Boxed Warnings

BOXED WARNINGS –  Q & A

What should a patient know about medical abortion Boxed Warnings?

A BOXED WARNING is used to highlight and describe certain contraindications, serious warnings, special problems, or serious adverse drug reactions particularly those that may lead to death or serious injury, may be required by the FDA to be presented in a box. ^{(1) (2)}

Adverse Drug Reactions (ADRs) are believed to be a leading cause of death in the United States. Many ADRs are discovered only after a drug has been on the market for years. ⁽³⁾

The boxed warning ordinarily must be based on clinical data, but serious animal toxicity may also be the basis of a boxed warning in the absence of clinical data. ⁽¹⁾

The box must briefly explain the risk and refer to more detailed information in the "Contraindications" or "Warnings and Precautions" section of the drug labeling. ⁽¹⁾

“A boxed warning means that there is reasonable evidence of an association of a serious hazard with the drug. A definite causal relationship to the drug does not have to be established.”  ^(1) (2)

A boxed warning (sometimes called a black box warning) is the highest level of 5 possible warning categories added to the package insert at the direction of the U.S. Food and Drug Administration (FDA). ⁽⁴⁾

The most severe warning is the ‘‘Boxed,’’ followed in descending order of importance by ‘‘Contraindications,’’ ‘‘Warnings,’’ ‘‘Precautions,’’ and ‘‘Adverse Reactions.’’ ⁽⁴⁾

BOXED WARNINGS – MIFEPRISTONE ^{(5) (6)}

What important health risk information should a patient know about the Boxed Warnings for Mifepristone?

MIFEPREX® (U.S. Brand Name for Mifepristone)

Mifepristone: Tablets, 200 mg

For Oral Administration Only

Serious and sometimes fatal infections and bleeding occur very rarely following spontaneous, surgical, and medical abortions, including following Mifeprex (mifepristone) use. No causal relationship between the use of Mifeprex (mifepristone) and misoprostol and these events has been established.

Before prescribing Mifeprex, inform the patient about the risk of these serious events and discuss the MEDICATION GUIDE and the PATIENT AGREEMENT. Ensure that the patient knows whom to call and what to do, including going to an Emergency Room if none of the provided contacts are reachable, if she experiences sustained fever, severe abdominal pain, prolonged heavy bleeding, or syncope, or if she experiences abdominal pain or discomfort or general malaise (including weakness, nausea, vomiting or diarrhea) more than 24 hours after taking misoprostol.

• Atypical Presentation of Infection. Patients with serious bacterial infections (e.g. Clostridium sordellii) and sepsis can present without fever, bacteremia or significant findings on pelvic examination following an abortion. Very rarely, deaths have been reported in patients who presented without fever, with or without abdominal pain, but with leukocytosis with a marked left shift, tachycardia, hemoconcentration, and general malaise. A high index of suspicion is needed to rule out serious infection and sepsis (see WARNINGS).
• Bleeding. Prolonged heavy bleeding may be a sign of incomplete abortion or other complications and prompt medical or surgical intervention may be needed. Advise patients to seek immediate medical attention if they experience prolonged heavy vaginal bleeding (see WARNINGS).

Patients should be advised to take their MEDICATION GUIDE with them if they visit an emergency room or another health care provider who did not prescribe Mifeprex, so that provider will be aware that the patient is undergoing a medical abortion.

For More Information:

• Mifeprex (mifepristone) Labeling Revision 4/22/09 ⁽⁵⁾
• Mifeprex (Mifepristone) Tablets, 200mg ⁽⁶⁾
• Healthcare-associated Infections: Clostridium sordellii ⁽⁷⁾
• Mifeprex (mifepristone) Information ⁽⁸⁾
• Mifeprex Questions and Answers ⁽⁹⁾

BOXED WARNINGS – MISOPROSTOL ^{(10) (11)}

What important health risk information should a patient know about the Boxed Warnings for Misoprostol?

Cytotec® (U.S. Brand Name for Misoprostol)

Misoprostol Oral Tablets (100 mcg or 200 mcg)

CYTOTEC (MISOPROSTOL) ADMINISTRATION TO WOMEN WHO ARE PREGNANT CAN CAUSE ABORTION, PREMATURE BIRTH, OR BIRTH DEFECTS.

UTERINE RUPTURE HAS BEEN REPORTED WHEN CYTOTEC WAS ADMINISTERED IN PREGNANT WOMEN TO INDUCE LABOR OR TO INDUCE ABORTION BEYOND THE EIGHTH WEEK OF PREGNANCY (see also PRECAUTIONS and LABOR AND DELIVERY).

CYTOTEC SHOULD NOT BE TAKEN BY PREGNANT WOMEN TO REDUCE THE RISK OF ULCERS INDUCED BY NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS).

PATIENTS MUST BE ADVISED OF THE ABORTIFACIENT PROPERTY AND WARNED NOT TO GIVE THE DRUG TO OTHERS.

Cytotec should not be used for reducing the risk of NSAID-induced ulcers in women of childbearing potential unless the patient is at high risk of complications from gastric ulcers associated with use of the NSAID, or is at high risk of developing gastric ulceration. In such patients, Cytotec may be prescribed if the patient

• has had a negative serum pregnancy test within 2 weeks prior to beginning therapy.
• is capable of complying with effective contraceptive measures.
• has received both oral and written warnings of the hazards of misoprostol, the risk of
• possible contraception failure, and the danger to other women of childbearing
• potential should the drug be taken by mistake.
• will begin Cytotec only on the second or third day of the next normal menstrual period.

For More Information:

• Cytotec (misoprostol) Labeling Revision , 09/11/2009 ⁽¹⁰⁾
• CYTOTEC® (misoprostol tablets) ⁽¹¹⁾
• Misoprostol (marketed as Cytotec) Information,  ⁽¹²⁾