Narrator - Dr. Abel  00:00
Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. This podcast is

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provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy.

Narrator - Dr. Abel  00:17
This podcast contains general information for educational purposes only. This is not professional advice, and should not be used in lieu of obtaining advice from a qualified health care provider.

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And now on to the show.

Unknown Speaker  00:31
Welcome to HelixTalk episode 176 I'm your co host, Dr. Kane,

Dr. Khyati Patel  00:35
and I'm Dr. Patel. And once again, this is a part two episode of our episode 175 where we discussed hormonal harmony, a pharmacist guide to hormonal contraceptives, and we had Dr. Danielle Candelario as well as Dr. Nick super with us. So welcome back, both of you, and we're going to pick up right where we left off.

Dr. Sean Kane  00:57
So where we left off in part one was we were kind of summarizing combined oral contraceptives, and it seems kind of logical to go through a couple other dosage forms that are available that are not oral, but still contain estrogen and a progestin. The next one on our list here is the vaginal ring. Dr. Candelario, how is this available? And what does a healthcare provider need to know about the vaginal ring?

Speaker 1  01:19
So the vaginal ring is currently available on the market as one branded name NuvaRing. It's a combination of etonogestrel and ethinyl estradiol at 120 micrograms and 15 micrograms respectively. This looks like a little flexible ring. It actually fits in the palm of your hand. It's kind of like a small, thin, translucent ring, and it's to be inserted into the vaginal canal. It doesn't need to be removed for sexual intercourse, which is which is nice, but most partners and patients may actually describe a foreign body sensation, so it can actually and may be felt during sexual intercourse. But unlike intrauterine devices, which we'll talk about, placement can be done at home, which is nice. So the patient themselves inserts the NuvaRing at home, it's inserted on day one of the cycle, and then it's left in for three weeks, and then it's removed for one week. So I always talk to my patients about marking this on a calendar, or marking this and some type of alarm system, something that will alert them to making sure that they're removing the ring after three weeks and then having a hormone free week, which then allows for menstruation. And it's important to counsel patients on inserting the new ring on the same day every week. So talking to your patient about is a Sunday initiation most appropriate for them versus maybe Wednesday and what looks best for them based on their schedule or personal preferences?

Dr. Sean Kane  02:52
We can't not talk about one of the best warnings in a package insert for Nuva ring, and the title of this in the package insert is inadvertent urinary bladder insertion. And this you can't make up, folks, this is where patients, clearly that were not well educated on the placement of the product actually inadvertently inserted it into the urinary bladder, as opposed to in the vaginal canal. So it is important that patients understand how this product is inserted and where it's inserted in the body.

Speaker 1  03:22
Anatomically, I can see how that would possibly happen, right? So you need to make sure that patients understand that if they're having to force the Nuva ring in, that they probably maybe need to just remove the ring and reinsert they shouldn't have to force or use any additional effort to insert the NuvaRing, it should go in pretty easily.

Dr. Khyati Patel  03:44
So as the generic combination comes from both estrogen and progesterone, we're going to probably experience a similar type of side effects, the headache, the nausea, the breast tenderness, are little bit less than our oral combined contraceptives. As Dr. Candelario, you mentioned, there is that feeling of foreign body while having sexual intercourse, and then just one thing Additionally I noticed was decreased libido, which was also interesting. But as far as the efficacy is concerned, it works very similar to COC, Dr. super

Dr. Sean Kane  04:16
in terms of a missed dose. This feels different, because the patient the only way they're going to miss a dose is either if they don't insert it on the time that they're supposed to or if it falls out. So what are some of the instructions related to those two scenarios?

Speaker 2  04:30
So basically, what you're going to do is, regardless, you can use backup for a week, you know, with a barrier contraceptive, if the ring falls on, is out for more than three hours, or if they forget to insert that new ring at the start of the cycle. Likewise, if they're starting it on a day other than day one of their cycle, you want to use backup for a week. So golden rules. If you're in doubt with this, if you're not sure how long it was out for a week of backup with condoms, diaphragms, barriers, whatever type. Okay.

Speaker 1  05:00
Patient should also be reminded to rinse the ring. So if the ring does fall out and they're going to reinsert it, within that three hour window, they should be reminded to rinse the ring and then reinsert.

