doxercalciferol
Regulatory sources consulted
Approved indications
- Secondary hyperparathyroidism in adults with chronic kidney disease on dialysis.
Contraindications
Absolute
- Hypercalcemia, vitamin D toxicity, or hypersensitivity.
Clinical warnings
- Major warning · Monitor calcium, phosphorus, and PTH; hypercalcemia may cause arrhythmias, seizures, vascular calcification, or adynamic bone disease. — DailyMed, set_id 7d07fa4f-f2a2-4c2b-86bf-c0a4691c1a0a
- Major warning · Anaphylaxis and angioedema have been reported; stop and treat immediately. — DailyMed, set_id 7d07fa4f-f2a2-4c2b-86bf-c0a4691c1a0a
Drug interactions
- HighCalcium, vitamin D, and thiazides
Mechanism: They may increase hypercalcemia risk.
Recommendation: Monitor calcium more frequently and adjust or stop.
DailyMed, set_id 7d07fa4f-f2a2-4c2b-86bf-c0a4691c1a0a
- HighDigitalis glycosides
Mechanism: Hypercalcemia increases digitalis toxicity.
Recommendation: Monitor calcium, ECG, and toxicity signs.
DailyMed, set_id 7d07fa4f-f2a2-4c2b-86bf-c0a4691c1a0a
Adverse events
Common (≥1%)
Hypercalcemia, hyperphosphatemia, and edema
Rare but serious
Anaphylaxis, angioedema, arrhythmia, and adynamic bone disease
Pregnancy and lactation
Pregnancy data are insufficient; use only if benefit justifies risk. Make an individualized breastfeeding decision.
Recent literature (PubMed)
The use of small doses of vitamin D3 analogs or metabolites is common in the prevention of renal osteodystrophy. Their use in the treatment of osteoporosis has been limited by their potent adverse effects, causing hypercalcemia and hypercalciuria. We evaluated a vitamin D2 analog, i.e., 1α-hydroxyvitamin D2 (doxercalciferol), that has a lower incidence of adverse effects. In a 1-year pilot randomized double-blind, placebo-controlled study, 55 postmenopausal women (aged 60-71 years) with osteopenia were treated for a year with either doxercalciferol or placebo, and 41 women completed an optional second year. The dose of 1 µg was increased by 1 µg at weekly intervals to a maximum of 5 µg. The daily dose of doxercalciferol averaged 4.1 µg after 12 months and 3.6 µg after 24 months. Bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry (DEXA) of the spine and femoral neck were obtained at 6-month intervals for 24 months. The serum and urine calcium levels were measured frequently for safety. In the primary intention-to-treat (ITT) analysis at 12 months, there was no significant difference between the two groups for femoral neck and spine BMD. At 24 months, there was a significant difference in favor of doxercalciferol for femoral neck BMD, with the treatment/placebo difference being 1.70% (p < 0.047); for spine BMD, the treatment/placebo difference was 1.1% (p = 0.36). In the per-protocol analysis at 12 months, the doxercalciferol/placebo difference for femoral neck was 0.5% (p = 0.497) and for spine BMD was 1.6% (p = 0.071). At 24 months, the doxercalciferol/placebo difference for femoral neck BMD was 2.2% (p < 0.017) and for spine BMD was 2.4% (p < 0.041). Over 24 months, there were five mild hypercalcemia events, 2.54 mmol/L (>10.2 mg/dl), in five patients. The mean 24-h urine calcium increased by 3.75 mmol (150 mg), with 16 episodes of hypercalciuria, 10 mmol (>400 mg), in 12 patients. The results show that doxercalciferol treatment showed no d
Lifestyle habits and insufficient sunlight exposure lead to a high prevalence of vitamin D hypovitaminosis, especially in the elderly. Recent studies suggest that in central Europe more than 50% of people over 60 years are not sufficiently supplied with vitamin D. Since vitamin D hypovitaminosis is associated with many diseases, such as Alzheimer's disease (AD), vitamin D supplementation seems to be particularly useful for this vulnerable age population. Importantly, in addition to vitamin D, several analogues are known and used for different medical purposes. These vitamin D analogues differ not only in their pharmacokinetics and binding affinity to the vitamin D receptor, but also in their potential side effects. Here, we discuss these aspects, especially those of the commonly used vitamin D analogues alfacalcidol, paricalcitol, doxercalciferol, tacalcitol, calcipotriol, and eldecalcitol. In addition to their pleiotropic effects on mechanisms relevant to AD, potential effects of vitamin D analogues on comorbidities common in the context of geriatric diseases are summarized. AD is defined as a complex neurodegenerative disease of the central nervous system and is commonly represented in the elderly population. It is usually caused by extracellular accumulation of amyloidogenic plaques, consisting of amyloid (Aβ) peptides. Furthermore, the formation of intracellular neurofibrillary tangles involving hyperphosphorylated tau proteins contributes to the pathology of AD. In conclusion, this review emphasizes the importance of an adequate vitamin D supply and discusses the specifics of administering various vitamin D analogues compared with vitamin D in geriatric patients, especially those suffering from AD.
