THIS GREAT INFORMATION WAS PROVIDED BY CLINICAL CARE OPTIONS. THESE ARE COMMENTS ABOUT CLINICAL STUDY DESIGN ISSUES THAT I FOLLOW VERY CLOSELY AS AN ACTIVIST. IT IS VERY INTERESTING TO ME HOW SOME COMPANIES CHOSE TO SHOW THEIR DATA AND HURRY THEIR STUDY ENROLLMENT AT THE EXPENSE OF PATIENT VOLUNTEERS.
THE NEXT HIV DRUG TO BE APPROVED : MARAVIROC - COMMENTS FROM Daniel R. Kuritzkes, MD ABOUT MOTIVATE 1/2 STUDIES AND PFIZER'S EXCLUSION OF FUZEON DATA IN ITS ANALYSIS...
One interesting aspect of this study was that there was no discernable increase in the rate of virologic suppression among maraviroc patients who also received enfuvirtide. This contrasts with data from the A4001029 study, which evaluated the use of maraviroc in patients with dual/mixed-tropic virus; in this study, a similar reduction in HIV-1 RNA was observed with maraviroc vs placebo, but there was a slightly greater reduction in HIV-1 RNA when enfuvirtide was coadministered with maraviroc
One possible interpretation of why enfuvirtide had no discernable benefit in the MOTIVATE studies is that the background regimen may already have been so potent that the use of enfuvirtide did not result in any additional HIV-1 RNA reduction. Moreover, the virologic response data did not differentiate between enfuvirtide recipients who were using enfuvirtide for the first time from those with previous enfuvirtide experience. Overall, approximately 60% of the study population was enfuvirtide naive at baseline, and 40% was enfuvirtide experienced. This suggests that perhaps one fourth to one third of the patients initiated enfuvirtide for the first time with maraviroc; this may be too small a proportion to have a discernable impact in the subgroup analysis.
*************************************************
THE NEXT DRUG TO BE APPROVED AFTER MARAVIROC: MK 518 (RALTEGRAVIR, MERCK'S INTEGRASE INHIBITOR) - COMMENTS FROM Daniel R. Kuritzkes, MD ABOUT THE BENCHMRK STUDY AND ITS OBR (OPTIMIZED BACKGROUND THERAPY)
Baseline resistance scores showed that approximately two thirds of patients had a genotypic susceptibility score of either 0 or 1 for the background regimen. It is worth noting that patients were considered to be resistant to a drug if the fold-change in susceptibility to that drug exceeded the lower cutoff in the phenotypic assay. The lower cutoff marks the transition between full activity and reduced activity, rather than no activity, so drugs that had partial activity could have been assigned a score of 0; in other words, the phenotypic susceptibility scores could have slightly underestimated the activity of the OBR. Approximately 20% of patients were naive to enfuvirtide at study entry; in the case that enfuvirtide was used in a previously enfuvirtide-naive patient, a score of 1 was assigned to the phenotypic susceptibility score. Phenotypic susceptibility testing for darunavir was not available at the study outset, so darunavir was also assigned an activity score of 1 when administered to a patient who had previously been darunavir naive; this approach may have overestimated the activity of darunavir in some patients. Approximately 25% of patients in BENCHMRK‑1 and nearly 50% in BENCHMRK‑2 were darunavir naive and received darunavir as part of their OBR; this is probably the major difference between the trials.
*******************************************
COMMENTS ABOUT GILEAD'S INTEGRASE INHIBITOR (ELVITEGRAVIR) STUDY AND ITS HURRIED IMPLEMENTATION THAT EXPOSED PATIENTS TO VIRTUAL MONOTHERAPY
Daniel R. Kuritzkes, MD:I agree that the failure kinetics of elvitegravir appear to resemble that of lamivudine or an NNRTI, with which a single-point mutation confers resistance and is associated with rapid viral rebound, whereas failure with raltegravir appears similar to failure with a PI, that is, resistance requires mutations at multiple loci and rebound is more gradual. Whether similar failure kinetics would have been observed with raltegravir if PIs had been excluded from the BENCHMRK studies is a matter of speculation.
Development of elvitegravir has been complicated somewhat by the fact that it has many drug-drug interactions. The manufacturer had to decide whether to elucidate all those interactions first, so that studies could allow the concomitant use of as many other drugs as possible, or to proceed with studies more rapidly but restrict the drugs that could be combined with elvitegravir. The consequences of choosing the latter approach was that in this treatment-experienced patient population, there were insufficient drugs available to provide an effective background regimen to support the integrase inhibitor. Most patients received NRTIs only, and approximately one half of them contributed no activity, meaning that those patients received de facto monotherapy with elvitegravir.
Joseph J. Eron, Jr, MD:Although I agree about the limitations of the current study, the goal of a phase IIb study is to identify the best dose to take forward into phase III development, and it does seems likely that the right dose of elvitegravir was identified.
Daniel R. Kuritzkes, MD:You are correct. However, if the investigators had chosen to perform a 14‑day study of different doses in treatment‑experienced patients, they might have come up with the same result. Unfortunately, the patients who received up to 16 weeks of treatment with the lowest dose (20 mg) before that arm was discontinued—as well as the patients who experienced virologic failure in the other arms because of the lack of an effective OBR—are now likely resistant to this integrase inhibitor and may or may not be cross‑resistant to other drugs in the class. The challenge for all investigational drugs is how to generate the key data that are essential for drug development while minimizing the risk to the patients enrolled in early studies.
Joseph J. Eron, Jr, MD:I agree. Patients in the elvitegravir study had an even higher median CD4+ cell count than those in the maraviroc and raltegravir trials, so most were not in urgent need of a new regimen, yet some of these patients may now have restricted future options because they received elvitegravir combined with NRTIs only.
****************************************************
COMMENTS ABOUT RELPIVIRINE (TMC 278- A NON NUCLEOSIDE) FROM TIBOTEC:
William G. Powderly, MD:The lipid data from this study were intriguing. Results in the efavirenz arm were as expected: a mean 31 mg/dL (0.80 mmol/L) increase in total cholesterol, a 16 mg/dL (0.41 mmol/L) increase in low density lipoprotein (LDL) cholesterol, and a 12 mg/dL (0.31 mmol/L) increase in high density lipoprotein (HDL) cholesterol. Triglyceride levels also increased in the efavirenz arm by a mean of 18 mg/dL (0.20 mmol/L). By contrast, there were virtually no significant lipid changes in the rilpivirine arms: a 5 mg/dL (0.13 mmol/L) median increase in total cholesterol, no change in LDL cholesterol, a 5 mg/dL (0.13 mmol/L) increase in HDL cholesterol, and a 10 mg/dL (0.11 mmol/L) decrease in triglycerides. This is a potential advantage to rilpivirine over efavirenz, although it is not clear how these changes might translate into differences in cardiovascular risk, since the larger increase in HDL cholesterol in the efavirenz arm might counterbalance the larger increase in LDL cholesterol and triglycerides also seen in that arm.
This is the second time that a study of a novel agent in treatment-naive patients has demonstrated fewer lipid effects than efavirenz. The first was a phase II study in which raltegravir was associated with significantly smaller changes in cholesterol and triglycerides than those observed with efavirenz (P < .05 for 200-mg, 400-mg, and 600-mg doses of raltegravir) . This type of result challenges the notion that a proportion of the lipid changes observed in treatment-naive patients who start antiretroviral therapy represent a “return to normal” in the form of a reversal of the effects of unchecked HIV replication. The results of these studies question that hypothesis and raise the possibility that lipid changes may indeed be a form of drug toxicity in the majority of patients. ******************************************************** COMMENTS ABOUT THE X4 INHIBITOR AMD 11070:
Daniel R. Kuritzkes, MD: There were very few reports on agents in the early stages of development. Two pilot studies of AMD 11070, a CXCR4 inhibitor, were presented at this meeting. The ACTG 5210 trial was an open-label dose-escalating 10-day monotherapy study in patients who had been off therapy for ≥ 14 days and who had X4 or dual/mixed virus detected 18] A total of 6 patients in the first cohort were treated with AMD 11070 200 mg every 12 hours for 10 days (20 doses). Three of the 6 patients had ≥ 1 log10 reduction in the X4 virus population by Day 10 as measured by luciferase assay. Five of the 6 subjects had dual/mixed virus at Day 10, and the sixth had R5 virus. However, none of the patients experienced a ≥ 1 log10 copies/mL reduction in HIV-1 RNA.
The XACT study had similar results. This was a 10-day monotherapy study in treatment-naive and treatment-experienced patients with X4 virus detected (N = 10; 8 received 200 mg twice daily and 2 received 100 mg twice daily). One patient was unevaluable based on discrepancies in tropism assay results. Four of the remaining 9 patients had ≥ 1 log10 reduction in the X4 virus population by luciferase assay by Day 10, and 3 of these 4 had only R5 virus detected at Day 10. However, there were no changes in HIV-1 RNA or CD4+ cell count among the 4 responders.
The fact that reduction in X4 virus was not associated with an overall reduction in HIV-1 RNA would present a huge challenge for subsequent development of an X4 inhibitor because one is unable to demonstrate an impact on what are considered traditional endpoints—decrease in HIV-1 RNA and increase in CD4+ cell count. Development of AMD 11070 is now on hold because of serious toxicity demonstrated in animal models.
