Pemigatinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of pemigatinib.
Drugs List
Therapeutic Indications
Uses
Cholangiocarcinoma with FGFR2 fusion or rearrangement
Treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy.
Dosage
Adults
13.5mg once daily for 14 days followed by 7 days off therapy.
Patients with Renal Impairment
Severe renal impairment: Reduce dose by one dose level. See information below for dose reductions due to toxicities.
Patients with Hepatic Impairment
Severe hepatic impairment: Reduce dose by one dose level. See information below for dose reductions due to toxicities.
Additional Dosage Information
Dose reduction for management of toxicities
Recommended dose: 13.5mg once daily for 14 days followed by 7 days off therapy.
First dose reduction: 9mg once daily for 14 days followed by 7 days off therapy.
Second dose reduction: 4.5mg once daily for 14 days followed by 7 days off therapy.
Treatment should be permanently discontinued if the patient is unable to tolerate 4.5mg once daily.
Dose modifications for hyperphosphataemia
Serum phosphate greater than 5.5mg/dL to less than or equal to 7mg/dL: Continue at current dose of pemigatinib.
Serum phosphate greater than 7mg/dL to less than or equal to 10mg/dL: Continue at current dose of pemigatinib, initiate phosphate-lowering therapy, serum phosphate should be monitored weekly. Dose of phosphate-lowering therapy should be adjusted until serum phosphate level returns to less than 7mg/dL.
Withhold pemigatinib if serum phosphate levels do not return to less than 7mg/dL within 2 weeks of starting the phosphate-lowering therapy. Pemigatinib and phosphate-lowering therapy should be restarted at the same dose when serum phosphate level returns to less than 7mg/dL.
If serum phosphate level greater than 7mg/dL recurs with the phosphate-lowering therapy, then pemigatinib should be reduced one dose level as stated above.
Serum phosphate greater than 10mg/dL: Continue at current dose of pemigatinib, initiate phosphate-lowering therapy, serum phosphate should be monitored weekly. Dose of phosphate-lowering therapy should be adjusted until serum phosphate level returns to less than 7mg/dL.
Withhold pemigatinib if serum phosphate levels continue to be greater than 10mg/dL for 1 week. If serum phosphate level resolves to less than 7mg/dL, then pemigatinib and phosphate-lowering therapy should be re-started at one dose level lower.
If serum phosphate level greater than 10mg/dL recurs following 2 dose reductions, pemigatinib should be permanently discontinued.
Dose modifications for serous retinal detachment
Asymptomatic: Continue at current dose of pemigatinib.
Moderate decrease in visual acuity (best corrected visual acuity worse than 20/40 or better or less than or equal to 3 lines decreased vision from baseline); limiting instrumental activities of daily living: Withhold pemigatinib until resolution. If improved on subsequent examination, pemigatinib should be resumed at the next lower dose level. If symptoms recur or persist or examination does not improve then permanent discontinuation of pemigatinib should be considered.
Marked decrease in visual acuity (best corrected visual acuity worse than 20/40 or greater than or equal to 3 lines decreased vision from baseline up to 20/200); limiting instrumental activities of daily living: Withhold pemigatinib until resolution. If improved on subsequent examination, pemigatinib should be resumed at 2 dose levels lower. If symptoms recur or persist or examination does not improve then permanent discontinuation of pemigatinib should be considered.
Visual acuity worse than 20/200 in affected eye; limiting activities of daily living: Withhold pemigatinib until resolution. If improved on subsequent examination, pemigatinib should be resumed at 2 dose levels lower. If symptoms recur or persist or examination does not improve then permanent discontinuation of pemigatinib should be considered.
CYP3A4 inhibitors
If concomitant use of strong CYP3A4 inhibitors cannot be avoided during treatment with pemigatinib, then the dose of pemigatinib should be reduced.
Patients taking 13.5mg pemigatinib once daily should be reduced to 9mg once daily. Patients taking 9mg of pemigatinib once daily should be reduced to 4.5mg once daily.
Missed dose
If the dose of pemigatinib is missed by 4 or more hours, or if vomiting occurs, an additional dose should not be administered and dosing should resume with the next scheduled dose.
