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PEMAZYRE is a brand name for Pemigatinib, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: PEMAZYRE™ (pemigatinib) is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement. Clinical effectiveness of PEMAZYRE™ is based on overall response rate (ORR) and…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations Patients must be selected for the treatment of locally advanced or metastatic cholangiocarcinoma with PEMAZYRE™ based on the confirmation of an FGFR2 fusion or rearrangement by a validated test (see 7 WARNINGS AND PRECAUTIONS, General and 14 CLINICAL TRIALS).
Avoid concomitant use of strong or moderate CYP3A4 inhibitors with PEMAZYRE™. Reduce the PEMAZYRE™ dose if co-administration with a strong or moderate CYP3A inhibitor cannot be avoided (see 9 DRUG INTERACTIONS). Avoid concomitant use of strong or moderate CYP3A4 inducers with PEMAZYRE™ (see 9 DRUG INTERACTIONS).
PEMAZYRE™ Product Monograph Page 6 of 37 Dose reduction of PEMAZYRE™ is required in patients with severe renal or hepatic impairment (see 4 DOSAGE AND ADMINISTRATION, Special Populations). 5 mg/dL and consider adding a phosphate lowering therapy when level is > 7 mg/dL.
Adjust the dose of phosphate lowering therapy until phosphate level returns to < 7 mg/dL. Consider discontinuing phosphate lowering therapy during PEMAZYRE™ treatment breaks or if phosphate level falls below normal (see Table 1). 5 mg orally once daily for 14 consecutive days followed by 7 days off therapy, in 21 day cycles.
Continue treatment until disease progression or unacceptable toxicity. Health Canada has not authorized an indication for pediatric use (see 1 INDICATIONS, Pediatrics). 5 mg taken orally once daily, 14 days on, 7 days off therapy. 5 mg once daily See Table 1.
5 mg/dL - ≤ 7 mg/dL Continue PEMAZYRE™ at current dose Initiate a low phosphate diet > 7 mg/dL - ≤ 10 mg/dL Continue PEMAZYRE™ at current dose, continue a low phosphate diet, and initiate phosphate-binding therapy. Monitor serum phosphate weekly, and adjust dose of phosphate lowering therapy as needed until level returns to < 7 mg/dL.
Withhold PEMAZYRE™ if serum phosphate levels do not return to < 7 mg/dL within 2 weeks of starting a phosphate lowering therapy. Restart PEMAZYRE™ at the same dose when serum phosphate level returns to < 7 mg/dL. Upon recurrence of serum phosphate at > 7 mg/dL with phosphate-lowering therapy, reduce PEMAZYRE™ 1 dose level.
> 10 mg/dL Continue PEMAZYRE™ at current dose, maintain a low- phosphate diet, and adjust phosphate-binding therapy. Continue to monitor serum phosphate weekly and adjust dose of phosphate lowering therapy as needed until serum phosphate level returns to < 7 mg/dL.
). 5 mg/dL (see 7 WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests, and 4 DOSAGE AND ADMINISTRATION, Table 1). Recommendations for additional management of hyperphosphatemia include administration of phosphate-lowering therapy, and dose modification when required.
Calcium-based antacids and phosphate-based supplements should be avoided. 3% of patients. 4% of participants. None of the events were serious, led to discontinuation or to dose reduction. Severe hypophosphatemia may present with confusion, seizures, focal neurologic findings, heart failure, respiratory failure, muscle weakness, rhabdomyolysis, and hemolytic anemia.
Discontinuing phosphate-lowering therapy and diet should be considered during pemigatinib treatment breaks or if serum phosphate level falls below normal range. For patients presenting with hyperphosphatemia or hypophosphatemia, additional close monitoring and follow-up is recommended regarding dysregulation of bone mineralization.
