Loading…
CRYSVITA is a brand name for Burosumab, supplied as a solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: X-linked hypophosphatemia CRYSVITA (Burosumab Injection) is indicated for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older. Tumor-induced osteomalacia CRYSVITA is indicated for the treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO)…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations • Discontinue oral phosphate and active vitamin D analogues (calcitriol or alfacalcidol) at least 1 week prior to initiation of treatment. Non-active Vitamin D supplementation may be continued. • Fasting serum phosphorus concentration should be below the reference range for age prior to initiation of treatment.
8 mg/kg of body weight, rounded down to the nearest 1 mg, administered every two weeks. The minimum starting dose is 5 mg. 8 mg/kg of body weight, rounded to the nearest 10 mg, administered every two weeks. The minimum starting dose is 10 mg up to a maximum dose of 90 mg.
After initiation of treatment with CRYSVITA, measure fasting serum phosphorus every 4 weeks for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is within the lower limit of the reference range for age, continue treatment with the same dose.
Follow the dose adjustment schedule noted below to maintain serum phosphorus within the reference range for age. Patient weight should be checked periodically to ensure proper total dose for patient weight is being administered. 2 mg/kg, administered every two weeks.
The calculated dose should be rounded to the nearest 1 mg. 4 mg/kg intervals up to a maximum of 2 mg/kg, administered every two weeks. The calculated dose should be rounded to the nearest 10 mg with a maximum dose of 90 mg. Reassess fasting serum phosphorus level 4 weeks after dose adjustment.
Do not adjust CRYSVITA dose more frequently than every 4 weeks.
Dose decrease, all pediatric patients:
If serum phosphorus is above the reference range for age, withhold the next dose and reassess the serum phosphorus level in 4 weeks. The patient must have serum phosphorus below the reference range for age to reinitiate CRYSVITA. Once serum phosphorus is below the reference range for age, treatment may be restarted at half the dose level previously administered.
Reassess serum phosphorus level 4 weeks after dose adjustment. If the level is below the reference range for age after the re-initiation dose, the dose can be gradually increased according to the Dose Increase instructions. CRYSVITA (burosumab) Page 6 of 32 Adult Patients with X-linked Hypophosphatemia (18 years of age and older) The recommended dose regimen in adults is 1 mg/kg of body weight, rounded to the nearest 10 mg up to a maximum dose of 90 mg, administered every four weeks.
and 14 CLINICAL STUDIES]. Efficacy in pediatric patients with XLH is based on two open label studies of 52 pediatric patients 5 to 12 years of age (Study UX023-CL201), and 13 pediatric patients 1 to 4 years of age (Study UX023-CL205) and one phase 3, open-label, active control study (61 patients 1-12 years of age (Study UX023- CL301)) evaluating serum phosphorus and radiographic findings.
Dosing in patients 6 months to 1 year and adolescents (age 13-17) was derived using modeling and simulation of adult and pediatric (aged 1 to 12 years) PK and PD data. 4 Geriatrics Clinical studies of CRYSVITA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.
0). In Study UX023-CL301, serious treatment emergent CRYSVITA (burosumab) Page 11 of 32 adverse events (TEAEs) of craniosynostosis, viral infection and migraine were reported by 3 (10%) patients in the CRYSVITA arm (N=29). The rates of the TEAEs of craniosynostosis, viral infection and migraine in the CRYSVITA arm were comparable to those in the active comparator arm.
Common adverse reactions in pediatric patients are presented in Table 5. No pediatric patients discontinued CRYSVITA due to adverse events. There have been 175 adult XLH patients exposed to CRYSVITA for a mean duration of 61 weeks (min 12, max 184).
Common adverse reactions in adults are presented in Table 3. In clinical trials, 3 adults discontinued from treatment with CRYSVITA due to adverse events. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.
The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.
General Hyperphosphatemia and Risk of Ectopic Mineralization Increases in serum phosphorus to above the upper limit of normal may be associated with an increased risk of ectopic mineralization, most commonly nephrocalcinosis. For patients already taking CRYSVITA, dose interruption and/or dose reduction may be required based on the Route of Administration Dosage Form / Strength/Composition Non-Medicinal Ingredients Subcutaneous Injection Solution for Injection 10 mg/mL, 20 mg/mL or 30 mg/mL D-sorbitol, L-histidine, L-methionine, polysorbate 80, water for injection (USP), and hydrochloric acid may be used to adjust pH.
