Skip to main content

Bitter Orange

Scientific Name(s): Citrus aurantium L.
Common Name(s): Bigarade, Bitter orange, Bitter orange flower, Bitter orange peel, Green orange, Kijitsu, Laranja-amarga, Laranja-azeda, Laranja-cavalo, Neroli flowers, Neroli oil, Seville orange, Shangzhou zhiqiao, Sour orange, Zhi qiao, Zhi shi

Medically reviewed by Last updated on Nov 30, 2022.

Clinical Overview


Pharmacological actions for C. aurantium include antispasmodic, sedative, demulcent, digestive, tonic, and vascular stimulant; as an anti-inflammatory, antibacterial, and antifungal agent; and for reducing cholesterol. Clinical data are limited. Most medical literature focuses on the plant's safety and efficacy in OTC weight loss supplement formulations, with studies using small sample sizes and often focusing on combination products. Therefore, no recommendations for any indication can be made.


Follow manufacturer's dosage guidelines because synephrine content may vary in supplement formulations.


Because of potentially additive effects, avoid synephrine use in patients with hypertension, tachyarrhythmia, hyperthyroidism, or narrow-angle glaucoma.


Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.


C. aurantium inhibits intestinal CYP3A4 and intestinal efflux in the small intestine and may interact with numerous drugs.

Adverse Reactions

Bitter orange may cause photosensitization, particularly in people with fair skin. There are numerous case reports of adverse cardiac reactions associated with C. aurantium extract use.


Bitter orange is considered generally recognized as safe (GRAS) by the US Food and Drug Administration (FDA) when consumed in amounts found in foods. Medical literature primarily documents cardiovascular toxicity, especially due to the stimulant amines synephrine, octopamine, and N-methyltyramine, which may cause vasoconstriction as well as increased heart rate and blood pressure.

Scientific Family

  • Rutaceae


In addition to the hybrid C. aurantium, many varieties and subspecies have been described. Bitter orange includes the varieties amara, bergamia, bigaradia, and vulgaris Risso. It is also known as Aurantii pericarpium in pharmaceutical Latin. Bitter orange probably originated in Southeast Asia. During the 10th and 11th centuries, traders introduced the plant to several Mediterranean regions and it was widely cultivated. The plant is grown commercially in southern Europe, particularly in Spain and Portugal, as well as in Israel and various islands of the Caribbean. This evergreen tree grows up to 10 m in height and has long, leathery, dark green, gland-dotted leaves and scented white flowers with 5 to 8 petals. The membranes and pulp of the orange fruit are bitter and sour. The tree is very resistant to plant diseases compared with other citrus trees.(1, 2, 3, 4, 6, 7, 8, 9)


The Spanish and Portuguese brought bitter orange to the Americas in the 1500s. In Europe, bitter orange flowers and oil have been used as sedatives and as prophylactics for GI complaints, nervous conditions, gout, sore throat, and insomnia. The plant has been used to treat toxic and anaphylactic shock, heart conditions, cardiac exhaustion, and cancer.(1, 3) In Chinese folk medicine, bitter orange was used as a tonic and carminative to treat dyspepsia. Dried bitter orange was used to treat ptosis of the uterus and anus, to relieve abdominal distention and diarrhea, and for blood in feces.(1, 10) In modern times, the Chinese use "zhi shi" for its positive inotropic effects, particularly for treating shock.(11) In Brazilian folk medicine, bitter orange was used as an anticonvulsant and to treat anxiety and insomnia.(12) Uses in the United States have included prevention of skin, breast, and colon cancer. In Haiti, the plant has been used as an antiseptic and purgative; in Turkey, it has been used as a narcotic, sedative, and as treatment for scurvy. The plant has been used as a remedy for treatment-resistant fungal skin diseases, and the tincture or extract has been used for treating heartburn.(13)

Bitter orange oil is used to flavor many food products, alcoholic and nonalcoholic beverages, frozen dairy desserts, candy, baked goods, gelatins and puddings, meat and meat products, and condiments and relishes.(1)

Powdered extracts of the dried immature fruit or peel are used as an alternative to ephedra in many dietary supplements and herbal weight loss products.(13) On April 11, 2004, the FDA banned the sale of dietary supplements containing ephedrine alkaloids because of safety concerns. Many manufacturers of weight loss supplement formulations now offer ephedra-free products containing bitter orange extract. Because bitter orange extract contains a sympathomimetic, the safety and efficacy of these formulations are closely monitored.(10)


A number of phytochemicals of medicinal interest have been found in the plant, including in the leaf, flower, fruit, seeds, and peel.(13, 14)


The essential or volatile oil (0.2% to 0.4%) contains more than 90% monoterpene hydrocarbons, alcohols, flavonoid glycosides, aldehydes, ketone-free acids, esters, coumarins, and tetranortriterpenoids (limonin).(1, 15, 16, 17)


The essential or volatile oil (0.05% to 0.5%) contains monoterpene hydrocarbons, alcohols, and flavonoid glycosides similar to those contained in the leaf. Synephrine, 5,8-epidioxyergosta-6,22-dien-3 beta-ol, adenosine, asparagine, tyrosine, valine, isoleucine, alanine, beta-sitosterol, and beta-daucosterol are also found in the flowers.(1, 15, 18)


The fruit contains octopamine, synephrine, and tyramine. Synephrine is the main chemical constituent in the fruit (0.1% to 0.35%). The fruit primarily contains the glycosylated flavanones naringin and neohesperidin.(19, 20)


17-beta-D-glucopyranosides have been isolated from the seeds.(21, 22)


The essential or volatile oil (2%) contains monoterpene hydrocarbons (90% limonene), bitter and nonbitter flavonoids; furanocoumarins; flavonoid glycosides; mineral salts; pectin; organic acids; vitamins A, B1, and C; and carotenoid pigments.(1, 15, 23)

Additional coumarin glycosides have also been isolated from C. aurantium.(24, 25)

Numerous weight loss products contain adrenergic amines structurally similar to ephedrine alkaloids, including synephrine, octopamine, tyramine, N-methyltyramine, and hordenine.(26) Some literature documents the importance of distinguishing the alkaloid constituents in bitter orange because of the potential alpha-adrenergic and beta-adrenergic activity, particularly para-synephrine versus meta-synephrine.(27)

