Ibandronic acid (Concentrate) Instructions for Use

Marketing Authorization Holder

AkselFarm, LLC (Russia)

Manufactured By

Oncotarget, LLC (Russia)

ATC Code

M05BA06 (Ibandronic acid)

Active Substance

Ibandronic acid (Rec.INN registered by WHO)

Dosage Forms

	Ibandronic acid	Concentrate for solution for infusion 2 mg: vial 2 ml 1 pc.
		Concentrate for solution for infusion 6 mg: vial 6 ml 1 pc.

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion transparent colorless.

Excipients: sodium chloride, sodium acetate trihydrate, glacial acetic acid, water for injections.

2 ml – vials of colorless glass (type I) (1) – cardboard packs with an insert.

Concentrate for solution for infusion transparent colorless.

Excipients: sodium chloride, sodium acetate trihydrate, glacial acetic acid, water for injections.

6 ml – vials of colorless glass (type I) (1) – cardboard packs with an insert.

Clinical-Pharmacological Group

Bone resorption inhibitor. Bisphosphonate

Pharmacotherapeutic Group

Means for the treatment of bone diseases; agents affecting bone structure and mineralization; bisphosphonates

Pharmacological Action

An inhibitor of bone resorption, a nitrogen-containing bisphosphonate. It has a selective effect on bone tissue, which is due to a high affinity for hydroxyapatite, which makes up the mineral matrix of bone. Ibandronic acid suppresses bone resorption and does not have a direct effect on bone formation.

Ibandronic acid prevents bone destruction caused by the cessation of gonadal function, retinoids, tumors, and tumor extracts in vivo.

In postmenopausal women, it reduces the increased rate of bone turnover to the level of reproductive age, which leads to a progressive increase in bone mass.

Ibandronic acid prevents the development of new and reduces the growth of existing bone metastases. It has a dose-dependent inhibitory effect on tumor osteolysis.

Pharmacokinetics

After oral administration, Ibandronic acid is rapidly absorbed in the upper gastrointestinal tract. The time to reach C_max is 0.5-2 hours after administration on an empty stomach, the absolute bioavailability is 0.6%. Simultaneous intake of food or drinks (except plain water) reduces the bioavailability of ibandronic acid by 90%. Consumption of food or drinks 30 minutes after taking ibandronic acid reduces its bioavailability by 30%. When ibandronic acid is taken 60 minutes before a meal, no significant decrease in bioavailability is observed. The bioavailability of ibandronic acid decreases by up to 75% when taken 2 hours after a meal.

The concentration of ibandronic acid in plasma increases in proportion to the dose taken orally (up to 100 mg) or administered intravenously (up to 6 mg).

After entering the systemic circulation, Ibandronic acid is rapidly bound in bone tissue or excreted in the urine. The apparent final V_d is 90 L, the amount of active substance in bone tissue usually reaches 40-50% of the dose circulating in the blood. Binding to plasma proteins at therapeutic concentrations is 87%.

There are no data indicating that Ibandronic acid is metabolized (in both humans and animals).

40-50% of the amount of ibandronic acid circulating in the blood penetrates the bone tissue and accumulates there, the remaining amount is excreted unchanged by the kidneys. The value of the observed apparent final T_1/2 varies widely (10-60 hours) and depends on the dose and sensitivity of the assay. The concentration of ibandronic acid in the blood decreases rapidly and reaches 10% of C_max 3 hours after intravenous administration.

The total clearance of ibandronic acid is 84-160 ml/min. Renal clearance (60 ml/min in healthy postmenopausal women) accounts for 50-60% of total clearance and depends on creatinine clearance. The difference between total and renal clearance reflects the uptake of the substance into bone tissue.

Indications

Postmenopausal osteoporosis for the prevention of fractures.

Bone metastases to reduce the risk of hypercalcemia, pathological fractures, reduce pain, and reduce the need for radiation therapy for pain and the threat of fractures.

Hypercalcemia of malignancy.

