U.S. yellow fever vaccine stocks could be depleted within months

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Supply of the only U.S.-licensed yellow fever vaccine will be depleted by mid-2017 because of manufacturing issues, according to the Centers for Disease Control and Prevention.

Sanofi Pasteur, the manufacturer of the YF-VAX vaccine, notified the CDC and the Food and Drug Administration in 2016 there could be a shortage this year after the manufacturing complications during a factory switch over led to the loss of a large amount of vaccine supply, according to an article published online in the Morbidity and Mortality Weekly Report.

The shortage is expected to affect government workers and military personnel as well as private travelers, 8 million of whom traveled to at least one of 42 countries with endemic yellow fever virus transmission in 2015 (MMWR. 2017 Apr 28. doi: 10.15585/mmwr.mm6617e2).

The CDC, Sanofi Pasteur, and the FDA are working to supplement the shortage. The manufacturer submitted an expanded investigational new drug (eIND) application to the FDA in September 2016 for marketing permission for Stamaril, an alternative vaccine manufactured by Sanofi Pasteur France and used in around 70 countries.

The application included planning for strategic distribution sites, which the CDC is determining using a tiered system based on volume of doses ordered in 2016.

As of April 2017, 250 civilian sites have been invited to participate in the eIND program, significantly less than the 4,000 currently distributing YF-VAX.

The CDC will “monitor for critical gaps in vaccine access and collaborate to address any issues, including considering the possibility of recruiting additional clinics to participate as necessary,” according to a statement.

Updates on the shortage will be available on the CDC travel health website.

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Supply of the only U.S.-licensed yellow fever vaccine will be depleted by mid-2017 because of manufacturing issues, according to the Centers for Disease Control and Prevention.

Sanofi Pasteur, the manufacturer of the YF-VAX vaccine, notified the CDC and the Food and Drug Administration in 2016 there could be a shortage this year after the manufacturing complications during a factory switch over led to the loss of a large amount of vaccine supply, according to an article published online in the Morbidity and Mortality Weekly Report.

The shortage is expected to affect government workers and military personnel as well as private travelers, 8 million of whom traveled to at least one of 42 countries with endemic yellow fever virus transmission in 2015 (MMWR. 2017 Apr 28. doi: 10.15585/mmwr.mm6617e2).

The CDC, Sanofi Pasteur, and the FDA are working to supplement the shortage. The manufacturer submitted an expanded investigational new drug (eIND) application to the FDA in September 2016 for marketing permission for Stamaril, an alternative vaccine manufactured by Sanofi Pasteur France and used in around 70 countries.

The application included planning for strategic distribution sites, which the CDC is determining using a tiered system based on volume of doses ordered in 2016.

As of April 2017, 250 civilian sites have been invited to participate in the eIND program, significantly less than the 4,000 currently distributing YF-VAX.

The CDC will “monitor for critical gaps in vaccine access and collaborate to address any issues, including considering the possibility of recruiting additional clinics to participate as necessary,” according to a statement.

Updates on the shortage will be available on the CDC travel health website.

 

Supply of the only U.S.-licensed yellow fever vaccine will be depleted by mid-2017 because of manufacturing issues, according to the Centers for Disease Control and Prevention.

Sanofi Pasteur, the manufacturer of the YF-VAX vaccine, notified the CDC and the Food and Drug Administration in 2016 there could be a shortage this year after the manufacturing complications during a factory switch over led to the loss of a large amount of vaccine supply, according to an article published online in the Morbidity and Mortality Weekly Report.

The shortage is expected to affect government workers and military personnel as well as private travelers, 8 million of whom traveled to at least one of 42 countries with endemic yellow fever virus transmission in 2015 (MMWR. 2017 Apr 28. doi: 10.15585/mmwr.mm6617e2).

The CDC, Sanofi Pasteur, and the FDA are working to supplement the shortage. The manufacturer submitted an expanded investigational new drug (eIND) application to the FDA in September 2016 for marketing permission for Stamaril, an alternative vaccine manufactured by Sanofi Pasteur France and used in around 70 countries.

The application included planning for strategic distribution sites, which the CDC is determining using a tiered system based on volume of doses ordered in 2016.

As of April 2017, 250 civilian sites have been invited to participate in the eIND program, significantly less than the 4,000 currently distributing YF-VAX.

The CDC will “monitor for critical gaps in vaccine access and collaborate to address any issues, including considering the possibility of recruiting additional clinics to participate as necessary,” according to a statement.

Updates on the shortage will be available on the CDC travel health website.

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FDA issues warning to companies selling illegal cancer treatments

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The Food and Drug Administration has issued a warning to 14 U.S. companies that are illegally selling more than 65 products purported to prevent, diagnose, treat, or cure cancer, according to an FDA safety alert.

Product types include pills, topical creams, ointments, oils, drops, syrups, teas, and diagnostic tools. The affected products are usually sold online or through social media.

“Consumers should not use these or similar unproven products because they may be unsafe and could prevent a person from seeking an appropriate and potentially life-saving cancer diagnosis or treatment. Avoid purchasing products marketed to treat cancer without any proof they will work. Patients should consult with their health care professional about proper prevention, diagnosis, and treatment of cancer,” the FDA said in the press release.

Find the full safety alert on the FDA website.

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The Food and Drug Administration has issued a warning to 14 U.S. companies that are illegally selling more than 65 products purported to prevent, diagnose, treat, or cure cancer, according to an FDA safety alert.

Product types include pills, topical creams, ointments, oils, drops, syrups, teas, and diagnostic tools. The affected products are usually sold online or through social media.

“Consumers should not use these or similar unproven products because they may be unsafe and could prevent a person from seeking an appropriate and potentially life-saving cancer diagnosis or treatment. Avoid purchasing products marketed to treat cancer without any proof they will work. Patients should consult with their health care professional about proper prevention, diagnosis, and treatment of cancer,” the FDA said in the press release.