There are 6 possible isomers of synephrine and disagreement as to whether bitter orange contains para-synephrine, meta-synephrine, or both.(27) The distinction is important because there are potential differences in pharmacological properties that may affect safety and efficacy of commercial products. Para-synephrine occurs naturally in the human body, is an alpha-adrenergic agonist, and has some beta-adrenergic properties. The Canadian government has enacted dosage and usage restrictions for the para-synephrine alkaloid of C. aurantium. Meta-synephrine (often referred to as phenylephrine), an isomer of para-synephrine, is also an alpha-adrenergic agonist and has some beta-adrenergic agonist properties.(26, 28)

Uses and Pharmacology

There are numerous pharmacological actions recognized for C. aurantium. The leaf and flower have been studied for anticancer activity and as antispasmodics and sedatives. The peel has been studied as a digestive aid, demulcent, tonic, and vascular stimulant; as an anti-inflammatory, antibacterial, and antifungal agent; and for reducing cholesterol.(1, 15)

The most current literature focuses on the plant's safety and efficacy in OTC weight loss supplement formulations in which synephrine content may vary. Manufacturer dosage guidelines should be followed.


In vitro/animal data

In mice, the anxiolytic and sedative effects of bitter orange extract were compared with chlordiazepoxide 10 mg/kg, valproic acid 400 mg/kg, or diazepam 1.2 mg/kg. Mice were treated orally with 1 g/kg of the extract. After 30 minutes, each animal was injected with sodium pentobarbital 40 mg/kg. Sedative effects were measured in seconds by induction time (time from injection to loss of rightness reflex) and duration of sleep (time from loss of rightness reflex to awakening). The extract significantly increased the hypnotic effect of pentobarbital (P < 0.05). Several tests were used to examine the anxiolytic effect of the extract; however, the extract used in the elevated plus maze test produced an anxiolytic effect (P < 0.05).(4) The anxiolytic effects may be attributed to C. aurantium's effects on 5-HT1A receptors.(29)

Clinical data

In a study of 60 patients undergoing surgery, pretreatment with 1 mL/kg of C. aurantium blossom reduced preoperative anxiety, as noted by reductions in State-Trait Anxiety Inventory and Amsterdam Preoperative Anxiety and Information Scale scores. These parameters remained unchanged in the control group.(30) State- and trait-anxiety scores were observed to be statistically significantly improved with administration of bitter orange compared to placebo, but not significantly different to that of lavender, in 156 postmenopausal women enrolled in a triple-blind, randomized, controlled trial. At week 8, adjusted mean state- and trait-anxiety scores were each reduced by 4% compared to controls. The side effect that was higher with bitter orange than placebo was palpitations (4.2% vs 2.1%, respectively) Bitter orange capsules contained 500 mg whole dried herb (limonene 20%, linalool 32%, flavonoid 5%), no volatile oils, and were taken twice daily.(67)

In a randomized study of pregnant women, gauzes soaked in C. aurantium applied to the collar every 30 minutes during labor were found to decrease anxiety at 3 to 4 cm dilation (P < 0.001) and at 6 to 8 cm dilation (P < 0.001) compared with controls.(31)


Clinical data

The American Urology Association's update guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome (2022) states that self-care practices and behavioral modifications that can improve symptoms should be discussed and implemented as feasible, which includes avoidance of certain foods known to be common bladder irritants like citrus products (clinical principle).(137)


C. aurantium extract was found to improve learning and memory impairment caused by scopolamine in rats.(47)


In mice, para-synephrine may have antidepressant activity, as documented by immobility tests.(44) The antidepressant effects may be greater with the S isomer of para-synephrine.(45)

Effects on glucose

p-Synephrine was found to reduce glucose suppression as well as glucose-6-phosphatase and phosphoenol pyruvate carboxykinase levels in H4IIE rat liver cells.(46)

Labor pains

In a randomized, open-label study of primiparous women, gauzes soaked in C. aurantium applied to the collar every 30 minutes during labor were found to decrease pain severity at 3 to 4 cm dilation (P < 0.05), 5 to 7 cm dilation (P < 0.05), and 8 to 10 cm dilation (P < 0.05) compared with controls.(48)

Liver Injury

5-hydroxy-6,7,3’,4’-tetramethoxyflavone and limonexic acid, compounds derived from C. aurantium, were found to exert protective effects against carbon tetrachloride-induced liver injury as tested in human HL-7702 cells.(49)

Weight loss

Synephrine alkaloids increase energy expenditure and decrease food intake through activation of alpha- and beta-adrenergic receptors. Synephrine alkaloids may also decrease food intake by reducing gastric motility.(14, 26, 27, 32, 33, 34)

Animal data

Several studies have demonstrated that synephrine alkaloids reduce food intake and white fat cells in rats, hamsters, and dogs. Synephrine also promotes lipolysis in adipocytes through beta-adrenergic stimulation.(13, 26)

In a study of rats, the combination of C. aurantium 5.6 mg/kg with Rhodiola rosea 20 mg/kg was found to cause feeding suppression as well as visceral fat reduction, but not body weight reduction. The combination also caused a decrease in plasma norepinephrine levels.(35)

Clinical data

In a 6-week, double-blind, placebo-controlled, randomized study, 23 subjects with body mass indices more than 25 kg/m2 were assigned to 1 of 3 groups. Group A received a mixture containing C. aurantium 975 mg (6% synephrine alkaloid), St. John's wort 900 mg (3% hypericin), and caffeine 528 mg; group B received a maltodextrin placebo; and group C was a control without placebo. All patients completed a 3-day/week exercise program and received American Heart Association dietary counseling. Outcomes were measured at baseline and at 3 and 6 weeks and included changes in weight, percent body fat, fat mass, and basal metabolism. Patients in group A lost an average of 1.4 kg (P < 0.05); group B lost an average of 0.9 kg (P < 0.1); group C lost an average of 0.4 kg. No changes were noted in cardiovascular activity (ie, changes in laboratory tests, blood pressure, heart rate, or electrocardiograms). Reviewers of this study note that although the authors performed a statistical analysis of within-group changes in weight, they did not perform the same comparison among groups. No evidence was presented regarding changes in cardiovascular activity or adverse reactions.(8, 34, 36) Another trial involving 15 subjects examined the cardiovascular effects of a single dose of a commercially available product containing bitter orange, standardized to 6% synephrine. Outcome measures included changes in systolic and diastolic blood pressure and heart rate measured at baseline and every hour for 6 hours after oral administration. Changes or increases were found in systolic and diastolic blood pressure and heart rate for up to 5 hours after administration of a single dose of synephrine.(37)

