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OBJECTIVES: (1) Describe ADHD medication use, adherence and persistence. (2) Determine factors (e.g., medication type, demographics, concomitant medication use) associated with ADHD medication adherence and persistence. (3) Compare ADHD medication costs. METHODS: Continuously enrolled Texas Medicaid children (3-18 years) with ≥ 2 ADHD prescription claims (July 2002-December 2008) were included. Prescription claims were grouped by medication type (i.e., immediate-release, extended-release, prodrug, non-stimulant); medication class (i.e., stimulant, non-stimulant); and duration of action (i.e., long-acting, short-acting). Adherence, using medication possession ratio, was measured continuously and dichotomously (80% cut-off). Persistence was days of continuous therapy without a 30-day gap and medication costs were reimbursement amount paid to dispensing pharmacies. RESULTS: The study sample (n = 62,789) was primarily 6-12 years (61.7%) and male (69.2%). The majority of the subjects were prescribed extended-release agents (70.3%), stimulant agents (86.4%), and long-acting agents (84.5%). Adherence and persistence (adherence mean ± SD; adherence dichotomous; persistence mean ± SD) varied among medication type and was highest for non-stimulants (52.5 ± 30.9; 25.8%; 153.3 ± 124.3), followed by extended-release stimulants (52.1 ± 30.2; 24.1%; 143.7 ± 120.8), prodrug stimulants (47.6 ± 30.9; 21.1%; 113.3 ± 100.5) and immediate-release stimulants (37.2 ± 27.1; 9.8%; 95.4 ± 92.6). Logistic regression showed immediate-release stimulant users were 67% less adherent than non-stimulant users (p < 0.0001) and linear regression showed immediate-release, extended-release and long-acting users (p < 0.0001) were significantly less persistent than non-stimulant users. Females, increase in total number of medications, and comorbid medications were associated with better adherence and persistence. Non-stimulant agents ($4.04 ± $2.15) had the highest mean medication cost per patient per day and immediate-release stimulants had the lowest ($1.24 ± $0.97). CONCLUSIONS: ADHD medication adherence and persistence was suboptimal. Although there was no difference in adherence between long-acting stimulant and non-stimulant users, non-stimulant users were more persistent compared to stimulant users. This study was limited due to the use of retrospective prescription claims data, which cannot capture actual patient use patterns, ICD-9 diagnoses, family history and support, or side effect profiles. Because ADHD can be effectively treated with pharmacotherapy, providers should be proactive in identifying patients with poor adherence and intervene to address barriers to medication adherence and persistence.

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The study involves the condensation of acylimidazole derivatives of acaclofenac (AC) with dextran 10,000 and 20,000 to obtain aceclofenac-dextran prodrugs AC10 and AC20 respectively with an aim to improve aqueous solubility, increase therapeutic efficiency and reduce the gastrointestinal side effects. The structure of synthesized prodrugs was confirmed by IR and NMR spectroscopy. The molecular weight was determined by Mark-Howink Sakurada equation and the degree of substitution was obtained as 13.3 and 16 % for the prodrugs. In vitro hydrolysis carried out in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF) showed faster hydrolysis in SIF and SCF. The percentage anti-inflammatory activity of AC was found as 49.56 whereas an improved value of 56.44 and 61.82 % were obtained for AC10 and AC20 respectively. The prodrugs showed improved analgesia and reduced ulcerogenicity than aceclofenac, thereby proving to be better in action than the parent drug(AU)

El estudio se centra en la condensación de acilimidazoles derivados de aceclofenaco (AC) con dextrano 10.000 y 20.000 para obtener los profármacos de aceclofenaco-dextrano AC10 y AC20, respectivamente, con el objetivo de mejorar la hidrosolubilidad, aumentar la eficacia terapéutica y reducir los efectos secundarios gastrointestinales. La estructura de los profármacos sintetizados se ha confirmado a través de espectroscopia IR y RMN. El peso molecular ha sido determinado a través de la ecuación de Mark-Houwink-Sakurada y se ha obtenido un grado de sustitución de 13,3 y 16% para los profármacos. La hidrólisis in vitro llevada a cabo en fluido gástrico simulado (FGS), fluido intestinal simulado (FIS) y fluido colónico simulado (FCS) ha mostrado una hidrólisis más rápida en FIS y FCS. De ello ha resultado un porcentaje de actividad antiinflamatoria de AC de 49,56, mientras que para AC10 y AC20 se ha obtenido un valor aumentado de 56,44 y 61,82% respectivamente. Los profármacos han mostrado una mejor analgesia y una menor ulcerogenicidad que el aceclofenaco, por lo que se demuestra que su acción es mejor que la del fármaco base(AU)