CRYSVITA (burosumab) Page 9 of 32 patient’s serum phosphorus levels [see DOSAGE AND ADMINISTRATION]. , renal ultrasound) should be performed. Hypercalcemia and hyperparathyroidism Increases in serum calcium or parathyroid hormone have been reported in patients treated with CRYSVITA.
In patients with tertiary hyperparathyroidism, risk factors such as prolonged immobilization, dehydration, hypervitaminosis D, or renal impairment may increase the risk of moderate to severe hypercalcemia. Monitor serum calcium and parathyroid hormone levels before and during CRYSVITA treatment.
In patients with moderate to severe hypercalcemia, CRYSVITA should not be administered until the hypercalcemia is adequately managed. Injection Site Reactions Administration of CRYSVITA may result in local injection site reactions, especially in pediatric patients.
Discontinue CRYSVITA if severe injection site reactions occur and administer appropriate medical treatment [see ADVERSE REACTIONS]. Vitamin D Decrease During CRYSVITA treatment, monitoring of 25-hydroxy vitamin D (25(OH)D) concentration is advised.
If vitamin D levels decrease below the normal range, vitamin D supplementation may be needed. Active vitamin D analogues are contraindicated. Driving and Operating Machinery Patients experiencing dizziness while taking CRYSVITA should not drive or operate machinery.
• CRYSVITA 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 Dosage Forms, Strengths, Composition and Packaging.
• Do not use CRYSVITA with oral phosphate and/or active vitamin D analogues (calcitriol or alfacalcidol). • Do not initiate CRYSVITA treatment if serum phosphorus is within or above the normal range for age. • CRYSVITA is contraindicated in patients with severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism.
CRYSVITA (burosumab) Page 5 of 32
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Know a brand we are missing in Canada? Suggest a brand →
Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
Dose recalculation should be performed if there are changes in patient weight of ±10%. After initiation of treatment with CRYSVITA, measure fasting serum phosphorus on a monthly basis, measured 2 weeks post-dose, for the first 3 months of treatment, and thereafter as appropriate.
If serum phosphorus is within the normal range, continue with the same dose.
Dose increase:
CRYSVITA should not be administered at doses greater than 1 mg/kg in adults.
Dose decrease:
If serum phosphorus is above the normal range, withhold the next dose and reassess the serum phosphorus level after 4 weeks. The patient must have serum phosphorus below the normal range to be able to reinitiate CRYSVITA. Once serum phosphorus is below the normal range, treatment may be restarted at half the previous starting dose up to a maximum dose of 40 mg every 4 weeks.
Reassess serum phosphorus 2 weeks after any change in dose. Do not adjust CRYSVITA dose more frequently than every 4 weeks. 5 mg/kg body weight administered every 4 weeks, rounded to the nearest 10 mg, up to a maximum dose of 2 mg/kg, administered every 2 weeks.
After initiation of treatment with CRYSVITA, assess fasting serum phosphate on a monthly basis, measured 2 weeks post-dose, for the first 3 months of treatment, and thereafter as appropriate. If serum phosphate is within the normal range, continue with the same dose.
Follow the dose adjustment schedule below to maintain serum phosphorus within the reference range. Dose increase If serum phosphorus is below the normal range, the dose should be titrated in accordance with Table 1 up to the maximum dose of 2 mg/kg, administered every 2 weeks.
For those individuals not reaching a serum phosphorus greater than the lower limit of the normal range, physicians may consider dividing total dose administered every 4 weeks and administering every 2 weeks. 5 mg/kg every 2 weeks Increase to: 2 mg/kg every 2 weeks *Rounded to the nearest 10 mg.
**Do not adjust CRYSVITA more frequently than every 4 weeks. *** For those individuals not reaching a serum phosphorus greater than the lower limit of the normal range, physicians may […]
Adverse Reactions in Adult Patients with XLH The safety data described below reflect the results of a randomized, double-blind, placebo- controlled Phase 3 study in adults with XLH (Study UX023-CL303: CRYSVITA = 68, Placebo = 66) aged 20-63 years (mean age 41 years), of whom most were white/Caucasian (81%) and female (65%).
