Ibandronate is a medication that belongs to a class of drugs known as bisphosphonates. It is primarily used to treat and prevent osteoporosis, a condition characterized by weakened and brittle bones, which are more susceptible to fractures. Ibandronate works by inhibiting the breakdown of bone and increasing bone density, which helps to strengthen bones and reduce the risk of fractures.

Ibandronate (Bonviva) is a bisphosphonate that is used in the treatment and prevention of osteoporosis. It is primarily used in the treatment of vertebral osteoporosis. Evidence to treat non-vertebral fractures is limited.

Ibandronate (Bonviva) Uses:

• Osteoporosis:
  • Treatment and prevention of osteoporosis in postmenopausal females.

Note:

• Because of the lack of evidence for the prevention of hip or nonvertebral fracture, ibandronate is not an ideal preliminary agent compared to other offered bisphosphonates; however, initiation in patients needing vertebral efficiency may be fitting.
• Off Label Use of Ibandronate in Adults:
  • Breast cancer, metastatic bone disease (treatment)
  • Hypercalcemia of malignancy
  • Bone pain due to metastatic prostate cancer (alternative agent)

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• Prolia, Xgeva (Denosumab)

Ibandronate (Bonviva) Dose in Adults:

Note:

• If a doctor gives you medicine for weak bones (osteoporosis), and you don't get enough calcium and vitamin D from your food, the doctor will also suggest you take extra calcium and vitamin D.
• These nutrients are important to make your bones stronger.
• So, you'll need to take these extra supplements along with your medication if your diet doesn't provide enough of them.

Ibandronate (Bonviva) Dose in the treatment of metastatic bone disease in patients with breast cancer (off-label): 

• Ibandronate can be used to treat breast cancer that has spread to the bones (metastatic bone disease), although this use is considered "off-label."
• It is given as an intravenous (IV) injection.
• The typical dose is 6 mg, which is administered over 1 to 2 hours.
• This treatment can be repeated every 3 to 4 weeks.
• In some cases, it may be continued for up to 4 years.

Ibandronate (Bonviva) Dose in the treatment of Hypercalcemia of malignancy (off-label):

• Ibandronate can be used to treat high levels of calcium in the blood due to cancer (hypercalcemia of malignancy), although this use is considered "off-label."
• It is given as an intravenous (IV) injection.
• The dose typically ranges from 2 to 6 mg.
• The medication is administered as a single dose over 1 to 2 hours.
• This treatment can help lower high blood calcium levels associated with malignancy.

Ibandronate (Bonviva) Dose as an alternative agent in the treatment of osteoporosis and prevention of fractures in postmenopausal females:

In the treatment of osteoporosis for preventing fractures in postmenopausal females, the use of ibandronate is not typically preferred due to a lack of direct evidence for preventing hip or nonvertebral fractures.

However, in specific situations, ibandronate can be considered for high-risk patients or those with certain T-scores:

High Fracture Risk Patients (including those with fragility fracture history or specific T-scores):

• Treatment:
  • Oral: 150 mg once monthly.
  • IV: 3 mg every 3 months.

Patients with T-scores between -1 and -2.5 and not at high fracture risk:

• Prevention:
  • Oral: 150 mg once monthly.

Duration of Therapy:

• The ideal duration of ibandronate therapy is not firmly established.
• If the fracture risk remains high after the initial 3 years (IV) or 5 years (oral), the therapy may be extended (up to 6 years for IV and up to 10 years for oral) or an alternative treatment may be considered.
• Alternatively, if bone mineral density remains stable, and there have been no fragility fractures, a "drug holiday" (discontinuation) can be considered after the initial 3 years (IV) or 5 years (oral). This break from treatment may last for up to 5 years.
• The decision to resume therapy after a drug holiday depends on various factors, including changes in bone mineral density and risk factors for fracture.