Monitoring and Laboratory Tests Serum Phosphate Phosphate concentrations should be assessed 14 days after initiating PEMAZYRE™ and then monitored every 2 cycles (approximately 6 weeks) thereafter. For elevated phosphate concentrations, follow dose modification guidelines in Table 1 (see 4 DOSAGE AND ADMINISTRATION).
Ocular Testing Perform ophthalmological examination including visual acuity test, slit-lamp examination, fundoscopy, and OCT prior to initiation of therapy, and every 2 months for the first 6 months of treatment and every 3 months afterwards, and urgently at any time for visual symptoms.
PEMAZYRE™ Product Monograph Page 11 of 37 Increased Creatinine Pemigatinib may increase serum creatinine due to a blockade of tubular secretion via renal transporters OCT2 and MATE1. 2 mg/dL) and reached steady state by Day 8, and then decreased during the 7 days off therapy.
, Special Populations). 5%) were ≥ 65 years. No overall differences in safety or effectiveness were observed between elderly and younger patients. 2 CONTRAINDICATIONS PEMZYRE™ is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. 1 Dosing Considerations Patients must be selected for the treatment of locally advanced or metastatic cholangiocarcinoma with PEMAZYRE™ based on the confirmation of an FGFR2 fusion or rearrangement by a validated test (see 7 WARNINGS AND PRECAUTIONS, General and 14 CLINICAL TRIALS).
Avoid concomitant use of strong or moderate CYP3A4 inhibitors with PEMAZYRE™. Reduce the PEMAZYRE™ dose if co-administration with a strong or moderate CYP3A inhibitor cannot be avoided (see 9 DRUG INTERACTIONS). Avoid concomitant use of strong or moderate CYP3A4 inducers with PEMAZYRE™ (see 9 DRUG INTERACTIONS).
PEMAZYRE™ Product Monograph Page 6 of 37 Dose reduction of PEMAZYRE™ is required in patients with severe renal or hepatic impairment (see 4 DOSAGE AND ADMINISTRATION, Special Populations). 5 mg/dL and consider adding a phosphate lowering therapy when level is > 7 mg/dL.
Adjust the dose of phosphate lowering therapy until phosphate level returns to < 7 mg/dL. Consider discontinuing phosphate lowering therapy during PEMAZYRE™ treatment breaks or if phosphate level falls below normal (see Table 1). 5 mg orally once daily for 14 consecutive days followed by 7 days off therapy, in 21 day cycles.
Continue treatment until disease progression or unacceptable toxicity. Health Canada has not authorized an indication for pediatric use (see 1 INDICATIONS, Pediatrics). 5 mg taken orally once daily, 14 days on, 7 days off therapy. 5 mg once daily See Table 1.
PEMZYRE™ is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Withhold PEMAZYRE™ if serum phosphate levels continue > 10 mg/dL for 1 week. Restart PEMAZYRE™ 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, permanently discontinue PEMAZYRE™.
Serous Retinal Detachment Educational material to assist healthcare professionals with the diagnosis and management of serous retinal detachment is available through the manufacturer. Asymptomatic and stable on serial examination Continue PEMAZYRE™ at current dose.
Monitor as described in Warnings and Precautions (Section 7) PEMAZYRE™ Product Monograph Page 8 of 37 Guidance for Interruption/Discontinuation of PEMAZYRE™ Adverse Reaction PEMAZYRE™ Dose Modification Symptomatic or worsening on serial examination Withhold PEMAZYRE™.
If asymptomatic and improved on subsequent examination, resume PEMAZYRE™ at next lower dose level. If symptoms persist, consider permanent discontinuation of PEMAZYRE™. Other Adverse Reactions Grade 1 or Grade 2 Continue PEMAZYRE™ treatment and treat the toxicity; monitor as medically indicated.
Grade 3 Interrupt PEMAZYRE™ up to 2 weeks (14 days) until the toxicity has resolved to ≤ Grade 1. Restart PEMAZYRE™ at next lower dose if adverse reaction resolves within 2 weeks; monitor as medically indicated. Permanently discontinue PEMAZYRE™ if adverse reaction does not resolve within 2 weeks.
