March 19, 2019 — The U.S. Food and Drug Administration today approved Zulresso (brexanolone) injection for intravenous (IV) use for the treatment of postpartum depression (PPD) in adult women. This is the first drug approved by the FDA specifically for PPD.
“Postpartum depression is a serious condition that, when severe, can be life-threatening. Women may experience thoughts about harming themselves or harming their child. Postpartum depression can also interfere with the maternal-infant bond. This approval marks the first time a drug has been specifically approved to treat postpartum depression, providing an important new treatment option,” said Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “Because of concerns about serious risks, including excessive sedation or sudden loss of consciousness during administration, Zulresso has been approved with a Risk Evaluation and Mitigation Strategy (REMS) and is only available to patients through a restricted distribution program at certified health care facilities where the health care provider can carefully monitor the patient.”
PPD is a major depressive episode that occurs following childbirth, although symptoms can start during pregnancy. As with other forms of depression, it is characterized by sadness and/or loss of interest in activities that one used to enjoy and a decreased ability to feel pleasure (anhedonia) and may present with symptoms such as cognitive impairment, feelings of worthlessness or guilt, or suicidal ideation.
Zulresso will be available only through a restricted program called the Zulresso REMS Program that requires the drug be administered by a health care provider in a certified health care facility. The REMS requires that patients be enrolled in the program prior to administration of the drug. Zulresso is administered as a continuous IV infusion over a total of 60 hours (2.5 days). Because of the risk of serious harm due to the sudden loss of consciousness, patients must be monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring (monitors oxygen levels in the blood). While receiving the infusion, patients must be accompanied during interactions with their child(ren). The need for these steps is addressed in a Boxed Warning in the drug’s prescribing information. Patients will be counseled on the risks of Zulresso treatment and instructed that they must be monitored for these effects at a health care facility for the entire 60 hours of infusion. Patients should not drive, operate machinery, or do other dangerous activities until feelings of sleepiness from the treatment have completely gone away.
The efficacy of Zulresso was shown in two clinical studies in participants who received a 60-hour continuous intravenous infusion of Zulresso or placebo and were then followed for four weeks. One study included patients with severe PPD and the other included patients with moderate PPD. The primary measure in the study was the mean change from baseline in depressive symptoms as measured by a depression rating scale. In both placebo controlled studies, Zulresso demonstrated superiority to placebo in improvement of depressive symptoms at the end of the first infusion. The improvement in depression was also observed at the end of the 30-day follow-up period.
The most common adverse reactions reported by patients treated with Zulresso in clinical trials include sleepiness, dry mouth, loss of consciousness and flushing. Health care providers should consider changing the therapeutic regimen, including discontinuing Zulresso in patients whose PPD becomes worse or who experience emergent suicidal thoughts and behaviors.
The FDA granted this application Priority Review and Breakthrough Therapy designation.
Approval of Zulresso was granted to Sage Therapeutics, Inc.
March 5, 2019 — The U.S. Food and Drug Administration today approved Spravato (esketamine) nasal spray, in conjunction with an oral antidepressant, for the treatment of depression in adults who have tried other antidepressant medicines but have not benefited from them (treatment-resistant depression). Because of the risk of serious adverse outcomes resulting from sedation and dissociation caused by Spravato administration, and the potential for abuse and misuse of the drug, it is only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy (REMS).
“There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition,” said Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “Controlled clinical trials that studied the safety and efficacy of this drug, along with careful review through the FDA’s drug approval process including a robust discussion with our external advisory committees, were important to our decision to approve this treatment. Because of safey concerns, the drug will only be available through a restricted distribution system and it must be administered in a certified medical office where the health care provider can monitor the patient.”
Patients with major depressive disorder who, despite trying at least two antidepressant treatments given at adequate doses for an adequate duration in the current episode, have not responded to treatment are considered to have treatment-resistant depression.
The Spravato labeling contains a Boxed Warning that cautions that patients are at risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug. Because of the risk of sedation and dissociation, patients must be monitored by a health care provider for at least two hours after receiving their Spravato dose. The REMS requires the prescriber and the patient to both sign a Patient Enrollment Form that clearly states that the patient understands they should make arrangements to safely leave the health care setting to get home and that the patient should not drive or use heavy machinery for the rest of the day on which they receved the drug. Additionally, Spravato must be dispensed with a patient Medication Guide that outlines the drug’s uses and risks. The patient self-administers Spravato nasal spray under the supervision of a health care provider in a certified doctor’s office or clinic, and the spray cannot be taken home. The health care provider will instruct the patient on how to operate the nasal spray device. During and after each use of the nasal spray device, the health care provider will check the patient and determine when the patient is ready to leave.
The efficacy of Spravato was evaluated in three short-term (four-week) clinical trials and one longer-term maintenance-of-effect trial. In the three short-term studies, patients were randomized to receive Spravato or a placebo nasal spray. In light of the serious nature of treatment-resistant depresison and the need for patients to receive some form of treatment, all patients in these studies started a new oral antidepressant at the time of randomization and the new antidepressant was continued throughout the trials. The primary efficacy measure was the change from baseline on a scale used to assess the severity of depressive symptoms. In one of the short-term studies, Spravato nasal spray demonstrated statistically significant effect compared to placebo on the severity of depression, and some effect was seen within two days. The two other short-term trials did not meet the pre-specified statistical tests for demonstrating effectiveness. In the longer-term maintenance-of-effect trial, patients in stable remission or with stable response who continued treatment with Spravato plus an oral antidepressant experienced a statistically significantly longer time to relapse of depressive symptoms than patients on placebo nasal spray plus an oral antidepressant.
