Drug Interactions between black cohosh and dexamethasone / ketorolac / moxifloxacin

MONITOR CLOSELY: Concomitant administration of corticosteroids may potentiate the risk of tendinitis and tendon rupture associated with fluoroquinolone treatment. The mechanism is unknown. Tendinitis and tendon rupture have most frequently involved the Achilles tendon, although cases involving the rotator cuff (the shoulder), the hand, the biceps, and the thumb have also been reported. Some have required surgical repair or resulted in prolonged disability. Tendon rupture can occur during or up to several months after completion of fluoroquinolone therapy.

MANAGEMENT: Caution is recommended if fluoroquinolones are prescribed in combination with corticosteroids, particularly in patients with other concomitant risk factors (e.g., age over 60 years; recipient of kidney, heart, and/or lung transplant). Patients should be advised to stop taking the fluoroquinolone, avoid exercise and use of the affected area, and promptly contact their physician if they experience pain, swelling, or inflammation of a tendon. In general, fluoroquinolones should only be used to treat conditions that are proven or strongly suspected to be caused by bacteria and only if the benefits outweigh the risks.

MONITOR: The combined use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the potential for serious gastrointestinal (GI) toxicity, including inflammation, bleeding, ulceration, and perforation. In a large, case-control study of elderly patients, those who used corticosteroids and NSAIDs concurrently had an estimated relative risk (RR) for peptic ulcer disease and GI hemorrhage of 14.6 compared to those who used neither. Corticosteroid use was associated with a doubling of the risk (estimated RR = 2.0), but the risk was confined to those who also used NSAIDs. It is possible that both categories of agents are ulcerogenic and have additive effects on the GI mucosa during coadministration. Some investigators have also suggested that the primary effect of corticosteroids in this interaction is to delay healing of erosions caused by NSAIDs rather than cause de novo ulcerations.

MANAGEMENT: Caution is advised if corticosteroids and NSAIDs are used together, especially in patients with a prior history of peptic ulcer disease or GI bleeding and in elderly and debilitated patients. During concomitant therapy, patients should be advised to take the medications with food and to immediately report signs and symptoms of GI ulceration and bleeding such as severe abdominal pain, dizziness, lightheadedness, and the appearance of black, tarry stools. The selective use of prophylactic anti-ulcer therapy (e.g., antacids, H2-antagonists) may be considered.

GENERALLY AVOID: Concomitant use of black cohosh (Cimicifuga racemosa rhizome) with other agents that are known to induce hepatotoxicity may theoretically increase the risk of liver injury. Black cohosh has been suspected in rare cases of liver toxicity ranging from abnormal liver function tests and jaundice to various forms of hepatitis and hepatic failure requiring transplantation. The onset has typically been within the first 3 months after initiation of black cohosh. Although approximately half of the cases resulted in hospitalization, most improved or resolved following discontinuation of the product. Many of the cases were not well documented with respect to the specific herbal formulation and dose used or timeframe of treatment in relation to onset of reaction, or they were complicated by multiple confounding factors. Some of the cases also involved products containing multiple herbal or other medicinal substances. Nevertheless, the European Medicines Agency (EMEA) and the Committee on Herbal Medicinal Products (HMPC) reviewed 42 such cases and released an assessment statement in 2006 indicating a potential connection between products containing Cimicifuga racemosa rhizome and human hepatotoxicity. The Medicines and Healthcare products Regulatory Agency (MHRA) in the U.K. also issued an assessment report supporting a causal association after reviewing data from over 40 cases received through their reporting system and similar systems in other countries, as well as in the published literature. Hepatotoxicity warnings are currently required on products containing black cohosh marketed in many European countries and Australia.

MANAGEMENT: Until more information is available, patients should consider avoiding the use of black cohosh if they are receiving other potentially hepatotoxic agents (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; other herbals and nutritional supplements such as chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice.

MONITOR: Coadministration with nonsteroidal anti-inflammatory drugs (NSAIDs) may potentiate the risk of central nervous system toxicity sometimes associated with fluoroquinolone use. The interaction has been reported most often with enoxacin. It may occur with other fluoroquinolones as well, but is poorly documented. The exact mechanism of interaction is unknown. Some investigators suggest that the piperazine ring of fluoroquinolones may inhibit the binding of gamma-aminobutyric acid (GABA) to brain receptors and that NSAIDs may synergistically add to this effect. Patients with a history of seizures may be at greater risk.

MANAGEMENT: Clinical monitoring for signs of CNS stimulation such as tremors, involuntary muscle movements, hallucinations, or seizures is recommended if fluoroquinolone antibiotics are prescribed in combination with NSAIDs.

GENERALLY AVOID: Concomitant use of black cohosh (Cimicifuga racemosa rhizome) with other agents that are known to induce hepatotoxicity may theoretically increase the risk of liver injury. Black cohosh has been suspected in rare cases of liver toxicity ranging from abnormal liver function tests and jaundice to various forms of hepatitis and hepatic failure requiring transplantation. The onset has typically been within the first 3 months after initiation of black cohosh. Although approximately half of the cases resulted in hospitalization, most improved or resolved following discontinuation of the product. Many of the cases were not well documented with respect to the specific herbal formulation and dose used or timeframe of treatment in relation to onset of reaction, or they were complicated by multiple confounding factors. Some of the cases also involved products containing multiple herbal or other medicinal substances. Nevertheless, the European Medicines Agency (EMEA) and the Committee on Herbal Medicinal Products (HMPC) reviewed 42 such cases and released an assessment statement in 2006 indicating a potential connection between products containing Cimicifuga racemosa rhizome and human hepatotoxicity. The Medicines and Healthcare products Regulatory Agency (MHRA) in the U.K. also issued an assessment report supporting a causal association after reviewing data from over 40 cases received through their reporting system and similar systems in other countries, as well as in the published literature. Hepatotoxicity warnings are currently required on products containing black cohosh marketed in many European countries and Australia.

MANAGEMENT: Until more information is available, patients should consider avoiding the use of black cohosh if they are receiving other potentially hepatotoxic agents (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; other herbals and nutritional supplements such as chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice.