Drug & supplement interaction

Bitter Orange + Cobicistat

Cobicistat brand name: Tybost.

No Known Interaction

Medically reviewed by Dr. Brian Staiger, PharmD, BCPS · Updated July 2026 · Pair last verified Sep 13, 2026

The bottom line No known interaction

We found no known interaction between Bitter Orange and Cobicistat in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the label for Cobicistat states a food rule worth keeping to, and the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Bitter Orange and Cobicistat

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Cobicistat and Bitter Orange in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Bitter Orange safety at a glance

Bitter Orange overall Use caution Generally limited use may be tolerated, but the synephrine it contains can affect heart rate and blood pressure.

Pregnancy Likely Safe When used orally in the amounts found in foods. Bitter orange has Generally Recognized as Safe (GRAS) status in the US. Read the full pregnancy detail

Breastfeeding Likely Safe When used orally in the amounts found in foods. Bitter orange has Generally Recognized as Safe (GRAS) status in the US. Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center) — the full detail is in the Special populations card below. Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Cobicistat and Bitter Orange? Ask Dr. Brian Staiger, PharmD, BCPS directly ›

How we checked

Why No Interaction Is Listed for Cobicistat

Interactions in our licensed database are recorded against drug classes, not just single drug names. Cobicistat is filed under 2 classifications — cytochrome p450 3a4 (cyp3a4) inhibitors, oral drugs. Bitter Orange has documented interactions with 13 drug classes — the most serious being midazolam (versed) (major), monoamine oxidase inhibitors (maois) (major) and antidiabetes drugs (moderate) — and none of Cobicistat’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Bitter Orange Does Interact With Other Medications

Bitter Orange has 10 major, 876 moderate, 71 minor known drug interactions in our database — Cobicistat isn’t one of them. If you take anything else, check it against the full list below.

Major 10 Moderate 876 Minor 71 No known interaction 1,873 (incl. Cobicistat)

Taking anything else?

Check Another of Your Medications Against Bitter Orange

Covers the 2,830 medications we’ve checked against Bitter Orange. Pick one to open its full report.

What to actually watch for

No Interaction Found — But Data Suggests Bitter Orange and Cobicistat May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. One of them is worth acting on rather than waiting out — marked below.

Severe muscle breakdown Worth acting on Additional detail
Bitter Orange
“Unsteady gait has been noted in one case report of a patient taking bitter orange. In another case, an otherwise healthy, Black male with sickle cell trait, developed severe rhabdomyolysis following ingestion of a specific weight loss product (Lipo 6, Nutrex Research Inc.), which contained synephrine and caffeine.”

Bitter Orange · Natural Medicines adverse-effect record, reported in muscle breakdown.
4 sources cited

13091. Bouchard NC, Howland MA, Greller HA, et al. Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine. Mayo Clin Proc 2005;80:541-5. PubMed

16054. 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;172:656-8. PubMed

95657. Jung YP, Earnest CP, Koozehchian M, et al. Effects of acute ingestion of a pre-workout dietary supplement with and without synephrine on resting energy expenditure, cognitive function and exercise performance. J Int Soc Sports Nutr. 2017;14:3. doi: 10.118

95656. Jung YP, Earnest CP, Koozehchian M, et al. Effects of ingesting a pre-workout dietary supplement with and without synephrine for 8 weeks on training adaptations in resistance-trained males. J Int Soc Sports Nutr. 2017;3;14:1. doi: 10.1186/s12970-016-0158- PubMed
Cobicistat

Listed in the ADVERSE REACTIONS section of the FDA label for Cobicistat. Read the label on DailyMed ›
Headache Additional detail
Bitter Orange
“Dizziness, difficulty in concentrating, memory loss, syncope, seizure, and stroke have been noted in case reports following bitter orange administration. Theoretically, bitter orange may trigger a migraine or cluster headache due to its synephrine and octopamine content. When used as aromatherapy, bitter orange essential oil has also been reported to cause headache in some patients.”

