Source:  http://www.cdc.gov/h1n1flu/updates/international/map.htm

http://www.cdc.gov/h1n1flu/vaccination/acip.htm

With the new H1N1 virus continuing to cause illness, hospitalizations and deaths in the US during the normally flu-free summer months and some uncertainty about what the upcoming flu season might bring, CDC’s Advisory Committee on Immunization Practices has taken an important step in preparations for a voluntary novel H1N1 vaccination effort to counter a possibly severe upcoming flu season. On July 29, ACIP met to consider who should receive novel H1N1 vaccine when it becomes available.

Novel H1N1 Vaccine

Every flu season has the potential to cause a lot of illness, doctor’s visits, hospitalizations and deaths.  CDC is concerned that the new H1N1 flu virus could result in a particularly severe flu season this year.  Vaccines are the best tool we have to prevent influenza.  CDC hopes that people will start to go out and get vaccinated against seasonal influenza as soon as vaccines become available at their doctor’s offices and in their communities (this may be as early as August for some).  The seasonal flu vaccine is unlikely to provide protection against novel H1N1 influenza.  However a novel H1N1 vaccine is currently in production and may be ready for the public in the fall. The novel H1N1 vaccine is not intended to replace the seasonal flu vaccine – it is intended to be used along-side seasonal flu vaccine. 

CDC’s Advisory Committee on Immunization Practices (ACIP), a panel made up of medical and public health experts, met July 29, 2009, to make recommendations on who should receive the new H1N1 vaccine when it becomes available.  While some issues are still unknown, such as how severe the virus will be during the fall and winter months, the ACIP considered several factors, including current disease patterns, populations most at-risk for severe illness based on current trends in illness, hospitalizations and deaths, how much vaccine is expected to be available, and the timing of vaccine availability.

The groups recommended to receive the novel H1N1 influenza vaccine include:

• Pregnant women because they are at higher risk of complications and can potentially provide protection to infants who cannot be vaccinated;
• Household contacts and caregivers for children younger than 6 months of age because younger infants are at higher risk of influenza-related complications and cannot be vaccinated. Vaccination of those in close contact with infants less than 6 months old might help protect infants by “cocooning” them from the virus;
• Healthcare and emergency medical services personnel because infections among healthcare workers have been reported and this can be a potential source of infection for vulnerable patients. Also, increased absenteeism in this population could reduce healthcare system capacity;
• All people from 6 months through 24 years of age
  • Children from 6 months through 18 years of age because we have seen many cases of novel H1N1 influenza in children and they are in close contact with each other in school and day care settings, which increases the likelihood of disease spread, and
  • Young adults 19 through 24 years of age because we have seen many cases of novel H1N1 influenza in these healthy young adults and they often live, work, and study in close proximity, and they are a frequently mobile population; and,
• Persons aged 25 through 64 years who have health conditions associated with higher risk of medical complications from influenza.

We do not expect that there will be a shortage of novel H1N1 vaccine, but flu vaccine availability and demand can be unpredictable and there is some possibility that initially, the vaccine will be available in limited quantities.  So, the ACIP also made recommendations regarding which people within the groups listed above should be prioritized if the vaccine is initially available in extremely limited quantities. For more information see the CDC press release CDC Advisors Make Recommendations for Use of Vaccine Against Novel H1N1.  

Once the demand for vaccine for the prioritized groups has been met at the local level, programs and providers should also begin vaccinating everyone from the ages of 25 through 64 years. Current studies indicate that the risk for infection among persons age 65 or older is less than the risk for younger age groups. However, once vaccine demand among younger age groups has been met, programs and providers should offer vaccination to people 65 or older.

Source:  http://www.cdc.gov/h1n1flu/surveillanceqa.htm

Source:  http://www.cdc.gov/h1n1flu/surveillanceqa.htm

http://www.cdc.gov/h1n1flu/surveillanceqa.htm

Novel H1N1 Flu: Facts and Figures

Disease Characteristics

When the novel H1N1 flu outbreak was first detected in mid-April 2009, CDC began working with states to collect, compile and analyze information regarding the novel H1N1 outbreak. On July 24, 2009 official reporting of individual cases of confirmed and probable novel H1N1 infection was discontinued. Below is a summary of information gathered during the first weeks of the outbreak. These key disease characteristics are thought to remain an accurate representation of novel H1N1 flu.

