FDA Citizen Petition

To whom it may concern,

The undersigned submits this petition under the Federal Food, Drug and Cosmetic Act or the Public Health Service Act or any other statutory provision for which authority has been delegated to the Commissioner of Food and Drugs to request the Commissioner of Food and Drugs to take a form of administrative action.

Section A: Action Requested

I am requesting section 11 DESCRIPTION of the Full Prescribing Information to be updated to include all active ingredients in Premarin tablets.

From:

11 DESCRIPTION

PREMARIN® (conjugated estrogens tablets, USP) for oral administration contains a mixture of CE purified from pregnant mares’ urine and consists of the sodium salts of water-soluble estrogen sulfates blended to represent the average composition of material derived from pregnant mares’ urine. It is a mixture of sodium estrone sulfate and sodium equilin sulfate. It contains concomitant components as sodium sulfate conjugates, 17α-dihydroequilin, 17α-estradiol, and 17β-dihydroequilin. Tablets for oral administration are available in 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, and 1.25 mg strengths of CE.

To:

11 DESCRIPTION

PREMARIN® (conjugated estrogens tablets, USP) for oral administration contains a mixture of conjugated estrogens purified from pregnant mares’ urine and consists of the sodium salts of water-soluble estrogen sulfates and glucuronides blended to represent the average composition of material derived from pregnant mares’ urine.

Below are the top 250 active ingredients consistently present in Premarin, of which only 61 are identified. Beyond active ingredient 250, there are active ingredients (251 to >1000) inconsistently present in Premarin. Every active ingredient listed is unique. Some active ingredients share the same molecular formula as some active ingredients are isomers of each other.ⁱ

