Endocrine Society, ASBMR Issue Joint Statement on Natpara Recall

In response to the recent recall of Natpara for the treatment of hypoparathyroidism, the Endocrine Society and the American Society for Bone Mineral Research (ASBMR) have drafted the following guidance for clinicians.

The recall of NATPARA®, recombinant human PTH(1-84), in the United States has caused significant concerns and uncertainties for patients with hypoparathyroidism who are currently on NATPARA®.  Likewise, providers are faced with a myriad of questions.

The reason for the recall is the observation of some tiny but visible rubber particles in the NATPARA® solution. These particles originate from the rubber septum of the cartridge, which is punctured by the replaceable cartridge needle each time an injection is made. When the septum is repeatedly pierced, small pieces of rubber may apparently detach into the solution.

The European FDA equivalent (EMA) has decided not to recall NATPAR® (that is the trade name of NATPARA® in Europe), permitting those in Europe to be treated while Takeda is working with the FDA so that the US supply can resume as early as possible.

This commentary is meant to assist health care providers who are now faced with the urgent need to transition their patients back to the preNATPARA regimen, namely calcium and vitamin D formulations. There are two main options for patients on NATPARA:

1. Transition to calcium/calcitriol. When stopping NATPARA and switching to oral calcium and calcitriol, some patients transiently require much higher doses of calcium/calcitriol than before starting NATPARA. It is not possible to predict who will need higher doses and for how long.  While the etiology is unclear, an active bone uptake mechanism has been proposed. The transient increase in calcium/calcitriol requirements has also been described after stopping teriparatide [PTH(1-34)] (J Bone Miner Res. 2015 Nov;30(11):2112-8). There is no algorithm that applies to all patients. Each patient has to be considered individually.
   About twelve hours after the last NATPARA injection, the amount of calcitriol should be double (or triple) the pre-NATPARA dose of calcitriol. The amount of calcium would be similar to the pre-NATPARA calcium dose.

Check serum calcium several times for the first week or two and adjust the dose of calcitriol (and calcium) accordingly.  Standing lab orders for frequent testing gives the patients and providers better flexibility.
There is not enough experience to know how to taper the amount of calcitriol to doses that would be closer to the preNATPARA calcitriol dose.

2. Transition to teriparatide (Forteo), recombinant human PTH(1-34). Teriparatide is not FDA-approved for treatment of hypoparathyroidism. It has, however, been used for hypoparathyroidism in clinical trials at the NIH by Dr. Karen Winer and colleagues (Winer KK Bone 2019, 120, 535). Teriparatide’s effect to raise the serum calcium concentration is shorter-lived than NATPARA’s. Thus, if teriparatide is to be used in this interim period when NATPARA is not available, twice-daily or even thrice-daily injections are typically necessary. Since this is truly a crisis for our patients, pre-authorization requests to the insurance companies for an off-label indication and the more frequent dosing are appropriate, but reception will vary among health care plans. Insurance denials can be appealed, including a request for a peer-to-peer review. NORD’s Rare Action Network can help advocate on the patient’s behalf.
   Forteo comes in a pen and only in one strength. Each administration contains 20 mcg of Forteo. Subcutaneous injections in the thigh are recommended in the treatment of hypoparathyroidism.

The Hypoparathyroidism Patient Organization provides a questionnaire for patients that can be useful for the transition.

One question on everybody’s mind is about the projected length of the recall.  We have been assured that the supplier, Takeda, is working diligently to come up with a solution as soon as possible.