# Presentation: 734456

## NDAC/PADAC Joint Meeting 

- May 11, 2001
***Cazemiro R. Martin***
- Regulatory Review Chemist
- FDA, Division of OTC Drug Products

## Prescription Availability 

- Durham-Humphrey Amendment
- to the Federal FD&C Act
*(1951)*

## Durham-Humphrey Amendment

-   503(b)(1)(A) :  Because of toxicity or potentially   	                     harmful effects (not safe unless 		             used under supervision)
-                              ***or....***
-   503(b)(1)(B) :  Limited by approved application         	                     to use under supervision

## OTC Availability

-  *New Drug Application Process  (NDA)*
-   Prescription (Rx)-to-OTC Switch process
-   Marketed directly OTC
* **OTC Drug Monograph Process*
-   Established conditions under which OTC drug
-      products are generally recognized as safe and
-      effective  (GRAS/E)

## NDA ProcessRx-to-OTC

_***Considerations***_***:***
-   Can the condition be adequately
-      self-recognized?
-   Can the condition be successfully
-      self-treated?
-   Is the self-treatment product safe
-      and effective during consumer use?

## NDA ProcessRx-to-OTC

_***Switch Candidate***_:
-   Acceptable margin of safety based on prior
-      prescription marketing experience
-   OTC dosages/indications are relatively safe
-      -  ***low misuse potential***
-      -  ***minimal abuse potential***
-      -***  reasonable therapeutic window of safety***

## NDA ProcessRx-to-OTC 

_***Switch Candidate***_***  (cont.)***
-   Self-treatment and self-monitoring
-      with minimal physician supervision
-   Adequately labeled to allow safe
-      and effective use of the OTC drug
-   Benefits from the OTC switch clearly
-      outweigh the risks

## OTC Drug Monograph Process

-  Advisory Review Panel
-  Advance Notice of Proposed
-     Rulemaking** - ***advisory panel report*
-  Tentative Final Monograph
-   Final Monograph

## Advisory Review Panel

- OTC Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic      Drug Products

## Advanced Notice of Proposed Rulemaking - 1976

* *_*Panel’s*__* *__*Antihistamine Review*_
-  Effective in suppressing symptoms of allergic
-      rhinitis (such as hay fever)
-  Low order of acute and chronic toxicity

## Advisory Panel Report

*(Antihistamine Review** **-** **cont.)*
-   Common side effects -  rarely serious
-   CNS depression:  *drowsiness*
-   Anticholinergic:   *dryness of the mouth;          *
*        **urinary retention;  reduced bronchial       *
*        **secretions*
-   Rarely occurring side effects
*  **Cardiovascular, gastrointestinal, hematological*

## Advisory Panel Report

*(Antihistamine Review** **-** **cont.)*
-  Labeling recommendations:
_***Uses***_:   *temporary relief of symptoms associated         *
*            **with allergic rhinitis*
_***Warnings***_:
*  **may cause drowsiness *
* * *avoid driving or operating machinery*
-   *avoid alcoholic drinks*
*  **consult a physician before use if you have   *
*         **difficulty in urination or difficulty breathing** **	** *

## Tentative Final Monograph

- January 15, 1985

## Final Monograph - 1992 (OTC Antihistamines) 

_**21 CFR 341**_
-   13 antihistamine active ingredients marketed
-       under the OTC drug monograph system
-   Final rule addresses “allergy” indications only
**  **Labeling of OTC antihistamine drug products

## OTC Monograph Antihistamines21 CFR 341.12

- Brompheniramine maleate
- Chlorcyclizine HCl
- Chlorpheniramine maleate
- Dexbrompheniramine maleate
- Dexchlorpheniramine maleate
- Diphenhydramine citrate
- Diphenhydramine HCl

- Doxylamine succinate
- Phenindamine tartrate
- Pheniramine maleate
- Pyrilamine maleate
- Thonzylamine HCl
- Triprolidine HCl

## OTC NDA/ANDA Antihistamines

**         **_**Extended Release**_**:**
- 		  Brompheniramine maleate
- 		  Chlorpheniramine maleate
- 		  Dexbrompheniramine maleate
- 		  Triprolidine HCl
_**	**__**	**__**Immediate Release**_**:**
- 		  Clemastine fumarate

## Nonmonograph Ingredients

** ****Methapyrilene**** ****fumarate**
** ****Methapyrilene**** ****HCl**
** ****Phenyltoloxamine*** *
**      ****dihydrogen citrate**
** ****Promethazine**** ****HCl**
** ****Thenyldiamine**** ****HCl**
** ****Tripelennamine ****HCl**

- - *potential carcinogen*
*- potential carcinogen *
*- inadequate efficacy data*
*- tardive dyskinesia: causal role *
*- single ingredient:  no long-term*
*   **use*
*- inadequate efficacy data*
*- safe/effective:no data submitted*
*  *

## OTC Antihistamines

-                   ***Drug Facts Labeling***
- _21 CFR 201.66_
- Format and Content Requirements
- for OTC Drug Product Labeling

## Slide 19

## Summary

-  OTC Drug Products:
-  *acceptable margin of safety (minimal toxicity)*
-  *low potential for harmful effects*
-  *low misuse/minimal abuse potential*
-  *reasonable therapeutic window of safety*
-  Self-treatment and self-monitoring
-  Adequately labeled to allow safe and effective use
-  Benefits outweigh risks