LANTHANUM CARBONATE- lanthanum carbonate tablet, chewable 
Teva Pharmaceuticals USA, Inc.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use LANTHANUM CARBONATE CHEWABLE TABLETS safely and effectively. See full prescribing information for LANTHANUM CARBONATE CHEWABLE TABLETS.

LANTHANUM CARBONATE chewable tablets, for oral use
Initial U.S. Approval: 2004

RECENT MAJOR CHANGES

Warnings and Precautions (5.1)                                 05/2023

INDICATIONS AND USAGE

  • Lanthanum carbonate chewable tablets are a phosphate binder indicated to reduce serum phosphate in patients with end-stage renal disease (ESRD). (1)

DOSAGE AND ADMINISTRATION

  • The recommended initial total daily dose of lanthanum carbonate chewable tablets is 1,500 mg in divided doses. Titrate every 2 to 3 weeks based on serum phosphate level. (2)
  • Take lanthanum carbonate chewable tablets with or immediately after meals. (2)
  • Chew or crush tablet completely before swallowing. (2)

DOSAGE FORMS AND STRENGTHS

  • Chewable Tablets: 500 mg, 750 mg, and 1,000 mg. (3)

CONTRAINDICATIONS

  • Bowel obstruction, ileus, and fecal impaction. (4)

WARNINGS AND PRECAUTIONS

  • Serious cases of gastrointestinal obstruction, ileus, subileus, gastrointestinal perforation, and fecal impaction. Risks include altered gastrointestinal anatomy, hypomotility disorders, and concomitant medications. Advise patients to chew or crush the tablet completely. (5.1)
  • Lanthanum carbonate chewable tablets have radio-opaque properties and, therefore, may give the appearance typical of an imaging agent during abdominal X-ray procedures. (5.2)

ADVERSE REACTIONS

  • In controlled trials, the most common adverse reactions that were more frequent (≥5% difference vs. placebo) in lanthanum carbonate chewable tablets were nausea, vomiting, and abdominal pain. (6.1)
  • The following adverse reactions have been identified during post-approval use of lanthanum carbonate chewable tablets: constipation, dyspepsia, allergic skin reactions, and tooth injury while chewing the tablet. (6.2)

To report SUSPECTED ADVERSE REACTIONS, contact Teva  at 1-888-838-2872 or FDA at  1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

  • There is a potential for lanthanum carbonate chewable tablets to interact with compounds that bind to cationic antacids (i.e., aluminum-, magnesium-, or calcium-based); therefore, do not take such compounds within 2 hours of dosing with lanthanum carbonate chewable tablets. (7.1)
  • Oral quinolone antibiotics must be taken at least 1 hour before or 4 hours after lanthanum carbonate chewable tablets. (7.2)
  • Do not take thyroid hormone replacement therapy within 2 hours of dosing with lanthanum carbonate chewable tablets. Monitoring of TSH levels is recommended in patients receiving both medicinal agents. (7.3)
  • For oral medications where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, consider separation of the timing of the administration of the two drugs. (7.4)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 9/2023

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Gastrointestinal Adverse Effects

5.2 Diagnostic Tests

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Drugs Binding to Antacids

7.2 Quinolone Antibiotics

7.3 Levothyroxine

7.4 Use with Other Oral Medications

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

14.1 Double-Blind Placebo-Controlled Studies

14.2 Open-Label Active-Controlled Studies

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

17 PATIENT COUNSELING INFORMATION

*
Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Lanthanum carbonate chewable tablets are a phosphate binder indicated to reduce serum phosphate in patients with end-stage renal disease (ESRD).

Management of elevated serum phosphorus levels in patients with ESRD usually includes all of the following: reduction in dietary intake of phosphate, removal of phosphate by dialysis, and reduction of intestinal phosphate absorption with phosphate binders.

2 DOSAGE AND ADMINISTRATION

Divide the total daily dose of lanthanum carbonate chewable tablets and take with or immediately after meals. The recommended initial total daily dose of lanthanum carbonate chewable tablets is 1,500 mg. Titrate the dose every 2 to 3 weeks until an acceptable serum phosphate level is reached. Monitor serum phosphate levels as needed during dose titration and on a regular basis thereafter.

Lanthanum carbonate chewable tablets has the potential to bind other orally administered drugs; consider separating the administration of other oral medications [see Drug Interactions (7)].

In clinical studies of patients with ESRD, lanthanum carbonate chewable tablets doses up to 4,500 mg were evaluated. Most patients required a total daily dose between 1,500 mg and 3,000 mg to reduce plasma phosphate levels to less than 6.0 mg/dL. Doses were generally titrated in increments of 750 mg/day.

