Palliative Care

Palliative Care is "the active total care of patients whose disease is not responsive to curative treatment." The goal of palliative care is the achievement of the best possible quality of life for patients and their families.

Symptom Control involves therapies for pain management, nausea & vomiting, dry mouth & stomatitis, excessive pulmonary secretions/death rattle, radiation mucositis and proctitis, and wound care.

We work together with patient and practitioner to solve problems by customizing medications that meet the specific needs of each individual. Please contact our compounding pharmacist to discuss the dosage form, strength, and medication or combination that is most appropriate for your patient.

Nausea & Vomiting

Persistent nausea can often be effectively controlled by using a combination of medications tailored to meet that individual's specific needs. Dosage forms include transdermal gels, suppositories, lollipops, and more.

Promethazine is commonly compounded for topical or transdermal application to treat nausea, vomiting, and vertigo, but this preparation may be used as an antiemetic for cases ranging from chemotherapy to motion sickness. The dose is typically 25mg for adults, and the dose is decreased for children. The gel is applied to an area of soft skin, such as the inside of the wrist or arm, the side of the torso, or the inside of the thigh. For children, doses are often applied to the inside of one wrist, and then the wrists are rubbed together.
US Pharmacist, August 1999; 74-5

Lorazepam, diphenhydramine, haloperidol, and metoclopramide (known in combination as "ABHR") have been prepared as a rectal suppository and in other transdermal dosage forms. The rationale is to use a variety of medications which target various pathways such as vagal nerve stimulation, the vomiting center, and the CTZ for more severe cases. Researchers at Memorial Sloan-Kettering Cancer Centre have studied the antiemetic activity and safety of the antiemetic regimen of metoclopramide, dexamethasone, and diphenhydramine in patients receiving standard outpatient chemotherapy programs. Vomiting was prevented in over 70% of patients.

Cancer 1995 Sep 1;76(5):774-8
Oral combination antiemetics in patients with small cell lung cancer receiving cisplatin or cyclophosphamide plus doxorubicin.
Click here to access the PubMed abstract of this article.

Intranasal metoclopramide may significantly reduce the frequency of acute vomiting in patients receiving highly emetogenic chemotherapy, such cisplatin-induced delayed emesis. Intranasal metoclopramide caused minor irritation of the nasal membrane and unpleasant taste in some patients, but was otherwise well tolerated, with no report of serious extrapyramidal effects.

Drugs 1999 Aug;58(2):315-22; discussion 323-4
Intranasal metoclopramide.
Click here to access the PubMed abstract of this article.

ABH Transdermal Gel for Chemotherapy-Induced Nausea/Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is commonly cited by patients as being among the “most unpleasant and distressing” side effects associated with chemotherapy. CINV may impair quality of life significantly and necessitate chemotherapeutic dose reductions, treatment delays, and discontinuation of therapy. Finally, it may cause a substantial number of lost work days for patients and considerable costs to the healthcare system, resulting in a substantial economic burden.

Bleicher et al. of the Haematology/Oncology Division, Creighton University Medical Centre, Omaha, NE, investigated the efficacy of "ABH," a topical gel containing lorazepam (Ativan®), diphenhydramine (Benadryl®), and haloperidol (Haldol®), in reducing breakthrough CINV. Adults receiving standard recommended prophylactic antiemetics as outpatients were instructed to apply 0.5 mL of a transdermal gel (containing lorazepam 2 mg, diphenhydramine 25 mg, and haloperidol 2 mg) when they experienced significant CINV. When the severity of CINV was quantified on a scale of 0-10, the mean CINV score decreased significantly from a 6.1 before gel application to a 1.7 as evaluated 30 minutes following gel application. Topical use of ABH gel appears to be a promising and safe rescue therapy for breakthrough CINV that occurs despite prophylactic antiemetic therapy.1

Weschules noted that of 11,181 ABHR (ABH plus metoclopramide [Reglan®]) prescriptions provided for patients, 6,529 (58.4%) were for a topical gel, and 4,312 (38.6%) were for a rectal suppository.2 Less than 0.5% of patients discontinued treatment due to adverse side effects. Another retrospective study reported use of an ABHR gel to be 98% effective in hospice patients.3 There were no adverse reactions; however, problems arose when patients with bowel obstructions were treated.

1 J Support Oncol. 2008 Jan;6(1):27-32.
Lorazepam, diphenhydramine, and haloperidol transdermal gel for rescue from chemotherapy-induced nausea/vomiting: results of two pilot trials.
Click here to access the PubMed abstract of this article.

2 J Palliat Med 2008;8:1135–1143.
Tolerability of the compound ABHR in hospice patients.
Click here to access the PubMed abstract of this article.

3 Int J Pharm Compounding 2006;10:95–99.
ABHR Gel in the Treatment of Nausea and Vomiting in the Hospice Patient
Click here to access the abstract of this article.

Dry Mouth & Stomatitis

There are many factors that can interfere with the ability to eat when a person is receiving chemotherapy. Malnutrition may result, yet it is often preventable. Our pharmacy can compound medications to help combat mouth tenderness and infections, which may enable patients to enjoy eating again.

Cancer. 2002 Nov 15;95(10):2230-6
Effect of topical morphine [mouthwash] for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma.
Cerchietti LC, Navigante AH, Bonomi MR, Zaderajko MA, Menendez PR, Pogany CE, Roth BM.
Supportive Care Division, Department of Medical Oncology, Angel H. Roffo Cancer Institute, University of Buenos Aires, Buenos Aires, Argentina.
Click here to access the PubMed abstract of this article.