Permanently discontinue PEMAZYRE™ for recurrent Grade 3 adverse reaction after 2 dose reductions.
Grade 4 Permanently discontinue PEMAZYRE™ Special Populations Renal impairment:
For patients with severe renal impairment (GFR < 30 mL/min), the starting dose of PEMAZYRE™ should be reduced to 9 mg. No dose adjustment is required for patients with end stage renal disease who are receiving dialysis (see 10 CLINICAL PHARMACOLOGY, Pharmacokinetics).
No dose adjustment is recommended for patients with mild or moderate renal impairment (glomerular filtration rate (GFR) ≥ 30 to < 90 mL/min estimated by Modification of Diet in Renal Disease (MDRD) equation).
Hepatic impairment:
For patients with severe hepatic impairment (total bilirubin > 3 × ULN with any AST), the starting dose of PEMAZYRE™ should be reduced to 9 mg (see 10 CLINICAL PHARMACOLOGY, Pharmacokinetics). 5–3 × ULN with any AST).
Pediatric patients (< 18 years of age):
Health Canada has not authorized an indication for pediatric use.
Geriatric patients (≥ 65 years of age):
No overall differences in efficacy or safety were detected between these patients and in patients < 65 years of age. No specific dose PEMAZYRE™ Product Monograph Page 9 of 37 adjustments are considered necessary for elderly patients (see 10 CLINICAL PHARMACOLOGY, […]
Alternative markers of renal function should be considered if persistent elevations in serum creatinine are observed. Ophthalmologic Serous Retinal Detachment PEMAZYRE™ can cause serous retinal detachment events, which may present with symptoms such as blurred vision, visual floaters, or photopsia.
5% of all patients treated with PEMAZYRE™. 4%). 4%). 4% of patients. In about 50% of the patients with an event, the events were self -limiting or resolved following PEMAZYRE™ interruption, reduction, or discontinuation. Perform ophthalmological examination including visual acuity test, slit-lamp examination, fundoscopy, and OCT prior to initiation of therapy, and every 2 months for the first 6 months of treatment and every 3 months afterwards, and urgently at any time for visual symptoms.
Educational materials to assist healthcare professionals with the diagnosis and management of serous retinal detachment are available through the manufacturer. For serous retinal detachment events, follow the dose modification guidelines in Table 1 (see 4 DOSAGE AND ADMINISTRATION).
Reproductive Health:
Female and Male Potential Fertility No animal studies have been performed to evaluate whether or not PEMAZYRE™ affects fertility in females or males. Teratogenic Risk Based on the mechanism of action and findings in an animal reproduction study, PEMAZYRE™ may cause fetal harm when administered to a pregnant woman.
In an embryo-fetal toxicity study, oral administration of pemigatinib to pregnant rats during the period of organogenesis caused malformations and embryo-fetal death at maternal exposures that were less than the human exposure at the maximum recommended human dose based on area under the curve (AUC).
Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with PEMAZYRE™ and PEMAZYRE™ Product Monograph Page 12 of 37 for 1 month after the last dose.
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PEMAZYRE™ and for 1 month after the last dose. 1 Pregnant Women PEMAZYRE™ may cause fetal harm and potential loss of pregnancy when administered to pregnant women.
There are no clinical data on the use of PEMAZYRE™ in pregnant women. Verify pregnancy status of females of reproductive potential prior to initiating PEMAZYRE™. PEMAZYRE™ should not be used during pregnancy. If PEMAZYRE™ is used during pregnancy, or if the patient becomes pregnant while taking PEMAZYRE™, advise the patient of the potential hazard to the fetus and counsel the patient about her clinical and therapeutic options.
