The pathophysiology of nausea and vomiting, whether induced by
chemotherapy or other causes, is complex. It involves multiple organ systems,
including primarily the central nervous system, the gastrointestinal tract and
the peripheral nervous system. Multiple neurotransmitters and receptors are
involved, including serotonin, neurokinin, dopamine, histamine and muscaric
receptors, as well as others. For this reason, one single antiemetic agent is
rarely completely effective.
Multiple classes of antiemetic are used in the primary prevention and
treatment of nausea and vomiting. The primary ones are 5HT3 antagonists,
neurokinin-1 antagonists and dexamethasone. With a combination of these agents,
acute and delayed chemotherapy-induced nausea and vomiting is controlled in
most patients. Unfortunately, some patients have significant breakthrough
nausea and vomiting. In addition, patients with advanced disease not receiving
chemotherapy can have refractory nausea and vomiting.
Breakthrough symptoms are usually treated with one or more antiemetics
with different mechanisms of action. Commonly chosen agents include
prochlorperazine, promethazine, lorazepam, haloperidol, droperidol,
metoclopramide and cannabinoids. A newer agent, olanzapine, is showing promise
in treating breakthrough symptoms. It inhibits certain serotonin and dopamine
Some patients have such refractory symptoms that they require multiple
antiemetics to control their symptoms. Combinations of antiemetics with
different mechanisms of action can have added efficacy. Hospice patients, as
well as those who have refractory symptoms, may require alternate routes of
administration as well, such as rectally or topically.
ABHR in pluronic lecithin organogel (PLO) gel is a formulation of
multiple antiemetics compounded into a topical gel. It is not commercially
available and must be prepared by a compounding pharmacy. There are multiple
combinations and strengths available, so it can be tailored to the
patients needs. One common formulation is shown in the table. The usual
dose would be 1 g (1 mL) applied to the skin of the inner wrists every four to
The A represents lorazepam. The antiemetic mechanism of
action of benzodiazepines is not clear, but it inhibits the limbic system and
reduces cortical central nervous system input into the vomiting center of the
central nervous system. In addition, its action to reduce anxiety is important.
The B is diphenhydramine. It works as an antihistamine and
anticholinergic agent, and reduces the activity of the vestibular system. In
addition, it can reduce extrapyramidal adverse effects from dopamine
Lisa K. Lohr
The H stands for haloperidol, a potent dopamine antagonist.
The R is for metoclopramide. This agent works both as a
dopamine antagonist and to improve slowed gastrointestinal transit time. The
adverse effects expected from this combination are primarily drowsiness,
lethargy, confusion and muscle twitches. However, this combination is actually
well tolerated by most patients.
PLO gel is a two-part compounding gel that allows incorporation of
hydrophilic and lipophilic components. It is preferable to use the
pharmaceutical grade powder formulation of medications, instead of ground-up
tablets. The hydrophilic medications would be added to the aqueous pluronic
phase, and the lipophilic medications would be added to the organic
phospholipid phase. When the two phases are combined, the mixture automatically
gels up. This PLO gel enhances the permeability of the skin and improves drug
transport and absorption. However, it is unclear exactly what proportion of the
dose is absorbed.
Two authors have published results from non-comparative descriptions of
case series. One author (Weschules, 2005) described a series of more than 6,000
prescriptions of ABHR gel given to hospice patients. In addition, this study
looked at patients also receiving the ABHR compound through different dosage
forms, including rectal suppositories, and oral capsules and suspension. ABHR
was well tolerated, with few patients (0.5%) discontinuing this agent due to
adverse effects. Adverse effects were more common in the elderly. Those adverse
effects related to treatment discontinuation included sedation/somnolence,
agitation and confusion.
Another group of researchers (Bleicher, 2008) reported the results from
two pilot trials studying ABH (no R) gel for rescue treatment of
chemotherapy-induced nausea and vomiting. Thirty-three patients were given the
topical gel in a dose of lorazepam 2 mg/diphenhydramine 25 mg/haloperidol 2 mg.
In the first pilot of 23 patients, 74% reported decreased nausea and vomiting,
most within 30 minutes of application. In the second pilot of 10 patients, all
patients reported that the topical gel was effective, with mean symptoms score
dropping substantially. Adverse effects were experienced by a few patients.
Other combinations of antiemetics use dexamethasone with other agents.
BDR would be diphenhydramine 25 mg/dexamethasone 4 mg to 10
mg/metoclopramide 10 mg. In using this formulation, it is important to remember
how much dexamethasone the patient is receiving in total, in regards to
possible corticosteroid-related adverse effects.
None of these combinations of antiemetics are commercially available,
but they can be compounded not only into topical gels but into rectal
suppositories by a compounding pharmacy. In addition, suppositories can be
extemporaneously prepared by putting oral tablets/capsules into larger, empty
gelatin capsules. They can then be lubricated and administered rectally. Many
patients do not like rectal medications and would prefer topical administration
if the oral route is not suitable.
In summary, combinations of three or more antiemetics with different
mechanisms of action can be prepared for rectal or topical administration when
the oral route of administration is not available due to vomiting or bowel
obstruction. These products are effective in most, but not all patients. They
are well tolerated in most patients, and the adverse effects are similar to the
same agents given orally or intravenously.
Lisa K. Lohr, PharmD, BCPS, BCOP, is a Clinical Pharmacist in
Oncology and Bone Marrow Transplantation in the Department of Pharmacy Services
at the University of Minnesota Medical Center and is a HemOnc Today Editorial
For more information:
- Bleicher J. J Support Oncol. 2008:6:27-32.
- Moon RB. Int J Pharm Compound. 2006;10:95-98.
- Weschules DJ. J Pall Med. 2005;8:1135-1143.