Cinacalcet

Registered South African indications:

• Secondary hyperparathyroidism
• Parathyroid carcinoma

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypocalcaemia

Cautions

• Pregnancy
• Breastfeeding
• Moderate to severe hepatic impairment
• Cardiac failure
• Risk factors for QT prolongation
• Chronic kidney disease in patients not on dialysis
• Impaired cardiac function
• History of seizure disorders
• Lactose allergy
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Treatment of secondary hyperparathyroidism in patients with end-stage renal disease on
maintenance dialysis therapy

• Oral (tab): Initial: 30mg, dly; Titrate at 2-4 week intervals; Max: 180mg/24hrs

Parathyroid hormone levels should assessed at least 12 hours after dosing

Target parathyroid hormone in dialysis patients of between 150-300pg/ml (15.9-31.8pmol/l) in the intact parathyroid hormone assay

Reduction of hypercalcaemia in patients with parathyroid carcinoma
Primary hyperparathyroidism

• Oral (tab): Initial: 30mg, 12hrly; Titrate by 30mg, 12hrly at 2-4 week intervals; Max: 90mg, 6hrly

Take with food, or shortly thereafter

Do not cut/crush/chew/dissolve

Not registered for use in South Africa for children

Pregnancy

• Caution; not recommended
• There are no clinical data from the use of cinacalcet in pregnant women
• Animal studies do not indicate direct harmful effects with respect to pregnancy, parturition or postnatal development
• No embryonal/foetal toxicities were seen in studies in pregnant rats and rabbits with the exception of decreased foetal weights in rats at doses associated with maternal toxicities
• However, cincalcet should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. If a woman's condition requires cinacalcet, it should not be witheld during pregnancy

Breastfeeding

• Caution; not recommended
• It is not known whether cinacalcet is excreted in human milk
• Cinacalcet is excreted in the milk of lactating rats with high milk to plasma ratio
• The molecular weight (about 358 free base) and long terminal half-life (30-40 hours) suggest that the drug will be excreted into breast milk
• Following careful benefit/risk assessment, a decision should be made to either discontinue breast-feeding or to discontinue treatment with cinacalcet

Fertility

• There is no clinical data relating to the effect of cinacalcet on fertility. There were no effects on fertility in animal studies

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Moderate to severe: Caution; no dose adjustment recommended

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Seizures
• Dizziness
• Paraesthesia
• Headache
• Asthenia

Cardiovascular Disorders

• Worsening cardiac failure
• QT prolongation and ventricular arrhythmia secondary to hypocalcaemia
• Hypotension

Respiratory Disorders

• Upper respiratory infection
• Dyspnoea
• Cough

Gastrointestinal Disorders

• Nausea and vomiting
• Dyspepsia
• Diarrhoea
• Abdominal pain
• Constipation

Endocrine and Metabolic Disorders

• Anorexia
• Decreased appetite
• Hypocalcaemia
• Hyperkalaemia
• Reduced testosterone levels

Musculoskeletal Disorders

• Myalgia
• Muscle spasms
• Back pain

Skin and Subcutaneous Tissue Disorders

• Rash

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions

• Agents known to reduce serum calcium
• Etelcalcetide
• QT prolonging agents
• CYP3A4 inhibitors
• Ketoconazole
• Itraconazole
• Telithromycin
• Voriconazole
• Ritonavir
• CYP3A4 inducers
• Rifampicin
• CYP1A2 inhibitors
• CYP2D6 substrates
• Flecainide
• Propafenone
• Metoprolol
• Nortriptyline
• Clomipramine
• Desipramine
• Dextromethorphan
• Smoking

• Parathyroid hormone levels
  • Monitor 4 weeks after initiation or dose adjustment
  • Monitor every 1-3 months during maintenance
• Serum calcium
  • Monitor 1 week after initiation or dose adjustment
  • Monitor every 1-3 months during maintenance

Specific cases may require

• Serum phosphorus

Dose adjustment based on serum calcium levels

• Corrected serum calcium should be measured and monitored and should be at or above the lower limit of the normal range prior to administration of the first dose of cinacalcet
• The normal calcium range may differ depending on the methods used by your local laboratory
• During dose titration, serum calcium levels should be monitored frequently, and within 1 week of initiation or dose adjustment of cinacalcet. Once the maintenance dose has been established, serum calcium should be measured approximately monthly
• In the event that the corrected serum calcium levels fall/drop below normal ranges, and/or symptoms of hypocalcaemia occur, special recommendations can be adopted including:
  - Addition of calcium-containing phosphate binders and/or vitamin D sterols
  - Reduce or withhold dose of cinacalcet either temporarily or until serum calcium level recovery

The calcium sensing receptor on the surface of the chief cell of the parathyroid gland is the principal regulator of parathyroid hormone (PTH) secretion. Cinacalcet is a calcimimetic agent which directly lowers PTH levels by increasing the sensitivity of the calcium sensing receptor to extracellular calcium. The reduction in PTH is associated with a concomitant decrease in serum calcium levels.

Tablet 30mg

• Sensipar (Amgen) originator

Tablet 60mg

• Sensipar (Amgen) originator