Chew or crush lanthanum carbonate chewable tablets completely before swallowing. Do not swallow intact lanthanum carbonate chewable tablets.

Consider using the oral powder formulation in patients with poor dentition or who have difficulty chewing tablets.

3 DOSAGE FORMS AND STRENGTHS

Chewable Tablets: 500 mg, 750 mg, and 1,000 mg.

4 CONTRAINDICATIONS

Contraindicated in bowel obstruction, including ileus and fecal impaction.

5 WARNINGS AND PRECAUTIONS

5.1 Gastrointestinal Adverse Effects

Serious cases of gastrointestinal obstruction, ileus, subileus, gastrointestinal perforation, and fecal impaction have been reported in patients taking lanthanum, some requiring surgery or hospitalization. Consider discontinuing lanthanum carbonate chewable tablets in patients without another explanation for severe gastrointestinal symptoms.

Risk factors for gastrointestinal obstruction and gastrointestinal perforation identified from post-marketing reports in patients taking lanthanum carbonate chewable tablets include abnormal gastrointestinal anatomy (e.g., diverticular disease, peritonitis, history of gastrointestinal surgery, gastrointestinal cancer, gastrointestinal ulceration), hypomotility disorders (e.g., constipation, ileus, subileus, diabetic gastroparesis), and the use of medications known to potentiate these effects. Some cases were reported in patients with no history of gastrointestinal disease.

Patients with acute peptic ulcer, ulcerative colitis, Crohn’s disease, or bowel obstruction were not included in lanthanum carbonate chewable tablets clinical studies [see Contraindications (4)].

Advise patients who are prescribed lanthanum carbonate chewable tablets to chew the tablet completely and not to swallow them whole. Serious gastrointestinal complications have been reported in association with unchewed or incompletely chewed tablets [see Adverse Reactions (6.2)].

5.2 Diagnostic Tests

Lanthanum carbonate chewable tablets have radio-opaque properties and therefore may give the appearance typical of an imaging agent during abdominal X-ray procedures.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Overall, the safety profile of lanthanum carbonate chewable tablets has been studied in over 5,200 subjects in completed clinical trials. The most common adverse reactions for lanthanum carbonate chewable tablets were gastrointestinal events, such as nausea, vomiting, and abdominal pain and they generally abated over time with continued dosing.

In double-blind, placebo-controlled studies where a total of 180 and 95 patients with ESRD were randomized to lanthanum carbonate chewable tablet and placebo, respectively, for 4 to 6 weeks of treatment, the most common reactions that were more frequent (≥5% difference) in the lanthanum carbonate chewable tablet group were nausea, vomiting, and abdominal pain (Table 1).

Table 1. Adverse Reactions* That Were More Common on Lanthanum Carbonate Chewable Tablets in Placebo-Controlled, Double-Blind Studies with Treatment Periods of 4 to 6 Weeks

Lanthanum Carbonate Chewable Tablets %
(N=180)



Placebo

%

(N=95)

Nausea

11

5

Vomiting

9

4

Abdominal pain

5

0

*Expressed as the event rate for each term

In an open-label, long-term 2-year extension study in 93 patients who had transitioned from other studies, resulting in a total of up to 6 years treatment, mean baseline values and changes in transaminases were similar to those observed in the earlier comparative studies, with little change during treatment.

The safety of lanthanum carbonate chewable tablets was studied in two long-term, open-label clinical trials, which included 1,215 patients treated with lanthanum carbonate chewable tablets and 944 with alternative therapy. Fourteen percent (14%) of patients treated with lanthanum carbonate chewable tablets discontinued treatment due to adverse events. Gastrointestinal adverse reactions, such as nausea, diarrhea, and vomiting were the most common types of event leading to discontinuation.

In pooled active comparator controlled clinical trials, hypocalcemia was noted with an incidence of approximately 5% in both lanthanum and active comparator groups. A nonclinical study and a phase 1 study have shown reduced absorption of calcium in the intestine with lanthanum carbonate treatment.

In a crossover study in 72 healthy individuals comparing lanthanum carbonate chewable tablets to lanthanum carbonate oral powder, gastrointestinal adverse reactions such as nausea, diarrhea, and vomiting were more common for the oral powder formulation (18%) than for the chewable tablets (7%).

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of lanthanum carbonate chewable tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cases of constipation, intestinal perforation, intestinal obstruction, ileus, subileus, dyspepsia, allergic skin reactions, hypophosphatemia, and tooth injury while chewing the tablet have been reported.

