Pharmacologic Category – Calcimimetic
Dosage for adults:
1. Hyperparathyroidism, primary: Oral: Initial dosage: 30 mg daily, afterwards progressively increase the dosage every week 2 to 4 weeks (to 60 mg twice daily, 90mg twice daily, and 90mg 3 or 4 times a day) as required to revitalise the levels of serum calcium.
2. Hyperparathyroidism, secondary: Oral: Initial: 30mg once daily, afterwards progressively increase the dosage every 2 to 4 weeks (to 60mg once daily, 90 mg once daily, 120 mg once daily, and 180 mg once daily) as required to maintain intact parathyroid hormone (iPTH) level between 150 to 300 pg per mL. It can be used alone or combined with vitamin D and or with phosphate binders.
3. Conversion from etelcalcetide: It is recommended discontinuing etelcalcetide for a minimum of 4 weeks before starting with cinacalcet. (Not available in India).
4. Parathyroid carcinoma: Oral dosage: Initially 30mg twice daily is recommended, then it progressively dosage is to be increased every 2 to 4 weeks (to 60 mg twice daily, 90 mg twice daily, and 90mg 3 to 4 times daily) as required to regulate the levels of serum calcium.
5. Dosage adjustment for concomitant therapy: Significantly drug interactions exist, requiring the adjustment of the frequency of the dose or avoidance thereof. It is advisable to consult the drug interactions database for further added information.
6. Dosage adjustment for toxicity: Adult
a. Dosage adjustment for hypocalcemia:
If iPTH is more diminutive than 150pg per mL, then reduce the dose or discontinue cinacalcet and or vitamin D
b. Hyperparathyroidism, secondary: If serum calcium is more than 7.5mg per dL but less than 8.4 mg per dL, or if hypocalcemia symptoms occur, then it is recommended to use calcium-containing phosphate binders and or vitamin D to raise the level of calcium
If serum calcium is less than 7.5 mg per dL or if hypocalcemia symptoms persist and the dose of vitamin D cannot be increased then, abstain cinacalcet until the serum calcium is greater or equal to 8 mg per dL or symptoms of hypocalcemia resolve, then re-start the cinacalcet at the next lowest dose.
It is recommended to administer with food or shortly after the meal. Never crush, chew or break the tablet and have it whole.
The following unfavourable drug reactions and incidences are deprived of the product labelling unless otherwise mentioned:
· Cardiovascular: Hypotension – 12%
· Endocrine & Metabolic: Hypocalcemia (< 8.4 mg/dL: 6% to 75%; < 7.5 mg/dL: 29% to 33%), hyporparathyroidism (intact parathyroid hormone (iPTH) < 100 pg/mL: less than equal to 11%)
· Gastrointestinal: Nausea (29% to 31%), vomiting (26% to 27%), diarrhea (21%), abdominal pain (11%).
· Nervous system: Headache (12%)
· Neuromuscular & skeletal: Muscle spasm (11% to 18%), myalgia (15%), back pain (12%)
· Respiratory: Dyspnea (13%), cough (12%)
Serum calcium is less than the lower limit of the standard range
Warning and precautions
Concerns about adverse effects:
· Adynamic bone disease: This may develop if iPTH levels are repressed less than 100pg per mL. It is recommended to reduce the dosage or discontinue cinacalcet and vitamin D if iPTH levels decrease below 150 pg per mL.
· Cardiovascular effects
· GI effects
· Hypocalcemia: A life-threatening and fatal event about hypocalcemia has happened. Never go for the therapy if the corrected serum calcium is less than the lower limit of normal
Food increases bio-availability.
Management: It is recommended to administer dosage with food or shortly after a meal.
Reference range: CKD K/DOQI guidelines of stages: 1
1. Chronic disease is kidney damage or GFR less than 60 mL per minute per 1.73m² for more or equal to 3 months.
2. Stage 2: GFR 60 to 89 mL per minute per 1.73m². This causes damage to the kidney because of a mild decrease in GFR.
3. Stage 3: GFR 30 to 59 mL per minute 1.73m². This means a moderate decrease in GFR
4. Stage 4: GFR 15 to 29 mL per minute per 1.73m² means a severe decrease in GFR
5. Stage 5: GFR less than 15mL per minute per 1.73m² or dialysis. This is a kidney failure
The target range for iPTH: Adults:
Stage 3 CKD: 35 to 70pg per mL
Stage 4 CKD: 70 to 110 pg per mL
Stage 5 CKD: 150 to 300 pg per mL
Serum Phosphorus for adults
Stage 3 and 4 CKD: more significant than equal to 2.7 to less than 4.6 mg per dL
Stage 5: CKD: 3.5 to 5.5 mg per dL
Serum calcium-phosphorus product: Adults:
Stage 3 to 5 CKD: less than 55mg²/dL²
Process of action:
The drug increases the calcium-sensing receptor on the parathyroid gland, simultaneously lowering parathyroid hormone, serum calcium, and serum phosphorous levels, thereby preventing the growing bone disease and adverse events related to mineral metabolism disorders.