PHA 373 - Product Labeling L3

Label

Written, printed, or graphic information appearing on the immediate container of a drug product

Labeling

Information on the label, outside package, package inserts, patient package inserts, or pharmacy prescription labels

Adequate directions for use

Instructions written in layman's terms allowing safe and effective use of a drug

What separates OTC drugs from Rx-only drugs regarding labeling?

Adequate directions for use

Durham-Humphrey Amendment of 1951

Rx drugs do not require adequate directions for use if "Rx Only" appears on the label

OTC labeling requirement

Must contain sufficient information for a layperson to safely and effectively use the product

Misbranded

Something is wrong with the label

Adulterated

Something is wrong with the drug product itself

What happens if required labeling information is missing?

The product is considered misbranded

National Drug Code (NDC)

An 11-digit number that uniquely identifies a drug product

Do all OTC and prescription drugs require an NDC?

Yes

What are the three components of an NDC number?

Labeler code, Product code, Package code

Labeler code

5-digit code assigned by FDA identifying manufacturer, repackager, or distributor

Product code

4-digit code assigned by manufacturer identifying strength, dosage form, and formulation

Package code

Code assigned by manufacturer identifying package size and type

Who assigns the labeler code?

FDA

Who assigns the product code?

Manufacturer

Who assigns the package code?

Manufacturer

What does the labeler code identify?

Manufacturer, repackager, or distributor

What does the product code identify?

Strength, dosage form, and formulation

What does the package code identify?

Package size and type

Can leading zeros be omitted from an NDC?

Yes

GMP

Good Manufacturing Practice

Inactive ingredients are also called

Adjuvants

How should inactive ingredients be listed?

Alphabetically and separately from active ingredients

Examples of inactive ingredients

Fragrances and flavors

Can coloring agents be present in oral dosage forms?

Yes

Can coloring agents be present in topical dosage forms?

Yes

Can coloring agents be present in ophthalmic dosage forms?

No

Can coloring agents be present in parenteral dosage forms?

No

Why may inert gases be present in parenteral products?

For stability

Must inert gases be listed on the label?

No

Which four electrolytes may require labeling on oral OTC products?

Sodium, Calcium, Magnesium, Potassium

Why are electrolyte warnings included on OTC labels?

For patients with kidney disease or electrolyte-restricted diets

Electrolyte warning recommendation

Consult a physician before use

FD&C Yellow No. 5 (tartrazine) warning

May precipitate allergic reactions

Sulfite warning

May precipitate allergic reactions

Aspartame warning

Contains phenylalanine; notice required for phenylketonurics

Mineral oil warning

Use at bedtime only; avoid use in infants and pregnancy

Wintergreen oil warning

Products containing more than 5% methyl salicylate must warn misuse is dangerous and keep out of reach of children

Sodium phosphate warning

May not exceed 90 mL per OTC container

Isoproterenol inhalation warning

Do not exceed prescribed dose; contact physician if breathing difficulty persists

Acetophenetidine (Phenacetin) warning

May cause kidney damage if taken in large amounts or for long periods

Salicylate (Aspirin) warning

Associated with Reye's syndrome

Alcohol warning

Consult physician before use if consuming three or more alcoholic beverages daily

Which products require alcohol warnings?

Internal analgesics and antipyretics

(Acetaminophen, aspirin, ibuprofen, naproxen, ketoprofen, etc)

Examples of products requiring alcohol warnings

Acetaminophen, aspirin, ibuprofen, naproxen, ketoprofen

Ipecac syrup boxed warning

For emergency use to cause vomiting in poisoning; contact physician or poison center immediately

Ipecac syrup storage warning

Keep out of reach of children

When should ipecac not be used?

Corrosive poisonings, petroleum distillates, or strychnine poisoning

Usual dose of ipecac syrup

15 mL for patients older than 1 year

Maximum container size for ipecac syrup

1 ounce (30 mL)

Package Insert (PI)

Manufacturer information directed toward healthcare professionals

Who approves package insert information?

FDA

Required package insert sections

1. Description of drug,

2. clinical pharmacology,

3. indications and usage, contraindications,

4. warnings and precautions,

5. adverse reactions,

6. potential for abuse or dependence,

7. symptoms and treatment of overdose,

8. dosage and administration,

9. available dosage forms,

10. date of most recent revision, and

11. recommended or usual dosing

Pregnancy section requirements

Dosing information, fetal risk information, and pregnancy registry information

Lactation section requirements

Amount of drug in breast milk and potential effects on child

Females and Males of Reproductive Potential section

Pregnancy testing, contraception, and infertility information

Black Box Warning

Strongest FDA warning indicating risk of death or serious injury

What is another name for a boxed warning?

Black box warning

Patient Package Insert (PPI)

Patient-directed drug information required for certain medications

When were PPIs first required for oral contraceptives?

1970

Why were PPIs required for oral contraceptives?

Increased popularity and lack of awareness of serious side effects

Medication Guide (MedGuide)

Patient information required for drugs with serious risks or important adherence requirements

When were Medication Guides introduced?

1996

When is a MedGuide required?

When patient labeling could prevent serious adverse effects, serious risks exist, or adherence is crucial for effectiveness

What are the three reasons a MedGuide may be required?

Prevent serious adverse effects, inform patients of serious risks, or improve adherence necessary for effectiveness

REMS

Risk Evaluation and Mitigation Strategies

Which law authorized REMS?

Food and Drug Administration Amendments Act of 2007

Purpose of REMS

Manage known or potential serious risks associated with a drug

What is the key concept of REMS?

A safety feature where access requirements become increasingly restrictive

REMS Level 1

Professional labeling and package insert

REMS Level 2

Medication Guide (MedGuide)

REMS Level 3

Communication Plan

REMS Level 4

Elements To Assure Safe Use (ETASU)

REMS Level 5

Implementation System

Which REMS level is least restrictive?

Professional labeling and package insert

Which REMS level is most restrictive?

Implementation System

What does ETASU stand for?

Elements To Assure Safe Use

REMS example

iPledge for isotretinoin

REMS example

STEPS for thalidomide

REMS example

Clozaril National Registry

REMS example

OxyContin REMS Educational Program

Which REMS programs require prescriber, patient, and pharmacy enrollment?

iPledge, STEPS, Clozaril National Registry, Rosiglitazone programs

Which REMS program requires only prescriber enrollment?

OxyContin REMS Educational Program

Identification requirement for solid dosage forms

Solid oral dosage forms must be imprinted

Which dosage forms require imprints?

Tablets, capsules, and gel caps

What information must an imprint identify?

Manufacturer and specific drug product

Which regulation requires imprinting?

Code of Federal Regulations (CFR)

What does CFR stand for?

Code of Federal Regulations

Which drug is exempt from imprint requirements?

Nitroglycerin

Why is nitroglycerin exempt?

Tablets are too small and unstable when exposed to air

Off-label use

Use of a drug for an indication not approved by the NDA

Can prescribers prescribe drugs off-label?

Yes

Can pharmacists dispense drugs off-label?

Yes

Can manufacturers advertise off-label uses?

No

Can manufacturers distribute peer-reviewed off-label information?

Yes, if requested by a healthcare professional

Purpose of bar coding

Reduce medication errors

Which products must manufacturers barcode?

All drug products supplied to hospitals

Must hospitals use barcodes?

No