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Content Summary
2. The United States warns that long-term use of azithromycin after transplantation of stem cell donation increases the risk of cancer recurrence
3. Canada evaluates the serious risk of children exposed to methadone through breast milk
4. Canada warns infliximab potential linear IgA bullous skin disease risk
pharmacovigilance news 2018 Issue 9
(Total Issue 185)
The United States warns SGLT2 anti-glycemic drugs for rare and severe genital and peripheral genital infections
On August 29, 2018, the U.S. Food and Drug Administration (FDA) issued a warning message saying it received rare and severe genital and peripheral genital infection cases of sodium-glucose cotransporter 2 (SGLT2) inhibitor type 2 diabetes treatment drugs. This rare and severe infection is called perineal necrotizing fasciitis, also known as Fournier’s gangrene. The FDA believes new warnings about this risk need to be added to prescription information for all SGLT2 inhibitors and patient medication guidelines.
SGLT2 inhibitors are a class of drugs approved by the FDA to reduce blood sugar in adult patients with type 2 diabetes on a diet and exercise basis. They work by promoting the kidneys to excrete sugar from the urine. The drugs were first approved in 2013 and include: canagliflozin, dapagliflozin, empagliflozin and ertugliflozin. In addition, empagliflozin is approved to reduce the risk of dying from heart attacks and strokes in adult patients with type 2 diabetes and heart disease. Untreated type 2 diabetes can cause serious complications, including blindness, nerve and kidney damage, and heart disease.
patients should pay attention to
If there is any tenderness, redness, swelling in the genitals or areas from the genitals to the rectum, and a fever exceeding 100.4 degrees Fahrenheit or a whole body feels uncomfortable, please seek medical treatment immediately. These symptoms worsen rapidly, so be sure to seek medical treatment immediately.
When you get a prescription for SGLT2 inhibitor, read the patient's medication guide. Drug guidelines explain the benefits and risks of medication use and may have new or important additional information.
Medical staff should pay attention to
If the patient has the above symptoms, consider whether it is Fournier gangrene. If suspicious, use broad-spectrum antibiotics and surgical debridement treatment immediately.
disables SGLT2 inhibitors, closely monitors blood sugar levels, and provides appropriate alternative treatments for blood sugar control.
(US FDA website)
The United States warns that long-term use of azithromycin after stem cell donation transplantation will increase the risk of cancer recurrence
On August 3, 2018, the U.S. Food and Drug Administration (FDA) issued a message warning that patients undergoing stem cell transplantation due to blood and lymph node cancer should not use azithromycin for a long time to prevent certain lung infections. Results from a Phase I clinical trial found an increased incidence of recurrence in patients with blood and lymph node cancer, including death. The FDA is evaluating other data and will communicate relevant conclusions and recommendations when the assessment is completed.
The severe lung disease treated with azithromycin for a long time in the study is called occlusive bronchiolar syndrome, which is caused by infection and scarring of the lung airway and can lead to severe dyspnea and dry cough. Cancer patients undergoing stem cell donation transplantation are at risk of bronchiolititis obstruction syndrome. Azithromycin manufacturer is sending letters to remind medical staff who are nursing patients who receive stem cell donations to transplant patients to pay attention to this safety issue. The FDA approved azithromycin for the treatment of multiple infections in the lungs, sinuses, skin and other parts of the body; it was not approved for the prevention of obstructive bronchioles syndrome. The drug has been used for 26 years and is effective by inhibiting the growth of bacteria that cause infection.
French researchers found an increased risk of cancer recurrence and death in a clinical trial. This clinical trial studies the effectiveness of long-term use of azithromycin to prevent occlusive bronchioliitis syndrome in patients with blood and lymph node cancer who undergo donor or homosomal stem cell transplantation. The researchers concluded that the risk of long-term exposure to azithromycin after donor stem cell transplantation may outweigh the benefits. This clinical trial cannot determine the cause of high cancer recurrence and death in the azithromycin group.
investigators stopped the ALLOZITHRO1 clinical trial about 13 months after the study completed enrollment of 480 patients, as unanticipated increase in cancer recurrence and mortality were observed in the patient group using azithromycin. The azithromycin treatment group observed cancer recurrence in 77 patients (32.9%), and only 48 patients (20.8%) in the placebo group. A total of 95 patients died in the azithromycin group compared with 66 in the placebo group. Therefore, the 2-year survival rate of the azithromycin-treated group was 56.6% compared with 70.1% in the placebo group. In the first few months of the clinical trial, mortality rates were comparable in the azithromycin and placebo groups, however, an imbalance subsequently occurred, which lasted 2 years at the end of the study.
currently has no antibiotic known to be effective in preventing and treating bronchiolititis occlusion syndrome. Medical staff should not prescribe long-term use of azithromycin to patients undergoing stem cell donation transplants to prevent occlusive bronchiola syndrome, because this increases the potential risk of cancer recurrence and death. Patients who have undergone stem cell transplantation should not discontinue azithromycin before consulting with medical staff. Because there is no direct guidance from a doctor, it may cause harm to the patient. If you have any questions or concerns about the drug, please consult a medical staff.
(US FDA website)
Canada Assessment of Severe Risks of Children with Breast Milk Exposure to Methadone
On August 3, 2018, Health Canada released information on safety assessment of methadone drugs. The assessment found that methadone may be associated with the risk of serious injury, including death, in children exposed to the drug through breast milk.
