[Rich66]

Available Alternatives

5-HT3 antagonists:
http://en.wikipedia.org/wiki/5-HT3_antagonist

• Ondansetron (trade name Zofran in most countries) was the first 5-HT₃ antagonist, developed by Glaxo around 1984. Its efficacy was first established in 1987, in animal models,^[18][19] and it was extensively studied over the following years.^[20] Ondansetron was approved by the U.S. Food and Drug Administration in 1991, and has since become available in several other countries, including the UK, Ireland, Australia, Canada, France and Brazil. As of 2008, ondansetron and granisetron are the only 5-HT₃ antagonists available as a generic drug in the United States. Ondansetron may be given several times daily, depending on the severity of symptoms.
• Tropisetron (trade name Navoban) was also first described in 1984.^[21] It is available in several countries, such as the UK, Australia and France, but not in the United States. The effects of tropisetron last up to 24 hours, so it only requires once-daily administration.
• Granisetron (trade name Kytril) was developed around 1988.^[22] It is available in the U.S., UK, Australia and other countries. Clinical trials suggest that it is more effective than other 5-HT₃ antagonists in preventing delayed CINV (nausea and vomiting that occur more than 24 hours after the first dose of chemotherapy).^[23] It is taken once daily.
• Dolasetron (U.S. trade name Anzemet) was first mentioned in the literature in 1989.^[24] It is a prodrug, and most of its effects are due to its active metabolite, hydrodolasetron, which is formed in the liver by the enzyme carbonyl reductase. Dolasetron was approved by the FDA in 1997, and is also administered once daily.
• Palonosetron (trade name Aloxi) is the newest 5-HT₃ antagonist to become available in the U.S. market. It is an isoquinoline derivative, and is effective in preventing delayed CINV.^[25] Palonosetron was approved by the FDA in 2003,^[26] initially for intravenous use. An oral formulation was approved on August 22, 2008 for prevention of acute CINV alone, as a large clinical trial did not show oral administration to be as effective as IV use against delayed CINV.^[27]
• Ramosetron (trade name Nasea) is only available in Japan and certain Southeast Asian countries as of 2008.^[28] It has higher affinity for the 5-HT₃ receptor than the older 5-HT₃ antagonists, and maintains its effects over two days; it is therefore significantly more effective for delayed CINV.^[29] In animal studies, ramosetron was also effective against irritable bowel syndrome-like symptoms.^[30]

Alosetron and cilansetron—the latter being developed by Solvay—are not antiemetics; instead, they are indicated in the treatment of a subset of irritable bowel syndrome where diarrhea is the dominant symptom. Alosetron was withdrawn from the U.S. market in 2000 due to unacceptably frequent severe side effects, and is only available through a restrictive program to patients who meet certain requirements.^[31]
Certain prokinetic drugs such as cisapride, renzapride and metoclopramide, although not 5-HT₃ antagonists proper, possess some weak antagonist effect at the 5-HT₃ receptor. Galanolactone, a diterpenoid found in ginger, is a 5-HT₃ antagonist and is believed to at least partially mediate the anti-emetic activity of this plant.^[32][33] Mirtazapine (trade name Remeron) is a tetracyclic antidepressant with 5-HT₃ antagonist effects and strong anti-emetic properties. Studies show mirtazapine as equally effective in treating chemotherapy-related nausea and vomiting as standard treatments; it is also cheaper and has fewer side effects than typical anti-emetics, and its antidepressant qualities may be an added benefit for cancer populations.^[34] Mirtazapine has also been used in the treatment of the motility disorder gastroparesis due to its anti-emetic effects.^[35] Olanzapine (trade name Zyprexa), an atypical antipsychotic with anti-emetic properties similar to those of mirtazapine, also shows promise in treating chemotherapy-induced nausea and vomiting.^[34]

• • Mirtazapine (Remeron), an antidepressant that also has antiemetic effects.^{[citation needed]}
• Dopamine antagonists act in the brain and are used to treat nausea and vomiting associated with neoplastic disease, radiation sickness, opioids, cytotoxic drugs and general anaesthetics.
  • Domperidone
  • Droperidol, haloperidol, chlorpromazine, promethazine, prochlorperazine. Some of these drugs are limited in their usefulness by their extra-pyramidal and sedative side-effects.
  • Metoclopramide (Reglan) also acts on the GI tract as a pro-kinetic, and is thus useful in gastrointestinal disease; however, it is poor in cytotoxic or post-op vomiting.
  • Alizapride

