In my experience, it has been her pharmacist. Most medications are refilled monthly. Between quarterly or annual visits to the neurologist, I believe most concerns about Multiple Sclerosis are related to medications. And in my experience, the pharmacist is the more accessible, knowledgeable source of information about medications and their effects.

The most helpful professionals on my wife’s “treatment team” are the pharmacists at our local pharmacy. In fact, I imagine they know more about the current status of my wife’s health than does her neurologist. The pharmacists are so helpful, they’re on speed dial in my cell phone.

Here are some examples of how forming a relationship with a good pharmacist will make your role as a caregiver much, much easier.

1. Pharmacists know about drugs. Take advantage of the medication education a pharmacist will provide when a new medication is prescribed. Medications come with fact sheets (written in fine print). If you ask, a pharmacist will explain them for you in plain English. Examples of a few important questions to ask about each new medication include:

• What is this medication for?
• Will the patient’s other medications interact with this new drug?
• Do other medications she is taking effect when this one should be given?
• What side effects should we worry about?
• What if she forgets a dose?
• With or without food?

2. Pharmacists really understand drug interactions. It is important to ask a pharmacist about the potential consequences your patient’s prescribed medications may have with over-the-counter medications for such things as cold or allergies. Some drugs interact with each other to complicate or compound the side effects. The last thing you want is to create a problem while trying to treat symptoms of a cold. Pharmacists love to talk about drugs. It’s the reason they went to school for a long time! Take advantage of their knowledge.

3. Pharmacists know what works. Doctors specialize in your body. Pharmacists specialize in what medications do and can do to your body and its processes. More than once a good pharmacist has intervened on a patient’s behalf when he or she noticed the physician’s prescription may not be appropriate. A phone call to the doc is usually all it takes to fix the problem.

4. A good pharmacist can make traveling easier. Ever forget to take important medications on a trip? If you call your home pharmacist. he or she may be able to work with a local pharmacy where you are visiting to provide enough medication for your visit.

5. Your pharmacist can also be a great ally for you in your efforts to communicate with your insurance company about medication authorizations. Pharmacists really understand the whole medication approval process and can give you pointers about relating to insurance companies or provide information on your behalf.

6. Finally, my pharmacist serves an excellent gumbo from his front porch each Halloween night and sets tables in his yard for all the trick or treat parents!

After drug testing and before the FDA approves a new medication, a panel of health experts considers the drug studies and, if the panel is satisfied, recommends approval to the FDA for approval. The FDA usually does as the panel suggests.

The panel reviewing Gilenia recommends it as safe and effective for controlling tremors, concentration problems and other symptoms of relapsing remitting MS.

If the medication’s side effects do not derail the FDA’s approval later this year, Gilenia will be a welcomed medication for MS patients because it is the first MS treatment available in pill form. Approval would mean no more routine injections or infusions for those who take it — no more needles or injection site reactions.

Reported side effects of Gilenia include eye disorders, heart problems and lung problems. In spite of these, the panel recommend approval of the drug for the treatment of Multiple Sclerosis.

With each medication they choose to take, MS patients are faced with the persistent question, “Will my MS treatment be worse for me than the long term effects of the disease?” Because this is a new medication, there really isn’t an answer to this question yet. Not enough people have taken it for enough time for researchers to know the long term effects.

In light of the side effects, the panel did recommend Novartis study the effectiveness of lower doses of Gilenia.

More information about Gilenia:

• "First pill for multiple sclerosis safe, effective"
• "Novartis Gains After FDA Panel Backs First MS Pill"
• Novartis.com
• "FDA advisory committee unanimously recommends approval of Novartis investigational treatment FTY720 to treat relapsing remitting MS"

Dr. Andrew Goodman, chief of the University of Rochester Medical Center’s (URMC) Multiple Sclerosis Center, and his colleague Steven Schwid, M.D. who died in 2008, have studied the newly approved drug for more than 10 years.