Ibandronate (Bonviva) Dose in the treatment of bone pain due to metastatic prostatic cancer, (alternative agent if radiation therapy is not an option; off-label)

Dosage for Metastatic Prostate Cancer, Bone Pain:

• IV (Intravenous): A single dose of 6 mg given over 15 minutes.

Missed Doses:

• Oral (once-monthly): If you forget to take the oral dose, take it the morning after you remember, but only if the next month's scheduled dose is more than 7 days away. If the next month's dose is within 7 days, wait until that scheduled dose and then continue on your regular monthly schedule. Don't take more than 150 mg within 7 days.
• IV (once every 3 months): If you miss an IV dose, take it as soon as you can reschedule it. After that, continue with a dose every 3 months from the date of the last injection.

Use in Children:

Not indicated.

Ibandronate (Bonviva) Pregnancy Risk Category: C

• It's not clear if bisphosphonates can pass through the placenta to the developing baby, but it's expected that some of the drug may reach the fetus.
• Information about using ibandronate during pregnancy is limited.
• Bisphosphonates are absorbed into the bones and released slowly. How much ends up in the bloodstream depends on the specific drug, the dose, and how long it's taken.
• Theoretically, there might be a risk of harm to the baby if a pregnancy occurs after taking these drugs (like low calcium levels, low birth weight, and shorter pregnancy), but available data suggest that the risk of problems for the baby is not significantly increased.
• Babies exposed to bisphosphonates should be checked for low calcium levels after birth.
• To be on the safe side, most experts recommend that women who can become pregnant should stop taking bisphosphonates as early as possible before planning to have a baby.
• These drugs should be used in premenopausal women only in special situations when there is rapid bone loss, and the bisphosphonate with the shortest time in the body should be chosen.

Use during breastfeeding:

• It's uncertain whether ibandronate is found in breast milk.

Dose in Kidney Disease:

For the treatment of osteoporosis with ibandronate:

• If your kidney function, as measured by creatinine clearance (CrCl), is 30 mL per minute or higher, there is typically no need to adjust the dosage.
• However, if your CrCl is less than 30 mL per minute, it is generally not recommended to use ibandronate. This is because the medication may not be effectively eliminated from the body in individuals with significantly reduced kidney function, and it could potentially lead to safety concerns.

Dose in Liver Disease:

• The manufacturer's labeling for ibandronate does not provide specific dosage adjustments based on hepatic (liver) metabolism because ibandronate is not significantly processed by the liver.
• Instead, it primarily undergoes renal (kidney) excretion.
• As a result, the liver's function typically does not significantly impact the way the body handles ibandronate.

Common Side Effects of Ibandronate (Bonviva):

• Gastrointestinal:
  • Dyspepsia
• Neuromuscular & skeletal:
  • Back pain
• Respiratory:
  • Upper respiratory tract infection

Less Common Side Effects of Ibandronate (Bonviva):

• Cardiovascular:
  • Hypertension
• Central Nervous System:
  • Headache
  • Dizziness
  • Fatigue
  • Insomnia
  • Depression
• Dermatologic:
  • Skin Rash
• Gastrointestinal:
  • Abdominal Pain
  • Diarrhea
  • Nausea
  • Dental Disease
  • Constipation
  • Vomiting
  • Gastritis
  • Gastroenteritis
• Genitourinary:
  • Urinary Tract Infection
  • Cystitis
• Hypersensitivity:
  • Acute Phase Reaction-Like Symptoms
  • Hypersensitivity Reaction
• Infection:
  • Influenza
• Local:
  • Injection Site Reaction
• Neuromuscular & Skeletal:
  • Limb Pain
  • Arthralgia
  • Myalgia
  • Arthropathy
  • Weakness
  • Localized Osteoarthritis
  • Muscle Cramps
• Respiratory:
  • Bronchitis
  • Pneumonia
  • Nasopharyngitis
  • Flu-Like Symptoms
  • Pharyngitis

Contraindications to Ibandronate (Bonviva):

Ibandronate should not be used in the following situations:

• If you have a known allergy or hypersensitivity to ibandronate or any ingredient in the medication.
• If you have low levels of calcium in your blood (hypocalcemia).
• If you cannot sit or stand upright for at least 60 minutes after taking the oral tablets.
• If you have conditions affecting your esophagus that slow down the emptying of the esophagus, such as strictures or achalasia (a disorder that affects the ability of the esophagus to move food into the stomach).