**********************************
COMMENTS ABOUT RACIVIR
Joseph J. Eron, Jr, MD: Clinical data were also presented on racivir, a racemic mixture of enantiomers of an emtricitabine-like molecule.[20] In this study, patients failing therapy with M184V on a lamivudine-containing regimen were randomized 2 to 1 to substitute racivir for lamivudine (n = 26) or continue lamivudine (n = 16) in a double-blind fashion. Among those receiving racivir, the mean HIV-1 RNA change after 28 days was a decrease of 0.4 log10 copies/mL, whereas those on lamivudine experienced a 0.13 log10 copies/mL increase (P = .0004). In a subgroup analysis of patients with M184V < 3 thymidine analogue mutations with or without NNRTI or PI mutations (n = 14), the HIV-1 RNA decreased 0.7 log10 copies/mL over same period (P = .0002)
The lack of clinical data on drugs at early stages of development highlights an important concern. Within the next year, 3 new drugs may be approved. However, in the next few years beyond that, very few new drugs are likely to become available. Those that do become approved will most likely be second or third in class and therefore more likely to be of incremental benefit, as opposed to the potentially dramatic benefit that may be associated with the first agent in an entirely new class, to which even the most experienced patient is likely to remain fully susceptible. This underscores once again the critical importance of using the current batch of new agents optimally—in combination with other active agents and with the goal of achieving undetectable HIV-1 RNA—in the hope that today’s treatment-experienced patients can achieve durable responses.
-
The untold Side of the movie "Dallas Buyers Club"
The movie Dallas Buyers Club brings attention to a little-recognized part of the AIDS activist movement: ....
-
Exhorbitant Price New Hepatitis C Drug
Fair Pricing Coalition Condemns Gilead Sciences on the High Price of New Hepatitis C Drug Sovaldi™...
-
Six Promising HIV Drugs in the Pipeline (2013-2014)
What new HIV medications do we have to look forward to over the next few years? How will these newer drugs improve upon the older ones? To shed some light on these questions....
-
What Can We Look Forward to in HIV Cure Research
TheBodyPRO.com's Nelson Vergel sat down with leading HIV cure research activist Richard Jefferys for an update on current important aspects, and controversies, in HIV cure research....
-
What Supplements Can I take with HIV medications?
Is it ok to supplement with Creatine (Cell-Tech), and Protein (Nitro-Tech) along with Glutamine...
Friday, June 08, 2007
Interview for TheBody.com
I have to thank TheBody.com for the opportunity to tell my story
http://thebody.com/multidrug/stories_nelson.html
http://thebody.com/multidrug/stories_nelson.html
Ziagen (Abacavir) Can Cause Anxiety in Some Patients
I have received emails in the past about people asking why they feel anxious or moody on Ziagen. This problem has happened to me and others and it is rarely discussed in the literature or in physician-patient conversations.
***********************
In response to the persons who said they cannot sleep and feel anxious on Epzicom (Ziagen+Epivir or Abacavir+ 3TC)...
I took Ziagen and it caused horrible anxiety. I found out it was the drug when I stopped it for a week and restarted it again. The symptoms would disappear and reappear in one or two days. Several friends report the same problem. Only two reports were found in the literature. This problem has not been discussed in most HIV information sources.
More on abacavir-induced neuropsychiatric reactions:
[CORRESPONDENCE]
Foster, Russella; Taylor, Chrisb; Everall, Ian Paulc
aHIV Mental Health Team, Maudsley Hospital, London, UK; bDepartment of Sexual Health, Caldecot Centre, King's College Hospital, London, UK; and cDepartment of Psychiatry, University of California, San Diego, La Jolla, CA 92083-0603, USA.
Received: 8 September 2004; accepted: 27 September 2004.
It is increasingly recognized that antiretroviral medications may induce severe, but transient, changes in mental state. These are uncommon and idiosyncratic, with the literature containing only two published reports suggesting that abacavir (Ziagen), a nucleoside reverse transcriptase inhibitor, may induce a range of neuropsychiatric disorders in seropositive individuals. These include depression, suicidal thoughts, auditory hallucinations [1] and frank psychosis [2]. Of note is the fact that the subjects in these cases were all female with CD4 cell counts below 500 cells/µl. Here we report, for the first time, a case of a possible abacavir-induced neuropsychiatric reaction in a seropositive Caucasian man with a higher CD4 cell count.
The patient was a 44-year-old gay man who was diagnosed HIV positive in 1993. He was referred to psychiatric services in 2000 after the psychologist whom he had been seeing became concerned about the patient's ongoing depressive symptoms. He had previously been treated with various antidepressants and triple therapies for HIV, and was currently receiving citalopram 30 mg a day in addition to tenofovir 245 mg per day, nevirapine 200 mg twice a day and abacavir 300 mg twice a day. He had previously been taking didanosine, but this was changed to abacavir because of lipodystrophy.
Approximately one week after commencing abacavir, the patient started to complain of feeling tired and ‘stoned'. He also complained of headaches, which were described as ‘constant and throbbing’ and ‘located in the middle of my brain'. He reported the onset of bad dreams, which he referred to as ‘night terrors'. These were described as vivid and terrifying, but the actual content could not be recalled. He denied any associated physical symptoms such as night sweats or any recent physical illness. His CD4 cell count at this time was 557 cells/µl and his viral load was less than 50 copies/ml. Of note is the fact that despite his dreams he now felt that his previously low mood had improved to the extent that he was expressing the desire to cease taking citalopram.
Two weeks after reporting the above problems, the patient was reviewed by the HIV physician who changed the abacavir back to didanosine. Within 24 h of this the patient reported that his headaches and bad dreams had stopped, and that he was feeling less fatigued. At one month follow-up he remained free of these symptoms, and his mood remained settled. The citalopram was eventually reduced gradually and finally stopped.
This case suggests that abacavir may, in rare cases, induce unpleasant but non-specific neuropsychiatric side-effects, which can resolve rapidly upon stopping this medication. Although it has been suggested that abacavir may be associated with new-onset depression [1], this was not apparent in the current case. In that earlier publication [1], depression and night sweats were reported in one patient, with depression, suicidal ideation, headache, auditory hallucinations and anorexia in the second. The patients in those cases were both HIV positive Caucasian women. Similarly, a more recent publication described a case of putative abacavir-induced psychosis occurring in an African woman [2] who became symptom-free after the cessation and substitution of this medication.
The current report suggests that men can also be adversely affected by abacavir-associated neuropsychiatric problems, even at a higher CD4 cell count accompanied by a low viral load. Furthermore, symptoms may rapidly resolve upon discontinuation of abacavir and the substitution of a suitable alternative antiretroviral agent. It is possible that headache and mood alterations may be early indicators of neuropsychiatric sequelae associated with abacavir. These should be investigated and monitored closely to exclude possible organic factors. Management should be carried out in collaboration with both HIV physicians and specialist psychiatrists.
References
1. Colebunders R, Hilbrands R, De Roo A, Pelgrom J. Neuropsychiatric reaction induced by abacavir. Am J Med 2002; 113:616.
2. Foster R, Olajide D, Everall IP. Antiretroviral therapy-induced psychosis: case report and brief review of the literature. HIV Med 2003; 4:139–144. Accession Number: 00002030-200412030-00021
*******************************************************************************
Neuropsychiatric Reaction Induced by Abacavir in a Pediatric Human Immunodeficiency Virus-Infected Patient
[Departments: Letters to the Editors]
Palacin, Pere Soler MD; Aramburo, Angela; Moraga, Fernando A.; Cabañas, Maria Josep; Figueras, Concepció
Pediatric Infectious Diseases Unit, Vall d’Hebron Hospital, Barcelona, Spain(Palacin, Aramburo, Moraga, Figueras)
Pharmacy Service, Vall d’Hebron Hospital, Barcelona, Spain(Cabañas)
To the Editors:
Although most commonly reported abacavir-related side effects are mild and transient, and because of hypersensitivity reactions in the first 1 or 2 weeks after starting treatment with this drug, even severe neuropsychiatric reactions have been recently described in human immunodeficiency virus (HIV)-infected adult patients. These may include depression, suicidal thoughts, auditory hallucinations and frank psychosis. To our knowledge, there is no case described in pediatric HIV-infected population receiving abacavir (Ziagen; GlaxoSmithKline).
The patient we here describe is now an 11-year-old Caucasian boy who was found to be vertically transmitted HIV-positive at the age of 2 years. At the age of 3 years, he started taking antiretroviral drugs (zidovudine and lamivudine). He started highly active antiretroviral therapy (stavudine, lamivudine and nelfinavir) when he was 5 years old. He had been well since the present time with good virologic (plasma viral load below 50 copies/mL), immunologic (CD4% always >35%) and clinical situation (Centers for Disease Control and Prevention classification 1994 B2). The patient was admitted to the hospital at the age of 6 years because of indinavir-related nephrolithiasis. He did not present any acquired immunodeficiency syndrome-defining illness.
At the age of 11 years, his antiretroviral regimen was simplified to abacavir, lamivudine and efavirenz with the aim to change to lamivudine-abacavir when available, to reduce pill burden. One month after the initiation of this regimen, the parents referred that the patient had mood changes and complained of headaches, anxiety and bad dreams. During the following weeks, he developed major depression with refusal to attend school and to have any social interaction with both his friends and family. He was then referred to our center’s Department of Pedopsychiatry, the diagnosis of major depression was confirmed (DSM IV) and no exogenous triggering factor was observed. He then weighed 29 kg, and his height was 139 cm. No abnormalities were observed at physical examination. His CD4+ lymphocyte count was 888/mm3 (38%), and his plasma viral load was below 50 copies/mL. Neither the patient nor his parents had a history of psychiatric disorders.
Because of the coincidence of the beginning of neuropsychiatric manifestations and the start of a new antiretroviral drug (he had been taking lamivudine and efavirenz for a long period before) and the risk of abacavir-induced neuropsychiatric reactions, the drug was then discontinued and treatment was changed to stavudine. No other clinical or analytical signs of abacavir-related side effects were observed. Two weeks after the drug discontinuation, the patient began to improve without adding any antidepressive agent, bad dreams and headache disappeared and he accepted school attendance. After 3 months of follow-up, psychiatric problems did not reappear and the patient’s mood remained settled.
This case supports the idea that, as described in the adult HIV-infected population,1–3 abacavir can induce several neuropsychiatric side effects in pediatric patients that resolve rapidly when this medication is stopped. The appearance of symptoms a few weeks after starting the new antiretroviral regimen, coupled with the rapid resolution of symptoms with cessation of treatment, provides further support for abacavir as a possible cause of neuropsychiatric symptoms in our patient.
Because headache and mood alterations may be early indicators of neuropsychiatric manifestations in patients receiving abacavir or other antiretroviral drugs, these symptoms must be closely investigated. If early recognized, this situation can be easily managed by cessation of abacavir and change to other suitable antiretroviral regimen with symptomatic treatment (antipsychotics, antidepressive agents, etc) if necessary.
2Pere Soler Palacin, MD
Angela Aramburo
Fernando A. Moraga
Pediatric Infectious Diseases Unit
Maria Josep Cabañas
Pharmacy Service
Concepció Figueras
Pediatric Infectious Diseases Unit
Vall d’Hebron HospitalBarcelona, Spain
REFERENCES
1. Colebunders R, Hillbrands R, De Roo A, Pelgrom J. Neuropsychiatric reaction induced by abacavir. Am J Med. 2002;113:616.
2. Foster R, Olajide D, Everall IP. Antiretroviral therapy-induced psychosis: case report an brief report of the literature. HIV Med. 2003;4:139–144. \3. Foster R, Taylor C, Everall IP. More on abacavir-induced neuropsychiatric reactions. AIDS. 2004;18:2449.
***********************
In response to the persons who said they cannot sleep and feel anxious on Epzicom (Ziagen+Epivir or Abacavir+ 3TC)...
I took Ziagen and it caused horrible anxiety. I found out it was the drug when I stopped it for a week and restarted it again. The symptoms would disappear and reappear in one or two days. Several friends report the same problem. Only two reports were found in the literature. This problem has not been discussed in most HIV information sources.
More on abacavir-induced neuropsychiatric reactions:
[CORRESPONDENCE]
Foster, Russella; Taylor, Chrisb; Everall, Ian Paulc
aHIV Mental Health Team, Maudsley Hospital, London, UK; bDepartment of Sexual Health, Caldecot Centre, King's College Hospital, London, UK; and cDepartment of Psychiatry, University of California, San Diego, La Jolla, CA 92083-0603, USA.
Received: 8 September 2004; accepted: 27 September 2004.
It is increasingly recognized that antiretroviral medications may induce severe, but transient, changes in mental state. These are uncommon and idiosyncratic, with the literature containing only two published reports suggesting that abacavir (Ziagen), a nucleoside reverse transcriptase inhibitor, may induce a range of neuropsychiatric disorders in seropositive individuals. These include depression, suicidal thoughts, auditory hallucinations [1] and frank psychosis [2]. Of note is the fact that the subjects in these cases were all female with CD4 cell counts below 500 cells/µl. Here we report, for the first time, a case of a possible abacavir-induced neuropsychiatric reaction in a seropositive Caucasian man with a higher CD4 cell count.
The patient was a 44-year-old gay man who was diagnosed HIV positive in 1993. He was referred to psychiatric services in 2000 after the psychologist whom he had been seeing became concerned about the patient's ongoing depressive symptoms. He had previously been treated with various antidepressants and triple therapies for HIV, and was currently receiving citalopram 30 mg a day in addition to tenofovir 245 mg per day, nevirapine 200 mg twice a day and abacavir 300 mg twice a day. He had previously been taking didanosine, but this was changed to abacavir because of lipodystrophy.
Approximately one week after commencing abacavir, the patient started to complain of feeling tired and ‘stoned'. He also complained of headaches, which were described as ‘constant and throbbing’ and ‘located in the middle of my brain'. He reported the onset of bad dreams, which he referred to as ‘night terrors'. These were described as vivid and terrifying, but the actual content could not be recalled. He denied any associated physical symptoms such as night sweats or any recent physical illness. His CD4 cell count at this time was 557 cells/µl and his viral load was less than 50 copies/ml. Of note is the fact that despite his dreams he now felt that his previously low mood had improved to the extent that he was expressing the desire to cease taking citalopram.
Two weeks after reporting the above problems, the patient was reviewed by the HIV physician who changed the abacavir back to didanosine. Within 24 h of this the patient reported that his headaches and bad dreams had stopped, and that he was feeling less fatigued. At one month follow-up he remained free of these symptoms, and his mood remained settled. The citalopram was eventually reduced gradually and finally stopped.
This case suggests that abacavir may, in rare cases, induce unpleasant but non-specific neuropsychiatric side-effects, which can resolve rapidly upon stopping this medication. Although it has been suggested that abacavir may be associated with new-onset depression [1], this was not apparent in the current case. In that earlier publication [1], depression and night sweats were reported in one patient, with depression, suicidal ideation, headache, auditory hallucinations and anorexia in the second. The patients in those cases were both HIV positive Caucasian women. Similarly, a more recent publication described a case of putative abacavir-induced psychosis occurring in an African woman [2] who became symptom-free after the cessation and substitution of this medication.
The current report suggests that men can also be adversely affected by abacavir-associated neuropsychiatric problems, even at a higher CD4 cell count accompanied by a low viral load. Furthermore, symptoms may rapidly resolve upon discontinuation of abacavir and the substitution of a suitable alternative antiretroviral agent. It is possible that headache and mood alterations may be early indicators of neuropsychiatric sequelae associated with abacavir. These should be investigated and monitored closely to exclude possible organic factors. Management should be carried out in collaboration with both HIV physicians and specialist psychiatrists.
References
1. Colebunders R, Hilbrands R, De Roo A, Pelgrom J. Neuropsychiatric reaction induced by abacavir. Am J Med 2002; 113:616.
2. Foster R, Olajide D, Everall IP. Antiretroviral therapy-induced psychosis: case report and brief review of the literature. HIV Med 2003; 4:139–144. Accession Number: 00002030-200412030-00021
*******************************************************************************
Neuropsychiatric Reaction Induced by Abacavir in a Pediatric Human Immunodeficiency Virus-Infected Patient
[Departments: Letters to the Editors]
Palacin, Pere Soler MD; Aramburo, Angela; Moraga, Fernando A.; Cabañas, Maria Josep; Figueras, Concepció
Pediatric Infectious Diseases Unit, Vall d’Hebron Hospital, Barcelona, Spain(Palacin, Aramburo, Moraga, Figueras)
Pharmacy Service, Vall d’Hebron Hospital, Barcelona, Spain(Cabañas)
To the Editors:
Although most commonly reported abacavir-related side effects are mild and transient, and because of hypersensitivity reactions in the first 1 or 2 weeks after starting treatment with this drug, even severe neuropsychiatric reactions have been recently described in human immunodeficiency virus (HIV)-infected adult patients. These may include depression, suicidal thoughts, auditory hallucinations and frank psychosis. To our knowledge, there is no case described in pediatric HIV-infected population receiving abacavir (Ziagen; GlaxoSmithKline).
The patient we here describe is now an 11-year-old Caucasian boy who was found to be vertically transmitted HIV-positive at the age of 2 years. At the age of 3 years, he started taking antiretroviral drugs (zidovudine and lamivudine). He started highly active antiretroviral therapy (stavudine, lamivudine and nelfinavir) when he was 5 years old. He had been well since the present time with good virologic (plasma viral load below 50 copies/mL), immunologic (CD4% always >35%) and clinical situation (Centers for Disease Control and Prevention classification 1994 B2). The patient was admitted to the hospital at the age of 6 years because of indinavir-related nephrolithiasis. He did not present any acquired immunodeficiency syndrome-defining illness.
At the age of 11 years, his antiretroviral regimen was simplified to abacavir, lamivudine and efavirenz with the aim to change to lamivudine-abacavir when available, to reduce pill burden. One month after the initiation of this regimen, the parents referred that the patient had mood changes and complained of headaches, anxiety and bad dreams. During the following weeks, he developed major depression with refusal to attend school and to have any social interaction with both his friends and family. He was then referred to our center’s Department of Pedopsychiatry, the diagnosis of major depression was confirmed (DSM IV) and no exogenous triggering factor was observed. He then weighed 29 kg, and his height was 139 cm. No abnormalities were observed at physical examination. His CD4+ lymphocyte count was 888/mm3 (38%), and his plasma viral load was below 50 copies/mL. Neither the patient nor his parents had a history of psychiatric disorders.
Because of the coincidence of the beginning of neuropsychiatric manifestations and the start of a new antiretroviral drug (he had been taking lamivudine and efavirenz for a long period before) and the risk of abacavir-induced neuropsychiatric reactions, the drug was then discontinued and treatment was changed to stavudine. No other clinical or analytical signs of abacavir-related side effects were observed. Two weeks after the drug discontinuation, the patient began to improve without adding any antidepressive agent, bad dreams and headache disappeared and he accepted school attendance. After 3 months of follow-up, psychiatric problems did not reappear and the patient’s mood remained settled.
