Other safety alerts
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| Canada: CellCept (mycophenolate mofetil) and MYFORTIC (mycophenolate sodium) - Serious risk of teratogenicity in mycophenolate-containing products |
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Health Canada announced that a cumulative review of birth defects has confirmed that mycophenolate is a human teratogen. The evidence showed an increased rate of congenital malformations and spontaneous abortions associated with mycophenolate in comparison with other immunosuppressants.
CellCept (mycophenolate mofetil) is indicated for the prophylaxis of organ rejection in adult patients receiving allogeneic renal, cardiac or hepatic transplants. It is also indicated for the prophylaxis of organ rejection in pediatric patients (2 to 18 years of age) receiving allogeneic renal transplants. MYFORTIC (mycophenolate sodium) is indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal transplants. CellCept (mycophenolate mofetil) or MYFORTIC (mycophenolate sodium) are administered in combination with cyclosporine and corticosteroids.
Congenital malformations, including multiple malformations, have been reported post-marketing, in children of patients exposed to mycophenolate mofetil in combination with other immunosuppressants during pregnancy. The following malformations were most frequently reported:
• Facial malformations such as cleft lip, cleft palate, micrognathia and hypertelorism of the orbits;
• Abnormalities of the ear (e.g. abnormally formed or absent external/middle ear) and eye (e.g. coloboma, microphthalmos);
• Malformations of the fingers (e.g. polydactyly, syndactyly, brachydactyly);
• Cardiac abnormalities such as atrial and ventricular septal defects;
• Oesophageal malformations (e.g. oesophageal atresia);
• Nervous system malformations (such as spina bifida).
Based on evidence from medical literature, malformations occurred in 23 to 27% of live births in women exposed to mycophenolate mofetil during pregnancy, compared to 2 to 3% of live births in the overall population and approximately 4 to 5% in solid organ transplant patients treated with immunosuppressants other than mycophenolate mofetil. Cases of spontaneous abortions have been reported in 45 to 49% of patients exposed to mycophenolate mofetil during pregnancy, compared to a reported rate between 12 and 33% in solid organ transplant patients treated with other immunosuppressants.
Information for healthcare professionals is as follows:
Before the start of treatment with mycophenolate-containing products, female and male patients of reproductive potential should be made aware of the increased risk of pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention, and planning.
Before starting therapy with any mycophenolate-containing product, women of childbearing potential must have two negative serum or urine pregnancy tests with a sensitivity of at least 25 mIU/mL; the second test should be performed 8 to 10 days after the first one and immediately before starting any mycophenolate-containing product. Repeat pregnancy tests should be performed during routine follow-up visits. Results of all pregnancy tests should be discussed with the patient. Patients should be instructed to consult their physician immediately should pregnancy occur.
Women of child bearing potential should use two reliable forms of contraception simultaneously, including at least one highly effective method, before beginning mycophenolate therapy, during therapy, and for six weeks following discontinuation of therapy, unless abstinence is the chosen method of contraception.
Sexually active men should be informed to use condoms during treatment and for at least 90 days after cessation of treatment. Condom use applies for both reproductively competent and vasectomized men, because the risks associated with the transfer of seminal fluid also apply to men who have had a vasectomy. Men should be informed not to donate sperm/semen during therapy or for at least 90 days following discontinuation of mycophenolate. In addition, female partners of male patients should be informed to use highly effective contraception during treatment and for a total of 90 days after the last dose of any mycophenolate containing product.
Patients should be informed not to donate blood during treatment or for at least 6 weeks following discontinuation of any mycophenolate-containing product.
Please refer to the following website in Health Canada for details:
http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/../56690a-eng.php
In Hong Kong, there are 17 registered pharmaceutical products containing mycophenolate mofetil or mycophenolic acid. All products are prescription only medicines. Related news was issued by the EMA, MHRA and TGA, and was posted on the Drug Office website on 24 October 2015, 15 December 2015 and 22 December 2015 respectively. Letters to inform local healthcare professionals of the new advice to prevent pregnancy when using the products were issued on 26 October 2015.
Roche Hong Kong Limited (Roche) is the registration certificate holder of four branded pharmaceutical products containing mycophenolate mofetil, namely CellCept Cap 250mg (HK-41757), CellCept Tab 500mg (HK-44333), CellCept Powder for Infusion 500mg (HK-45089) and CellCept Powder for Oral Suspension 1g/5ml (HK-62451). On 7 December 2015, Roche notified the Department of Health (DH) that the company has issued a "Dear Healthcare Professional Letter" to inform local healthcare professionals about the teratogenic risk of the products, with important new pregnancy advice for women and men.
So far, DH has received six adverse drug reaction cases related to mycophenolic acid, and one of them was related to missed abortion after taking the drug. As previously reported, the matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board (the Committee). The information in the above Health Canada announcement will also be forwarded to the Committee for consideration.
Ends/ Tuesday, January 19, 2016
Issued at HKT 14:00
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