Fosrenol

Contraindications

Bowel obstruction

Ileus

Fecal impaction

Cautions

Use with caution in PUD, Crohn's disease, ulcerative colitis, bowel obstruction

Serious cases of gastrointestinal obstruction, ileus, subileus, gastrointestinal perforation and fecal impaction reported; risk factors for gastrointestinal obstruction and gastrointestinal perforation in patients taking chewable tablets include altered gastrointestinal anatomy (e.g., diverticular disease, peritonitis, history of gastrointestinal surgery, gastrointestinal colon cancer, gastrointestinal ulceration), hypomotility disorders (e.g., constipation, ileus, subileus, diabetic gastroparesis) and concomitant medications (e.g., calcium channel blockers); cases were reported in patients with no history of gastrointestinal disease; advise patients prescribed chewable tablets to chew tablet completely to reduce risk of serious adverse gastrointestinal events

Has radio-opaque properties and therefore may give the appearance typical of an imaging agent during abdominal X-ray procedures

Chewable tablets should be chewed completely to reduce the risk of serious adverse gastrointestinal events

Pregnancy, lactation

You should not use lanthanum carbonate if you are allergic to it, or if you have a bowel obstruction or severe constipation.

Before you take lanthanum carbonate, tell your doctor if you have a stomach ulcer, ulcerative colitis, Crohn's disease, diabetes, any type of bowel obstruction, or a history of colon cancer or intestinal surgery.

The chewable tablet should be chewed completely before you swallow it.

Take lanthanum carbonate with food or immediately after eating.

Tell your doctor about all other medicines you use, especially antibiotics, seizure medication, heart or blood pressure medication, or a blood thinner.

If you also take thyroid replacement medication, take it at least 2 hours before or after taking lanthanum carbonate. Do not take thyroid medication and lanthanum carbonate at the same time.

Avoid taking an antacid within 2 hours before or after you take lanthanum carbonate. Some antacids can make it harder for your body to absorb lanthanum carbonate.

If you need to have any type of x-ray or CT scan using a dye that is injected into your veins, tell the doctor ahead of time that you are using lanthanum carbonate.

Administration

Oral Administration

Administer orally in divided doses with or immediately after meals (in order to bind dietary phosphates efficiently).1 2

Chew tablets completely before swallowing; do not swallow intact tablets.1

Dosage

Available as lanthanum carbonate; dosage expressed in terms of lanthanum.1 2

Adults

Initially, 750 mg–1.5 g daily.1

Adjust dosage at 2- to 3-week intervals until serum phosphorus concentration is acceptable; generally titrated in increments of 750 mg daily in clinical studies.1 2

Dosage of 1.5–3 g daily usually is required to reduce serum phosphorus concentrations to <6 mg/dL;1 2 dosages up to 3.75 g daily have been studied.1

Monitor serum phosphorus concentrations as needed during titration and regularly thereafter.1

Absorption

Information regarding the mass balance of lanthanum in humans after oral administration is not available.1

Bioavailability

Minimally absorbed from the GI tract; bioavailability <0.002%.1 2 3 4 5

Minimal effect on systemic lanthanum concentrations.1

Mean plasma concentrations of the drug remain low (≤1.1 ng/mL) for up to 2 years of use.1 2 3 Plasma concentrations increase minimally with increasing dosages in the recommended range.1

Distribution

Extent

Distributed into bone; bone lanthanum concentrations increase over time (e.g., 4.5 years of administration).1

Does not appear to cross the blood-brain barrier in animals.1 2 5

Plasma Protein Binding

>99%.1

Elimination

Metabolism

Not metabolized.1

Elimination Route

In animals, excreted principally in the feces (94–99%), mainly as unabsorbed drug; systemically absorbed lanthanum is eliminated in the feces, principally via biliary excretion.1 2 5

Minimally excreted in urine in healthy individuals (renal clearance of IV lanthanum chloride [not commercially available in the US] is <2% of total plasma clearance).1 5

Half-life

Plasma: 53 hours.1

Bone: 2–3.6 years.1

Special Populations

In lanthanum-treated patients with ESRD, no quantifiable amounts were present in the dialysate.1

• Dissociates in the acidic environment of the upper GI tract to release trivalent lanthanum ions, which bind dietary phosphate released during digestion, thereby forming highly insoluble lanthanum phosphate complexes that are excreted fecally.1 2 5

• Lanthanum ions have a high affinity for phosphate; the drug binds about 97% of available phosphates in vitro at pH 3–5 (corresponding to that of gastric fluid) when in twofold molar excess to phosphates.1 2

• Reduces phosphate absorption, serum phosphorus concentrations, and serum calcium times phosphorus product (Ca × P).1 2 3

• Importance of adhering to instructions about diet.1

• Importance of taking lanthanum with or immediately after meals.1 12

• Importance of chewing tablets completely before swallowing, and not swallowing intact tablets.1

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

• Importance of informing patients of other important precautionary information. (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Fosrenol is a phosphate binder indicated to reduce serum phosphate in patients with end stage renal disease (ESRD).