Incomplete list of active ingredients in Premarin

1 ingredient C18H22O5S active hormone in unknown amount
2 ingredient C18H22O5S active hormone in unknown amount
3 ingredient C18H20O5S active hormone in unknown amount
4 ingredient C21H34O6S active hormone in unknown amount
5 ingredient C21H36O5S active hormone in unknown amount
6 ingredient C18H24O5S active hormone in unknown amount
7 ingredient C18H24O5S active hormone in unknown amount
8 ingredient C21H36O6S active hormone in unknown amount
9 ingredient C18H26O5S active hormone in unknown amount
10 ingredient C21H34O5S active hormone in unknown amount
11 ingredient C21H36O6S active hormone in unknown amount
12 ingredient C18H18O5S active hormone in unknown amount
13 ingredient C18H20O5S active hormone in unknown amount
14 ingredient C19H30O5S active hormone in unknown amount
15 ingredient C18H20O5S active hormone in unknown amount
16 ingredient C18H22O5S active hormone in unknown amount
17 ingredient C18H26O5S active hormone in unknown amount
18 ingredient C25H38O8 active hormone in unknown amount
19 ingredient C27H44O9 active hormone in unknown amount
20 ingredient C19H30O5S active hormone in unknown amount
21 ingredient C18H22O5S active hormone in unknown amount
22 ingredient C19H30O6S active hormone in unknown amount
23 ingredient C19H32O5S active hormone in unknown amount
24 ingredient C19H24O6S active hormone in unknown amount
25 ingredient C21H34O6S active hormone in unknown amount
26 ingredient C18H28O5S active hormone in unknown amount
27 ingredient C21H34O6S active hormone in unknown amount
28 ingredient C21H34O5S active hormone in unknown amount
29 ingredient C21H34O6S active hormone in unknown amount
30 ingredient C18H24O5S active hormone in unknown amount
31 ingredient C18H22O6S active hormone in unknown amount
32 ingredient C21H36O6S active hormone in unknown amount
33 ingredient C21H36O6S active hormone in unknown amount
34 ingredient C18H26O5S active hormone in unknown amount
35 ingredient C21H36O6S active hormone in unknown amount
36 ingredient C18H24O5S active hormone in unknown amount
37 ingredient C21H32O5S active hormone in unknown amount
38 ingredient C21H36O5S active hormone in unknown amount
39 ingredient C19H30O6S active hormone in unknown amount
40 ingredient C18H24O5S active hormone in unknown amount
41 ingredient C18H26O5S active hormone in unknown amount
42 ingredient C19H30O6S active hormone in unknown amount
43 ingredient C19H28O5S active hormone in unknown amount
44 ingredient C18H20O5S active hormone in unknown amount
45 ingredient C19H32O6S active hormone in unknown amount
46 ingredient C19H32O6S active hormone in unknown amount
47 ingredient C21H32O5S active hormone in unknown amount
48 ingredient C21H34O6S active hormone in unknown amount
49 ingredient C21H34O6S active hormone in unknown amount
50 ingredient C21H34O6S active hormone in unknown amount
51 ingredient C21H34O6S active hormone in unknown amount
52 ingredient C18H24O5S active hormone in unknown amount
53 ingredient C27H44O9 active hormone in unknown amount
54 ingredient C19H22O6S active hormone in unknown amount
55 ingredient C19H30O6S active hormone in unknown amount
56 ingredient C19H28O5S active hormone in unknown amount
57 ingredient C21H34O6S active hormone in unknown amount
58 ingredient C19H30O6S active hormone in unknown amount
59 ingredient C19H26O6S active hormone in unknown amount
60 ingredient C21H34O6S active hormone in unknown amount
61 ingredient C21H34O6S active hormone in unknown amount
62 ingredient unidentified active hormone in unknown amount
63 ingredient unidentified active hormone in unknown amount
64 ingredient unidentified active hormone in unknown amount
65 ingredient unidentified active hormone in unknown amount
66 ingredient unidentified active hormone in unknown amount
67 ingredient unidentified active hormone in unknown amount
68 ingredient unidentified active hormone in unknown amount
69 ingredient unidentified active hormone in unknown amount
70 ingredient unidentified active hormone in unknown amount
71 ingredient unidentified active hormone in unknown amount
72 ingredient unidentified active hormone in unknown amount
73 ingredient unidentified active hormone in unknown amount
74 ingredient unidentified active hormone in unknown amount
75 ingredient unidentified active hormone in unknown amount
76 ingredient unidentified active hormone in unknown amount
77 ingredient unidentified active hormone in unknown amount
78 ingredient unidentified active hormone in unknown amount
79 ingredient unidentified active hormone in unknown amount
80 ingredient unidentified active hormone in unknown amount
81 ingredient unidentified active hormone in unknown amount
82 ingredient unidentified active hormone in unknown amount
83 ingredient unidentified active hormone in unknown amount
84 ingredient unidentified active hormone in unknown amount
85 ingredient unidentified active hormone in unknown amount
86 ingredient unidentified active hormone in unknown amount
87 ingredient unidentified active hormone in unknown amount
88 ingredient unidentified active hormone in unknown amount
89 ingredient unidentified active hormone in unknown amount
90 ingredient unidentified active hormone in unknown amount
91 ingredient unidentified active hormone in unknown amount
92 ingredient unidentified active hormone in unknown amount
93 ingredient unidentified active hormone in unknown amount
94 ingredient unidentified active hormone in unknown amount
95 ingredient unidentified active hormone in unknown amount
96 ingredient unidentified active hormone in unknown amount
97 ingredient unidentified active hormone in unknown amount
98 ingredient unidentified active hormone in unknown amount
99 ingredient unidentified active hormone in unknown amount
100 ingredient unidentified active hormone in unknown amount
101 ingredient unidentified active hormone in unknown amount
102 ingredient unidentified active hormone in unknown amount
103 ingredient unidentified active hormone in unknown amount
104 ingredient unidentified active hormone in unknown amount
105 ingredient unidentified active hormone in unknown amount
106 ingredient unidentified active hormone in unknown amount
107 ingredient unidentified active hormone in unknown amount
108 ingredient unidentified active hormone in unknown amount
109 ingredient unidentified active hormone in unknown amount
110 ingredient unidentified active hormone in unknown amount
111 ingredient unidentified active hormone in unknown amount
112 ingredient unidentified active hormone in unknown amount
113 ingredient unidentified active hormone in unknown amount
114 ingredient unidentified active hormone in unknown amount
115 ingredient unidentified active hormone in unknown amount
116 ingredient unidentified active hormone in unknown amount
117 ingredient unidentified active hormone in unknown amount
118 ingredient unidentified active hormone in unknown amount
119 ingredient unidentified active hormone in unknown amount
120 ingredient unidentified active hormone in unknown amount
121 ingredient unidentified active hormone in unknown amount
122 ingredient unidentified active hormone in unknown amount
123 ingredient unidentified active hormone in unknown amount
124 ingredient unidentified active hormone in unknown amount
125 ingredient unidentified active hormone in unknown amount
126 ingredient unidentified active hormone in unknown amount
127 ingredient unidentified active hormone in unknown amount
