cinacalcet
Regulatory sources consulted
Approved indications
- Secondary hyperparathyroidism in adults with chronic kidney disease on dialysis.
- Reduction of hypercalcemia in adults with parathyroid carcinoma or primary hyperparathyroidism when parathyroidectomy is indicated but unsuitable or contraindicated.
Contraindications
Absolute
- Hypocalcemia or hypersensitivity.
Clinical warnings
- Major warning · It may cause fatal hypocalcemia, seizures, QT prolongation, and ventricular arrhythmia. Monitor calcium before starting, after adjustments, and during maintenance. — CIMA/AEMPS, ficha técnica 83888
- Major warning · Excessive PTH suppression may cause adynamic bone disease; adjust using PTH and calcium. — CIMA/AEMPS, ficha técnica 83888
Drug interactions
- HighEtelcalcetide or other calcium-lowering drugs
Mechanism: They increase hypocalcemia risk; cinacalcet and etelcalcetide must not be combined.
Recommendation: Do not combine with etelcalcetide and monitor calcium with other calcium-lowering drugs.
CIMA/AEMPS, ficha técnica 83888
- ModerateStrong CYP3A4 inhibitors or inducers
Mechanism: They may double or reduce cinacalcet exposure.
Recommendation: Monitor calcium and PTH and adjust when starting or stopping the modulator.
CIMA/AEMPS, ficha técnica 83888
- HighNarrow-therapeutic-index CYP2D6 substrates
Mechanism: Cinacalcet is a strong CYP2D6 inhibitor and may increase exposure to flecainide, propafenone, metoprolol, and tricyclic antidepressants.
Recommendation: Monitor response and toxicity; the CYP2D6 substrate dose may need to be reduced.
CIMA/AEMPS, ficha técnica 83888
Adverse events
Common (≥1%)
Nausea and vomiting
Rare but serious
Severe hypocalcemia, seizures, and ventricular arrhythmia
Pregnancy and lactation
Use during pregnancy only if potential benefit justifies risk. During breastfeeding, decide whether to stop breastfeeding or treatment.
Recent literature (PubMed)
Primary hyperparathyroidism (PHPT) is an endocrine disorder resulting from the hyperfunction of one or more parathyroid glands, with hypersecretion of parathyroid hormone (PTH). It can be managed by parathyroidectomy (PTX) or non-surgically. Medical therapy with pharmacological agents is an alternative for those patients with asymptomatic PHPT who meet guidelines for surgery but are unable or unwilling to undergo PTX. In this review, we focus upon these non-surgical aspects of PHPT management. We emphasize the most studied and widely used pharmacological alternatives: bisphosphonates, denosumab, cinacalcet and hormone therapy, in addition to combined therapy. We also address the relevant aspects of perioperative management.
Cancer-related hypercalcemia is a common finding typically seen in patients with advanced cancer and occurs in about 20 to 30 percent of cases. The most common cause of hypercalcemia in hospitalized patients is hypercalcemia due to malignancy.This clinical problem is seen in patients with both solid tumors and patients with hematologic malignancies. Hypercalcemia is associated with a poor prognosis in oncology patients. This pathologic condition can occur due to many different mechanisms but is usually caused by abnormal calcium use resulting from bone resorption, intestinal absorption, or renal excretion. Hypercalcemia may present with a wide range of symptoms ranging from gastrointestinal system symptoms to neurologic symptoms. Timely diagnosis and initiation of treatment by the physician significantly reduce the risk of complications. Treatment aims to decrease serum calcium by increasing calciuresis, decreasing bone resorption, and decreasing intestinal calcium absorption. The mainstays of treatment are IV hydration, bisphosphonates and calcitonin, denosumab, and in some patients, prednisone, and cinacalcet. Patients with underlying advanced kidney disease and refractory severe hypercalcemia should be evaluated for hemodialysis. Every physician dealing with oncology patients should know the fastest and most effective management of hypercalcemia. We aimed to contribute in this sense.
Primary hyperparathyroidism (PHPT) is a frequently diagnosed endocrine condition most commonly caused by a single parathyroid adenoma. Our understanding of the epidemiology and management of PHPT have evolved in the past few decades. Asymptomatic PHPT has been the most common presentation in developed countries since the advent of routine biochemical screening. Symptomatic disease is now also decreasing in developing nations. Normocalcemic PHPT is a newer phenotype that can be diagnosed in the setting of elevated parathyroid hormone concentrations with persistently normal serum calcium; however, evaluation for secondary causes of hyperparathyroidism is critical as it is a diagnosis of exclusion. Genetic testing can be helpful in patients younger than 30 years of age and/or patients with intermediate or equivocal ranges of the urinary calcium to creatinine ratio (between 0.01 and 0.02) to differentiate PHPT from familial hypocalciuric hypercalcemia and to evaluate for other genetic etiologies that may affect management. Surgery is the recommended treatment modality for symptomatic PHPT, and patients with asymptomatic PHPT meeting recommended criteria should also be considered for parathyroidectomy. "Asymptomatic" patients should be screened for the presence of nephrolithiasis and/or vertebral fracture, since many will be reclassified as having symptomatic disease with further investigation. For poor surgical candidates or patients not meeting criteria for surgery, medical therapy includes cinacalcet for hypercalcemia and antiresorptive therapies for osteoporosis. The spectrum of CDC73-related disorders includes the following phenotypes: Hyperparathyroidism-jaw tumor (HPT-JT) syndrome. Primary hyperparathyroidism occurs in a vast majority of affected individuals, with onset typically in late adolescence or early adulthood. HPT-JT syndrome-associated primary hyperparathyroidism is usually caused by a single parathyroid adenoma. In at least 10%-15% of individuals, prima