FDA Approves Second Drug, Vyleesi, to Help Women With Low Libido

In continuation of my update on bremelanotide

The U.S. Food and Drug Administration on Friday gave its approval to Vyleesi, the second medication so far approved to help women with low sexual desire.

In a news release, the FDA said that Vyleesi (bremelanotide) is a drug that would be administered by injection prior to having sex.

It's been specifically approved for premenopausal women with a condition known as acquired, generalized hypoactive sexual desire disorder (HSDD).

"There are women who, for no known reason, have reduced sexual desire that causes marked distress, and who can benefit from safe and effective pharmacologic treatment," said Dr. Hylton Joffe, who directs the FDA's Center for Drug Evaluation and Research's Division of Bone, Reproductive and Urologic Products.

"Today's approval provides women with another treatment option for this condition," Hylton said in the news release.

According to the agency, HSDD is not caused by any medical or psychiatric condition, relationship issues or drug side effects.

Instead, women with HSDD have "previously experienced no problems with sexual desire," the FDA said. "Generalized HSDD refers to HSDD that occurs regardless of the type of sexual activity, situation or partner."

The exact way in which Vyleesi helps stimulate sexual desire remains unclear, but it works on melanocortin receptors on cells, the FDA said.

The drug is injected under the skin of the abdomen or thigh at least 45 minutes prior to a sexual encounter, although the best timeframe for dosing could vary from user to user.

Side effects can occur, the FDA added, and include nausea and vomiting, flushing, injection site reactions and headache. Nausea was especially common, affecting 40% of users in the clinical study that led to approval.

That study involved 1,247 premenopausal women with HSDD who received Vyleesi or a placebo in one of two 24-week trials.

"In these trials, about 25% of patients treated with Vyleesi had an increase of 1.2 or more in their sexual desire score (scored on a range of 1.2 to 6.0, with higher scores indicating greater sexual desire) compared to about 17% of those who took placebo," the FDA noted.

Still, the overall benefit was not large. "There was no difference between treatment groups in the change from the start of the study to end of the study in the number of satisfying sexual events. Vyleesi does not enhance sexual performance," the FDA said.

And there was one other caveat: Vyleesi can hike blood pressure, so people with heart disease or high blood pressure should not take it, the FDA said.

Vyleesi should also not be taken by anyone who is also taking the drug naltrexone, used to combat opioid dependency, because Vyleesi reduces naltrexone's effectiveness.

Vyleesi is not the first drug approved to enhance flagging libido in women. In 2015 the FDA approved Addyi (flibanserin) for the purpose, but the drug did not become widely used because it cannot be taken with alcohol and only certain certified health care providers are allowed to prescribe it.

According to CNN, Vyleesi's maker, AMAG Pharmaceuticals, said the new drug will not be available until September, and pricing and reimbursement have yet to be determined.

One expert in female sexual health said it remains to be seen how widely Vyleesi will be used.

"Female sexual dysfunction is more complicated in some ways than male sexual dysfunction, so it's more difficult to treat," Dr. Nicole Cirino, co-director of the Menopause and Sexual Therapy Clinic at Oregon Health and Science University's Center for Women's Health, told CNN. She had no role in Vyleesi's development.

Cirini suspects Vyleesi probably will not be the first option women with HSDD turn to, but it might prove a useful adjunct to standard psychotherapy and Addyi.

Vyleesi, like Addyi, probably won't be overprescribed, Cirino added. When Addyi was introduced, there were concerns "that doctors would just be prescribing this medication to anybody that came in saying that they were having an issue with their libido," she said. "And I think we have to give physicians more credit than that. In fact, that didn't happen at all."

Still, Vyleesi could help some women, Cirino said

https://en.wikipedia.org/wiki/Bremelanotide

Ketamine’s role in treatment of depression: Study

In continuation of my update on Ketamine

The anaesthetic drug Ketamine has been shown to be beneficial in some cases of depression and suicidal ideation which have typically failed to respond to other standard antidepressant medications. A new study has explored the actual workings of ketamine in depression and found that the drug can act on the same receptors as opioid pain relievers.

The latest study was published in the American Journal of Psychiatry.

For this the researchers from the Stanford’s Neurosciences Institute included 12 volunteers at first. These cases were all of treatment-resistant depression.

The participants were all given infusion of Ketamine. In addition some were administered naltrexone and others normal saline infusion. Naltrexone is a drug that can block the effects of opioids.

Results showed that those on ketamine and saline combination found relief from their depressive symptoms quickly compared to those on ketamine and naltrexone combination. In fact those on ketamine and saline placebo reported at least a 90 percent reduction in their symptoms within the first three days of the infusion.

No such improvement was seen among those on ketamine and naltrexone. This proved that when the opioid actions are blocked, the ketamine cannot function as an antidepressant. Both groups faced certain side effects of ketamine such as an “out-of-the-body” experience, dysphoric feelings, tripping etc. This also showed that the antidepressant action of Ketamine was separate from its usual actions, which were seen in all participants in either group.

The initial trial plan was to include 30 patients. Due to the dramatic improvement seen in one group and no changes in the other, the team decided to stop the trial prematurely. This was to spare patients useless treatment.

Ketamine has been in news recently due to its unexplored potential as an antidepressant. If proven, researchers believe, this could impact depression research significantly. Ketamine has gathered interest mainly because it does not change the brain chemistry unlike other antidepressants. Co-author Boris Heifets, a clinical assistant professor of anesthesiology, perioperative and pain medicine at Stanford explained that ketamine blocks the brain’s receptors for glutamate. Glutamate is an important neurotransmitter in the brain. Many researchers have thought that glutamate could be the key zone where ketamine acts as an antidepressant. Heifets added that ketamine is not a simple drug and has varied targets which could be responsible for its antidepressant activities. A lot of money has been spent on developing agents that could work on the glutamate receptors and try to mimic ketamine’s antidepressant actions.

This study shows that the approach is incorrect and glutamates are not the target lead author Nolan Williams explained. Co-senior study author Dr. Alan Schatzberg, a professor of psychiatry and behavioral sciences at Stanford explained that the ketamine was not working as “everyone thought it was working.”

Heifets noted that ketamine is a drug of abuse (called “Special K” in party circuits) that has been in use for a long time and there is an abuse potential of this drug acting on the opioid receptors to provide such effects. He warned that this abuse potential should be kept in mind before ketamine comes into the market as an antidepressant.

However the whole team agrees that this new study shows how ketamine can help patients who have intractable depression. New drugs could be developed in the same lines they explain. These drugs could possibly activate the opioid receptors without having abuse potential they add. Williams added that ketamine has been seen to provide relief of symptoms in other mental ailments such as obsessive compulsive disorders and now is the time to explore if opioids play a role in these diseases as well.

Mark George, a professor of psychiatry, radiology and neuroscience at the Medical University of South Carolina in an editorial accompanying the article wrote that this study is a small one and so should be confirmed in larger trials before conclusions could be drawn.

Ref : https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2018.18020138

https://en.wikipedia.org/wiki/Ketamine

Drug to treat alcohol addiction also helps with suppression of HIV

In continuation of my update  on naltrexone

A medication commonly prescribed to treat alcohol use disorder also appears to help maintain or improve suppression of HIV among individuals at risk for a lapse in HIV treatment, Yale researchers said.

In a new study, a research team led by Dr. Sandra Springer conducted a placebo-controlled, randomized trial involving individuals incarcerated in Connecticut who had both HIV and alcohol use disorders. Upon release, the 100 study participants were given either extended-release naltrexone—an FDA-approved drug that treats alcohol addiction—or a placebo. The researchers followed the individuals for six months from the time of release.

At the end of the study period, the research team found that the study participants taking extended-release naltrexone were more likely to have either maintained or improved suppression of HIV.

The study findings confirm the benefit of extended-release naltrexone for people who have alcohol use disorders and HIV disease, and demonstrate its effectiveness in helping patients to meet the goals of HIV treatment. The paper is published in the Journal of Acquired Immune Deficiency Syndrome.

More information: Sandra A. Springer et al. Extended-release naltrexone improves viral suppression levels in prisoners with HIV and alcohol use disorders who are transitioning to the community, JAIDS Journal of Acquired Immune Deficiency Syndromes (2018)

FDA Approves Sublocade (buprenorphine) Once-Monthly Injection for Opioid Use Disorder

In continuation of my update on Sublocade (buprenorphine)

The U.S. Food and Drug Administration today approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe opioid use disorder (OUD) in adult patients who have initiated treatment with a transmucosal (absorbed through mucus membrane) buprenorphine-containing product. It is indicated for patients that have been on a stable dose of buprenorphine treatment for a minimum of seven days.

Buprenorphine for the treatment of OUD is currently approved to administer as a tablet or film that dissolves in the mouth, or as an implant. Sublocade provides a new treatment option for patients in recovery who may value the benefits of a once-monthly injection compared to other forms of buprenorphine, such as reducing the burden of taking medication daily as prescribed (medical adherence). An independent FDA advisory committee supported the approval of Sublocade at a meeting held last month.

"Given the scale of the opioid crisis, with millions of Americans already affected, the FDA is committed to expanding access to treatments that can help people pursue lives of sobriety. Everyone who seeks treatment for opioid use disorder deserves the opportunity to be offered the treatment best suited to the needs of each individual patient, in combination with counseling and psychosocial support, as part of a comprehensive recovery plan,” said FDA Commissioner Scott Gottlieb, M.D. “As part of our ongoing work in supporting the treatment of those suffering from addiction to opioids, the FDA plans to issue guidance to expedite the development of new addiction treatment options. We’ll continue to pursue efforts to promote more widespread use of existing, safe and effective FDA-approved therapies to treat addiction.”

Improving access to prevention, treatment and recovery services, including the full range of medication-assisted treatments (MAT), is a focus of the FDA’s ongoing work to reduce the scope of the opioid crisis and one part of the U.S. Department of Health and Human Services’ Five-Point Strategy to Combat the Opioid Crisis.

OUD is the diagnostic term used for a chronic neurobiological disease characterized by a problematic pattern of opioid use leading to significant impairment or distress and includes signs and symptoms that reflect compulsive, prolonged self-administration of opioid substances for no legitimate medical purpose or, if another medical condition is present that requires opioid treatment, the opioid is used in doses far greater than the amount needed for treatment of that medical condition.

MAT is a comprehensive approach that combines approved medications (currently, methadone, buprenorphine or naltrexone) with counseling and other behavioral therapies to treat patients with OUD. Regular adherence to MAT with buprenorphine reduces opioid withdrawal symptoms and the desire to use opioids, without causing the cycle of highs and lows associated with opioid misuse or abuse. At proper doses, buprenorphine also decreases the pleasurable effects of other opioids, making continued opioid abuse less attractive. According to the Substance Abuse and Mental Health Services Administration, patients receiving MAT for their OUD cut their risk of death from all causes in half.

Sublocade should be used as part of a complete treatment program that includes counseling and psychosocial support. Sublocade is a drug-device combination product that utilizes buprenorphine and the Atrigel Delivery System in a pre-filled syringe. It is injected by a health care professional (HCP) under the skin (subcutaneously) as a solution, and the delivery system forms a solid deposit, or depot, containing buprenorphine. After initial formation of the depot, buprenorphine is released by the breakdown (biodegradation) of the depot. In clinical trials, Sublocade provided sustained therapeutic plasma levels of buprenorphine over the one-month dosing interval.

The safety and efficacy of Sublocade were evaluated in two clinical studies (one randomized controlled clinical trial and one open-label clinical trial) of 848 adults with a diagnosis of moderate-to-severe OUD who began treatment with buprenorphine/naloxone sublingual film (absorbed under the tongue). Once the dose was determined stable, patients were given Sublocade by injection. A response to MAT was measured by urine drug screening and self-reporting of illicit opioid use during the six-month treatment period. Results indicated that Sublocade-treated patients had more weeks without positive urine tests or self-reports of opioid use, and a higher proportion of patients had no evidence of illicit opioid use throughout the treatment period, compared to the placebo group.

The most common side effects from treatment with Sublocade include constipation, nausea, vomiting, headache, drowsiness, injection site pain, itching (pruritus) at the injection site and abnormal liver function tests. The safety and efficacy of Sublocade have not been established in children or adolescents less than 17 years of age. Clinical studies of Sublocade did not include participants over the age of 65.

The FDA is requiring postmarketing studies to assess which patients would benefit from a higher dosing regimen, to determine whether Sublocade can be safely initiated without a dose stabilization period of sublingual buprenorphine, to assess the feasibility of administering Sublocade at a longer inter-dose interval than once-monthly and to determine a process for transitioning patients with long-term stability on a transmucosal buprenorphine dose to a monthly dose of Sublocade without the use of a higher dose for the first two months of treatment (loading dose).