FDA NEWS RELEASE (http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm174780.htm)

For Immediate Release: July 31, 2009

Media Inquiries: Karen Riley, 301-796-4674, karen.riley@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA Approves New Drug Treatment for Type 2 Diabetes

The U.S. Food and Drug Administration today approved Onglyza (saxagliptin), a once-daily tablet to treat Type 2 diabetes in adults. The medication is intended to be used with diet and exercise to control high blood sugar levels.

The hormone insulin keeps blood sugar (glucose) levels within a narrow range in people who don’t have diabetes. People with Type 2 diabetes are either resistant to insulin or do not produce enough insulin to maintain normal blood sugar levels.

Onglyza is in a class of drugs known as dipeptidyl peptidase-4 (DPP-4) inhibitors which stimulate the pancreas to make more insulin after eating a meal.

“Keeping blood sugar levels in adequate control is essential to the good health of the 24 million people in the United States with Type 2 diabetes,” said Mary Parks, M.D., director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research. “High blood sugar levels can cause blurry vision and excessive urination and eventually result in such serious conditions as kidney and eye disease.”

The most common side effects observed with Onglyza are upper respiratory tract infection, urinary tract infection, and headache. Other side effects include allergic-like reactions such as rash and hives.

Approval of Onglyza was primarily based on the results of eight clinical trials. The application seeking FDA approval was submitted before December 2008 when the agency recommended that manufacturers of new diabetes drugs carefully design and evaluate their clinical trials for cardiovascular safety. Although Onglyza was not associated with an increased risk for cardiovascular events in patients who were mainly at low risk for these events, the FDA is requiring a postmarket study that will specifically evaluate cardiovascular safety in a higher risk population.

Onglyza is manufactured by Bristol-Myers Squibb Co. of Princeton, N.J., and marketed by Bristol-Myers and AstraZeneca Pharmaceuticals LP, of Wilmington, Del.

31 JULY 2009 | GENEVA — Research conducted in the USA and published 29 July in The Lancet [1] has drawn attention to an increased risk of severe or fatal illness in pregnant women when infected with the H1N1 pandemic virus.

Several other countries experiencing widespread transmission of the pandemic virus have similarly reported an increased risk in pregnant women, particularly during the second and third trimesters of pregnancy. An increased risk of fetal death or spontaneous abortions in infected women has also been reported.

Increased risk for pregnant women

Evidence from previous pandemics further supports the conclusion that pregnant women are at heightened risk.

While pregnant women are also at increased risk during epidemics of seasonal influenza, the risk takes on added importance in the current pandemic, which continues to affect a younger age group than that seen during seasonal epidemics.

WHO strongly recommends that, in areas where infection with the H1N1 virus is widespread, pregnant women, and the clinicians treating them, be alert to symptoms of influenza-like illness.

WHO recommendations for treatment

Treatment with the antiviral drug oseltamivir should be administered as soon as possible after symptom onset. As the benefits of oseltamivir are greatest when administered within 48 hours after symptom onset, clinicians should initiate treatment immediately and not wait for the results of laboratory tests.

While treatment within 48 hours of symptom onset brings the greatest benefits, later initiation of treatment may also be beneficial. Clinical benefits associated with oseltamivir treatment include a reduced risk of pneumonia (one of the most frequently reported causes of death in infected people) and a reduced need for hospitalization.

WHO has further recommended that, when pandemic vaccines become available, health authorities should consider making pregnant women a priority group for immunization.

Danger signs in all patients

Worldwide, the majority of patients infected with the pandemic virus continue to experience mild symptoms and recover fully within a week, even in the absence of any medical treatment. Monitoring of viruses from multiple outbreaks has detected no evidence of change in the ability of the virus to spread or to cause severe illness.

In addition to the enhanced risk documented in pregnant women, groups at increased risk of severe or fatal illness include people with underlying medical conditions, most notably chronic lung disease (including asthma), cardiovascular disease, diabetes, and immunosuppression. Some preliminary studies suggest that obesity, and especially extreme obesity, may be a risk factor for more severe disease.

Within this largely reassuring picture, a small number of otherwise healthy people, usually under the age of 50 years, experience very rapid progression to severe and often fatal illness, characterized by severe pneumonia that destroys the lung tissue, and the failure of multiple organs. No factors that can predict this pattern of severe disease have yet been identified, though studies are under way.

Clinicians, patients, and those providing home-based care need to be alert to danger signs that can signal progression to more severe disease. As progression can be very rapid, medical attention should be sought when any of the following danger signs appear in a person with confirmed or suspected H1N1 infection:

• shortness of breath, either during physical activity or while resting
• difficulty in breathing
• turning blue
• bloody or coloured sputum
• chest pain
• altered mental status
• high fever that persists beyond 3 days
• low blood pressure.

In children, danger signs include fast or difficult breathing, lack of alertness, difficulty in waking up, and little or no desire to play.

________________________________

[1] Jamiesan DG et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009; published online July 29, 2009

http://www.pediatricsupersite.com/view.aspx?rid=41527

 Continuation of the Summer Series  by James H. Brien, DO

An 11-year-old male was admitted to the hospital last month for evaluation and treatment of severe facial swelling. The history of the chief complaint was that swelling of the face with pain and itching was noticed 48 hours earlier, when he awoke with the problem. His parents had been giving him Benadryl and applying some over-the-counter cream for symptomatic relief, but these were not helping, and the swelling seemed to be worsening in degree and distribution. There was also some blistering, which was concerning for a staphylococcal infection by the referring physician, even though there has been no fever with this problem.

There was dramatic swelling of the patient’s face, with the inability to open his right eye, and with multiple areas of weeping lesions with some intact vesicles, predominantly on both sides of his face, both ears and anterior and posterior neck. All photos courtesy of James H. Brien

His past medical history is unremarkable except for an undocumented history of previous staphylococcal infections and multiple episodes of poison ivy contact dermatitis in past years. On further review of old records, he had a positive culture from a poison ivy lesion a year earlier that grew coagulase-negative Staphylococcus.

He is otherwise healthy with up to date immunizations.

He has no known drug allergies and the only medication being taken is Benadryl and the topical cream noted above.

James H. Brien, DO

Pediatric Infectious Disease, Scott and White’s Children’s Health Center and Associate Professor of Pediatrics,
Texas A&M University, College of Medicine, Temple, Texas.
e-mail:jhbrien@aol.com

His family history is unremarkable and no one else at home is sick or has a similar rash. However, he had been out hiking with his grandparents in some nearby woods the day before waking up with the rash, and they may have seen some poison ivy along the way.

Examination on arrival to the hospital revealed normal vital signs. His only positive finding was the dramatic swelling of his face, with the inability to open his right eye, and with multiple areas of weeping lesions with some intact vesicles, predominantly on both sides of his face, both ears and anterior and posterior neck (Figures 1 – 3). There were a few patches of mild erythema at other more distant sites, including the groin. The rest of his examination was otherwise completely normal.

Lab tests done included a normal complete blood count, a negative Gram stain from one of the weeping lesions and cultures of blood and lesion are pending. The admission team began treatment with IV Ceftriaxone and Clindamycin.

What’s your diagnosis?

1. Facial cellulitis
2. Sunburn
3. Cutaneous herpes simplex
4. Contact dermatitis due to poison ivy

Case Discussion

In spite of the severity and suggestion that he may have had a staphylococcal infection, this turned out to be a severe case of otherwise uncomplicated contact dermatitis due to poison ivy exposure (D). I don’t recall a summer when we did not admit at least one patient, usually boys, for poison ivy of the face. This results when susceptible individuals come in contact with urushiol, which is the oily chemical in the sap produced by Toxicodendron radicans, sometimes referred to as Rhus toxicodendron, but usually referred to as poison ivy. This can happen by direct contact with the plant or by contact with and animal (like your dog or cat) or an inanimate object that has the oil on its surface.

