Boniva

Tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking, especially:

• Angiogenesis inhibitors such as Afinitor and Zortress (everolimus), Avastin (bevacizumab), Nexavar (sorafenib), Sutent (sunitinib), or Votrient (pazopanib)
• Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), such as Advil, Ibu-Tab, Motrin, and others (ibuprofen); or Aleve, Naprelan, Naprosyn, and others (naproxen)
• Chemotherapy for cancer
• Oral steroids such as Decadron (dexamethasone), Medrol (methylprednisolone), or Rayos (prednisone)

Be sure to take any oral medicines, including vitamins and supplements, at least an hour after taking Boniva.

Boniva and Alcohol

Avoid consuming large amounts of alcohol while taking Boniva.

Talk to your doctor about how much alcohol is safe to drink if you're taking Boniva or any other prescription drug.

GENERIC AVAILABLE: Yes

IV Administration

Direct IV injection over 15-30 seconds

Administer over 1 hour for metastatic bond disease

Administer over 2 hours for hypercalcemia of malignancy

Before receiving Boniva tell your doctor about all of your medical conditions including if you:

• Have problems with swallowing
• Have stomach or digestive problems
• Have low blood calcium
• Plan to have dental surgery or teeth removed
• Have kidney problems
• Have been told you have trouble absorbing minerals in your stomach or intestines (malabsorption syndrome)

Tell your doctor if you are pregnant or breastfeeding.

Tell your doctor and dentist about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. 

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Boniva falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans, though. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

It is not known if Boniva crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Boniva.

Take Boniva exactly as your doctor tells you.

Oral:

• Boniva works only if taken on an empty stomach.
• Take 1 Boniva tablet after you get up for the day and before taking your first food, drink, or other medicine.
• Take Boniva while you are sitting or standing.
• Do not chew or suck on a tablet of Boniva.
• Swallow Boniva tablet with a full glass (6-8 oz) of plain water only.
• Do not take Boniva with mineral water, coffee, tea, soda, or juice.
• After swallowing Boniva tablet, wait at least 60 minutes before:
  • lying down. You may sit, stand or walk, and do normal activities like reading.
  • you take your first food or drink except for plain water
  • you take other medicines, including antacids, calcium, and other supplements and vitamins
• Do not lie down for at least 60 minutes after you take Boniva and do not eat your first food of the day for at least 60 minutes after you take Boniva.
• If you miss a dose of Boniva, do not take it later in the day. Call your doctor for instructions.

Injectable:

• This medication is also available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Does not induce or inhibit CYP isoenzymes (i.e., CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, or 3A4)4 7 and is not metabolized.1 4 7

Antacids or Mineral Supplements Containing Divalent Cations

Pharmacokinetic interaction (decreased absorption of ibandronate) when tablets are used concomitantly with antacids or mineral supplements containing divalent cations (e.g., aluminum, calcium, magnesium, iron).1 5 44 Administer tablets ≥60 minutes prior to such drugs or supplements.1 5

Drugs Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interactions unlikely.1

Drugs Excreted through Renal Tubular Transport

Based on limited data in animals, not excreted through renal tubular transport.1 4 7 Pharmacokinetic interaction unlikely.1 4

Nephrotoxic Agents

Potential pharmacologic interaction (increased risk of renal toxicity). 4 7 8 9 10 11 12 Assess patients taking concomitant nephrotoxic agents.1 7 (See Renal Effects under Cautions.)

Specific Drugs and Tests

Important Administration Instructions

Boniva Injection must be administered intravenously only by a health care professional. Care must be taken not to administer intra-arterially or paravenously as this could lead to tissue damage [see Warnings and Precautions (5.4)].

• Appropriate medical support and monitoring measures should be readily available when Boniva Injection is administered. If anaphylactic or other severe hypersensitivity/allergic reactions occur, immediately discontinue the injection and initiate appropriate treatment [see Warnings and Precautions (5.2)].
• Visually inspect the liquid in the prefilled syringe for particulate matter and discoloration before administration. Do not use prefilled syringes with particulate matter or discoloration.
• Administer only with the enclosed needle.
• Discard any unused portion.
• Do not mix with calcium-containing solutions or other intravenously administered drugs.
• Prefilled syringes are for single use only.

