Yasmin and gallbladder disease

Hi there... I came off of Yasmin just 2 weeks ago and thought I should share with you my story since yours is a skin issue. I took Yasmin for 3 years. This past year I would wake up some bumps on my lip.. then on my hands.. then (this is over a period of months) I would wake up and have a slightly swollen lip... this was over the last year or so. I would also get a feeling in my throat, like something was in it and swallowing felt funny.
WELL, 2 weeks ago, I took my bc like I always do, right before I go to bed and my lip starts to tingle and itch.. and in the morning my face was swollen 3x the normal size on on side, mostly at the lips... I couldn't really talk.. it was like those awful photos on google. It was angioedema and can kill you by swelling of the throat. I had also for about a year- an ear issue.. it would sound like I was talking under water and felt like swimmer's ear- related to the swelling I found out later. Turns out I'm allergic. I developed this allergy over the period of time I was exposed.

I just want to say to anyone out there that has FACIAL/LIP SWELLING, or swelling of the hands... GO TO THE ER. It can kill you. I got lucky.. my swelling started slow and after about a year if was full blown. It is not something to mess around with!I was prescribed an epi pen. I developed an allergy to a preservative in it and I'm not an allergen sensitive person. That was just the parms/doctor guess I might add.

The first year I took Yasmin I had numb and tingling toes. and the whole tie I've had on and off leg pain.. no sex drive, that's the truth..definite bloating issues about 6 lbs weight gain, sometimes more without change in diet. I haven't noticed any hair loss thankfully. Migraines. Lots of nausea in the morning, every morning like morning sickness. Car sick even when driving.. not normal! I used to work on an airplane and I never got motion sickness.

I'm now on day 4 of Mirena IUD and I'm having having severe diarrhea and trouble sleeping.. I really, really don't want to get pregnant. Our next step is a vasectomy for the hubby. I'm 25 and I weigh 140 5'10 if that helps. I wasn't an 'at risk' like the pamphlet said.

I was on yaz for close to 4-5 years. I started taking antibiotics and my husband and I became pregnant while on the pill. We were well aware of chances of becoming pregnant. From the day I found out i was pregnant I started throwing up. I LOST 15 pounds during my pregnancy due to being sick all of the time. I had constant heartburn and choked all of this up to being pregnant with a little girl with a head full of black hair! The day my husband was suppose to go back to work from his leave (exactly 2 weeks after having my baby) i started throwing up at about 3am due to intense stomach pain that radiated into my chest and back and couldn't stop. He stayed home. The next day it happened again, my husband assumed i had postpartum depression and told me i would be fine and left for work. I tried to go back to bed but couldn't stop throwing up long enough to go into the next room and check on my crying newborn. I had to beg him to come home from work, we got a babysitter, went to the hospital, they did an ultrasound and admitted me. 12 hrs later I was on the operating table having my gallbladder removed. I now suffer with DAILY diarrhea immediately after I eat ANYTHING and stomach pain. I try to stick to a low fat diet but it doesn't help!!!! i have constant stomach pain, headaches, nausea and heartburn. Not to mention the FOUR scars that i have from the surgery. When i started taking Yasmin and eventually yaz NOWHERE did it say that it could cause gallbladder disease!

I too have been experiencing the same side effects listed by most of you. I have also been seeing a gastroenterologist for about 9 months now because of stomach issues. All symptoms point to gallbladder disease but the tests come back normal. I called my gyne today and they seem unconcerned with what I have told them and advised me to continue to take my pills until my annual visit in October. I'm done with this pack on Saturday and am thinking of going sans pills for the next month until my appt. Any advice on what pill I should switch to when I do see my dr.?

sweats, fatigue, anxiety, major leg cramps, weight gain after getting of it! terrible sleep and insomnia! I am now using nuvaring...no trouble. any and everything seems to make my stomach swell after having used it...i also developed a golf ball sized cyst...and got gall bladder disease. major nausea for no apparent reason! I got off of it when i couldn't stand the idea of having another period after already have 5 in a 60day span. I am still not better after three months! Ugghhh! After being sick with gallbladder disease and these symptoms/side effects...I am feeling hopeless and terrible! Yasmin sucks! But it was taken in hopes of a clearer complexion...it's odd that it actually got worse.

God Bless all of the others who have and are going through what I am...

SIDE EFFECTS OF YASMIN AS NOTED ON THE INISERT THAT COMES WITH THE PRESCRIPTION:
Nausea
vomiting
headache
diarrhea
bleeding between menstrual periods (spotting)
weight gain
acne
stomach cramps
rash
swelling or bloating
skin spots
breast tenderness
or difficulty wearing contact lenses may occur.

If any of these effects persist or worsen, notify your doctor promptly. Tell your doctor immediately if any of these serious side effects occur:
dizziness
flu-like symptoms (e.g., fever, cough, unusual weakness/fatigue, sore throat, muscle aches)
mental/mood changes
trouble sleeping
hair loss
vaginal infections.