Dr. Sean Kane  05:09
And I could actually see that not being intuitive, because a patient may think that they're washing off some of the drug or something like that. So that is a really important counseling point, kind of moving on to a different route of administration. We also have a transdermal patch, Dr. super. What can you tell us about

Speaker 2  05:24
this one? So the patch is available in a single brand name now in Zulan, previously called Ortho Evra, and it's got 150 mics a day of norelgestromin, which is an older progestin, and 35 mics a day of ethinyl estradiol, so pretty high dose of estrogen there. So this is a pretty small patch, like size, like a large coin that the patient can apply to the buttocks, abdomen, upper torso or their upper arm. And as far as the timing goes, it's the same as with the with the ring. So you place at the start of the cycle, and then weekly for the same day for three weeks, and then one week patch free at the end of the cycle. The biggest thing we see with this is with that increased ethanol, estradiol dose, an increase in breast tenderness and potential increase for any estrogen related side effects that we reviewed earlier. But it does allow like throwing that improved level of adherence just applying it once a week, if you have a patient who can set reminders or find some way of staying steady with that day of the week. And that's really the big barrier with this one is is missing that correct day of application. One kind of unique thing you want to mention here with this medic with this patch, is also with that increased estrogen dose. You want to be especially careful in patients who are a little older and who smoke. You know those warnings in general for estrogen use. We want to be very careful in those patients with this and do avoid it, and those patients were over 35 or those who smoke and as well as those who are obese, because there is some data to suggest that you get lower drug levels of this patch in obese patients, and the BMI cut off used at this point is 30 kilograms per meter square for BMI. So another thing to keep in mind with the patch here.

Dr. Khyati Patel  07:00
So, Dr, Super, thank you for explaining. You know, the population, you probably should be careful using this particular formulation in but then, why would we use this over the combined oral version of contraceptives?

Speaker 2  07:14
The big reason I've seen in practice is just convenience. You know, there are a lot of patients out there that struggle with daily compliance, and particularly patients who are busy. You know, we're talking about younger women who may have families, to juggle, jobs to juggle. It's really hard to get that pill in every day. Or as a patch, you put it on the calendar every Monday I'm putting this patch on it's much easier. As well as I have found that people tend to have fewer side effects with the patch. Now that seems counterintuitive, with the higher estradiol levels, it might be related to progestin side effects that they have less of, but overall, patients tend to tolerate it pretty well, and it's a convenience aspect, I would say,

Dr. Khyati Patel  07:52
Dr. Candelario, you're going to explain so patches, you know, like there are other medication that come in Patch I have CGM sensors. People complain about falling off, like, what do we do if you know if a missed dose occurs with patch?

Speaker 1  08:07
So if the patch falls off, the patient should just reapply a new patch and then use backup for seven days. These patches don't fall off, or we don't have as many reports of the patches falling off as some of the other hormonal patches that we see on the market that are used for other indications, but it has been known that patches do fall off, so make sure that your patients are applying the patch correctly to a dry, clean area, and perhaps even applying pressure to the patch for about, you know, 10 to 20 seconds to help with increasing the adhesive. But if they again, if the patch falls off, just have them reapply a new patch and use backup for seven days.

Dr. Khyati Patel  08:43
That sounds good. And I think, as we described earlier, these two formulation just provide additional options if patients don't want to consider oral version of the combined homo contraceptives. But then again, like, we compare and contrast with the oral how do they compare to each other, like, do we see more people going with vaginal ring versus the patch? What is that difference that we make? US elections for the

Speaker 2  09:09
difference in these between these two. So they're both super convenient options once a week. They have the advantage of convenience and simplicity in some ways, but the difference is that estrogen dose. So the Zulan patch has a fairly high dose of estrogen versus the ring, which has a quite low dose of estrogen. So you care, you have with that a decreased risk of side effects, estrogen related side effects, so breast tenderness, as well, as you know, the thromboembolic concerns with the ring, you have lower risks compared to the patch based on the estrogen dose. And you also may favor that ring in patients who are maybe at a higher cardiovascular risk or have some remote history of a thromboembolic event that was, say, provoked so, patients who are a little bit higher risk for those estrogen side effects and concerns, you would lean towards the ring over the patch overall. That's that's the main determining factor in choosing between these two. Because, can we. Means wise, they're the same. Someone may not like the invasiveness of the brain as much as the patch, which is just applied to the skin, but I have not seen the application of the ring be a major concern in practice, since it is pretty simple, perfect.

