jueves, 27 de agosto de 2015

Edurant (rilpivirine) labeling updated

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Information about FDA HIV product approvals, safety warnings, medical product labeling changes, notices of upcoming public meetings, and notices about proposed regulatory guidances.

On August 26, 2015 the Edurant (rilpivirine) product labeling was updated to include the use of rilpivirine in combination with other antiretroviral agents for the treatment of HIV-1 infection to include treatment-naïve pediatric patients from 12 to less than 18 years of age with HIV-1 RNA less than or equal to 100,00 copies/mL. The summary of the changes are provided below. In addition to the addition of the adolescent data to the label, changes were made the Warnings and Precautions with respect to Depressive Disorders and updates to the adrenal function subsection in section 6 Adverse Reactions.
Section 2: DOSAGE AND ADMINISTRATION was updated as follows:
The recommended dosage of EDURANT in patients 12 years of age and older and weighing at least 35 kg is one 25 mg tablet once daily taken orally with a meal. EDURANT is not recommended for patients less than 12 years of age.
Section 5 Warnings and Precautions was updated as follows:
5.3 Depressive Disorders
The adverse reaction depressive disorders (depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) has been reported with EDURANT. Patients with severe depressive symptoms should seek immediate medical evaluation to assess the possibility that the symptoms are related to EDURANT, and if so, to determine whether the risks of continued therapy outweigh the benefits.
During the Phase 3 trials in adults (N = 1368) through 96 weeks, the incidence of depressive disorders (regardless of causality, severity) reported among EDURANT (n = 686) or efavirenz (n = 682) was 9% and 8%, respectively. Most events were mild or moderate in severity. The incidence of Grade 3 and 4 depressive disorders (regardless of causality) was 1% for both EDURANT and efavirenz. The incidence of discontinuation due to depressive disorders among EDURANT or efavirenz was 1% in each arm. Suicidal ideation was reported in 4 subjects in each arm while suicide attempt was reported in 2 subjects in the EDURANT arm.
During the Phase 2 trial in pediatric subjects 12 to less than 18 years of age (N = 36) receiving EDURANT through 48 weeks, the incidence of depressive disorders (regardless of causality, severity) was 19.4% (7/36). Most events were mild or moderate in severity. The incidence of Grade 3 and 4 depressive disorders (regardless of causality) was 5.6% (2/36). None of the subjects discontinued due to depressive disorders. Suicidal ideation and suicide attempt were reported in 1 subject.
Section 6: ADVERSE REACTIONS – Adults was revised as follows
Adrenal Function
In the pooled Phase 3 trials, at Week 96, there was an overall mean change from baseline in basal cortisol of -0.69 (-1.12, 0.27) micrograms/dL in the EDURANT group and of -0.02 (-0.48, 0.44) micrograms/dL in the efavirenz group.
In the EDURANT group, 43/588 (7.3%) of subjects with a normal 250 micrograms ACTH stimulation test at baseline developed an abnormal 250 micrograms ACTH stimulation test (peak cortisol level < 18.1 micrograms/dL) during the trial compared to 18/561 (3.2%) in the efavirenz group. Of the subjects who developed an abnormal 250 micrograms ACTH stimulation test during the trial, fourteen subjects in the EDURANT group and nine subjects in the efavirenz group had an abnormal 250 micrograms ACTH stimulation test at Week 96. Overall, there were no serious adverse events, deaths, or treatment discontinuations that could clearly be attributed to adrenal insufficiency. The clinical significance of the higher abnormal rate of 250 micrograms ACTH stimulation tests in the EDURANT group is not known.
Section 6.2: Clinical Trials Experience: Pediatric Patients was added as follows.
The safety assessment is based on the Week 48 analysis of the single-arm, open-label, Phase 2 trial, TMC278 C213, in which 36 antiretroviral treatment naïve HIV 1 infected patients 12 to less than 18 years of age and weighing at least 32 kg received EDURANT (25 mg once daily) in combination with other antiretroviral agents [see Clinical Studies (14.2)]. The median duration of exposure was 63.5 weeks. There were no patients who discontinued treatment due to ADRs. No new ADRs were identified compared to those seen in adults.
ADRs were reported in nineteen pediatric subjects (52.8%). Most ADRs were Grade 1 or 2. The most common ADRs reported in at least 2 subjects (regardless of severity) include headache (19.4%), depression (19.4%), somnolence (13.9%), nausea (11.1%), dizziness (8.3%), abdominal pain (8.3), vomiting (5.6%) and rash (5.6%).
Observed laboratory abnormalities were comparable to those in adults.
Adrenal Function
In trial TMC278 C213, at Week 48, the overall mean change from baseline in basal cortisol showed an increase of 1.59 (0.24, 2.93) micrograms/dL.
Six of 30 (20%) subjects with a normal 250 micrograms ACTH stimulation test at baseline developed an abnormal 250 micrograms ACTH stimulation test (peak cortisol level < 18.1 micrograms/dL) during the trial. Three of these subjects had an abnormal 250 micrograms ACTH stimulation test at Week 48. Overall, there were no serious adverse events, deaths, or treatment discontinuations that could clearly be attributed to adrenal insufficiency. The clinical significance of the abnormal 250 micrograms ACTH stimulation tests is not known.
Section 12 Clinical Pharmacology was updated to include the adolescent pharmacokinetic data
Section 14 Clinical Studies section was added as follows:
14.2 Treatment-Naïve Pediatric Subjects (12 to less than 18 years of age)
The pharmacokinetics, safety, tolerability and efficacy of EDURANT 25 mg once daily, in combination with an investigator-selected background regimen (BR) containing two NRTIs, was evaluated in trial TMC278-C213, a single-arm, open-label Phase 2 trial in antiretroviral treatment-naïve HIV-1 infected pediatric subjects 12 to less than 18 years of age and weighing at least 32 kg. Thirty six (36) subjects were enrolled in the trial to complete at least 48 weeks of treatment. The 36 subjects had a median age of 14.5 years (range: 12 to 17 years), and were 55.6% female, 88.9% Black and 11.1% Asian.
In the efficacy analysis, most subjects (75%; 28/36) had baseline HIV RNA <100 123="" 28="" 2="" 445.5="" 44="" 983="" and="" baseline="" cd4="" cell="" cells="" copies="" count="" for="" hiv-1="" median="" ml.="" ml="" mm3="" nbsp="" p="" plasma="" range:="" rna="" subjects="" the="" these="" to="" was="">
Among the subjects who had baseline HIV RNA ≤ 100,000, the proportion with HIV 1 RNA <50 48="" 50.0="" 79="" at="" copies="" in="" ml="" those="" versus="" was="" week="" with="">100,000 copies/mL. The proportion of virologic failures among subjects with a baseline viral load ≤100,000 copies/mL was 21.4% (6/28), versus 37.5% (3/8) in those with >100,000 copies/mL. At Week 48, the mean increase in CD4+ cell count from baseline was 201.2 cells/mm3.
You can view the complete label at drugs@fda or dailymed.
Richard Klein
Office of Health and Constituent Affairs
Food and Drug Administrationn
Kimberly Struble
Division of Antiviral Products
Food and Drug Administration
Steve Morin
Office of Health and Constituent Affairs
Food and Drug Administration

