A quick question for fellow U.S. readers out there. Has this happened to you recently? You walk out of the doctor’s office with your usual prescription. A quick check to make sure everything is the same. In the middle of the barely-legible-doctor-scribble you make out “testosterone cypionate”, “200”, and “10”. Two refills. Three 10ml bottles should last you 6 months. Everything looks good. You drop it off at the pharmacy, only to hear “wait a minute” as you are walking away. “We can’t fill this”, says the pharmacist. There’s a 28-day rule. We need to switch you to 1mL vials. Here are 4. Come back next month. You’ve been filling the same prescription for years. What gives?
It seems pharmacists are more actively following a rule clarification that came down from the FDA several years ago. It is called the “28-day rule”. It states that any sterile injectable vial must be discarded within 4 weeks after it has been punctured (exposed to air and bacteria) for the first time. Note that some solutions may have longer or shorter shelf lives after first use. Such information must be presented on the product packaging, however. Otherwise, the 28-day rule applies. The healthcare accreditation origination The Join Commission explains the reasoning behind the FDA rule in the following statement.
“Multi-dose vials are to be discarded 28 days after first use unless the manufacturer specifies otherwise (shorter or longer). Manufacturers are only required by law to test the effectiveness of the bacteriostatic agent used in the multi-dose vial for a period of 28 days. Manufacturers are allowed by the FDA to provide extended dating in the package insert if they have conducted testing beyond the 28 days. Multi-dose pens, such as those used to inject medications such as insulin and Byetta, are included.”
Simply put, 4 weeks is the standard threshold that the pharmaceutical companies are required to meet in testing. They can’t guarantee sterility beyond that. The 28-day rule is, likewise, an important safety measure. The use of preservative agents in injectable solutions generally doesn’t protect them from bacterial contamination completely. They slow development, not eliminate it. Bactera can actually grow in these vials just fine, albeit more slowly in comparison to most water-based solutions. Case in point, the most bacteria-laden steroid vial I ever sent to an analytical lab was a vial of oil-based testosterone that had been punctured months earlier but not completely used.
This change is a concern for many U.S. patients. Using these smaller 1mL vials considerably increases the overall cost of medication, especially if paying out of pocket. Typically, we’re seeing the cost of four (4) 1mL vials of testosterone cypionate running about the same as a single 10mL vial. That’s roughly $100 at the pharmacy! Therefore, this switch in prescription can represent an increase in the cost of treatment by 2.5 times, overnight. It also seems there would be little incentive to continue making 10ml vials, as they provide simply too much hormone for the 28-day rule. Granted, using a 10mL vial for 10 weeks is quite a stretch. I wouldn’t argue it is always safe. Still, many have been doing it without issue, and are quite upset at the recent cost increase. It is of note that this rule goes back years. It just seems that lately, some of the pharmacies, particularly some of the larger chains, are being more active at enforcing it.
What has been your experience? Anyone else recently have to switch to 1ml vials?