Cresemba
- Generic Name: isavuconazonium sulfate injection and capsules
- Brand Name: Cresemba
Cresemba (Isavuconazonium Sulfate Injection and Capsules) side effects drug center
Cresemba Side Effects Center
What Is Cresemba?
Cresemba (isavuconazonium sulfate) is an azole antifungal drug used to treat invasive aspergillosis and invasive mucormycosis.
What Are Side Effects of Cresemba?
Common side effects of Cresemba include:
- nausea,
- vomiting,
- abdominal pain,
- diarrhea,
- headache,
- abnormal liver blood tests,
- low blood potassium (hypokalemia),
- constipation,
- indigestion,
- cough,
- swelling of the extremities,
- back pain,
- fatigue,
- chest pain,
- injection site reactions,
- decreased appetite,
- back pain,
- insomnia,
- anxiety,
- shortness of breath,
- rash or itching, and
- low blood pressure.
Dosage for Cresemba
Cresemba is administered intravenously and a physician will determine the dose.
What Drugs, Substances, or Supplements Interact with Cresemba?
Cresemba may interact with ketoconazole, lopinavir, ritonavir, rifampin, carbamazepine, St. John's wort, barbiturates, atorvastatin, sirolimus, tacrolimus, midazolam, bupropion or digoxin. Tell your doctor all medications and supplements you use.
Cresemba During Pregnancy or Breastfeeding
During pregnancy, Cresemba should be taken only if prescribed. This drug passes into breast milk. Breastfeeding is not recommended while using Cresemba.
Additional Information
Our Cresemba (isavuconazonium sulfate) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
Cresemba Consumer Information
Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).
Some side effects may occur during the injection. Tell your caregiver right away if you feel dizzy, light-headed, difficult breathing, chilled, or have any numbness, tingling, or changes in your sense of touch.
Call your doctor at once if you have:
- liver problems--loss of appetite, stomach pain (upper right side), tiredness, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
- low potassium level--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.
Common side effects may include:
- nausea, vomiting, diarrhea, constipation;
- swelling in your arms or legs;
- headache, back pain;
- cough, shortness of breath;
- low potassium; or
- abnormal liver function tests.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Cresemba (Isavuconazonium Sulfate Injection and Capsules)
Cresemba Professional Information
SIDE EFFECTS
The following are discussed in more detail in other sections of the labeling:
- Hepatic Adverse Drug Reactions [see WARNINGS AND PRECAUTIONS]
- Infusion-Related Reactions [see WARNINGS AND PRECAUTIONS]
- Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
- Embryo-Fetal Toxicity [see WARNINGS AND PRECAUTIONS]
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of CRESEMBA cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.
Clinical Trial Experience
A total of 403 patients were exposed to CRESEMBA in two clinical trials. The most frequently reported adverse reactions among CRESEMBA-treated patients were nausea (26%), vomiting (25%), diarrhea (22%), headache (17%), elevated liver chemistry tests (16%), hypokalemia (14%), constipation (13%), dyspnea (12%), cough (12%), peripheral edema (11%), and back pain (10%). Serious adverse reactions occurred in 223/403 (55%) of patients and 56/403 (14%) of patients permanently discontinued treatment with CRESEMBA due to an adverse reaction in the two trials. The adverse reactions which most often led to permanent discontinuation of CRESEMBA therapy during the clinical trials were: confusional state (0.7%), acute renal failure (0.7%), increased blood bilirubin (0.5%), convulsion (0.5%), dyspnea (0.5%), epilepsy (0.5%), respiratory failure (0.5%), and vomiting (0.5%).
Patients in the clinical trials were immunocompromised with underlying conditions including hematological malignancy, neutropenia post-chemotherapy, graft-versus-host disease, and hematopoietic stem cell transplant. The patient population was 61% male, had a mean age of 51 years (range 17-92, including 85 patients aged greater than 65 years), and was 79% white and 3% black. One hundred forty-four (144) patients had a duration of CRESEMBA therapy of greater than 12 weeks, with 52 patients receiving CRESEMBA for over six months.
In Trial 1, a randomized, double-blind, active-controlled clinical trial for treatment of invasive aspergillosis, treatment-emergent adverse reactions occurred in 247/257 (96%), and 255/259 (99%) patients in the CRESEMBA and voriconazole treatment groups, respectively. Treatment-emergent adverse reactions resulting in permanent discontinuation were reported in 37 (14%) CRESEMBA-treated patients and 59 (23%) voriconazole-treated patients. Table 2 includes selected treatment-emergent adverse reactions which were reported at an incidence of ≥ 5% during CRESEMBA therapy in Trial 1.
