Lanthanum Carbonate
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Hyperphosphatemia in ESRD — reduction of serum phosphate | Adults | Component of CKD-MBD management (with dietary restriction and dialysis) | FDA Approved |
Lanthanum carbonate is a non-calcium phosphate binder that uses the trivalent lanthanum cation to bind dietary phosphate in the gastrointestinal lumen, forming insoluble lanthanum phosphate complexes that are excreted in faeces. It was approved by the FDA in 2004 for ESRD patients. Although it contains a metal cation (a rare earth element), its pharmacokinetic profile differs fundamentally from aluminium: lanthanum has minimal systemic absorption and is eliminated via the hepatobiliary pathway rather than renally, avoiding aluminium-like accumulation. It offers an advantage of lower pill burden compared to sevelamer, and like sevelamer, it avoids the calcium load and associated vascular calcification risk seen with calcium-based binders.
Hyperphosphatemia in CKD not yet on dialysis (evidence: limited) — Although the FDA indication specifies ESRD, some clinicians use lanthanum carbonate in pre-dialysis CKD patients with progressive hyperphosphatemia, consistent with KDIGO 2017 guidance suggesting phosphate-lowering treatment when levels are persistently elevated.
Dosing
Adult Dosing — Hyperphosphatemia in ESRD
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Phosphate binder–naïve patient on dialysis | 1500 mg/day in divided doses with meals | 1500–3000 mg/day | 4500 mg/day (max studied) | Titrate by 750 mg/day every 2–3 weeks to target Typical: 500 mg TID or 750 mg TID as starting regimen |
| Patient switching from calcium-based binder | 1500 mg/day (standard start) | Titrate to phosphorus target | 4500 mg/day | No direct mg-for-mg conversion available Monitor phosphorus q2–3wk during transition |
| Patient with difficulty chewing tablets | Same dose using oral powder formulation (750 mg or 1000 mg packets) | Sprinkle on applesauce or similar food; consume immediately Higher GI side effects with powder vs tablet (18% vs 7% for nausea/vomiting/diarrhea) | ||
Lanthanum carbonate tablets must be chewed or crushed completely before swallowing — intact tablets must never be swallowed whole, as serious GI complications including obstruction and perforation have been reported with unchewed tablets. The tablet formulation has been associated with tooth injury in postmarketing reports. Consider the oral powder in patients with poor dentition. At a typical maintenance dose of 1500–3000 mg/day, the pill burden is 3–6 tablets daily (divided among meals), which is lower than sevelamer (average 9 tablets/day), representing an adherence advantage.
Lanthanum carbonate has radio-opaque properties and may mimic the appearance of an imaging agent on abdominal X-rays. Product residue has also been reported during endoscopic procedures. Clinicians should be aware of this when interpreting imaging studies in patients taking Fosrenol.
Pharmacology
Mechanism of Action
Lanthanum carbonate dissociates in the acidic environment of the upper gastrointestinal tract, releasing trivalent lanthanum ions (La³+). These ions bind dietary phosphate released from food during digestion, forming highly insoluble lanthanum phosphate complexes that cannot be absorbed across the intestinal epithelium. The bound complexes pass through the GI tract and are eliminated in faeces. In vitro, lanthanum binds approximately 97% of available phosphate at pH 3–5 (gastric conditions) and 67% at pH 7 (intestinal conditions) when present in a twofold molar excess. Unlike sevelamer, which is a large polymer, lanthanum is a small ionic binder, allowing for a higher phosphate-binding capacity per gram and consequently lower pill burden. Bile acids have not been shown to interfere with lanthanum’s phosphate-binding affinity, and lanthanum does not alter gastric pH.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Bioavailability <0.002%; mean Cmax in ESRD patients 1.0 ng/mL; minimal increase with dose escalation within therapeutic range | Negligible systemic exposure; low risk of systemic toxicity |
| Distribution | >99% bound to plasma proteins (albumin, α1-acid glycoprotein, transferrin); tissue deposition in GI tract, mesenteric lymph nodes, bone, and liver in animal studies; bone elimination t½ estimated 2.0–3.6 years | Lanthanum does not cross the intact blood–brain barrier; bone deposition observed but no toxicity in biopsies up to 4.5 years; does not accumulate like aluminium |
| Metabolism | Not metabolized; not a substrate or inhibitor of CYP1A2, 2C9, 2C19, 2D6, or 3A4/5 | No metabolic drug interactions; no dose adjustment for hepatic impairment (though hepatobiliary excretion warrants caution) |
| Elimination | ~99% of oral dose recovered in faeces (rats/dogs); biliary excretion is primary route for absorbed lanthanum; renal clearance <2% of total plasma clearance; plasma elimination t½ 53 h after discontinuation | Hepatobiliary elimination means no renal accumulation; use with caution in biliary obstruction |
Side Effects
Adverse reaction data from placebo-controlled studies (N=180 lanthanum carbonate chewable tablets vs N=95 placebo, 4–6 weeks) and two long-term open-label trials (N=1215 lanthanum, N=944 alternative therapy). The safety profile has been studied in over 5,200 subjects (FDA PI).