Contraindications
Children under 18 years
Breastfeeding
Pregnancy
Precautions and Warnings
Central nervous system metastasis
History of eye disorder
Hyperphosphatemia
Hypophosphataemia
Severe hepatic impairment
Severe renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Confirm FGFR2 fusion status prior to treatment
Treatment to be initiated by specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Perform ophthalmological exam before therapy & every 2 months for 6 months
Monitor serum phosphate levels periodically
Advise patient to report any symptoms of retinal detachment immediately
Ocular demulcent should be used to prevent or treat dry eyes
Consider other markers of renal function if creatinine is constantly raised
May affect tests for creatinine
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Female: Contraception required during and for 1 week after treatment
Male & female: Two methods of contraception required (including barrier)
Male: Contraception required during and for 1 week after treatment
Breastfeeding: Do not breastfeed during & for 1 week after treatment
Avoid concurrent use of proton pump inhibitors
Serum phosphate levels
Hyperphosphataemia is expected with pemigatinib administration. Prolonged hyperphosphataemia can cause precipitation of calcium-phosphate crystals that can lead to hypocalcaemia, soft tissues mineralization, anaemia, secondary hyperparathyroidism, muscle cramps, seizure activity, QT interval prolongation and arrhythmias. Hyperphosphataemia can be managed by restricting dietary phosphate, administration of phosphate-lowering therapy and dose modification of pemigatinib.
Severe hypophosphataemia may present with confusion, seizures, focal neurologic findings, heart failure, respiratory failure, muscle weakness, rhabdomyolysis and haemolytic anaemia.
Discontinuing phosphate-lowering therapy and diet should be considered during pemigatinib treatment breaks or if serum phosphate levels drop below normal range. For patients presenting with hyperphosphataemia or hypophosphataemia, close monitoring and follow-up is recommended regarding dysregulation of bone mineralization.
Serous retinal detachment
Pemigatinib can cause serous retinal detachment which may present with symptoms such as blurred vision, visual floated or photopsia. Ophthalmological examination including optical coherence tomography (OCT) should be performed prior to initiation of therapy and every 2 months for the first 6 months of treatment, every 3 months afterwards and at any time for visual symptoms.
Blood creatinine increase
Pemigatinib may increase blood creatinine levels by decreasing renal tubular secretion of creatinine. Alternative markers of renal function should be considered if persistent elevations in serum creatinine are observed.
Pregnancy and Lactation
Pregnancy
Pemigatinib is contraindicated during pregnancy.
The manufacturer recommends that pemigatinib should not be used in pregnancy unless the clinical condition of the woman requires treatment. There are no data available for the use of pemigatinib in pregnant women, although studies in animals have shown reproductive toxicity.
Lactation
Pemigatinib is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding should be discontinued during treatment with pemigatinib and for one week following completion of therapy. It is unknown whether pemigatinib or its metabolites are excreted in human milk, therefore a risk to the breastfed child cannot be excluded.
Side Effects
Alopecia
Arthralgia
Blurred vision
Constipation
Detachment of the retinal pigment epithelium
Diarrhoea
Discolouration of nails (temporary)
Dry eyes
Dry mouth
Dry skin
Dysgeusia
Fatigue
Hair growth abnormal
Hyperphosphataemia
Hyponatraemia
Hypophosphataemia
Maculopathy
Nail disorders
Nail dystrophy
Nail ridges
Nausea
Non-arteritic anterior ischaemic optic neuropathy (NAION)
Onychoclasis
Onycholysis
Onychomycosis
Palmar-Plantar Erythrodysaesthesia syndrome
Paronychia
Punctate keratitis
Retinal artery occlusion
Retinal detachment
Retinal disturbances
Serum creatinine increased
Soft tissue calcification
Stomatitis
Trichiasis
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: November 2021
Reference Sources
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 November 2021
Summary of Product Characteristics: Pemazyre 4.5 mg tablets. Incyte Biosciences UK Ltd. Revised September 2021.
Summary of Product Characteristics: Pemazyre 9 mg tablets. Incyte Biosciences UK Ltd. Revised September 2021.
Summary of Product Characteristics: Pemazyre 13.5 mg tablets. Incyte Biosciences UK Ltd. Revised September 2021.
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