Ibandronic Acid; Uses, Side Effects, Interactions, Pragnancy

Ibandronic Acid is a third-generation amino-bisphosphonate with anti-resorptive and anti-hypercalcemic activities. Ibandronic acid binds to and adsorbs onto the surface of hydroxyapatite crystals in the bone matrix, thereby preventing osteoclast resorption. This agent also inhibits farnesyl pyrophosphate synthase, an enzyme involved in the mevalonate pathway. Inhibition of this enzyme prevents the formation of isoprenoids, thereby leading to a reduction in the farnesylation and geranylgeranylation of signaling proteins of G protein-coupled signaling, and, eventually, inducing apoptosis of osteoclasts. By inhibiting osteoclast-mediated bone resorption, ibandronic acid increases bone mineral density, decreases bone remodeling and turnover, as well as reduces bone pain.

Ibandronate is a nitrogen-containing bisphosphonate in the same class as alendronate and risedronate. Ibandronate inhibits osteoclast-mediated bone resorption. All of the bisphosphonates prevent the breakdown of bone by bone cells called osteoclasts. In persons who are at high risk for osteoporosis, bisphosphonates not only result in increased amounts of bone and bone strength, they also reduce the risk of hip fractures and other bone fractures.

Mechanism of Action Ibandronic Acid

The action of ibandronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate, and zoledronate) appear to act as analogs of isoprenoid diphosphate lipids, thereby inhibiting farnesyl pyrophosphate (FPP) synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signaling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.

Indications of Ibandronic Acid

• Bone Metastases
• Hypercalcemia of Malignancy
• Bone destruction
• Osteoporosis
• Prevention of Osteoporosis
• Treatment of bone metastases in patients with prostate cancer.
• Treatment of postmenopausal osteoporosis in patients at risk of vitamin D insufficiency.
• It reduces the risk of vertebral and hip fractures.
  is indicated for the treatment of postmenopausal osteoporosis in women at risk of vitamin D insufficiency. It reduces the risk of vertebral and hip fractures.
• Treatment of osteoporosis in post-menopausal women to prevent fractures
• Treatment of osteoporosis in men to prevent fractures
• Prevention and treatment of corticosteroid-induced osteoporosis and prevention of bone loss in post-menopausal women considered at risk of developing osteoporosis.
• Prophylaxis and treatment of female osteoporosis
• Bone destruction
• Prevention and treatment of corticosteroid-associated osteoporosis together with supplements of calcium and vitamin D
• Treatment of Paget’s disease.
• Postmenopausal osteoporosis.
• Osteoporosis prophylaxis in women with breast cancer
• In general, this drug is used to increase bone mass leading to stronger bones and reducing the risk of fractures in osteoporosis after the menopause and in breast cancer which has spread to the bones.
• Benefits of being on this drug can include increased bone mass and a reduced risk of getting a bone fracture (of the spine).
• Treatment of weak bones (osteoporosis) in postmenopausal women at increased risk of fracture
• Prevention of bone fractures and bone complications requiring radiotherapy or surgery in people with breast cancer and cancer which has spread to the bone
• Treatment of high blood calcium due to a tumor.

Osteoporosis in patients with chronic kidney disease – Management renal impairment.

•  Ibandronate – Ibandronate is also available in an IV preparation (3 mg IV every three months). However, there is no direct fracture efficacy data for IV ibandronate. While there are no

The use of osteoclast inhibitors in patients with multiple myeloma

• Treatment of hypercalcemia patients may have a better response to ZA. Ibandronate effectively treats hypercalcemia of malignancy. In combined trials with over 320 patients, ibandronate doses of 2 mg IV administered over two hours

• Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors clodronate and ibandronate – Clodronate and ibandronate are approved for use in metastatic bone disease outside the United States. Oral ibandronate has similar efficacy to intravenous ibandronate. Patients

• Bone metastases in advanced prostate cancer: Management usage and there is no evidence that beta emitting radioisotopes prolong survival. Intravenous ibandronate or other bisphosphonates may offer an alternative to external beam RT for the management of pain.

Overview of the use of osteoclast inhibitors in early breast cancer

• Treatment of osteoporosis in men less often for the treatment of osteoporosis in men. Intravenous (IV) bisphosphonates, ZA, and ibandronate offer an alternative option for individuals who cannot tolerate oral bisphosphonates or who find.

