Drug-Induced Hypersomnolence.

Sleep Med Clin. 2017 Sep;12(3):383-393

Authors: Pagel JF

Abstract
Daytime somnolence is among the most commonly reported drug side effects. The United States has the highest rate of motor vehicular accident (MVA) deaths with sedating drug use a factor in more than 30%. Sedating drug use extends beyond drugs of abuse to sedating medications. This paper presents pharmacodynamics, performance and driving tests, and MVAs for somnolence inducing agents classified as hypnotics, sedatives, and/or sedation as a side effect. This classification, based on the drug tendency to induce next-day sedation after nighttime use, can be cogently used by prescribers, pharmacists, regulatory agencies, and in direct to consumer marketing.

PMID: 28778236 [PubMed - in process]

Amantadine for Antipsychotic-Related Weight Gain: Meta-Analysis of Randomized Placebo-Controlled Trials.

J Clin Psychopharmacol. 2017 Jun;37(3):341-346

Authors: Zheng W, Wang S, Ungvari GS, Ng CH, Yang XH, Gu YH, Li M, Xiang YQ, Xiang YT

Abstract
PURPOSE: Weight gain associated with antipsychotics in schizophrenia has been an ongoing concern. This meta-analysis examined the efficacy and safety of amantadine as an adjunctive treatment of weight gain in schizophrenia by systematically searching and analyzing randomized controlled trials (RCTs). RCTs comparing adjunctive amantadine with placebo in adult patients with schizophrenia were included in the meta-analysis.
METHODS: Two independent investigators searched the literature and extracted data. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio ± 95% confidence intervals were calculated.
RESULTS: Five RCTs (n = 265) with double-blinded design lasting 8.2 ± 5.9 weeks were included in the analysis. Amantadine outperformed placebo regarding weight reduction with moderate effect size (trials, 3; n = 205; WMD -2.22 kg; P = 0.001, I = 45%). Amantadine also outperformed placebo at endpoint in the negative symptom (the Positive and Negative Syndrome Scale [PANSS] [1 trial] and the Scale for the Assessment of Negative Symptoms [1 trial]) scores (trials, 2; n = 84; SMD, -0.56; P = 0.01, I = 12%), but not in the PANSS total scores (trials, 2) (SMD, -0.31; P = 0.16, I = 0%) and the positive symptom (PANSS [1 trial] and the Scale for the Assessment of Positive Symptoms [1 trial]) scores (SMD, 0.13; P = 0.54, I = 0%). Except for insomnia (P = 0.007; number needed to harm, 6; 95% confidence interval, 4-16), all-cause discontinuation (risk ratio, 1.12; P = 0.54, I = 0%) and other adverse events were similar between the amantadine and placebo groups.
CONCLUSIONS: According to this meta-analysis of 5 RCTs, adjunctive amantadine seems to be an effective option for attenuating antipsychotic-related weight gain in patients with schizophrenia. More RCTs are needed to inform clinical recommendations.

PMID: 28383359 [PubMed - indexed for MEDLINE]

Lithiumeter: Version 2.0.

Bipolar Disord. 2016 Dec;18(8):631-641

Authors: Malhi GS, Gershon S, Outhred T

Abstract
BACKGROUND: The Lithiumeter was developed as a visual and practical guide for determining lithium levels in the management of bipolar disorder (BD). It appears to have been well received, as evidenced by its increasing popularity amongst doctors as a deskside clinical aide, and adoption and reproduction of the schematic in clinical guidelines and texts. However, since its publication 5 years ago, key basic neuroscience and clinical research developments pertaining to lithium have significantly advanced our understanding, necessitating further refinement of guidance concerning the practicalities of lithium therapy.
METHODS: Literature concerning the indications for, and therapeutic levels of, lithium and the associated acute and chronic risks of therapy was scrutinized as part of updating clinical practice guidelines. We have reviewed these updates and identified significant areas of change with respect to the previous Lithiumeter (version 1.0).
RESULTS: Since 2011, updated clinical practice guidelines have narrowed the indicated plasma lithium concentration for maintenance therapy, suggesting that additional guidance is necessary for optimizing treatment. Relevant updated clinical guidance was integrated to constitute the Lithiumeter 2.0, which provides a more comprehensive overview of the practical aspects of lithium therapy while maintaining a focus on optimization of lithium levels, such as differential titration of lithium depending on the current mood state.
CONCLUSIONS: The Lithiumeter 2.0 is an update that clinicians will find useful for their practice. By addressing some of the issues faced in clinical practice, translational clinical research will continue to inform the Lithiumeter in future updates.