7 DRUG INTERACTIONS

7.1 Drugs Binding to Antacids

There is a potential for lanthanum carbonate chewable tablets to interact with compounds which bind to cationic antacids (i.e., aluminum-, magnesium-, or calcium-based); therefore, do not administer such compounds within 2 hours of dosing with lanthanum carbonate chewable tablets. Examples of relevant classes of compounds where antacids have been demonstrated to reduce bioavailability include antibiotics (such as quinolones, ampicillin, and tetracyclines), thyroid hormones, ACE inhibitors, statin lipid regulators, and anti-malarials.

7.2 Quinolone Antibiotics

Coadministration of lanthanum carbonate chewable tablets with quinolone antibiotics may reduce the extent of their absorption. The bioavailability of oral ciprofloxacin was decreased by approximately 50% when taken with lanthanum carbonate chewable tablets in a single-dose study in healthy volunteers. Administer oral quinolone antibiotics at least 1 hour before or 4 hours after lanthanum carbonate chewable tablets. When oral quinolones are given for short courses, consider eliminating the doses of lanthanum carbonate chewable tablets that would normally be scheduled near the time of quinolone intake to improve quinolone absorption [see Clinical Pharmacology (12.3)].

7.3 Levothyroxine

The bioavailability of levothyroxine was decreased by approximately 40% when taken together with lanthanum carbonate chewable tablets. Administer thyroid hormone replacement therapy at least 2 hours before or 2 hours after dosing with lanthanum carbonate chewable tablets and monitor thyroid stimulating hormone (TSH) levels [see Clinical Pharmacology (12.3)].

7.4 Use with Other Oral Medications

There are no empirical data on avoiding drug interactions between lanthanum carbonate chewable tablets and most concomitant oral drugs. For oral medications where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, consider separation of the timing of the administration of the two drugs. The duration of separation depends upon the absorption characteristics of the medication concomitantly administered, such as the time to reach peak systemic levels and whether the drug is an immediate-release or an extended-release product. Consider monitoring clinical responses or blood levels of concomitant medications that have a narrow therapeutic range.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Available data from case reports with use of lanthanum carbonate chewable tablets in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of lanthanum carbonate to pregnant rats and rabbits during organogenesis at doses 3 and 2.5 times, respectively, the maximum recommended human dose (MRHD), resulted in no adverse developmental effects. In rabbits, lanthanum carbonate doses 5 times the MRHD was associated with maternal toxicity and resulted in increased post-implantation loss, reduced fetal weights, and delayed fetal ossification (see Data). Deposition of lanthanum into developing bone, including growth plate, was observed in juvenile animals in long-term animal studies with lanthanum carbonate [see Use in Specific Populations (8.4)]. Use a non-lanthanum containing phosphate binder in a pregnant woman. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

In pregnant rats, oral administration of lanthanum carbonate at doses as high as 2,000 mg/kg/day during organogenesis resulted in no evidence of harm to the fetus. The MRHD for lanthanum carbonate chewable tablets is 5,725 mg, representing a dose of 95.4 mg/kg, or 3,530 mg/m2 for a 60-kg patient. The 2,000-mg/kg/day dose in the rat is equivalent to 12,000 mg/m2, 3 times the MRHD. In pregnant rabbits, oral administration of lanthanum carbonate at 1,500 mg/kg/day (18,000 mg/m2; 5 times the daily MRHD) during organogenesis was associated with increased postimplantation loss, reduced fetal weights, and delayed fetal ossification. No effects on the pregnant rabbits or fetuses were observed at 750 mg/kg/day (9,000 mg/m2; 2.5 times the MRHD).

In a pre- and postnatal development study in the rat, pregnant rats were dosed at up to 2,000 mg/kg/day (12,000 mg/m2/day; equivalent to 3 times the MRHD) from day 6 of pregnancy through 20 days postpartum (including lactation). At 2,000 mg/kg/day, no maternal toxicity was observed, nor were any changes seen with respect to gestational length or delivery; however, piloerection/pallor, delayed eye opening, decreased body weight, and delayed sexual development were observed in the offspring at 2,000 mg/kg/day. At 200 and 600 mg/kg/day (equivalent to 0.3 and 1 time the MRHD, respectively), slight delays in sexual development (delayed vaginal opening) were observed in the female offspring [see Nonclinical Toxicology (13.2)].

8.2 Lactation

Risk Summary

There are no data on the presence of lanthanum carbonate from lanthanum carbonate chewable tablets in human milk, the effects on the breastfed infant, or the effects on milk production. Deposition of lanthanum into developing bone, including growth plate, was observed in juvenile animals in long-term animal studies with lanthanum carbonate [see Use in Specific Populations (8.4)]. Use a non-lanthanum containing phosphate binder in a lactating woman.

