Loading Dose

Issues of Concern

When prescribing a loading dose of a new medication, there are many factors that a clinician must consider. Through the formulas above, the loading dose of any drug is influenced by many of the pharmacokinetic variables. Loading doses are challenging to calculate, as they necessitate multistep calculations utilizing patient data (such as weight) and the specific drug (eg, the estimated volume of distribution or drug half-life). Staff may mistakenly continue loading doses instead of lowering to maintenance doses, particularly when patients transfer between care settings (such as from the emergency department to being admitted to the floor or at discharge from the hospital back to outpatient status).

Bioavailability is typically affected by the route of administration of the medication. Each medication typically has a route of administration that provides the best bioavailability. For example, in one study, researchers found that sublingual administration of misoprostol had significantly higher bioavailability than oral administration.[3] 

Higher bioavailability allows for the utilization of a lower loading dose to reach the same steady-state concentration, leading to better medication safety and efficacy. Patient comorbidities can also affect medication bioavailability. For example, celiac disease causes atrophy of the duodenal villi, which can hinder the absorption and bioavailability of medications given orally. As a result, other drugs have been developed to allow proper treatment for these patients, such as a medication to increase iron absorption in patients with celiac disease and iron deficiency anemia.[4]

Further, various physiological factors can affect the concentration and pharmacokinetics of medication. One study found that the clearance of ciprofloxacin significantly decreases with age and worsening kidney function.[5] Failure to adjust for these factors could lead to toxicity or other related side effects. Ultimately, it is essential to consider all factors while dosing medications, as any change in these variables, will inevitably affect the loading dose and, consequently, steady-state concentration.

Clinical Significance

A medication’s loading dose has many vital clinical applications. In emergencies, drugs must reach therapeutic concentration rapidly, often requiring a loading dose. For example, studies have found that a loading dose of levetiracetam is essential for adequate treatment of status epilepticus.[6] Loading doses require 

Also, knowing factors that may affect a medication’s loading dose is imperative to pharmacological treatments for chronic conditions. For example, initiation of dofetilide for treating atrial fibrillation requires an initial loading dose before reaching therapeutic concentrations. As a clinician administers this medication, they must monitor creatinine clearance and QTc interval length and adjust the dosage accordingly to avoid potentially deadly side effects such as ventricular tachycardia.[7]

Nursing, Allied Health, and Interprofessional Team Interventions

Using pharmacological therapy to treat a patient's underlying condition is common in today's medical field. Although these therapies can be beneficial, they can also cause significant harm to the patient. One study found that almost 11% of prescriptions have errors, and 16% of these errors result in harm to the patient.[8] This situation makes it essential that dosing medications are done with an interprofessional team to ensure efficacy and safety. Ways to help facilitate this would be by:

• Having an open line of communication between all clinicians and specialties – this is especially true in instances of transition of care
• Ensure clinicians and pharmacists work together to ensure proper dosing and medication choice
• Order drug blood concentrations when clinically appropriate
• Educate family and patient about potential adverse drug reactions
• Ensure appropriate specialties are involved with the care of a patient when deemed appropriate
• Computerized prescribing and order entry systems should have dosing checks to flag potential dosing errors and offer recommendations for correct dosing.

Interprofessional efforts become even more essential when a situation with a patient becomes more critically ill, requiring higher levels of care. By working in an interprofessional team, patient outcomes can improve, and medication errors can be avoided.[9] [Level 4]