Additionally, while there is limited information about cross-reactivity between bisphosphonates (a class of drugs that includes ibandronate) in terms of allergies, it's possible that there could be some cross-sensitivity due to similarities in their chemical structures or how they work. This means that if you have had an allergic reaction to one bisphosphonate, there is a chance you might also react to others in this drug class, and this should be considered.

Warnings and precautions

Bone fractures:

• In some cases, people taking bisphosphonate medications for bone health have experienced unusual fractures in their thigh bones.
• These fractures can happen in the area just below the hip joint or along the long part of the thigh bone.
• Some individuals may feel pain in their thighs weeks or months before the actual fracture occurs.
• It's not entirely clear if bisphosphonate treatment is the direct cause of these fractures because they have also been seen in people not taking these medications and in those using glucocorticoids.
• However, people who take bisphosphonates for a long time, like more than 3 to 5 years, might have a higher risk of these unusual fractures.
• Still, the benefits of bisphosphonate therapy, especially in those at high risk of regular fractures, usually outweigh the risk of these unusual fractures in the first 5 years of treatment.
• If someone has thigh or groin pain and has been on bisphosphonates, they should be checked for a possible thigh bone fracture.
• In cases of a thigh bone fracture, doctors may consider stopping bisphosphonate therapy and checking the other thigh for fractures too.

Bone/joint/muscle pain:

• Occasionally, people taking bisphosphonate medications may experience severe and sometimes very painful issues with their bones, joints, or muscles.
• This pain can start suddenly and last for a single day or even several months.
• If patients develop severe symptoms, they should stop receiving intravenous ibandronate therapy.
• Typically, when the treatment is discontinued, the symptoms improve.
• However, in some cases, patients who tried the same drug again or another bisphosphonate experienced a recurrence of these painful symptoms.
• So, if someone has a history of these severe symptoms related to bisphosphonate therapy, it's best to avoid using these medications.

GI mucosa irritation:

• Bisphosphonate medications can sometimes irritate the lining of the upper digestive tract.
• This irritation can lead to conditions like esophagitis (inflammation of the esophagus), dysphagia (difficulty swallowing), esophageal ulcers, esophageal erosions, and very rarely, esophageal stricture (narrowing of the esophagus).
• The risk of these issues is higher in people who cannot follow the dosing instructions correctly.
• If you have difficulties swallowing (dysphagia), esophageal problems, or issues like gastritis, duodenitis, or ulcers, you should be cautious when using these medications because they may worsen these conditions.

Hypersensitivity

• Some people may have allergic reactions to bisphosphonate medications, which can be severe and even life-threatening.
• These reactions may include anaphylactic reactions or shock (which can be fatal), angioedema (swelling under the skin), bronchospasm (narrowing of the airways, making it hard to breathe), worsening of asthma, skin rashes, and serious skin conditions like Stevens-Johnson syndrome, erythema multiforme, and dermatitis bullous.
• If you experience any signs of a hypersensitivity reaction, it's crucial to stop using the medication and seek immediate medical attention.

Hypocalcemia:

• The use of bisphosphonate medications can lead to low levels of calcium in the blood, a condition known as hypocalcemia.
• Before starting this treatment, it's essential to make sure that your calcium levels are normal.
• You should also ensure that you are getting enough calcium and vitamin D in your diet or through supplements because these nutrients are important for bone health.

Influenza-like illness, acute-phase reaction

• After the initial infusion of certain medications, including bisphosphonates, some people may experience a short-lived acute phase reaction.
• This reaction can include symptoms such as fever, chills, pain or muscle aches, or other symptoms similar to the flu.
• These symptoms typically appear within 3 days after the infusion and usually go away within 48 hours after they start.
• However, in rare cases, these symptoms may last for more than 7 days.
• It's important to be aware of this potential reaction, but it's usually temporary and not a cause for major concern.