This case supports the idea that, as described in the adult HIV-infected population,1–3 abacavir can induce several neuropsychiatric side effects in pediatric patients that resolve rapidly when this medication is stopped. The appearance of symptoms a few weeks after starting the new antiretroviral regimen, coupled with the rapid resolution of symptoms with cessation of treatment, provides further support for abacavir as a possible cause of neuropsychiatric symptoms in our patient.
Because headache and mood alterations may be early indicators of neuropsychiatric manifestations in patients receiving abacavir or other antiretroviral drugs, these symptoms must be closely investigated. If early recognized, this situation can be easily managed by cessation of abacavir and change to other suitable antiretroviral regimen with symptomatic treatment (antipsychotics, antidepressive agents, etc) if necessary.
2Pere Soler Palacin, MD
Angela Aramburo
Fernando A. Moraga
Pediatric Infectious Diseases Unit
Maria Josep Cabañas
Pharmacy Service
Concepció Figueras
Pediatric Infectious Diseases Unit
Vall d’Hebron HospitalBarcelona, Spain
REFERENCES
1. Colebunders R, Hillbrands R, De Roo A, Pelgrom J. Neuropsychiatric reaction induced by abacavir. Am J Med. 2002;113:616.
2. Foster R, Olajide D, Everall IP. Antiretroviral therapy-induced psychosis: case report an brief report of the literature. HIV Med. 2003;4:139–144. \3. Foster R, Taylor C, Everall IP. More on abacavir-induced neuropsychiatric reactions. AIDS. 2004;18:2449.
Wednesday, May 30, 2007
LECTURES IN FLORIDA - JUNE 2007
TOPIC: SURVIVING HIV RESISTANCE- How to avoid mistakes in using new HIV drugs
Reserve any lecture by calling 1-800- 810-3703 or email HIVSeminars@aol.com
TUESDAY, JUNE 12: MIAMI
11 am- Noon
Jackson Health System
1622 NW 12 Ave ACC West Room 125
WEDNESDAY, JUNE 13- PORT SAINT LUCIE
10:30 am- noon
5150 NW Milner Dr (off Midway Road)
WEDNESDAY, JUNE 13- FORT LAUDERDALE
6:30 pm- 8 pm
ArtServe Library
1350 East Sunrise Blvd
THURSDAY, JUNE 14- TAMPA
Baker & Company General Store & Antique Emporium
2502 N Howard
Reserve any lecture by calling 1-800- 810-3703 or email HIVSeminars@aol.com
TUESDAY, JUNE 12: MIAMI
11 am- Noon
Jackson Health System
1622 NW 12 Ave ACC West Room 125
WEDNESDAY, JUNE 13- PORT SAINT LUCIE
10:30 am- noon
5150 NW Milner Dr (off Midway Road)
WEDNESDAY, JUNE 13- FORT LAUDERDALE
6:30 pm- 8 pm
ArtServe Library
1350 East Sunrise Blvd
THURSDAY, JUNE 14- TAMPA
Baker & Company General Store & Antique Emporium
2502 N Howard
Thursday, May 10, 2007
Companies Abandon AIDS Wasting Patients
On March 20, Watson Laboratories stopped the production of nandrolone decanoate (old brand name: Deca Durabolin), a low cost injectable anabolic used for HIV wasting, citing lack of raw material suppliers for the product. Patients found out when they went to their pharmacies for a prescription a week later.
Although there are other generic makers of the nandrolone internationally (easily located on the Internet), this offers little help to U.S. patients. Anabolic steroids and testosterone are designated by the Drug Enforcement Administration (DEA) as class III drugs, which are illegal to import even for personal and medical uses.
In the past 20 years, anabolic steroids have suffered from a lot of bad publicity and misconceptions due to their use in sports and bodybuilding. However, that did not stop activists in the 90’s from convincing doctors and researchers to look into these medicines to help those with HIV related wasting syndrome. Since then, over 8 studies have been performed that showed nandrolone and oxandrolone ( brand name Oxandrin, an oral anabolic) to be effective and safe for increasing lean body mass (LBM) and strength in men and women with HIV. Many physicians quickly learned how to prescribe them and monitor their use for helping their HIV positive patients to survive what used to be one of the main causes of AIDS mortality.
Watson Laboratories are the only suppliers of thirteen of the 50 AIDS Drug Assistance Programs (ADAPs) that decided to cover payment for these two anabolic agents for patients with low income. "This is the safest and most cost effective anabolic steroid in the world and now we have no manufacturer in the U.S." says Vergel.
While Watson was abandoning nandrolone, another company was making a decision that would also strain options for HIV wasting patients. Savient Pharmaceuticals informed patients in April 2007 that they stopped their 10 year old patient assistance program (PAP) that gave free Oxandrin (oxandrolone) to HIV patients with no insurance and third-party payment sources. Oxandrin, another anabolic agent used for weight gain in HIV, costs $1300 a month and most people cannot afford it. This PAP was set up by BTG Pharmaceuticals (bought out by Savient later on) in 1996 after activists pressured the company to provide the drug for free to those with no access or means. Like nandrolone, only 13 states include Oxandrin in the ADAPs , so many patients will have no way to afford this drug. Savient informed patients that Watson Pharmaceutical was to sell generic Oxandrin, and thus, there was no further need for patient assistance. Unfortunately, the generic price for Oxandrin sold by Watson is no different than the brand name product, which will still be sold by Savient. Watson will not provide free Oxandrin via a PAP either. This is the first time in AIDS history that a company stops a PAP while still selling the drug.
Oxandrin is an oral anabolic steroid used in HIV wasting and it is approved to treat unintentional weight loss due to illness. It has been shown to be midly effective in men, women and kids with HIV wasting. The advantages of this drug is that it can be taken by mouth daily (nandrolone needs to be injected in the butt once a week) and that it is approved for a weight loss related indication. However, unlike nandrolone, Oxandrin (oxandrolone) can increase liver enzymes and could be problematic for people with liver disease, taking medications heavy on the liver, HIV medications like Reyataz, and those with Hepatitis B and C.
A month supply of Oxandrin (brand name or generic) costs around $1300 for 20 mg a day. Watson’s nandrolone costed around $200 a month for 200 mg a week.
"The decisions of these two companies have a huge impact in many of my patients’ health" said Dr. Richard Loftus, a San Francisco physician with a large HIV practice. "We use nandrolone extensively in patients who have problems gaining weight and who feel fatigued, even with undetectable viral loads. Many of my patients feel better and have experienced no side effects at the doses we use in HIV”, added Dr Loftus.
Even though wasting syndrome has improved dramatically since protease inhibitors were introduced 10 years ago, some patients still need extra help to hang on to their muscle to sustain health and productivity. A study performed at Tufts University School of Medicine by Wanke et al. reported that as many as 29 percent of people with HIV in the era of HAART are still losing weight or lean body mass, despite undetectable viral loads. In the 80’s, researcher Dr Donald Kotler found that the loss of lean body mass can dramatically decrease survival in HIV-positive people
A patient and a doctor himself, Dr. Nathan Sherlock knows first hand about the importance of nandrolone for his health and that of his partner. ”My partner has had a significant problem with wasting due to AIDS and the only way he has been able to stop the dangerous weight loss is to use anabolic steroids. He is also hepatitis B positive. His doctor first prescribed Oxandrin in 1998. Within a couple of weeks he had chemical induced hepatitis with the symptoms of nausea, vomiting, loss of appetite and jaundice. His liver enzymes were all elevated. He stopped Oxandrin and the symptoms promptly resolved. His doctor then prescribed nandrolone 200mg/week and he regained weight back to his norm with no side effects. When he stops taking it the wasting returns so he has been on nandrolone for close to 9 years now”
When asked about his own experience, Dr. Sherlock adds : “I have been taking nandrolone for wasting due to AIDS for over 10 years. Every time I have stopped taking nandrolone I experience rapid weight loss that can only be reversed by resuming the use of nandrolone.”
This belief is also shared by Al Benson, a HIV treatment advocate in Los Angeles."Nandrolone is truly ‘the Lazarus drug’ …it has brought me back from the brink, restored my health and made all the difference in the quality of my life, " added Benson.
Compounding Pharmacies- A threatened last option for wasting treatments
Many doctors and patients do not know that nandrolone and oxandrolone can also be obtained legally by prescription in small quantities through compounding pharmacies at a lower cost, but those pharmacies are at risk of being shut down. The DEA has raided several in the past few months, according to one of the owners of one of the pharmacies. Senator Kennedy have tried to pass legislation to regulate these companies more heavily with the help of large pharmaceutical companies. So, no one knows how much longer this option for economical medicines will be available. Fortunately, there is a strong consumer movement to protect these outfits from closure by the government (visit savemymedicine.org)
Compounding pharmacies like Applied Pharmacy (appliedphramacyrx.com), Kronos (Kronospharmacy.com), the Compounding Shop (gotocompoundingshop.com), College Pharmacy ( collegepharmacy.com) and other companies are still economical sources of nandrolone, oxandrolone, and testosterone gels and injections. However, they do not process insurance claims and are not equipped to supply AIDS Drug Assistance Programs (ADAPs), insurance, Medicaids and Medicare Part D vendors.
What other HIV Wasting drugs are out there?
