Cinacalcet

BRAND NAMES

• Sensipar

• Mimpara

MECHANISM OF ACTION 

Cinacalcet acts as a calcimimetic agent by increasing the sensitivity of the calcium-sensing receptor on the parathyroid gland to extracellular calcium. This enhanced sensitivity makes the gland perceive higher calcium levels than actually present, leading to suppression of parathyroid hormone secretion. As a result, there is a decrease in PTH levels, which subsequently lowers serum calcium and helps correct calcium–phosphate imbalance.

PHARMACOKINETICS

Absorption

Cinacalcet is well absorbed after oral administration, especially when taken with food. Food increases its bioavailability, leading to higher and more consistent plasma concentrations. Peak blood levels are typically reached within 2–6 hours after dosing.

Distribution

Cinacalcet is widely distributed throughout the body and is highly bound to plasma proteins (about 97%). It has a large volume of distribution, indicating extensive tissue uptake beyond the bloodstream.

Metabolism

Cinacalcet is extensively metabolized in the liver, primarily by the cytochrome P450 enzyme system, especially CYP3A4, CYP2D6, and CYP1A2. It undergoes oxidative metabolism to form inactive metabolites, which are later eliminated from the body.

Excretion

Cinacalcet is mainly excreted as inactive metabolites through the urine (major route) and to a lesser extent in the feces. Only a small amount of unchanged drug is eliminated. The elimination half-life is approximately 30–40 hours, allowing once-daily dosing in most patients.

PHARMACODYNAMICS

Cinacalcet increases the sensitivity of the calcium-sensing receptor in the parathyroid gland, leading to decreased secretion of parathyroid hormone and resulting in lower serum calcium levels.

ADMINISTRATION

Cinacalcet is administered orally as a tablet, usually taken once daily with food to improve absorption. The dose is started low and adjusted based on serum calcium and parathyroid hormone levels. Regular monitoring is required during therapy.

DOSAGE AND STRENGTH

Cinacalcet is available in tablet strengths of 30 mg, 60 mg, and 90 mg. The usual starting dose is 30 mg once daily, taken with food. Depending on serum calcium and parathyroid hormone levels, the dose may be gradually adjusted every 2–4 weeks up to a maximum of about 180 mg per day. Dose is individualized based on patient response and laboratory monitoring.

DRUG INTERACTIONS

Cinacalcet is metabolized mainly by the liver enzyme system cytochrome P450 enzyme system, so drugs that affect these enzymes can change its levels. Strong CYP3A4 inhibitors (like ketoconazole) may increase cinacalcet levels, while CYP3A4 inducers (like rifampicin) may reduce its effectiveness. It can also increase the levels of drugs such as warfarin and may enhance the risk of hypocalcemia when used with other calcium-lowering agents.

FOOD INTERACTIONS

Cinacalcet is recommended to be taken with food, as food increases its absorption and improves its effectiveness. Taking it on an empty stomach can reduce drug levels, so consistent administration with meals is advised. No specific food restrictions are required.

CONTRAINDICATIONS

Cinacalcet is contraindicated in patients with hypocalcemia (low serum calcium levels), as it can further reduce calcium and cause serious complications. It should also not be used in individuals with known hypersensitivity to the drug or its components. Careful monitoring is required in patients with chronic kidney disease or those at risk of severe calcium imbalance.

SIDE EFFECTS

• Nausea

• Vomiting

• Diarrhea

• Loss of appetite

• Muscle cramps or tingling

• Dizziness

• Weakness

• Rarely, seizures in severe hypocalcemia

OVERDOSE

Overdose of cinacalcet causes severe hypocalcemia, leading to muscle cramps, tingling, and seizures, and is treated by stopping the drug and giving calcium supplements.

TOXICITY

Cinacalcet toxicity is mainly due to excessive lowering of parathyroid hormone, resulting in severe hypocalcemia. This may cause muscle cramps, tingling, seizures, and heart rhythm disturbances, and is managed by stopping the drug and correcting calcium levels.