Because most MS treatments are studied in terms of the way they slow the disease progression or prevent relapses, this medication required a new way of thinking about evaluating a Multiple Sclerosis medication. Because fampridine-SR restores some function, the study protocols developed at URMC were designed to measure functional outcomes. One study protocol measured the walking speed improvements over 25 feet.

According to the news release on the URMC web site, a significant number of study participants with Multiple Sclerosis increased walking speed by 25%, reported they could walk farther, climb stairs better and stand longer.

In short, this seems like a promising new drug! Acorda Therapeutics, Inc., the manufacturer of Ampyra, has developed a website to provide additional information to patients and physicians.

As with all MS drugs and therapies, there are significant potential side effects. The Ampyra Medication Guide offers these safety precautions:

• “Your chance of having a seizure is higher if you take too much AMPYRA or if you have kidney problems.
• Do not take AMPYRA if you have ever had a seizure.
• Before taking AMPYRA tell your doctor if you have kidney problems.
• Take AMPYRA exactly as prescribed by your doctor.”

Important Links

Ampyra Web Site
URMC News Release

Part of the reason is that drugs are made by corporations that must return value to shareholders. To do this, they must sell drugs. To sell drugs, pharmaceutical companies have paid doctors to promote their drugs. The money paid to doctors is an expense which increases the cost of drugs. That’s the business.

One step beyond the business, though, is corruption. At least one drug company has pleaded guilty for paying doctors to recommend drugs for diseases for which the drug was not approved. And there are new allegations the drug company may have known the drug was not even effective against the diseases for which it was being promoted.

That’s all background.

Pfizer Inc., the world’s biggest drugmaker and the company that created Neurontin, has said it will begin (next year) disclosing all payments of more than $500 it makes to doctors.

According to the MSNBC article, “Pfizer to disclose payments to doctors next year“, Pfizer is doing this “after introduction last month of legislation to require such disclosures, and revelations of astronomical payments to some doctors that were not revealed to universities and hospitals that employed them.” In other words, this is an example of another corporate entity becoming interested in transparency only after regulatory requirements change.

While politicians suggest this is a good move because there is so much public money that passes to drug companies, I believe the real value in this is that it makes transparent the relationship between a doctor and the medications the doctor prescribes.

Here’s what I like about it: suppose a doctor makes a presentation to an MS support group and talks extensively about one of the MS injection therapies and only mentions the others in passing.

Don’t you want to know whether the doctor is focusing on the one medication because he or she finds it really is the best medication and not because he or she is being paid to give a speech? As I wrote in September of 2007 in “MS Medication, Insurance Coverage and 2 Ounces of Gold“, I sure want to know!

Here’s why Pfizer’s decision to report these payments to doctors is important. Pfizer pleaded guilty in a legal settlement related to an accusation it had illegally paid doctors to prescribe Neurontin for uses not approved by the FDA. Pfizer paid penalties of $430 million for paying doctors to prescribe billions of dollars of Neurontin to patients with diseases for which there was no evidence of Neurontin’s effectiveness.

Newsweek has a good article that summarizes the Pfizer/Neurontin legal issues: “Pfizer’s Headache: Lawsuit charges drugmaker was deceptive about Neurontin.”

Pfizer’s behavior offers the clearest example of why transparency in the doctor/pharmaceutical company relationship is important.

Interesting to me is that while Pfizer paid $430 million (about one quarter’s sales of Neurontin), no physician was charged. I think this must be why: Doctors have to be able to trust the information they receive from pharmaceutical companies. Certainly, no physician with integrity would prescribe or promote a drug they did not believe to be effective.

Caregiver Tip: The quickest way to get to the point of this issue with a doctor about a prescription medication is to ask, “Do you receive money from the drug company that makes this medication?” Once that is on the table, you can then talk about whether or not the medication is being prescribed because your doctor really does believe it will be effective.

