NATPAR

General Treatment should be supervised by a physician or other qualified healthcare professional experienced in the management of patients with hypoparathyroidism. 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: • Confirm 25-OH vitamin D stores are sufficient. • Confirm serum magnesium is within the reference range. Posology Initiating Natpar 1. Initiate treatment with 50 micrograms once daily as a subcutaneous injection in the thigh (alternate thigh every day).

25 mmol/L, a starting dose of 25 micrograms can be considered. 2. 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. 55 mmol/L, this measurement should be repeated the following day.

5. , 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:

Summary of the safety profile The most frequent adverse reactions among patients treated with Natpar were hypercalcaemia, hypocalcaemia, and their associated clinical manifestations including headache, diarrhoea, vomiting, paraesthesia, hypoaesthesia and hypercalciuria.

1). Tabulated list of adverse reactions Adverse reactions for Natpar-treated patients in the placebo-controlled study and in post-marketing experience are listed below by MedDRA system organ class and frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), and not known (cannot be estimated from the available data).

All adverse reactions identified in post-marketing experience are italicised. System organ class Very common (≥1/10) Common (≥1/100 to <1/10) Not known (cannot be estimated from the available data) Immune system dysorders Hypersensitivity reactions, (dyspnoea, angioedema, urticaria, rash) Metabolism and nutrition disorders hypercalcaemia, hypocalcaemia hypomagnesaemia†, tetany† Psychiatric disorders anxiety†, insomnia* Nervous system disorders headache*,†, hypoaesthesia†, paraesthesia† somnolence* Cardiac disorders palpitations*,† Vascular disorders hypertension* Respiratory, thoracic and mediastinal disorders cough† Gastrointestinal disorders diarrhoea*,†, nausea*, vomiting* abdominal pain upper* Musculoskeletal and connective tissue disorders arthralgia*, muscle spasms† muscle twitching†, musculoskeletal pain†, myalgia†, neck pain†, pain in extremity Renal and urinary disorders hypercalciuria*, pollakiuria† General disorders and administration site conditions asthenia*, chest pain†, fatigue, injection site reactions, thirst* Investigations anti-PTH antibody positive, blood 25-hydroxycholecalc iferol decreased†, vitamin D decreased *Signs and symptoms potentially associated with hypercalcaemia that were observed in the clinical trials.

†Signs and symptoms potentially associated with hypocalcaemia that were observed in the clinical trials. Description of selected adverse reactions Hypercalcaemia and hypocalcaemia were commonly encountered during the dose titration period.

Traceability In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded. 55 mmol/L. 2). 7 mmol/L. 2). Hypercalcaemia Hypercalcaemia was reported in clinical trials with Natpar.

Hypercalcaemia commonly occurred during the titration period, during which doses of oral calcium, active vitamin D, and Natpar were being adjusted. Hypercalcaemia may be minimised by following the recommended dosing, the monitoring information, and asking patients about any symptoms of hypercalcaemia.

0 mmol/L or above upper limit of normal with symptoms) develops, hydration and temporarily stopping Natpar, calcium and active vitamin D should be considered until serum calcium returns to the normal range. 8). Hypocalcaemia Hypocalcaemia, a common clinical manifestation of hypoparathyroidism, was reported in clinical trials with Natpar.

Most of the hypocalcaemic events occurring in the clinical trials were mild to moderate in severity. In the post-marketing setting, cases of symptomatic hypocalcaemia, including cases that resulted in seizures, have been reported in patients being treated with Natpar.

The risk for serious hypocalcaemia is highest after Natpar is withheld, missed or abruptly discontinued, but can occur at any time. Temporary or permanent discontinuation of Natpar must be accompanied by monitoring of serum calcium levels and increase of exogenous calcium and/or active vitamin D sources as necessary.

8). Concomitant use with cardiac glycosides Hypercalcaemia of any cause may predispose to digitalis toxicity. 5). Severe renal or hepatic disease Natpar should be used with caution in patients with severe renal or hepatic disease because they have not been evaluated in clinical trials.

3). Use in elderly patients Clinical studies of Natpar did not include sufficient numbers of subjects aged 65 and over to determine whether response in these subjects is different from younger subjects. Tachyphylaxis The calcium-raising effect of Natpar may diminish over time in some patients.

1 - who are receiving or who have previously received radiation therapy to the skeleton - with skeletal malignancies or bone metastases - who are at increased baseline risk for osteosarcoma such as patients with Paget’s disease of bone or hereditary disorders - with unexplained elevations of bone-specific alkaline phosphatase - with pseudohypoparathyroidism.