2010年7月2日，Strativa制药公司宣布美国FDA已经批准其癌症辅助治疗药物昂丹司琼（ondansetron，Zuplenz）口服可溶薄膜制剂用于防止术后及癌症放化疗引起的恶心和呕吐。本品是首个获得FDA批准的昂丹司琼口服可溶薄膜制剂。

本品应用了一种新的、可靠且使用方便的新剂型，采用了MonoSol Rx公司的药物薄膜专利技术，不用喝水即可在口中溶解吸收。这样的设计对于吞咽不便的癌症患者十分有用。本品包括4 mg和8 mg两种剂量。本品有望在2010年第三季度上市。

本品的常见不良反应有头痛、头晕、心神不宁、疲劳、便秘以及腹泻等。使用本品后，头痛的发生率较安慰剂组有明显提高。

 
ondansetron，Zuplenz

Indication(s):

Prevention of nausea and vomiting associated with highly emetogenic chemotherapy, including cisplatin ≥50mg/m². Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy. Prevention of nausea and vomiting associated with radiotherapy in patients receiving total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen. Prevention of post-op nausea and/or vomiting.

Pharmacology:

Ondansetron is a selective antagonist of serotonin 5-HT₃ receptors. These receptors are located peripherally on vagal nerve terminals as well as centrally at the chemoreceptor trigger zone. The antiemetic effects of ondansetron may be due to the inhibition of serotonergic activity peripherally, centrally, or in both sites. However, cytotoxic chemotherapy appears to be associated with serotonin release from the enterochromaffin cells of the small intestine. Additionally, urinary excretion of 5-hydroxyindoleacetic acid, the main metabolite of serotonin, increases after cisplatin administration in parallel with the onset of emesis. Antagonism of the released serotonin at the 5-HT₃ receptors of the vagal nerve terminals may inhibit the vomiting reflex.

Clinical Trials:

Oral ondansetron was demonstrated to be statistically significantly superior to placebo in the prevention of chemotherapy-induced nausea and vomiting in two double-blind, monotherapy trials in patients receiving highly emetogenic chemotherapy, as well as multiple studies in adult and pediatric patients receiving initial and repeat courses of moderately emetogenic chemotherapy. The first trial compared oral doses of ondansetron in 357 adult patients receiving highly emetogenic chemotherapy regimens containing cisplatin ≥50mg/m². At primary endpoint, 66% of patients receiving ondansetron 24mg once daily, 55% receiving 8mg twice daily, and 55% receiving 32mg once daily completed the 24-hour study period with no emetic episodes and no rescue antiemetic medications. All 3 doses were shown to be significantly superior to placebo.

In a study conducted in 67 patients receiving moderately emetogenic cyclophosphamide-based chemotherapy containing doxorubicin, 61% of patients receiving ondansetron experienced no emetic episodes compared to 6% in the placebo group (p<0.001). Uncontrolled studies evaluating ondansetron given during subsequent chemotherapy courses (396 total) in 148 patients showed that ondansetron prevented emesis following 79% of re-treatment courses. Three open-label, uncontrolled trials were performed in 182 children 4–18 years old with cancer who were given a variety of cisplatin or non-cisplatin regimens. An initial dose of ondansetron HCl injection was followed by administration of oral ondansetron for 3 days. In these studies, 58% of the 170 evaluable patients had no emetic episodes on day 1.

Three double-blind studies evaluated the efficacy of oral ondansetron in the prevention of radiation-induced nausea and vomiting. The first randomized study, involving 20 patients, showed that oral ondansetron given before each fraction of total body radiation was significantly more effective than placebo in preventing emesis. The second study compared oral ondansetron to metoclopramide in 105 patients receiving single high-dose radiotherapy over an anterior or posterior field size of ≥80cm² to the abdomen. Ondansetron was significantly more effective than metoclopramide in achieving complete control of emesis (0 emetic episodes). In a third trial, involving 135 patients, oral ondansetron was significantly more effective in achieving complete control of emesis compared to prochlorperazine in patients receiving a 1- to 4-week course of fractionated radiotherapy over a field size of >100cm² to the abdomen.

The efficacy of oral ondansetron in preventing post-op nausea and vomiting was studied in two double-blind trials involving 865 female patients undergoing inpatient surgical procedures. Patients received ondansetron one hour prior to induction of anesthesia. Ondansetron was shown to be significantly more effective than placebo in preventing post-op nausea and vomiting.

Legal Classification:

Rx

Adults:

Allow each film to dissolve completely before taking the next film. Dissolve on tongue for 4–20 secs before swallowing. Highly emetogenic: 24mg (given successively as three 8mg films) 30mins before start of single-day chemotherapy (multi-day, single-dose not studied). Moderately emetogenic: 8mg every 8hrs for 2 doses beginning 30mins before chemotherapy, then 8mg every 12hrs for 1–2 days after chemotherapy completed. Total body irradiation: 8mg 1–2hrs before each fraction of radiotherapy administered each day, then every 8hrs. Single high-dose fraction radiotherapy to abdomen: 8mg 1–2hrs before radiotherapy, then 8mg every 8hrs after 1st dose for 1–2 days after radiation completed. Daily fractionated radiotherapy to abdomen: 8mg 1–2hrs before radiotherapy, then 8mg every 8hrs after 1st dose for each day of radiotherapy. Post-op prophylaxis: 16mg (given successively as two 8mg films) 1hr before induction of anesthesia. For all: severe hepatic dysfunction: max 8mg/day.

Children:

Highly emetogenic chemotherapy, radiotherapy, post-op prophylaxis or <4yrs of age: not recommended. Allow each film to dissolve completely before taking the next film. Dissolve on tongue for 4–20 secs before swallowing. 4–11yrs: moderately emetogenic: 4mg every 4hrs for 3 doses beginning 30mins before chemotherapy, then 4mg every 8hrs for 1–2 days after chemotherapy completed.

Contraindication(s):

Concomitant apomorphine: risk of profound hypotension or loss of consciousness.

Warnings/Precautions:

May mask progressive ileus and/or gastric distention (esp. after abdominal surgery or patients with chemotherapy-induced nausea/vomiting). Do not use as alternative to nasogastric suction. Hepatic dysfunction. Pregnancy (Cat.B). Nursing mothers.

Interaction(s):

Antagonized by potent CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampicin). May reduce analgesic activity of tramadol.

Adverse Reaction(s):

Headache, malaise/fatigue, constipation, diarrhea, rash; rare: bronchospasm, anaphylaxis, transient ECG changes, including QT prolongation (esp. IV form).

How Supplied:

Soluble film—10

Last Updated:

10/7/2010