Find the full safety alert on the FDA website.

 

The Food and Drug Administration has issued a warning to 14 U.S. companies that are illegally selling more than 65 products purported to prevent, diagnose, treat, or cure cancer, according to an FDA safety alert.

Product types include pills, topical creams, ointments, oils, drops, syrups, teas, and diagnostic tools. The affected products are usually sold online or through social media.

“Consumers should not use these or similar unproven products because they may be unsafe and could prevent a person from seeking an appropriate and potentially life-saving cancer diagnosis or treatment. Avoid purchasing products marketed to treat cancer without any proof they will work. Patients should consult with their health care professional about proper prevention, diagnosis, and treatment of cancer,” the FDA said in the press release.

Find the full safety alert on the FDA website.

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Renflexis approved as second infliximab biosimilar

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Infliximab-abda is the second infliximab biosimilar approved by the Food and Drug Administration, the agency announced April 21.

 

Infliximab-abda, to be marketed as Renflexis, is approved for all indications as the reference product, including Crohn’s diseases in adults and children, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis, according to the product label.

To gain FDA approval, infliximab-abda demonstrated that it has no clinically meaningful differences in terms of safety and effectiveness from the reference product (Remicade). Specifically, it meets the FDA regulations because it has only minor differences in clinically inactive components, has the same mechanism of action (to the extent that it is known) and route of administration, dosage form, and strength as the reference product.

Like Remicade, Renflexis will come with a boxed warning and a Medication Guide that describes important information about its uses and risks, which include serious infections, lymphoma and other malignancies, liver injury, blood problems, lupuslike syndrome, psoriasis, and in rare cases, nervous system disorders.

Renflexis will be marketed by Merck Sharp & Dohme and is manufactured by Samsung Bioepis.
 

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Infliximab-abda is the second infliximab biosimilar approved by the Food and Drug Administration, the agency announced April 21.

 

Infliximab-abda, to be marketed as Renflexis, is approved for all indications as the reference product, including Crohn’s diseases in adults and children, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis, according to the product label.

To gain FDA approval, infliximab-abda demonstrated that it has no clinically meaningful differences in terms of safety and effectiveness from the reference product (Remicade). Specifically, it meets the FDA regulations because it has only minor differences in clinically inactive components, has the same mechanism of action (to the extent that it is known) and route of administration, dosage form, and strength as the reference product.

Like Remicade, Renflexis will come with a boxed warning and a Medication Guide that describes important information about its uses and risks, which include serious infections, lymphoma and other malignancies, liver injury, blood problems, lupuslike syndrome, psoriasis, and in rare cases, nervous system disorders.

Renflexis will be marketed by Merck Sharp & Dohme and is manufactured by Samsung Bioepis.
 

 

Infliximab-abda is the second infliximab biosimilar approved by the Food and Drug Administration, the agency announced April 21.

 

Infliximab-abda, to be marketed as Renflexis, is approved for all indications as the reference product, including Crohn’s diseases in adults and children, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis, according to the product label.

To gain FDA approval, infliximab-abda demonstrated that it has no clinically meaningful differences in terms of safety and effectiveness from the reference product (Remicade). Specifically, it meets the FDA regulations because it has only minor differences in clinically inactive components, has the same mechanism of action (to the extent that it is known) and route of administration, dosage form, and strength as the reference product.

Like Remicade, Renflexis will come with a boxed warning and a Medication Guide that describes important information about its uses and risks, which include serious infections, lymphoma and other malignancies, liver injury, blood problems, lupuslike syndrome, psoriasis, and in rare cases, nervous system disorders.

Renflexis will be marketed by Merck Sharp & Dohme and is manufactured by Samsung Bioepis.
 

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DTC genetic health risk tests: Beware

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The Food and Drug Administration recently authorized 23andMe to provide consumers with results of germline DNA sequence variants associated with risk for 10 health conditions, among them hereditary hemochromatosis, alpha-1 antitrypsin deficiency, celiac disease, Alzheimer’s disease, and Parkinson’s disease. After they submit a saliva sample and pay a test fee, customers ordering the online test will receive a report delineating their ancestry markers and informing them whether they carry any of the genetic variants associated with selected health risks included on the targeted DNA sequencing panel.

Dr. Elena M. Stoffel
The FDA initially had issued a warning to 23andMe preventing them from including information about health risks on these direct-to-consumer (DTC) test reports. However, the current DTC test appears to meet the FDA’s requirements for test accuracy and reproducibility. Yet, it is important to note that the FDA’s authorization is not an endorsement of the validity or clinical utility of DTC health risk tests, which simply analyze whether an individual’s DNA carries a genetic variant associated with “increased” risk for the condition in question. In fact, the American College of Medical Genetics warns that DTC genetic tests, which interpret genomic information in the absence of individuals’ clinical and family history, have the potential to be misleading for both clinicians and patients, resulting in unnecessary worry and/or additional testing. When examining results of DTC health risk tests, the following truths should be self-evident: First, being a carrier of a genetic marker associated with a disease does not mean that a person has the disease or will necessarily ever develop the disease. Second, a negative DTC genetic test result does not exclude the disease.

As more consumers partake in “recreational genomic testing,” clinicians should understand the limitations of DTC genetic tests and should be prepared to discuss with patients why these should not supersede clinical diagnostic evaluations.
 

Dr. Stoffel is a gastroenterologist, assistant professor of internal medicine, and director of the cancer genetics clinic at the University of Michigan, Ann Arbor. She has no disclosures.

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The Food and Drug Administration recently authorized 23andMe to provide consumers with results of germline DNA sequence variants associated with risk for 10 health conditions, among them hereditary hemochromatosis, alpha-1 antitrypsin deficiency, celiac disease, Alzheimer’s disease, and Parkinson’s disease. After they submit a saliva sample and pay a test fee, customers ordering the online test will receive a report delineating their ancestry markers and informing them whether they carry any of the genetic variants associated with selected health risks included on the targeted DNA sequencing panel.

