Lanthanum Carbonate

LANTHANUM CARBONATE — lanthanum carbonate tablet, chewable
Lupin Pharmaceuticals, Inc.

1 INDICATIONS AND USAGE

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

In clinical studies 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.

Information for lanthanum carbonate chewable tablets
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

Lanthanum Carbonate Chewable Tablets: 500 mg, 750 mg, and 1000 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.
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.

During treatment with lanthanum carbonate chewable tablets, physicians and patients should remain vigilant for signs and symptoms of gastrointestinal disorders, especially constipation and abdominal pain/distention, which may indicate bowel obstruction, ileus, or subileus.

Treatment with lanthanum carbonate chewable tablets should be re-evaluated in patients who develop severe constipation or other severe gastrointestinal signs and symptoms.

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.

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:

• Gastrointestinal Adverse Effects [see Warnings and Precautions (5.1)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 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 have 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 tablets 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 tablets group were nausea, vomiting, and abdominal pain (Table 1).

Table 1: Adverse Reactions* That Were More Common on Lanthanum Carbonate Chewable

* Expressed as the event rate for each term
	Lanthanum Carbonate Chewable Tablets % (N=180)	Placebo % (N=95)
Nausea	11	5
Vomiting	9	4
Abdominal pain	5	0

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 chewable tablets to lanthanum 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.