128 ingredient unidentified active hormone in unknown amount
129 ingredient unidentified active hormone in unknown amount
130 ingredient unidentified active hormone in unknown amount
131 ingredient unidentified active hormone in unknown amount
132 ingredient unidentified active hormone in unknown amount
133 ingredient unidentified active hormone in unknown amount
134 ingredient unidentified active hormone in unknown amount
135 ingredient unidentified active hormone in unknown amount
136 ingredient unidentified active hormone in unknown amount
137 ingredient unidentified active hormone in unknown amount
138 ingredient unidentified active hormone in unknown amount
139 ingredient unidentified active hormone in unknown amount
140 ingredient unidentified active hormone in unknown amount
141 ingredient unidentified active hormone in unknown amount
142 ingredient unidentified active hormone in unknown amount
143 ingredient unidentified active hormone in unknown amount
144 ingredient unidentified active hormone in unknown amount
145 ingredient unidentified active hormone in unknown amount
146 ingredient unidentified active hormone in unknown amount
147 ingredient unidentified active hormone in unknown amount
148 ingredient unidentified active hormone in unknown amount
149 ingredient unidentified active hormone in unknown amount
150 ingredient unidentified active hormone in unknown amount
151 ingredient unidentified active hormone in unknown amount
152 ingredient unidentified active hormone in unknown amount
153 ingredient unidentified active hormone in unknown amount
154 ingredient unidentified active hormone in unknown amount
155 ingredient unidentified active hormone in unknown amount
156 ingredient unidentified active hormone in unknown amount
157 ingredient unidentified active hormone in unknown amount
158 ingredient unidentified active hormone in unknown amount
159 ingredient unidentified active hormone in unknown amount
160 ingredient unidentified active hormone in unknown amount
161 ingredient unidentified active hormone in unknown amount
162 ingredient unidentified active hormone in unknown amount
163 ingredient unidentified active hormone in unknown amount
164 ingredient unidentified active hormone in unknown amount
165 ingredient unidentified active hormone in unknown amount
166 ingredient unidentified active hormone in unknown amount
167 ingredient unidentified active hormone in unknown amount
168 ingredient unidentified active hormone in unknown amount
169 ingredient unidentified active hormone in unknown amount
170 ingredient unidentified active hormone in unknown amount
171 ingredient unidentified active hormone in unknown amount
172 ingredient unidentified active hormone in unknown amount
173 ingredient unidentified active hormone in unknown amount
174 ingredient unidentified active hormone in unknown amount
175 ingredient unidentified active hormone in unknown amount
176 ingredient unidentified active hormone in unknown amount
177 ingredient unidentified active hormone in unknown amount
178 ingredient unidentified active hormone in unknown amount
179 ingredient unidentified active hormone in unknown amount
180 ingredient unidentified active hormone in unknown amount
181 ingredient unidentified active hormone in unknown amount
182 ingredient unidentified active hormone in unknown amount
183 ingredient unidentified active hormone in unknown amount
184 ingredient unidentified active hormone in unknown amount
185 ingredient unidentified active hormone in unknown amount
186 ingredient unidentified active hormone in unknown amount
187 ingredient unidentified active hormone in unknown amount
188 ingredient unidentified active hormone in unknown amount
189 ingredient unidentified active hormone in unknown amount
190 ingredient unidentified active hormone in unknown amount
191 ingredient unidentified active hormone in unknown amount
192 ingredient unidentified active hormone in unknown amount
193 ingredient unidentified active hormone in unknown amount
194 ingredient unidentified active hormone in unknown amount
195 ingredient unidentified active hormone in unknown amount
196 ingredient unidentified active hormone in unknown amount
197 ingredient unidentified active hormone in unknown amount
198 ingredient unidentified active hormone in unknown amount
199 ingredient unidentified active hormone in unknown amount
200 ingredient unidentified active hormone in unknown amount
201 ingredient unidentified active hormone in unknown amount
202 ingredient unidentified active hormone in unknown amount
203 ingredient unidentified active hormone in unknown amount
204 ingredient unidentified active hormone in unknown amount
205 ingredient unidentified active hormone in unknown amount
206 ingredient unidentified active hormone in unknown amount
207 ingredient unidentified active hormone in unknown amount
208 ingredient unidentified active hormone in unknown amount
209 ingredient unidentified active hormone in unknown amount
210 ingredient unidentified active hormone in unknown amount
211 ingredient unidentified active hormone in unknown amount
212 ingredient unidentified active hormone in unknown amount
213 ingredient unidentified active hormone in unknown amount
214 ingredient unidentified active hormone in unknown amount
215 ingredient unidentified active hormone in unknown amount
216 ingredient unidentified active hormone in unknown amount
217 ingredient unidentified active hormone in unknown amount
218 ingredient unidentified active hormone in unknown amount
219 ingredient unidentified active hormone in unknown amount
220 ingredient unidentified active hormone in unknown amount
221 ingredient unidentified active hormone in unknown amount
222 ingredient unidentified active hormone in unknown amount
223 ingredient unidentified active hormone in unknown amount
224 ingredient unidentified active hormone in unknown amount
225 ingredient unidentified active hormone in unknown amount
226 ingredient unidentified active hormone in unknown amount
227 ingredient unidentified active hormone in unknown amount
228 ingredient unidentified active hormone in unknown amount
229 ingredient unidentified active hormone in unknown amount
230 ingredient unidentified active hormone in unknown amount
231 ingredient unidentified active hormone in unknown amount
232 ingredient unidentified active hormone in unknown amount
233 ingredient unidentified active hormone in unknown amount
234 ingredient unidentified active hormone in unknown amount
235 ingredient unidentified active hormone in unknown amount
236 ingredient unidentified active hormone in unknown amount
237 ingredient unidentified active hormone in unknown amount
238 ingredient unidentified active hormone in unknown amount
239 ingredient unidentified active hormone in unknown amount
240 ingredient unidentified active hormone in unknown amount
241 ingredient unidentified active hormone in unknown amount
242 ingredient unidentified active hormone in unknown amount
243 ingredient unidentified active hormone in unknown amount
244 ingredient unidentified active hormone in unknown amount
245 ingredient unidentified active hormone in unknown amount
246 ingredient unidentified active hormone in unknown amount
247 ingredient unidentified active hormone in unknown amount
248 ingredient unidentified active hormone in unknown amount
249 ingredient unidentified active hormone in unknown amount
250 ingredient unidentified active hormone in unknown amount

