What dose of cinacalcet (calcimimetic agent) can be started in a patient with impaired renal function (eGFR 41), hypercalcemia, and elevated parathyroid hormone (PTH) levels who is not a candidate for parathyroid surgery?

Starting Dose of Cinacalcet in This Patient

Start cinacalcet at 30 mg once daily, taken with food, as this is the FDA-approved starting dose for both secondary hyperparathyroidism in CKD and primary hyperparathyroidism when surgery is contraindicated. 1

Clinical Context

This patient presents with:

• Stage 3b CKD (eGFR 41 mL/min/1.73m²)
• Hypercalcemia (calcium 11 mg/dL, normal ~8.5-10.5)
• Elevated PTH (97 pg/mL, suggesting primary hyperparathyroidism given the hypercalcemia)
• Surgical refusal

The combination of hypercalcemia with elevated PTH indicates primary hyperparathyroidism rather than secondary hyperparathyroidism from CKD (which would present with hypocalcemia or normal calcium). 2

Dosing Algorithm

Initial Dosing

• Start at 30 mg once daily with food or shortly after a meal 1
• Tablets must be swallowed whole, not crushed, chewed, or divided 1

Dose Titration Schedule

• Measure serum calcium within 1 week after starting treatment 1
• Titrate dose every 2 to 4 weeks through sequential doses: 30 mg twice daily → 60 mg twice daily → 90 mg twice daily → 90 mg 3-4 times daily as necessary to normalize serum calcium 1
• The goal is to normalize serum calcium levels, not necessarily normalize PTH in primary hyperparathyroidism 1

Monitoring Requirements

• Serum calcium: Check within 1 week of initiation or dose adjustment, then every 2 months once stable 1
• PTH levels: May decrease but often do not normalize in primary hyperparathyroidism; this is acceptable as long as calcium normalizes 3
• Renal function: Monitor stability given baseline CKD 4

Important Safety Considerations

Hypocalcemia Risk

• While this patient is currently hypercalcemic, cinacalcet increases the risk of hypocalcemia 7-fold overall (RR 7.38) 5, 6
• In primary hyperparathyroidism patients, the goal is calcium normalization, not suppression 1
• If calcium drops below normal range, hold cinacalcet temporarily and restart at a lower dose once calcium normalizes 1

Gastrointestinal Side Effects

• Nausea (RR 2.05) and vomiting (RR 1.95) are common 5, 7, 6
• Starting with food helps minimize GI symptoms 1
• These effects may lead to dose reduction or discontinuation in some patients 3

Drug Interactions

• Cinacalcet is metabolized by CYP3A4, 2D6, and 1A2 8
• Strong CYP3A4 inhibitors (ketoconazole, erythromycin, itraconazole) may increase cinacalcet levels—monitor calcium and PTH closely if co-administered 8
• Cinacalcet strongly inhibits CYP2D6; adjust doses of narrow therapeutic index drugs metabolized by this pathway (flecainide, tricyclic antidepressants, thioridazine) 8

Expected Outcomes

Efficacy

• Calcium normalization occurs in most patients with primary hyperparathyroidism at doses of 30-60 mg daily 3
• Calcium reduction is evident within the first week of treatment 3
• PTH typically decreases but may not normalize; this is acceptable as the primary goal is calcium control 9, 3

Mortality and Morbidity

• Cinacalcet prevents parathyroidectomy (RR 0.49) in patients where surgery is contraindicated 5, 6
• No significant effect on all-cause mortality, but this is primarily data from dialysis patients 5, 6
• The main benefit in this patient is avoiding surgical complications while controlling hypercalcemia-related symptoms and complications

Common Pitfalls to Avoid

• Do not start at higher doses thinking faster control is better—this increases GI side effects and hypocalcemia risk 1
• Do not expect PTH normalization in primary hyperparathyroidism; focus on calcium control 3
• Do not crush or split tablets as this alters pharmacokinetics 1
• Do not forget to take with food—bioavailability increases 1.5-1.8 fold with meals, which is factored into dosing recommendations 8
• Monitor calcium closely in the first weeks, as the patient's baseline hypercalcemia may drop rapidly 1, 3