Tell your doctor immediately if any of these unlikely but serious side effects occur:
severe headache
pain in the lower legs or groin
trouble breathing
chest pain
vision changes
severe stomach pain
one-sided weakness
yellowing eyes or skin
lumps in the breast.

If you notice any other effects not listed above, contact your doctor or pharmacist.

PRECAUTIONS: Tell your doctor your medical history, especially of:
heart problems
stroke
gallbladder disease
diabetes
high cholesterol or triglyceride levels
high blood pressure
migraines
seizures
irregular vaginal bleeding
depression
any allergies.

This medication is not recommended for use if you have the following medical conditions:
liver problems
kidney or adrenal gland problems
history of blood clots (thrombophlebitis)
blood vessel problems (e.g., cerebral vascular disease, coronary artery disease)
history of certain cancers (especially endometrial or breast cancer)
heavy smoking (especially if older than 35 years of age).
If you are near-sighted or wear contact lenses you may develop vision problems or have trouble wearing your contact lenses.

Contact your eye doctor if this occurs. If you stop taking this birth control medicine and want to become pregnant, it may take a longer time than is usually seen with women not taking birth control medicine. Consult your doctor.

Do not smoke cigarettes. Birth control pills combined with smoking cigarettes, especially in women older than 35 years of age, puts you at a much higher risk of developing serious health problems than with birth control pills alone. Consult your doctor or pharmacist for more information.

If you will be having surgery, be confined to a chair or bed for a long period of time (e.g., a long plane flight), or have recently delivered a baby, notify your doctor beforehand. Special precautions may need to be taken in these circumstances while you are taking this drug. This medication must not be used during pregnancy. If you become pregnant or think you may be pregnant, inform your doctor immediately. This medication passes into breast milk and has had undesirable effects on nursing infants. Consult your doctor before breast- feeding.

DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service Food and Drug Administration
Rockville, MD 20857
TRANSMITTED BY FACSIMILE

Nancy Konnerth
Associate Director,
Advertising and Labeling
Drug Regulatory Affairs
Berlex Laboratories
340 Changebridge Road P.O. Box 1000 Montville,
NJ 07045-1000

RE: NDA 21-098 Yasmin (drospirenone/ethinyl estradiol) Tablets
MACMIS ID# 11730

Dear Ms. Konnerth:

This letter notifies Berlex Laboratories (Berlex) that the Division of Drug Marketing, Advertising, and Communications (DDMAC) has identified a direct-to-consumer (DTC) broadcast advertisement (TV ad) for Yasmin (drospirenone/ethinyl estradiol) Tablets that is misleading and in violation of the Federal Food, Drug, and Cosmetic Act (Act) and applicable implementing regulations. Specifically, the 60-second TV ad entitled "Goodbye Kiss" is misleading because it makes implied clinical superiority claims to other combination oral contraceptives and minimizes the important risk information that distinguishes Yasmin from other combination oral contraceptives. As a result, the TV ad raises significant public health and safety concerns. Background Yasmin is a combination oral contraceptive ("COC" or "birth control pill") prescription drug product. Yasmin, like any oral contraceptive, is associated with increased risks of several serious conditions (including myocardial infarction, thromboembolism, stroke, hepatic neoplasia, gallbladder disease, and hypertension), although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors.

The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as hypertension, hyperlipidemias, obesity, and diabetes. (See the WARNINGS section of the Yasmin approved physician labeling (PI)) Yasmin contains the estrogen ethinyl estradiol and the progestin drospirenone. Drospirenone has antimineralocorticoid properties, which means that it can work against the body's normal mechanism for regulating salt and water balance, a situation that can lead to hyperkalemia in high risk patients, resulting in potentially serious heart and health problems. This additional risk is described in the Bolded Warning of Yasmin's PI: Nancy Konnerth. 2 Berlex Laboratories NDA 21-098 Yasmin contains 3 mg of the progestin drospirenone that has antimineralocorticoid activity, including the potential for hyperkalemia in highrisk patients, comparable to a 25 mg dose of spironolactone . Yasmin should not be used in patients with conditions that predispose to hyperkalemia (i.e., renal insufficiency, hepatic dysfunction and adrenal insufficiency). Women receiving daily, long-term treatment for chronic conditions or diseases with medications that may increase serum potassium, should have their serum potassium level checked during the first treatment cycle. Drugs that may increase serum potassium include ACE inhibitors, angiotensin -- II receptor antagonists, potassium-sparing diuretics, heparin, aldosterone antagonists, and NSAIDs.