PMID: 28063207 [PubMed - indexed for MEDLINE]

[Follow-up of patients treated by VKA: Interest of a pharmaceutical link between the hospital and the retail pharmacies].

Ann Pharm Fr. 2017 Jan;75(1):45-53

Authors: Bidon D, Lecoeur A, Segui E, Seguette N, Le Mercier F, Bauler S

Abstract
Vitamin K antagonists (VKA) are used by 1,7% of the French population. Patient education and monitoring can decrease the number of iatrogenic hospitalizations due to VKA. We assessed the impact of a communication between hospital and retail pharmacists about patient's knowledge on VKA. The aim of our study has been to evaluate the value added by the link between the hospital pharmacist and the community pharmacist on the follow-up of patients treated by vitamin K antagonist. Patient information about VKA treatment is offered to inpatients in our hospital. An information form is filled for each patient treated by VKA. Patient's knowledge is assessed on the document (Name of VKA, cause of treatment, monitoring, risks of overdose, compliance…). This form is sent to the community pharmacist after the training when the patient leaves the hospital (by fax or by email). The form is sent back by the community pharmacist after the second training. Sixty-eight patients received the training, 48 forms have been sent to the retail pharmacists and 43 forms have been sent back to the hospital. Seven retail pharmacists replied spontaneously. Twenty-eight patients increased their knowledge (in average+21%) and 12 patients stabilized their knowledge. The best-known concepts were the INR target, the time of drug intake, the risks of overdose and the information of the family. The improvement of knowledge is significant for the name of VKA, the cause of treatment, efficacy assessment and signs of overdose. The implementation of a communication between the hospital and the retail pharmacies is time-consuming but the follow-up of those patients seems essential to keep a good knowledge.

PMID: 27234455 [PubMed - indexed for MEDLINE]

Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island.

J Gerontol A Biol Sci Med Sci. 2016 Jul;71(7):841-9

Authors: Arriola Apelo SI, Lamming DW

Abstract
Rapamycin (sirolimus) is a macrolide immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) protein kinase and extends lifespan in model organisms including mice. Although rapamycin is an FDA-approved drug for select indications, a diverse set of negative side effects may preclude its wide-scale deployment as an antiaging therapy. mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Over the past decade, it has become clear that although genetic and pharmacological inhibition of mTORC1 extends lifespan and delays aging, inhibition of mTORC2 has negative effects on mammalian health and longevity and is responsible for many of the negative side effects of rapamycin. In this review, we discuss recent advances in understanding the molecular and physiological effects of rapamycin treatment, and we discuss how the use of alternative rapamycin treatment regimens or rapamycin analogs has the potential to mitigate the deleterious side effects of rapamycin treatment by more specifically targeting mTORC1. Although the side effects of rapamycin are still of significant concern, rapid progress is being made in realizing the revolutionary potential of rapamycin-based therapies for the treatment of diseases of aging.

PMID: 27208895 [PubMed - indexed for MEDLINE]

Etiology and pathogenesis of dental erosion.

Quintessence Int. 2016 Apr;47(4):275-8

Authors: Kanzow P, Wegehaupt FJ, Attin T, Wiegand A

Abstract
The condition of dental erosion is defined as acid-related loss of tooth structure which does not involve microorganisms. Depending on the origin of the acid, extrinsic (usually caused by acids in food) and intrinsic (caused by endogenous acid) erosion can be distinguished. The presence and severity of erosive defects depend on various parameters such as nutrition, saliva, general diseases, and mechanical stress by abrasion and attrition. As an example, dietary habits which involve frequent intake of acidic food and beverages, occupational acid exposure, as well as certain drugs or diseases that affect saliva flow rate are accompanied by an increased risk of erosive dental hard tissue defects. By a thorough clinical examination and an accurate anamnesis, various erosion-related risk factors can be identified and strategies to reduce or eliminate these factors be identified.

PMID: 27022647 [PubMed - indexed for MEDLINE]

Absence of human herpesvirus 6B detection in association with illness in children undergoing cancer chemotherapy.

