39. Tetracycline, doxycycline, and minocycline

Doctor Jacob here, and we're talking today about tetracycline, doxycycline and minocycline. These are all members of the tetracycline family of antibiotics, and tetracycline was the first of them to be used. They've been around for decades and decades and they're relatively safe, but with some exceptions.

Let's start historically with tetracycline. This is a drug which used to be the go-to treatment for acne. Pretty safe, some issues with sun sensitivity, but recently the drug was off the market, it was very hard to get, and now it's very expensive to get because for some reason the price has gone up - very, very confusing to me, but it needs to be taken four times a day for the treatment of acne, so it basically has fallen out of favor. It's been replaced with extended release versions of doxycycline or minocycline, or even just plain old doxy and minocycline. They're just better drugs for the treatment of acne, more convenient, so tetracycline is essentially out.

Like all the tetracycline family, tetracycline does have anti-microbial activity within the anaerobic spectrum, so it can cause the side effects of loose stool, yeast infection and with prolonged courses of it can increase the risk of inflammatory bowel disease, just like any of the tetracycline antibiotics.

But let's move on and talk about doxycycline, which is the most popular antibiotic in use for the treatment of acne, that and minocycline. Doxycycline, as you may guess, is an antibiotic in the tetracycline family. It's pretty effective for the treatment of acne, and it comes in several dosing forms. It's usually taken with meals and it's really, really not safe for pregnant women or women who are trying to conceive, or women who are breastfeeding.

It's really good at treating the red, pus-filled pimples of acne, but it doesn't quite get the deep acne cysts to the same degree as for example Accutane will. It certainly won't treat clogged pores, such as blackheads or whiteheads.

Let's talk a little bit about potential side effects. They kind of fall into two categories: those associated with taking the drug by mouth or swallowing it, such as nausea, irritation of the swallow tube or the esophagus, heart burn and even potentially vomiting. The second category of potential side effects with this drug involves the drug circulating throughout the body. Loose stools can result, as can yeast infection in women. Easy sunburning can occur as the drug is in the skin. It photosensitizes the skin to sunburning at a lower dose of ultraviolet energy.

Taking doxycycline with meals helps prevent the side effects in the first category, while taking the sub-antimicrobial doses helps to minimize the chances of experiencing those side effects in the second category. We've talked a bit about sub-antimicrobial dosing in the previous episode, but just as a reminder, high dose doxycycline or full dose doxycycline inhibits growth of bacteria, whereas at the sub-antimicrobial doses you have an anti-inflammatory action without actually killing the bacteria.

I generally prefer to use sub-antimicrobial dosing whenever possible. There is a trade name drug called Oracea, a 40 mg capsule of doxycycline combining 30 mg immediate release with 10 mg delayed release. It's now generic, 40 mg doxycycline, and while it is FDA-approved to treat rosacea, it's also pretty effective for the treatment of acne in my experience, or at least for the maintenance of clearance in patients with somewhat refractory acne. You don't have the issues with loose stools and yeast infection, and also nausea, heartburn and stomach upset are rarely seen.

Sometimes easy sunburning can still happen though, but it typically happens less often than at the full dose. Of course, an intangible benefit to the use of sub-antimicrobial dosing is that it really decreases the chance of antibacterial resistance in the community.

There are some other things that you should know about doxycycline. If you take a lot of vitamins that contain calcium and magnesium, such as in certain antiacids or certain vitamin supplements or mineral supplements, it can impair your absorption of doxycycline. So don't take it with [unintelligible 00:05:00] and I don't recommend taking it with milk, because you just won't absorb the doxycycline as well.

As a reminder, doxycycline is not safe for those who are pregnant, conceiving or breastfeeding. For those who have kidney disease, doxycycline is safe because it's mostly excreted in the stool. For those with advanced liver disease, I would prefer a different antibiotic.

Children who are under eight years old should not take doxycycline or any other tetracycline because this could impair the formation of healthy teeth. That's pretty much it for doxycycline.

Now let's talk about minocycline, the cousin of doxycycline. Minocycline is one of the stronger antibiotics used in the treatment of acne. Like all members of the tetracycline family, minocycline treats the red pimples of acne, but it doesn't really improve the clogged pores, such as blackheads or whiteheads.

