 doses (48 hours). Maintenance: 2 capsules (372 mg isavuconazonium sulfate, equivalent to 200 mg isavuconazole) orally once daily, starting 12 to 24 hours after the last loading dose.
Condition-Specific Dosing:
Invasive Aspergillosis:
Standard dosing as above.
Invasive Mucormycosis:
Standard dosing as above.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established for invasive aspergillosis or mucormycosis.
Adolescent:
Not established for invasive aspergillosis or mucormycosis.
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required.
Moderate:
No dose adjustment required.
Severe:
No dose adjustment required.
Dialysis:
No dose adjustment required; not dialyzable.
Hepatic Impairment:
Mild:
No dose adjustment required.
Moderate:
No dose adjustment required.
Severe:
Not studied in patients with severe hepatic impairment (Child-Pugh C); use with caution and monitor for drug-related adverse reactions.
Pharmacology
Mechanism of Action
Isavuconazole is an azole antifungal agent. It inhibits cytochrome P450-dependent 14-alpha-lanosterol demethylation, which is an essential step in fungal ergosterol synthesis. This inhibition leads to the depletion of ergosterol in the fungal cell membrane and the accumulation of methylated sterol precursors, resulting in the disruption of fungal cell membrane integrity and function, thereby inhibiting fungal growth.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 98%
Tmax:
2-4 hours
FoodEffect:
No clinically significant effect of food on absorption.
Distribution:
Vd:
Approximately 450 L (large volume of distribution)
ProteinBinding:
>99% (primarily to albumin)
CnssPenetration:
Limited data, but detected in cerebrospinal fluid (CSF).
Elimination:
HalfLife:
Approximately 79 hours
Clearance:
Not readily quantifiable due to extensive metabolism and long half-life.
ExcretionRoute:
Approximately 46% via feces and 46% via urine (primarily as metabolites).
Unchanged:
<1% (in urine)
Pharmacodynamics
OnsetOfAction:
Not precisely defined for clinical effect, but drug levels are achieved rapidly with loading dose.
PeakEffect:
Steady-state concentrations are generally achieved within 6 days of once-daily dosing.
DurationOfAction:
Related to the long half-life and sustained drug levels.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat. In rare cases, allergic reactions can be fatal.
Signs of kidney problems: inability to pass urine, changes in urine output, blood in the urine, or significant weight gain.
Signs of electrolyte problems: mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, balance changes, abnormal heartbeat, seizures, loss of appetite, or severe nausea and vomiting.
Chest pain or pressure, rapid heartbeat, or abnormal heartbeat.
Confusion.
Shortness of breath.
Swelling in the arms or legs.
Dizziness or fainting.
Flushing.
Excessive sweating.
Liver problems: this medication can cause liver damage, which can be fatal in people with severe underlying health conditions. Seek medical help immediately if you experience dark urine, fatigue, decreased appetite, stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Severe skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis): this rare but potentially life-threatening condition can cause severe health problems and death. Seek medical help immediately if you experience red, swollen, blistered, or peeling skin (with or without fever), red or irritated eyes, or sores in your mouth, throat, nose, or eyes.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor or seek medical attention:
Back pain.
Constipation, diarrhea, stomach pain, nausea, vomiting, or decreased appetite.
Cough.
Fatigue or weakness.
Headache.
Trouble sleeping.
* Anxiety.
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat. In rare cases, allergic reactions can be fatal.
Signs of kidney problems: inability to pass urine, changes in urine output, blood in the urine, or significant weight gain.
Signs of electrolyte problems: mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, balance changes, abnormal heartbeat, seizures, loss of appetite, or severe nausea and vomiting.
Chest pain or pressure, rapid heartbeat, or abnormal heartbeat.
Confusion.
Shortness of breath.
Swelling in the arms or legs.
Dizziness or fainting.
Flushing.
Excessive sweating.
Liver problems: this medication can cause liver damage, which can be fatal in people with severe underlying health conditions. Seek medical help immediately if you experience dark urine, fatigue, decreased appetite, stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Severe skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis): this rare but potentially life-threatening condition can cause severe health problems and death. Seek medical help immediately if you experience red, swollen, blistered, or peeling skin (with or without fever), red or irritated eyes, or sores in your mouth, throat, nose, or eyes.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor or seek medical attention:
Back pain.