Poison ivy has a three-leaf configuration.

These ubiquitous plants have a distinctive appearance, with their three-leaf configuration as shown in figure 4, and tend to be bright green, sometimes with a shiny surface and with the middle leaf having a slightly longer stem. They typically are camouflaged by other brush, as shown in figure 5 (poison ivy within the square). Therefore, it’s easy to see how one comes in contact without knowing it, while doing routine gardening work, hiking or other outdoor activity. The rash will usually be on the extremities, as shown in figure 6, with the characteristic linear and / or patchy raised erythematous rash. But when children get in touch with the plant, they will frequently spread it to their face. Usually girls will have less severe spread (Figure 7) than boys, as shown in the case presented. Boys are also more likely to spread the rash to the groin, especially those who grow up to be baseball pitchers (sorry, no pictures).

Poison ivy is often camouflaged by other plants.

Prevention by avoidance is best, but when contact occurs, one can try to remove the oil with rubbing alcohol and then rinsing with water. If the rash occurs, usually a topical steroid cream will speed the resolution (Figures 8 & 9 – the same patient in figure 6). Occasionally, systemic steroids are used, as in the case presented. We usually start with 2 mg/kg/day of either oral prednisone or equivalent IV dose of methylprednisolone for about five days. You can either stop then or taper the dose over a week. Some find the application of topical Domeboro astringent solution to be helpful.

Cellulitis is always a consideration and is sometimes the driving factor in admitting these children with facial poison ivy. The same patient with severe contact dermatitis on the arm or leg would probably be treated at home with oral steroids. But there’s something about involving the face that makes us want to be more aggressive. Most of the patients we have had admitted over the years arrive already on antibiotics. However, it’s fairly uncommon for contact dermatitis to get secondarily infected (I have never seen it). Cellulitis will always have some spreading erythema that may also have some blistering similar to that seen with poison ivy.

The rash will usually be on the extremities with the characteristic linear pattern.

The patient in figure 10 was admitted with the diagnosis of facial cellulitis and was taken off the antibiotics upon arrival to the ward and treated with steroids as noted above with near complete resolution in a matter of days (Figure 11).

Usually girls will have less severe rash spread than boys.

Sunburn will certainly cause erythema and swelling of the face, but simple history of sun exposure and appearance of sun-protected areas with more diffuse redness will usually make it easy to differentiate. Beware, however, some may have poison ivy AND sunburn. Such was the case presented.

Lastly, cutaneous herpes simplex virus infections of the face are common and are usually limited to a single patch or area, with vesicular lesions (Figure 12).

Columnist comments

I would like to thank my wife, Ellen, for letting me photograph the poison ivy in her garden before she condemned it to oblivion after getting it on her arm (again) (Figures 6, 8 and 9) while doing some yard work. Since I can’t seem to keep her out of the bushes, we keep a supply of Triamcinolone cream and a Medrol Dose Pack handy, just in case. (Hopefully I can get this issue out of the mailbox before she does).

A topical steroid cream will speed the resolution (figure 8: before, Figure 9: after).

I want to thank those of you who have responded to Dr. Burnett’s book drive for some of the Afghanistan clinics. It is a decent, humanitarian thing to do, the sort of thing that wins the hearts of the people, in this case the Afghan physicians trying to cope with a very difficult situation. Please refer to the last two issues for the APO addresses.

A patient admitted for cellulitis was treated with steroids (figure 10: before, Figure 11: after).

Speaking of books, the handiest pocket book I have ever used is Nelson’s Pocket Book of Pediatric Antimicrobial Therapy by John D. Nelson, MD. The oldest copy I can find in my office is the 4th edition (1981-1982, and signed by John Nelson). Well, now this venerable pocket reference is in its 17th edition (2009) and is edited by John S. Bradley and John D. Nelson, and is published and sold by the American Academy of Pediatrics for $19.95 for AAP members or $24.95 for nonmembers (a bargain at twice the price).