Ocular effects

• In some cases, ibandronate can lead to eye issues such as uveitis (inflammation inside the eye) and scleritis (inflammation of the white part of the eye).
• If you experience symptoms or signs of eye inflammation, it's important to seek further evaluation from an eye specialist (ophthalmologist).
• This will help determine the cause and the best course of action to address the issue and protect your eye health.

Osteonecrosis in the jaw:

• Osteonecrosis of the jaw (ONJ), also known as medication-related osteonecrosis of the jaw (MRONJ), is a condition that has been reported in patients taking bisphosphonate medications.
• Several factors can increase the risk of MRONJ, including invasive dental procedures like tooth extractions and dental implants, a diagnosis of cancer, concurrent use of other therapies like chemotherapy and corticosteroids, poor oral hygiene, poorly fitting dentures, and underlying medical conditions such as anemia, blood clotting disorders, infections, or preexisting dental or gum diseases.
• The risk of MRONJ may also go up with longer use of bisphosphonates.
• The risk of MRONJ is significantly higher in cancer patients who are receiving antiresorptive therapy (including bisphosphonates) compared to those using these drugs for osteoporosis treatment.
• Monthly intravenous (IV) antiresorptive therapy carries a higher risk than oral bisphosphonate use, although even oral bisphosphonates can pose a risk if used for more than 4 years.
• According to the American Association of Maxillofacial Surgeons (AAOMS), discontinuing bisphosphonates before invasive dental procedures may reduce the risk of ONJ, but it's important for healthcare providers to use their clinical judgment.
• The AAOMS also suggests that there's currently no evidence that stopping oral bisphosphonate therapy affects the risk of ONJ after tooth extraction, provided patients have taken the medication for less than 4 years and have no clinical risk factors, although special considerations apply to patients with dental implants.
• On the other hand, patients who have taken oral bisphosphonates for more than 4 years or who have used them along with corticosteroids or antiangiogenic medications might consider a two-month drug-free period before invasive dental procedures, based on theoretical benefits.
• If a patient develops ONJ while on bisphosphonate therapy, they should receive care from an oral surgeon.
• The decision to discontinue oral bisphosphonate therapy in patients who develop ONJ should be considered based on a risk/benefit evaluation.

Bariatric surgery

• After undergoing bariatric surgery, it's generally advisable to avoid taking oral bisphosphonate medications.
• This is because the surgery can lead to changes in how your body absorbs medications, making it difficult for oral bisphosphonates to work effectively.
• Additionally, there's a risk of potential ulceration in the areas where the surgery was done.
• If you still need bisphosphonate therapy after bariatric surgery, it's recommended to use the intravenous (IV) form of these medications instead of the oral version.
• IV-administered bisphosphonates are typically a better option in this situation to ensure proper absorption and reduce the risk of complications.

Renal impairment

• If you have severe kidney impairment with a creatinine clearance (CrCl) of less than 30 mL per minute, the use of bisphosphonates is generally not recommended.
• In particular, intravenous bisphosphonate use has been linked to the worsening of kidney function, including cases of acute renal failure.

Ibandronate: Drug Interaction

Monitoring parameters:

Monitoring for Osteoporosis

• Bone Mineral Density (BMD) Evaluation:
  • Baseline BMD assessment is essential.
  • During treatment, assess BMD every 1 to 3 years. The first check is usually around 2 years after starting treatment.
  • The frequency of BMD assessments may vary based on individual factors and the stability of BMD.
  • During a "drug holiday" (a break from medication), evaluate BMD every 2 to 4 years.
• Serum Creatinine Testing:
  • Check serum creatinine levels before each intravenous (IV) dose.
• Height and Weight Measurements:
  • Conduct annual measurements of height and weight.
• Assessment of Chronic Back Pain:
  • Evaluate and discuss any chronic back pain concerns.
• Serum Calcium and Vitamin D Levels:
  • Monitor serum calcium and 25(OH)D (vitamin D) levels.
• Bone Turnover Markers:
  • Consider measuring biochemical markers of bone turnover (e.g., fasting serum CTX or urinary NTX) at baseline, 3 months, and 6 months.
  • These tests help assess the response to treatment, adherence to therapy, and the possibility of malabsorption.

