The Best Antihistamines for Sneezing and Nasal Congestion

Photo Credit: Jon Lebkowsky

About 1 in every 5 people suffer from hay fever, also known as allergic rhinosinusitis by doctors, and I am one of them. Some people suffer all the time (perennial, persistent, constant), usually due to allergies to indoor allergens such as dust mites, molds, animal dander, or cockroaches. Others have allergic symptoms only during certain seasons, because they have become sensitized to grass, tree, or weed pollens. I've had hay fever since preschool days -- a rather typical case.

When we lived in Minnesota, I only had symptoms during the summer, especially when I cut grass or raked leaves, but after moving to southern Arizona, I now have perennial allergic rhinitis (PAR), since weeds release pollen into the air almost any time of the year. After I get a cold or after I am exposed to a high dose of allergens (such as using a line-trimmer to cut weeds), my allergic rhinitis often worsens to include sinusitis.

As a child, my mom gave me Benadryl or Chlor-Trimeton pills. They worked for a few hours to suppress my sneezing, stuffy nose, and itchy eyes, but made me drowsy -- probably a good side-effect from the viewpoint of my mother, considering my hyperactivity. In fact, these first generation antihistamines are also sold OTC (over-the-counter) as sleeping pills. I also got allergy shots and injections of my own urine (from a quack allergist), which "cured me" from complaining anymore about my allergies. I did avoid exposure to grass and weeds (also called secondary prevention) by not playing field sports (baseball, football, soccer) and by refusing to cut the grass.

I can't tell you "what 9 out of 10 doctors recommend for hay fever," but I can tell you what I've done, and tell you what's been published from research studies (controlled clinical trials) of antihistamines. For many years, I got prescriptions for a second-generation, once-a-day, non-sedating antihistamine. They cost about 3 dollars per pill and even with insurance, the co-pay was over $100 per year, so I took them only when I had symptoms. Many others must have done the same, since the U.S. market for prescription antihistamines was then over 4 billion dollars per year.

Everything changed around Christmas, 2002 when the patent for Claritin expired and Wellpoint successfully petitioned the FDA to switch non-sedating antihistamines to OTC. Since then, I've taken generic loratidine every morning; and it only costs $20 a year (for a small bottle of 300 little white pills). Despite the doom and gloom prophecies of allergists and big pharma in 2001, it became a win-win situation. The quality of my life and others improved because we rarely have allergy symptoms anymore, and the profits of the manufacturers of loratidine improved (with 30% market share and 1.4 billion dollars in annual sales).

Allergy sufferers got another Christmas present in 2007 when the patent on Zyrtec, another non-sedating antihistamine, expired. Zertec is now available OTC for about a dollar a pill for the brand name product, while the generic cetirizine costs only $15 to $45 for a bottle of 90 tablets -- enough to get through 3 months of the allergy season for those with seasonal allergic rhinitis. It's also available as a chewable tablet or liquid for children (at a lower dose) and combined with a Decongestant in a capsule.

As an allergy sufferer in the United States, your choices have now been expanded: You can buy generic Claritin OTC, generic Zyrtec OTC, or ask your doctor for a prescription for Clarinex, Allegra, or Xyzal. To determine which is best antihistamine, I read the most recent studies, which are summarized in an excellent review by Doctors Lehman and Blaiss from the University of Tennessee (in the journal Drugs 2006), and a similar review, written for physician assistants, which you can download without cost.

In summary, second-generation antihistamines are the first-line therapy for both seasonal and perennial allergic rhinitis (SAR and PAR). They are very effective, very safe, and last for more than 24 hours. They are much less likely to cause sedation (drowsiness or fatigue) when compared to the old first generation antihistamines. For any of these drugs, the higher the dose, the more likely sedation will be noticed. At the recommended doses for adults, Zyrtec and its twin brother Xyzal are more likely to cause sedation (5-10%) when compared to the others (1-2%).

A small advantage for Zyrtec and Xyzal is that their onset of action may be shorter (about an hour) when compared to the others (1-3 hours). However, a somewhat slower onset of action is not a problem when these drugs are taken every morning (when you brush your teeth) to PREVENT the release of histamine in your nose and eyes later in the day. Antihistamines are much less effective if you wait to take them until you have symptoms.

