Herb-Drug Interactions: Cat’s claw

2011

Uncaria tomentosa DC, Uncaria guianensis J.F.Gmel. (Rubiaceae)

Synonym(s) and related species

Life-giving vine of Peru, Samento, Saventaro, Una de gato.

Pharmacopoeias

Cat’s Claw (US Ph 32); Powdered Cat’s Claw (US Ph 32); Powdered Cat’s Claw Extract (US Ph 32); Cat’s Claw Tablets (US Ph 32); Cat’s Claw Capsules (The United States Ph 32).

Constituents

The main constituents of both the closely related species of cat’s claw include the tetracyclic oxindole alkaloids, isorhynchophylline and rhynchophylline, and the indole alkaloids, dihydrocoryynantheine, hirsutine, and hirsuteine. Quinovic acid glycosides have also been isolated.

Note that there are two chemotypes of Uncaria tomentosa, one primarily containing the tetracyclic oxindole alkaloids, isorhynochophylline and rhynchopylline, and one primarily containing the pentacychc oxindole alkaloids, (iso)pteropodine and (iso)mitraphylline.

Use and indications

Cat’s claw roots, bark and leaves have been used for gastric ulcers, arthritis, gonorrhoea, dysentry, herpes zoster, herpes simplex and HIV, and as a contraceptive. In various preclinical studies, antiviral, anti-inflammatory, antirheumatic, immunostimulating, antimutagenic, antitumour and hypotensive properties have been shown. There is some evidence that the tetracyclic oxindole alkaloids antagonise the immunomodulating effects of the pentacychc oxindole alkaloids, and some preparations for arthritis are standardised to contain little or no tetracyclic oxindole alkaloids. Other preparations are essentially free of oxindole alkaloids.

Pharmacokinetics

In two in vitro studies, alcoholic extracts of Uncaria tomentosa were found to be a potent inhibitors of the cytochrome P450 isoenzyme CYP3A4. Inhibitory effects on CYP2D6, CYP2C9 and CYP2C19 were minor (in order of decreasing potency). It was suggested that Uncaria tomentosa might have the potential to interfere with the metabolism of substrates of CYP3A4, but note that St John’s wort was an inhibitor of CYP3A4 in this study, whereas, clinically (multiple dose use), it is an inducer of CYP3A4. This serves as a reminder that in vitro studies cannot be directly extrapolated to the clinical situation, and that the findings need confirmation in a clinical setting.

Interactions overview

Cat’s claw has some antiplatelet and antihypertensive effects, which may be additive to those of conventional drugs. Data from a clinical study suggest that cat’s claw may safely be given with sulfasalazine and hydroxychloroquine. An isolated case reports an increase in the levels of atazanavir, ritonavir and saquinavir in a patient also taking cat’s claw.

Cat’s claw + Antihypertensives

The interaction between cat’s claw and antihypertensives is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

Isorhynchophylline 10 mg/kg, a tetracyclic oxindole alkaloid from cat’s claw, given intravenously was found to lower systolic arterial blood pressure, diastolic arterial blood pressure and heart rate by about 9%, 21% and 14%, respectively, in normotensive rats and about 9%, 6% and 19%, respectively, in hypertensive rats in an experimental study. The effect appears to be dose dependent because isorhynchophylline 20mg/kg, given via the duodenum, lowered the systolic pressure by about 25%, diastolic pressure by about 38% and heart rate by about 25% in normotensive rats. A similar effect was seen in dogs)

Mechanism

It is suggested that the hypotensive effect is mainly due to a vasodilating effect and transient reduction in the heart rate and force of cardiac contraction. Additive blood pressure-lowering effects with conventional antihypertensives might therefore occur.

Importance and management

Evidence appears to be limited to experimental data and an interaction is not established. Uncaria species are commonly used in traditional medicine for hypertension, and the preclinical evidence shows that isorhynchophylline, a tetracyclic oxindole alkaloid from cat’s claw, has antihypertensive activity. However, not all varieties of Uncaria tomentosa contain isorhynchophylline, and some preparations are specifically standardised not to contain this constituent, so not all cat’s claw products will interact. Nevertheless, despite the lack of clinical evidence, there is the potential for an additive blood pressure-lowering effect if cat’s claw containing isorhynchophylline is given with any antihypertensive. Concurrent use need not be avoided, but patients should be made aware of the possibility of increased antihypertensive effects.