The most common side effects experienced by patients treated with Spravato in the clinical trials were disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting and feeling drunk.
Patients with unstable or poorly controlled hypertension or pre-existing aneurysmal vascular disorders may be at increased risk for adverse cardiovascular or cerebrovascular effects. Spravato may impair attention, judgment, thinking, reaction speed and motor skills. Patients should not drive or operate machinery until the next day after a restful sleep. Spravato may cause fetal harm and women of reproductive potential should consider pregnancy planning and prevention; women should not breastfeed while being treated.
Esketamine is the s-enantiomer of ketamine. Ketamine is a mixture of two enantiomers (mirror image molecules). This is the first FDA approval of esketamine for any use. The FDA approved ketamine (Ketalar) in 1970.
The FDA granted this application Fast Track and Breakthrough Therapy designations.
The FDA granted the approval of Spravato to Janssen Pharmaceuticals, Inc.
STAMFORD, Conn.–(BUSINESS WIRE) March 01, 2019 –Adlon Therapeutics L.P., a subsidiary of Purdue Pharma L.P., announced that the U.S. Food and Drug Administration (FDA) approved Adhansia XR (methylphenidate hydrochloride) extended-release capsules CII, a central nervous system (CNS) stimulant, for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in patients six years and older. In a simulated Adult Workplace Environment (AWE) study, Adhansia XR demonstrated statistically significant improvement over placebo at 1, 2, 5, 8, 11, and 16 hours post-dose, but not at hour 14 post-dose.1
“Methylphenidate medications, when used as prescribed and in conjunction with behavioral therapy and lifestyle interventions, are one of the preferred first-line treatments for certain patients diagnosed with ADHD,” said Marcelo Bigal, MD, PhD, chief medical officer, Purdue Pharma, and general manager, Adlon Therapeutics. “We are pleased to receive FDA approval for Adhansia XR, a new option for appropriate patients with ADHD who may benefit from a treatment with efficacy demonstrated at one hour and 16 hours post-dose in adults, and we look forward to making it available later this year.”
The Full Prescribing Information for Adhansia XR contains a boxed warning for abuse and dependence. CNS stimulants, including Adhansia XR, other methylphenidate-containing products, and amphetamines have a high potential for abuse and dependence. Healthcare professionals should assess the risk of abuse prior to prescribing Adhansia XR and monitor for signs of abuse and dependence while patients are on therapy.
“Some of my patients with ADHD, especially those who are balancing school or work and participating in social or civic activities, require the ability to sustain attention throughout the day,” said Andrew J. Cutler, MD, chief medical officer, Meridien Research, and an investigator on Adhansia XR clinical studies. “The approval of Adhansia XR offers a methylphenidate treatment option with a longer duration of efficacy, which may be appropriate for these patients.”
Adhansia XR is not appropriate for all patients, and healthcare professionals should work with their patients to determine the most appropriate treatment option. Additionally, Adhansia XR is contraindicated in patients with a known hypersensitivity to methylphenidate or product components, as well as patients receiving concurrent treatment with a monoamine oxidase inhibitor (MAOI) or who have used an MAOI within the preceding 14 days.
The Full Prescribing Information for Adhansia XR, including Boxed Warning, is available at this link. Additionally, please see Important Safety Information for Adhansia XR below, including the Boxed Warning, Contraindications, Warnings and Precautions including the potential for abuse and dependence, serious cardiovascular events, blood pressure and heart rate increases, psychiatric adverse reactions, priapism, peripheral vasculopathy, long-term suppression of growth, allergic-type reactions, and Adverse Reactions.
“ADHD affects a significant number of adolescents and adults and, when not optimally treated, can negatively impact various aspects of their lives. A subset of these patients experience impairment throughout the day. While Adhansia XR is not appropriate for all patients, a methylphenidate medication available in a single daily dose that, in adults, demonstrated efficacy at one hour and at 16 hours post-dose, has the potential to address the needs of certain individuals with ADHD,” said Craig Landau, MD, president and CEO, Purdue Pharma. “We are committed to providing information on safe prescribing practices for this medication and initiatives to support the responsible use, storage, and disposal of all medications in this class.”
