Cinacalcet oral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of cinacalcet.
Drugs List
Therapeutic Indications
Uses
Hypercalcaemia in primary HPT when parathyroidectomy contraindicated
Secondary hyperparathyroidism in chronic renal failure pts on haemodialysis
Treatment of secondary hyperparathyroidism (HPT) in adults and children aged 3 and over with end-stage renal disease (ESRD) on maintenance dialysis therapy. Children should be considered for treatment only when not adequately controlled with standard therapy.
Reduction of hypercalcaemia in adults with parathyroid carcinoma or with primary HPT in whom parathyroidectomy is not indicated.
Dosage
Adults
Secondary hyperparathyroidism
Initial dose: 30mg once daily.
Titration should occur at intervals of 2 to 4 weeks up to a maximum dose of 180mg once daily, to reach the target parathyroid hormone (PTH) levels in dialysis patients of 150-300pg/ml (15.9-31.8pmol/l), using the intact PTH assay (iPTH). PTH levels should be assessed at least 12 hours after cinacalcet dose, 1 to 4 weeks after the initiation of therapy and/or dose adjustment, and every 1 to 3 months during maintenance therapy.
Dose adjustment based on serum calcium levels or clinical symptoms of hypocalcaemia
Serum calcium should be at or above the lower limit of normal range prior to the first dose of cinacalcet. Monitor serum calcium frequently during dose titration and within one week of initiation or dose adjustment. During maintenance treatment, measure serum calcium approximately monthly.
Corrected serum calcium less than 8.4mg/dL (2.1mmol/L) and greater than 7.5mg/dL (1.9mmol/L) or symptoms of hypocalcaemia: If necessary raise serum calcium through the use of calcium-containing phosphate binders, vitamin D sterols and/or adjustment of dialysis fluid calcium concentrations.
Corrected serum calcium less than 8.4mg/dL (2.1mmol/L) and greater than 7.5mg/dL (1.9mmol/L) or persistent symptoms of hypocalcaemia despite attempts to increase serum calcium: Reduce or withhold dose of cinacalcet.
Corrected serum calcium less than or equal to 7.5mg/dL (1.9mmol/L) or persistent symptoms of hypocalcaemia and vitamin D cannot be increased: Withhold cinacalcet until serum calcium levels reach 8.0mg/dL (2.0mmol/L) and/or symptoms of hypocalcaemia have resolved. Reinitiated treatment at the next lowest dose.
Parathyroid carcinoma and primary hyperparathyroidism
Initial dose: 30mg twice daily.
Titration should occur at intervals of 2 to 4 weeks using sequential doses of 30mg twice daily, 60mg twice daily, 90mg twice daily and 90mg three or four times daily. Maximum dose is 90mg four times daily.
Target is to reduce serum calcium levels to or below the upper limit of normal. Measure within 1 week of initiation of therapy or dose adjustment. Once maintenance dose is established, serum calcium should be measured every 2 to 3 months. Periodically monitor serum calcium after titration to the maximum dose. If sufficient reductions in serum calcium are not maintained consider discontinuation of therapy.
Children
Children aged 3 to 18 years
Secondary hyperparathyroidism
Initial dose: Less than or equal to 0.2mg/kg once daily.
Dose should be increased no more frequently than every 4 weeks and up to a maximum dose of 2.5mg/kg per day. Do not exceed a total daily dose of 180mg. For specific daily dosing, adjusted to paediatric patient dry weight, please refer to manufacturer's guidelines.
Dose adjustment based on PTH levels
PTH levels should be assessed at least 12 hours after cinacalcet dose, 1 to 4 weeks after the initiation of therapy and dose adjustment.
If iPTH is less than 150pg/mL (15.9pmol/L) and greater than or equal to 100pg/mL (10.6pmol/L): Decrease dose of cinacalcet to next lower dose.
If iPTH is less than 100pg/mL (10.6pmol/L): Stop cinacalcet treatment. Restart cinacalcet at the next lower dose once iPTH is greater than 150pg/mL (15.9pmol/L). If cinacalcet treatment has been stopped for more than 14 days, restart at the recommended starting dose.
Dose adjustment based on serum calcium level or clinical symptoms of hypocalcaemia
Corrected serum calcium level less than the age specified lower limit of normal or if symptoms of hypocalcaemia occur, regardless of calcium levels: Stop treatment. Administer calcium supplements, calcium-containing phosphate binders and/or vitamin D sterols, as clinically indicated.
