Cannabis (marijuana) contains more than 60 pharmacologically active cannabinoids; delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best known. THC is the main psychoactive constituent of cannabis. CBD, unlike THC, does not produce intoxication or euphoria.

The FDA has warned that the IV emulsion formulation of the substance P/neurokinin 1 (NK1) receptor antagonist rolapitant (Varubi) has been associated in postmarketing reports with serious hypersensitivity reactions including anaphylaxis and anaphylactic shock.1 Rolapitant was approved by the FDA as an oral tablet in 2015 for adjunctive prevention of delayed nausea and vomiting associated with cancer chemotherapy in adults2; the IV emulsion formulation of the drug was approved for the same indication in 2017.

The reported hypersensitivity reactions occurred during or shortly after infusion of rolapitant IV emulsion, and hospitalization was required in some cases. Rolapitant emulsion contains soybean oil; patients with known allergies to legumes or other related allergens may be at increased risk of developing a hypersensitivity reaction. IV fosaprepitant (Emend), the other parenteral substance P/NK1 inhibitor formulation approved by the FDA, does not contain soybean oil, but has also been associated with serious hypersensitivity reactions.

Patients with a history of hypersensitivity to soybean oil should not be treated with IV rolapitant. Those with known allergies to legumes or other related allergens should be monitored for signs of hypersensitivity during and following infusion of the emulsion. If a serious reaction occurs, use of rolapitant IV emulsion should be permanently discontinued.

1. FDA. Varubi (rolapitant) injectable emulsion: health care provider letter – anaphylaxis and other serious hypersensitivity reactions. January 16, 2018. Available at: www.fda.gov. Accessed January 18, 2018.
2. Rolapitant (Varubi) for prevention of delayed chemotherapy-induced nausea and vomiting. Med Lett Drugs Ther 2016; 58:17.

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In the US, 25 states and the District of Columbia now permit some medical use of botanical marijuana (Cannabis sativa). It has been used for centuries to treat various ailments, but non-standardization of dosage makes available data difficult to interpret. Cannabis contains >60 pharmacologically active cannabinoids.

The FDA has approved rolapitant (Varubi – Tesaro), an oral substance P/neurokinin 1 (NK₁) receptor antagonist, for use with other antiemetics to prevent delayed nausea and vomiting associated with cancer chemotherapy in adults. It is the third substance P/NK₁ receptor antagonist to be approved in the US; aprepitant (Emend) and netupitant (only available in combination with the 5-HT₃ receptor antagonist palonosetron as Akynzeo) were approved earlier for prevention of both acute and delayed chemotherapy-induced nausea and vomiting.

The FDA has approved Akynzeo (Helsinn/Eisai), an oral fixed-dose combination of the substance P/neurokinin 1 (NK₁) receptor antagonist netupitant and the serotonin-3 (5-HT₃) receptor antagonist palonosetron, for prevention of acute and delayed nausea and vomiting associated with cancer chemotherapy in adults. Akynzeo is the first product to combine drugs from these two classes. Palonosetron (Aloxi) is also available as a single agent for prevention of chemotherapy-induced and postoperative nausea and vomiting. Netupitant is the second substance P/NK₁ receptor antagonist to be approved in the US; aprepitant (Emend) was the first.

The FDA has announced that the single 32-mg IV dose of ondansetron (Zofran, and generics) used for prevention of cancer chemotherapy-associated nausea and vomiting has been withdrawn from the market because it can prolong the QT interval and could possibly cause a torsades de pointes cardiac arrhythmia. For this indication, the only recommended dose of IV ondansetron is 0.15 mg/kg (maximum 16 mg/dose) every 4 hours for 3 doses. There are no changes in the recommended dosing regimens for oral ondansetron or for IV ondansetron used for prevention of postoperative nausea and vomiting.

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Fourteen states in the US - Alaska, California, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Jersey, New Mexico, Oregon, Rhode Island, Vermont and Washington - now permit, or soon will permit, some medical use of marijuana (Cannabis sativa). In some states, licensed facilities dispense botanical cannabis by prescription. In others, limited self-cultivation is permitted for medical use.

The treatment of choice to prevent emesis due to highand moderate-risk emetogenic drugs used in cancer chemotherapy is aprepitant plus a serotonin receptor antagonist plus dexamethasone. Four serotonin receptor antagonists are available in the US in intravenous (IV) formulations for prevention of nausea and vomiting due to cancer chemotherapy, and 3 of these are also available for oral use. Now the FDA has approved one of these, granisetron, in a transdermal formulation (Sancuso - ProStrakan).

Nabilone, an oral synthetic cannabinoid similar to delta-9-tetrahydrocannabinol (THC), the active ingredient in marijuana, has recently been reintroduced to the US market (Cesamet - Valeant) after a 17-year absence. The previous manufacturer discontinued marketing of the drug for commercial reasons. Nabilone is classified as a Schedule II controlled substance.

Palonosetron (Aloxi - Helsinn Healthcare SA, Switzerland, distributed in the US by MGI Pharma) is the fourth serotonin (5-HT₃) receptor antagonist to become available in the US and the first to be approved by the FDA for prevention of both acute and delayed nausea and vomiting due to moderately emetogenic cancer chemotherapy. It is also approved for prevention of acute nausea and vomiting due to highly emetogenic drugs such as cisplatin (Platinol, and others). Aprepitant (Emend), a substance P/neurokinin-1 receptor antagonist, was approved last year for use with a 5-HT₃ antagonist and dexamethasone to prevent both acute and delayed nausea and vomiting due to highly emetogenic drugs (Medical Letter 2003; 45:62).

Aprepitant (Emend - Merck), the first substance P/neurokinin 1 (NK₁) receptor antagonist to be approved by the FDA, is now available for oral use with corticosteroids and selective serotonin (5-HT₃) receptor antagonists to prevent nausea and vomiting caused by highly emetogenic anticancer drugs such as cisplatin.