This year I learned about a new tool.  It’s called a “plan sponsor override“.  And, in my experience, it works.

Here’s how it worked.

First, Provigil is not a Food and Drug Administration-approved medication for the treatment of Multiple Sclerosis.  Many medications used in the treatment of Multiple Sclerosis are not FDA-approved for MS.

While the injectible medications like Copaxone®, Avonex®, Betaseron®, etc. were designed for MS and have been tested and approved by the FDA for treatment of Multiple Sclerosis, Provigil has not been.  However, Provigil is commonly prescribed for MS patients because neurologists find it helps with fatigue, one of the most common symptoms of Multiple Sclerosis.  Another example of an “off label” prescription is Aricept®, which is FDA-approved for the treatment of Alzheimer’s.  Neurologist often prescribe it for MS patients to aid with memory and cognitive difficulties.

It may be too simple, but I think about it like this: imagine that Pepto-Bismol® required a prescription (it doesn’t … we’re imagining).  Imagine, too, that it had been tested and was FDA-approved for treatment of nausea, but not for heartburn.  Your insurance company would cover your prescription if you had nausea, but would decline it if you had heartburn.  Even though, it is highly effective against both!

That’s how prescription coverage works.  Insurance companies use the FDA as their excuse to deny coverage.

Second, my health insurance company outsources the medication and prescription benefits to a third company, Medco, a $20 billion dollar, public corporation listed on the NYSE as MHS.  In their efforts to return value to shareholders, Medco denies coverage for my wife’s medications prescribed by her neurologist for non-FDA-approved purposes.

On one hand, this practice makes sense (from a capitalistic perspective).  Why should an insurance company pay for medications being used for purposes not approved by the U.S. Food and Drug Administration?

On the other hand, who wants to assume a government agency knows as much about the treatment of a disease as neurologists do?

Looking at both hands, I believe Medco is more interested in shareholder value than in patient care.  They’re a public corporation, they have to be.

Anyway, after several denials, appeals and denials, I finally heard a Medco employee say something I had never heard, “Perhaps you should request a plan sponsor override.”

“What’s that?”, I asked.

“Ask your insurance company to override our denial,” she replied.

“That’s it?”

“We’ll honor it.”

I called my insurance company and spoke with several people until they found someone who could speak to me about requesting a plan sponsor override.  Long story, short: I faxed my insurance company the last appeal letter I had sent to Medco.  Two days later Medco agreed to cover the medication.

Caregiver Tip:  If prescription coverage is repeatedly denied by a third party, ask your health insurance company about a plan sponsor override.

MSNBC.com : Multiple sclerosis drug linked to liver injury

Information about this new warning is available from the FDA web site, too:

Read the revisions to the Warnings and Precautions section of the full Prescribing Information:

http://www.fda.gov/medwatch/safety/2008/Tysabri_dhcp_letter.pdf

(Notice, too, I’ve added a link to the Food and Drug Administration’s web site to the “MS Resource Sites”. The FDA is at: http://www.fda.gov)

The liver is an incredible organ which often goes unappreciated. Because it cleans the blood, anything in the bloodstream can impact the health of the liver. MedicineNet.com has a good article titled, “Drug-Induced Liver Disease” by Dennis Lee, MD. If you care for an MS patient, this article should be required reading.

Caregiver Tip: Whether the person you care for takes Tysabri or other medications, read “Drug-Induced Liver Disease” and pay attention to signs and symptoms of liver damage.

Well, according to an Associated Press article released today, Tainted Pills Hit U.S. Mainland.  The article reports 13 of the 20 best-selling drugs in the US come from Puerto Rico and quality control measures are lax.

Is this article reason to be overly concerned or avoid taking medications?  No.  It should only serve as a reminder to inspect medications before they are taken.

Apparently, poor quality control has been an industry concern for years, yet industry professionals report the tainted medications are safe and effective.