ICD codes

Dosage Regimen

Administer intravenously only after dilution. Do not administer as a bolus or intra-arterially.

For postmenopausal osteoporosis, administer a 3 mg intravenous infusion over 15-30 seconds every 3 months.

For hypercalcemia of malignancy, administer a single 2 mg or 4 mg intravenous infusion. The 4 mg dose is for patients with severe hypercalcemia. Infuse over a minimum of 2 hours.

For bone metastases, administer a 6 mg intravenous infusion over at least 15 minutes every 3-4 weeks.

Prior to infusion, hydrate the patient adequately. Assess renal function and correct hypocalcemia before initiation.

Dilute the concentrate in 100 mL of sterile 0.9% sodium chloride or 5% dextrose solution. Use the diluted solution immediately.

Do not mix with calcium-containing infusion solutions. Monitor serum calcium, phosphate, and magnesium levels during therapy.

In patients with mild to moderate renal impairment (creatinine clearance ≥30 mL/min), no dosage adjustment is required. Contraindicated in severe renal impairment (creatinine clearance <30 mL/min).

Adverse Reactions

From the digestive system frequently – dyspepsia (nausea, abdominal pain), flatulence, diarrhea, constipation, gastritis, gastroenteritis, with oral administration – esophagitis, gastroesophageal reflux disease; infrequently with oral administration – esophagitis, including esophageal ulceration or strictures, dysphagia, vomiting; rarely – duodenitis.

From the nervous system and psyche frequently – headache, dizziness, insomnia.

From the skin and subcutaneous tissues frequently – rash.

Allergic reactions rarely – angioedema, facial edema, urticaria.

From the musculoskeletal system frequently – arthralgia, myalgia, limb pain, osteoarthritis, back pain, musculoskeletal pain; infrequently – bone pain; rarely – atypical subtrochanteric and diaphyseal femoral fractures (characteristic of the bisphosphonate class); very rarely – osteonecrosis of the jaw.

From the organ of vision rarely – inflammatory eye diseases.

From the body as a whole frequently – flu-like syndrome, weakness; infrequently – asthenia.

Others frequently – nasopharyngitis, cystitis, urinary tract infections, bronchitis, upper respiratory tract infections, arterial hypertension, hypercholesterolemia; infrequently – reactions at the injection site, phlebitis, thrombophlebitis; rarely – hypersensitivity reactions; with intravenous administration, a short-term decrease in serum calcium levels is possible.

Contraindications

For oral and intravenous administration: hypocalcemia, severe renal impairment (creatinine clearance <30 ml/min), esophageal lesions leading to delayed emptying, such as stricture or achalasia (for oral administration), pregnancy, lactation (breastfeeding), children and adolescents under 18 years of age, hypersensitivity to ibandronic acid.

For oral administration: esophageal lesions leading to delayed emptying, such as stricture or achalasia; inability to remain in a sitting or standing position for 60 minutes.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation.

Use in Renal Impairment

Contraindicated in severe renal failure (serum creatinine level more than 5 mg/dL, or 442 µmol/L).

Pediatric Use

There is no clinical experience of use in children.

Special Precautions

Use with caution in patients with hypersensitivity to other bisphosphonates.

During treatment, renal function, plasma levels of calcium, phosphorus, and magnesium should be monitored. Excessive hydration should be avoided in patients with circulatory insufficiency.

It should be borne in mind that the use of bisphosphonates may cause bronchospasm in patients with bronchial asthma and with hypersensitivity to acetylsalicylic acid.

Do not administer intra-arterially.

Products containing calcium and other polyvalent cations (e.g., aluminum, magnesium, iron), including milk and solid food, may interfere with the absorption of ibandronic acid (they should be consumed no earlier than 30 minutes after oral administration of the drug).

Drug Interactions

With simultaneous use with aminoglycosides, hypocalcemia may develop (since these active substances reduce serum calcium levels for a long time); hypomagnesemia is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.