Chronic hypoparathyroidism

Dose recommendations of palopegteriparatide refer to micrograms of PTH. The dose should be individualised based on serum calcium. The optimal dose after titration is the minimum dose required to prevent hypocalcaemia. This is the dose that maintains serum calcium within the normal range without the need for active forms of vitamin D or calcium supplementation beyond recommended nutritional supplementation for the general population (generally less than 600 mg per day). Doses of active forms of vitamin D and calcium supplements will need to be adjusted prior to initiating and during treatment with palopegteriparatide based on serum calcium value.

Patients receiving the maximum palopegteriparatide dose of 60 mcg per day who experience ongoing hypocalcaemia may require co-administration of therapeutic calcium and/or active forms of vitamin D.

Before initiation of palopegteriparatide

Serum 25(OH) vitamin D should be within the normal range and serum calcium should be stable within or slightly below the normal range (1.95-2.64 mmol/L [7.8-10.6 mg/dL]) on at least 1 laboratory value at least two weeks prior to first dose of treatment.

Initiation of palopegteriparatide

The recommended starting dose is 18 mcg once daily with dose adjustments in 3 mcg increments thereafter every 7 days. The dose range is 6 to 60 mcg per day.

When initiating treatment with palopegteriparatide, the dose of active vitamin D or calcium supplements should be adjusted:

• If taking active vitamin D:
  • If serum calcium is ≥2.07 mmol/L [≥8.3 mg/dL], active vitamin D (calcitriol or alfacalcidol) should be discontinued on the same day as the first dose of palopegteriparatide. Doses of calcium supplements should be maintained.
  • If serum calcium is <2.07 mmol/L [<8.3 mg/dL], active vitamin D should be reduced by ≥50% on the same day as the first dose of palopegteriparatide. Doses of calcium supplements should be maintained.
• If not taking active vitamin D:
  • Calcium supplements should be decreased by at least 1 500 mg on the same day as the first dose of palopegteriparatide. If taking elemental calcium doses ≤1 500 mg per day, calcium supplements should be discontinued entirely.
• If calcium supplements are indicated to meet dietary requirements, continuing dietary calcium supplements at doses ≤600 mg per day may be considered instead of discontinuing entirely.

Dose adjustment and maintenance of palopegteriparatide

Serum calcium concentration must be monitored during titration. Palopegteriparatide dose may be increased in increments of 3 mcg if at least 7 days have elapsed since a prior dose change. The dose must not be increased more often than every 7 days. Palopegteriparatide may be reduced in increments of 3 mcg no more often than every 3 days in response to hypercalcaemia.

Serum calcium should be measured 7 days after the first dose and palopegteriparatide, active vitamin D, and calcium supplement dosing should be appropriate. After any subsequent dose change in palopegteriparatide, active vitamin D, or calcium supplements, serum calcium should be measured within 7 to 14 days and patients should be monitored for clinical symptoms of hypocalcaemia or hypercalcaemia. Palopegteriparatide, active vitamin D, and/or calcium supplements should be adjusted accordingly. Dose adjustments of palopegteriparatide, active vitamin D, and calcium supplements should be made on the same day.

The maintenance dose should be the dose that achieves serum calcium within the normal range, without the need for active vitamin D or therapeutic doses of calcium. Optionally, calcium supplementation sufficient to meet dietary requirements (≤600 mg per day) may be continued. Serum calcium and 25(OH) vitamin D should be measured as per standard of care when a maintenance dose is achieved. 25(OH) vitamin D (non-active vitamin D) supplementation may be needed to reach normal serum levels.

Missed dose

If a dose is missed by less than 12 hours, it should be administered as soon as possible. If a dose is missed by more than 12 hours, it should be skipped and the next dose should be administered as scheduled.

Interruption or discontinuation of palopegteriparatide

Interruption of daily administration should be avoided to minimise serum PTH fluctuations. Interruption or discontinuation of treatment can result in hypocalcaemia. When interrupting or discontinuing treatment for 3 or more consecutive doses, patients should be monitored for signs and symptoms of hypocalcaemia and consider to measure serum calcium. If indicated, treatment with calcium supplements and active vitamin D should be resumed. Treatment at the prescribed dose should be resumed as soon as possible after an interruption. When resuming treatment after an interruption, serum calcium should be measured and doses of palopegteriparatide, active vitamin D, and calcium supplements should be adjusted accordingly.

Palopegteriparatide must be administered as a subcutaneous injection to the abdomen or front of the thigh. The injection site should be rotated daily between four possible sites; abdomen (left or right) and front of the thigh (left or right).