Medicinal Products

DESFERAL 100 mg / mL

Generic drug of the therapeutic class: Toxicology
Active ingredients: Powder: Deferoxamine
laboratory: Novartis Pharma SA

Powder and solvent for solution for injection
Box of 1 bottle of powder + 20 ml solvent ampoule
All forms

Indication

- Primary hemochromatosis not curable by bloodletting.
- Secondary haemosiderosis.
- Acute martial poisoning.
- Aluminum poisoning in renal failure dialysis.
- Diagnostic indications - Desferal test:
. detection of iron overload by assaying iron deficiency,
. diagnosis of hemochromatosis, treatment orientation and detection of latent forms in families of hemochromatosis patients,
. diagnosis of aluminum intoxication, in particular when the aluminemia is between 1 and 3 μmol / L (27 to 81 μg / L).

Dosage DESFERAL 100 mg / mL Powder and solvent for solution for injection Box of 1 Bottle of powder + 20 ml solvent ampoule

These recommendations concern the adult and the child.
Administration mode :
Deferoxamine can be administered either:
. subcutaneously as an infusion. By SC, the injection technique is very important: the subcutaneous perfusion needle should not be installed too close to the dermis,
. intravenous infusion,
. intramuscularly,
. intraperitoneally [recommended in patients receiving continuous ambulatory peritoneal dialysis (CAPD) or continuous cyclical dialysis (DPCC) or automated peritoneal dialysis].
- The recommended route for intensive treatment, except in dialysis patients, is subcutaneous infusion (see dosage). - The 10% deferoxamine solution can be diluted in standard infusion liquids (see instructions for use, handling and disposal). Dosage:
PRIMITIVE HEMOCHROMATOSIS NOT CURABLE BY BIRDS AND SECONDARY HEMOSIDEROSES:
- The average daily dose is usually between 20 and 60 mg / kg regardless of the route of administration. It is recommended to start treatment with deferoxamine after the first 20 transfusions or when serum ferritin levels reach 1000 ng / ml. - The prescription in a child under 3 years is reserved for specialists . Stunting may occur when excessive doses of Desféral are administered. If treatment is started before the age of 3, regular growth control should be instituted, and the average daily dose should not exceed 40 mg / kg.
- The dose and method of administration can be determined individually and adapted during treatment depending on the severity of the iron overload of the patient. The smallest effective dose should be used.
. At the initiation of treatment, the evaluation of the response can be performed daily by a 24-hour control of iron excretion of iron. Once the dose of Desferal is adjusted, urinary iron excretion rates can be evaluated at intervals of several weeks.
. The average daily dose can also be adjusted according to ferritin values ​​in order to maintain the therapeutic index below 0.025 [therapeutic index: average daily dose (mg / kg) / serum ferritin level (μg / L)].
In general, patients with a serum ferritin level of less than 2000 ng / ml respond to a dose of approximately 25 mg / kg / day. For patients with a rate between 2000 and 3000 ng / ml the usual dose is about 35 mg / kg / day.
- In patients with higher serum ferritin levels, up to 55 mg / kg / day may be required. It is not prudent to regularly exceed an average daily dose of 50 mg / kg / day except when intensive treatment is required in patients who have completed their growth.
- If the ferritin values ​​decrease below 1000 ng / ml, the risk of Desferal toxicity increases, it is important to monitor these patients carefully and to consider possibly reducing the total weekly dose.
- The doses administered are the average daily doses. Most patients taking the treatment less than 7 days a week, the effective dose per dose is different from the average daily dose (eg if the average daily dose is 40 mg / kg / day and the patient receives 5 administrations per week each infusion should contain 56 mg / kg).
- Regular treatment with Desferal has been shown to increase the life expectancy of patients with thalassemia.
- The slow subcutaneous route, using a portable miniaturized infusion pump, for a period of 8 to 12 hours is recommended and is particularly suitable for ambulatory patients. It is also possible to extend the duration of the infusion to 24 hours.
The pump will be used 5-7 times a week.
The Desferal formulation is not suitable for subcutaneous bolus administration.
- Intravenous infusion during a blood transfusion :
At the same time, the blood transfusion makes it possible to carry out the intravenous infusion of deferoxamine without any additional discomfort for the patient, since a venous approach is already available. This method is particularly useful when the observance of subcutaneous treatment is insufficient.
The Desferal solution should not be introduced into the blood bag, but administered with a Y infusion near the venous approach. Desferal will be administered as a slow infusion using the pump.
Patients and healthcare staff should be alerted to the risk of collapse due to rapid infusion (see section on warnings and precautions for use).
- Continuous intravenous infusion :
. Implantable systems can be used for intensive chelation treatment.
. Continuous IV infusion is indicated in patients who are unable to continue to receive deferoxamine SC and in the presence of cardiac iron overload.
The dose of deferoxamine will depend on the severity of this overload.
A 24-hour dose of sideruria should be performed regularly when intensive chelation (IV) therapy is required and the dose adjusted accordingly.
. Caution is advised when rinsing the infusion line to avoid abrupt administration of residual Desferal that may be present in the dead space of the infusion line, due to the risk of collapse (see section 4.4). precautions for use).
- The intramuscular route of administration will only be used if subcutaneous (more effective) infusions are impossible.
- Whichever route of administration is chosen, the individual maintenance dose will be based on the patient's iron excretion rate.