Dr. Elena M. Stoffel
The FDA initially had issued a warning to 23andMe preventing them from including information about health risks on these direct-to-consumer (DTC) test reports. However, the current DTC test appears to meet the FDA’s requirements for test accuracy and reproducibility. Yet, it is important to note that the FDA’s authorization is not an endorsement of the validity or clinical utility of DTC health risk tests, which simply analyze whether an individual’s DNA carries a genetic variant associated with “increased” risk for the condition in question. In fact, the American College of Medical Genetics warns that DTC genetic tests, which interpret genomic information in the absence of individuals’ clinical and family history, have the potential to be misleading for both clinicians and patients, resulting in unnecessary worry and/or additional testing. When examining results of DTC health risk tests, the following truths should be self-evident: First, being a carrier of a genetic marker associated with a disease does not mean that a person has the disease or will necessarily ever develop the disease. Second, a negative DTC genetic test result does not exclude the disease.

As more consumers partake in “recreational genomic testing,” clinicians should understand the limitations of DTC genetic tests and should be prepared to discuss with patients why these should not supersede clinical diagnostic evaluations.
 

Dr. Stoffel is a gastroenterologist, assistant professor of internal medicine, and director of the cancer genetics clinic at the University of Michigan, Ann Arbor. She has no disclosures.

 

The Food and Drug Administration recently authorized 23andMe to provide consumers with results of germline DNA sequence variants associated with risk for 10 health conditions, among them hereditary hemochromatosis, alpha-1 antitrypsin deficiency, celiac disease, Alzheimer’s disease, and Parkinson’s disease. After they submit a saliva sample and pay a test fee, customers ordering the online test will receive a report delineating their ancestry markers and informing them whether they carry any of the genetic variants associated with selected health risks included on the targeted DNA sequencing panel.

Dr. Elena M. Stoffel
The FDA initially had issued a warning to 23andMe preventing them from including information about health risks on these direct-to-consumer (DTC) test reports. However, the current DTC test appears to meet the FDA’s requirements for test accuracy and reproducibility. Yet, it is important to note that the FDA’s authorization is not an endorsement of the validity or clinical utility of DTC health risk tests, which simply analyze whether an individual’s DNA carries a genetic variant associated with “increased” risk for the condition in question. In fact, the American College of Medical Genetics warns that DTC genetic tests, which interpret genomic information in the absence of individuals’ clinical and family history, have the potential to be misleading for both clinicians and patients, resulting in unnecessary worry and/or additional testing. When examining results of DTC health risk tests, the following truths should be self-evident: First, being a carrier of a genetic marker associated with a disease does not mean that a person has the disease or will necessarily ever develop the disease. Second, a negative DTC genetic test result does not exclude the disease.

As more consumers partake in “recreational genomic testing,” clinicians should understand the limitations of DTC genetic tests and should be prepared to discuss with patients why these should not supersede clinical diagnostic evaluations.
 

Dr. Stoffel is a gastroenterologist, assistant professor of internal medicine, and director of the cancer genetics clinic at the University of Michigan, Ann Arbor. She has no disclosures.

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FDA warns against use of codeine, tramadol in children

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The Food and Drug Administration is restricting the use of two opiates – codeine and tramadol – in children, and also warns they are potentially dangerous to infants of breastfeeding women.

Codeine is approved to treat pain and cough; tramadol is approved to treat pain.

“We understand that there are limited options when it comes to treating pain or cough in children, and that these changes may raise some questions for health care providers and parents. However, please know that our decision today was made based on the latest evidence and with this goal in mind: keeping our kids safe,” Douglas Throckmorton, MD, the deputy center director for regulatory programs at the FDA Center for Drug Evaluation and Research, said in a statement.

In a drug safety alert, FDA officials wrote that medicines containing codeine or tramadol should not be used in children younger than 12 years, because of the risks of slowed or difficult breathing and death. The agency also warned against the use of these drugs in children who are obese or have respiratory conditions such as sleep apnea or asthma. There is also the potential risk of respiratory depression in infants of breastfeeding mothers taking these medicines.

In 2013, the FDA updated prescription codeine labeling to contain a boxed warning and contraindication for children up to age 18 years regarding the risk of slowed breathing from codeine prescribed after tonsillectomy and/or adenoidectomy. And in 2015, the agency issued warnings about the risk of serious breathing problems in children who had ultrarapid metabolism of codeine and tramadol.

In the current safety statement, the FDA said it will require additional labeling changes, including contraindications for use of codeine or tramadol in all children younger than 12 years of age and a new contraindication for tramadol in children younger than 18 years being treated for pain after tonsillectomy and/or adenoidectomy, warnings about their use in children 12-18 years of age with certain medical conditions, and a stronger warning recommending against their use in nursing mothers.

Single-ingredient codeine and all tramadol-containing products are FDA-approved only for use in adults, the agency noted.

The agency cited particular concerns over those who are “ultra-rapid metabolizers” of substrates of the cytochrome P450 isoenzyme 2D6 (CYP2D6) genotype. These people more quickly convert codeine into potentially dangerously high levels of morphine, which can lead to fatal respiratory depression.

Supporting the restrictions and warning were data on 64 cases of respiratory depression that occurred worldwide between 1969 and 2015, when a codeine-based medicine was used in children younger than 18 years. Twenty-four of these children died.

The most frequently cited medicines in the cases were acetaminophen with codeine and promethazine with codeine with or without phenylephrine, either given to soothe postoperative pain, general pain, sore or strep throat pain, or cough and cold.

Ten of the 64 cases implicated the CYP2D6 genotype. Seven of the patients were “ultrarapid metabolizers,” five of whom died.

Data cited on tramadol included nine worldwide cases of tramadol-related respiratory depression occurring between 1969 and 2016, resulting in the deaths of three children, all under the age of 6 years, and all of whom were taking the drug for postoperative pain or fever.

