BONVIVA

Active material: Ibandronic acid
When ATH: M05BA06
CCF: Bone resorption inhibitor. Bisfosfonat
ICD-10 codes (testimony): M81.0, M81.1
When CSF: 16.04.04.01
Manufacturer: F.Hoffmann-La Roche Ltd. (Switzerland)

Pharmaceutical form, composition and packaging

Pills, coated film-White, or almost white, oblong, on one side of the engraving “BNVA”, another – “150”.

Excipients: lactose monohydrate, povidone (K25), microcrystalline cellulose, krospovydon, stearic acid, colloidal silicon dioxide (anhydrous).

The composition of the shell: É 00A28646 (gipromelloza, Titanium dioxide (E171), talc), macrogol 6000.

1 PC. – blisters (1) – packs cardboard.
3 PC. – blisters (1) – packs cardboard.

The solution for the on / in the clear, colorless.

Excipients: sodium chloride, sodium acetate trihydrate, acetic acid glacial, water d / and.

3 ml – ampin (1) complete with sterile needle – packs cardboard.

Pharmacological action

Bone resorption inhibitor and activity of osteoclasts, highly azotsoderžaŝij bisfosfonat.

Ibandronic acid in vivo prevents bone destruction, caused by the blockade sex glands, retinoid, tumors and tumor extracts.

Does not infringe on bone mineralization in the appointment at doses, more than 5000 times higher than the dose for the treatment of osteoporosis.

Does not affect the process of replenishing the pool of osteoclasts. Selective effect of ibandronova acid on bone tissue due to its high affinity to gidroksiapatitu, constituting the mineral matrix of bones.

Ibandronic acid dozozawisimo inhibits bone resorption and has no direct influence on the formation of bone tissue. Women in menopause reduces increased bone renewal rate up to the level of reproductive age, that leads to a common progressive increase in bone mass, decline in splitting the bone collagen (concentrations of deoksipiridinolina and cross stitched with- and N-telopeptidov collagen type I) in urine and serum, incidence of fractures and increased bone mineral density (IGC).

High activity and therapeutic range provides flexibility and intermittent dosing regime destination with a long period without treatment at relatively low doses.

Bone mineral density (IGC)

Receiving medication Bonviva^® dose 150 mg 1 Once a month during the year increases the average IPC of the lumbar vertebrae, hips, Hip and spit on 4.9%, 3.1%, 2.2% and 4.6%. Regardless of the length of the menopause and the degree of the original bone mass loss, application of Bonviva^® leads to more credibly tenable change IPC, than placebo. The effect of treatment during the year, defined as the increase in the IPC, observed in 83.9% patients.

In/in the introduction of the drug Bonviva^® 3 mg 1 once every 3 month during the year increases the average IPC hips, femoral neck, spit on 2.4%, 2.3%, 3.8%, respectively. Regardless of the length of the menopause and bone mass loss from source, application of Bonviva^® leads to more credibly tenable change IPC, than placebo. The effect of treatment during the year, defined as the increase in the IPC, observed in 92.1% patients.

Biochemical markers of bone resorption

The decrease in serum concentration of c-Terminal peptide of procollagen type I (CTX) on 28% noted already in 24 hours after the first reception Bonvivy^® dose 150 mg, maximum reduction is 68% through 6 days. After the third and fourth dose Bonviva^® dose 150 mg maximum reduction of serum CTX on 74% observed through 6 d. Through 28 days after taking the fourth dose supression decreased bone resorption biochemical markers to 56%.

Clinically significant reduction in serum CTX compared with initial value obtained through 3, 6 and 12 months of therapy. After a year of therapy with Bonviva^® when administered in a dose of 150 mg reduction is 76%, the on/in infusions in the dose 3 mg – 58.6%. Decline in STH more 50% compared to the original value noted from 83.5% patients, receiving medication Bonviva^® dose 150 mg 1 once every 28 days.

Clinically significant reduction in serum C-terminal peptide of procollagen type I

Clinically significant reduction in serum c-Terminal peptide of procollagen type I (CTX) obtained through 3, 6 and 12 months of therapy. After a year of therapy with Bonviva^® 3 mg in/in the reduction of STH is 58.6% compared to the original value.

Pharmacokinetics

Not identified direct dependence of the efficiency of the ibandronova acid from the concentration of the substance in blood plasma.