  A three-drug mouthwash (lidocaine, diphenhydramine and sodium bicarbonate in normal saline) can provide effective symptomatic relief in patients with chemotherapy-induced mucositis.

Support Care Cancer. 2000 Jan;8(1):55-8
Efficacy of treatment to relieve mucositis-induced discomfort. Turhal NS, Erdal S, Karacay S.
Click here to access the PubMed abstract of this article.

Loss of saliva (xerostomia) is one of the most common complaints among patients who have received radiation therapy of the head and neck. Xerostomia contributes to radiation-induced periodontal infection, dental caries, osteoradionecrosis, and poor digestion of carbohydrates. Ask us about sialogogues (saliva stimulants) in customized dosage forms.

The following article discusses the benefits of using pilocarpine in a sustained release dosage form to treat xerostomia.

Yakugaku Zasshi. 1997 Jan;117(1):59-64
[Preparation and evaluation of solid dispersions of pilocarpine hydrochloride for alleviation of xerostomia]
[Article in Japanese] Oda M, Sato M, Yagi N, Ohno K, Miyazaki S, Watanabe S, Takada M.
Click here to access the PubMed abstract of this article.

Transdermal Anticholinergics for the Treatment of "Death Rattle" and Excessive Secretions

Difficulty clearing upper airway secretions (death rattle) is a problem for half of all dying patients. Treatment often includes the use of anticholinergic drugs, such as scopolamine (also known as hyoscine) or atropine. Transdermal scopolamine has several indications for symptom control in patients with end-stage disease: control of excess salivary secretions, management of terminal secretions, and control of nausea.

Palliat Med. 2002 Sep;16(5):369-74
Using anti-muscarinic drugs in the management of death rattle: evidence-based guidelines for palliative care.
Click here to access the PubMed abstract.

J Pain Symptom Manage. 2002 Apr;23(4):310-7
Death rattle: prevalence, prevention and treatment.
Click here to access the PubMed abstract.

Prescrire Int. 2001 Aug;10(54):99-101
Scopolamine: new preparations. Reference treatment for death rattle.
Click here to access the PubMed abstract.

Otolaryngol Head Neck Surg. 1990 Oct;103(4):615-8
Reduction of salivary flow with transdermal scopolamine: a four-year experience.
Click here to access the PubMed abstract of this article.

Drooling is a serious social handicap experienced by some neurologically impaired patients. No one method has been identified to control drooling for all patients, however, anticholinergic drugs have been utilized. In the following case study, transdermal scopolamine was found to be effective for controlling drooling in a traumatic brain-injured patient for whom more conservative methods failed. From a baseline saliva flow rate, saliva flow decreased up to 59%. No significant side effects were observed with treatment, and the decrease in drooling was maintained for a 4-month period. Although transdermal scopolamine may represent one acceptable facet of long-term treatment, it must be stressed that efficacy is variable across patient populations and that treatment approaches must be individualized.

Am J Phys Med Rehabil. 1991 Aug;70(4):220-2
The use of transdermal scopolamine to control drooling. A case report.
Click here to access the PubMed abstract of this article.

Pain management is essential because, even when the underlying disease process is stable, uncontrolled pain prevents patients from working productively, enjoying recreation, or taking pleasure in their usual roles in the family and society. Chronic pain may have a myriad of causes and perpetuating factors, and therefore can be much more difficult to manage than acute pain, requiring a multidisciplinary approach and customized treatment protocols to meet the specific needs of each patient.

Optimal treatment may involve the use of medications that possess pain-relieving properties, including some antidepressants, anticonvulsants, antiarrhythmics, anesthetics, antiviral agents, and NMDA (N-methyl-D-aspartate) antagonists. Palliative care often involves the use of opioid analgesics. NMDA-receptor antagonists, such as dextromethorphan and ketamine, can block pain transmission in dorsal horn spinal neurons, reduce nociception, and decrease tolerance to and the need for opioid analgesics. [Anesth Analg 2001 Mar;92(3):739-44] By combining various agents which utilize different mechanisms to alter the sensation of pain, physicians have found that smaller concentrations of each medication can be used.

Topical and transdermal creams and gels can be formulated to provide high local concentrations at the site of application (e.g., NSAIDs for joint pain), for trigger point application (e.g., combinations of medications for neuropathic pain), or in a base that will allow systemic absorption. Side effects associated with oral administration can often be avoided when medications are used topically. Studies suggest that there are no great restrictions on the type of drug that can be incorporated into a properly compounded transdermal gel. When medications are administered transdermally, they are not absorbed through the gastrointestinal system and do not undergo first-pass hepatic metabolism.

We work together with prescriber and patient to solve problems by customizing medications that meet the specific needs of each individual. Please contact our compounding pharmacist to discuss the dosage form, strength, and medication or combination that is most appropriate for your patient.

Effectiveness of Topical Administration of Opioids in Palliative Care

The discovery of peripheral opioid receptors has become the scientific basis for topical use of opioids in malignant and nonmalignant ulcers and oropharyngeal mucositis. A systematic review assessed the quality of published literature and examined whether topical opioids are effective in controlling pain in palliative care settings. Eighteen studies favored topical opioids in pain relief, but time to onset and duration of analgesia varied widely, perhaps due to variances in formulations. “N-of-1 trials should be encouraged for specific clinical circumstances.”

J Pain Symptom Manage. 2009 May;37(5):913-7.
Effectiveness of topical administration of opioids in palliative care: a systematic review.
Click here to access the PubMed abstract of this article.