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nausea | 11% vs 5% placebo | Most common adverse reaction; generally abates over time with continued dosing; more frequent with powder (18%) than chewable tablets (7%) |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Vomiting | 9% vs 4% placebo | Often co-occurs with nausea; improves over time in most patients |
| Abdominal pain | 5% vs 0% placebo | Evaluate promptly if severe — may indicate GI obstruction or perforation |
| Hypocalcemia | ~5% (both lanthanum and comparator) | Lanthanum reduces intestinal calcium absorption; monitor serum calcium; supplement as needed |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| GI obstruction / ileus / subileus | Rare (postmarketing) | Variable; risk higher with abnormal GI anatomy, hypomotility, or unchewed tablets | Discontinue; surgical consultation; supportive care |
| GI perforation | Rare (postmarketing) | Variable | Emergency surgical evaluation; discontinue permanently |
| Fecal impaction | Rare (postmarketing) | Gradual; preceded by worsening constipation | Disimpaction; re-evaluate therapy; aggressive bowel regimen |
| Tooth injury | Uncommon (postmarketing) | During chewing; associated with tablet hardness | Switch to powder formulation; dental assessment |
GI complaints are the leading cause of lanthanum carbonate discontinuation. These effects generally diminish with continued treatment. Strategies include starting at 1500 mg/day and titrating gradually, ensuring tablets are fully chewed, and switching to the powder formulation in patients with tablet-related difficulties (though powder may cause more GI symptoms). Patients should report severe constipation or new abdominal pain promptly.
Drug Interactions
Lanthanum carbonate has minimal systemic absorption and does not interact with CYP enzymes. It does not alter gastric pH. Interactions occur via intraluminal binding — lanthanum ions can bind to drugs containing anionic groups (carboxyl, carbonyl, hydroxyl) in the GI tract, reducing their absorption.
Monitoring
- Serum PhosphorusEvery 2–3 weeks during titration; regularly once stable
RoutineTarget: 3.5–5.5 mg/dL (KDOQI). Most patients require 1500–3000 mg/day to achieve phosphorus <6.0 mg/dL. Titrate in 750 mg/day increments. - Serum CalciumMonthly
RoutineHypocalcemia occurs in ~5% of patients. Lanthanum reduces intestinal calcium absorption. Supplement calcium and vitamin D as part of CKD-MBD management. - iPTHEvery 3–6 months
RoutineKDIGO target for dialysis: 2–9 times upper normal limit. Monitor as part of CKD-MBD assessment. - GI SymptomsEvery visit
RoutineAssess for constipation, abdominal pain/distention, and dysphagia. These may indicate obstruction, ileus, or subileus and warrant therapy re-evaluation. - TSHIf taking levothyroxine concurrently
Trigger-basedLanthanum reduces levothyroxine bioavailability by ~40%. Separate dosing and monitor TSH to ensure adequate thyroid hormone replacement. - Liver FunctionPeriodically
RoutineLanthanum is excreted via the hepatobiliary pathway. Studies up to 6 years showed no clinically relevant liver enzyme changes. Monitor as part of routine CKD care.
Contraindications & Cautions
Absolute Contraindications
- Bowel obstruction, ileus, or fecal impaction — lanthanum tablets or powder may worsen existing obstruction; contraindicated in all formulations.
Relative Contraindications (Specialist Input Recommended)
- Abnormal GI anatomy (diverticular disease, history of GI surgery, GI cancer, GI ulceration) — identified as risk factors for obstruction and perforation in postmarketing reports.
- Hypomotility disorders (severe constipation, diabetic gastroparesis) — these patients were excluded from clinical trials.
- Active peptic ulcer, ulcerative colitis, Crohn’s disease — excluded from clinical studies.
- Pregnancy — FDA recommends use of a non-lanthanum-containing phosphate binder in pregnant women due to bone deposition findings in animal studies.
- Lactation — FDA recommends use of a non-lanthanum-containing binder in lactating women.
Use with Caution
- Hepatic impairment or biliary obstruction — lanthanum is eliminated via the hepatobiliary pathway; impaired biliary excretion may alter the clearance of the small absorbed fraction.
- Pediatric patients — lanthanum deposits in developing bone including the growth plate in animal studies; safety and efficacy not established; use is not recommended.
- Concomitant use of medications known to potentiate constipation or hypomotility — may increase risk of obstruction when combined with lanthanum.
