AREDIA 30 mg

AREDIA 30 mg
€ 199.00
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The drug substance is disodium 3-amino-l-hydroxypropylidene-l, l-biphosphonate pentahydrate (Pamidronat disodium) [disodium 3-amino-1-hydroxypropylidene-1, 1 - bisphosphonate pentahydrate (disodium pamidronate)].
One vial contains 30 mg of sterile lyophilized pamidronate disodium. Vials are supplied solvent ampoules. One solvent ampoule contains 10 ml of sterile water for injection.

AREDIA 30 mg

 
 
QUALITATIVE AND QUANTITATIVE COMPOSITION
The drug substance is disodium 3-amino-l-hydroxypropylidene-l, l-biphosphonate pentahydrate (Pamidronat disodium) [disodium 3-amino-1-hydroxypropylidene-1, 1 - bisphosphonate pentahydrate (disodium pamidronate)].
One vial contains 30 mg of sterile lyophilized pamidronate disodium. Vials are supplied solvent ampoules. One solvent ampoule contains 10 ml of sterile water for injection.
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Powder and solvent for solution for infusion.
4. CLINICAL DATA
4.1 Therapeutic indications
Treatment of conditions associated with increased osteoclast activity:
• predominantly lytic bone metastases and multiple myeloma
• tumor-induced hypercalcaemia
• Paget's disease
4.2 Posology and method of administration
Aredia never be given as a bolus injection (see 4.4 Special warnings and precautions for use). A freshly prepared solution of Aredia powder in vials should be diluted with solutions containing calcium (e.g. 0.9% sodium chloride or 5% dextrose solution) and infused slowly.
The infusion rate should not exceed 60 mg / h (1 mg / min), the concentration of Aredia in the infusion solution should not exceed 90 mg/250 ml. A dose of 90 mg should normally be administered as a period of 2 hours in 250 ml of infusion solution. In patients with multiple myeloma, however, as well as in patients with tumor-induced hypercalcaemia, it is recommended not to exceed 90 mg in 500 ml solution for 4 hours.
To minimize local reactions at the infusion site, abokatat must be placed into a large vein.

Adults and elderly
Predominantly lytic bone metastases and multiple myeloma
The recommended dose for the treatment of Aredia predominantly lytic bone metastases and multiple myeloma is 90 mg, a single infusion every 4 weeks.
Patients with bone metastases who receive chemotherapy at 3-week intervals could receive 90 mg Aredia over three weeks.

Tumor-induced hypercalcaemia
Patients should be adequately rehydrated before or during the treatment with Aredia.
The total dose of Aredia, which is used for the treatment course, depend on the initial level of serum calcium to the patient. The following guidelines are derived from clinical data on uncorrected calcium levels. Doses within those can also be used for calcium values corrected for protein or albumin in rehydrated patients.
Table 1.
Initial serum kaltsiyPreporachvana total dose
mmol/1mg% dose (mg)
to 3.0 to 12.015-30
3,0-3,512-14,030-60
3,5-4,014,0-16,060-90
> 4,090
The total dose of Aredia may be administered either as a single infusion or as multiple infusions over 2-4 consecutive days. The maximum dose per treatment course is 90 mg for both initial and repeated courses.
A significant decrease in serum calcium is generally observed 24 to 48 hours after administration of Aredia, and normalization is usually within 3 to 7 days. If you do not reach normocalcaemia that time may be given an additional dose. Duration of response may vary from patient to patient, and treatment can be repeated whenever hypercalcaemia recurs. Clinical experience shows that Aredia becomes less efficient with increasing number of treatments.

Paget disease of bone
The recommended total dose of Aredia per treatment course is 180 to 210 mg. It can be administered either as a single doses of 6 of 30 mg once a week (total dose 180 mg), or in the 3 single doses of 60 mg every other week. If using a single dose of 60 mg, it is recommended to begin treatment with the initial dose of 30 mg (total dose 210 mg). This mode, omitting the initial dose of 30 mg, can be repeated after 6 months to achieve remission of the disease at relapse.

renal impairment
Aredia should not be used in patients with severe renal impairment (creatinine clearance <30 ml / min), except in cases of life-threatening hypercalcemia, where the benefit outweighs the potential risk.
As with other i.V. bisphosphonates, monitoring of renal function, such as measurement of serum creatinine prior to each dose of Aredia. In patients receiving Aredia for bone metastases or multiple myeloma patients who show evidence of deterioration in renal function, Aredia treatment should be withheld until renal function returns to 10% of baseline. This recommendation is based on a clinical study in which renal deterioration was defined as follows:
• For patients with normal baseline creatinine, increase of 0,5 mg / dl
• For patients with abnormal baseline creatinine, increase of 1,0 mg / dl.
A pharmacokinetic study conducted in patients with cancer and normal or impaired renal function showed that no dose adjustment is required in mild (creatinine clearance 61-90 ml / min) or moderate renal impairment (creatinine clearance 30-60 ml / min). In such patients, the infusion rate should not exceed 90 mg / 4 h (approximately 20-22 hrg / h).

hepatic impairment
Pharmacokinetic study indicates that no dosage adjustment in patients with mild to moderate hepatic dysfunction (see 5.2 Pharmacokinetic properties and liver damage). Aredia has not been studied in patients with severe hepatic impairment (see 4.4 Special warnings and precautions for use).

