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 a 2016 systematic review did not find evidence 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.
However, many 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).Rxlist: Zemplar
References