New FDA Watch List Covers 27 Drugs and Drug Classes

October 04, 2016

The US Food and Drug Administration (FDA) has put 27 drugs and drug classes on its latest watch list based on reports of adverse events earlier this year, the agency announced last week.

In the case of one drug class — direct-acting antivirals for hepatitis C virus (HCV) infections — the FDA already has taken swift action. Today the agency warned that patients currently or previously infected with hepatitis B virus (HBV) risk life-threatening HBV reactivation if they take any of nine direct-acting antivirals for HCV. Seven of these nine drugs, which include simeprevir (Olysio, Janssen Therapeutics) and sofosbuvir (Sovaldi, Gilead Sciences), are among the drugs and drug classes on the watch list of possible safety issues collected by the FDA Adverse Event Reporting System (FAERS) in the second quarter of 2016. The other listed drugs treat illnesses ranging from diabetes and depression to multiple sclerosis and hypertension.

The appearance of a drug together with an adverse event on a quarterly FAERS watch list normally doesn't mean that the FDA has concluded there is a causal relationship, but rather that the FDA intends to investigate whether one exists. If its study uncovers a link, the FDA could collect more data to better describe the threat, revise the drug's label, or order a Risk Evaluation and Mitigation Strategy. In rare cases, it could pull the drug from the market.

Look-alike Drug Names

Sometimes the FDA is not the first to single out a drug in the wake of unexpected adverse events. The FDA said in its latest watch list, for example, that it would study reports of fatal infections among patients taking idelalisib (Zydelig, Gilead Sciences) for three forms of cancer including chronic lymphocytic leukemia. The European Medicines Agency also looked into the matter and announced in July that, although the drug increased the risk for serious infection, the benefits outweighed the risks. EMA recommended that patients receiving idelalisib also receive prophylactic antibiotics.

The watch list cited two drugs because they have similar names that confuse physicians and cause prescribing errors. They are hydralazine for hypertension and congestive heart failure, and hydroxyzine for allergic itching and anxiety.

 

Potential Signals of Serious Risks/New Safety Information Identified by FAERS, April to June, 2016

Product Name: Trade (Active Ingredient) or Product Class Potential Signal of a Serious Risk / New Safety Information Additional Information (as of September 30, 2016)
Antidepressants Stress cardiomyopathy FDA is evaluating the need for regulatory action.

Beta Interferons :

Avonex (interferon beta-1a) injection

Betaseron (interferon beta-1b) subcutaneous injection

Extavia (interferon beta-1b) subcutaneous injection

Plegridy and Plegridy PEN (peginterferon beta-1a) subcutaneous injection

Rebif and Rebif Rebidose (interferon beta-1a) subcutaneous injection

Drug-induced lupus FDA is evaluating the need for regulatory action.
Corlanor (ivabradine) tablet Concomitant use of ivabradine with drugs that slow the heart rate (e.g. beta blockers, clonidine, digoxin, diltiazem, ivabradine, and verapamil) may increase risk of bradycardia.

FDA decided that no action is necessary for ivabradine at this time based on available information.

The "Drug Interactions" section of the labeling for other negative chronotropes was updated to include information about bradycardia when ivabradine is used concomitantly.

Dipeptidyl peptidase 4 (DPP-4) inhibitor tablets :

Glyxambi (empagliflozin/ linagliptin) tablets

Kazano (alogliptin /metformin hydrochloride) tablets

Janumet (sitagliptin /metformin hydrochloride) tablets

Janumet XR (sitagliptin /metformin hydrochloride) extended-release tablets

Januvia (sitagliptin) tablets

Jentadueto XR (linagliptin /metformin hydrochloride) extended-release tablets

Jentadueto (linagliptin/metformin hydrochloride ) tablets

Kombiglyze XR (saxagliptin /metformin hydrochloride) extended-release tablets

Nesina (alogliptin) tablets

Onglyza (saxagliptin) tablets

Oseni (alogliptin /pioglitazone) tablets

Tradjenta (linagliptin) tablets

Pemphigoid FDA is evaluating the need for regulatory action.
Diphenhydramine QT Prolongation FDA is evaluating the need for regulatory action.

Direct-acting antivirals :

Daklinza (daclatasvir) tablets

Harvoni (ledipasvir and sofosbuvir) tablets

Olysio (simeprevir) capsules

Sovaldi (sofosbuvir) tablets

Technivie (ombitasvir, paritaprevir, and ritonavir) tablets

Viekira Pak (ombitasvir, paritaprevir, and ritonavir; dasabuvir) tablets

Zepatier (elbasvir and grazoprevir) tablets

Hepatitis B reactivation

These HCV drugs will receive a boxed warning about the risk of HBV reactivation in co-infected individuals.

