Paricalcitol

Paricalcitol (chemically it is 19-nor-1,25-(OH)2-vitamin D2. Marketed by Abbott Laboratories under the trade name Zemplar) is a drug used for the prevention and treatment of secondary hyperparathyroidism (excessive secretion of parathyroid hormone) associated with chronic kidney failure. It is an analog of 1,25-dihydroxyergocalciferol, the active form of vitamin D2 (ergocalciferol).
It was patented in 1989 and approved for medical use in 1998.
Medical uses
Its primary use in medicine is in the treatment of secondary hyperparathyroidism associated with chronic kidney disease. However current evidence is not sufficient to demonstrate an advantage of paricalcitol over non-selective vitamin D derivatives for this indication.
Adverse effects
Adverse effects by frequency:
Very common (>10% frequency):
Nausea
Common (1-10% frequency):
Diarrhoea†
Oedema
Allergic reaction
Arthritis
Dizziness†
Stomach discomfort‡
Gastroesophageal reflux disease†
Acne†
Hypercalcaemia†
Hypocalcaemia†
Hyperphosphataemia
Decreased appetite†
Headache
Breast tenderness†
Taste changes
Hypoparathyroidism
Vertigo
Rash‡
Uncommon (0.1-1% frequency):
Abnormal hepatic enzymes‡
Constipation‡
Dry mouth‡
Itchiness‡
Hives
Hypersensitivity‡
Muscle spasms‡
Bleeding time prolonged
Aspartate aminotransferase increased
Laboratory test abnormal
Weight loss
Elevated blood creatinine
Cardiac arrest
Arrhythmia
Atrial flutter
Anaemia
Leucopenia
Lymphadenopathy
Coma
Stroke
Transient ischemic attack
Fainting
Myoclonus
Hypoaesthesia
Paraesthesia
Glaucoma
Conjunctivitis
Ear disorder
Pulmonary oedema
Asthma
Shortness of breath
Nose bleed
Cough
Rectal haemhorrhage
Colitis
Gastritis
Indigestion
Difficulty swallowing
Gastrointestinal disorder
Gastrointestinal haemorrhage
Bullous dermatitis
Hair loss
Hirsutism
Hyperhidrosis
Joint pain
Joint stiffness
Back pain
Muscle twitching
Muscle aches
Hyperparathyroidism
Hyperkalaemia
Hypocalcemia
Breast cancer
Sepsis
Pneumonia
Infection
Pharyngitis
Vaginal infection
Influenza
High blood pressure
Hypotension
Gait disturbance
Injection site pain
Fever
Chest pain
Condition aggravated
Muscle weakness
Malaise
Thirst
Breast pain
Impotence
Confusional state
Delirium
Depersonalization
Agitation
Insomnia
Nervousness
‡ These are adverse effects only seen in patients with grade 3 or 4 chronic kidney disease.
† These are adverse effects only seen in patients with grade 5 chronic kidney disease.
Contraindications
Contraindications include:
Vitamin D intoxication
Hypercalcaemia
Hypersensitivity to paricalcitol or any of its excipients
whereas cautions include:
Impaired liver function
It is also advised that physicians regularly monitor their patients' calcium and phosphorus levels.
Interactions
Drugs that may interact with paricalcitol include:
Ketoconazole, as it may interfere with paricalcitol's metabolism in the liver.
Digitoxin, hypercalcaemia due to any cause can exacerbate the toxicity of digitoxin.
Thiazide diuretics or calcium supplements as hypercalcaemia may be induced by this combination
Magnesium-containing products such as antacids may increase the risk of hypermagnesemia.
Aluminium-containing products such as antacids may increase the risk of aluminium toxicity.
Drugs that interfere with the absorption of fat-soluble vitamins, such as cholestyramine may interfere with the absorption of paricalcitol.
Overdose
Electrolyte abnormalities (e.g. hypercalcaemia and hyperphosphataemia) are common overdose symptoms. Treatment is mostly supportive, with particular attention being paid to correcting electrolyte anomalies and reducing intake of calcium in both the form of supplementation and diet. As it is so heavily bound to plasma proteins haemodialysis is unlikely to be helpful in cases of overdose.
Early symptoms of overdose can include:
Weakness
Headache
Somnolence
Nausea
Vomiting
Dry mouth
Constipation
Muscle pain
Bone pain
Metallic taste in the mouth.
It is worth noting, however, that may of these symptoms are also indicative of kidney failure and hence may be masked by the patient's condition.
Late symptoms of overdose include:
Loss of appetite
Weight loss
Conjunctivitis (calcific)
Pancreatitis
Photophobia
Rhinorrhoea
Pruritus
Hyperthermia
Decreased libido
Elevated BUN
Hypercholesterolaemia
Elevated AST and ALT
Ectopic calcification
Hypertension
Cardiac arrhythmias
Somnolence
Death
Psychosis (rare)
Mechanism of action
Like 1,25-dihydroxyergocalciferol, paricalcitol acts as an agonist at the vitamin D receptor and thereby lowers parathyroid hormone levels in the blood.
Pharmacokinetics
The plasma concentration of paricalcitol decreases rapidly and log-linearly within two hours after initial intravenous administration. Therefore, it is not expected to accumulate with multiple dosing, since paricalcitol is usually given no more frequently than every other day (3 times per week).
References
Secosteroids
Vitamin D
AbbVie brands