Changes in blood pressure and pulse were examined in 12 subjects in a randomized, open-label, placebo-controlled, crossover design study. Patients consumed either C. aurantium juice (synephrine 13 to 14 mg) or a water placebo. Blood pressure and pulse were measured hourly for 5 hours in patients who consumed the juice. It was determined that C. aurantium juice had no effects on blood pressure or pulse.(38) Another clinical trial in 18 subjects documented no changes in the QT interval or blood pressure after a single oral dose of 27 mg of meta-synephrine or para-synephrine.(39)

Changes in cardiovascular activity (ie, systolic and diastolic pressure, heart rate) were examined in 10 subjects in a randomized, double-blind, placebo-controlled crossover study. Two commercial supplements were tested in patients (C. aurantium alone [synephrine 45 mg] or a multicomponent supplement containing synephrine 5.5 mg), with a 1-week washout period between treatments. Patients using the multicomponent drug supplement experienced clinical and statistical changes in cardiovascular activity. However, because an 8-fold higher dose of synephrine had no effect on blood pressure, it was concluded that the pressor effects were not caused by C. aurantium but by other stimulants in the supplement.(40) The same research team documented similar cardiovascular stimulant activity in another study in 10 healthy normotensive adults.(41) A study examining the physiological effects of a multicomponent drug supplement containing synephrine 6 mg found no changes in 10 sedentary men with more than 20% body fat when evaluated at rest and during treadmill walking.(42)

A 60-day, double-blind, placebo-controlled safety study (n = 67 evaluable) was conducted in moderately overweight adults (mean body mass index, 30.8). The 3 treatment assignments were p-synephrine 24.4 mg (Advantra Z), a combination product (p-synephrine 24.6 mg plus hesperidin 50.1 mg plus naringin 288 mg), or placebo; participants were instructed to take 1 capsule twice daily. Compared with baseline, there were no differences among the 3 groups for any blood chemistry changes, including lipid profiles, liver enzymes, serum electrolytes, and complete blood counts. No differences were seen among the 3 groups for systolic or diastolic blood pressure compared with baseline. The placebo group experienced a significant reduction from baseline in heart rate compared with each of the active treatments (P = 0.01); heart rate in the p-synephrine group was significantly lower than with the combination product (P = 0.01). No data were provided on body weight changes, and no serious adverse reactions were seen.(43)


Follow manufacturer's dosage guidelines because synephrine content may vary in supplement formulations. There is evidence of effective weight loss at a synephrine dose of 32 mg/day, and doses up to 80 mg/day have been used for treatment of obesity.(5, 26, 33) Another reference suggests 4 to 6 g of dried peel (C. aurantium) administered as a tea.(9)

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.(13) In a study of rats, there were no developmental toxicities with synephrine doses up to 100 mg/kg.(50)


C. aurantium inhibits intestinal CYP3A4 and intestinal efflux (P-glycoprotein) in the small intestine and may interact with numerous drugs.(5)

Antivirals: In an open-label, crossover study in 13 healthy volunteers, subjects received indinavir 800 mg every 8 hours for 1 day and a single 800 mg dose the next morning with 240 mL of water or Seville orange juice.(52) Compared with water, taking indinavir with Seville orange juice prolonged the time to reach the indinavir Cmax by 50% (from 1.25 to 1.87 hours). This change is not likely to be clinically important.

Aripiprazole: CYP3A4 inhibitors (weak) may increase the serum concentration of aripiprazole. Monitor therapy. Further dose reductions may be recommended with concomitant use of a CYP2D6 inhibitor. Aripiprazole dose reductions may be recommended in CYP2D6 "poor metabolizers." Aripiprazole dose reduction is not recommended when used as adjunctive therapy for major depressive disorder.(68, 69, 70, 71, 72)

Atomoxetine: Atomoxetine may enhance the hypertensive effect of sympathomimetics. Atomoxetine may enhance the tachycardic effect of sympathomimetics. Monitor therapy.(73, 74, 75, 76, 77, 78, 79)

Bosutinib: Bitter orange may increase the serum concentration of bosutinib. Avoid combination.(52, 53, 54, 80, 81)

Calcium channel blockers: In a randomized, crossover study involving 10 healthy volunteers taking a felodipine 10 mg extended-release tablet with 240 mL of Seville orange juice, the area under the curve and Cmax of felodipine increased 76% and 61%, respectively, compared with felodipine taken with water.(53)

Cannabinoid: Cannabinoid-containing products may enhance the tachycardic effect of sympathomimetics. Monitor therapy.(82, 83, 84, 85, 86, 87, 88)

Cocaine (topical): Cocaine (topical) may enhance the hypertensive effect of sympathomimetics. Consider therapy modification.(89, 90, 91, 92, 93, 94, 95, 96)

Colchicine: Bitter orange may decrease the serum concentration of colchicine. No action needed.(53, 109, 130, 135)

Dextromethorphan: In a study of 11 healthy volunteers, dextromethorphan 30 mg taken with 200 mL of Seville orange juice increased the bioavailability of dextromethorphan from 0.1 to 0.46 compared with dextromethorphan taken with water.(54)

Dofetilide: Inhibitors (weak) may increase the serum concentration of dofetilide. Monitor therapy.(97, 98, 99)

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of doxofylline. Monitor therapy.(100)

Felodipine: CYP3A4 inhibitors (weak) may increase the serum concentration of felodipine. No action needed.(53, 131, 132, 133, 134)

Flibanserin: CYP3A4 inhibitors (weak) may increase the serum concentration of flibanserin. Monitor therapy.(101)

