USFDA Drug Alerts


অ্যালকোহল ভিত্তিক হ্যান্ড স্যানিটাইজার

এফডিএ সতর্ক করেছে যে অ্যালকোহল ভিত্তিক হ্যান্ড স্যানিটাইজার থেকে বাষ্পের পার্শ্বপ্রতিক্রিয়া হতে পারে। একটি ভাল বায়ুচলাচল এলাকায় হ্যান্ড স্যানিটাইজার প্রয়োগ করুন।


এফডিএ কোন নিরাপত্তা উদ্বেগ ঘোষণা করছে?

ইউএস ফুড অ্যান্ড ড্রাগ অ্যাডমিনিস্ট্রেশন (এফডিএ) সতর্ক করে দিচ্ছে যে ত্বকে অ্যালকোহল-ভিত্তিক হ্যান্ড স্যানিটাইজার প্রয়োগ করার পরে মাথাব্যথা, বমি বমি ভাব এবং মাথা ঘোরা ইত্যাদি লক্ষণ দেখা দিতে পারে। এই লক্ষণগুলি হ্যান্ড স্যানিটাইজার থেকে বাষ্পের কারণে ঘটেছে, সম্ভবত ঘরের মধ্যে বা দুর্বল বায়ু চলাচলের জায়গাগুলিতে এক্সপোজার থেকে।


ভোক্তাদের কি করা উচিত?

ভোক্তাদের একটি ভাল বায়ুচলাচল এলাকায় হ্যান্ড স্যানিটাইজার ব্যবহার করা উচিত। আপনি যদি গাড়ির মতো ঘেরা এলাকায় হ্যান্ড স্যানিটাইজার ব্যবহার করেন, তাহলে হ্যান্ড স্যানিটাইজার শুকানো এবং বাষ্প পরিষ্কার না হওয়া পর্যন্ত বায়ুচলাচল উন্নত করতে একটি জানালা খুলুন। তাপ, স্ফুলিঙ্গ, স্থির বিদ্যুৎ, বা খোলা আগুনের সাথে জড়িত কোন কাজ করার আগে নিশ্চিত করুন যে আপনার হাত সম্পূর্ণ শুকনো এবং বাষ্প পরিষ্কার হয়েছে। ওটিসি ড্রাগ ফ্যাক্টস লেবেলে নির্দেশাবলী এবং সতর্কতাগুলি পড়ুন এবং অনুসরণ করুন।

What safety concern is FDA announcing?

The U.S. Food and Drug Administration (FDA) is warning that symptoms such as headache, nausea, and dizziness can occur after applying alcohol-based hand sanitizers to the skin. These symptoms are likely to have occurred because of vapors from the hand sanitizer, potentially from exposure in enclosed spaces or places with poor air circulation.


What should consumers do?

Consumers should use hand sanitizers in a well-ventilated area. If you are using hand sanitizer in an enclosed area such as a car, open a window to improve ventilation until the hand sanitizer is dry and the vapors have cleared. Make sure your hands are completely dry and vapors have cleared before doing any activities involving heat, sparks, static electricity, or open flames. Read and follow the directions and warnings on the OTC Drug Facts label.


FOR MORE DETAILS, PL SEE THE ATTACHED *pdf.

FDA Drug Safety Communication

FDA requiring Boxed Warning updated to improve safe use of benzodiazepine drug class. Includes potential for abuse, addiction, and other serious risks.


What safety concern is FDA announcing?

To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines. Benzodiazepines are widely used to treat many conditions, including anxiety, insomnia, and seizures. The current prescribing information for benzodiazepines does not provide adequate warnings about these serious risks and harms associated with these medicines so they may be prescribed and used inappropriately. This increases these serious risks, especially when benzodiazepines are used with some other medicines and substances.


Benzodiazepines can be an important treatment option for treating disorders for which these drugs are indicated. However, even when taken at recommended dosages, their use can lead to misuse, abuse, and addiction. Abuse and misuse can result in overdose or death, especially when benzodiazepines are combined with other medicines, such as opioid pain relievers, alcohol, or illicit drugs. Physical dependence can occur when benzodiazepines are taken steadily for several days to weeks, even as prescribed. Stopping them abruptly or reducing the dosage too quickly can result in withdrawal reactions, including seizures, which can be life-threatening.


What should health care professionals do?

When deciding whether the benefits of prescribing a benzodiazepine outweigh the risks, health care professionals should consider the patient’s condition and the other medicines being taken, and assess the risk of abuse, misuse, and addiction. Particular caution should be taken when prescribing benzodiazepines with opioids and other medicines that depress the central nervous system (CNS), which has resulted in serious side effects, including severe respiratory depression and death. Advise patients to seek immediate medical attention if they experience symptoms, such as difficulty breathing.


Limit the dosage and duration of each medicine to the minimum needed to achieve the desired clinical effect when prescribing benzodiazepines, alone or in combination with other medicines. Throughout therapy, monitor the patient for signs and symptoms of abuse, misuse, or addiction. If a substance use disorder is suspected, evaluate the patient and institute, or refer them for, early substance abuse treatment, as appropriate.


To reduce the risk of acute withdrawal reactions, use a gradual taper to reduce the dosage or to discontinue benzodiazepines. No standard benzodiazepine tapering schedule is suitable for all patients; therefore, create a patient-specific plan to gradually reduce the dosage, and ensure ongoing monitoring and support as needed to avoid serious withdrawal symptoms or worsening of the patient’s medical condition.

Take precautions when benzodiazepines are used in combination with opioid addiction medications. Careful medication management by health care professionals can reduce the increased risk of serious side effects.


FOR MORE DETAILS, PL SEE THE ATTACHED *pdf.

FDA removes Boxed Warning about risk of leg and foot amputations for the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR)


Based on a U.S. Food and Drug Administration (FDA) review of new data from three clinical trials, we have removed the Boxed Warning about amputation risk from the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR) prescribing information.


We required the Boxed Warning in 2017 based on our assessment that the risk of amputations was very serious in relation to the potential benefit of canagliflozin, which was initially approved to be used with diet and exercise to lower blood sugar in adults with type 2 diabetes. Subsequent FDA reviews of new clinical trial data demonstrated additional heart- and kidney-related benefits, which led to additional approved uses. Specifically, in 2018, canagliflozin was approved to reduce the risk of major heart-related events such as heart attack, stroke, or death in patients with type 2 diabetes who have known heart disease; and, in 2019, it was approved to reduce the risk of end-stage kidney disease, worsening of kidney function, heart-related death, and being hospitalized for heart failure in certain patients with type 2 diabetes and diabetic kidney disease.


Collectively, these newly identified effects of canagliflozin on heart and kidney disease show significantly enhanced benefit of this medicine. Safety information from recent clinical trials also suggests that the risk of amputation, while still increased with canagliflozin, is lower than previously described, particularly when appropriately monitored. Based upon these considerations, we have concluded that the Boxed Warning should be removed. The amputation risk with canagliflozin remains and is still described in the Warnings and Precautions section of the prescribing information.


Health care professionals and patients should continue to recognize the importance of preventative foot care and monitor for new pain, tenderness, sores, ulcers, and infections in the legs and feet. Risk factors that may predispose patients to the need for amputation should be considered when choosing antidiabetic medicines.


Canagliflozin belongs to a class of medicines called sodium-glucose cotransporter-2 (SGLT2) inhibitors. It lowers blood sugar by causing the kidneys to remove sugar from the body through the urine. Untreated, type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease.


We urge health care professionals and patients to report side effects involving canagliflozin and other medicines to the FDA MedWatch program, using the information in the “Contact FDA”

box at the bottom of the page.


FOR MORE DETAILS, PL. SEE THE ATTACHED *pdf

FDA strengthens warning that untreated constipation caused by schizophrenia medicine clozapine (Clozaril) can lead to serious bowel problems. Risk increased at higher doses or when taken with other constipating medicines


What safety concern is FDA announcing?

The Food and Drug Administration (FDA) is strengthening an existing warning that constipation caused by the schizophrenia medicine clozapine (Clozaril, Fazaclo ODT, Versacloz, generics) can, uncommonly, progress to serious bowel complications. This can lead to hospitalization or even death if constipation is not diagnosed and treated quickly. Constipation is a frequent and known side effect of clozapine, but serious and fatal events continue to be reported.


Clozapine affects how the intestines (bowels) function in the majority of patients. It produces effects ranging from constipation (trouble having a bowel movement), which is a common occurrence, to serious but uncommon bowel problems, including complete blockage of the bowel. We found that because of the way clozapine works this risk is greater with clozapine than with the other schizophrenia medicines in its drug class. The risk is further increased at higher doses of clozapine and when it is co-prescribed with a type of medicine called anticholinergics, which can slow the movement in the intestines, and other medicines that cause constipation, including opioids. Many different kinds of medicines have these anticholinergic effects.


What should patients and caregivers do?

Patients may not feel or be aware of constipation symptoms. However, you should contact your health care professional if your bowel movements are less frequent than normal for you, especially if you do not have a bowel movement at least three times a week, you have hard or dry stools, or you have difficulty passing gas. You should contact your health care professional right away if you have symptoms which can be associated with serious bowel problems such as nausea and vomiting, bloating or belly swelling, or belly pain.


To prevent constipation, you should eat more fruits, vegetables, and grains that are high in fiber; drink plenty of water and other liquids; and get enough exercise. You may also need to take a laxative, so ask a health care professional which type of laxative is right for you. You should not stop taking your clozapine medicine without first talking with your health care professional, as stopping treatment can cause your schizophrenia symptoms to return or worsen.


What should health care professionals do?

Health care professionals should evaluate bowel function before starting a patient on clozapine and avoid co-prescribing clozapine with other anticholinergic medicines that can cause gastrointestinal hypomotility. Advise patients frequently of the significant risk of constipation and life-threatening bowel issues and the need to stay hydrated to prevent constipation.


Question patients about the frequency and quality of their bowel movements throughout treatment. Advise patients to contact a health care professional right away if they have difficulty having a bowel movement or passing stools, do not have a bowel movement at least three times a week or less than their normal frequency, or are unable to pass gas. Monitor patients for symptoms of potential complications associated with gastrointestinal hypomotility such as nausea, abdominal distension or pain, and vomiting. Consider prophylactic laxative treatment when starting clozapine in patients with a history of constipation or bowel obstruction.


FOR MORE DETAILS, PL. SEE THE ATTACHED *pdf

FDA warns about serious problems with high doses of the allergy medicine diphenhydramine (Benadryl). Teen misuse sparked by dangerous “Benadryl Challenge” promoted on social media


The U.S. Food and Drug Administration (FDA) is warning that taking higher than recommended doses of the common over-the-counter (OTC) allergy medicine diphenhydramine (Benadryl) can lead to serious heart problems, seizures, coma, or even death. We are aware of news reports of teenagers ending up in emergency rooms or dying after participating in the “Benadryl Challenge” encouraged in videos posted on the social media application TikTok.


We are investigating these reports and conducting a review to determine if additional cases have been reported. We will update the public once we have completed our review or have more information to share. We also contacted TikTok and strongly urged them to remove the videos from their platform and to be vigilant to remove additional videos that may be posted.


Consumers, parents, and caregivers should store diphenhydramine and all other OTC and prescription medicines up and away and out of children’s reach and sight. FDA recommends you lock up medicines to prevent accidental poisonings by children and misuse by teens, especially when they are home more often due to the COVID-19 pandemic and may be more likely to experiment.


Always read the Drug Facts label included on all OTC medicines to find out if they contain diphenhydramine, how much and how often you should take them, and important safety information. Do not take more than the dose listed on the label, as doing so can cause serious problems. If someone takes too much diphenhydramine and is hallucinating, can’t be awakened, has a seizure, has trouble breathing, or has collapsed, immediately get medical attention or contact poison control at 1-800-222-1222 or online.


Health care professionals should be aware that the “Benadryl Challenge” is occurring among teens and alert their caregivers about it. Encourage teens and caregivers to read and follow the Drug Facts label. In the event of an overdose, health care professionals should attempt to determine whether a patient with a suspected overdose took diphenhydramine.


Diphenhydramine is an antihistamine used to temporarily relieve symptoms due to hay fever, upper respiratory allergies, or the common cold, such as runny nose and sneezing. It works by blocking histamine in the body, which is a substance that causes allergic symptoms. When used as recommended, it is a safe and effective medicine. Diphenhydramine is marketed under the brand-name Benadryl, store brands, and generics. It is also available in combination with pain relievers, fever reducers, and decongestants.


We urge health care professionals and consumers to report side effects involving diphenhydramine and other medicines to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page.

FDA warns about serious breathing problems when Gabapentin is used with CNS depressants or in patients with lung problems. The elderly are also at higher risk for this difficulty. CNS depressants include opioids, anti-anxiety medicines, antidepressants and antihistamines.


FDA Drug Safety Communication FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems.


What safety concern is FDA announcing?

The FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin and other QT prolonging medicines. We are also aware of increased use of these medicines through outpatient prescriptions. Therefore, we would like to remind health care professionals and patients of the known risks associated with both hydroxychloroquine and chloroquine. FDA will continue to investigate risks associated with the use of hydroxychloroquine and chloroquine for COVID-19 and communicate publicly when we have more information.


Hydroxychloroquine and chloroquine have not been shown to be safe and effective for treating or preventing COVID-19. They are being studied in clinical trials for COVID-19, and we authorized their temporary use during the COVID-19 pandemic for treatment of the virus in hospitalized patients when clinical trials are not available, or participation is not feasible, through an Emergency Use Authorization (EUA). The medicines being used under the hydroxychloroquine/chloroquine EUA are supplied from the Strategic National Stockpile, the national repository of critical medical supplies to be used during public health emergencies. This safety communication reminds physicians and the public of risk information set out in the hydroxychloroquine and chloroquine healthcare provider fact sheets that were required by the EUA.


Hydroxychloroquine and chloroquine can cause abnormal heart rhythms such as QT interval prolongation and a dangerously rapid heart rate called ventricular tachycardia. These risks may increase when these medicines are combined with other medicines known to prolong the QT interval, including the antibiotic azithromycin, which is also being used in some COVID-19 patients without FDA approval for this condition. Patients who also have other health issues such as heart and kidney disease are likely to be at increased risk of these heart problems when receiving these medicines.


What should patients and parents/caregivers do?

Patients taking hydroxychloroquine or chloroquine for FDA-approved indications to treat malaria or autoimmune conditions should continue taking their medicine as prescribed. The benefits of these medicines outweigh the risks at the recommended doses for these conditions. Do not stop taking your medicine without first talking to your health care professional, and talk to them if you have any questions or concerns.

Be aware that there are no proven treatments for COVID-19 and no vaccine. If you are receiving hydroxychloroquine or chloroquine for COVID-19 and experience irregular heartbeats, dizziness, or fainting, seek medical attention right away.


Do not buy these medicines from online pharmacies without a prescription from your health care professional. Consumers should not take any form of chloroquine that has not been prescribed for them by a healthcare professional. Serious poisoning and death have been reported after mistaken use of a chloroquine product not intended to be taken by humans. If you have these medicines in your home, keep them in childproof containers out of the reach of children to prevent accidental poisoning.


What should health care professionals do?

