NEW FDA WATCH LIST

Cardiovascular and cancer therapies dominate the latest watch list of drugs with possible safety issues that was released by the US Food and Drug Administration (FDA) earlier this month.

The list is based on potential signals of serious risk or new safety information collected by the FDA Adverse Event Reporting System (FAERS) in the third quarter of 2016.

Four anticoagulants made the third-quarter list owing to reports of patients experiencing vasculitis. Three of the anticoagulants — apixaban (Eliquis, Bristol-Myers Squibb), edoxaban tosylate (Savaysa, Daiichi Sankyo), and rivaroxaban (Xarelto, Janssen Pharmaceuticals) — are direct factor Xa inhibitors. The fourth, dabigatran etexilate mesylate (Pradaxa, Boehringer Ingelheim Pharmaceuticals), is a direct thrombin inhibitor.

The watch list includes two other cardiovascular drugs. The FDA is evaluating a potential signal of ventricular arrhythmias for ivabradine (Corlanor, Amgen), indicated for heart failure. Midodrine hydrochloride (ProAmatine, Shire), indicated for orthostatic hypotension, is under scrutiny because of reports of interaction with monoamine oxidase inhibitors (MAOIs) for depression that could trigger a stroke.

A drug's appearance on a quarterly FAERS watch list does not mean the agency has determined there is a cause-and-effect relationship between the drug and the cited adverse event. Rather, the agency evaluates the need for regulatory action. If its investigation does uncover a causal link, the FDA could gather more information to better describe the threat, revise the drug's label, require a risk evaluation and mitigation strategy, or pull the drug from the market.

An Eye Out for Hepatitis B Reactivation

Of the nine drugs or drug classes appearing in the FAERS watch list for the third quarter, two are prescribed for cancer. Talimogene laherparepvec suspension (Imygic, Amgen) is injected into melanoma lesions that can't be surgically removed. The potential signal risk here is disseminated herpetic infection.

Also on the list are three tyrosine kinase inhibitors indicated chiefly for leukemia: imatinib mesylate (Gleevec, Novartis Pharmaceuticals), dasatinib (Sprycel, Bristol-Myers Squibb), and nilotinib (Tasigna, Novartis Pharmaceuticals). They're being checked out because of reports of hepatitis B virus reactivation. The FDA has already updated label warnings for the three drugs to reflect the question mark about this adverse event.

Table. Potential Signals of Serious Risks/New Safety Information Identified by FAERS, July to September, 2016

Product Name: Trade (Active Ingredient) or Product Class	Potential Signal of a Serious Risk / New Safety Information	Additional Information (as of November 3, 2016)
Corlanor (ivabradine) tablets, for oral use	Ventricular arrhythmias	FDA is evaluating the need for regulatory action.
Eliquis (apixaban) tablets, for oral use Pradaxa (dabigatran etexilate mesylate) capsules, for oral use Savaysa (edoxaban tosylate) tablets, for oral use Xarelto (rivaroxaban) tablets, for oral use	Vasculitis	FDA is evaluating the need for regulatory action.
Imlygic (talimogene laherparepvec) suspension for injection	Disseminated herpetic infection	FDA is evaluating the need for regulatory action.
Kybella (deoxycholic acid) injection, for subcutaneous use	Injection-site alopecia	FDA is evaluating the need for regulatory action.
ProAmatine (midodrine hydrochloride) tablets	Interaction with MAOIs may lead to a risk for cerebrovascular accident	FDA is evaluating the need for regulatory action.
Sensipar (cinacalcet) tablets, for oral use	Gastrointestinal bleeding	FDA is evaluating the need for regulatory action.
Stelara (ustekinumab) injection, for subcutaneous use	Thrombotic thrombocytopenic purpura	FDA is evaluating the need for regulatory action.
Tyrosine kinase inhibitors:  Gleevec (imatinib mesylate) tablets  Sprycel (dasatinib) tablets  Tasigna (nilotinib) capsules	Hepatitis B virus reactivation	The “Postmarketing Experience” section of the labeling for Gleevec and Sprycel and the “Additional Data from Clinical Trials” section of the labeling for Tasigna were updated to include information about Hepatitis B reactivation.  Gleevec labeling Sprycel labeling Tasigna labeling
Viberzi (eluxadoline) tablets, for oral use	Pancreatitis/sphincter of Oddi spasm	FDA is evaluating the need for regulatory action.