Guanethidine: Guanethidine may enhance the arrhythmogenic effect of sympathomimetics. Guanethidine may enhance the hypertensive effect of sympathomimetics. Monitor therapy.(102, 103, 104, 105, 106, 107)

Ibrutinib: Bitter orange may increase the serum concentration of ibrutinib. Avoid combination.(53, 108, 109)

Indinavir: Bitter orange may increase the serum concentration of indinavir. No action needed.(136)

Ivacaftor: Bitter orange may increase the serum concentration of ivacaftor. Avoid combination.(53, 109, 110)

Linezolid: Linezolid may enhance the hypertensive effect of sympathomimetics. Consider therapy modification.(111, 112)

Lomitapide: CYP3A4 inhibitors (weak) may increase the serum concentration of lomitapide. Consider therapy modification.(113, 114)

Lonafarnib: Bitter orange may increase the serum concentration of lonafarnib. Avoid combination.(129)

Nimodipine: CYP3A4 inhibitors (weak) may increase the serum concentration of nimodipine. Monitor therapy.(115)

Olaparib: Bitter orange may increase the serum concentration of olaparib. Avoid combination.(53, 109, 116)

Pimozide: CYP3A4 inhibitors (weak) may increase the serum concentration of pimozide. Avoid combination.(117, 118, 119, 120)

Saquinavir: Bitter orange may increase the serum concentration of saquinavir. Monitor therapy.(109, 121)

Sildenafil: Bitter orange may increase the serum concentration of sildenafil. No action needed.(130)

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of solriamfetol. Monitor therapy.(122)

Sympathomimetics: Sympathomimetics may enhance the adverse/toxic effect of other sympathomimetics. Monitor therapy.(123, 124)

Tedizolid: Tedizolid may enhance the hypertensive effect of sympathomimetics. Tedizolid may enhance the tachycardic effect of sympathomimetics. Monitor therapy.(112, 125, 126, 127)

Venetoclax: Bitter orange may increase the serum concentration of venetoclax. Avoid combination.(128)

Adverse Reactions

Bitter orange may cause photosensitization, particularly in people with fair skin.(5, 11) Numerous case reports of adverse reactions and events associated with bitter orange have been reported to the FDA; however, many of the cases occurred with dietary supplements containing bitter orange in combination with other products, such as caffeine, making the cause and association more difficult to determine, particularly in cases of cardiovascular adverse reactions.(55, 56) A review of the literature found that p-synephrine alone or in combination with other products did not increase heart rate or blood pressure but did increase resting metabolic rate and energy expenditure.(57)

Cardiovascular system

A 38-year-old man suffered an ischemic stroke after taking a dietary supplement containing synephrine daily for 1 week. The patient had no notable medical history or atherosclerotic risk factors and took no medications. Other possible causes of ischemic stroke proved to be unlikely.(58)

A 52-year-old woman developed unremitting tachycardia after consuming a daily dose of C. aurantium extract 500 mg (synephrine 30 mg/day). She had been taking thyroxine 50 mcg/day for hypothyroidism for about 10 years.(59)

Another case report documented a 55-year-old woman with an acute lateral wall myocardial infarction. The patient was taking a dietary supplement containing C. aurantium 300 mg for weight loss for 1 year. She had numerous risk factors for myocardial infarction.(4)

A 22-year-old male experienced a non-ST–elevation myocardial infarction following 3 weeks of ingesting 2 dietary supplements containing C. aurantium and 1,2-dimethylamylamine, among other ingredients, daily prior to exercise. He had no family history of early coronary artery disease or sudden death. Upon treatment and discontinuation of the supplement, he was symptom free with no evidence of ischemia.(28)

A 28-year-old man suffered a massive myocardial infarction after abusing synephrine tablets (dose not provided).(13)

There is also a case report of variant angina occurring with bitter orange.(60)

Muscular system

A 22-year-old man developed rhabdomyolysis after consuming a synephrine-containing weight-loss formula. While exercising, the patient developed fatigue, dehydration, and myalgias.(61)


Bitter orange is considered GRAS by the FDA when consumed in amounts found in foods.(5)

Animal studies document the potential cardiac toxicity. N-methyltyramine increased renal and cerebral resistance in dogs. Additionally, synephrine induced dose-dependent portal hypotensive effects and ventricular arrhythmias with enlargement of QRS complex in rats.(6, 32, 62, 63, 64)

C. aurantium contains the stimulant amines synephrine, octopamine, and N-methyltyramine.(65) These amines may cause vasoconstriction as well as increased heart rate and blood pressure. Sympathomimetics also cause resistant hypertension.(66)

Because of potentially additive effects, avoid synephrine use in patients with hypertension, tachyarrhythmia, hyperthyroidism, or narrow-angle glaucoma.

An overdose of synthetic synephrine in children caused nausea, vomiting, irritation, tachycardia, and a rapid increase in blood pressure.(13)

Index Terms

  • Aurantii pericarpium
  • Citrus aurantium subsp. amara
  • Citrus aurantium subsp. bigaradia
  • Citrus bergamia
  • Citrus vulgaris