Concentration in plasma dozozawisimo increases with increasing doses of 500 micrograms to 6 mg.

Absorption

After intake of ibandronic acid is rapidly absorbed from the upper gastrointestinal divisions. Concentration in plasma dozozawisimo increases with increasing doses up to 50 mg and much more – further dose. T_max is 0.5-2 no (median – 1 no) After taking prandial, absolute bioavailability 0.6%. Simultaneous intake of food or drink (In addition to the pure water) reduces the bioavailability of ibandronova acid 90%. When taking ibandronova acid 60 minutes before eating a meaningful decrease bioavailability is not observed. Food or liquid in less than a 60 minutes after ibandronova acid reduces its bioavailability and caused an increase in the IPC.

Distribution

After falling into the bloodstream quickly acid ibandronic binds in the bone or excreted in the urine. 40-50% the number of drug, circulating in the blood it penetrates into bone tissue and accumulates it. The seemingly final V_d sostavlâet90 l. Plasma protein binding – 85-87%.

Metabolism

Information about, ibandronic acid that is not metabolized.

Ibandronate not ingibiruet enzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A4 zitohroma r450.

Deduction

40-50% vsosavšejsâ oral dose in the bloodstream binds in the bones, and the remainder is excreted unchanged in urine. Nevsosavšijsâ drug is excreted unchanged in the faeces.

After the on / in the 40-50% dose is associated in the bones, the rest of the place in an unmodified form with urine.

Terminal T_1/2 10-72 no. The concentration of the drug in the blood decreases rapidly and is 10% the maximum through 8 hours after oral ingestion and through 3 h after i / v administration.

The total clearance of ibandronova acid 84-160 ml / min. Renal clearance (60 mL/min in healthy women in menopause) is 50-60% General clearance and depends on QC. The difference between the General and the ground substance capture reflects renal bone.

Pharmacokinetics in special clinical situations

Pharmacokinetics of ibandronova acid is not dependent on sex.

Not revealed clinically significant race difference distribution of ibandronova acid from persons to southern European and Asian race. Regarding the Negroid race data are insufficient.

In patients with impaired kidney kidney klirens ibandronova acid is linearly dependent on QC. In the human kidney mild or moderate (QC ≥ 30 mL/min) dose adjustment is required. In patients with severe renal impairment (CC <30 ml / min), receiving the drug inside the dose 10 mg for 21 day, the concentration of ibandronova acid in the blood plasma in 2-3 times higher, than in patients with normal renal function (total clearance 129 ml / min). In dire human kidney total clearance of ibandronova acid is reduced to 44 ml / min. In patients with severe renal impairment (CC <30 ml / min), receiving drug dose 0.5 mg / in, general, Kidney and nepočečnyj klirensy ibandronova acid decreased 67%, 77% and 50%, respectively. However, the system does not affect the tolerance of the drug concentration.

Farmakokinetike ibandronova acid in patients with impaired liver function is missing. Liver plays no significant role in clearance ibandronova acid, that is not metabolized, and report the news, and by capturing in the bone. Therefore, for patients with impaired liver dose adjustment is not required. Unnecessarily. in therapeutic concentrations ibandronic acid moderately associated with blood plasma proteins (85%), probably, that severe gipoproteinemia liver does not result in clinically important higher concentrations of free stuff in the blood.

Pharmacokinetic parameters examined do not depend on age. Should take into account the possible reduced kidney function in elderly patients.

Testimony

is post-menopausal osteoporosis to prevent fractures.

Dosage regimen

The drug is prescribed inside by 150 mg (1 tab.) 1 times / month (preferably on the same day of each month), for 60 minutes before the first meal of the day, liquids (except water) or other drugs and dietary supplements. The tablets should be swallowed whole, with a glass (180-240 ml) clean water, sitting or standing. Should not fall within the 60 minutes after administration. Tablets should not be chewed or dissolve due to possible ulceration upper gastrointestinal divisions. You cannot use a mineral water with a high content of calcium.

If you skip a scheduled reception should adopt 1 tab. medication Bonviva^®, If before the scheduled admission remains more 7 days, continue to take medication Bonviva^® 1 times/months in accordance with the established schedule. If until the next scheduled admission less than 7 days, You must wait until the next-to-plan (BTP) reception, and further reception in accordance with the established schedule. Do not take more 1 tab. medication Bonviva^® in Week.