Ingredients 251 to >1000 are unidentified active hormones in unknown amounts inconsistently present in Premarin.

251 ingredient unidentified active hormone in unknown amount
252 ingredient unidentified active hormone in unknown amount
253 ingredient unidentified active hormone in unknown amount
254 ingredient unidentified active hormone in unknown amount
255 ingredient unidentified active hormone in unknown amount
256 ingredient unidentified active hormone in unknown amount
257 ingredient unidentified active hormone in unknown amount
258 ingredient unidentified active hormone in unknown amount
259 ingredient unidentified active hormone in unknown amount
260 ingredient unidentified active hormone in unknown amount
261 ingredient unidentified active hormone in unknown amount
262 ingredient unidentified active hormone in unknown amount
263 ingredient unidentified active hormone in unknown amount
264 ingredient unidentified active hormone in unknown amount
265 ingredient unidentified active hormone in unknown amount
266 ingredient unidentified active hormone in unknown amount
267 ingredient unidentified active hormone in unknown amount
268 ingredient unidentified active hormone in unknown amount
269 ingredient unidentified active hormone in unknown amount
270 ingredient unidentified active hormone in unknown amount
271 ingredient unidentified active hormone in unknown amount
272 ingredient unidentified active hormone in unknown amount
273 ingredient unidentified active hormone in unknown amount
274 ingredient unidentified active hormone in unknown amount
275 ingredient unidentified active hormone in unknown amount
276 ingredient unidentified active hormone in unknown amount
277 ingredient unidentified active hormone in unknown amount
278 ingredient unidentified active hormone in unknown amount
279 ingredient unidentified active hormone in unknown amount
280 ingredient unidentified active hormone in unknown amount
281 ingredient unidentified active hormone in unknown amount
282 ingredient unidentified active hormone in unknown amount
283 ingredient unidentified active hormone in unknown amount
284 ingredient unidentified active hormone in unknown amount
285 ingredient unidentified active hormone in unknown amount
286 ingredient unidentified active hormone in unknown amount
287 ingredient unidentified active hormone in unknown amount
288 ingredient unidentified active hormone in unknown amount
289 ingredient unidentified active hormone in unknown amount
290 ingredient unidentified active hormone in unknown amount
291 ingredient unidentified active hormone in unknown amount
292 ingredient unidentified active hormone in unknown amount
293 ingredient unidentified active hormone in unknown amount
294 ingredient unidentified active hormone in unknown amount
295 ingredient unidentified active hormone in unknown amount
296 ingredient unidentified active hormone in unknown amount
297 ingredient unidentified active hormone in unknown amount
298 ingredient unidentified active hormone in unknown amount
299 ingredient unidentified active hormone in unknown amount
300 ingredient unidentified active hormone in unknown amount

>1000 ingredient unidentified active hormone in unknown amount

Section B: Statement of Grounds

The Federal Food, Drug, and Cosmetic Act (FD&C Act), Section 502(e) mandates that drug labels clearly state the name and quantity of each active ingredient. Specifically, § 201.10 Drugs; statement of ingredients (b), which states

The term ingredient applies to any substance in the drug, whether added to the formulation as a single substance or in admixture with other substances.

