Cresemba 200 mg IV

/ Pfizer

Loading dose: The recommended loading dose is one vial after reconstitution and dilution (equivalent to 200 mg of isavuconazole) every 8 hours for the first 48 hours (6 administrations in total).
Maintenance dose: The recommended maintenance dose is one vial after reconstitution and dilution (equivalent to 200 mg of isavuconazole) once daily, starting 12 to 24 hours after the last loading dose.
Duration of therapy should be determined by the clinical response.
For long-term treatment beyond 6 months, the benefit-risk balance should be carefully considered.
Switch to oral isavuconazole: This drug  is also available as hard capsules containing 100 mg isavuconazole, equivalent to 186 mg isavuconazonium sulfate.
On the basis of the high oral bioavailability (98%), switching between intravenous and oral administration is appropriate when clinically indicated.
Elderly: No dose adjustment is necessary for elderly patients; however the clinical experience in elderly patients is limited.
Renal impairment: No dose adjustment is necessary in patients with renal impairment, including patients with end-stage renal disease.
Hepatic impairment: No dose adjustment is necessary in patients with mild or moderate hepatic impairment (Child-Pugh Classes A and B).
The drug has not been studied in patients with severe hepatic impairment (Child-Pugh Class C). Use in these patients is not recommended unless the potential benefit is considered to outweigh the risks.
Paediatric population: The drug  is not indicated for children aged below 18 years.
Method of administration: Intravenous use.
Precautions to be taken before handling or administering the medicinal product: This drug must be reconstituted and then further diluted to a concentration corresponding to approximately 0.8 mg/mL isavuconazole prior to administration by intravenous infusion over a minimum of 1 hour to reduce the risk of infusion-related reactions. The infusion must be administered via an infusion set with an in-line filter with a microporous membrane made of polyethersulfone (PES) and with a pore size of 0.2 μm to 1.2 μm. The drug must only be given as an intravenous infusion.
See prescribing information for full details.

Indicated in adults for the treatment of: Invasive aspergillosis, mucormycosis in patients for whom amphotericin B is inappropriate.
Consideration should be given to official guidance on the appropriate use of antifungal agents.

Hypersensitivity to the active substance or to any of the excipients.
Co-administration with ketoconazole.
Co-administration with high-dose ritonavir (>200 mg every 12 hours).
Co-administration with strong CYP3A4/5 inducers such as rifampicin, rifabutin, carbamazepine, long-acting barbiturates (e.g. phenobarbital), phenytoin and St. John’s wort or with moderate CYP3A4/5 inducers such as efavirenz, nafcillin and etravirine.
Patients with familial short QT syndrome.

Hypersensitivity:Hypersensitivity to isavuconazole may result in adverse reactions that include: anaphylactic reaction, hypotension, respiratory failure, dyspnoea, drug eruption, pruritus, and rash . In case of anaphylactic reaction, isavuconazole should be discontinued immediately and appropriate medical
treatment should be initiated.
Caution should be used in prescribing isavuconazole to patients with hypersensitivity to other azole antifungal agents.
Infusion-related reactions: During intravenous administration of isavuconazole, infusion-related reactions including hypotension, dyspnoea, dizziness, paraesthesia, nausea, and headache were reported. The infusion should be stopped if these reactions occur.
Severe cutaneous adverse reactions: Severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, have been reported during treatment with azole antifungal agents. If a patient develops a severe cutaneous adverse reaction, isavuconazole should be discontinued.
Cardiovascular- QT shortening: Isavuconazole is contraindicated in patients with familial short QT syndrome.
Caution is warranted when prescribing isavuconazole to patients taking other medicinal products known to decrease the QT interval, such as rufinamide.
Elevated liver transaminases or hepatitis: The elevations in liver transaminases rarely required discontinuation of Isavuconazole. Monitoring of hepatic enzymes should be considered, as clinically indicated. Hepatitis has been reported with azole antifungal agents including Isavuconazole.
Severe hepatic impairment: Isavuconazole has not been studied in patients with severe hepatic impairment (Child-Pugh Class C). Use in these patients is not recommended unless the potential benefit is considered to outweigh the risks. These patients should be carefully monitored for potential drug toxicity.
See prescribing information for full details.

Most common: Elevated liver enzymes, nausea, vomiting, dyspnea, abdominal pain, diarrhea, injection site reaction, headache, hypokalaemia, and rash.
See prescribing information for full details.

Potential of medicinal products to affect the pharmacokinetics of isavuconazole: Isavuconazole is a substrate of CYP3A4 and CYP3A5. Co-administration of medicinal products which are inhibitors of CYP3A4 and/or CYP3A5 may increase the plasma concentrations of isavuconazole. Co-administration of medicinal products which are inducers of CYP3A4 and/or CYP3A5 may decrease the plasma concentrations of isavuconazole.
Medicinal products that inhibit CYP3A4/5: Co-administration of Isavuconazole with the strong CYP3A4/5 inhibitor ketoconazole is contraindicated, since this medicinal product can significantly increase plasma concentrations of isavuconazole.
For the strong CYP3A4 inhibitor lopinavir/ritonavir, a two-fold increase in isavuconazole exposure was observed. For other strong CYP3A4 inhibitors, such as clarithromycin, indinavir and saquinavir, a less pronounced effect can be expected, based on their relative potency. No dose adjustment of Isavuconazole is necessary when co-administered with strong CYP3A4/5 inhibitors; however caution is advised as adverse drug reactions may increase.
No dose adjustment is warranted for moderate to mild CYP3A4/5 inhibitors.
Medicinal products that induce CYP3A4/5: Co-administration of Isavuconazole with potent CYP3A4/5 inducers such as rifampicin, rifabutin, carbamazepine, long-acting barbiturates (e.g., phenobarbital), phenytoin and St. John’s wort, or with moderate CYP3A4/5 inducers such as efavirenz, nafcillin and etravirine, is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole.
Co-administration with mild CYP3A4/5 inducers such as aprepitant, prednisone and pioglitazone, may result in mild to moderate decreases of isavuconazole plasma levels; co-administration with mild CYP3A4/5 inducers should be avoided unless the potential benefit is considered to outweigh the risk.
Co-administration with high-dose ritonavir (>200 mg twice daily) is contraindicated, as at high doses ritonavir may induce CYP3A4/5 and decrease isavuconazole plasma concentrations.
See prescribing information for full details.

Pregnancy: There are no data from the use of Isavuconazole in pregnant women. CRESEMBA must not be used during pregnancy except in patients with severe or potentially lifethreatening fungal infections, in whom isavuconazole may be used if the anticipated benefits outweigh the possible risks to the foetus.
Lactation: Breast-feeding should be discontinued during treatment with Isavuconazole.
See prescribing information for full details.

Symptoms: Symptoms reported more frequently at supratherapeutic doses of this drug (equivalent to isavuconazole 600 mg/day) evaluated in a QT study than in the therapeutic dose group (equivalent to isavuconazole 200 mg/day dose) included: headache, dizziness, paraesthesia, somnolence, disturbance in attention, dysgeusia, dry mouth, diarrhoea, oral hypoaesthesia, vomiting, hot flush, anxiety, restlessness, palpitations, tachycardia, photophobia and arthralgia.
Management of overdose: Isavuconazole is not removed by haemodialysis. There is no specific antidote for isavuconazole. In the event of an overdose, supportive treatment should be instituted.

Storage: Store in a refrigerator (2°C to 8°C).