Constipation, diarrhea, stomach pain, nausea, vomiting, or decreased appetite.
Cough.
Fatigue or weakness.
Headache.
Trouble sleeping.
* Anxiety.
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of liver problems: unusual tiredness, dark urine, yellowing of the skin or eyes (jaundice), severe stomach pain, nausea, vomiting.
- Signs of an allergic reaction: rash, hives, itching, swelling of the face, lips, tongue, or throat, difficulty breathing or swallowing.
- Severe skin reactions: blistering, peeling, or red skin rash.
- Severe or persistent diarrhea, nausea, or vomiting.
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced.
If you have been diagnosed with Familial Short QT syndrome.
If you are currently taking any of the following medications: Carbamazepine, ketoconazole, phenobarbital or similar drugs, rifampin, ritonavir, St. John's wort, or vincristine.
If you are breastfeeding. Note that you should not breastfeed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications (including prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced.
If you have been diagnosed with Familial Short QT syndrome.
If you are currently taking any of the following medications: Carbamazepine, ketoconazole, phenobarbital or similar drugs, rifampin, ritonavir, St. John's wort, or vincristine.
If you are breastfeeding. Note that you should not breastfeed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications (including prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular blood tests will be necessary, as directed by your doctor, to monitor your condition. Be sure to discuss any concerns or questions with your doctor.
This medication can pose a risk to an unborn baby if taken during pregnancy. If you are of childbearing potential, it is crucial to use effective birth control methods while taking this drug and for a specified period after the last dose. Consult your doctor to determine the recommended duration of birth control use. If you become pregnant or suspect you may be pregnant, notify your doctor immediately.
This medication can pose a risk to an unborn baby if taken during pregnancy. If you are of childbearing potential, it is crucial to use effective birth control methods while taking this drug and for a specified period after the last dose. Consult your doctor to determine the recommended duration of birth control use. If you become pregnant or suspect you may be pregnant, notify your doctor immediately.
Overdose Information
Overdose Symptoms:
- Limited data on human overdose. Symptoms may include headache, dizziness, nausea, vomiting, diarrhea, or elevated liver enzymes.
What to Do:
In case of suspected overdose, contact a poison control center immediately (e.g., 1-800-222-1222 in the US) or seek emergency medical attention. Management should be supportive and symptomatic. Isavuconazole is highly protein-bound and not significantly removed by hemodialysis.
Drug Interactions
Contraindicated Interactions
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) - significantly decrease isavuconazole plasma concentrations.
- Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) - significantly increase isavuconazole plasma concentrations.
Major Interactions
- Moderate CYP3A4 inducers (e.g., efavirenz) - may decrease isavuconazole concentrations; consider alternative.
- Moderate CYP3A4 inhibitors (e.g., erythromycin, diltiazem) - may increase isavuconazole concentrations; monitor for adverse effects.
- Sirolimus - Isavuconazole may increase sirolimus concentrations; monitor sirolimus levels and adjust dose.
- Cyclosporine - Isavuconazole may increase cyclosporine concentrations; monitor cyclosporine levels and adjust dose.
- Tacrolimus - Isavuconazole may increase tacrolimus concentrations; monitor tacrolimus levels and adjust dose.
- P-glycoprotein (P-gp) substrates (e.g., dabigatran, digoxin) - Isavuconazole is a weak inhibitor of P-gp; monitor for increased substrate exposure.
Moderate Interactions
- Rifabutin - May decrease isavuconazole concentrations; monitor for efficacy.
- Oral Contraceptives - Isavuconazole may increase ethinyl estradiol and norethindrone concentrations; clinical significance unknown.
- Mycophenolate Mofetil - Isavuconazole may increase mycophenolic acid concentrations; monitor for toxicity.
Minor Interactions
- Proton Pump Inhibitors/H2-receptor antagonists/Antacids - No clinically significant interaction.