8.4 Pediatric Use

The safety and efficacy of lanthanum carbonate chewable tablets in pediatric patients have not been established. While growth abnormalities were not identified in long-term animal studies, lanthanum was deposited into developing bone, including growth plate. The consequences of such deposition in developing bone in pediatric patients are unknown; therefore, the use of lanthanum carbonate chewable tablets in this population is not recommended.

8.5 Geriatric Use

Of the total number of patients in clinical studies of lanthanum carbonate chewable tablets, 32% (538) were ≥65 years of age, while 9.3% (159) were ≥75 years of age. No overall differences in safety or effectiveness were observed between patients ≥65 years of age and younger patients.

10 OVERDOSAGE

The symptoms associated with overdose are adverse reactions such as headache, nausea and vomiting. In clinical trials in healthy adults, gastrointestinal (GI) symptoms were reported with daily doses up to 6,000 mg/day of lanthanum carbonate administered with food. Given the topical activity of lanthanum in the gut, and the excretion of the majority of the dose in feces, supportive therapy is recommended for overdosage. Lanthanum carbonate was not acutely toxic in animals by the oral route. No deaths and no adverse effects occurred in mice, rats, or dogs after single oral doses of 2,000 mg/kg (1.7, 3.4, and 11.3 times the MRHD, respectively, on a mg/m2 basis).

11 DESCRIPTION

Lanthanum carbonate chewable tablets contain lanthanum carbonate with molecular formula La2(CO3)3 xH2O (on average x=4 to 5 moles of water) and molecular weight 457.8 (anhydrous mass). Lanthanum carbonate is described as white to almost-white powder. Lanthanum carbonate is practically insoluble in water and is insoluble in organic solvents; it dissolves in dilute mineral acids with effervescence.

Each white to off-white, lanthanum carbonate chewable tablet contains lanthanum carbonate hydrate equivalent to 500 mg, 750 mg, or 1,000 mg of elemental lanthanum and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, dextrates (hydrated), and magnesium stearate.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Lanthanum carbonate is a phosphate binder that reduces absorption of phosphate by forming insoluble lanthanum phosphate complexes that pass through the GI tract unabsorbed. Both serum phosphate and calcium phosphate product are reduced as a consequence of the reduced dietary phosphate absorption.

12.2 Pharmacodynamics

In vitro studies have shown that lanthanum binds phosphate in the physiologically relevant pH range of 3 to 7. In simulated gastric fluid, lanthanum binds approximately 97% of the available phosphate at pH 3 to 5 and 67% at pH 7, when lanthanum is present in a two-fold molar excess to phosphate. Bile acids have not been shown to affect the phosphate binding affinity of lanthanum. In order to bind dietary phosphate, lanthanum carbonate chewable tablets must be administered with or immediately after meals.

In five phase 1 pharmacodynamic studies comparing the reduction from baseline of urinary phosphorus excretion in healthy volunteers (N=143 taking lanthanum carbonate), it was shown that the mean intestinal phosphate binding capacity of lanthanum ranged from 235 to 468 mg phosphorus/day when lanthanum was administered at a dose of 3 g per day with food. By comparison, in one study with an untreated control group (n=10) and another study with a placebo group (n=3), the corresponding mean changes from baseline were 3 mg phosphorus/day and 87 mg phosphorus/day, respectively.

In healthy subjects, lanthanum carbonate oral powder and lanthanum carbonate chewable tablets produced similar effects on urinary phosphate excretion.

12.3 Pharmacokinetics

Absorption and Distribution - Following single- or multiple-dose oral administration of lanthanum carbonate chewable tablets to healthy subjects, the concentration of lanthanum in plasma was very low (bioavailability <0.002%). Following oral administration in patients, the mean lanthanum Cmax was 1.0 ng/mL. During long-term administration (52 weeks) in patients with ESRD, the mean lanthanum concentration in plasma was approximately 0.6 ng/mL. There was a minimal increase in plasma lanthanum concentrations with increasing doses within the therapeutic dose range. The timing of food intake relative to lanthanum administration (during and 30 minutes after food intake) has a negligible effect on the systemic level of lanthanum.

Systemic exposure to lanthanum was approximately 30% higher following administration of lanthanum carbonate oral powder when compared to lanthanum carbonate chewable tablets. However, systemic exposure to lanthanum from both formulations in this study was within the range seen in previous pharmacokinetic studies of Chewable Tablets in healthy individuals.

