Doxercalciferol

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Doxercalciferol Prescribing Information

Before initiating treatment, ensure serum calcium is not above the upper limit of normal. (
2.1 Prior to Initiation of Doxercalciferol Injection
- Ensure serum calcium is not above the upper limit of normal before initiating treatment with doxercalciferol injection
  [see Warnings and Precautions ].
)
Dosage for doxercalciferol injection in patients with CKD on dialysis
: Initiate dosing at 4 mcg by bolus intravenous administration three times weekly at the end of dialysis (no more frequently than every other day). Maximum dose is 18 mcg weekly. (
2.4 Important Administration Instructions for Doxercalciferol Injection
- Administer doxercalciferol injection intravenously as a bolus dose at the end of dialysis.
- Inspect doxercalciferol injection visually prior to administration; the solution should appear clear and colorless. Do not use if the solution is not clear or particles are present.
- After initial vial use, store opened multi-dose vial for up to 3 days at 2°C to 8°C (36°F to 46°F). Discard unused portion of multi-dose vial after 3 days
  [see How Supplied/Storage and Handling ].
)
Target the maintenance dose of doxercalciferol injection to intact parathyroid hormone (PTH) levels within the desired therapeutic range and serum calcium within normal limits. (
2 DOSAGE AND ADMINISTRATION
Before initiating treatment, ensure serum calcium is not above the upper limit of normal.
Dosage for doxercalciferol injection in patients with CKD on dialysis
: Initiate dosing at 4 mcg by bolus intravenous administration three times weekly at the end of dialysis (no more frequently than every other day). Maximum dose is 18 mcg weekly.
Target the maintenance dose of doxercalciferol injection to intact parathyroid hormone (PTH) levels within the desired therapeutic range and serum calcium within normal limits.
See Full Prescribing Information for dose titration, laboratory monitoring, and important administration instructions.
2.1 Prior to Initiation of Doxercalciferol Injection
Ensure serum calcium is not above the upper limit of normal before initiating treatment with doxercalciferol injection
[see Warnings and Precautions ].
2.4 Important Administration Instructions for Doxercalciferol Injection
Administer doxercalciferol injection intravenously as a bolus dose at the end of dialysis.
Inspect doxercalciferol injection visually prior to administration; the solution should appear clear and colorless. Do not use if the solution is not clear or particles are present.
After initial vial use, store opened multi-dose vial for up to 3 days at 2°C to 8°C (36°F to 46°F). Discard unused portion of multi-dose vial after 3 days
[see How Supplied/Storage and Handling ].
2.5 Dosage Recommendations for Doxercalciferol Injection in Patients with CKD on Dialysis
Initiate doxercalciferol injection at a dose of 4 mcg given by bolus intravenous administration three times weekly at the end of dialysis (no more frequently than every other day).
Target the maintenance dose of doxercalciferol to intact parathyroid hormone (PTH) levels within the desired therapeutic range and serum calcium within normal limits.
Monitor serum calcium, phosphorus, and intact PTH levels weekly after initiation of therapy or dose adjustment.
Titrate the dose of doxercalciferol injection based on intact PTH. The dose may be increased at 8-week intervals by 1 mcg to 2 mcg if intact PTH is not lowered by 50% and fails to reach the target range. The maximum dose is 18 mcg weekly. Prior to raising the dose, ensure serum calcium is within normal limits.
Suspend or decrease the dose if intact PTH is persistently and abnormally low to reduce the risk of adynamic bone disease
[see Warnings and Precautions ]
or if serum calcium is consistently above the normal range to reduce the risk of hypercalcemia
