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Drugs Oct 2017A once-daily tablet formulation (Isentress HD; Isentress 600 mg) of the integrase strand transfer inhibitor raltegravir is now available for the treatment of HIV-1... (Review)
Review
A once-daily tablet formulation (Isentress HD; Isentress 600 mg) of the integrase strand transfer inhibitor raltegravir is now available for the treatment of HIV-1 infection. The 600 mg tablet has improved bioavailability versus the existing twice-daily 400 mg tablet (due, at least in part, to differences in tablet dissolution) and the recommended dosage is 1200 mg (i.e. two 600 mg tablets) once daily. In combination with emtricitabine/tenofovir disoproxil fumarate in treatment-naïve adults, once-daily raltegravir 1200 mg provided virological suppression non-inferior to that seen with twice-daily raltegravir 400 mg over 48 and 96 weeks in the phase 3 ONCEMRK trial. The once-daily raltegravir regimen was also generally well tolerated in this study, displaying a tolerability profile similar to that of the twice-daily regimen. The once-daily tablet simplifies and improves the convenience of raltegravir regimens, although its impact on adherence has yet to be determined. Thus, once-daily raltegravir tablets are a convenient alternative to twice-daily raltegravir tablets for the treatment of HIV-1, further expanding the therapeutic options available to meet the diverse needs of this patient population.
Topics: Adult; Anti-HIV Agents; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Emtricitabine; Female; HIV Infections; HIV-1; Humans; Male; Raltegravir Potassium; Tablets; Tenofovir
PubMed: 29071467
DOI: 10.1007/s40265-017-0827-9 -
The Lancet. Infectious Diseases Jun 2021
Topics: Alkynes; Benzoxazines; Coinfection; Cyclopropanes; HIV Infections; Humans; Raltegravir Potassium; Tuberculosis
PubMed: 33667407
DOI: 10.1016/S1473-3099(20)30937-3 -
Expert Opinion on Drug Safety Feb 2018Raltegravir (RAL) was the first commercialized agent from a new drug class with an innovative target, the integrase. Since its introduction in clinical practice RAL has... (Review)
Review
Raltegravir (RAL) was the first commercialized agent from a new drug class with an innovative target, the integrase. Since its introduction in clinical practice RAL has become widely used for the treatment of HIV-1 infected patients. A decade after its approval, this article reviews key evidence from RAL with a special interest on safety outcomes. Areas covered: Pharmacologic, safety and efficacy data of RAL from clinical trials and post-commercialization published reports are hereby summarized after a literature review including PubMed search, relating proceedings and abstracts from relevant international HIV conferences, assessment reports from European and United States regulatory agencies and treatment guidelines (World Health Organization, United States Department of Health and Human Services and European AIDS Clinical Society), up to October 2017. Most frequent search terms were 'raltegravir', 'safety', 'adverse events', 'efficacy' and 'integrase-inhibitors'. Expert opinion: Despite the arrival of new integrase strand transfer inhibitors (INSTIs) with advantages in terms of dosing convenience (elvitegravir, ELV) and higher genetic barrier (dolutegravir, DTG), RAL has stood the test of time and its overall favourable safety profile, without significant appearance of unexpected adverse events, vouch for its relevance in the antiretroviral armamentarium.
Topics: HIV Infections; HIV Integrase; HIV Integrase Inhibitors; Humans; Raltegravir Potassium
PubMed: 29199485
DOI: 10.1080/14740338.2018.1411903 -
Journal of Pharmaceutical Sciences Feb 2022Early assessment of pH-dependent drug-drug-interactions (DDIs) for salts of poorly soluble weakly acidic compounds offers various advantages for patient safety, the...
BACKGROUND
Early assessment of pH-dependent drug-drug-interactions (DDIs) for salts of poorly soluble weakly acidic compounds offers various advantages for patient safety, the pharmaceutical industry, and regulatory bodies. Biorelevant media and tests reflecting physiological changes during acid-reducing agent (ARA) co-administration can be used to explore and predict the extent of the pH effect during therapy with ARAs.