A patient with cutaneous herpes simplex infection on the face.

You can find it by going to the AAP web site (www.AAP.org) and follow the publications tab. I still carry this book in my white coat pocket in the hospital, and use it every day. You would think I would know everything in it by now, but alas I don’t, and never will. Its well-worn exterior is testimony to that fact.

Lastly, start making plans to attend the 44th Annual Uniformed Services Pediatric Seminar (USPS) in San Diego, March 7 – 10, 2010. There’s probably not much posted yet, but you can find out more about it at the following site – http://www.aap.org/sections/uniformedservices/usps.htm. I’ll hope to see you there.

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm174315.htm

Information for Healthcare Professionals: New Safety Information for Colchicine (marketed as Colcrys)

During the drug application review, FDA identified two previously uncharacterized safety concerns associated with the use of colchicine (marketed as Colcrys).

First, FDA analyzed safety data for colchicine from adverse events reported to the Agency, the published literature, and company-sponsored pharmacokinetic and drug interaction studies. This analysis revealed cases of fatal colchicine toxicity reported in certain patients taking standard therapeutic doses of colchicine and concomitant medications that interact with colchicine, such as clarithromycin. These reports suggest that drug interactions affecting the gastrointestinal absorption and/or hepatic metabolism of colchicine play a central role in the development of colchicine toxicity.

Second, data submitted supporting the safety and efficacy of Colcrys in acute gout flares demonstrated that a substantially lower dose of colchicine was as effective as the higher dose traditionally used. Moreover, patients receiving the lower dose experienced significantly fewer adverse events compared to the higher dose.

Based on this information, FDA is highlighting important safety considerations found in the approved prescribing information to assure safe use of Colcrys.

FDA recommends:

• Healthcare professionals not use P-glycoprotein (P-gp) or strong CYP3A4 inhibitors in patients with renal or hepatic impairment who are currently taking colchicine. 
• Healthcare professionals consider a dose reduction or interruption of colchicine treatment in patients with normal renal and hepatic function if treatment with a P-gp or a strong CYP3A4 inhibitor is required.
• Healthcare professionals prescribe the FDA-approved Colcrys dose for the treatment of acute gout flares: 1.2 mg followed by 0.6mg in 1 hour (total 1.8mg).
• Healthcare professionals refer to Colcrys’ approved prescribing information for specific dosing recommendations and additional drug interaction information.
• Patients review the Medication Guide for important safety information

To report any unexpected adverse or serious events associated with the use of this drug, please contact the FDA MedWatch programusing the information at the bottom of this page.

• Be aware that there is now an FDA-approved single-ingredient colchicine product, Colcrys
• Understand that the recommended dose of Colcrys (colchicine) for Familial Mediterranean Fever (FMF) and acute gout flares are different
• Be aware that concomitant use of P-gp and strong CYP3A4 inhibitors may cause severe drug interactions with colchicine, including death
• Evaluate patients’ underlying susceptibility for colchicine toxicity due to renal and hepatic impairment or age
• Understand that concomitant use of colchicine and P-gp or strong CYP3A4 inhibitors is contraindicated in patients with renal or hepatic impairment.
• Be aware that Colcrys has a Medication Guide and urge patients, their families, and caregivers to review the Medication Guide carefully
• Inform patients who are taking colchicine to check with healthcare professionals before taking any new medicine

 Information for patients, family members, and caregivers:

• Understand that colchicine (Colcrys) is not a pain medication and should not be used for other causes of pain
• Understand that life-threatening and fatal drug interactions can occur with Colcrys if it is given with certain medications.  These interactions can occur even at prescribed Colcrys doses, and with medications that are given for a limited time, such as antibiotics
• Review the Medication Guide that accompanies Colcrys.
• Discuss with healthcare professionals all medications being taken and check with them before starting any new medications
• Avoid consuming grapefruit and grapefruit juice while using colchicine
• Pay close attention for any signs or symptoms of colchicine toxicity such as muscle weakness or pain, numbness or tingling in the fingers or toes, unusual bleeding or bruising, severe diarrhea or vomiting, feeling weak or tired, increased infections, and pale or gray color of the lips, tongue, or palms of hands. If any of these symptoms occur, seek medical attention right away