In vitro, lanthanum is highly bound (>99%) to human plasma proteins, including human serum albumin, α1-acid glycoprotein, and transferrin. Binding to erythrocytes in vivo is negligible in rats.

In animal studies, lanthanum concentrations in several tissues, particularly gastrointestinal tract, mesenteric lymph nodes, bone, and liver, increased over time to levels several orders of magnitude higher than those in plasma. The level of lanthanum in the liver was higher in renally impaired rats due to higher intestinal absorption. Lanthanum was found in the lysosomes and the biliary canal consistent with transcellular transport. Steady state tissue concentrations in bone and liver were achieved in dogs between 4 and 26 weeks. Relatively high levels of lanthanum remained in these tissues for longer than 6 months after cessation of dosing in dogs. There is no evidence from animal studies that lanthanum crosses the blood-brain barrier.

In 105 bone biopsies from patients treated with lanthanum carbonate chewable tablets for up to 4.5 years, rising levels of lanthanum were noted over time. Estimates of elimination half-life from bone ranged from 2.0 to 3.6 years. Steady state bone concentrations were not reached during the period studied.

Metabolism and Elimination - Lanthanum is not metabolized. Lanthanum was cleared from plasma of patients undergoing dialysis with an elimination half-life of 53 hours following discontinuation of therapy.

No information is available regarding the mass balance of lanthanum in humans after oral administration. In rats and dogs, the mean recovery of lanthanum after an oral dose was about 99% and 94%, respectively, and was essentially all from feces. Biliary excretion is the predominant route of elimination for circulating lanthanum in rats. In healthy volunteers administered intravenous (IV) lanthanum as the soluble chloride salt (120 mcg), renal clearance was less than 2% of total plasma clearance.

Drug Interactions

Lanthanum carbonate chewable tablets have a low potential for systemic drug-drug interactions because of the very low bioavailability of lanthanum and because it is not a substrate or inhibitor of major cytochrome P450 enzyme groups involved in drug metabolism (CYP1A2, CYP2C9/10, CYP2C19, CYP2D6, and CYP3A4/5).

Lanthanum carbonate chewable tablets do not alter gastric pH; therefore, lanthanum carbonate chewable tablets drug interactions based on altered gastric pH are not expected.

In an in vitro investigation, lanthanum did not form insoluble complexes when mixed in simulated gastric fluid with warfarin, digoxin, furosemide, phenytoin, metoprolol, and enalapril. Clinical studies have shown that lanthanum carbonate chewable tablets (three doses of 1,000 mg on the day prior to exposure and one dose of 1,000 mg on the day of coadministration) administered 30 minutes earlier did not alter the pharmacokinetics of oral warfarin (10 mg), digoxin (0.5 mg), or metoprolol (100 mg). Potential pharmacodynamic interactions between lanthanum and these drugs (e.g., bleeding time or prothrombin time) were not evaluated. None of the drug interaction studies were done with the maximum recommended therapeutic dose of lanthanum carbonate. No drug interaction studies assessed the effects of drugs on phosphate binding by lanthanum carbonate.

Ciprofloxacin

In a randomized, two-way crossover study in healthy volunteers examining the interaction potential of a single oral dose of ciprofloxacin (750 mg) alone and with lanthanum carbonate (1 g three times a day), the maximum plasma concentration of ciprofloxacin was reduced by 56% and the area under the ciprofloxacin plasma concentration-time curve was reduced by 54%. The 24-hour urinary recovery of ciprofloxacin was reduced 52% by lanthanum carbonate chewable tablets [see Drug Interactions (7.2)].

Levothyroxine

In a single-dose crossover study of levothyroxine (1 mg) with or without simultaneous administration of a single dose of lanthanum carbonate chewable tablets (500 mg) in six euthyroid normal healthy volunteers, the area under the serum T4 concentration-time curve was decreased by 40% [see Drug Interactions (7.3)].

Fat-Soluble Vitamins

Lanthanum carbonate chewable tablets appear not to affect the availability of fat-soluble vitamins (A, D, E, and K) or other nutrients [see Clinical Studies (14.2)].

Citrate

Citrate did not increase the absorption of lanthanum.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Oral administration of lanthanum carbonate to rats for up to 104 weeks, at doses up to 1,500 mg of the salt per kg/day (2.5 times the MRHD of 5,725 mg, on a mg/m2 basis, assuming a 60-kg patient) revealed no evidence of carcinogenic potential. In the mouse, oral administration of lanthanum carbonate for up to 99 weeks, at a dose of 1,500 mg/kg/day (1.3 times the MRHD) was associated with an increased incidence of glandular stomach adenomas in male mice.