Per a prescription order, a formulation can be compounded to contain the proper combination of active ingredients, in the most appropriate base, to treat a specific type of wound. We customize medications to meet each individual's specific needs. For example, the choice of cream, ointment, or gel can be clinically significant. Each time a wound needs to be cleaned, there is the potential for disruption of new tissue growth. Gels, which are more water soluble than creams or ointments, may be preferable for wound use because a gel can be rinsed from the wound by irrigation. Ointments may contain polyethylene glycol (PEG), which can be absorbed from open wounds and damaged skin. If the wound is quite large and too much PEG is absorbed, it can lead to renal toxicity. Another useful dosage form is the "polyox bandage" - which can be puffed onto a wound and will adhere even if exudate is present. A polyox bandage can be compounded to contain the active ingredient(s) of your choice.

Decubitus Ulcers

Phenytoin has been used topically to speed the healing of decubitus ulcers, pressure sores, venous stasis and diabetic ulcers, traumatic wounds, skin autograft donor sites, and burns. Ketoprofen may be used to control inflammation and pain, lidocaine provides topical anesthesia, and pentoxifylline may improve microcirculation at the wound margins and promote healing of the injured area. Misoprostol, a prostaglandin analog, is often included in wound care formulations to promote healing. Debridement of necrotic eschar with 40% urea paste may also speed healing. Medications which improve capillary blood flow can be added to a compounded medication to enhance circulation at the wound margins and promote healing of the injured area.

Topical Phenytoin for Wound Healing

Phenytoin may promote wound healing by a number of mechanisms, including stimulation of fibroblast proliferation, facilitation of collagen deposition, glucocorticoid antagonism, and antibacterial activity. Rhodes et al compared the healing of stage II decubitus ulcers with topically applied phenytoin and two other standard topical treatment procedures in 47 patients in a long-term care setting. Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing. Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications. The mean time to healing in the phenytoin group was 35.3 +/- 14.3 days compared with 51.8 +/- 19.6 and 53.8 +/- 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively. Healthy granulation tissue in the phenytoin group appeared within 2 to 7 days in all subjects, compared to 6 to 21 days in the standard treatment groups. The phenytoin-treated group showed no detectable serum phenytoin concentrations.

Anstead et al. described a patient with a massive grade IV pressure ulcer that was unresponsive to conventional treatment, yet responded rapidly to treatment with topical phenytoin. Song and Cheng reported phenytoin improved wound breaking strength in normal and radiation-impaired wounds. The results of their study indicated that topical phenytoin accelerated normal and irradiation-impaired wound healing by increasing the number of wound macrophages and improving the macrophage function. Pendse et al evaluated the effectiveness of topical phenytoin in healing chronic skin ulcers in a controlled trial of 75 inpatients. At the end of the fourth week, 29 of 40 phenytoin-treated ulcers had healed completely versus 10 of 35 controls. They concluded: "topical phenytoin appears to be an effective, inexpensive, and widely available therapeutic agent in wound healing."

The effectiveness of topical phenytoin as a wound healing agent was compared with that of OpSite and a conventional topical antibiotic dressing (Soframycin) in a controlled study of 60 patients with partial-thickness skin autograft donor sites on the lower extremities. Mean pain scores were lower and mean time to complete healing (complete epithelialization) was best in the phenytoin-treated group (6.2 +/- 1.6 days). Topical phenytoin compared very favorably with, and in some aspects was superior to, occlusive dressings.

No study reported any significant adverse effects secondary to topical phenytoin therapy.

Phenytoin references:

Ann Pharmacother 2001 Jun;35(6):675-81
Topical phenytoin treatment of stage II decubitus ulcers in the elderly.
Click here to access the PubMed abstract of this article.

Biochem Pharmacol 1999 May 15;57(10):1085-94
Role of phenytoin in wound healing--a wound pharmacology perspective.
Click here to access the PubMed abstract of this article.

Ann Pharmacother 1996 Jul-Aug;30(7-8):768-75
Phenytoin in wound healing.
Click here to access the PubMed abstract of this article.

Int J Dermatol 1993 Mar;32(3):214-7
Topical phenytoin in wound healing.
Click here to access the PubMed abstract of this article.

Chung Hua I Hsueh Tsa Chih 1997 Jan;77(1):54-7
[The effect of systemic and local irradiation on wound macrophages and the repair promoting action of phenytoin sodium]
Click here to access the PubMed abstract of this article.

Burns 1993 Aug;19(4):306-10
Topical phenytoin in the treatment of split-thickness skin autograft donor sites: a comparative study with polyurethane membrane drape and conventional dressing.
Click here to access the PubMed abstract of this article.

Diabetes Care 1991 Oct;14(10):909-11
Topical phenytoin in diabetic foot ulcers.
Click here to access the PubMed abstract of this article.

Benzoyl Peroxide for Treatment of Decubitus Ulcers

Benzoyl peroxide is a powerful oxidizing agent with broad spectrum germicidal activity and good liposolubility. Therefore, it may represent a good agent for prevention of wound infection in areas with high density of sebaceous glands. Topical treatment of pressure sore with 20% benzoyl peroxide in O/W emulsion yielded very satisfactory results. In another study, 10% benzoyl peroxide gel was used prophylactically once a day for 7 days before surgery. The researchers concluded that topical benzoyl peroxide is an efficacious, harmless, and inexpensive agent for prevention of wound infections in seborrheic regions.

