Updated on 22/08/2011 and displayed until Current
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Reasons for adding or updating:
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Change to section 5.1 - Pharmacodynamic Properties
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| Date of revision of text on the SPC: 26-Jul-2011 |
| Legal Category: POM |
| Black Triangle (CHM):
NO |
Free-text change information supplied by the pharmaceutical company
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5.1
Mechanism of Action
Paricalcitol is a synthetic, biologically active vitamin D analog of calcitriol with modifications to the side chain (D2) and the A (19-nor) ring.
Unlike calcitriol, paricalcitol is a allowing for selective vitamin D receptor (VDR) activation activator. Paricalcitol selectively upregulates the VDR in the parathyroid glands without increasing VDR in the intestine and is less active on bone resorption. Paricalcitol also upregulates the calcium sensing receptor in the parathyroid glands. As a result, paricalcitol reduces parathyroid hormone (PTH) levels by inhibiting parathyroid proliferation and decreasing PTH synthesis and secretion, with minimal impact on calcium and phosphorus levels, and can act directly on bone cells to maintain bone volume and improve mineralization surfaces. Correcting abnormal PTH levels, with normalisation of calcium and phosphorus homeostasis, may prevent or treat the metabolic bone disease associated with chronic kidney disease.
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Updated on 08/07/2011 and displayed until 22/08/2011
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Reasons for adding or updating:
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Change to section 4.4 - Special warnings and precautions for Use
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Change to section 4.8 - Undesirable Effects
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Change to section 4.9 - Overdose
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| Date of revision of text on the SPC: 06-Jul-2011 |
| Legal Category: POM |
| Black Triangle (CHM):
NO |
Free-text change information supplied by the pharmaceutical company
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| 4.4 Special warnings and precautions for use
Over suppression of parathyroid hormone may result in elevations of serum calcium levels and may lead to metabolic bone disease. Patient monitoring and individualized dose titration is required to reach appropriate physiological endpoints.
If clinically significant hypercalcemia develops, and the patient is receiving a calcium-based phosphate binder, the dose of the calcium-based phosphate binder should be reduced or interrupted.
Chronic hypercalcaemia may be associated with generalized vascular calcification and other soft-tissue calcification.
Digitalis toxicity is potentiated by hypercalcemia of any cause, so caution should be applied when digitalis is prescribed concomitantly with paricalcitol (see section 4.5).
Caution should be exercised if co-administering paricalcitol with ketoconazole (see section 4.5).
This medicinal product contains 20% v/v of ethanol (alcohol). Each dose may contain up to 1.3g ethanol. Harmful for those suffering from alcoholism. To be taken into account in pregnant or breast-feeding women, children and high risk groups such as patients with liver disease or epilepsy.
4.8 Undesirable effects
Approximately 600 patients were treated with Zemplar in Phase II/III/IV clinical trials. Overall, 6% of the Zemplar treated patients reported adverse reactions.
The most common adverse reaction associated with Zemplar therapy was hypercalcaemia, occurring in 4.7% of patients. Hypercalcaemia is dependent on the level of PTH oversuppression and can be minimised by proper dose titration.
Adverse events at least possibly related to paricalcitol, both clinical and laboratory are displayed by MedDRA System Organ Class, Preferred Term and frequency. The following frequency groupings are used: Very common ( ≥ 1/10); common (≥ 1/100, <1/10); uncommon (≥ 1/1000, <1/100); rare (≥ 1/10,000, <1/1000); very rare (<1/10000), not known (can not be estimated from the available data).
