A nurse, who is also an HG survivor, asked me why women with hyperemesis gravidarum are not prescribed granisetron (Kytril, Sancuso). My search sent me on a scavenger hunt for information.
At the moment, there is not a standardized protocol among practitioners and around the world for treating hyperemesis gravidarum. It all depends on what insurance you have (if you have any), where you live and what doctor you see. Even medical professionals within the same practice will recommend different strategies to ease the suffering. There is, however, a pattern that most medical practitioners follow. Once the initial medications prove worthless in easing nausea and vomiting, the next standard is ondansetron (Zofran). Due to a couple of extremely small and possibly flawed studies that link it to birth defects, many doctors are understandably cautious and tell pregnant women not to take it. For more information on the Zofran studies, see this HER Foundation page. At the moment there’s a large spectrum of advice from doctors that ranges from patients being told not to take it at all, to not to take it during the first trimester, to take it any of the nine months if needed. With this controversy, another option is to try another medication in the same pharmaceutical class.
Granisetron (Kytril, Sancuso) is an antiemetic in the same pharmaceutical class as ondansetron (Zofran). Both are serotonin (HT3) antagonists, so why is ondansetron readily available when granisetron is difficult to get? My first thought was that it is expensive and therefore not on many, if any, insurance formularies, but I had a feeling the reason was more complicated than that.
Since I have heard from many women that granisetron really helped with their HG, I decided to start by contacting the manufacturer. For the record, pharmaceutical manufactures LOVE sharing information about their products. In fact, they have a department just for this purpose. You can call them anytime they’re open, usually east coast business hours, and they’ll happily answer questions about their medications for you. This is why I was surprised to have a difficult time finding out who the manufacturer is. They must not have many sales representatives promoting their product, which is traditionally how doctors learn about medications, and then use that information in determining what to prescribe to patients.
Who Manufactures Granisetron?
A Google search sent me to multiple dead ends: pharmaceutical companies that have been bought out and then resold, brand names that have been discontinued and formulations that are not being manufactured. I then reached out to an oncology pharmacist, since it’s commonly used in cancer treatments. He replied that his patients have a better response in general with granisetron than ondansetron, and that the one used at the hospital is manufactured by Westward Pharmaceutical. After many more Google searches, left voicemails and unanswered emails, I received responses from Hikma Pharmaceuticals USA (formerly West-Ward Pharmaceuticals Corp), who manufactures tablets and injections of granisetron, and Kyowa Kirin who manufactures a patch under the brand name Sancuso. Note that Sancuso is a patch only approved to use for five days for chemotherapy patients but has a different dosing regiment for nausea and vomiting in pregnancy.
Since all the granisetron products are only FDA approved for cancer treatment, it is considered “off-label” to use them for other health conditions. Off-label happens when the clinical studies for the medication were not tested in a specific health condition or patient population, yet the medication is known to work and be safe “relatively” for that condition. (I say relatively, because everything we put in our body has a risk versus benefit ratio, even everyday foods and drinks). Very few, if any, medications are clinically tested in pregnant women or children because it would be unethical to do so. No one would risk taking an unknown medication in this population, and no one would give a placebo with which to compare the medication and therefore leave the disease state untreated. (Since ondansetron and granisetron are clinically proven to work in cancer patients, I have to wonder who were the first pregnant women to try them. I am definitely grateful to them!) Since granisetron does not have an FDA approval for hyperemesis gravidarum for the reason stated, I was beyond delighted to see in the information received that both companies listed their products as Pregnancy Category B.
Here is the Summary of studies from Kyowa Kirin:
- A Phase 1 PK/PD study examined the pharmacodynamics of Sancuso therapy in women with nausea and vomiting associated with pregnancy. Sixteen women with baseline Pregnancy Unique Quantification of Emesis and Nausea (PUQE) scores of at least 6 were recruited into the study. Patients received intravenous (IV) granisetron, followed by Sancuso, with a washout period of at least 48 hours between treatments. PUQE scores indicate that the symptoms of nausea and vomiting were significantly improved with both IV granisetron and Sancuso. No serious side effects associated with either treatment were reported. The possible effects of granisetron upon pregnancy outcome were not reported.” (Caritis S, Zhao Y, Chen HJ, Venkataramanan R. Pharmacodynamics of transdermal granisetron in women with nausea and vomiting of pregnancy. Am J Obstet Gynecol. 2016;215(1):93.e1-4.)
- “An observational small case series reported on the need for rescue antiemetics (additional medications to stop vomiting) in patients using Sancuso or oral ondansetron for nausea and vomiting associated with pregnancy. None of the patients using Sancuso required rescue medication. Two patients taking ondansetron were prescribed rescue promethazine. The possible effects of Sancuso upon pregnancy outcome were not reported.” (Le TN, Adler MT, Ouillette H, Berens P, Smith JA. Observational case series evaluation of the granisetron transdermal patch system (Sancuso) for the management of nausea and vomiting of pregnancy. Am J Perinatol. 2017;34(9):851-855.)
In addition to the details on how it received the Pregnancy Category B rating, both companies included disclaimers about using their products in pregnancy. Kyowa Kirin stated it “does not encourage or support off-label use of any of its products,” Hikma’s products were tested in rats and rabbits which “revealed no evidence of impaired fertility or harm to the fetus due to granisetron”. They also added “there are however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.” You and your doctor should decide if your hyperemesis gravidarum falls into the category of “clearly needed.”
Financial Assistance
Adding to encouraging use of granisetron for HG, Hikma included the information on how to afford it. Although they “do not have a patient assistance program since they are a generic manufacturer, patients can see if they’re eligible for financial assistance through the Pharmaceutical Research and Manufacturers of America’s “Partnership for Prescription Assistance” clearinghouse. For eligibility requirements, contact the PhrMA at 1 (800) 477-2669 or visit the Partnership for Prescription Assistance website at www.pparx.org.”
Sancuso offers a co-pay assistance card, but it does have many limitations. Click here to see if you qualify.
The newest research
Adding to this clinical data, results from a clinical study that “aimed to determine the association between early pregnancy exposure to granisetron and fetal/neonatal outcomes” was just published in the European Journal of Obstetrics & Gynecology and Reproductive Biology in November 2019. This study compared 100 women that were exposed to granisetron to 108 women who were not exposed. The results showed similar rates of major malformation in both groups, and the group with granisetron had a significantly lower rate of miscarriages.
While granisetron is an antiemetic that doctors do not regularly prescribe due to possible lack of knowledge and formulary limitations, the evidence supports its use. Given the information provided from the manufacturers, I encourage hyperemesis gravidarum patients to discuss the possible use of granisetron with their doctors and reach out to the manufacturer to find out where and how to get it, if their insurance does not cover it, or if their local pharmacy does not carry it.
If you would like a copy of the pharmaceutical company responses, send me a request at info@hgpharmacist.com. If you have used any form of granisetron for HG, please share your experiences, good or bad, with me at info@hgpharmacist.com, or complete the form below, as I would love to compile the results and share them with you.
