Medical Editor: John P. Cunha, DO, FACOEP
Natpara (parathyroid hormone) for Injection is a parathyroid hormone used as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism. Common side effects of Natpara include:
- tingling/burning/prickling sensation of your skin
- high or low blood calcium levels
- reduced sensitivity to sensory stimuli or reduced sense of touch
- joint pain
- elevated calcium in the urine
- pain in extremities
- upper respiratory tract infection
- abdominal pain
- sinus infection
- high blood pressure, or
- neck pain
The recommended Natpara dose is the minimum dose required to prevent both hypocalcemia and hypercalciuria. Natpara may interact with alendronate and digoxin. Tell your doctor all medications and supplements you use. During pregnancy, Natpara should only be used if prescribed. It is unknown if this drug passes into breast milk. Consult your doctor before breastfeeding.
Our Natpara (parathyroid hormone) for Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
The following serious adverse reactions are described in greater detail in other sections of the label:
- Osteosarcoma [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
- Hypercalcemia [see WARNINGS AND PRECAUTIONS]
- Hypocalcemia [see WARNINGS AND PRECAUTIONS]
- Hypersensitivity [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS]
Adverse Reactions In Clinical Trials For Hypoparathyroidism
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice.
NATPARA was studied in a placebo-controlled trial [see Clinical Studies].
The data described in Table 1 below reflect exposure to NATPARA in 84 patients, including 78 exposed for 24 weeks. The mean age of the trial population was 47 years and ranged from 19 to 74 years old. Seventy-nine percent (79%) were females. Ninety-six percent (96%) were Caucasian, 0.8% were Black, and 1.6% were Asian. Patients had had hypoparathyroidism for on average 15 years and hypoparathyroidism was caused by post-surgical complications in 71% of cases, idiopathic hypoparathyroidism in 25% of cases, DiGeorge Syndrome in 3% of cases, and auto-immune hypoparathyroidism in 1% of cases. Prior to trial enrollment, participants were receiving a median (interquartile range) daily oral calcium dose of 2000 (1250, 3000) mg and a median daily oral active vitamin D dose equivalent to 0.75 (0.5, 1) mcg of calcitriol. The mean eGFR at baseline was 97.4 mL/min/1.73 m² and 45%, 10% and 0% had mild, moderate and severe renal impairment, respectively, at baseline. During the trial, most patients received 100 mcg and the dose range was 50 to 100 mcg administered subcutaneously once daily in the thigh.
Table 1 lists common adverse reactions associated with NATPARA use in the clinical trial. Common adverse reactions were reactions that occurred in ≥5% of subjects and occurred more commonly on NATPARA than on placebo.
Table 1: Common Adverse Reactions associated with
NATPARA use in Subjects with Hypoparathyroidism
|Pain in extremity||8||10|
|Upper respiratory tract infection||5||8|
|Abdominal pain upper||3||7|
|Blood 25-hydroxycholecalciferol decreased||3||6|
|* Hypocalcemia combines reported events of hypocalcemia and blood calcium decreased; hypercalciuria combines reported events of hypercalciuria and urine calcium increased; and hypercalcemia combines reported events of hypercalcemia and blood calcium increased.|
In the overall pivotal trial a greater proportion of patients on NATPARA had albumin-corrected serum calcium above the normal range (8.4 to 10.6 mg/dL). During the entire trial duration 3 patients on NATPARA and 1 patient on placebo had a calcium level above 12 mg/dL. Table 2 displays the number of subjects who had albumin-corrected serum calcium levels above the normal range (8.4 to 10.6 mg/dL) by study treatment period in the placebo-controlled study based on routine monitoring at each trial visit. More patients randomized to NATPARA had hypercalcemia in both phases of the study (note: all trial participants underwent a 50% reduction in active vitamin D dose at randomization).