The FDA approval of Adhansia XR was based on four clinical studies evaluating the efficacy and safety of Adhansia XR in patients who met DSM-5 criteria for ADHD. Eight hundred and eighty-three (883) patients were exposed to Adhansia XR during 1- to 4-week long, controlled treatment periods (434 adult patients and 449 pediatric patients [156 (6 to 12 years); 293 (12 to 17 years)] from two clinical studies in adults, one analog classroom trial over a 13-hour study day in pediatric patients ages 6 to 12 years, and one safety and efficacy study in pediatric patients ages 12 to 17 years). The safety data for adult patients are based on two randomized, double-blind, placebo-controlled studies in doses of 25 mg to 100 mg per day. The safety data for pediatric patients (6 to 17 years) are based on randomized, double-blind, placebo-controlled studies in doses of 25 mg to 85 mg per day.1
A double-blind, randomized, placebo-controlled crossover AWE study evaluated Adhansia XR in adult patients with ADHD. Efficacy assessments were conducted at pre-dose and 1, 2, 5, 8, 11, 14, and 16 hours post-dose. The primary endpoint was the mean Permanent Measure of Performance Total scores (PERMP-T), averaged across all time points compared to placebo. PERMP-T, an objective, validated skill-adjusted math test, is the combined score obtained by adding PERMP-A (number of math problems attempted) and PERMP-C (number of math problems answered correctly).1
While receiving Adhansia XR, adults achieved statistically significant improvement over placebo, achieving greater mean PERMP-T scores averaged across all time points on the AWE days (post-dose score of 281.3 vs. 254.5; difference of 26.80, 95% CI [15.19, 38.41]). The secondary efficacy endpoints were onset and duration of clinical effect, as assessed by the treatment difference in PERMP-T scores at post-dose time points. Adhansia XR demonstrated statistically significant improvement over placebo at 1, 2, 5, 8, 11, and 16 hours post-dose, but not at hour 14 post-dose.1
In this study, 10% of Adhansia XR-treated patients discontinued due to adverse reactions compared to 0% of placebo-treated patients. The following adverse reactions led to discontinuation at a frequency of 2% of Adhansia XR-treated patients: nausea, bronchitis, viral gastroenteritis, viral infection, increased blood pressure, and hypomania.1
Sudden death, stroke and myocardial infarction have occurred in patients treated with CNS stimulants at recommended doses. Additional information about serious cardiovascular risks can be found in the Important Safety Information section below.
Adhansia XR will be available in six capsule strengths (25, 35, 45, 55, 70, and 85 mg), allowing for flexible dosing. The recommended starting dose of Adhansia XR for patients six years or older is 25 mg once daily. Healthcare professionals should titrate the dose in increments of 10 mg to 15 mg at intervals of no less than five days. Adhansia XR should be taken orally once daily in the morning, with or without food. Capsules may be taken whole or, for patients who have difficulty swallowing, capsules may be opened and the entire contents sprinkled onto a tablespoon of applesauce or yogurt. The entire mixture should be consumed without crushing or chewing, immediately or within 10 minutes. If the mixture is not consumed within 10 minutes after mixing, it should be discarded and not stored. The dose of a single capsule should not be divided and patients should not take anything less than one capsule per day. In the event of a missed dose, patients should not take their medication later in the day.1
Prior to initiating treatment with Adhansia XR, healthcare professionals should also assess for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam). Healthcare professionals should assess the risk of abuse prior to prescribing Adhansia XR and monitor for signs of abuse and dependence while patients are on therapy. After prescribing and while patients are on therapy, healthcare professionals should maintain careful prescription records, educate patients and their families about abuse and proper storage and disposal of CNS stimulants, and periodically re-evaluate the need for Adhansia XR use.1
Dosages above 85 mg daily in adults and 70 mg and above daily in pediatric patients are associated with disproportionate increases in the incidence of certain adverse reactions. If paradoxical aggravation of symptoms or other adverse reactions occur, healthcare professionals should reduce the dosage, or, if necessary, discontinue treatment with Adhansia XR. Treatment with Adhansia XR should also be periodically discontinued to assess the patient’s condition. If improvement is not observed in a patient after appropriate dosage adjustment over a one-month period, healthcare providers should discontinue treatment with Adhansia XR.1 Healthcare professionals should refer to the Full Prescribing Information for additional Dosage and Administration information.
Prescription stimulants, which include methylphenidate, the active ingredient in Adhansia XR, are federally controlled substances (CII) and have a high potential for abuse and dependence.1,2 The selling or giving away of methylphenidate medications may harm others or lead to death, and is against the law.1,3 It is important for healthcare professionals to ask patients if they or a family member have ever misused prescription medicines or abused alcohol or street drugs.1,4 Patients should be counseled that they should not give Adhansia XR to anyone else, and to keep methylphenidate medications in a safe place, such as a locked cabinet, to help prevent accidental exposure, diversion, and abuse.1,5 They should also be advised to dispose of remaining, unused, or expired Adhansia XR by a medicine take-back program at authorized collection sites such as pharmacies or law enforcement locations, if available.1,6 If no take-back program or authorized collector is available, patients should mix Adhansia XR with an undesirable, nontoxic substance to make it less appealing to children and pets, place the mixture in a container such as a sealed plastic bag, and discard of it in the household trash.1 Patients should be encouraged to read the Medication Guide that accompanies their stimulant prescription, which contains the most important FDA-approved information that a patient should know about the medication.7
According to the National Institute of Mental Health and the Centers for Disease Control and Prevention, medications for ADHD should be used as a part of a total treatment program that may include psychotherapy, education or training, or a combination of treatments.8,9 Only a healthcare professional can diagnose ADHD, and diagnosis requires a comprehensive patient evaluation. Diagnostic criteria is provided in the American Psychiatric Association’s Diagnostic and Statistical Manual, Fifth edition (DSM-5).10
Please see Important Safety Information, including Boxed Warning, Warnings & Precautions, and Adverse Reactions below.
WARNING: ABUSE AND DEPENDENCE
CNS stimulants, including ADHANSIA XR, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy.
IMPORTANT SAFETY INFORMATION
Adhansia XR is contraindicated in patients with a known hypersensitivity to methylphenidate or other components of Adhansia XR. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other methylphenidate products. Adhansia XR is also contraindicated in patients receiving concomitant treatment with monoamine oxidase inhibitors (MAOIs), and also within 14 days following discontinuation of treatment with a MAOI, because of the risk of hypertensive crisis.