Bitter Orange · Natural Medicines adverse-effect record, reported in cluster headache.
5 sources cited

13091. Bouchard NC, Howland MA, Greller HA, et al. Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine. Mayo Clin Proc 2005;80:541-5. PubMed

13039. Nasir JM, Durning SJ, Ferguson M, et al. Exercise-induced syncope associated with QT prolongation and ephedra-free Xenadrine. Mayo Clin Proc 2004;79:1059-62.. PubMed

35768. Calapai, G., Firenzuoli, F., Saitta, A., Squadrito, F. R., Arlotta, M., Costantino, G., and Inferrera, G. Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: a preliminary report. Fitoterapia 12-1-1999;70(6):586-592. DOI

104187. Karimzadeh Z, Azizzadeh Forouzi M, Tajadini H, Ahmadinejad M, Roy C, Dehghan M. Effects of lavender and Citrus aurantium on pain of conscious intensive care unit patients: a parallel randomized placebo-controlled trial. J Integr Med 2021:S2095-4964(21)000 PubMed

95655. Gutiérrez-Hellín J, Salinero JJ, Abían-Vicen J, Areces F, Lara B, Gallo C, et al. Acute consumption of p-synephrine does not enhance performance in sprint athletes.J. Appl Physiol Nutr Metab. 2016;41(1):63-9. doi: 10.1139/apnm-2015-0299.
Cobicistat

Listed in the ADVERSE REACTIONS section of the FDA label for Cobicistat. Read the label on DailyMed ›

Reported for Bitter Orange but not commonly for Cobicistat: a heart attack, an irregular heartbeat, a stroke or mini-stroke and raised blood pressure.

Effects for Cobicistat come from the ADVERSE REACTIONS section of its FDA label; effects for Bitter Orange come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 20,779 voluntary FDA FAERS reports for Cobicistat that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Special populations

Bitter Orange in Pregnancy & Breastfeeding

Pregnancy And Lactation Likely Safe

When used orally in the amounts found in foods. Bitter orange has Generally Recognized as Safe (GRAS) status in the US.

Pregnancy And Lactation Possibly Unsafe

When used orally for medicinal purposes. There are case reports of cardiotoxicity including tachyarrhythmia, syncope, and myocardial infarction in otherwise healthy adults who have taken bitter orange extract alone or in combination with other stimulants such as caffeine. The effects of bitter orange during lactation are unknown; avoid use.

DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.© 2026 Therapeutic Research Center

How to take them

Some Cobicistat Products Have a Food Rule — Bitter Orange Should Not Break It

At least one FDA label for a product containing Cobicistat says to take it with food. If you take Bitter Orange on an empty stomach out of habit, keep them separate — and take Cobicistat with a meal where the label says to.

This may not be true of your version. Food instructions belong to the product, not the ingredient: two Cobicistat products can carry different directions, and extended-release forms often differ from immediate-release ones. The label we read is quoted below — check the directions on your own box or bottle, or ask your pharmacist, for how to take the exact product you were given.

2 DOSAGE AND ADMINISTRATION TYBOST must be coadministered with atazanavir or darunavir at the same time, with food, and in combination with other HIV-1 antiretroviral agents.

From the Dosage and Administration section of the FDA label we read for Cobicistat — where that label names a specific product, the instruction is that product's. Read the label on DailyMed ›

A food rule is not an interaction — it is about how much of the medicine you absorb. The directions that came with your own product, and your pharmacist, outrank anything on this page.

Everything else you take

See Every Supplement That Interacts With Cobicistat

This page covers Bitter Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Cobicistat page lists 30 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Adrafinil (moderate), Cannabidiol (cbd) (moderate), Cannabinol (cbn) (moderate) and Cannabis (moderate).

By severity: 1 major · 19 moderate · 10 minor.

From our pharmacist’s overview on the Cobicistat page

“Activated charcoal is the one entry to understand first if you take cobicistat (Tybost). Charcoal soaks up drugs in the gut, and since cobicistat's entire job is boosting an HIV medicine to protective levels, blunting its absorption can put the whole regimen at risk.”

Reviewed by 2 · Jul 18, 2026

Open the Cobicistat interaction page

One more smart check

Taking Bitter Orange as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,000 real supplement products containing Bitter Orange, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bitter Orange. Even though Bitter Orange itself has no known interaction with Cobicistat, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Bitter Orange and Cobicistat Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Bitter Orange

Top 25%

#169 of 1,452 supplements looked up here in the last 7 days

29 days ago today

Medication Cobicistat

Steady interest

#1,720 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Where does our data come from?

Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Bitter Orange reference on this page ↓
Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Bitter Orange and Cobicistat records this page draws on were last updated July 10, 2026.
What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.