All but one case of respiratory depression occurred within the first 24 hours of taking the drug. One of the patients was genotyped for CYP2D6, and found to have three functional alleles consistent with ultrarapid metabolism.

Mothers who are ultrarapid metabolizers of codeine can have high levels of morphine in their breast milk that are dangerous to their breastfed infants, whereas there is less of a threat posed by women with normal codeine metabolism because the amount of codeine secreted into the breast milk is low and dose dependent.

The FDA stated that data reveal numerous reports of respiratory depression and at least one death in infants of breastfeeding mothers taking these medicines, particularly mothers with the CYP2D6 genotype. Although there are FDA-cleared tests for ultrarapid metabolism, they are not commonly used.

The agency stated that breastfeeding women taking any opioid pain medicine, including codeine or tramadol should contact their health care provider if they notice the infant is sleeping more than 4 hours at a time, or if the infant is having difficulty breastfeeding or seems limp.

Clinicians are urged to report side effects that occur while using codeine or tramadol to the FDA’s MedWatch Adverse Event Reporting program.

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The Food and Drug Administration is restricting the use of two opiates – codeine and tramadol – in children, and also warns they are potentially dangerous to infants of breastfeeding women.

Codeine is approved to treat pain and cough; tramadol is approved to treat pain.

“We understand that there are limited options when it comes to treating pain or cough in children, and that these changes may raise some questions for health care providers and parents. However, please know that our decision today was made based on the latest evidence and with this goal in mind: keeping our kids safe,” Douglas Throckmorton, MD, the deputy center director for regulatory programs at the FDA Center for Drug Evaluation and Research, said in a statement.

In a drug safety alert, FDA officials wrote that medicines containing codeine or tramadol should not be used in children younger than 12 years, because of the risks of slowed or difficult breathing and death. The agency also warned against the use of these drugs in children who are obese or have respiratory conditions such as sleep apnea or asthma. There is also the potential risk of respiratory depression in infants of breastfeeding mothers taking these medicines.

In 2013, the FDA updated prescription codeine labeling to contain a boxed warning and contraindication for children up to age 18 years regarding the risk of slowed breathing from codeine prescribed after tonsillectomy and/or adenoidectomy. And in 2015, the agency issued warnings about the risk of serious breathing problems in children who had ultrarapid metabolism of codeine and tramadol.

In the current safety statement, the FDA said it will require additional labeling changes, including contraindications for use of codeine or tramadol in all children younger than 12 years of age and a new contraindication for tramadol in children younger than 18 years being treated for pain after tonsillectomy and/or adenoidectomy, warnings about their use in children 12-18 years of age with certain medical conditions, and a stronger warning recommending against their use in nursing mothers.

Single-ingredient codeine and all tramadol-containing products are FDA-approved only for use in adults, the agency noted.

The agency cited particular concerns over those who are “ultra-rapid metabolizers” of substrates of the cytochrome P450 isoenzyme 2D6 (CYP2D6) genotype. These people more quickly convert codeine into potentially dangerously high levels of morphine, which can lead to fatal respiratory depression.

Supporting the restrictions and warning were data on 64 cases of respiratory depression that occurred worldwide between 1969 and 2015, when a codeine-based medicine was used in children younger than 18 years. Twenty-four of these children died.

The most frequently cited medicines in the cases were acetaminophen with codeine and promethazine with codeine with or without phenylephrine, either given to soothe postoperative pain, general pain, sore or strep throat pain, or cough and cold.

Ten of the 64 cases implicated the CYP2D6 genotype. Seven of the patients were “ultrarapid metabolizers,” five of whom died.

Data cited on tramadol included nine worldwide cases of tramadol-related respiratory depression occurring between 1969 and 2016, resulting in the deaths of three children, all under the age of 6 years, and all of whom were taking the drug for postoperative pain or fever.

All but one case of respiratory depression occurred within the first 24 hours of taking the drug. One of the patients was genotyped for CYP2D6, and found to have three functional alleles consistent with ultrarapid metabolism.

Mothers who are ultrarapid metabolizers of codeine can have high levels of morphine in their breast milk that are dangerous to their breastfed infants, whereas there is less of a threat posed by women with normal codeine metabolism because the amount of codeine secreted into the breast milk is low and dose dependent.

The FDA stated that data reveal numerous reports of respiratory depression and at least one death in infants of breastfeeding mothers taking these medicines, particularly mothers with the CYP2D6 genotype. Although there are FDA-cleared tests for ultrarapid metabolism, they are not commonly used.

The agency stated that breastfeeding women taking any opioid pain medicine, including codeine or tramadol should contact their health care provider if they notice the infant is sleeping more than 4 hours at a time, or if the infant is having difficulty breastfeeding or seems limp.

Clinicians are urged to report side effects that occur while using codeine or tramadol to the FDA’s MedWatch Adverse Event Reporting program.


The Food and Drug Administration is restricting the use of two opiates – codeine and tramadol – in children, and also warns they are potentially dangerous to infants of breastfeeding women.

Codeine is approved to treat pain and cough; tramadol is approved to treat pain.

“We understand that there are limited options when it comes to treating pain or cough in children, and that these changes may raise some questions for health care providers and parents. However, please know that our decision today was made based on the latest evidence and with this goal in mind: keeping our kids safe,” Douglas Throckmorton, MD, the deputy center director for regulatory programs at the FDA Center for Drug Evaluation and Research, said in a statement.

In a drug safety alert, FDA officials wrote that medicines containing codeine or tramadol should not be used in children younger than 12 years, because of the risks of slowed or difficult breathing and death. The agency also warned against the use of these drugs in children who are obese or have respiratory conditions such as sleep apnea or asthma. There is also the potential risk of respiratory depression in infants of breastfeeding mothers taking these medicines.

