Table 3.
Adverse event management strategies—gastrointestinal
 Gastrointestinal
|
|---|
| Diarrhea |
| Prophylaxis |
| Instruct patients to monitor food and fluid intake [113] |
| Recommended water intake per day (from all beverages and food) [114]: 2.7 L (91 oz) for women, 3.7 L (125 oz) for men |
| Advise patients to keep a stool diary and to promptly report diarrhea to their healthcare provider [63, 115] |
| Advise patients to avoid foods that may cause GI events such as lactose-containing foods, caffeine, high-fat or high-fiber food (e.g., nuts, seeds, legumes), and raw fruit and vegetables [83, 84] |
| Implement dehydration prevention management through oral rehydration with electrolytes [115] |
| Supportive care |
| Administer loperamide at the first sign of diarrhea [57, 115, 116] |
| 4 mg orally followed by 2 mg every 2 h until 2–24 h after last bowel movement (maximum of 16 mg in 24 h) |
| For chronic diarrhea, 2–4 mg twice daily, titrated as needed |
| Alternatives to loperamide include diphenoxylate and tincture of opium [57] |
| Implement supportive dietary modifications (continuous oral hydration; correction of fluid and electrolytes; small, frequent meals; avoid lactose-containing food and drink) [83, 84] |
| The BRAT (bananas, rice, applesauce, toast) diet may help to alleviate mild diarrhea [84] |
| If there are signs of severe dehydration, administer IV fluid replacement (isotonic saline or balanced salt solution) [83] |
| Rule out non-treatment-related causes (e.g., infectious diarrhea) [83] |
| Decreased appetite |
|---|
| Prophylaxis |
| Advise patients to monitor their appetite and weight [63] |
| Encourage patients to consume high-protein, calorie-rich food; fruit and vegetables; nutritional supplements that they may snack on throughout the day [63, 81] |
| Advise patients to pre-prepare and freeze nutritional, preferred food [81] |
| Supportive care |
| Treat underlying nausea [63] |
| Consider involving a dietitian, who may recommend scheduled eating times [117] |
| Recommend a high-calorie diet [63] |
| Provide dietary education alongside dietary modifications and/or nutritional/vitamin supplements [118] |
| Use a pharmacologic agent to stimulate appetite, such as a CB1 receptor agonist (dronabinol) [63, 119], systemic corticosteroid (methylprednisolone) [74, 118], progestin (megestrol acetate) [63, 118], or mirtazapine [89, 90] |
| Nausea/vomiting |
|---|
| Prophylaxis |
| Assess risk factors for nausea/vomiting prior to treatment [120] |
| Metoclopramide may be administered prophylactically [87] |
| Advise patients to avoid foods that are overly sweet, greasy, fried, or spicy [81] |
| Supportive care |
| Antiemetic agents such as dopamine receptor antagonists (e.g., metoclopramide, prochlorperazine) or 5-HT3 receptor agonists (e.g., ondansetron) are recommended for management of nausea or vomiting [87, 88] |
| Certain NK-1 receptor agonists (e.g., aprepitant and netupitant) and dexamethasone are inducers, inhibitors, and/or substrates of CYP3A4 and thus could alter cabozantinib exposure [87, 88]; however, the potential for ondansetron to prolong the QT interval must also be considered [121] |
| There is moderate evidence for olanzapine, an antipsychotic drug that blocks multiple neurotransmitters, as an antiemetic in this setting [87] |
| Mucosal inflammation/stomatitis |
|---|
| Prophylaxis |
| A comprehensive dental examination should be conducted prior to treatment to identify potential complications [85] |
| Mitigation of potential risk factors [85, 122] |
| Modification of ill-fitting dentures |
| Appropriate care for pre-existing dental problems such as caries, ulcers, etc. |
| Regular oral assessments should be conducted throughout treatment [85, 122] |
| Educate patients on good oral hygiene and oral care protocols, including written instructions [122] |
| The oral cavity should be washed using saline-containing mouthwash up to four times daily, and dentures should be regularly cleaned [85] |
| Painful stimuli (e.g., smoking, alcohol, hot food/drink, sharp or spicy food) should be avoided [85, 123] |
| Supportive care |
| Treat pain with doxepin 0.5% mouthwash or viscous lidocaine 2% [85, 124] |
| Lactobacillus lozenges may be used to reduce inflammation [125] |
| Obtain bacterial/viral culture if oral infection is suspected and treat infection as clinically indicated [126] |
5-HT3 5-hydroxytryptamine, CB1 cannabinoid, CYP3A4 cytochrome P450 3A4, GI gastrointestinal, IV intravenous, NK neurokinin