The SC and IM routes of administration are preferred over the IV route when it is desirous to slow the onset of the effect of a medication or prolong its duration of action, or when a patient is combative and it is too problematic to insert an IV line. Obesity can alter the rate and absorption of medications, especially those that are lipophilic. It may change the depth of both skin and SC tissue layers. This may necessitate the use of a different needle size to avoid the inadvertent administration of IM medications into the SC tissue, which may delay absorption and peak concentrations.
A primer was published to address the implications of obesity on the administration of SC and IM medications in acutely ill patients, in particular, obesity's effect on drug absorption. Among the topics addressed are the influence of skin and SC layer thickness on medication absorption and the implications of obesity for medications commonly administered via the SC or IM routes (e.g., insulins, vaccines, epinephrine, benzodiazepines, antipsychotics, anticoagulants, sumatriptan, and monoclonal antibodies).
Among the general considerations identified for SC and IM administration are that absorption is influenced by the site of administration, concentration of the drug, volume administered, and blood flow and may be delayed or incomplete in acutely ill patients who have tissue ischemia, edema, or are on vasopressors. For protein-based medications, other factors affect absorption, such as molecular weight, charge, viscosity, pH, stability of formulations, first-pass (both SC and IM avoid the first-pass effect) and draining by the lymphatics. Heat or physical activity can increase SC absorption.
In obesity, there is an increase in SC tissue, which can affect the administration of IM injections if the proper needle length is not chosen. There is a lack of studies addressing the effects of acute illness on SC and IM dosing.
For insulin, obesity is associated with a delay in absorption due to decreased capillary density and blood flow in the SC tissue. Delays in absorption and peak hypoglycemic effect have been observed for insulin lispro in obese individuals. Accidental administration of insulin IM instead of SC can result in more rapid absorption and episodes of hypoglycemia.
For vaccines, if an IM injection is given SC instead of IM, a patient may experience more adverse events. This is likely due to the presence of immunocompetent cells in the skin and deep dermis. Even the injection site can affect antibody response for vaccines with a lower response seen for hepatitis B when it is administered in the buttocks compared with the arm.
While dosing adjustments are not needed when using an epinephrine autoinjector, questions have been raised about the adequacy of the needle length in patients who are obese. Other factors may also affect drug concentrations achieved such as sex, compression of soft tissue, and the propulsive force of the needle used in an IM injection.
Lorazepam and midazolam are the only benzodiazepines which can be administered via a route other than IV. However, there is a paucity of data of the effects of obesity on the disposition of these medications with limited data indicating that midazolam's peak concentration may be affected.
Even though IM haloperidol has been used for decades, there is no information available on the effect of obesity on this drug's disposition. Data are also limited for the IM administration of second-generation antipsychotics in obese patients, although one study involving aripiprazole did not demonstrate a difference in relapse rate in this population.
A significant association has been observed between the area under the curve, BMI, and SC sumatriptan administration. Migraine response to SC sumatriptan has been shown to be dependent on body size.
Numerous factors affect the bioavailability of SC administered monoclonal antibodies such as molecular size, transport throughout the lymphatics, specific product formulation, and the device used for administration (including needle length, volume of SC injection, viscosity, aggregation issues, and the use of adjuvant agents such as hyaluronidase as a dispersing agent). However, the effect of obesity has not been studied.
Pharmacists need to be aware of the limited data that are available regarding the effect obesity has on rate of absorption and bioavailability of IM and SC drug formulations, as these may have the potential to affect clinical outcome.
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