Table 8: Additional Herbal-Drug Interactions of Note Herbal-Drug Interaction
Interaction Rating by Lexicomp and the Natural Medicines Comprehensive Database
Implications for Dentistry
St. John’s wort – P-glycoprotein substrates (doxycycline, tetracycline, and glucocorticoids) St. John’s wort – CYP3A4 substrates (clarithromycin, erythromycin, clindamycin, glucocorticoids, hydrocodone, and lidocaine)
Risk rating = D Level of evidence = B Severity = High Occurrence = Probable Risk rating = D Level of evidence = B Severity = High Occurrence = Possible
When P-glycoprotein is induced in the gastrointestinal tract, it can prevent the absorption of some medications. St. John’s wort can induce cytochrome CYP3A4 metabolism of drugs, causing decreased drug levels.
*CNS = Central nervous system. Note. dapted from “Lexicomp Online for Dentistry, by Wolters Kluwer, n.d., retrieved from http://webstore.lexi.com/ONLINE-Software-for- Dentists; and “About Natural Medicines Comprehensive Database,” by the Natural Medicines Comprehensive Database, n.d.a, retrieved from http://naturaldatabase.therapeuticresearch.com/Content.aspx?cs=&s=ND&page=aboutdbhtml&xsl=generic#ratings Acacia
gastrointestinal spasms, preventing nausea and vomiting, diarrhea, infections, the common cold, and loss of appetite. Topically, cassia cinnamon is used as a mosquito repellent. Despite all of these indications for use, and others, the medical literature has insufficient reliable evidence to confirm this herbal medication’s effectiveness. Cassia cinnamon seems to lower blood glucose levels and cause additive effects in patients treated with antidiabetic agents such that dose adjustments to diabetes medications are often necessary in patients who routinely consume this herbal medication (Akilen, Tsiami, Devendra, & Robinson, 2010; Bernardo et al., 2015; Crawford, 2009; Davis & Yokoyama, 2011; Khan, Safdar, Ali Khan, Khattak, & Anderson, 2003; Lu et al., 2012; Medagama, 2015). For type 1 or type 2 diabetes, 1 to 6 g (1 teaspoon = 5 g) of cassia cinnamon daily for up to 4 months has been used (Baker, Gutierrez-Williams, White, Kluger, & Coleman, 2008; Bernardo et al., 2015; Crawford, 2009; Khan et al., 2003; Medagama, 2015). From a dental perspective, be aware of patients with diabetes who may routinely consume cinnamon, and request that they do not suddenly start or stop taking this herbal medication before the dental procedure; OHCPs will want patients to be as stable as possible when they are seen in the office. As with all patients with diabetes, routine blood glucose monitoring is paramount, dental appointments should be kept relatively short, and patients should maintain their normal nutritional routine. In patients with controlled diabetes, this potential herbal-drug interaction can be easily managed. Cocoa Human research suggests that intake of cocoa can inhibit platelet adhesion, aggregation, and activity (Flammer et al., 2007; Flammer et al., 2012; Heptinstall, May, Fox, Kwik- Uribe, & Zhao, 2006; Innes, Kennedy, McLaren, Bancroft, & Belch, 2003; Murphy et al., 2003; Ostertag et al., 2013; Pearson et al., 2002; Rein et al., 2000) and increase aspirin- induced bleeding time (Zubair et al. 2011). Theoretically, cocoa may increase the risk of bleeding when used with other antiplatelet or anticoagulant drugs. Ephedra Ephedra may have an additive effect with drugs that prolong the QT interval. This additive effect may increase the risk of ventricular arrhythmias when combined with drugs such as the macrolide antibiotics (azithromycin, clarithromycin, and erythromycin; Maffè et al., 2013; McBride et al., 2004). Grapefruit Grapefruit juice can inhibit cytochrome CYP3A4 metabolism of drugs, causing increased drug levels and potentially
Acacia can reduce the absorption of amoxicillin, the doses of which should be separated by at least 4 hours (Eltayeb, Awad, Elderbi, & Shadad, 2004). Alcohol Metronidazole can cause a disulfiram-like reaction when taken with alcohol (Fjeld & Raknes, 2014; Fraser, 1997; Jang & Harris, 2007). Concomitant use of excessive amounts of alcohol- containing beverages, such as beer or wine, with acetaminophen can increase the risk of hepatotoxicity (de Oliveira, Rocha, & Abreu, 2014; Fraser, 1997; Jang & Harris, 2007; Thummel et al., 2000). Studies of concomitant use of beer with antihistamines, barbiturates, benzodiazepines, and tricyclic antidepressants found that the combination may increase sedative and other adverse effects (Fraser, 1997; Jang & Harris, 2007). Arsenic Up to 40% of patients treated with prescription arsenic trioxide have a prolonged QT interval on their electrocardiograms (Zhang et al., 2013). Theoretically, arsenic could have an additive effect when combined with drugs such as the macrolide antibiotics (azithromycin, clarithromycin, and erythromycin) that prolong the QT interval and potentially increase the risk of ventricular arrhythmias. Berberine Clinical research suggests that berberine can lower blood glucose levels (Wei, Zhang, et al., 2016; Wei, Zhao, et al., 2012; Yin, Xing, & Ye, 2008; Yu et al., 2015; Zhang et al., 2008; Zhang et al., 2010). Theoretically, therefore, berberine may have additive effects when used with antidiabetic drugs and could increase the risk of hypoglycemia. Bitter orange Bitter orange can significantly inhibit CYP3A4 metabolism of midazolam and can potentially increase drug levels and adverse effects (Loue & Tod, 2014; Malhotra, Bailey, Paine, & Watkins, 2001). Cinnamon There are many types of cinnamon. Cinnamomum verum (Ceylon cinnamon) and Cinnamomum aromaticum (cassia cinnamon, or Chinese cinnamon) are commonly used. In many cases, the cinnamon spice purchased in food stores contains a combination of these different types of cinnamon. So far, only cassia cinnamon has been shown to have any effect on blood glucose in humans. However, Cinnamomum verum also contains the hydroxychalcone polymer thought to be responsible for lowering blood sugar (Anderson et al., 2004; Bernardo et al., 2015; Medagama, 2015). Orally, cassia cinnamon is used for diabetes, flatulence, muscle and
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