Med Cutan Ibero Lat Am 1988;16(5):427-9.
[Benzoyl peroxide in the treatment of decubitus ulcers]
Click here to access the PubMed abstract of this article.

When illness is incurable or the cause is irreversible and the goal is palliation, systemic opioids are the first-line therapy for symptomatic management of dyspnea.

Palliat Med. 1997 Jul;11(4):277-81.
Oral morphine as symptomatic treatment of dyspnoea in patients with advanced cancer.
Click here to access the PubMed abstract of this article.

N Engl J Med. 1981 Dec 31;305(27):1611-6.
Effects of dihydrocodeine, alcohol, and caffeine on breathlessness and exercise tolerance in patients with chronic obstructive lung disease and normal blood gases.
Click here to access the PubMed abstract of this article.

Education for Physicians on End-of-life Care (EPEC) Participant’s Handbook
EPEC Project, 1999. The Project to Educate Physicians on End-of-life Care from the Institute for Ethics at the American Medical Association.

BMJ. 2003 Sep 6;327(7414):523-8
Randomized, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea
Click here to access the PubMed abstract of this article.

Radiation proctitis is a known complication of radiation therapy for prostate cancer. Commercially available treatments are often ineffective and have focused on relieving symptoms after damage has occurred, although options exist for prevention.

A prospective, randomized, placebo-controlled, double-blinded trial concluded that misoprostol rectal suppositories significantly reduce acute and chronic radiation proctitis symptoms in patients receiving radiation therapy for prostate cancer.

Am J Gastroenterol 2000 Aug;95(8):1961-6
A prospective randomized placebo-controlled double-blinded pilot study of misoprostol rectal suppositories in the prevention of acute and chronic radiation proctitis symptoms in prostate cancer patients.
Click here to access the PubMed abstract of this article.

Seven patients with radiation proctitis completed an open pilot study to evaluate the effectiveness of short chain fatty acid (SCFA) enemas. Four weeks of treatment resulted in clinical improvement in all patients, and modest changes in endoscopic and pathological parameters.

Am J Gastroenterol. 1996 Sep;91(9):1814-6
Evaluation of short-chain fatty acid enemas: treatment of radiation proctitis.
Click here to access the PubMed abstract of this article.

Topical sucralfate may induce a lasting remission in a majority of patients with moderate to severe rectal bleeding due to radiation proctosigmoiditis.

Dig Dis Sci 1999 May;44(5):973-8
Natural history of late radiation proctosigmoiditis treated with topical sucralfate suspension.
Click here to access the PubMed abstract of this article.

Topical morphine is effective in relieving mucositis-associated pain following concomitant chemoradiotherapy in head and neck carcinoma. Three patients, who had been treated previously with oral morphine with no relief from esophagitis pain, swallowed from 2 to 10 mL of 0.1% morphine viscous gel three times a day, 5 to 60 minutes before eating. The gel covered esophageal surfaces and produced topical anesthesia. Benefit continued to increase over several days of use. In prior studies, relief of oral mucositis pain was obtained by a topical 0.1% morphine solution. The major advantages of topical morphine administration are simplicity, low incidence of side effects, and low cost.

J Pain Symptom Manage. 2005 Aug;30(2):107-9.
Chemoradiotherapy-induced esophagitis pain relieved by topical morphine: three cases.
Click here to access the PubMed abstract of this article.

“Mucositis is a common adverse event related to many antineoplastic regimens... Ketamine is a potent N-methyl-D-aspartate (NMDA) receptor channel blocker that can lead to decreased nocioception and inhibit the inflammatory cascade… Also, ketamine acts on a number of other pathways that may attenuate pain.”

Ketamine mouthwash (20 mg/5 ml) administered using the “swish and spit” technique may be a viable treatment option in refractory mucositis pain.

J Palliat Med. 2009 Nov;12(11):989-91.
Ketamine mouthwash for mucositis pain.
Click here to access the PubMed abstract of this article.

Systemic doxepin, a tricyclic antidepressant, has been used for pain management of patients with chronic pain. Practitioners at major US universities and in private practice assessed pain reduction after topical doxepin rinse in fifty-one patients with painful oral mucositis attributable solely to cancer therapy. A significant reduction of oral pain was recorded after doxepin was administered. At 5 minutes, on average, patients reported a 41% decrease in pain, and the median duration of pain reduction lasted for almost 2½ hours. Taste was acceptable and discomfort/burning with use was minimal. These findings are in contrast to typical complaints of taste and discomfort/burning associated with topical application of local anesthetics.

Anesth Analg 2006;103:465–70
Oral Doxepin Rinse: The Analgesic Effect and Duration of Pain Reduction in Patients with Oral Mucositis Due to Cancer Therapy
Click here to access the PubMed abstract of this article.

The following list is just a few of the preparations that we can compound for palliative care. All formulations are customized per prescription to meet the unique needs of each patient. Please call us to discuss the dosage form, medication, and strength which are most appropriate for your patient.

• ABHR - gel and troche
• Cholestyramine ointment
• Dextromethorphan single agent and oral modified release preparations
• Hydrocodone without acetaminophen
• Lidocaine -Tetracaine spray
• Metoclopramide- nasal spray and suppository
• Misoprostol – suppository and oral preparations
• Morphine transdermal
• Pilocarpine – gel, lollipop, or oral modified release preparations
• Promethazine gel
• Scopolamine gel
• Short chain fatty acid enemas
• Sucralfate oral adhesive paste, cream, and enema

Palliative Care

Palliative Care is "the active total care of patients whose disease is not responsive to curative treatment." The goal of palliative care is the achievement of the best possible quality of life for patients and their families.