Dosage Information

The recommended dose of Boniva Injection for the treatment of postmenopausal osteoporosis is 3 mg every 3 months administered intravenously over a period of 15 to 30 seconds. Do not administer more frequently than once every 3 months.

Laboratory Testing and Oral Examination Prior to Administration

Prior to administration of each dose obtain a serum creatinine [see Warnings and Precautions (5.3)]. Given that bisphosphonates have been associated with osteonecrosis of the jaw (ONJ), perform a routine oral examination prior to administration of Boniva Injection.

Calcium and Vitamin D Supplementation

Instruct patients to take supplemental calcium and vitamin D if their dietary intake is inadequate [see Warnings and Precautions (5.1)].

Dosing After Missed Dose

If the dose is missed, administer as soon as it can be re-scheduled. Thereafter, Boniva Injection should be scheduled every 3 months from the date of the last injection.

Dosage Modifications in Patients with Renal Impairment

Do not administer to patients with severe renal impairment (creatinine clearance less than 30 mL/minute) [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)]. No dose adjustment is necessary for patients with mild or moderate renal impairment (creatinine clearance greater than or equal to 30 mL/min) [see Clinical Pharmacology (12.3)].

Boniva is contraindicated in patients with the following conditions:

• Hypocalcemia [see Warnings and Precautions (5.1)]
• Known hypersensitivity to Boniva Injection or to any of its excipients. Cases of anaphylaxis, including fatal events, have been reported. [see Warnings and Precautions (5.2), Adverse Reactions (6.2)]

Adverse reactions that appear in other sections of the labeling include:

• Hypocalcemia and Mineral Metabolism [see Warnings and Precautions (5.1)]
• Anaphylactic Reaction [see Warnings and Precautions (5.2)]
• Renal Impairment [see Warnings and Precautions (5.3)]
• Tissue Damage Related to Inappropriate Drug Administration [see Warnings and Precautions (5.4)]
• Osteonecrosis of the Jaw [see Warnings and Precautions (5.5)]
• Musculoskeletal Pain [see Warnings and Precautions (5.6)]
• Atypical Subtrochanteric and Diaphyseal Femoral Fractures [see Warnings and Precautions (5.7)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the 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.

Quarterly Intravenous Injection –

In a 1-year, double-blind, multicenter study comparing Boniva Injection administered intravenously as 3 mg every 3 months to Boniva 2.5 mg daily oral tablet in women with postmenopausal osteoporosis, the overall safety and tolerability profiles of the two dosing regimens were similar. The incidence of serious adverse reactions was 8.0% in the Boniva 2.5 mg daily group and 7.5% in the Boniva Injection 3 mg once every 3 months group. The percentage of patients who withdrew from treatment due to adverse reactions was approximately 6.7% in the Boniva 2.5 mg daily group and 8.5% in the Boniva Injection 3 mg every 3 months group. Table 1 lists the adverse reactions reported in greater than 2% of patients.

Acute Phase Reaction-like Events

Symptoms consistent with acute phase reaction (APR) have been reported with intravenous bisphosphonate use. The overall incidence of patients with APR-like events was higher in the intravenous treatment group (4% in the Boniva 2.5 mg daily oral tablet group vs. 10% in the Boniva Injection 3 mg once every 3 months group). These incidence rates are based upon reporting of any of 33 potential APR-like symptoms within 3 days of an intravenous dose and lasting 7 days or less. In most cases, no specific treatment was required and the symptoms subsided within 24 to 48 hours.

Injection Site Reactions

Local reactions at the injection site, such as redness or swelling, were observed at a higher incidence in patients treated with Boniva Injection 3 mg every 3 months (1.7%; 8/469) than in patients treated with placebo injections (0.2%; 1/465). In most cases, the reaction was of mild to moderate severity.

