Vivanat Rompharm (Solution) Instructions for Use

Marketing Authorization Holder

S.C. Rompharm Company S.R.L. (Romania)

ATC Code

M05BA06 (Ibandronic acid)

Active Substance

Ibandronic acid (Rec.INN registered by WHO)

Dosage Form

Vivanat Rompharm

Solution for intravenous administration 1 mg/1 ml: 3 ml syringes 1 or 4 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous administration transparent, colorless.

Excipients : sodium acetate trihydrate – 0.2 mg, glacial acetic acid – 0.5 mg, sodium chloride – 8.6 mg, acetic acid (1% solution) – to adjust pH to 3.7-4.0, water for injections – up to 1 ml.

3 ml – disposable syringes (1) – contour cell packaging (1) with 1 disposable needle for injections – cardboard packs.
3 ml – disposable syringes (1) – contour cell packaging (4) with 4 disposable needles for injections – cardboard packs.

Clinical-Pharmacological Group

Bone resorption inhibitor. Bisphosphonate

Pharmacotherapeutic Group

Bone resorption inhibitor – bisphosphonate

Pharmacological Action

An inhibitor of bone resorption, a nitrogen-containing bisphosphonate. It has a selective effect on bone tissue, which is due to its 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, absolute bioavailability is 0.6%. Concurrent 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 plasma concentration of ibandronic acid increases proportionally to the dose taken orally (up to 100 mg) or administered intravenously (up to 6 mg).

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

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

40-50% of the amount of ibandronic acid circulating in the blood penetrates into bone tissue and accumulates there, the remaining amount is excreted unchanged by the kidneys. The observed apparent final T_1/2 varies widely (10-60 hours) and depends on the dose and assay sensitivity. 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 as a slow injection over 15-30 minutes.

For postmenopausal osteoporosis, administer 3 mg intravenously every 3 months.

For hypercalcemia of malignancy, administer a single 2-4 mg dose; the maximum recommended single dose is 4 mg.

For bone metastases, administer 6 mg intravenously every 3-4 weeks.

Ensure adequate hydration prior to administration for hypercalcemia of malignancy.

Do not administer as an intra-arterial injection.

Do not mix with calcium-containing solutions or other intravenously administered medications.

Monitor renal function and serum calcium, phosphate, and magnesium levels before and during therapy.

Assess for hypocalcemia and other disturbances of bone and mineral metabolism prior to initiation; correct these conditions before starting treatment.

Discontinue treatment if renal function deteriorates significantly.

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.

Other 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 stand or sit upright 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 greater 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.

Intra-arterial administration is not permitted.

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.