Adjunctive therapy with 25-hydroxyvitamin D and articles therefor
Methods, compositions, and kits for adjunctive therapy using 25-hydroxyvitamin D are disclosed. The 25-hydroxyvitamin D may be administered with an agent that increases the risk of hypocalcemia, such as cinacalcet or a salt thereof, and/or an anticancer agent. The adjunctive therapy is effective to treat and prevent iatrogenic hypocalcemia and/or secondary hyperparathyroidism, as well as delay cancer progression and the time to a post-treatment skeletal related event.
1. A method of managing iatrogenic hypocalcemia and secondary hyperparathyroidism in a patient receiving therapy with cinacalcet or a salt thereof, comprising administering to said patient a pharmaceutical formulation comprising (a) a 25-hydroxyvitamin D compound and (b) an agent that increases the risk of hypocalcemia, optionally cinacalcet or a salt thereof.
2. The method of claim 1 , wherein the patient has impaired renal function, optionally associated with Chronic Kidney Disease Stage 1, 2, 3, 4, or 5.
3. The method of claim 1 , wherein the patient is receiving dialysis.
4. The method of claim 1 , wherein the patient is not on dialysis.
5. The method of claim 1 , wherein the effective amount of 25-hydroxyvitamin D is effective to restore or maintain the patient's serum calcium level to at least about 8.0 mg/dL, optionally in a range of about 8.3 mg/dL to about 11.6 mg/dL.
6. The method of claim 1 , wherein the effective amount of 25-hydroxyvitamin D is effective to safely increase the patient's serum level of 25-hydroxyvitamin D to at least 30 ng/mL, optionally in a range of about 30 ng/mL to about 100 ng/mL.
7. The method of claim 1 , wherein the effective amount of 25-hydroxyvitamin D is effective to decrease the patient's serum parathyroid hormone level, optionally by 30% or more.
8. The method of claim 1 , wherein the effective amount of 25-hydroxyvitamin D is administered in an oral modified release formulation, optionally a sustained release formulation.
9. The method of claim 1 , wherein the 25-hydroxyvitamin D is co-administered in an oral formulation comprising cinacalcet or a salt thereof.
10. The method of claim 1 , wherein the 25-hydroxyvitamin D comprises 25-hydroxyvitamin D 3 , 25-hydroxyvitamin D 2 , or a combination thereof.
11. The method of claim 10 , wherein the 25-hydroxyvitamin D comprises 25-hydroxyvitamin D 3 .
12. The method of claim 1 , wherein the 25-hydroxyvitamin D is administered in a dosage of 1 mcg to 1000 mcg per day.
13. The method of claim 1 , wherein the cinacalcet or salt thereof comprises cinacalcet HCI.
14. The method of claim 1 , wherein the patient is receiving cinacalcet administered in a dosage of 1 mg to 400 mg per day.
15. A method of treating secondary hyperparathyroidism in Chronic Kidney Disease in a patient on dialysis comprising administering to said patient an effective amount of a 25-hydroxyvitamin D compound by modified release and an effective dose of cinacalcet or a salt thereof in an amount of less than 360 mg daily, wherein said effective amount of cinacalcet is a reduced dose compared to the effective dose of cinacalcet in the absence of said 25-hydroxyvitamin D administration.
16. The method of claim 15 , comprising an initial dose of cinacalcet in a range of about 20 mg to about 25 mg once daily.
17. A method of treating hypercalcemia in a patient with parathyroid carcinoma, comprising administering to said patient an effective amount of a 25-hydroxyvitamin D compound by modified release and an effective dose of cinacalcet or a salt thereof in an amount of less than 360 mg daily, wherein said effective amount of cinacalcet or a salt thereof is a reduced dose compared to the effective dose of cinacalcet in the absence of said 25-hydroxyvitamin D administration.
18. A method of treating severe hypercalcemia in a patient with primary hyperparathyroidism who is unable to undergo parathyroidectomy, comprising administering to said patient an effective amount of a 25-hydroxyvitamin D compound by modified release and an effective dose of cinacalcet or a salt thereof in an amount of less than 360 mg daily, wherein said effective amount of cinacalcet or a salt thereof is a reduced dose compared to the effective dose of cinacalcet in the absence of said 25-hydroxyvitamin D administration.
19. The method of claim 17 , comprising an initial dose of cinacalcet in a range of about 20 mg to about 25 mg once daily.
20. The method of claim 1 , wherein the effective amount of 25-hydroxyvitamin D is in a range of about 100 mcg to about 300 mcg.
21. A method of treating a patient treated with an agent that increases the risk of hypocalcemia to (i) increase bone mineral density, (ii) decrease the blood level of a bone resorption marker, (iii) treat bone pain, (iv) increase the time to the first post-treatments skeletal-related event, said method comprising administering to the patient an effective amount of 25-hydroxyvitamin D, optionally, wherein 25-hydroxyvitamin D is administered in an amount effective to effectively and safely restore blood 25-hydroxyvitamin D levels to at least 30 ng/mL and to maintain blood 25-hydroxyvitamin D levels at such optimal levels.
22. A method of lowering elevated serum parathyroid hormone levels and/or stabilizing serum calcium levels in a patient having a bone metastasis and treated with an antiresorptive agent comprising administering an effective amount of 25-hydroxyvitamin D.