Retsevmo Special Precautions

Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, or fatal cases of ILD/pneumonitis have been reported in patients treated with selpercatinib (see Adverse Reactions). Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis. Selpercatinib should be withheld, and patients should be promptly investigated for ILD if they present with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnoea, cough, and fever), and treated as medically appropriate. Based on the severity of ILD/pneumonitis, the dose of selpercatinib should be interrupted, reduced, or permanently discontinued (see Dosage & Administration).
Increased alanine aminotransferase (ALT)/aspartate aminotransferase (AST): Grade ≥3 increased ALT and Grade ≥3 increased AST were reported in patients receiving selpercatinib (see Adverse Reactions). ALT and AST should be monitored prior to the start of selpercatinib therapy, every 2 weeks during the first 3 months of treatment, monthly for the next 3 months of treatment, and otherwise as clinically indicated. Based on the level of ALT or AST elevations, selpercatinib may require dose modification (see Dosage & Administration).
Hypertension: Hypertension was reported in patients receiving selpercatinib (see Adverse Reactions). Patient blood pressure should be controlled before starting selpercatinib treatment, monitored during selpercatinib treatment and treated as needed with standard anti-hypertensive therapy. Based on the level of increased blood pressure, selpercatinib may require dose modification (see Dosage & Administration). Selpercatinib should be discontinued permanently if medically significant hypertension cannot be controlled with antihypertensive therapy.
QT interval prolongation: QT interval prolongation was reported in patients receiving selpercatinib (see Pharmacology: Pharmacodynamics under Actions). Selpercatinib should be used with caution in patients with such conditions as congenital long QT syndrome or acquired long QT syndrome or other clinical conditions that predispose to arrhythmias. Patients should have a QTcF interval of ≤470 ms and serum electrolytes within normal range before starting selpercatinib treatment. Electrocardiograms and serum electrolytes should be monitored in all patients after 1 week of selpercatinib treatment, at least monthly for the first 6 months and otherwise, as clinically indicated, adjusting frequency based upon risk factors including diarrhoea, vomiting, and/or nausea. Hypokalaemia, hypomagnesaemia and hypocalcaemia should be corrected prior to initiating selpercatinib and during treatment. Monitor the QT interval with ECGs more frequently in patients who require treatment with concomitant medications known to prolong the QT interval.
Selpercatinib may require dose interruption or modification (see Dosage & Administration).
Hypothyroidism: Hypothyroidism has been reported in patients receiving selpercatinib (see Adverse Reactions). Baseline laboratory measurement of thyroid function is recommended in all patients. Patients with pre-existing hypothyroidism should be treated as per standard medical practice prior to the start of selpercatinib treatment. All patients should be observed closely for signs and symptoms of thyroid dysfunction during selpercatinib treatment. Thyroid function should be monitored periodically throughout treatment with selpercatinib. Patients who develop thyroid dysfunction should be treated as per standard medical practice, however patients could have an insufficient response to substitution with levothyroxine (T4) as selpercatinib may inhibit the conversion of levothyroxine to liothyronine (T3) and supplementation with liothyronine may be needed (see Interactions).
Strong CYP3A4 inducers: Concomitant use of strong CYP3A4 inducers should be avoided due to the risk of decreased efficacy of selpercatinib (see Interactions).
Women of childbearing potential/Contraception in females and males: Women of childbearing potential must use highly effective contraception during treatment and for at least one week after the last dose of selpercatinib. Men with female partners of childbearing potential should use effective contraception during treatment and for at least one week after the last dose of selpercatinib (see Use in Pregnancy & Lactation).
Fertility: Based on nonclinical safety findings, male and female fertility may be compromised by treatment with Retsevmo (see Use in Pregnancy & Lactation and Pharmacology: Toxicology: Preclinical safety data under Actions). Both men and women should seek advice on fertility preservation before treatment.
Hypersensitivity: Hypersensitivity was reported in patients receiving selpercatinib with a majority of events observed in patients with NSCLC previously treated with anti-PD-1/PD-L1 immunotherapy (see Adverse Reactions).
Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or elevated aminotransferases.
Suspend selpercatinib if hypersensitivity occurs, and begin steroid treatment. Based on the grade of hypersensitivity reactions, selpercatinib may require dose modification (see Dosage & Administration). Steroids should be continued until patient reaches target dose and then tapered. Permanently discontinue selpercatinib for recurrent hypersensitivity.
Haemorrhages: Serious including fatal haemorrhagic events were reported in patients receiving selpercatinib (see Adverse Reactions).
Permanently discontinue selpercatinib in patients with life-threatening or recurrent severe haemorrhage (see Dosage & Administration).
Tumour lysis syndrome (TLS): Cases of TLS have been observed in patients treated with selpercatinib. Risk factors for TLS include high tumour burden, pre-existing chronic renal insufficiency, oliguria, dehydration, hypotension, and acidic urine. These patients should be monitored closely and treated as clinically indicated, and appropriate prophylaxis including hydration should be considered.
Effects on ability to drive and use machines: Retsevmo may have minor influence on the ability to drive and use machines. Patients should be advised to be cautious when driving or using machines in case they experience fatigue or dizziness during treatment with Retsevmo (see Adverse Reactions).