Background and Data Summary:  Severe Drug Interactions
During the drug application review, FDA analyzed safety data for colchicine-related deaths described in the published literature, adverse events reported to FDA’s Adverse Event Reporting System (AERS), and company-sponsored pharmacokinetic and drug interaction studies. The analysis found 169 deaths associated with the use of oral colchicine. 

Of the 169 deaths, 117 were not reported as overdoses; i.e., the majority of reported deaths had colchicine doses within the therapeutic range of less than or equal to 2 mg per day.  The reported death cases did not contain information regarding patients’ renal or hepatic function. Sixty of the 117 reported deaths (51%) involved patients who were concomitantly using clarithromycin.* These reports suggest alterations in the pharmacokinetics of colchicine played a central role in the development of toxicity.

The pharmacokinetics of colchicine may be affected in several ways. The absorption of colchicine from the gastrointestinal tract is thought to be limited by the multidrug resistance efflux transporter P-glycoprotein (P-gp).  Additionally, colchicine is a substrate of intestinal and hepatic cytochrome P450 3A4 (CYP3A4), which catalyzes demethylation of colchicine to inactive metabolites.  Colchicine is primarily eliminated by hepatobiliary excretion through the stool.  Renal excretion accounts for 10-20% of colchicine elimination in patients with normal renal function. 

Consistent with the current understanding of colchicine metabolism, certain drugs increase the potential for colchicine toxicity via modulation of P-gp and CYP3A4 activity.  Life-threatening and fatal drug interactions have been reported in patients treated with colchicine when P-gp and strong CYP3A4 inhibitors, particularly clarithromycin, were also being used.  In the majority of cases, the doses of colchicine were within the therapeutic range. 

Fatal and non-fatal cases of colchicine toxicity have also been reported in the literature with concomitant use of other CYP3A4 and P-gp inhibitors, such as cyclosporine, erythromycin, and calcium channel antagonists such as verapamil and diltiazem. Other examples of P-gp and strong CYP3A4 inhibitors include telithromycin, ketoconazole, itraconazole, HIV protease inhibitors, and nefazodone. Toxicity has also been reported in a patient who began to regularly consume a liter of grapefruit juice daily while being treated chronically with colchicine. Additionally, cases of myopathy and/or rhabdomyolysis in patients receiving colchicine have been reported with concomitant use of statins, fenofibrate/gemfibrozil, cyclosporine, or digoxin. 

Based on this information, FDA concludes there is a risk for severe drug interactions in certain patients treated with colchicine and concomitant P-gp or strong CYP3A4 inhibitors. FDA recommends that P-gp or strong CYP3A4 inhibitors not be used in patients with renal or hepatic impairment who are currently taking colchicine. Furthermore, FDA recommends that healthcare professionals consider a dose reduction or interruption of colchicine in patients with normal renal and hepatic function if treatment with a P-gp or a strong CYP3A4 inhibitor is required. The FDA-approved prescribing information for Colcrys contains recommended dosage adjustments.

* The FDA approved prescribing information for clarithromycin (marketed as Biaxin, Biaxin Filmtab, Biaxin XL) was updated in 2005 and 2006  to include this warning: There have been post-marketing reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, especially in the elderly, some of which occurred in patients with renal insufficiency. Deaths have been reported in some such patients.

Data Summary: Acute Gout

For the treatment of acute gout flares, medical texts typically recommend that patients take orally 1.2mg of colchicine followed by 0.6mg every hour until the flare resolves or until gastrointestinal toxicity occurs. However, adequate studies to determine the optimal dose of colchicine in acute gout flares have never been conducted. As part of the application for approval, the manufacturer of Colcrys submitted data from a clinical trial to evaluate the safety and efficacy of a low-dose regimen of oral colchicine for treatment of acute gout flares compared to the traditional high-dose regimen. 