We recommend initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials that investigate these medicines for the treatment or prevention of COVID-19. Monitoring may include baseline ECG, electrolytes, renal function and hepatic tests. Be aware that hydroxychloroquine or chloroquine can:


• cause QT prolongation

• increase the risk of QT prolongation in patients with renal insufficiency or failure

• increase insulin levels and insulin action causing increased risk of severe hypoglycemia

• cause hemolysis in patients with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency

• interact with other medicines that cause QT prolongation even after discontinuing the medicines due to their long half-lives of approximately 30-60 days


If a healthcare professional is considering use of hydroxychloroquine or chloroquine to treat or prevent COVID-19, FDA recommends checking www.clinicaltrials.gov for a suitable clinical trial and consider enrolling the patient. Consider using resources available to assess a patient’s risk of QT prolongation and mortality.


FOR MORE DETAILS, PL. SEE THE ATTACHED *pdf

FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Approved uses also being limited to certain patients.


What safety concern is FDA announcing?

Based on a completed U.S. Food and Drug Administration (FDA) review of a large randomized safety clinical trial, we have concluded there is an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death with the arthritis and ulcerative colitis medicines Xeljanz and Xeljanz XR (tofacitinib). This trial compared Xeljanz with another type of medicine used to treat arthritis called tumor necrosis factor (TNF) blockers in patients with rheumatoid arthritis. The trial’s final results also showed an increased risk of blood clots and death with the lower dose of Xeljanz. A prior DSC based upon earlier results from this trial, reported an increased risk of blood clots and death only seen at the higher dose.


We are requiring new and updated warnings for two other arthritis medicines in the same drug class as Xeljanz, called Janus kinase (JAK) inhibitors, Olumiant (baricitinib) and Rinvoq (upadacitinib). Olumiant and Rinvoq have not been studied in trials similar to the large safety clinical trial with Xeljanz, so the risks have not been adequately evaluated. However, since they share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial.


Two other JAK inhibitors, Jakafi (ruxolitinib) and Inrebic (fedratinib), are not indicated for the treatment of arthritis and other inflammatory conditions and so are not a part of the updates being required to the prescribing information for Xeljanz, Xeljanz XR, Olumiant, and Rinvoq. Jakafi and Inrebic are used to treat blood disorders and require different updates to their prescribing information. If FDA becomes aware of any additional safety information or data that warrants updates to the prescribing information for these medicines, we may take further action and will alert the public.


What should patients do?

Those taking Xeljanz/Xeljanz XR, Olumiant, or Rinvoq should tell your health care professional if you are a current or past smoker, or have had a heart attack, other heart problems, stroke, or blood clots in the past as these may put you at higher risk for serious problems with the medicines. Patients starting these medicines should also tell your health care professional about these risk factors. Seek emergency help right away if you have any symptoms that may signal a heart attack, stroke, or blood clot, including:


o Discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back

o Severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw

o Unusual pain or discomfort in your arms, back, neck, jaw, or stomach

o Shortness of breath with or without chest discomfort

o Breaking out in a cold sweat

o Nausea or vomiting

o Feeling lightheaded

o Weakness in one part or on one side of your body

o Slurred speech

o Drooping on one side of your mouth

o Swelling of a leg or arm

o Leg pain or tenderness, or red or discolored skin in the painful or swollen leg or arm


Treatment with these medicines is associated with an increased risk of certain cancers including lymphoma and lung cancer, so inform your health care professional if you experience signs and symptoms such as swelling of lymph nodes in your neck, armpits, or groin; constantly feeling tired; fever; night sweats; persistent or worsening cough; difficulty breathing; hoarseness or wheezing; or unexplained weight loss. Talk to your health care professional if you have any questions or concerns.


What should health care professionals do?

Health care professionals should consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Xeljanz/Xeljanz XR, Olumiant, or Rinvoq. This is particularly the case in patients who are current or past smokers, those with other cardiovascular risk factors, those who develop a malignancy, and those with a known malignancy other than a successfully treated nonmelanoma skin cancer. Reserve these medicines for patients who have had an inadequate response or intolerance to one or more TNF blockers. Counsel patients about the benefits and risks of these medicines and advise them to seek emergency medical attention if they experience signs and symptoms of a heart attack, stroke, or blood clot.


FOR MORE DETAILS, PL SEE THE ATTACHED *pdf.

Studies show increased risk of heart rhythm problems with seizure and mental health medicine lamotrigine (Lamictal) in patients with heart disease


Safety Announcement

A U.S. Food and Drug Administration (FDA) review of study findings showed a potential increased risk of heart rhythm problems, called arrhythmias, in patients with heart disease who are taking the seizure and mental health medicine lamotrigine (Lamictal). We want to evaluate whether other medicines in the same drug class have similar effects on the heart and are requiring safety studies on those also. We will update the public when additional information from these studies becomes available.


FDA required these studies, called in vitro studies, to further investigate Lamictal’s effects on the heart after we received reports of abnormal electrocardiographic (ECG) findings and some other serious problems. In some cases, problems including chest pain, loss of consciousness, and cardiac arrest occurred. In vitro studies are studies done in test tubes or petri dishes and not in people or animals. We first added information about this risk to the lamotrigine prescribing information and Medication Guides in October 2020, which we have updated.


Lamotrigine is used alone or with other medicines to treat seizures in patients 2 years and older. It may also be used as maintenance treatment in patients with the mental health condition bipolar disorder to help delay the occurrence of mood episodes such as depression, mania, or hypomania. Lamotrigine has been approved and on the market for more than 25 years and is available under the brand name Lamictal and as generics.


Patients should not stop taking your medicine without first talking to your prescriber because stopping lamotrigine can lead to uncontrolled seizures, or new or worsening mental health problems. Contact your health care professional right away or go to an emergency room if you experience an abnormal heart rate or irregular rhythm, or symptoms such as a racing heartbeat, skipped or slow heartbeat, shortness of breath, dizziness, or fainting.


Health care professionals should assess whether the potential benefits of lamotrigine outweigh the potential risk of arrhythmias for each patient. Laboratory testing performed at therapeutically relevant concentrations has shown that lamotrigine can increase the risk of serious arrhythmias, which can be life-threatening, in patients with clinically important structural or functional heart disorders. Clinically important structural and functional heart disorders include heart failure, valvular heart disease, congenital heart disease, conduction system disease, ventricular arrhythmias, cardiac channelopathies such as Brugada syndrome, clinically important ischemic heart disease, or multiple risk factors for coronary artery disease. The risk of arrhythmias may increase further if used in combination with other medicines that block sodium channels in the heart. Other sodium channel blockers approved for epilepsy, bipolar disorder, and other indications should not be considered safer alternatives to lamotrigine in the absence of additional information (see List of Sodium Channel Blockers Required to Conduct Postmarket Studies).


We previously communicated safety information associated with lamotrigine in April 2018 (serious immune system reaction), August 2010 (aseptic meningitis warning), and September 2006 (possible association between Lamictal exposure during pregnancy and oral clefts in newborns). Lamotrigine was also covered as part of a May 2009 safety alert concerning suicidal thoughts and behavior with the entire class of anti-seizure medicines.

All medicines have side effects even when used correctly as prescribed. It is important to know that people respond differently to all medicines depending on their health, the diseases they have, genetic factors, other medicines they are taking, and many other factors. As a result, we cannot determine how likely it is that someone will experience these side effects when taking lamotrigine. Your health care professionals know you best, so talk to them if you have questions or concerns.


FOR MORE INFORMATION, PL. CHECK THE ATTACHED *pdf.

FDA requests the withdrawal of the weight-loss drug Belviq, Belviq XR (lorcaserin) from the market


What safety concern is FDA announcing?