J Med Virol. 2016 Aug;88(8):1427-37

Authors: Goldfarb J, Borges N, Gowans LK, Kohn D, Worley S, Li L, Yen-Lieberman B, Lach D, Danziger-Isakov L, Yee-Guardino S, Trunick C, Pellett PE

Abstract
The lymphotropic herpesviruses, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus 6B (HHV-6B) can reactivate and cause disease in organ transplant recipients; the contributions of HHV-6A and HHV-7 to disease are less certain. Less is known about their pathogenic roles in children undergoing treatment for malignancies. Children with newly diagnosed cancer were followed for 24 months. Clinical information and blood samples were collected during routine visits and during acute visits for fever or possible viral infections. Lymphotropic herpesvirus DNA in blood was measured by polymerase chain reaction (PCR). Although HHV-6B DNA was detected at least once in about half of the patients; the other viruses were seldom detected. There was no association between HHV-6B detection and individual acute clinical events, however, HHV-6B detection was more common in children who experienced more frequent acute clinical events. In children being treated for various malignancies, HHV-6B detection was common, but was not associated with individual events of acute illness. Thus, if HHV-6B is not assessed longitudinally, clinical events may be misattributed to the virus. The elevated frequency of detection of HHV-6B in sicker children is consistent with prior reports of its detection during apparently unrelated acute clinical events. J. Med. Virol. 88:1427-1437, 2016. © 2016 Wiley Periodicals, Inc.

PMID: 26815906 [PubMed - indexed for MEDLINE]

Real-world experience of afatinib as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma.

Oncotarget. 2017 Jul 26;:

Authors: Liang SK, Hsieh MS, Lee MR, Keng LT, Ko JC, Shih JY

Abstract
We evaluated the real-world efficacy and side effects of afatinib as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma. The medical records of patients receiving afatinib as a first-line therapy after National Health Insurance reimbursement between May 2014 and January 2016 were reviewed, and information on patient characteristics and treatment courses were collected consecutively. Rebiopsy tissue was collected for EGFR mutation and MET amplification analyses. MET amplification was detected by fluorescence in situ hybridization and immunohistochemistry. In total, 140 patients were enrolled (median follow-up, 18.0 months). No significant differences in side effects, treatment responses, progression-free survival, or brain metastasis control were observed between patients receiving 40 mg versus < 40 mg of afatinib during the first 6 months. Patients with significant pretreatment weight loss (> 10.0% in 6 months) had a shorter median progression-free survival. Patients with brain metastases had a poorer Eastern Cooperative Oncology Group performance status and were associated with a shorter median progression-free survival. Nine patients (32.1%) had a p.T790M mutation and only 1 patient gained MET amplifications after disease progression. Afatinib is effective as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma. Afatinib dosage does not affect clinical efficacy and drug-related side effects.

PMID: 28767414 [PubMed - as supplied by publisher]

Cisplatin and cisplatin analogues perfusion through isolated rat heart: the effects of acute application on oxidative stress biomarkers.

Mol Cell Biochem. 2017 Aug 01;:

Authors: Stojic IM, Zivkovic VI, Srejovic IM, Nikolic TR, Jeremic NS, Jeremic JN, Djuric DM, Jovicic N, Radonjic KG, Bugarcic ZD, Jakovljevic VLJ, Novokmet SS

Abstract
Drug-induced oxidative stress can occur in numerous tissues and organ systems (liver, kidney, ear, nervous system, and cardiovascular system). Cancer therapy with cisplatin is associated with side effects to which oxidative stress may contribute. We have compared the influences of cisplatin (reference compound) and its' analogues (dichloro(1,2-diaminocyclohexane)platinum(II) and chloro(2,2':6',2″-terpyridine)platinum(II)) in a model of isolated rat heart using the Langendorff technique. The production of oxidative stress biomarkers, antioxidant enzymes, myocardial damage, and expression of Bax, OH-1, and SODs were studied. Cisplatin and the analogues were perfused at concentration of 10(-6) and 10(-5) M during 30 min. The results of this study showed that examined platinum complexes had different ability to induce oxidative stress of isolated perfused rat heart. Varying the carrier ligands, such as 1,2-diaminocyclohexane and 2,2':6',2″-terpyridine, related to amino ligands (cisplatin) directly influenced the strength to induce production of oxidative stress biomarkers. Introducing 2,2':6',2″-terpyridine ligands provoked the smallest changes in antioxidant enzymes activity, lipid peroxidation, and expression of heme oxygenase-1, that undoubtedly indicated that this complex had the lowest impact on redox status in heart tissue. These findings may be useful in synthesis of novel platinum analogues with lower potential for oxidative stress induction. However, the fact that platinum complexes could induce toxic effects in the heart by other mechanisms should be taken into the consideration.