Lanthanum carbonate tested negative for mutagenic activity in an in vitro Ames assay using Salmonella typhimurium and Escherichia coli strains and in vitro HGPRT gene mutation and chromosomal aberration assays in Chinese hamster ovary cells. Lanthanum carbonate also tested negative in an oral mouse micronucleus assay at doses up to 2,000 mg/kg (1.7 times the MRHD), and in micronucleus and unscheduled DNA synthesis assays in rats given IV lanthanum chloride at doses up to 0.1 mg/kg, a dose that produced plasma lanthanum concentrations greater than 2,000 times the peak human plasma concentration.

Lanthanum carbonate, at doses up to 2,000 mg/kg/day (3.4 times the MRHD), did not affect fertility or mating performance of male or female rats.

13.2 Animal Toxicology and/or Pharmacology

In pregnant rats, oral administration of lanthanum carbonate at doses as high as 2,000 mg/kg/day (3.4 times the MRHD) resulted in no evidence of harm to the fetus. In pregnant rabbits, oral administration of lanthanum carbonate at 1,500 mg/kg/day (5 times the MRHD) was associated with a reduction in maternal body weight gain and food consumption, increased post-implantation loss, reduced fetal weights, and delayed fetal ossification. No effects on pregnant rabbits or fetuses were observed at 750 mg/kg/day (2.5 times the MRHD). Lanthanum carbonate administered to rats from implantation through lactation at 2,000 mg/kg/day (3.4 times the MRHD) caused delayed eye opening, reduction in body weight gain, and delayed sexual development (preputial separation and vaginal opening) of the offspring. At 200 and 600 mg/kg/day (equivalent to 0.3 and 1 time the MRHD, respectively), slight delays in vaginal opening were observed in the female offspring.

14 CLINICAL STUDIES

The effectiveness of lanthanum carbonate chewable tablets in reducing serum phosphorus in patients with ESRD was demonstrated in one short-term, placebo-controlled, double-blind dose-ranging study; two placebo-controlled, randomized withdrawal studies; and two long-term, active-controlled, open-label studies in patients undergoing either hemodialysis or  peritoneal dialysis.

14.1 Double-Blind Placebo-Controlled Studies

One-hundred and forty-four patients with chronic renal failure undergoing hemodialysis and with elevated phosphate levels were randomized to double-blind treatment at a fixed dose of lanthanum carbonate of 225 mg (n=27), 675 mg (n=29), 1,350 mg (n=30), or 2,250 mg (n=26) or placebo (n=32) in divided doses with meals. Fifty-five percent of subjects were male, 71% black, 25% white, and 4% of other races. The mean age was 56 years and the duration of dialysis ranged from 0.5 to 15.3 years. Steady-state effects were achieved after two weeks. The effect after six weeks of treatment is shown in Figure 1.

Figure 1. Difference in Phosphate Reduction in the Lanthanum Carbonate Chewable Tablets and Placebo Group in a 6-Week, Dose-Ranging, Double-Blind Study in Patients with ESRD (with 95% Confidence Intervals)

fig1

One-hundred and eighty-five patients with ESRD undergoing either hemodialysis (n=146) or peritoneal dialysis (n=39) were enrolled in two placebo-controlled, randomized withdrawal studies. Sixty-four percent of subjects were male, 28% black, 62% white, and 10% of other races. The mean age was 58.4 years and the duration of dialysis ranged from 0.2 to 21.4 years. After titration of lanthanum carbonate to achieve a phosphate level between 4.0 and 5.6 mg/dL in one study (doses up to 2,250 mg/day) or ≤5.9 mg/dL in the second study (doses up to 3,000 mg/day) and maintenance through 6 weeks, patients were randomized to lanthanum or placebo. During the placebo-controlled, randomized withdrawal phase (four weeks), the phosphorus concentration rose in the placebo group by 1.7 mg/dL in one study and 1.9 mg/dL in the other study relative to patients who remained on lanthanum carbonate therapy.

14.2 Open-Label Active-Controlled Studies

Two long-term open-label studies were conducted, involving a total of 2,028 patients with ESRD undergoing hemodialysis. Patients were randomized to receive lanthanum carbonate chewable tablets or alternative phosphate binders for up to six months in one study and two years in the other. The daily lanthanum carbonate chewable tablet doses, divided and taken with meals, ranged from 375 mg to 3,000 mg. Doses were titrated to reduce serum phosphate levels to a target level. The daily doses of the alternative therapy were based on current prescribing information or those commonly utilized. Both treatment groups had similar reductions in serum phosphate of about 1.8 mg/dL. Maintenance of reduction was observed for up to three years in patients treated with lanthanum carbonate chewable tablets in long-term, open-label extensions.