Methadone is a synthetic opioid used to treat adult opioid addiction (such as heroin) and its function is to prevent the symptoms of withdrawal from opioids, that is, side effects caused by stopping opioids. Methadone is used as an anesthetic and is purchased based on prescription only. The drugs evaluated include Methadose (oral concentrate of methadone hydrochloride) and Metadol-D (methadone hydrochloride tablets, oral solution and concentrate), which were marketed in Canada in 2013 and 2014, respectively, for addiction treatment of adult opioids. In 2017, Canada issued approximately 11 million Methadose and Metadol-D prescriptions.
Health Canada initiated the assessment because it noticed a published article reporting two deaths from Canadian children, whose blood levels of methadone increased because their mothers participated in the opioid addiction treatment program (Methadone Maintenance Program) and breastfeeded their children.
Canadian and international opioid addiction treatment guidelines encourage mothers participating in the methadone maintenance program to breastfeed, but both mothers and children should be closely monitored. Reports of severe side effects (including death) in breastfeeding children are rare in methadone maintenance programs.
At the time of evaluation, only 2 Canadian children were exposed to the toxicity of methadone through breast milk, and both involved death. Both of these two cases found a possible correlation between severe adverse reactions (including death) and child exposure to methadone through breast milk. The safety assessment also investigated 13 international cases of children with exposure to methadone through breast milk, with 10 of which involved deaths. Among these cases, 12 found a possible correlation between the risk of severe injury (including death) and the child's exposure to methadone through breast milk, and the remaining cases do not have sufficient data to evaluate. Small amounts of methadone can be passed to children through breast milk, and in very rare cases breastfeeding can put children at risk of serious side effects, including dyspnea (severe respiratory depression), heart disease, and death. Genetic factors may be the reason why some children are more sensitive to methadone than others, but these genetic factors have not been well studied. In the 2 cases involving deaths, genetic testing showed that these children may be particularly sensitive to the effects of methadone. Scientific literature and various Canadian and international guidelines encourage mothers to use methadone for breastfeeding, however, the benefits and risks of breastfeeding during methadone maintenance treatment should be carefully considered.Among all the cases evaluated, there are factors that make case assessment difficult, including lack of mothers’ dose of methadone, cause of death, improper medical history or combined medications, which are very important for the assessment. The product information of
Methadose and Metadol-D recommends caution in the treatment of lactating women. Both product information states that the benefits and risks of breastfeeding should be carefully weighed during methadone treatment and that breastfeeding mothers and children should be closely monitored. European Drug Administration and the U.S. Food and Drug Administration have similar product information, listing the risks of serious harm to children through breast milk exposure.
Health Canada will work with manufacturers of Methadose and Metadol-D to strengthen product information revisions and warn children exposed to methadone through breast milk that may suffer serious injuries, including death. Health Canada encourages consumers and medical staff to report any related side effects. Health Canada will continue to monitor safety information about methadone.
Reference information
1.Madadi P, Kelly L, Ross C, Kepron C, Edwards J, Koren G. Forensic Investigation of Methadone Concentrations in Deceased Breastfed Infants. Journal of Forensic Sciences. 2016;61:1-5
2.College of Physicians and Surgeons of Ontario: Methadone Maintenance Treatment Program Standards and Clinical Guidelines https://www.cpso.on.ca/uploadedFiles/members/MMT-Guidelines.pdf (consulted on February 2, 2018)
(Health Canada website)
Canada warns the potential risk of linear IgA bullous skin disease
On July 23, 2018, the Health Canada issued an announcement stating that infliximab (trade name is Keke) may cause skin herpes risk, also known as linear IgA bullous skin disease.
infliximab is approved in Canada for the treatment of infections in the skin (psoriasis), joints (rheumatoid or psoriatic arthritis) and intestinal tract ( Crohn's disease and ulcerative colitis) in adults and children, which are caused by imbalance in the body's defense system (autoimmune disease). Agrico is an immune system protein (antibodies) that blocks TNF-α (tumor necrosis factor alpha) that causes infection in the body. Lecco is a prescription drug in Canada and has been marketed in Canada since 2001.
Health Canada evaluated the potential risk of linear IgA bullous dermatosis in patients with Cetaceans, mainly published case reports on the risk of Cetaceans. Health Canada evaluated the information currently available and concluded that there might be a correlation between the risk of gnecoidal and linear IgA bullous skin disease. Health Canada and Cerrox manufacturers have jointly updated the risk of skin herpes into product safety information.
During the evaluation period, the Canadian Ministry of Health received a case of skin herpes in China after the use of Croatia treatment. The report shows a possible correlation between Germjewel use and dermal herpes. This safety evaluation also reviewed 6 individual reports from Lecco manufacturers (including 1 Canadian report). It was confirmed that 4 of the cases of dermatological herpes disease may be related to Czech treatment, while 2 cases cannot be evaluated due to lack of information. Evaluation results of
above cases and scientific literature support a possible association between the use of Germa and the risk of dermatological herpes. Since skin herpes has been reported in only a few patients with Germaco, it is inferred that such risks occur with Germacoco. The European Food and Drug Administration has updated its product safety information to include this risk. Product safety information in the United States does not include any information about this risk.
Health Canada will continue to monitor security information on Cerk and will take further regulatory measures if any new risks are identified.
(Health Canada website)
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