- Concomitant administration of vitamin C :
Patients with iron overload usually develop vitamin C deficiency, probably by oxidation of the vitamin by iron. In hemosiderosterics, concomitant administration of vitamin C (150 to 200 mg / day orally in adults) increases the excretion of the ferrioxamine-iron complex (see section cautionary statements and precautions for use). . In children under 10 years, 50 mg of vitamin C is usually sufficient, and 100 mg for older children.
Higher doses of vitamin C do not increase the excretion of the ferric complex.
. Vitamin C should not be used during the first month of treatment with deferoxamine (see section on warnings and precautions for use).
ACUTE MARTIAL INTOXICATION: - Deferoxamine is an adjunct to standard measures commonly used in the treatment of acute intoxication. - Treatment with Desferal is indicated in each of the following situations :. any symptomatic patient with more than transient minor symptoms (eg more than one episode of vomiting or soft stool emission);
- patients with signs of lethargy, severe abdominal pain, hypovolemia or acidosis; - patients with an X-ray showing multiple abdominal opacities, (the vast majority of these patients will develop symptomatic martial intoxication);
- any symptomatic patient with serum iron levels greater than 300 to 350 μg / dl irrespective of the total iron binding capacity. It has also been suggested that a conservative approach, without treatment with Desferal or otherwise, should be considered when serum iron levels are in the range of 300 to 500 μg / dL in asymptomatic or monosymptomatic patients limited to non-haemorrhagic vomiting. or diarrhea without other symptoms.
Administration mode :
Administration is preferably continuous IV at the recommended rate of 15 mg / kg / hour.
It should be reduced as soon as the situation allows, usually after 4 to 6 hours, so that the total intravenous dose never exceeds the recommended dose of 80 mg / kg / 24 hours.
Criteria for discontinuation of treatment by Desféral:
- The chelation treatment must be continued until all the following criteria are met:
. Absence of signs or symptoms of martial intoxication.
. A corrected rate of normal or low serum iron (<100 μg / dl). Since it is not possible to accurately measure concentrations in the presence of Desferal, it is acceptable to discontinue Desferal treatment when all other criteria are met if serum iron concentration is not elevated.
. Several abdominal radiographs showing the disappearance of previously observed opacities should be performed before discontinuing treatment. They serve as markers for the continuous absorption of iron.
. If the patient has initially developed a wine-rosy colouration of the urine during treatment with Desferal, it seems reasonable to wait until the color returns to normal before stopping treatment (the absence of vin-rosé coloration is not not sufficient in itself to indicate the discontinuation of the Desféral). - The effectiveness of the treatment depends on an adequate urinary elimination. In case of oliguria or anuria, peritoneal dialysis, hemodialysis or haemofiltration may become necessary. TEST AT THE DESFERAL:
This test is based on the fact that Desferal does not increase the excretion of iron and aluminum above a certain threshold, in healthy subjects.
- Ferric overloads:
Inject 500 mg of deferoxamine intramuscularly, then collect the urine for the next 6 hours and determine the amount of iron excreted: between 1 and 1.5 mg (18 to 27 μmol) within 6 hours, suspect overload. Above 1.5 mg (27 μmol) the values ​​can be considered pathological.
The test only gives reliable results in the presence of normal renal function.
- Screening for aluminum intoxication in hemodialysis:
It is recommended to perform a Desferal test in patients whose plasma glucose level exceeds 2.2 μmol / L (60 μg / L) and whose serum ferritin is greater than 100 ng / mL.
A blood sample will be taken immediately prior to hemodialysis in order to have baseline values ​​of aluminum oxide before treatment.
A slow IV infusion of 5 mg / kg will be administered during the last hour of hemodialysis.
At the beginning of the next hemodialysis, a second blood sample will be used to determine the aluminum level again.
The Desferal test is considered positive if the increase of the aluminum level from the initial values ​​exceeds 5.6 μmol / L (150 μg / L). However, a negative result is not enough to rule out any aluminum overload.
- Aluminum poisoning in chronic renal failure patients with dialysis:
. The deferoxamine-iron and deferoxamine-aluminum complexes are dialyzable.
. In patients with renal failure, their elimination will be increased by dialysis.
. Treatment should be considered in patients with signs of aluminum overload, or asymptomatic but with an elevated blood glucose level greater than 2.2 μmol / L (60 μg / L) and a positive Desferal test.
- In the hemodialysis subject:
. In patients with serum aluminum levels up to 300 μg / L after the Desferal test, Desferal should be administered as a slow IV infusion during the last hour of dialysis. In patients with serum aluminum levels greater than 300 μg / L after the Desferal test, Desferal should be administered as a slow IV infusion 5 hours before dialysis.
. Desferal will be tested after the first 3-month course, with a free interval of 4 weeks.
It is not recommended to continue the treatment, if in 2 Desferal tests consecutive one month apart, the aluminum level exceeds the initial values ​​of less than 1.87 μmol / L (50 μg / L).
- In the subject treated by peritoneal dialysis:
In patients receiving continuous ambulatory peritoneal dialysis (CAPD), continuous cyclic peritoneal dialysis (CCPD) or automated peritoneal dialysis, deferoxamine will be administered once a week at a dose of 5 mg / kg before the last day of cleansing. It is recommended to use the intraperitoneal route in these patients, however, deferoxamine can also be administered IM or as a slow infusion SC or IV.

