Paricalcitol: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
Marked this version for translation |
||
| Line 1: | Line 1: | ||
<languages /> | <languages /> | ||
<translate> | <translate> | ||
<!--T:1--> | |||
{{short description|Chemical compound}} | {{short description|Chemical compound}} | ||
{{Drugbox | {{Drugbox | ||
| Line 60: | Line 61: | ||
}} | }} | ||
<!--T:2--> | |||
'''Paricalcitol''' (chemically it is '''19-nor-1,25-(OH)<sub>2</sub>-vitamin D<sub>2</sub>'''. Marketed by [[Abbott Laboratories]] under the trade name '''Zemplar''') is a [[pharmaceutical drug|drug]] used for the prevention and treatment of [[secondary hyperparathyroidism]] (excessive secretion of [[parathyroid hormone]]) associated with [[chronic kidney failure]]. It is an [[analog (chemistry)|analog]] of 1,25-dihydroxyergocalciferol, the active form of [[Vitamin D2|vitamin D<sub>2</sub>]] (ergocalciferol). | '''Paricalcitol''' (chemically it is '''19-nor-1,25-(OH)<sub>2</sub>-vitamin D<sub>2</sub>'''. Marketed by [[Abbott Laboratories]] under the trade name '''Zemplar''') is a [[pharmaceutical drug|drug]] used for the prevention and treatment of [[secondary hyperparathyroidism]] (excessive secretion of [[parathyroid hormone]]) associated with [[chronic kidney failure]]. It is an [[analog (chemistry)|analog]] of 1,25-dihydroxyergocalciferol, the active form of [[Vitamin D2|vitamin D<sub>2</sub>]] (ergocalciferol). | ||
<!--T:3--> | |||
<!-- Society and culture --> | <!-- Society and culture --> | ||
It was patented in 1989 and approved for medical use in 1998. | It was patented in 1989 and approved for medical use in 1998. | ||
<!--T:4--> | |||
==Medical uses== | ==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. | 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. | ||
<!--T:5--> | |||
==Adverse effects== | ==Adverse effects== | ||
'''Adverse effects by frequency:'''<br /> | '''Adverse effects by frequency:'''<br /> | ||
| Line 73: | Line 78: | ||
* Nausea | * Nausea | ||
<!--T:6--> | |||
'''Common (1-10% frequency):''' | '''Common (1-10% frequency):''' | ||
{{div col|colwidth=18em}} | {{div col|colwidth=18em}} | ||
| Line 95: | Line 101: | ||
{{div col end}} | {{div col end}} | ||
<!--T:7--> | |||
'''Uncommon (0.1-1% frequency):''' | '''Uncommon (0.1-1% frequency):''' | ||
{{div col|colwidth=18em}} | {{div col|colwidth=18em}} | ||
| Line 176: | Line 183: | ||
{{div col end}} | {{div col end}} | ||
<!--T:8--> | |||
<sup>‡</sup> These are adverse effects only seen in patients with grade 3 or 4 chronic kidney disease. | <sup>‡</sup> These are adverse effects only seen in patients with grade 3 or 4 chronic kidney disease. | ||
<sup>†</sup> These are adverse effects only seen in patients with grade 5 chronic kidney disease. | <sup>†</sup> These are adverse effects only seen in patients with grade 5 chronic kidney disease. | ||
<!--T:9--> | |||
==Contraindications== | ==Contraindications== | ||
Contraindications include: | Contraindications include: | ||
| Line 185: | Line 194: | ||
* Hypersensitivity to paricalcitol or any of its excipients | * Hypersensitivity to paricalcitol or any of its excipients | ||
<!--T:10--> | |||
whereas cautions include: | whereas cautions include: | ||
* Impaired liver function | * Impaired liver function | ||
* It is also advised that physicians regularly monitor their patients' [[calcium]] and [[phosphorus]] levels. | * It is also advised that physicians regularly monitor their patients' [[calcium]] and [[phosphorus]] levels. | ||
<!--T:11--> | |||
==Interactions== | ==Interactions== | ||
Drugs that may interact with paricalcitol include: | Drugs that may interact with paricalcitol include: | ||
| Line 200: | Line 211: | ||
{{div col end}} | {{div col end}} | ||
<!--T:12--> | |||
==Overdose== | ==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. | 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. | ||
<!--T:13--> | |||
Early symptoms of overdose can include: | Early symptoms of overdose can include: | ||
{{div col|colwidth=18em}} | {{div col|colwidth=18em}} | ||
| Line 218: | Line 231: | ||
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. | 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. | ||
<!--T:14--> | |||
Late symptoms of overdose include: | Late symptoms of overdose include: | ||
{{div col|colwidth=18em}} | {{div col|colwidth=18em}} | ||
| Line 240: | Line 254: | ||
{{div col end}} | {{div col end}} | ||
<!--T:15--> | |||
==Mechanism of action== | ==Mechanism of action== | ||
[[File:Paricalcitol structure.svg|thumb|left|3D structure of paricalcitol]]{{clear left}} | [[File:Paricalcitol structure.svg|thumb|left|3D structure of paricalcitol]]{{clear left}} | ||
Like 1,25-dihydroxyergocalciferol, paricalcitol acts as an [[agonist]] at the [[vitamin D receptor]] and thereby lowers [[parathyroid hormone]] levels in the blood. | Like 1,25-dihydroxyergocalciferol, paricalcitol acts as an [[agonist]] at the [[vitamin D receptor]] and thereby lowers [[parathyroid hormone]] levels in the blood. | ||
<!--T:16--> | |||
==Pharmacokinetics== | ==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). | 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). | ||
<!--T:17--> | |||
{{Vitamins}} | {{Vitamins}} | ||
{{Calcium homeostasis}} | {{Calcium homeostasis}} | ||
{{Vitamin D receptor modulators}} | {{Vitamin D receptor modulators}} | ||
<!--T:18--> | |||
{{二次利用|date=20 December 2023}} | {{二次利用|date=20 December 2023}} | ||
[[Category:Secosteroids]] | [[Category:Secosteroids]] | ||
Latest revision as of 23:14, 12 April 2024
 | |
 | |
| Clinical data | |
|---|---|
| Trade names | Zemplar |
| Other names | (1R,3S)-5-[2-[(1R,3aR,7aS)-1-[(2R,5S)-6-hydroxy-5,6-dimethyl-3E-hepten-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-cyclohexane-1,3-diol |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682335 |
| Pregnancy category |
|
| Routes of administration | Oral, Intravenous |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 72% |
| Protein binding | 99.8% |
| Metabolism | Hepatic |
| Elimination half-life | 14-20 hours |
| Excretion | Faeces (74%), urine (16%) |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C27H44O3 |
| Molar mass | 416.646 g·mol−1 |
| |
  (what is this?) (verify) | |
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).
 | この記事は、クリエイティブ・コモンズ・表示・継承ライセンス3.0のもとで公表されたウィキペディアの項目Paricalcitol(20 December 2023編集記事参照)を素材として二次利用しています。 Item:Q22025  |