Monitoring
Baseline Monitoring
Liver Function Tests (ALT, AST, bilirubin)
Rationale: To establish baseline hepatic function and identify pre-existing impairment, as isavuconazole is metabolized by the liver and can cause hepatotoxicity.
Timing: Prior to initiation of therapy.
Renal Function (Serum Creatinine, eGFR/CrCl)
Rationale: To assess baseline renal function, although no dose adjustment is needed for renal impairment, it's important for overall patient assessment.
Timing: Prior to initiation of therapy.
Electrolytes (Potassium, Magnesium)
Rationale: To ensure baseline electrolyte balance, especially if patient has other risk factors for arrhythmias, though isavuconazole does not prolong QTc.
Timing: Prior to initiation of therapy.
Routine Monitoring
Liver Function Tests (ALT, AST, bilirubin)
Frequency: Periodically, or as clinically indicated, especially if signs/symptoms of hepatic dysfunction develop.
Target: Within normal limits or stable from baseline.
Action Threshold: Significant elevation (e.g., >3-5x ULN) or signs of liver injury; consider dose modification or discontinuation.
Clinical Response to Therapy
Frequency: Daily during acute phase, then regularly throughout treatment.
Target: Improvement in signs and symptoms of fungal infection.
Action Threshold: Lack of improvement or worsening of infection; consider alternative therapy.
Adverse Drug Reactions
Frequency: Daily during acute phase, then regularly throughout treatment.
Target: Absence or manageable level of side effects.
Action Threshold: Development of severe or intolerable adverse effects (e.g., severe GI upset, rash, signs of hepatotoxicity); consider dose modification or discontinuation.
Symptom Monitoring
- Nausea
- Vomiting
- Diarrhea
- Headache
- Elevated liver enzymes (fatigue, dark urine, yellowing skin/eyes, abdominal pain)
- Rash
- Hypersensitivity reactions (swelling of face/throat, difficulty breathing)
- Infusion-related reactions (if IV formulation used)
Special Patient Groups
Pregnancy
Based on animal data, Cresemba may cause fetal harm. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Advise pregnant women of the potential risk to a fetus.
Trimester-Specific Risks:
First Trimester:
Potential for fetal harm based on animal studies.
Second Trimester:
Potential for fetal harm based on animal studies.
Third Trimester:
Potential for fetal harm based on animal studies.
Lactation
It is not known whether isavuconazole is excreted in human milk. Due to the potential for serious adverse reactions in a breastfed infant, advise women not to breastfeed during treatment with Cresemba and for 48 hours after the last dose.
Infant Risk:
Unknown, but potential for serious adverse reactions.
Pediatric Use
Safety and effectiveness in pediatric patients (less than 18 years of age) have not been established for invasive aspergillosis or mucormycosis. Limited data suggest potential for use in specific pediatric populations for other indications in some regions, but generally not established for these severe infections in the US.
Geriatric Use
No dose adjustment is required for elderly patients. Clinical studies did not identify differences in safety or efficacy between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Clinical Information
Clinical Pearls
- Unlike many other azole antifungals (e.g., voriconazole, posaconazole), isavuconazole does NOT prolong the QTc interval; in fact, it has been shown to cause QTc shortening in some patients.
- No therapeutic drug monitoring (TDM) is required for isavuconazole, simplifying patient management.
- The prodrug formulation (isavuconazonium sulfate) is rapidly converted to the active drug (isavuconazole) by esterases.
- Can be taken with or without food, offering dosing flexibility.
- Effective against a broad spectrum of fungi, including Aspergillus and Mucorales species, making it a valuable option for invasive mold infections.
Alternative Therapies
- Voriconazole (for invasive aspergillosis)
- Posaconazole (for invasive aspergillosis and mucormycosis)
- Amphotericin B formulations (e.g., liposomal amphotericin B for invasive aspergillosis and mucormycosis)
- Echinocandins (e.g., caspofungin, micafungin, anidulafungin - primarily for Candida, but sometimes used in combination for molds)
Cost & Coverage
Average Cost:
High (typically several thousand USD) per 30 capsules
Insurance Coverage:
Tier 3 or 4 (Specialty Drug)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.