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.
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Cite this: New FDA Watch List Covers 27 Drugs and Drug Classes - Medscape - Oct 04, 2016.
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