Dr. Sean Kane  10:12
So why don't we go ahead and transition away from our estrogen and progestin combination products, just to our progestin only pills in this case. So plps are progestin only pills, and we have a couple of these on the market. We've talked about a variety of progestins already. The difference here is that these don't contain estrogen, so it's only progestin Why would we do that? Dr. kindelario, what is the logic of not having that estrogen? What are the kind of benefits and then downsides of not having that

Speaker 1  10:42
well, we know inherently that estrogen can increase the risk of VTE or thrombolic disorder, and so one of the main reasons we may use a progestin only pill is for a patient who has a risk of VTE or who may be at a high risk for vte, including those who are over The age of 35 and who smoke, so combining those two can put a patient at higher risk for VTE. So progestin only pills are a great option in those patients. The other area in which we often see progestin only pills recommended or prescribed for a patient is breastfeeding, so estrogen can decrease the breast milk supply. And therefore, if you're starting a contraception postpartum, usually at that six week mark, you're going to consider progestin only if the mother is breastfeeding.

Dr. Khyati Patel  11:35
Are there any downside to picking progestin only option

Speaker 1  11:41
in terms of ADRs, which we've already kind of discussed, and how to manage those, I think it's the timing for progestin only pills. In terms of when the contraception is taken, we had talked about missed dosings For combined oral contraceptives in the previous episode, but here we have a slightly smaller room for error. Generally, what they would consider about three hours progestin really impacts the cervical mucose thickening, so preventing the sperm entry, and that effect can wear off quickly. Therefore, if the patient misses a dose more than three hours from their typical timing, that's considered a true missed dose, and therefore the misdosing instructions are a little bit different than what we would see with the CoCs. So Dr

Dr. Khyati Patel  12:30
super what would you do in the case where patient did miss a dose? Practically, what do you do in the clinic?

Speaker 2  12:37
So as Dr. Candelaria alluded to, if it's past three hours since that dose was due, we counted as a missed dose. So at that point, the patient needs to take the medication right away. As soon, whatever time it is that the patient realizes they are late on the dose or missed the dose, they need to take it right away. And if it happens to be, let's say the next day, if it's you know, they take their medication at 8am and it's 8am the next day, they realize I missed my dose yesterday. They should take two pills at once, so yesterday's dose and today's dose at the same time. And they also should use a backup method of a barrier contraception for at least until they've taken the pill on schedule two days in a row. And likewise, with all these patients, we also should discuss emergency contraception as well, and they should consider that really, if they've had any unprotected sex in that period of time of two days after missing that dose or being laid on that dose. And for all my patients who take pops, I always encourage and offer emergency contraception as often as possible, because it is such a quick warehouse time with these medications. And I

Dr. Sean Kane  13:37
think it's worth mentioning just the difference between what you just described Dr. super, and then the missed dose instructions and the lack of a need for backup barrier methods for the combined oral contraceptives if a single dose is missed. So could you just remind the audience how what you just mentioned differs from the combined oral contraceptives?

Speaker 2  13:57
The main thing we talked about with CoCs and missing doses is you have that 48 hour window. So you have the 48 hour window in which you're pretty much free. You know, if you miss a dose, it's okay with that 48 hours to be late, but if you miss more than two doses, if you're more than 48 hours late, that's when it gets more complicated, and it varies product to product. And if you're past that 48 hour limit, you need to use the backup. But within that 48 hour limit, you don't need to worry about the backup at all. And emergency contraception here is also worth discussing, but not nearly as vital as progestin only pills because it's such a short window.

Dr. Sean Kane  14:29
So then there are some pretty clear advantages disadvantages specific patient populations that maybe a progestin only pill would be more appropriate in. What are some of the formulations that are available, both as prescription and then kind of exciting and a new over the counter product as well. Dr. C, Can you fill us in on some of the progestin only formulations, both prescription and OTC prescription?

Speaker 1  14:50
You may be familiar with some brand names like micro noir or Provera. Those are typically the pops that you're going to see on the market. Obviously, most of them are available. Generic at this point, and then most recently, the FDA did approve an over the counter or non prescription progestin only pill by the brand name of opil. This is nordgestrol, 0.075 milligrams. This should be available on the market, according to the manufacturer's website, by early first quarter 2024 right now we don't know what the price is going to be. The company has said that it may be anywhere upwards of $30 or so, but they haven't finalized that pricing, so we're yet to see what that actually will be.

