The recall of Natpara in the US has caused significant concerns and uncertainties for patients with hypoparathyroidism who are currently on Natpara (PTH1-84) and their providers.
The recall notice can be found here.
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 punctured, small pieces of rubber may detach into the solution.
What can be done?
I see the following issues and options. These are my personal opinions and are in no way intended to be professional management recommendations.
- Patients and providers will have to decide whether to continue Natpara until the available stock of Natpara has been exhausted.
The European FDA equivalent (EMA) has decided not to recall Natpar (that is the trade name of Natpara in Europe), while Takeda is looking for a fix. That is a sign that the risk-benefit assessment differs between regulatory agencies in Europe and the United States.
- 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. We cannot predict who will need higher doses and for how long. The transient increase in calcium/calcitriol requirements has also been described by Drs. Gafni and Collins in 2015 (J Bone Miner Res. 2015 Nov;30(11):2112-8).
One possible way of transitioning to calcium/calcitriol:
- Start 12 hours after the last Natpara injection with double (or triple) the pre-Natpara dose of calcitriol and the (unchanged) pre-Natpara calcium dose.
- Check serum calcium and albumin often (every two days?) and adjust the dose of calcitriol (and calcium) accordingly
- I once tapered Natpara instead of stopping it abruptly but found that this approach required much more extended times of intense blood calcium monitoring.
- Transition to Forteo (PTH1-34). PTH1-34 has been used for hypoparathyroidism in clinical trials at the NIH by Dr. Karen Winer and colleagues, giving us ample data on it. However, Forteo’s effect of increasing blood calcium is shorter-lived than Natpara’s, and it is not approved for hypoparathyroidism. Therefore, twice-daily injections are typically necessary; pre-authorization requests to the insurance companies have to be dealt with.
Forteo is only 34 amino acids long compared to the 84 amino acids of Natpara. The molecular weight of Forteo is 2.29-fold smaller than that of Natpara. Practically, this means you have to divide the microgram (mcg) of Natpara by 2.29 to get the equivalent dose of Forteo.
For example, 100 mcg of Natpara is around 44 mcg of Forteo. But if Forteo is given twice daily, a lower total daily dose of it is needed (about 50%) compared to once-daily. Forteo comes in doses of 20 mcg.