Management of elevated serum phosphorus levels in end stage renal disease patients 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.

Contraindicated in bowel obstruction, including ileus and fecal impaction.

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

There are no empirical data on avoiding drug interactions between Fosrenol 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 Fosrenol 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 Fosrenol. 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 Fosrenol with quinolone antibiotics may reduce the extent of their absorption. The bioavailability of oral ciprofloxacin was decreased by approximately 50% when taken with Fosrenol in a single dose study in healthy volunteers. Administer oral quinolone antibiotics at least 1 hour before or 4 hours after Fosrenol. When oral quinolones are given for short courses, consider eliminating the doses of Fosrenol 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 Fosrenol. Administer thyroid hormone replacement therapy at least 2 hours before or 2 hours after dosing with Fosrenol and monitor thyroid stimulating hormone (TSH) levels [see Clinical Pharmacology (12.3)] .

Advise the patient to read the FDA-approved patient labelling (Medication Guide).

Advise patients to take Fosrenol with or immediately after meals [see Dosage and Administration (2)] .

Instruct patients on concomitant medications that should be dosed apart from Fosrenol [see Drug Interactions (7)]

Instruct patients who are prescribed Fosrenol Chewable Tablets to chew or crush tablets completely before swallowing. Emphasize that Fosrenol Chewable Tablets should not be swallowed intact. Consider crushing Fosrenol 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)].

Instruct patients who are prescribed Fosrenol Oral Powder to sprinkle powder on a small quantity of applesauce or other similar food. Patients should be instructed to consume the entire dose immediately. Fosrenol Oral Powder is insoluble so no attempt should be made to dissolve the powder in liquid for administration [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 Fosrenol from the dosing of the affected drug by several hours [see Drug Interactions (7)].

Advise patients to notify their physician that they are taking Fosrenol prior to an abdominal X-ray or if they have a history of gastrointestinal disease [see Warnings and Precautions (5.1, 5.2)].

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

Fosrenol Oral Powder manufactured by Catalent Germany Schorndorf GmbH,
Steinbeisstrasse 1-2
D-73614 Schorndorf
Germany

Manufactured for Shire US Inc., 300 Shire Way, Lexington, MA 02421.

Fosrenol ® is registered in the U.S. Patent and Trademark Office.
© 2016 Shire US Inc.

This product is covered by US patents 5,968,976, 7,465,465, 8,980,327 and 9,023,397.

MEDICATION GUIDE
Fosrenol® (foss-wren-all)
(lanthanum carbonate)

Read this Medication Guide before you start taking Fosrenol 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 Fosrenol?

Fosrenol 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 Fosrenol 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 Fosrenol Chewable Tablets whole. Chew tablets completely before swallowing. If you can not chew tablets completely, you may crush the tablets thoroughly before swallowing or discuss the oral powder formulation with your healthcare provider.

What is Fosrenol?

Fosrenol 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 Fosrenol?

Do not take Fosrenol if you:

• have blocked bowels
• have severe constipation

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

What should I tell my healthcare provider before taking Fosrenol?

Fosrenol may not be right for you. Before starting Fosrenol, 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. It is not known if Fosrenol will harm your unborn baby

Tell your healthcare provider about all of 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 Fosrenol?

• Take Fosrenol exactly as prescribed by your healthcare provider
• Your healthcare provider will tell you how much Fosrenol 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.
• Oral Powder – Sprinkle powder on a small quantity of applesauce or other similar food. Consume the entire dose immediately. Fosrenol Oral Powder will not dissolve in liquid.
• Take Fosrenol with or right after meals
• If you take an antacid medicine, take the antacid 2 hours before or 2 hours after you take Fosrenol
• If you take medicine for your thyroid (levothyroxine), take the thyroid medicine 2 hours before or 2 hours after you take Fosrenol
• If you take an antibiotic medicine, take the antibiotic 1 hour before or 4 hours after you take Fosrenol

What are possible or reasonably likely side effects of Fosrenol?

See " What is the most important information I should know about Fosrenol?"

The most common side effects of Fosrenol 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 Fosrenol. 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 Fosrenol?

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

Keep Fosrenol and all medicines out of the reach of children.

General information about Fosrenol

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

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

For more information go to www.Fosrenol.com or call 1-800-828-2088.

What are the ingredients in Fosrenol?

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.

© 2016 Shire US Inc.

300 Shire Way, Lexington, MA 02421.

Issued [02/2016]

NDC 54092-252-45

Fosrenol ®
(lanthanum carbonate)
chewable tablets

500 mg

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

ATTENTION PHARMACIST: Each patient is required
to receive the enclosed Medication Guide.

45 TABLETS
Rx only
Shire

NDC 54092-253-90

Fosrenol ®
(lanthanum carbonate)
chewable tablets

750 mg

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

6 bottles/15 chewable tablets each

Rx only

Shire

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

Inactive Ingredients:
Colloidal silicon dioxide,
dextrates, and magnesium
stearate.

See package insert for full
prescribing information.
Store at 25°C (77°F)
excursions permitted to
15-30°C (59-86°F)
[see USP Controlled Room
Temperature]

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.