No effects of lanthanum carbonate chewable tablets on serum levels of 25-dihydroxy vitamin D3, vitamin A, vitamin B12, vitamin E, and vitamin K were observed in patients who were monitored for 6 months.

Paired bone biopsies (at baseline and at one or two years) in 69 patients randomized to either lanthanum carbonate chewable tablets or calcium carbonate in one study and 99 patients randomized to either lanthanum carbonate chewable tablets or alternative therapy in a second study showed no differences in the development of mineralization defects between the groups.

Vital status was known for over 2,000 patients, 97% of those participating in the clinical program during and after receiving treatment. The adjusted yearly mortality rate (rate/years of observation) for patients treated with lanthanum carbonate chewable tablets or alternative therapy was 6.6%.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Lanthanum carbonate chewable tablets are available as:

500 mg: White to off-white, round, flat-faced, beveled-edge tablet, debossed with stylized b over 1137 on one side and plain on the other side. Available in a Patient Pack: 2 Bottles of 45 Tablets (NDC 0093-5938-98).

750 mg: White to off-white, round, flat-faced, beveled-edge tablet, debossed with stylized b over 750 on one side and plain on the other side. Available in a Patient Pack: 6 Bottles of 15 Tablets (NDC 0093-5939-98).

1,000 mg: White to off-white, round, flat-faced, beveled-edge tablet, debossed with stylized b over 1139 on one side and plain on the other side. Available in a Patient Pack: 9 Bottles of 10 Tablets (NDC 0093-5940-98).

Storage and Handling

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

Manufactured In India By:
Watson Pharma Private Limited
Verna, Salcette Goa 403 722 India

Manufactured For:
Teva Pharmaceuticals USA, Inc.
North Wales, PA 19454

Rev. A 9/2023

MEDICATION GUIDE

Lanthanum Carbonate (lan' tha num kar' bo nateChewable Tablets

Read this Medication Guide before you start taking lanthanum carbonate chewable tablets and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

What is the most important information I should know about lanthanum carbonate chewable tablets?

Lanthanum carbonate chewable tablets may cause a bowel blockage, a hole in the bowel, or severe constipation, which can be serious, and sometimes lead to surgery or treatment in a hospital.

Do not swallow lanthanum carbonate chewable tablets whole. Chew tablets completely before swallowing. If you cannot chew tablets completely, you may crush the tablets thoroughly before swallowing or discuss the oral powder formulation with your healthcare provider.

What are lanthanum carbonate chewable tablets?

Lanthanum carbonate chewable tablets are a prescription medicine used in people with end-stage renal disease (ESRD) to lower the amount of phosphate in the blood.

Who should not take lanthanum carbonate chewable tablets?

Do not take lanthanum carbonate chewable tablets if you:

Lanthanum carbonate chewable tablets have not been studied in children and adolescents under 18 years of age.

What should I tell my healthcare provider before taking lanthanum carbonate chewable tablets?

Lanthanum carbonate chewable tablets may not be right for you. Before starting lanthanum carbonate chewable tablets, tell your healthcare provider if you:

Especially tell your healthcare provider if you take:

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.

How should I take lanthanum carbonate chewable tablets?

What are possible or reasonably likely side effects of lanthanum carbonate chewable tablets?

See “What is the most important information I should know about lanthanum carbonate chewable tablets?”

The most common side effects of lanthanum carbonate chewable tablets include:

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the side effects of lanthanum carbonate chewable tablets. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store lanthanum carbonate chewable tablets?

Keep lanthanum carbonate chewable tablets and all medicines out of the reach of children.

General information about lanthanum carbonate chewable tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use lanthanum carbonate chewable tablets for a condition for which they were not prescribed. Do not give lanthanum carbonate chewable tablets to other people, even if they have the same condition. It may harm them.

This Medication Guide summarizes the most important information about lanthanum carbonate chewable tablets. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about lanthanum carbonate chewable tablets that is written for healthcare professionals.

For more information call Teva  at 1-888-838-2872.

What are the ingredients in lanthanum carbonate chewable tablets?

Active ingredient: lanthanum carbonate
Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, dextrates (hydrated), and magnesium stearate.

This Medication Guide has been approved by the US Food and Drug Administration.

Manufactured In India By:
Watson Pharma Private Limited
Verna, Salcette Goa 403 722 India

Manufactured For:
Teva Pharmaceuticals USA, Inc.
North Wales, PA 19454

Rev. A 9/2023

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 0093-5938-98

Lanthanum Carbonate Chewable Tablets

500 mg*

*Active Ingredient: Each tablet contains 500 mg of lanthanum as lanthanum carbonate hydrate.