WARNINGS AND PRECAUTIONS
Potential for Abuse and Dependence
CNS stimulants, including Adhansia XR, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy.
Serious Cardiovascular Events
Sudden death, stroke and myocardial infarction have occurred in adults treated with CNS stimulant treatment at recommended doses. Sudden death has occurred in pediatric patients with structural cardiac abnormalities and other serious cardiac problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during treatment during Adhansia XR treatment.
Blood Pressure and Heart Rate Increases
CNS stimulants cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 bpm). Individuals may have larger increases. Monitor all patients for hypertension and tachycardia.
Psychiatric Adverse Reactions
CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.
CNS stimulants may induce a manic or mixed episode in patients. Prior to initiating treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression).
CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. If such symptoms occur, consider discontinuing Adhansia XR. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared to 0% in placebo-treated patients.
Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products, in both pediatric and adult patients. Priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose. Priapism has also appeared during a period of drug withdrawal (drug holidays or during discontinuation). Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.
Peripheral Vasculopathy, including Raynaud’s Phenomenon
CNS stimulants, including Adhansia XR, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.
Long-Term Suppression of Growth
CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Careful follow-up of weight and height in pediatric patients ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated pediatric patients over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated pediatric patients (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development.
Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including Adhansia XR. Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.
Allergic-Type Reactions FD&C Yellow No. 5
Adhansia XR 45 mg capsules contain FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.
The most common (≥5% and twice the rate of placebo) adverse reactions occurring with Adhansia XR in adults are insomnia, dry mouth, and decreased appetite.
The most common (≥5% and twice the rate of placebo) adverse reactions occurring with Adhansia XR in pediatric patients are decreased appetite, insomnia, and decreased weight.
PREGNANCY EXPOSURE REGISTRY
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Adhansia XR during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388.
Please read the Full Prescribing Information, including Boxed Warning.
To report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma at 1-888-726-7535; or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Prescription Medications: Risks of Addiction, Misuse, Abuse, and Diversion
For information on addiction, misuse, abuse, and diversion of prescription medications, please visit the National Institute on Drug Abuse.
Addiction is a chronic, relapsing disease that can last a lifetime and lead to death, and requires treatment. The Substance Abuse and Mental Health Services Administration’s (SAMHSA) confidential and anonymous Behavioral Health Treatment Services Locator can be accessed here, and their free and confidential National Helpline can be reached through 1-800-662-HELP (4357) and 1-800-487-4889 (TTY).
About Adhansia XR
Adhansia XR was developed by Purdue Pharma (Canada). The medication was granted marketing authorization from Health Canada in December 2017 and is currently marketed in Canada as FOQUEST™ for the treatment of ADHD in adults.11
Adhansia XR capsules contain multilayered beads, which are composed of an immediate-release layer which contains approximately 20 percent of the methylphenidate dose, and a controlled-release layer which contains approximately 80 percent of the methylphenidate dose, for oral administration.1 The MLR® (multi-layer release) technology is a controlled-release delivery system patented by Purdue Pharma.
Adhansia XR will be commercialized by Adlon Therapeutics, a subsidiary of Purdue Pharma L.P.
About Adlon Therapeutics L.P.
Adlon Therapeutics L.P. is a biopharmaceutical company dedicated to developing and providing treatment options for Attention-Deficit/Hyperactivity Disorder (ADHD) and related disorders. Our initial focus is on adults and adolescents who have been diagnosed with ADHD. Adlon is a subsidiary of Purdue Pharma L.P. For more information, please visit www.adlontherapeutics.com.
1 Purdue Pharma L.P. Adhansia XR Full Prescribing Information. Feb 2019. Accessed Mar 1, 2019. Retrieved from http://app.adlontherapeutics.com/adhansia-xr/fpi.pdf.
2 United States Drug Enforcement Administration. Drug Scheduling. Accessed Jan 2, 2019. Retrieved from https://www.dea.gov/drug-scheduling.
3 Legal Information Institute. 21 U.S. Code § 829 – Prescriptions. Accessed Jan 4, 2019. Retrieved from https://www.law.cornell.edu/uscode/text/21/829.
4 National Institutes of Health, National Institute of Drug Abuse. Research Report Series: Prescription Drug Abuse. Revised October 2011. Accessed Jan 11, 2019. Retrieved from https://www.drugabuse.gov/sites/default/files/rxreportfinalprint.pdf.
5 Rannazzisi JT and Caverly MW. United States Department of Justice, Drug Enforcement Administration, Office of Diversion Control. Practitioner’s manual: an informational outline of the Controlled Substances Act. 2006. Accessed Jan 2, 2019. Accessed Jan 2, 2019. Retrieved from https://www.deadiversion.usdoj.gov/pubs/manuals/pract/pract_manual012508.pdf.
6 National Institute on Drug Abuse. Misuse of Prescription Drugs: How can prescription drug misuse be prevented? 2018. Accessed on Jan 4, 2019. Retrieved from https://www.drugabuse.gov/publications/research-reports/misuse-prescription-drugs/how-can-prescription-drug-misuse-be-prevented.
7 U.S. Food and Drug Administration. Medication Guides. Page last updated: August 8, 2018. Accessed Jan 2, 2019. Retrieved from: https://www.fda.gov/Drugs/DrugSafety/ucm085729.htm.
8 The National Institute of Mental Health Information Resource Center, National Institute of Mental Health. Attention-deficit/hyperactivity disorder (ADHD). Page last updated March 2016. Accessed Jan 2, 2019. Retrieved from https://www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorder-adhd/index.shtml.