One of the FDA approved products to treat HIV wasting or appetite loss, Megace (megestrol acetate), tends to produce its weight gain due to increases in fat rather than lean body mass -- and adding fat during AIDS wasting has not been shown to improve survival. Megace, a female sex hormone based product, has also been associated with side effects such as diabetes, blood clots, impotence and the development of female sex characteristics. Another agent approved to treat HIV wasting, Serostim (recombinant human growth hormone), can cost as much as $6,000 a month, so most insurance companies do not want to pay for it and many ADAPs have limited its use due to prior bribes and scandals created by its manufacturer (Serono). Serostim requires daily injections and can cause joint aches, swelling and diabetes.FDA-approved appetite stimulants such as Marinol contain the psychoactive ingredient in marijuana (THC) that can be an issue for many people with HIV who are in recovery. Also, it's theorized that Marinol may simply owe its ability to increase weight to a side effect of the THC high -- that people get the munchies and tend to eat more.
What can you do?
A nationwide network of activists is swinging into action around this issue. Vergel says, "I feel very strongly that "quality of life" drugs need as much advocacy efforts as HIV antivirals, especially in this era when we are living longer. After all we have done as actvists to secure anti-wasting medicines, I hope we do not lose ground now and fall asleep when important medicines like nandrolone are dropped without notice.”
For more information or to find out how to help, please visit
http://savehivwastingmeds.blogspot.com/
Although there are other generic makers of the nandrolone internationally (easily located on the Internet), this offers little help to U.S. patients. Anabolic steroids and testosterone are designated by the Drug Enforcement Administration (DEA) as class III drugs, which are illegal to import even for personal and medical uses.
In the past 20 years, anabolic steroids have suffered from a lot of bad publicity and misconceptions due to their use in sports and bodybuilding. However, that did not stop activists in the 90’s from convincing doctors and researchers to look into these medicines to help those with HIV related wasting syndrome. Since then, over 8 studies have been performed that showed nandrolone and oxandrolone ( brand name Oxandrin, an oral anabolic) to be effective and safe for increasing lean body mass (LBM) and strength in men and women with HIV. Many physicians quickly learned how to prescribe them and monitor their use for helping their HIV positive patients to survive what used to be one of the main causes of AIDS mortality.
Watson Laboratories are the only suppliers of thirteen of the 50 AIDS Drug Assistance Programs (ADAPs) that decided to cover payment for these two anabolic agents for patients with low income. "This is the safest and most cost effective anabolic steroid in the world and now we have no manufacturer in the U.S." says Vergel.
While Watson was abandoning nandrolone, another company was making a decision that would also strain options for HIV wasting patients. Savient Pharmaceuticals informed patients in April 2007 that they stopped their 10 year old patient assistance program (PAP) that gave free Oxandrin (oxandrolone) to HIV patients with no insurance and third-party payment sources. Oxandrin, another anabolic agent used for weight gain in HIV, costs $1300 a month and most people cannot afford it. This PAP was set up by BTG Pharmaceuticals (bought out by Savient later on) in 1996 after activists pressured the company to provide the drug for free to those with no access or means. Like nandrolone, only 13 states include Oxandrin in the ADAPs , so many patients will have no way to afford this drug. Savient informed patients that Watson Pharmaceutical was to sell generic Oxandrin, and thus, there was no further need for patient assistance. Unfortunately, the generic price for Oxandrin sold by Watson is no different than the brand name product, which will still be sold by Savient. Watson will not provide free Oxandrin via a PAP either. This is the first time in AIDS history that a company stops a PAP while still selling the drug.
Oxandrin is an oral anabolic steroid used in HIV wasting and it is approved to treat unintentional weight loss due to illness. It has been shown to be midly effective in men, women and kids with HIV wasting. The advantages of this drug is that it can be taken by mouth daily (nandrolone needs to be injected in the butt once a week) and that it is approved for a weight loss related indication. However, unlike nandrolone, Oxandrin (oxandrolone) can increase liver enzymes and could be problematic for people with liver disease, taking medications heavy on the liver, HIV medications like Reyataz, and those with Hepatitis B and C.
A month supply of Oxandrin (brand name or generic) costs around $1300 for 20 mg a day. Watson’s nandrolone costed around $200 a month for 200 mg a week.
"The decisions of these two companies have a huge impact in many of my patients’ health" said Dr. Richard Loftus, a San Francisco physician with a large HIV practice. "We use nandrolone extensively in patients who have problems gaining weight and who feel fatigued, even with undetectable viral loads. Many of my patients feel better and have experienced no side effects at the doses we use in HIV”, added Dr Loftus.
Even though wasting syndrome has improved dramatically since protease inhibitors were introduced 10 years ago, some patients still need extra help to hang on to their muscle to sustain health and productivity. A study performed at Tufts University School of Medicine by Wanke et al. reported that as many as 29 percent of people with HIV in the era of HAART are still losing weight or lean body mass, despite undetectable viral loads. In the 80’s, researcher Dr Donald Kotler found that the loss of lean body mass can dramatically decrease survival in HIV-positive people
A patient and a doctor himself, Dr. Nathan Sherlock knows first hand about the importance of nandrolone for his health and that of his partner. ”My partner has had a significant problem with wasting due to AIDS and the only way he has been able to stop the dangerous weight loss is to use anabolic steroids. He is also hepatitis B positive. His doctor first prescribed Oxandrin in 1998. Within a couple of weeks he had chemical induced hepatitis with the symptoms of nausea, vomiting, loss of appetite and jaundice. His liver enzymes were all elevated. He stopped Oxandrin and the symptoms promptly resolved. His doctor then prescribed nandrolone 200mg/week and he regained weight back to his norm with no side effects. When he stops taking it the wasting returns so he has been on nandrolone for close to 9 years now”
When asked about his own experience, Dr. Sherlock adds : “I have been taking nandrolone for wasting due to AIDS for over 10 years. Every time I have stopped taking nandrolone I experience rapid weight loss that can only be reversed by resuming the use of nandrolone.”
This belief is also shared by Al Benson, a HIV treatment advocate in Los Angeles."Nandrolone is truly ‘the Lazarus drug’ …it has brought me back from the brink, restored my health and made all the difference in the quality of my life, " added Benson.
Compounding Pharmacies- A threatened last option for wasting treatments
Many doctors and patients do not know that nandrolone and oxandrolone can also be obtained legally by prescription in small quantities through compounding pharmacies at a lower cost, but those pharmacies are at risk of being shut down. The DEA has raided several in the past few months, according to one of the owners of one of the pharmacies. Senator Kennedy have tried to pass legislation to regulate these companies more heavily with the help of large pharmaceutical companies. So, no one knows how much longer this option for economical medicines will be available. Fortunately, there is a strong consumer movement to protect these outfits from closure by the government (visit savemymedicine.org)
Compounding pharmacies like Applied Pharmacy (appliedphramacyrx.com), Kronos (Kronospharmacy.com), the Compounding Shop (gotocompoundingshop.com), College Pharmacy ( collegepharmacy.com) and other companies are still economical sources of nandrolone, oxandrolone, and testosterone gels and injections. However, they do not process insurance claims and are not equipped to supply AIDS Drug Assistance Programs (ADAPs), insurance, Medicaids and Medicare Part D vendors.
What other HIV Wasting drugs are out there?
One of the FDA approved products to treat HIV wasting or appetite loss, Megace (megestrol acetate), tends to produce its weight gain due to increases in fat rather than lean body mass -- and adding fat during AIDS wasting has not been shown to improve survival. Megace, a female sex hormone based product, has also been associated with side effects such as diabetes, blood clots, impotence and the development of female sex characteristics. Another agent approved to treat HIV wasting, Serostim (recombinant human growth hormone), can cost as much as $6,000 a month, so most insurance companies do not want to pay for it and many ADAPs have limited its use due to prior bribes and scandals created by its manufacturer (Serono). Serostim requires daily injections and can cause joint aches, swelling and diabetes.FDA-approved appetite stimulants such as Marinol contain the psychoactive ingredient in marijuana (THC) that can be an issue for many people with HIV who are in recovery. Also, it's theorized that Marinol may simply owe its ability to increase weight to a side effect of the THC high -- that people get the munchies and tend to eat more.
What can you do?
A nationwide network of activists is swinging into action around this issue. Vergel says, "I feel very strongly that "quality of life" drugs need as much advocacy efforts as HIV antivirals, especially in this era when we are living longer. After all we have done as actvists to secure anti-wasting medicines, I hope we do not lose ground now and fall asleep when important medicines like nandrolone are dropped without notice.”