In 2013, the FDA updated prescription codeine labeling to contain a boxed warning and contraindication for children up to age 18 years regarding the risk of slowed breathing from codeine prescribed after tonsillectomy and/or adenoidectomy. And in 2015, the agency issued warnings about the risk of serious breathing problems in children who had ultrarapid metabolism of codeine and tramadol.

In the current safety statement, the FDA said it will require additional labeling changes, including contraindications for use of codeine or tramadol in all children younger than 12 years of age and a new contraindication for tramadol in children younger than 18 years being treated for pain after tonsillectomy and/or adenoidectomy, warnings about their use in children 12-18 years of age with certain medical conditions, and a stronger warning recommending against their use in nursing mothers.

Single-ingredient codeine and all tramadol-containing products are FDA-approved only for use in adults, the agency noted.

The agency cited particular concerns over those who are “ultra-rapid metabolizers” of substrates of the cytochrome P450 isoenzyme 2D6 (CYP2D6) genotype. These people more quickly convert codeine into potentially dangerously high levels of morphine, which can lead to fatal respiratory depression.

Supporting the restrictions and warning were data on 64 cases of respiratory depression that occurred worldwide between 1969 and 2015, when a codeine-based medicine was used in children younger than 18 years. Twenty-four of these children died.

The most frequently cited medicines in the cases were acetaminophen with codeine and promethazine with codeine with or without phenylephrine, either given to soothe postoperative pain, general pain, sore or strep throat pain, or cough and cold.

Ten of the 64 cases implicated the CYP2D6 genotype. Seven of the patients were “ultrarapid metabolizers,” five of whom died.

Data cited on tramadol included nine worldwide cases of tramadol-related respiratory depression occurring between 1969 and 2016, resulting in the deaths of three children, all under the age of 6 years, and all of whom were taking the drug for postoperative pain or fever.

All but one case of respiratory depression occurred within the first 24 hours of taking the drug. One of the patients was genotyped for CYP2D6, and found to have three functional alleles consistent with ultrarapid metabolism.

Mothers who are ultrarapid metabolizers of codeine can have high levels of morphine in their breast milk that are dangerous to their breastfed infants, whereas there is less of a threat posed by women with normal codeine metabolism because the amount of codeine secreted into the breast milk is low and dose dependent.

The FDA stated that data reveal numerous reports of respiratory depression and at least one death in infants of breastfeeding mothers taking these medicines, particularly mothers with the CYP2D6 genotype. Although there are FDA-cleared tests for ultrarapid metabolism, they are not commonly used.

The agency stated that breastfeeding women taking any opioid pain medicine, including codeine or tramadol should contact their health care provider if they notice the infant is sleeping more than 4 hours at a time, or if the infant is having difficulty breastfeeding or seems limp.

Clinicians are urged to report side effects that occur while using codeine or tramadol to the FDA’s MedWatch Adverse Event Reporting program.

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FDA approves new treatment for episodic cluster headaches in adults

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The Food and Drug Administration announced April 18 the approval of the gammaCore device to treat pain associated with episodic cluster headache in adult patients.

The agency based its approval of the noninvasive vagus nerve stimulator device on subgroup analyses of episodic cluster headache patients in the ACT1 and ACT2 trials, which were double-blind, placebo-controlled, randomized studies.

In the ACT1 trial of 85 patients, 34.2% experienced a reduction in pain (defined as the percentage of patients who reported mild or no pain 15 minutes after treatment initiation with gammaCore), compared with 10.6% of patients treated with placebo (P = .008). Of 27 patients in the ACT2 trial, 47.5% of patients using the device were pain free at 15 minutes after the onset of pain from cluster headache, with no use of rescue medication through the 30-minute treatment period, which was significantly greater than for placebo (6.2%; P = .003).

In both trials, gammaCore was found to be safe and well tolerated, and the majority of adverse events were mild and transient and occurring during the time of active treatment.

“Cluster headache is a rare, debilitating, and difficult to treat disorder with few effective acute therapies,” Stephen Silberstein, MD, director of the Headache Center at Jefferson University, Philadelphia, said in a statement from the manufacturer, electroCore. “The FDA release of gammaCore is an important advance in the treatment of the pain associated with cluster headache. It is a way for patients to treat their symptoms as often as they need to use the device. It does not have the side effects or dose limitations of commonly prescribed treatments or the need for invasive implantation procedures, which can be inconvenient, costly, and high-risk.”

The gammaCore device works by transmitting a mild electrical stimulation to the vagus nerve through the skin, resulting in a reduction of pain. Currently, gammaCore is in use only outside of the United States, including in the European Union. Commercial availability of gammaCore in the United States is expected to begin early in the third quarter of 2017, the company said.

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The Food and Drug Administration announced April 18 the approval of the gammaCore device to treat pain associated with episodic cluster headache in adult patients.

The agency based its approval of the noninvasive vagus nerve stimulator device on subgroup analyses of episodic cluster headache patients in the ACT1 and ACT2 trials, which were double-blind, placebo-controlled, randomized studies.

In the ACT1 trial of 85 patients, 34.2% experienced a reduction in pain (defined as the percentage of patients who reported mild or no pain 15 minutes after treatment initiation with gammaCore), compared with 10.6% of patients treated with placebo (P = .008). Of 27 patients in the ACT2 trial, 47.5% of patients using the device were pain free at 15 minutes after the onset of pain from cluster headache, with no use of rescue medication through the 30-minute treatment period, which was significantly greater than for placebo (6.2%; P = .003).

In both trials, gammaCore was found to be safe and well tolerated, and the majority of adverse events were mild and transient and occurring during the time of active treatment.

“Cluster headache is a rare, debilitating, and difficult to treat disorder with few effective acute therapies,” Stephen Silberstein, MD, director of the Headache Center at Jefferson University, Philadelphia, said in a statement from the manufacturer, electroCore. “The FDA release of gammaCore is an important advance in the treatment of the pain associated with cluster headache. It is a way for patients to treat their symptoms as often as they need to use the device. It does not have the side effects or dose limitations of commonly prescribed treatments or the need for invasive implantation procedures, which can be inconvenient, costly, and high-risk.”

