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DDAVP Spray (desmopressin acetate nasal spray) and DDAVP Rhinyle (desmopressin acetate nasal solution) have been associated with an increased risk of hyponatremia - For Health Professionals
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(PDF Version - 60 K)Contact: Marketed Health Products Directorate (MHPD)
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This is duplicated text of a letter from Ferring Pharmaceuticals.
Contact the company for a copy of any references, attachments or enclosures.
Health Canada Endorsed Important Safety Information on desmopressin (DDAVP Spray and DDAVP Rhinyle Solution)
July 15, 2008
Subject: New Safety Information regarding the antidiuretic drug desmopressin (DDAVP® Spray and DDAVP® Rhinyle Solution)
Dear Health Care Professional,
Ferring Pharmaceuticals, in collaboration with Health Canada, wishes to inform you that all intranasal formulations of desmopressin including DDAVP Spray and DDAVP Rhinyle Solution are no longer indicated for the treatment of Primary Nocturnal Enuresis (PNE) due to an increased risk of hyponatremia with the intranasal formulations.
- All intranasal formulations of desmopressin are now contraindicated for the treatment of PNE.
- All patients using intranasal formulations of desmopressin for treatment of PNE should be reassessed to determine their need for continued treatment and to discuss other options. If ongoing treatment is considered necessary, patients should be switched to the lowest starting dose of an oral formulation, with the dose increased only if necessary to control symptoms.
- New patients treated for PNE with desmopressin should only be prescribed an oral formulation.
- Fluid intake and desmopressin dosage should be adjusted carefully in order to reduce the possibility of water retention and hyponatremia especially in very young and elderly patients or when significant daily variables occur such as hot climate conditions, intense exercise or other situations where increased water intake can be expected.
- Prodromal symptoms such as headache, nausea or vomiting may herald impending hyponatremia. A patient treated with desmopressin for PNE and/or their guardian should be advised that if such symptoms occur, desmopressin should be discontinued and medical attention sought immediately.
Hyponatremia is a rare but serious, potentially fatal adverse reaction caused by water retention resulting from the potent antidiuretic effect of desmopressin. If unrecognized, hyponatremia can lead to seizures and death.
Worldwide post-marketing data indicate a higher incidence of hyponatremia in patients being treated with the desmopressin intranasal formulations compared to the oral formulations. Hyponatremia has been reported at a rate of approximately 5 cases per 10 million doses for nasal formulations and about 1 case per 10 million doses for oral formulations.
Prescribing Advice
When desmopressin treatment is needed physicians should discuss with the patient and/or guardian the importance of limiting the amount of fluid intake one hour before taking the medication and during the 8 hours post dose.
Please refer to the Product Monograph for dosing instructions for DDAVP Melt and DDAVP Tablets for children over the age of 5 for PNE. The risk of hyponatremia occurring with oral desmopressin can be further reduced by closely following the dose titration guidelines and advice in the Canadian Product Monograph and Consumer Information leaflet (package insert).
DDAVP Spray and DDAVP Rhinyle Solution remain available for the treatment of patients with Central Diabetes Insipidus (CDI).
Changes to the Canadian Product Monograph
The following sections of the DDAVP Spray and DDAVP Rhinyle Solution Product Monograph have been revised:
Indications and Clinical Use
The indication for the treatment of primary nocturnal enuresis has been removed.
Contraindications
Worldwide post-marketing data indicate a higher incidence of hyponatremia in patients being treated with the desmopressin intranasal formulations compared to the oral formulations (DDAVP Tablet and DDAVP Melt ). Since safer formulations are available, intranasal formulations are contraindicated for use in primary nocturnal enuresis.
Warnings and Precautions
Hyponatremia is the most important adverse event reported for desmopressin, resulting from water retention caused by the potent antidiuretic effect of desmopressin. Desmopressin may lead to water intoxication and/or hyponatremia. Unless properly diagnosed and treated, hyponatremia can be fatal. Therefore, fluid restriction is recommended and should be discussed with the patient and/or guardian. Careful medical supervision is required.
Fluid intake or desmopressin dosage should be adjusted in order to reduce the possibility of water retention and hyponatremia especially in very young and elderly patients or when significant daily variables occur such as hot climate conditions, intense exercise or other situations where increased water intake can be expected (see Dosage and Administration). Particular attention should be paid to the risk of an extreme decrease in plasma osmolality and resulting seizures in young children. Should prodromal symptoms (headache, nausea and vomiting) which may herald impending hyponatremia occur, treatment should be discontinued immediately and the patient should seek medical assessment.
Post-Market Adverse Drug Reactions
Hyponatremia has been reported at an approximate rate of 5 cases per 10 million doses from worldwide post marketing experience in patients treated with DDAVP intranasal formulations. The reported rate for DDAVP oral formulations worldwide is considerably less at about 1 case per 10 million doses. Patients are recommended to take the oral formulations (e.g., DDAVP Melt) which are available for children with PNE. Desmopressin is a potent antidiuretic, which may lead to water intoxication and/or hyponatremia. Unless properly diagnosed and treated, hyponatremia can be fatal. Therefore, fluid restriction is recommended and should be discussed with the patient and/or guardian. Careful medical supervision is required.
Drug-drug Interaction
The selective serotonin reuptake inhibitors (SSRIs, e.g. venlafaxine and citalopram) and the neuroleptic risperidone have been associated with water intoxication and hyponatremia in rare cases.
Dosage and Administration
In order to minimize the risk of hyponatremia, the following should be considered a part of individualized dosage titration;
- Desmopressin should be given with caution and the dosage adjusted as necessary during acute illness, febrile episodes, hot days and other conditions with increased water intake.
Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of hyponatremia or other serious or unexpected adverse reactions in patients receiving DDAVP Spray and DDAVP Rhinyle Solution should be reported to Ferring Inc., Canada or Health Canada at the following addresses:
Ferring Inc,
200 Yorkland Boulevard, Suite 800
North York, Ontario
M2J 5C1
Tel: 1-800- 263-4057
Fax: 416-493-1692
Any suspected adverse reaction can also be reported to:
Canada Vigilance Program
Marketed Health Products Directorate
HEALTH CANADA
Address Locator: 0701C
Ottawa, Ontario, K1A 0K9
Tel: 613-957-0337 or Fax: 613-957-0335
To report an Adverse Reaction, consumers and health professionals may call toll free:
Tel: 866-234-2345
Fax: 866-678-6789
CanadaVigilance@hc-sc.gc.ca
The Adverse Reaction Reporting Form and the Adverse Reaction Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.
For other inquiries related to this communication, please contact Health Canada at:
Marketed Health Products Directorate (MHPD)
E-mail: MHPD_DPSC@hc-sc.gc.ca
Tel.: 613-954-6522
Fax: 613-952-7738
Should you have any questions or require additional information regarding the use of DDAVP Spray and DDAVP Rhinyle Solution please contact Ferring Inc., Medical Information at 1-800-263-4057.
Sincerely,
original signed by
Dr. Anne Brusby M.D., MRCP (UK) FRCPC
Medical Director
Ferring Inc., Canada