PMID: 28766171 [PubMed - as supplied by publisher]

Phase 1 dose-escalation study of the anti-CD70 antibody ARGX-110 in Advanced Malignancies.

Clin Cancer Res. 2017 Aug 01;:

Authors: Aftimos P, Rolfo C, Rottey S, Offner F, Bron DD, Maerevoet M, Soria JC, Moshir M, Dreier T, van Rompaey L, Michot JM, Silence K, Hultberg A, Gandini D, De Haard H, Ribrag V, Peeters M, Thibault A, Leupin N, Awada A

Abstract
PURPOSE: The purpose of this study was to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary antitumor efficacy of ARGX-110, a glyco-engineered monoclonal antibody, targeting CD70, in patients with CD70 expressing advanced malignancies. <br /><br />Experimental Design: <p>Dose escalation with a sequential 3+3 design was performed in five steps at the 0.1, 1, 2, 5, and 10 mg/kg dose levels (N=26). ARGX-110 was administered intravenously every three weeks until progression or intolerable toxicity. Dose limiting toxicity was evaluated in the 21 days following the first ARGX-110 administration (Cycle 1). Samples for pharmacokinetics and pharmacodynamics were collected.</p> <br /><br />Results: <p>Dose limiting toxicity was not observed and the maximum tolerated dose was not reached. ARGX-110 was generally well tolerated, with no dose-related increase in treatment-emergent adverse events (TEAE). The most common TEAE were fatigue and drug related infusion-related reactions (IRRs). Of the 20 SAEs reported, 5 events, all IRRs, were considered related to ARGX‑110.</p> <p>ARGX-110 demonstrates dose proportionality over the dose range 1-10 mg/kg, but not at 0.1 mg/kg and a terminal half-life of 10-13 days.</p> <p>The best overall response was stable disease (14/26) in all 26 evaluable patients with various malignancies and the mean duration of treatment was 15 weeks. No dose-response related anti-tumor activity was observed, but biomarker readouts provided signs of biological activity, particularly in patients with hematological malignancies.</p> <br /><br />Conclusions:This dose-escalation phase I trial provides evidence of good tolerability of ARGX-110, pharmacokinetics and preliminary anti-tumor activity at all dose levels in generally heavily pretreated patients with advanced CD70-positive malignancies.

PMID: 28765328 [PubMed - as supplied by publisher]

Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: Recommendation Statement.

Am Fam Physician. 2016 Oct 15;94(8):Online

Authors:

PMID: 27929224 [PubMed - indexed for MEDLINE]

Higher rates of neuropsychiatric adverse events leading to dolutegravir discontinuation in women and older patients.

HIV Med. 2017 Jan;18(1):56-63

Authors: Hoffmann C, Welz T, Sabranski M, Kolb M, Wolf E, Stellbrink HJ, Wyen C

Abstract
OBJECTIVES: Dolutegravir (DTG), a second-generation integrase strand transfer inhibitor (INSTI), is now among the most frequently used antiretroviral agents. However, recent reports have raised concerns about potential neurotoxicity.
METHODS: We performed a retrospective analysis of a cohort of HIV-infected patients who had initiated an INSTI in two large German out-patient clinics between 2007 and 2016. We compared discontinuation rates because of adverse events (AEs) within 2 years of starting treatment with dolutegravir, raltegravir or elvitegravir/cobicistat. We also evaluated factors associated with dolutegravir discontinuation.
RESULTS: A total of 1950 INSTI-based therapies were initiated in 1704 patients eligible for analysis within the observation period. The estimated rates of any AE and of neuropsychiatric AEs leading to discontinuation within 12 months were 7.6% and 5.6%, respectively, for dolutegravir (n = 985), 7.6% and 0.7%, respectively, for elvitegravir (n = 287), and 3.3% and 1.9%, respectively, for raltegravir (n = 678). Neuropsychiatric AEs leading to dolutegravir discontinuation were observed more frequently in women [hazard ratio (HR) 2.64; 95% confidence interval (CI) 1.23-5.65; P = 0.012], in patients older than 60 years (HR: 2.86; 95% CI: 1.42-5.77; P = 0.003) and in human leucocyte antigen (HLA)-B*5701-negative patients who initiated abacavir at the same time (HR: 2.42; 95% CI: 1.38-4.24; P = 0.002).
CONCLUSIONS: In this large cohort, the rate of discontinuation of dolutegravir because of neuropsychiatric adverse events was significantly higher than for other INSTIs, at almost 6% within 12 months. Despite the limitations of this retrospective study, the almost three-fold higher discontinuation rates observed amongst women and older patients underscore the need for further investigation, especially in patient populations usually underrepresented in clinical trials.

