By Moon, Richard B
Hospice patients at the end stages of life often suffer nausea and vomiting, distressing symptoms that are either side effects of medications or direct effects of the underlying disease state. Such symptoms can greatly diminish the hospice patient’s quality of life. Effective pharmacotherapy is available, but in many cases traditional dosage forms are incompatible with the patient’s physical condition, cause discomfort, or are difficult for family members to administer. In such cases, a compounded preparation containing lorazepam, diphenhydramine, haloperidol, and metoclopramide-commonly referred to as ABHR gel-has proven highly effective. A number of case reports are presented to illustrate the effectiveness of ABHR gel in relieving the symptoms of nausea and vomiting in hospice patients. Also discussed are the causes of vomiting and the mechanisms of each of the medications contained in the ABHR gel.
Lorazepam, diphenhydramine, haloperidol, and metoclopramide are the drugs contained in the compounded gel commonly referred to as ABHR. The gel was named after the brand names Ativan, Benadiyl, Haldol, and Reglan, under which these drugs were originally marketed. This gel is an option that has proven highly effective for relieving the symptoms of nausea and vomiting for terminally ill hospice patients. This combination of drugs works to block each physical pathway that is responsible for nausea and vomiting. Case reports are provided to illustrate ABHR gel’s effectiveness in relieving these symptoms.
Pathophysiology and Overview of Nausea and Vomiting
Boomsma published an excellent review of the mechanisms involved in nausea and vomiting and the medications used in the treatment of these symptoms in hospice patients.1 There are three distinct stages of vomiting (Table 1). The body’s vomiting center (VC) is the final pathway that controls all vomiting. The VC does not respond directly to chemical stimuli but is triggered by four different mechanisms, as follows:
* Chemoreceptor trigger zone (CTZ): The CTZ incorporates various receptors (serotonin, dopamine, and opiate) that mediate the emetic effects of blood toxins and drugs. The CTZ is unable to induce vomiting without an intact VC.2,3
* Afferent impulses from the periphery: Stimulation of the VC from outside the central nervous system occurs when chemical stimulation and physical factors cause afferent impulses from the periphery. Serotonin, dopamine, and opiate receptors are the mediators of emesis.2,4
* Vestibular apparatus: The vestibular apparatus is located near the VC. Motion induces stress, which transmits an impulse to the vestibular apparatus. Norepinephrine and acetylcholine are the receptors in the vestibular apparatus.2,5,6
* Conical structures: Cortical structures are areas in the higher brain stem that are able to initiate vomiting. Impulses (sight, smell, taste, or unpleasant memories) sent to the cortex of the VC may stimulate this pathway.2,4
The ABHR gel treatment works by blocking each of the pathways that trigger nausea and/or vomiting.
Table 1. Stages of Vomiting.
Obstacles in the Treatment of Nausea and Vomiting
Obstacles to treating nausea and vomiting in the hospice population are as follows:
* Traditional single-agent therapy is not always effective.
* The delivery of medication to a patient via the oral route can be problematic in a nauseous patient.
* Some patients lose their ability to swallow.
* Caregivers, who are often elderly, may be uncomfortable dosing with injections and suppositories.
Attempts to solve these problems have led to the use of compounded transdermal combinations of medications, including the frequently used ABHR gel. This and similar combinations are used clinically for chemotherapy patients, although often with an injectable route of administration. The two most commonly used topical doses are lorazepam 2 mg/diphenhydramine 50 mg/haloperidol 2 mg/metoclopramide 40 mg per milliliter and lorazepam 4 mg/ diphenhydramine 100 mg/haloperidol 4 mg/metoclopramide 80 mg per milliliter. The common dosage is 0.25 mL applied to the inner wrist four times a day. Table 2 summarizes the drug classes, nausea and vomiting pathways affected, therapeutic effects, and side effects of the drugs that constitute ABHR gel.
Table 2. ABHR Gel: Components and Actions on Nausea and Vomiting Pathways.
An additional factor in the choice of these agents and use of the transdermal route of administration is the cost of the preparation weighed against the costs of continued nausea or vomiting and administering the agents separately. The convenience of the topical gel is another factor to consider, as it minimizes the confusion created when dosing with multiple medications or when an antiemetic regimen changes frequently.
