Lanthanum Carbonate (Page 3 of 4)

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 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 and Placebo Group in a 6-Week, Dose-Ranging, Double-Blind Study in Patients with ESRD (with 95% Confidence Intervals)

Figure 1
(click image for full-size original)

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 or alternative phosphate binders for up to six months in one study and two years in the other. The daily LANTHANUM CARBONATE 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 in long-term, open-label extensions.

No effects of LANTHANUM CARBONATE 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 or calcium carbonate in one study and 99 patients randomized to either LANTHANUM CARBONATE 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 or alternative therapy was 6.6%.

16 HOW SUPPLIED/STORAGE AND HANDLING

LANTHANUM CARBONATE is supplied as a chewable tablet in three dosage strengths for oral administration: 500-mg tablets, 750-mg tablets, and 1,000-mg tablets. Each chewable tablet is white to off-white round, flat with a beveled edge, and debossed on one side with ‘S405’ above the dosage strength corresponding to the content of elemental lanthanum.

500-mg Patient Pack (2 bottles of 45 tablets, NDC 66993-422-47, per each patient pack) NDC 66993-422-85.

750-mg Patient Pack (6 bottles of 15 tablets, NDC 66993-423-53, per each patient pack) NDC 66993-423-85.

1,000-mg Patient Pack (9 bottles of 10 tablets, NDC 66993-424-75, per each patient pack) NDC 66993-424-85.

Storage and Handling

Store LANTHANUM CARBONATE Chewable Tablets at 25°C (77°F): excursions permitted to 15°C to 30°C (59°F to 86°F).
[See USP controlled room temperature.]

17 PATIENT COUNSELING INFORMATION

  • Advise the patient to read the FDA-approved patient labeling (Medication Guide).
  • Advise patients to take LANTHANUM CARBONATE with or immediately after meals [see Dosage and Administration (2)].
  • Instruct patients on concomitant medications that should be dosed apart from LANTHANUM CARBONATE [see Drug Interactions (7)].
  • Instruct patients who are prescribed LANTHANUM CARBONATE Chewable Tablets to chew or crush tablets completely before swallowing. Emphasize that LANTHANUM CARBONATE Chewable Tablets should not be swallowed intact. Consider crushing LANTHANUM CARBONATE Chewable Tablets completely or prescribing the oral powder formulation for patients with poor dentition or who have difficulty chewing tablets [see Dosage and Administration (2)].
  • Advise patients who are taking an oral medication where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy to separate the dosing of LANTHANUM CARBONATE from the dosing of the affected drug by several hours [see Drug Interactions (7)].
  • Advise patients to notify their physician that they are taking LANTHANUM CARBONATE prior to an abdominal X-ray or if they have a history of gastrointestinal disease [see Warnings and Precautions (5.1, 5.2)].

LANTHANUM CARBONATE Chewable Tablets manufactured by Patheon Manufacturing
Services LLC,
5900 Martin Luther King Jr. Highway
Greenville, NC 27834

Distributed by:
Prasco Laboratories
Mason, OH 45040 USA

Patented: see www.takeda.com/en-us/patents

MEDICATION GUIDE LANTHANUM CARBONATE (LAN-tha-num KAR-bo-nate)

Read this Medication Guide before you start taking LANTHANUM CARBONATE 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?

LANTHANUM CARBONATE 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.

  • You may have a higher risk of bowel blockage, a hole in the bowel, or severe constipation if you take LANTHANUM CARBONATE and have:
    • a history of surgery, ulcers or cancer in the stomach or bowel
    • a history of bowel blockage, or problems resulting in a decreased movement of food through your stomach and bowel (e.g., feeling full quickly after eating or constipation)
    • an infection or inflammation of the stomach/bowel (peritonitis)

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 is LANTHANUM CARBONATE?

LANTHANUM CARBONATE is 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?

Do not take LANTHANUM CARBONATE if you:

  • have blocked bowels
  • have severe constipation

LANTHANUM CARBONATE has not been studied in children and adolescents under 18 years of age.

What should I tell my healthcare provider before taking LANTHANUM CARBONATE?

LANTHANUM CARBONATE may not be right for you. Before starting LANTHANUM CARBONATE, tell your healthcare provider if you:

  • have a history of surgery, ulcers or cancer in the stomach or bowel
  • have a history of a bowel blockage, constipation, or problems resulting in a decreased movement of food through your stomach and bowel especially if you also have diabetes
  • have ulcerative colitis, Crohn’s disease or an infection or inflammation of the stomach/bowel (peritonitis)
  • plan to have an X-ray of your stomach (abdomen)
  • have any other medical conditions
  • are pregnant, plan to become pregnant, or plan to breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Especially tell your healthcare provider if you take:

  • antacids
  • antibiotics
  • thyroid medicine

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?

  • Take LANTHANUM CARBONATE exactly as prescribed by your healthcare provider
  • Your healthcare provider will tell you how much LANTHANUM CARBONATE to take
  • Your healthcare provider may change your dose if needed
  • Chewable Tablets — Do not swallow tablets whole. Chew tablets completely before swallowing. If you cannot chew tablets completely, or if you have tooth disease, you may crush the tablets thoroughly before swallowing or discuss the oral powder formulation with your healthcare provider.
  • Take LANTHANUM CARBONATE with or right after meals
  • If you take an antacid medicine, take the antacid 2 hours before or 2 hours after you take LANTHANUM CARBONATE
  • If you take medicine for your thyroid (levothyroxine), take the thyroid medicine 2 hours before or 2 hours after you take LANTHANUM CARBONATE
  • If you take an antibiotic medicine, take the antibiotic 1 hour before or 4 hours after you take LANTHANUM CARBONATE

What are possible or reasonably likely side effects of LANTHANUM CARBONATE?

See What is the most important information I should know about LANTHANUM CARBONATE?

The most common side effects of LANTHANUM CARBONATE include:

  • nausea
  • vomiting
  • diarrhea
  • stomach pain

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. 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?

  • Store LANTHANUM CARBONATE between 59°F to 86°F (15°C to 30°C).

Keep LANTHANUM CARBONATE and all medicines out of the reach of children.

General information about LANTHANUM CARBONATE

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use LANTHANUM CARBONATE for a condition for which it was not prescribed. Do not give LANTHANUM CARBONATE 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. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about LANTHANUM CARBONATE that is written for healthcare professionals.

For more information call 1-800-828-2088.

What are the ingredients in LANTHANUM CARBONATE?

Active ingredient: lanthanum carbonate

Inactive ingredients: colloidal silicon dioxide NF, dextrates (hydrated) NF, and magnesium stearate NF.

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

Distributed by:
Prasco Laboratories
Mason, OH 45040 USA

Rev [8/2020]

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