Sublocade has a boxed warning that provides important safety information, including the risks of intravenous self-administration. If the product were to be administered intravenously rather than subcutaneously, the solid mass could cause occlusion (blockage), tissue damage or embolus (solid material that is carried in the blood and can become lodged in a blood vessel, which can lead to death). Sublocade must be prescribed and dispensed as part of a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the product is not distributed directly to patients. Sublocade will be provided to HCPs through a restricted program, administered only by HCPs in a health care setting, and will require health care settings and pharmacies that dispense Sublocade to complete an enrollment form attesting that they have procedures in place to ensure that Sublocade is dispensed only to HCPs and not directly to patients.

FDA Approves Sublocade (buprenorphine) Once-Monthly Injection for Opioid Use Disorder

Diet Drugs: Which Ones Work?

Any of the prescription weight-loss drugs on the market can help obese people shed pounds, although some seem more effective than others, a new study finds.

Currently, five drugs are approved in the United States for managing obesity. But little has been known about how they stack up against one another, said Dr. Siddharth Singh, the lead researcher on the new study.

The findings  based on more than 29,000 people in total show all five drugs can work. But people on certain drugs tended to be more successful, at least over one year.

Specifically, people using Qsymia (phentermine-topiramate) or Victoza (liraglutide) had the highest odds of shedding at least 5 percent of their initial weight. Those taking Xenical (orlistat) had the lowest odds.

phentermine liraglutide

 orlistat  lorcaserin

 Bupropion/naltrexone 

However, there is no single drug that's "best" for everyone, stressed Singh, an assistant clinical professor at the University of California, San Diego.

He cautioned that his team's numbers are just averages across study groups. Plus, he said, the side effects of each medication vary, and that is an important factor in treatment decisions.

"Obesity treatment always needs to be personalized," Singh said.

Nikhil Dhurandhar, a spokesman for the Obesity Society, agreed that people respond differently to any given weight-loss drug.

"In general, if you give drug 'X,' there will be a wide variation in patients' responses," said Dhurandhar, who is also a professor of nutritional sciences at Texas Tech University in Lubbock. He wasn't involved in the study.

Some people will have "zero" weight loss   or even gain weight -- while others will see the pounds drop off, Dhurandhar said.

He also stressed that there is no such thing as a magic weight-loss pill.

"These drugs can help you eat less through effects on appetite," Dhurandhar explained. "But you have to change your diet and get regular exercise."

"Medications are supplements, not substitutes, to your efforts," he said.

For the study, Singh's team analyzed findings from 28 clinical trials testing the five approved drugs for obesity: Qsymia, Victoza and Xenical, along with Belviq (lorcaserin) and Contrave (naltrexone-bupropion).

On average, the researchers found, each drug worked better than a placebo in helping obese adults lose weight over a year. But certain medications seemed more effective than others.

People on Qsymia typically lost the most weight -- almost 20 pounds more, versus study patients given placebo pills. They were also nine times more likely to drop at least 5 percent of their initial weight, the researchers found.

People taking Xenical or Belviq tended to shed the fewest pounds -- 6 to 7 pounds more than placebo users. Contrave and Victoza patients typically lost 11 to 12 pounds more, compared with placebo.

But not everyone benefited. In studies of all of the drugs, Singh noted, a significant number of people dropped out because of side effects.

And those dropouts were more common with certain medications, the study found. People taking Contrave or Victoza were almost three times more likely to quit a trial over side effects, compared with placebo users. According to Victoza's maker, the drug can cause inflammation of the pancreas or kidney problems.

Just as people vary in their weight-loss success with any given drug, their risks of side effects will differ, too, Singh said.

He pointed to Contrave as an example. Because it contains the antidepressant bupropion, it carries a boxed warning about the potential risk of suicidal thoughts. So it might not be the best choice for someone with psychiatric conditions that could make them more vulnerable, Singh said.

Victoza, meanwhile, is an injection drug prescribed for controlling high blood sugar in people with type 2 diabetes. So if a patient needs medication for diabetes as well as weight loss, Victoza might be a good option, Singh said.

Most of the medications have been approved only in the past few years, so one question is whether they maintain their effects over the long run, Singh said.

"We do need more long-term data," Dhurandhar agreed.

Still, he said, medications are an important option for managing obesity. And if one does not work, Dhurandhar added, he'd recommend trying another.

First buprenorphine implant for opioid dependence treatment gets FDA approval

The U.S. Food and Drug Administration today approved Probuphine, the first buprenorphine implant for the maintenance treatment of opioid dependence. Probuphine is designed to provide a constant, low-level dose of buprenorphine for six months in patients who are already stable on low-to-moderate doses of other forms of buprenorphine, as part of a complete treatment program.

