Oral antibiotics for acne

Dr, BaldwinDermatologists turn to oral antibiotics for treating acne when topical medications have failed or are too irritating, as well as when the disease is widespread and it becomes too cumbersome to apply creams to all the affected areas.

“Oral antibiotics are also used with severe disease or when isotretinoin or oral contraceptive pills (OCPs) are refused or contraindicated,” Hilary Baldwin, M.D., medical director for the Acne Treatment and Research Center in Morristown, N.J., tells Dermatology Times.  

In an interview following her presentation on oral antibiotics at the American Academy of Dermatology (AAD) Acne Boot Camp in March (Orlando, 2017), Dr. Baldwin says that antibiotic resistance is a major medical challenge according to the Centers for Disease Control and Prevention (CDC).

“In 2013, for example, there were over 2 million illnesses and 23,000 deaths directly attributable to antibiotic resistance,” Dr. Baldwin says. “This is particularly important for acne, as we now believe it to be primarily an inflammatory condition.  As such, we are prescribing antibiotics less for their antibiotic effects than for their anti-inflammatory properties.”

Dr. Baldwin discussed the ongoing debate between the antibiotics doxycycline and minocycline for efficacy and safety.

“Compared to tetracycline, both of these drugs are more lipophilic and enter the sebaceous glands better,” she says. “They are also truly once- or twice-a day medications, and cause less gastrointestinal (GI) distress and phototoxicity than tetracycline.” 

Doxycycline “is not technically FDA approved for the treatment of acne, but rather approved for adjunctive therapy of severe acne,” Dr. Baldwin notes.

The three formulations for doxycycline are standard (100 to 200 mg/day); delayed-release, enteric-coated (75 to 200 mg/day), which was intended to reduce the incidence of GI upset; and a newer, modified polymer-coated tablet for even further delayed release (120 mg/day), which reduces the absorption in the stomach by roughly 15%.

All forms of doxycycline should be taken with 8 ounces of water and the patient should be told to stay upright for at least 30 minutes to prevent pill esophagitis.

“The No 1 side effect of doxycycline is GI upset, but this can be reduced by using the delayed-release formulations, or by switching from doxycycline hyclate to doxycycline monohydrate, which causes less GI distress,” Dr. Baldwin conveys. 

Doxycycline can also cause phototoxicity, especially when prescribing over 100 mg/day. “Therefore, patients need to be advised to be cautious with sun protection,” Dr. Baldwin says. “Conversely, phototoxicity is virtually negligible with minocycline.”

Other side effects from doxycycline are quite rare, including pseudotumor cerebri and drug hypersensitivity.

Minocycline, on the other hand, is available in two formulations: immediate release (100 to 200 mg/day) and extended release (weight-based at 1 mg/kg/day).

“The extended-release formulation is the only acne antibiotic that has gone through rigorous FDA trials,” Dr. Baldwin notes. Dose-ranging studies have been performed and the drug tested as a once-a-day therapy.

Minocycline is also highly lipophilic and has many anti-inflammatory effects.

Moreover, minocycline has been reported to have a lower incidence of antibiotic resistance compared to doxycycline and can be consumed with dairy products “ Additionally, stomach contents do not affect the bioavailability of the drug,” Dr. Baldwin says.

Vestibular side effects from minocycline are the most common side effects of immediate-release minocycline but “are less common with the extended-release formulation,” Dr. Baldwin says.

Although rare, minocycline is more likely to cause drug-induced lupus-like eruptions and drug hypersensitivity than doxycycline. “Drug hypersensitivity can result in serious consequences, including hepatitis, pneumonitis, and even death,” Dr. Baldwin states.

There is also the possibility of minocycline-induced hyperpigmentation, which manifests in three forms: dark pigmentation deposited in the base of pitted acne scars; a widespread hyperpigmentation; or dark macules, typically on the lower legs.  “Fortunately, this side effect is late-onset, requiring several years and high cumulative dose,” Dr. Baldwin says.

As to which is the more efficacious drug -- doxycycline or minocycline – “there are no head-to-head comparisons,” says Dr. Baldwin, an associate professor of clinical dermatology at Rutgers Robert Wood Johnson Medical Center in Newark. “Many small studies suggest that there is no evidence that one works better than the other.”

However, often the side effect profile determines which drug is chosen.  Doxycycline has more short-term and nuisance side effects, whereas minocycline has more rare, serious adverse events.

Dr. Baldwin prescribes both drugs at her own practice, without favoring one over the other. “But with the worry about phototoxicity from doxycycline during the summer, you might start a patient on minocycline in warmer weather,” she says. “Some prescribers use minocycline during the summer and doxycycline during the winter.”

Occasionally, other antibiotics are used. Sulfamethoxazole-trimethoprim  “works very well for acne,” Dr. Baldwin says. “However, we tend to avoid this antibiotic due to its side effect profile and its importance in treating serious infections like methicillin-resistant Staphylococcus (MRSA).”

Azithromycin has been evaluated for acne in several studies, “but it is not as good an anti-inflammatory drug as the tetracyclines, and antibiotic resistance is again a concern with this important drug, “Dr. Baldwin says.

Dr. Baldwin reports a financial interest in Valeant, Mayne and Galderma.