In Trial 2, an open-label, non-comparative trial of CRESEMBA in patients with invasive aspergillosis and renal impairment or invasive mucormycosis, treatment-emergent adverse reactions occurred in 139/146 (95%) of patients in the CRESEMBA treatment group. Adverse reactions resulting in permanent discontinuation were reported in 19 (13%) CRESEMBA-treated patients. The frequencies and types of adverse reactions observed in CRESEMBA-treated patients were similar between Trial 1 and Trial 2.
Table 2. Selected Treatment-Emergent Adverse Reactions with Rates of 5% or Greater in CRESEMBA-treated Patients in Trial 1
| System Organ Class Preferred Term |
Trial 1 | |
| CRESEMBA (N=257) n (%) |
Voriconazole (N=259) n (%) |
|
| Gastrointestinal disorders | ||
| Nausea | 71 (27.6) | 78 (30.1) |
| Vomiting | 64 (24.9) | 73 (28.2) |
| Diarrhea | 61 (23.7) | 60 (23.2) |
| Abdominal pain | 43 (16.7) | 59 (22.8) |
| Constipation | 36 (14.0) | 54 (20.8) |
| Dyspepsia | 16 (6.2) | 14 (5.4) |
| General disorders and administration site conditions | ||
| Edema peripheral | 39 (15.2) | 46 (17.8) |
| Fatigue | 27 (10.5) | 18 (6.9) |
| Chest pain | 23 (8.9) | 16 (6.2) |
| Injection site reaction | 16 (6.2) | 4 (1.5) |
| Hepatobiliary disorders | ||
| Elevated liver laboratory tests1 | 44 (17.1) | 63 (24.3) |
| Metabolism and nutrition disorders | ||
| Hypokalemia | 49 (19.1) | 58 (22.4) |
| Decreased appetite | 22 (8.6) | 28 (10.8) |
| Hypomagnesemia | 14 (5.4) | 27 (10.4) |
| Musculoskeletal and connective tissue disorders | ||
| Back pain | 26 (10.1) | 19 (7.3) |
| Nervous system disorders | ||
| Headache | 43 (16.7) | 38 (14.7) |
| Psychiatric disorders | ||
| Insomnia | 27 (10.5) | 25 (9.7) |
| Delirium2 | 22 (8.6) | 30 (11.6) |
| Anxiety | 21 (8.2) | 18 (6.9) |
| Renal and urinary disorders | ||
| Renal failure | 26 (10.1) | 21 (8.1) |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnea | 44 (17.1) | 35 (13.5) |
| Acute respiratory failure | 19 (7.4) | 22 (8.5) |
| Skin and subcutaneous tissue disorders | ||
| Rash | 22 (8.6) | 36 (13.9) |
| Pruritus | 21 (8.2) | 15 (5.8) |
| Vascular disorders | ||
| Hypotension | 21 (8.2) | 28 (10.8) |
| 1. Elevated liver laboratory tests include reactions of increased alanine aminotransferase, aspartate aminotransferase, blood alkaline phosphatase, blood bilirubin, and gamma-glutamyl transferase. 2. Delirium includes adverse reactions of agitation, confusional state, delirium, disorientation, and mental status changes. |
||
The following adverse reactions occurred in less than 5% of all CRESEMBA-treated patients in Trial 1 or 2. The list does not include reactions presented in Table 2. This listing includes adverse reactions where a causal relationship to isavuconazole cannot be ruled out or those which may help the physician in managing the risks to the patients.
- Blood and lymphatic system disorders: agranulocytosis, leukopenia, pancytopenia
- Cardiac disorders: atrial fibrillation, atrial flutter, bradycardia, reduced QT interval on electrocardiogram, palpitations, supraventricular extrasystoles, supraventricular tachycardia, ventricular extrasystoles, cardiac arrest
- Ear and labyrinth disorders: tinnitus, vertigo
- Eye disorders: optic neuropathy
- Gastrointestinal disorders: abdominal distension, gastritis, gingivitis, stomatitis
- General disorders and administration site conditions: catheter thrombosis, malaise, chills
- Hepatobiliary disorders: cholecystitis, cholelithiasis, hepatitis, hepatomegaly, hepatic failure
- Immune system disorders: hypersensitivity
- Injury, poisoning and procedural complications: fall
- Metabolism and nutrition disorders: hypoalbuminemia, hypoglycemia, hyponatremia
- Musculoskeletal and connective tissue disorders: myositis, bone pain, neck pain
- Nervous system disorders: convulsion, dysgeusia, encephalopathy, hypoesthesia, migraine, peripheral neuropathy, paresthesia, somnolence, stupor, syncope, tremor
- Psychiatric disorders: confusion, hallucination, depression
- Renal and urinary disorders: hematuria, proteinuria
- Respiratory, thoracic and mediastinal disorders: bronchospasm, tachypnea
- Skin and subcutaneous tissue disorders: alopecia, dermatitis, exfoliative dermatitis, erythema, petechiae, urticaria
- Vascular disorders: thrombophlebitis
Laboratory Effects
In Trial 1, elevated liver transaminases (alanine aminotransferase or aspartate aminotransferase) greater than three times the upper limit of normal were reported at the end of study treatment in 4.4% of patients who received CRESEMBA. Elevations of liver transaminases greater than ten times the upper limit of normal developed in 1.2% of patients who received CRESEMBA.
