Actonel with Calcium

Actonel with Calcium is a co-package product containing ACTONEL (risedronate sodium tablets, 35 mg) for once weekly dosing and calcium carbonate tablets, USP (1250 mg, equivalent to 500 mg elemental calcium) for daily dosing for the remaining 6 days of the week. Each package contains a 28-day course of therapy.

ACTONEL

ACTONEL (risedronate sodium tablets) is a pyridinyl bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism. Each ACTONEL tablet in the Actonel with Calcium co-package contains the equivalent of 35 mg of anhydrous risedronate sodium in the form of the hemi-pentahydrate with small amounts of monohydrate. The empirical formula for risedronate sodium hemi-pentahydrate is C7H10NO7P2Na •2.5 H2O. The chemical name of risedronate sodium is [1-hydroxy-2-(3-pyridinyl)ethylidene]bis[phosphonic acid] monosodium salt. The chemical structure of risedronate sodium hemi-pentahydrate is the following:

Risedronate sodium is a fine, white to off-white, odorless, crystalline powder. It is soluble in water and in aqueous solutions, and essentially insoluble in common organic solvents.

CALCIUM

The empirical formula for calcium carbonate is CaCO3 and the molecular weight is 100.09.

Calcium carbonate is supplied as a calcium carbonate tablet, USP containing 1250 mg calcium carbonate (equivalent to 500 mg elemental calcium). Calcium carbonate is a fine, white, odorless, tasteless powder. It is stable and non-hygroscopic.

Calcium carbonate is formulated per USP standards to meet disintegration or dissolution, weight, purity, and potency requirements.

Inactive Ingredients:

Crospovidone, ferric oxide red, ferric oxide yellow, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, silicon dioxide, titanium dioxide.

Pregelatinized starch, sodium starch glycolate, FD&C Blue #2, magnesium stearate, polyethylene glycol 3350, hypromellose, Opaspray Light Blue, polysorbate 80.

ACTONEL

• Hypocalcemia (see PRECAUTIONS, General)
• Known hypersensitivity to any component of this product
• Inability to stand or sit upright for at least 30 minutes

CALCIUM

• Hypercalcemia from any cause including, but not limited to, hyperparathyroidism, hypercalcemia of malignancy, or sarcoidosis.
• Known hypersensitivity to any component of the product.

Dosage Forms & Strengths

tablet

• 5mg
• 30mg
• 35mg
• 150mg

tablet, delayed release

• 35mg

Postmenopausal Osteoporosis

Treatment and prevention

5 mg PO once daily or 35 mg PO once weekly or 150 mg PO once monthly

35 mg once-weekly dosing copackaged with calcium carbonate 1250 mg for remaining 6 days of week

Glucocorticoid-Induced Osteoporosis

5 mg/day PO

Paget Disease

30 mg/day PO for 2 months

Monitor serum alkaline phosphatase

Osteoporosis in Men

35 mg PO once weekly

Osteogenesis Imperfecta (Orphan)

Orphan indication sponsor

• Warner Chilcott Pharmaceuticals; 100 Enterprise Drive; Rockaway, NJ 07866

Dosing Modifications

Renal impairment

• CrCl >30 mL/min: No dose adjustment necessary
• CrCl <30 mL/min: Not recommended

Hepatic impairment

• Safety and efficacy not established
• No dose adjustment suggested; drug does not undergo hepatic metabolism

Administration

Immediate release

• Take at least 30 minutes with 6-8 oz water before first food or drink of day
• Swallow with plain water only, not coffee or juice
• Stand or sit upright; do not lie down for 30 minutes after taking to avoid esophageal irritation

Delayed release

• Administer in morning immediately after breakfast; compared with immediate-release risedronate, Atelvia resulted in significantly higher incidence of abdominal pain when administered before breakfast under fasting conditions
• To facilitate delivery to stomach, swallow whole while in upright position and with ≥4 oz plain water
• Tablets should not be chewed, cut, or crushed
• Do not lie down for 30 minutes after taking medication

Safety and efficacy not established

Mechanism of Action

Bisphosphonate; binds to hydroxyapatite crystals in bone and inhibits osteoclast-mediated bone resorption

Absorption

Bioavailability: 0.54-0.75%

Peak plasma time: 1-3 hr

Distribution

Protein bound: 24%

Vd: 13.8 L/kg

Metabolism

Not metabolized

Elimination

Half-life: Initial, 1.5 hr; terminal, 480 hr

Renal clearance: 105 mL/min

Total body clearance: 122 mL/min

Excretion: Urine (up to 85%), feces (unabsorbed drug)

Instructions

Immediate release

• Take at least 30 minutes with 6-8 oz water before first food or drink of day
• Swallow with plain water only, not coffee or juice
• Stand or sit upright; do not lie down for 30 minutes after taking to avoid esophageal irritation

Delayed release

• Administer in morning immediately after breakfast; compared with immediate-release risedronate, Atelvia resulted in significantly higher incidence of abdominal pain when administered before breakfast under fasting conditions
• To facilitate delivery to stomach, swallow whole while in upright position and with ≥4 oz plain water
• Tablets should not be chewed, cut, or crushed
• Do not lie down for 30 minutes after taking medication

You should not use Actonel with Calcium if you have low levels of calcium in your blood (hypocalcemia), or a problem with the movement of muscles in your esophagus.