For more information or to find out how to help, please visit
http://savehivwastingmeds.blogspot.com/
Serono and Serostim's Corruption
This was first brough to light by Michael Mooney in 1999. It took years but Serono is now paying for this troublesome corporate decision. You can read the original article in 1999 here:
http://medibolics.com/kickback2.htm
Ex-Serono executives acquitted in USA of bribing doctors
04/05/2007
www.pharmatimes.com
A federal grand jury has acquitted four former executives of Switzerland's Serono, which has just been acquired by Merck KGaA, of charges that they illegally promoted its human growth hormone product, Serostim to treat muscle wasting in patients with AIDS.The US District Court jury in Boston set aside all charges brought in 2005 against the executives (Mary Stewart, John Bruens, Melissa Vaughan and Marc Sirockman) at Serono, which included conspiracy and giving doctors expenses-paid trips to Cannes, France for a medical conference in 1999 where they agreed to write up to 30 prescriptions for Serostim (somatropin), typically costing $21,000 for a 12-week treatment.At about the same time the US Food and Drug Administration approved the drug, protease inhibitors came on the market, making patients less prone to AIDS wasting. Demand for Serostim began to fall and at a meeting in Boston in March 1999, Mr Bruens and Ms Stewart told Mr Vaughn, Mr Sirockman and several other regional sales directors that they needed to "dig their way out" of a financial crisis, according to the indictment.Sales reps were required to identify the highest prescribing physicians in their region and then target them with free trips to boost prescriptions to $6 million in 6 days, prosecutors had claimed."We believed this is a case that should not have been brought and the speed with which the jury returned its verdict (just three hours) confirmed our beliefs," said Adam Hoffinger, an attorney for Ms Vaughn. He added that the trip was not offered in exchange for writing prescriptions for Serostim, noting that the defendants "had no intent to bribe any doctors, and they did not bribe any doctors. It was a legitimate medical conference."Serono agreed a deal with the US Justice Department in October 2005 to plead guilty and pay $704 million to settle charges that it knowingly encouraged the submission of fraudulent claims for Serostim reimbursement under government health programmes.ReutersIt also agreed in 2005 to plead guilty to two criminal charges and to pay a $137 million fine resolving an investigation into how the company marketed the drug called Serostim, which was approved by the U.S. Food and Drug Administration in 1996.The drug was marketed in the United States by Serono Inc. of Rockland, Massachusetts.Also in 2005, Serono agreed to pay $567 million to settle civil charges that it knowingly caused the submission of false claims for Serostim that were not eligible for reimbursement under government health programs.>From 2005 Boston Globe:Some HIV/AIDS advocates have said the "bad blood" with Serono will not affect their position on new uses for Serostim, the Globe reports. However, "it's clear this vocal and influential constituency, which often weighs in with regulators on AIDS drugs, now doesn't trust Serono and will be skeptical of any new promises or clinical claims from the company," according to the Globe
IF YOU HAVE PAID FOR ANY PART OF SEROSTIM'S PRESCRIPTION IN THE PAST, READ THIS:
Mr. Vergel:
I am an attorney involved in the settlement of litigation against Serono. There's about $2 million available to reimburse anyone who paid anything out of pocket for Serostim. Despite our best efforts to date to spread the word about the settlement and the availability of the money, very few have filed proofs of claim and most of the money is at risk of going unclaimed.
If you think you can help publicize this, please contact me. Your services would not be compensated, so you'd have to be interested in this as a pro bono project.
Richard W. Cohen
Lowey Dannenberg Bemporad Selinger & Cohen, P.C.
White Plains Plaza
One North Broadway, 5th Floor
White Plains, NY 10601
914-997-0500 (main line)
914-733-7239 (direct line)
rcohen@lowey.com
http://medibolics.com/kickback2.htm
Ex-Serono executives acquitted in USA of bribing doctors
04/05/2007
www.pharmatimes.com
A federal grand jury has acquitted four former executives of Switzerland's Serono, which has just been acquired by Merck KGaA, of charges that they illegally promoted its human growth hormone product, Serostim to treat muscle wasting in patients with AIDS.The US District Court jury in Boston set aside all charges brought in 2005 against the executives (Mary Stewart, John Bruens, Melissa Vaughan and Marc Sirockman) at Serono, which included conspiracy and giving doctors expenses-paid trips to Cannes, France for a medical conference in 1999 where they agreed to write up to 30 prescriptions for Serostim (somatropin), typically costing $21,000 for a 12-week treatment.At about the same time the US Food and Drug Administration approved the drug, protease inhibitors came on the market, making patients less prone to AIDS wasting. Demand for Serostim began to fall and at a meeting in Boston in March 1999, Mr Bruens and Ms Stewart told Mr Vaughn, Mr Sirockman and several other regional sales directors that they needed to "dig their way out" of a financial crisis, according to the indictment.Sales reps were required to identify the highest prescribing physicians in their region and then target them with free trips to boost prescriptions to $6 million in 6 days, prosecutors had claimed."We believed this is a case that should not have been brought and the speed with which the jury returned its verdict (just three hours) confirmed our beliefs," said Adam Hoffinger, an attorney for Ms Vaughn. He added that the trip was not offered in exchange for writing prescriptions for Serostim, noting that the defendants "had no intent to bribe any doctors, and they did not bribe any doctors. It was a legitimate medical conference."Serono agreed a deal with the US Justice Department in October 2005 to plead guilty and pay $704 million to settle charges that it knowingly encouraged the submission of fraudulent claims for Serostim reimbursement under government health programmes.ReutersIt also agreed in 2005 to plead guilty to two criminal charges and to pay a $137 million fine resolving an investigation into how the company marketed the drug called Serostim, which was approved by the U.S. Food and Drug Administration in 1996.The drug was marketed in the United States by Serono Inc. of Rockland, Massachusetts.Also in 2005, Serono agreed to pay $567 million to settle civil charges that it knowingly caused the submission of false claims for Serostim that were not eligible for reimbursement under government health programs.>From 2005 Boston Globe:Some HIV/AIDS advocates have said the "bad blood" with Serono will not affect their position on new uses for Serostim, the Globe reports. However, "it's clear this vocal and influential constituency, which often weighs in with regulators on AIDS drugs, now doesn't trust Serono and will be skeptical of any new promises or clinical claims from the company," according to the Globe
IF YOU HAVE PAID FOR ANY PART OF SEROSTIM'S PRESCRIPTION IN THE PAST, READ THIS:
Mr. Vergel:
I am an attorney involved in the settlement of litigation against Serono. There's about $2 million available to reimburse anyone who paid anything out of pocket for Serostim. Despite our best efforts to date to spread the word about the settlement and the availability of the money, very few have filed proofs of claim and most of the money is at risk of going unclaimed.
If you think you can help publicize this, please contact me. Your services would not be compensated, so you'd have to be interested in this as a pro bono project.
Richard W. Cohen
Lowey Dannenberg Bemporad Selinger & Cohen, P.C.
White Plains Plaza
One North Broadway, 5th Floor
White Plains, NY 10601
914-997-0500 (main line)
914-733-7239 (direct line)
rcohen@lowey.com
Thursday, April 19, 2007
AIDS activists upset by dropped wasting drug
Copyright © 2006 Bay Area Reporter, a division of Benro Enterprises, Inc.
AIDS activists upset by dropped wasting drug
by Heather Cassellh.cassell@ebar.com
AIDS activists are mobilizing after Watson Pharmaceuticals last month dropped a common off-label drug used to assist patients with combating wasting and picked up a generic brand of an approved AIDS-related wasting medication that they maintain is not as effective.
"Taking this drug away from people with wasting syndrome is like taking insulin away from diabetics," said Jason Riggs, deputy director of the Stop AIDS Project. "Thousands of people with HIV depend on this drug to reverse wasting syndrome, a life-threatening illness."
Patricia Eisenhaur, director of investor relations for Watson Pharmaceuticals, confirmed that Deca-Durabolin, also known as nandrolone decanoate, an anabolic steroid prescribed by physicians to combat AIDS wasting, was discontinued on March 20.
According to Eisenhaur, the active ingredient to manufacture the drug was no longer available from the Food and Drug Administration-approved supplier. Eisenhaur was unable to provide the name of the supplier, which was the only approved manufacturer of the active ingredient. She told the Bay Area Reporter that the supplier did not provide Watson with a particular reason for not being able to provide the ingredient for the medication.
"We depleted all of our existing inventory and we've done everything we can to keep the product on the market," said Eisenhaur. "But without access to the active ingredient we obviously can no longer manufacture and distribute this product."
Eisenhaur told the B.A.R. that Watson notified its customers – mainly hospitals, wholesalers, and those who purchase products directly from the company – about the discontinuation of the medication through its normal communications process. Watson did not issue a news release regarding its decision and the company does not plan on making any further public announcements, according to Eisenhaur.
AIDS activists upset
On April 4, Sanford Gross, an associate professor at Illinois College of Optometry, posted on the Yahoo Group PozHealth his discovery that Deca-Durabolin was discontinued by Watson.
AIDS physicians and activists don't believe that the raw ingredient used to make the medication isn't available. During an AIDS Treatment Activist Coalition phone conference on April 13 to discuss actions to mobilize to have the medication returned to the market, there was speculation about Watson's decision. Their suspicions grew through this week as they learned that Savient Pharmaceuticals canceled its patient assistance program for Oxandrin, the second most prescribed drug to combat wasting.
Savient made that decision soon after Watson was approved to manufacture a generic brand of Oxandrin in December 2006.
"The company has always been pleased to provide the patient assistant programs over the past several years," said Anne Marie Fields, investor relations of Savient. "That's pretty common to cancel patient assistant program for a drug when it goes generic. It just makes sense. The increase of the introduction of the generic and reduction of the price makes the product more accessible for the patients that need them."
"We are one of the broadest distributors of generic products of the United States," said Watson's Eisenhaur. "So having an opportunity to offer new products to our customers is important to us."
Eisenhaur told the B.A.R. that the decisions for both drugs were unrelated. According to Eisenhaur, Deca-Durabolin "in terms of Watson's overall revenues, it is a small product."
AIDS doctors and activists aren't satisfied with responses from Watson and Savient.
"I think it's important for citizens to realize that our health care system for the last 30 years has slowly been hijacked by corporations," said Dr. Richard Loftus of California Pacific Medical Center, Davis Campus.
But not all activists were quick to blame Watson.