9 Division of Human Development and Disability, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention. Attention-deficit/hyperactivity disorder (ADHD). Page last updated September 2018. Accessed Jan 2, 2019. Retrieved from https://www.cdc.gov/ncbddd/adhd/treatment.html.
10 American Psychiatric Association. Attention-deficit/hyperactivity disorder. In Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA: American Psychiatric Publishing; 2013.
11 Purdue Pharma (Canada). Foquest Product Monograph. Dec 5, 2017. Accessed Feb 19, 2019. Retrieved from http://purdue.ca/wp-content/uploads/2017/12/Foquest-PM-EN.pdf.
Bagsværd, Denmark, 19 February 2019 – Novo Nordisk today announced that the US Food and Drug Administration (FDA) has approved the Biologics License Application for Esperoct for the treatment of adults and children with hemophilia A.
Esperoct is the brand name for turoctocog alfa pegol, N8-GP. Esperoct is indicated for use in adults and children with hemophilia A (congenital factor VIII deficiency) for routine prophylaxis to reduce the frequency of bleeding episodes, on-demand treatment and control of bleeding episodes and perioperative management of bleeding.
The approval of Esperoct is based on the results from the largest pre-registration clinical programme conducted in hemophilia A, which included 270 previously treated people (PTPs) with severe hemophilia A and more than 5 years of clinical exposure. Esperoct was shown to provide effective routine prophylaxis in people with severe hemophilia A through a simple, fixed dosing regimen of one injection every 4 days in adults and adolescents or every 3-4 days (twice-weekly) in children. Esperoct provided effective prophylaxis and maintained a low median ABR of 1.18 when dosed at 50 IU/kg every 4 days in adults and adolescents. Furthermore, Esperoct was found to be efficacious in treatment and control of bleeding episodes and perioperative management. Across the clinical trials and age groups, Esperoct was well tolerated and no safety concerns were identified. The overall safety profile of Esperoct is similar to what has been reported for other long-action FVIII products.
“We are excited about the approval of Esperoct in the US, and we consider it an important expansion of the treatment options Novo Nordisk can offer people with hemophilia A”, said Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk. “We are confident that Esperoct will provide people with hemophilia A a less burdensome and simple, fixed dosing regimen for prophylaxis and treatment of bleeding episodes, resulting in improved quality of life.”
Due to third-party IP agreements, Novo Nordisk will not be able to launch Esperoct before 2020 in the USA.
Esperoct (turoctocog alfa pegol, N8-GP) is an extended half-life factor VIII molecule for replacement therapy in people with hemophilia A, which provides a 1.6-fold half-life prolongation in adults/adolescents and a 1.9-fold half-life prolongation in children, compared to standard half-life factor VIII products.
About the pathfinder clinical programme
Esperoct has been evaluated in 270 people (202 adults/adolescents and 68 children) in five prospective, multi-centre clinical trials in previously treated people (PTPs) with severe hemophilia A (<1% endogenous FVIII activity) and no history of inhibitors. Total exposure to Esperoct was 80,425 exposure days corresponding to 889 patient years of treatment. Esperoct was well tolerated across all age groups and indications, and no safety concerns were identified after more than 5 years of clinical exposure.
Horsham, PA, February 12, 2019 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) has approved a split-dosing regimen for Darzalex® (daratumumab), providing healthcare professionals and patients with multiple myeloma an option to split the first infusion over two consecutive days. The U.S. FDA approval is based on data from the Phase 1b EQUULEUS (MMY1001) clinical study, which demonstrated Darzalex pharmacokinetic (PK) concentrations were comparable at the end of weekly dosing, regardless of whether the first dose was administered as a split infusion or as a single infusion.1
“The first infusion of Darzalex is an important first step in a patient’s course of therapy, and this approval provides added flexibility for how patients may receive initial treatment,” said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Janssen Research & Development, LLC. “We are committed to exploring options that may improve the overall treatment experience for patients.”
The U.S. FDA approval of a split-dosing regimen for Darzalex is based on data from the global, multi-arm, Phase 1b EQUULEUS (MMY1001) study in multiple myeloma, which evaluated Darzalex in combination with various treatment regimens.1 Splitting the first dose of Darzalex over two consecutive days effectively reduced the duration of the first infusion and resulted in a similar rate and pattern of infusion reactions.1 Data from the study demonstrated that Darzalex concentrations were comparable at the end of weekly dosing regardless of whether the first 16 mg/kg dose was administered as a split infusion or single first infusion.1
The safety profile of DARZALEX was comparable when administered initially as a split or single dose, and no new safety events were observed with a split first dose.1
This approval follows approvals in Canada and the European Union in December 2018 for the Darzalex initial infusion split-dosing regimen.
About Darzalex (daratumumab) Injection for Intravenous Infusion
Darzalex is the first and only CD38-directed antibody to receive regulatory approval to treat multiple myeloma. In the U.S., Darzalex (daratumumab) first received FDA approval in November 2015 as a monotherapy for patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double refractory to a PI and an immunomodulatory agent. Darzalex received additional approvals in November 2016 in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. In June 2017, Darzalex received approval in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a PI. Most recently, in May 2018, Darzalex received approval in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant, making it the first monoclonal antibody approved for newly diagnosed patients with this disease.
In August 2012, Janssen Biotech, Inc. and Genmab A/S entered into a global license and development agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize Darzalex. For the full U.S. Prescribing Information, please visit www.DARZALEX.com.
