Oral RET fusion-positive locally advanced non-small cell lung cancer, RET fusion-positive metastatic non-small cell lung cancer
Adult: Patients weighing <50 kg: 120 mg bid (approx 12 hourly); ≥50 kg: 160 mg bid (approx 12 hourly). Continue treatment until disease progression or unacceptable toxicity occurs. Dose reduction, dosing interruption, or discontinuation may be required according to the severity of the adverse reactions and individual risk-benefit assessment (refer to detailed product guidelines).
Oral RET fusion-positive metastatic thyroid cancer, RET-mutant metastatic medullary thyroid cancer
Adult: Patients weighing <50 kg: 120 mg bid (approx 12 hourly); ≥50 kg: 160 mg bid (approx 12 hourly). Continue treatment until disease progression or unacceptable toxicity occurs. Dose reduction, dosing interruption, or discontinuation may be required according to the severity of the adverse reactions and individual risk-benefit assessment (refer to detailed product guidelines). Child: ≥12 years Same as adult dose.
Oral RET fusion-positive locally advanced solid tumours, RET fusion-positive metastatic solid tumours
Adult: In patients with disease progression on or following prior systemic treatment or who have no satisfactory alternative treatment options: Patients weighing <50 kg: 120 mg bid (approx 12 hourly); ≥50 kg: 160 mg bid (approx 12 hourly). Continue treatment until disease progression or unacceptable toxicity occurs. Dose reduction, dosing interruption, or discontinuation may be required according to the severity of the adverse reactions and individual risk-benefit assessment (refer to detailed product guidelines).
Special Patient Group
Patients taking moderate CYP3A4 inhibitors: Reduce the current dose by 40 mg bid (e.g. from 120 mg bid to 80 mg bid or from 160 mg to 120 mg bid). If the CYP3A4 inhibitor is stopped, selpercatinib dose must be increased back to the original dose after an interval of 3-5 half-lives of the inhibitor has passed.
Patients taking strong CYP3A4 inhibitors: Reduce the current dose by 80 mg bid (e.g. from 120 mg bid to 40 mg bid or from 160 mg to 80 mg bid). If the CYP3A4 inhibitor is stopped, selpercatinib dose must be increased back to the original dose after an interval of 3-5 half-lives of the inhibitor has passed.
Hepatic Impairment
Severe (Child-Pugh class C): 80 mg bid.
Administration
May be taken with or without food. Swallow whole, & do not break/crush/open. Coadministration w/ acid-reducing agents may reduce selpercatinib's plasma concentration. Consult product literature for specific recommendations.
Contraindications
Uncontrolled hypertension. Lactation.
Special Precautions
Patient with risk factors for QT prolongation (e.g. congenital or acquired long QT syndrome, clinically significant bradyarrhythmias, severe or uncontrolled heart failure) or tumour lysis syndrome (e.g. high tumour burden, pre-existing chronic renal insufficiency, dehydration, rapidly growing tumours). Patient taking strong or moderate CYP3A4 inhibitors or acid-reducing agents (e.g. PPIs, H2-receptor antagonists, or locally-acting antacids). Avoid concomitant use with moderate and strong CYP3A4 inducers. Withhold treatment for at least 7 days before elective surgery; do not administer for at least 2 weeks after major surgery and until adequate wound healing. Hepatic impairment. Children. Pregnancy.
Adverse Reactions
Significant: Hepatotoxicity (e.g. increased ALT and AST), hypertension, QT interval prolongation, hypersensitivity reaction, hypothyroidism, impaired wound healing, increased creatinine. Rarely, tumour lysis syndrome. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain, constipation, dry mouth. General disorders and administration site conditions: Pyrexia, fatigue, oedema. Investigations: Decreased lymphocytes, platelets, Hb, neutrophils, serum Mg, serum albumin, and serum Ca; increased total cholesterol, serum K, serum alkaline phosphatase, and serum bilirubin; decreased or increased serum glucose. Metabolism and nutrition disorders: Decreased appetite. Musculoskeletal and connective tissue disorders: Arthralgia. Nervous system disorders: Headache, dizziness. Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea. Skin and subcutaneous tissue disorders: Rash. Potentially Fatal: Haemorrhagic events (e.g. cerebral haemorrhage, tracheostomy site haemorrhage, haemoptysis), ILD/pneumonitis.
