Information for Healthcare Professionals

If you are

On a medicine prescribed by your Doctor
Have a chronic/longterm condition (eg Diabetes, Crohn disease)
If you have acid reflux/ gastritis or similar conditions, and also may be taking over the counter medications for these conditions

DO NOT subscribe to Calocurb until you have consulted with your Medical Health Professional/ Doctor.

Hops extract and prescribed medicines

The active ingredient in calocurb is an extract from hops. Preparations containing hops extract (Humulus lupulus) are used for a variety of conditions including weight management. Taken at the recommended dose, hops extract can have some side effects in a small percentage of consumers. These are mainly gastro-intestinal effects such as nausea, stomach cramps and diarrhoea. If a consumer suffers from these side effects which are not subsiding within 48 hours we would recommend discontinuation. In the case of any other side effects we would recommend discontinuation.

Hops extract can potentially interfere with the action of some other medicines making them less effective. It does this by causing enzymes in the liver and gut to breakdown some medicines faster than usual.

Hops extract information for healthcare professionals

The active ingredient in calocurb is an extract from hops. Preparations containing hops extract (Humulus lupulus) are used for a variety of purposes including weight management.

The European Medicines Agency (EMA), the European Union’s drug-approval regulatory agency counterpart to the US FDA, evaluated the use of hops extracts for use as an herbal medicine. (EMA 2014).

They concluded:

“In view of its long term use and present use in humans hops is considered to be non-toxic and safe with no significant adverse effects in the condition of use proposed for the monograph. In conclusion, the safety assessment of hops and hop preparations is mainly based on many years of experience from the extensive use in humans, which indicate hop preparations to be safe pharmaceutical agents.”

In the US the use of hops extract, or hops oleoresin, is approved by the U.S. FDA as an essential oil, oleoresin (solvent-free), and natural extractive (including its distillate) which are generally recognized as safe (GRAS).

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.20

Hops extracts potential interaction with prescribed medicines

It appears that hops extracts may interact with some medicines either by increasing the rate of their metabolism or increasing levels of neurotransmitters. The effect on metabolism appears to occur by induction of certain cytochrome P450 isoenzymes in the liver and gut (particularly CYP 3A4, but also 1A2 and 2C9) reducing the blood levels and effectiveness of some medicines.

Many medicines, including carbamazepine and phenytoin, are potent enzyme inducers which act at the CYP 3A4 site. Several naturally occurring substances including grapefruit juice, red wine and broccoli have also been found to have effects on these enzyme systems. The most closely related example of a cytochrome P450 inductor is St John’s Wort and the table below has been prepared based on the Medsafe analysis on St John’s Wort: http://www.medsafe.govt.nz/profs/PUarticles/sjw.htm

Which medicines interact with hops extract?

The table below lists medicines for which there is varying degrees of evidence of a possible interaction with St John’s Wort and therefore potentially hops extract due to the same potential effect on cytochrome P450. For some (e.g. cyclosporin, warfarin, indinavir, carbamazepine) the loss of clinical effectiveness is potentially serious. The table gives an indication of the nature and strength of the evidence of interaction, describes the effect of an interaction should it occur, and provides advice on the management of patients. For some of the medicines listed there is at present no more than a theoretical possibility of interaction.

The table is not exhaustive, but it covers the information available to date. Other medicines not included in this list therefore may also interact with hops extract. In general, the following medicines are not likely to interact with hops extract:

topical medicines with limited systemic absorption (inhalers, skin creams and ointments, eye and ear drops, enemas etc.)
non-psychotropic medicines which are principally renally excreted

Reporting suspected interactions

Please contact hello@calocurb.com for more information on and support with any suspected interactions.

Patients taking these medicines should not start taking hops extract without seeking medical advice

Medicine	Evidence base	Evidence and effect of interaction with St John’s Wort	Suggested management of patients already taking hops extract (HE)
HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir)	Strong	A clinical study has demonstrated reduced blood levels with possible loss of HIV suppression.	Measure HIV RNA viral load and stop HE.
Immunosuppressants (cyclosporin, tacrolimus)	Strong	Case reports have demonstrated reduced blood levels with transplant rejection.	Check cyclosporin or tacrolimus blood levels and stop HE. Levels may increase on stopping HE. The dose of immunosuppressant may need adjusting.
HIV non-nucleoside reverse transcriptase inhibitors (efavirenz, nevirapine, delavirdine)	Theoretical	Reduced blood levels with possible loss of HIV suppression is theoretically possible.	Measure HIV RNA viral load and stop HE.
Warfarin	Moderate	Case reports of reduced anticoagulant effect and need for increased warfarin dose have been reported.	Check INR and stop HE. Monitor INR closely as this may rise on stopping HE. The dose of warfarin may need adjusting.
Anticonvulsants (carbamazepine, phenobarbitone, phenytoin)	Theoretical	Reduced blood levels with risk of seizures theoretically possible.	Check anticonvulsant levels and stop HE. Anticonvulsant levels may increase on stopping HE. The dose of anticonvulsant may need adjusting.
Digoxin	Moderate	Isolated case reports of reduced blood levels have been reported. Theoretical loss of control of heart rhythm or heart failure.	Check digoxin levels and stop HE. Digoxin levels may increase on stopping HE. The dose of digoxin may need adjusting.
Oral contraceptives	Weak	Small numbers of case reports of breakthrough bleeding, Contraceptive failure theoretically possible but no case reports of contraceptive failure have been reported.	Weigh the benefits of continuing HE against theoretical possibility of reduced contraceptive efficacy.
Theophylline	Theoretical	Reduced blood levels and loss of bronchodilator effect theoretically possible.	Check theophylline levels and review use of HE. Weigh the benefits of continuing HE against possible adverse effects. Theophylline levels may increase on stopping HE. The dose of theophylline may need adjusting.

Note: Other medicines not included in this list may also interact with hops extract.