• Metabolic bone disease in inflammatory bowel disease alternative option for patients unable to tolerate or absorb oral bisphosphonates. In a small trial, IV ibandronate (1 mg every three months) significantly improved BMD in patients with CD.

Contra-Indications of Ibandronic Acid

• Hypersensitivity to ibandronic acid or to any of the excipients.
• Hypocalcemia
• Abnormalities of the esophagus which delay oesophageal emptyings such as stricture or achalasia
• Acute inflammations of the gastrointestinal tract (esophagitis, gastritis, ulcerations)
• Clinically manifest osteomalacia
• Certain malformations and malfunctions of the esophagus (strictures, achalasia)
• Inability to stand, walk, or sit for 30 minutes after oral administration
• Renal impairment with a creatinine clearance below 30ml/min
• Patients below 18 yrs. of age, as no clinical data exists
• Signs of colic, which is usually self-limiting, occurs in 30-45% of horses.
• Electrolyte disturbances – primarily calcium, magnesium, and potassium, which can last for several hours. Caution should be used in horses with disease processes that could be affected by electrolyte disturbances, such as hyperkalemic periodic paralysis or cardiac disease.
• Kidney damage – it is eliminated by the kidney and is not recommended for use in animals with impaired renal function.
• Less serious reactions include stiffness of the neck, decreased appetite, fever, and increased urination.
• Inability to stand, walk, or sit for 30 minutes after oral administration
• Renal impairment with a creatinine clearance below 30ml/min
• Hypocalcemia
• Pregnancy and breastfeeding

The dosage of Ibandronic Acid

Strengths: 2.5 mg; 150 mg; 3 mg/3 mL

Prevention of Osteoporosis

• PO Prophylaxis of skeletal events in patients w/ breast cancer and bone metastases 50 mg/day.

Treatment and prophylaxis of postmenopausal osteoporosis

• 150 mg once mthly on the same date each mth, or 2.5 mg/day. IV Hypercalcaemia of malignancy 2-4 mg as a single infusion. Max: 6 mg.
• Postmenopausal osteoporosis 3 mg by inj once every 3 mth. Prophylaxis of skeletal events in patients w/ breast cancer and bone metastases 6 mg by infusion 3-4 wkly.

Side Effects of Ibandronic Acid

• Heartburn
• The most common (a burning feeling in the chest, behind the breastbone or gullet)
• Abdominal or stomach pain
• pain, warmth and/or swelling in a leg or in the pelvis
• sudden tingling or coldness in an arm or leg
• Burning, itching, stinging, redness, or other sign of irritation at the application site, rash
• Indigestion
• Constipation
• High blood pressure
• Nausea, vomiting,
• painful or swollen gums
• numbness or heavy feeling in the jaw
• dull, aching pain in the hip, groin, or thigh
• liver problems,
• stomach pain,
• Dizziness
• a headache,
• reversible hair loss or thinning, and
• fever.

Common

• chills or fever
• headache, severe and throbbing
• joint or back pain
• muscle aching or cramping
• muscle pains or stiffness
• chest pressure or squeezing pain in chest
• excessive sweating
• sudden drowsiness or need to sleep
• sharp pain when taking a deep breath
• coughing up blood
• rust colored urine
• liver problems–nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes)
• decreased amount of urine

Rare

• Anxiety
• change in vision
• chest pain or tightness
• confusion
• cough
• Agitation
• arm, back, or jaw pain
• blurred vision
• chest pain or discomfort
• convulsions
• extra heartbeats
• hallucinations
• headache
• irritability
• lightheadedness
• muscle pain or cramps
• muscle spasm or jerking of all extremities
• severe pain in your upper stomach spreading to your back, nausea and vomiting;

Pregnancy & Lactation Ibandronic Acid

FDA Pregnancy category C

Ibandronate is not indicated for use in women of reproductive potential. There are no data of ibandronate use during human pregnancy to inform of any drug-associated risks. Based on animal studies and the known class effects of bisphosphonates, fetal harm may occur. Reproductive studies in animals indicate that ibandronate may be associated with increased incidence of fetal renal pelvis ureter (RPU) syndrome, impaired infant neuromuscular development, maternal hypocalcemia, postimplantation fetal loss, dystocia, and maternal periparturient death, and maternal and fetal death.

Lactation

Ibandronic acid tablets are for use only by postmenopausal women and must not be taken by women who could still have a baby. Do not take ibandronic acid if you’re pregnant or breastfeeding.

References