Serious cases of gastrointestinal obstruction, ileus, subileus, gastrointestinal perforation, and fecal impaction have been reported in patients taking lanthanum, some requiring surgery or hospitalization. Risk factors include abnormal GI anatomy, hypomotility disorders, and concomitant constipating medications. Patients prescribed chewable tablets must chew or crush them completely before swallowing. Treatment should be re-evaluated in patients who develop severe constipation or other severe GI symptoms.
Patient Counselling
Purpose of Therapy
Lanthanum carbonate helps control high phosphorus levels in the blood by binding to phosphorus from food in the digestive tract, preventing it from being absorbed into the body. Controlling phosphorus is essential for protecting bones and blood vessels in kidney disease.
How to Take
Take lanthanum carbonate with or immediately after every meal. Tablets must be chewed completely or crushed before swallowing — never swallow tablets whole. For the powder form, sprinkle the contents onto a small amount of applesauce or similar soft food and eat immediately. Follow your prescribed phosphorus-restricted diet.
Sources
- FOSRENOL (lanthanum carbonate) chewable tablets and oral powder — Full Prescribing Information. Shire US Inc. Revised 05/2020. FDA LabelPrimary source for all dosing, contraindications, adverse reactions (Table 1), drug interaction data, and pharmacokinetic parameters.
- Hutchison AJ, Barnett ME, Krause R, Kwan JTC, Siami GA; SPD405-309 Lanthanum Study Group. Long-term efficacy and safety profile of lanthanum carbonate: results for up to 6 years of treatment. Nephron Clin Pract. 2008;110(1):c15–c23. doi:10.1159/000149239Longest published phosphate binder study at time of publication (N=93, up to 6 years); confirmed sustained phosphate control and no evidence of hepatic, bone, or neurological toxicity with long-term lanthanum use.
- Hutchison AJ, Maes B, Vanwalleghem J, et al. Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomized, comparative trial versus calcium carbonate. Nephron Clin Pract. 2005;100(1):c8–c19. doi:10.1159/000084653Phase 3 randomized trial vs calcium carbonate; demonstrated equivalent phosphate control with lower incidence of hypercalcemia (6% vs 49%) and favourable effects on bone turnover markers.
- D’Haese PC, Spasovski GB, Sikole A, et al. A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients. Kidney Int Suppl. 2003;(85):S73–S78. doi:10.1046/j.1523-1755.63.s85.18.xPaired bone biopsy study (N=98): lanthanum was well tolerated, with lower hypercalcemia than calcium carbonate and a trend toward normalization of bone turnover in lanthanum-treated patients.
- Finn WF; SPD405-307 Lanthanum Study Group. Lanthanum carbonate versus standard therapy for the treatment of hyperphosphatemia: safety and efficacy in chronic maintenance hemodialysis patients. Clin Nephrol. 2006;65(3):191–202. doi:10.5414/cnp65191Two-year open-label active-controlled study of lanthanum vs alternative therapy in 1359 HD patients; confirmed sustained efficacy and comparable long-term safety profile.
- Hutchison AJ, Whelton A, Thadhani R, et al. Long-term mortality and bone safety in patients with end-stage renal disease receiving lanthanum carbonate. Nephron. 2018;140(4):265–274. doi:10.1159/000492603Five-year observational study (SPD405-404) using USRDS data; median survival and bone fracture rates in lanthanum-treated patients were comparable to those receiving other phosphate binders.
- KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD. Kidney Int Suppl. 2017;7(1):1–59. doi:10.1016/j.kisu.2017.04.001Current global guideline for CKD-MBD management; recommends phosphate-lowering therapy for progressive hyperphosphatemia and suggests restricting calcium-based binder use.
- Hutchison AJ, Wilson RJ, Garafola S, Copley JB. Lanthanum carbonate: safety data after 10 years. Nephrology (Carlton). 2016;21(12):987–994. doi:10.1111/nep.12864Comprehensive 10-year safety review including bone biopsy data, liver safety, and SPD405-404 interim results; after >850,000 person-years of exposure, no evidence of adverse long-term safety outcomes.
- Cernaro V, Calimeri S, Laudani A, Santoro D. Clinical evaluation of the safety, efficacy and tolerability of lanthanum carbonate in the management of hyperphosphatemia in patients with end-stage renal disease. Ther Clin Risk Manag. 2020;16:871–880. doi:10.2147/TCRM.S196805Recent clinical review summarising efficacy, GI tolerability, bone and liver safety data, and drug interactions from all available evidence.
- Sprague SM, Ross EA, Nath SD, Zhang P, Pratt RD, Krause R. Lanthanum carbonate vs. sevelamer hydrochloride for the reduction of serum phosphorus in hemodialysis patients: a crossover study. Clin Nephrol. 2009;72(4):252–258. doi:10.5414/cnp72252Head-to-head crossover comparison with sevelamer showing equivalent phosphate control; lanthanum required fewer daily tablets, supporting its lower pill burden advantage.