Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.3 · PDF-Seite 4

HOS-126246 · Präparat HOS-096231

• Hypersensitivity to the active substance, to other bisphosphonates or to any of the excipients listed in section 6.1 • Breast-feeding (see section 4.6

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Wechselwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 6

HOS-126247 · Präparat HOS-096231

In clinical studies, zoledronic acid has been administered concomitantly with commonly used anticancer agents, diuretics, antibiotics and analgesics without clinically apparent interactions occurring. Zoledronic acid shows no appreciable binding to plasma proteins and does not inhibit human P450 enzymes in vitro (see section 5.2), but no formal clinical interaction studies have been performed.

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Wechselwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 6

HOS-126248 · Präparat HOS-096231

Caution is advised when bisphosphonates are administered with aminoglycosides, calcitonin or loop diuretics, since these agents may have an additive effect, resulting in a lower serum calcium level for longer periods than required (see section 4.4).

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): calcium (HOS-085615) calcitonin (HOS-108441)

Wechselwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 6

HOS-126249 · Präparat HOS-096231

Caution is indicated when zoledronic acid is used with other potentially nephrotoxic medicinal products. Attention should also be paid to the possibility of hypomagnesaemia developing during treatment.

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Wechselwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 6

HOS-126250 · Präparat HOS-096231

In multiple myeloma patients, the risk of renal dysfunction may be increased when zoledronic acid is used in combination with thalidomide.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): thalidomide (HOS-108445)

Wechselwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 6

HOS-126251 · Präparat HOS-096231

Caution is advised when zoledronic acid is administered with anti-angiogenic medicinal products as an increase in the incidence of ONJ has been observed in patients treated concomitantly with these medicinal products.

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Nebenwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-126252 · Präparat HOS-096231

Summary of the safety profile

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Nebenwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-126253 · Präparat HOS-096231

Within three days after zoledronic acid administration, an acute phase reaction has commonly been reported, with symptoms including bone pain, fever, fatigue, arthralgia, myalgia, rigors and arthritis with subsequent joint swelling; these symptoms usually resolve within a few days (see description of selected adverse reactions).

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Nebenwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-126254 · Präparat HOS-096231

The following are the important identified risks with zoledronic acid in the approved indications: Renal function impairment, osteonecrosis of the jaw, acute phase reaction, hypocalcaemia, atrial fibrillation, anaphylaxis, interstitial lung disease. The frequencies for each of these identified risks are shown in Table 1.

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Nebenwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-126255 · Präparat HOS-096231

Tabulated list of adverse reactions

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Nebenwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8–9

HOS-126256 · Präparat HOS-096231

The following adverse reactions, listed in Table 1, have been accumulated from clinical studies and post-marketing reports following predominantly chronic treatment with 4 mg zoledronic acid: Table 1

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Nebenwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 9

HOS-126257 · Präparat HOS-096231

Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).

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Nebenwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 9–10

HOS-126258 · Präparat HOS-096231

Blood and lymphatic system disorders Common: Anaemia Uncommon: Thrombocytopenia, leukopenia Rare: Pancytopenia Immune system disorders Uncommon: Hypersensitivity reaction Rare: Angioneurotic oedema Psychiatric disorders Uncommon: Anxiety, sleep disturbance Rare: Confusion Nervous system disorders Common: Headache Uncommon: Dizziness, paraesthesia, dysgeusia, hypoaesthesia, hyperaesthesia, tremor, somnolence Very rare: Convulsions, hypoaesthesia and tetany (secondary to hypocalcaemia) Eye disorders Common: Conjunctivitis Uncommon: Blurred vision, scleritis and orbital inflammation Rare: Uveitis Very rare: Episcleritis Cardiac disorders Uncommon: Hypertension, hypotension, atrial fibrillation, hypotension leading to syncope or circulatory collapse Rare: Bradycardia, cardiac arrhythmia (secondary to hypocalcaemia) Respiratory, thoracic and mediastinal disorders Uncommon: Dyspnoea, cough, bronchoconstriction Rare: Interstitial lung disease Gastrointestinal disorders Common: Nausea, vomiting, decreased appetite Uncommon: Diarrhoea, constipation, abdominal pain, dyspepsia, stomatitis, dry mouth Skin and subcutaneous tissue disorders Uncommon: Pruritus, rash (including erythematous and macular rash), increased sweating Musculoskeletal and connective tissue disorders Common: Bone pain, myalgia, arthralgia, generalised pain Uncommon: Muscle spasms, osteonecrosis of the jaw Very rare: Osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction) and other anatomical sites including femur and hip Renal and urinary disorders Common: Renal impairment Uncommon: Acute renal failure, haematuria, proteinuria Rare: Acquired Fanconi syndrome Not known: Tubulointerstitial nephritis General disorders and administration site conditions Common: Fever, flu-like syndrome (including fatigue, rigors, malaise and flushing) Uncommon: Asthenia, peripheral oedema, injection site reactions (including pain, irritation, swelling, induration), chest pain, weight increase, anaphylactic reaction/shock, urticaria Rare: Arthritis and joint swelling as a symptom of acute phase reaction Investigations Very common: Hypophosphataemia Common: Blood creatinine and blood urea increased, hypocalcaemia Uncommon: Hypomagnesaemia, hypokalaemia Rare: Hyperkalaemia, hypernatraemia