Advise patients to contact their healthcare professional or if they become pregnant or pregnancy is suspected while being treated with PEMAZYRE™ and up to 1 month afterwards. 2 Breast-feeding There are no data on the presence of pemigatinib or its metabolites in human milk or their effects on either the breastfed child or on milk production.
Because of the potential for serious adverse reactions in breastfed children with PEMAZYRE™, advise women not to breastfeed during treatment and for 1 month after the final dose. 3 Pediatrics […]
5 mg/dL - ≤ 7 mg/dL Continue PEMAZYRE™ at current dose Initiate a low phosphate diet > 7 mg/dL - ≤ 10 mg/dL Continue PEMAZYRE™ at current dose, continue a low phosphate diet, and initiate phosphate-binding therapy. Monitor serum phosphate weekly, and adjust dose of phosphate lowering therapy as needed until level returns to < 7 mg/dL.
Withhold PEMAZYRE™ if serum phosphate levels do not return to < 7 mg/dL within 2 weeks of starting a phosphate lowering therapy. Restart PEMAZYRE™ at the same dose when serum phosphate level returns to < 7 mg/dL. Upon recurrence of serum phosphate at > 7 mg/dL with phosphate-lowering therapy, reduce PEMAZYRE™ 1 dose level.
> 10 mg/dL Continue PEMAZYRE™ at current dose, maintain a low- phosphate diet, and adjust phosphate-binding therapy. Continue to monitor serum phosphate weekly and adjust dose of phosphate lowering therapy as needed until serum phosphate level returns to < 7 mg/dL.
Withhold PEMAZYRE™ if serum phosphate levels continue > 10 mg/dL for 1 week. Restart PEMAZYRE™ 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, permanently discontinue PEMAZYRE™.
Serous Retinal Detachment Educational material to assist healthcare professionals with the diagnosis and management of serous retinal detachment is available through the manufacturer. Asymptomatic and stable on serial examination Continue PEMAZYRE™ at current dose.
Monitor as described in Warnings and Precautions (Section 7) PEMAZYRE™ Product Monograph Page 8 of 37 Guidance for Interruption/Discontinuation of PEMAZYRE™ Adverse Reaction PEMAZYRE™ Dose Modification Symptomatic or worsening on serial examination Withhold PEMAZYRE™.
If asymptomatic and improved on subsequent examination, resume PEMAZYRE™ at next lower dose level. If symptoms persist, consider permanent discontinuation of PEMAZYRE™. Other Adverse Reactions Grade 1 or Grade 2 Continue PEMAZYRE™ treatment and treat the toxicity; monitor as medically indicated.
Grade 3 Interrupt PEMAZYRE™ up to 2 weeks (14 days) until the toxicity has resolved to ≤ Grade 1. Restart PEMAZYRE™ at next lower dose if adverse reaction resolves within 2 weeks; monitor as medically indicated. Permanently discontinue PEMAZYRE™ if adverse reaction does not resolve within 2 weeks.
Permanently discontinue PEMAZYRE™ for recurrent Grade 3 adverse reaction after 2 dose reductions.
Grade 4 Permanently discontinue PEMAZYRE™ Special Populations Renal impairment:
For patients with severe renal impairment (GFR < 30 mL/min), the starting dose of PEMAZYRE™ should be reduced to 9 mg. No dose adjustment is required for patients with end stage renal disease who are receiving dialysis (see 10 CLINICAL PHARMACOLOGY, Pharmacokinetics).
No dose adjustment is recommended for patients with mild or moderate renal impairment (glomerular filtration rate (GFR) ≥ 30 to < 90 mL/min estimated by Modification of Diet in Renal Disease (MDRD) equation).
Hepatic impairment:
For patients with severe hepatic impairment (total bilirubin > 3 × ULN with any AST), the starting dose of PEMAZYRE™ should be reduced to 9 mg (see 10 CLINICAL PHARMACOLOGY, Pharmacokinetics). No dose adjustment is recommended for patients with […]