Inactive Ingredients: Colloidal silicon dioxide, croscarmellose sodium, dextrates (hydrated) and magnesium stearate.

Do not swallow tablets whole.
Chew or crush tablets completely before swallowing.
Take with or immediately after meals.

Pharmacist: Dispense the accompanying Medication Guide to each patient.

PATIENT PACK ONE MONTH SUPPLY

Rx only

2 BOTTLES/45 CHEWABLE TABLETS EACH

500 mg Carton

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 0093-5939-98

Lanthanum Carbonate Chewable Tablets

750 mg*

*Active Ingredient: Each tablet contains 750 mg of lanthanum as lanthanum carbonate hydrate.

Inactive Ingredients: Colloidal silicon dioxide, croscarmellose sodium, dextrates (hydrated) and magnesium stearate.

Do not swallow tablets whole.

Chew or crush tablets completely before swallowing.

Take with or immediately after meals.

Pharmacist: Dispense the accompanying Medication Guide to each patient.

PATIENT PACK ONE MONTH SUPPLY

Rx only

6 BOTTLES/15 CHEWABLE TABLETS EACH

Carton 750 mg

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 0093-5940-98

Lanthanum Carbonate Chewable Tablets

1000 mg*

*Active Ingredient: Each tablet contains 1000 mg of lanthanum as lanthanum carbonate hydrate.

Inactive Ingredients: Colloidal silicon dioxide, croscarmellose sodium, dextrates (hydrated) and magnesium stearate.

Do not swallow tablets whole.

Chew or crush tablets completely before swallowing.

Take with or immediately after meals.

Pharmacist: Dispense the accompanying Medication Guide to each patient.

PATIENT PACK ONE MONTH SUPPLY

9 BOTTLES/10 CHEWABLE TABLETS EACH

Carton 1000 mg
LANTHANUM CARBONATE 
lanthanum carbonate tablet, chewable
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0093-5938
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
LANTHANUM CARBONATE (UNII: 490D9F069T) (LANTHANUM CATION (3+) - UNII:O7FU5X12W5) LANTHANUM CATION (3+)500 mg
Inactive Ingredients
Ingredient NameStrength
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)  
DEXTRATES (UNII: G263MI44RU)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
Product Characteristics
Colorwhite (White to off-white) Scoreno score
ShapeROUNDSize18mm
FlavorImprint Code b;1137
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:0093-5938-982 in 1 CARTON05/25/2022
1NDC:0093-5938-5445 in 1 BOTTLE; Type 0: Not a Combination Product
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA09097705/25/2022
LANTHANUM CARBONATE 
lanthanum carbonate tablet, chewable
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0093-5939
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
LANTHANUM CARBONATE (UNII: 490D9F069T) (LANTHANUM CATION (3+) - UNII:O7FU5X12W5) LANTHANUM CATION (3+)750 mg
Inactive Ingredients
Ingredient NameStrength
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)  
DEXTRATES (UNII: G263MI44RU)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
Product Characteristics
Colorwhite (White to off-white) Scoreno score
ShapeROUNDSize20mm
FlavorImprint Code b;750
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:0093-5939-986 in 1 CARTON05/25/2022
1NDC:0093-5939-8515 in 1 BOTTLE; Type 0: Not a Combination Product
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA09097705/25/2022
LANTHANUM CARBONATE 
lanthanum carbonate tablet, chewable
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0093-5940
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
LANTHANUM CARBONATE (UNII: 490D9F069T) (LANTHANUM CATION (3+) - UNII:O7FU5X12W5) LANTHANUM CATION (3+)1000 mg
Inactive Ingredients
Ingredient NameStrength
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)  
DEXTRATES (UNII: G263MI44RU)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
Product Characteristics
Colorwhite (White to off-white) Scoreno score
ShapeROUNDSize22mm
FlavorImprint Code b;1139
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:0093-5940-989 in 1 CARTON05/25/2022
1NDC:0093-5940-4010 in 1 BOTTLE; Type 0: Not a Combination Product
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA09097705/25/2022
Labeler - Teva Pharmaceuticals USA, Inc. (001627975)

Revised: 9/2023
Document Id: c7a37d6c-c06f-440c-8c13-37508567f1fc
Set id: e4b88992-ecb0-455b-b68c-5c4e6d3cf521
Version: 5
Effective Time: 20230929
 
Teva Pharmaceuticals USA, Inc.