Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Takeda Pharmaceuticals International AG Ireland Branch, Block 3 Miesian Plaza, 50 – 58 Baggot Street Lower, Dublin 2, Ireland
Natpar is indicated as adjunctive treatment of adult patients with chronic hypoparathyroidism who cannot be adequately controlled with standard therapy alone.
Treatment should be supervised by a physician or other qualified healthcare professional experienced in the management of patients with hypoparathyroidism.
The goal of treatment with Natpar is to achieve calcaemic control and to reduce symptoms (see also section 4.4). The optimisation of parameters of calcium-phosphate metabolism should be in line with current therapeutic guidelines for the treatment of hypoparathyroidism.
Prior to initiating and during treatment with Natpar:
1. Initiate treatment with 50 micrograms once daily as a subcutaneous injection in the thigh (alternate thigh every day). If pre-dose serum calcium is >2.25 mmol/L, a starting dose of 25 micrograms can be considered.
2. In patients using active vitamin D, decrease the dose of active vitamin D by 50%, if pre-dose serum calcium is above 1.87 mmol/L.
3. In patients using calcium supplements, maintain calcium supplement dose.
4. Measure pre-dose serum calcium concentration within 2 to 5 days. If pre-dose serum calcium is below 1.87 mmol/L or above 2.55 mmol/L, this measurement should be repeated the following day.
5. Adjust dose of active vitamin D or calcium supplement or both based on serum calcium value and clinical assessment (i.e., signs and symptoms of hypocalcaemia or hypercalcaemia). Suggested adjustments to Natpar, active vitamin D and calcium supplements based on serum calcium levels are provided below:
| Pre-dose serum calcium | Adjust first | Adjust second | Adjust third |
| Natpar | Active vitamin D forms | Calcium supplement | |
| Above the upper limit of normal (ULN) (2.55 mmol/L)* | Consider reducing or stopping Natpar and re-assess by means of serum calcium measurement | Decrease or discontinue** | Decrease |
| Greater than 2.25 mmol/L and below the upper limit of normal (2.55 mmol/L)* | Consider reduction | Decrease or discontinue** | No change, or decrease if active vitamin D was already discontinued before this titration step |
| Less than or equal to 2.25 mmol/L and above 2 mmol/L | No change | No change | No change |
| Lower than 2 mmol/L | Consider increase after at least 2-4 weeks at a stable dose | Increase | Increase |
* The value of ULN may vary by laboratory
** Discontinue in patients receiving the lowest available dose
6. Repeat steps 4 and 5 until target pre-dose serum calcium concentration is within the range of 2.0-2.25 mmol/L, active vitamin D has been discontinued and calcium supplementation is sufficient to meet daily requirements.
Serum calcium concentration must be monitored during titration (see section 4.4).
The dose of Natpar may be increased by 25 microgram increments approximately every 2 to 4 weeks, up to a maximum daily dose of 100 micrograms. Downward titration to a minimum of 25 micrograms can occur at any time.
It is recommended to measure the albumin-corrected serum calcium 8-12 hours after dosing Natpar. If post-dose serum calcium is >ULN, then first reduce active vitamin D and calcium supplements and monitor progress. Measurements of pre- and post-dose serum calcium should be repeated and confirmed to be within an acceptable range before titration to a higher dose of Natpar is considered. If post-dose serum calcium remains >ULN, oral calcium supplementation should be further reduced or discontinued (see also adjustment table under Initiating Natpar).
At any dose level of Natpar, if post-dose albumin-corrected serum calcium exceeds the ULN and all active vitamin D and oral calcium have been withheld, or symptoms suggesting hypercalcaemia are present, the dose of Natpar should be reduced (see section 4.4).
In the case of a missed dose, Natpar must be administered as soon as reasonably feasible and additional exogenous sources of calcium and/or active vitamin D must be taken based on symptoms of hypocalcaemia.
Abrupt interruption or discontinuation of Natpar can result in severe hypocalcaemia. Temporary or permanent discontinuation of Natpar treatment must be accompanied by monitoring of serum calcium levels and adjustment, as necessary, of exogenous calcium and/or active vitamin D (see section 4.4).
See section 5.2.
No dose adjustment is necessary in patients with mild to moderate renal impairment (creatinine clearance 30 to 80 mL/min). There are no data available in patients with severe renal impairment (see section 4.4).
No dose adjustment is necessary for patients with mild or moderate hepatic impairment (total score of 7 to 9 on the Child-Pugh scale). There are no data available in patients with severe hepatic impairment (see section 4.4).
The safety and efficacy of Natpar in children less than 18 years of age have not yet been established.
No data are available.
Natpar is suitable for patient self-administration. Patients must be trained on the proper injection techniques by the prescriber or nurse, in particular during initial use.
Each dose must be administered as a subcutaneous injection once a day in alternating thighs.
For instructions on reconstitution of the medicinal product before administration and for using the pre-filled pen, see section 6.6 and the instructions included with the package leaflet.
Natpar must not be administered intravenously or intramuscularly.
Overdose can cause hypercalcaemia, the symptoms of which may include heart palpitations, ECG changes, hypotension, nausea, vomiting, dizziness and headache. Severe hypercalcaemia may be a life-threatening condition requiring urgent medical care and careful monitoring (see section 4.4).
3 years.
Reconstituted solution:
After reconstitution, chemical and physical in-use stability of the solution has been demonstrated for up to 14 days when stored in a refrigerator (2°C–8°C) and for up to 3 days when stored outside the refrigerator not above 25°C during the 14-day use peri
Keep the pen containing a reconstituted cartridge tightly closed in order to protect from light.
Store in a refrigerator (2°C–8°C).
Do not freeze.
Keep the pre-filled pen in the outer carton in order to protect from light.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
The glass dual-chamber cartridge inside the cartridge holder is made from type I glass with 2 bromobutyl rubber stoppers and a crimp cap (aluminium) with a bromobutyl rubber seal.
Natpar 25 micrograms: Each cartridge in the purple cartridge holder contains 350 micrograms of parathyroid hormone (rDNA) as powder in the first chamber and 1000 microlitres of solvent in the second chamber (corresponding to 14 doses).
Natpar 50 micrograms: Each cartridge in the red cartridge holder contains 700 micrograms of parathyroid hormone (rDNA) as powder in the first chamber and 1000 microlitres of solvent in the second chamber (corresponding to 14 doses).
Natpar 75 micrograms: Each cartridge in the grey cartridge holder contains 1050 micrograms of parathyroid hormone (rDNA) as powder in the first chamber and 1000 microlitres of solvent in the second chamber (corresponding to 14 doses).
Natpar 100 micrograms: Each cartridge in the blue cartridge holder contains 1400 micrograms of parathyroid hormone (rDNA) as powder in the first chamber and 1000 microlitres of solvent in the second chamber (corresponding to 14 doses).
Pack size: Carton containing 2 cartridges.
Carton/cartridge colours are used to indicate the different strengths:
25 micrograms – Purple
50 micrograms – Red
75 micrograms – Grey
100 micrograms – Blue
Parathyroid hormone (rDNA) is injected using the cartridge with a reusable pen. Each pen must be used by only one patient. A new sterile needle must be used for every injection. Use 31 G x 8 mm pen needles. After reconstitution, the liquid must be colourless and practically free of foreign particles; parathyroid hormone (rDNA) must not be used if the reconstituted solution is cloudy, coloured, or contains visible particles.
DO NOT SHAKE during or after reconstitution; shaking may cause denaturation of the active substance.
Read the instructions for use provided in the package leaflet before using the reusable pen.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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