Symptom Control involves therapies for pain management, nausea & vomiting, dry mouth & stomatitis, excessive pulmonary secretions/death rattle, radiation mucositis and proctitis, and wound care.

We work together with patient and practitioner to solve problems by customizing medications that meet the specific needs of each individual. Please contact our compounding pharmacist to discuss the dosage form, strength, and medication or combination that is most appropriate for your patient.

Nausea & Vomiting

Persistent nausea can often be effectively controlled by using a combination of medications tailored to meet that individual's specific needs. Dosage forms include transdermal gels, suppositories, lollipops, and more.

Promethazine is commonly compounded for topical or transdermal application to treat nausea, vomiting, and vertigo, but this preparation may be used as an antiemetic for cases ranging from chemotherapy to motion sickness. The dose is typically 25mg for adults, and the dose is decreased for children. The gel is applied to an area of soft skin, such as the inside of the wrist or arm, the side of the torso, or the inside of the thigh. For children, doses are often applied to the inside of one wrist, and then the wrists are rubbed together.
US Pharmacist, August 1999; 74-5

Lorazepam, diphenhydramine, haloperidol, and metoclopramide (known in combination as "ABHR") have been prepared as a rectal suppository and in other transdermal dosage forms. The rationale is to use a variety of medications which target various pathways such as vagal nerve stimulation, the vomiting center, and the CTZ for more severe cases. Researchers at Memorial Sloan-Kettering Cancer Centre have studied the antiemetic activity and safety of the antiemetic regimen of metoclopramide, dexamethasone, and diphenhydramine in patients receiving standard outpatient chemotherapy programs. Vomiting was prevented in over 70% of patients.

Cancer 1995 Sep 1;76(5):774-8
Oral combination antiemetics in patients with small cell lung cancer receiving cisplatin or cyclophosphamide plus doxorubicin.
Click here to access the PubMed abstract of this article.

Intranasal metoclopramide may significantly reduce the frequency of acute vomiting in patients receiving highly emetogenic chemotherapy, such cisplatin-induced delayed emesis. Intranasal metoclopramide caused minor irritation of the nasal membrane and unpleasant taste in some patients, but was otherwise well tolerated, with no report of serious extrapyramidal effects.

Drugs 1999 Aug;58(2):315-22; discussion 323-4
Intranasal metoclopramide.
Click here to access the PubMed abstract of this article.

ABH Transdermal Gel for Chemotherapy-Induced Nausea/Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is commonly cited by patients as being among the “most unpleasant and distressing” side effects associated with chemotherapy. CINV may impair quality of life significantly and necessitate chemotherapeutic dose reductions, treatment delays, and discontinuation of therapy. Finally, it may cause a substantial number of lost work days for patients and considerable costs to the healthcare system, resulting in a substantial economic burden.

Bleicher et al. of the Haematology/Oncology Division, Creighton University Medical Centre, Omaha, NE, investigated the efficacy of "ABH," a topical gel containing lorazepam (Ativan®), diphenhydramine (Benadryl®), and haloperidol (Haldol®), in reducing breakthrough CINV. Adults receiving standard recommended prophylactic antiemetics as outpatients were instructed to apply 0.5 mL of a transdermal gel (containing lorazepam 2 mg, diphenhydramine 25 mg, and haloperidol 2 mg) when they experienced significant CINV. When the severity of CINV was quantified on a scale of 0-10, the mean CINV score decreased significantly from a 6.1 before gel application to a 1.7 as evaluated 30 minutes following gel application. Topical use of ABH gel appears to be a promising and safe rescue therapy for breakthrough CINV that occurs despite prophylactic antiemetic therapy.1

Weschules noted that of 11,181 ABHR (ABH plus metoclopramide [Reglan®]) prescriptions provided for patients, 6,529 (58.4%) were for a topical gel, and 4,312 (38.6%) were for a rectal suppository.2 Less than 0.5% of patients discontinued treatment due to adverse side effects. Another retrospective study reported use of an ABHR gel to be 98% effective in hospice patients.3 There were no adverse reactions; however, problems arose when patients with bowel obstructions were treated.

1 J Support Oncol. 2008 Jan;6(1):27-32.
Lorazepam, diphenhydramine, and haloperidol transdermal gel for rescue from chemotherapy-induced nausea/vomiting: results of two pilot trials.
Click here to access the PubMed abstract of this article.

2 J Palliat Med 2008;8:1135–1143.
Tolerability of the compound ABHR in hospice patients.
Click here to access the PubMed abstract of this article.

3 Int J Pharm Compounding 2006;10:95–99.
ABHR Gel in the Treatment of Nausea and Vomiting in the Hospice Patient
Click here to access the abstract of this article.

Dry Mouth & Stomatitis

There are many factors that can interfere with the ability to eat when a person is receiving chemotherapy. Malnutrition may result, yet it is often preventable. Our pharmacy can compound medications to help combat mouth tenderness and infections, which may enable patients to enjoy eating again.

Cancer. 2002 Nov 15;95(10):2230-6
Effect of topical morphine [mouthwash] for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma.
Cerchietti LC, Navigante AH, Bonomi MR, Zaderajko MA, Menendez PR, Pogany CE, Roth BM.
Supportive Care Division, Department of Medical Oncology, Angel H. Roffo Cancer Institute, University of Buenos Aires, Buenos Aires, Argentina.
Click here to access the PubMed abstract of this article.