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow., Refractory cancer occurs when a patient’s disease is resistant to treatment or in the case of multiple myeloma, when patients progress within 60 days of their last therapy., Relapsed cancer means the disease has returned after a period of initial, partial or complete remission. In 2019, it is estimated that 32,110 people will be diagnosed, and 12,960 will die from the disease, in the United States. While some patients with multiple myeloma have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood counts, fatigue, high calcium levels, kidney problems or infections.
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science.
We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com. Follow us at @JanssenGlobal and @JanssenUS. Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
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This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding the benefits of Darzalex® (daratumumab) for the treatment of patients with multiple myeloma. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc., and any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; [product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 31, 2017, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, the company’s subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither the Janssen Pharmaceutical Companies of Johnson & Johnson nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
 Janssen Research & Development, LLC. A Study of JNJ-54767414 (HuMax CD38) (Anti-CD38 Monoclonal Antibody) in Combination With Backbone Treatments for the Treatment of Patients With Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT01998971 Identifier: NCT01998971
 Darzalex Prescribing Information, June 2018.
 Janssen Biotech, Inc. “Darzalex® (daratumumab) Approved by U.S. FDA: First Human Anti-CD38 Monoclonal Antibody Available for the Treatment of Multiple Myeloma.” Issued November 16, 2015.
 Janssen Biotech, Inc. “Darzalex® (daratumumab) Approved by U.S. FDA in Combination with Two Standard of Care Regimens for the Treatment of Patients with Multiple Myeloma Who Have Received At Least One Prior Therapy.” Issued November 21, 2016.
 Janssen Biotech, Inc. “Darzalex® (daratumumab) Approved by the U.S. FDA in Combination with Pomalidomide and Dexamethasone for Patients with Multiple Myeloma Who Have Received At Least Two Prior Therapies.” Issued June 16, 2017.
 Janssen Pharmaceutical Companies of Johnson & Johnson. “Janssen Announces Darzalex® (daratumumab) U.S. FDA Approval for Newly Diagnosed Patients with Multiple Myeloma who are Transplant Ineligible.” Issued May 7, 2018.
 Janssen Biotech, Inc. “Janssen Biotech Announces Global License and Development Agreement for Investigational Anti-Cancer Agent Daratumumab.” Issued August 30, 2012.
 Kumar, SK et al. Leukemia. 2012 Jan; 26(1):149-57.
 American Cancer Society. “What Is Multiple Myeloma?” Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed August 2018. Accessed February 2019.
 National Cancer Institute. “NCI Dictionary of Cancer Terms: Refractory.” Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=350245. Accessed February 2019.
 Richardson, et al. “The Treatment of Relapsed and Refractory Multiple Myeloma.” ASH Education Book. January 1, 2007 vol. 2007 no. 1 317-323.
 National Cancer Institute. “NCI Dictionary of Cancer Terms: Relapsed.” Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=45866. Accessed February 2019.
 American Cancer Society. “Key Statistics for Multiple Myeloma.” Available at: https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html. Accessed February 2019.
 American Cancer Society. “Diagnosing Multiple Myeloma From Test Results.” Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed February 2019.
Source: Janssen Pharmaceutical Companies of Johnson & Johnson
NEWPORT BEACH, Calif., Feb. 01, 2019 (GLOBE NEWSWIRE) — Evolus, Inc. (NASDAQ: EOLS) today announced that the U.S. Food and Drug Administration (“FDA”) has approved its lead product, Jeuveau, for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adults.
David Moatazedi, President and Chief Executive Officer of Evolus, stated, “Evolus is the first company in nearly a decade to enter the fast-growing U.S. aesthetic neurotoxin market. What makes Evolus unique is our focus on delivering performance beauty products with a customer-centric approach. We are pleased to introduce Jeuveau™, the first FDA approved neurotoxin dedicated to aesthetics and manufactured in a state-of-the-art facility using Hi-Pure™ technology.”
Ava Shamban, MD, Board Certified Dermatologist and clinical investigator, commented, “The outcomes I’ve seen for my clinical trial patients firsthand, combined with the comprehensive clinical data set for Jeuveau provide a compelling new treatment option for physicians and their aesthetic patients. The TRANSPARENCY program involved the study of over 2,100 patients globally, which included two U.S. pivotal Phase III trials and a European & Canadian Phase III head-to-head trial versus Botox®, in which all the primary and secondary endpoints were met. Importantly, there were no serious drug related adverse events reported. The comprehensive data set generated by Evolus through the TRANSPARENCY clinical program will give my peers the utmost level of confidence in providing Jeuveau to their patients. I look forward to incorporating Jeuveau into my aesthetic product offering.”
Mr. Moatazedi added, “We are focusing our efforts on ensuring a successful launch of Jeuveau and have initiated the recruitment of a high-quality, specialized U.S. sales force. The launch of Jeuveau™ will be powered by our technology platform designed to eliminate the friction points that exist for customers today. Prior to our U.S. launch, we expect publication of our U.S. Phase III results and to submit for publication our European and Canadian head-to-head Phase III study versus Botox®. I would like to thank all the Evolus employees, clinical investigators, patients and our partner Daewoong for their diligent efforts in bringing a new option to the market.”
Jeuveau is expected to be available throughout the United States at physician offices starting in Spring 2019. Physicians and consumers are encouraged to visit www.evolus.com and sign up for updates on product availability.