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Nebenwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 10

HOS-126259 · Präparat HOS-096231

Description of selected adverse reactions Renal function impairment Zoledronic acid has been associated with reports of renal dysfunction. In a pooled analysis of safety data from zoledronic acid registration trials for the prevention of skeletal-related events in patients with advanced malignancies involving bone, the frequency of renal impairment adverse events suspected to be related to zoledronic acid (adverse reactions) was as follows: multiple myeloma (3.2%), prostate cancer (3.1%), breast cancer (4.3%), lung and other solid tumours (3.2%). Factors that may increase the potential for deterioration in renal function include dehydration, pre-existing renal impairment, multiple cycles of zoledronic acid or other bisphosphonates, as well as concomitant use of nephrotoxic medicinal products or using a shorter infusion time than currently recommended. Renal deterioration, progression to renal failure and dialysis have been reported in patients after the initial dose or a single dose of 4 mg zoledronic acid (see section 4.4).

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Nebenwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 10

HOS-126260 · Präparat HOS-096231

Osteonecrosis of the jaw Cases of osteonecrosis of the jaw have been reported, predominantly in cancer patients treated with medicinal products that inhibit bone resorption, such as zoledronic acid (see section 4.4). Many of these patients were also receiving chemotherapy and corticosteroids and had signs of local infection including osteomyelitis. The majority of the reports refer to cancer patients following tooth extractions or other dental surgeries.

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Nebenwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 10

HOS-126261 · Präparat HOS-096231

Atrial fibrillation In one 3-year, randomised, double-blind controlled trial that evaluated the efficacy and safety of zoledronic acid 5 mg once yearly vs. placebo in the treatment of postmenopausal osteoporosis (PMO), the overall incidence of atrial fibrillation was 2.5% (96 out of 3,862) and 1.9% (75 out of 3,852) in patients receiving zoledronic acid 5 mg and placebo, respectively. The rate of atrial fibrillation serious adverse events was 1.3% (51 out of 3,862) and 0.6% (22 out of 3,852) in patients receiving zoledronic acid 5 mg and placebo, respectively. The imbalance observed in this trial has not been observed in other trials with zoledronic acid, including those with zoledronic acid 4 mg every 3-4 weeks in oncology patients. The mechanism behind the increased incidence of atrial fibrillation in this single clinical trial is unknown.

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Nebenwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 10–11

HOS-126262 · Präparat HOS-096231

Acute phase reaction This adverse drug reaction consists of a constellation of symptoms that includes fever, myalgia, headache, extremity pain, nausea, vomiting, diarrhoea, arthralgia and arthritis with subsequent joint swelling. The onset time is ≤ 3 days post-zoledronic acid infusion, and the reaction is also referred to using the terms “flu-like” or “post-dose” symptoms. Atypical fractures of the femur During post-marketing experience the following reactions have been reported (frequency rare): Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction).

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Nebenwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 11

HOS-126263 · Präparat HOS-096231

Hypocalcaemia-related ADRs Hypocalcaemia is an important identified risk with zoledronic acid in the approved indications. Based on the review of both clinical trial and post-marketing cases, there is sufficient evidence to support an association between zoledronic acid therapy, the reported event of hypocalcaemia, and the secondary development of cardiac arrhythmia. Furthermore, there is evidence of an association between hypocalcaemia and secondary neurological events reported in these cases including; convulsions, hypoaesthesia and tetany (see section 4.4).

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Nebenwirkungen · Zoledronic acid Mylan

Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 11

HOS-126264 · Präparat HOS-096231

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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