Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
The most common adverse reactions were hyperphosphataemia (60.5 %), alopecia (49.7 %), diarrhoea (47.6 %), nail toxicity (44.9 %), fatigue (43.5 %), nausea (41.5 %), , stomatitis (38.1 %), constipation (36.7 %), dysgeusia (36.1 %) dry mouth (34.0 %), arthralgia (29.9 %), dry eye (27.9 %), hypophosphataemia (23.8 %), dry skin (21.8 %), and palmar-plantar erythrodysaesthesia syndrome (16.3 %).

The most common serious adverse reactions were hyponatremia (2.0 %) and blood creatinine increase (1.4 %). No serious adverse reaction led to pemigatinib dose reduction. One serious adverse reaction of hyponatremia (0.7 %) led to dose interruption. One serious adverse reaction of blood creatinine increase (0.7 %) led to dose discontinuation.

Eye disorders serious adverse reactions were retinal detachment (0.7 %), non-arteritic optic ischemic neuropathy (0.7 %) and retinal artery occlusion (0.7 %).


Tabulated list of adverse reactions
Adverse reactions are presented in table 4. Frequency categories are very common (≥ 1/10) and common (≥ 1/100 to < 1/10) and uncommon (≥1/1,000 to <1/100). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Table 4:     Adverse reactions reported in clinical studies.
System organ class                Frequency             Adverse reactions Metabolism and nutrition                                Hyponatraemia, Hyperphosphataemiaa, Very common disorders                                               Hypophosphataemiab Nervous system disorders          Very common           Dysgeusia
Very common           Dry eye
Eye disorders                                           Serous retinal detachmentc, Punctate Common keratitis, Vision blurred, Trichiasis
Nausea, Stomatitis, Diarrhoea,
Gastrointestinal disorders        Very common
Constipation, Dry mouth
Palmar-plantar erythrodysaesthesia
Very common           syndrome, Nail toxicityd, Alopecia, Dry
Skin and subcutaneous tissue skin disorders
Common                Hair growth abnormal
Uncommon              Cutaneous calcification
Musculoskeletal and connective
Very common           Arthralgia tissue disorders
General disorders and
Very common           Fatigue administration site conditions
Investigations                    Very common           Blood creatinine increased a Includes Hyperphosphataemia and Blood phosphorous increased. See below “Hyperphosphataemia”.
b Includes Hypophosphataemia and Blood phosphorous decreased c Includes Serous retinal detachment, Retinal detachment, Detachment of retinal pigmented epithelium, Retinal thickening, 
Subretinal fluid, Chorioretinal folds, Chorioretinal scar, and Maculopathy. See below “Serous retinal detachment”.
d Includes Nail toxicity, Nail disorder, Nail discolouration, Nail dystrophy, Nail hypertrophy, Nail ridging, Nail infection, 
Onychalgia, Onychoclasis, Onycholysis, Onychomadesis, Onychomycosis and Paronychia 
Description of selected adverse reactions

Hyperphosphataemia
Hyperphosphataemia was reported in 60.5 % of all patients treated with pemigatinib.
Hyperphosphataemia above 7 mg/dL and 10 mg/dL was experienced by 27.2 % and 0.7 % of patients, respectively. Hyperphosphataemia usually develops within the first 15 days.
None of the reactions were ≥ Grade 3 in severity, serious or led to discontinuation of pemigatinib.
Dose interruption occurred in 1.4 % patients and reduction in 0.7 % of patients. These results suggest that dietary phosphate restriction and/or administration of phosphate-lowering therapy along with the 1-week dose holiday were effective strategies for managing this on-target effect of pemigatinib.

Recommendations for management of hyperphosphataemia are provided in sections 4.2 and 4.4.

Serous retinal detachment
Serous retinal detachment occurred in 4.8 % of all patients treated with pemigatinib. Reactions were generally Grade 1 or 2 (4.1 %) in severity; ≥ Grade 3 and serious reactions included retinal detachment in 1 patient (0.7 %). Two adverse reactions of retinal detachment (0.7 %) and detachment of retinal pigment epithelium (0.7 %) led to dose interruption. None of the reactions led to dose reduction or discontinuation.

Recommendations for management of serous retinal detachment are provided in sections 4.2 and 4.4.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/