Pemazyre (magnesium)

Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of pemigatinib may be necessary in patients experiencing certain adverse effects. When dosage modification of pemigatinib is necessary, the dosage of pemigatinib should be reduced as described in Table 1.

Table 1. Dosage Reduction for Pemigatinib Toxicity.

Dosage Reduction Level Recommended Dosage Recommended Dosage (Initial Dose = 13.5 mg (Initial Dose = 13.5 mg once daily on days 1-14 once daily on a of each 21-day cycle) continuous basis) First Resume at 9 mg once 9 mg once daily daily on days 1-14 of each 21-day cycle Second Resume at 4.5 mg once 4.5 mg once daily daily on days 1-14 of each 21-day cycle Third Permanently discontinue 4.5 mg once daily for drug first 14 days of each 21-day cycle

Permanently discontinue if unable to tolerate 4.5 mg once daily for 14 days of each 21-day cycle.

Pemigatinib is administered orally once daily without regard to food at approximately the same time of day. The tablets should be swallowed whole and should not be split, crushed, chewed, or dissolved.

If a dose of pemigatinib is missed and cannot be taken within 4 hours or if vomiting occurs, the missed or vomited dose should be skipped and the next dose should be taken at the regularly scheduled time.

The tablets should be stored at 20-25degreesC (excursions permitted between 15-30degreesC).

No dosing information is available for this tab.

Pemigatinib is metabolized principally by cytochrome P-450 (CYP) isoenzyme 3A4. In vitro, pemigatinib is not an inhibitor of CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4 or an inducer of CYP isoenzymes 1A2, 2B6, or 3A4.

In vitro studies indicate that pemigatinib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). In vitro, pemigatinib is an inhibitor of P-gp, organic cation transporter (OCT) 2, and multidrug and toxin extrusion (MATE) 1.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Pemigatinib/Strong And Moderate Cyp3a4 Inducers

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may increase the metabolism of pemigatinib by CYP3A4.(1)

CLINICAL EFFECTS: The concurrent use of strong and moderate CYP3A4 inducers and pemigatinib may result in decreased levels and clinical effectiveness of pemigatinib.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: Avoid concomitant use of strong and moderate CYP3A4 inducers with pemigatinib.(1)

DISCUSSION: Rifampin, a strong CYP3A4 inducer, decreased pemigatinib maximum concentration (Cmax) by 62% and area-under-curve (AUC) by 85% following a single pemigatinib oral dose of 13.5 mg. Concomitant use of a moderate CYP3A4 inducer is predicted to decrease pemigatinib exposure by more than 50%. Strong and moderate CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, belzutifan, bosentan, carbamazepine, cenobamate, dabrafenib, efavirenz, elagolix, encorafenib, enzalutamide, etravirine, fexinidazole, fosphenytoin, ivosidenib, lesinurad, lorlatinib, mavacamten, lumacaftor, mitapivat, mitotane, modafinil, nafcillin, pacritinib, pexidartinib, phenobarbital, phenytoin, primidone, repotrectinib, rifabutin, rifampin, rifapentine, St. John's wort, sotorasib, telotristat, thioridazine, and tovorafenib.(3)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Pemigatinib/Strong And Moderate Cyp3a4 Inhibitors

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Inhibitors of CYP3A4 may inhibit the metabolism of pemigatinib.(1)

CLINICAL EFFECTS: Concomitant use of a strong or moderate CYP3A4 inhibitor increases pemigatinib plasma concentrations, which may increase the incidence and severity of adverse reactions.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of pemigatinib states that coadministration with strong or moderate CYP3A4 inhibitors should be avoided. If coadministration cannot be avoided, the dosage of pemigatinib should be reduced as follows: -Reduce dose from 13.5 mg to 9 mg. -Reduce dose from 9 mg to 4.5 mg. If the strong or moderate CYP3A4 inhibitor is discontinued, resume the pemigatinib dose that was taken prior to the initiation of the inhibitor after 3 half-lives of the CYP3A4 inhibitor have elapsed.(1)