Caregiver’s Tip: Always check the appearance of medications when they are administered. Know what the medications should look like. For example, clear liquids should be clear. Pills should not be contaminated with foreign material, paint flecks or other particles. Any medication that looks odd should be returned to your pharmacist.

First, why are the costs for the 4 MS therapies so similar?

I’ve just checked the prices on Drugstore.com for a typical one-month supply of each of the four MS “therapies”. Here is what I found on January 29, 2008 (in alphabetical order):

Avonex (Four 30mcg/0.5ml Syringes) $1,720.99
Betaseron (15 vials 0.3mg Solution) $1,699.99
Copaxone (1 box of 30 prefilled syringes $1,886.89
Rebif (6 ml, 44mcg/0.5ml Solution) $1,893.62

These four medications were developed at different times, by different companies, and are manufactured differently. The difference in prices between the most expensive and the least expensive is only $193.63 per month. That amount may seem large, but it represents a price spread of only 10.2% of the cost of the most expensive, Rebif.

Also, where can one find a list of neurologists who have never benefited financially from an association with one of these companies?

I ponder this because of an article I read last night in the Wall Street Journal HealthBlog which quoted two MDs who are dismissive of one of the newer MS “therapies”. However, readers of the blog left comments indicating they believe the two docs may benefit from their relationships with another MS therapy manufacturer and, thus, their opinion may be tainted.

I’d like a list of doctors who haven’t been influenced, lobbied, etc.  It seems like a list a doctor would be proud to sign.

Here’s one that really makes me wonder. If the average time between exacerbations in Relapsing Remitting MS is two years, why does it seem many of drug studies I’ve read on Avonex, Betaseron, Copaxone and Rebif are limited to two years? I can’t help but wonder if this is by design so the studies are not negatively impacted by participants who cross the two year average and increase their chances of an exacerbation, thus ruining the desired outcome of the study.

And where can I find a study that compares all four of these medications against each other. I have found studies of each against a placebo (and some make placebos look pretty good … they have fewer side effects), but I can find no single study that compares Avonex against Betaseron against Copaxone against Rebif against a placebo.

So help me! If you can answer my questions or provide links to studies that can, please leave a message in the comments. I’d love to find the answers.

Caregiver Tip: Always ask questions.

MedWatch is the FDA’s web site for reporting current medication safety information about drugs and medical products which are regulated by the U.S. Food and Drug Administration. The “What’s New” column on the left side of the home page is where the news is posted as it becomes available. You can subscribe to receive safety alerts by email.

On 10/24/2007 the FDA and Cephalon (manufacturer of Provigil) notified healthcare professionals of an updated WARNINGS section of the prescribing information for the drug. According to the posting,

“Physicians should instruct their patients to immediately discontinue the use of Provigil and contact them if a rash or other hypersensitivity reaction occurs. Healthcare professionals and consumers should also be aware that Provigil is not approved for use in pediatric patients for any indication. In addition, psychiatric adverse experiences (including anxiety, mania, hallucinations, and suicidal ideation) have been reported in patients treated with Provigil. Caution should be exercised when Provigil is given to patients with a history of psychosis, depression, or mania.”

Obviously, this is good information to know. Other than the specific side effects, it means Provigil is like any medication. One must balance the side effects (and potential side effects) against the good the medication does. The information about these additional side effects serve as a reminder than any chemical one uses to modify the way a brain works may hold unexpected dangers.

It’s good to know that should my wife suddenly experience any of these side effects, her Provigil may be the reason. Of course, these additional potential side effects are also listed in the prescribing information for a couple of her other medications, too. Modifying brain chemistry is a tricky thing.

Here’s what surprises me. I did not learn of the FDA’s updated warnings from a healthcare provider. Nor did my wife receive information about the updated warnings from a doctor, pharmacist or the drug manufacturer.