The U.S. Food and Drug Administration (FDA) has requested that the manufacturer of Belviq, Belviq XR (lorcaserin) voluntarily withdraw the weight-loss drug from the U.S. market because a safety clinical trial shows an increased occurrence of cancer. The drug manufacturer, Eisai Inc,. has submitted a request to voluntarily withdraw the drug.


What should patients do?

Patients should stop taking lorcaserin and talk to your health care professionals about alternative weight-loss medicines and weight management programs. It’s best to dispose of unused lorcaserin using a drug take back location, but if you can’t get to one you can dispose of lorcaserin in your household trash:


1. Mix the pills with an unappealing substance such as dirt, cat litter, or used coffee grounds; do not crush them.

2. Place the mixture in a container such as a sealed plastic bag.

3. Throw away the container in your trash at home.

4. Remove or delete all personal information on the prescription label of empty medicine bottles or packaging, then throw away or recycle them.


FDA is not recommending special screening for patients who have taken lorcaserin. Talk to your health care professional if you have questions.


What should health care professionals do?

Health care professionals should stop prescribing and dispensing lorcaserin to patients. Contact patients currently taking lorcaserin, inform them of the increased occurrence of cancer seen in the clinical trial, and ask them to stop taking the medicine. Discuss alternative weight-loss medicines or strategies with your patients.

FDA is not recommending special screening for patients who have taken lorcaserin. As with any individual patient, regardless of prior lorcaserin treatment, standard screening recommendations for cancer should be implemented.

FDA requires Boxed Warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis.


What safety concern is FDA announcing?

The U.S. Food and Drug Administration (FDA) is strengthening existing warnings about serious behavior and mood-related changes with montelukast (Singulair and generics), which is a prescription medicine for asthma and allergy.


We are taking this action after a review of available information led us to reevaluate the benefits and risks of montelukast use. Montelukast prescribing information already includes warnings about mental health side effects, including suicidal thoughts or actions; however, many health care professionals and patients/caregivers are not aware of the risk. We decided a stronger warning is needed after conducting an extensive review of available information and convening a panel of outside experts, and therefore determined that a Boxed Warning was appropriate.


Because of the risk of mental health side effects, the benefits of montelukast may not outweigh the risks in some patients, particularly when the symptoms of disease may be mild and adequately treated with other medicines. For allergic rhinitis, also known as hay fever, we have determined that montelukast should be reserved for those who are not treated effectively with or cannot tolerate other allergy medicines. For patients with asthma, we recommend that health care professionals consider the benefits and risks of mental health side effects before prescribing montelukast.


What should patients and parents/caregivers do?

Patients and parents/caregivers should stop montelukast and discuss with a health care professional right away if you or your child experience behavior or mood-related changes while taking the medicine. These may include:


• agitation, including aggressive behavior or hostility

• attention problems

• bad or vivid dreams

• depression

• disorientation or confusion

• feeling anxious

• hallucinations (seeing or hearing things that are not really there)

• irritability

• memory problems

• obsessive-compulsive symptoms

• restlessness

• sleepwalking

• stuttering

• suicidal thoughts and actions

• tremor or shakiness

• trouble sleeping

• uncontrolled muscle movements


You should take montelukast for allergic rhinitis or hay fever only if you cannot tolerate other medicines or they do not work for you. Many other safe and effective allergy medicines are widely available, including over-the-counter medicines without a prescription. These include antihistamines such as loratadine (Alavert, Claritin), fexofenadine (Allegra), cetirizine (Zyrtec), levocetirizine (Xyzal), and diphenhydramine (Benadryl), as well as steroid nasal sprays such as fluticasone (Flonase), triamcinolone (Nasacort), and budesonide (Rhinocort).


Alternatively, allergy shots have been shown to decrease symptoms of allergic rhinitis. Talk to your pharmacist or health care professional for help deciding which might be best.


What should health care professionals do?

Health care professionals should consider the risks and benefits of montelukast when deciding to prescribe or continue patients on the medicine. Counsel all patients receiving montelukast about mental health side effects, and advise them to stop the medicine and contact a health care professional immediately if they develop any symptoms included but not limited to those listed in the table above. Be aware that some patients have reported neuropsychiatric events after discontinuation of montelukast.

Only prescribe montelukast for allergic rhinitis in patients who have an inadequate response or intolerance to alternative therapies.


FOR MORE INFORMATION, PL. SEE THE ATTACHED *pdf

FDA recommends health care professionals discuss naloxone with all patients when prescribing opioid pain relievers or medicines to treat opioid use disorder


What safety concern is FDA announcing?

To reduce the risk of death from opioid overdose, the U.S. Food and Drug Administration (FDA) is making the following recommendations about the opioid reversal medicine, naloxone:


For all patients who are prescribed opioid pain relievers, health care professionals should discuss the availability of naloxone, and consider prescribing it to patients who are at increased risk of opioid overdose, such as patients who are also using benzodiazepines or other medicines that depress the central nervous system, who have a history of opioid use disorder (OUD), or who have experienced a previous opioid overdose. Health care professionals should also consider prescribing naloxone if the patient has household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose.


For all patients who are prescribed medicines to treat OUD, health care professionals should discuss the availability of naloxone and strongly consider prescribing it. For methadone and buprenorphine-containing products, health care professionals should also consider prescribing naloxone if the patient has household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose.


For other patients at increased risk of opioid overdose, health care professionals should consider prescribing naloxone, even if the patient is not receiving a prescription for an opioid pain reliever or medicine to treat OUD. This may include people with a current or past diagnosis of OUD or who have experienced a previous opioid overdose.


Opioid pain relievers are medicines that can help manage pain when other treatments and medicines are not able to provide enough pain relief. Certain opioids are also used to treat OUD. Opioids have serious risks, including misuse and abuse, addiction, overdose, and death. Naloxone can help reverse opioid overdose to prevent death.


What should health care professionals do?

Routinely discuss the availability of naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat OUD. Consider prescribing naloxone to patients prescribed medicines to treat OUD and patients prescribed opioid analgesics who are at increased risk of opioid overdose. Patients receiving medicines to treat OUD have a lower risk of opioid overdose than those with OUD who are not being treated; however, they are still at risk of relapse and opioid overdose. Also, consider prescribing naloxone when a patient has household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose.


Additionally, even if the patients are not receiving a prescription for an opioid analgesic or medicine to treat OUD, consider prescribing naloxone to them if they are at increased risk of opioid overdose.


Educate patients and caregivers on how to recognize respiratory depression and how to administer naloxone. Inform them about their options for obtaining naloxone as permitted by their individual state dispensing and prescribing requirements or guidelines for naloxone. Emphasize the importance of calling 911 or getting emergency medical help right away, even if naloxone is administered.


What should patients and caregivers do?

Talk to your health care professionals about the benefits of naloxone and how to obtain it. Your health care professional can give you a prescription for naloxone. Additionally, in most states and the District of Columbia, you can obtain naloxone from a pharmacy under a standing order that takes the place of an individual prescription. Some states also allow you to obtain naloxone without a prescription from a community-based program or pharmacy. Check with your state Health Department for more information.


Recognize the signs and symptoms of a possible opioid overdose. These include slowed, shallow, or difficult breathing, severe sleepiness, or not being able to respond or wake up. If you know or think someone is overdosing, give the person naloxone if you have access to it, and always call 911 or go to an emergency room right away. Naloxone is a temporary treatment, so repeat doses may be required. Even if you give naloxone, you still need to get emergency medical help right away.


If you have naloxone, make sure to tell your caregivers, household members, and other close contacts that you have it, where it is stored, and how to properly use it in the event of an overdose. When using opioid medicines away from home, carry naloxone with you and let those you are with know you have it, where it is, and how to use it. Read the Patient Information leaflet or other educational material and Instructions for Use that comes with your naloxone because it explains important information, including how to use the medicine. It is important to do this before an emergency happens, so you and others know what to do.


