Vitamin D2 Analog

Doxercalciferol

Approved 24 Jan 2022InjectionInjectable

The FDA lists this product in 29 strengths and forms.

Indications

Doxercalciferol injection is indicated for the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease (CKD) on dialysis. Doxercalciferol is a synthetic vitamin D 2 analog: Doxercalciferol injection is indicated for the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease (CKD) on dialysis. ( 1 )

Contraindications

Doxercalciferol is contraindicated in patients with: Hypercalcemia [see Warnings and Precautions (5.1) ] Vitamin D toxicity [see Warnings and Precautions (5.1) ] Known hypersensitivity to doxercalciferol or any of the inactive ingredients of doxercalciferol injection; serious hypersensitivity reactions including anaphylaxis and angioedema have been reported [see Warnings and Precautions (5.3) , Adverse Reactions (6.2) ].

Hypercalcemia ( 4 ) Vitamin D toxicity ( 4 ) Know hypersensitivity to doxercalciferol or any of the inactive ingredients of doxercalciferol injection ( 4 )

Warnings and precautions

Hypercalcemia : Can occur during treatment with doxercalciferol and can lead to cardiac arrhythmias and seizures. Severe hypercalcemia may require emergency attention. Risk may be increased when used concomitantly with high dose calcium preparations, thiazide diuretics, or vitamin D compounds. Monitor serum calcium prior to initiation and during treatment and adjust dose accordingly. ( 2 , 5.1 ) Digitalis Toxicity : Hypercalcemia increases the risk of digitalis toxicity.

In patients using digitalis compounds, monitor serum calcium and patients for signs and symptoms of digitalis toxicity. Increase frequency of monitoring when initiating or adjusting the dose of doxercalciferol. ( 5.2 ) Serious Hypersensitivity Reactions : Anaphylaxis, with symptoms of angioedema, hypotension, unresponsiveness, chest discomfort, shortness of breath, and cardiopulmonary arrest, has been reported in hemodialysis patients after administration of doxercalciferol.

Monitor patients upon treatment initiation for hypersensitivity reactions. Should a reaction occur, discontinue and treat. ( 5.3 ) Adynamic Bone Disease : May develop and increase risk of fractures if intact PTH levels are suppressed to abnormally low levels. Monitor intact PTH levels to avoid oversuppression and adjust dose if needed. ( 5.4 )

5.1Hypercalcemia

Hypercalcemia may occur during doxercalciferol treatment. Acute hypercalcemia may increase the risk of cardiac arrhythmias and seizures and may potentiate the effect of digitalis on the heart [see Warnings and Precautions (5.2) ] . Chronic hypercalcemia can lead to generalized vascular calcification and other soft-tissue calcification. Severe hypercalcemia may require emergency attention. Hypercalcemia may be exacerbated by concomitant administration of high doses of calcium-containing preparations, thiazide diuretics, or other vitamin D compounds [see Drug Interactions (7) ].

At a glance

Brand name: Doxercalciferol
Pharmacologic class: Vitamin D2 Analog
Route: Injection
Dosage form: Injectable
Applicant: Eugia Pharma
Status: Discontinued
FDA approval: 24 Jan 2022
Application: ANDA213717-001

Indications

Contraindications

Hypercalcemia ( 4 ) Vitamin D toxicity ( 4 ) Know hypersensitivity to doxercalciferol or any of the inactive ingredients of doxercalciferol injection ( 4 )

Warnings and precautions

5.1Hypercalcemia

Interactions

Table 3 includes clinically significant drug interactions with doxercalciferol. Table 3: Clinically Significant Drug Interactions with Doxercalciferol Injection Drugs that May Increase the Risk of Hypercalcemia Clinical Impact Concomitant administration of high doses of calcium-containing preparations or other vitamin D compounds may increase the risk of hypercalcemia. Thiazide diuretics are known to induce hypercalcemia by reducing excretion of calcium in the urine.

Examples Calcium-containing products, other vitamin D compounds or thiazide diuretics Intervention Monitor serum calcium concentrations more frequently and adjust doxercalciferol dose as needed [see Warnings and Precautions (5.1) ]. Digitalis Compounds Clinical Impact Doxercalciferol can cause hypercalcemia which can potentiate the risk of digitalis toxicity. Intervention Monitor patients for signs and symptoms of digitalis toxicity and increase frequency of serum calcium monitoring when initiating or adjusting the dose of doxercalciferol in patients receiving digitalis compounds [see Warnings and Precautions (5.2) ].

Cytochrome P450 Inhibitors Clinical Impact Doxercalciferol is activated by CYP 27 in the liver. Cytochrome P450 inhibitors may inhibit the 25-hydroxylation of doxercalciferol and thus reduce the formation of active doxercalciferol moiety [see Clinical Pharmacology (12.3) ]. Examples Ketoconazole and erythromycin Intervention If a patient initiates or discontinues therapy with a cytochrome P450 inhibitor, dose adjustment of doxercalciferol may be necessary.

Monitor intact PTH and serum calcium concentrations closely. Enzyme Inducers Clinical Impact Doxercalciferol is activated by CYP 27 in the liver. Enzyme inducers may affect the 25-hydroxylation of doxercalciferol [see Clinical Pharmacology (12.3) ]. Examples Glutethimide and phenobarbital Intervention If a patient initiates or discontinues therapy with an enzyme inducer, dose adjustment of doxercalciferol may be necessary.

Monitor intact PTH and serum calcium concentrations closely. Magnesium-containing Products Clinical Impact Concomitant administration of doxercalciferol and high doses of magnesium-containing products may increase the risk of hypermagnesemia. Examples Magnesium-containing products such as antacids Intervention Avoid use of magnesium-containing products and doxercalciferol in patients on chronic renal dialysis. Cytochrome P450 inhibitors : Formation of the active doxercalciferol moiety may be hindered and may necessitate dosage adjustment.

Monitor intact PTH and serum calcium concentrations closely. ( 7 ) Enzyme inducers : Formation of the active doxercalciferol moiety may be affected and may necessitate dosage adjustment. Monitor intact PTH and serum calcium concentrations closely. ( 7 ) Magnesium-containing products : Combined use may cause hypermagnesemia. Monitor serum magnesium concentrations more frequently and adjust dose as needed. ( 7 )

Adverse reactions

The following adverse reactions are discussed in greater detail in another section of the label: Hypercalcemia [see Warnings and Precautions (5.1) ] Serious Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Adynamic Bone Disease [see Warnings and Precautions (5.4) ] The most common adverse reactions in patients with CKD on dialysis (incidence >5%) were headache, malaise, edema, nausea/vomiting, dyspnea, dizziness, pruritus, and bradycardia.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eugia US LLC at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Doxercalciferol Capsules Adverse reactions in patients with CKD on dialysis Doxercalciferol capsules have been evaluated in two placebo-controlled, double-blind studies in patients with CKD on hemodialysis.

Patients were treated with doxercalciferol capsules (n=61) or placebo (n=61). After randomization to two groups, eligible patients underwent an 8-week washout period during which no vitamin D derivatives were administered to either group. Subsequently, all patients received doxercalciferol capsules in an open-label fashion for 16 weeks followed by a double-blind period of 8 weeks during which patients received either doxercalciferol capsules or placebo.

Adverse reactions occurring in the doxercalciferol capsule groups at a frequency of 2% or greater, and more frequently than in the placebo group are presented in Table 2. Table 2: Adverse Reactions Occurring in ≥2% Doxercalciferol Capsule-Treated Patients with CKD on Dialysis and Greater than Placebo in Two Double-Blind Clinical Studies * A patient who reported the same medical term more than once was counted only once for that medical term.

Adverse Reaction* Doxercalciferol (n=61) % Placebo (n=61) % Edema 34 21 Malaise 28 20 Headache 28 18 Nausea/Vomiting 21 20 Dizziness 12 10 Dyspnea 12 7 Pruritus 8 7 Bradycardia 7 5 Anorexia 5 3 Dyspepsia 5 2 Arthralgia 5 0 Weight increase 5 0 Abscess 3 0 Sleep disorder 3 0 Doxercalciferol Injection Adverse reactions in patients with CKD on hemodialysis Doxercalciferol injection has been studied in 70 patients with CKD on hemodialysis in two 12-week, open-label, single-arm, multicenter studies [see Clinical Studies (14.3) ] .

The incidence of hypercalcemia and hyperphosphatemia increased during therapy with doxercalciferol injection. Patients with higher pretreatment serum levels of calcium (>10.5 mg/dL) or phosphorus (>6.9 mg/dL) were more likely to experience hypercalcemia or hyperphosphatemia. There was no placebo group included in the studies of doxercalciferol injection. Adverse reactions in patients with CKD on hemodialysis receiving doxercalciferol injection are expected to be similar to those reported in placebo-controlled studies of doxercalciferol capsules presented in Table 2.

6.2Postmarketing Experience

The following adverse reactions have been identified during postapproval use of doxercalciferol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or to establish a causal relationship to drug exposure. Hypersensitivity reactions, including fatal outcome, have been reported in patients on hemodialysis following administration of doxercalciferol injection.

Hypersensitivity reactions include anaphylaxis with symptoms of angioedema (involving face, lips, tongue and airways), hypotension, unresponsiveness, chest discomfort, shortness of breath, cardiopulmonary arrest, pruritus, and skin burning sensation.

Doxercalciferol

Indications

Contraindications

Warnings and precautions

5.1Hypercalcemia

At a glance

Two medicines in one question?

Doxercalciferol

Indications

Contraindications

Warnings and precautions

5.1Hypercalcemia

At a glance

Two medicines in one question?

5.2Digitalis Toxicity

5.3Serious Hypersensitivity Reactions

5.4Adynamic Bone Disease

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information