Ferrous sulfate is an iron supplement used to treat and prevent iron-deficiency anaemia, the most common anaemia worldwide. It improves tiredness, pallor and shortness of breath within a few weeks.
Also known as: Ferro, Feosol
Ferrous sulphate reduces levothyroxine absorption, potentially causing undertreated hypothyroidism if taken together.
Iron binds thyroxine in the gastrointestinal tract; Annex 7 (Iron): "Drugs whose absorption is reduced by iron: ... Thyroxine".
TSH and free T4 6–8 weeks after any regimen change.
Fatigue, weight gain, oedema (hypothyroidism signs).
Separate doses by at least 4 hours; reassess TSH after 6–8 weeks if co-administration continues.
INFARMED Prontuário Terapêutico (11th ed., 2012), Annex 7 — Iron: "Thyroxine" among drugs with reduced absorption; DailyMed — Levothyroxine Sodium Tablet label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=255ad500-6656-4cd0-b4d1-10cc22f9e61b
Iron + zinc: they compete for intestinal absorption.
Iron and zinc share common intestinal transporters (e.g., DMT1, divalent metal transporters) and compete with each other for absorption when given simultaneously, especially at high doses. In patients taking combined iron and zinc supplementation (common in multiple deficiencies, pregnancy or malabsorption), absorption of both can decrease. Separate the doses (e.g., iron at breakfast and zinc at dinner) or give them at different times of day; taking them with food may reduce competition but also decreases absorption of both.
Iron + zinc: compete for intestinal absorption. Separate the doses.
Iron and zinc share intestinal transport mechanisms, reducing absorption of both when taken together.
Response to supplementation.
Persistent deficiency despite supplementation.
Separate dosing by at least 2 hours.
DailyMed (FDA) — approved Iron label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e88a847-397b-4ddb-83d7-42c9b963a0b7 ; 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)
Iron and zinc compete for the same intestinal absorption pathway and mutually reduce each other, so simultaneous supplementation may correct neither deficiency.
Competition for the divalent cation transporter (DMT1) in the intestinal mucosa: the Prontuário (Iron 4.1.1) states that "Iron absorption is reduced by: antacids, penicillins, tetracyclines, trientine and zinc" and that "iron salts reduce the absorption of ... zinc".
Full blood count and ferritin, serum zinc, adherence and gastrointestinal tolerance.
Non-correcting anaemia, zinc deficiency symptoms (dermatitis, diarrhoea, taste changes).
Separate the doses by at least 2 h and avoid co-administration; reassess ferritin and serum zinc after 8–12 weeks on a separated schedule.
INFARMED Prontuário Terapêutico (11th ed., 2012), Iron 4.1.1 — zinc among drugs reducing iron absorption and vice versa.
Ascorbic acid increases oral iron absorption; the effect is often used intentionally but requires caution in iron overload states.
Reduction of ferric to ferrous iron and maintenance of its solubility in the small intestine: the Prontuário (Iron 4.1.1) states that "ascorbic acid potentiates absorption (30 mg per 200 mg of iron)".
Haematological response (haemoglobin), ferritin; iron and transferrin saturation in patients at risk of overload.
Signs of iron overload (arthralgia, hyperpigmentation, diabetes, cardiomyopathy).
Use the potentiation to correct iron deficiency anaemia; avoid pharmacological vitamin C doses in haemochromatosis, thalassaemia or other iron overload states.
INFARMED Prontuário Terapêutico (11th ed., 2012), Iron 4.1.1 — "Ascorbic acid potentiates absorption (30 mg per 200 mg of iron)".
Iron + calcium: calcium inhibits oral iron absorption.
Calcium reduces the absorption of non-haem iron in the gastrointestinal tract, both by competing for shared transporters and by forming complexes in the lumen. In patients with iron-deficiency anaemia taking iron supplements and, simultaneously, calcium supplements (common in women and older people), iron absorption can be impaired and delay correction of the anaemia. Separate the doses by at least 2 hours (e.g., iron at breakfast and calcium at dinner), and consider vitamin C (which enhances iron absorption) with the iron dose.
Calcium + iron: calcium inhibits oral iron absorption. Separate administration by 2 h.
Calcium competes with iron for intestinal transport.
Haematological response and adherence.
Persistent iron-deficiency anaemia.
Separate iron and calcium dosing by at least 2 hours.
DailyMed (FDA) — approved Iron label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e88a847-397b-4ddb-83d7-42c9b963a0b7 ; 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)
Minocycline + Iron: minocycline absorption is impaired by chelation with preparations containing iron. Separate dosing times.