Table 2 : Proportion of
Subjects with Albumin-Corrected Serum Calcium Greater Than Upper Limit of
Normal (10.6 mg/dL) During the Treatment Period
|Albumin-corrected serum calcium||Titration Period (Weeks 0-12)*||Maintenance Period (Weeks 12-24)|
|>10.6 to ≤12 mg/dL||0%||30%||0%||10%|
|>12 to ≤13 mg/dL||0%||2%||3%||0%|
|*NATPARA was only titrated upwards for up to Week 6|
Table 3 displays the number of subjects who had albumin-corrected serum calcium levels below 8.4 mg/dL by treatment period in the placebo-controlled study based on routine monitoring at each trial visit. More patients randomized to placebo had hypocalcemia of less than 7 mg/dL in the titration phase (note:all trial participants underwent a 50% reduction in active vitamin D dose at randomization). More patients randomized to NATPARA had hypocalcemia of less than 7 mg/dL in the dose maintenance phase.
Table 3 : Proportion of
Subjects with Albumin-Corrected Serum Calcium Below the Lower Limit of Normal
(8.4 mg/dL) During the Treatment Period
|Albumin-corrected serum calcium||Titration Period (Weeks 0-12)||Maintenance Period (Weeks 12-24)|
|≥7 to <8.4 mg/dL||98%||79%||75%||71%|
The risk of hypocalcemia increases when NATPARA is withdrawn. At the end of the trial, NATPARA and placebo were withdrawn, calcium and active vitamin D were returned to baseline doses and subjects were followed for 4 weeks. During this withdrawal phase, more patients previously randomized to NATPARA experienced an albumin-corrected serum calcium value of less than 7 mg/dL (5.0% versus 17% for previous treatment with placebo and NATPARA respectively). Twenty subjects (24%) previously randomized to NATPARA experienced adverse reactions of hypocalcemia in the post-treatment phase compared to three subjects (8%) previously randomized to placebo. Five subjects previously randomized to NATPARA with albumin-corrected serum calcium below 7 mg/dL required treatment with IV calcium gluconate to correct hypocalcemia.
Treatment with NATPARA did not lower 24-hour urinary calcium excretion in the placebo-controlled trial. The proportion of subjects with hypercalciuria (defined as urine calcium levels of >300 mg/24 hours) was similar at baseline and trial end in the NATPARA and placebo groups. The median (IQR) 24-hour Urine Calcium at trial end was similar between NATPARA [231 (168-351) mg/24 hours], and placebo [232 (139-342) mg/24 hours]. At trial end, serum calcium values between NATPARA and placebo were also similar. Risk of hypercalciuria throughout the trial was related to serum calcium levels. To minimize the risk of hypercalciuria, NATPARA should be dosed to a target albumin-corrected total serum calcium within the lower half of the normal range (i.e., between 8 and 9 mg/dL) [see DOSAGE AND ADMINISTRATION].
NATPARA may trigger the development of antibodies. In the placebo-controlled study in adults with hypoparathyroidism, the incidence of anti-PTH antibodies was 8.6% (3/35) and 5.9% (1/17) in subjects who received subcutaneous administration of 50 to 100 mcg NATPARA or placebo once daily for 24 weeks, respectively.
Across all clinical studies in subjects with hypoparathyroidism following treatment with NATPARA for up to 2.6 years, the immunogenicity incidence rate was 16.1% (14/87). These 14 subjects had low titer anti-PTH antibodies and, of these, 3 subjects subsequently became antibody negative. One of these subjects had antibodies with neutralizing activity; this subject maintained a clinical response with no evidence of immune-related adverse reactions. Anti-PTH antibodies did not appear to affect efficacy or safety during the clinical trials but their longer-term impact is unknown.
Immunogenicity assay results are highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying diseases. For these reasons, comparison of the incidence of antibodies to NATPARA with the incidence of antibodies to other products may be misleading.
The following adverse reactions have been identified during post-approval use of NATPARA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Hypersensitivity reactions (e.g., anaphylaxis, dyspnea, angioedema, urticaria, and rash).
- Seizures due to hypocalcemia
Read the entire FDA prescribing information for Natpara (Parathyroid Hormone for Injection)