2 mg/kg) at Week 24. Adverse reactions reported in more than 5% of CRYSVITA-treated patients and ≥2 patients than with placebo from the 24-week placebo-controlled portion of UX023-CL303 are shown in Table 3. 1) CRYSVITA (N=68) n (%) Placebo (N=66) n (%) Back pain 10 (15) 6 (9) Headache1 9 (13) 6 (9) Tooth infection2 9 (13) 6 (9) Restless legs syndrome 8 (12) 5 (8) Vitamin D decreased3 8 (12) 3 (5) Dizziness 7 (10) 4 (6) Constipation 6 (9) 0 (0) Muscle spasm 5 (7) 2 (3) Blood phosphorus increased4 4 (6) 0 (0) n = number of patients with an event; N = total number of patients who received at least one dose of CRYSVITA or placebo 1 Headache includes: headache, and head discomfort 2 Tooth infection includes: tooth abscess, and tooth infection 3 Vitamin D decreased includes: vitamin D deficiency, blood 25-hydroxycholecalciferol decreased, and vitamin D decreased 4 Blood phosphorus increased includes: blood phosphorus increased, and hyperphosphatemia CRYSVITA (burosumab) Page 12 of 32 Hypersensitivity Reactions In the double-blind period of UX023-CL303 in adults, approximately 6% of patients in both the CRYSVITA and placebo treatment groups experienced a hypersensitivity event.
The events were mild or moderate and did not require discontinuation. 5 mg/dL [the upper limit of normal for adults] on two occasions). The hyperphosphatemia was managed with dose reduction. 5 mg/kg. 25 mg/kg for continued hyperphosphatemia.
g. injection site reaction, erythema, rash, bruising, pain, pruritus, and hematoma) at the site of the injection. Injection site reactions were generally mild in severity, occurred within 1 day of injection, lasted approximately 1 to 3 days, required no treatment, and resolved in almost all instances.
Restless Leg Syndrome (RLS) In the double-blind period of UX023-CL303, approximately 12% of the CRYSVITA treatment group had worsening of baseline restless leg syndrome (RLS) or new onset RLS of mild to moderate severity; these events did not lead to dose discontinuation.
Non-serious RLS has also been reported in other repeat dose adult XLH studies; in one case, worsening baseline RLS was attributed to dose limiting toxicity and led to drug discontinuation and subsequent resolution of the event. Spinal Stenosis Spinal stenosis (sometimes with cord compression) is known to occur in adults with XLH.
In CRYSVITA clinical trials, 6 patients (of 176) underwent spinal surgery. It is unknown if CRYSVITA is associated with new or exacerbated spinal stenosis or spinal cord compression. Adverse […]
g. rash, urticaria, facial swelling) have been reported in patients with CRYSVITA. Discontinue CRYSVITA if serious hypersensitivity reactions occur and initiate appropriate medical treatment [see ADVERSE REACTIONS].
Reproductive Health:
Female and Male Potential • Fertility There are no available data on the effects of CRYSVITA on human fertility to inform a drug- associated risk of adverse fertility outcomes. In addition, no dedicated fertility studies have been conducted in animals.
In a 40-week repeat-dose toxicity study conducted in cynomolgus monkeys, no adverse effects on female reproductive organs or menstrual length were observed at doses up to 30 mg/kg. In male monkeys, minimal mineralization in the rete testis or seminiferous tubules associated with hyperphosphatemia was observed at doses ≥3 mg/kg.
Semen analysis did not show any adverse effects at any dose [see 15 NON-CLINICAL TOXICOLOGY]. 1 Pregnancy There are no available data on CRYSVITA use in pregnant women to inform a drug-associated risk of adverse developmental outcomes.
In utero, burosumab exposure in non-XLH pregnant cynomolgus monkeys did not result in teratogenic effects. Adverse effects, such as fetal loss and pre-term birth, were observed in pregnant cynomolgus monkeys. Fetal loss was observed at an exposure higher than that provided by the maximum recommended human dose of 2 mg/kg and was accompanied by maternal hyperphosphatemia and placental mineralization.
Pre-term birth was observed at an exposure less than that provided by the maximum recommended human dose. In addition, burosumab was detected in serum from monkey fetuses indicating transport across the placenta [see 15 NON-CLINICAL TOXICOLOGY].
Animal studies are not always predictive of human response; therefore, it is unknown whether CRYSVITA can cause fetal harm when administered to a pregnant woman. Report pregnancies to the Kyowa Kirin Adverse Event reporting line at 1-866-590-9508.
The use of CRYSVITA during pregnancy is not recommended. In woman of childbearing potential, an effective contraception method should be used during treatment with CRYSVITA and for at least 14 weeks after stopping treatment. 2 Breastfeeding CRYSVITA has not been studied in lactating women.
It is unknown if the drug is excreted in human milk. Because many drugs are excreted in human milk precaution should be exercised. 3 Pediatrics No patients less than 1 year of age were enrolled in XLH clinical trials with CRYSVITA. There is no efficacy and safety experience with CRYSVITA in pediatric patients less than 1 year of age.
Safety and efficacy of CRYSVITA have been established in pediatric patients aged 1-12 years with XLH [see