PMID: 27860104 [PubMed - indexed for MEDLINE]

Direct-acting antivirals in hepatitis C virus (HCV)-infected and HCV/HIV-coinfected patients: real-life safety and efficacy.

HIV Med. 2017 Apr;18(4):284-291

Authors: Milazzo L, Lai A, Calvi E, Ronzi P, Micheli V, Binda F, Ridolfo AL, Gervasoni C, Galli M, Antinori S, Sollima S

Abstract
OBJECTIVES: Clinical trials of all-oral direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection reported high response rates in HCV/HIV coinfection, similar to those obtained in HCV monoinfection. We evaluated the safety and efficacy of these regimens in a clinical practice setting.
METHODS: In this prospective observational study, all the HCV-monoinfected and HCV/HIV-coinfected patients undergoing HCV treatment with all-oral DAA regimens in a routine clinical setting from December 2014 to December 2015 were included in the analysis. Sustained virological response 12 weeks after the end of therapy (SVR12) and reported adverse events (AEs) were evaluated. Resistance-associated variants (RAVs) were analysed in a subgroup of patients at baseline and at the time of viral rebound in those with virological failure.
RESULTS: One-hundred and nine patients (51 HCV-infected and 58 HCV/HIV-coinfected) were enrolled in the study. Sixty per cent had cirrhosis and 52% were pegylated interferon and ribavirin (pegIFN/RBV)-experienced. Thirty-six per cent received ombitasvir + paritaprevir/ritonavir + dasabuvir, 25% sofosbuvir + daclatasvir, 16% sofosbuvir + simeprevir, 17% sofosbuvir + ribavirin and 6% sofosbuvir + ledipasvir; ribavirin was used in 57% of subjects. The SVR12 rate was 91% and 96% in HIV-infected and uninfected patients, respectively (P = 0.44). The 4-week HCV viral decline was similar in the two groups. RAVs were found at baseline in 23 of 49 patients and did not affect SVR12. No predictors of SVR12 were identified in our cohort.
CONCLUSIONS: Treatment with all-oral DAA combinations of patients infected with HCV and with HCV/HIV under real-life conditions led to high and similar rates of SVR12. Moreover, the historical factors associated with a sustained virological response to pegIFN/RBV were not predictive of the response to all-oral DAAs.

PMID: 27477612 [PubMed - indexed for MEDLINE]

Week 96 efficacy and safety of darunavir/ritonavir monotherapy vs. darunavir/ritonavir with two nucleoside reverse transcriptase inhibitors in the PROTEA trial.

HIV Med. 2017 Jan;18(1):5-12

Authors: Girard PM, Antinori A, Arribas JR, Ripamonti D, Bicer C, Netzle-Sveine B, Hadacek B, Moecklinghoff C

