Lanthanum Carbonate Tablets

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

Lanthanum in lanthanum carbonate chewable tablets has the potential to bind to drugs with anionic (e.g., carboxyl, carbonyl and hydroxyl) groups. Lanthanum carbonate chewable tablets may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.
 

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.

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.

Quinolone Antibiotics

Co-administration 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 be normally scheduled near the time of quinolone intake to improve quinolone absorption [see Clinical Pharmacology (12.3)].

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)].

Lanthanum carbonate chewable tablet contains lanthanum carbonate dihydrate with molecular formula La2(CO3)3 .2H2O and molecular weight 457.8 (anhydrous mass). Lanthanum carbonate is described as white to off-white powder.  Lanthanum carbonate is soluble in dilute hydrochloric acid and practically insoluble in water.

Each lanthanum carbonate chewable tablets, white to off-white,  chewable tablet contains lanthanum carbonate dihydrate equivalent to 500, 750 or 1000 mg of elemental lanthanum and the following inactive ingredients: colloidal silicon dioxide, dextrates, hydroxy propyl cellulose, magnesium stearate and talc.

The effectiveness of lanthanum carbonate chewable tablets in reducing serum phosphorus in ESRD patients 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 both hemodialysis and peritoneal dialysis (PD) patients.

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), 1350 mg (n=30) or 2250 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 ESRD Patients (with 95% Confidence Intervals)

One-hundred and eighty-five patients with end stage renal disease 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 2250 mg/day) or <5.9 mg/dL in the second study (doses up to 3000 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.

Open-Label Active-Controlled Studies

Two long-term open-label studies were conducted, involving a total of 2028 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 tablets dose, divided and taken with meals, ranged from 375 mg to 3000 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 2000 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%.

Lanthanum carbonate chewable tablets

Lanthanum carbonate chewable tablets are supplied in three dosage strengths as lanthanum for oral administration: 500 mg tablets, 750 mg tablets, and 1000 mg tablets.
 
Lanthanum carbonate chewable tablets, 500 mg (as lanthanum) are white to off white round shaped tablets debossed ‘NAT’ on one side and ‘500’ on other side, supplied in patient pack (2 bottles of 45 chewable tablets each NDC 68180-819-52) NDC 68180-819-42.

Lanthanum carbonate chewable tablets, 750 mg (as lanthanum) are white to off white round shaped tablets debossed ‘NAT’ on one side and ‘750’ on other side, supplied in patient pack (6 bottles of 15 chewable tablets each NDC 68180-820-53) NDC 68180-820-46.

Lanthanum carbonate chewable tablets, 1000 mg (as lanthanum) are white to off white round shaped tablets debossed ‘NAT’ on one side and ‘1000’ on other side, supplied in patient pack (9 bottles of 10 chewable tablets each  NDC 68180-821-10) NDC 68180-821-47.

Storage - Store at 25ºC (77ºF): excursions permitted to 15º to 30˚C (59º to 86ºF). [See USP controlled room temperature].

Label artwork:
NDC 68180-820-53
Bottle of 15 tablets
Each chewable tablet contains 750 mg of lanthanum as lanthanum carbonate dihydrate

Carton artwork:
NDC 68180-820-46
Each chewable tablet contains 750 mg of lanthanum as lanthanum carbonate dihydrate
PATIENT PACK ONE MONTH SUPPLY
ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide