A majority of Parkinson’s disease (PD) patients with “off” episodes successfully tolerated titration to an effective and tolerable dose of a sublingual apomorphine film (SL-Apo; Kynmobi, Sunovion Pharmaceuticals) without the use of antiemetic drugs, new research shows .
“The bottom line was that the majority of patients did not experience dose-limiting nausea or vomiting,” co-investigator William Ondo, MD, of the Houston Methodist Neurological Institute, Texas, told Medscape Medical News. “And although there really is no prospective, placebo-controlled use of [trimethobenzamide antiemetic]… versus not using [it], anecdotally and based on historical data, even without the nausea drugs, the nausea really seemed about the same. “
The results were presented at the virtual International Congress on Parkinson’s and Movement Disorders (MDS) 2021.
This study was the dose titration phase to determine the effective and tolerable dose of the drug as part of an extended safety and efficacy study.
Only 13% of the patients suffered from nausea and / or vomiting, of which 74% were mild and 26% were moderate. These nausea / vomiting rates were lower than those observed when trimethobenzamide (Tigan, Pfizer) was to be administered during the titration phase at the investigator’s discretion.
176 patients (mean age 64.4 years) who had had idiopathic Parkinson’s disease for an average of 8.0 years and had not previously been exposed to SL-Apo, with modified Hoehn- and Yahr stages 1 to 3 disease (83% stage 2 or 2.5 during the “on” time).
Study participants had a mini-mental state exam score greater than 25, were receiving stable levodopa / carbidopa doses, and had 1 or more (average 4.2) “off” episodes per day with a daily “off” time of 2 hours or more in total. Patients with oral cancer or wounds within 30 days of screening were excluded.
Open dose titration was performed during consecutive visits to the doctor while patients were “off”, increasing doses from 10 to 35 mg in 5 mg increments to determine a tolerable dose that would result in a complete “on” within 45 minutes. Phase led. Patients self-administered this achieved dose of SL-Apo for up to 5 “off” episodes per day with a minimum of 2 hours between doses for the entire 48 week study period.
The study protocol prohibited the use of antiemetics unless clinically justified in the investigator’s discretion. Of the 176 patients, 31 (18%) received the antiemetic trimethobenzamide and 145 (82%) did not.
Of the 176 patients, 76% received their effective and tolerable dose within the first 3 doses. Slightly more than half (55%) received 10 mg or 15 mg. Only 24% received the highest doses of 25 mg or 30 mg.
Treatment-related nausea occurred in 52% of patients who received trimethobenzamide and vomiting occurred in 13%; In comparison, 13% who did not receive trimethobenzamide had nausea and 1% had vomiting. Ten percent of the patients in the former group and none in the latter dropped out of the study because of nausea and / or vomiting.
|variable||Patients receiving trimethobenzamide (n = 31) (%)||Patients not receiving trimethobenzamide (n = 145) (%)|
|Degree of severity|
|Degree of severity|
|Discontinued the study because of nausea / vomiting||10||0|
aIndicates the proportion of patients who experience the side effect.
The sublingual apomorphine film has “the advantage of ease of use compared to the injectable form,” said Ondo. “I think the injectable form, based purely on anecdotal experience, might act a minute or two faster than the sublingual form, but overall I’d say the effectiveness in terms of potency of turning on and consistency of turning on is comparable.”
In addition to the known side effects of nausea, vomiting, and hypotension from using apomorphine, he said long-term use of the sublingual form can cause gum irritation. Two recommendations are to relocate the film and use a more basic toothpaste, e.g. B. one with baking powder, as the acidity of the apomorphine can cause irritation.
Commenting on the study to Medscape Medical News, Ludy Shih, MD, MMSc, of Boston University School of Medicine in Massachusetts noted that the drug label reports that “13-15% had oropharyngeal soft tissue swelling or pain … and 7% oral “ulcers and stomatitis.”
In addition, oral trimethobenzamide has been discontinued, although an injectable form is still available. This situation can be a problem, she said. “Most nausea drugs block dopamine, so … I would say they are contraindicated for treating Parkinson’s patients. But trimethobenzamide in particular is one that we reach for a lot … but that seems limited and can be expensive for patients. “
Regarding the study results, she said that they suggest that “not everyone needs a prophylactic intake of trimethobenzamide before ingesting the sublingual film with apomorphine.”
Although some patients experienced mild nausea, she said the fact that no needle is involved could attract some patients. In addition, this medication may be easier to take than giving an injection during an “off” episode.
Dr. Ondo is a consultant to Sunovion Pharmaceuticals, which sponsored the study. Dr. Shih had no relevant information.
International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2021. Abstract 394. September 2021.
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