Dr. Khyati Patel  15:39
Interestingly enough, when I was looking at, you know, the manufacturer's website has a little study piece, and they did adherence study, apparently, for their patient population, and they said that 95% of the patients were adherent to the regimen. And out of those, upwards of 85% of the patients actually they followed the barrier method for two days, following one single missed dose. So apparently the concern was that without instructions and provider input, people might not be able to understand the gravity of that shorter window that they have available for pops. But the this little study says the patients did good on their own,

Speaker 1  16:19
and I think certainly the FDA was going to approve a non prescription over the counter product, one with just progestin is probably where you would want to be. Considering all the things that we've talked about when you include the estrogen component, patients who may be contraindicated in taking it, drug interactions, those kind of things are really limited when you're just talking about a Protestant only pill. So the where we place this as OTC or non prescription, in terms of, will it be located behind the pharmacy or in front of the pharmacy, will probably be up, logistically to the individual companies. We're not sure right now if it will be covered by insurance as an OTC product. So still, a lot of things to kind of sort out as we move into 2024 to see how this will land and what what it will look like in the non prescription space.

Dr. Sean Kane  17:09
So just like our combined oral contraceptives, where we had a variety of other non oral dosage forms, progestins are the same way, we have a couple different dosage forms that we're going to chat about. One that I was familiar with prior to kind of research in this episode, is the injectable progestin, Depo Provera. Dr. super. Can you tell us a little bit more about this one, and your experience, how often you see it, kind of pros and cons of the injectable progestins.

Speaker 2  17:34
This was historically a pretty popular option. We know it. Brand name wise, has depo provera and it's Petrovsky progesterone, 150 milligrams. It's given as I am, every 12 weeks, so once every three months. There's also a subcutaneous formulation, typically is given in clinic, but can be given at home for an appropriately trained patient in the VA we use the im formulation and give it quarterly. And this is one that, though, in recent years, has fallen a bit out of favor for a variety of reasons, in part, because there's such a wide variety of Protestant only formulations now, and so one of the principal advantages of this formulation is it is progestin only, so you avoid all those estrogen related risks and side effects. And there's the advantage of convenience, you know, come in once a quarter to your doctor's office, get your shot, and you don't need to worry about anything in the meantime. And there's also the fact that it can be used to treat abnormal uterine bleeding. So patients who have unexplained uterine bleeding, they can use medroxyprogesterone quite effectively, and it has a role as an adjunctive or palliative treatment in endometrial carcinoma. One of the things that can be a benefit or a kind of drawback on this medication, depending on your patient, is that about half of patients end up with amenorrhea, so they stop having periods after about a year on this medication. So that think that historically, was something the patients did kind of like, but varies patient to patient. Of course, what's kind of taken away from this medication's popularity in recent years is the kind of growing understanding of the side effect profile, pretty common, weight gain, fluid retention, which are common progestin side effects, but we do see quite a bit of it, as well as some bleeding abnormalities, and one that's drawn a lot of attention, rightfully so, I would say, is a risk of decreased bone density, bone mass, and this has been observed consistently, but has not been correlated with an increased fracture risk. So in light of the decreased bone mineral density, with this agent, though, it's recommended not use it beyond two years, and we should avoid it in patients who are otherwise at higher risk of fractures or osteoporosis, so say those who use chronic prednisone, or those with a history of fractures, those with RA or thyroid disorders. And one thing to keep in mind with this one is, if you have a patient who's a patient who's on depo provera for those two years, let's say, on average, their cycles will take six months to return after stopping the injections. So that's that's a bit longer than than most formulations. So something to keep in mind there with this one, but overall, I would say it's falling a bit. Out of favor in recent years.

Dr. Khyati Patel  20:02
Dr. Candelario a quick input on what do we do if you know, patient missed the appointment right and didn't come or missed their dose at home they were giving sub q at home, how do we make up the dose?

