CINATAB 30

Description

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamic properties:

Mechanism of action

Cinacalcet directly lowers parathyroid hormone levels by increasing the sensitivity of the calcium sensing receptors to activation by extracellular calcium, resulting in the inhibition of PTH secretion. The reduction in PTH is associated with a concomitant decrease in serum calcium levels.

Pharmacodynamic effects

Cinacalcet is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues). Secondary hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) is a progressive disease, associated with increases in parathyroid hormone (PTH) levels and derangements in calcium and phosphorus metabolism. Cinacalcet reduces calcium levels by increasing the sensitivity of the calcium sensing receptor to extracellular calcium.

Pharmacokinetic properties:

Absorption

After oral administration of cinacalcet, maximum plasma cinacalcet concentration is achieved in approximately 2 to 6 hours. Based on between-study comparisons, the absolute bioavailability of cinacalcet in fasted subjects has been estimated to be about 20-25%. Administration of cinacalcet with food results in an approximate 50-80% increase in Cinacalcet bioavailability.

Distribution

The volume of distribution is high (approximately 1,000 liters), indicating extensive distribution. Cinacalcet is approximately 97% bound to plasma proteins and distributes minimally into red blood cells.

Biotransformation

Cinacalcet is metabolised by multiple enzymes, predominantly CYP3A4 and CYP1A2 (the contribution of CYP1A2 has not been characterized clinically). The major circulating metabolites are inactive. Cinacalcet is a strong inhibitor of CYP2D6, but is neither an inhibitor of other CYP enzymes at concentrations achieved clinically, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP3A4 nor an inducer of CYP1A2, CYP2C19 and CYP3A4.

Elimination

Cinacalcet is metabolized by multiple enzymes, primarily CYP3A4, CYP2D6 and CYP1A2. Renal excretion of metabolites was the primary route of elimination of radioactivity. Approximately 80% of the dose was recovered in the urine and 15% in the faeces.

THERAPEUTIC CLASS: Calcimimetic

 

CLINICAL PARTICULARS:

Therapeutic Indication:

• Increased amounts of parathyroid hormone (PTH), Calcium and Phosphorus in people with long term kidney disease who are on dialysis.
• Increased amounts of Calcium in people with and overactive parathyroid gland.
• Hypercalcemia in adult’s patients with parathyroid carcinoma.
• Secondary hyperparathyroidism in adults and children with end stage renal disease.

Posology and method of Administration:

Posology:

The recommended starting dose for adults is 30 mg once per day. Cinacalcet should be titrated every 2 to 4 weeks to a maximum dose of 180 mg once daily to achieve a target parathyroid hormone (PTH).

Method of administration

For oral administration:

Tablets should be swallowed intact and should not be crushed, chewed or broken into pieces prior to administration.

Missed Dose:

If one dose is missed, this dose should be omitted and the next dose should be taken at the usual time with a meal. Do not take a double dose to make up for a forgotten dose.

 

CONTRAINDICATIONS:

• Hypersensitivity to the drug or any ingredient
• Low calcium levels in blood (Hypocalcaemia)
• Congestive Heart Failure (CHF)
• Hepatic Impairment

 

SIDE EFFECTS:

Nausea, Vomiting, Diarrhea, Dizziness, Weakness, Chest Pain & Myalgia

 

SPECIAL WARNINGS AND PRECAUTIONS FOR USE:

• Cinacalcet treatment should not be initiated in patients with a serum calcium (corrected for albumin) below the lower limit of the normal range.
• Cinacalcet is not indicated for CKD patients not on dialysis

 

OTHER MEDICINES AND URSODEOXYCHOLIC ACID TABLETS:

The effect of the following drugs can be influenced (interactions):

• Concurrent administration of other medicinal products known to reduce serum calcium and Cinacalcet may result in an increased risk of hypocalcaemia. Patients receiving Cinacalcet should not be given etelcalcetide.
• Co-administration of calcium carbonate (single 1,500 mg dose) did not alter the pharmacokinetics of cinacalcet.
• Concurrent administration of 90 mg cinacalcet once daily with 50 mg desipramine, a tricyclic antidepressant metabolised primarily by CYP2D6, significantly increased desipramine exposure 3.6-fold (90% CI 3.0, 4.4) in CYP2D6 extensive metabolisers.
• Multiple doses of 50 mg cinacalcet increased the AUC of 30 mg dextromethorphan (metabolised primarily by CYP2D6) by 11-fold in CYP2D6 extensive metabolisers.

 

PREGNANCY AND BREAST-FEEDING

Pregnancy: Cinacalcet should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Breast-feeding: This medicine is not recommended for use in breastfeeding women unless necessary.

 

DRIVING AND USING MACHINES

Cinacalcet may have major influence on the ability to drive and use machines, since dizziness and seizures have been reported by patients taking this medicinal product.

 

OVER DOSE:

Overdose of cinacalcet may lead to hypocalcaemia.

Stomach ache, nausea and vomiting.