Use in children
There is no clinical experience of Aredia in children.
4.3 Contraindications
Aredia is contraindicated in:
• patients with known hypersensitivity to pamidronate, other bisphosphonates, or any of the excipients of Aredia.
• pregnancy
• breastfeeding.
4.4 Special warnings and precautions for use General
Aredia should not be administered as a bolus injection, but should always be diluted and administered by slow intravenous infusion (see section 4.2. Dosage and method of administration). Prior to initiation of therapy with Aredia must ensure that patients are well hydrated. This is particularly important in patients using diuretics.
At the start of treatment with Aredia should be monitored serum levels of electrolytes, calcium and phosphorus. Patients with previous surgery of the thyroid gland are especially prone to developing hypocalcaemia due to relative hypoparathyroidism. In patients with cardiac disease, especially in the elderly, additional saline infusion may trigger or worsen heart failure (left ventricular failure or congestive heart failure). Fever (flu like symptoms) may also contribute to this deterioration.

renal failure
Bisphosphonates, including Aredia, have been associated with renal toxicity manifested as deterioration of renal function and potential renal failure. Deterioration of renal function in renal failure and dialysis have been reported in patients after administration of a single dose or starting Aredia. Deterioration in renal function (including renal failure) have been reported after prolonged treatment with Aredia in patients with multiple myeloma.

Aredia is excreted unchanged by the kidney (see 5.2), and therefore the risk of side effects on the kidneys may be greater in patients with renal impairment.
Due to the risk of clinically significant deterioration in renal function, which may progress to renal failure, single doses of Aredia should not exceed 90 mg and the recommended infusion time should be observed (see 4.2. Dosage and method of administration).

As with other i.V. bisphosphonates, monitoring of renal function, such as measurement of serum creatinine prior to each dose of Aredia. Patients who receive frequent infusions of Aredia for prolonged periods of time, especially those with pre-existing renal disease or a predisposition to renal impairment (i.e., patients with multiple myeloma and / or tumor-induced hypercalcemia), should be periodically follow standard laboratory and clinical parameters of renal function before each dose of Aredia.

Therapy should be discontinued in deterioration of renal function in patients treated with Aredia for bone metastases or multiple myeloma (see 4.2. Dosage and method of administration).
Aredia should not be administered concomitantly with other bisphosphonates, as their combined effects have not been studied.

hepatic failure
As no clinical data in patients with severe hepatic impairment can not be given specific recommendations for this patient population (see section 4.2 Posology and method of administration and 5.2).

Adding calcium and vitamin D
In the absence of hypercalcemia patients with predominantly lytic bone metastases or multiple myeloma who are at high risk of a deficiency of calcium and vitamin D, and patients with Paget's bone disease, should receive oral calcium and vitamin D to reduce the risk of hypocalcemia.

Osteonecrosis of the jaw
Osteonecrosis of the jaw (ONJ) has been reported predominantly in cancer patients treated with bisphosphonates, including Aredia. Many of these patients were also receiving chemotherapy and corticosteroids. Many had signs of local infection including osteomyelitis.

Post marketing experience and the literature suggest a greater frequency of reporting of ONJ associated with tumor type (advanced breast cancer, multiple myeloma) and dental status (dental extraction, periodontal, local trauma, including uncomfortable dentures).
Cancer patients should maintain good oral hygiene and conduct preventive dental examinations prior to treatment with bisphosphonates. During treatment, these patients should, if possible, avoid invasive dental procedures. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. The treatment plan should be guided by clinical judgment of the treating physician for each patient based on individual assessment of the benefit / risk ratio.

Musculoskeletal pain
In post-marketing studies reported severe and occasionally incapacitating bone, joint and / or muscle pain after taking bisphosphonates. However, these reports are uncommon. This group of drugs includes Aredia (pamidronate disodium infusion). The time to onset of symptoms varied from one day to several months after starting therapy. After cessation of therapy in most patients symptoms disappear. In some patients, the renewal of treatment with the same drug or another bisphosphonate observed symptoms recur.
4.5 Interaction with other medicinal products and other forms of interaction
Aredia is administered concomitantly with commonly used anticancer drugs without interactions occurring.

Aredia is used in combination with calcitonin in patients with severe hypercalcaemia as a result of a synergistic effect, resulting in a more rapid fall in serum calcium.

Caution should be exercised when Aredia is used with other potentially nephrotoxic drugs.

