One concept to reduce the adverse effects of opioids is the use of very small doses of opioid antagonists. 25 – 28 The rationale is that agents such as naloxone (Narcan) have a biphasic effect whereby very low doses reduce the incidence of opioid adverse effects and may augment the analgesic effect. 25 , 28 Much of the data are limited to the inpatient setting with intravenous administration of the opioid antagonist. 25 – 27 Concomitant administration of intravenous naloxone with morphine infusions has been studied, but the results have been mixed. 25 – 27 More research is needed before this treatment is implemented as part of routine practice.
The influence of renal impairment on the pharmacokinetics of haloperidol has not been evaluated. About one-third of a haloperidol dose is excreted in urine, mostly as metabolites. Less than 3% of administered haloperidol is eliminated unchanged in the urine. Haloperidol metabolites are not considered to make a significant contribution to its activity, although for the reduced metabolite of haloperidol, back-conversion to haloperidol cannot be fully ruled out. Even though impairment of renal function is not expected to affect haloperidol elimination to a clinically relevant extent, caution is advised in patients with renal impairment, and especially those with severe impairment, due to the long half-life of haloperidol and its reduced metabolite, and the possibility of accumulation (see section ).
The intravenous route is not FDA approved and is generally not recommended except when no other alternatives are available. Intravenous administration appears to be associated with a higher risk of QT prolongation and torsade de pointes (TdP) than other forms of administration. The manufacturer recommends ECG monitoring for QT prolongation and arrhythmias if IV administration is required. A dose in the range of 1 to 5 mg IV has been suggested, with the dose being repeated at 30 to 60 minute intervals, if needed. A maximum IV dose has not been established. The lowest effective dose should be used in conjunction with conversion to oral therapy as soon as possible.