FOR MORE DETAILS, PL. SEE THE ATTACHED *pdf

FDA recommends avoiding use of NSAIDs in pregnancy at 20 weeks or later because they can result in low amniotic fluid


What safety concern is FDA announcing?

The U.S. Food and Drug Administration (FDA) is warning that use of nonsteroidal anti-inflammatory drugs (NSAIDs) around 20 weeks or later in pregnancy may cause rare but serious kidney problems in an unborn baby. This can lead to low levels of amniotic fluid surrounding the baby and possible complications. NSAIDs are commonly used to relieve pain and reduce fevers. They include medicines such as aspirin, ibuprofen, naproxen, diclofenac, and celecoxib. After around 20 weeks of pregnancy, the unborn babies’ kidneys produce most of the amniotic fluid, so kidney problems can lead to low levels of this fluid. Amniotic fluid provides a protective cushion and helps the unborn babies’ lungs, digestive system, and muscles develop.


Although this safety concern is well known among certain medical specialties, we wanted to communicate our recommendations more widely to educate other health care professionals and pregnant women. This issue affects all NSAIDs that are available by prescription and those that can be bought over-the-counter (OTC) without a prescription.


What should pregnant women do?

Pregnant women should not use NSAIDs at 20 weeks or later unless specifically advised to do so by your health care professional because these medicines may cause problems in your unborn baby. Talk with your health care professional about the benefits and risks of these medicines during pregnancy before using them, especially at 20 weeks or later. Because many OTC medicines contain NSAIDs, it is important to read the Drug Facts labels to find out if the medicines contain NSAIDs. If you are unsure if a medicine contains NSAIDs, ask a pharmacist or health care professional for help.


Other medicines, such as acetaminophen, are available to treat pain and fever during pregnancy. Talk to your pharmacist or health care professional for help deciding which might be best.


What should health care professionals do?

We recommend that health care professionals should limit prescribing NSAIDs between 20 to 30 weeks of pregnancy and avoid prescribing them after 30 weeks of pregnancy. If NSAID treatment is determined necessary, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours and discontinue the NSAID if oligohydramnios is found.



FOR MORE DETAILS, PL. SEE THE ATTACHED *pdf

Due to risk of serious liver injury, FDA restricts use of Ocaliva (obeticholic acid) in primary biliary cholangitis (PBC) patients with advanced cirrhosis


What safety concern is FDA announcing?

The U.S. Food and Drug Administration (FDA) is restricting the use of the liver disease medicine Ocaliva (obeticholic acid) in patients having primary biliary cholangitis (PBC) with advanced cirrhosis of the liver because it can cause serious harm. PBC is a rare, chronic disease affecting the ducts in the liver that carry bile, which helps with digestion. Some PBC patients with cirrhosis who took Ocaliva, especially those with evidence of advanced cirrhosis, developed liver failure, sometimes requiring liver transplant.


Based on the original clinical trials, FDA believes the benefits of Ocaliva outweigh the risks for PBC patients who do not have advanced cirrhosis. We will continue to monitor and evaluate the clinical benefit and adverse events of Ocaliva and will communicate any new information to the public if it becomes available.


What should patients and parents/caregivers do?

Patients with PBC who have cirrhosis and are taking Ocaliva should talk to your health care professional about these new warnings. Contact your prescriber immediately if you develop any of the following symptoms, which may be signs of worsening liver injury or development of advanced cirrhosis:


Any of these specific symptoms


• Swollen belly

• Yellow eyes or skin

• Bloody or black stools

• Coughing up or vomiting blood

• Mental status changes such as confusion, slurred speech, mood swings, changes in personality, or increased sleepiness or difficulty waking up


Any of these general symptoms if they are severe or do not go away after a few days


• Belly pain

• Nausea, vomiting, or diarrhea

• Loss of appetite or weight loss

• New or worsening tiredness

• Weakness

• Fever and chills

• Lightheadedness

• Less frequent urination


What should health care professionals do?

Health care professionals should determine before starting Ocaliva whether a patient with PBC has advanced cirrhosis as the medicine is contraindicated in these patients. Advanced cirrhosis is defined as cirrhosis with current or prior evidence of hepatic decompensation (e.g., encephalopathy, coagulopathy) or portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia). Routinely monitor patients during Ocaliva treatment for progression of PBC with laboratory and clinical assessments to determine whether the medicine needs to be discontinued. Permanently discontinue Ocaliva in patients with cirrhosis who progress to advanced cirrhosis.


Also monitor patients for clinically significant liver-related adverse reactions that may manifest as development of acute-on-chronic liver disease with nausea, vomiting, diarrhea, jaundice, scleral icterus, and/or dark urine. Permanently discontinue Ocaliva in patients developing these symptoms.


FOR MORE INFORMATION, PL. CHECK THE ATTACHED *pdf.





What safety concern is FDA announcing?

The U.S. Food and Drug Administration (FDA) is warning that serious breathing difficulties may occur in patients using gabapentin (Neurontin, Gralise, Horizant) or pregabalin (Lyrica, Lyrica CR) who have respiratory risk factors. These include the use of opioid pain medicines and other drugs that depress the central nervous system, and conditions such as chronic obstructive pulmonary disease (COPD) that reduce lung function. The elderly are also at higher risk. Gabapentin and pregabalin are FDA-approved for a variety of conditions, including seizures, nerve pain, and restless legs syndrome. Our evaluation shows that the use of these medicines, often referred to as gabapentinoids, has been growing for prescribed medical use, as well as misuse and abuse. Gabapentinoids are often being combined with CNS depressants, which increases the risk of respiratory depression. CNS depressants include opioids, anti-anxiety medicines, antidepressants, and antihistamines. There is less evidence supporting the risk of serious breathing difficulties in healthy individuals taking gabapentinoids alone. We will continue to monitor these medicines as part of our routine monitoring of all FDAapproved drugs.


What is FDA doing?

We are requiring new warnings about the risk of respiratory depression to be added to the prescribing information of the gabapentinoids. We have also required the drug manufacturers to conduct clinical trials to further evaluate their abuse potential, particularly in combination with opioids, because misuse and abuse of these products together is increasing, and co-use may increase the risk of respiratory depression. Special attention will be paid to the respiratory depressant effects during this abuse potential evaluation. What are gabapentinoids and how can they help me? Gabapentinoids are FDA-approved to treat a variety of conditions including partial seizures and nerve pain from spinal cord injury, shingles, and diabetes. Other approved uses include fibromyalgia and restless legs syndrome. Gabapentin was first approved in 1993 and pregabalin was first approved in 2004. Gabapentin is marketed under the brand names Neurontin and Gralise, and also as generics. Gabapentin enacarbil is marketed under the brand name Horizant. Pregabalin is marketed under the brand names Lyrica and Lyrica CR, and also as generics. Pregabalin is a Schedule V controlled substance, which means it has a lower potential for abuse among the drugs scheduled by the Drug Enforcement Administration (DEA), but may lead to some physical or psychological dependence.


What should patients and caregivers do?