Allegra (fexofenadine, still by prescription only) is slightly more effective in relieving itchy, watery, red eyes, and less likely to cause sedation at higher (off-label) doses, when compared to Claritin and Clarinex. Blood levels of Allegra are increased by about 40% if you take it with grapefruit juice, erythromycin (an antibiotic), or ketoconazole (an antifungal), but these drug-drug interactions are unlikely to significantly increase the risk of sedation from Allegra.

Bottom line, I will continue to take generic Claritin every morning, because it's effective, doesn't cause sedation at the recommended dose, and cheap. I may try generic Zyrtec when the cost drops towards that of generic Claritin. I will still keep a bottle of generic Benedryl for insect stings and severe allergic reactions, realizing that after taking it I will feel like a space cadet or sleepy. Despite heavy advertising, I personally see no reason to ask my doctor for a prescription for Clarinex, Allergra, or Xyzal, but I am sure that a few patients will feel that these expensive antihistamines are more effective.

Related Topics:

• Plagued by Pollen
• WebMD Video: The Truth About Allergies

Technorati Tags: hay fever, pollen, allergic rhinitis, sinusitis, Benedryl, Chlor-Trimeton, antihistamines, Claritin, Zyrtec, Clarinex, Allegra, Xyzal, allergies

Are Chantix Side Effects Worth the Risk?

The risks of continuing to smoke far outweigh the risks of trying to quit. Consider these facts:

• One billion people will die from smoking in this century.
• Half of persistent cigarette smokers are killed by their habit.
• Smoking cessation at age 50 cuts this risk in half.
• Smoking cessation before age 30 avoids almost all of the risk.
• The success of smoking cessation improves by using nicotine gum; improves more by using Xyban; and improves even more by using Chantix.
• About half of those who take Chantix remain non-smokers one year later.

Before Chantix (varenicline) was released by the FDA in the United States (in June 2006), it was clear that it caused minor side effects such as nausea, mood alterations, drowsiness, vivid dreams, or an allergic rash in up to one-third of patients. Many patients have reported these symptoms on Internet message boards. Now, after about 4 million smokers have taken Chantix, about 40 suicides have been reported to the FDA associated with Chantix and about 400 cases of suicidal thinking or behavior. In industry talk, these are called SAEs (serious adverse events), but individuals who experience an SAE (or their loved ones) appropriately use much stronger words.

All drugs have side effects, so doctors and patients considering starting a drug must always weigh the potential benefits against the risk of side-effects. (You can do the math using the above statistics.) Once you notice a side effect (or one is found by your doctor using laboratory tests), the severity of your side effects must be weighed against the benefit obtained by continuing the drug. Sometimes you and your doctor compromise by lowering the dose of the drug or switching to a different drug.

If you are an adult and feel blue (depressed), switching from Chantix to Zyban may be a good idea since Zyban is a low dose of an antidepressant (bupropion). If you get an itchy rash while taking Chantix, stop taking it until you can discuss this with your local pharmacist (free) or physician (good luck). Allergic reactions to drugs can become life-threatening if you ignore them and keep taking the drug.

This week, an FDA spokesperson said that "health care professionals should closely monitor patients for behavior and mood changes if they are are taking this drug." However, in my opinion, it is much more reasonable to advise the patient and their family and friends about this risk. The press and legal community have already done an excellent job of warning people (judging from their websites). It is encouraging that the FDA has responded much more rapidly in releasing the preliminary results of "post-marketing surveillance" for newly released drugs (such as Chantix) since the Vioxx/Celebrex fiasco.

However, their surveillance system is passive, waiting for doctors and patients to report drug side effects. This means that the SAE rates are probably seriously underreported. Perhaps only 1% of SAEs which occur are reported to the FDA after a drug is approved for sale.

Many experts believe that to better protect the public, surveillance should be proactive, with costs and responsibilities to be shared by the FDA and the company which profits from sales of the drug. In my opinion, in the case of Chantix, pro-active surveillance could easily have been paid for by spending a small fraction of the 25% profit from the $681 million in 2007 sales of Chantix.

Smoking cessation is a process for most smokers, who are addicted to nicotine. Before turning to drug therapy, I suggest trying to quit with the help of a support group. Call the smoking cessation helpline in your state or country, such as 1-800-QUITNOW in the United States.

Now for some interesting disclosures. Most of the smoking statistics I listed at the top are from a research paper which you can download for free and read. The renowned first author of this paper, Sir Richard Doll, died at age 92, one year after it was published in the British Medical Journal. After his death, it was disclosed that he had received, but not reported, large consulting fees from chemical companies during his career.

