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Product
Anti-asthmatic Products (Aerocort Inhaler)
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Kelfer (Deferiprone Capsules)
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Kelfer
Deferiprone Capsules
COMPOSITION
Kelfer-250 Capsules
Each capsule contains Deferiprone 250 mg
Kelfer-500 Capsules
Each capsule contains Deferiprone 500 mg
Description
Deferiprone (L1) is an oral iron chelating agent belonging to the group of hydroxypyridones. Deferiprone forms neutral complexes with iron at physiological pH. It mobilizes iron from the iron storage proteins ferritin and haemosiderin; and from iron saturated transferrin and lactoferrin, but not from haemoglobin and myoglobin. The water soluble complex of iron formed is rapidly excreted in the urine thus reducing pathological iron deposits in organs and tissues.
Indications
Kelfer is indicated in transfusion haemosiderosis, especially in cases of thalassaemia, other haemolytic anaemias, aplastic anaemia and myelodysplastic syndromes, acute iron poisoning, siderosis associated with liver cirrhosis and for the diagnosis of iron-storage diseases.
Dosage And Administration
In adults and children the optimum dose of Kelfer to achieve a negative iron balance is 75 mg/kg/day to be administered in 2-4 divided doses. In some patients a lesser dose of 50 mg/kg/day may be adequate while in others the dose may be increased to 100 mg/kg/day.
Contraindications
Hypersensitivity to the active substance or any of the excipients. History of recurrent episodes of neutropenia. History of agranulocytosis. Pregnancy or breast-feeding. Due to the unknown mechanism of deferiprone-induced |
neutropenia, patients should not take medicinal products known to be associated with neutropenia or those that can cause agranulocytosis.
Warnings And Precautions
Drug Interactions
Since deferiprone binds to metallic cations, the potential exists for interactions between deferiprone and trivalent cation-dependent medicinal products such as aluminium-based antacids.
The safety of concurrent use of deferiprone and Vitamin C has not been formally studied. Based on the reported adverse interaction that can occur between deferoxamine and Vitamin C, caution should be used when administering concurrent deferiprone and Vitamin C.
Neutropenia/Agranulocytosis
Deferiprone has been shown to cause neutropenia, including agranulocytosis. It is recommended that a patient`s neutrophil count be monitored every 1-2 weeks, or as recommended by the treating physician. In clinical trials this has been effective in identifying cases of neutropenia and agranulocytosis. Neutropenia and agranulocytosis resolved once therapy was withdrawn. If the patient develops an infection, deferiprone therapy should be interrupted and the neutrophil count monitored more frequently. Patients should be advised to report immediately to their physician any symptoms indicative of infection such as: fever, sore throat and flu-like symptoms.
The suggested management of cases of neutropenia is outlined below. It is recommended that such a management protocol be in place prior to initiating any patient on deferiprone therapy.
Treatment with deferiprone should not be initiated if the patient is neutropenic. The risk of agranulocytosis and neutropenia is higher, if the baseline ANC count is less than 1.5 X 10 9/l.
In the event of neutropenia:
Instruct the patient to immediately discontinue deferiprone and all other medications with a potential to cause medicinal product-associated neutropenia. The patient should be advised to limit contact with other individuals in order to reduce the risk of potential infection. Obtain a complete blood cell count, corrected white blood cell count, neutrophil count, and a platelet count immediately upon diagnosing the event and then repeat daily. It is recommended that following recovery of the neutrophil count, weekly Complete Blood Cell count (CBC), corrected White Blood Cell count (WBC), neutrophil and platelet counts continue to be obtained for three consecutive weeks, to ensure that the patient recovers fully. Should any evidence of infection develop concurrent with the neutropenia, the appropriate cultures and diagnostic procedures should be performed and an appropriate antibiotic regimen instituted.
In the event of severe neutropenia or agranulocytosis:
Follow the guidelines above and administer appropriate therapy such as granulocyte growth factors, beginning the same day that the event is identified; administer daily until the neutrophil count recovers. Provide protective isolation and if clinically indicated admit patient to the hospital.
Limited data are available regarding challenge. Therefore in the event of neutropenia rechallenge is not recommended. In the event of agranulocytosis a rechallenge is contraindicated.
Serum Ferritin Concentrations/Plasma Zn 2+
It is recommended that serum ferritin concentrations be monitored every 3-4 months or as recommended by the treating physician, to assess the long-term effectiveness of the chelation regimen in controlling the body iron load. Interruption of therapy with deferiprone should be considered if serum ferritin measurements fall below 500 m g/l.
A monitoring of plasma Zn 2+ , as well as supplementation in case of a deficiency is recommended.
Discolouration Of Urine
Excretion of the iron complex may cause reddish brown discoloration of the urine.