Patients and caregivers should seek medical attention immediately if you or someone you are caring for experiences symptoms of respiratory problems, because these can be lifethreatening. Symptoms to watch for include:

• Confusion or disorientation

• Unusual dizziness or lightheadedness

• Extreme sleepiness or lethargy

• Slowed, shallow, or difficult breathing

• Unresponsiveness, which means a person doesn’t answer or react normally or you can’t wake them up

• Bluish-colored or tinted skin, especially on the lips, fingers, and toes


Always inform your health care professional about all the drugs you are taking, including prescription and over-the-counter (OTC) medicines and other substances such as alcohol. What should health care professionals do? Health care professionals should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when co-prescribing gabapentinoids with an opioid or other central nervous system (CNS) depressant such as a benzodiazepine. Patients with underlying respiratory disease and elderly patients are also at increased risk and should be managed similarly. We recognize that incorporating one or more medications with non-drug therapies is the prevailing approach for optimizing analgesia. However, pairing an opioid with any CNS depressant – a gabapentinoid, benzodiazepine, sedating antidepressant, sedating antipsychotic, antihistamine, or other product – will increase the risk of respiratory depression. Shifting treatment from one CNS depressant to another may pose similar risks. Be aware of the potential additive effects of all these CNS depressants and plan accordingly, by starting with low doses, titrating carefully, and informing patients of the potential for CNS and respiratory depression and their symptoms. The gabapentinoid prescribing information already includes guidance for health care professionals to caution patients about dizziness, somnolence, and the potential for impaired ability to operate a car or complex machinery.


What did FDA find?

We reviewed several sources of data, including case reports submitted to FDA or published in the medical literature, observational studies, clinical trials, and animal studies. Reports submitted to FDA and data from the medical literature show that serious breathing difficulties can occur when gabapentinoids are taken by patients with preexisting respiratory risk factors.1-6, 8 Among 49 case reports submitted to FDA over the 5-year period from 2012 to 2017, 12 people died from respiratory depression with gabapentinoids, all of whom had at least one risk factor. This number includes only reports submitted to FDA,* so there may be additional cases about which we are unaware. We also reviewed the results of two randomized, double-blind, placebo-controlled clinical trials in healthy people, three observational studies, and several studies in animals. One trial showed that using pregabalin alone and using it with an opioid pain reliever can depress breathing function.7,8 The other trial showed gabapentin alone increased pauses in breathing during sleep. The three observational studies at one academic medical center showed a relationship between gabapentinoids given before surgery and respiratory depression occurring after different kinds of surgeries.9-11 We also reviewed several animal studies that showed pregabalin alone and pregabalin plus opioids can depress respiratory function.12-14 * The cases were reported to the FDA Adverse Event Reporting System (FAERS) database. What is my risk? All medicines have side effects even when used correctly as prescribed, but in general the benefits of taking a medicine outweigh these risks. It is important to know that people respond differently to all medicines depending on their health, other medicines they are taking, the diseases they have, genetics, and many other factors. As a result, we cannot determine the likelihood that someone will experience these side effects when taking gabapentinoids. Your personal health care professional knows you best, so always tell them about all other medicines you are taking and if you experience any side effects while taking your medicines. How do I report side effects from gabapentinoids? To help FDA track safety issues with medicines, we urge patients and health care professionals to report side effects involving gabapentin, pregabalin, or other medicines to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page. Facts about Gabapentinoids • Gabapentinoids include gabapentin and pregabalin. They are FDA-approved to treat a variety of conditions including partial seizures; pain from damaged nerves that follows spinal cord injury, healing of shingles, or diabetes; fibromyalgia; and moderate to severe primary restless legs syndrome. • Gabapentin is marketed under the brand names Neurontin and Gralise, and as generics. Gabapentin enacarbil is a prodrug of gabapentin marketed under the brand name Horizant. o Gabapentin is not scheduled by the Drug Enforcement Administration (DEA) as a controlled substance. A human abuse liability evaluation was not conducted when gabapentin was developed in the 1980s and early 1990s. o Gabapentin is available as a tablet, capsule, solution, and extended-release tablet. • Pregabalin is marketed under the brand names Lyrica and Lyrica CR, and as generics. o Pregabalin is a Schedule V controlled substance, which means that among the drugs scheduled by the DEA because of their abuse potential, it has a lower potential for abuse but may lead to some physical or psychological dependence. o Pregabalin is available as a capsule, solution, and extended-release tablet. • Common side effects of gabapentinoids include drowsiness, dizziness, blurry or double vision, difficulty with coordination and concentration, and swelling of the hands, legs, and feet. Additional Information for Patients and Caregivers • FDA is warning that serious breathing difficulties may occur when gabapentin (Neurontin, Gralise, Horizant) or pregabalin (Lyrica, Lyrica CR) is taken with other medicines that depress the central nervous system (CNS) such as opioids, in those patients who have underlying respiratory problems, or in the elderly. There is less evidence supporting the risk of serious breathing difficulties with gabapentinoids alone in otherwise healthy individuals, and we will continue to monitor this population for additional evidence. • Respiratory problems can be life-threatening, so seek medical attention immediately if you or someone you are caring for experiences the following symptoms: o Confusion or disorientation o Unusual dizziness or lightheadedness o Extreme sleepiness o Slowed, shallow, or difficult breathing o Unresponsiveness, which means the person doesn’t answer or react normally or you can’t wake them up o Bluish-colored or tinted skin, especially on the lips, fingers, and toes • Always take gabapentinoids as prescribed. Do not take more of the medicine or take it more often than prescribed because doing so can cause serious problems or death. • Always tell all your health care professionals about all the medicines you are taking, including prescription and over-the-counter (OTC) medicines. It is helpful to keep a list of all your current medicines in your wallet or another location where it is easily retrieved. You can fill out and print a copy of My Medicine Record. • Read the patient Medication Guide every time you receive a prescription for a gabapentinoid. The Medication Guide will be updated with new or other important information about your medicine. The Medication Guide explains the important things that you need to know. These include the side effects, what the medicine is used for, interactions with other medicines, how to take and store it properly, and other things to watch out for when you are taking the medicine. • Talk to your health care professional if you have any questions or concerns. • To help FDA track safety issues with medicines, report side effects from gabapentin, pregabalin, or other medicines to the FDA MedWatch program, using the information in the "Contact FDA" box at the bottom of this page. Additional Information for Health Care Professionals • FDA is warning that serious, life-threatening, and fatal respiratory depression has been reported with the gabapentinoids, gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR). Most cases occurred in association with coadministered central nervous system (CNS) depressants, especially opioids, in the setting of underlying respiratory impairment, or in the elderly. • Our evaluation of respiratory depression with the gabapentinoids provides some evidence contrary to the widely held belief that gabapentinoids lack drug interactions and have wide therapeutic indices. Published studies demonstrate these drugs can behave in an additive way to potentiate central nervous system (CNS) and respiratory depression. • When co-prescribing gabapentinoids with another CNS depressant, particularly an opioid, or in patients with underlying respiratory impairment, initiate the gabapentinoid at the lowest dose. • Adjust the dose of both gabapentin and pregabalin in patients with renal impairment and patients undergoing hemodialysis, because both drugs are excreted by the kidneys. • Monitor for symptoms of respiratory depression and sedation, especially when coprescribing gabapentinoids with an opioid or other CNS depressant such as a benzodiazepine or when prescribing to patients with underlying respiratory impairment, or elderly patients. • The management of respiratory depression may include close observation, supportive measures, and reduction or withdrawal of CNS depressants, including the gabapentinoid. Gabapentinoids used for analgesia or seizure control should be tapered prior to discontinuation. See the prescribing information for specific tapering guidance. • Encourage patients to read the Medication Guide they receive with each gabapentinoid prescription, which explains the safety risks and provides other important information. • To help FDA track safety issues with medicines, report adverse events involving gabapentin, pregabalin, or other medicines to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of this page. Data Summary We reviewed several sources of data including case reports submitted to FDA or published in the medical literature, observational studies, human trials, and animal studies. Gabapentinoids are increasingly being prescribed for medical uses, and misuse and abuse of these medications are growing. Between 2012 and 2016, the number of patients who filled a gabapentin prescription increased from 8.3 million to 13.1 million annually, and the number of patients who filled a pregabalin prescription increased from 1.9 million to 2.1 million annually.16 Gabapentinoids are commonly co-administered with opioids for prescribed medical uses and abused in combination with opioids. Data collected in 2016 from an office-based physician survey showed that 14 percent and 19 percent of patient encounters involving gabapentin and pregabalin, respectively, also involved opioids.17 Several small cross-sectional studies suggest that in the U.S. and Europe, approximately 15 percent to 26 percent of patients with opioid use disorder (OUD) concomitantly misuse or abuse gabapentin, and approximately 7 percent to 21 percent of patients with OUD concomitantly misuse or abuse pregabalin. However, these studies were small, so the prevalence estimates may not be generalizable to all populations of patients with OUD.17-22 We reviewed data from the FDA Adverse Event Reporting System (FAERS) database and the medical literature1-6 which show that respiratory depression can occur when gabapentinoids are administered in combination with opioids or other central nervous system (CNS) depressants or in patients with underlying respiratory impairment. A small number of reports were in patients only on gabapentinoids. A search of FAERS from January 1, 2012, to October 26, 2017, identified 49 cases of respiratory depression with gabapentinoids. Fifteen cases were reported with gabapentin and 34 cases with pregabalin. Ninety-two percent of the cases reported either a respiratory risk factor, including age-related loss of lung function, or the use of a CNS depressant. Twenty-four percent of the cases resulted in death (n=12). All 12 death cases reported at least one risk factor for developing respiratory depression or concomitant use of a CNS depressant. Several small randomized trials of healthy volunteers showed that gabapentinoids alone and in combination with opioids depress respiratory function. Myhre et al.7 conducted a small randomized, double-blind, placebo-controlled cross-over trial in 12 healthy volunteers exposed to placebo, pregabalin alone, the opioid remifentanil alone, or a combination of pregabalin plus remifentanil. End-tidal CO2 rose with exposure to the drugs together in an additive way. Piovezan and colleagues8 carried out a small randomized, double-blind, placebo-controlled cross-over trial of eight healthy volunteers. The subjects were older non-obese men without sleep complaints or sleep apnea. Subjects were given a single dose of gabapentin or placebo followed by a sleep study. After a washout period, subjects were again given a single dose of treatment (crossing over to the alternate treatment) followed by another sleep study. The number of hourly apneic episodes during gabapentin exposure exceeded those during placebo exposure. Observational studies suggest that patients exposed to preoperative gabapentinoids have an increased risk of postoperative respiratory depression compared to those not exposed to gabapentinoids preoperatively. A Mayo Clinic research group published a case-control study describing the relationship between preoperative gabapentin exposure and the risk of postoperative respiratory depression in more than 11,000 arthroplasty patients.9 They defined respiratory depression as apnea, hypopnea, oxyhemoglobin desaturation, or an episode of severe pain despite moderate to profound sedation (i.e., “pain-sedation” mismatch) during recovery in the postanesthesia care unit. In this study, when compared to patients not exposed to preoperative gabapentin, the risk of respiratory depression was increased 60 percent for patients using regional anesthesia (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.27, 2.02) and 47 percent for those using general anesthesia (OR 1.47, 95% CI 1.26, 1.70) when the preoperative anesthesia regimen included gabapentin doses greater than 300 mg. This same research group conducted another case-control study describing the relationship between preoperative gabapentin exposure and the risk of postoperative respiratory depression in more than 8,000 laparoscopy patients.10 Respiratory depression was defined as apnea, hypopnea, oxyhemoglobin desaturation, pain-sedation mismatch, naloxone administration, failure to extubate, need to reintubate, or non-invasive positive pressure ventilation (NIPPV) use in patients who were not previously prescribed such a device. In this study, preoperative gabapentin increased the risk of postoperative respiratory depression by 26 percent (OR 1.26, 95% CI 1.02, 1.58) compared to those not exposed to preoperative gabapentin. Animal studies have shown that gabapentinoids can cause respiratory depression alone and in combination with opioids.12-14 Kozer and colleagues12 showed that rabbits given morphine after gabapentin had greater CO2 retention than rabbits given saline after gabapentin. Lyndon and colleagues13 studied the respiratory depressant effects of a high intraperitoneal dose of pregabalin with and without medium dose morphine in six mice. Pregabalin produced a dose-dependent decrease in respiration rate. A pregabalin bolus given alone depressed mouse minute ventilation to the same extent as a morphine bolus given alone. The respiratory depressant effects of morphine and pregabalin were additive, not multiplicative. Collectively, the published animal studies suggest that gabapentinoids have an independent dose-dependent depressive effect on respiration and can augment the respiratory depression caused by opioids.