Cat’s claw + Antiplatelet drugs

The interaction between cat’s claw and antiplatelet drugs is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

A study in rabbits found that rhynchophylline, a tetracyclic oxindole alkaloid from cat’s claw, caused a concentration-dependent inhibition of platelet aggregation by up to about 78%. Rhynchophylline also inhibited venous thrombosis by up to about 70% in rats. Similar results were seen in a second experimental study in rats.

Mechanism

The authors suggest that the antiplatelet effect may be due to the suppression of the release of arachidonic acid (an inducer of platelet aggregation) from platelet membranes, and the reduction of other release products. Theoretically, additive antiplatelet effects are possible with antiplatelet drugs, which might increase the risk of bleeding.

Importance and management

Evidence is limited to these experimental studies. Any interaction is complicated because not all varieties of Uncaria tomentosa contain rhynchophylline, and some preparations are specifically standardised not to contain this constituent, so not all cat’s claw products will necessarily interact. What is known suggests that some cat’s claw products may possibly have antiplatelet effects, which may be additive to conventional antiplatelet drugs. Concurrent use need not be avoided (indeed combinations of antiplatelet drugs are often prescribed together) but it may be prudent to be aware of the potential for increased bleeding if cat’s claw is given with other antiplatelet drugs such as aspirin and clopidogrel. Warn patients to discuss any episode of prolonged bleeding with a healthcare professional.

Cat’s claw + Antirheumatics

No additional adverse effects appear to occur when cat’s claw is taken with sulfasalazine or hydroxychloroquine.

Evidence, mechanism, importance and management

A cat’s claw preparation (without tetracyclic oxindole alkaloids) was used for 52 weeks in a small clinical study in patients taking sulfasalazine or hydroxychloroquine. There were no safety concerns from the use of the combination when compared with placebo, and a modest clinical benefit. Although this study does not exclude the possibility of a drug interaction, it provides some evidence that cat’s claw can be combined with these established drugs without a problem.

Cat’s claw + Food

No interactions found.

Cat’s claw + Herbal medicines

No interactions found.

Cat’s claw + Protease inhibitors

An isolated case report describes raised atazanavir, ritonavir and saquinavir levels following the use of cat’s claw.

Clinical evidence

An HIV-positive woman awaiting liver transplantation, taking atazanavir 300 mg daily, ritonavir 100 mg daily and saquinavir 1 g daily, in combination with abacavir 600 mg daily and lamivudine 300 mg daily, was found to have an increased trough level of all three protease inhibitors. Atazanavir trough levels were 1.22 micrograms/mL (expected range of 0.15 to 0.18 micrograms/mL), ritonavir trough levels were 6.13 micrograms/mL (expected level of 2.1 micrograms/mL) and saquinavir trough levels were 3.4 micrograms/mL (expected range 0.1 to 0.25 micrograms/mL). On further questioning, the patient reported no change in her compliance with the medication but reported that she been taking a herbal supplement containing cat’s claw for the previous 2 months. No evidence of protease inhibitor-related toxicity was found and the patient reported no adverse effects. The supplement was stopped and by day 15 the levels of all three drugs had returned to within normal limits.

Experimental evidence

No relevant data found.

Mechanism

An in vitro studies suggested that cat’s claw may inhibit the cytochrome P450 isoenzyme CYP3A4, the main isoenzyme responsible for the metabolism of atazanavir, ritonavir and saquinavir; however, the results of this study are questionable. See under Pharmacokinetics.

Importance and management

Evidence appears to be limited to one case report from which it is difficult to draw general conclusions. What it illustrates is that more research is needed into the use of cat’s claw with protease inhibitors. Patients taking drugs for serious conditions such as HIV infection should carefully consider the risks and benefits of adding herbal medicines to their existing regimen, where the outcome of concurrent use is unknown.