Estradiol Patch Non-Responder Profile: Who Doesn't Get Relief and Why

How do the patch labels set the dose?

The Climara label says to start at 0.025 mg per day applied once weekly, adjust the dose based on clinical response, and attempt to taper or discontinue at 3- to 6-month intervals [1]. The Vivelle-Dot label says to start at 0.0375 mg per day applied twice weekly for vasomotor symptoms and adjust to clinical response [2].

What can stop a patch from delivering its dose?

For Climara, the labeled application sites are clean, dry skin on the lower abdomen below the navel or upper buttock; the breasts are excluded. The label describes pressing the patch firmly for at least 10 seconds, especially around the edges [1]. If the system lifts, the label describes applying pressure to maintain adhesion; if it falls off, reapplying it to a different location or applying a new system for the remainder of the 7-day interval, with only one system worn at a time [1]. The same label states that swimming, bathing or sauna use has not been studied and may decrease adhesion of the system and the delivery of estradiol [1].

For Vivelle-Dot, the labeled sites are a clean, dry area of the lower abdomen or buttocks, not the breasts [2].

Which medicines can lower estrogen levels?

The drug interaction sections of both patch labels state that estrogens are metabolized partly by CYP3A4, so inducers such as St. John's wort, phenobarbital, carbamazepine and rifampin may reduce plasma concentrations of estrogens, possibly decreasing therapeutic effects or changing the uterine bleeding profile [1][2]. Inhibitors such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations and cause adverse reactions [1][2].

What side effects do the labels report?

In the Climara hot-flush trials, breast pain was reported by 5% of women at 0.025 mg per day, 8% at 0.05 mg per day and 29% at 0.1 mg per day, versus 4% on placebo (placebo n=72) [1]. The most common reactions, at 10% or more, were breast pain, upper respiratory infection, headache, abdominal pain, pain and edema [1]. Application-site reaction appears among Climara's postmarketing reports, which are voluntary and come from a population of uncertain size, so a frequency cannot be reliably estimated [1]. Vivelle-Dot's postmarketing list includes application-site erythema, irritation, burning, discomfort, dryness, edema, papules and vesicles [2].

Do the large hormone trials apply to patches?

The labels' boxed warning notes that only daily oral conjugated estrogens 0.625 mg were studied in the WHI estrogen-alone substudy, so the relevance of those findings to lower doses or other routes of administration is not known [1][2].