FDA: New assessment discourages morcellation for fibroids

December 19, 2017

An updated review of evidence by the US Food and Drug Administration (FDA) underscores concerns expressed in 2014 by the agency about use of laparoscopic power morcellators (LPM) for treatment of uterine fibroids. Plus: Prescription habits show ob/gyns not well informed about opioids, according to a study. Also: Does ADHD medication use during pregnancy increase risk of congenital malformations?

An updated review of evidence by the US Food and Drug Administration (FDA) underscores concerns expressed in 2014 by the agency about use of laparoscopic power morcellators (LPM) for treatment of uterine fibroids. Conducted by the Center for Devices and Radiological Health (CDRH), the analysis spanned 42 studies, 4 systematic reviews, 4 decision analyses, and also medical device reports (MDRs) and data on changes in rates of hysterectomy or myomectomy in the past 3 years.  

The goals of the review were assessment of (1) prevalence of sarcoma in women undergoing myomectomy or hysterectomy for presumed benign uterine fibroids; (2) clinical outcomes in patients diagnosed with cancer following morcellation during myomectomy or hysterectomy to treat presumed uterine fibroids; and (3) differences in patient outcome electric power morcellation versus manual morcellation and/or no morcellation.    

In April 2014, FDA issued a safety communication warning against use of LPMs during most surgeries for fibroids. Seven months later, recommendations were made for labeling LPMs for gynecological or general indications with contraindication statements and a “black box” warning. The actions followed reports suggesting an association between use of LPMs during surgery in women with presumed fibroids and dissemination and upstaging of undiagnosed uterine sarcomas.

The new review showed a 1 in 225 to 1 in 580 prevalence of uterine sarcoma in women undergoing surgery for presume fibroids and a 1 in 495 to 1 in 1100 prevalence for leiomyosarcoma (LMS). In studies published from 2014 to 2017 in a fixed effects model, prevalence of uterine sarcoma was 0.328% (95% confidence interval [CI] 0.303-0.352) corresponding to 1 in 305 and prevalence of LMS was 0.175% (95% CI 0.148-0.202) corresponding to 1 in 750 women. Limited data showed an increase in occult sarcoma with age for both uterine sarcoma and LMS, with significant increases noted in women aged 60 and older.    

Of the 262 MDRs received by FDA through April 17, 2017 that described dissemination of malignant cells in association with LPMs, 18 specifically claimed that the device was associated with upstaging of disease. The authors of the analysis noted, however, that submission of an MDR does not provide causality between a device and the reported event. Data on trends in use of LPMs since the issuance of the safety communications indicated that the rate of use of the devices in hysterectomies has fallen to < 0.1 procedures per 1000.  

“While minimally invasive surgery conveys several significant advantages over open surgery for women with fibroids,” the report’s authors said, “the use of LPMs during these surgeries poses a risk due to the potential presence of unsuspected sarcoma in this population. FDA continues to caution against the use of LPMs in the majority of women undergoing myomectomy or hysterectomy for treatment of fibroids.”

NEXT: Study: Prescription habits show ob/gyns not well informed about opioids


Study: Prescription habits show ob/gyns not well informed about opioids

Using a cross-sectional survey of American obstetricians and gynecologists, a group of researchers examined the opioid prescribing habits of the specialty and found that ob/gyns need to become better informed about prescribing the drugs, more aware of misuse, and educate their patients about proper disposal. The study was published in Obstetrics and Gynecology.

The researchers reached out to 300 American College of Obstetricians and Gynecologists (ACOG) Fellows and Junior Fellows who are part of the Collaborative Ambulatory Research Network. Of the 300 solicited members, 179 (60%) members responded. The respondents reported prescribing a median of 26 (5-80) pills per patient across all indications. The most common indication was for surgery, of which 98% of the respondents reported prescribing opioids. More specifically, 97% prescribed opioids after abdominal hysterectomy, 94% after cesarean delivery, 89% after laparoscopic hysterectomy, and 86% after vaginal hysterectomy. In regard to nonsurgical indications, 30% of respondents reported prescribing opioids for ovarian cysts, 24% for endometriosis, 22% for pain after vaginal birth, and 18% prescribed for chronic pelvic pain of unknown cause. Overall, physicians were more comfortable prescribing opioids for acute pain than for chronic pain.   

In regard to the type of opioids that respondents were prescribing, 34% prescribed acetaminophen with hydrocodone, 29% prescribed acetaminophen with oxycodone, 13% prescribed acetaminophen with codeine, 8% prescribed oxycodone, 3% prescribed hydrocodone, and 1% prescribed hydromorphone. The largest number of pills prescribed varied by indication, but the most pills were prescribed after laparotomies for cesarean delivery and abdominal hysterectomy (median, 30; range 8-80). The largest variation in pills prescribed was for chronic endometriosis and pelvic pain of unknown cause (range 9-60 pills).

Beyond prescribing habits, the researchers also looked at adherence to four practices recommended by state and federal agencies as well as by ACOG. These included: screening for dependence; prescribing the smallest effective dose; tailoring prescriptions; and counseling patients on the risks and benefits of proper use, storage, and disposal of the medication. Of the respondents, 57 (19%) reported adherence to at least three of the recommended practices. Only 22% of respondents said they typically performed an opioid dependence screen and just 17% regularly told patients about proper disposal of unused opioids. The majority of respondents (67%) reported that they usually review inpatient pain medication use and 47% prescribe outpatient opioids based on the level of pain medication a patient required during hospitalization.