References

1. Klein-Schwartz W, Shepherd JG, Gorman S, Dahl B. Characterization of gabapentin overdose using a poison center case series. J Toxicol Clin Toxicol 2003;41:11-5. 2. Wills B, Reynolds P, Chu E, Murphy C, Cumpston K, Stromberg P, et al. Clinical outcomes in newer anticonvulsant overdose: a poison center observational study. J Med Toxicol 2014;10:254-60. 3. Verma A, St Clair EW, Radtke RA. A case of sustained massive gabapentin overdose without serious side effects. Ther Drug Monit 1999;21:615-7. 4. Schauer SG, Varney SM. Gabapentin overdose in a military beneficiary. Mil Med 2013;178:e133-5. 5. Damilini J, Radosevich JJ. Gabapentin toxicity and associated blood levels in emergency room patients with renal insufficiency case reports. Pharmacotherapy 2016;36:e294. 6. Middleton O. Suicide by gabapentin overdose. J Forensic Sci 2011;56:1373-5. 7. Myhre M, Diep LM, Stubhaug A. Pregabalin has analgesic, ventilatory, and cognitive effects in combination with remifentanil. Anesthesiology 2016;124:141- 9. 8. Piovezan RD, Kase C, Moizinho R, Tufik S, Poyares D. Gabapentin acutely increases the apnea-hypopnea index in older men: data from a randomized, double-blind, placebo-controlled study. J Sleep Res 2017;26:166-70. 9. Weingarten TN, Jacob AK, Njathi CW, Wilson GA, Sprung J. Multimodal analgesic protocol and postanesthesia respiratory depression during phase I recovery after total joint arthroplasty. Reg Anesth Pain Med 2015;40:330-6. 10. Cavalcante AN, Sprung J, Schroeder DR, Weingarten TN. Multimodal analgesic therapy with gabapentin and its association with postoperative respiratory depression. Anesth Analg 2017;125:141-6. 11. Deljou A, Hedrick SJ, Portner ER, Schroeder DR, Hooten WM, Sprung J, et al. Pattern of perioperative gabapentinoid use and risk for postoperative naloxone administration. Br J Anaesth 2018;120:798-806. 12. Kozer E, Levichek Z, Hoshino N, Kapur B, Leombruno J, Taguchi N, et al. The effect of amitriptyline, gabapentin, and carbamazepine on morphine-induced hypercarbia in rabbits. Anesth Analg 2008;107:1216-22. 13. Lyndon A, Audrey S, Wells C, Burnell ES, Ingle S, Hill R, et al. Risk to heroin users of polydrug use of pregabalin or gabapentin. Addiction 2017;112:1580-9. 14. Hill R, Dewey WL, Kelly E, Henderson G. Oxycodone-induced tolerance to respiratory depression: reversal by ethanol, pregabalin and protein kinase C inhibition. Br J Pharmacol 2018;175:2492-503. 15. Total Patient Tracker (TPT). Data years 2012-2016. Data extracted May 2017. 16. Syneos Health Research & Insights, LLC., TreatmentAnswers™ and TreatmentAnswers™ with Pain Panel (formerly known as InVentiv Health Research & Insights, LLC, TreatmentAnswers™). Data year 2016. Data extracted May 2017. 17. Bastiaens L, Galus J, Mazur C. Abuse of gabapentin is associated with opioid addiction. Psychiatr Q 2016;87:763-7. 18. Dahlman D, Abrahamsson T, Kral AH, Hakansson A. Nonmedical use of antihistaminergic anxiolytics and other prescription drugs among persons with opioid dependence. J Addict 2016;2016:9298571. 19. Grosshans M, Lemenager T, Vollmert C, Kaemmerer N, Schreiner R, Mutschler J, et al. Pregabalin abuse among opiate addicted patients. Eur J Clin Pharmacol 2013;69:2021-5. 20. McNamara S, Stokes S, Kilduff R, Shine A. Pregabalin abuse amongst opioid substitution treatment patients. Ir Med J 2015;108:309-10. 21. Smith RV, Lofwall MR, Havens JR. Abuse and diversion of gabapentin among nonmedical prescription opioid users in Appalachian Kentucky. Am J Psychiatry 2015;172:487-8. 22. Wilens T, Zulauf C, Ryland D, Carrellas N, Catalina-Wellington I. Prescription medication misuse among opioid dependent patients seeking inpatient detoxification. Am J Addict 2015;24:173-7.

