Medicinal Products

ZOLEDRONIC ACID TEVA PHARMA 5 mg Perfusion box of 1 vial of 100 ml

Generic drug from Aclasta
Therapeutic class: Rheumatology
active ingredients: Zoledronic acid
laboratory: Teva Sante

Injection solution for IV infusion
All forms

Indication

Treatment of osteoporosis

■ in postmenopausal women

■ in adult men

in patients at high risk of fracture, especially in patients who have had a recent hip fracture secondary to moderate trauma.

Treatment of osteoporosis associated with long-term systemic corticosteroid therapy

■ in postmenopausal women

■ in adult men at high risk of fractures.

Treatment of Paget's disease in adults.

Posology ZOLEDRONIC ACID TEVA PHARMA 5 mg Perfusion box of 1 vial of 100 ml

Treatment of osteoporosis

■ in postmenopausal women

■ in adult men

in patients at high risk of fracture, especially in patients who have had a recent hip fracture secondary to moderate trauma.

Treatment of osteoporosis associated with long-term systemic corticosteroid therapy

■ in postmenopausal women

■ in adult men at high risk of fractures.

Treatment of Paget's disease in adults.

Against indications

- Hypersensitivity to the active substance, other bisphosphonates or to any of the excipients listed under Composition .

- Patients with hypocalcemia (see section Warnings and precautions for use ).

- Severe renal insufficiency with creatinine clearance <35 ml / min (see Warnings and Precautions section )

- Pregnancy or breastfeeding (see section Pregnancy and lactation ).

Adverse effects Zoledronic acid Teva Pharma

Summary of the security profile

The overall percentage of patients who experienced adverse events after administration was 44.7%, 16.7% and 10.2% after the first, second and third infusions, respectively. The individual incidence of these adverse events after the first administration was: fever (17.1%), myalgia (7.8%), flu-like symptoms (6.7%), arthralgia (4.8%) and headache (5.1%). The incidence of these effects decreased significantly with the annual sucrose doses of zoledronic acid. The majority of these effects occurred within the first three days after zoledronic acid administration, were mild to moderate and disappeared within three days of their onset. The percentage of patients with adverse events was 19.5%, 10.4%, 10.7% after the first, second and third infusions, respectively, in a smaller study where preventive treatment against the occurrence of adverse effects occurred. adverse effects had been used.

In the HORIZON-PFT pivotal study (postmenopausal osteoporosis) (see section 5.1 ), the overall incidence of atrial fibrillation was 2.5% (96 of 3 862) and 1.9% (75%). 3, 852) in patients receiving zoledronic acid and placebo, respectively. The rate of atrial fibrillation classified as serious adverse events was 1.3% (51/3862) in patients treated with zoledronic acid compared to 0.6% (22/3852) in patients receiving placebo. The mechanism of increase of this incidence of atrial fibrillation is not known. In the HORIZON-PFT and HORIZON-RFT studies (hip fracture study), the overall incidence of atrial fibrillation was comparable between the zoledronic acid group (2.6%) and the placebo group (2.1)%. The overall incidence of atrial fibrillations reported as a serious adverse event was 1.3% for the zoledronic acid group and 0.8% for the placebo group.

Tabulated list of adverse effects

Adverse effects in Table 1 are listed according to the MedDRA system organ class classification and by frequency category. Frequency categories are defined according to the following convention: very common (≥ 1/10); frequent (≥ 1/100 to <1/10); uncommon (≥ 1/1000 to <1/100); rare ≥ 1/10 000 to <1/1000); very rare (<1 / 10, 000); indeterminate frequency (can not be estimated based on available data). Within each frequency group, adverse effects are presented in descending order of severity.

Table 1

Infections and infestations

Rare

Flu, nasopharyngitis

Hematological disorders

and the lymphatic system

Rare

Anemia

Immune system disorders

Not known frequency **

Hypersensitivity reactions including

rare cases of bronchoconstriction, urticaria and angioedema and very rare cases of

or anaphylactic shock

Metabolism disorders and

of nutrition

Frequent

hypocalcemia *

Rare

Anorexia, decreased appetite

Psychiatric disorders

Rare

Insomnia

System conditions

nervous

Frequent

Headache, vertigo

Rare

Lethargy, paresthesia, drowsiness,

tremors, syncope, dysgeusia

Eye disorders

Frequent

Rare

Rare

Not known frequency **

Ocular hyperemia

Conjunctivitis, eye pain

Uveitis, episcleritis, iritis

Scleritis and Ocular Inflammation

Affections of the ear and labyrinth

Rare

Dizziness

Heart conditions

Frequent Uncommon

Palpitations atrial fibrillation

Vascular disorders

Uncommon Not known

Hypertension, flushing

Hypotension (in patients with underlying risk factors)

Respiratory, thoracic and mediastinal disorders

Rare

Cough dyspnea

Gastrointestinal disorders

intestinal

Frequent

Nausea, vomiting, diarrhea

Rare

Dyspepsia, high abdominal pain, abdominal pain, gastroesophageal reflux, constipation, dry mouth, esophagitis, dental pain, gastritis #

