6 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)]
6.1 Clinical 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.
The safety of Doxercalciferol Injection has been established from adequate and well-controlled studies of doxercalciferol capsules and from studies of another doxercalciferol injection product (doxercalciferol injection) [see Clinical Studies (14)]. Below is a display of the adverse reactions of doxercalciferol capsules and doxercalciferol injection from these studies.
Doxercalciferol capsules for oral use were 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 capsules groups at a frequency of 2% or greater, and more frequently than in the placebo group are presented in Table 1.
| 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 was studied in 70 patients with CKD on hemodialysis in two 12-week, open-label, single-arm, multi-center studies [see Clinical Studies (14)]. The incidence of hypercalcemia and hyperphosphatemia increased during therapy with doxercalciferol injection. Patients with higher pre-treatment 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 1.
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of Doxercalciferol Injection. 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.