• NK1 receptor antagonist
• • Aprepitant (Emend) Commercially available NK1 Receptor antagonist-note: may interfere with Tamoxifen/CYP450 pathway
  • Casopitant Investigational NK1 receptor antagonist
• Antihistamines (H₁ histamine receptor antagonists), effective in many conditions, including motion sickness, morning sickness in pregnancy, and to combat opiate nausea.
  • Cyclizine
  • Diphenhydramine (Benadryl)
  • Dimenhydrinate (Gravol, Dramamine)
  • Meclizine (Bonine, Antivert)
  • Promethazine (Pentazine, Phenergan, Promacot) Promethazine can be administered via a rectal suppository for adults and children over 2 years of age.
  • Hydroxyzine
• • Hydroxyzine
• Cannabinoids are used in patients with cachexia, cytotoxic nausea, and vomiting, or who are unresponsive to other agents.
  • Cannabis - Medical marijuana, in the U.S., it is a Schedule I drug.^{[citation needed]}
  • Dronabinol (Marinol) - a Schedule III drug in the U.S.^{[citation needed]}
  • Nabilone (Cesamet) - Put back on the market in late 2006. In the U.S., it is a Schedule II substance.
  • Sativex is an oral spray containing THC and CBD. It is currently legal in Canada and a few countries in Europe but not in legal the U.S.^{[citation needed]}
• Benzodiazepines
  • Midazolam given at the onset of anesthesia has been shown in recent trials to be as effective as ondansetron.^{[citation needed]}
  • Lorazepam said to be very good as an adjunct treatment for nausea along with first line medications such as Compazine or Zofran.^[citation
  Other
• Prochlorperazine (Compazine, Stemzine, Buccastem, Stemetil, Phenotil)
• Trimethobenzamide; thought to work on the CTZ
• Ginger
• Emetrol also claimed to be an effective antiemetic.
• Propofol given intravenously. It has been used in an acute care setting in hospital as a rescue therapy for emesis.^{[citation needed]}
• Peppermint claimed to help nausea or stomach pain when added into a tea or peppermint candies.
• Muscimol purported as such^[1]
• Ajwain purported to be antiemetic. It is a popular spice in India, Ethiopia and Eritrea.
• Zolpidem has been reported to be a newer antiemetic used for patients that have been unresponsive to other first-line typical antiemetics.^{[citation needed]}

http://kytril.com/
Kytril is Granisetron available as IV, tablets or liquid.

http://www.sancuso.com/hcp/efficacy/...FYJx5QodFy7jqQ

SANCUSO is the first and only patch (Granisetron) for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately and/or highly emetogenic chemotherapy regimens (MEC and/or HEC) of up to 5 consecutive days' duration.¹
Preventing CINV can make a positive impact on a patient's emotional and physical recovery

Read more about the occurrence of CINV, patient fear, and problems with adherence to CINV medication below.

• Underestimated CINV
• Conquering patient fear
• Adherence issues

SANCUSO—a selective 5-HT₃ receptor antagonist

The SANCUSOpatch delivers 34.3 mg of granisetron, a selective 5-HT₃ receptor antagonist, at a rate of 3.1 mg per day through the skin and into the bloodstream.¹. It’s an optimal choice for patients at risk for CINV, and those who would benefit from 5 continuous days of coverage.
SANCUSO starts working before chemotherapy begins

One key to successful CINV prevention is to address the situation before it even begins and to offer continuous CINV prevention at a steady state during and after each round of chemotherapy.
SANCUSO is applied a minimum of 24 to 48 hours before chemotherapy and provides up to 5 days of continuous coverage for the prevention of chemotherapy-induced nausea and vomiting.¹ Coverage prior to symptoms on a long-term basis can relieve your patients' anxieties and help them stay positive about their treatment overall.

Masui. 1996 Sep;45(9):1096-9.
Treatment of postoperative nausea and vomiting with ondansetron in patients administered anti-neoplastic agents

[Article in Japanese]
Morimoto Y, Nakamura M, Tamura T, Kunii T, Shimizu K, Miyauchi Y.
Department of Anesthesiology and Critical Care, Tokuyama Central Hospital.
The antiemetic effect of ondansetron (a 5-HT3 antagonist) was evaluated in patients treated with intraperitoneally administered anti-neoplastic agents (cisplatin and mitomycin-C) during surgery for ovarian cancer. Anesthesia was induced with intravenous thiopental 5 mg x kg-1 and maintained with nitrous oxide 66% in oxygen and isoflurane. After surgery, 6 patients received a single intravenous dose of ondansetron 4 mg (group O), 6 others did not receive ondansetron (group C). Both groups received an intravenous dose of methyl-prednisolone 500 mg. An intravenous dose of metoclopramide 10 mg was provided in case of continued vomiting or at the patient's request as a rescue antiemetic. The incidence of vomiting was 13% in group O and 87% in group C (P < 0.05). Nausea scores (range 1-4) were significantly lower in group O as compared with group C at 4 h and 8 h after surgery. Total dose of metoclopramide was 20 +/- 13 mg (mean +/- SD) in group C and 2 +/- 4 mg in group O. Administration of anti-neoplastic agents during surgery caused severe nausea and vomiting after surgery and ondansetron prevented the occurrence of nausea and vomiting almost completely. We conclude that ondansetron is an effective antiemetic for preventing postoperative nausea and vomiting in patients administered anti-neoplastic agents.