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CONTEXT: Recent trials have found that ximelagatran and warfarin are equally effective in stroke prevention for patients with atrial fibrillation. Because ximelagatran can be taken in a fixed, oral dose without international normalized ratio monitoring and may have a lower risk of hemorrhage, it might improve quality-adjusted survival compared with dose-adjusted warfarin. OBJECTIVE: To compare quality-adjusted survival and cost among 3 alternative therapies for patients with chronic atrial fibrillation: ximelagatran, warfarin, and aspirin. DESIGN: Semi-Markov decision model. PATIENTS: Hypothetical cohort of 70-year-old patients with chronic atrial fibrillation, varying risk of stroke, and no contraindications to anticoagulation therapy. MAIN OUTCOME MEASURES: Quality-adjusted life-years (QALYs) and costs in US dollars. RESULTS: For patients with atrial fibrillation but no additional risk factors for stroke, both ximelagatran and warfarin cost more than 50,000 dollars per QALY compared with aspirin. For patients with additional stroke risk factors and low hemorrhage risk, ximelagatran modestly increased quality-adjusted survival (0.12 QALY) at a substantial cost (116,000 dollars per QALY) compared with warfarin. For ximelagatran to cost less than 50,000 dollars per QALY it would have to cost less than 1100 dollars per year or be prescribed to patients who have an elevated risk of intracranial hemorrhage (>1.0% per year of warfarin) or a low quality of life with warfarin therapy. CONCLUSION: Assuming equal effectiveness in stroke prevention and decreased hemorrhage risk, ximelagatran is not likely to be cost-effective in patients with atrial fibrillation unless they have a high risk of intracranial hemorrhage or a low quality of life with warfarin.

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BACKGROUND: Capecitabine is an oral prodrug of 5-fluorouracil and has been studied for the treatment of colorectal cancer. In 2 Phase III trials, capecitabine was at least as effective as 5-fluorouracil plus leucovorin and had a more favorable toxicity profile. OBJECTIVE: A cost-benefit analysis was used to assess the pharmacoeconomic profile of capecitabine compared with 5-fluorouracil/leucovorin, given according to the Mayo regimen, for colorectal cancer patients treated in the Netherlands. METHODS: The medical files of patients treated for colorectal cancer at a single center from 1999 to 2002 were examined to determine the numbers of outpatient visits for 5-fluorouracil/leucovorin administration, health care use and medication to manage adverse effects, and travel distance to and from the hospital. The costs of capecitabine treatment were simulated by assuming that the same patients were treated with capecitabine instead of 5-fluorouracil/leucovorin. Toxicity data for capecitabine were derived from 2 Phase III studies that compared capecitabine and 5-fluorouracil/leucovorin. RESULTS: The files of 65 patients were reviewed. Thirty-two patients received adjuvant treatment and 33 patients were treated palliatively for metastatic disease. The mean total costs of palliative treatment were Euro 4004 with capecitabine and Euro 5614 with 5-fluorouracil/leucovorin. These results were robust in sensitivity analyses. The cost savings were primarily related to the number of outpatient visits for capecitabine versus the number of day-care treatment days for 5-fluorouracil/leucovorin, despite the higher acquisition costs of capecitabine. CONCLUSIONS: Based on this analysis, treatment of colorectal cancer with oral capecitabine is cost saving in the Netherlands compared with 5-fluorouracil plus leucovorin administered according to the Mayo regimen. Baseline savings were estimated at Euro 1610 for palliative treatment and Euro 934 for adjuvant treatment.