Against indications

CONTRAINDICATED:
- History of hypersensitivity to deferoxamine, unless effective desensitization permits treatment.
- Severe renal insufficiency not dialyzed.
- Evolutionary bacterial infection.
NOT RECOMMENDED :
- Pregnancy: no teratogenic effect was detected in rats and mice. Studies in rabbits at maternally toxic doses have shown a possible teratogenic effect. In clinical practice, the use of deferoxamine in a very limited number of pregnancies has apparently not revealed any particular malformative or foetotoxic effect to date. However, further studies are needed to evaluate the consequences of exposure in pregnant women. From the few pregnancies exposed, we can provide the following: in cases of severe maternal intoxication with iron, there is no parallel increase in serum iron levels in children; the treatment of the mother with deferoxamine seems to have no effect on the iron concentrations of the child. Therefore, the use of deferoxamine should be considered during pregnancy only if necessary.
- Breast-feeding: In the absence of information on the passage of the active substance into the mother's milk, the expected benefit for the mother and the risks to the child should be balanced.

Desferal side effects

- The undesirable effects are classified in order of decreasing frequency using the following convention: very frequent (> = 1/10), frequent (> = 1/100, = 1/1000, = 1/10000, <1/1000), very rare (<1/10000) including isolated cases.
- It should be kept in mind that some of the symptomatology attributed to adverse effects may in fact be due to the underlying involvement (overload martial and / or aluminum).
- Infections and infestations:
. Rare : Mucormycoses.
. Very rare : Infections with Yersinia pseudotuberculosis and Yersinia enterocolitica (enteritis, acute enterocolitis including disseminated forms) (see section on warnings and precautions for use).
- Hematological and lymphatic system disorders:
Very rare : Hematologic abnormalities (including thrombocytopenia).
- Immune system disorders:
Very rare : Anaphylactic / anaphylactoid reactions with or without shock, Quincke's edema.
- disorders of the nervous system:
. Common : Headache
. Very rare : Neurological disorders, dizziness, abrupt onset or worsening of aluminum encephalopathy of dialysis, sensory, motor or mixed neuropathy, paraesthesia (see precautions for use).
- Eye disorders:
Rare : Scotoma, retinopathies (retinal pigment degeneration), optic neuritis, cataract, decreased visual acuity, blurred vision, decreased night vision (nyctalopia), impaired visual field, impaired color perception (dyschromatopsia) ), corneal opacities, blindness.
- Affections of the ear and labyrinthine:
Uncommon : Neurosensory deafness at high frequencies and tinnitus.
- Vascular disorders:
Rare : Hypotension may occur if the recommended precautions when administering Desferal are not followed (see section cautionary and precautions for use).
- Respiratory, thoracic and mediastinal disorders:
. Uncommon : Asthma.
. Very rare : infiltrative pneumopathies that may cause acute respiratory distress syndrome.
- Gastrointestinal disorders:
. Common : Nausea
. Uncommon : Vomiting, abdominal pain.
. Very rare : Diarrhea.
- Skin and subcutaneous tissue disorders:
. Common : Urticaria.
. Very rare : Generalized rash.
- Musculoskeletal and systemic disorders:
. Very common : Arthralgia / myalgia.
. Frequent : Growth delays and bone changes (eg metaphyseal dysplasia) (see section on warnings and precautions for use).
- Renal and urinary disorders:
. Very rare : Renal function disorders (see section cautionary statements and precautions for use).
- General disorders and anomalies at the site of administration:
. Very common : Injection site reactions including pain, swelling, infiltration, erythema, pruritus, ulcerations / crusts.
. Common : Fever
. Uncommon : Injection site reactions including vesicles, localized edema, burning sensation.
- Specific remarks:
. High frequency sensorineural deafness and tinnitus are infrequent if the doses are consistent with the recommendations and if they are decreased when ferritin levels fall (ratio of the average daily dose divided by the ferritin level below 0.025).
. Ocular disorders are rare, except when high doses are administered (see section on warnings and precautions for use).
. Stunting and bone changes (eg metaphyseal dysplasia) are common in patients receiving doses above 60 mg / kg, particularly when treatment started before the age of 3 years. When doses are maintained at 40 mg / kg or below, the risk is greatly reduced.
. At the site of injection, pain, swelling, infiltration, erythema, pruritus and ulcerations / scabs are common, vesicles, localized edema, burning sensation are infrequent. Local manifestations may be accompanied by systemic reactions such as arthralgia / myalgia (very common), headache (common), urticaria (common), nausea (common), fever (common), vomiting (uncommon), abdominal pain ( uncommon), or asthma (uncommon).

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