METHODS
Solubility, one-stage and two-stage dissolution of tablets containing potassium raltegravir, the marketed salt form of this poorly soluble, weakly acidic drug, was investigated using biorelevant media specially designed to reflect administration without and during ARA co-therapy. The dissolution data were then converted into parameters suitable for input into an in silico model (Simcyp™) and the simulated plasma profiles were compared with available pharmacokinetic (PK) data from the literature.
RESULTS
Dissolution of the potassium raltegravir formulation in media reflecting ARA co-administration, and thus elevated gastric pH, was faster and more complete than in experiments reflecting the low gastric pH observed in the absence of ARA co-administration. Simulations using data from dissolution experiments with ARA media appropriately bracketed the in vivo data for ARA co-administration in healthy volunteers.
CONCLUSION
Dissolution data from in vitro experiments in biorelevant media reflecting physiological changes due to ARA co-administration provide valuable information about potassium raltegravir's behavior during concomitant ARA therapy. The approach may also be suitable for salts forms of other poorly soluble, weakly acidic drugs.
Topics: Computer Simulation; Drug Interactions; Humans; Hydrogen-Ion Concentration; Models, Biological; Potassium; Raltegravir Potassium; Salts
PubMed: 34597624
DOI: 10.1016/j.xphs.2021.09.037 -
Zentralblatt Fur Chirurgie Aug 2017
Topics: Accidents, Occupational; Acute Disease; Delayed Diagnosis; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Expert Testimony; Follow-Up Studies; Germany; Heart Valves; Hepatitis C; Humans; Infectious Disease Transmission, Patient-to-Professional; Liver Function Tests; Male; Needlestick Injuries; Occupational Diseases; Physician Assistants; Raltegravir Potassium; Suture Techniques
PubMed: 27389576
DOI: 10.1055/s-0042-110659 -
Antimicrobial Agents and Chemotherapy Dec 2015Raltegravir pharmacokinetics was studied in 20 patients included in the ANRS HC30 QUADRIH Study before and after addition of anti-hepatitis C virus (anti-HCV)...
Raltegravir pharmacokinetics was studied in 20 patients included in the ANRS HC30 QUADRIH Study before and after addition of anti-hepatitis C virus (anti-HCV) quadritherapy, including pegylated-interferon-ribavirin and asunaprevir plus daclatasvir. Raltegravir pharmacokinetic parameters remained unchanged whether administered on or off anti-HCV therapy. In addition, concentrations of raltegravir, asunaprevir, and daclatasvir were not affected by liver cirrhosis. These data suggest that in human immunodeficiency virus (HIV)-HCV-coinfected patients, whether cirrhotic or not, asunaprevir and daclatasvir could be administered safely with raltegravir.
Topics: Adult; Antiviral Agents; Carbamates; Coinfection; Drug Therapy, Combination; Female; HIV Infections; HIV-1; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Interferon-alpha; Isoquinolines; Liver; Liver Cirrhosis; Male; Middle Aged; Polyethylene Glycols; Pyrrolidines; Raltegravir Potassium; Recombinant Proteins; Ribavirin; Sulfonamides; Valine
PubMed: 26438504
DOI: 10.1128/AAC.01603-15 -
AIDS (London, England) Nov 2010
Topics: Cerebellar Ataxia; Female; HIV Infections; HIV-1; Humans; Middle Aged; Nitriles; Pyridazines; Pyrimidines; Pyrrolidinones; Raltegravir Potassium; Treatment Outcome
PubMed: 20980871
DOI: 10.1097/QAD.0b013e32833fca42 -
Journal of Acquired Immune Deficiency... Jun 2016Raltegravir was previously considered an alternative antiretroviral in pregnancy because of limited data, but recent pregnancy guidelines recommend raltegravir as a... (Review)
Review
Raltegravir was previously considered an alternative antiretroviral in pregnancy because of limited data, but recent pregnancy guidelines recommend raltegravir as a preferred integrase treatment option. Data from published articles and preliminary meeting reports between 2001 and July 2015 are reviewed. The literature includes a total of 278 maternal-infant pairs who received raltegravir during pregnancy. The standard raltegravir dose seems safe and effective in preventing mother-to-child transmission in late pregnancy presenters with unknown or unsuppressed viral load, or in multidrug resistance. Viral decay was rapid allowing most women to deliver at undetectable viral levels. Raltegravir was well tolerated, with the exception of a few cases of transient increases in maternal transaminases. No infant adverse effect was consistently reported. Existing data support the use of raltegravir in antiretroviral-naive and experienced pregnant women.