The gammaCore device works by transmitting a mild electrical stimulation to the vagus nerve through the skin, resulting in a reduction of pain. Currently, gammaCore is in use only outside of the United States, including in the European Union. Commercial availability of gammaCore in the United States is expected to begin early in the third quarter of 2017, the company said.

 

The Food and Drug Administration announced April 18 the approval of the gammaCore device to treat pain associated with episodic cluster headache in adult patients.

The agency based its approval of the noninvasive vagus nerve stimulator device on subgroup analyses of episodic cluster headache patients in the ACT1 and ACT2 trials, which were double-blind, placebo-controlled, randomized studies.

In the ACT1 trial of 85 patients, 34.2% experienced a reduction in pain (defined as the percentage of patients who reported mild or no pain 15 minutes after treatment initiation with gammaCore), compared with 10.6% of patients treated with placebo (P = .008). Of 27 patients in the ACT2 trial, 47.5% of patients using the device were pain free at 15 minutes after the onset of pain from cluster headache, with no use of rescue medication through the 30-minute treatment period, which was significantly greater than for placebo (6.2%; P = .003).

In both trials, gammaCore was found to be safe and well tolerated, and the majority of adverse events were mild and transient and occurring during the time of active treatment.

“Cluster headache is a rare, debilitating, and difficult to treat disorder with few effective acute therapies,” Stephen Silberstein, MD, director of the Headache Center at Jefferson University, Philadelphia, said in a statement from the manufacturer, electroCore. “The FDA release of gammaCore is an important advance in the treatment of the pain associated with cluster headache. It is a way for patients to treat their symptoms as often as they need to use the device. It does not have the side effects or dose limitations of commonly prescribed treatments or the need for invasive implantation procedures, which can be inconvenient, costly, and high-risk.”

The gammaCore device works by transmitting a mild electrical stimulation to the vagus nerve through the skin, resulting in a reduction of pain. Currently, gammaCore is in use only outside of the United States, including in the European Union. Commercial availability of gammaCore in the United States is expected to begin early in the third quarter of 2017, the company said.

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FDA: REMS no longer necessary for epoetin, darbepoetin

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The Food and Drug Administration no longer requires certification of doctors and hospitals to prescribe epoetin alfa (Procrit, Epogen) or darbepoetin alfa (Aranesp) for chemotherapy anemia.

A Risk Evaluation and Mitigation Strategy (REMS) program was put in place in 2011 to make sure that the benefits of erythropoiesis-stimulating agents (ESAs) outweighed the risks when prescribed. Under the program, providers were required to become certified in the ESA REMS and to demonstrate that each patient had received counseling on the benefits and risks of the therapies prior to use.

The FDA has determined the REMS is no longer necessary, based on survey data submitted by Amgen, marketer of Epogen and Aranesp, and on additional FDA analyses to understand the impact that various regulatory and other actions have had on the use of ESAs.

Amgen’s prescriber surveys demonstrated “acceptable knowledge” of the need to counsel patients about the risks. Utilization data indicated “appropriate prescribing” as an alternative to transfusion.

In addition, in an evaluation of the impact of multiple regulatory actions, the FDA determined that full implementation of the ESA REMS in 2011 had minimal impact on trends in ESA utilization metrics, the FDA wrote.

The FDA concluded that regulatory actions and label changes – and the cut in payments for nonrenal indications from the Center for Medicare & Medicaid Services – were enough to reduce overuse in chemotherapy.

However, while the REMS is no longer necessary, the FDA says serious risks of shortened overall survival and/or increased risk of tumor progression or recurrence associated with these drugs remain and health care providers should continue to discuss the risks and benefits of using ESAs with each patient before initiating use.
 

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The Food and Drug Administration no longer requires certification of doctors and hospitals to prescribe epoetin alfa (Procrit, Epogen) or darbepoetin alfa (Aranesp) for chemotherapy anemia.

A Risk Evaluation and Mitigation Strategy (REMS) program was put in place in 2011 to make sure that the benefits of erythropoiesis-stimulating agents (ESAs) outweighed the risks when prescribed. Under the program, providers were required to become certified in the ESA REMS and to demonstrate that each patient had received counseling on the benefits and risks of the therapies prior to use.

The FDA has determined the REMS is no longer necessary, based on survey data submitted by Amgen, marketer of Epogen and Aranesp, and on additional FDA analyses to understand the impact that various regulatory and other actions have had on the use of ESAs.

Amgen’s prescriber surveys demonstrated “acceptable knowledge” of the need to counsel patients about the risks. Utilization data indicated “appropriate prescribing” as an alternative to transfusion.

In addition, in an evaluation of the impact of multiple regulatory actions, the FDA determined that full implementation of the ESA REMS in 2011 had minimal impact on trends in ESA utilization metrics, the FDA wrote.

The FDA concluded that regulatory actions and label changes – and the cut in payments for nonrenal indications from the Center for Medicare & Medicaid Services – were enough to reduce overuse in chemotherapy.

However, while the REMS is no longer necessary, the FDA says serious risks of shortened overall survival and/or increased risk of tumor progression or recurrence associated with these drugs remain and health care providers should continue to discuss the risks and benefits of using ESAs with each patient before initiating use.
 

 

The Food and Drug Administration no longer requires certification of doctors and hospitals to prescribe epoetin alfa (Procrit, Epogen) or darbepoetin alfa (Aranesp) for chemotherapy anemia.

A Risk Evaluation and Mitigation Strategy (REMS) program was put in place in 2011 to make sure that the benefits of erythropoiesis-stimulating agents (ESAs) outweighed the risks when prescribed. Under the program, providers were required to become certified in the ESA REMS and to demonstrate that each patient had received counseling on the benefits and risks of the therapies prior to use.