Data structure & sourcing designed and verified by Dr. Brian Staiger, PharmD, BCPS.

Supplement

About Bitter Orange

What is Bitter Orange?

Weight loss
Athletic performance and energy
Digestive upset
Appetite control
Aromatherapy for stress (neroli oil)

Bitter orange is a citrus fruit whose extracts contain synephrine, a mild stimulant often added to weight-loss and energy supplements. Evidence that it works for weight loss or performance is limited, and because it can raise heart rate and blood pressure, people with heart problems, high blood pressure, or who are pregnant should avoid it. Talk to your pharmacist or doctor before using it, especially if you take other stimulants.

Citrus aurantium · Rutaceae · Fruit (especially the dried immature fruit and peel), flowers, and essential oil (neroli) · Capsules, tablets, extracts, dried peel, tea, and essential oil

An interaction check asks whether these two react with each other — it does not ask whether Bitter Orange is a good idea for someone in your situation. Here is what our Bitter Orange record says about it on its own.

Bitter Orange: dosing

There is no well-established, proven dose for bitter orange. Products vary widely, and many are standardized to a certain amount of synephrine and often combined with caffeine or other ingredients.Because of this variability and the potential heart-related risks, it is best to follow the directions on the product label and not exceed them.

From our Bitter Orange monograph — the full record covers uses, side effects and every documented interaction.

Read the full Bitter Orange monograph & all interactions

Medication

About Cobicistat

What Is Cobicistat Used For?

Brand name: Tybost

Tybost (cobicistat) is not itself an HIV treatment — it works by slowing the breakdown of certain HIV medicines so they stay active in your body long enough to work. Specifically, Tybost is used to boost the HIV medicines atazanavir or darunavir (once-daily dosing) as part of a complete HIV-1 treatment regimen in adults and in children weighing at least 14 kg (about 31 lbs).

Tybost is not interchangeable with ritonavir (another booster) for all HIV medicines. It is not recommended with darunavir twice-daily, fosamprenavir, saquinavir, or tipranavir.

Most-Reported Side Effects for Cobicistat

From FAERS, the FDA’s public side-effect reporting system (20,779 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Bone density decreased 8,112 reports

Chronic kidney disease 4,754 reports

Renal injury 4,577 reports

Tooth loss 4,186 reports

Bone loss 4,107 reports

See full Cobicistat drug information

Keep checking

Other Drugs & Bitter Orange

Browse every other medication we’ve checked against Bitter Orange — both the ones with a known interaction and the ones without. Select any drug for the full detail.

10Major

876Moderate

71Minor

1,872No known interaction

10 Major 876 Moderate 71 Minor 1,872 No interaction

Major

10 interactions

Moderate

876 interactions

Showing 60 of 876 moderate interactions — see all 876 on the Bitter Orange page.

Minor

71 interactions

Showing 60 of 71 minor interactions — see all 71 on the Bitter Orange page.

No interaction 1,872 drugs checked — show the list

We also checked Bitter Orange against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,872 medications checked with no known interaction — see the full Bitter Orange list.

See the full Bitter Orange interactions page

See every supplement checked against Cobicistat, ranked by severity

Evidence & sources

Bitter Orange References

The 47 references that drive our Bitter Orange monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

