Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Incyte Biosciences Distribution B.V., Paasheuvelweg 25, 1105 BP Amsterdam, Netherlands
Pemazyre monotherapy is indicated for the 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.
Therapy should be initiated by a physician experienced in the diagnosis and treatment of patients with biliary tract cancer.
FGFR 2 fusion positivity status must be known prior to initiation of Pemazyre therapy. Assessment for FGFR 2 fusion positivity in tumor specimen should be performed with an appropriate diagnostic test.
The recommended dose is 13.5 mg pemigatinib taken once daily for 14 days followed by 7 days off therapy.
If a dose of pemigatinib is missed by 4 or more hours or vomiting occurs after taking a dose, an additional dose should not be administered and dosing should be resumed with the next scheduled dose.
Treatment should be continued as long as the patient does not show evidence of disease progression or unacceptable toxicity.
In all patients, a low-phosphate diet should be initiated when serum phosphate level is >5.5 mg/dL and adding a phosphate-lowering therapy should be considered when level is >7 mg/dL. The dose of phosphate-lowering therapy should be adjusted until serum phosphate level returns to <7 mg/dL. Prolonged hyperphosphataemia can cause precipitation of calcium-phosphate crystals that can lead to hypocalcaemia, soft tissue mineralization, muscle cramps, seizure activity, QT interval prolongation, and arrhythmias (see section 4.4).
Discontinuing phosphate-lowering therapy and diet should be considered during Pemazyre treatment breaks or if serum phosphate level falls below normal range. Severe hypophosphataemia may present with confusion, seizures, focal neurologic findings, heart failure, respiratory failure, muscle weakness, rhabdomyolysis, and haemolytic anemia (see section 4.4).
Concurrent use of strong CYP3A4 inhibitors, including grapefruit juice, should be avoided during treatment with pemigatinib. If co-administration with a strong CYP3A4 inhibitor is necessary, the dose of patients who are taking 13.5 mg pemigatinib once daily should be reduced to 9 mg once daily and the dose of patients who are taking 9 mg pemigatinib once daily should be reduced to 4.5 mg once daily (see sections 4.4 and 4.5).
Dose modifications or interruption of dosing should be considered for the management of toxicities.
Pemigatinib dose reductions levels are summarised in table 1.
Table 1. Recommended pemigatinib dose reduction levels:
| Dose | Dose reduction levels | |
|---|---|---|
| First | Second | |
| 13.5 mg taken orally once daily for 14 days followed by 7 days off therapy | 9 mg taken orally once daily for 14 days on, followed by 7 days off therapy | 4.5 mg taken orally once daily for 14 days on, followed by 7 days off therapy |
Treatment should be permanently discontinued if patient is unable to tolerate 4.5 mg pemigatinib once daily.
Dose modifications for hyperphosphataemia are provided in table 2.
Table 2. Dose modifications for hyperphosphataemia:
| Adverse reaction | pemigatinib dose modification |
|---|---|
| > 5.5 mg/dL - ≤ 7 mg/dL | • pemigatinib should be continued at current dose. |
| > 7 mg/dL - ≤ 10 mg/dL | • pemigatinib should be continued at current dose, phosphate- lowering therapy should be initiated, serum phosphate should be monitored weekly, dose of phosphate lowering therapy should be adjusted as needed until level returns to < 7 mg/dL. • pemigatinib should be withheld if levels do not return to <7 mg/dL within 2 weeks of starting a phosphate lowering therapy. pemigatinib and phosphate-lowering therapy should be restarted at the same dose when level returns to < 7 mg/dL. • Upon recurrence of serum phosphate at > 7 mg/dL with phosphate-lowering therapy, pemigatinib should be reduced 1 dose level. |
| > 10 mg/dL | • pemigatinib should be continued at current dose, phosphate- lowering therapy should be initiated, serum phosphate should be monitored weekly and dose of phosphate lowering therapy should be adjusted as needed until level returns to < 7 mg/dL. • pemigatinib should be withheld if levels continue > 10 mg/dL for 1 week. pemigatinib and phosphate-lowering therapy should be restarted 1 dose level lower when serum phosphate is <7 mg/dL. • If there is recurrence of serum phosphate > 10 mg/dL following 2 dose reductions, pemigatinib should be permanently discontinued. |
Dose modifications for serous retinal detachment are provided in table 3.
Table 3. Dose modifications for serous retinal detachment:
| Adverse reaction | pemigatinib dose modification |
|---|---|
| Asymptomatic | • pemigatinib should be continued at current dose. Monitoring should be performed as described in section 4.4. |
| Moderate decrease in visual acuity (best corrected visual acuity 20/40 or better or ≤ 3 lines of decreased vision from baseline); limiting instrumental activities of daily living | • pemigatinib should be withheld until resolution. If improved on subsequent examination, pemigatinib should be resumed at the next lower dose level. • If it recurs, symptoms persist or examination does not improve, permanent discontinuation of pemigatinib should be considered based on clinical status. |
| Marked decrease in visual acuity (best corrected visual acuity worse than 20/40 or > 3 lines decreased vision from baseline up to 20/200); limiting activities of daily living | • pemigatinib should be withheld until resolution. If improved on subsequent examination, pemigatinib may be resumed at 2 dose levels lower. • If it recurs, symptoms persist or examination does not improve, permanent discontinuation of pemigatinib should be considered, based on clinical status. |
| Visual acuity worse than 20/200 in affected eye; limiting activities of daily living | • pemigatinib should be withheld until resolution. If improved on subsequent examination, pemigatinib may be resumed at 2 dose levels lower. • If it recurs, symptoms persist or examination does not improve, permanent discontinuation of pemigatinib should be considered, based on clinical status. |
The dose of pemigatinib is the same in elderly patients as younger adult patients (see section 5.1).
Dose adjustment is not required for patients with mild, moderate renal impairment or End Stage Renal Disease (ESRD) on haemodialysis. For patients with severe renal impairment, the dose of patients who are taking 13.5 mg pemigatinib once daily should be reduced to 9 mg once daily and the dose of patients who are taking 9 mg pemigatinib once daily should be reduced to 4.5 mg once daily (see section 5.2).
Dose adjustment is not required for patients with mild or moderate hepatic impairment. For patients with severe hepatic impairment, the dose of patients who are taking 13.5 mg pemigatinib once daily should be reduced to 9 mg once daily and the dose of patients who are taking 9 mg pemigatinib once daily should be reduced to 4.5 mg once daily (see section 5.2).
The safety and efficacy of Pemazyre in patients less than 18 years of age have not been established. No data are available.
Pemazyre is for oral use. The tablets should be taken at approximately the same time every day. Patients should not crush, chew, split or dissolve the tablets. Pemigatinib may be taken with or without food.
There is no information on overdose of pemigatinib.
4 years.
This medicinal product does not require any special storage conditions.
PVC/Al blister containing 14 tablets. Carton box containing 14 or 28 tablets.
Not all pack sizes may be marketed.
No special requirements for disposal.
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