Over the past 3 years, I have been paid a total of about $20,000 by Pfizer for reviewing the quality of spirometry tests done for a study of the effectiveness of Chantix in patients with COPD. My consulting for them on this project continues. Last year, Pfizer also paid me about $4,000 for helping them to produce educational videos to describe how spirometry should be used to evaluate diabetic patients for whom Exubera was being considered. To learn more about the fate of Exubera, click here.

Related Topics:

• How to Quit Smoking
• WebMD Video: Quit Smoking for Good

Technorati Tags: chantix, smoking, quit smoking, FDA, side effects

A New Study of Inhalers to Prevent COPD: Flies in the Ointment

The treatment of chronic obstructive pulmonary disease (COPD, formerly known as emphysema or chronic bronchitis with airway obstruction) is a rapidly expanding 5 billion dollar per year market for inhaler manufacturers. Large COPD public awareness (promotional) campaigns were started in 2007 by the U.S. National Heart, Lung, and Blood Institute (NHLBI), and the manufacturers of the two inhalers which have been approved by the FDA for COPD: Spiriva (tiotropium) and high dose Advair (a combination of 500 mcg fluticasone and 50mcg salmeterol).

The results of INSPIRE, the second of three very large, international COPD treatment studies were published in the January 2008 issue of the most prestigious pulmonary journal (AJRCCM, aka “the blue journal”). INSPIRE directly compared the effectiveness and safety of these two inhalers in over 1300 patients with severe treated COPD for two years.

Twice as many patients randomly selected to take Spiriva died during the two years of the study when compared to those randomly selected to take Advair. In the patients who also had some type of heart disease or hypertension when they started the study (about half of them), there were 24 deaths in those taking Spiriva, but only 9 deaths in those taking Advair. The higher death rate in those taking Spiriva was apparent just three months into the study. Unfortunately, sudden death from heart disease in individual patients with COPD is rarely even considered as possibly due to a side-effect of their inhalers, because smoking is the most common cause of death from heart disease.

Over 8 million patients with COPD have been prescribed Spiriva since it became available five years ago. Spiriva temporarily relieves shortness of breath in about half of patients with severe COPD, and may slightly reduce the risk of a subsequent exacerbation in those who have previously required hospitalization for a COPD exacerbation. Some adults with asthma are prescribed Spiriva, but the evidence that it helps them is so scanty that the FDA has not approved it for asthma.

More than 15 years ago, I was an investigator of the NHLBI-sponsored Lung Health Study in which 5000 smokers with mild to moderate COPD were randomized to take Atrovent (ipratropium) or a placebo for five years. We reported that study participants taking Atrovent were twice as likely to die, and more likely to be hospitalized with a serious cardiac arrhythmia (heart rhythm disturbance) than those taking the placebo inhaler. Since then, other investigators have also reported that patients with COPD taking Spiriva were more likely to experience a cardiac arrhythmia. Spiriva and Atrovent are both anticholinergic bronchodilator inhalers, but Spiriva is ultra long-acting.

More than one-third of the patients who were enrolled into the INSPIRE study were current cigarette smokers -- the cause of their severe lung disease. The study sponsors apparently did nothing to help them to stop smoking, although smoking cessation is the only treatment proven to halt the rapid progression of COPD. On the other hand, the study investigators did not include a placebo comparison group because "it was deemed unethical to withhold known effective therapies."

I worry that prescribing expensive inhalers for patients with COPD who continue to smoke makes them think that they are “getting the cure” and don’t need to quit. All smokers should be helped with the process of smoking cessation.

Related Topics:

• Living with COPD
• WebMD Video: A Breath of Fresh Air for Emphysema Patients

Technorati Tags: COPD, smoking cessation, Advair, Spiriva, health, wellness, heart disease, lung disease

Asthma Inhaler Price Relief

The Only Cheap ($4/month) Asthma Quick Relievers Left in the United States

I just got back from an asthma conference in Phoenix, with 20 experts from around the United States. Dr. Stuart Stoloff, an active member of the committee which wrote the new EPR-3 asthma clinical practice guidelines, decried the lack of a generic asthma controller medication in the United States.

Sadly, as I've mentioned here before, the FDA and the inhaler manufacturers have worked together during the past couple of years to ensure that new patents for all asthma inhalers which contain an inhaled corticosteroid (ICS) will not expire for another 15 years. The prices of $100 to $300 per month for an ICS will be maintained since no generics will be introduced.