Regular monitoring is crucial to track the effectiveness of osteoporosis treatment and ensure the best care for your bone health.

How to administer Ibandronate (Bonviva)?

Oral Administration:

• Take the medication 60 minutes before having your first meal or drink of the day (except water) and before taking any other oral medications or supplements, such as calcium, antacids, or vitamins.
• When taking ibandronate, be in an upright position (sitting or standing) and swallow the tablet whole with a full glass of plain water (6 to 8 ounces).
• Avoid lying down for at least 60 minutes after taking ibandronate to reduce the chances of experiencing gastrointestinal (GI) side effects.
• Do not consume mineral water with a high calcium content on the same day you take ibandronate.
• Refrain from eating or drinking anything (except water) for 60 minutes after taking ibandronate.

Intravenous (IV) Administration:

• Administer ibandronate as a quick 15 to 30 second bolus IV injection.
• Avoid giving the medication through a nearby vein (paravenous) or into an artery (intraarterial) because it may cause damage to the tissues.
• Do not mix ibandronate with solutions that contain calcium or other drugs.
• For the treatment of osteoporosis, avoid administering ibandronate more frequently than once every 3 months.

Off-label Rates for IV Administration:

• When using ibandronate for the treatment of metastatic bone disease due to breast cancer and for the management of hypercalcemia of malignancy, the IV infusion may be done over 1 to 2 hours.
• In the case of metastatic bone pain due to prostate cancer, the IV infusion should take about 15 minutes.

These guidelines help ensure that ibandronate is taken in the most effective and safe way for your specific medical condition.

Mechanism of action of Ibandronate (Bonviva):

• Ibandronate is a type of medication called a bisphosphonate.
• It works by reducing bone resorption, which is the process where bone tissue is broken down by cells called osteoclasts or their precursors.
• By slowing down bone resorption, ibandronate indirectly helps increase bone mineral density, making the bones stronger.

Distribution:

• Terminal Volume of Distribution: 90 liters.
• Approximately 40% to 50% of circulating ibandronate binds to bone.

Protein Binding:

• Ibandronate is highly bound to proteins in the blood, ranging from 85.7% to 99.5%.

Metabolism:

• Ibandronate is not metabolized in the body.

Bioavailability:

• When taken orally, ibandronate has minimal bioavailability, and its absorption is reduced by approximately 90% when taken with a standard breakfast.

Half-life Elimination:

• For an oral 150 mg dose, the terminal half-life ranges from 37 to 157 hours.
• For intravenous (IV) administration, the terminal half-life is approximately 5 to 25 hours.

Time to Peak in Plasma:

• When taken orally, ibandronate reaches peak plasma levels between 0.5 to 2 hours after administration.

Excretion:

• Ibandronate is primarily excreted in the urine, accounting for 50% to 60% of the absorbed dose, and it is excreted in its unchanged form.
• Unabsorbed drug is excreted in the feces.

International Brand Names of Ibandronate:

• Boniva
• Abrion
• Ai Ben
• Anabon
• Bandrobon
• Bandroxylate
• Bondex
• Bondria
• Bondronat
• Bondronat IV
• Bondrova
• Boni-M
• Bonprove
• Bonviva
• Drofen
• Etanorden
• Fosfonat
• Ibabon
• Iban
• Ibandro
• Ibonate
• Ibrac
• Idena
• Ipexal
• Oseban
• Ostex
• Pelnexon
• Ribonne
• Tefal  

Ibandronate Brand Names in Pakistan: