Pralsetinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of pralsetinib.
Drugs List
Therapeutic Indications
Uses
RET fusion positive advanced non-small cell lung cancer (NSCLC)
Monotherapy treatment of adults with rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer (NSCLC) not previously treated with a RET inhibitor.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
400mg once daily.
Additional Dosage Information
Dose reductions
Recommended dose: 400mg once daily.
First dose reduction: 300mg once daily.
Second dose reduction: 200mg once daily.
Third dose reduction: 100mg once daily.
In patients unable to tolerate 100mg once daily, treatment with pralsetinib should be permanently discontinued.
Dose modifications due to adverse reactions
Pneumonitis/Interstitial lung disease (ILD)
Grade 1 or 2: Interrupt treatment with pralsetinib until resolution, then resume at a reduced dose. If pneumonitis/ILD recurs then pralsetinib should be permanently discontinued.
Grade 3 or 4: Permanently discontinue treatment with pralsetinib.
Hypertension
Grade 3 that persists despite optimal antihypertensive treatment: Interrupt treatment with pralsetinib. Once hypertension is controlled, then resume at a reduced dose.
Grade 4: Permanently discontinue treatment with pralsetinib.
Transaminase elevations
Grade 3 or 4: Interrupt treatment with pralsetinib until resolution to Grade 1 or baseline, then resume at a reduced dose. If transaminase elevations recur at Grade 3 or higher, then permanently discontinue treatment with pralsetinib.
Haemorrhagic events
Grade 3 or 4: Interrupt treatment with pralsetinib until resolution to Grade 1, then resume at a reduced dose. If life-threatening or recurrent severe haemorrhagic events occur, pralsetinib should be permanently discontinued.
QT prolongation
Grade 3: Interrupt treatment with pralsetinib if QT interval is greater than 500 milliseconds, until QT interval returns to less than 470 milliseconds. Upon resolution, resume pralsetinib treatment at the same dose if the factors that cause QT prolongation are identified and corrected. Or resume pralsetinib at a reduced dose if other risk factors of QT prolongations are not identified.
Grade 4: Permanently discontinue treatment with pralsetinib.
Other adverse reactions
Grade 3 or 4: Interrupt treatment with pralsetinib until resolution to less than or equal to Grade 2, then resume at a reduced dose. Permanently discontinue treatment with pralsetinib if Grade 4 adverse reactions recur.
Dose modifications due to co-administration with strong CYP3A4 inhibitors or combined P-gp and strong CYP3A4 inhibitors
Concomitant use of pralsetinib with strong CYP3A4 inhibitors or combined P-gp and strong CYP3A4 inhibitors should be avoided. If co-administration cannot be avoided, then the current dose of pralsetinib should be reduced as stated below. After the strong CYP3A4 inhibitor or combined P-gp and strong CYP3A4 inhibitor have been discontinued for 3 to 5 elimination half-lives, the pralsetinib dose that was taken prior to the use of the inhibitor should be resumed.
Current dose 400mg: recommended dose 200mg
Current dose 300mg: recommended dose 200mg
Current dose 200mg: recommended dose 100mg
Dose modifications due to co-administration with strong CYP3A4 inducers
If concomitant use with strong CYP3A4 inducers cannot be avoided, then the dose of pralsetinib should be increased to double the current pralsetinib dose starting on Day 7 of co-administration of pralsetinib with the strong CYP3A4 inducer. After the strong CYP3A4 inducer has been discontinued for 14 days, the pralsetinib dose that was taken prior to the use of the inducer should be resumed.
Contraindications
Children under 18 years
Breastfeeding
Interstitial lung disease
Long QT syndrome
Moderate hepatic impairment
Pneumonitis
Pregnancy
Torsade de pointes
Uncontrolled hypertension
Precautions and Warnings
Family history of long QT syndrome
Electrolyte imbalance
History of torsade de pointes
Hypertension
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Confirm RET gene fusion or mutation status prior to treatment
Ensure hypertension is controlled prior to treatment
Give pre-treatment counselling and consideration of oocyte cryopreservation
Give pre-treatment counselling and consideration of sperm cryopreservation
Treatment to be initiated and supervised by a specialist
Advise patient to take on an empty stomach 1 hr before or 2 hrs after food
Consult local policy on the safe use of anti-cancer drugs
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Perform ECG before and during treatment
Monitor blood pressure after 1 week and then monthly thereafter
Monitor for signs and symptoms of interstitial lung disease
Monitor for signs and symptoms of pneumonitis
Monitor serum electrolytes
Monitor serum transaminases every 2 weeks for 3 months, then monthly
Advise patient to report any new or worsening respiratory symptoms
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Advise patient to seek advice at first indications of pregnancy
Discontinue if grade 3 or greater interstitial lung disease occurs
Discontinue if recurrent grade 1 or 2 pneumonitis or ILD occurs
Discontinue permanently if QT prolongation and life threatening arrhythmias
Discontinue treatment if grade 3 or greater pneumonitis occurs
Interrupt treatment if grade 3 haemorrhagic events occur
Interrupt treatment if QTc exceeds 500msec and consider dose modification
Permanently discontinue if grade 3 hepatic transaminase elevations recur
Permanently discontinue if grade 4 hypertension occurs
Permanently discontinue if life threatening haemorrhagic events occur
Permanently discontinue if severe haemorrhagic events recur
Suspend treatment if grade 3 or higher elevations of hepatic transaminases
Suspend treatment in severe hypertension that cannot be controlled
Suspend/reduce dose if grade 1 or 2 pneumonitis or ILD occurs
Suspend treatment/reduce dose if grade 3 adverse reactions occur
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Advise patient to avoid Seville (sour) orange products
May cause impaired fertility
Female: Non-hormonal contraception required during and for 2 weeks after
Male: Contraception required during and for 1 week after treatment
Breastfeeding: Do not breastfeed during & for 1 week after treatment
Pregnancy and Lactation
Pregnancy
Pralsetinib is contraindicated during pregnancy.
The manufacturer recommends that pralsetinib is not used during pregnancy unless the clinical condition of the woman requires treatment with pralsetinib. There are no data from the use of pralsetinib in pregnant women, however, animal studies have shown reproductive toxicity. Therefore pralsetinib may cause foetal harm.
Lactation
Pralsetinib is contraindicated during breastfeeding.
The manufacturer recommends that women should not breastfeed during and for 1 week after treatment with pralsetinib. It is unknown whether pralsetinib or its metabolites are excreted in human milk, therefore a risk to the breastfed infant cannot be excluded.
Side Effects
Abdominal pain
Alanine aminotransferase increased
Anaemia
Aspartate aminotransferase increased
Constipation
Cough
Creatine phosphokinase increased
Diarrhoea
Dry mouth
Dyspnoea
Fatigue
Haemorrhage
Headache
Hyperbilirubinaemia
Hyperphosphataemia
Hypertension
Hypoalbuminaemia
Hypocalcaemia
Hyponatraemia
Hypophosphataemia
Increase in alkaline phosphatase
Leukopenia
Lymphopenia
Musculoskeletal pain
Nausea
Neutropenia
Oedema
Pneumonia
Pneumonitis
Prolongation of QT interval
Pyrexia
Rash
Serum creatinine increased
Stomatitis
Taste disturbances
Thrombocytopenia
Urinary tract infections
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: August 2022
Reference Sources
Summary of Product Characteristics: Gavreto 100 mg hard capsules. Roche Products Ltd. Revised April 2022.
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