Boxed Warning (sometimes referred to in lay terms as a “black-box warning”)
- Contains contraindications or warnings about serious adverse reactions2 that may lead to death or serious injury
- Placed prominently at the beginning of the Full Prescribing Information
- Words are bolded and surrounded by a single black line (box)
1 Indications and Usage
FDA-approved uses that are supported by substantial evidence of effectiveness, with benefits that outweigh risks
2 Dosage and Administration
- Recommended dosage (recommended dose and dosing frequency)
- Dosage range
- Recommended starting dosage and titration schedule
- Maximum recommended dosage
- Route(s) of administration
- Pre-medication or concomitant medicines
- Dosage modifications due to drug interactions with other medicines or foods
- Recommended dosage in specific populations (e.g., pediatric patients, patients with renal or hepatic impairment)
- Preparation instructions (reconstitution of the supplied powder, dilution)
- Administration instructions
3 Dosage Forms and Strengths
Approved dosage forms, strengths, and identifying characteristics (e.g., shape, color, scoring, imprinting)
4 Contraindications
Situations when the risk from use clearly outweighs any possible therapeutic benefit, and the medicine must not be used
5 Warnings and Precautions
Description of clinically significant adverse reactions or risks with the medicine.
- Numerical estimate or rate of adverse reactions or risks
- Outcomes
- Known risk factors
- Information, when known, on how to prevent, mitigate, or monitor adverse reactions or risks
6 Adverse Reactions
- Overall adverse reaction profile of the medicine from clinical studies and adverse reactions from spontaneous reports
- Description of the clinical trial database (study designs, number of patients, dosage, duration, demographics)
- Most common adverse reactions at or above a specified rate, typically in tabular format
7 Drug Interactions
Description of clinically significant drug interactions with other medicines, drug classes, or foods.
- Specific practical instructions for preventing or managing the drug interactions (e.g., dosage modification, avoiding concomitant use, additional or increased frequency of monitoring)
- Clinical effects (e.g., increased risks of adverse reactions, decreased effectiveness), and
- Mechanism of action of these drug interactions
8 Use in Specific Populations
Information on use of the medicine in:
- Pregnant females
- Lactating females
- Females and males of reproductive potential
- Pediatric patients,
- Geriatric patients, and
- Patients with certain coexisting conditions (e.g., patients with renal or hepatic impairment)
9 Drug Abuse and Dependence
Information on a medicine’s potential for abuse, misuse, addiction, dependence, and tolerance and about a medicine’s abuse-deterrent properties
10 Overdosage
Signs, symptoms, laboratory findings, and complications of overdosage and how to treat an overdosage
11 Description
Brand name, generic name or proper name, dosage form(s), route(s) of administration, and chemistry characteristics of the medicine (e.g., chemical and structural formula, a list of active and inactive ingredients in the medicine)
12 Clinical Pharmacology
- Mechanism of action
- Medicine’s pharmaco*kinetic, pharmacodynamic, and pharmacogenomic effects, and
- For antimicrobial medicines, microbiology information including information on resistance, interaction with other antimicrobials, antimicrobial activity, and susceptibility testing
13 Nonclinical Toxicology
Information on the propensity of the medicine to cause cancers in animals, for mutagenesis, effects of the medicine on animal fertility, and other animal toxicology/pharmacology findings
14 Clinical Studies
Summary of the trial designs, baseline demographics and important disease characteristics, and results that established substantial evidence of effectiveness for all of the approved indications
15 References
Usually omitted, unless there are authoritative reference(s) that contain information not in the labeling that is important for the healthcare professional
16 How Supplied/Storage and Handling
Dosage forms, strengths, quantity of medicine available for prescribing (e.g., bottles of 100 tablets, 60-gram tubes), identifying characteristics including the National Drug Code (NDC) numbers, and special storage and handling conditions (e.g., store in refrigerator, protect from light)
17 Patient Counseling Information
Important information that the healthcare professional should convey to the patient or caregiver when a counseling decision is taking place (e.g., major risks of the medicine, critical administration instructions)