Dispensing Review and Case Reports
Over a period of 366 days (March 1, 2003 to February 29, 2004), 55 of our hospice patients received at least one prescription for a 2-week supply of ABHR gel. Of these 55 patients, 28 refilled their prescription at least once, while 27 received a single dispensing. The 27 patients who received only one prescription unfortunately died before they could refill their prescription. Among the 55 patients, no treatment failures were reported by the nursing staff; however, treatment was reported by the attending physician as being unsuccessful in one case. The nurses reported that the only dosing problems they experienced were with patients who had bowel obstruction.
Patient 1: 72-year-old woman
Diagnosis: Malignant neoplasm in the bronchi and lungs
Treatment: The patient received 14 prescriptions (13 refills) of ABHR gel on a regular basis, beginning with her admission into hospice and continuing until she died 7 months later. Prochlorperazine suppositories were added to her regimen as needed to treat new symptoms.
Treatment results: The compound worked well for the patient. As she came to the preterminal stage of her disease, about 2 weeks before she died, she started reporting increased pain and nausea, and began vomiting more frequently. Prochlorperazine suppositories were added to her regimen as needed to treat the nausea and vomiting. The suppositories seemed to alleviate some of her discomfort.10
Patient 2: 60-year-old man
Diagnosis: Secondary malignant neoplasm of the liver
Treatment: The patient was in hospice care for only 2 months before he died. During that time he received four prescriptions (three refills) of ABHR gel. In addition to ABHR gel, he received haloperidol 1-mg tablets, prochlorperazine suppositories, and ondansetron tablets for nausea.
Treatment results: The patient stated that he experienced nausea and/or vomiting when he missed a dose of the ABHR gel.
Patient 3: 81-year-old woman
Diagnosis: Malignant neoplasm of the ovary
Treatment: The patient was in hospice care for approximately 1 month before she died. In that short time, she received five prescriptions (four refills) of ABHR gel to treat her escalating discomfort.
Treatment results: A few days after receiving her first dosage of ABHR gel, the patient experienced hallucinations, which her family attributed to the ABHR gel. It should be noted that this symptom occurred as her disease state advanced, and there was no way to relate it directly to the ABHR gel. The hospice team continued to order the medication with no further hallucinatory episodes noted.
Patient 4: 88-year-old man
Diagnosis: Malignant neoplasm of the prostate
Treatment: Over the 3-month period the patient was enrolled in hospice care, was dispensed the ABHR gel a total of five times, all within the last 6 weeks of his life.
Treatment results: A couple of weeks after initiating the ABHR gel, the patient stated that he was not experiencing any nausea or vomiting. His symptoms were well controlled on his medication regimen.
Patient 5: 93-year-old woman
Diagnosis: Adult failure to thrive
Treatment: The patient had been in hospice for close to 2 years. She received 14 prescriptions (13 refills) of ABHR gel over a 6- month period.
Treatment results: The patient related nausea with pain, and shortly after starting the ABHR gel therapy her pain diminished. A couple of months later she again reported abdominal pain. Her physician believed that this pain was nausea; therefore, he increased the ABHR gel dose and her pain disappeared.
Additional Case Report Findings
Seven other case reports published between 2000 and 2002 in the RxTriad newsletter of the International Journal of Pharmaceutical Compounding relate the successful use of ABHR gel and other combination drug therapies in hospice patients.10-16
One notable case report described a 78-year-old woman who had stomach cancer. The patient’s chief complaint was nausea, and the prescribed trimethobenzamide suppositories were not effectively treating this symptom. As an alternative, ABH gel (ABHR without metoclopramide) was suggested, but the patient still experienced some nausea. Metoclopramide was then added to the gel, and after two doses of the second preparation, the patient’s nausea was relieved. She followed the ABHR gel protocol and experienced relief from nausea for over a year until her death.11
A second case report described a 74-year-old woman who suffered from canc\er of the liver and bone. Prochlorperazine maleate capsules were providing little or no relief, and alternative routes of administration were being explored. The patient’s physician prescribed ABHR gel with instructions to apply 0.5 mL to the wrist every 4 to 6 hours as needed. With this formula and dose, the patient experienced relief from nausea and diminished anxiety as her life ended.12
In another case, ABHR gel was effective in the treatment of opioid-related nausea in a patient receiving both extended-release and immediate-release forms of oxycodone to control pain. Administration of ABHR gel helped to relieve the patient’s nausea and improve her quality of life.11
Similar combinations of the four drugs involved with ABHR gel therapy may be used in intravenous form or, in appropriate cases, in an ambulatory infusion manager pump.12 Variations of the ABHR gel protocol may include the use of phenothiazines such as prochlorperazine, or butyrophenones such as droperidol; one or more ingredients may be omitted to suit each patient’s unique needs.13,14
Nausea and vomiting are great concerns to hospice patients, who are generally in the preterminal stages of their life. ABHR gel is one of the combination drug therapies that have demonstrated clinical effectiveness for a wide variety of hospice patients suffering from symptoms of nausea or vomiting. ABHR gel is easily administered, causes little or no discomfort to the patient, can be a cost-effective tool in the management of nausea and vomiting, and for many patients enhances quality of life as life nears its end.