In multiple myeloma patients, the risk of renal failure can be improved when Aredia is administered in combination with thalidomide.
4.6 Pregnancy and lactation
In rats, it was found that Aredia crosses the placenta, and in rats and rabbits induces the expression of transferred maternal no teratogenic embryo / fetal effects (see 5.3 Preclinical safety data)
There are no adequate studies in pregnant women and clinical studies supporting the use of Aredia in pregnant women. Therefore Aredia should not be used during pregnancy (see 4.3 Contraindications).
A study in lactating rats showed that pamidronate passes into breast milk. Therefore, mothers treated with Aredia should not breastfeed.
4.7 Effects on ability to drive and use machines
Patients should be warned that in rare cases after infusion of Aredia may experience drowsiness and / or dizziness in these cases should not be driving, and to work with potentially dangerous machinery or to perform activities causing hazard due to the risk of reduced attention.
4.8 Undesirable effects
Aredia side effects are usually mild and temporary. The most frequent adverse events were fever and subclinical hypocalcemia (an increase in body temperature of 1 -2 ° C), which are usually observed within the first 48 hours after the infusion. Fever usually resolves spontaneously develop and require no further treatment. Symptomatic hypocalcemia is rare.
Frequency estimate: very common (> 1/10), common (> 1/100, <1/10), uncommon (> 1/1000, <1/100), rare (> 1/10000, <1/1000 ), very rare (<1/10000), including isolated reports.
Table 2_

Infections and infestations
Very rare:
Reactivation of Herpes simplex, Herpes zoster reactivation

Blood and lymphatic system
Common:
Anemia, thrombocytopenia, lymphocytopenia
Very rare:
leukopenia

Immune system disorders
Uncommon:
Allergic reactions, including anaphylactic reactions, bronchospasm / dyspnea, angioneurotic edema Quincke (Quincke)
Very rare:
anaphylactic shock

Metabolism and nutrition
Very common:
Hypocalcemia, hypophosphatemia.
Common:
Hypokalaemia, hypomagnesaemia.
Very rare:
Hyperkalaemia, hypernatraemia.

Nervous System Disorders
Common:
Symptomatic hypocalcaemia (paraesthesia, tetany), headache, insomnia, somnolence.
Uncommon:
Seizures, agitation, dizziness, lethargy: -
Very rare:
Confusion, hallucinations. -

Eye disorders
Common:
Conjunctivitis.
Uncommon:
Uveitis (iritis, iridocyclitis).
Very rare:
Scleritis, episcleritis, xanthopsia.

cardiac disorders
Very rare:
Left ventricular heart failure (dyspnoea,
pulmonary edema), congestive heart failure
(edema) due to fluid retention.

vascular disorders
Common:
hypertension
Uncommon:
Hypotension.

Gastrointestinal Disorders
Common:
Nausea, vomiting, anorexia, abdominal pain,
diarrhea, constipation, gastritis.
Uncommon:
Dyspepsia.

Skin and subcutaneous tissue disorders
Common:
Rash.
Uncommon:
Pruritus.

Disorders of the musculoskeletal system and connective tissue
Common:
Transient bone pain, arthralgia, myalgia,
generalized pain.
Uncommon:
Muscle cramps.

Renal and urinary disorders
Uncommon:
Acute renal failure
rare:
Focal segmental glomerulosclerosis including the
collapse, nephrotic syndrome.
Very rare:
Worsening of existing kidney disease
haematuria.

General disorders and administration site conditions
Very common:
Fever and flu-like symptoms, sometimes accompanied by nausea, stiffness, fatigue and hot flushes.
Common:
Site reactions (pain, swelling,
induration, phlebitis, thrombophlebitis).

research
Common:
Serum creatinine.
Uncommon:
Abnormal liver function tests, elevations in serum urea.
Many of these side effects may be related to the underlying disease.

Atrial fibrillation:
In a clinical study comparing the effects of zoledronic acid (4 mg) and pamidronate (90 mg), the number of adverse events associated with atrial fibrillation was greater in the group with pamidronate (12/556, 2.2%) versus receiving zoledronic acid (3/563, 0.5%). In several studies with other bisphosphonates have also seen instances of increased incidence of adverse events associated with atrial fibrillation. The mechanism is due to the increased incidence of atrial fibrillation in some individual studies with bisphosphonates, including Aredia, is unknown.

Postmarketing experience
The following adverse reactions have been reported with administration of Aredia after its launch. Since the messages are from a population of uncertain size and dependent on various
factors, it is difficult to determine the incidence of adverse events and causality.

Cases of osteonecrosis (primarily of the jaws) have been reported predominantly in cancer patients treated with bisphosphonates, including Aredia (uncommon). Many of these patients had signs of local infection including osteomyelitis and the majority of the reports refer to cancer patients following tooth extractions or other dental surgeries. Osteonecrosis of the jaws has a plurality of well-documented risk factors, including diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiation therapy, steroids) and comorbidities (e.g., anemia, coagulopathies, infection, pre-existing conditions of the oral cavity). Although it is not possible to establish causality, it is recommended to avoid dental surgery as recovery period may be extended (see section 4.4 Special warnings and precautions for use). The data shows a higher frequency of reporting ONJ associated with tumor types (advanced breast cancer, multiple myeloma).
Very rare cases of orbital inflammation were reported.
4.9 Overdose
Patients who have received doses higher than those recommended should be carefully monitored. In the case of hypocalcaemia with paraesthesia, tetany and hypotension required infusion of calcium gluconate.
 
 
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