Doxycycline is a tetracycline antibiotic, used in many infections: respiratory, chlamydial, rickettsial (such as Rocky Mountain spotted fever), cholera, plague, anthrax, brucellosis and malaria prophylaxis in travellers. It is also used in acne. It should not be taken with milk, antacids or iron, and can cause photosensitivity.
Rifampin lowers Doxycycline levels — risk of underdosing (e.g. malaria prophylaxis, brucellosis, rickettsial infections).
Rifampicin induces the hepatic enzymes that metabolise doxycycline and can reduce its half-life and concentrations by about 50%, compromising the treatment of brucellosis, rickettsioses and other zoonoses (a classically documented combination). Avoid the association; if unavoidable, consider doubling the doxycycline dose (with monitoring) or choosing an alternative regimen.
Doxycycline + rifampicin: rifampicin accelerates doxycycline metabolism and lowers its levels by ~50%, with risk of therapeutic failure. Avoid or use a doubled dose.
Enzymatic induction accelerating Doxycycline elimination.
Clinical response to infection.
Persistent fever, treatment failure.
Consider an alternative antibiotic or adjust the dose.
DailyMed/FDA (NIH/NLM) — approved Rifampin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; approved Doxycycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cf95b2ca-2cf8-49a8-8e3a-f9b0f5b2072c
Reduced Doxycycline absorption through cation chelation.
Doxycycline, like other tetracyclines, forms insoluble chelates with di- and trivalent cations (calcium, magnesium, aluminium, iron, zinc), reducing its oral absorption and plasma concentrations — with a risk of therapeutic failure in infections such as brucellosis, rickettsioses, Lyme disease or severe acne. The doxycycline label and the Portuguese Prontuário Terapêutico recommend separating antacids (and calcium/iron supplements and dairy products) by at least 2–3 hours. Warn the patient not to take the antibiotic with milk or with the antacid.
Antacids + doxycycline: cations (Al, Mg, Ca) chelate tetracyclines and reduce absorption. Separate administration by at least 2–3 hours.
Chelation of the tetracycline with aluminium, magnesium, calcium and iron in the gut.
Antibiotic efficacy.
Persistent fever, pain or discharge — infection possibly uncontrolled.
Separate the antacid dose from Doxycycline by 2–3 hours.
DailyMed/FDA (NIH/NLM) — approved Antacids label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c72f0736-ee20-45b4-baf0-b80f1e3fa9cb ; approved Doxycycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cf95b2ca-2cf8-49a8-8e3a-f9b0f5b2072c
Doxycycline + calcium: chelation reduces tetracycline absorption.
Tetracyclines, including doxycycline, form insoluble chelates with divalent and trivalent cations (calcium, magnesium, aluminium, iron, zinc) in the gastrointestinal tract, reducing oral absorption and plasma concentrations — with risk of therapeutic failure in infections such as brucellosis, rickettsioses or Lyme disease. The doxycycline label recommends separating antacids, calcium supplements and dairy products by at least 2–3 hours. Warn the patient not to take the antibiotic with milk, yoghurt or the calcium supplement, and adjust timing to maintain efficacy.
Calcium + doxycycline: chelation with reduced tetracycline absorption. Separate administration by 2–3 h.
Calcium cations chelate doxycycline, reducing its oral bioavailability.
Clinical response to antibiotic therapy.
Unresolved infection, persistent fever.
Separate dosing by at least 2 hours; give doxycycline with water.
DailyMed (FDA) — approved Doxycycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fe8cd3c6-36d6-4d92-bc5c-833cd6f9cb32 ; approved Calcium carbonate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=348d3dfa-6a52-4583-96e3-83c4bf2df45b — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Doxycycline + zinc: chelation reduces tetracycline absorption.
Tetracyclines, including doxycycline, form insoluble chelates with divalent and trivalent cations (zinc, calcium, magnesium, iron, aluminium) in the gastrointestinal tract, reducing the oral absorption and plasma concentrations of the antibiotic. The doxycycline label recommends separating zinc supplements (and other cations) by at least 2–3 hours. Warn the patient about the spacing of doses and check the times on the prescription, especially in patients taking zinc supplements during the antibiotic course.
Zinc + doxycycline: chelation with reduced absorption. Separate by 2–3 h.
Zinc chelates doxycycline, reducing its bioavailability.
Clinical response to antibiotic therapy.
Unresolved infection.
Separate dosing by at least 2 hours.
DailyMed (FDA) — approved Doxycycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fe8cd3c6-36d6-4d92-bc5c-833cd6f9cb32 ; approved Zinc (zinc sulfate) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2bd646d2-2a2a-4376-8da0-c7f08b0511ac — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
The combination of Isotretinoin with tetracyclines (Doxycycline) should be avoided: both may cause pseudotumor cerebri (benign intracranial hypertension).