The solution is intended only for I / introduction. Should be avoided in/and the imposition of a solution of the drug or their falling into the surrounding tissue.

The drug should enter only specialist. Before the introduction of the solution should be inspected for extraneous matter or discoloration.

You should use needles with syringe-tubes. Spric-tubik is intended only for a single injection.

The drug is injected in a dose 3 mg in/in bolusno (during 15-30 sec) 1 once every 3 Months. Additionally, you should recommend drugs calcium and vitamin D.

If you skip a planned injection, the injection should be held immediately, as soon as the possibility of. Further, the introduction of the drug continue every 3 months after the last injection.

You cannot assign the drug more often 1 times a 3 of the month.

During treatment should monitor kidney function, contents of serum calcium, phosphorus and magnesium.

At abnormal liver function dose adjustment is required.

At low and moderately expressed violation of the kidney (CC >30 ml / min) dose adjustment is required. At CC < 30 ml / min the decision to appoint Bonvivy^® should be taken on the basis of an individual assessment of the balance of risks and benefits of therapy for the individual patient.

Elderly patients dose adjustment is required.

Side effect

From the digestive system: dyspepsia (nausea, vomiting, stomach ache, dysphagia, flatulence), diarrhea, constipation, esophagitis, ulcers or esophageal stricture, hastroэzofahealnыy reflux, gastritis, gastroenteritis, duodenitis.

CNS: headache, dizziness.

On the part of the musculoskeletal system: myalgia, arthralgia, muscle stiffness, muscle spasm, pain in the limbs, ostealgias, osteoarthritis; rarely – osteonecrosis of the jaw.

From the urinary system: at / in the introduction – cystitis, urinary tract infection.

The respiratory system: at / in the introduction – infection of the upper respiratory ways, bronchitis.

Dermatological reactions: rash.

Allergic reactions: angioedema, hives.

Other: flu-like symptoms; at / in the introduction – injection site reactions, phlebitis, tromboflebit, arterial hypertension, hypercholesterolemia, uveitis, scleritis.

Bonviva^®, like other bisphosphonates, the on/in the introduction can cause a short-term reduction in the level of calcium in blood serum.

Contraindications

- Hypocalcemia;

-hypersensitivity to ibandronova acid or other components of the drug.

FROM caution the drug should be used with heavy human kidney function (serum creatinine > 2.3 mg / dL or KK<30 ml / min).

Pregnancy and lactation

Category C. Clinical experience of application of Bonviva^® during pregnancy is not.

Unknown, whether ibandronic acid is secreted in breast milk in humans.

IN experimental studies oral introduction rats and krolikam acid ibandronova no indication of direct embryotoxicity or teratogenicity; the dose of the drug, exceeding dose for a person, at least, in 35 time, not found adverse effects on offspring development in rats F1. Adverse effects of ibandronova acid in reproductive toxicity studies in rats were the same, like all bisphosphonates – reducing the number of embryos, violation of the birth process, an increase in the frequency of visceral anomalies (syndrome of narrowing the pelvic-ureteric segment).

Excreted in breast milk in rats. Through 24 h concentration of ibandronova acid in plasma and milk are the same and correspond to 5% Larger.

Cautions

Osteoporosis can be confirmed by identifying low IPC (T index < -2.0 SD [Standard deviation – standard deviation]) and fracture (incl. history) or low bone mineral density (T index <-2.5 SD) in the absence of a confirmed the fracture.

Before applying the product Bonviva^® should skorrigirovat′ gipocalziemia and other violations of bone metabolism and electrolyte balance. Patients should consume adequate amounts of calcium and vitamin D.

If the patient receives insufficient dietary intake of calcium and vitamin D, You should additionally take them in the form of food supplements.

Side effects of the drug are usually weakly or moderately expressed. Transient grippopodobnyy syndrome noted after the first dose and allowed yourself without correction therapy. There has been an increase in the frequency of adverse effects from the upper gastrointestinal divisions in patients with gastrointestinal diseases (including peptic ulcer without hemorrhage and hospitalization, dyspepsia or gastroèzofageal′nuû reflûksnuû disease).