The FDA has determined the REMS is no longer necessary, based on survey data submitted by Amgen, marketer of Epogen and Aranesp, and on additional FDA analyses to understand the impact that various regulatory and other actions have had on the use of ESAs.

Amgen’s prescriber surveys demonstrated “acceptable knowledge” of the need to counsel patients about the risks. Utilization data indicated “appropriate prescribing” as an alternative to transfusion.

In addition, in an evaluation of the impact of multiple regulatory actions, the FDA determined that full implementation of the ESA REMS in 2011 had minimal impact on trends in ESA utilization metrics, the FDA wrote.

The FDA concluded that regulatory actions and label changes – and the cut in payments for nonrenal indications from the Center for Medicare & Medicaid Services – were enough to reduce overuse in chemotherapy.

However, while the REMS is no longer necessary, the FDA says serious risks of shortened overall survival and/or increased risk of tumor progression or recurrence associated with these drugs remain and health care providers should continue to discuss the risks and benefits of using ESAs with each patient before initiating use.
 

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FDA sends baricitinib application back for revision

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The Food and Drug Administration will not be able to approve a new drug application for baricitinib, a Janus kinase (JAK) inhibitor for moderate to severe rheumatoid arthritis, according to a statement from manufacturer Eli Lilly.

The FDA complete response letter cited the need for additional data to determine the most appropriate doses for the once-daily oral medication and to suss out safety concerns across treatment arms.

“We are disappointed with this action. We remain confident in the benefit/risk of baricitinib as a new treatment option for adults with moderate to severe RA,” Christi Shaw, president of Lilly Bio-Medicines, said in a statement. “We will continue to work with the FDA to determine a path forward and ultimately bring baricitinib to patients in the U.S.”

In the recently published RA-BEAM trial, a manufacturer-sponsored, international, randomized, double-blind, phase III clinical trial involving 1,305 adults with moderate to severe active RA, 70% of patients taking baricitinib plus background therapy with methotrexate met the primary efficacy end point – the proportion of patients at week 12 who showed an ACR 20 response – compared with 40% for placebo (N Engl J Med. 2017;376:652-62).

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The Food and Drug Administration will not be able to approve a new drug application for baricitinib, a Janus kinase (JAK) inhibitor for moderate to severe rheumatoid arthritis, according to a statement from manufacturer Eli Lilly.

The FDA complete response letter cited the need for additional data to determine the most appropriate doses for the once-daily oral medication and to suss out safety concerns across treatment arms.

“We are disappointed with this action. We remain confident in the benefit/risk of baricitinib as a new treatment option for adults with moderate to severe RA,” Christi Shaw, president of Lilly Bio-Medicines, said in a statement. “We will continue to work with the FDA to determine a path forward and ultimately bring baricitinib to patients in the U.S.”

In the recently published RA-BEAM trial, a manufacturer-sponsored, international, randomized, double-blind, phase III clinical trial involving 1,305 adults with moderate to severe active RA, 70% of patients taking baricitinib plus background therapy with methotrexate met the primary efficacy end point – the proportion of patients at week 12 who showed an ACR 20 response – compared with 40% for placebo (N Engl J Med. 2017;376:652-62).

 

The Food and Drug Administration will not be able to approve a new drug application for baricitinib, a Janus kinase (JAK) inhibitor for moderate to severe rheumatoid arthritis, according to a statement from manufacturer Eli Lilly.

The FDA complete response letter cited the need for additional data to determine the most appropriate doses for the once-daily oral medication and to suss out safety concerns across treatment arms.

“We are disappointed with this action. We remain confident in the benefit/risk of baricitinib as a new treatment option for adults with moderate to severe RA,” Christi Shaw, president of Lilly Bio-Medicines, said in a statement. “We will continue to work with the FDA to determine a path forward and ultimately bring baricitinib to patients in the U.S.”

In the recently published RA-BEAM trial, a manufacturer-sponsored, international, randomized, double-blind, phase III clinical trial involving 1,305 adults with moderate to severe active RA, 70% of patients taking baricitinib plus background therapy with methotrexate met the primary efficacy end point – the proportion of patients at week 12 who showed an ACR 20 response – compared with 40% for placebo (N Engl J Med. 2017;376:652-62).

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Polycythemia vera test detects JAK2 V617F/G1849T mutation

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The ipsogen JAK2 RGQ PCR Kit has been given marketing authorization by the Food and Drug Administration.

This is the first FDA-authorized test for use in evaluating patients for suspected polycythemia vera, according to an FDA press release. Manufactured by Qiagen, the kit detects the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood.

The presence of JAK2 mutations is one of the major criteria for clinical confirmation of polycythemia vera. The V617F/G1849T mutation is detected in more than 94% of these patients. This test does not detect less common mutations including mutations in exon 12 and is not intended for stand-alone diagnosis, which is based on other clinicopathological factors of polycythemia vera.

Marketing authorization, granted March 27, 2017, was based on data from a clinical study of 216 patients with suspected polycythemia vera. The study compared results from the ipsogen JAK2 RGQ PCR Kit with results obtained with Sanger sequencing. In the study, the ipsogen JAK2 RGQ PCR Kit test detected polycythemia vera with 94.6% sensitivity and 98.1% specificity.

Further information about the JAK2 RGQ PCR Kit is available at https://www.accessdata.fda.gov/cdrh_docs/pdf16/DEN160028.pdf.

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The ipsogen JAK2 RGQ PCR Kit has been given marketing authorization by the Food and Drug Administration.

This is the first FDA-authorized test for use in evaluating patients for suspected polycythemia vera, according to an FDA press release. Manufactured by Qiagen, the kit detects the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood.

The presence of JAK2 mutations is one of the major criteria for clinical confirmation of polycythemia vera. The V617F/G1849T mutation is detected in more than 94% of these patients. This test does not detect less common mutations including mutations in exon 12 and is not intended for stand-alone diagnosis, which is based on other clinicopathological factors of polycythemia vera.

