title: Medication adherence and the use of new pharmaceutical formulations: the case of levothyroxine.
abstract: According to World Health Organization, medication adherence refers not only to pharmacological treatment, but also extends to all behaviors which guarantee patient's health. Poor medication adherence is the main cause of low efficacy of pharmacological therapy and it is more common in chronic diseases. For example, among hypothyroid patients, it was estimated that after 5 years of levothyroxine therapy 21.5% of patients still have a TSH level >5.0 mU/L due to poor medication adherence. Moreover, it was found that almost 40% of pediatric patients had at least one episode of non-compliance following thyroidectomia. Several strategies can be adopted in order to improve medication adherence. These include self-monitoring drug therapy and self-management programs, simplified dosing regimens, directly involving pharmacists in drug therapy management, use of pharmaceutical formulations more attractive to the patient and through the therapeutic drug monitoring. The effects mediated by the thyroid gland, the clinical symptoms of hypothyroidism and the main characteristics of levothyroxine therapy have been discussed. In order to give an overview of interactions with food and drinks, pharmacokinetic characteristics, efficacy/safety profile, as well as the impact on medication adherence of levothyroxine in oral solution and soft gel capsule formulations, a literature search was performed. The results of 21 clinical studies were reviewed. Levothyroxine oral solution and soft gel capsule formulations showed irrelevant interactions with food and drinks, with a dissolution profile minimally influenced by pH variations. According to pharmacokinetic study results, bioequivalence between these formulations and levothyroxine tablets was confirmed. Regarding the efficacy/safety profile, while some studies did not detect any difference between levothyroxine formulations, other studies suggested that oral solution and soft gel capsule were associated to a higher efficacy compared to levothyroxine tablet. It was also demonstrated that removing the demand for fasting, patients would prefer to take the medication at breakfast. Therefore, most of the patients treated with levothyroxine oral solution preferred to continue this therapy instead of treatment with tablets. An increase in patient's compliance was observed. All the characteristics of new levothyroxine oral liquid formulations allow to administer the drug also in patients with gastrointestinal comorbidities or patients who are already treated with other drugs. The availability of different dosages let the clinician to adapt the treatment for each individual patient. These benefits contribute to a better medication adherence and to the maintenance of normal TSH levels. In conclusion, the use of different pharmaceutical formulations represents a therapeutic approach innovative, effective and inexpensive in the treatment of the hypothyroid patient.
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, Naples, Italy - cristina.scavone@unina2.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Scavone
authors.forename: Liberata
authors.initials: L
authors.lastname: Sportiello
authors.forename: Daniela
authors.initials: D
authors.lastname: Cimmaruta
authors.forename: Maria G
authors.initials: MG
authors.lastname: Sullo
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Vitelli
authors.forename: Concetta
authors.initials: C
authors.lastname: Rafaniello
authors.forename: Tiziano
authors.initials: T
authors.lastname: Fossati
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
mesh_terms: D004339:Drug Compounding; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy*; D055118:Medication Adherence; D012648:Self Care; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000627:therapeutic use*
chemical_list: D013972:Thyrotropin; D013974:Thyroxine