Patients with Hypoparathyroidism Warned of Extended NATPARA Recall

with Sara Lubitz, MD, Natalie Cusano MD, MS, and Bart L. Clarke, MD

Hypoparathyroidism is a rare condition noted by the inability of the parathyroid glands to produce parathyroid hormone (PTH). This, in turn, leads to low circulating calcium levels and an increase in blood phosphorus.

When NATPARA a synthetically derived injectable form of parathyroid hormone (PTH) was introduced, in January 2015,1 to manage hypoparathyroidism, many patients hailed this drug therapy as life-changing and lifesaving.

Parathyroid hormone injected desired treatment for people with hypoparathryoidism.Awaiting availability of NATPARA (PTH hormone replacement) means putting life on hold for many individuals with hypoparathyroidism. Photo: Demkat @ iStock

Status of Patients Requiring Treatment for Hypoparathyroidism

Now, four months after the sudden recall of NATPARA—the only available prescription hormone replacement approved to manage hypoparathyroidism in patients whose disease cannot be sufficiently managed with   activated vitamin D and calcium supplementation–‑in September 2019, patients and doctors are still coming to terms with the fallout.

Many individuals with chronic hypoparathyroidism are now faced with frequent doctor visits, and even hospitalizations, in the absence of the only effective agent to improve symptoms and address the low parathyroid hormone levels.

NATPARA was voluntarily pulled off the market by the manufacturer (Takeda) after small particles of rubber were found in some samples of the solution as a result of the reusable injection system. The Food and Drug Administration (FDA) considered the situation serious enough to advise all patients to stop using the drug immediately and to contact their healthcare provider for an alternative treatment plan.

No Good Alternative to Manage Deficiency of PTH  

Patients have been faced with returning to activated vitamin D and calcium even as this treatment proved ineffective or attempting to gain approval for special continued use of NATPARA if the clinician would certify that their life is at risk without it; or prescribe Forteo (teriparatide) twice a day in an off label use.

For the many patients returning to the traditional treatment of supplemental calcium and vitamin D, it has meant constant doctor appointments for testing and management of symptoms resulting from low calcium, such as joint and muscle pain, brain fog, and fatigue—even regular admissions to the hospital to gain relief from symptoms when it becomes unbearable.

“I received a lot of panicked calls,” said Sara Lubitz, MD, program director for the endocrinology, diabetes, and metabolism fellowship at the Robert Wood Johnson Medical School in New Brunswick, New Jersey. Indeed, those calls of distress came flooding in even before the company had alerted her or she became aware of the recall.

Dr. Lubitz said that although the recall was because rubber was detected in drug samples, no patient has reported any adverse effects based on the contamination. “It is a theoretical risk, yet the FDA recommended immediate stoppage even as NATPARA remains on the market in Europe [as NATPAR], which indicates that its removal from the market probably has been an abundance of caution that lead to the recall [in the US].”

Most patients did not want to discontinue taking NATPARA, preferring to take their chances. Dr. Lubitz heard stories of patients hoarding the drug: “This is a medication that had changed their lives. Before this PTH hormone replacement was an option, some individuals required repeated hospitalizations, which they wanted to avoid at any cost. Others were worried about the risk of contamination and wanted to be tested for rubber in their blood.”

Current Status—What Options Are Available, and What Works?

Dr. Lubitz has five patients with hypothyroidism who were being managed beautifully with NATPARA, and now she is in almost constant email communication with all of them. One of the individuals has   such severe symptoms in her hands that she has become unable to move the steering wheel of her car, making it impossible to drive. “Worse still, these patients are experiencing life-threatening side effects without the hormone therapy,” she told EndocrineWeb.

We were forced to switch our patients back to the vitamin D/Calcium regimen. “But no one knew how much to give each patient,” she said, “and they had to come in for blood tests every couple of days so we could adjust the supplements and monitor patient symptoms. Several patients required hospital admission for infusions.” It took weeks to stabilize some of our patients.

Another issue Dr. Lubitz noted as a common challenge was that taking calcium around the clock interfered with regular thyroid medication that all of these former thyroid cancer patients have to take. “There have been a lot of emergency office visits for these patients.”

Only after patients were stable on traditional therapy did Dr. Lubitz begin work to get as many as possible approved for Forteo, which has been found in some National Institutes of Health studies to be an effective treatment for hypoparathyroidism.

Not every insurance company approved the new treatment, which is twice the dose that those using Forteo are using for osteoporosis. It retails from about $3,300 to $4,700 per month for osteoporosis patients, although there are copay programs that reduce the cost to $50 per month.  

Like other doctors, Dr. Natalie Cusano, the director of the bone metabolism program at Lenox Hill Hospital in New York, New York found out via a patient about the recall. “My patients were more concerned about coming off of [NATPARA] than of the recall for a possible defect of the drug,” she says.

All three of her NATPARA patients were able to move to Forteo–after an appeal to their health insurer. “We had to document the reasons why treatment was started, sent in research studies showing that teriparatide has been successfully used in hypoparathyroidism, and in one case sent a letter in the patients’ own words why interruption of treatment would be harmful.”

Quality of Life Declines as Care Requires Significant Attention

Despite the use of Forteo, there is still a need for frequent blood tests, particularly during the transition, says Dr. Cusano. And any drug has its own potential side effects that can impact quality of life. “One of my patients is experiencing chronic headaches that she attributes to Forteo, and we are trying to maintain her on the lowest possible dose.”

Anyone with a diagnosis of hypoparathyroidism can expect to face: 2

  • Increased risk of diminishing kidney function
  • Forming kidney stones
  • Developing cataracts
  • Experiencing intracerebral calcification.

On the upside, despite having a calcium imbalance, there is no apparent worry about increased risk of bone fractures, heart disease or cancer.2

Dr. Bart L. Clarke, a professor of medicine at Mayo Clinic in Minnesota heard from the company and a patient via email at just about the same time. He has 15 patients who were on the drug. One has applied for the special use program, but most of the rest are using conventional therapy again.

“Some are interested in clinical trials with new medications for hypoparathyroidism, and three patients are on Forteo.” Others have been denied coverage for Forteo use, he says.

My patients are mostly doing well, says Dr. Clarke, although some have seen their quality of life regress on the conventional therapy, and that’s why they are seeking approval for Forteo or acceptance into the special use program. To date, only 358 patients across the United States have been granted “special use” permission to continue receiving NATPARA.   

The lack of access to NATPARA has proved intrusive and burdensome for both doctors and patients. Patients must submit to frequent monitoring: having their blood calcium levels checked every two to three days, which interferes with all aspects of their lives and requires that their doctors adjust their treatment repeatedly, he says.

This grueling focus on disease management has left some patients facing medical crashes that have required hospitalization for infusions of calcium. For now, that’s all we can do for our patients, says Dr. Clark. The rest is just “waiting for the FDA to release NATPARA back on the market.”

Manufacturer Says Availability of Parathyroid Hormone Delayed Another Year

As timing would have it—On January 23, 2020, Takeda (the company that produces NATPARA) issued a patient letter to anyone who had been prescribed this parathyroid hormone therapy,2 which Dr. Lubitz shared with EndocrineWeb.

The news is disappointing at best—the manufacturer informed patients that based on feedback from the Food and Drug Administration, additional testing and product modifications are necessary before NATPARA will be granted permission to return to market.

The company indicates that this is likely to postpone product available for another year. Dr. Lubitz indicated that her office was “flooded with calls and emails from patients who are freaking out” about this news, and she is faced with trying to find ways to address the concerns and care of her patients.

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