Penzak SR, Jann MW, Cold JA, et al. Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults. J Clin Pharmacol 2001;41:1059-63. PubMed
Electronic Code of Federal Regulations. Title 21. Part 182 -- Substances Generally Recognized As Safe. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=182
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;70:586-92. DOI
Keogh AM, Baron DW. Sympathomimetic abuse and coronary artery spasm. Br Med J 1985;291:940.
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;69:14-23. PubMed
Pellati F, Benvenuti S, Melegari M, Firenzuoli F. Determination of adrenergic agonists from extracts and herbal products of Citrus aurantium L. var. amara by LC. J Pharm Biomed Anal 2002;29:1113-9. . PubMed
Colker CM, Kalman DS, Torina GC, et al. 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 1999;60:145-153. DOI
Penzak SR, Acosta EP, Turner M, et al. Effect of Seville orange juice and grapefruit juice on indinavir pharmacokinetics. J Clin Pharmacol 2002;42:1165-70. PubMed
Edwards DJ, Fitzsimmons ME, Schuetz EG, et al. 6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther 1999;65:237-44. PubMed
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;71:1149-60. PubMed
Visentin V, Morin N, Fontana E, et al. Dual action of octopamine on glucose transport into adipocytes: inhibition via beta3-adrenoceptor activation and stimulation via oxidation by amine oxidases. J Pharmacol Exp Ther 2001;299:96-104.
Nykamp DL, Fackih MN, Compton AL. Possible association of acute lateral-wall myocardial infarction and bitter orange supplement. Ann Pharmacother 2004;38:812-6. PubMed
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 2004;229:698-704.
Suzuki O, Matsumoto T, Oya M, Katsumata Y. Oxidation of synephrine by type A and type B monoamine oxidase. Experientia 1979;35:1283-4. PubMed
Nasir JM, Durning SJ, Ferguson M, et al. Exercise-induced syncope associated with QT prolongation and ephedra-free Xenadrine. Mayo Clin Proc 2004;79:1059-62.. PubMed
Firenzuoli F, Gori L, Galapai C. Adverse reaction to an adrenergic herbal extract (Citrus aurantium). Phytomedicine 2005;12:247-8. PubMed
Bouchard NC, Howland MA, Greller HA, et al. Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine. Mayo Clin Proc 2005;80:541-5. PubMed
Haller CA, Benowitz NL, Jacob P 3rd. Hemodynamic effects of ephedra-free weight-loss supplements in humans. Am J Med 2005;118:998-1003.. PubMed
Bui LT, Nguyen DT, Ambrose PJ. Blood pressure and heart rate effects following a single dose of bitter orange. Ann Pharmacother 2006;40:53-7. PubMed
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;25:1719-24. PubMed
Gange CA, Madias C, Felix-Getzik EM, et al. Variant angina associated with bitter orange in a dietary supplement. Mayo Clin Proc 2006;81:545-8. PubMed
Jordan S, Murty M, Pilon K. Products containing bitter orange or synephrine: suspected cardiovascular adverse reactions. Canadian Adverse Reaction Newsletter 2004;14:3-4.
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;172:656-8. PubMed
Gray, S. and Woolf, A. D. Citrus aurantium used for weight loss by an adolescent with anorexia nervosa. J Adolesc.Health 2005;37(5):414-415. PubMed
Haller, C. A., Duan, M., Jacob, P., III, and Benowitz, N. Human pharmacology of a performance-enhancing dietary supplement under resting and exercise conditions. Br J Clin Pharmacol 2008;65(6):833-840. PubMed
Thomas, J. E., Munir, J. A., McIntyre, P. Z., and Ferguson, M. A. STEMI in a 24-year-old man after use of a synephrine-containing dietary supplement: a case report and review of the literature. Tex.Heart Inst.J 2009;36(6):586-590.
Campbell-Tofte, J. I., Molgaard, P., Josefsen, K., Abdallah, Z., Hansen, S. H., Cornett, C., Mu, H., Richter, E. A., Petersen, H. W., Norregaard, J. C., and Winther, K. Randomized and double-blinded pilot clinical study of the safety and anti-diabetic ef
Seifert, J. G., Nelson, A., Devonish, J., Burke, E. R., and Stohs, S. J. Effect of acute administration of an herbal preparation on blood pressure and heart rate in humans. Int J Med Sci 2011;8(3):192-197. PubMed
Stohs, S. J., Preuss, H. G., Keith, S. C., Keith, P. L., Miller, H., and Kaats, G. R. Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes. Int J Med
Wason, S., DiGiacinto, J. L., and Davis, M. W. Effects of grapefruit and Seville orange juices on the pharmacokinetic properties of colchicine in healthy subjects. Clin Ther 2012;34(10):2161-2173. PubMed
Kaats, G. R., Miller, H., Preuss, H. G., and Stohs, S. J. A 60day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract. Food Chem Toxicol. 2013;55:358-362.
Calapai, G., Firenzuoli, F., Saitta, A., Squadrito, F. R., Arlotta, M., Costantino, G., and Inferrera, G. Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: a preliminary report. Fitoterapia 12-1-1999;70(6):586-592. DOI
Colker, C., Kalman, D., and Torina, G. 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 1999;60:145-153. DOI
Shara M, Stohs SJ. Safety evaluation of Bitter orange extract (p-synephrine) in healthy volunteers. J.Amer.Coll.Nutr. 2011;30:358.
Lynch B. Review of the safety of p-synephrine and caffeine. Intertek-Cantox Report, 2013;1-20.
Smith TB, Staub BA, Natarajan GM, et al. Acute myocardial infarction associated with dietary supplements containing 1,3-dimethylamylamine and Citrus aurantium. Tex Heart Inst J 2014;41(1):70-2. PubMed
Shara M, Stohs SJ, Mukattash TL. Cardiovascular safety of oral p-synephrine (bitter orange) in healthy subjects: a randomized placebo-controlled cross-over clinical trial. Phytother Res. 2016;30(5):842-7.
Liu Y, Santillo MF. Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements. Drug Test Anal. 2016;8(3-4):307-10. PubMed
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 Sep;16(3):271-278. PubMed
Gutiérrez-Hellín J, Salinero JJ, Abían-Vicen J, Areces F, Lara B, Gallo C, et al. Acute consumption of p-synephrine does not enhance performance in sprint athletes.J. Appl Physiol Nutr Metab. 2016;41(1):63-9. doi: 10.1139/apnm-2015-0299.
Jung YP, Earnest CP, Koozehchian M, et al. Effects of ingesting a pre-workout dietary supplement with and without synephrine for 8 weeks on training adaptations in resistance-trained males. J Int Soc Sports Nutr. 2017;3;14:1. doi: 10.1186/s12970-016-0158- PubMed
Jung YP, Earnest CP, Koozehchian M, et al. Effects of acute ingestion of a pre-workout dietary supplement with and without synephrine on resting energy expenditure, cognitive function and exercise performance. J Int Soc Sports Nutr. 2017;14:3. doi: 10.118
Vatsavai LK, Kilari EK. Interaction of p-synephrine on the pharmacodynamic and pharmacokinetics of gliclazide in animal models. J Ayurveda Integr Med 2017; S0975-9476(16)30487-9. doi: 10.1016/j.jaim.2017.04.010.
Ratamess NA, Bush JA, Stohs SJ, et al. Acute cardiovascular effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine in human subjects: A placebo-controlled, double-blind study. Phytother Res. 2018;32(1):94-102.
Gutiérrez-Hellín J, Ruiz-Moreno C, Del Coso J. Acute p-synephrine ingestion increases whole-body fat oxidation during 1-h of cycling at Fatmax. Eur J Nutr. 2019 Nov 5. PubMed
Karimzadeh Z, Azizzadeh Forouzi M, Tajadini H, Ahmadinejad M, Roy C, Dehghan M. Effects of lavender and Citrus aurantium on pain of conscious intensive care unit patients: a parallel randomized placebo-controlled trial. J Integr Med 2021:S2095-4964(21)000 PubMed
Koncz D, Tóth B, Bahar MA, Roza O, Csupor D. The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis. Nutrients 2022;14(19):4019. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Bitter Orange and Cobicistat Together: Common Questions