The trial was a multicenter, randomized, double-blind, placebo-controlled trial of patients meeting American College of Rheumatology criteria for gout who were  assigned to one of three treatment groups within 12 hours of a gout flare, as follows:

• Group 1: high-dose colchicine (1.2 mg, then 0.6 mg hourly for 6 hours [4.8 mg total])
• Group 2: low-dose colchicine (1.2 mg, then 0.6 mg in 1 hour [1.8 mg total] followed by 5 placebo doses hourly)
• Group 3: placebo (2 capsules, then 1 capsule hourly for 6 hours).

The trial found that a statistically significantly greater proportion of patients in the low-dose (38%) and high-dose (33%) colchicine groups achieved a 50% reduction in pain in the target joint compared to placebo (16%). Additionally, the rate of gastrointestinal adverse events (diarrhea, nausea, vomiting, abdominal pain) was considerably lower in low-dose patients (26%) compared to high-dose patients (77%). In addition, there were no severe adverse events reported in low-dose patients compared to 10 reported in high-dose patients.

These findings suggest that prior use of high-dose colchicine may have exposed patients to increased toxicity with no greater efficacy than the low-dose regimen. Based on this trial, FDA recommends that healthcare professionals prescribe the approved Colcrys dose of 1.2mg at onset of acute gout flare followed by 0.6mg in 1 hour, for a total of 1.8mg, and carefully consider the need for additional subsequent dosing. Healthcare professionals should also monitor patients for signs and symptoms of colchicine toxicity.

For Immediate Release: July 30, 2009 (http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm174620.htm)

Media Inquiries: Karen Riley, 301-796-4674, karen.riley@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA Approves Colchicine for Acute Gout, Mediterranean Fever
Agency also provides new information to physicians regarding safe use of drug

The U.S. Food and Drug Administration has approved Colcrys to treat acute flairs in patients with gout, a recurrent and painful form of arthritis, and patients with familial Mediterranean fever (FMF), an inherited inflammatory disorder. The medication’s active ingredient is colchicine, a complex compound derived from the dried seeds of a plant known as the autumn crocus or meadow saffron (Colchicum autumnale).

Colchicine has been used by healthcare practitioners for many years to treat gout but had not been approved by the FDA. The FDA has an initiative underway to bring unapproved, marketed products like colchicine under its regulatory framework. This initiative promotes the goal of assuring that all marketed drugs meet modern standards for safety, effectiveness, quality and labeling.

Physicians historically have given colchicine hourly for acute gout flares until the flare subsided or they had to stop treatment because the patient began experiencing gastrointestinal problems. A dosing study required as part of FDA approval demonstrated that one dose initially and a single additional dose after one hour was just as effective as continued hourly dosing for acute gout flares, but much less toxic. As a result, the drug is being approved for acute gout flares with the lower recommended dosing regimen.

The FDA is alerting healthcare professionals to this new dosing regimen and also warning about the potential for severe drug interactions when patients take colchicine.

The medicinal value of using colchicum was first identified in the first century A.D. and its use for treating acute gout dates back to 1810. Physicians have prescribed the medication since then. Although single-ingredient colchicine has not been approved by the FDA until now, a combination product containing colchicine and an agent that increased the excretion of uric acid in the urine was approved by the FDA in 1939.

FMF is the most common of the hereditary periodic fever syndromes and is characterized by recurrent episodes of fever, arthritis and painful inflammation of the lining layers of the lungs and abdomen.  Though rare in the United States, it is more common in Mediterranean countries. Physicians have prescribed colchicine for FMF for many years based on studies showing that it reduced the frequency of attacks but use of colchicine for FMF had never been approved. With this approval, Colcrys becomes the first drug approved to treat FMF.

Colcrys is manufactured by Mutual Pharmaceutical Company, Inc., Philadelphia.