The researchers also said that, according to the responses from the survey, relatively few doctors were well-informed about opioids. They noted that 81% of the respondents did not know that the predominant sources of misused opioids are friends or relatives. Almost half (44%) of the respondents also didn’t know how to properly dispose of unused prescription opioids.

The authors identified a few limitations to their study. These include recall bias, using a small sample of ACOG members, and the issue of self-reporting. However, the study showed a wide variance in prescribing habits, which highlights the need for continued development and promotion of educational efforts to emphasize the role of the physician in fighting the opioid epidemic.

NEXT: Does ADHD medication use during pregnancy increase risk of congenital malformations?




Does ADHD medication use during pregnancy increase risk of congenital malformations?

A new study published in JAMA Psychiatry has found that methylphenidate, a medication used to treat attention deficit hyperactivity disorder (ADHD), slightly increases the risk of heart defects during early pregnancy. The study, conducted at Brigham and Women’s Hospital, was the first to use data from the International Pregnancy Safety Study (InPreSS) consortium, which works to provide data on the safety of prescription medications during pregnancy.   

The primary analyses for this study came from the 2000-2013 nationwide Medicaid Analytic eXtract, which looks at pregnant women aged 12 to 55 who were enrolled in Medicaid from the time of their last menstrual period (LMP) to 1 month after delivery. The researchers also used information from the Nordic health registries as validation analyses. The five Nordic countries included were Sweden, Norway, Iceland, Denmark, and Finland and the data were on all pregnancies resulting in singleton live births. However, each participating country contributed data from different periods according to data availability (Denmark, 2005-2012; Finland, 1996-2010; Iceland, 2003-2012; Norway, 2005-2012; and Sweden, 2006-2013). A total of 1 813 894 women were considered for the study and among them, 2072 (0.11%) had filled a prescription for an ADHD medication during their first trimester. 

For the study, a pregnancy was considered exposed if a woman filled a prescription for a stimulant during the first 90 days of pregnancy. There were two different exposure groups that were examined: methylphenidate or amphetamine and dextroamphetamine. The researchers then looked at inpatient and outpatient International Classification of Diseases, Ninth Revision diagnoses and procedure codes in the maternal and infant health records to identify congenital malformations. An infant was considered to have a major congenital malformation if any of 13 specific malformation groups (central nervous system, ear, eye, cardiovascular, other vascular, respiratory, oral cleft, gastrointestinal, genital, urinary, musculoskeletal, limb, and other) were present.

Malformations were diagnosed in 62966 infants who were not exposed to a stimulant during the first trimester (35.0 malformations per 1000 infants). The prevalence was higher among methylphenidate-exposed (n = 95; 45.9 per 1000) and among amphetamine-exposed n = 253; 45.4 per 1000) infants. The incidence of cardiovascular malformations was increased among methylphenidate-exposed infants (18.8 vs 12.7 per 1000 unexposed infants) and among amphetamine-exposed infants (15.4 per 1000). After the researchers adjusted for psychiatric morbidity, the associations with malformations overall were reduced for both methylphenidate (relative risk [RR], 1.16, 95% CI, 0.95-1.41) and amphetamines (RR, 1.18, 95% CI, 1.04-1.33). In terms of cardiovascular malformations, the risk remained slightly elevated for methylphenidate (RR, 1.27, 95% CI, 0.93-1.73) but not for amphetamines (RR, 1.07; 95% CI, 0.86-1.32). In fully adjusted analyses, the associations with malformations overall and with cardiovascular malformations were null for amphetamines. For any malformations, relative risk was 1.05 (95% CI, 0.93-1.19) and 0.96 (95% CI, 0.78-1.19) for cardiac malformations. The fully adjusted RRs for methylphenidate were 1.11 (95% CI, 0.91-1.35) for any malformation and 1.28 (95% CI, 0.94-1.74) for cardiac malformations.

In the validation analyses, the Nordic cohort included 2,560,069 pregnancies resulting in a singleton live birth. Among these pregnancies, 1402 infants (0.05%) were exposed to methylphenidate. The prevalence of malformations was slightly lower than in the US cohort: 28.5 per 1000 infants for any malformation and 17.1 per 1000 infants for cardiovascular malformations. In unexposed pregnancies, the prevalence was 37.8 per 1000 infants for any malformation and 13.3 per 1000 infants for cardiovascular malformations. The adjusted estimates for first-trimester methylphenidate exposure from the US and the Nordic data resulted in RRs of 1.07 (95% CI, 0.91-1.26) for any malformation and 1.28 (95% CI, 1.00-1.64) for cardiovascular malformations. The researchers found a 28% increased prevalence of cardiac malformations after first-trimester exposure to methylphenidate.

The authors noted that the major strength of the study was the collected data from 6 countries which helped provide a large pool of data and limited the risk of recall bias. However, since the data used did not track adherence to the prescription, it is possible that some of the pregnancies may have been misclassified. Another limitation noted is that both cohorts were restricted to live births, which could have resulted in underestimation of relative risk due to selection bias. Ultimately, the researchers noted that, when possible, women with mild to moderate ADHD symptoms should try to forego ADHD treatment during pregnancy. If daily function is difficult for the patient, however, she should be informed of the potential risk for cardiac malformation with methylphenidate.