Jeuveau (prabotulinumtoxinA-xvfs) is a proprietary 900 kDa purified botulinum toxin type A formulation indicated for the temporary improvement in the appearance of moderate to severe glabellar lines in adults. Jeuveau is produced under strict quality and safety standards in a state-of-the art facility, specifically built to manufacture Jeuveau. The safety and efficacy of Jeuveau has been evaluated in clinical studies with over 2,100 patients enrolled.
FDA approval of Jeuveau was supported by clinical data from two U.S. Phase III randomized, multi-center, double-blind, placebo-controlled clinical trials both of which met the primary endpoint and demonstrated efficacy compared with placebo in the reduction of the severity of glabellar lines, defined as a 2-point composite improvement agreed upon by physician and patient, at Day 30. 67.5% of subjects in study one (EV-001) and 70.4% of subjects in study two (EV-002) met the primary endpoint, compared to 1.2% and 1.3% of patients in each placebo arm respectively.
IMPORTANT SAFETY INFORMATION FOR JEUVEAU (prabotulinumtoxinA-xvfs)
Jeuveau may cause serious side effects that can be life threatening. Get medical help right away if you have any of these problems any time (hours to weeks) after injection of Jeuveau:
Problems swallowing, speaking, or breathing, due to weakening of associated muscles, can be severe and result in loss of life. You are at the highest risk if these problems are pre-existing before injection. Swallowing problems may last for several months.
Spread of toxin effects. The effect of botulinum toxin may affect areas away from the injection site and cause serious symptoms including: loss of strength and all-over muscle weakness, double vision, blurred vision and drooping eyelids, hoarseness or change or loss of voice, trouble saying words clearly, loss of bladder control, trouble breathing, trouble swallowing.
Do not use Jeuveau if you: are allergic to any of the ingredients in Jeuveau (see Medication Guide for ingredients); had an allergic reaction to any other botulinum toxin product such as rimabotulinumtoxinB (MYOBLOC®), onabotulinumtoxinA (BOTOX®/BOTOX® Cosmetic), abobotulinumtoxinA (DYSPORT®), or incobotulinumtoxinA (XEOMIN®); have a skin infection at the planned injection site; or are a child.
Jeuveau dosing units are not the same as, or comparable to, any other botulinum.
Tell your healthcare provider about all your muscle or nerve conditions, such as ALS or Lou Gehrig’s disease, Myasthenia gravis, or Lambert-Eaton syndrome, as you may be at increased risk of serious side effects including difficulty swallowing and difficulty breathing from typical doses of Jeuveau.
Tell your healthcare provider about all your medical conditions, including: any side effects from botulinum toxin products, including dry eye; breathing, swallowing, bleeding, or heart problems; plans to have surgery; weakness of forehead muscles; drooping eyelids; had surgery on your face; are pregnant or breastfeeding or plan to become pregnant or breastfeed (it is not known if Jeuveau can harm your unborn baby or passes into breast milk).
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Using Jeuveau with certain other medicines may cause serious side effects. Do not start any new medicines until you have told your healthcare provider that you have received Jeuveau in the past.
Especially tell your healthcare provider if you: have received any other botulinum toxin product in the past and the last 4 months. and exactly which product you received (such as Botox, Botox Cosmetic, Myobloc, Dysport, or Xeomin).
Jeuveau may cause loss of strength or general muscle weakness, vision problems, or dizziness within hours to weeks of treatment with Jeuveau. If this happens, do not drive a car, operate machinery, or do other dangerous activities.
Jeuveau can cause other serious side effects including: allergic reactions (such as itching, rash, red itchy welts, wheezing, asthma symptoms, or dizziness or feeling faint), heart problems (such as irregular heartbeat and heart attack), and eye problems (including dry eye, reduced blinking, and corneal problems). Tell your healthcare provider or get medical emergency help right away if you experience a serious side effect.
The most common side effects include: headache; eyelid drooping, upper respiratory tract infection, and increased white blood cell count in your blood.
Jeuveau is a prescription medicine that is injected into muscles and used in adults for a short period of time (temporary) to improve the look of moderate to severe frown lines between the eyebrows (glabellar lines).
The risk information provided here is not complete. For more information about Jeuveau, the full Prescribing Information including BOXED WARNING, and Medication Guide, visit www.evolus.com or talk to your healthcare provider.
To report side effects associated with use of Jeuveau, please call 1-877-386-5871. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
Manufactured by: Evolus, Inc., 1027 Garden St., Santa Barbara, CA 93101
Evolus is a performance beauty company with a customer-centric approach focused on delivering breakthrough products. In 2019, the U.S. Food and Drug Administration approved Jeuveau (prabotulinumtoxinA-xvfs), the first and only neurotoxin dedicated exclusively to aesthetics and manufactured in a state-of-the-art facility using Hi-Pure™ technology. Jeuveau is powered by Evolus’ unique technology platform and is designed to transform the aesthetic market by eliminating the friction points existing for customers today. Visit us at: www.evolus.com.