This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

More about bitter orange

1. Khan IA, Abourashed EA. Leung's Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics. 3rd ed. Hoboken, NJ: Wiley; 2009.
2. Bissett N, ed. Herbal Drugs and Phytopharmaceuticals. Stuttgart, Germany: Scientific Publishers; 1994.
3. Huang KC. The Pharmacology of Chinese Herbs. 2nd ed. Boca Raton, Florida: CRC Press; 1999.
4. Orange. In: The Encyclopedia Americana International Edition. Danbury, CT: Grolier Incorporated; 1989:9-11.
5. Ulbricht C, Costa D, Giese N, et al. An evidence-based systematic review of bitter orange (Citrus aurantium) by the Natural Standard Research Collaboration. J Diet Suppl. 2013;10(4):391-431.24237193
6. Chevallier A. The Encyclopedia of Medicinal Plants. New York, NY: DK Publishing; 1996.
7. Bent S, Padula A, Neuhaus J. Safety and efficacy of Citrus aurantium for weight loss. Am J Cardiol. 2004;94(10):1359-1361.15541270
8. Blumenthal M. Bitter orange peel and synephrine. HerbalGram. 2005;66. Accessed February 23, 2015.
9. van Wyk BE, Wink M, eds. Medicinal Plants of the World. Portland, OR: Timber Press Inc; 2004.
10. Nykamp DL, Fackih MN, Compton AL. Possible association of acute lateral-wall myocardial infarction and bitter orange supplement. Ann Pharmacother. 2004;38(5):812-816.15026566
11. Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine; Expanded Commission. Newton, MA: Integrative Medicine Communications; 2000.
12. Carvalho-Freitas M, Costa M. Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L. Biol Pharm Bull. 2002;25(12):1629-1633.12499653
13. National Toxicology Program. Bitter orange (Citrus aurantium var. amara) extracts and constituents (+/−) p-synephrine [CAS No. 94-07-5] and (+/−) p-octopamine [CAS No. 104-14-3]. Review of the Toxicological Literature. 2004:1-73. Accessed February 23, 2015.
14. Slezak T, Francis PS, Anastos N, Barnett NW. Determination of synephrine in weight-loss products using high performance liquid chromatography with acidic potassium permanganate chemiluminescence detection. Anal Chim Acta. 2007;593(1):98-102.17531829
15. Arias BA, Ramón-Laca L. Pharmacological properties of citrus and their ancient and medieval uses in the Mediterranean region. J Ethnopharmacol. 2005;97(1):89-95.15652281
16. Del Rio JA, Benavente O, Castillo J, Borrego F. Neodiosmin, a flavone glycoside of Citrus aurantium. Phytochemistry. 1992;31(2):723-724.
17. Carnat A, Carnat AP, Fraisse D, Lamaison JL. Standardization of the sour orange flower and leaf. Ann Pharm Fr. 1999;57(5):410-414.10520514
18. Huang S, Hu S, Shi J, Yang Y. Studies on chemical constituents from the flower of Citrus aurantium. Zhong Yao Cai. 2001;24(12):865-867.11917843
19. Pellati F, Benvenuti S, Melegari M. High-performance liquid chromatography methods for the analysis of adrenergic amines and flavanones in Citrus aurantium L. var. amara. Phytochem Anal. 2004;15(4):220-225.15311840
20. Synephrine. In: Buckingham J, exec ed. Dictionary of Natural Products, Vol 5: R-Z. New York: Chapman and Hall;1994:5307-5308.
21. Bennett RD, Miyake M, Ozaki Y, Hasegawa S. Limonoid glucosides in Citrus aurantium. Phytochemistry. 1991;30(11):3803-3805.
22. Bennett RD, Hasegawa S. Isolimonic acid, a new citrus limonoid. Phytochemistry. 1980;19(11):2417-2419.
23. Sarin PS, Seshadri TR. New components of Citrus aurantium. Tetrahedron. 1960;8:64-66.
24. McHale D, Khopkar PP, Sheridan JB. Coumarin glycosides from Citrus flavedo. Phytochemistry. 1987;26:2547-2549.
25. Fugh-Berman A, Myers A. Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research. Exp Biol Med (Maywood). 2004;229(8):698-704.15337824
26. Haaz S, Fontaine KR, Cutter G, Limdi N, Perumean-Chaney S, Allison DB. Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update. Obesity Rev. 2006;7(1):79-88.16436104
27. Allison DB, Cutter G, Poehlman ET, Moore DR, Barnes S. Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain? Int J Obes (Lond). 2005;29(4):443-446.15700046
28. Smith TB, Staub BA, Natarajan GM, Lasorda DM, Poornima IG. Acute myocardial infarction associated with dietary supplements containing 1,3-dimethylamylamine and Citrus aurantium. Tex Heart Inst J. 2014;41(1):70-72.24512406
29. Costa CA, Cury TC, Cassettari BO, Takahira RK, Flório JC, Costa M. Citrus aurantium L. essential oil exhibits anxiolytic-like activity mediated by 5-HT1A-receptors and reduces cholesterol after repeated oral treatment. BMC Complement Altern Med. 2013;13:42.23432968
30. Akhlaghi M, Shabanian G, Rafieian-Kopaei M, Parvin N, Saadat M, Akhlaghi M. Citrus aurantium blossom and preoperative anxiety. Rev Bras Anestesiol. 2011;61(6):702-712.22063371
31. Namazi M, Akbari SAA, Mojab F, Talebi F, Majd HA, Jannesari S. Aromatherapy with Citrus aurantium oil and anxiety during the first stage of labor. Iran Red Crescent Med J. 2014;16(6):e18371.25068058
32. Calapai G, Firenzuoli F, Saitta A, et al. Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: a preliminary report. Fitoterapia. 1999;70:586-592.
33. Moro CO, Basile G. Obesity and medicinal plants. Fitoterapia. 2000;71(suppl 1):S73-S82.10930716
34. Preuss HG, DiFerdinando D, Bagchi M, Bagchi D. Citrus aurantium as a thermogenic, weight-reduction replacement for ephedra: an overview. J Med. 2002;33(1-4):247-264.12939122
35. Verpeut JL, Walters AL, Bello NT. Citrus aurantium and Rhodiola rosea in combination reduce visceral white adipose tissue and increase hypothalamic norepinephrine in a rat model of diet-induced obesity. Nutr Res. 2013;33(6):503-512.2374656710.1016/j.nutres.2013.04.001
