DSB Reports & Updates – August 2017 Save

RheumNow will periodically report safety issues as Drug Safety Bulletins. These will update you with safety issues, label changes and reports of new, ongoing and resolved drug shortages that will affect rheumatology. If you have suggestions or information about specific drug shortages or drug safety issues please email us at: info@rheumnow.com

Baricitinib Delayed by FDA. On July 25, 2017, the Food and Drug Administration (FDA) notified Eli Lilly & Co. there would be a delay in the decision on baricitinib for use in rheumatoid arthritis (RA). The agency noted a potential risk of thromboembolic disease. In over 3100 RA patients in 6 large clinical trials they found no thromboembolic events (VTE) with placebo or the 2 mg baricitinib patients, but found 5 cases in the 4 mg bariticinib group (https://buff.ly/2uYy5nP). RA patients have a constitutive 2 fold increased risk of VTE (~5-6 VTE per 1000 person years) http://buff.ly/2tAHGRO); it is not clear If these results are due to RA or high dose baricitinib. (https://buff.ly/2wLXqTL)  On August 30th the companies announced that they would resubmit a new/revised NDA by Jan. 2018 that will be subject to at least a 6 month review by the FDA. This news manticipated approval time moved up the potential FDA verdict to mid to late 2018. https://buff.ly/2x66SUN 

Expired Drugs May Still be Potent. NPR reviewed the subject of drug expiration labels, noting that an expired drug may still be potent, especially if in pill form. The regulation that drugs beyond their expiration date must not be sold and should be discarded are intended to maintain patient safety and ensure drug potency. But this practice often leads to hundreds of thousands of dollars worth of medicine being trashed yearly by big hospitals. Many are calling for refining the dating process so as to limit the waste seen with current rules.  https://buff.ly/2x0YXor

Etanercept Effective at Room Temperature. Study of all marketed forms of etanercept has shown the drug to be stable, and hence useable, when taken out of refridgeration and kept at at conditions of 25°C±2°C (77°F) for up to 1 month within expiration period dates. I have been instructing my patients who travel to either: a) take their biologic a few days to a week early or late (so as to avoid traveling with a biologic) or b) to take the biologic, wrap it in bubble wrap, keep it dark and cool or at room temperature until they use it a week or two later. Hence they can put it in their purse or briefcase and take it on the plane to their destination. https://buff.ly/2vx2nkU

Consumer Reports Features on Drug Safety. The August 3rd edition featured this articles (I find these to be worthwhile reprints for patients-JC)

• Too Many Meds? America's Love Affair With Prescription Medication https://buff.ly/2i2sUBP
• What Older People Need to Know About Prescription Drug Risks  https://buff.ly/2fI1fWj
• Is It Time for a Medication Reconciliation?  https://buff.ly/2i2dZaP
• How to Get Off Prescription Drugs   https://buff.ly/2fIsfon
• Give Your Drugs a Checkup: Reviewing Your Medication List Can Prevent Errors https://buff.ly/2fIcH40
• From Pill Organizers to Apps, How to Manage Your Meds  https://buff.ly/2uFB09q 

No Association Between Alzheimers and Proton Pump inhibitors. A nationwide Finnish study of nearly 71,000 Alzheimer's disease patients and 283,000 controls without the disease has confirmed that PPI use was not associated with risk of Alzheimers disease.  https://buff.ly/2vG2Rmr 

AHRQ Review of Opioid Drug Safety.  Using data from the 2015  National Survey on Drug Use and Health (NSDUH), researchers estimate about 38 percent of U.S. adults (or 92 million people) were prescribed an opioid in 2015. Opiod use is highest in older people, females and non-college graduates. Overall 5% reported misusing opioids. This was higher in those taking prescription opioids (12.5%), and 16.7% reported a prescription opioid use disorder. Misuse was more common amongst the unemployed, low income, or those with behavioral health problems.  https://buff.ly/2wj9ldv 

No Increase in Malformations with Etanercept Use During Pregnancy.  Analysis of claims data was used to quantify prevalence estimates of pregnancy and infant outcomes with etanercept (ETN) exposure in women with chronic inflammatory arthritis (cIA) or psoriasis (PsO) and compared to the general population (GP) estimates. In the cIA cohort major congenital malformations were seen in 6.1% (ETN exposed), 5.5% (unexposed), and 5.7% (GP cohort). Lower numbers were seen among PsO cohort; MCM estimates were 2.0% (ETN exposed), 4.2% (unexposed), and 4.7% (GP cohort). https://buff.ly/2xNVZns 

FDA Safety Labeling Changes: drug label changes October 2016 – January 2017: 

Ambien (Mar 2017):  CYP3A4 inducers (e.g., rifampin, ketoconazole, St. John’s wort) may significantly reduced the exposure to and the pharmacodynamic effects of zolpidem; use in combination with zolpidem may decrease the efficacy of zolpidem and is not recommended.

Prolia (May 2017): Prolia is contraindicated for use in pregnant women because it may cause harm to a fetus. There are insufficient data with denosumab use in pregnant women to inform any drug-associated risks for adverse developmental outcomes. In utero denosumab exposure from cynomolgus monkeys dosed monthly with denosumab throughout pregnancy at a dose 50-fold higher than the recommended human dose based on body weight resulted in increased fetal loss, stillbirths, and postnatal mortality, and absent lymph nodes, abnormal bone growth, and decreased neonatal growth. 

Ultram (Aug 2017): Tramadol is contraindicated in children under age 18 yrs. Added to boxed warning - WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF TRAMADOL AND OTHER RISK FACTORS FOR LIFE- THREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Life-threatening respiratory depression and death have occurred in children who received tramadol. Some of the reported cases followed tonsillectomy and/or adenoidectomy; in a t l ea s t one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism (see WARNINGS). ULTRAM is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy (see CONTRAINDICATIONS). Avoid the use of ULTRAM in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol.

Xeljanz  (Aug 2017): appendicitis was added to the list of potential serious infections (Warnings). Also added: Caution is also recommended in patients with a history of chronic lung disease, or in those who develop interstitial lung disease, as they may be more prone to infections. Risk of infection may be higher with increasing degrees of lymphopenia and consideration should be given to lymphocyte counts when assessing individual patient risk of infection. Discontinuation and monitoring criteria for lymphopenia are discussed in Dosage Modifications due to Serious Infections and Cytopenias.

Reported Drug Shortages as of August 2017