Consequently, Yasmin can exacerbate serious heart and health problems, in addition to the potential problems common to all COCs. Women taking Yasmin must be concerned about drug interactions that will increase potassium, in addition to the drug interactions common to all COCs. Therefore, these women and their healthcare providers must weigh Yasmin's additional health risks when considering Yasmin over COCs without drospirenone. Misleading Efficacy and Safety Presentations Prescription drug ads are false or misleading if they contain a drug comparison that represents or suggests that a prescription drug is more effective or safer than another drug when it has not been demonstrated to be safer or more effective by substantial evidence or substantial clinical experience (21 CFR 202.1(e)(6)(ii)). The TV ad misleadingly overstates the efficacy and safety of Yasmin by suggesting that Yasmin is unique and therefore clinically superior to other birth control pills because it contains the chemically different progestin drospirenone. The unifying theme of the ad, typified by the tagline "Ask about Yasmin, and the difference a little chemistry can make" (emphasis added) suggests that Yasmin is better than other birth control pills because of drospirenone and the way in which it is metabolized in the body. This "chemistry" difference is presented as a product benefit. FDA is not aware of substantial evidence or substantial clinical experience demonstrating that Yasmin is superior to other COCs or that the drospirenone in Yasmin is clinically beneficial. On the contrary, FDA is aware of the added clinical risks associated with drospirenone as communicated in the Warnings/Bolded Warning, and Precautions/Drug Interactions sections of the PI.

Specifically, the following claims in the TV ad address Yasmin's efficacy: "You don't settle when it comes to the guy...so why settle when it comes to the pill? The Yasmin birth control pill uses a different kind of hormone. One that may work with your body chemistry. Yasmin is over 99% effective at preventing pregnancy. So when you're looking for the right pill, ask your doctor about the difference a little chemistry can make." (emphasis added) These claims are misleading because they suggest that Yasmin's "different kind of hormone" offers unique "chemistry" benefits and that this difference contributes to the high rate of drug efficacy. Moreover, these claims are misleading because they imply superiority to other COCs (and thus do not offer the same product benefits as Yasmin Tablets) when such has not been demonstrated by substantial evidence or substantial clinical experience. Finally, these claims are misleading because they misrepresent Yasmin's mechanism of action by stating that Yasmin "uses a different kind of hormone. One that may work with your body Nancy Konnerth. 3 Berlex Laboratories NDA 21-098 chemistry." However, COCs, including Yasmin, prevent ovulation by working against the usual body chemistry of a woman of childbearing potential by suppressing endogenous gonadotropins and, thereby, inhibiting ovulation and altering other changes associated with the menstrual cycle.

In addition, the statement "Yasmin contains a different progestin, which may increase potassium" is misleading because the "may increase potassium" disclosure fails to communicate that the potential to increase potassium is a risk. Furthermore, consumers may interpret the statement as a product benefit claim rather than a risk disclosure due to the overall positive message that Yasmin's "chemistry" is a product benefit. The ad conveys this positive message to consumers, notwithstanding the disclosure that "You should not take Yasmin if you have kidney, liver, or adrenal disease," because the "different kind of hormone" and "chemistry'" messages are never clearly identified as potentially leading to increased potassium levels or that increased serum potassium can be dangerous. This important risk information is in a Bolded Warning in the PI and clearly conveyed in the Yasmin Brief Summary Patient Package Insert and in the Detailed Patient Package Insert: Yasmin is different from other birth-control pills because it contains the progestin drospirenone. Drospirenone may increase potassium. Therefore, you should not take Yasmin if you have kidney, liver, or adrenal disease because this could cause serious heart and health problems. Other drugs may also increase potassium. If you are currently on daily, long-term treatment for a chronic condition with any of the medications below, you should consult your healthcare provider about whether Yasmin is right for you, and during the first month that you take Yasmin, you should have a blood test to check your potassium level. Thus, by failing to add the necessary context to clarify that increased blood potassium is a safety risk rather than a clinical benefit, the ad misleadingly represents or suggests that Yasmin is safer than has been demonstrated by substantial evidence or substantial clinical experience. In summary, the TV ad not only misleads consumers about the efficacy of Yasmin, the ad also minimizes important context about the health risks of the drug. ]

Conclusions and Requested Actions
Berlex should immediately discontinue the TV ad and all other promotional materials and activities for Yasmin that contain the same or similar violative presentations. Berlex should submit a written response to DDMAC on or before July 24, 2003, describing its intent and plans to comply with the above. In its letter to DDMAC, Berlex should include the date on which these and other similarly violative materials were discontinued.

Berlex should direct its response to the undersigned by facsimile at (301) 594-6771, or at the Food and Drug Administration, Division of Drug Marketing, Advertising, and Communications HFD-42, Rm. 8B-45, 5600 Fishers Lane, Rockville, Maryland 20857.

Nancy Konnerth. 4 Berlex Laboratories NDA 21-098 In all future correspondence on this matter, please refer to MACMIS ID# 11730 as well as the NDA number. DDMAC reminds Berlex that only written communications are considered official. Sincerely, {See appended electronic signature page} Joan Hankin Consumer Promotion Analyst Division of Drug Marketing, Advertising, and Communications

--------------------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. -------------------------------------------------------------------------------------------------------------------- /s/ --------------------Joan Hankin 7/10/03 03:40:53 PM