Version May 2024
Cholangiocarcinoma, unresectable, locally advanced or metastatic, with susceptible fibroblast growth factor receptor 2 genetic alteration: Oral: 13.5 mg once daily on days 1 to 14 of a 21-day cycle; continue until disease progression or unacceptable toxicity (Ref).
Myeloid/lymphoid neoplasms, relapsed/refractory, with fibroblast growth factor receptor 1 rearrangement: Oral: 13.5 mg once daily (on a continuous basis); continue until disease progression or unacceptable toxicity.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Missed or vomited doses: If a dose is missed by ≥4 hours or if vomiting occurs, resume pemigatinib with the next scheduled dose the following day.
Note: GFR estimated by the Modification of Diet in Renal Disease equation.
eGFR 30 to 89 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 15 to 29 mL/minute/1.73 m2: Reduce dose to 9 mg once daily (either intermittent or continuous, depending on the indication).
End-stage renal disease receiving intermittent hemodialysis (eGFR <15 mL/minute/1.73 m2): No dosage adjustment is recommended.
Mild (total bilirubin >1 to 1.5 times ULN or AST > ULN) or moderate (total bilirubin >1.5 to 3 times ULN with any AST) impairment: No dosage adjustment necessary.
Severe impairment (totally bilirubin >3 times ULN with any AST): Reduce dose to 9 mg once daily (either intermittent or continuous, depending on the indication).
|
Dose Levels |
Cholangiocarcinoma |
Myeloid/lymphoid neoplasms |
|---|---|---|
|
a Permanently discontinue pemigatinib if unable to tolerate 4.5 mg once daily for 14 days of a 21-day cycle. | ||
|
Usual initial dose |
13.5 mg once daily on days 1 to 14 of a 21-day cycle |
13.5 mg once daily (on a continuous basis) |
|
First dose reduction |
9 mg once daily on days 1 to 14 of a 21-day cycle |
9 mg once daily (continuously) |
|
Second dose reduction |
4.5 mg once daily on days 1 to 14 of a 21-day cyclea |
4.5 mg once daily (continuously) |
|
Third dose reduction |
Permanently discontinue pemigatinib. |
4.5 mg once daily on days 1 to 14 of a 21-day cyclea |
|
Adverse reaction |
Severity |
Pemigatinib dose modification |
|---|---|---|
|
Hyperphosphatemia |
Serum phosphate level >5.5 to ≤7 mg/dL |
Monitor for hyperphosphatemia and initiate a low-phosphate diet. Continue pemigatinib at current dose. |
|
Serum phosphate level >7 to ≤10 mg/dL |
Initiate phosphate-lowering therapy; monitor serum phosphate weekly. If phosphate level is not <7 mg/dL within 2 weeks of initiating phosphate binders, withhold pemigatinib. Resume pemigatinib at the same dose when phosphate level is <7 mg/dL (for first occurrence); resume pemigatinib at a lower dose level for subsequent occurrences of hyperphosphatemia. | |
|
Serum phosphate level >10 mg/dL |
Initiate phosphate-lowering therapy; monitor serum phosphate weekly. If phosphate level is not ≤10 mg/dL within 1 week of initiating phosphate binders, withhold pemigatinib. Resume pemigatinib at the next lower dose level when phosphate level is <7 mg/dL. | |
|
Recurrence of serum phosphate level >10 mg/dL (after 2 dose reductions) |
Permanently discontinue pemigatinib. | |
|
Ocular toxicity |
Dry eye symptoms |
Administer dry eye prophylaxis/treatment (with ocular demulcents) as needed. |
|
Retinal pigment epithelial detachment: Asymptomatic and stable |
If retinal pigment epithelial detachment is asymptomatic and stable on serial ophthalmological examination, continue pemigatinib. | |
|
Retinal pigment epithelial detachment: Symptomatic or worsening |
If retinal pigment epithelial detachment is symptomatic or worsening on serial ophthalmological examination, withhold pemigatinib. If retinal pigment epithelial detachment is asymptomatic and improved on subsequent examination, resume pemigatinib at a lower dose. If symptoms persist or examination does not improve, consider permanent discontinuation of pemigatinib (depending on clinical status). | |
|
Other adverse reactions |
Grade 3 |
Withhold pemigatinib therapy until improvement to grade 1 or baseline. If toxicity resolves within 2 weeks, resume pemigatinib at the next lower dose. If toxicity does not resolve within 2 weeks, or for recurrent grade 3 toxicity (after 2 dose reductions), permanently discontinue pemigatinib. |
|
Grade 4 |
Permanently discontinue pemigatinib. |
Refer to adult dosing.