For more information about the HIV Liaison Program visit the FDA Patient Network

8 comentarios:

  1. • This is real take it serious, i am JOHNSON JUDITH i am from Ireland. Who will believe that a herbal medicine can cure HIV/AIDS, I never believe that this will work, i have spend a lot money getting drugs from the hospital to keep me and my son healthy, it got to a point that i was waiting for death to come because i was broke, one day i heard about this great man called Dr ODUWA who is well known for Herpes, HIV, and Cancer cure, i decided to email him I didn't believe him that much, I just wanted to give him a try, he replied my mail and Needed some Information about me, then I sent them to him, he prepared a herbal medicine (CURE) and, he gave my details to the Courier Office. they told me that 4-8 days I will receive the package and after receiving it, i took the medicine as prescribed by him at the end of the two weeks, he told me to go to the hospital for a checkup, and i went, surprisingly after the test the doctor confirm me HIV/AIDS negative, and my son and i thought it was a joke, i went to other hospital and was also negative, thank you for saving our life's, I promise I will always testify of your good works. If you are HIV/AIDS patient, contact him and I am sure you will get cured, contact him via: dr.oduwaspellhome@gmail.com or whatsapp him at +2348070685053.
    THESE ARE THE THINGS Dr ODUWA CURE
    . COLD SORE
    . HIV/AIDS
    . CANCER
    . HPV
    . LASSA FEVER
    . GONORRHEA