Speaker 1  20:15
So if the patient has missed their dose and it's been two weeks, so if they're two weeks later than when they were supposed to receive the injection, then you're want to confirm with a negative pregnancy test. If the pregnancy test is negative, then you're going to want to give the dose and have the patient use backup for seven days. And this may be a reason why you would want to start a patient on injectable progestins, meaning that they have to come back to the office to receive it right, particularly possibly with the im or the sub q, which may increase adherence in some patients if they get that reminder that they have an appointment scheduled for next weeks for their injection. For some patients, they like to have that provider contact every 12 weeks or 13 weeks. And so it may improve their adherence if we're administering the injection for them. So a very important example of a contraception that we can give in the office, although it is encouraged now that patients, if they are appropriate, can do it at home, but it can be something that we can keep track of for them, and it may increase their adherence if they're amenable or agreeable to it,

Dr. Khyati Patel  21:22
yeah, along the same topics of improved adherence, because, you know, it's something that's administered by a healthcare provider, we are right along the course to move on and talk about hormonal intrauterine devices, we call it IUDs, that are also progestin only. And obviously these are placed at the doctor's office, and so Dr. Kinder Lario again, what? What is the generic and the brand that are available? And if you can kind of walk us through, why do we use them?

Speaker 1  21:52
So as you mentioned, these are placed at the provider office, and we can talk about, certainly, what that process is like, what it looks like, and what is the experience of a female going through that? But there's several on the market. They're all progestin only, typically levonorgestrel, and they're they vary based on the duration in which they can remain in the body. And this you may decide to use one over the other, depending on the female and their long term goals, or goals of when they would like to start a family or not, and what that timeframe may be. So the different types of hormonal intrauterine devices range anywhere from three years to up to eight years, so depending on where they are, and there is one for five right in the middle, but the brand names that you may have heard of are things like kylena, liletta, Morena and Skyla, again, with all of them having different durations of time for the amount of placements that they can have, these are typically placed in the office by the healthcare provider. Implantation can be uncomfortable for the woman. They will usually feel some type of cramping or pain when they're grading getting the IUD placed, and the pain can be worse for some more than others, but luckily, it usually only lasts for about a minute or two. IUDs are really nice because we get an instant return to fertility upon cessation of use, which is really attractive for some women who may have put off family for some time, they know that once the IUD is removed, that fertility will return quite immediately, which is not the same case with some of the other medications. And because it is implanted and you you have very limited chance of manipulation or changing or missing doses, it has a very high efficacy, and again, it's good for that long term planning in terms of ADRs, we do get some vaginal inflammation and some abdominal pain, but more importantly, what we hear the most from our patients is bleeding pattern alteration. So in the first three to six months, you'll actually get perhaps some heavy menstrual bleeding, which is less than if you did a copper IUD but but still, something for patients to be aware of, that menstrual bleeding may be increased compared to their kind of usual menstrual flow.

Speaker 2  24:15
On the theme of, you know, things happening kind of early on in the IUD lifespan is the risk of inflammation, vaginal or public inflammatory disease is the highest in the first month or so after insertion. So after that first month or so, someone hasn't had inflammation, they're on that they develop it thereafter. But also, in fact, like over time, you're less worried about all adverse effects, because these agents all have a decreasing dose of progestin over time. They're all tapering over time, so you do have a decreasing risk of progestin related side effects, although that carries with it the risk of over time and return of sort of irregular bleeding patterns. You know, because you have a lower dose of progestin, as we talked about earlier, with that lower dose of progestin, you may have an increased rate of late cycle bleeding. So you can see that. Last time goes on, not terribly likely, but it can happen with these tapering doses.

Dr. Sean Kane  25:06
So then moving on to our final progestin only dosage form. We have our subdermal implants. Nextplanon is the brand name for this Dr. super. Can you tell us a little bit more about this in terms of how it's given? Any pros and cons of this dosage form versus, let's say, the injectable that seems somewhat similar to it. Yeah.

Speaker 2  25:25
So the next one on is the etonogestrel. So it's also an older progestin, 68 milligrams, and it's inserted into the upper arm in the provider's office, and it requires local anesthesia to insert. And the duration for this medication is about three years. So otherwise, efficacy wise, it's similar to IUDs, and it's got the same, you know, more or less same convenience aspect, although it's more invasive, you know, you do have to have considered under the skin, and it tends to lead to some irregular bleeding for that first year, as Dr. Candelaria mentioned with IUDs, this one tends to have a little bit longer period of, say, irregular bleeding issues at six to 12 months, as well as a tendency towards longer and heavier periods or spotting, and an increase in one progestin related side effect we've mentioned many times with weight gain, fluid retention. We do see more of that with it, with the implant than with the IUDs. This is also extremely effective. Like the IUD is 98 99% plus effective, and can be used during breastfeeding. And like IUDs, also, once that duration of three years is over, you have a very rapid return to fertility. So on top of the avoidance of estrogen side effects, lots of advantages to this one, outside of the fact that it's got an invasive administration procedure.

Dr. Sean Kane  26:44
So Dr. Candelario, in terms of size, we had mentioned with Nuva ring that, you know, there's a foreign body feeling associated with it. How large would a typical IUD be? Or even these next plan on implants, you know, is it big enough that a patient would potentially feel it? Can you give us some sense of size here?

Speaker 1  27:05
So the IUDs are T shaped, kind of plastic insertions, and they're about the size of a quarter. And a subdermal implant is about the size of possibly, like a match stick, and only about two millimeters thick. And like Dr. super said, it's placed under the skin, and most patients will not feel the implants or the IUDs. But I have had patients tell me that they feel like they have them in, or they know that they're in and do report foreign body sensation. So typically, most of your patients will not feel it. But I have had patients who have reported increased pain upon insertion and have reported actually feeling them. But most of your patients will not.

Dr. Khyati Patel  27:49
I think there was an excellent summary of our combined hormonal contraceptives as well as progestin only contraceptives kind of taking a little different direction. And while we are almost ready to wrap up, the episode is, how do we select the contraceptives? I think both Dr. Candelario and Dr. super you mentioned there's a lot of things to consider, even some lab work or, you know, Screening Questionnaire that needs to be done. I remember seeing those very complicated tables that CDC puts out as part of their US MediCal eligibility criteria. What is that criteria, and what are some of the other considerations to have when we are selecting the right product, the right formulation for the patient?

Speaker 2  28:33
Okay, so that big table you're referring to is, it is an eyesore. It's so full of information, but it's briefly, it's, it's abbreviated as the MEC. So the CDC developed this table, this system called the MediCal eligibility criteria for contraceptive use. So this was in response to, you know, just kind of the general confusion over who can and can't use contraceptives and which kinds. So the MEC system has four basic ratings for for a condition with relation to use of hormonal contraceptives. So they're increasing levels of risk. So risk one is the lowest risk. So MEC one is a condition for which there's no restriction, no concerns with using hormonal contraceptions. MEC two is for one where there are some concerns about the advantages will outweigh the drawbacks. Whereas MEC three is really when you get into the situation where the risks tend to outweigh the benefits, but not absolutely, and then category four is where the risks of using hormonal contraception absolutely unequivocally outweigh the advantages of using it. So this is kind of quick and easy way to think about it, as far as there's increasing levels of risk for various conditions, and most things in medicine, again, are gray. But there are some conditions which we want to be really careful, really cautious with the use of these contraceptives.

Speaker 1  29:52
The MEC categories are nicely laid out within these tables, and they're color coordinated. But just to be clear, the. VC categories don't necessarily imply that the method is the best choice for that patient. There are other factors, such as effectiveness, availability and acceptability, that may play a key role in determining the most appropriate choice for your patient.

Dr. Khyati Patel  30:15
That is very important to also consider, because sometimes you get bogged down with the tables and no not know how to interpret them. So that that that is important, going back to some of the comorbidities and the risks that you mentioned as part of explaining four different levels of categories, Dr. super, can you tell us, what are some of those conditions that we're keeping in mind? What are some of those factors that we are keeping in mind as the risks?

Speaker 2  30:41
So in general, the risks that would the risks or the pre existing conditions that would drive us towards using great caution or even avoiding hormonal contraceptives in a patient, are things that are associated with either an increased cardiovascular risk or an increased risk of estrogen dependent tumors. So we're thinking of smoking older age, which is 35 or older by these definitions, but depending on who you are, I mean, I consider that to be older, but nonetheless, 35 and older history of hypertension, hyperlipidemia, patients who are obese and then getting back to the thromboembolic risk we've mentioned several times, patients with a history of PE or DVT, as Well as those with a history of atherosclerotic events, patients who have had a history of breast cancer or a strong family history of breast cancer as well. You want to be very cautious and talk at length with these patients about those risks. And in most cases, you're going to avoid this the hormonal contraceptives in those patients. And one that has come up more and more in recent years is the issue of migraine. So patients who have migraine with aura are considered have a contraindication using combined oral contraceptives, because they'll have they've been found to have an increased risk of stroke, a significantly increased risk of stroke when receiving estrogen containing contraceptives. So those patients should not, under any circumstances, receive a contraceptive with estrogen in it, so no CoCs in those patients migraine without aura is a much grayer area.

Dr. Sean Kane  32:03
And then, just to clarify, are progestin only contraceptives Okay, or is it still of concern in that patient population?

Speaker 1  32:13
The CDC, per the MEC eligibility criteria, indicates that progestin only contraceptives, for patients with migraine with or without, Aura can use progestin only contraceptives.

Dr. Sean Kane  32:24
And I think just as a good clinical Pearl, good take home point, we do see estrogen contain oral contraceptives having this increased risk of thromboembolism, and in general, with the progestins, we don't see it nearly as much, if at all, depending on the type of progestin that you're looking at,

Dr. Khyati Patel  32:42
yeah, and I think the elaboration on migraine is great, because that comes across very often. A couple other things that we look for as the risk is, you know, patients postpartum status, as we talked about earlier, and then patients with HIV and on our on antiretroviral therapy, and that's mainly because of the risk of interaction, and that lands us to the very last section of this two part episode. How do we deal with drug interactions? Right? It's bread and butter of pharmacists, and that's that's the kind of questions I come across when it comes to use of or contraceptives for patients in the outpatient arena. So in general, Dr. Candelario, what are some of the drug classes that come to mind that interact the most, or are the concerns when used along with the hormonal contraceptives

Speaker 1  33:29
the MEC, in addition to highlighting some medical conditions for consideration for contraception use, also highlights drug interactions. So this is a really great resource at the end on the second page, you'll notice drug interactions as well, if you need a quick reference. But the top three classes of medications that interact with contraception the most are antiretrovirals, used for the prevention and treatment of HIV, anti convulsant therapies and antibiotic antimicrobial therapies, as well as St John's Wort in general. The concept here is, the lower the door, the dose of hormone, the greater the risk of the drug interaction, which can impact either the effectiveness of the contraception or the effectiveness of the interacting medication.

Dr. Khyati Patel  34:17
So if I were to pick on antibiotics, because you know how many times patients need to go on antibiotics while they are using these type of chronic medications? Do all of them interact? And do we advise patients to consider alternatives, like a backup method, or is there one in particular that has more of a higher risk than the others?

Speaker 1  34:38
I think at one time or another, these interactions were kind of blanketed to all types of antibiotics, antifungals and anti parasitics. But I think the literature has really directed us that this, probably this drug interaction, is more targeted towards rifampin or RIFA, but in therapy with antifungals and broad spectrum antibiotics. Addicts and anti parasitics. There's actually no clinically significant drug interactions. It's considered a category one for the MEC, so no backup method is recommended. Where we start to get into the significant drug interaction is with the rifampin. So although it's not harmful to women, this interaction, it's likely to reduce the effectiveness of the combined hormonal contraception, which could lead to pregnancy if, if that's what it's being used for. So for women who are using contraception, we should potentially encourage them to use a medication that does not interact, which would be a progestin only contraception. Or we could have women switch to an ethinyl estradiol product that has more than 30 micrograms in the formulation, so considering a higher dose of estrogen to kind of overcome that drug interaction.

Speaker 2  35:54
Another thing we can suggest sometimes for patients, let's say, who begin contraception, or come to our office looking for contraception and they have a history of epilepsy or HIV, we might discuss or skew them towards, say, a copper IUD or a progestin only IUD as well. Data so far, I suggested progesterone only IUDs may bypass a lot of these interactions, primarily because they act so locally.

Speaker 1  36:16
And when it comes to any convulsants, really, the ones that we have to be concerned about are Lamotrigine. So there are PK studies that show that Lamotrigine will decrease significantly in patients on combined oral contraceptive use, which is concerning, because we could increase seizure activity. So we really want to be careful when looking at the different types of anticonvulsants and which ones they're on. Lamotrigine reduces its levels in combination. But the other ones, like phenytoin, carbamazepine, barbiturates, all of those are going to reduce the effectiveness of the combined hormonal contraception. So two different types of interactions important to understand. Both. But again here the recommendation, as Dr. super has mentioned, is, let's do a progestin only implant and maybe even consider a copper IUD if that works with the patient's family planning expectations.