DRUG INTERACTIONS
Isavuconazole is a sensitive substrate of CYP3A4. CYP3A4 inhibitors or inducers may alter the plasma concentrations of isavuconazole.
Isavuconazole is a moderate inhibitor of CYP3A4, and a mild inhibitor of P-glycoprotein (P-gp), and organic cation transporter 2 (OCT2).
Drug interaction studies were conducted to investigate the effect of coadministered drugs on the pharmacokinetics of isavuconazole and the effect of isavuconazole on the pharmacokinetics of coadministered drugs [see CLINICAL PHARMACOLOGY].
Table 3. Drug(s) Affecting Pharmacokinetics of CRESEMBA
| Recommendation | Comments | |
| Ketoconazole | Contraindicate coadministration of all potent CYP3A4 inhibitors | There is more than a 5-fold increase in exposure of isavuconazole upon coadministration with ketoconazole [see CLINICAL PHARMACOLOGY]. |
| Lopinavir/ritonavir1 | Caution is advised when CRESEMBA is coadministered with lopinavir/ritonavir | There is a 96% increase in exposure of isavuconazole when coadministered with lopinavir/ritonavir [see CLINICAL PHARMACOLOGY]. |
| Rifampin | Contraindicate coadministration of all potent CYP3A4 inducers | There is a 97% decrease in exposure of isavuconazole upon coadministration with rifampin [see CLINICAL PHARMACOLOGY]. |
| 1. 400 mg of lopinavir in combination with 100 mg of ritonavir. | ||
Table 4. The Effect of CRESEMBA on the Pharmacokinetics of Other Drugs
| Recommendation | Comments | |
| Lopinavir/ritonavir1 | Use with Caution | Concomitant administration of lopinavir/ritonavir and CRESEMBA resulted in decreased exposure of lopinavir and ritonavir that could possibly result in loss of antiviral efficacy [see CLINICAL PHARMACOLOGY]. |
| Atorvastatin | Use with Caution | Caution should be used when atorvastatin is used with CRESEMBA due to a potential increase in atorvastatin exposure. Monitor patients for adverse reactions that are typical of atorvastatin. |
| Cyclosporine | Use with Caution | Concomitant administration of CRESEMBA and cyclosporine results in increase in cyclosporine exposure. Monitor drug concentrations of cyclosporine and adjust dose as needed [see CLINICAL PHARMACOLOGY]. |
| Sirolimus | Use with Caution | Concomitant administration of CRESEMBA and sirolimus results in increase in sirolimus exposure. Monitor drug concentrations of sirolimus and adjust dose as needed [see CLINICAL PHARMACOLOGY]. |
| Tacrolimus | Use with Caution | Concomitant administration of CRESEMBA and tacrolimus results in increase in tacrolimus exposure. Monitor drug concentrations of tacrolimus and adjust dose as needed [see CLINICAL PHARMACOLOGY]. |
| Midazolam | Use with Caution | Concomitant administration of CRESEMBA and midazolam results in increase in midazolam exposure. Consider dose reduction of midazolam when isavuconazole is coadministered [see CLINICAL PHARMACOLOGY]. |
| Bupropion | Use with Caution | Concomitant administration of CRESEMBA and bupropion results in decrease in bupropion exposure. Dose increase of bupropion may be necessary when coadministered with CRESEMBA, but should not exceed the maximum recommended dose [see CLINICAL PHARMACOLOGY]. |
| Mycophenolate Mofetil | Use with Caution | Concomitant administration of CRESEMBA and MMF results in increase in MMF exposure. Patients receiving CRESEMBA concurrently with MMF should be monitored for MPA-related toxicities [see CLINICAL PHARMACOLOGY]. |
| Digoxin | Use with Caution | Concomitant administration of CRESEMBA and digoxin results in increase in digoxin exposure. Serum digoxin concentrations should be monitored and used for titration when dosed concurrently with CRESEMBA [see CLINICAL PHARMACOLOGY]. |
| 1. 400 mg of lopinavir in combination with 100 mg of ritonavir. | ||
Read the entire FDA prescribing information for Cresemba (Isavuconazonium Sulfate Injection and Capsules)
© Cresemba Patient Information is supplied by Cerner Multum, Inc. and Cresemba Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.