Herb-Drug Interactions

A 74-year-old man had been taking digoxin for many years to control atrial fribrillation. His serum digoxin level has been maintained at 0.9 to 2.2 nmol/L for more than a decade, the therapeutic range being from 0.6 to 2.6 nmol//L.

A routine measurement of the serum digoxin level was reported as 5.2 nmol/L. The patient had no complaints at this time, no signs of digoxin poisoning.

Digoxin therapy was held, resumed at a reduced dose and finally discontinued; but even though the serum digoxin level remained high. The patient ended asking if the Siberian ginseng capsules he had been taking since the previous summer might be a factor. The herbal medicine was stopped in the same day, and seven days later his serum digoxin level fell to 2,2 nmol/L. Digoxin was gradually reintroduced once the level entered the low therapeutic range.

For the next 6 months the patient continued digoxin therapy, and the serum digoxin level remained between 0.8 and 1.1 nmol/L. But the patient resumed taking ginseng again; and approximately one month later the digoxin levels rose to 1.9 nmol/L, and to weeks after that to 3.2 nmol/L. The ginseng intake was stopped again and six days later the serum digoxin level was back in the normal range at 1.2 nmol/L. The patient continued to take digoxin at the same doses throughout this period and remained asymptomatic.

Samples of the Siberian ginseng capsules were analysed and no digoxin or digitoxin contamination was found.

Bibliography
McRae, S. Elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. Can. Med. Asso. J. 1996; 155: 293–295.

A 36-year-old woman with depression and hypercholesterolaemia attended to a gyneacology appointment with an unexpected pregnancy confirmed by ultrasound.

The drug history revealed regular use of the combined oral contraceptive Valette® (ethinylestradiol/dienogesterol) over the last year. She had been treated with fluvastatin (20 mg day-1) for 2 years, and with different antidepressants including selective serotonin reuptake inhibitors and tricyclic antidepressants after an attempted suicide in 1995.

The patient began self-medication with the over-the-counter Hypericum perforatum extract with daily doses up to 1700 mg approximately 3 months prior to conception, and until conception no other medication was taken except the hormonal contraceptive.

A therapeutic abortion was carried out on the seventh week of pregnancy.

Bibliography
Schwarz, U. I.; Buschel, B.; Kirch, W. Unwanted pregnancy on self-medication with St John’s wort despite hormonal contracepcion. Br J Clin Pharmacol 2003 55:112-113

A 72-year old Italian woman was admitted to the hospital with symptoms of acute jaundice.

Laboratory tests revealed high levels of bilirubin (total bilirubin 18 mg/dL), ALT and AST (both greater than 700 U / L). A liver biopsy showed a cholestatic hepatitis and a granulomatous cholangitis.

The woman mentioned that she was taking two supplements (prescribed by her ophthalmologist): Epinerve ® (SIFI, Italy) - 2 tablets / day - and Luteinofta ® (SOOFT, Italy) - 1 tablet / day.

The Epinerve ® is composed by an aqueous green tea’s extract, and Luteinofta ® is composed by lutein and vitamin E.

After she stopped taking the supplements and received pharmacological treatment, liver enzymes’ levels decreased progressively to standard values. The patient was then discharged.

A year later, in follow-up appointment, the parameters remained within normal values.

Bibliography
Mazzanti, G. et al. Hepatoxicity from green tea: a review of the literature and two unpublished cases. Eur J Clin Pharmacol 2009 65:331-341

A 46-year old woman was referred to the Gastroenterology Department of Covilhã’s University Hospital with the fallowing symptoms: fatigue, jaundice and itching.

The patient hadn’t history or clinical evidence of viral hepatitis, autoimmune hepatitis, Wilson disease or hemochromatosis.

Further investigation revealed that 14 days before hospital admission, the patient started self-medication with CLA, in order to decrease body fat.

There was a suspicion of hepatotoxicity, which was confirmed by liver biopsy.

After stopping CLA intake, liver enzyme level’s normalized, and there was complete hepatitis’ regression.

Bibliography
Ramos, R. et al . Conjugated Linolenic Acid - induced Toxic Hepatites: First case report. Dig Dis Sci 2009 54:1141-1143

A 35-year old woman lost an excessive amount of blood – 5L – during a surgery for the extraction of a hemangioma on the left tight.

In face of the medication used in the surgery (between many, the sevoflurane) and the surgery itself, it was expected a blood loss of 2,5 L.

The patient had consumed, during two weeks prior to hospital admission, 4 pills per day of Aloe vera, due to a study on the use of Traditional Chinese Medicine. The attending anesthesiologist was unaware that she had taken Aloe vera.

Further investigation led to a potential plant-medicine interaction – between Aloe vera and sevoflurane – based on the antiplatelet property that both have; they may have caused such a huge blood loss by a cumulative process.

Bibliography
Lee, A. et al. Possible interaction Between Sevoflurane and Aloé vera. Ann Pharmacother 2004; 38:1651-4

A 71-year-old Caucasian man arrived at an anticoagulation clinic where he had a routine appointment to monitor the INR. A value of 7.1 was detected (therapeutic range, 2.0-3.0).

His medication, doses and dosage had been stable for the previous 9 months, including warfarin – 47,5mg per week - and an INR between 1.9 and 3.3. The only change was the inclusion of bee pollen granules (one teaspoon, orally twice daily) one month before.

He denied the use of alcohol, tobacco, changes in dietary vitamin k intake, missed or extra doses, acute illness or diarrhea.

Despite education about the potential interaction between bee-pollen and warfarin, the patient expressed a strong desire to continue taking it.

Warfarin was withheld for some days and later restarted, but with a 11% inferior weekly dose (42,5mg).

All INR values during the next seven months were within or near the therapeutic range.

The potential mechanism for this interaction is the following: flavonoids contained in bee-pollen can inhibit CYP 2C9, an enzyme that is responsible for the metabolism of warfarin. The result led to increased bioavailability of warfarin, which justifies the elevation of INR.

Reducing the weekly dose of warfarin was enough to reduce the warfarin bioavailable, and therefore achieve a stable INR.

Bibliography
Hurren, K. M.; Lewis, C.L. Probable interaction between warfarin and bee pollen. Am J Health-Syst Pharm 2010 67:2034-2037.

A 78-year-old white male who had been taking warfarin at a total weekly dose of 45 mg for atrial fibrillation presented at one healthcare center with an International Normalized Ratio(INR) of 6.45.

The patient´s INR never exceeded 2.96 within the year prior to the event. Three weeks prior to this elevated INR, his INR was within normal therapeutic range, at 2.18.

The patient had been receiving a stable total weekly warfarin dose of 45 mg for the previous 3 months.

The patient reported that in the previous week he had drunk about a half gallon of cranberry/apple juice.

The patient was instructed to refrain from cranberry juice, and with readjustments made to therapy, his INR came back to normal levels.

Bibliography
Paeng, C. H.; Sprangue, M.; Jackevicius, C.A. Interaction Between Warfarin and Cranberry Juice. Clin Ther 2007; 29:1730-1735

It describes the case of a seventy-year old woman that while treated with warfarin, consumed camomile-based products (tea and body lotion). The woman was admitted on the hospital with multiple internal hemorrhages.
The patient had taken camomile’s tea to ease throat ache’s symptoms, and had used camomile’s body lotion to decrease the edema localized in both inferior members.
Matricaria recutita is largely used due to its sedative, spasmolytic and anti-inflammatory properties.

Bibliography
Segal,R.; Pilote, L. Warfarin interaction with Matricaria chamomilla. CMAJ 2006; 174(9): 1281-2