[see Warnings and Precautions ].
If suspended, the drug should be restarted one week later at a dose that is at least 1 mcg lower.
2.6 Drug Interactions that May Require Dosage Adjustments of Doxercalciferol Injection
Increased monitoring of serum calcium and dose adjustment of doxercalciferol may be necessary when given concomitantly with drugs that may increase the risk of hypercalcemia
[see Drug Interactions ].
Increased monitoring of both serum calcium and intact PTH as well as dose adjustment of doxercalciferol may be necessary when given concomitantly with cytochrome P450 inhibitors or enzyme inducers
[see Drug Interactions ].
)
See Full Prescribing Information for dose titration, laboratory monitoring, and important administration instructions. (
2 DOSAGE AND ADMINISTRATION
Before initiating treatment, ensure serum calcium is not above the upper limit of normal.
Dosage for doxercalciferol injection in patients with CKD on dialysis
: Initiate dosing at 4 mcg by bolus intravenous administration three times weekly at the end of dialysis (no more frequently than every other day). Maximum dose is 18 mcg weekly.
Target the maintenance dose of doxercalciferol injection to intact parathyroid hormone (PTH) levels within the desired therapeutic range and serum calcium within normal limits.
See Full Prescribing Information for dose titration, laboratory monitoring, and important administration instructions.
2.1 Prior to Initiation of Doxercalciferol Injection
Ensure serum calcium is not above the upper limit of normal before initiating treatment with doxercalciferol injection
[see Warnings and Precautions ].
2.4 Important Administration Instructions for Doxercalciferol Injection
Administer doxercalciferol injection intravenously as a bolus dose at the end of dialysis.
Inspect doxercalciferol injection visually prior to administration; the solution should appear clear and colorless. Do not use if the solution is not clear or particles are present.
After initial vial use, store opened multi-dose vial for up to 3 days at 2°C to 8°C (36°F to 46°F). Discard unused portion of multi-dose vial after 3 days
[see How Supplied/Storage and Handling ].
2.5 Dosage Recommendations for Doxercalciferol Injection in Patients with CKD on Dialysis
Initiate doxercalciferol injection at a dose of 4 mcg given by bolus intravenous administration three times weekly at the end of dialysis (no more frequently than every other day).
Target the maintenance dose of doxercalciferol to intact parathyroid hormone (PTH) levels within the desired therapeutic range and serum calcium within normal limits.
Monitor serum calcium, phosphorus, and intact PTH levels weekly after initiation of therapy or dose adjustment.
Titrate the dose of doxercalciferol injection based on intact PTH. The dose may be increased at 8-week intervals by 1 mcg to 2 mcg if intact PTH is not lowered by 50% and fails to reach the target range. The maximum dose is 18 mcg weekly. Prior to raising the dose, ensure serum calcium is within normal limits.
Suspend or decrease the dose if intact PTH is persistently and abnormally low to reduce the risk of adynamic bone disease
[see Warnings and Precautions ]
or if serum calcium is consistently above the normal range to reduce the risk of hypercalcemia
[see Warnings and Precautions ].
If suspended, the drug should be restarted one week later at a dose that is at least 1 mcg lower.
2.6 Drug Interactions that May Require Dosage Adjustments of Doxercalciferol Injection
Increased monitoring of serum calcium and dose adjustment of doxercalciferol may be necessary when given concomitantly with drugs that may increase the risk of hypercalcemia
[see Drug Interactions ].
Increased monitoring of both serum calcium and intact PTH as well as dose adjustment of doxercalciferol may be necessary when given concomitantly with cytochrome P450 inhibitors or enzyme inducers
[see Drug Interactions ].
)