  A three-drug mouthwash (lidocaine, diphenhydramine and sodium bicarbonate in normal saline) can provide effective symptomatic relief in patients with chemotherapy-induced mucositis.

Support Care Cancer. 2000 Jan;8(1):55-8
Efficacy of treatment to relieve mucositis-induced discomfort. Turhal NS, Erdal S, Karacay S.
Click here to access the PubMed abstract of this article.

Loss of saliva (xerostomia) is one of the most common complaints among patients who have received radiation therapy of the head and neck. Xerostomia contributes to radiation-induced periodontal infection, dental caries, osteoradionecrosis, and poor digestion of carbohydrates. Ask us about sialogogues (saliva stimulants) in customized dosage forms.

The following article discusses the benefits of using pilocarpine in a sustained release dosage form to treat xerostomia.

Yakugaku Zasshi. 1997 Jan;117(1):59-64
[Preparation and evaluation of solid dispersions of pilocarpine hydrochloride for alleviation of xerostomia]
[Article in Japanese] Oda M, Sato M, Yagi N, Ohno K, Miyazaki S, Watanabe S, Takada M.
Click here to access the PubMed abstract of this article.

Transdermal Anticholinergics for the Treatment of "Death Rattle" and Excessive Secretions

Difficulty clearing upper airway secretions (death rattle) is a problem for half of all dying patients. Treatment often includes the use of anticholinergic drugs, such as scopolamine (also known as hyoscine) or atropine. Transdermal scopolamine has several indications for symptom control in patients with end-stage disease: control of excess salivary secretions, management of terminal secretions, and control of nausea.

Palliat Med. 2002 Sep;16(5):369-74
Using anti-muscarinic drugs in the management of death rattle: evidence-based guidelines for palliative care.
Click here to access the PubMed abstract.

J Pain Symptom Manage. 2002 Apr;23(4):310-7
Death rattle: prevalence, prevention and treatment.
Click here to access the PubMed abstract.

Prescrire Int. 2001 Aug;10(54):99-101
Scopolamine: new preparations. Reference treatment for death rattle.
Click here to access the PubMed abstract.

Otolaryngol Head Neck Surg. 1990 Oct;103(4):615-8
Reduction of salivary flow with transdermal scopolamine: a four-year experience.
Click here to access the PubMed abstract of this article.

Drooling is a serious social handicap experienced by some neurologically impaired patients. No one method has been identified to control drooling for all patients, however, anticholinergic drugs have been utilized. In the following case study, transdermal scopolamine was found to be effective for controlling drooling in a traumatic brain-injured patient for whom more conservative methods failed. From a baseline saliva flow rate, saliva flow decreased up to 59%. No significant side effects were observed with treatment, and the decrease in drooling was maintained for a 4-month period. Although transdermal scopolamine may represent one acceptable facet of long-term treatment, it must be stressed that efficacy is variable across patient populations and that treatment approaches must be individualized.

Am J Phys Med Rehabil. 1991 Aug;70(4):220-2
The use of transdermal scopolamine to control drooling. A case report.
Click here to access the PubMed abstract of this article.

Pain management is essential because, even when the underlying disease process is stable, uncontrolled pain prevents patients from working productively, enjoying recreation, or taking pleasure in their usual roles in the family and society. Chronic pain may have a myriad of causes and perpetuating factors, and therefore can be much more difficult to manage than acute pain, requiring a multidisciplinary approach and customized treatment protocols to meet the specific needs of each patient.

Optimal treatment may involve the use of medications that possess pain-relieving properties, including some antidepressants, anticonvulsants, antiarrhythmics, anesthetics, antiviral agents, and NMDA (N-methyl-D-aspartate) antagonists. Palliative care often involves the use of opioid analgesics. NMDA-receptor antagonists, such as dextromethorphan and ketamine, can block pain transmission in dorsal horn spinal neurons, reduce nociception, and decrease tolerance to and the need for opioid analgesics. [Anesth Analg 2001 Mar;92(3):739-44] By combining various agents which utilize different mechanisms to alter the sensation of pain, physicians have found that smaller concentrations of each medication can be used.

Topical and transdermal creams and gels can be formulated to provide high local concentrations at the site of application (e.g., NSAIDs for joint pain), for trigger point application (e.g., combinations of medications for neuropathic pain), or in a base that will allow systemic absorption. Side effects associated with oral administration can often be avoided when medications are used topically. Studies suggest that there are no great restrictions on the type of drug that can be incorporated into a properly compounded transdermal gel. When medications are administered transdermally, they are not absorbed through the gastrointestinal system and do not undergo first-pass hepatic metabolism.

We work together with prescriber and patient to solve problems by customizing medications that meet the specific needs of each individual. Please contact our compounding pharmacist to discuss the dosage form, strength, and medication or combination that is most appropriate for your patient.

Effectiveness of Topical Administration of Opioids in Palliative Care

The discovery of peripheral opioid receptors has become the scientific basis for topical use of opioids in malignant and nonmalignant ulcers and oropharyngeal mucositis. A systematic review assessed the quality of published literature and examined whether topical opioids are effective in controlling pain in palliative care settings. Eighteen studies favored topical opioids in pain relief, but time to onset and duration of analgesia varied widely, perhaps due to variances in formulations. “N-of-1 trials should be encouraged for specific clinical circumstances.”

J Pain Symptom Manage. 2009 May;37(5):913-7.
Effectiveness of topical administration of opioids in palliative care: a systematic review.
Click here to access the PubMed abstract of this article.