36. Colker CM, Kaiman DS, Torina GC, Perlis T, Street C. Effects of Citrus aurantium extract, caffeine, and St. John's wort on body fat loss, lipid levels, and mood states in overweight healthy adults. Curr Ther Res Clin Exp. 1999;60:145-153.
37. Bui LT, Nguyen DT, Ambrose PJ. Blood pressure and heart rate effects following a single dose of bitter orange. Ann Pharmacother. 2006;40(1):53-57.16317106
38. Penzak SR, Jann MW, Cold JA, Hon YY, Desai HD, Gurley BJ. Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults. J Clin Pharmacol. 2001;41(10):1059-1063.11583473
39. Min B, Cios D, Kluger J, White CM. Absence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjects. Pharmacotherapy. 2005;25(12):1719-1724.16305290
40. Haller C, Duan M, Jacob P III, Benowitz N. Synephrine pharmacokinetics and cardiovascular changes after ingestion of Citrus aurantium dietary supplements. Clin Pharmacol Ther. 2005;77:P5.
41. Haller CA, Benowitz NL, Jacob P 3rd. Hemodynamic effects of ephedra-free weight-loss supplements in humans. Am J Med. 2005;118(9):998-1003.16164886
42. Sale C, Harris RC, Delves RC, Corbett J. Metabolic and physiological effects of ingesting extracts of bitter orange, green tea and guarana at rest and during treadmill walking in overweight males. Int J Obes (Lond). 2006;30(5):764-773.16418760
43. Kaats GR, Miller H, Preuss HG, Stohs SJ. A 60-day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract. Food Chem Toxicol. 2013;55:358-362.2335439410.1016/j.fct.2013.01.013
44. Song DK, Suh HW, Jung JS, Wie MB, Son KH, Kim YH. Antidepressant-like effects of p-synephrine in mouse models of immobility tests. Neurosci Lett. 1996;214(2-3):107-110.8878095
45. Kim KW, Kim HD, Jung JS, et al. Characterization of antidepressant-like effects of p-synephrine stereoisomers. Naunyn Schmiedebergs Arch Pharmacol. 2001;364(1):21-26.11485034
46. Cui Z, Lee Y, Lee Y, Park D. p-Synephrine suppresses glucose production but not lipid accumulation in H4IIE liver cells. J Med Food. 2015;18(1):76-82.25379695
47. Rahnama S, Rabiei Z, Alibabaei Z, Mokhtari S, Rafieian-kopaei M, Deris F. Anti-amnesic activity of Citrus aurantium flowers extract against scopolamine-induced memory impairments in rats [published online November 4, 2014]. Neurol Sci.2536740410.1007/s10072-014-1991-2
48. Namazi M, Akbari SAA, Mojab F, Talebi A, Majd HA, Jannesari S. Effects of Citrus aurantium (bitter orange) on the severity of first-stage labor pain. Iran J Pharm Res. 2014;13(3):1011-1018.25276203
49. Lu Q, Yang L, Zhao HY, Jiang JG, Xu XL. Protective effect of compounds from the flowers of Citrus aurantium L. var. amara Engl against carbon tetrachloride-induced hepatocyte injury. Food Chem Toxicol. 2013;62:432-435.23985451
50. Hansen DK, Juliar BE, White GE, Pellicore LS. Developmental toxicity of Citrus aurantium in rats. Birth Defects Res B Dev Reprod Toxicol. 2011;92(3):216-223.21594979
51. Rodrigues M, Alves G, Falcão A. Investigating herb-drug interactions: the effect of Citrus aurantium fruit extract on the pharmacokinetics of amiodarone in rats. Food Chem Toxicol. 2013;60:153-159.23886819
52. Penzak SR, Acosta EP, Turner M, et al. Effect of Seville orange juice and grapefruit juice on indinavir pharmacokinetics. J Clin Pharmacol. 2002;42(10):1165-1170.12362932
53. Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther. 2001;69(1):14-23.11180034
54. Di Marco MP, Edwards DJ, Wainer IW, Ducharme MP. The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein. Life Sci. 2002;71(10):1149-1160.12095536
55. Stohs SJ. Assessment of the adverse event reports associated with Citrus aurantium (bitter orange) from Apri 2004 to October 2009. J Funct Foods. 2010;2:235-238.
56. Stohs SJ, Preuss HG, Shara M. The safety of Citrus aurantium (bitter orange) and its primary protoalkaloid p-synephrine. Phytother Res. 2011;25(10):1421-1428.21480414
57. Stohs SJ, Preuss HG, Shara M. A review of the human clinical studies involving Citrus aurantium (bitter orange) extract and its primary protoalkaloid p-synephrine. Int J Med Sci. 2012;9(7):527-538.22991491
58. Bouchard NC, Howland MA, Greller HA, Hoffman RS, Nelson LS. Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine. Mayo Clin Proc. 2005;80(4):541-545.15819293
59. Firenzuoli F, Gori L, Galapai C. Adverse reaction to an adrenergic herbal extract (Citrus aurantium). Phytomedicine. 2005;12(3):247-248.15830849
60. Gange CA, Madias C, Felix-Getzik EM, Weintraub EM, Estes NA 3rd. Variant angina associated with bitter orange in a dietary supplement. Mayo Clinic Proc. 2006;81(4):545-548.16610576
61. Burke J, Seda G, Allen D, Knee TS. A case of severe exercise-induced rhabdomyolysis associated with a weight-loss dietary supplement. Mil Med. 2007;172(6):656-658.17615852
62. Kubo K, Kiyose C, Ogino S, Saito M. Suppressive effect of Citrus aurantium against body fat accumulation and its safety. J Clin Biochem Nutr. 2005;36(1):11-17.
63. Chen X, Liu LY, Deng HW, Fang YX, Ye YW. The effects of Citrus aurantium and its active ingredient N-methyltyramine on the cardiovascular receptors. Yao Xue Xue Bao. 1981;16(4):253-259.7257808
64. Huang YT, Lin HC, Chang YY, Yang YY, Lee SD, Hong CY. Hemodynamic effects of synephrine treatment in portal hypertensive rats. Jpn J Pharmacol. 2001;85(2):183-188.11286401
65. Klontz KC, Timbo BB, Street D. Consumption of dietary supplements containing Citrus aurantium (bitter orange)—2004 California Behavioral Risk Factor Surveillance Survey (BRFSS). Ann Pharmacother. 2006;40(10):1747-1751.16968826
66. Chobanian AV, Bakris GL, Black HR, et al; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42 (6):1206-1252.14656957
