Gavreto Special Precautions

Pneumonitis/ILD: Severe, life-threatening or fatal cases of pneumonitis/ILD have been reported in patients who received pralsetinib in clinical trials (see Adverse Reactions). Patients who present with clinically symptomatic pneumonitis or ILD were excluded from clinical trials.
Patients should be advised to contact their healthcare provider immediately to report new or worsening respiratory symptoms.
Patients who present with acute or worsening of respiratory symptoms indicative of pneumonitis/ILD (e.g., dyspnoea, cough, and fever) should be investigated to exclude other potential causes. If pneumonitis/ILD is considered to be related to pralsetinib, the dose of Gavreto should be interrupted, reduced or permanently discontinued based on severity of confirmed pneumonitis/ILD (see Dosage & Administration).
Hypertension: Hypertension was observed in pralsetinib-treated patients in clinical trials (see Adverse Reactions). Treatment-related hypertension was most commonly managed with anti-hypertensive medicinal products.
Treatment with Gavreto should not be initiated in patients with uncontrolled hypertension. Pre-existing hypertension should be adequately controlled before starting Gavreto treatment. Monitoring of blood pressure is recommended after 1 week, at least monthly thereafter and as clinically indicated. Anti-hypertensive therapy should be initiated or adjusted as appropriate. The dose should be interrupted, reduced, or permanently discontinued based on the severity of hypertension observed during treatment with Gavreto (see Dosage & Administration).
Transaminase elevations: Severe cases of transaminase elevations have been reported in patients who received pralsetinib in clinical trials (see Adverse Reactions).
ALT and AST should be monitored prior to initiating Gavreto, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Treatment with Gavreto should be interrupted, reduced or permanently discontinued based on severity of the transaminase elevation observed during treatment with Gavreto (see Dosage & Administration).
Haemorrhagic events: Severe, including fatal, haemorrhagic events can occur with Gavreto. In patients with life-threatening or recurrent severe haemorrhage, Gavreto should be permanently discontinued (see Dosage & Administration).
QT prolongation: Prolongation of the QT interval has been observed in patients who received Gavreto in clinical trials (see Adverse Reactions). Therefore, before starting Gavreto treatment, patients should have a QTc interval ≤470 ms and serum electrolytes within normal range. Hypokalaemia, hypomagnesaemia, and hypocalcaemia should be corrected both prior and during Gavreto treatment. Electrocardiograms (ECGs) and serum electrolytes should be monitored at the end of the first week and of the first month of Gavreto treatment, then periodically, as clinically indicated, depending also on presence of other risk factors (e.g. intercurrent diarrhoea, vomiting, nausea, concomitant medications).
Pralsetinib should be used with caution in patients with medical history of cardiac arrhythmias or QT interval prolongation, as well as in patients on strong CYP 3A4 inhibitors or on medicinal products known to be associated with QT/QTc prolongation.
Gavreto may require interruption, dose modification, or discontinuation (see Dosage & Administration).
Drug interactions: Co-administration of Gavreto with strong CYP3A4 inhibitors or combined P-gp and strong CYP3A4 inhibitors should be avoided because they may increase the plasma concentration of pralsetinib (see Dosage & Administration and Interactions).
Co-administration of Gavreto with strong CYP3A4 inducers should be avoided because they may decrease the plasma concentration of pralsetinib (see Dosage & Administration and Interactions).
Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per hard capsule, that is to say essentially "sodium-free".
Effects on ability to drive and use machines: Gavreto has minor influence on the ability to drive and use machines. Caution should be exercised when driving or operating machines as patients may experience fatigue while taking Gavreto (see Adverse Reactions).
Use in Pregnancy: Fertility and pregnancy: During treatment with Gavreto and for at least 1 week after the final dose, male patients with female partners of childbearing potential must use effective contraception (see Use in Pregnancy & Lactation).
Women of childbearing potential should be advised to avoid becoming pregnant while receiving Gavreto. A highly effective non-hormonal method of contraception is required for female patients during treatment with pralsetinib, because pralsetinib can render hormonal contraceptives ineffective. If a hormonal method of contraception is unavoidable, then a condom must be used in combination with the hormonal method. Effective contraception must be continued for at least 2 weeks after the final dose (see Use in Pregnancy & Lactation).