"I'm reluctant to put this squarely on the shoulders of Watson Pharmaceuticals," wrote Tim Horn, senior writer and editor for http://www.AIDSmeds.com, in a e-mail. "The fact is, we – treatment activists – dropped the ball. We should have been pushing for the approval of nandrolone as a bona fide treatment for HIV/AIDS-related wasting 10 years ago ... I just don't see how we're to be at all effective in terms of pushing a company to continue manufacturing a drug for an indication it doesn't even have."
Which can possibly explain some of AIDS physicians' complaints that Watson didn't notify them. Deca-Durabolin isn't approved by the FDA for doctors to prescribe to their HIV-positive and AIDS patients to treat AIDS-related wasting. It was approved for treating anemia, according to Horn.
According to the FDA's Web site, Deca-Durabolin is an anabolic steroid that was first approved by the FDA in 1962. The Web site also stated that there is no alternative therapy.
This wasn't news to physicians treating AIDS patients and activists who are troubled by the changes. The medication was highly successful with low side effects, was cost effective, and was included in the AIDS Drug Assistance Program.
According to Loftus and AIDS activists, there aren't very many viable options available on the market to assist patients with combating AIDS-related wasting. What is also troublesome to them is that the options aren't as effective treating the condition.
AIDS physicians and activists repeatedly cited the fact that Deca-Durobolin was studied thoroughly, including for AIDS-related wasting. The studies showed that the medication has many benefits, according to Loftus and those that participated in the conference call. One of the benefits is that it has few side effects compared to alternative steroids, such as Oxandrin, Loftus noted.
He said that the problem with Oxandrin is that it has common side effects, but more important, it damages the liver. Deca-Durabolin did not. Oxandrin, the second most prescribed anabolic steroid, is also more expensive.
According to Nelson Vergel, founder of the Program for Wellness Restoration in Houston, Texas, who coordinated the conference call, AIDS-related wasting isn't the "number two HIV killer anymore in the United States, it is now number eight." He believes this is due to life-expanding medications, such as protease inhibitors, commonly referred to as "cocktails."
That doesn't make a difference to Loftus, who prescribes the medication, or patients who depend on the medication to help them continue living healthy lives.
"We have a real urgent need to treat weight loss in these patients for the sake of survival," said Loftus.
This isn't the first time Deca-Durabolin was removed from the market. Organon International, a New Jersey pharmaceutical company, dropped the drug from distribution in 2002 with no plans to return it to the market. AIDS activists mobilized at that time as well. Eventually, Watson picked up the medication. ATAC is hoping this will happen again.
"This is a decision that effects many people's health that was made by a corporation that did not even have the courteousness to consult patient groups about this decision," said Loftus. "This goes back to an old adage that we used to say in ACT UP 15 years ago, 'Their right to own the drug is more important than our right to have access to it to save our lives.'"
Loftus said about 90 percent of his patients with full-blown AIDS and 40 percent of his HIV-positive patients are on Deca-Durabolin. He sees about 300 AIDS and 1,700 HIV-positive patients. He found out about Deca-Durabolin's discontinuation from Gross's posting on PozHealth, but he never received a notification from Watson. According to Loftus, Walgreens pharmacy confirmed Watson's decision on April 17.
For more information on the campaign to put Deca-Durabolin, back on the market, visit http://watsonboycott.blogspot.com/.
04/19/2007
AIDS activists upset by dropped wasting drug
by Heather Cassellh.cassell@ebar.com
AIDS activists are mobilizing after Watson Pharmaceuticals last month dropped a common off-label drug used to assist patients with combating wasting and picked up a generic brand of an approved AIDS-related wasting medication that they maintain is not as effective.
"Taking this drug away from people with wasting syndrome is like taking insulin away from diabetics," said Jason Riggs, deputy director of the Stop AIDS Project. "Thousands of people with HIV depend on this drug to reverse wasting syndrome, a life-threatening illness."
Patricia Eisenhaur, director of investor relations for Watson Pharmaceuticals, confirmed that Deca-Durabolin, also known as nandrolone decanoate, an anabolic steroid prescribed by physicians to combat AIDS wasting, was discontinued on March 20.
According to Eisenhaur, the active ingredient to manufacture the drug was no longer available from the Food and Drug Administration-approved supplier. Eisenhaur was unable to provide the name of the supplier, which was the only approved manufacturer of the active ingredient. She told the Bay Area Reporter that the supplier did not provide Watson with a particular reason for not being able to provide the ingredient for the medication.
"We depleted all of our existing inventory and we've done everything we can to keep the product on the market," said Eisenhaur. "But without access to the active ingredient we obviously can no longer manufacture and distribute this product."
Eisenhaur told the B.A.R. that Watson notified its customers – mainly hospitals, wholesalers, and those who purchase products directly from the company – about the discontinuation of the medication through its normal communications process. Watson did not issue a news release regarding its decision and the company does not plan on making any further public announcements, according to Eisenhaur.
AIDS activists upset
On April 4, Sanford Gross, an associate professor at Illinois College of Optometry, posted on the Yahoo Group PozHealth his discovery that Deca-Durabolin was discontinued by Watson.
AIDS physicians and activists don't believe that the raw ingredient used to make the medication isn't available. During an AIDS Treatment Activist Coalition phone conference on April 13 to discuss actions to mobilize to have the medication returned to the market, there was speculation about Watson's decision. Their suspicions grew through this week as they learned that Savient Pharmaceuticals canceled its patient assistance program for Oxandrin, the second most prescribed drug to combat wasting.
Savient made that decision soon after Watson was approved to manufacture a generic brand of Oxandrin in December 2006.
"The company has always been pleased to provide the patient assistant programs over the past several years," said Anne Marie Fields, investor relations of Savient. "That's pretty common to cancel patient assistant program for a drug when it goes generic. It just makes sense. The increase of the introduction of the generic and reduction of the price makes the product more accessible for the patients that need them."
"We are one of the broadest distributors of generic products of the United States," said Watson's Eisenhaur. "So having an opportunity to offer new products to our customers is important to us."
Eisenhaur told the B.A.R. that the decisions for both drugs were unrelated. According to Eisenhaur, Deca-Durabolin "in terms of Watson's overall revenues, it is a small product."
AIDS doctors and activists aren't satisfied with responses from Watson and Savient.
"I think it's important for citizens to realize that our health care system for the last 30 years has slowly been hijacked by corporations," said Dr. Richard Loftus of California Pacific Medical Center, Davis Campus.
But not all activists were quick to blame Watson.
"I'm reluctant to put this squarely on the shoulders of Watson Pharmaceuticals," wrote Tim Horn, senior writer and editor for http://www.AIDSmeds.com, in a e-mail. "The fact is, we – treatment activists – dropped the ball. We should have been pushing for the approval of nandrolone as a bona fide treatment for HIV/AIDS-related wasting 10 years ago ... I just don't see how we're to be at all effective in terms of pushing a company to continue manufacturing a drug for an indication it doesn't even have."
Which can possibly explain some of AIDS physicians' complaints that Watson didn't notify them. Deca-Durabolin isn't approved by the FDA for doctors to prescribe to their HIV-positive and AIDS patients to treat AIDS-related wasting. It was approved for treating anemia, according to Horn.
According to the FDA's Web site, Deca-Durabolin is an anabolic steroid that was first approved by the FDA in 1962. The Web site also stated that there is no alternative therapy.
This wasn't news to physicians treating AIDS patients and activists who are troubled by the changes. The medication was highly successful with low side effects, was cost effective, and was included in the AIDS Drug Assistance Program.
According to Loftus and AIDS activists, there aren't very many viable options available on the market to assist patients with combating AIDS-related wasting. What is also troublesome to them is that the options aren't as effective treating the condition.
AIDS physicians and activists repeatedly cited the fact that Deca-Durobolin was studied thoroughly, including for AIDS-related wasting. The studies showed that the medication has many benefits, according to Loftus and those that participated in the conference call. One of the benefits is that it has few side effects compared to alternative steroids, such as Oxandrin, Loftus noted.
He said that the problem with Oxandrin is that it has common side effects, but more important, it damages the liver. Deca-Durabolin did not. Oxandrin, the second most prescribed anabolic steroid, is also more expensive.
According to Nelson Vergel, founder of the Program for Wellness Restoration in Houston, Texas, who coordinated the conference call, AIDS-related wasting isn't the "number two HIV killer anymore in the United States, it is now number eight." He believes this is due to life-expanding medications, such as protease inhibitors, commonly referred to as "cocktails."
That doesn't make a difference to Loftus, who prescribes the medication, or patients who depend on the medication to help them continue living healthy lives.
"We have a real urgent need to treat weight loss in these patients for the sake of survival," said Loftus.
This isn't the first time Deca-Durabolin was removed from the market. Organon International, a New Jersey pharmaceutical company, dropped the drug from distribution in 2002 with no plans to return it to the market. AIDS activists mobilized at that time as well. Eventually, Watson picked up the medication. ATAC is hoping this will happen again.
"This is a decision that effects many people's health that was made by a corporation that did not even have the courteousness to consult patient groups about this decision," said Loftus. "This goes back to an old adage that we used to say in ACT UP 15 years ago, 'Their right to own the drug is more important than our right to have access to it to save our lives.'"
Loftus said about 90 percent of his patients with full-blown AIDS and 40 percent of his HIV-positive patients are on Deca-Durabolin. He sees about 300 AIDS and 1,700 HIV-positive patients. He found out about Deca-Durabolin's discontinuation from Gross's posting on PozHealth, but he never received a notification from Watson. According to Loftus, Walgreens pharmacy confirmed Watson's decision on April 17.