Both isotretinoin and tetracyclines (doxycycline) are associated with cases of pseudotumor cerebri, a benign intracranial hypertension with a risk of visual damage. The isotretinoin label documents cases with concomitant tetracycline use and recommends avoiding the combined treatment. The mechanism is additive, with no defined safe dose. If the combination is unavoidable, monitor early signs — persistent headache, nausea, vomiting and visual disturbances — and refer urgently if papilledema appears. In severe acne, consider therapeutic alternatives that do not combine the two classes.
Isotretinoin + doxycycline: avoid the combination — risk of pseudotumor cerebri (benign intracranial hypertension) by additive effect.
Both isotretinoin and tetracyclines are associated with cases of pseudotumor cerebri; concomitant use increases the risk additively.
Monitor for headache, nausea, vomiting, visual disturbances and papilledema.
Persistent headache, visual disturbances, papilledema.
Avoid the combination. If unavoidable, monitor for early signs of pseudotumor cerebri.
DailyMed/FDA (NIH/NLM) — approved Isotretinoin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5a26c5e-9c3e-4781-8c08-62b91d21a68d ; approved Doxycycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f0fbf63a-e75c-40cf-b2e9-429deaac899d
Acitretin + tetracyclines (Doxycycline) is CONTRAINDICATED: both may cause increased intracranial pressure.
The acitretin label states that, since both acitretin and tetracyclines can cause increased intracranial pressure (pseudotumor cerebri), their combined use is contraindicated. Doxycycline is the most commonly used tetracycline in dermatology, making this the most relevant pair of the class. In psoriasis requiring acitretin and an infection requiring a tetracycline, choose an alternative antibiotic class and monitor persistent headache, nausea and visual disturbances after accidental exposure.
Acitretin + doxycycline: CONTRAINDICATED — both may cause increased intracranial pressure.
Since both acitretin and tetracyclines can cause increased intracranial pressure (pseudotumor cerebri), their combined use is contraindicated.
Monitor for headache, visual disturbances and papilledema in case of exposure.
Persistent headache, visual disturbances, papilledema.
Do not use the combination.
DailyMed/FDA (NIH/NLM) — approved Acitretin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6546625-acb8-460e-b34e-f795bfb3680a ; approved Doxycycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f0fbf63a-e75c-40cf-b2e9-429deaac899d
Alcohol does not interact directly with doxycycline, but may worsen GI effects.
Limit alcohol during treatment.
DailyMed/FDA (NIH/NLM) — approved Doxycycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcc95094-80ed-4023-b2a6-955a4810bfbe
Calcium in dairy chelates doxycycline and reduces its absorption; the effect is smaller than with other tetracyclines, but relevant.
Separate dairy intake 2 hours before or 6 hours after dosing.
DailyMed/FDA (NIH/NLM) — approved Doxycycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcc95094-80ed-4023-b2a6-955a4810bfbe
Tetracyclines cause photosensitivity; sun exposure can cause severe burns.
Avoid sun exposure and use protection during treatment.
DailyMed/FDA (NIH/NLM) — approved Doxycycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcc95094-80ed-4023-b2a6-955a4810bfbe
Doxycycline may worsen liver disease; caution is required in severe hepatic impairment.
Use with caution and monitor liver function.
DailyMed/FDA (NIH/NLM) — approved Doxycycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcc95094-80ed-4023-b2a6-955a4810bfbe
Tetracyclines cause fetal bone and dental changes (tooth discolouration, enamel hypoplasia) after the 4th month.
Contraindicated in the 2nd and 3rd trimesters; avoid whenever alternatives exist.
Excreted into breast milk; avoid while breastfeeding (risk of dental discolouration in the infant).
Advise effective contraception if treatment is prolonged.
DailyMed/FDA (NIH/NLM) — approved Doxycycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcc95094-80ed-4023-b2a6-955a4810bfbe ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 2, Drugs and Breastfeeding: Use an alternative antibiotic.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Broad-spectrum bacteriostatic tetracycline (Gram-positives and Gram-negatives, atypical bacteria), indicated in many infections (respiratory, urinary, skin, sexually transmitted, Lyme disease, brucellosis, cholera, plague, etc.). Almost completely absorbed orally; serum half-life of 18-22 hours independent of renal function (can be used in renal impairment without adjustment).
Inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit; bacteriostatic activity against a broad range of Gram-positive and Gram-negative bacteria. Cross-resistance with other tetracyclines is common.
Virtually completely absorbed after oral administration. Following a 200 mg dose, normal adults achieve mean peak serum levels of 2.6 mcg/mL at 2 hours, decreasing to 1.45 mcg/mL at 24 hours. Tetracyclines are readily absorbed and bound to plasma proteins to a varying degree.
Concentrated by the liver in the bile and excreted in urine and faeces at high concentrations and in a biologically active form. Renal excretion of about 40%/72 hours in individuals with normal function (creatinine clearance ~75 mL/min), which may fall to 1-5%/72 h in severe renal insufficiency; haemodialysis does not alter serum half-life. Tetracyclines cross the placenta and are found in fetal tissues.
Serum half-life of 18-22 hours, with no significant difference between individuals with normal renal function and severe renal impairment (which distinguishes it from the other, renally eliminated tetracyclines). Haemodialysis does not alter the half-life.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