67. Farshbaf-Khalili A, Kamalifard M, Namadian M. Comparison of the effect of lavender and bitter orange on anxiety in postmenopausal women: a triple-blind, randomized, controlled clinical trial. Complement Ther Clin Pract. 2018;31:132-138.29705445
68. Abilify (aripiprazole) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; February 2011.
69. Abilify Maintena (aripiprazole) [prescribing information]. Rockville, MD: Otsuka America Pharmaceutical, Inc; February 2013.
70. Aung GL, O'Brien JG, Tien PG, Kawamoto LS. Increased aripiprazole concentrations in an HIV-positive male concurrently taking duloxetine, darunavir, and ritonavir. Ann Pharmacother. 2010;44(11):1850-1854.20978219
71. Azuma J, Hasunuma T, Kubo M, et al. The relationship between clinical pharmacokinetics of aripiprazole and CYP2D6 genetic polymorphism: effects of CYP enzyme inhibition by coadministration of paroxetine or fluvoxamine. Eur J Clin Pharmacol, 2012;68(1):29-37.21739267
72. Kubo M, Koue T, Inaba A, et al. Influence of itraconazole co-administration and CYP2D6 genotype on the pharmacokinetics of the new antipsychotic aripiprazole. Drug Metab Pharmacokinet. 2005;20(1):55-64.15770075
73. Cantilena L, Kahn R, Duncan CC, Li SH, Anderson A, Elkashef A. Safety of atomoxetine in combination with intravenous cocaine in cocaine-experienced participants. J Addict Med. 2012;6(4):265-273.22987022
74. Hammerness P, Georgiopoulos A, Doyle RL, et al. An open study of adjunct OROS-methylphenidate in children who are atomoxetine partial responders: II. Tolerability and pharmacokinetics. J Child Adolesc Psychopharmacol. 2009;19(5):493-499.19877973
75. Kelly RP, Yeo KP, Teng CH, et al. Hemodynamic effects of acute administration of atomoxetine and methylphenidate. J Clin Pharmacol. 2005;45:851-855.15951476
76. Michelson D, Adler L, Spencer T, et al. Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies. Biol Psychiatry. 2003;53:112-120.12547466
77. Sofuoglu M, Poling J, Hill K, Kosten T. Atomoxetine attenuates dextroamphetamine effects in humans. Am J Drug Alcohol Abuse. 2009;35(6):412-416.20014909
78. Spencer T, Heiligenstein JH, Biderman J, et al. Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2002;63(12):1140-1147.12523874
79. Strattera (atomoxetine) [prescribing information]. Indianapolis, IN: Lilly USA, LLC; May 2017.
80. Bosulif (bosutinib) [product monograph]. Kirkland, Quebec, Canada: Wyeth LLC; July 2015.
81. Bosulif (bosutinib) [prescribing information]. New York, NY: Pfizer Inc; November 2014.
82. Benowitz NL, Jones RT. Prolonged delta-9-tetrahydrocannabinol ingestion. Effects of sympathomimetic amines and autonomic blockades. Clin Pharmacol Ther. 1977;21(3):336-342.837652
83. Foltin RW, Fischman MW, Pedroso JJ, Pearlson GD. Marijuana and cocaine interactions in humans: cardiovascular consequences. Pharmacol Biochem Behav, 1987;28(4):459-464.2829241
84. Foltin RW,Fischman MW. The effects of combinations of intranasal cocaine, smoked marijuana, and task performance on heart rate and blood pressure. Pharmacol Biochem Behav. 1990;36(2):311-315.2162543
85. Foltin RW, Fischman MW,Levin FR. Cardiovascular effects of cocaine in humans: laboratory studies. Drug Alcohol Depend. 1995;37(3):193-210.7796714
86. Gash A, Karliner JS, Janowsky D, Lake CR. Effects of smoking marihuana on left ventricular performance and plasma norepinephrine: studies in normal men. Ann Intern Med. 1978;89(4):448-452.697222
87. Lukas SE, Sholar M, Kouri E, Fukuzako H, Mendelson JH. Marihuana smoking increases plasma cocaine levels and subjective reports of euphoria in male volunteers. Pharmacol Biochem Behav. 1994;48(3):715-721.7938127
88. Williamson EM, Evans FJ. Cannabinoids in clinical practice. Drugs. 2000;60(6):1303-1314.11152013
89. McGovern E, Moylett E, McMahon CJ. Myocardial ischaemia following cocaine and adrenaline exposure in a child during an ophthalmological procedure. Ir Med J. 2015;108(3):89-90.25876303
90. Sundboll J, Pareek M, Hogsbro M, Madsen EH. Iatrogenic takotsubo cardiomyopathy induced by locally applied epinephrine and cocaine. BMJ Case Rep. 2014;2014.24554679
91. Laffey JG, Neligan P, Ormonde G. Prolonged perioperative myocardial ischemia in a young male: due to topical intranasal cocaine? J Clin Anesth. 1999;11(5):419-424.10526815
92. Barnett P. Cocaine toxicity following dermal application of adrenaline-cocaine preparation. Pediatr Emerg Care. 1998;14(4):280-281.9733253
93. Nicholson KE, Rogers JE. Cocaine and adrenaline paste: a fatal combination? BMJ. 1995;311(6999):250-251.7627047
94. Lormans P, Gaumann D, Schwieger I, Tassonyi E. Ventricular fibrillation following local application of cocaine and epinephrine for nasal surgery. ORL J Otorhinolaryngol Relat Spec. 1992;54(3):160-162.1518666
95. Ashchi M, Wiedemann HP, James KB. Cardiac complication from use of cocaine and phenylephrine in nasal septoplasty. Arch Otolaryngol Head Neck Surg. 1995;121(6):681-684.7772323
96. Miller SA, Mieler WF. Systemic reaction to subconjunctival phenylephrine. Can J Ophthalmol. 1978;13(4):290-293.743613
97. Tikosyn (dofetilide) [prescribing information]. New York, NY: Pfizer Inc; February 2011.
98. Walker DK, Alabaster CT, Congrave GS, et al. Significance of metabolism in the disposition and action of the antidysrhythmic drug, dofetilide. in vitro studies and correlation with in vivo data. Drug Metab Dispos. 1996;24(4):447-455.8801060
99. Johnson BF, Cheng SL and Venitz J. Transient kinetic and dynamic interactions between verapamil and dofetilide, a class III antiarrhythmic. J Clin Pharmacol. 2001;41(11):1248-1256.11697758