Renal And Hepatic Impairment
Since deferiprone is excreted mainly via the kidneys, Kelfer should be used with caution in this category of patients.
Since the drug is metabolized in the liver, it should be used with caution in patients with impaired hepatic function.
In thalassaemia patients there is an association between liver fibrosis and hepatitis C. Special care must be taken to ensure that iron chelation in patients with hepatitis C is optimal. In these patients careful monitoring of liver histology is recommended.
Renal and hepatic function should be monitored in this patient population during deferiprone therapy. If there is a persistent increase in serum ALT, interruption of deferiprone therapy should be considered.
Pregnancy
Deferiprone is not recommended for use in pregnant women. Women of childbearing potential should be advised to avoid pregnancy due to the mutagenic and clastogenic properties of the product. These women should be counseled to take contraceptive measures and should be advised to immediately stop taking deferiprone should they become pregnant or plan to become pregnant.
Lactation
It is not known whether deferiprone is secreted into breast milk. In such cases, benefits to the mother must be weighed against the risks to the child.
Paediatric Use
There is no clinical experience of Kelfer in children below two years of age. Therefore its use is not recommended.
Side Effects
Agranulocytosis And Neutropenia
The most serious adverse effect of therapy reported in clinical trials with deferiprone is agranulocytosis (neutrophils < 0.5 X 10 9 /l) with an incidence of 1.2%(0.6 cases per 100 patient years of treatment). The observed incidence of the less severe form of neutropenia (neutrophils < 1.5X10 9 /l) is 6.5% (3.5 cases per 100 patient years). This rate should be considered in context of the underlying elevated incidence of neutropenia in thalassaemia patients, particularly in those with hypersplenism. ( See also Patient Monitoring).
Discolouration Of Urine
The most common side effect reported with deferiprone was reddish brown urine, reported to be due to the excretion of the iron-deferiprone complex.
Gastrointestinal Tract
Other common effects include: nausea, vomiting, abdominal pain and increased appetite. These effects are more frequent at the beginning of therapy with deferiprone and in most patients are resolved within a few weeks without the discontinuation of treatment. In some patients it may be beneficial to reduce the dose of deferiprone and then scale it back up to the total 75 mg/kg/day. Episodes of diarrhoea, mostly mild and transient, have been reported in patients treated with deferiprone.
Arthropathy
Joint pains have been reported in 10-30% of patients receiving deferiprone. These usually involve knees, ankles, elbows, hip and the lower back. In a few patients the small joints of the hands and feet have been involved. In some patients swelling of the joints with effusion has been seen. The exact mechanism of this arthropathy is not known, but it appears to be by a mechanism other than immunological. Joint pains have been seen more commonly in patients with a higher serum ferritin and those on higher dose of deferiprone. These may be related to deposition of iron in the joints (due to the chelation process) leading to an inflammatory reaction in the joints. If joint pains occur, it may be necessary to stop the drug for a short while or reduce the dosage. The joint pains usually disappear and the drug may be restarted at lower doses. Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibrupofen or diclofenac may be used to control the pain. In a few patients however, joint pains may recur on restarting the drug and thus such patients may be unable to tolerate the drug (See also Patient Monitoring).
Elevated Liver Enzymes
Increased ALT values have been reported in patients taking deferiprone. In the majority of these patients this increase was asymptomatic and transient, and their ALT values returned to baseline without discontinuation or decreasing the dose of deferiprone.
Zinc Depletion
Zinc depletion has been reported on prolonged treatment leading to dermatopathy in 1% of patients. This can be easily corrected by giving zinc supplements.
Patient Monitoring
The minimum monitoring which is essential for deferiprone therapy is as follows:
• Haemoglobin, total and differential white cell counts and platelet counts at 1-2 weekly intervals or as recommended by the treating physician.
• Serum ferritin at 3-4 monthly intervals or as recommended by the treating physician.
Note
If the total white cell count drops to less than 3000/cmm or Absolute Neutrophil Count (ANC) falls to less than 1,000/cmm or platelet count falls to less than 1,00,000/cmm the drug should be discontinued.
If the patient develops fever, sore throat or flu-like symptoms, the drug should be stopped and a complete blood count done immediately. If neutropenia is seen, appropriate therapy should be instituted. The patient may have to be hospitalized till the counts come back to normal. In such patients deferiprone should not be restarted.
In case the patient develops severe joint pain, swelling or difficulty in squatting/walking and no relief is obtained by administering ibuprofen/diclofenac or any other suitable NSAID, the therapy should be discontinued. The drug should not be restarted if joint pains recur.
Overdosage
There have been no reports of acute overdosage with deferiprone.
Presentation
Kelfer – 250 Capsules Container of 50 capsules
Kelfer – 500 Capsules Container of 50 capsules
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