Abstract
OBJECTIVES: PROTEA is a randomized controlled trial to assess the efficacy and safety of darunavir/ritonavir (DRV/r) monotherapy as an alternative to triple therapy.
METHODS: Patients fully suppressed on first-line antiretrovirals (viral load < 50 HIV-1 RNA copies/mL) were switched to DRV/r 800/100 mg once daily, either as monotherapy (n = 137) or with two nucleoside reverse transcriptase inhibitors (NRTIs) (n = 136). Treatment failure was HIV-1 RNA level ≥ 50 copies/mL at week 96 or discontinuation of study treatment [Food and Drug Administration (FDA) snapshot algorithm].
RESULTS: Patients were mainly male and white, with mean age 44 years. In the primary efficacy analysis, the percentage of patients with HIV-1 RNA < 50 copies/mL by week 96 [intent to treat (ITT)] was lower in the DRV/r monotherapy arm (103 of 137 patients; 75%) than in the triple therapy arm (116 of 136 patients; 85%) [difference -10.1%; 95% confidence interval (CI) -19.5, -0.7%]. In the switch-included analysis, monotherapy was noninferior to triple therapy. In a post hoc analysis, for patients with nadir CD4 count ≥ 200 cells/μL, rates of HIV-1 RNA suppression were 82 of 96 patients (85%) in the DRV/r monotherapy arm and 88 of 106 patients (83%) in the triple therapy arm. No treatment-emergent primary protease inhibitor mutations were detected in either arm. The frequency of adverse events was similar in the two arms; however, one patient in the monotherapy arm was hospitalized with HIV encephalitis and elevated cerebrospinal fluid HIV-1 RNA.
CONCLUSIONS: In this study, in patients with HIV-1 RNA < 50 copies/mL at baseline, switching to DRV/r monotherapy showed lower efficacy vs. triple therapy at week 96 in the primary ITT switch-equals-failure analysis, particularly in patients with CD4 counts < 200 cells/μL.

PMID: 27279571 [PubMed - indexed for MEDLINE]

31 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

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34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/08/02

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/08/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

A Janus tale of the two faces of corticosteroid therapy: A potential for adverse effects versus a steroid-sparing benefit of certain therapies.

Allergy Asthma Proc. 2016 Nov;37(6):423-425

Authors: Bellanti JA, Settipane RA

PMID: 27931295 [PubMed - indexed for MEDLINE]

Levetiracetam in toxic seizures.

Clin Toxicol (Phila). 2017 Jul 28;:1-7

Authors: Lee T, Warrick BJ, Sarangarm P, Alunday RL, Bussmann S, Smolinske SC, Seifert SA

Abstract
BACKGROUND/OBJECTIVES: The use of levetiracetam (LEV) in the management of drug-induced seizures has not been systematically investigated. Repetitive and continuous seizures that do not respond to benzodiazepines require second line therapy. Levetiracetam has a unique receptor binding site, rapid absorption, no known cardiac effects at therapeutic doses, and is theoretically a good candidate for use in drug-induced seizures. We evaluate the safety of LEV and its association with seizure cessation in this retrospective chart review of patients who received LEV as a control agent in drug-induced seizures.
METHODS: We identified the medical records of patients presenting to an urban, level 1 trauma center between 1 January 2010 and 31 May 2015 by ICD-9 codes based on the following: (1) a poisoning diagnosis, (2) a seizure diagnosis, and (3) administration of LEV. We included patients with a drug-induced seizure based on history, electroencephalogram results, blood alcohol concentrations, urine drug screens, and adequate documentation. We excluded patients with alcohol withdrawal, anoxic brain injury, subtherapeutic concentrations of other antiepileptics, hypoglycemia, and pseudoseizures. Primary outcomes of interest included cessation of active seizures or the prevention of seizure recurrence. We assessed safety by the presence or absence of adverse drug effects (ADE) attributed to the administration of LEV.
RESULTS: Thirty-four patients met inclusion and exclusion criteria. Half of the study cohort (17) presented with generalized tonic-clonic seizures (TCS); half (17) presented in generalized convulsive status epilepticus (GCSE). Six patients in GCSE received LEV during their seizures; 2 also received fosphenytoin. One improved immediately following LEV administration, and the remaining 5 had seizure control. Eleven GCSE patients (65%) remained seizure free after LEV therapy. The patients with TCS (17) received LEV after seizure(s) control. Sixteen (94%) were seizure-free during their hospital course. We found no adverse drug effects. In total, 27 of 34 patients (79%) had a return to baseline neurological and physical health. Six had long-term sequelae; none of which are known LEV side-effects. We identified 46 toxic substances and 22 known seizurogenic agents (48%). The median length of stay was 3.7 days (0.4-96), and the median duration of in-hospital LEV therapy was 1.6 days (0-49).
CONCLUSIONS: Levetiracetam used as a second-line agent was associated with control of drug-induced seizures and prevention of seizure recurrence without obvious adverse effects. A prospective study is needed to confirm these results.

PMID: 28753046 [PubMed - as supplied by publisher]

Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial.

