From the Guidelines
Doxycycline's side effects can be categorized by their frequency of occurrence, with gastrointestinal disturbances being the most common, affecting 15.7% of patients, as reported in a 2024 study published in the Journal of the American Academy of Dermatology 1. The most frequent side effects of doxycycline include:
- Gastrointestinal disturbances, such as nausea, vomiting, and diarrhea, which can be reduced by taking the medication with food and adequate fluids in the upright position
- Esophagitis and phototoxicity, which can be minimized by taking the medication with plenty of water and using sun protection Less common side effects of doxycycline include:
- Intracranial hypertension, which is a rare but serious side effect
- Treatment withdrawal due to adverse effects, which was more common with doxycycline compared to placebo in 3 trials (1.3% vs 0.3%; RR, 2.25 [0.38,13.21]) 1 It is essential to note that the incidence of side effects may vary depending on the dose and duration of treatment, as well as individual patient factors. To minimize the risk of side effects, patients should take doxycycline with food and adequate fluids, use sun protection, and report any severe reactions to their healthcare provider immediately, as recommended by the 2024 guidelines of care for the management of acne vulgaris 1.
From the FDA Drug Label
Adverse Reactions Due to oral doxycycline’s virtually complete absorption, side effects of the lower bowel, particularly diarrhea, have been infrequent The following adverse reactions have been observed in patients receiving tetracyclines: Gastrointestinal: anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region. Skin: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, maculopapular and erythematous rashes. Renal toxicity: Rise in BUN has been reported and is apparently dose related. Hypersensitivity reactions: urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and exacerbation of systemic lupus erythematosus. Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported. Other: bulging fontanels in infants and intracranial hypertension in adults.
The side effects of doxycycline by incidence are not explicitly stated in the drug label. However, the label does provide a list of possible adverse reactions, including:
- Gastrointestinal side effects such as anorexia, nausea, vomiting, diarrhea
- Skin reactions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme
- Renal toxicity with a reported rise in BUN
- Hypersensitivity reactions including urticaria, angioneurotic edema, anaphylaxis
- Blood disorders such as hemolytic anemia, thrombocytopenia, neutropenia
- Other reactions including bulging fontanels in infants and intracranial hypertension in adults 2
From the Research
Doxycycline Side Effects by Incidence
- The incidence of gastrointestinal (GI) adverse effects due to doxycycline use was reported in a study published in 2023 3, where 12 patients (6.3%) experienced GI adverse effects, resulting in discontinuation of doxycycline in 5 patients (2.6%).
- Esophagitis was reported in 3 patients (1.6%) in the same study 3.
- Photosensitivity is another known side effect of doxycycline, with clinical symptoms ranging from light sunburn-like sensation to large-area photodermatitis, as reported in a systematic review published in 2017 4.
- A study published in 1987 found that doxycycline had a higher frequency of side effects, including nausea or vomiting, which was at least 3-fold higher compared to other antibiotics, and skin rash, which was at least 4 times more frequent 5.
- The study published in 2023 also found that the incidence of GI adverse effects was significantly higher in patients who were ≥ 50 years old and in those who received a daily dose of 200 mg of doxycycline 3.
Comparison of Side Effects
- Doxycycline is considered to be generally comparable in side effects to other tetracyclines and penicillins, with the exception of increased photosensitivity 5.
- A study published in 1982 reviewed the chemistry, mode of action, antimicrobial activity, pharmacokinetics, and therapeutic efficacy of doxycycline, but did not provide detailed information on side effects by incidence 6.