Sustained 30% reductions of intact parathyroid hormone (iPTH) with extended-release calcifediol (ERC) are associated with slower decline in estimated glomerular filtration rate (eGFR) in non-dialysis chronic kidney disease (ND-CKD) patients with secondary hyperparathyroidism (SHPT). Such iPTH reductions usually require elevation of serum total 25-hydroxyvitamin D (25D) to ≥50 ng/mL, but achieving these reductions can be limited by the ERC dose ceiling (60 μg/day), raising the question of whether adjunctive active vitamin D (adj AVD) might be appropriate to further reduce iPTH. This randomized controlled trial (RCT) examined whether adj AVD could safely increase iPTH reductions achieved with ERC and further reduce the rate of eGFR decline in 78 ND-CKD adults treated with ERC for 38 weeks. Participants had mean age of 66 years, body mass index of 35 kg/m2, were 41% female, 63% white, 36% black, 19% Hispanic. At ERC initiation, participants had plasma iPTH 85-<500 pg/mL, eGFR 15-<60 mL/min/1.73 m2, serum 25D 10-<30 ng/mL, corrected serum calcium (Ca) 8.4-<9.8 mg/dL, serum phosphorus (P) 2.0-<5.0 mg/dL, and absence of macroalbuminuria (>3 g/g creatinine). At baseline (BL; week 38), participants had plasma iPTH >70 pg/mL and serum Ca <9.8 mg/dL and were randomized 3:1:1:1 to daily ERC (60 μg) for 14 additional weeks with (n = 40) or without (n = 38) adj daily oral calcitriol (0.25 μg), doxercalciferol (0.5 μg), or paricalcitol (1.0 μg). Measurements of eGFR, iPTH, 25D, Ca, P, and fibroblast growth factor 23 (FGF23) were obtained at BL and through end of treatment (EOT). No significant intergroup differences were observed at BL. Mean 25D at BL was 65 ng/mL and rose 14 ng/mL by EOT in both groups (p < 0.001). Mean BL iPTH was 137 pg/mL and fell by a further 35.4% (p < 0.001) with adj AVD therapy versus 2.2% without. Mean Ca, P, and FGF23 increased with adj AVD by 0.40 mg/dL (p < 0.001), 0.27 mg/dL (p < 0.01), and 49.1 pg/mL (155%; p < 0.001), respectively, but remained unc
Introduction: Secondary hyperparathyroidism (SHPT) is a common and major complication of chronic kidney disease (CKD) among patients on dialysis and in patients with CKD stage G3 to G5. SHPT in CKD is caused by disturbances in metabolic parameters. Paricalcitol (PCT), other active vitamin D analogous (doxercalciferol and alfacalcidol), and active vitamin D (calcitriol) have been commonly used to treat SHPT in non-dialysis CKD (ND-CKD) for several years. However, recent studies indicate that these therapies adversely increase serum calcium, phosphate, and fibroblast growth factor 23 (FGF-23) levels. Extended release calcifediol (ERC) has been developed as an alternative treatment for SHPT in ND-CKD. The present meta-analysis compares the effect of ERC against PCT in the control of PTH and calcium levels. Methods: A systematic literature review was conducted, according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines to identify studies for inclusion in the Network Meta-Analysis (NMA). Results: 18 publications were eligible for inclusion in the network meta-analysis and 9 articles were included in the final NMA. The estimated PTH reduction from PCT (-59.5 pg/ml) was larger than the PTH reduction from ERC (-45.3 pg/ml), but the difference in treatment effects did not show statistical significance. Treatment with PCT caused statistically significant increases in calcium vs. placebo (increase: 0.31 mg/dl), while the marginal increase in calcium from treatment with ERC (increase: 0.10 mg/dl) did not reach statistical significance. Conclusions: The evidence suggests that both PCT and ERC are effective in reducing levels of PTH, whereas calcium levels tended to increase from treatment with PCT. Therefore, ERC may be an equally effective, but more tolerable treatment alternative to PCT.