Statements made in this press release that relate to future plans, events, prospects or performance are forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including statements containing the words “planned,” “expect,” “believes,” “strategy,” “opportunity,” “anticipates,” “outlook,” “designed,” and similar words. While these forward-looking statements are based on the current expectations and beliefs of management, such forward-looking statements are subject to a number of risks, uncertainties, assumptions and other factors that could cause actual results to differ materially from the expectations expressed in this press release, including the risks and uncertainties disclosed in Evolus’ periodic filings with the Securities and Exchange Commission, including factors described in the section entitled ”Risk Factors” in its Annual Report on Form 10-K for the year ended December 31, 2017 and its Quarterly Report on Form 10-Q for the Quarter ended September 30, 2018, as filed with the Securities and Exchange Commission on March 29, 2018 and November 5, 2018, respectively, all of which are available online at www.sec.gov. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by law, Evolus undertakes no obligation to update or revise any forward-looking statements to reflect new information, changed circumstances or unanticipated events.
Jeuveau is a trademark of Evolus, Inc.
Hi-Pure is a trademark of Daewoong Pharmaceutical Co, Ltd.
Botox®, Botox® Cosmetic, Myobloc®, Dysport®, and Xeomin® are registered trademarks of their respective owners.
Although many of the FDA’s risk-benefit assessments and decisions are straightforward, sometimes the benefits and risks are uncertain and may be difficult to interpret or predict. The agency and the drug maker may reach different conclusions after analyzing the same data, or there may be differences of opinion among members of the FDA’s review team. As a science-led organization, FDA uses the best scientific and technological information available to make decisions through a deliberative process.
In some cases, the approval of a new drug is expedited. Accelerated Approval can be applied to promising therapies that treat a serious or life-threatening condition and provide therapeutic benefit over available therapies. This approach allows for the approval of a drug that demonstrates an effect on a “surrogate endpoint” that is reasonably likely to predict clinical benefit, or on a clinical endpoint that occurs earlier but may not be as robust as the standard endpoint used for approval. This approval pathway is especially useful when the drug is meant to treat a disease whose course is long, and an extended period of time is needed to measure its effect. After the drug enters the market, the drug maker is required to conduct post-marketing clinical trials to verify and describe the drug’s benefit. If further trials fail to verify the predicted clinical benefit, FDA may withdraw approval.
Since the Accelerated Approval pathway was established in 1992, many drugs that treat life-threatening diseases have successfully been brought to market this way and have made a significant impact on disease course. For example, many antiretroviral drugs used to treat HIV/AIDS entered the market via accelerated approval, and subsequently altered the treatment paradigm. A number of targeted cancer-fighting drugs also have come onto the market through this pathway.
American consumers benefit from having access to the safest and most advanced pharmaceutical system in the world. The main consumer watchdog in this system is FDA’s Center for Drug Evaluation and Research (CDER).
The center’s best-known job is to evaluate new drugs before they can be sold. CDER’s evaluation not only prevents quackery, but also provides doctors and patients the information they need to use medicines wisely. The center ensures that drugs, both brand-name and generic, work correctly and that their health benefits outweigh their known risks.
Drug companies seeking to sell a drug in the United States must first test it. The company then sends CDER the evidence from these tests to prove the drug is safe and effective for its intended use. A group of physicians, statisticians, chemists, pharmacologists, and other scientists reviews the company’s data and proposed labeling. If this independent and unbiased review establishes that a drug’s health benefits outweigh its known risks, the drug is approved for sale. The center doesn’t actually test drugs itself, although it does conduct limited research in the areas of drug quality, safety, and effectiveness standards.
Before a drug can be tested in people, the drug company or sponsor performs laboratory and animal tests to discover how the drug works and whether it’s likely to be safe and work well in humans. Next, a series of tests in people is begun to determine whether the drug is safe when used to treat a disease and whether it provides a real health benefit.
FDA approval of a drug means that data on the drug’s effects have been reviewed by CDER, and the drug is determined to provide benefits that outweigh its known and potential risks for the intended population. The drug approval process takes place within a structured framework that includes:
Analysis of the target condition and available treatments—FDA reviewers analyze the condition or illness for which the drug is intended and evaluate the current treatment landscape, which provide the context for weighing the drug’s risks and benefits. For example, a drug intended to treat patients with a life-threatening disease for which no other therapy exists may be considered to have benefits that outweigh the risks even if those risks would be considered unacceptable for a condition that is not life threatening.
Assessment of benefits and risks from clinical data—FDA reviewers evaluate clinical benefit and risk information submitted by the drug maker, taking into account any uncertainties that may result from imperfect or incomplete data. Generally, the agency expects that the drug maker will submit results from two well-designed clinical trials, to be sure that the findings from the first trial are not the result of chance or bias. In certain cases, especially if the disease is rare and multiple trials may not be feasible, convincing evidence from one clinical trial may be enough. Evidence that the drug will benefit the target population should outweigh any risks and uncertainties.
Strategies for managing risks—All drugs have risks. Risk management strategies include an FDA-approved drug label, which clearly describes the drug’s benefits and risks, and how the risks can be detected and managed. Sometimes, more effort is needed to manage risks. In these cases, a drug maker may need to implement a Risk Management and Mitigation Strategy (REMS).
For body aches, doctors suggest you give your child over-the-counter (OTC) acetaminophen, ibuprofen, or naproxen sodium. Don’t give aspirin to anyone under 19 years old. It’s linked with Reye’s syndrome, a sometimes fatal illness that affects children and teens. To avoid stomach upset, take ibuprofen with food.
Don’t give OTC cough medicines to kids under 4. They don’t work. Homemade cough remedies with honey do help. After your child is 1 year old, you can use ½ to 1 teaspoon of honey as needed.
Lozenges with licorice and slippery elm: They ease sore throats and coughs from all that gunk running down the back of your throat. (Doctors call this postnasal drip.)