This indicates that patients started on metformin were prescribed conservative doses of cardiovascular risk-modifying drugs.
Therefore, a conservative dosing of UFH is recommended in patients with severe renal impairment to avoid supra-therapeutic anticoagulation [ 18, 19].
The relatively conservative dosing of cisplatin (75 rather than 100 mg m−2) and 5-FU (4 rather than 5 days) was an attempt to limit the risk that chemotherapy-induced toxicity might delay the start of chemo-radiotherapy, which is considered to be the most important curative component of the treatment approach.
Higher GMFCS levels (IV,V) and higher doses of BoNT-A were associated with increased incidence of adverse events, leading the authors to recommend conservative dosing for children classified GMFCS IV-V [ 29].
In addition, as suggested by the sponsor, the modest differences seen in serum sodium may have been partially a result of a conservative dose titration scheme.
Since scaling most likely would decrease the values of the TIACs and, consequently, the absorbed doses, we preferred, for this study, to provide a conservative dose assessment without performing inter-species scaling.
Important age-related factors, as well as the pharmacokinetics of aripiprazole (eg, longer elimination half-life), dictate the need for conservative dosing; the avoidance of polypharmacy when possible; careful monitoring for the development of adverse events and/or drug interactions; and more careful titration and tapering strategies.
Given the limited previous human exposure of NS2359, a conservative low dose of the medication was chosen for safety considerations that may have under treated the entire spectrum of ADHD.
However, in view of the overlapping toxicity (myelosuppression) of the drugs, a conservative starting dose of 100 mg b.i.d. was chosen for this trial, thus allowing a substantial safety margin.
However, the conservative dosing regimen adopted at the start of deferasirox treatment meant that overall median serum ferritin levels did not decrease below baseline during the first 2 years, when the average actual dose was <20 mg/kg per d.