Another speaker, well connected with the FDA and major inhaler manufacturers, showed the expected FDA approval dates for about 8 new ICS or combination ICS plus LABA inhalers during the next 8 years. All of these are "me too" inhalers, with any differences between them and existing ICS or combo inhalers possibly exaggerated in an attempt to gain a slice of the $10 billion per year worldwide market for asthma and COPD inhalers. Of course, all of these new inhalers will be priced about the same as the existing ones ($100 to $300 per month). No truly innovative inhalers are "in the pipeline" (in phase II or III clinical trials). This is a sad situation for under-insured folks in the United States with asthma (or a child with asthma).

Okay, back to the title of this blog. Asthma drugs can generally be categorized into 1) controllers (which you take every day), and 2) quick relievers, which are bronchodilators which are to be used only to temporarily relieve asthma symptoms. Once inhaled, they "kick-in" in less than 5 minutes, and last about an hour or two. These puffers contain beta-2 agonists (aka short-acting bronchodilators); albuterol (called salbutamol outside of the U.S.) is the most popular. It's available as a metered-dose inhaler (MDI, aka an asthma puffer), a solution to be placed in a nebulizer, and a pill. Albuterol MDIs are wildly popular because they are very small, take less than a minute to take a couple of puffs, and are relatively cheap. The albuterol solution is more cumbersome, since it must be placed in a nebulizer and takes 5-10 minutes to inhale the 2-3 milliliters of the liquid. Very few asthma experts ever use albuterol pills, because they are much more likely to cause side-effects (rapid heart rate, nervousness, and tremor), and they take 20-30 minutes to become effective.

Generic albuterol MDIs have been available in the U.S. for several years, and have cost as little as $6 each (less than most insurance copays). Sadly, the FDA has decreed that they be banned, starting in December, 2008. Already, it is rare to find them, as wholesale houses deplete their inventory and don't buy more. The FDA also plans to ban Primatine Mist (quick relief) inhalers, which are currently over the counter (without a prescription) for about $16 each. The new branded HFA MDI inhalers (Ventolin, Proventil, ProAir, and Xopenex) now cost between $30 to $65 each. There is no convincing evidence that any of them are more effective or are less likely to cause side-effects when compared with each other or generic albuterol.

What's left for poor folks? Wal-Mart, Target, and Dey Pharmaceuticals have "come to the rescue," but their solutions (pun intended) are not ideal. Dey makes generic albuterol and generic ipratropium single dose vials with 2.5 mL of liquid to pour into a nebulizer, and Wal-Mart and Target pharmacies sell a "typical" one month supply of these vials (60-75) for only four dollars! Wow, that's about one-tenth the price of the branded albuterol MDIs. What's the catch? Well, you need to have a compressor which plugs into the wall ($20 to $120 each, depending whether you buy it at a local pharmacy or DME store versus Ebay) and some nebulizers ($3 to $30 each, again depending on the source). An alternative is a battery-powered, hand-held ultrasonic nebulizer, which cost from $30 to $150 each, depending on the source. These solutions require larger equipment when compared to an MDI and a handful of vials, and take longer to administer the drug, but silver lining is that the nebulizer+compressor combination is the same as the bronchodilator treatment you will get in most emergency rooms.

So what about the generic ipratropium solution from Dey, which was just added to Wal-Mart's $4/month program? Ipratropium has been around for decades, branded by Boehringer (a German drug company) as Atrovent. Ipratropium has two major disadvantages as an asthma rescue medication when compared to albuterol: 1) it takes 45 minutes to an hour to take effect, and 2) it only works for a relatively small minority of children or young adults with asthma. However, ipratropium brings temporary relief of shortness of breath for about half of patients with COPD due to smoking. For those in whom it is effective, it lasts for 4 to 6 hours. The bronchodilator effect of ipratropium adds to the bronchodilator effect of albuterol, so many years ago, Boehringer introduced a combination MDI inhaler called Combivent. They apparently fell behind in the development of an HFA or DPI inhaler to replace the old CFC Combivent (and thus get another 15 year patent), so they have petitioned the FDA for an delay (beyond 2008) in the ban on CFC Combivent. Meanwhile, the Mothers of Asthmatics have attacked compounding pharmacies for substituting low cost generic combinations of ipratropium and albuterol solutions for the expensive Combivent brand name solution for nebulizers.