Skin and subcutaneous tissue disorders

Rare

Rash, hyperhydrosis, pruritus,

erythema

Musculoskeletal and systemic disorders

Frequent

Myalgia, arthralgia, bone pain,

spinal pain, pain at the level

ends

Rare

Cervicalgia, musculoskeletal stiffness, joint swelling, muscle spasms, shoulder pain, musculoskeletal chest pain, musculoskeletal pain, joint stiffness, arthritis,

muscular weakness

Rare

Atypical subtrochanteric and diaphyseal femoral fractures (class-related adverse effects of bisphosphonates)

Not known frequency **

Osteonecrosis of the jaw (see

sections Warnings and precautions for use and undesirable effects Class effects)

Kidney disorders and

urinary tract

Rare

Not known frequency **

Increased creatinine, pollakiuria, proteinuria

Alteration of renal function. Cases

impaired renal function requiring

dialysis and rare cases having an outcome

have been reported in patients

with pre-existing renal impairment

or other risk factors such as

Concomitant use of nephrotoxic drugs, diuretic therapy

or in case of dehydration occurring after

infusion (see sections Warnings and Precautions and Adverse Reactions Class Effects)

General disorders and administration site conditions

Very common

Fever

Frequent

Flu-like syndrome, chills, fatigue, asthenia, pain, malaise, reaction to the site

infusion

Rare

Peripheral edema, thirst, reaction

acute inflammatory, chest pain

non-cardiac

Frequency

unlimited **

Dehydration secondary to post-administration symptoms such as fever,

vomiting

and diarrhea

investigations

Frequent

Increased C-reactive protein

Rare

hypocalcemia

# Observe in patients taking concomitant corticosteroid therapy.

* Frequent in case of Paget's disease only.

** Based on post-marketing data. The frequency can not be estimated on the basis of available data.

Identified since commercialization.

Description of selected adverse reactions

Class effects:

Alteration of renal function

Zoledronic acid has been associated with impaired renal function manifesting as deterioration of renal function (ie increased serum creatinine) and in rare cases acute renal failure. Impairment of renal function has been observed after zoledronic acid administration, particularly in patients with pre-existing renal impairment or additional risk factors (eg, elderly patients, chemotherapy for cancer, concomitant nephrotoxic drugs, diuretic therapy concomitant, severe dehydration, etc.). The majority of these patients received a dose of 4 mg every 3 to 4 weeks, but renal dysfunction was also observed in patients receiving a single administration.

In clinical studies in osteoporosis, changes in creatinine clearance (measured each year prior to injection) and the incidence of renal impairment were comparable in both treatment groups (zoledronic acid and placebo) over a period of three years. A transient increase in serum creatinine was observed in 10 days in 1.8% of patients treated with zoledronic acid versus 0.8% of patients treated with placebo.

hypocalcemia

In clinical studies in osteoporosis, approximately 0.2% of patients experienced a significant decrease in serum calcium (less than 1.87 mmol / l) following administration of zoledronic acid. No cases of symptomatic hypocalcemia were observed.

In patients with Paget's disease, symptomatic hypocalcemia was observed in approximately 1% of patients. In all patients, hypocalcemia was resolving.

Based on the evaluation of biological parameters from a large clinical study, transient and asymptomatic serum calcium values ​​below baseline (less than 2.10 mmol / l) were observed in 2.3 % of patients treated with zoledronic acid compared to 21% of patients treated with zoledronic acid in Paget's disease studies. The frequency of hypocalcemia was much lower with subsequent infusions.

All patients received vitamin D and calcium supplementation: in the study on postmenopausal osteoporosis, in the study on the prevention of clinical fractures after hip fracture as well as in studies of Paget (see also section Dosage and method of administration ). In the study on the prevention of clinical fractures after recent hip fracture, vitamin D levels were not measured routinely, but a vitamin D loading dose was given to most patients before acid administration. zoledronic acid (see section Dosage and method of administration ).

Local reactions

In a large study, local reactions at the perfusion site, such as redness, swelling, and / or pain (0.7%), were observed after administration of zoledronic acid.

Osteonecrosis of the jaw

Cases of osteonecrosis of the jaw have been reported, mainly in cancer patients treated with bone resorption inhibiting drugs, including zoledronic acid (see Warnings and Precautions ). In a large clinical study in 7, 736 patients, one case of osteonecrosis of the jaw was reported in one patient treated with zoledronic acid and one patient treated with placebo. Cases of osteonecrosis of the jaw have been reported since the marketing of Zoledronic Acid Teva Pharma.

Reporting of suspected adverse reactions

The reporting of suspected adverse reactions after authorization of the drug is important. It allows continuous monitoring of the benefit / risk ratio of the drug. Health professionals report any suspected adverse reactions via the national reporting system - see Annex V.

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