For more information on the campaign to put Deca-Durabolin, back on the market, visit http://watsonboycott.blogspot.com/.
04/19/2007
Wednesday, April 11, 2007
My Upcoming Lecture in Wilmington , DE
Surviving HIV Resistance in the new era of HAART
Date: 04/25/2007
Time: 12-2 p.m.
Place: Doubletree Hotel
Address: 700 King St.
City: Wilmington
State: Delaware
Zip: 19801
Contact Person: Lori Campbell
Organization/Company: AIDS Delaware
Contact Email: campbell@aidsdelaware.org
Contact Phone: 302-652-6776
Contact Fax:
Event Description:
A lecture for patients and clinicians. Topics include how to avoid serious mistakes in choosing the right combinations, data on new medications and how to predict the best response in the treatment of patients with multi-drug resistance. Nelson Vergel,BsChE, founder of salvagetherapies.org, powerusa.org and the Body Positive Wellness Clinic in Houston, will be the featured speaker.
http://www.delawarehiv.org/calendar_view_details.cfm?new_event_date=04/25/2007&id=285&type=state
Date: 04/25/2007
Time: 12-2 p.m.
Place: Doubletree Hotel
Address: 700 King St.
City: Wilmington
State: Delaware
Zip: 19801
Contact Person: Lori Campbell
Organization/Company: AIDS Delaware
Contact Email: campbell@aidsdelaware.org
Contact Phone: 302-652-6776
Contact Fax:
Event Description:
A lecture for patients and clinicians. Topics include how to avoid serious mistakes in choosing the right combinations, data on new medications and how to predict the best response in the treatment of patients with multi-drug resistance. Nelson Vergel,BsChE, founder of salvagetherapies.org, powerusa.org and the Body Positive Wellness Clinic in Houston, will be the featured speaker.
http://www.delawarehiv.org/calendar_view_details.cfm?new_event_date=04/25/2007&id=285&type=state
Tuesday, April 10, 2007
STOP CONGRESS FROM DENYING US COMPOUNDED MEDICINES
Compounded medications have greatly improved the quality of the lives of many people living with HIV. Several of these medications (hormone therapies, wasting therapies, quality of life therapies) are not cover by most insurance or ADAP/Medicare/Medicaid formularies, so patients rely on access through compounding pharmacies. Now, access to these medications is facing a huge threat.
A small but powerful group of senators is on the verge of introducing legislation that would severely restrict and possibly deny access to critical medications that many patients rely on, such as women prescribed bioidentical hormones, hospice care patients and children.
Even if you don't currently rely on compounded medicines yourself, you may need them someday - and you know someone who needs them now. Please join me in contacting Congress to stop this legislation and protect patient access to compounded drugs! Visit www.savemymedicine.org to take action.
This is a copy of the letter that savemymedicine.org sends to your congress people after you input your name and address.
Apr 9, 2007
Senator John Cornyn
United States Senate
517 Hart Senate Office Building
Washington, DC 20510-0001
Dear Senator Cornyn,
I know that you are committed to protecting patients and, as a result,
I hope that you share my concerns about the draft Safe Drug
Compounding Act of 2007 that may soon be introduced by Senators Edward Kennedy, Richard Burr and Pat Roberts.
I rely on compounded medications. Without access to them, I will
suffer.
The Safe Drug Compounding Act would restrict and possibly even deny my access to vital compounded medications, medications that my doctor
has determined I need.
As your constituent, I strongly urge you to oppose this legislation
and look forward to hearing your response.
Sincerely,
Mr. Nelson Vergel
*************************************************************************
A small but powerful group of senators is on the verge of introducing legislation that would severely restrict and possibly deny access to critical medications that many patients rely on, such as women prescribed bioidentical hormones, hospice care patients and children.
Even if you don't currently rely on compounded medicines yourself, you may need them someday - and you know someone who needs them now. Please join me in contacting Congress to stop this legislation and protect patient access to compounded drugs! Visit www.savemymedicine.org to take action.
This is a copy of the letter that savemymedicine.org sends to your congress people after you input your name and address.
Apr 9, 2007
Senator John Cornyn
United States Senate
517 Hart Senate Office Building
Washington, DC 20510-0001
Dear Senator Cornyn,
I know that you are committed to protecting patients and, as a result,
I hope that you share my concerns about the draft Safe Drug
Compounding Act of 2007 that may soon be introduced by Senators Edward Kennedy, Richard Burr and Pat Roberts.
I rely on compounded medications. Without access to them, I will
suffer.
The Safe Drug Compounding Act would restrict and possibly even deny my access to vital compounded medications, medications that my doctor
has determined I need.
As your constituent, I strongly urge you to oppose this legislation
and look forward to hearing your response.
Sincerely,
Mr. Nelson Vergel
*************************************************************************
Friday, April 06, 2007
WATSON PHARMACEUTICALS ABANDONS AIDS WASTING DRUG
FOR MORE INFORMATION ABOUT THIS GO TO http://watsonboycott.blogspot.com/
April 4, 2007
Allen Chao, PhD
Chairman and CEO
Watson Pharmaceuticals
Corporate Headquarters
311 Bonnie Circle
Corona, California 92880
Dear Dr Chao :
I am writing to ask you to reverse your decision of stopping the manufacture of nandrolone decanoate. I am a national treatment advocate and person living with AIDS who has used your product in the past to reverse wasting syndrome and sustain my lean body mass and quality of life. Several HIV studies have shown that nandrolone prevents and reverses the loss of lean body mass (LBM) that has been linked to increased risk of death in HIV while increasing strength and functional capacity. Your decision to abandon this compound affects me, my work, and thousands of people who needed it to keep living a productive life.
At an average cost of $200 a month for dose of 200 mg a week, nandrolone is a lot more cost effective and more tolerable wasting treatment than recombinant human growth hormone (Serostim) ( cost: $6000 a month). You are the sole supplier of several federal-funded AIDS Drug Assistance and Medicaid programs that have recognized its value and have included nandrolone in their formularies to treat thousands of low income HIV-positive patients nationwide.
I have been told by people in your company that you do not have a source of raw materials anymore. It seems that several raw material suppliers are still available. I certainly hope that your decision has not been originated by the DEA and media frenzy over anabolic steroid use in sports. This negative media exposure completely ignores the important medical uses of this medication. For whatever reason, it is irresponsible for Watson to stop supplying this product without a successor that can guarantee that patients in need get access to this important drug.
Thus, unless you decide to reverse your unfortunate decision of abandoning nandrolone decanoate, our organization and many key stakeholders will start a campaign to boycott Androderm and Watson's other products via press releases, emails and direct mailings to physicians. I certainly hope we do not have to go to these extreme measures and that you show compassion towards people living with HIV.
Please have someone from your medical and legal department call me directly at 713-539-1978 to discuss this matter before the patient and physician communities are activated.
Sincerely,
Nelson R. Vergel
Director
cc:
Mr Jeff Murray- Food and Drug Administration
Ms Karen Tandy- Drug Enforcement Administration
Mr Steve Baragona- HIV Medicine Association (HIVMA)
Mr Rob Banaszak- The American Academy of HIV Medicine (AAHIVM)
Ms. Cathy Olufs- President- The AIDS Treatment Activist Coalition (ATAC)
April 4, 2007
Allen Chao, PhD
Chairman and CEO
Watson Pharmaceuticals
Corporate Headquarters
311 Bonnie Circle
Corona, California 92880
Dear Dr Chao :
I am writing to ask you to reverse your decision of stopping the manufacture of nandrolone decanoate. I am a national treatment advocate and person living with AIDS who has used your product in the past to reverse wasting syndrome and sustain my lean body mass and quality of life. Several HIV studies have shown that nandrolone prevents and reverses the loss of lean body mass (LBM) that has been linked to increased risk of death in HIV while increasing strength and functional capacity. Your decision to abandon this compound affects me, my work, and thousands of people who needed it to keep living a productive life.
At an average cost of $200 a month for dose of 200 mg a week, nandrolone is a lot more cost effective and more tolerable wasting treatment than recombinant human growth hormone (Serostim) ( cost: $6000 a month). You are the sole supplier of several federal-funded AIDS Drug Assistance and Medicaid programs that have recognized its value and have included nandrolone in their formularies to treat thousands of low income HIV-positive patients nationwide.
I have been told by people in your company that you do not have a source of raw materials anymore. It seems that several raw material suppliers are still available. I certainly hope that your decision has not been originated by the DEA and media frenzy over anabolic steroid use in sports. This negative media exposure completely ignores the important medical uses of this medication. For whatever reason, it is irresponsible for Watson to stop supplying this product without a successor that can guarantee that patients in need get access to this important drug.
Thus, unless you decide to reverse your unfortunate decision of abandoning nandrolone decanoate, our organization and many key stakeholders will start a campaign to boycott Androderm and Watson's other products via press releases, emails and direct mailings to physicians. I certainly hope we do not have to go to these extreme measures and that you show compassion towards people living with HIV.
Please have someone from your medical and legal department call me directly at 713-539-1978 to discuss this matter before the patient and physician communities are activated.
Sincerely,
Nelson R. Vergel
Director
cc:
Mr Jeff Murray- Food and Drug Administration
Ms Karen Tandy- Drug Enforcement Administration
Mr Steve Baragona- HIV Medicine Association (HIVMA)
Mr Rob Banaszak- The American Academy of HIV Medicine (AAHIVM)
Ms. Cathy Olufs- President- The AIDS Treatment Activist Coalition (ATAC)
Support PoWeR
Posts