FDA warns that abuse and misuse of the nasal decongestant propylhexedrine causes serious harm.


What safety concern is FDA announcing?

The U.S. Food and Drug Administration (FDA) is warning that the abuse and misuse of the over-the-counter (OTC) nasal decongestant propylhexedrine can lead to serious harm such as heart and mental health problems. Some of these complications, which include fast or abnormal heart rhythm, high blood pressure, and paranoia, can lead to hospitalization, disability, or death. Reports of individuals abusing and misusing propylhexedrine have increased in recent years. Propylhexedrine is safe and effective when used as directed.


What should consumers do?

Consumers should only use propylhexedrine according to the directions on the Drug Facts label. Do not use it in ways other than by inhalation because doing so can cause serious harm, such as heart and mental health problems. Some of these problems can lead to death. Seek medical attention immediately by calling 911 or poison control at 1-800-222-1222 for anyone using propylhexedrine who experiences the following:


  • • Severe anxiety or agitation, confusion, hallucinations, or paranoia
  • • Rapid heartbeat or abnormal heart rhythm
  • • Chest pain or tightness


Ask a pharmacist or your health care professional if you have any questions about propylhexedrine, how to use it, or whether a medicine you are taking may interact with it. Always tell your health care professionals about all medicines you are taking, including OTC medicines.


What should health care professionals do?

Health care professionals should be aware that some individuals are abusing or misusing propylhexedrine, particularly using it by routes other than nasal inhalation, which can result in serious cardiac and psychiatric adverse events or death. In the event of a suspected overdose, attempt to determine whether a patient used propylhexedrine alone or with other substances. There is no specific reversal agent in cases of acute intoxication, so symptomatic and supportive care should be provided. (See Additional Information for Health Care Professionals for more information).


FOR MORE INFORMATION, PL. CHECK THE ATTACHED *pdf

FDA requests removal of strongest warning against using cholesterol-lowering statins during pregnancy; still advises most pregnant patients should stop taking statins. Breastfeeding not recommended in patients who require statins.


What safety information is FDA announcing?

The U.S. Food and Drug Administration (FDA) is requesting removal of its strongest warning against using cholesterol-lowering statin medicines in pregnant patients. Despite the change, most patients should stop statins once they learn they are pregnant. We have conducted a comprehensive review of all available data and are requesting that statin manufacturers make this change to the prescribing information as part of FDA’s ongoing effort to update the pregnancy and breastfeeding information for all prescription medicines.


Patients should not breastfeed when taking a statin because the medicine may pass into breast milk and pose a risk to the baby. Many can stop statins temporarily until breastfeeding ends. However, patients requiring ongoing statin treatment should not breastfeed and instead use infant formula or other alternatives.


What should patients do?

Patients taking statins should notify your health care professionals if you become pregnant or suspect you are pregnant. Your health care professional will be able to advise whether you should stop taking the medicine during pregnancy and whether you may stop your statin temporarily while breastfeeding. Patients who are at high risk of heart attack or stroke who require statins after giving birth should not breastfeed and should use alternatives such as infant formula.


What should health care professionals do?

Health care professionals should discontinue statin therapy in most pregnant patients, or they can consider the ongoing therapeutic needs of the individual patient, particularly those at very high risk for cardiovascular events during pregnancy. Because of the chronic nature of cardiovascular disease, treatment of hyperlipidemia is not generally necessary during pregnancy. Discuss with patients whether they may discontinue statins temporarily while breastfeeding. Advise those who require a statin because of their cardiovascular risk that breastfeeding is not recommended because the medicine may pass into breast milk.


We hope the revised language in the prescribing information will help reassure health care professionals that statins are safe to prescribe in patients who can become pregnant, and help them reassure patients with unintended statin exposure in early pregnancy or before pregnancy is recognized that the medicine is unlikely to harm the unborn baby.


FOR MORE INFORMATION, PL. CHECK THE ATTACHED *pdf.

Initial safety trial results find increased risk of serious heart-related problems and cancer with arthritis and ulcerative colitis medicine Xeljanz, Xeljanz XR (tofacitinib)


FDA Drug Safety Communication

The U.S. Food and Drug Administration (FDA) is alerting the public that preliminary results from a safety clinical trial show an increased risk of serious heart-related problems and cancer with the arthritis and ulcerative colitis medicine Xeljanz, Xeljanz XR (tofacitinib) compared to another type of medicine called tumor necrosis factor (TNF) inhibitors. FDA required the safety trial, which also investigated other potential risks including blood clots in the lungs and death. Those final results are not yet available.


We will evaluate the clinical trial results we have received to date and will work with the drug manufacturer to obtain further information as soon as possible. We will communicate our final conclusions and recommendations when we have completed our review or have more information to share.


Patients should not stop taking tofacitinib without first consulting with your health care professionals, as doing so may worsen your condition. Talk to your health care professionals if you have any questions or concerns.


Health care professionals should consider the benefits and risks of tofacitinib when deciding whether to prescribe or continue patients on the medicine. Continue to follow the recommendations in the tofacitinib prescribing information.


Tofacitinib was first approved in 2012 to treat adults with rheumatoid arthritis (RA) who did not respond well to the medicine methotrexate. In RA, the body attacks its own joints, causing pain, swelling, and loss of function. In 2017, we approved tofacitinib to treat patients with a second condition that causes joint pain and swelling, psoriatic arthritis (PsA), who did not respond well to methotrexate or other similar medicines. In 2018, we approved the medicine to treat ulcerative colitis, which is a chronic, inflammatory disease affecting the colon. Tofacitinib works by decreasing the activity of the immune system; an overactive immune system contributes to RA, PsA, and ulcerative colitis.


When FDA first approved tofacitinib, we required the manufacturer, Pfizer, to conduct a safety clinical trial in patients with RA who were taking methotrexate to evaluate the risk of serious heart-related events, cancer, and infections. The trial studied two doses of tofacitinib (5 mg twice daily, which is the approved dosage for RA, and a higher 10 mg twice daily dosage) in comparison to another type of RA medicine called a TNF inhibitor. Patients in the trial were required to be at least 50 years old and have at least one cardiovascular risk factor. In February 2019 and July 2019, we warned that interim trial results showed an increased risk of blood clots

and death with the higher 10 mg twice daily dosage, and as a result, approved a Boxed Warning to the tofacitinib prescribing information. The clinical trial is now complete and initial results show a higher occurrence of serious heart-related events and cancer in RA patients treated with both doses of tofacitinib compared to patients treated with a TNF inhibitor. FDA is awaiting additional results from the trial.


FOR MORE INFORMATION, PL. CHECK THE ATTACHED *pdf