Do not take an Actonel tablet if you cannot sit upright or stand for at least 30 minutes. Risedronate can cause serious problems in the stomach or esophagus (the tube that connects your mouth and stomach).

You should not use Actonel with Calcium if you are allergic to calcium carbonate or risedronate, or if you have:

• low levels of calcium in your blood (hypocalcemia); or

• a problem with the movement of muscles in your esophagus.

Do not take an Actonel tablet if you cannot sit upright or stand for at least 30 minutes. Risedronate can cause serious problems in the stomach or esophagus (the tube that connects your mouth and stomach). You will need to stay upright for at least 30 minutes after taking this medication.

To make sure Actonel with Calcium is safe for you, tell your doctor if you have:

• low or high levels of calcium in your blood;

• kidney disease;

• trouble swallowing; or

• an ulcer in your stomach or esophagus.

In rare cases, this Actonel with Calcium may cause bone loss (osteonecrosis) in the jaw. Symptoms include jaw pain or numbness, red or swollen gums, loose teeth, or slow healing after dental work. The longer you use Actonel with Calcium, the more likely you are to develop this condition.

Osteonecrosis of the jaw may be more likely if you have cancer or received chemotherapy, radiation, or steroids. Other risk factors include blood clotting disorders, anemia (low red blood cells), and a pre existing dental problem.

Talk with your doctor about the risks and benefits of using this Actonel with Calcium.

It is not known whether Actonel with Calcium will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether calcium carbonate and risedronate passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Take Actonel with Calcium exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Actonel with Calcium is packaged as two separate medicines: 4 risedronate tablets and 24 calcium tablets. Take a risedronate tablet one day per week, first thing in the morning, at least 30 minutes before you eat or drink anything or take any other medicine. Take a calcium tablet with food every day for the 6 days in between your risedronate doses.

Only the calcium tablet should be taken with food. Actonel must be taken on an empty stomach.

Take the Actonel tablet first thing in the morning, at least 30 minutes before you eat or drink anything or take any other medicine. Take the Actonel tablet on the same day each week and always first thing in the morning.

Take the Actonel tablet with a full glass (6 to 8 ounces) of water. Use only plain water (not mineral water) when taking a Actonel tablet.

Do not crush, chew, or suck the tablet. Swallow the pill whole.

After taking an Actonel tablet, carefully follow these instructions:

• Do not lie down or recline for at least 30 minutes.

• Do not eat or drink anything other than plain water.

• Do not take any other medicines including vitamins, calcium, or antacids for at least 30 minutes. It may be best to take your other medicines at a different time of the day. Talk with your doctor about the best dosing schedule for your other medicines.

Actonel with Calcium is only part of a complete program of treatment that may also include diet changes, exercise, and taking vitamin supplements. Follow your diet, medication, and exercise routines very closely.

Take only the amount of calcium that your doctor recommends. Do not use other calcium supplements unless your doctor has told you to.

Your bone mineral density will need to be checked often. You may not need to take this medication for longer than 3 to 5 years if you take it for osteoporosis.

Store Actonel with Calcium at room temperature away from moisture and heat.

Usual Adult Dose for Osteoporosis:

Prevention and treatment of osteoporosis in postmenopausal women:

risedronate: 35 mg orally once a week.
calcium carbonate: 1250 mg orally with food once daily on each of the remaining 6 days of the week.

Get emergency medical help if you have signs of an allergic reaction to Actonel with Calcium: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using this medication and call your doctor at once if you have:

• chest pain, new or worsening heartburn;

• difficulty or pain when swallowing;

• pain or burning under the ribs or in the back;

• severe joint, bone, or muscle pain;

• new or unusual pain in your thigh or hip;

• jaw pain, numbness, or swelling; or

• severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common Actonel with Calcium side effects may include:

• mild heartburn, nausea, or stomach upset;

• diarrhea, gas, or constipation;

• muscle, joint, or back pain;

• pain or burning with urination;

• mild skin rash; or

• headache or depressed mood.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.