100. Doxofylline tablets [KR prescribing information]. Available at: Accessed December 15, 2015.
101. Addyi (flibanserin) [prescribing information]. Raleigh, NC: Sprout Pharmaceuticals Inc; August 2015.
102. Simonyi J, Krassoi A, Decsy J, et al. Guanethidine (Sanotensin)-induced changes in alpha and beta receptor sensitivity. Ther Hung. 1972;20(1):47-55.
103. Laurence DR, Nagle RE. The effects of bretylium and guanethidine on the pressor responses to noradrenaline and angiotensin. Br J Pharmacol Chemother. 1963;21:403-413.14110739
104. Muelheims GH, Entrup RW, Paiewonsky D, Mierzwiak DS. Increased sensitivity of the heart to catecholamine-induced arrhythmias following guanethidine. Clin Pharmacol Ther. 1965;6(6):757-762.5846408
105. Gulati OD, Dave BT, Gokhale SD, Shah KM. Antagonism of adrenergic neuron blockade in hypertensive subjects. Clin Pharmacol Ther. 1966;7(4):510-514.5939974
106. Deshmankar BS, Lewis JA. Ventricular tachycardia associated with the administration of methylphenidate during guanethidine therapy. Can Med Assoc J. 1967;97(19):1166-1167.6057135
107. Ismelin (guanethidine) [summary of product characteristics]. Basildon, Essex, UK: Amdipharm UK Limited; July 2014.
108. Imbruvica (ibrutinib) [prescribing information]. Sunnyvale, CA: Pharmacyclics Inc; January 2015.
109. Mouly SJ, Matheny C, Paine MF, et al. Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5. Clin Pharmacol Ther. 2005;78(6):605-618.16338276
110. Kalydeco (ivacaftor) [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; March 2015.
111. Zyvox (linezolid) [prescribing information]. New York, NY: Pharmacia and Upjohn Company; June 2010.
112. Hendershot PE, Antal EJ, Welshman IR, Batts DH, Hopkins NK. Linezolid: pharmacokinetic and pharmacodynamic evaluation of coadministration with pseudoephedrine HCl, phenylpropanolamine HCl, and dextromethorpan HBr. J Clin Pharmacol. 2001;41(5):563-572.11361053
113. Patel G, King A, Dutta S, et al. Evaluation of the effects of the weak CYP3A inhibitors atorvastatin and ethinyl estradiol/norgestimate on lomitapide pharmacokinetics in healthy subjects. J Clin Pharmacol. 2016;56(1):47-55.26120010
114. Juxtapid (lomitapide) [prescribing information]. Cambridge, MA: Aegerion Pharmaceuticals, Inc.; March 2016.
115. Nimodipine [prescribing information]. Montvale, NJ: Ascend Laboratories LLC; April 2015.
116. Lynparza (olaparib) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; December 2014.
117. Desta Z, Kerbusch T, and Flockhart DA. Effect of clarithromycin on the pharmacokinetics and pharmacodynamics of pimozide in healthy, poor, and extensive metabolizers of cytochrome P450 2D6 (CYP2D6). Clin Pharmacol Ther, 1999;65(1):10-20.9951426
118. Orap (pimozide) [prescribing information]. Sellersville, PA: Teva Pharmaceuticals USA; August 2011.
119. Flockhart DA, Richard E, Woosely RL, et al. A metabolic interaction between clarithromycin and pimozide may result in cardiac toxicity. Clin Pharmacol Ther, 1996;59:189.
120. Desta Z, Kerbusch T, Soukhova N, Richard E, Ko JW, Flockhart DA.. Identification and characterization of human cytochrome P450 isoforms interacting with pimozide. J Pharmacol Exp Ther. 1998;285(2):428-437.9580580
121. Invirase (saquinavir) [prescribing information].South San Francisco, CA: Genetech USA Inc; November 2012.
122. Sunosi (solriamfetol) [prescribing information]. Palo Alto, CA: Jazz Pharmaceuticals, Inc.; March 2019.
123. Foradil (formoterol) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; September 2001.
124. ProAmatine (midodrine) [prescribing information]. Lexington, MA: Shire US Inc; February 2017.
125. Sivextro (tedizolid phosphate) [prescribing information]. Lexington, MA: Cubist Pharmaceuticals US; June 2014.
126. Flanagan S, Bartizal K, Minassian SL, Fang E, Prokocimer P. In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions. Antimicrob Agents Chemother. 2013;57(7):3060-3066.23612197
127. Zyvox (linezolid) [prescribing information]. New York, NY: Pfizer Inc; September 2013.
128. Venclexta (venetoclax) [prescribing information]. North Chicago, IL: AbbVie Inc; April 2016.
129. Zokinvy (lonafarnib) [prescribing information]. Palo Alto, CA: Eiger BioPharmaceuticals, Inc.; November 2020.
130. Abdelkawy KS, Donia AM, Turner RB, Elbarbry F. Effects of lemon and Seville orange juices on the pharmacokinetic properties of sildenafil in healthy subjects. Drugs R D. 2016;16(3):271-278.27550653
131. Dresser GK, Wacher V, Wong S, Wong HT, Bailey DG. Evaluation of peppermint oil and ascorbyl palmitate as inhibitors of cytochrome P4503A4 activity in vitro and in vivo. Clin Pharmacol Ther. 2002;72(3):247-255.12235445
132. Felodipine [prescribing information]. Carlsbad, CA: Carlsbad Technology Inc; December 2020.
133. Madsen JK, Jensen JD, Jensen LW, Pedersen EB. Pharmacokinetic interaction between cyclosporine and the dihydropyridine calcium antagonist felodipine. Eur J Clin Pharmacol. 1996;50(3):203-208.8737760
134. Mavyret (glecaprevir and pibrentasvir) [prescribing information]. North Chicago, IL: AbbVie Inc; April 2020.
135. Wason S, DiGiacinto JL, Davis MW. Effects of grapefruit and Seville orange juices on the pharmacokinetic properties of colchicine in healthy subjects. Clin Ther. 2012;34(10):2161-2173.22940371
136. Penzak SR, Acosta EP, Turner M, et al. Effect of Seville orange juice and grapefruit juice on indinavir pharmacokinetics. J Clin Pharmacol. 2002;42(10):1165-1170.12362932
137. Clemens JQ, Erickson DR, Varela NP, Lai HH. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2022;208(1):34-42. doi:10.1097/JU.000000000000275635536143

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.