Use of oral bisphosphonates is often accompanied by violation of the swallowing, esophagitis and formation of ulcers of esophagus and stomach, It is therefore necessary to pay particular attention to the recommendations on the admission of the drug (sitting or standing for 60 minutes after administration).

When symptoms of possible lesions of esophagus (the emergence or intensification of violations of swallowing, pain when swallowing, chest pain, heartburn) the patient should stop taking Bonvivy^® and consult a doctor.

Before each injection should determine the content of serum creatinine.

Should carefully monitor the condition of patients with concomitant diseases, where possible deterioration of kidney function, and patients, receiving drugs with nefrotoksicski effect.

When assigning other bisphosphonate rarely celebrated osteonecrosis jaw. Most of the cases registered in cancer patients during dental procedures, several cases – in patients with postmenopauznym osteoporosis or other conditions. Risk factors for osteonekroza jaw include established the diagnosis of cancer, concomitant therapy (chemotherapy, radiation therapy, GCS) and other violations (anemia, coagulopathy, infection, gum disease in history). The majority of the cases noted in the on/in the appointment of bisphosphonate, but individual cases have been observed in patients, treated with drugs inside.

Surgical dental intervention on bisfosfonatami therapy can strengthen the manifestations of osteonekroza jaw. Unknown, reduces the risk of osteonekroza cancellation of bisphosphonate. The decision about treatment should be taken for each patient individually after assessing the risk/benefit ratio.

When taking bisphosphonates, incl. and Bonvivy^®, You may experience severe pain: joint pain, the bones and muscles. Pain emerged as the next day, and a few months from the beginning of the reception of the drug, most patients were resolved after cessation of therapy, some of these symptoms were renewed after the reappointment of the same or different drug.

Postmarketing experience of applying Bonvivy^® limited.

Use in Pediatrics

Safety and efficacy have children and adolescents up to 18 years not set.

Overdose

Symptoms: possible ingestion – dyspepsia, heartburn, esophagitis, gastritis, ulcer, hypocalcemia; at / in the introduction – hypocalcemia, gipofosfatemiя, gipomagnemiâ.

Treatment: specific information missing. To associate a ibandronova acid used milk or antacids. Due to the risk of esophageal irritation should not induce vomiting, You must remain erect when standing.

Clinically significant reduction in calcium, phosphates and magnesium in the serum can be adjusted/with the introduction of Calcium Gluconate, potassium or sodium phosphate and magnesium sulfate, respectively.

Dialysis nyeeffyektivyen, If a later 2 hours after injection.

Drug Interactions

Products, calcium-containing and other polyvalent cations (eg, aluminum, magnesium, iron), incl. milk and solid foods, can interfere with absorption of the drug, they should be eaten no earlier than 60 minutes after taking the Bonvivy^® inside.

Nutritional supplements with calcium, Antacids and medications, containing polivalentne cations (eg, aluminum, magnesium, iron) can interfere with the absorption of ibandronova acid, Therefore, they should be taken no earlier than 60 minutes after taking the Bonvivy^®.

Bisphosphonates and NSAIDS can cause irritation of mucous membrane syndrome. You should exercise extreme caution when applying NSAIDS concurrently with medication Bonviva^®. When acetylsalicylic acid or NSAIDs and a medication Bonviva^® during 1 year frequency of side effects from the upper gastrointestinal divisions was the same.

Ranitidine in the on/in the introduction increases the bioavailability of ibandronova acid 20%. Correction doses ibandronova acid together with blokatorami gistaminovykh n₂-receptors or other drugs, increase the pH in the stomach, not required.

Ibandronic acid has no effect on the activity of the major cytochrome P450 system Isoenzymes. In therapeutic concentrations ibandronic acid is weakly associated with blood plasma proteins, and so it is unlikely, that it would displace other protein binding sites medicines. Ibandronic acid only appears kidneys and does not undergo any biotransformation. Apparently, way of deducing ibandronova acid does not include any transportation systems, involved in excretion of other drugs.

Bonviva^® solution for the on/in the introduction is not compatible with kal′cijsoderžaŝimi solutions and other solutions for the on/in the introduction.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

Tablets should be stored in a place inaccessible to children, safe dry place at a temperature of no higher than 30° c. Shelf life – 3 year.

Solution for the on/in the introduction should be stored out of the reach of children at a temperature of no higher than 30° c. Shelf life – 2 year.