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Cytomegalovirus (CMV) infection and disease, with its extensive direct and indirect consequences, adds considerably to the cost of patient management in both solid organ and bone marrow transplantation. Antiviral prophylaxis for CMV infection can offer cost advantages over preemptive therapy and "wait-and-treat" approaches. Valacyclovir has demonstrated efficacy for CMV prophylaxis in renal, heart, and bone marrow transplantation and is cost-effective when compared with placebo in renal transplant recipients at high risk of CMV infection. In reducing CMV infection and disease, valacyclovir prophylaxis appears to be associated with reductions in indirect effects of CMV (acute graft rejection, other opportunistic infections) and, if these effects are considered, the potential exists for even greater savings to be made with valacyclovir therapy. Benefits of valacyclovir in transplantation extend beyond CMV to other herpesviruses and may be increased in some clinical situations by prolonging prophylaxis beyond 3 months.

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The objective of the study was to evaluate how often intravenous (IV) fosphenytoin is used when oral phenytoin loading is possible. The methods included a retrospective chart review of all patients receiving IV fosphenytoin in the emergency department. We prospectively derived criteria that identify patients with seizures who could receive oral phosphenytoin loading (awake on arrival, alert, no emesis, and lack of endotracheal intubation, repeated seizures, or status epilepticus after arrival). The setting of the study was at an urban, university hospital emergency department with an annual census of 55,000 patients. The outcomes included the number of patients receiving IV fosphenytoin who could have received oral phenytoin loading. From February 1997 to June 1999, 55 patients received IV fosphenytoin. Thirty of these patients (55%, 95% confidence interval 41%-68%) were felt to have received fosphenytoin appropriately. The remaining 25 (45%, 95% confidence interval 32%-59%) patients could have been loaded orally with phenytoin. In a single institution, fosphenytoin administration is inappropriate almost half the time. Oral phenytoin loading is less expensive and safe.

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STUDY OBJECTIVE: To determine the value of fosphenytoin compared with phenytoin for treating patients admitted to an emergency department following a seizure. DESIGN: Cost-minimization analysis performed from a hospital perspective. SETTING: Hospital emergency department. PATIENTS: Two hundred fifty-six patients participating in a comparative clinical trial. INTERVENTION: Estimation of adverse event rates and resource use. MEASUREMENTS AND MAIN RESULTS: In our base case, phenytoin was the preferred option, with an expected total treatment cost of $5.39 compared with $110.14 for fosphenytoin. One-way sensitivity analyses showed that the frequency and cost of treating purple glove syndrome (PGS) possibly could affect the decision. Monte Carlo simulation showed phenytoin to be the preferred option 97.3% of the time. CONCLUSION: When variable costs of care are used to calculate the value of phenytoin compared with fosphenytoin in the emergency department, phenytoin is preferred. The decision to administer phenytoin was very robust and changed only when both the frequency and cost of PGS was high.

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Advantages and disadvantages of Fosphenytoin. Advantages. More rapid intravenous administration than phenytoin and no need for an in-line filter. May be administered by intramuscular injection. Lower potential for local tissue and cardiac toxicity than phenytoin. Associated with less pain and phlebitis at the injection site, fewer reductions in infusion rate and fewer changes of administration site because of injection site complications than phenytoin. Benefits in terms of ease of administration and improved tolerability vs phenytoin have pharmacoeconomic implications which may translate into an overall cost advantage. Disadvantages. Approximately 10-fold higher acquisition cost vs phenytoin. Fosphenytoin is a parenterally administered prodrug of phenytoin, used in the treatment of patients with seizures. Advantages of fosphenytoin over phenytoin include more rapid intravenous administration, no need for an intravenous filter, and a lower potential for local tissue and cardiac toxicity. Unlike phenytoin, fosphenytoin may also be administered by intramuscular injection. Pharmacoeconomic data from a small study of patients with acute seizures in a US emergency department showed an overall cost advantage of fosphenytoin over phenytoin, despite a considerably greater acquisition cost of fosphenytoin. The main cost drivers for phenytoin therapy were treatment costs associated with adverse events. In view of the limited pharmacoeconomic data currently available, it is in the interests of individual institutions to conduct their own formal pharmacoeconomic studies applying local cost data and patterns of clinical practise to determine whether fosphenytoin should replace phenytoin on their formularly list.

