Calcitriol (calcitriol)

During therapy with calcitriol, dosage depends on the nature and severity of the patient's hypocalcemia and must be individualized to maintain serum calcium concentrations of 9-10 mg/dL. The manufacturers recommend that serum calcium concentrations be measured at least twice weekly during initial dosage adjustments and after subsequent dosage changes; however, some clinicians recommend that serum calcium concentrations be measured at least weekly for the first 12 weeks of therapy and monthly after stabilization of dosage.

Nephrology experts state that the optimal intact parathyroid hormone (iPTH) concentration for patients with stage 3a (estimated glomerular filtration rate (eGFR) 45-59 mL/minute per 1.73 m2) to stage 5 (eGFR less than 15 mL/minute per 1.73 m2) chronic kidney disease (CKD) who are not undergoing dialysis is unknown, but modest increases in iPTH concentration may represent an appropriate adaptive response to declining renal function. For patients with stage 5 CKD undergoing dialysis, some experts suggest that iPTH concentrations may be maintained within a range of approximately 2-9 times the assay's upper limit of normal (ULN) (which may correspond to a range of approximately 130-600 pg/mL for commercially available assays ). Although some clinicians suggest that this range is too broad, available assays for PTH exhibit substantial variability; the previously recommended range of 150-300 pg/mL for patients with stage 5 CKD requiring dialysis was based on an assay that is no longer commercially available. Oversuppression of PTH may increase the risk of adynamic bone disease and should be avoided. (See Uses: Mineral and Bone Disorder Secondary to Chronic Renal Disease, in the Vitamin D Analogs General Statement 88:16.) Nephrology experts currently recommend that the individual values for serum calcium and phosphorus (evaluated together) be used instead of the mathematical construct of calcium times phosphorus product to guide clinical practice.

Calcitriol is administered orally, usually in a single daily dose, or by IV injection, usually 3 times weekly.

No dosing information is available for this tab.

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

Oral Phosphates; Active Vitamin D Analogs/Burosumab

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: Both burosumab and phosphates or vitamin D may increase serum phosphate levels. This combination may lead to greater increases in serum phosphate than anticipated.

CLINICAL EFFECTS: The combination of burosumab with oral phosphates or active vitamin D analogs may result in hyperphosphatemia and may increase the risk of nephrocalcinosis.(1)

PREDISPOSING FACTORS: Patients with renal impairment have alterations in mineral metabolism that may increase the risk of hyperphosphatemia.(1)

PATIENT MANAGEMENT: The concomitant use of burosumab with oral phosphates or active vitamin D analogs is contraindicated. Discontinue oral phosphate and/or active vitamin D analogs one week before starting burosumab.(1)

DISCUSSION: Burosumab restores dysfunctional renal phosphate reabsorption and renal production of 1,25-dihydroxyvitamin D to treat X-linked hypophosphatemia. Additional oral phosphates and/or active vitamin D analogs may raise serum phosphate higher than anticipated.

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

Serum Phosphate Level-Altering Drugs/Erdafitinib

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

MECHANISM OF ACTION: Medications that alter serum phosphate may interfere with interpretation of phosphate levels that are needed to determine initial erdafitinib dose.(1)

CLINICAL EFFECTS: Serum phosphate levels that are elevated by concomitant medications may result in an inappropriately low dose and decreased effectiveness of erdafitinib. Serum phosphate levels that are decreased by concomitant medications may result in an inappropriately high dose and increased toxicity from erdafitinib.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of erdafitinib states that agents that alter serum phosphate levels should be avoided before the initial dose increase period for erdafitinib based on serum phosphate levels (days 14 to 21).(1)

DISCUSSION: Concomitant administration of serum phosphate level-altering agents during the initial dose increase period of erdafitinib based on serum phosphate levels (days 14 to 21) may interfere with serum phospate levels and lead to incorrect dosing of erdafitinib.(1) Agents that may alter serum phosphate levels linked to this monograph include: aluminum carbonate, aluminum hydroxide, calcium acetate, calcium carbonate, calcium citrate, cod liver oil, ferric citrate, lanthanum, magnesium carbonate, magnesium hydroxide, potassium phosphate, sevelamer, sodium phosphate, sucroferric oxyhydroxide, tenapanor, and vitamin D.(1)

There are no moderate interactions for this drug.

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• Hypervitaminosis D

• Hypercalcemia
• Hyperphosphatemia
• Kidney stone

• Kidney disease with reduction in glomerular filtration rate (GFr)
• Sarcoidosis

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Rare or Very Rare

• Abnormal hepatic function tests
• Acute pancreatitis
• Anaphylaxis
• Bone pain
• Cardiac arrhythmia
• Conjunctivitis
• Dehydration
• Drug-induced psychosis
• Erythema multiforme
• Fever
• Hypercalcemia
• Hypersensitivity drug reaction
• Hypertension
• Urinary tract infection

Rare or Very Rare

• Abdominal pain with cramps
• Anorexia
• Constipation
• Drowsy
• Dysgeusia
• General weakness
• Headache disorder
• Hypercholesterolemia
• Libido changes
• Myalgia
• Nausea
• Nocturia
• Photophobia
• Polydipsia
• Polyuria
• Proteinuria
• Pruritus of skin
• Rhinorrhea
• Vomiting
• Weight loss
• Xerostomia

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