Topics: Anti-HIV Agents; Female; HIV Infections; HIV Integrase Inhibitors; HIV-1; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Raltegravir Potassium; Treatment Outcome; Viral Load
PubMed: 27183177
DOI: 10.1097/QAI.0000000000000932 -
AIDS (London, England) Aug 2017To compare the frequency and risk factors of toxicity-related treatment discontinuations between raltegravir and dolutegravir.
OBJECTIVE
To compare the frequency and risk factors of toxicity-related treatment discontinuations between raltegravir and dolutegravir.
DESIGN
Prospective cohort study.
METHODS
All antiretroviral therapy (ART)-naïve and ART-experienced HIV-infected individuals from the Swiss HIV Cohort Study who initiated raltegravir or dolutegravir between 2006 and 2015 were investigated concerning treatment modification within the first year.
RESULTS
Of 4041 patients initiating ART containing raltegravir (n = 2091) or dolutegravir (n = 1950), 568 patients discontinued ART during the first year, corresponding to a rate of 15.5 [95% confidence interval (CI) 14.5-16.9] discontinuations per 100 patient-years. Only 10 patients on raltegravir (0.5%) and two patients on dolutegravir (0.1%) demonstrated virologic failure. The main reason for ART discontinuation was convenience expressed as patient's wish, physician's decision, or treatment simplification (n = 302). Toxicity occurred in 4.3% of patients treated with raltegravir and 3.6% with dolutegravir, respectively. In multivariable analysis, the only independent risk factor for discontinuing ART because of toxicity was female sex (hazard ratio 1.98, 95% CI 1.45-2.71, P < 0.001).Neuropsychiatric complaints were the most commonly reported toxic adverse events and more frequent in the dolutegravir (n = 33, 1.7%) compared with the raltegravir group (n = 13, 0.6%). Risk of discontinuation for neurotoxicity was lower for raltegravir than for dolutegravir in multivariable analysis (hazard ratio 0.46, 95% CI 0.22-0.96, P = 0.037).
CONCLUSION
In this, large cohort raltegravir and dolutegravir-containing regimen demonstrated a high virologic efficacy. Drug toxicity was infrequent and discontinuation because of neuropsychiatric events within the first year of treatment was only marginal higher with dolutegravir compared with raltegravir. However, monitoring of neurotoxic side-effects of dolutegravir is important.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-HIV Agents; Drug-Related Side Effects and Adverse Reactions; Female; HIV Infections; Heterocyclic Compounds, 3-Ring; Humans; Male; Mental Disorders; Middle Aged; Oxazines; Piperazines; Prospective Studies; Pyridones; Raltegravir Potassium; Switzerland; Withholding Treatment; Young Adult
PubMed: 28692533
DOI: 10.1097/QAD.0000000000001590 -
British Journal of Clinical Pharmacology Nov 2009
Topics: Anti-HIV Agents; Cyclohexanes; Humans; Maraviroc; Pyrrolidinones; Raltegravir Potassium; Triazoles
PubMed: 19916987
DOI: 10.1111/j.1365-2125.2009.03503.x