It comes in a couple different strengths, as well as in extended release formulation, just as doxycycline does. It's more effective, in my view, than doxycycline because it penetrates into the lipid layers of the skin and into the pores better. So it gets a little bit better into the target of the oil glands where the bacteria are, and where the inflammation is.

There haven't been any head-to-head studies with doxycycline, but that's based on the experience that I've had, as well as the general consensus amongst many dermatologists. However, even though it's a little bit more effective, I typically don't recommend minocycline first line, I recommend doxycycline because of safety concerns. There are some rare, but potentially devastating side effects which can happen with minocycline, which simply do not occur with doxycycline, which is a much safer drug.

I do consider prescribing minocycline for patients with refractory acne, for patients with very easy sunburning with doxycycline, and for patients who have other acne-related conditions such as hidradenitis suppurativa, which is deep boils in the underarms and groins, or dissecting cellulitis of the scalp, which is a related problem where there are deep boils on the scalp.

Let's talk now about some of the side effects that minocycline can have. Most of the time, patients do really well with this drug, but sometimes, maybe less than 10% of the time, patients taking the immediate release formulation - the generic Minocycline - can experience some dizziness, which medically speaking is called vertigo. It's the sensation that the room is spinning when it actually is not. Of the patients that experience this vertigo, some become nauseous and may even vomit. As I mentioned, this side effect can be mitigated with the delayed release formulation of the drug. It happens because of minocycline's effect on the vestibular system, which controls our balance.

As with any antibiotic, women may develop a yeast infection, especially at higher doses. Additionally, diarrhea or loose stools can occur, and can be mitigated by eating either yogurt or taking a probiotic supplement.

There is a type of pigmentation which is blue and gray in color, which can occur on the skin, particularly at the forearms and the shins, or other areas where there are scars. This type of coloration can even involve the tongue, gums and teeth and the whites of the eyes and the beds of the nails. It happens when minocycline is taken for long, long, long courses, typically with over one year of use, though rarely it can be seen with shorter durations.

All these side effects are dose-dependent, which means that if you take a low dose, your chances of developing them are quite reduced. If you visit our website, I can show you on the treatment page of minocycline a patient who's been taking it for over 20 years, who has blue-colored sclera, meaning the whites of the eyes have turned blue, and the nail beds have turned to night sky blue color.

For most acne patients we're talking about short courses of this drug, so that's really not relevant.

These are all relatively non-serious or minor side effects, but the reason I don't prescribe minocycline so frequently are rare, but potentially devastating serious side effects. Unfortunately, these can and do occur.

There is a type of allergic reaction called drug hypersensitivity syndrome, also know as DRESS syndrome, which stands for Drug Rash with Eosinophilia and Systemic Symptoms. This is not something you want to get. Patients typically have a rash with facial swelling, fever and feel very ill and seek medical attention. It's a severe reaction that can damage the internal organs, such as the liver. Hospitalization is generally required. Rarely, if the drug is not stopped and if appropriate treatment is not given, liver damage can potentially be irreversible.

Also, minocycline can cause another issue called pseudotumor cerebri. This is an issue in which there is an increase of pressure inside the head, which presents as a severe headache. This generally would require emergency treatment. It's more likely to occur in heavyset individuals and particularly women, and patients taking concomitant birth control pills are particularly at risk.

Also, like with all tetracycline-type antibiotics, the use of full dose, full antimicrobial dose can raise the risk of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease.

So that's pretty much why I tend to shy away from giving minocycline as my initial prescription. As with all tetracyclines, minocycline is not safe for pregnant, conceiving or breastfeeding women, and children under the age of eight years should not take minocycline because it can impair the formation of healthy teeth.

Minocycline can be taken with food, including a wide variety of dairy products. It does not have the same issues that tetracycline has with absorption. Minocycline is excreted by the kidney, and people with bad kidneys, with chronic kidney disease must lower their dose.

I know it's a long episode today, where we talked about tetracycline, doxycycline and minocycline. In summary, tetracycline is seldom used for acne any longer, whereas doxycycline is a go-to drug because of its relative safety, as well as its effectiveness. Minocycline is reserved for more severe cases because of potential, rare but serious adverse effects that can occur.

I'm Doctor Jacob, we'll see you next time.