Selpercatinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of selpercatinib.
Drugs List
Therapeutic Indications
Uses
Aggressive and symptomatic medullary thyroid cancer: treatment
Locally advanced/metastatic Non-Small Cell Lung Cancer (NSCLC)
Treatment of locally advanced or metastatic differentiated thyroid cancer
Monotherapy treatment of adults with advanced RET fusion-positive non-small cell lung cancer (NSCLC) who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.
Monotherapy treatment of adults with advanced RET fusion-positive thyroid cancer who require systemic therapy following prior treatment with sorafenib and/or lenvatinib.
Monotherapy for the treatment of adults and adolescents 12 years and older with advanced RET-mutant medullary thyroid cancer (MTC) who require systemic therapy following prior treatment with cabozantinib and/or vandetanib.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Prior to initiation of treatment, the presence of a RET gene fusion (NSCLC and non-medullary thyroid cancer) or mutation (MTC) should be confirmed by a validated test.
Adults
Bodyweight 50kg and over: 160mg twice daily.
Bodyweight less than 50kg: 120mg twice daily.
Treatment should be continued until disease progression or unacceptable toxicity.
Children
Children aged 12 to 18 years
Advanced RET-mutant medullary thyroid cancer
(See Dosage; Adult).
Additional Dosage Information
Missed doses or vomits
If a patient vomits or misses a dose, the patient should take the next dose at its scheduled time; an additional dose should not be taken.
Use with strong CYP3A inhibitors
Dose should be reduced by 50%.
If CYP3A inhibitor is discontinued the selpercatinib dose should be increased (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor.
Dose Modification
Management of adverse reactions may require interruption and/or reduction of dose.
Adults and adolescents 50kg and over:
Starting dose: 160mg twice daily.
First dose reduction: 120mg twice daily.
Second dose reduction: 80mg twice daily.
Third dose reduction: 40mg twice daily.
Adults and adolescents less than 50kg:
Starting dose: 120mg twice daily.
First dose reduction: 80mg twice daily.
Second dose reduction: 40mg twice daily.
Third dose reduction: Not applicable.
Increased ALT or AST
Grade 3 or 4: Suspend dose until toxicity resolves to baseline. Resume at a dose reduced by 2 levels. If after at least 2 weeks, increased ALT or AST has not recurred, increase dose by 1 dose level. If after at least 4 weeks, increased ALT or AST has not recurred, increase to dose taken prior to the onset of Grade 3 or 4 ALT or AST increases. Permanently discontinue selpercatinib if Grade 3 or 4 ALT or AST increases recur despite dose modifications.
Hypersensitivity
All grades: Suspend dose until toxicity resolves and begin corticosteroids at a dose of 1mg/kg. Resume selpercatinib treatment at 40mg twice daily while continuing with steroid treatment. Discontinue for recurrent hypersensitivity. If after at least 7 days, selpercatinib is tolerated without recurrent hypersensitivity, incrementally increase dose by 1 dose level each week, until the dose taken prior to the onset of hypersensitivity is reached. Taper the steroid dose after selpercatinib has been tolerated for at least 7 days at the final dose.
QT interval prolongation
Grade 3: Suspend dose for QTcF greater than 500ms until QTcF returns to less than 470ms or baseline. Resume treatment at the next lower dose level.
Grade 4: Discontinue if QT prolongation remains uncontrolled after two dose reductions or if the patient has signs or symptoms of arrhythmia.
Hypertension
Grade 3: Temporarily suspend for medically significant hypertension until controlled with antihypertensive therapy. Dose should be resumed at the next lower dose if clinically indicated.
Grade 4: Discontinue permanently if medically significant hypertension cannot be controlled.
Haemorrhagic events
Grade 3 or 4: Suspend until recovery to baseline. Discontinue for severe or life-threatening haemorrhagic events.
Other adverse reactions
Grade 3 or 4: Suspend until recovery to baseline. Discontinue for severe or life-threatening events.
Contraindications
Children under 12 years
Breastfeeding
Long QT syndrome
Pregnancy
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
Females of childbearing potential
History of treatment with anthracyclines
Electrolyte imbalance
End stage renal disease
History of torsade de pointes
Renal dialysis
Severe hepatic impairment
Correct electrolyte disorders before treatment
Reduce dose in patients with severe hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Avoid H2 antagonists 10 hours before or 2 hours after dose
Confirm RET gene fusion or mutation status prior to treatment
Consider use of corticosteroids if adverse reactions occur
Ensure hypertension is controlled prior to treatment
Treatment to be initiated and supervised by a specialist
Advise patient to take with a meal if used concomitantly with a PPI
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor serum transaminases before treatment
Perform ECG before and during treatment
Consider interrupting treatment if QTc > 500msec
Monitor for haemorrhage especially intracranial bleeds
Monitor hepatic function in patients with hepatic impairment
Monitor serum electrolytes
Monitor serum transaminases every 2 weeks for 3 months, then monthly
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Consider discontinuing therapy if serious cardiac arrhythmias occur
Discontinue if grade 3 or greater adverse reaction that recurs/persists
Discontinue if hepatic enzymes (AST or ALT) become persistently raised
Discontinue if persistent hypertension unresponsive to therapy occurs
Discontinue if severe haemorrhage occurs
Interrupt therapy if severe hypertension requiring medical treatment occurs
Suspend treatment if grade 3 or greater adverse reaction occurs
Suspend treatment if grade 3 or higher elevations of hepatic transaminases
Advise patient not to take St John's wort concurrently
Male & female: May cause infertility
Female: Contraception required during and for 1 week after treatment
Male: Contraception required during and for 1 week after treatment
Breastfeeding: Do not breastfeed during & for 1 week after treatment
Pregnancy and Lactation
Pregnancy
Selpercatinib is contraindicated during pregnancy.
The manufacturer does not recommend using selpercatinib during pregnancy. At the time of writing, there is no available data on the use of selpercatinib in pregnant women. Animal studies have shown reproductive toxicity. Selpercatinib should only be used during pregnancy if the potential benefits outweighs the risk to the foetus.
Lactation
Selpercatinib is contraindicated during breastfeeding.
The manufacturer recommends discontinuing breastfeeding during treatment and for at least one week after the last dose. It is unknown whether selpercatinib is excreted in human milk. Risk to infants cannot be excluded.
Side Effects
Abdominal pain
Alanine aminotransferase increased
Arthralgia
Aspartate aminotransferase increased
Constipation
Decreased appetite
Diarrhoea
Dizziness
Dry mouth
Fatigue
Haemorrhage
Headache
Hypersensitivity reactions
Hypertension
Hypomagnesaemia
Increase in creatinine
Infertility
Lymphopenia
Maculopapular rash
Myalgia
Nausea
Oedema
Prolongation of QT interval
Pyrexia
Rash
Thrombocytopenia
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: June 2021
Reference Sources
Summary of Product Characteristics: Retsevmo 40mg & 80mg hard capsules. Eli Lilly and Company Limited. Revised February 2021.
Summary of Product Characteristics: Retsevmo 40mg & 80mg hard capsules (Northern Ireland). Eli Lilly and Company Limited. Revised February 2021.
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