PMID: 8905945 [PubMed - indexed for MEDLINE]

http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70109-3/abstract

Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial

http://www.webmd.com/cancer/aprepitant

Aprepitant

Examples

Generic Name	Brand Name
aprepitant	Emend

Emend is available as a capsule you can swallow in either 80 mg or 125 mg doses.
How It Works

Aprepitant prevents and controls nausea and vomiting by blocking the effects of a chemical in the brain. That chemical is called P/neurokinin 1 (NK1) receptor antagonist.

note: may interfere with Tamoxifen/CYP450 pathway

Why It Is Used

Aprepitant is used to prevent and control nausea and vomiting caused by chemotherapy. It is always used in combination with serotonin antagonists (such as ondansetron) and dexamethasone.
Aprepitant is not approved for the treatment of chronic nausea or vomiting. It is most often used when the other drugs used to treat nausea and vomiting have not worked well enough.
How Well It Works

Aprepitant, when combined with ondansetron and dexamethasone as part of a 3-day regimen, prevents both acute and delayed nausea and vomiting caused by chemotherapy.
Side Effects

Side effects can occur with aprepitant and may include:

• Dehydration.
• Dizziness.
• Diarrhea.
• Hiccups.
• Weakness and fatigue.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)
What To Think About

Aprepitant should be used only under the supervision of a medical oncologist or hematologist. It is approved for use only in combination with ondansetron and dexamethasone for the treatment of nausea and vomiting caused by chemotherapy. It also may do a better job than other drugs at controlling nausea and vomiting that occurs more than 1 day after treatment.
Aprepitant interacts with many other drugs. Be sure that your doctor knows all the prescription and over-the-counter drugs you are taking.
Blood-thinning drugs, such as warfarin, may not work as well when you take aprepitant. If you are taking a blood thinner, you will need frequent blood tests to make sure that your dose is high enough.
Aprepitant decreases the effectiveness of birth control pills. If you are taking birth control pills, your doctor will help you choose another method of birth control.

Study: Ginger can help reduce nausea after chemotherapy

By Liz Szabo, USA TODAY
Ginger capsules can relieve the nausea caused by chemotherapy, a new study shows.
Up to 70% of patients become nauseated after chemo, according to a study of 644 people released Thursday, in advance of the annual meeting of the American Society of Clinical Oncology, which begins in two weeks in Orlando.

Although drugs such as Kytril can prevent vomiting, they don't always relieve nausea, says author Julie Ryan, assistant professor of dermatology and radiation oncology at the University of Rochester Medical Center.
Ginger, however, reduced patients' nausea levels by half, according to the study, funded by the National Cancer Institute. On a scale of one to seven — in which seven represents the worst nausea — chemo patients given placebos rated their nausea as a 5 or 6, or very nauseous.
Those given ginger, however, rated their nausea level as only 2 or 3, Ryan says.
Patients took ginger three days before and three days after getting chemo, Ryan says. Patients took three capsules, twice a day. The most effective doses were 1 gram and 0.5 gram a day, which are equal to half a teaspoon or one-quarter of a teaspoon of ground ginger.
All patients also got standard drugs to prevent vomiting, Ryan says.
Significantly, ginger caused no side effects.
Doctors were careful to monitor patients' platelet levels, because some earlier research suggested that ginger might act like a blood thinner, Ryan says.
"That's why we're so excited. This is something that people have access to, that won't harm them," says Ryan, who notes that ginger capsules are commonly sold in health food stores.
Although ginger has been used as a folk remedy for nausea for centuries, this is the first time that it has been so rigorously tested for chemo patients, says Richard Schilsky, oncology society president, who wasn't involved in the study. He describes the trial's results as "conclusive."
Several studies have shown that ginger can relieve morning sickness during pregnancy, says Linda Lee, director of the Johns Hopkins Integrative Medicine & Digestive Center. Doctors don't yet understand exactly why it works.
Lee notes that the Food and Drug Administration doesn't regulate supplements such as ginger the same way as it regulates drugs.
"One of the challenges about recommending a ginger supplement is that not all brands are created equal," Lee says. "One study looked at several ginger supplements on the market, only to find a few of them did not contain gingerol, one of the active compounds in ginger."
And Schilsky notes that, because researchers didn't test powdered or fresh ginger, they don't know if these types of ginger are as effective as capsules.
"How do you translate ginger in a capsule to the ginger in your spice rack?" Schilsky asks. "Can you drink a six pack of ginger ale?"
Douglas Blayney, incoming president of the oncology society, says cancer patients should resist the temptation to indulge in too much ginger soda or cookies, however. Some studies show that cancer patients who gain weight are more likely to relapse.
Studies show up to two-thirds of cancer patients try herbal remedies or other alternative therapies.
Cancer researchers are increasingly interested in testing these approaches.
In 2007, researchers at the cancer society meeting showed that ginseng could help relieve cancer patients' fatigue.
After eight weeks of treatment in that study, roughly 27% of those who took the two highest ginseng doses rated their fatigue as "moderately" or "very much" better, she says. Only 10% of those who took placebos or the lowest ginseng dose improved that much.
And while alternative therapies can relieve some treatment-related symptoms, researchers haven't shown the these folk remedies actually treat cancer. At the 2007 meeting, researchers found that shark cartilage had no effect on lung cancer.