If you are concerned that the $4 per month generic short-acting bronchodilators may be less effective than the branded versions, get a peak flow meter (or even better a PiKo-1 pocket spirometer to measure your FEV1) and compare the improvement between the cheap and the expensive solutions (after ten minutes for albuterol and after 45 minutes for ipratropium or the combination. Of course, always, always work with your doctor when contemplating a change in your asthma treatments.

Related Topics:

• Asthma Medications
• Treating Asthma: Preventing Damage to the Airways

Technorati Tags: asthma, inhalers, medication, health and wellness

Managing Mild Asthma

Singulair versus Flovent versus Advair for Mild Persistent Asthma?

There is no question that in general Advair is more effective than Flovent and that Flovent is more effective than Singulair for controlling asthma. Most patients with mild asthma only go to see a doctor during an asthma exacerbation - that's certainly not optimal, but that's human nature. There are so many other responsibilities in life that you tend to ignore problems unless they become severe. The doctor then prescribes what she knows are the most likely drugs to "get you back on your feet" as soon as possible. That usually means a combination asthma controller inhaler (Advair or newcomer Symbicort) and, if your asthma severity is really worrisome, or if you've previously needed hospitalization for an asthma attack, she will prescribe a burst of prednisone.

[Strangely enough, the 10-14 days of prednisone (the strongest medication) will cost less than ten dollars, while each inhaler will cost somebody up to $200. ]

Anyway, within a few weeks, you will be feeling better and back into the yellow zone, and several weeks after that, you will probably be back into the green zone, demonstrating that your asthma is back in good control. What then? What asthma controller medications should you then be "stepped down" to? There are several options.

A new, large study addressed just that question. The investigators randomly assigned 500 children and adults with well-controlled mild asthma to step down to one of three options:

1. Advair (100mcg fluticasone plus 50mcg salmeterol once each night);
2. Flovent (100mcg fluticasone twice a day); or
3. Singulair (a 5 or 10mg monteleukast pill every night; 5mg for kids, 10mg for adults).

About one-third of the patients had experienced an asthma exacerbation during the previous 12 months. About two-thirds of the patients also had allergic rhinitis. This study started in the summer of 2003 at 19 sites in the United States, and was funded by Glaxo (the company that makes Advair and Flovent inhalers) and the American Lung Association (published in NEJM May 2007). A colleague and friend of mine, Dr. Robert Wise at Johns Hopkins, was the principal investigator at the coordinating center. The measures of successful treatment were:

• the number of days before another asthma exacerbation
• the percentage of days free from asthma symptoms.

So what happened during the 4 months of follow-up for each study participant?

The percentage of asthma-free days was about 80% for all 3 groups, which means that on the average, they didn't need to take albuterol for asthma symptoms for 4 of every 5 days.

About 20% of those who took the low dose Advair once-a-day and 20% of those who took the low dose Flovent every night had an asthma exacerbation, compared to 30% of those who only took a Singulair pill every night. There were 8 different events which were considered an asthma exacerbation (aka an event), including urgent care visits for asthma, the need for a burst of prednisone, the need for an excessive amount of albuterol for two or more days in a row, or a worrisome fall in lung function (FEV1 or peak flow). Half of the exacerbations were because the FEV1 had decreased more than 20% from the beginning of the study (even though the patient may have felt fine).

Side-effect rates (aka adverse events) were similar in the 3 groups, except that those taking Singulair reported fewer upper respiratory infections (27% versus 38%), fewer lower respiratory infections (7% versus 14%), and fewer episodes of fever (15% versus 25%). Hmmm, it sounds like even a low daily dose of fluticasone substantially increased the risk of viral respiratory infections, but reduced the risk of an asthma exacerbation. Since respiratory viruses are the most common cause of asthma exacerbations, this is a paradox.

I agree with the authors' conclusion that "individual patients and their physicians must choose a treatment regimen for asthma that balances efficacy with actual or perceived risks and maximizes adherence. No single approach will provide the best combination of these factors for all patients with asthma."

Don't let your doctor practice "cookbook medicine" (one size fits all) for your asthma therapy. Once your asthma is well-controlled, ask her about stepping down your therapy. Learn all that you can about your asthma and asthma medicines. WebMD provides many resources for those with asthma.

Related Topics:

• Keeping an Asthma Diary
• Asthma Treatment and Care

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