    ResponderEliminar
    Respuestas
    1. Hello everyone in this forum i am LEOKADIA STELLA from USA. i was waiting for this days to come so that i will share a testimony of how i was cure of my hiv/aids by DR ODUWA the great healer. i will never forget this two days in my life the day i tested hiv positive and the day i tested negative. the day i tested positive was the saddest day for me but the day i tested negative was the happiest day for me, but who was the source of my happiness is God and DR ODUWA the great healer, that is the reason i am taking all my time to share this testimony so that people who might also need help of curing their sickness to contact him through his email: dr.oduwaspellhome@gmail.com as i earlier did when i was searching for help. This man brought countless joy into my life and my family as well. Well i have really believe that God sent you to heal his people from this deadly disease. i will forever give thanks to you for healing me from hiv. Please kindly contact this great healer if you need his help because he can save your soul he just saved mine. Contact email address: dr.oduwaspellhome@gmail.com

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    2. My names is Sandra I was diagnosed of Herpes disease 2017, I was told by my doctor that there’s no cure. I was so worried anytime i think about it,i was spending alot on medication,and i was sacked from work,because i was always sick,infact my life was a mess..i was just researching online I saw a lot of testimonials about Dr Odila on how he uses herbal medicine to cure so many deadly disease …. I contacted him via email: drodilaherbalhome@gmail.com and told him my problems, then he said i will be totally cured within 14days,my heart was full on joy when he said that i will be totally cured within 14days ,i just had faith and believe,then i purchased the herbal medicine and sent him my details such as NAME,HOME ADDRESS,PHONE NUMBER ,Then Dr Odila sent me the herbal medicine to me through courier service and I used the herbal medicine for good 14days, then I went for check-up and my doctor confirmed thats am totally free from Herpes it work like a miracle to me ,please viewers out there this is real am so happy to share this testimony .thanks to perfect health GOD WILL BLESS U . contact him through drodilaherbalhome@gmail.com or whatsapp +2348159047935. here is my private email sandraprecious100@gmail.com

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    3. Having herpes is not the end of life there many treatment to cure herpes infection with the help of Dr Edidia herbal product.
      I was positive to the deadly virus called HERPES and i lost hope because i
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      i searched on-line to know and enquirer about cure for HERPES and i read
      someone testimony on how he was cured from HSV-2 so i decided to contact
      the same herbalist Call Dr Edidia because i know that nature has the power
      to heal everything.
      i contacted him to know how he can help me and he told me never to worry
      that he will help me with the natural herbs from God!
      after 2 days of contacting him, he told me that the cure has been ready and
      he sent it to me via UPS SPEED POST and it got to me after 3 days!
      i used the medicine as he instructed me (MORNING and EVENING) and i was
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      thats the reason i decided to also add more comment of Him so that more can
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      here is the Dr website http://dredidiaherbalhome.weebly.com/
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      I,m rosesharon and you can get intouch with me via rosesharon915@gmail.com also view website to know him.

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  2. • This is real take it serious, i am JOHNSON JUDITH i am from Ireland. Who will believe that a herbal medicine can cure HIV/AIDS, I never believe that this will work, i have spend a lot money getting drugs from the hospital to keep me and my son healthy, it got to a point that i was waiting for death to come because i was broke, one day i heard about this great man called Dr ODUWA who is well known for Herpes, HIV, and Cancer cure, i decided to email him I didn't believe him that much, I just wanted to give him a try, he replied my mail and Needed some Information about me, then I sent them to him, he prepared a herbal medicine (CURE) and, he gave my details to the Courier Office. they told me that 4-8 days I will receive the package and after receiving it, i took the medicine as prescribed by him at the end of the two weeks, he told me to go to the hospital for a checkup, and i went, surprisingly after the test the doctor confirm me HIV/AIDS negative, and my son and i thought it was a joke, i went to other hospital and was also negative, thank you for saving our life's, I promise I will always testify of your good works. If you are HIV/AIDS patient, contact him and I am sure you will get cured, contact him via: dr.oduwaspellhome@gmail.com or whatsapp him at +2348070685053.
    THESE ARE THE THINGS Dr ODUWA CURE
    . COLD SORE
    . HIV/AIDS
    . CANCER
    . HPV
    . LASSA FEVER
    . GONORRHEA

