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, in the United States. The company was founded by Chicago physician Wallace Calvin Abbott in 1888 to formulate k ...

under the trade name Zemplar) is a

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

used for the prevention and treatment of secondary hyperparathyroidism (excessive secretion of

parathyroid hormone Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates serum calcium and phosphate through its actions on the bone, kidneys, and small intestine. PTH incre ...

) associated with

chronic kidney failure Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

. 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 Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands ( primary hyperparathyroidism) or as response to external stimuli ( secondary hyperparathyroi ...

associated with

chronic kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

. 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 Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may inclu ...

* Allergic reaction *

Arthritis Arthritis is a general medical term used to describe a disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, Joint effusion, swelling, and decreased range of motion of ...

* Dizziness^† * Stomach discomfort^‡ *

Gastroesophageal reflux disease Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is a chronic upper gastrointestinal disease in which stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/or ...

^† *

Acne Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

^† *

Hypercalcaemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defin ...

^† * Hypocalcaemia^† * Hyperphosphataemia * Decreased appetite^† * Headache * Breast tenderness^† * Taste changes *

Hypoparathyroidism Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary m ...

* Vertigo * Rash^‡ Uncommon (0.1-1% frequency): * Abnormal hepatic enzymes^‡ * Constipation^‡ * Dry mouth^‡ *

Itchiness An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...

^‡ *

Hives Hives, also known as urticaria, is a kind of skin rash with red or flesh-colored, 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 typically ...

* Hypersensitivity^‡ * Muscle spasms^‡ * Bleeding time prolonged * Aspartate aminotransferase increased * Laboratory test abnormal * Weight loss * Elevated blood creatinine * Cardiac arrest * Arrhythmia * Atrial flutter *

Anaemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availab ...

Leucopenia Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections. Signs and symptoms Symptoms may include: * sk ...

* Lymphadenopathy * Coma *

Stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

* Transient ischemic attack *

Fainting Syncope , commonly known as fainting or passing out, is a loss of consciousness and muscle strength characterized by a fast onset, short duration, and spontaneous recovery. It is caused by a decrease in blood flow to the brain, typically from ...

Myoclonus Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle, a joint, or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus ( myo- "muscle", clonus "spasm") describes a medical sign and, ...

* Hypoaesthesia *

Paraesthesia Paresthesia is a sensation of the skin that may feel like numbness (''hypoesthesia''), tingling, pricking, chilling, or burning. It can be temporary or chronic and has many possible underlying causes. Paresthesia is usually painless and can oc ...

Glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

Conjunctivitis Conjunctivitis, also known as pink eye or Madras eye, is inflammation of the conjunctiva, the thin, clear layer that covers the white surface of the eye and the inner eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness ...

* Ear disorder * Pulmonary oedema * Asthma *

Shortness of breath Shortness of breath (SOB), known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing discomfort that con ...

* Nose bleed * Cough * Rectal haemhorrhage *

Colitis Colitis is swelling or inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and ...

Gastritis Gastritis is the inflammation of the lining of the stomach. It may occur as a short episode or may be of a long duration. There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain (see dyspepsia). Othe ...

Indigestion Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier ...

Difficulty swallowing Dysphagia is difficulty in swallowing. Although classified under " symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or li ...

* Gastrointestinal disorder * Gastrointestinal haemorrhage * Bullous dermatitis *

Hair loss Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarring ...

Hirsutism Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a male pattern of hair growth in a female that ma ...

Hyperhidrosis Hyperhidrosis is a medical condition in which a person exhibits excessive perspiration, sweating, more than is required for the Thermoregulation, regulation of body temperature. Although it is primarily a physical burden, hyperhidrosis can deterio ...

Joint pain Arthralgia () literally means 'joint pain'. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication Medication (also called medicament, medicine, pharmaceutic ...

* Joint stiffness * Back pain * Muscle twitching * Muscle aches *

Hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands ( primary hyperparathyroidism) or as response to external stimuli ( secondary hyperparathyroi ...

Hyperkalaemia Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occ ...

Hypocalcemia Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), while levels less than 2.1 ...

Breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

Sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...

Pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...

* Infection *

Pharyngitis Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a hoarse vo ...

* Vaginal infection * Influenza *

High blood pressure Hypertension, also known as high blood pressure, 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 itself. It is, however, a major ri ...

Hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

* Gait disturbance * Injection site pain *

Fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

* 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, includ ...

Malaise In medicine, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. It is considered a vague termdescribing the state of simply not feeling well. The word has exist ...

* Thirst * Breast pain *

Impotence Erectile dysfunction (ED), also referred to as impotence, is a form of sexual dysfunction in males characterized by the persistent or recurring inability to achieve or maintain a Human penis, penile erection with sufficient rigidity and durat ...

* 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 *

* 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 Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

and

phosphorus Phosphorus is a chemical element; it has Chemical symbol, symbol P and atomic number 15. All elemental forms of phosphorus are highly Reactivity (chemistry), reactive and are therefore never found in nature. They can nevertheless be prepared ar ...

levels.

Interactions

Drugs that may interact with paricalcitol include: *

Ketoconazole Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal drug, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin inf ...

, as it may interfere with paricalcitol's metabolism in the liver. *

Digitoxin Digitoxin is a cardiac glycoside used for the treatment of heart failure and certain kinds of heart arrhythmia. It is a phytosteroid and is similar in structure and effects to digoxin, though the effects are longer-lasting. Unlike digoxin, whic ...

, hypercalcaemia due to any cause can exacerbate the toxicity of digitoxin. *

Thiazide Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The firs ...

diuretics or calcium supplements as

hypercalcaemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defin ...

may be induced by this combination *

Magnesium Magnesium is a chemical element; it has Symbol (chemistry), symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 ...

-containing products such as antacids may increase the risk of

hypermagnesemia Hypermagnesemia is an electrolyte disorder in which there is a high level of magnesium in the blood. Symptoms include weakness, confusion, decreased breathing rate, and decreased reflexes. Hypermagnesemia can greatly increase the chances of adv ...

. *

Aluminium Aluminium (or aluminum in North American English) is a chemical element; it has chemical symbol, symbol Al and atomic number 13. It has a density lower than that of other common metals, about one-third that of steel. Aluminium has ...

-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 Colestyramine ( INN) or cholestyramine ( USAN) (trade names Questran, Questran Light, Cholybar, Olestyr, Quantalan, Vasosan) is a bile acid sequestrant, which binds bile in the gastrointestinal tract to prevent its reabsorption. It is a strong i ...

may interfere with the absorption of paricalcitol.

Overdose

Electrolyte abnormalities (e.g.

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 Hemodialysis, also spelled haemodialysis, or simply ''"'dialysis'"'', is a process of filtering the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as c ...

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 Anorexia is a medical term for a loss of appetite. While the term outside of the scientific literature is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while o ...

* Weight loss *

(calcific) *

Pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormone A hormone (from the Ancient Greek, Greek participle , "se ...

* 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 (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

at the

vitamin D receptor The vitamin D receptor (VDR also known as the calcitriol receptor) is a member of the nuclear receptor family of transcription factors. Calcitriol (the active form of vitamin D, 1,25-(OH)2vitamin D3) binds to VDR, which then forms a heterodi ...

and thereby lowers

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
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References

{{Vitamin D receptor modulators Secosteroids Vitamin D Drugs developed by AbbVie