HCV Direct-Acting Antivirals Drug Safety Communication (October 4, 2016)

Entresto (sacubitril/valsartan) tablets Risk of rhabdomyolysis with concomitant use of statin therapy FDA is evaluating the need for regulatory action.
First and second generation histamine H1 antagonists Seizures FDA is evaluating the need for regulatory action.
Fluroquinolone antibiotics Drug-induced side effects

The "Boxed Warning" and "Warnings and Precautions" sections of the labeling were updated with information about disabling and potentially irreversible serious adverse reactions that have occurred together.

Fluroquinolone Antibiotics Drug Safety Communication (May 12, 2016)

Granix (tbo-filgrastime) injection for subcutaneous use Glomerulonephritis FDA is evaluating the need for regulatory action.
Harvoni (ledipasvir and sofosbuvir) tablets

Drug-Drug Interaction :

ledipsavir/sofosbuvir and lopinavir/ritonavir

FDA is evaluating the need for regulatory action.
HMG-CoA reductase inhibitors Interstitial lung disease FDA is evaluating the need for regulatory action.

Hydralazine hydrochloride tablets

Hydroxyzine hydrochloride tablets

Hydroxyzine pamoate capsules

Increase in medication error reports associated with confusion between hydroxyzine and hydralazine FDA is evaluating the need for regulatory action.
Krystexxa (pegloticase) injection for intravenous use Hemolytic anemia and methemoglobinemia FDA is evaluating the need for regulatory action.

Ophthalmic products :

container closure system

Manufacturing problem :

loose or unsecured tamper evident rings can fall off the bottle neck onto patients' eyes when bottle is tilted or inverted to apply eye drops

FDA required changes to the container closure design to either secure the tamper-evident ring or change the container closure design.

Ophthalmic Products Drug Safety Communication (March 15, 2016)

Opsumit (macitentan) tablets Hepatic and hepatobiliary disorders FDA is evaluating the need for regulatory action.
Rapivab (peramivir) injection for intravenous use Anaphylaxis/Angioedema The "Contraindications," "Warnings and Precautions," "Adverse Reactions," "Postmarketing Experience," and "Patient Counseling Information" sections of the labeling were updated to include information on hypersensitivity and anaphylaxis.

SGLT2 inhibitors :

Farxiga (dapagliflozin) tablets

Glyxambi (empagliflozin /linagliptin) tablets

Invokamet (canagliflozin /metformin hydrochloride) tablets

Invokana (canagliflozin) tablets

Jardiance (empagliflozin) tablets

Synjardy (empagliflozin /metformin hydrochloride) tablets

Xigduo XR (dapagliflozin/metformin hydrochloride) extended-release tablets

Acute pancreatitis FDA is evaluating the need for regulatory action.
Tecfidera (dimethyl fumarate) delayed-release capsules Idiosyncratic drug-induced liver injury (DILI) FDA is evaluating the need for regulatory action.

Lamisil (terbinafine hydrochloride) tablets

Terbinafine hydrochloride-containing oral drugs

Thrombotic microangiopathy FDA is evaluating the need for regulatory action.
Tracleer (bosentan) tablets

Anaphylaxis

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

FDA is evaluating the need for regulatory action.

Treanda (bendamustine hydrochloride) infusion

Bendeka (bendamustine hydrochloride) injection

Drug Reaction with Eosinophilia and Systematic Symptoms (DRESS) FDA is evaluating the need for regulatory action.

Treanda (bendamustine hydrochloride) injecton

Bendeka (bendamustine hydrochloride) injection

Hepatic and hepatobiliary disorders FDA is evaluating the need for regulatory action.
Unituxin (dinutuximab) injection for intravenous use Transverse myelitis FDA is evaluating the need for regulatory action.

Vistaril (hydroxyzine pamoate capsules, suspension

Xyzal (levocetirizine dihydrochloride) tablets, solution

Zyrtec (cetirizine hydrochloride) tablets, capsules, Children’s syrup

Acute generalized exanthematous pustulosis (AGEP) FDA is evaluating the need for regulatory action.
Zecuity (sumatriptaniontophoretic) transdermal system Burns and Scars

Teva has temporarily suspended sales, marketing, and distribution to investigate the cause of burns and scars associated with the Zecuity patch.

FDA is continuing to evaluate this issue and the need for regulatory action.

Zecuity Drug Safety Communication (June 10, 2016)

Zydelig (idelalisib) tablets Fatal infections FDA is evaluating the need for regulatory action.

 

Source: FDA

 

More information on FAERS and its quarterly watch lists is available on the FDA website.

Follow Robert Lowes on Twitter @LowesRobert

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