    ResponderEliminar
  3. I can’t believe this is really true I never believe there is cure to this hsv 2 because all the hospital have told me there is no cure to it, few months ago I saw this man email DR.AZIEGBE on internet from a testimony share by someone who he help with his herbal cure I contact his email and ask for his help also, that is how he inform me about the cure process and this man sent me a herbal medicine which I took according to the way he instructed for 2 week I can’t believe when I go for test my result come out negative i am so happy to share this to the world there is real cure to herpes you can also contact DR.AZIEGBE through his email now DRAZIEGBE1SPELLHOME@GMAIL.COM and also WhatsApp him +2349035465208. or my assistant text me +1 (601) 452-8622 or email: JAMESAVA0001@GMAIL.COM...

    ResponderEliminar
  4. Hello everyone in this forum i am LEOKADIA STELLA from USA. i was waiting for this days to come so that i will share a testimony of how i was cure of my hiv/aids by DR ODUWA the great healer. i will never forget this two days in my life the day i tested hiv positive and the day i tested negative. the day i tested positive was the saddest day for me but the day i tested negative was the happiest day for me, but who was the source of my happiness is God and DR ODUWA the great healer, that is the reason i am taking all my time to share this testimony so that people who might also need help of curing their sickness to contact him through his email: dr.oduwaspellhome@gmail.com as i earlier did when i was searching for help. This man brought countless joy into my life and my family as well. Well i have really believe that God sent you to heal his people from this deadly disease. i will forever give thanks to you for healing me from hiv. Please kindly contact this great healer if you need his help because he can save your soul he just saved mine. Contact email address: dr.oduwaspellhome@gmail.com

    ResponderEliminar
  5. HELLO EVERYONE.. FEW MUNINETS TO REDY THIS INFOR ON HERPES CURE 2018..
    2017 MY MOTHER WAS DIAGNOSED OF HERPES/ KNOWN AS GENITAL WARTS ,I SPENT A LOT OF MONEY ON HER MEDICATION TILL A POINT I EVEN LOST HOPE,BECAUSE MY MOTHER WAS GRADUALLY DYING AND LOST HER MEMORY TOO, I WAS SO DESPERATE TO GET MY MOTHER BACK TO NORMAL, ONE DAY MY UNCLE WHO LIVES IN LONDON UNITED KINGDOM TOLD ME ABOUT DR OLIHA ,WHO HELPED HIM GET RID OF HERPES /GENITAL WART WITH HERBAL MEDICINE AND HIS HERBAL SOAP ,I WAS SO SHOCKED WHEN HE TOLD ME ABOUT THIS ,ALTHOUGH I NEVER BELIEVE IN HERB BUT, I KEEP TO BELIEVE BECAUSE MY UNCLE CAN'T TELL ME LIES WHEN IT COMES TO HEALTH CONDITION I CONTACTED DR OLIHA VIA HIS EMAIL; OLIHA.MIRACLEMEDICINE@GMAIL.COM , YOU CAN TALK TO HIM VIA CALL OR WHATSAPP MESSENGER ON +2349038382931 , HE REPLIED AND ASK ME TO SEND MY HOME ADDRESS AND MY MOTHER'S DETAIL AND THEN I PURCHASED THE HERBAL MEDICINE,SENT ME THE HERBAL MEDICINE THROUGH COURIER SERVICE, WHEN I RECEIVED THIS HERBAL MEDICINE USED IT FOR 2 WEEKS, AND 4 DAYS OF USAGE THE WARTS FELL OFF, MY MOTHER I NOW TOTALLY CURED AND MY MOTHER IS LIVING FREE AND HAPPY AGAIN. YOU CAN TALK TO DR VIA HIS MOBILE NUMBER OR WHATS APP HIM ON +2349038382931.ALL THANKS TO DOCTOR DR OLIHA

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