Corrected serum calcium level above the age specified lower limit of normal and symptoms of hypocalcaemia have resolved: Restart at next lowest dose. If cinacalcet treatment has been stopped for more than 14 days, restart at the recommended starting dose. If patient was receiving the lowest dose (1mg/day) prior to discontinuation, restart at the same dose (1mg/day).
Additional Dosage Information
Switching from etelcalcetide
Patients that have discontinued etelcalcetide should not initiate cinacalcet treatment until at least three subsequent haemodialysis sessions have been completed and serum calcium measured. Ensure serum calcium levels are within the normal range before initiating cinacalcet treatment.
Administration
Cinacalcet tablets should be taken whole, with or after a meal.
Cinacalcet granules can be administered orally or through nasogastric or gastrostomy tubes and should be taken, if possible, with or after a meal.
Contraindications
Children under 3 years
Breastfeeding
Hypocalcaemia
Precautions and Warnings
Children aged 3 to 18 years
Cardiac impairment
Galactosaemia
Glucose-galactose malabsorption syndrome
History of seizures
Lactose intolerance
Moderate hepatic impairment
Pregnancy
Advise patient dizziness may affect ability to drive or operate machinery
Seizure threshold is lowered by serum calcium level reductions
Some formulations contain lactose
Monitor parathyroid levels in secondary hyperparathyroidism
Monitor patient closely during titration of dose
Monitor patients with hepatic impairment
Monitor serum calcium levels
Risk of adynamic bone disease if PTH chronically suppressed below target
Reduce dose or discontinue treatment if hypocalcaemia persists
Risk of hypotension and/or worsening of heart failure in cardiac impairment
Dose adjustment required if patient starts/stops smoking during therapy
Not licensed for all indications in all age groups
Advise patient/carer of signs and symptoms of hypocalcaemia
If serum calcium levels drop below the normal range adjust concurrent phosphate binders, Vitamin D sterols and/or adjust dialysis fluid calcium to raise levels. Low calcium levels may also precipitate paraesthesias, myalgias, cramping, tetany and convulsions. Decreases in serum calcium can also prolong the QT interval, potentially resulting in ventricular arrhythmia. Cases of QT prolongation and ventricular arrhythmia have been reported in patients treated with cinacalcet. Caution is advised in patients with other risk factors for QT prolongation such as patients with known congenital long QT syndrome or patients receiving medicinal products known to cause QT prolongation.
There is an increased risk for hypocalcaemia in chronic kidney disease (CKD) patients not on dialysis.
If iPTH levels drop below 1.5 times the upper limit of normal, adynamic bone disease may develop. If levels drop below the target range, the dose of cinacalcet and/or Vitamin D sterols should be reduced or therapy discontinued.
Testosterone levels may be decreased by cinacalcet therapy although the clinical significance of this is unknown.
Pregnancy and Lactation
Pregnancy
Use cinacalcet with caution during pregnancy.
The manufacturer advises cinacalcet may be used during pregnancy providing the potential benefits justify the potential risk to the foetus. Available animal reports indicate no increased risk of teratogenic or developmental effects, however there is limited published information regarding the use of cinacalcet during pregnancy. Potential risks are unknown.
Lactation
Cinacalcet is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues cinacalcet or discontinues breastfeeding. Animal data reports significant levels of cinacalcet in the breast milk, however the presence in human breast milk is unknown.
Counselling
Patient should be advised to inform their doctor if they start or stop smoking during treatment.
Advise patient/carer of signs and symptoms of hypocalcaemia.
Advise patient dizziness may affect ability to drive or operate machinery.
Side Effects
Abdominal pain
Aggravation of cardiac failure
Anorexia
Asthenia
Back pain
Constipation
Cough
Decrease in plasma testosterone (transient)
Decreased appetite
Diarrhoea
Dizziness
Dyspepsia
Dyspnoea
Headache
Hyperkalaemia
Hypersensitivity reactions
Hypocalcaemia
Hypotension
Muscle spasm
Myalgia
Nausea
Paraesthesia
QT prolongation secondary to hypocalcaemia
Rash
Seizures
Upper respiratory tract infection
Ventricular arrhythmias secondary to hypocalcaemia
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: October 2019
Reference Sources
Summary of Product Characteristics: Mimpara 30mg, 60mg, 90mg tablets. Amgen Ltd. Revised July 2019.
Summary of Product Characteristics: Mimpara 1mg, 2.5mg, 5mg granules in capsules for opening. Amgen Ltd. Revised July 2019.
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