Per a prescription order, a formulation can be compounded to contain the proper combination of active ingredients, in the most appropriate base, to treat a specific type of wound. We customize medications to meet each individual's specific needs. For example, the choice of cream, ointment, or gel can be clinically significant. Each time a wound needs to be cleaned, there is the potential for disruption of new tissue growth. Gels, which are more water soluble than creams or ointments, may be preferable for wound use because a gel can be rinsed from the wound by irrigation. Ointments may contain polyethylene glycol (PEG), which can be absorbed from open wounds and damaged skin. If the wound is quite large and too much PEG is absorbed, it can lead to renal toxicity. Another useful dosage form is the "polyox bandage" - which can be puffed onto a wound and will adhere even if exudate is present. A polyox bandage can be compounded to contain the active ingredient(s) of your choice.

Decubitus Ulcers

Phenytoin has been used topically to speed the healing of decubitus ulcers, pressure sores, venous stasis and diabetic ulcers, traumatic wounds, skin autograft donor sites, and burns. Ketoprofen may be used to control inflammation and pain, lidocaine provides topical anesthesia, and pentoxifylline may improve microcirculation at the wound margins and promote healing of the injured area. Misoprostol, a prostaglandin analog, is often included in wound care formulations to promote healing. Debridement of necrotic eschar with 40% urea paste may also speed healing. Medications which improve capillary blood flow can be added to a compounded medication to enhance circulation at the wound margins and promote healing of the injured area.

Topical Phenytoin for Wound Healing

Phenytoin may promote wound healing by a number of mechanisms, including stimulation of fibroblast proliferation, facilitation of collagen deposition, glucocorticoid antagonism, and antibacterial activity. Rhodes et al compared the healing of stage II decubitus ulcers with topically applied phenytoin and two other standard topical treatment procedures in 47 patients in a long-term care setting. Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing. Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications. The mean time to healing in the phenytoin group was 35.3 +/- 14.3 days compared with 51.8 +/- 19.6 and 53.8 +/- 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively. Healthy granulation tissue in the phenytoin group appeared within 2 to 7 days in all subjects, compared to 6 to 21 days in the standard treatment groups. The phenytoin-treated group showed no detectable serum phenytoin concentrations.

Anstead et al. described a patient with a massive grade IV pressure ulcer that was unresponsive to conventional treatment, yet responded rapidly to treatment with topical phenytoin. Song and Cheng reported phenytoin improved wound breaking strength in normal and radiation-impaired wounds. The results of their study indicated that topical phenytoin accelerated normal and irradiation-impaired wound healing by increasing the number of wound macrophages and improving the macrophage function. Pendse et al evaluated the effectiveness of topical phenytoin in healing chronic skin ulcers in a controlled trial of 75 inpatients. At the end of the fourth week, 29 of 40 phenytoin-treated ulcers had healed completely versus 10 of 35 controls. They concluded: "topical phenytoin appears to be an effective, inexpensive, and widely available therapeutic agent in wound healing."

The effectiveness of topical phenytoin as a wound healing agent was compared with that of OpSite and a conventional topical antibiotic dressing (Soframycin) in a controlled study of 60 patients with partial-thickness skin autograft donor sites on the lower extremities. Mean pain scores were lower and mean time to complete healing (complete epithelialization) was best in the phenytoin-treated group (6.2 +/- 1.6 days). Topical phenytoin compared very favorably with, and in some aspects was superior to, occlusive dressings.

No study reported any significant adverse effects secondary to topical phenytoin therapy.

Phenytoin references:

Ann Pharmacother 2001 Jun;35(6):675-81
Topical phenytoin treatment of stage II decubitus ulcers in the elderly.
Click here to access the PubMed abstract of this article.

Biochem Pharmacol 1999 May 15;57(10):1085-94
Role of phenytoin in wound healing--a wound pharmacology perspective.
Click here to access the PubMed abstract of this article.

Ann Pharmacother 1996 Jul-Aug;30(7-8):768-75
Phenytoin in wound healing.
Click here to access the PubMed abstract of this article.

Int J Dermatol 1993 Mar;32(3):214-7
Topical phenytoin in wound healing.
Click here to access the PubMed abstract of this article.

Chung Hua I Hsueh Tsa Chih 1997 Jan;77(1):54-7
[The effect of systemic and local irradiation on wound macrophages and the repair promoting action of phenytoin sodium]
Click here to access the PubMed abstract of this article.

Burns 1993 Aug;19(4):306-10
Topical phenytoin in the treatment of split-thickness skin autograft donor sites: a comparative study with polyurethane membrane drape and conventional dressing.
Click here to access the PubMed abstract of this article.

Diabetes Care 1991 Oct;14(10):909-11
Topical phenytoin in diabetic foot ulcers.
Click here to access the PubMed abstract of this article.

Benzoyl Peroxide for Treatment of Decubitus Ulcers

Benzoyl peroxide is a powerful oxidizing agent with broad spectrum germicidal activity and good liposolubility. Therefore, it may represent a good agent for prevention of wound infection in areas with high density of sebaceous glands. Topical treatment of pressure sore with 20% benzoyl peroxide in O/W emulsion yielded very satisfactory results. In another study, 10% benzoyl peroxide gel was used prophylactically once a day for 7 days before surgery. The researchers concluded that topical benzoyl peroxide is an efficacious, harmless, and inexpensive agent for prevention of wound infections in seborrheic regions.

