Cresemba - Isavuconazole

What is Cresemba - Isavuconazole and what is it used for?

Cresemba is an antifungal medicine used to treat adults suffering from invasive as well as mucormycosis, two life-threatening fungal infections. In the treatment of mucormycosis, Cresemba is used when treatment with amphotericin B is not appropriate.

Since the number of patients suffering from these diseases is low, these are considered "rare" and Cresemba was qualified as an "orphan medicine" (a medicine used in rare diseases) on 4 June 2014 (for mucormycosis) and on 4 July 2014 ( for aspergillosis).

Cresemba contains the active substance isavuconazole.

How is Cresemba - Isavuconazole used?

Cresemba is available as a powder to be made up into a solution for infusion (drip into a vein) and as capsules to be taken by mouth.

The dose for infusions and capsules is the same: 6 doses of 200 mg every 8 hours for 48 hours, followed by a maintenance dose of 200 mg once a day. The duration of therapy depends on how the patient responds to therapy.

If necessary, it is possible to switch from the infusion to the oral capsule. The medicine can only be obtained with a prescription.

How does Cresemba - Isavuconazole work?

The active substance in Cresemba, isavuconazole, belongs to the "triazolic" class of antifungal medicines. It works by blocking the formation of ergosterol, an important constituent of fungal cell membranes. Without a functional cell membrane, the fungi die or can no longer spread.

What benefit has Cresemba - Isavuconazole shown during the studies?

Studies show that patient survival after Cresemba-based therapy is similar to that seen with other therapies.

In one main study involving 516 patients with invasive aspergillosis, the 42-day mortality rate in patients treated with Cresemba was similar (19%) to the mortality rate observed in patients treated with another antifungal drug (voriconazole, 20%).

In another main study carried out on 146 patients suffering from invasive or mucormycosis aspergillosis, among the 37 patients with mucormycosis treated with Cresemba the mortality rate recorded after 84 days was 43%. The mortality rate observed in this study is similar to the rates collected in the published literature for standard therapies. Furthermore, Cresemba has the advantage that it can be used in patients with reduced renal function.

What is the risk associated with Cresemba - Isavuconazole?

The most common side effects of Cresemba (which may affect less than 10% of the patients studied) are abnormal liver tests, nausea, vomiting, difficulty breathing, abdominal pain, diarrhea, reactions at the injection site, headache, low potassium levels in the blood and skin rash. For the full list of all side effects reported with Cresemba, see the package leaflet.

Cresemba should not be used in patients treated with any of the following medicines:

ketoconazole (an antifungal medicine);
high dose ritonavir (a medicine used to treat HIV);
certain medicines that promote the absorption of isavuconazole in the body (strong inducers of CYP3A4 / 5, see the package leaflet).

It must also not be used in patients with familial short QT syndrome, a cardiac arrhythmia.

Why has Cresemba - Isavuconazole been approved?

Invasive aspergillosis and mucormycosis are life-threatening infections associated with a high mortality rate. In studies the efficacy of Cresemba in the treatment of invasive aspergillosis was comparable to that of voriconazole. Although amphotericin B is the first-line treatment for mucormycosis, there is a need for alternative therapies and Cresemba will offer benefits to patients for whom amphotericin B treatment is not appropriate. As for safety, Cresemba was generally well tolerated.

The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that Cresemba's benefits are greater than its risks and recommended that it be approved for use in the EU.

What measures are being taken to ensure the safe and effective use of Cresemba - Isavuconazole?

A risk management plan has been developed to ensure that Cresemba is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Cresemba, including the appropriate precautions to be followed by healthcare professionals and patients.