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* Lichter I, Hunt E. The last 48 hours of life. J Palliat Care 1990; 6(4): 7-15.
* Lindley-Davis B. Process of dying. Defining characteristics. Cancer Nurs 1991; 14(6): 328-333.
* Peralta A Jr. Symptom management in hospice and palliative care. Tex Med 2001; 97(8): 42-51.
1. Boomsma D. Nausea and vomiting in hospice patients. IJPC 2000; 4(4): 250-251.
2. Young LY, Koda-Kimble MA, eds. Applied Therapeutics: The Clinical Use of Drugs. 6th ed. Vancouver, WA: Applied Therapeutics; 1995: 105.1-105.10.
3. Seigel LJ, Longo DL. The control of chemotherapy-induced emesis. Ann Intern Med 1981; 95(3): 352-359.
4. [No author listed.] Lexicom. Latest Drugs. [Lexicom Website] November 2004. Available at: www.lexi.com. Accessed November 2004.
5. Borison HL. Physiology and pharmacology of vomiting. Pharmacol Rev 1953; 5(2): 193-230.
6. Wood C, Graybiel A. A theory of motion sickness based on pharmacological reactions. Clin Pharmacol Ther 1970; 11:621-629.
7. Malik IA, Khan WA, Qazilbash M et al. Clinical efficacy of lorazepam in prophylaxis of anticipatory, acute, and delayed nausea and vomiting induced by high doses of cisplatin. A prospective randomized trial. Am J Clin Oncol 1995; 18(2): 170-175.
8. Dipiros JT, Talbert RL, Yee GC et al. Pharmacotherapy: A Pathophysiologic Approach. 5th ed. New York, NY: McGraw-Hill; 2002.
9. Rousseau P. Antiemetic therapy in adults with terminal disease: A brief review. Am J Hosp Palliat Care 1995; 12(1): 13-18.
10. Herr J. Case report: Ibuprofen and prednisone rectal suppositories for the relief of metastatic cancer pain. IJPC RxTriad December 2002: 1-2.
11. Herr J, Farkus J. Case report: Ativan, benadryl, and haldol (ABH) gel and Ativan, Benadryl, Haldol, and metoclopramide (ABHM) gel in the treatment of nausea. IJPC RxTriad Match 2001:1.
12. Petrin R. Case report: ABHR gel in Pluronic lecithin organogel. IJPC RxTriad September 2000:1-2.
13. Simonetti D. Case report: Treatment of opioid-related nausea in a terminal cancer patient. IJPC RxTriad May 2000:2.
14. Karolchyk S, Covalesky B, Molhatra V. Case report: Multiple therapy for a dying patient. IJPC RxTriad May 2001:2.
15. Sherman J. Case report: Droperidol 10 mg/mL in Pluronic lecithin organogel for the treatment of severe nausea and vomiting. IJFC RxTriad September 2000:1.
16. Simonetti D, Faulkner K. Case report: Prochlorperazine and metoclopramide in a PLO for analgesia in a patient with terminal colon cancer. IJPC RxTriad November 2000:1-2.
Richard B. Moon, PharmD, RPh, FIACP
Jamestown, New York
Address correspondence to Richard B. Moon, PharmD, RPb, FIACP, Pharmacy Innovations, 863 Fairmount Avenue, Jamestown, NY 14701. E- mail: [email protected]
Copyright International Journal of Pharmaceutical Compounding Mar/ Apr 2006
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