HPLC-Based Analysis of Impurities in Sapropterin Branded and Generic Tablets.
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ABSTRACT:
SUBMITTER: Scudellaro E
PROVIDER: S-EPMC7237990 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
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HPLC-Based Analysis of Impurities in Sapropterin Branded and Generic Tablets.
Scudellaro Emanuela E Tartaglione Luciana L Varriale Fabio F Dell'Aversano Carmela C Taglialatela-Scafati Orazio O
Pharmaceutics 20200403 4
This work was aimed at the definition of a chromatographic method able to separate and quantify impurities present in sapropterin-containing drugs during an accelerated stability study. The chromatographic method was applied to the orphan drug Kuvan<sup>®</sup> and to its corresponding generic sapropterin Dipharma (Diterin<sup>®</sup>), both of which are approved for the treatment of hyperphenylalaninemia-induced symptoms. The two products tested had a similar manufacture date and both had an ap ...[more]
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Project description:ObjectivesTo identify patient demographics and characteristics associated with compliance to statin therapy after switching from branded to generic agentsDesignRetrospective cohort study using electronic health records and pharmacy claims data from Sutter Health's ambulatory-care medical networkPatientsManaged-care beneficiaries, ≥ 18 years of age, who were switched from branded to generic statins between 1 January 2003 and 31 December 2012 MAIN MEASURES: Compliance was calculated as days of therapy dispensed divided by days from first to last generic prescription fill over 6 months, and was defined as a medication possession ratio ≥ 0.80. We used multivariable logistic regression to assess factors associated with compliance. Adjusted ORs and 95% CI were generated.Key resultsWe identified 5,156 patients who were switched from branded to generic statins; 73% of patients were compliant in the 6 months after switching. After statistical adjustment, higher compliance was associated with each 10-year increase in age (OR: 1.13; 95% CI: 1.07, 1.19; p < 0.001), receipt of a generic statin equivalent in potency to the prior branded statin (OR: 1.41; 95% CI: 1.16, 1.70; p < 0.001), and compliance with prior branded statin (OR: 4.68; 95% CI: 4.07, 5.39; p < 0.001). Lower compliance was seen among Hispanic patients compared to non-Hispanic white patients (OR: 0.68; 95% CI: 0.52, 0.91; p = 0.009). Also, a switch to a higher potency generic statin, regardless of prior dose/potency, was negatively associated with compliance after switching (OR: 0.87; 95% CI: 0.80, 0.94; p = 0.001).ConclusionsThe majority of patients switched from branded to generic agents were compliant with therapy in the first 6 months after switching. The potential for non-compliance to generic statin therapy, particularly among younger or Hispanic patients or when dose/potency changes are made, should be considered prior to switching. For these patients, counseling or close monitoring may be required to optimize generic interchange.
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Project description:ImportanceSwitching between generic antiepileptic drugs is a highly debated issue that affects both clinical care and overall health care costs.ObjectiveTo evaluate the single-dose pharmacokinetic bioequivalence of 3 (1 branded and 2 generic drugs) on-market, immediate-release lamotrigine drug products.Design, setting, and participantsThe Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy (EQUIGEN) single-dose study is a crossover, prospective, sequence-randomized, replicate pharmacokinetic study conducted at 5 US academic epilepsy centers. Fifty adults (≥18 years) with epilepsy who were taking concomitant antiepileptic drugs and not currently receiving lamotrigine were enrolled between July 18, 2013, and January 19, 2015. Every participant was randomly assigned to 1 of 3 equivalent sequences, each comprising 6 study periods, during which they had blood draws before and after medication administration. Forty-nine participants were included in intention-to-treat analyses.InterventionsParticipants received a single 25-mg dose of immediate-release lamotrigine at the start of each period, with the branded and the 2 most disparate generic products each studied twice. Lamotrigine was selected as the antiepileptic drug of interest because of its wide use, publications indicating problems with generic switches, and complaints to the US Food and Drug Administration regarding generic products. Both participants and study personnel were blinded to the specific generic products selected.Main outcomes and measuresThe primary outcome was bioequivalence between products. Maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) were compared, and average bioequivalence (ABE) was established if the 90% CIs of the ratios of the 2 products were within equivalence limits (80%-125%).ResultsOf the 50 randomized participants, 49 (98%) received all 3 lamotrigine products and completed at least 3 pharmacokinetic assessments and 46 (92%) completed all 6 pharmacokinetic assessments. Among the 49 participants, 28 (57%) were men and 21 (43%) were women, 42 (86%) self-identified as white, and 46 (16) years was the mean (SD) age. The 3 drug products were considered bioequivalent because the 90% CIs were within equivalence limits (lowest and highest CI limits for Cmax, 92.6% and 110.4%; for AUC0-96, 96.9% and 101.9%). Replicate testing demonstrated no significant differences in within-subject variability across the 3 products (likelihood ratios, χ22 for log-transformed variables: AUC0-96, 2.58; Cmax, 0.64; and AUC0-∞, 4.05; P ≥ .13) and that the 3 products were also bioequivalent according to scaled ABE and individual bioequivalence criteria with no subject × formulation interaction (Cmax, 0.00; AUC0-96, 0.54; and AUC0-∞, 0.36; P ≥ .76).Conclusions and relevanceThis study provides evidence that the disparate lamotrigine products studied are bioequivalent when tested in people with epilepsy taking concomitant antiepileptic drugs.Trial registrationclinicaltrials.gov Identifier: NCT01733394.
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Project description:BackgroundAim of this study was to evaluate the efficacy and the safety of switching from branded to generic antiretrovirals in patients with HIV-RNA <50 copies/mL.MethodsMatched-cohort study of patients followed at a single clinical center. Since September 2014, all patients with HIV-RNA <50 copies/mL who were receiving branded lamivudine or zidovudine/lamivudine or efavirenz were switched to the generic compound (switchers) and matched, in a ratio 1:1, for age (±5 years), gender, anti-HCV antibodies, nadir and (±50 cells/μL) baseline CD4+ count (±100 cells/μL), duration of antiretroviral therapy (±1 year), with patients with HIV-RNA <50 copies/mL, on treatment with unavailable generic compounds (non-switchers). Incidence rates (IR) of different outcomes were calculated and compared by Poisson regression model. A confirmed HIV-RNA ≥50 copies/mL defined virological failure; any change in the antiretroviral regimen was defined as treatment discontinuation.ResultsFour hundred forty patients were switched to generic compounds (268 [61%] on lamivudine, 65 [15%] on zidovudine/lamivudine, 87 [20%] on efavirenz and 20 [4%] on efavirenz and either lamivudine or zidovudine/lamivudine). Over a median follow-up of 15.0 (12.1-15.7) months, virological failure occurred in four switchers (IR: 0.07 [0.02-0.18]/100-person months of follow-up [PMFU]) and in ten non-switchers (IR: 0.20 [0.10-0.35]/100-PMFU) (p = 0.0003), while treatment discontinuation occurred in 118 switchers (IR: 2.05 [1.70-2.44]/100-PMFU) and in 128 non-switchers (IR: 2.37 [1.99-2.81]/100-PMFU) (p = 0.699).ConclusionsAfter more than one year of follow-up, we found no evidence of increased risk of reduced efficacy or increased toxicity after switching from branded to generic lamivudine or zidovudine/lamivudine or efavirenz.
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