Pemigatinib can cause hyperphosphatemia, leading to soft tissue mineralization, cutaneous calcification, calcinosis, and non-uremic calciphylaxis. In clinical trials, 33% of patients required phosphate-binder therapy; a low-phosphate diet may also have been necessary (Ref).
Mechanism: Dose-related; related to the pharmacologic action (Ref). Pemigatinib inhibits fibroblast growth factor receptor, resulting in increased serum phosphate concentrations.
Onset: Varied; median time to onset is 8 days (range: 1 to 169 days)
Dry eye syndrome (some necessitating treatment with ophthalmic lubricant) has commonly occurred. Retinal pigment epithelial detachment (RPED) has occurred as well as other ophthalmic disorders including increased lacrimation, keratitis, maculopathy, meibomianitis, punctate keratitis, and retinopathy. Overall, ocular toxicities are common, although grade 3 and 4 ocular toxicities rarely occur.
Mechanism: Dose-related; related to the pharmacologic action. Pemigatinib causes subretinal fluid accumulation potentially due to fibroblast growth factor receptor inhibition and the consequential inhibition of the mitogen-activating protein kinase pathway, resulting in dysregulation of the outer retinal barrier or functions of the retinal pigment epithelium (Ref).
Onset: Delayed; median time to first onset of RPED was 56 days in clinical trials; resolution or improvement to grade 1 toxicity occurred in 76% of patients after dose adjustments.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Peripheral edema (18% to 21%)
Dermatologic: Alopecia (49% to 59%), changes in nails (43% to 62%; including nail bed changes, nail discoloration, onychoclasis, onycholysis, onychomadesis, onychomycosis, paronychia), palmar-plantar erythrodysesthesia (15% to 18%), skin rash (35%; including acneiform eruption, dermatitis, exfoliation of skin, and lichen planus), xeroderma (20% to 24%)
Endocrine & metabolic: Decreased serum albumin (34%), decreased serum calcium (17% to 26%), decreased serum glucose (11%), decreased serum potassium (24% to 26%), decreased serum sodium (39% to 41%), dehydration (15%), hyperphosphatemia (60% to 93%), hypophosphatemia (23%), increased serum calcium (26% to 43%), increased serum glucose (33% to 36%), increased serum potassium (12%), increased uric acid (18% to 30%), weight loss (16%)
Gastrointestinal: Abdominal pain (23% to 35%), constipation (32% to 35%), decreased appetite (24% to 33%), diarrhea (47% to 50%; grades 3/4: 3%), dysgeusia (40%), dyspepsia (24%), nausea (21% to 40%; grades 3/4: 2%), stomatitis (35% to 53%; grades 3/4: 5% to 15%), vomiting (27%; grades 3/4: 1%), xerostomia (32% to 34%)
Genitourinary: Urinary tract infection (16%)
Hematologic & oncologic: Anemia 35%; grades 3/4: 18%), decreased neutrophils (45%; grades 3/4: 12%), decreased platelet count (28% to 29%; grades 3/4: 3% to 15%), increased INR (grade 1/2: ≤16%), leukocytosis (27%; grades 3/4: <1%), leukopenia (18% to 65%; grades 3/4: 1% to 15%), lymphocytopenia (36% to 65%; grades 3/4: 8% to 16%), prolonged prothrombin time (grades 1/2: ≤16%)
Hepatic: Increased serum alanine aminotransferase (43% to 50%), increased serum alkaline phosphatase (41% to 62%), increased serum aspartate aminotransferase (43% to 47%), increased serum bilirubin (21% to 26%)
Nervous system: Dizziness (21%), fatigue (42% to 44%; including asthenia), headache (16%)
Neuromuscular & skeletal: Arthralgia (25%), back pain (20% to 24%), limb pain (19% to 26%)
Ophthalmic: Blurred vision (21%), dry eye syndrome (31% to 50%; including increased lacrimation, keratitis, meibomianitis, punctate keratitis), misdirected growth of eyelashes (18%), retinal pigment epithelium detachment (11% to 26%; including maculopathy and retinopathy)
Renal: Increased serum creatinine (41% to 44%)
Respiratory: Epistaxis (29%)
Miscellaneous: Fever (18%)
1% to 10%: Neuromuscular & skeletal: Bone fracture (2%; pathological fracture: <1%)
Frequency not defined:
Cardiovascular: Heart failure, hypotension, prolonged QT interval on ECG, syncope, vascular calcification (non-uremic calciphylaxis)
Dermatologic: Cutaneous calcification
Endocrine & metabolic: Calcinosis
Gastrointestinal: Cholangitis (including infective), intestinal obstruction
Renal: Acute kidney injury
Respiratory: Pleural effusion
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to pemigatinib or any component of the formulation.
