COMBIPATCH SIDE EFFECTS
- Generic Name: estradiol, norethindrone acetate transdermal system
- Brand Name: CombiPatch
- Drug Class: Estrogens/Progestins-HRT
SIDE EFFECTS
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Table 1. All Adverse Reactions Regardless of Relationship Reported at a Frequency of Greater than or Equal to 5 percent with CombiPatch
| VASOMOTOR SYMPTOM STUDIES | |||
| CombiPatch 0.05/0.14 mg per day† |
CombiPatch 0.05/0.25 mg per day† |
Placebo | |
| n=113 | n=112 | n=107 | |
| Body as a Whole | 46% | 48% | 41% |
| Abdominal Pain | 7% | 6% | 4% |
| Accidental Injury | 4% | 5% | 8% |
| Asthenia | 8% | 12% | 4% |
| Back Pain | 11% | 9% | 5% |
| Flu Syndrome | 9% | 5% | 7% |
| Headache | 18% | 20% | 20% |
| Pain | 6% | 4% | 9% |
| Digestive | 19% | 23% | 24% |
| Diarrhea | 4% | 5% | 7% |
| Dyspepsia | 1% | 5% | 5% |
| Flatulence | 4% | 5% | 4% |
| Nausea | 11% | 8% | 7% |
| Nervous | 16% | 28% | 28% |
| Depression | 3% | 5% | 9% |
| Insomnia | 3% | 6% | 7% |
| Nervousness | 3% | 5% | 1% |
| Respiratory | 24% | 38% | 26% |
| Pharyngitis | 4% | 10% | 2% |
| Respiratory Disorder | 7% | 12% | 7% |
| Rhinitis | 7% | 13% | 9% |
| Sinusitis | 4% | 9% | 9% |
| Skin and Appendages | 8% | 17% | 16% |
| Application Site Reaction* | 2% | 6% | 4% |
| Urogenital | 54% | 63% | 28% |
| Breast Pain | 25% | 31% | 7% |
| Dysmenorrhea | 20% | 21% | 5% |
| Leukorrhea | 5% | 5% | 3% |
| Menstrual Disorder | 6% | 12% | 2% |
| Papanicolaou Smear Suspicious | 8% | 4% | 5% |
| Vaginitis | 6% | 13% | 5% |
| †Represents milligrams of estradiol/NETA delivered daily by each system. *Application site reactions includes localized bleeding, bruising, burning, discomfort, dryness, eczema, edema, erythema, inflammation, irritation, pain, papules, paresthesia, pruritus, rash, skin discoloration, skin pigmentation, swelling, urticaria, and vesicles. |
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Table 2. All Adverse Reactions Regardless of Relationship Reported at a Frequency of Greater than or Equal to 5 percent with CombiPatch
| ENDOMETRIAL HYPERPLASIA STUDIES | |||
| CombiPatch 0.05/0.14 mg per day† |
CombiPatch 0.05/0.25 mg per day† |
Vivelle 0.05 mg per day |
|
| n=325 | n=312 | n=318 | |
| Body as a Whole | 61% | 60% | 59% |
| Abdominal Pain | 12% | 14% | 16% |
| Accidental Injury | 10% | 11% | 8% |
| Asthenia | 10% | 13% | 11% |
| Back Pain | 15% | 14% | 13% |
| Flu Syndrome | 14% | 10% | 7% |
| Headache | 25% | 17% | 21% |
| Infection | 5% | 3% | 3% |
| Pain | 19% | 15% | 13% |
| Digestive | 42% | 32% | 31% |
| Constipation | 2% | 5% | 3% |
| Diarrhea | 14% | 9% | 7% |
| Dyspepsia | 8% | 6% | 5% |
| Flatulence | 7% | 5% | 6% |
| Nausea | 8% | 12% | 11% |
| Tooth Disorder | 6% | 4% | 1% |
| Metabolic and Nutritional Disorders | 12% | 13% | 11% |
| Peripheral Edema | 6% | 6% | 5% |
| Musculoskeletal | 17% | 17% | 15% |
| Arthralgia | 6% | 6% | 5% |
| Nervous | 33% | 30% | 28% |
| Depression | 8% | 9% | 8% |
| Dizziness | 6% | 7% | 5% |
| Insomnia | 8% | 6% | 4% |
| Nervousness | 5% | 6% | 3% |
| Respiratory | 45% | 43% | 40% |
| Bronchitis | 5% | 3% | 4% |
| Pharyngitis | 9% | 9% | 8% |
| Respiratory Disorder | 13% | 9% | 13% |
| Rhinitis | 19% | 22% | 17% |
| Sinusitis | 10% | 12% | 12% |
| Skin and Appendages | 38% | 37% | 31% |
| Acne | 4% | 5% | 4% |
| Application Site Reaction* | 20% | 23% | 17% |
| Rash | 6% | 5% | 3% |
| Urogenital | 71% | 79% | 74% |
| Breast Enlargement | 2% | 7% | 2% |
| Breast Pain | 34% | 48% | 40% |
| Dysmenorrhea | 30% | 31% | 19% |
| Leukorrhea | 10% | 8% | 9% |
| Menorrhagia | 2% | 5% | 9% |
| Menstrual Disorder | 17% | 19% | 14% |
| Vaginal Hemorrhage | 3% | 6% | 12% |
| Vaginitis | 9% | 13% | 13% |
| †Represents milligrams of estradiol/NETA delivered daily by each system. *Application site reactions includes localized bleeding, bruising, burning, discomfort, dryness, eczema, edema, erythema, inflammation, irritation, pain, papules, paresthesia, pruritus, rash, skin discoloration, skin pigmentation, swelling, urticaria, and vesicles. |
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Postmarketing Experience
The following additional adverse reactions have been identified during post-approval use of CombiPatch. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Genitourinary System
Endometrial hyperplasia, endocervical polyp, uterine leiomyomata, fallopian tube cyst, uterine spasms.
Breast
Breast cancer.
Cardiovascular
Hypertension, varicose veins.
Gastrointestinal
Jaundice cholestatic, cholelithiasis, gall bladder disorder, transaminases increased.
Skin
Skin discoloration.
Central Nervous System
Affect lability, libido disorder, migraine, vertigo, paresthesia.
Miscellaneous
Angioedema, hypersensitivity, weight increased.
SRC: NLM .