Risk Summary

The limited available data with doxercalciferol in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with chronic kidney disease in pregnancy

[see

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Chronic kidney disease in pregnancy increases the risk for maternal hypertension and preeclampsia, miscarriage, preterm delivery polyhydramnios, stillbirth, and low-birth-weight infants.

]

. In reproduction studies in rats and rabbits administered doxercalciferol during organogenesis at up to 20 mcg/kg/day and 0.1 mcg/kg/day, respectively (approximately 25 times (rats) and less than (rabbits) the maximum recommended human oral dose of 60 mcg/week based on mcg/m² body surface area), no adverse developmental effects were observed

[see

Data

Animal data

There were no adverse effects on fetal development when doxercalciferol was administered at doses up to 20 mcg/kg/day in pregnant rats or doses up to 0.1 mcg/kg/day in pregnant rabbits during the period of organogenesis.

]

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.

Doxercalciferol is contraindicated in patients with:

Hypercalcemia
[see Warnings and Precautions (
5.1 Hypercalcemia
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 ]
. 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 ].
In addition, high intake of calcium and phosphate concomitantly with vitamin D compounds may lead to hypercalciuria and hyperphosphatemia. Patients with a history of hypercalcemia prior to initiating therapy may be at increased risk for development of hypercalcemia with doxercalciferol. In these circumstances, frequent serum calcium monitoring and doxercalciferol dose adjustments may be required.
When initiating doxercalciferol or adjusting doxercalciferol dose, measure serum calcium frequently (weekly in patients with CKD on dialysis or every 2 weeks for patients with stage 3 or 4 CKD). Once a maintenance dose has been established, measure serum calcium monthly for 3 months and then every 3 months. If hypercalcemia occurs, reduce the dose or discontinue doxercalciferol until serum calcium is normal
[see Dosage and Administration ]
.
Inform patients about the symptoms of elevated calcium (feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination and weight loss) and instruct them to report new or worsening symptoms when they occur.
)]
Vitamin D toxicity
[see Warnings and Precautions (
5.1 Hypercalcemia
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 ]
. 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 ].
In addition, high intake of calcium and phosphate concomitantly with vitamin D compounds may lead to hypercalciuria and hyperphosphatemia. Patients with a history of hypercalcemia prior to initiating therapy may be at increased risk for development of hypercalcemia with doxercalciferol. In these circumstances, frequent serum calcium monitoring and doxercalciferol dose adjustments may be required.
When initiating doxercalciferol or adjusting doxercalciferol dose, measure serum calcium frequently (weekly in patients with CKD on dialysis or every 2 weeks for patients with stage 3 or 4 CKD). Once a maintenance dose has been established, measure serum calcium monthly for 3 months and then every 3 months. If hypercalcemia occurs, reduce the dose or discontinue doxercalciferol until serum calcium is normal
[see Dosage and Administration ]
.
Inform patients about the symptoms of elevated calcium (feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination and weight loss) and instruct them to report new or worsening symptoms when they occur.
)]
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 Serious Hypersensitivity Reactions
Serious hypersensitivity reactions, including fatal outcome, have been reported post marketing 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, and cardiopulmonary arrest. These reactions may occur separately or together.
Monitor patients receiving doxercalciferol upon initiation of treatment for hypersensitivity reactions. Should a hypersensitivity reaction occur, discontinue doxercalciferol, monitor and treat if indicated
[see Contraindications ].
), Adverse Reactions (
6.2 Postmarketing 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.
)].

