Paricalcitol (chemically it is 19-nor-1,25-(OH)₂-vitamin D₂. Marketed by

Abbott Laboratories Abbott Laboratories is an American multinational medical devices and health care company with headquarters in Abbott Park, Illinois, United States. The company was founded by Chicago physician Wallace Calvin Abbott in 1888 to formulate known dr ...

under the trade name Zemplar) is a

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

used for the prevention and treatment of secondary hyperparathyroidism (excessive secretion of parathyroid hormone) associated with chronic kidney failure. It is an

analog Analog or analogue may refer to: Computing and electronics * Analog signal, in which information is encoded in a continuous variable ** Analog device, an apparatus that operates on analog signals *** Analog electronics, circuits which use analo ...

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 Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

. 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 *

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* 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 Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

* 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 *

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* Transient ischemic attack * Fainting * Myoclonus *

Hypoaesthesia Hypoesthesia or numbness is a common side effect of various medical conditions that manifests as a reduced sense of touch or sensation, or a partial loss of sensitivity to sensory stimuli. In everyday speech this is generally referred to as num ...

* 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 Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

* Hypotension * Gait disturbance * Injection site pain * Fever * Chest pain * Condition aggravated *

Muscle weakness Muscle weakness is a lack of muscle strength. Its causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, includi ...

Malaise As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century. The term is often used ...

* 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 Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candid ...

, 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 An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

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
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References

{{Vitamin D receptor modulators Secosteroids Vitamin D AbbVie brands