I first learned about the new prescription warnings by reading it on a financial news web site.  TheStreet.com posted an article on 10/24/07, by Elizabeth Trotta, titled “FDA Warns on Cephalon’s Provigil“.  The Multiple Sclerosis Foundation has a good article about this issue, too: “New Warnings for Provigil“.

Cephalon’s “Newsroom”, the page on their corporate web site for news releases, provides no mention of the updated warning (I’m exploring the Cephalon site on 11/04/07). Cephalon’s web site has a page of corporate information for investors, but nothing there is about the 10/24/07 FDA announcement of the updated prescription warning.

Cephalon also has a product-specific web site for Provigil at www.provigil.com. The Provigil.com web site offers a lot of good information about the medication and its uses. If you or someone you know takes Provigil, the Provigil.com web site is a great resource for you. The important information for patients about side effects and medication use is available from the upper right hand link, “Patient Information”. The information is dated August 2007 (before the FDA MedWatch notice).

The lesson for patients and caregivers? Use MedWatch AND the web sites of drug manufacturers to stay on top of important drug safety information.

How Drug Safety Information Seems to Flow

MedWatch is the official place to read the latest drug safety information. Generally, this seems to be how drug safety information flows: Drug safety news appears initially on MedWatch. Next, the news media (medical news and financial news) pick up on the MedWatch postings and write articles to inform the public of significant drug safety news. Then drug manufacturers and medical professionals inform patients.

However, in Cephalon’s case with Provigil, the drug manufacturer was ahead of the FDA MedWatch posting. The Provigil FDA Approved Labeling (PDA File) was updated on August 17, 2007 and on September 12, 2007, a “Dear Healthcare Provider” letter (PDF File) was produced which details the updated information and warnings.

Good job, Cephalon.

Caregiver Tip: Know the names of all the drugs taken by the MS patient for whom you care. Check MedWatch regularly to learn about drug safety news related to these medications. I’ve added a link to MedWatch in the right hand column. Also, visit the web sites of the drug makers for current information. As they say, “knowledge is power”.

I’ll write a “thank you” letter to the Coverage Review Board.

I wonder why some medications require no coverage review, while others like Provigil, Aricept and Betaseron do. Generally, it seems the more a drug costs, the more likely it is that the insurance company requires a review.

I enjoy math and have played with a few numbers lately. It’s no secret that health care is expensive, but when you look at the details, the costs can shock you. Amazing, too, is that the costs for a particular drug are apparently different depending upon who does the buying.

I’ll begin with the cost issue. Let’s start with gold and use it as the standard. According to Kitco.com’s 24-hour Spot Chart for Gold, the high price for 1 ounce of gold on the New York gold market today, Sept 7, 2007, was $700.10. That’s our gold standard, $700 per ounce. For our purposes, we’ll call anything that costs $700 per ounce expensive!

A one month supply of Provigil at 2 x 100 mg tablets per day is 6000 mg. per month. 6000 mg is a bit more than 0.19 ounces or about a fifth of an ounce. 60 tablets of Provigil costs me $429.16 out of pocket.

That means Provigil costs about $2,124.80 per ounce, making it more than 3 times as costly as solid gold at $700 per ounce.

Is that not insane? It’s a white, powdery chemical compound compressed into tablet form. It’s patented, though, and there are no generics or “therapeutic substitutes” available yet.

But that the cost varies depending upon who is buying the medication is what really strikes me as odd.

The pharmacy charges my insurance company less than they charge me for the medication if I purchase it out of pocket without insurance coverage. My personal cost (without coverage) is $429.16.

My insurance company pays only $316.88, or $112.28 less per month than I would pay if I didn’t have insurance. As an individual consumer, my out of pocket costs for the Provigil would be $1,347.36 more per year than my insurance company’s costs for the drug.

I could almost buy 2 full ounces of gold with the savings my insurance company receives from my pharmacy! I just scratch my head and wonder.

Caregiver Tip: Remember to write “Thank You” letters to the doctors and review boards.