Med Cutan Ibero Lat Am 1988;16(5):427-9.
[Benzoyl peroxide in the treatment of decubitus ulcers]
Click here to access the PubMed abstract of this article.

When illness is incurable or the cause is irreversible and the goal is palliation, systemic opioids are the first-line therapy for symptomatic management of dyspnea.

Palliat Med. 1997 Jul;11(4):277-81.
Oral morphine as symptomatic treatment of dyspnoea in patients with advanced cancer.
Click here to access the PubMed abstract of this article.

N Engl J Med. 1981 Dec 31;305(27):1611-6.
Effects of dihydrocodeine, alcohol, and caffeine on breathlessness and exercise tolerance in patients with chronic obstructive lung disease and normal blood gases.
Click here to access the PubMed abstract of this article.

Education for Physicians on End-of-life Care (EPEC) Participant’s Handbook
EPEC Project, 1999. The Project to Educate Physicians on End-of-life Care from the Institute for Ethics at the American Medical Association.

BMJ. 2003 Sep 6;327(7414):523-8
Randomized, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea
Click here to access the PubMed abstract of this article.

Radiation proctitis is a known complication of radiation therapy for prostate cancer. Commercially available treatments are often ineffective and have focused on relieving symptoms after damage has occurred, although options exist for prevention.

A prospective, randomized, placebo-controlled, double-blinded trial concluded that misoprostol rectal suppositories significantly reduce acute and chronic radiation proctitis symptoms in patients receiving radiation therapy for prostate cancer.

Am J Gastroenterol 2000 Aug;95(8):1961-6
A prospective randomized placebo-controlled double-blinded pilot study of misoprostol rectal suppositories in the prevention of acute and chronic radiation proctitis symptoms in prostate cancer patients.
Click here to access the PubMed abstract of this article.

Seven patients with radiation proctitis completed an open pilot study to evaluate the effectiveness of short chain fatty acid (SCFA) enemas. Four weeks of treatment resulted in clinical improvement in all patients, and modest changes in endoscopic and pathological parameters.

Am J Gastroenterol. 1996 Sep;91(9):1814-6
Evaluation of short-chain fatty acid enemas: treatment of radiation proctitis.
Click here to access the PubMed abstract of this article.

Topical sucralfate may induce a lasting remission in a majority of patients with moderate to severe rectal bleeding due to radiation proctosigmoiditis.

Dig Dis Sci 1999 May;44(5):973-8
Natural history of late radiation proctosigmoiditis treated with topical sucralfate suspension.
Click here to access the PubMed abstract of this article.

Topical morphine is effective in relieving mucositis-associated pain following concomitant chemoradiotherapy in head and neck carcinoma. Three patients, who had been treated previously with oral morphine with no relief from esophagitis pain, swallowed from 2 to 10 mL of 0.1% morphine viscous gel three times a day, 5 to 60 minutes before eating. The gel covered esophageal surfaces and produced topical anesthesia. Benefit continued to increase over several days of use. In prior studies, relief of oral mucositis pain was obtained by a topical 0.1% morphine solution. The major advantages of topical morphine administration are simplicity, low incidence of side effects, and low cost.

J Pain Symptom Manage. 2005 Aug;30(2):107-9.
Chemoradiotherapy-induced esophagitis pain relieved by topical morphine: three cases.
Click here to access the PubMed abstract of this article.

“Mucositis is a common adverse event related to many antineoplastic regimens... Ketamine is a potent N-methyl-D-aspartate (NMDA) receptor channel blocker that can lead to decreased nocioception and inhibit the inflammatory cascade… Also, ketamine acts on a number of other pathways that may attenuate pain.”

Ketamine mouthwash (20 mg/5 ml) administered using the “swish and spit” technique may be a viable treatment option in refractory mucositis pain.

J Palliat Med. 2009 Nov;12(11):989-91.
Ketamine mouthwash for mucositis pain.
Click here to access the PubMed abstract of this article.

Systemic doxepin, a tricyclic antidepressant, has been used for pain management of patients with chronic pain. Practitioners at major US universities and in private practice assessed pain reduction after topical doxepin rinse in fifty-one patients with painful oral mucositis attributable solely to cancer therapy. A significant reduction of oral pain was recorded after doxepin was administered. At 5 minutes, on average, patients reported a 41% decrease in pain, and the median duration of pain reduction lasted for almost 2½ hours. Taste was acceptable and discomfort/burning with use was minimal. These findings are in contrast to typical complaints of taste and discomfort/burning associated with topical application of local anesthetics.

Anesth Analg 2006;103:465–70
Oral Doxepin Rinse: The Analgesic Effect and Duration of Pain Reduction in Patients with Oral Mucositis Due to Cancer Therapy
Click here to access the PubMed abstract of this article.

The following list is just a few of the preparations that we can compound for palliative care. All formulations are customized per prescription to meet the unique needs of each patient. Please call us to discuss the dosage form, medication, and strength which are most appropriate for your patient.

• ABHR - gel and troche
• Cholestyramine ointment
• Dextromethorphan single agent and oral modified release preparations
• Hydrocodone without acetaminophen
• Lidocaine -Tetracaine spray
• Metoclopramide- nasal spray and suppository
• Misoprostol – suppository and oral preparations
• Morphine transdermal
• Pilocarpine – gel, lollipop, or oral modified release preparations
• Promethazine gel
• Scopolamine gel
• Short chain fatty acid enemas
• Sucralfate oral adhesive paste, cream, and enema

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