Generic drug of the therapeutic class: Rheumatology
active ingredients: Sodium pamidronate
laboratory: Novartis Pharma SA
Powder and solvent for solution for IV infusion
- Treatment of severe hypercalcemia of malignant origin.
Treatment of stage III myeloma with at least one bone lesion.
- Palliative treatment of osteolysis of malignant origin with or without hypercalcemia in addition to the specific treatment of the tumor.
- Treatment of Paget's disease.
AREDIA dosage 15 mg / 5 ml Powder and solvent for solution for infusion Box of 4 vials of powder + 5 ml solvent ampoules
- In the absence of hypercalcemia the 90 mg (which corresponds to the maximum daily dose or cure) are diluted in 250 ml of a solution for infusion and are perfused for 2 hours.
- In case of hypercalcemia, it is recommended to administer the 90 mg (which corresponds to the maximum daily dose or per cure) in 4 hours in 500 ml.
- After reconstitution with its solvent (water ppi) AREDIA should be administered as a slow intravenous infusion, diluted in a compatible solution (for example: sodium chloride 0.9% or serum glucose 5%) without added calcium.
The infusion should be placed in a vein of sufficient size to minimize local reactions.
- It must be ensured that the powder is completely dissolved before dilution into the infusion solution.
SEVERE HYPERCALCEMIA OF MALIGNANT ORIGIN:
- Patients should be properly hydrated before and during the treatment period with the necessary precautions in heart failure patients.
- The duration of the treatment is limited to the time necessary for the normalization of the calcemia.
- Initial treatment:
. The total dose of AREDIA for a therapeutic cure can be administered in a single infusion or in several infusions spread over 2 to 4 consecutive days.
. The recommended total dose to be used for a therapeutic cure is based on the initial serum calcium value. The following indications are derived from clinical data using uncorrected serum calcium. However, the proposed dosages are also applicable for calemia values corrected for albuminemia or protidemia in rehydrated patients.
Initial Calcium: Total recommended dose for a cure.
Up to 3 mmol / L (up to 120 mg / L): 15-30 mg.
3-3.5 mmol / L (120-140 mg / L): 30-60 mg.
3.5-4 mmol / L (140-160 mg / L): 60-90 mg.
greater than 4 mmol / L (greater than 160 mg / L): 90 mg.
- Repetition of cures:
. If hypercalcemia recurs, or if serum calcium does not begin to decrease within 2 days of start of treatment, AREDIA infusions may be repeated following the same dosing instructions as for initial therapy.
. In the current clinical experience, there is a possibility of decreasing the therapeutic efficacy due to the aggravation of the cancerous disease and / or in case of repeated administration of the product.
. The maximum dose per therapeutic treatment is 90 mg, whether during an initial treatment or during subsequent courses, it is recommended to administer the 90 mg in 4 hours in 500 ml.
. The use of higher doses does not seem to bring additional clinical benefits.
MYELOME STAGE III WITH AT LEAST ONE BONE INJURY:
- 90 mg every 4 weeks.
- It is recommended to administer the 90 mg in 4 hours in 500 ml.
MALIGNANT OSTEOLYSIS WITH OR WITHOUT HYPERCALCEMIA:
- The recommended dose of AREDIA is 90 mg every 4 weeks.
- In patients with bone metastases treated with chemotherapy every 3 weeks, the administration of AREDIA (90 mg) may be performed every 3 weeks.
- The recommended dose is 120 to 180 mg divided in 2 to 3 consecutive days.
Clinical and biological monitoring can evaluate the effects of treatment.
- In case of insufficient results and / or resumption of the evolution of Paget's disease, it is possible to repeat a new course of 120 to 180 mg, at least six months after the first treatment.
AREDIA is contraindicated in the following cases:
- History of hypersensitivity to sodium pamidronate, excipients or bisphosphonates.
- Breast-feeding: If treated with this medicine, breast-feeding is contraindicated.