Daily Oral Tablet -

The safety of Boniva 2.5 mg once daily in the treatment and prevention of postmenopausal osteoporosis was assessed in 3577 patients aged 41 – 82 years. The duration of the trials was 2 to 3 years, with 1134 patients exposed to placebo and 1140 exposed to Boniva 2.5 mg. Patients with pre-existing gastrointestinal disease and concomitant use of non-steroidal anti-inflammatory drugs, proton pump inhibitors and H2 antagonists were included in these clinical trials. All patients received 500 mg calcium plus 400 international units vitamin D supplementation daily.

The incidence of all-cause mortality was 1% in the placebo group and 1.2% in the Boniva 2.5 mg daily group. The incidence of serious adverse reactions was 20% in the placebo group and 23% in the Boniva 2.5 mg daily oral tablet group. The percentage of patients who withdrew from treatment due to adverse reactions was approximately 17% in both the placebo group and the Boniva 2.5 mg daily oral tablet group. Table 2 lists adverse reactions from the Treatment and Prevention Studies reported in greater than or equal to 2% of patients and in more patients treated with Boniva 2.5 mg daily oral tablet than patients treated with placebo.

Gastrointestinal Adverse Reactions

The incidence of selected gastrointestinal adverse reactions in the placebo and Boniva 2.5 mg daily groups were: dyspepsia (10% vs. 12%), diarrhea (5% vs. 7%), and abdominal pain (5% vs. 6%).

Musculoskeletal Adverse Reactions

The incidence of selected musculoskeletal adverse reactions in the placebo and Boniva 2.5 mg daily groups were: back pain (12% vs. 14%), arthralgia (14% vs. 14%) and myalgia (5% vs. 6%).

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Boniva Injection. 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.

Hypersensitivity: Allergic reactions including anaphylaxis with fatalities, angioedema, asthma exacerbation, bronchospasm, rash, Stevens-Johnson syndrome, erythema multiforme, and dermatitis bullous [see Contraindications (4), Warnings and Precautions (5.2)].

Hypocalcemia: Hypocalcemia [see Warnings and Precautions (5.1)].

Renal Toxicity: Acute renal failure [see Warnings and Precautions (5.3)].

Osteonecrosis of the Jaw: Osteonecrosis of the jaw and other oro-facial sites, including the external auditory canal [see Warnings and Precautions (5.5)].

Musculoskeletal Pain: Bone, joint, or muscle pain (musculoskeletal pain), described as severe or incapacitating [see Warnings and Precautions (5.6)].

Atypical Femoral Shaft Fracture: Atypical, low-energy, or low-trauma fractures of the femoral shaft [see Warnings and Precautions (5.7)].

Eye Inflammation: Iritis and uveitis. In some cases with other bisphosphonates, these events did not resolve until the bisphosphonate was discontinued.

No cases of overdose were reported in premarketing studies with Boniva Injection. Overdosage with intravenous bisphosphonates may result in hypocalcemia, hypophosphatemia, and hypomagnesemia. Clinically relevant reductions in serum levels of calcium, phosphorus, and magnesium should be corrected by intravenous administration of calcium gluconate, potassium or sodium phosphate, and magnesium sulfate, respectively.

Dialysis would not be beneficial unless it is administered within 2 hours following the overdose.

Boniva (ibandronate sodium) is a nitrogen-containing bisphosphonate that inhibits osteoclast-mediated bone resorption. The chemical name for ibandronate sodium is 3-(N-methyl-N-pentyl)amino-1-hydroxypropane-1,1-diphosphonic acid, monosodium salt, monohydrate with the molecular formula C9H22NO7P2Na•H2O and a molecular weight of 359.24. Ibandronate sodium is a white- to off-white powder. It is freely soluble in water and practically insoluble in organic solvents. Ibandronate sodium has the following structural formula:

Boniva Injection is intended for intravenous administration only. Boniva Injection is available as a sterile, clear, colorless, ready-to-use solution in a prefilled syringe that delivers 3.375 mg of ibandronate monosodium salt monohydrate in 3 mL of solution, equivalent to a dose of 3 mg ibandronate free acid. Inactive ingredients include sodium chloride, glacial acetic acid, sodium acetate and water.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• aspirin or other NSAIDs (nonsteroidal anti-inflammatory drugs) - ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others.

This list is not complete. Other drugs may interact with ibandronate, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.