What is cinacalcet's pharmacological category?
Cinacalcet, marketed under the brand name Sensipar®, is classified pharmacologically as a calcimimetic agent. This drug category is named for its ability to 'mimic' the action of calcium on the body's tissues. Specifically, cinacalcet works by modulating the calcium-sensing receptor (CaSR), which is the primary regulator of parathyroid hormone (PTH) synthesis and secretion in the parathyroid glands. By increasing the sensitivity of these receptors to extracellular calcium, cinacalcet tricks the parathyroid glands into reducing PTH production, ultimately lowering PTH, calcium, and phosphorus levels in the blood.
Mechanism of action: Mimicking calcium to regulate hormones
At a molecular level, cinacalcet acts as an allosteric activator of the CaSR. These receptors, located on the surface of the parathyroid chief cells, typically act as a brake on PTH release when they detect sufficient levels of calcium in the blood. In conditions like hyperparathyroidism, this normal feedback mechanism is disrupted. Cinacalcet binds to a site on the CaSR different from the calcium-binding site, but this binding causes a conformational change that amplifies the receptor's response to calcium. This increased sensitivity allows the parathyroid glands to sense even slightly elevated calcium levels as high enough to warrant a reduction in hormone secretion. The resulting decrease in PTH helps to manage the underlying cause of the condition.
Clinical indications and use
Cinacalcet is used to treat several conditions where PTH and/or calcium levels are abnormally high. Its primary applications include:
- Secondary Hyperparathyroidism (HPT) in Chronic Kidney Disease (CKD) on Dialysis: Patients with CKD often develop secondary HPT, where the parathyroid glands become overactive in response to low vitamin D and high phosphate levels. Cinacalcet helps lower PTH levels in these patients.
- Hypercalcemia in Parathyroid Carcinoma: This is a rare cancer of the parathyroid gland that can cause significantly elevated calcium levels. Cinacalcet helps to control hypercalcemia in these patients.
- Primary HPT: For adult patients with primary HPT who have high serum calcium levels but are unable to undergo surgery (parathyroidectomy), cinacalcet can help manage the condition.
Pharmacokinetics and dosing
Cinacalcet is administered orally and should be taken with food to increase absorption. After absorption, it is extensively metabolized by liver enzymes, primarily CYP3A4, CYP2D6, and CYP1A2. Because cinacalcet is a potent inhibitor of CYP2D6, it is important to monitor for potential drug interactions with other medications metabolized by this enzyme. Cinacalcet is mostly eliminated via renal excretion. Dosage is typically titrated based on blood calcium and PTH levels, which must be monitored regularly.
A comparison of calcimimetics: Cinacalcet vs. Etelcalcetide
While cinacalcet was the first of its class, a newer intravenous calcimimetic, etelcalcetide (brand name Parsabiv), is also available. Their differences lie in their administration and potential efficacy in certain patient populations.
| Feature | Cinacalcet (Sensipar) | Etelcalcetide (Parsabiv) |
|---|---|---|
| Route of Administration | Oral tablet | Intravenous (IV) injection |
| Dosing Frequency | Typically once daily | Typically three times weekly, at the end of hemodialysis sessions |
| Mechanism of Action | Allosteric activator of CaSR on parathyroid glands | Binds to and activates the CaSR |
| Comparative Efficacy | Found to be less effective in lowering PTH in some studies compared to etelcalcetide | Some studies show superior efficacy in PTH reduction in dialysis patients |
| Adherence Considerations | Depends on patient adherence to oral dosing regimen | Adherence is ensured by administration during dialysis sessions |
| Safety Considerations | Risks include hypocalcemia, GI bleeding | Reported side effects include higher rates of hypocalcemia and heart failure events compared to cinacalcet in some studies |
Adverse effects and monitoring
Common side effects of cinacalcet include nausea, vomiting, and diarrhea. More serious adverse effects are related to its main action of lowering calcium. Hypocalcemia (low blood calcium) is a risk, and severe or prolonged cases can lead to serious complications such as seizures, muscle cramps, prolonged QT interval, and arrhythmia. Patients with pre-existing risk factors for upper gastrointestinal bleeding or heart conditions also require close monitoring. Oversuppression of PTH can lead to adynamic bone disease. Regular monitoring of serum calcium and PTH levels is crucial to ensure the medication's effectiveness and safety.
Conclusion
In summary, cinacalcet's category is calcimimetic, a class of drugs that uniquely acts on the calcium-sensing receptors of the parathyroid gland to reduce hormone and mineral levels in the blood. This oral medication offers a valuable treatment option for patients with secondary hyperparathyroidism on dialysis, as well as those with hypercalcemia resulting from parathyroid carcinoma or primary HPT. While alternative treatments like intravenous etelcalcetide exist, cinacalcet remains an important tool in the management of these complex endocrine and renal disorders, emphasizing the need for regular monitoring to balance therapeutic benefits with the risks of hypocalcemia and other side effects.
Visit the official MedlinePlus Cinacalcet page for comprehensive drug information
