The da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA) has become available in recent years for use in laparoscopic prostatectomy, gynecological procedures, general surgery, otolaryngology and cardiothoracic procedures.

Use of a selective serotonin reuptake inhibitor (SSRI) is common in women taking tamoxifen (Nolvadex, and others) for breast cancer, both to treat depression and to decrease hot flashes. However, tamoxifen must be metabolized by CYP2D6 to become pharmacologically fully active (MJ Higgins et al. J Natl Compr Canc Netw 2009; 7:203), and the SSRIs fluoxetine (Prozac, and others) and paroxetine (Paxil, and others) are strong inhibitors of CYP2D6. Sertraline (Zoloft, and others) inhibits CYP2D6 to a lesser extent. Citalopram (Celexa, and others) and escitalopram (Lexapro), the 2 other SSRIs approved for treatment of depression, are only weak inhibitors of CYP2D6.

Two observational studies presented at a recent meeting of the American Society of Clinical Oncology (45th annual meeting, May 29-June 2, 2009, Orlando, FL abstracts CRA508, CRA509) examined the effect of strong inhibitors of CYP2D6 on the success rate of tamoxifen in preventing recurrence of breast cancer. One found that women who took fluoxetine, paroxetine or sertraline (or bupropion, duloxetine, terbinafine, quinidine or long-term diphenhydramine) with tamoxifen had a higher 2-year recurrence rate (13.9% vs. 7.5%). The other study found no association between cancer recurrence and use of a CYP2D6 inhibitor.

There is no good evidence that any one SSRI is more effective than any other for treatment of depression. For women who are taking tamoxifen and need to begin treatment with an SSRI to treat depression, citalopram or escitalopram might be the safest choice (Treat Guidel Med Lett 2006; 4:35). Use of an SSRI to treat hot flashes in women taking tamoxifen should probably be reconsidered.

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Milnacipran (Savella - Forest), an oral selective serotonin and norepinephrine reuptake inhibitor (SNRI), is the third drug approved by the FDA for management of fibromyalgia. The 2 others are pregabalin, a gammaaminobutyric acid (GABA) analog also approved for treatment of diabetic neuropathy, post-herpetic neuralgia and epilepsy, and duloxetine, an SNRI also approved for treatment of depression, diabetic neuropathy and generalized anxiety disorder.

The FDA has approved an oral, fixed-dose combination (Treximet - GlaxoSmithKline) of the selective serotonin receptor agonist ("triptan") sumatriptan (Imitrex) and the nonsteroidal anti-inflammatory drug (NSAID) naproxen sodium (Anaprox, and others) for acute treatment of migraine attacks.

A reader expressed disappointment that our recent listing of “Some Warfarin Drug Interactions”1 did not include acetaminophen. Perhaps it should have. Acetaminophen can increase the anticoagulant effect of warfarin, particularly with continued use, but it does so inconsistently. The mechanism of this interaction has not been established, but may be related to an acetaminophen metabolite inhibiting vitamin K-epoxide reductase, the target for warfarin’s anticoagulant effect.2

Patient susceptibility varies, possibly on a genetic basis; occasional use of acetaminophen generally has little or no effect on the international normalized ratio (INR) in patients on chronic warfarin therapy, but in some, even a few grams of the drug may cause a dramatic increase in INR. One study in healthy subjects found no effect of acetaminophen 4 g per day for 2 weeks, while another study in patients with the same acetaminophen dose for the same period of time found a moderate increase in INR.3,4 It might be prudent to monitor INR in patients on chronic warfarin therapy more closely than usual when they take more than 2 g per day of acetaminophen for more than a few days.

1. Pharmacogenetic-based dosing of warfarin. Med Lett Drugs Ther 2008; 50:39.
2. HH Thijssen et al. Paracetamol (acetaminophen) warfarin interaction: NAPQI, the toxic metabolite of paracetamol, is an inhibitor of enzymes in the vitamin K cycle. Thromb Haemost 2004; 92:797.
3. D Kwan et al. The effects of acetaminophen on pharmacokinetics and pharmacodynamics of warfarin. J Clin Pharmacol 1999; 39:68.
4. I Mahe et al. Paracetamol: A haemorrhagic risk factor in patients on warfarin. Br J Clin Pharmacol 2005; 59:371.

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Sitagliptin (Januvia) and metformin (Glucophage, and others) are now available in a single tablet (Janumet - Merck) for treatment of type 2 diabetes. The combination is approved by the FDA for use in patients not adequately controlled by sitagliptin or meformin alone or in those already taking both drugs. Metformin is also available in combination with the thiazolidinediones pioglitazone and rosiglitazone and with the sulfonylureas glipizide and glyburide.

Gadolinium-based contrast agents, which are used mainly for magnetic resonance imaging and angiography, were first introduced partly because of the discovery in the 1990’s that iodine-based contrast agents could cause nephrotoxicity and acute renal failure. Some recent reports have suggested, however, that gadolinium-based agents may also be nephrotoxic.1 One patient who developed acute renal failure after use of gadolinium-based contrast had a renal biopsy that showed acute tubular injury.2

Moreover, after exposure to gadolinium-based contrast, some patients with severe renal insufficiency, or liver disease with any degree of renal insufficiency, have developed nephrogenic systemic fibrosis, with sclerodermalike changes in the skin, connective tissues and other organs, which has sometimes been fatal.3,4 The mechanism is unknown; release of free gadolinium ions, which are toxic, has been suggested.5

Gadolinium-containing contrast agents are marketed in the US as Magnevist, MultiHance, Omniscan, OptiMARK, and ProHance (www.fda.gov). In patients with renal insufficiency, especially those requiring dialysis, use of any contrast agent should be avoided if possible.

1. C Briguori et al. Gadolinium-based contrast agents and nephrotoxicity in patients undergoing coronary artery procedures. Cath Cardiovasc Interven 2006; 67:175.

2. H Akgun et al. Are gadolinium-based contrast media nephrotoxic? A renal biopsy study. Arch Pathol Lab Med 2006; 130:1354.

3. AS Boyd et al. Gadolinium deposition in nephrogenic fibrosing dermopathy. J Am Acad Dermatol 2007; 56:27.

4. A Deo et al. Nephrogenic systemic fibrosis: a population study examining the relationship of disease development to gadolinium exposure. Clin J Am Soc Nephrol 2007; 2:264.

5. T Grobner and FC Prischl. Gadolinium and nephrogenic systemic fibrosis. Kidney Int 2007 May 16; epub ahead of print.

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