CRYSVITA
Clinical safety rating
cautionComprehensive clinical and safety monograph for CRYSVITA (CRYSVITA).
Comprehensive clinical and safety monograph for CRYSVITA (CRYSVITA).
Treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients aged 1 year and olderTreatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized
Fibroblast growth factor 23 (FGF23) inhibitor; increases renal phosphate reabsorption and 1,25-dihydroxyvitamin D production by blocking FGF23 activity.
| Metabolism | Metabolized into small peptides and amino acids via catabolic pathways; not metabolized by cytochrome P450 enzymes. |
| Excretion | Renal (minimal, as intact antibody); catabolized into small peptides and amino acids; no biliary/fecal elimination of intact drug. |
| Half-life | 16.4 days (terminal elimination half-life); supports monthly subcutaneous dosing. |
| Protein binding | Target-mediated binding to FGF23; low nonspecific binding to other plasma proteins (typical for mAbs). |
| Volume of Distribution | 3.8 L (approximately 0.05 L/kg for a 70 kg adult); indicates limited extravascular distribution (confined mainly to plasma volume). |
| Bioavailability | Subcutaneous: ~78% relative to intravenous administration (absolute bioavailability not determined due to lack of IV formulation). |
| Onset of Action | Subcutaneous: serum phosphorus increases within 1 week; maximal effect within 2-4 weeks. |
| Duration of Action | ~4 weeks (one monthly dose maintains serum phosphorus within target range); clinical effect wanes by end of dosing interval. |
| Molecular Weight | 199000 |
1 mg/kg subcutaneously once monthly; maximum dose 90 mg. Administer at a fixed date each month.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required in renal impairment. Safety and efficacy not established in severe renal impairment (eGFR <30 mL/min/1.73 m²) or on dialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | 1 mg/kg subcutaneously once monthly; maximum dose 90 mg. Administer at a fixed date each month. |
| Geriatric use | No specific dose adjustment recommended for elderly patients (≥65 years). Use based on weight and clinical response. |
| 1st trimester | No adequate human data; animal studies show increased fetal loss and skeletal abnormalities at high doses. Avoid use unless benefit outweighs risk. |
| 2nd trimester | No adequate human data; potential for fetal harm due to phosphate metabolism disruption. Use only if clearly needed. |
| 3rd trimester | No adequate human data; may affect fetal bone mineralization. Use only if maternal benefit justifies potential fetal risk. |
Clinical note
Comprehensive clinical and safety monograph for CRYSVITA (CRYSVITA).
| Placental transfer | Expected to cross placenta due to IgG-based fusion protein; molecular weight 199,000 Da suggests transfer via FcRn. |
| Breastfeeding | Unknown if distributed in human milk; due to high molecular weight, likely low levels. Caution recommended; consider risk versus benefit. |
| Lactation Rating | L3 (Limited Data - Probably Compatible) |
| Teratogenic Risk | CRYSVITA (burosumab) is a monoclonal antibody that inhibits fibroblast growth factor 23 (FGF23). There are no adequate and well-controlled studies in pregnant women. In animal studies, administration of burosumab to pregnant monkeys during organogenesis resulted in no teratogenic effects at doses up to 5.9 times the human dose. However, due to the mechanism of action, potential risks include disturbances in phosphate and vitamin D metabolism which may affect fetal skeletal development. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. |
| Fetal Monitoring | Monitor serum phosphorus, calcium, and vitamin D levels regularly during pregnancy and postpartum. Assess renal function and monitor for potential adverse effects such as hyperphosphatemia or hypophosphatemia. Fetal monitoring should include ultrasound for skeletal development if clinically indicated. |
| Fertility Effects | No specific fertility studies have been conducted with burosumab. In animal studies, no adverse effects on male or female fertility were observed at doses up to 5.9 times the human dose. However, the impact on human fertility is unknown. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to burosumab or any excipientConcomitant use with oral phosphate supplements or active vitamin D analogs
| Precautions | Hypersensitivity reactions including anaphylaxis, Hyperphosphatemia and risk of nephrocalcinosis/nephrolithiasis, Dental abscesses and infections, Local injection site reactions |
| Food/Dietary | Avoid high-phosphorus foods and beverages (e.g., dairy products, nuts, seeds, whole grains, cola, chocolate, organ meats) while on CRYSVITA, as they may increase serum phosphorus levels and risk of hyperphosphatemia. Dietary phosphate restriction is recommended. No specific food-drug interactions known; however, maintain consistent phosphorus intake between doses. |
| Clinical Pearls | CRYSVITA (burosumab) is a recombinant human monoclonal IgG1 antibody to fibroblast growth factor 23 (FGF23), indicated for X-linked hypophosphatemia (XLH) in adult and pediatric patients aged 1 year and older. Administer subcutaneously every 2 weeks (pediatric: starting 0.8 mg/kg, max 1.2 mg/kg; adult: 1.0 mg/kg, max 90 mg). Monitor serum phosphorus closely, aiming for age-appropriate normal range. Do not initiate if serum phosphorus is within normal range. Concomitant use with oral phosphate and active vitamin D analogs is not recommended. May cause injection site reactions, headache, and hyperphosphatemia. Discontinue if severe hypersensitivity occurs. Pregnancy and breastfeeding: limited data; use only if clearly needed. |
| Patient Advice | CRYSVITA is given as an injection under the skin every 2 weeks. Do not miss doses. · Do not take phosphate supplements or active vitamin D (e.g., calcitriol) while on CRYSVITA unless specifically instructed by your doctor. · Report symptoms of high phosphorus levels: muscle cramps, numbness, tingling, or irregular heartbeat. · Common side effects include injection site reactions (redness, pain, swelling), headache, and back pain. · Pregnancy and breastfeeding: inform your doctor if you are pregnant, plan to become pregnant, or are nursing. · Store CRYSVITA in the refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. Protect from light. Allow to reach room temperature before injecting. |
Loading safety data…