Preparations containing iron chelate minocycline in the gastrointestinal lumen, reducing its absorption and efficacy — an interaction documented in the tetracycline class. Relevant in patients with iron-deficiency anaemia treated with ferrous sulfate. Separate dosing by at least 2–4 hours and, ideally, take minocycline on an empty stomach. Monitor the clinical response to infection.
Minocycline + iron: absorption is impaired by chelation — separate dosing by 2–4 hours.
Preparations containing iron chelate minocycline in the gastrointestinal lumen, reducing its absorption and efficacy.
Monitor antibiotic efficacy.
Therapeutic failure of the infection.
Separate minocycline dosing from iron supplements by at least 2–4 hours.
DailyMed/FDA (NIH/NLM) — approved Minocycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a5fc4d50-50b2-46e0-b722-4c6b2ec47d06 ; approved Iron label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=73d1f079-d8eb-44f4-b33d-05fb25b80c8f
Mycophenolate + iron: iron reduces oral mycophenolate absorption, potentially decreasing exposure — separate doses by at least 2 hours.
QUADRO 2 of the Prontuário (Iron) lists mycophenolate among drugs whose absorption is reduced with iron ("Drugs whose absorption is reduced with iron: ... Mycophenolate"). Chelation in the gut lumen with iron salts reduces the oral bioavailability of mycophenolate.
Watch immunosuppressive efficacy during iron supplementation.
Signs of rejection or MPA levels below target with simultaneous iron intake.
Give mycophenolate and iron at least 2 hours apart; ideally take iron at a different time of day from mycophenolate.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, Table 2 (Iron) ; DailyMed/FDA (NIH/NLM) — approved CellCept label (Genentech): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40
Tetracycline + Iron: tetracycline absorption is impaired by chelation with preparations containing iron. Separate dosing times.
Preparations containing iron chelate tetracycline in the gastrointestinal lumen, reducing its absorption and efficacy — an interaction documented in the label. It is especially relevant in patients with iron-deficiency anaemia treated with ferrous sulfate. Separate tetracycline dosing from iron by at least 2–4 hours and, ideally, take tetracycline on an empty stomach. Monitor the clinical response to infection, especially in urinary tract infections.
Tetracycline + iron: absorption is impaired by chelation — separate dosing by 2–4 hours.
Preparations containing iron chelate tetracycline in the gastrointestinal lumen, reducing its absorption and efficacy.
Monitor antibiotic efficacy.
Therapeutic failure of the infection.
Separate tetracycline dosing from iron supplements by at least 2–4 hours.
DailyMed/FDA (NIH/NLM) — approved Tetracycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=02e88b4a-57ae-4ef6-ba48-97c657202b94 ; approved Iron label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=73d1f079-d8eb-44f4-b33d-05fb25b80c8f
Omeprazole may reduce the absorption of oral iron, particularly non-heme iron.
Non-haem iron absorption (present in oral supplements) depends on acidic gastric pH, which keeps iron in the more absorbable ferrous form; omeprazole, by suppressing acid secretion, can reduce absorption and the efficacy of supplementation in patients with iron deficiency anaemia. In patients on a PPI with an unsatisfactory response to oral iron, consider increasing the dose, separating administrations, preferring haem iron or alternate-day dosing, and assess the need for intravenous iron.
Iron + omeprazole: raised pH reduces non-haem iron absorption. Monitor the response to supplementation and consider parenteral iron if needed.
Gastric acid suppression by the PPI impairs the reduction of Fe3+ to Fe2+, essential for duodenal iron absorption.
Monitor the therapeutic response of iron-deficiency anaemia.
Persistent iron-deficiency anaemia despite treatment.
Consider monitoring the response to iron (haemoglobin, ferritin); separate administration times.
DailyMed (FDA) — approved Iron label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=73d1f079-d8eb-44f4-b33d-05fb25b80c8f ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ea9a6f3-b756-4cdf-b3db-f666a2c17d66 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Iron markedly reduces ciprofloxacin absorption through chelation.
Iron salts (ferrous, ferrous fumarate, etc.) release divalent cations that chelate ciprofloxacin in the gastrointestinal tract, reducing its oral bioavailability and potentially compromising antibacterial treatment. The ciprofloxacin label recommends administering the antibiotic 2 hours before or 6 hours after iron supplements (the same applies to antacids, calcium and zinc). This precaution is especially relevant in anaemic patients taking iron supplements during an antibiotic — check the schedules at prescription.
Ciprofloxacin + iron: iron cations chelate ciprofloxacin and reduce absorption. Administer 2 hours before or 6 hours after iron.
Fe2+/Fe3+ cations chelate the fluoroquinolone in the GI tract, reducing its bioavailability.
Monitor antibiotic efficacy (signs of persistent infection).
Therapeutic failure of ciprofloxacin; unresolved infection.
Give ciprofloxacin at least 2 hours before or 4 hours after iron.