Until today, buprenorphine for the treatment of opioid dependence was only approved as a pill or a film placed under the tongue or on the inside of a person's cheek until it dissolved. While effective, a pill or film may be lost, forgotten or stolen. However, as an implant, Probuphine provides a new treatment option for people in recovery who may value the unique benefits of a six-month implant compared to other forms of buprenorphine, such as the possibility of improved patient convenience from not needing to take medication on a daily basis. An independent FDA advisory committee supported the approval of Probuphine in a meeting held earlier this year.

"Opioid abuse and addiction have taken a devastating toll on American families. We must do everything we can to make new, innovative treatment options available that can help patients regain control over their lives," said FDA Commissioner Robert M. Califf, M.D. "Today's approval provides the first-ever implantable option to support patients' efforts to maintain treatment as part of their overall recovery program."

Expanding the use and availability of medication-assisted treatment (MAT) options like buprenorphine is an important component of the FDA's opioid action plan and one of three top priorities for the U.S. Department of Health and Human Services' Opioid Initiative aimed at reducing prescription opioid and heroin related overdose, death and dependence.

Opioid dependence is the diagnostic term used for the more common concept, "addiction," in the Probuphine clinical trials. Addiction is defined as a cluster of behavioral, cognitive and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use, persisting in drug use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, as well as the possibility of the development of tolerance or development of physical dependence. Physical dependence is not the same as addiction. Newer diagnostic terminology uses the term "opioid use disorder," which includes both milder forms of problematic opioid use as well as addiction.

MAT is a comprehensive approach that combines approved medications (currently, methadone, buprenorphine or naltrexone) with counseling and other behavioral therapies to treat patients with opioid use disorder. Regular adherence to MAT with buprenorphine reduces opioid withdrawal symptoms and the desire to use, without causing the cycle of highs and lows associated with opioid misuse or abuse. At sufficient doses, it also decreases the pleasurable effects of other opioids, making continued opioid abuse less attractive. According to the Substance Abuse and Mental Health Services Administration, patients receiving MAT for their opioid use disorder cut their risk of death from all causes in half.

"Scientific evidence suggests that maintenance treatment with these medications in the context of behavioral treatment and recovery support are more effective in the treatment of opioid use disorder than short-term detoxification programs aimed at abstinence," said Nora Volkow, M.D., director of the National Institute on Drug Abuse at the National Institutes of Health. "This product will expand the treatment alternatives available to people suffering from an opioid use disorder."

Probuphine should be used as part of a complete treatment program that includes counseling and psychosocial support. Probuphine consists of four, one-inch-long rods that are implanted under the skin on the inside of the upper arm and provide treatment for six months. Administering Probuphine requires specific training because it must be surgically inserted and removed. Only a health care provider who has completed the training and become certified through a restricted program called the Probuphine Risk Evaluation and Mitigation Strategy (REMS) program should insert and remove the implants. If further treatment is needed, new implants may be inserted in the opposite arm for one additional course of treatment. The FDA is requiring postmarketing studies to establish the safety and feasibility of placing the Probuphine implants for additional courses of treatment.

The safety and efficacy of Probuphine were demonstrated in a randomized clinical trial of adults who met the clinical criteria for opioid dependence and were considered stable after prior buprenorphine treatment. A response to MAT was measured by urine screening and self-reporting of illicit opioid use during the six month treatment period. Sixty-three percent of Probuphine-treated patients had no evidence of illicit opioid use throughout the six months of treatment – similar to the 64 percent of those who responded to sublingual (under the tongue) buprenorphine alone.

The most common side effects from treatment with Probuphine include implant-site pain, itching, and redness, as well as headache, depression, constipation, nausea, vomiting, back pain, toothache and oropharyngeal pain. The safety and efficacy of Probuphine have not been established in children or adolescents less than 16 years of age. Clinical studies of Probuphine did not include participants over the age of 65.

Probuphine has a boxed warning that provides important safety information for health care professionals, including a warning that insertion and removal of Probuphine are associated with the risk of implant migration, protrusion, expulsion and nerve damage resulting from the procedure. Probuphine must be prescribed and dispensed according to the Probuphine REMS program because of the risks of surgical complications and because of the risks of accidental overdose, misuse and abuse if an implant comes out or protrudes from the skin. As part of this program, Probuphine can only be prescribed and dispensed by health care providers who are certified with the REMS program and have completed live training, among other requirements.