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 DOSAGE AND ADMINISTRATION
Before initiating treatment, ensure serum calcium is not above the upper limit of normal.
Dosage for doxercalciferol injection in patients with CKD on dialysis
: Initiate dosing at 4 mcg by bolus intravenous administration three times weekly at the end of dialysis (no more frequently than every other day). Maximum dose is 18 mcg weekly.
Target the maintenance dose of doxercalciferol injection to intact parathyroid hormone (PTH) levels within the desired therapeutic range and serum calcium within normal limits.
See Full Prescribing Information for dose titration, laboratory monitoring, and important administration instructions.
2.1 Prior to Initiation of Doxercalciferol Injection
Ensure serum calcium is not above the upper limit of normal before initiating treatment with doxercalciferol injection
[see Warnings and Precautions ].
2.4 Important Administration Instructions for Doxercalciferol Injection
Administer doxercalciferol injection intravenously as a bolus dose at the end of dialysis.
Inspect doxercalciferol injection visually prior to administration; the solution should appear clear and colorless. Do not use if the solution is not clear or particles are present.
After initial vial use, store opened multi-dose vial for up to 3 days at 2°C to 8°C (36°F to 46°F). Discard unused portion of multi-dose vial after 3 days
[see How Supplied/Storage and Handling ].
2.5 Dosage Recommendations for Doxercalciferol Injection in Patients with CKD on Dialysis
Initiate doxercalciferol injection at a dose of 4 mcg given by bolus intravenous administration three times weekly at the end of dialysis (no more frequently than every other day).
Target the maintenance dose of doxercalciferol to intact parathyroid hormone (PTH) levels within the desired therapeutic range and serum calcium within normal limits.
Monitor serum calcium, phosphorus, and intact PTH levels weekly after initiation of therapy or dose adjustment.
Titrate the dose of doxercalciferol injection based on intact PTH. The dose may be increased at 8-week intervals by 1 mcg to 2 mcg if intact PTH is not lowered by 50% and fails to reach the target range. The maximum dose is 18 mcg weekly. Prior to raising the dose, ensure serum calcium is within normal limits.
Suspend or decrease the dose if intact PTH is persistently and abnormally low to reduce the risk of adynamic bone disease
[see Warnings and Precautions ]
or if serum calcium is consistently above the normal range to reduce the risk of hypercalcemia
[see Warnings and Precautions ].
If suspended, the drug should be restarted one week later at a dose that is at least 1 mcg lower.
2.6 Drug Interactions that May Require Dosage Adjustments of Doxercalciferol Injection
Increased monitoring of serum calcium and dose adjustment of doxercalciferol may be necessary when given concomitantly with drugs that may increase the risk of hypercalcemia
[see Drug Interactions ].
Increased monitoring of both serum calcium and intact PTH as well as dose adjustment of doxercalciferol may be necessary when given concomitantly with cytochrome P450 inhibitors or enzyme inducers
[see Drug Interactions ].
,
5.1 Hypercalcemia
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 ]
. 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 ].
In addition, high intake of calcium and phosphate concomitantly with vitamin D compounds may lead to hypercalciuria and hyperphosphatemia. Patients with a history of hypercalcemia prior to initiating therapy may be at increased risk for development of hypercalcemia with doxercalciferol. In these circumstances, frequent serum calcium monitoring and doxercalciferol dose adjustments may be required.
When initiating doxercalciferol or adjusting doxercalciferol dose, measure serum calcium frequently (weekly in patients with CKD on dialysis or every 2 weeks for patients with stage 3 or 4 CKD). Once a maintenance dose has been established, measure serum calcium monthly for 3 months and then every 3 months. If hypercalcemia occurs, reduce the dose or discontinue doxercalciferol until serum calcium is normal
[see Dosage and Administration ]
.
Inform patients about the symptoms of elevated calcium (feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination and weight loss) and instruct them to report new or worsening symptoms when they occur.
)
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 Digitalis Toxicity
Doxercalciferol can cause hypercalcemia
[see Warnings and Precautions ]
which increases the risk of digitalis toxicity. In patients using doxercalciferol concomitantly with digitalis compounds, monitor both serum calcium and patients for signs and symptoms of digitalis toxicity. Increase the frequency of monitoring when initiating or adjusting the dose of doxercalciferol
[see Drug Interactions ].
)
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 Serious Hypersensitivity Reactions
Serious hypersensitivity reactions, including fatal outcome, have been reported post marketing 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, and cardiopulmonary arrest. These reactions may occur separately or together.
Monitor patients receiving doxercalciferol upon initiation of treatment for hypersensitivity reactions. Should a hypersensitivity reaction occur, discontinue doxercalciferol, monitor and treat if indicated
[see Contraindications ].
)
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 Adynamic Bone Disease
Adynamic bone disease with subsequent increased risk of fractures may develop if intact PTH levels are suppressed by doxercalciferol to abnormally low levels. Monitor intact PTH levels to avoid oversuppression and adjust the doxercalciferol dose, if needed
[see Dosage and Administration ].
)

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