DailyMed (FDA) — approved Iron label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=73d1f079-d8eb-44f4-b33d-05fb25b80c8f ; approved Ciprofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c527d138-e32c-418f-9573-a3d8a796279f — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Penicillamine + iron: iron reduces penicillamine absorption — separate administration.
The FDA label documents that iron reduces penicillamine absorption ("Food, antacids, and iron reduce absorption of the drug") and the Prontuário Terapêutico records "Ferrous sulphate (reduces its serum concentrations)". Iron forms chelates with penicillamine in the GI tract, reducing the chelator bioavailability and, conversely, prolonged penicillamine treatment may worsen iron deficiency (urinary metal losses and absorption interference). The interaction is relevant in chelation patients who also need iron supplementation — common in Wilson disease with associated anaemia and in chronic poisonings. The practical guidance is to separate administration by at least 2 hours and give penicillamine on an empty stomach, monitoring clinical response to treatment.
Penicillamine + iron: iron chelates penicillamine and reduces its absorption — separate administration by at least 2 hours.
The FDA label documents that iron reduces penicillamine absorption ("Food, antacids, and iron reduce absorption of the drug") and the Prontuário records "Ferrous sulphate (reduces its serum concentrations)". Iron chelates penicillamine in the GI tract; the combination may reduce the chelator efficacy and, conversely, penicillamine may worsen iron deficiency.
Monitor clinical response and blood count (iron) during the combination.
Lack of response to chelating treatment or worsening of iron-deficiency anaemia.
Separate penicillamine and iron by at least 2 hours; give penicillamine on an empty stomach.
DailyMed/FDA (NIH/NLM) — approved Penicillamine label (CUPRIMINE): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=80e736d3-2017-4d68-94b4-38255c3c59c6 ; approved Iron label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=73d1f079-d8eb-44f4-b33d-05fb25b80c8f ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Penicillamine, 17
Tannins in tea and coffee bind non-haem iron and reduce absorption by up to 60–90% when taken together.
Space iron from tea and coffee by at least 1–2 h (site monograph: space from tea, coffee).
Site monograph (ferrous sulfate — space from tea, coffee, milk, antacids ≥ 2 h); Prontuário 8 (iron).
Calcium in milk and dairy competes with iron for intestinal transport, reducing its absorption.
Avoid taking iron with milk, yoghurt or cheese; separate doses by 2 hours.
EMC-UK (MHRA) — approved Iron SmPC: https://www.medicines.org.uk/emc/product/102243/smpc
Calcium-rich meals decrease iron absorption, mainly non-heme iron.
Separate iron from calcium-rich meals (2 hours).
EMC-UK (MHRA) — approved Iron SmPC: https://www.medicines.org.uk/emc/product/102243/smpc
Calcium from milk and dairy competes with iron for carriers and reduces ferrous sulfate absorption.
Space iron from milk and dairy by at least 2 h.
Site monograph (ferrous sulfate — space from milk ≥ 2 h); Prontuário 8 (iron — calcium reduces absorption).
Do not treat anaemia without diagnosis — it may mask occult bleeding or other serious causes.
Investigate the cause before starting iron (site monograph).
Site monograph (ferrous sulfate — investigate cause before starting).
Iron overload is an absolute contraindication — supplementation worsens overload and organ damage.
Exclude haemochromatosis/overload before supplementing.
Prontuário Terapêutico INFARMED (iron — contraindicated in haemochromatosis); BD vocabulary (haemochromatosis).
No restrictive Annex 1 entry: iron-deficiency anaemia in pregnancy is associated with prematurity and low birth weight, and iron supplementation (60 mg elemental iron/day, WHO) is standard practice. Gastrointestinal adverse effects are common but carry no fetal risk.
Compatible and frequently indicated; combine with folic acid for routine prophylaxis (WHO).
Compatible; little iron passes into milk (regulated by ferroportin) and maternal supplementation does not overdose the infant.
No specific additional contraception.
Prontuário Terapêutico INFARMED — 8.3 (Antianaemics); WHO/UNICEF — antenatal iron-folate supplementation guideline.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Correction of iron-deficiency anaemia; reticulocytosis in 7–10 days and haemoglobin normalisation in 6–8 weeks.
Fe2+ enters the enterocyte via DMT1, is stored as ferritin or exported via ferroportin (hepcidin-regulated); incorporated into protoporphyrin IX to form heme.
Duodenal absorption regulated by hepcidin; 10–15% in normal state, up to 30% in deficiency; vitamin C improves, phytates/tannins/antacids reduce.
No hepatic metabolism; iron is recycled by macrophages and stored in ferritin/haemosiderin; losses only through bleeding and desquamation.
~ 6 h (oral); marrow utilisation takes weeks.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