Women of childbearing potential and men with partners of childbearing potential must use highly effective contraception during therapy and for at least 1 week after stopping the treatment. Women who are breastfeeding should not breastfeed during treatment and for at least 1 week after the last dose.
Monitoring Parameters
Verify the presence of rearranged during transfection (RET) gene fusion (for non-small cell lung cancer, non-medullary thyroid cancer, and other solid tumours) or mutation (for medullary thyroid cancer) prior to treatment initiation. Evaluate pregnancy status in women of childbearing potential before treatment. Monitor ECG and serum electrolytes (after 1st week of treatment, at least monthly for the 1st 6 months, or as clinically indicated); ALT and AST (before treatment, every 2 weeks during the 1st 3 months, then monthly thereafter and as clinically indicated); thyroid function (at baseline and periodically during treatment); blood pressure (at baseline, after 1 week, at least monthly thereafter and as clinically indicated). Correct hypokalaemia, hypomagnesaemia, and hypocalcaemia before initiation and during treatment. Monitor for signs or symptoms of hypersensitivity reaction, pulmonary toxicity, haemorrhage, impaired wound healing, and tumour lysis syndrome. Observe growth plates in adolescents with open growth plates.
Drug Interactions
Increased plasma concentration with moderate and strong CYP3A4 inhibitors (e.g. diltiazem, fluconazole, verapamil, itraconazole). Decreased plasma concentration with moderate and strong CYP3A4 inducers (e.g. bosentan, efavirenz, rifampicin), PPIs, locally-acting antacids, and H2-antagonists. May increase the plasma concentrations of sensitive substrates of CYP2C8 (e.g. repaglinide, amodiaquine, paclitaxel, selexipag, dasabuvir) and CYP3A4 (e.g. midazolam, lomitapide, naloxegol, simvastatin, triazolam). May increase the risk of QT interval prolongation with agents known to prolong QT interval.
Food Interaction
May decrease plasma concentration with St. John's wort.
Action
Description: Mechanism of Action: Selpercatinib is an inhibitor of multiple receptor tyrosine kinases, including wild-type and mutated rearranged during transfection (RET) isoforms as well as vascular endothelial growth factor receptors (VEGFR) 1 and 3 and fibroblast growth factor receptor (FGFR) 1, 2, and 3. It has shown antitumour activity in cells harbouring constitutive activation of RET proteins (oncogenic drivers) resulting from gene fusions and mutations (including CCDC6-RET, KIF5B-RET, RET V804M, and RET M918T). Pharmacokinetics: Absorption: Rapidly absorbed. Bioavailability: 73.2% (range: 60.2-81.5%). Time to peak plasma concentration: Approx 2 hours. Distribution: Plasma protein-binding: 96%. Metabolism: Metabolised mainly by the CYP3A4 isoenzyme. Excretion: Via faeces (69%; 14% as unchanged drug); urine (24%; 11.5% as unchanged drug). Elimination half-life: 32 hours.
Chemical Structure
Selpercatinib Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 134436906, Selpercatinib. https://pubchem.ncbi.nlm.nih.gov/compound/Selpercatinib. Accessed Feb. 23, 2023.
Storage
Store between 20-25°C. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
L01EX22 - selpercatinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.
References
Anon. Selpercatinib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 08/02/2023.Anon. Selpercatinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/02/2023.Buckingham R (ed). Selpercatinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/02/2023.Joint Formulary Committee. Selpercatinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/02/2023.Retevmo Capsule (Eli Lilly and Company). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 08/02/2023.Retsevmo 80 mg Hard Capsules (Eli Lilly Nederland B.V.). MHRA. https://products.mhra.gov.uk. Accessed 08/02/2023.
Sign Out