Probuphine implants contain a significant amount of drug that can potentially be expelled or removed, resulting in the potential for accidental exposure or intentional misuse and abuse if the implant comes out of the skin. Patients should be seen during the first week after insertion and a visit schedule of no less than once-monthly is recommended for continued counseling and psychosocial support.

First buprenorphine implant for opioid dependence treatment gets FDA approval: The U.S. Food and Drug Administration today approved Probuphine, the first buprenorphine implant for the maintenance treatment of opioid dependence. Probuphine is designed to provide a constant, low-level dose of buprenorphine for six months in patients who are already stable on low-to-moderate doses of other forms of buprenorphine, as part of a complete treatment program.

Valeant and Progenics Announce FDA Approves Relistor Tablets for the Treatment of Opioid-Induced Constipation in Adults with Chronic Non-Cancer Pain

In continuation of my update on Naltrexone

Valeant Pharmaceuticals International, Inc.  and Progenics Pharmaceuticals, Inc. today announced that the U.S. Food and Drug Administration has approved Relistor (methylnaltrexone bromide) Tablets for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain. Valeant expects to commence sales of Relistor Tablets in the U.S. in the third quarter of 2016.

"Opioid-induced constipation represents a long-lasting and potentially debilitating side effect of opioid therapy for millions of patients suffering from chronic pain," commented Joseph C. Papa, Chief Executive Officer of Valeant. "We believe Oral Relistor represents a new alternative treatment for OIC, and we look forward to introducing the more convenient oral formulation as soon as practicable."

"We are delighted that this milestone for Relistor has been achieved, and that patients suffering from OIC will have this new treatment option," said Mark Baker, Chief Executive Officer of Progenics. "We expect the market to be receptive to a more convenient oral tablet formulation of Relistor's well-established subcutaneous preparation. We would like to thank, in particular, Dr. Tage Ramakrishna and Dr. Robert Israel of Valeant for their work over many years in the clinical development of Relistor."

"Relistor has a unique mechanism of action that binds to mu-opioid receptors without impacting the opioid-mediated analgesic effects on the central nervous system," said Richard L. Rauck, MD, Medical Director, Center for Clinical Research, President, Carolinas Pain Institute, President of the Sceptor Pain Foundation of which he is a founding member, and Immediate Past President of the World Institute of Pain. "This represents a true breakthrough in the treatment of OIC, and addresses a large and growing need in the field of pain management." Today, the FDA approved Relistor Tablets (450 mg once daily) for the treatment of OIC in adults with chronic non-cancer pain. Previously, Relistor Subcutaneous Injection (12 mg and 8 mg) was approved in 2008 for the treatment of OIC in adults with advanced illness who are receiving palliative care and in 2014 for the treatment of OIC in adults with chronic non-cancer pain. About the Phase 3 Clinical Trial of Oral Relistor for OIC in Chronic Non-Cancer Pain (NCP) A randomized, double-blind, Phase 3 trial was conducted to evaluate once-daily dosing of 450 mg (n=200) methylnaltrexone (MNTX) tablets compared to placebo (n=201) in adults with chronic NCP. In the 450 mg treatment arm, MNTX tablets demonstrated statistically significant improvements in rescue-free bowel movement (RFBM) within 4 hours of administration over 28 days of dosing when compared to placebo treatment, achieving the primary endpoint. The 450 mg treatment group also achieved statistical significance for the first key secondary efficacy endpoint where a higher percentage of responders (i.e., had ≥3 RFBMs/week, with an increase of ≥1 RFBM/week from baseline for at least 3 of the 4 weeks) was observed with MNTX treatment as compared to placebo. Overall, efficacy of oral methylnaltrexone in this study was comparable to that reported in clinical studies of subcutaneous methylnaltrexone in subjects with chronic, non-cancer pain. The overall observed safety profile seen in patients treated with oral methylnaltrexone was comparable to placebo in this study.

Important Safety Information

Relistor (methylnaltrexone bromide) Tablets is contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation.

Cases of gastrointestinal perforation have been reported in adult patients with OIC and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie's syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using Relistor in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn's disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue Relistor in patients who develop this symptom.

If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with Relistor and consult their healthcare provider.

Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with Relistor. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia. Take into account the overall risk-benefit profile when using Relistor in such patients. Monitor for adequacy of analgesia and symptoms of opioid withdrawal in such patients.

Avoid concomitant use of Relistor with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal. The most common adverse reactions (≥ 12%) in adult patients with opioid-induced constipation and chronic non-cancer pain receiving Relistor tablets were abdominal pain, diarrhea, headaches, abdominal distention, hyperhidrosis, anxiety, muscle spasms, rhinorrhea, and chills. Adverse reactions of abdominal pain, diarrhea, hyperhidrosis, anxiety, rhinorrhea, and chills may reflect symptoms of opioid withdrawal.

About Relistor

Progenics has exclusively licensed development and commercialization rights for its first commercial product, Relistor, to Valeant. Relistor Tablets (450 mg once daily) is approved in the United States for the treatment of OIC in patients with chronic non-cancer pain. Relistor Subcutaneous Injection (12 mg and 8 mg) is a treatment for opioid-induced constipation approved in the United States and worldwide for patients with advanced illness and chronic non-cancer pain.

FDA Approves New Obesity Drug Contrave

In continuation of my update on Contrave

The U.S. Food and Drug Administration's approval of a new weight-loss drug on Wednesday marks the third time the agency has given its blessing to a new diet medication since 2012.

Called Contrave, the medicine is a combination of two approved drugs: naltrexone, which treats alcohol and drug addiction, and bupropion, which treats depression and seasonal affective disorder and is used to help smokers quit.

The agency said in a news release that Contrave can be used by obese adults and by overweight adults who have at least one other weight-related condition or illness, such as high blood pressure or type 2 diabetes.

According to the U.S. Centers for Disease Control and Prevention, more than one-third of adults in the United States are obese, the FDA said in its news release.

"Obesity continues to be a major public health concern," said Dr. Jean-Marc Guettier, director of the division of metabolism and endocrinology products in the FDA's Center for Drug Evaluation and Research. "When used as directed in combination with a healthy lifestyle that includes a reduced-calorie diet and exercise, Contrave provides another treatment option for chronic weight management."

FDA Approves New Obesity Drug Contrave  

FDA Approves Contrave (bupropion/naltrexone) for Weight Management

In continuation of my update on bupropion/naltrexone

The U.S. Food and Drug Administration today approved Contrave (naltrexone hydrochloride and bupropion hydrochloride extended-release tablets) as treatment option for chronic weight management in addition to a reduced-calorie diet and physical activity.

FDA Approves Contrave (bupropion/naltrexone) for Weight Management

Drug May Help Women Who Quit Smoking Avoid Weight Gain - Drugs.com MedNews

In continuation of my update on Naltrexone

We know that, Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. It is marketed in generic form as its hydrochloridesalt, naltrexone hydrochloride, and marketed under the trade names Revia andDepade. In some countries including the United States, a once-monthly extended-release injectable formulation is marketed under the trade name Vivitrol. Also in the US, Methylnaltrexone Bromide, a closely related drug, is marketed as Relistor, for the treatment of opioid induced constipation.

Naltrexone should not be confused with naloxone (which is used in emergency cases of overdose rather than for longer-term dependence control) nor nalorphine. Using naloxone in place of naltrexone can cause far worse withdrawal symptoms; conversely, using naltrexone in place of naloxone in an overdose can lead to insufficient opiate antagonism and fail to reverse the overdose.

Drug May Help Women Who Quit Smoking Avoid Weight Gain - Drugs.com MedNews

FDA accepts Orexigen's Contrave NDA for treatment of obesity

Orexigen Therapeutics, Inc., a biopharmaceutical company focused on the treatment of obesity, recently anounced that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company's New Drug Application (NDA) for Contrave(R) (see structrures below ; naltrexone SR   and bupropion SR), its investigational drug for the treatment of obesity. The NDA is based on a substantial body of evidence gathered through the Contrave Obesity Research (COR) clinical program, which included over 4,500 patients.....

"We are pleased the FDA has accepted our NDA for filing and look forward to working with the Agency during the review process," said Michael Narachi, President and CEO of Orexigen. "If approved, we believe Contrave will become an important therapeutic option for obese patients, making weight loss and weight maintenance an achievable cornerstone in the treatment of obesity and its common co-morbidities."

Ref : http://ir.orexigen.com/phoenix.zhtml?c=207034&p=irol-newsArticle&ID=1432740&highlight=