High risk for severe hypocalcemia
If PTH is stopped abruptly, calcium levels will likely plummet, a phenomenon sometimes referred to as hungry bone syndrome, placing patients at risk for the consequences of severe hypocalcemia, Dr. Khan added.
(Hungry bone syndrome refers to the rapid, profound, and prolonged hypocalcemia associated with hypophosphatemia and hypomagnesemia, which is exacerbated by suppressed PTH).
One report suggests at least 100 patients who had to stop Natpara because of the FDA recall had to seek hospitalization to have calcium levels restored intravenously.
And even if the transition from injectable PTH back to calcium supplements and calcitriol goes smoothly, patients can still feel pretty awful.
“When you look at my blood levels on and off Natpara, they look very similar,” Danette Astolfi, a former Natpara user in the United States who recently transitioned from the injectable to standard of care, said in an interview.
“But I felt much, much better on Natpara, so this is an interesting ‘wild card’ that patients have with this drug – they just feel better on it. They don’t have the fatigue, they don’t have the brain fog, they don’t have the aches and pains even if their calcium levels are normal,” Ms. Astolfi said.
So patients who are candidates for injectable PTH therapy are by definition those who do not do very well on standard-of-care calcium and calcitriol.
“With the recall, patients are going back to this regimen they already did not have great success with,” Ms. Astolfi explained. “And that’s the tricky part because if you fall into this category, as I do, there is not much you can do about it.”
Ms. Astolfi, who is also on the board of directors of the Hypoparathyroidism Association in Pennsylvania, was lucky because she did not have to stop treatment with injectable PTH abruptly.
“I was fortunate. My physician did not want me to stop the drug right away, so we had time to develop a discontinuation plan,” she noted.
Transitioning safely to other therapies
Dr. Khan has advice for endocrinologists dealing with patients who were previously on Natpara and no longer have access to the drug.
First, “endocrinologists need to be aware that when you stop PTH treatment suddenly, patients’ need for calcium supplements and calcitriol may be as high as two times what they were on before they started PTH therapy,” she noted.
Physicians also need to follow patients closely by monitoring not only calcium and vitamin D levels but also phosphate and magnesium almost daily.
Dr. Khan said she does this because it’s difficult to predict how much calcium and calcitriol a patient will require and doses will likely have to be titrated up or down based on lab results.
It is noteworthy that a joint statement on the Natpara recall by the Endocrine Society and the American Society of Bone and Mineral Research (ASBMR) also emphasizes these points.
And Dr. Khan – as well as the Endocrine Society and ASBMR – also point out that patients may be transitioned from Natpara to teriparatide (Forteo), another recombinant form of PTH that is licensed for use in osteoporosis but has not been approved for hypoparathyroidism.
In Dr. Khan’s experience, patients often do quite well on teriparatide.
The big downside of prescribing teriparatide in the United States, however, is that the drug has to be used off label, and as such, insurance companies are unlikely to pick up the tab for what is an expensive treatment, she explained.
Furthermore, teriparatide has a very short shelf-life once injected so patients may need to use up to four needles a day to stabilize calcium levels.
If teriparatide is prescribed, subcutaneous injections given in the thigh are recommended for the treatment of hypoparathyroidism, according to the joint Endocrine Society/ASBMR statement.