- Do not administer concurrently with other bisphosphonates or other agents (particularly mithramycin) commonly used to treat hypercalcemia due to the possible potentiation of the anti-resorptive effect.
NOT RECOMMENDED :
- AREDIA should generally not be used during pregnancy: studies in animals have shown a teratogenic effect at high doses, with bone alterations affecting the skeleton and teeth. When administered throughout pregnancy, this drug causes bone mineralization disorders, mainly affecting the long bones and resulting in angular deformities. Most often, these abnormalities are observed at high doses and are reversible after farrowing. This effect is likely to account for the mechanism of action of the molecule, by chelation of calcium. In clinical practice, there are currently no data of sufficient relevance to evaluate a potential malformative or foetotoxic effect of pamidronate when administered during pregnancy. As a result, the use of pamidronate is not recommended during pregnancy. This element does not constitute the argument for counseling a termination of pregnancy but leads to an attitude of caution and oriented antenatal surveillance.
- There is currently no clinical experience using this product in children under 15 years of age. AREDIA should be prescribed in this case only when life-threatening conditions are involved.
Aredia side effects
Side effects are usually mild and transient.
- General signs:
. Frequently : Hyperthermia (increase in body temperature from 1 to 2 ° C) transient: it occurs on average on the 2nd day of treatment, lasts 24 to 48 hours and seems of no clinical consequence.
Flu-like syndrome with discomfort, rigidity, asthenia and vasomotor reactions.
. Rarely : Systemic allergic reactions of bronchospasm types, dyspnoea, angioedema, anaphylactoid reaction.
. Very rarely : Anaphylactic shock.
- Local reactions:
Occasionally : Injection site reactions (pain, redness, swelling, induration, phlebitis, thrombophlebitis).
- Locomotor device :
. Occasionally : transient bone pain, myalgia, arthralgia, generalized pain.
. Rarely : Muscle cramps.
. Very rare : Very rare cases of osteonecrosis (mainly jaw) have been reported in patients treated with bisphosphonates. The majority of cases involve cancer patients who have undergone tooth extraction or other dental surgeries. The many well-known risk factors for osteonecrosis of the jaw include the diagnosis of cancer, associated treatments (eg chemotherapy, radiotherapy, corticosteroids) and associated diseases (eg anemia, bleeding disorders, infection, pre-existing oral disease). Although the causality is not established, it would be prudent to avoid dental surgery, the healing of which could be delayed.
. Occasionally : Nausea, vomiting.
. Rarely : Anorexia, abdominal pain, diarrhea, constipation, dyspepsia.
. Isolated cases : Gastritis.
- Central nervous system :
. Occasionally : Headache.
. Rarely : Symptomatic hypocalcemia (paresthesia, tetany), agitation, confusion, dizziness, insomnia, drowsiness, lethargy.
. Isolated cases : Convulsions, visual hallucinations.
- Blood :
. Occasionally : Lymphocytopenia (lasts for a few days and seems of no clinical consequence).
. Rarely : Anemia, leukopenia.
. Isolated cases : Thrombocytopenia.
- Cardiovascular system :
. Rarely : Hypotension, hypertension.
. Isolated cases : Left ventricular failure (dyspnea, pulmonary edema), congestive heart failure (edema) due to fluid overload.
Isolated cases : Hematuria, deterioration of pre-existing renal insufficiency, acute renal failure.
Rarely : Rash, pruritus.
- Organs of the senses:
Isolated cases : Conjunctivitis, uveitis (iritis, iridocyclitis), scleritis, episcleritis, xanthopsia.
Very rare : Reactivation of herpes simplex and herpes zoster.
. Frequently : Hypocalcemia (often asymptomatic), hypophosphatemia.
. Occasionally : Hypomagnesemia.
. Rarely : Hyperkalemia, hypokalemia, hypernatremia.
. Isolated cases : Abnormal liver function tests, increased creatinine and serum urea.
The occurrence of many of these side effects may be related to the disease being treated.