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The economic impact of famciclovir therapy for postherpetic neuralgia (PHN) in patients with acute herpes zoster was studied. A decision-analytic model of the treatment of herpes zoster and PHN was used to compare the cost of PHN between patients treated with oral famciclovir 500 mg three times daily for seven days and patients not receiving any antiviral therapy. The effects of famciclovir on PHN in the model were based on the results of a randomized, double-blind trial in 419 adult outpatients. The cost of the course of famciclovir therapy (21 tablets) was estimated as the sum of the drug's wholesale acquisition cost and the pharmacy dispensing cost. The cost of treating PHN (physician visits, medications, and miscellaneous nondrug therapy) was estimated by consulting a panel of physicians. According to the model, the cost of treating PHN was $85 lower per famciclovir recipient ($294 for famciclovir versus $379 for no antiviral therapy). The net cost of famciclovir therapy was $23 per patient ($108 for acquisition and dispensing minus the $85 savings). Among patients 50 years of age or older, famciclovir reduced the average cost of PHN by $155 ($414 for famciclovir versus $569 for no antiviral therapy) and yielded a net savings of $7 per patient. A model for the use of famciclovir to treat acute herpes zoster showed that the cost of such therapy was largely offset by savings in the cost of treating this complication.

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Fosphenytoin is a phenytoin prodrug that received an approvable letter from the Food and Drug Administration in February 1996. It was designed to overcome many of the shortcomings associated with parenteral phenytoin sodium. Specifically, fosphenytoin is a highly water-soluble, phosphate ester of phenytoin that has no known pharmacologic activity before its conversion to phenytoin. Dosing of fosphenytoin uses phenytoin equivalents (PE) to minimize dosage errors when converting from the conventional formulation. Pharmacokinetic studies documented that the agent is rapidly and completely converted to phenytoin after intravenous and intramuscular dosing. Reported conversion half-lives after intravenous administration range from 8-15 minutes. The absorption rate appears to be the rate-limiting step in the conversion of fosphenytoin to phenytoin after intramuscular administration (half-life range 22-41 min). Bioavailability of phenytoin derived from both intravenous and intramuscular fosphenytoin is essentially 100%. As a consequence of concentration-dependent protein binding, fosphenytoin is bioequivalent to phenytoin sodium at intravenous infusion rates of 100-150 mg PE/minute and 50 mg/minute, respectively. In clinical studies to date, fosphenytoin is safe and significantly better tolerated than phenytoin sodium when administered intravenously. It is also well tolerated when given intramuscularly, and this is a valuable alternative route of administration when intravenous access or cardiographic monitoring is unavailable. Its pharmacoeconomic advantages over phenytoin have not been documented in formal studies to date, although the likelihood of savings based on cost-effectiveness analyses is high. Hence, fosphenytoin has the potential as a safe, well-tolerated, and effective means of delivering phenytoin parenterally in a variety of clinical settings.

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A prospective economic evaluation was undertaken as part of a randomised clinical trial conducted in French general practice. Its aim was to compare the costs and therapeutic outcomes of a 5-day course of cefpodoxime proxetil 100 mg twice daily with 10-day courses of phenoxymethylpenicillin (penicillin V) 1 MIU 3 times daily and amoxicillin-clavulanic acid 500/125 mg 3 times daily for the treatment of recurrent pharyngotonsillitis in 575 adults. Over the 6-month study period, the total cost to society per patient treated with cefpodoxime proxetil was 123 French francs (FF; 1993 values) lower than that for patients treated with phenoxymethylpenicillin and FF227 lower than that for patients treated with amoxicillin-clavulanic acid. This cost saving was primarily attributable to a lower initial drug acquisition cost, and a reduction in the cost associated with lost productivity and general practitioner consultations. Furthermore, as a consequence of a lower relapse rate, the cost-saving ratio for cefpodoxime proxetil, expressed as FF per month free of recurrence, was FF50 less than for phenoxymethylpenicillin and FF60 less than for amoxicillin-clavulanic acid. Thus, a 5-day course of cefpodoxime proxetil is likely to be less costly for treatment of pharyngotonsillitis in the general practice setting than standard 10-day courses of phenoxymethylpenicillin and amoxicillin-clavulanic acid.

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