Minneapolis, St Paul Fen Phen Attorney

OVERVIEW: Faris & Faris is currently representing clients who were prescribed Fen-Phen for weight loss.

PRESCRIBED FOR WEIGHT LOSS:
The drugs, fenfluramine and phentermine, appetite suppressants, were prescribed in combination with each other and with dexfenfluramine, which is promoted under the name of “Redux.” Fenfluramine is also promoted under the name of “Pondimin.” Fenfluramine and Dexfenfluramine contain essentially the same active ingredient. The combination use of these three drugs is not approved by the United States Food and Drug Administration (FDA), but was not illegal when these drugs were on the market. Doctors are generally permitted to make “off-label,” or non-approved, uses of drugs if the drugs are approved for any use.

SIGNS AND SYMPTOMS:
Shortness of breath (dyspnea) is usually the first symptom of damage from these diet drugs. There are primarily two serious conditions that are associated with the use of these appetite suppressants: VALVULAR DYSFUNCTION and PRIMARY PULMONARY HYPERTENSION (PPH).

1997 MAYO CLINIC STUDY: VALVULAR DYSFUNCTION:
The Mayo Clinic in Rochester, Minnesota released an emergency report on July 8, 1997. This report linked the use of phentermine and fenfluramine to unusual, potentially life-threatening, valvular dysfunction and blood “regurgitation,” or leaking backwards, in 24 women. This study suggests that as many as one-third of a patient sampling of Fen-Phen diet pill users had evidence of heart valve disease. The report observed that cardiovascular testing procedures, principally the electrocardiogram and echocardiogram, revealed that each of 24 patients in the Mayo study had one or more heart valves that were thickened and that blood was regurgitating. This condition of insufficient blood flow forces the heart work to harder to pump blood throughout the body. Cardiac surgical intervention, to replace bad valves, was required in five of the 24 patients as of July 9, 1997.

According to Mayo Clinic cardiologist, Heidi Connolly, who published the 1997 Mayo Clinic Fen-Phen study, the valve damage in the Fen-Phen user is different from other diseases. Under the microscope, the damaged valves are identical to valves seen in patients who have carcinoid heart disease and valve damage attributable to the migraine medications, methysergide and ergotamine. Heart valve damage involves leaks of the aortic valve and the mitral valve (heart murmur). The valves damaged by Fen-Phen are different from valves seen in rheumatic heart disease and in valves damaged by infection. In the Fen-Phen user, the valve becomes thickened and doesn’t function normally. The valve leaflet is intact and looks normal, but there is fibrous material that is layered onto the valve leaflet. The fibrous material encases the valve and has a ‘stuck-on’ appearance. Grossly, it has a glistening-white appearance similar again to what is seen in patients who have ergotamine-induced or carcinoid valve disease.

In a leaky heart valve, it means that blood is pumped backward through the valve when the valve should be closed. The mitral valve separates the left atrium (top chamber) from the left ventricular (bottom pumping chamber). In mitral regurgitation, blood leaks backward from the bottom chamber into the top chamber and subsequently backs up into the lungs and causes the heart to work harder. When severe regurgitation is present, the patient my have a lack of energy, shortness of breath, and eventually, congestive heart failure.

It is also known that any person with an abnormal heart murmur is at risk to develop infection on the valve after a dental procedure or other invasive procedure that could cause bacteria to enter the bloodstream.

TREATMENT OF DEFECTIVE HEART VALVES:
Valvulopathy occurs when the heart-valves do not open and close properly, causing regurgitation of blood. If the valves are seriously impaired, secondary pulmonary hypertension may result. The treatment can include medication, a valvoplasty, or a repair of the damaged heart valves, and/or heart valve replacement surgery.

DIAGNOSIS OF DEFECTIVE HEART VALVES:
Heart valve damage can be detected by an echocardiogram also known as an “echo.” An echo is an ultrasound imaging which results in a video picture of the heart. An EKG is not an appropriate test to determine valve damage.

1997 MAYO CLINIC STUDY: PRIMARY PULMONARY HYPERTENSION:
The same Mayo Clinic report also observed that eight of the 24 patients in the study had newly-documented primary pulmonary hypertension. PPH is a rare disease that results in the progressive narrowing of the blood vessels of the lungs (narrowing or obliteration of the small and medium pulmonary arteries), causing high blood pressure in the arteries that transfer blood from the heart to the lungs and eventually leading to heart failure. When this blood flow is hindered, the lack of oxygen causes the shortness of breath.

SIGNS OF PPH:

1. Shortness of breath following exertion
2. Excessive fatigue
3. Dizziness, fainting and weakness
4. Ankle swelling
5. Bluish lips and skin
6. Chest pain

DIAGNOSIS OF PPH:
It is difficult to detect PPH in a routine medical examination. Even when the disease has progressed, the signs and symptoms may be confused with other conditions that affect the heart and the lungs. To determine if a patient has pulmonary hypertension, a physician may recommend a series of tests. First, a pulmonary function test is used to establish that there is hypertension. Then, a series of tests are given to rule out other potential causes for the hypertension. If no other causes for the hypertension is found, the hypertension will be classified as “primary.”

TREATMENT OF PPH:
The prognosis for patients with PPH can vary. Some patients can be treated with vasodilators, which help to dilate the blood vessels in the lung, reducing the blood pressure in them. PPH can also be treated with oxygen or through a heart-lung transplant. The median period of survival is three years after diagnosis, although the survival rate is generally longer for those patients without heart failure and for those patients diagnosed after 40.

FDA REMOVAL:
In September 1997, The FDA withdrew pondimin, fenfluramine and redux from the market. Phentermine has not been withdrawn.

MANUFACTURERS’ AWARENESS OF PROBLEMS:
The manufacturers of these diet drugs were aware of the results of the International Primary Pulmonary Hypertension (PPH) study by at least November 1995, but did not warn the public or the physicians of the risk of contracting PPH.

Wyeth-Ayerst Laboratories manufactured Pondimin, known chemically as fenfluramine.

Interneuron Pharmaceuticals manufactured Redux, known chemically as dexfenfluramine.

The drugs, Fen-Phen, suppress the appetite by boosting levels of serontonin, a chemical that relays messages in the brain. Heavy doses of both drugs appear to interfere with an enzyme called monoamineoxidase, or MAO, inhibitors. This means that they interfere with the body’s natural mechanism to destroy excess serotonin in the body. It is this excess serotonin that is thought to cause heart valve injury and the narrowing of the pulmonary artery that causes pulmonary hypertension which is referred to as PPH.

Fenfluramine alters serotonin metabolism by promoting its release and decreasing its re-uptake in the brain. It is also known that the “Phen” may have some effect on serotonin metabolism in the body. Excess serotonin appears to be related to valve disease. The two drugs taken together destroy the body’s ability to control the amount of serotonin in blood plasma. In the carcinoid syndrome, patients with high circulating levels of serotonin are more likely to have valve disease than those with lower levels.