DISCUSSION: Itraconazole, a strong CYP3A4 inhibitor, increased the maximum concentration (Cmax) by 17% and area-under-curve (AUC) by 88% following a single oral pemigatinib dose of 4.5 mg. Concomitant use of moderate CYP3A4 inhibitors is predicted to increase pemigatinib exposure by approximately 50-80%.(1) Strong inhibitors of CYP3A4 include: adagrasib, boceprevir, ceritinib, clarithromycin, cobicistat, ensitrelvir, grapefruit, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, levoketoconazole, lonafarnib, lopinavir/ritonavir, mibefradil, mifepristone, nefazodone, nelfinavir, nirmatrelvir/ritonavir, paritaprevir, posaconazole, relacorilant, ribociclib, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, tucatinib, and voriconazole.(2) Moderate CYP3A4 inhibitors include: amprenavir, aprepitant, atazanavir, avacopan, berotralstat, clofazimine, conivaptan, crizotinib, darunavir, diltiazem, dronedarone, duvelisib, erythromycin, fedratinib, fluconazole, fluvoxamine, fosamprenavir, fosnetupitant, imatinib, isavuconazonium, lenacapavir, letermovir, netupitant, nilotinib, rilzabrutinib, schisandra, stiripentol, tofisopam, treosulfan, and verapamil.(2)

There are no moderate interactions for this drug.

*None.

• Lactation

• Child-pugh class C hepatic impairment
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Hyperphosphatemia
• Pregnancy
• Retinal pigment epithelial detachment
• Severe hepatic disease

• Hypophosphatemia

Adverse reactions reported in 20% or more of patients with cholangiocarcinoma receiving pemigatinib include hyperphosphatemia, alopecia, diarrhea, nail toxicity, fatigue, dysgeusia, nausea, constipation, stomatitis, dry eyes, dry mouth, decreased appetite, vomiting, arthralgia, abdominal pain, hypophosphatemia, back pain, and dry skin.

Adverse reactions reported in 20% or more of patients with myeloid/lymphoid neoplasms receiving pemigatinib include hyperphosphatemia, alopecia, diarrhea, nail toxicity, fatigue, nausea, constipation, stomatitis, dry eyes, dry mouth, decreased appetitie, abdominal pain, back pain, dry skin, rash, anemia, epistaxis, serous retinal detachment, extremity pain, dyspepsia, back pain, blurred vision, peripheral edema, and dizziness.

More Frequent

• Hyperphosphatemia
• Hyponatremia
• Hypophosphatemia

Less Frequent

• Cholangitis
• Dehydration
• Gastrointestinal obstruction
• Hyperbilirubinemia
• Hypercalcemia
• Hypotension
• Increased alanine transaminase
• Increased aspartate transaminase
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Onychomadesis
• Pleural effusions
• Retinal pigment epithelial detachment

Rare or Very Rare

• Calcinosis cutis
• Calciphylaxis
• Sepsis

More Frequent

• Acute abdominal pain
• Alopecia
• Anorexia
• Arthralgia
• Back pain
• Constipation
• Diarrhea
• Dry eye
• Dry skin
• Dysgeusia
• Fatigue
• Nail disorders
• Nausea
• Stomatitis
• Vomiting
• Xerostomia

Less Frequent

• Blurred vision
• Dizziness
• Epistaxis
• Hyperuricemia
• Pain
• Palmar-plantar erythrodysesthesia
• Peripheral edema
• Trichiasis
• Urinary tract infection
• Weight loss

No enhanced messaging available.

Safety and efficacy of pemigatinib have not been established in pediatric patients.

In animal toxicology studies, pemigatinib has been associated with changes in growing teeth (complete loss of ameloblasts with associated secondary changes) and bones (physeal and cartilage dysplasia). Complete recovery was not observed 6 weeks after the last dose. In a 13-week study, misaligned, whitened, broken, and trimmed/thinned incisors also were reported.

Pemigatinib may cause fetal harm if administered to pregnant females based on its mechanism of action and animal findings.

It is not known whether pemigatinib or its metabolites are distributed into human milk. The effects of the drug on nursing infants or on the production of milk are unknown.

Because of the potential for adverse reactions to pemigatinib in nursing infants, females should be advised not to nurse while receiving the drug and for 1 week after the final dose.

The manufacturer makes no specific dosage recommendations for geriatric patients.

In the principal efficacy study evaluating pemigatinib in patients with previously treated locally advanced or metastatic cholangiocarcinoma, 32% of patients were 65 years of age or older and 8% were 75 years of age or older. In the principal efficacy study evaluating pemigatinib in patients with myeloid/lymphoid neoplasms, 44% of patients were 65 years of age or older and 2.9% were 75 years of age or older. No clinically important differences in safety or efficacy were observed between geriatric patients and younger adults.