Section 10 · Monograph

Ferrous sulfate

Reviewed Nov 2026FDA label

generic onlyIron supplement

Indications

Iron deficiency (low serum ferritin, with or without anemia) contributing to restless legs syndrome (RLS)/Willis-Ekbom disease — foundational, guideline-directed therapy per the AASM/International RLS Study Group (IRLSSG) clinical practice guideline when serum ferritin ≤75 ng/mL and/or transferrin saturation <20%.FDA-labeled
Iron-deficiency anemia and iron deficiency without anemia (general hematinic use) — the standard indication under which ferrous sulfate is marketed as an OTC iron supplement/generic oral iron salt.FDA-labeled

Ferrous sulfate is a generic OTC supplement, not an FDA-reviewed prescription drug; its use for RLS-associated iron deficiency is consensus/guideline-directed (AASM, IRLSSG) rather than product-labeled.Off-label
Sometimes trialed empirically for a short period in RLS patients with ferritin in the 75-100 ng/mL range when IV iron is not readily accessible, although IV iron is the guideline-preferred option in that specific ferritin range.Off-label

Ferrous sulfate supplies iron in the ferrous (Fe2+) oxidation state, which is absorbed more efficiently than ferric (Fe3+) iron via divalent metal transporter 1 (DMT1) in duodenal enterocytes.
RLS-specific rationale: iron is a required cofactor for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Neuroimaging, CSF, and autopsy studies in RLS patients demonstrate reduced brain (particularly substantia nigra) iron stores even when peripheral iron indices are only borderline-low, believed to drive the dopaminergic dysfunction underlying RLS symptoms.
Because CNS iron status cannot be measured or targeted directly in routine practice, peripheral iron repletion is used as the clinically actionable surrogate for improving presumed CNS iron deficiency and RLS symptom severity.

RLS-specific regimen: oral ferrous sulfate 325 mg (≈65 mg elemental iron) once daily is a commonly used starting regimen; once-daily dosing is as effective as divided dosing and produces fewer GI side effects.
Evening/bedtime dosing is often preferred in RLS specifically, based on the rationale that nocturnal iron redistribution toward the brain is greater at night than during the day.
Take on an empty stomach when tolerated, together with ~200 mg vitamin C or a vitamin C-rich beverage to enhance nonheme iron absorption.
Avoid calcium supplements/dairy, tea, and coffee within about 2 hours of dosing; separate from antacids, H2 blockers, and proton pump inhibitors.
If GI intolerance limits adherence, taking with a small amount of food improves tolerability at the cost of somewhat reduced absorption.
Recheck iron studies (ferritin, transferrin saturation) approximately 3 months after starting oral therapy; discontinue supplements for at least 2 days before the blood draw.

Pediatric threshold: oral (or IV) iron is recommended for RLS when serum ferritin <50 ng/mL.

Hemochromatosis or other iron-overload states.
Hemolytic anemia or anemias not caused by iron deficiency (e.g., anemia of chronic disease/inflammation with normal-to-high ferritin).
Known hypersensitivity to ferrous sulfate or product excipients.

Proton pump inhibitors, H2-receptor antagonists, and antacids reduce gastric acidity and can produce a suboptimal absorptive response to oral iron therapy.
Calcium supplements/dairy products, tea, and coffee reduce nonheme iron absorption when taken concurrently; separate dosing by ≥2 hours.
Iron reduces the absorption of levothyroxine, tetracyclines/fluoroquinolones, bisphosphonates, and levodopa/carbidopa via chelation — clinically relevant in RLS patients also receiving dopaminergic therapy; separate administration by several hours.
Vitamin C (ascorbic acid) enhances nonheme iron absorption — a desired, intentionally exploited interaction in RLS dosing regimens.

Gastrointestinal: nausea, constipation, abdominal cramping/pain, vomiting, diarrhea — dose-related and more likely when taken on an empty stomach.
Dark or black stools — expected and harmless, but should be distinguished from melena if GI bleeding is a concern.
Gastric irritation or, rarely, gastric mucosal erosion with prolonged high-dose use.
Iron overload/hemosiderosis with inappropriate or excessive supplementation, particularly in patients with undiagnosed hereditary hemochromatosis or when iron is continued without monitoring after ferritin normalizes.
Accidental pediatric ingestion of iron tablets is a recognized cause of serious and potentially fatal poisoning — counsel patients on safe storage away from children.

Obtain baseline serum ferritin and transferrin saturation, ideally fasting/morning, after avoiding iron-containing supplements and foods for at least 24 hours.
Recheck iron studies approximately 3 months after initiating oral therapy.
Target serum ferritin >75-100 ng/mL and/or transferrin saturation ≥20% as the guideline goal associated with RLS symptom improvement.
If ferritin fails to rise adequately after 3 months of appropriately dosed oral therapy, or if ferritin is persistently in the 75-100 ng/mL range, refer for IV iron rather than continuing indefinite oral trials.
Track RLS symptom severity in parallel with iron indices.
Watch for signs of iron overload with prolonged or repeated supplementation.

Iron requirements increase during pregnancy, and RLS is common in pregnancy, often related to iron deficiency; ferrous sulfate is commonly used and generally considered safe at recommended supplemental doses, but dosing and ferritin thresholds should be individualized with the obstetric provider.
Compatible with breastfeeding at standard supplemental doses; transfer into breast milk is minimal relative to maternal iron stores.
Iron supplementation should not be given empirically without a confirmed deficiency in either pregnancy or lactation.