Dr. Sean Kane  37:12
And I think, from my perspective, one important take home point is this MEC document contains information about these drug interactions. This is definitely not something that someone's going to memorize. And as Dr. candelara mentioned, sometimes you see unexpected effects of the drug interaction. So sometimes hormone levels will go down when you would have expected them to go up, because you have an enzyme inhibitor, for example, or you wouldn't expect Lamotrigine levels to go down, but they do in response to these oral contraceptives, so it's more complex and something that can just be memorized as a pattern. And that's why the MEC document, which is linked in our show notes, HelixTalk.com could be a really important resource when these types of clinical questions come up, as opposed to using micro medics or up to date or something like that that won't have as much detail as that MEC document,

Dr. Khyati Patel  38:00
yeah, and kind of just last comment about our antiretrovirals that are used for HIV treatment pipeline has burst. I mean, there are lots and lots of agents now, and so I again recommend practitioners to look up that very detailed table that lays out all different types of antiretrovirals, like the NRTI, the NRTIs, the protease inhibitors, the integrase inhibitors, all that stuff. So again, saying that there is this wonderful tool available, and they lay out these drug interactions from category one to category three. For most category one interactions, you know, we're not going to take any action, maybe patient education, but there is no need to take any clinical action. But category three, as Dr. canovario explained earlier with rifampin interaction, you might have to take some interventions, right? You might have to choose a different type of birth control or higher dose, etc. So again, these recommendations are laid out very nicely, and I did want to mention that both of these resources are referenced in our show notes, so you can access the document directly from there.

Dr. Sean Kane  39:08
So I think that wraps up today's in the previous episode as a combined episode, quite nicely. We've covered a ton of topics. Clearly, this is a very complex area, and it really highlights the role of an interprofessional team, including the pharmacist, in terms of patient education, selecting an appropriate product, monitoring for drug interactions, and so much more. Maybe we can kind of wrap up the content we covered today with a couple clinical pearls. For me, one was how important it is with the progestin only pill, the pop to not miss a dose. And you really have this very narrow three hour window, where if you exceed that three hour window, you have to have two days worth of barrier contraception immediately after. And if you miss too many, there are other instructions that you may have to follow.

Dr. Khyati Patel  39:53
And in addition to our general oral either combined or progestin only contraception. Is, I mean, the formulations are vast. You know, if oral contraceptives are not a patient's cup of tea, we have the patches, the vaginal ring, the implants, the IUDs, all sorts of options are available. Again, that's really patient decision making in, you know, conjunction with the healthcare provider and helping them choose the right product.

Speaker 2  40:23
A big takeaway here is that MEC document the MediCal eligibility criteria for use of contraceptives, the increasing scale of risk from one to four that addresses both conditions and interacting medications and the risk they pose as far as affecting contraception use. So as you go from one to four, increasing levels of risk that would steer us away from using a hormonal contraceptive to the point where, in level four, you shouldn't use it at all. And three, you've got to make an intervention of some kind. And then two, you should be having a discussion with the patient about those risks, at least.

Speaker 1  40:56
And I think with all the nuances of all of these formulations and side effects and how to use I think patient follow up is probably the key concept for me, ensuring that you're following up with your patient, you know, three to six months after initiating a contraception and identifying how they're feeling it their comfort with the product, if they're experiencing any adverse effects, And what their experiences are is important to adjusting either their dose or adjusting adjusting the formulation and changing it over to another contraception. But the first selection isn't always the last selection, so being sure that we're staying in touch with our patients and providing them with follow up is important.

Dr. Sean Kane  41:39
I love that. So that wraps up 176 quite nicely. Our two part episode, Dr. Candelario and Dr. super thank you so much for your expertise. I learned an incredible amount over the last two episodes, way more than I would have expected. And I hope for the audience, you appreciate the amount of research, clinical expertise and time that it goes into producing these episodes. So I do appreciate both of your expertise in this episode. So thank you very much.

Dr. Khyati Patel  42:06
And I'm going to say I concur. Thank you so much for your time and expertise.

Unknown Speaker  42:12
Well, thank you both. It's been a pleasure.

Speaker 1  42:14
Yeah, thank you so much for having us. This was great. Lot of fun.

Dr. Sean Kane  42:17
So for the listeners, if you want to see show notes and the references, it's available at HelixTalk.com Again, this is a combo episode of 175 and 176 we're also on iTunes, or wherever you get your podcast, and we love the five star reviews. We have a mailing list, and you can sign up at our website, HelixTalk.com so with that, I'm Dr. Kane.

Dr. Khyati Patel  42:36
I'm Dr. Patel. And again, thank you, Dr. kendelario and Dr. super. And to our audience, study hard.

Narrator - Dr. Abel  42:43
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Narrator - ?  42:54
to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.