Marketing authorization, granted March 27, 2017, was based on data from a clinical study of 216 patients with suspected polycythemia vera. The study compared results from the ipsogen JAK2 RGQ PCR Kit with results obtained with Sanger sequencing. In the study, the ipsogen JAK2 RGQ PCR Kit test detected polycythemia vera with 94.6% sensitivity and 98.1% specificity.

Further information about the JAK2 RGQ PCR Kit is available at https://www.accessdata.fda.gov/cdrh_docs/pdf16/DEN160028.pdf.

 

The ipsogen JAK2 RGQ PCR Kit has been given marketing authorization by the Food and Drug Administration.

This is the first FDA-authorized test for use in evaluating patients for suspected polycythemia vera, according to an FDA press release. Manufactured by Qiagen, the kit detects the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood.

The presence of JAK2 mutations is one of the major criteria for clinical confirmation of polycythemia vera. The V617F/G1849T mutation is detected in more than 94% of these patients. This test does not detect less common mutations including mutations in exon 12 and is not intended for stand-alone diagnosis, which is based on other clinicopathological factors of polycythemia vera.

Marketing authorization, granted March 27, 2017, was based on data from a clinical study of 216 patients with suspected polycythemia vera. The study compared results from the ipsogen JAK2 RGQ PCR Kit with results obtained with Sanger sequencing. In the study, the ipsogen JAK2 RGQ PCR Kit test detected polycythemia vera with 94.6% sensitivity and 98.1% specificity.

Further information about the JAK2 RGQ PCR Kit is available at https://www.accessdata.fda.gov/cdrh_docs/pdf16/DEN160028.pdf.

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FDA approves Sovaldi, Harvoni for HCV in ages 12-plus

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The Food and Drug Administration has approved the use of Sovaldi (sofosbuvir) and Harvoni (ledipasvir and sofosbuvir) for the treatment of hepatitis C virus (HCV) in children aged 12 years and older.

The drugs – the first direct-acting, potentially curative antiviral treatments approved for children and adolescents with HCV – previously were approved for adults. The supplemental applications submitted by Gilead Sciences, which markets the drugs, were approved by the FDA on April 7 and expand the use of these drugs to pediatric patients aged 12 and up who weigh at least 77 pounds, and who have either mild or no cirrhosis; Sovaldi is indicated for those with HCV genotypes 2 or 3, and Harvoni is indicated for those with HCV genotypes 1, 4, 5, or 6.
 

 

“These approvals will help change the landscape for HCV treatment by addressing an unmet need in children and adolescents,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a press statement.

The safety, pharmacokinetics, and efficacy of the drugs as established in trials leading to their approval for adults were confirmed in open-label trials in the pediatric population. Adverse effects with Sovaldi, which was studied in combination with ribavirin, included headache and fatigue.

Of note, hepatitis B virus (HBV) reactivation has been reported in adults with HCV/HBV coinfection who were treated with these drugs, but who were not receiving HBV antiviral therapy; therefore, all patients should be screened for evidence of current or prior HBV infection before starting treatment with Harvoni or Sovaldi, according to the FDA statement.
 

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The Food and Drug Administration has approved the use of Sovaldi (sofosbuvir) and Harvoni (ledipasvir and sofosbuvir) for the treatment of hepatitis C virus (HCV) in children aged 12 years and older.

The drugs – the first direct-acting, potentially curative antiviral treatments approved for children and adolescents with HCV – previously were approved for adults. The supplemental applications submitted by Gilead Sciences, which markets the drugs, were approved by the FDA on April 7 and expand the use of these drugs to pediatric patients aged 12 and up who weigh at least 77 pounds, and who have either mild or no cirrhosis; Sovaldi is indicated for those with HCV genotypes 2 or 3, and Harvoni is indicated for those with HCV genotypes 1, 4, 5, or 6.
 

 

“These approvals will help change the landscape for HCV treatment by addressing an unmet need in children and adolescents,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a press statement.

The safety, pharmacokinetics, and efficacy of the drugs as established in trials leading to their approval for adults were confirmed in open-label trials in the pediatric population. Adverse effects with Sovaldi, which was studied in combination with ribavirin, included headache and fatigue.

Of note, hepatitis B virus (HBV) reactivation has been reported in adults with HCV/HBV coinfection who were treated with these drugs, but who were not receiving HBV antiviral therapy; therefore, all patients should be screened for evidence of current or prior HBV infection before starting treatment with Harvoni or Sovaldi, according to the FDA statement.
 

The Food and Drug Administration has approved the use of Sovaldi (sofosbuvir) and Harvoni (ledipasvir and sofosbuvir) for the treatment of hepatitis C virus (HCV) in children aged 12 years and older.

The drugs – the first direct-acting, potentially curative antiviral treatments approved for children and adolescents with HCV – previously were approved for adults. The supplemental applications submitted by Gilead Sciences, which markets the drugs, were approved by the FDA on April 7 and expand the use of these drugs to pediatric patients aged 12 and up who weigh at least 77 pounds, and who have either mild or no cirrhosis; Sovaldi is indicated for those with HCV genotypes 2 or 3, and Harvoni is indicated for those with HCV genotypes 1, 4, 5, or 6.
 

 

“These approvals will help change the landscape for HCV treatment by addressing an unmet need in children and adolescents,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a press statement.

The safety, pharmacokinetics, and efficacy of the drugs as established in trials leading to their approval for adults were confirmed in open-label trials in the pediatric population. Adverse effects with Sovaldi, which was studied in combination with ribavirin, included headache and fatigue.

Of note, hepatitis B virus (HBV) reactivation has been reported in adults with HCV/HBV coinfection who were treated with these drugs, but who were not receiving HBV antiviral therapy; therefore, all patients should be screened for evidence of current or prior HBV infection before starting treatment with Harvoni or Sovaldi, according to the FDA statement.
 

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