Is it safe to take Bitter Orange with Cobicistat?

We do not list a known interaction between Bitter Orange and Cobicistat. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.

Do Bitter Orange and Cobicistat have any of the same side effects?

Yes — our sources link each of them separately to 2 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.

Should I take Bitter Orange and Cobicistat at the same time of day?

At least one FDA label for a product containing Cobicistat says to take it with food. If you take Bitter Orange on an empty stomach out of habit, keep them separate and take Cobicistat with a meal where the label says to. Food instructions belong to the product rather than the ingredient — two Cobicistat products can differ — so check the directions on your own box. This is about absorption, not an interaction.

How was the Bitter Orange and Cobicistat combination checked?

Interactions in our licensed database are recorded against drug classes. Cobicistat is filed under 2 classifications, and Bitter Orange has documented interactions with 13 drug classes — none of Cobicistat's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.

Does Bitter Orange interact with any other medications?

Yes. Bitter Orange has 957 documented drug interactions in our database — Cobicistat is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.

Does Cobicistat interact with any supplements?

Yes. Cobicistat has documented interactions with 30 supplements in our database — Bitter Orange is not one of them. The Cobicistat interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

Bitter Orange monograph Uses, safety profile, and every drug interaction in one place Cobicistat drug information The full plain-English guide to this medication Cobicistat supplement interactions Every supplement checked against Cobicistat, ranked by severity Supplement interaction checker Check any supplement or product against your medications Browse medications A–Z Every drug we’ve checked against herbs & supplements References The 47 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Cobicistat and Bitter Orange?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.