Disease-related concerns:
• Renal function: Elevations in serum creatinine (mean increase of 0.2 mg/dL) occurred during the initial 3-week pemigatinib cycle, reaching steady state by day 8 and decreasing during the 7 days off therapy. If persistent serum creatinine elevations are observed, consider alternative markers for renal function evaluation.
Other warnings/precautions:
• Fibroblast growth factor receptor alteration: Pemigatinib is approved for the treatment of locally advanced or metastatic cholangiocarcinoma in patients based on the presence of a fibroblast growth factor receptor (FGFR) 2 fusion or rearrangement and for the treatment of relapsed/refractory myeloid/lymphoid neoplasms in patients with FGFR 1 rearrangement. Information on available approved tests may be found at http://www.fda.gov/CompanionDiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Pemazyre: 4.5 mg, 9 mg, 13.5 mg
No
Tablets (Pemazyre Oral)
4.5 mg (per each): $1,545.86
9 mg (per each): $1,545.86
13.5 mg (per each): $1,545.86
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Pemazyre: 4.5 mg, 9 mg, 13.5 mg
Oral: Administer with or without food at approximately the same time each day. Swallow tablets whole; do not crush, chew, split, or dissolve tablets.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Pemigatinib may cause reproductive toxicity and teratogenicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Cholangiocarcinoma, unresectable, locally advanced or metastatic: Treatment of previously treated, unresectable locally advanced or metastatic cholangiocarcinoma in adults with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement (as detected by an approved test).
Myeloid/lymphoid neoplasms, relapsed/refractory: Treatment of relapsed or refractory myeloid/lymphoid neoplasms in adults with fibroblast growth factor receptor 1 (FGFR1) rearrangement.
Pemigatinib may be confused with brigatinib, erdafitinib, pazopanib, pegaptanib, pembrolizumab, pemetrexed, pexidartinib, ponatinib.
This medication is in a class the Institute for Safe Medication Practices includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of BCRP/ABCG2, CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Pemigatinib. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Pemigatinib. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the moderate inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the strong inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider therapy modification
Erdafitinib: Serum Phosphate Level-Altering Agents may diminish the therapeutic effect of Erdafitinib. Management: Avoid coadministration of serum phosphate level-altering agents with erdafitinib before initial dose increase period based on serum phosphate levels (Days 14 to 21). Risk D: Consider therapy modification
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Evaluate pregnancy status prior to use in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during pemigatinib therapy and for 1 week after the last dose. Patients with partners who could become pregnant should use effective contraception during therapy and for 1 week after the last pemigatinib dose.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to pemigatinib may cause fetal harm.
It is not known if pemigatinib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 1 week after the last pemigatinib dose.
Assess for susceptible fibroblast growth factor receptor (FGFR) 2 genetic alteration in cholangiocarcinoma or for FGFR 1 rearrangement in myeloid/lymphoid neoplasms; serum phosphate level as clinically necessary (monitor weekly if hyperphosphatemia develops). Evaluate pregnancy status prior to use in patients who could become pregnant. Ophthalmological exams (including optical coherence tomography) at baseline and then every 2 months for the first 6 months of pemigatinib therapy, then every 3 months thereafter, and as clinically necessary (if retinal pigment epithelial detachment occurs, follow up evaluations every 3 weeks until resolved or until pemigatinib is discontinued). Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Pemigatinib is a fibroblast growth factor receptor (FGFR) kinase inhibitor that binds to and inhibits FGFR1, FGFR2, and FGFR3 enzyme activity. FGFR phosphorylation inhibition results in decreased FGFR-related signaling and decreased cell viability in cell lines expressing FGFR genetic alterations, leading to decreased proliferation and survival of malignant cells.
Distribution: Vd: ~235 L.
Protein binding: ~91%.
Metabolism: Primarily hepatic via CYP3A4.
Half-life elimination: 15.4 hours.
Time to peak: ~1 hour (range: 0.5 to 6 hours).
Excretion: Feces: 82.4% (1.4% as unchanged drug); urine: 12.6% (1% as unchanged drug).
Clearance: 10.6 L/hour.
Altered kidney function: The geometric mean pemigatinib AUC0-inf increased by 59% in patients with severe renal impairment (eGFR 15 to 29 mL/minute/1.73 m2) compared to subjects with normal renal function.
Hepatic function impairment: The geometric mean pemigatinib AUC0-inf increased by 136% in subjects with severe hepatic impairment (total bilirubin >3 × ULN) compared to subjects with normal hepatic function.
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