The US FDA notified healthcare professionals and patients that the antidepressant Celexa (citalopram hydrobromide) should no longer be used at doses greater than 40 mg per day because it can cause abnormal changes in the electrical activity of the heart. Changes in the electrical activity of the heart (prolongation of the QT interval of the electrocardiogram [ECG]) can lead to an abnormal heart rhythm (including Torsade de Pointes), which can be fatal. Patients at particular risk for developing prolongation of the QT interval include those with underlying heart conditions and those who are predisposed to low levels of potassium and magnesium in the blood.

Studies did not show a benefit in the treatment of depression at doses higher than 40 mg per day. Previously, the citalopram drug label stated that certain patients may require a dose of 60 mg per day. The citalopram drug label has been revised to include the new drug dosage and usage recommendations, as well as information about the potential for QT interval prolongation and Torsade de Pointes. See the FDA Drug Safety Communication Data Summary for additional information.

BACKGROUND: Celexa (citalopram hydrobromide) is in a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs).

RECOMMENDATION: Citalopram causes dose-dependent QT interval prolongation. Citalopram should no longer be prescribed at doses greater than 40 mg per day. Citalopram should not be used in patients with congenital long QT syndrome. Patients with congestive heart failure, bradyarrhythmias, or predisposition to hypokalemia or hypomagnesemia because of concomitant illness or drugs, are at higher risk of developing Torsade de Pointes. See the FDA Drug Safety Communication for additional recommendations for healthcare professionals and patients.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

  • Complete and submit the report Online: www.fda.gov/MedWatch/report.htm
  • Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

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Editor Emeritus on August 20th, 2011

A note from the Vitamin D Council.

A group in Canada, led by Dr. Julia Knight at Mount Sinai Hospital, discovered that administration of 24,000 IU/week for four weeks was associated with lower estrogen levels and progesterone levels. Per 4 ng/ml increase in vitamin D, progesterone levels decreased by 10% and estrogen decreased by 3%. Unlike men, the study was confounded by what estrous cycle phase the women were in.

Knight JA, Wong J, Blackmore KM, Raboud JM, Vieth R. Vitamin D association with estradiol and progesterone in young women. Cancer Causes Control. 2010 Mar;21(3):479-83.

The favorable implications for breast cancer come immediately to mind, but as an old GP, I can tell you that lower female hormones sometimes help women in all kinds of ways, including psychologically. I suspect the women also became more fertile.

The studies about vitamin D are pouring out, and I am happy to summarize these studies and offer my personal insight to the general public through these pieces. Soon, these write-ups will only be offered in full to members of the blog we’re launching (by the end of the month!). This new system will help the Vitamin D Council continue its work and support our programs. So take a minute, consider donating or becoming a member. It is not expensive, but it really does make my day to see that people still care in these rocky economic times.

John J. Cannell MD
Vitamin D Council

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Editor Emeritus on August 20th, 2011

A note from the Vitamin D Council.

I have written before that vitamin D increases testosterone levels in men. It is not a minor effect.

Pilz S, Frisch S, Koertke H, Kuhn J, Dreier J, Obermayer-Pietsch B, Wehr E, Zittermann A. Effect of vitamin D supplementation on testosterone levels in men. Horm Metab Res. 2011 Mar;43(3):223-5.

John J. Cannell MD
Vitamin D Council

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Editor Emeritus on August 18th, 2011

Here is news from the Vitamin D Council.

Professor Hector Palmer and his co-researchers at the Vall d’Hebron Institute of Oncology in Barcelona, Spain, announced this morning the reason vitamin D may be an effective treatment early in the course of colon cancer, yet have little effect later as the cancer becomes more widely spread.

Larriba MJ, Ordóñez-Morán P, Chicote I, Martín-Fernández G, Puig I, et al. 2011 Vitamin D Receptor Deficiency Enhances Wnt/β-Catenin Signaling and Tumor Burden in Colon Cancer. PLoS ONE 6(8): e23524. doi:10.1371/journal.pone.0023524

Vitamin D, in the form of the vitamin D receptor, slows the action of a key carcinogenic protein, beta-catenin. The problem arises when the tumor start to grow and, like in many cancers, reduces the presence of VDR, and finally there is simply not enough VDR to counteract the beta-catenin. And then the tumor takes over.

However, what I really like is Professor Palmer’s statement about what vitamin D can be expected to do. He says, “In light of these findings, chronic vitamin D deficiency represents a risk factor in the development of more aggressive colon tumors.” I also like United Press International’s summary of the study: “Patients in the initial stages of colon cancer, when the vitamin D receptor still has a substantial presence in the cells, could benefit from vitamin D3, but this would not be useful in the advanced stages when the presence of the vitamin D receptor is very much reduced.”

Vitamin D receptor slows colon tumors

That is pretty much what we see in studies of patients with colon cancer. High vitamin D levels appear to slow the growth of colon cancer only in some people, and we now can suspect those people are mainly patients with early stages of colon cancer and healthy numbers of VDRs.

It is a common and sad story. One of the first things most cancers do, early in their growth, is ramp-down the machinery that increases vitamin D production in the cell and ramp-up production of the machinery that gets rid of vitamin D in the cell.

What we hope (and some think it’s more than just hope) is that maintaining physiological vitamin D levels for years and years before you get cancer will ward off the disease. Although some studies support that, not all do, and only time will tell if our hope is grounded in reality.

John J. Cannell MD
Vitamin D Council

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The MedWatch July 2011 Safety Labeling Changes posting includes 32 products with safety labeling changes to the following sections: BOXED WARNINGS, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, PATIENT PACKAGE INSERT, and MEDICATION GUIDE.

The “Summary Page” available via the following link provides a listing of drug names and safety labeling sections revised:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm266122.htm

Clicking on a drug product name in the Summary View will take you to the “detailed view” page, which identifies safety labeling sections and subsections revised, along with a brief summary of new or modified safety information.

The following drugs had modifications to the BOXED WARNINGS, CONTRAINDICATIONS and WARNINGS sections: Epogen/Procrit (epoetin alfa) and Aranesp (darbepoetin alfa)

  • Dostinex (cabergoline) Tablets
  • Nitrostat (nitroglycerin, USP) Sublingual Tablets
  • Paxil (paroxetine HCl) tablets, oral solution and Paxil CR tablets
  • Ranexa (Ranolazine) Extended-Release Tablets
  • Rotavirus Vaccine, Live, Oral, Pentavalent (RotaTeq)
  • Arava (leflunomide) Tablets
  • Bentyl (dicyclomine hydrochloride, USP) Capsules/Tablets, Oral Syrup, Injection
  • Chantix (varenicline) Tablets
  • Flomax (tamsulosin hydrochloride) Capsules
  • Gilenya (fingolimod) capsules 0.5 mg
  • Kenalog-10 (triamcinolone acetonide) Injection, Kenalog-40 (triamcinolone acetonide) Injection
  • Micardis (telmisartan) Tablets
  • Prograf (tacrolimus) Capsules, Injection
  • Seroquel (quetiapine fumarate) Tablets, Seroquel (quetiapine fumarate) XR
  • Tev-Tropin (somatropin [rDNA origin]) for injection
  • Truvada (emtricitabine/tenofovir disoproxil fumarate) tablets
  • Zegerid OTC (omeprazole 20mg and sodium bicarbonate 1100 mg) capsules

Remember, never have or take any drug that you don’t absolutely need. Never be persuaded that you need a drug on the basis of advertising or recommendations from those already taking it. All drugs are dangerous.

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