System Organ Class
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Preferred Term
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Frequency
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Investigations
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Bleeding time prolonged, aspartate aminotransferase increased, laboratory test abnormal, weight decreased
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Uncommon
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Cardiac disorders
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Cardiac arrest, arrhythmia, atrial flutter
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Uncommon
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Blood and lymphatic system disorders
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Anaemia, leukopenia, lymphadenopathy
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Uncommon
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Nervous system disorders
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Headache, dysgeusia
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Common
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Coma,cerebrovascular accident, transient ischemic attack, syncope, myoclonus, hypoaesthesia, paraesthesia, dizziness
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Uncommon
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Eye disorders
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Glaucoma, conjunctivitis
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Uncommon
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Ear and labyrinth disorders
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Ear disorder
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Uncommon
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Respiratory, thoracic and mediastinal disorders
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Pulmonary oedema, asthma, dyspnoea, epistaxis, cough
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Uncommon
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Gastrointestinal disorders
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Rectal haemhorrhage, colitis, diarrhoea, gastritis, dyspepsia, dysphagia, abdominal pain, constipation, nausea, vomiting, dry mouth, gastrointestinal disorder
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Uncommon
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Gastrointestinal haemorrhage
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unknown
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Skin and subcutaneous tissue disorders
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Pruritus
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Common
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Bullous dermatitis, alopecia, hirsutism, rash, hyperhidrosis
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Uncommon
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Musculoskeletal and connective tissue disorders
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Arthralgia, joint stiffness, back pain, muscle twitching, myalgia
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Uncommon
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Endocrine Disorders
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Hypoparathyrodism
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Common
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Hyperparathyrodism
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Uncommon
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Metabolism and nutrition disorders
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Hypercalcaemia, Hyperphosphataemia
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Common
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Hyperkalaemia, hypocalcemia, anorexia,
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Uncommon
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Infections and infestations
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Sepsis, pneumonia, infection , pharyngitis, vaginal infection, influenza
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Uncommon
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Neoplasms benign, malignant and unspecified (including cysts and polyps)
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Breast cancer
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Uncommon
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Vascular disorders
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Hypertension, hypotension
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Uncommon
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General disorders and administration site conditions
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Gait disturbance, oedema, peripheral oedema, pain, injection site pain, pyrexia, chest pain, condition aggravated, asthenia, malaise, thirst
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Uncommon
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Immune system disorders
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Hypersensitivity
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Uncommon
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Laryngeal oedema, angioedema, urticaria
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Not Known
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Reproductive system and breast disorders
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Breast pain, erectile dysfunction
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Uncommon
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Psychiatric disorders
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Confusional state, delirium, depersonalization, agitation, insomnia, nervousness
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Uncommon
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4.9 Overdose
No case of overdose has been reported.
Overdosage of paricalcitol may lead to hypercalcemia., hypercalciuria, hyperphosphatemia, and over suppression of PTH (see section 4.4).
In the event of an overdose, signs and symptoms of hypercalcemia (serum calcium levels) should be monitored and reported to a physician. Treatment should be initiated as appropriate.
Paricalcitol is not significantly removed by dialysis. Treatment of patients with clinically significant hypercalcaemia consists of immediate dose reduction or interruption of paricalcitol therapy and includes a low calcium diet, withdrawal of calcium supplements, patient mobilisation, attention to fluid and electrolyte imbalances, assessment of electrocardiographic abnormalities (critical in patients receiving digitalis), and haemodialysis or peritoneal dialysis against a calcium-free dialysate, as warranted.
When serum calcium levels have returned to within normal limits, paricalcitol may be reinitiated at a lower dose. If persistent and markedly elevated serum calcium levels occur, there are a variety of therapeutic alternatives that may be considered. These include the use of drugs such as phosphates and corticosteroids as well as measures to induce diuresis.
Zemplar solution for injection contains 30% v/v of propylene glycol as an excipient. Isolated cases of Central Nervous System depression, haemolysis and lactic acidosis have been reported as toxic effect associated with propyleneglycol administration at high doses. Although they are not expected to be found with Zemplar administration as propyleneglycol is eliminated during the dialysis process, the risk of toxic effect in overdosing situations has to be taken into account.
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Updated on 29/11/2010 and displayed until 08/07/2011
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Reasons for adding or updating:
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Removal of Black Triangle
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| Date of revision of text on the SPC: 17-Jun-2010 |
| Legal Category: POM |
| Black Triangle (CHM):
NO |
Free-text change information supplied by the pharmaceutical company
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| The Black Triangle has been removeed from the Zemplar product range.
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Updated on 28/06/2010 and displayed until 29/11/2010
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Reasons for adding or updating:
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Change to section 7 - Marketing Authorisation Holder
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Change to section 10 date of revision of the text
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| Date of revision of text on the SPC: 17-Jun-2010 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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| The address of the Marketing Authorisation Holder has changed. The date of revision has been updated in respect of this.
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Updated on 01/06/2010 and displayed until 28/06/2010
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Reasons for adding or updating:
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Change to MA holder contact details
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Change due to harmonisation of SPC
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Change to section 10 date of revision of the text
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| Date of revision of text on the SPC: 05-May-2010 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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- SmPC completely reformatted to align with the QRD template
- Update to the address of the UK MAH from Queenborough, Kent to Abbott House, Maidenhead
- Date of revision updated to reflect approvals
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Updated on 18/01/2010 and displayed until 01/06/2010
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Reasons for adding or updating:
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Change to section 5.1 - Pharmacodynamic Properties
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Change to section 10 date of revision of the text
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| Date of revision of text on the SPC: 21-Oct-2009 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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| Section 5.1 has been updated to change the pharmacotherapeutic group from 'vitamin d and analogues A11CC' to 'Anti-parathyroid agents H05BX02'.
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Updated on 25/10/2007 and displayed until 18/01/2010
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Reasons for adding or updating:
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Change to section 6. 3 - Shelf Life
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Change to section 9 - Date of first Authorisation/renewal of the Authorisation
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Change to section 10 date of revision of the text
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| Date of revision of text on the SPC: 10/2007 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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6.3 Shelf life
2 years.
After opening, use immediately
9. Date of first authorisation/renewal of THE authorisation
Date of first authorisation: 9 August 2002
Date of Last renewal: 9 August 2007
10. Date of revision of the text
4 October 2007
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Updated on 01/03/2007 and displayed until 25/10/2007
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Reasons for adding or updating:
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Change to section 4.4 - Special warnings and precautions for Use
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Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
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Change to section 4.8 - Undesirable Effects
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| Date of revision of text on the SPC: 12/2006 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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4.4 Special warnings and precautions for use
Caution should be exercised if co-administering paricalcitol with ketoconazole.
4.5 Interaction with other medicinal products and other forms of interaction
Ketoconazole: The effect of multiple doses of ketaconazole administered as 200 mg, twice daily (BID) for 5 days on the pharmacokinetics of paricalcitol capsule has been studied in healthy subjects. The Cmax of paricalcitol was minimally affected, but AUC0-‡ approximately doubled in the presence of ketoconazole. The mean half-life of paricalcitol was 17.0 hours in the presence of ketoconazole as compared to 9.8 hours, when paricalcitol was administered alone (See PRECAUTIONS Section 4.4)
4.8 Undesirable effects
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Body System
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Frequency
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Adverse Reaction
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Endocrine system
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Common
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parathyroid disorder
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Haematological and lymphatic system
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Uncommon
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Anaemia, leucopoenia, lymphadenopathy, increased bleeding time
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Immune system disorder
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Common
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pruritus
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Uncommon
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allergic reaction, rash
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Metabolic and nutrition disorders
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Common
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Hypercalcemia, hyperphosphatemia,
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Nervous system
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Uncommon
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oedema, , peripheral oedema, increased AST, and weight loss
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Uncommon
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confusion, delirium, dizziness, abnormal gait, agitation, depersonalisation, hypesthesia, insomnia, myoclonus, nervousness, paraesthesia and stupor
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Special senses
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Common
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taste perversion,
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Uncommon
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conjunctivitis, ear disorder, and glaucoma
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Cardiovascular system
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Uncommon
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Hypotension, arrhythmia, atrial flutter, cerebral ischaemia, cerebrovascular accident, cardiac arrest, hypertension, and syncope
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Respiratory System
Digestive system
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Uncommon
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asthma, increased cough, dyspnoea, epistaxis, pulmonary oedema, pharyngitis, and pneumonia
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Uncommon
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anorexia, colitis, constipation, diarrhoea, dry mouth, dysphagia, gastrointestinal disorder, gastritis, rectal haemmorrhage, thirst, nausea, vomiting, dyspepsia
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Skin and Appendages
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Common
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pruritus
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Uncommon
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alopecia, hirsutism, rash, sweating, and vesiculobullous, rash
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Musculoskeletal System
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Uncommon
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arthralgia, myalgia, joint disorder, and twitching
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Urogenitial system
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Uncommon
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Impotence, breast carcinoma, breast pain, and vaginitis
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Body as a whole
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Common
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Headache
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Uncommon
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injection site pain, pain, asthenia, allergic reaction back pain, chest pain, fever, flu syndrome, infection, malaise, and sepsis
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Post -Marketing Adverse Reactions
Immune system disorders, hypersensitivity.
Angioedema, laryngeal oedema and urticaria have been reported rarely.
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Updated on 01/03/2007 and displayed until 01/03/2007
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Reasons for adding or updating:
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Change to section 4.4 - Special warnings and precautions for Use
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Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
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Change to section 4.8 - Undesirable Effects
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| Date of revision of text on the SPC: 12/2006 |
| Legal Category: POM |
| Black Triangle (CHM):
NO |
Free-text change information supplied by the pharmaceutical company
|
4.4 Special warnings and precautions for use
Caution should be exercised if co-administering paricalcitol with ketoconazole.
4.5 Interaction with other medicinal products and other forms of interaction
Ketoconazole: The effect of multiple doses of ketaconazole administered as 200 mg, twice daily (BID) for 5 days on the pharmacokinetics of paricalcitol capsule has been studied in healthy subjects. The Cmax of paricalcitol was minimally affected, but AUC0-‡ approximately doubled in the presence of ketoconazole. The mean half-life of paricalcitol was 17.0 hours in the presence of ketoconazole as compared to 9.8 hours, when paricalcitol was administered alone (See PRECAUTIONS Section 4.4) The magnitude of drug interaction between paricalcitol injection and ketoconazole is expected to be lower than that observed between paricalcitol capsule and ketoconazole.
4.8 Undesirable effects
Approximately 600 patients were treated with Zemplar in Phase II/III/IV clinical trials. Overall, 6% of the Zemplar treated patients reported adverse reactions.
The most common adverse reaction associated with Zemplar therapy was hypercalcaemia, occurring in 4.7% of patients. Hypercalcaemia is dependent on the level of PTH oversuppression and can be minimised by proper dose titration. .
Adverse reactions from clinical trials that were possibly, probably or definitely related to paricalcitol are presented in the following table by body system and frequency. The following frequency categories are used: Very common (>1/10); common (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10,000, <1/1000); very rare (<1/10000, including isolated reports).
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Body System
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Frequency
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Adverse Reaction
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Endocrine system
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Common
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parathyroid disorder
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Haematological and lymphatic system
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Uncommon
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Anaemia, leucopoenia, lymphadenopathy, increased bleeding time
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Immune system disorder
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Common
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pruritus
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Uncommon
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allergic reaction, rash
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Metabolic and nutrition disorders
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Common
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Hypercalcemia, hyperphosphatemia,
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Nervous system
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Uncommon
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oedema, , peripheral oedema, increased AST, and weight loss
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Uncommon
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confusion, delirium, dizziness, abnormal gait, agitation, depersonalisation, hypesthesia, insomnia, myoclonus, nervousness, paraesthesia and stupor
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Special senses
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Common
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taste perversion,
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Uncommon
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conjunctivitis, ear disorder, and glaucoma
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Cardiovascular system
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Uncommon
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Hypotension, arrhythmia, atrial flutter, cerebral ischaemia, cerebrovascular accident, cardiac arrest, hypertension, and syncope
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Respiratory System
Digestive system
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Uncommon
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asthma, increased cough, dyspnoea, epistaxis, pulmonary oedema, pharyngitis, and pneumonia
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Uncommon
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anorexia, colitis, constipation, diarrhoea, dry mouth, dysphagia, gastrointestinal disorder, gastritis, rectal haemmorrhage, thirst, nausea, vomiting, dyspepsia
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Skin and Appendages
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Common
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pruritus
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Uncommon
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alopecia, hirsutism, rash, sweating, and vesiculobullous, rash
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Musculoskeletal System
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Uncommon
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arthralgia, myalgia, joint disorder, and twitching
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Urogenitial system
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Uncommon
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Impotence, breast carcinoma, breast pain, and vaginitis
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Body as a whole
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Common
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Headache
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Uncommon
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injection site pain, pain, asthenia, allergic reaction back pain, chest pain, fever, flu syndrome, infection, malaise, and sepsis
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Post -Marketing Adverse Reactions
Immune system disorders, hypersensitivity.
Angioedema, laryngeal oedema and urticaria have been reported rarely.
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Updated on 25/09/2006 and displayed until 01/03/2007
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Reasons for adding or updating:
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-
Change to section 4.2 - Posology and Method of Administration
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Change to section 5.1 - Pharmacodynamic Properties
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| Date of revision of text on the SPC: 03/2006 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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4.2 Posology and method of administration
Data in pediatric patients are limited and no data for children under the age of 5 are available. See Section 5.1 for study results.
5.1 Pharmacodynamic properties
Paediatric clinical data: The safety and effectiveness of Zemplar were examined in a 12-week randomised, double-blind, placebo-controlled study of 29 pediatric patients, aged 5-19 years, with end-stage renal disease on hemodialysis. The six youngest Zemplar-treated patients in the study were 5 - 12 years old. The initial dose of Zemplar was 0.04 mcg/kg 3 times per week, based on baseline iPTH level of less than 500 pg/mL, or 0.08 mcg/kg 3 times a week based on baseline iPTH level of ¡Ý 500 pg/mL, respectively. The dose of Zemplar was adjusted in 0.04 mcg/kg increments based on the levels of serum iPTH, calcium, and Ca x P. 67% of the Zemplar-treated patients and 14% placebo-treated patients completed the trial. 60% of the subjects in the Zemplar group had 2 consecutive 30% decreases from baseline iPTH compared with 21% patients in the placebo group. 71% of the placebo patients were discontinued due to excessive elevations in iPTH levels. No subjects in either the Zemplar group or placebo group developed hypercalcemia. No data are available for patients under the age of 5.
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Updated on 28/06/2005 and displayed until 25/09/2006
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Reasons for adding or updating:
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Improved Electronic Presentation
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Pending awaiting re-submission
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Updated on 26/05/2005 and displayed until 28/06/2005
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Reasons for adding or updating:
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Correction of spelling/typing errors
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Updated on 26/05/2005 and displayed until 26/05/2005
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Reasons for adding or updating:
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Change to section 8 - MA number
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Updated on 26/05/2005 and displayed until 26/05/2005
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Reasons for adding or updating:
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Correction of spelling/typing errors
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Updated on 25/05/2005 and displayed until 26/05/2005
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Reasons for adding or updating:
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New SPC for new product
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Pending awaiting re-submission
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