Lancet. 2017 Jul 21;:

Authors: Margolis DA, Gonzalez-Garcia J, Stellbrink HJ, Eron JJ, Yazdanpanah Y, Podzamczer D, Lutz T, Angel JB, Richmond GJ, Clotet B, Gutierrez F, Sloan L, Clair MS, Murray M, Ford SL, Mrus J, Patel P, Crauwels H, Griffith SK, Sutton KC, Dorey D, Smith KY, Williams PE, Spreen WR

Abstract
BACKGROUND: Cabotegravir and rilpivirine are antiretroviral drugs in development as long-acting injectable formulations. The LATTE-2 study evaluated long-acting cabotegravir plus rilpivirine for maintenance of HIV-1 viral suppression through 96 weeks.
METHODS: In this randomised, phase 2b, open-label study, treatment-naive adults infected with HIV-1 initially received oral cabotegravir 30 mg plus abacavir-lamivudine 600-300 mg once daily. The objective of this study was to select an intramuscular dosing regimen based on a comparison of the antiviral activity, tolerability, and safety of the two intramuscular dosing regimens relative to oral cabotegravir plus abacavir-lamivudine. After a 20-week induction period on oral cabotegravir plus abacavir-lamivudine, patients with viral suppression (plasma HIV-1 RNA <50 copies per mL) were randomly assigned (2:2:1) to intramuscular long-acting cabotegravir plus rilpivirine at 4-week intervals (long-acting cabotegravir 400 mg plus rilpivirine 600 mg; two 2 mL injections) or 8-week intervals (long-acting cabotegravir 600 mg plus rilpivirine 900 mg; two 3 mL injections) or continued oral cabotegravir plus abacavir-lamivudine. Randomisation was computer-generated with stratification by HIV-1 RNA (<50 copies per mL, yes or no) during the first 12 weeks of the induction period. The primary endpoints were the proportion of patients with viral suppression at week 32 (as defined by the US Food and Drug Administration snapshot algorithm), protocol-defined virological failures, and safety events through 96 weeks. All randomly assigned patients who received at least one dose of study drug during the maintenance period were included in the primary efficacy and safety analyses. The primary analysis used a Bayesian approach to evaluate the hypothesis that the proportion with viral suppression for each long-acting regimen is not worse than the oral regimen proportion by more than 10% (denoted comparable) according to a prespecified decision rule (ie, posterior probability for comparability >90%). Difference in proportions and associated 95% CIs were supportive to the primary analysis. The trial is registered at ClinicalTrials.gov, number NCT02120352.
FINDINGS: Among 309 enrolled patients, 286 were randomly assigned to the maintenance period (115 to each of the 4-week and 8-week groups and 56 to the oral treatment group). This study is currently ongoing. At 32 weeks following randomisation, both long-acting regimens met primary criteria for comparability in viral suppression relative to the oral comparator group. Viral suppression was maintained at 32 weeks in 51 (91%) of 56 patients in the oral treatment group, 108 (94%) of 115 patients in the 4-week group (difference 2·8% [95% CI -5·8 to 11·5] vs oral treatment), and 109 (95%) of 115 patients in the 8-week group (difference 3·7% [-4·8 to 12·2] vs oral treatment). At week 96, viral suppression was maintained in 47 (84%) of 56 patients receiving oral treatment, 100 (87%) of 115 patients in the 4-week group, and 108 (94%) of 115 patients in the 8-week group. Three patients (1%) experienced protocol-defined virological failure (two in the 8-week group; one in the oral treatment group). Injection-site reactions were mild (3648 [84%] of 4360 injections) or moderate (673 [15%] of 4360 injections) in intensity and rarely resulted in discontinuation (two [<1%] of 230 patients); injection-site pain was reported most frequently. Serious adverse events during maintenance were reported in 22 (10%) of 230 patients in the intramuscular groups (4-week and 8-week groups) and seven (13%) of 56 patients in the oral treatment group; none were drug related.
INTERPRETATION: The two-drug combination of all-injectable, long-acting cabotegravir plus rilpivirine every 4 weeks or every 8 weeks was as effective as daily three-drug oral therapy at maintaining HIV-1 viral suppression through 96 weeks and was well accepted and tolerated.
FUNDING: ViiV Healthcare and Janssen R&D.

PMID: 28750935 [PubMed - as supplied by publisher]