Currently, the prescribing label for Premarin is misbranded as all of the active ingredients are not disclosed on Premarin’s prescribing label.

I am requesting the FDA correct the misbranding of Premarin and disclose all the active ingredients in Premarin on Premarin’s prescribing label.

The peer reviewed paper, written by FDA scientists and published in 2015, Marketplace Analysis of Conjugated Estrogens: Determining the Consistently Present Steroidal Content with LC-MS Marketplace, confirms that the USP monograph for Premarin listed 10 active ingredients.ⁱⁱ Today, July 2026, the FDA approved package label for Premarin lists 5 active ingredients for all dosages, 0.30 mg, 0.45 mg, 0.625 mg, 0.90 mg, 1.25 mg.ⁱⁱⁱ

1. sodium estrone sulfate
2. sodium equilin
3. 17α-dihydroequilin
4. 17α-estradiol
5. 17β-dihydroequilin

Listing only 5 ingredients of >1000 ingredients means that all of the active ingredients in Premarin have not been listed on its prescribing label which means Premarin is currently misbranded.

In 2015, the FDA scientists who wrote this paper, Marketplace Analysis of Conjugated Estrogens: Determining the Consistently Present Steroidal Content with LC-MS Marketplace said the USP for Premarin in 2015 listed Premarin as having 10 active ingredients which are listed below,

1. sodium estrone sulfate
2. sodium equilin sulfate
3. sodium Δ8,9-dehydroestrone sulfate
4. sodium equilenin sulfate
5. sodium 17α-estradiol sulfate
6. sodium 17β-estradiol sulfate
7. sodium 17α-dihydroequilin sulfate
8. sodium 17β-dihydroequilin sulfate
9. sodium 17α dihydroequilenin sulfate
10. sodium 17β-dihydroequilenin sulfate

Therefore, in 2015, Premarin was misbranded because only 10 ingredients were listed on the Premarin label.

These FDA scientists also stated in this paper,

The ten conjugated estrogens identified in the USP monograph and other additional estrogens reported elsewhere are among the 60 steroidal components reported here.

Just to be clear, steroidal components are active components.

This paper clearly documents that 50 other named steroidal components are consistently in Premarin and are not listed on the prescribing label for Premarin. Additionally, it documents another 190 active components that are always present in Premarin in consistent amounts and over 750 further active components that are present in unknown, inconsistent amounts.

These FDA scientists acknowledged the misbranding of Premarin. Since this paper has been published the FDA has not corrected the misbranding of Premarin.

A woman has a right to know what she puts into her body.

Like a Trojan Horse, the Premarin pill a woman takes every day delivers over a thousand active steroidal ingredients without her knowledge or consent. Women think they are getting just 5 ingredients when, in reality, they are getting over 1000 ingredients, replenished every day, with a daily Premarin pill.

It is critical to the consumer that a manufacturer disclose all active and inactive ingredients of a prescribed drug on the drug’s prescribing label. By listing all of the active and inactive ingredients patients can make informed and safe healthcare decisions for themselves.

It is also the law. I am asking the FDA to enforce Federal Food, Drug, and Cosmetic Act (FD&C Act), Section 502 which would correct the misbranding of Premarin by including a list of all of the active ingredients in Premarin.

Section C: Environmental Impact

According to section § 25.30 General subsection (a) and § 25.31 Human drugs and biologics subsection (a) there is no requirement to provide an environmental impact.

Section D: Economic Impact

not applicable at this time

Section E: Certification

The undersigned certifies, that, to the best knowledge and belief of the undersigned, this petition includes all information and views on which the petition relies, and that it includes representative data and information known to the petitioner which are unfavorable to the petition.

(Signature) ____________________

(Name of petitioner) Beth Rosenshein

(Mailing address) Diamond Research Foundation, 300 Center Dr #248, Superior CO, 80027

(Telephone number) 425-417-9091

ⁱ 12248_2015_9805_Article 1438..1445 Marketplace Analysis of Conjugated Estrogens: Determining the Consistently Present Steroidal Content with LC-MS

ⁱⁱⁱ labeling.pfizer.com/showlabeling.aspx?id=131 Full Prescribing Information