The Day the Lyrics Lied

This post was written by Dr Irene Campbell-Taylor, a former Clinical Neuroscientist and Assistant Professor of Medicine at the University of Toronto.

It is essential to read the marketing copy of pharmaceutical companies with care and attention for critical hidden details. It is rare to find an announcement with such obvious errors and dangerous suggestions up front as those contained in the latest media material on Pfizer’s Lyrica (pregabalin), an anticonvulsant drug used for neuropathic pain, partial seizures and generalized anxiety disorder.

In June 2007, Lyrica became the first medication approved by the U.S. Food and Drug Administration for the treatment of fibromyalgia. Sales reached a record $3.1 billion in 2010.

In 2009, Lyrica was one of four drugs, along with Bextra, Geodon and Zyvox, which a subsidiary of Pfizer pleaded guilty to misbranding “with the intent to defraud or mislead”. Pfizer agreed to pay $2.3 billion in settlement, and entered a corporate integrity agreement. The investigation was triggered by allegations made by six whistle-blowers.

“to put issues that diminish trust behind us”

A spokesperson for Pfizer said earlier this year that it would pay the fine “to put issues that diminish trust behind us”.

Now, in the EU, Pfizer announces that it is producing a liquid form of Lyrica for patients with dysphagia. This term applies to people who, usually as a result of neurological impairment, have difficulty swallowing. There are two types of dysphagia: oropharyngeal, caused by damage to the nerves and muscles of the mouth and throat and esophageal dysphagia in which there are problems passing food down the esophagus and into the stomach.

Pfizer appears to be directing its campaign toward oropharyngeal dysphagia but clearly has not consulted anyone with knowledge of the condition. Berkeley Phillips, Medical Director of Pfizer Ltd declared:

“By bringing pregabalin oral solution to the UK market, we can provide patients who are candidates for treatment but experience difficulty swallowing, with an alternative option. The difficulties associated with dysphagia for those who are required to take medicines orally are widely accepted. It is our hope that this new oral solution formulation will provide an appropriate alternative, which will be more convenient for these patients…..Dysphagia is linked to certain diseases and disorders, such as diabetes, epilepsy, multiple sclerosis (MS) and Parkinson’s disease (PD) and can also occur as a side effect to some types of medication. The risk of dysphagia increases with age and the condition can make it difficult for patients to swallow medications that are in solid form.”

American pie

This sounds American as apple pie – what could be wrong? The critically important detail is that these patients have difficulty swallowing liquids – not solids. Contrary to popular belief, the most difficult consistency to swallow is thin liquid because the damaged muscles within the mouth cannot control it and aspiration into the lungs becomes highly probable. Some companies such as Sandoz make millions selling “thickeners” for liquids to be ingested by people with dysphagia. Many of these products in fact do little other than cause dehydration.

But now we have Pfizer proposing that a medication be provided in a form that will increase the likelihood of its ending up in the lungs instead of the stomach.

The company goes on to state: “5% of over 79 year olds and 16% of those aged over 87 years are reported to suffer from symptoms of dysphagia. These figures rise to up to 60% amongst the elderly who live in nursing homes or sheltered accommodation. 24% of patients who are mildly impaired due to MS suffer from permanent dysphagia, however, the prevalence increases progressively together with rising disability, with 65% of severely disabled MS sufferers experiencing permanent dysphagia. According to estimates, almost 40% of patients who suffered a stroke also suffer from swallowing problems.….”

“According to research,” they continue, “patients who experience difficulty in swallowing pills have poorer health outcomes and higher health care costs.” After 25 years of treating dysphagic patients, I have no knowledge of any such research.

Martin Johnson, GP and RCGP Pain Champion explained:

“A wide range of patients with dysphagia will benefit from the introduction of the new oral formulation. The introduction of the oral solution will help us in our treatment of peripheral and central neuropathic pain in the elderly, those with epilepsy, diabetes, multiple sclerosis, stroke and Parkinson’s disease, and of course palliative patients as well.”

Breathless

This is such a potentially dangerous statement that it leaves me breathless.

“According to recommendations from the National Electronic Library for Medicine, doctors should wherever available administer licensed alternatives, like oral solutions to those patients who are unable to take medicines in solid oral dosage forms.”

The suggestion for dysphagic patients is to change to suppository, or topical (on the skin) format, or medications that melt on the tongue but never to oral solution.

The known adverse effects of Lyrica are frightening

Our story, however, gets worse. The known adverse effects of Lyrica are frightening. Remember that this drug is recommended for people who already have neurological disorders. The admitted adverse effects include:

• Mood or behavior changes, depression, anxiety, agitation, hostility, restlessness, hyperactivity (mentally or physically), thoughts about suicide or self-harm.

Patients are advised to: “Call your doctor at once if you have any of these serious side effects”:

• Muscle pain, weakness, or tenderness (especially if you also have a fever and feel tired); easy bruising or bleeding; or swelling in your hands or feet, rapid weight gain.

Less serious side effects may include:

• Dizziness or drowsiness, anxiety, blurred vision, loss of balance or coordination, problems with memory or concentration, dry mouth, skin rash or itching, constipation, stomach pain; increased appetite; or joint or muscle pain.

What is the most important information I should know about pregabalin (Lyrica)?

“You may have thoughts about suicide while taking this medication. Your doctor will need to check you at regular visits. Do not miss any scheduled appointments. This is not a complete list of side effects and others may occur.”

A spoonful of liquid helps the medicine go down – in the most delightful way

The advertising so far has been aimed at adults and elderly patients. But the availability of a liquid formulation makes it easier to give a medication to people who don’t like pills. How long before we see it offered to infants and children as has happened with multiple other drugs never intended for paediatrics.

There appears to be no end to the number of dangers that the gullibility of both the public and physicians can enable companies to sell for enormous profits. For Pfizer a billion dollar fine is just the cost of doing business. A civilization earns the name by its readiness to protect and care for the vulnerable and the needy – by the quality of its healthcare. Sometimes it seems like the barbarians are at the gates.