DESFERAL Sterile, lyophilised powder Ref.[2723] Active ingredients: Deferoxamine

Renal impairment

Desferal should be used with caution in patients with renal impairment since the metal complexes are excreted via the kidneys. In these patients, dialysis will increase the elimination of chelated iron and aluminium. Isolated cases of acute renal failure have been reported (see also section 4.8 Undesirable effects). Monitoring patients for changes in renal function (e.g. increased serum creatinine) should be considered.

Neurological impairment

Used alone Desferal may exacerbate neurological impairment in patients with aluminium-related encephalopathy. This deterioration (manifest as seizures) is probably related to an acute increase in brain aluminium secondary to elevated circulating levels. Pretreatment with clonazepam has been shown to afford protection against such impairment. Also, treatment of aluminium overload may result in decreased serum calcium and aggravation of hyperparathyroidism.

Rapid intravenous infusion

Treatment with Desferal by the intravenous route should only be administered in the form of slow infusions. Rapid intravenous infusion may lead to hypotension and shock (e.g. flushing, tachycardia, collapse and urticaria).

Instructions for use and handling

Desferal should not be administered s.c. in concentrations and/or doses higher than those recommended as local irritation at the site of administration may occur more frequently.

Infections

Patients suffering from iron overload are particularly susceptible to infection. There have been reports of Desferal promoting some infections such as Yersinia enterocolitica and Y. pseudotuberculosis. If patients develop fever with pharyngitis, diffuse abdominal pain or enteritis/enterocolitis, Desferal therapy should be stopped, and appropriate treatment with antibiotics should be instituted. Desferal therapy may be resumed once the infection has cleared.

In patients, receiving Desferal for aluminium and/or iron overload there have been rare reports of mucormycosis (a severe fungal infection), some with fatal outcome. If any characteristic signs or symptoms occur Desferal treatment should be discontinued, mycological tests carried out and appropriate treatment immediately instituted. Mucormycosis has been reported to occur in dialysis patients not receiving Desferal, thus no causal link with the use of the drug has been established.

Visual and hearing impairment

Disturbances of vision and hearing have been reported during prolonged Desferal therapy. In particular, this has occurred in patients on higher than recommended therapy or in patients with low serum ferritin levels. Patients with renal failure who are receiving maintenance dialysis and have low ferritin levels may be particularly prone to adverse reactions, visual symptoms having been reported after single doses of Desferal. Therefore, ophthalmological and audiological tests should be carried out both prior to the institution of long-term therapy with Desferal and at 3-monthly intervals during treatment. By keeping the ratio of the mean daily dose (mg/kg of Desferal) divided by the serum ferritin (micro g/L) below 0.025 the risk of audiometric abnormalities may be reduced in thalassaemia patients. A detailed ophthalmological assessment is recommended (visual field measurements, fundoscopy, and colour vision testing using pseudoisochromatic plates and the Farnsworth D-15 colour test, slit lamp investigation, visual evoked potential studies).

If disturbances of vision or hearing do occur, treatment with Desferal should be stopped. Such disturbances are usually reversible. If Desferal therapy is re-instituted later at a lower dosage, close monitoring of ophthalmological/auditory function should be carried out with due regard to the risk-benefit ratio.

Paediatrics: growth retardation

The use of inappropriately high doses of Desferal in patients with low ferritin levels or young children (<3 years at commencement of treatment) has also been associated with growth retardation; dose reduction has been found to restore the growth rate to pretreatment levels in some cases. Three monthly checks on body weight and height are recommended in children.

Growth retardation if associated with excessive doses of Desferal must be distinguished from growth retardation from iron overload. Growth retardation from Desferal use is rare if the dose is kept below 40 mg/kg; if growth retardation has been associated with doses above this value, then reduction of the dose may result in return in growth velocity, however, predicted adult height is not attained.

Acute respiratory distress syndrome

Acute respiratory distress syndrome has been described following treatment with excessively high i.v. doses of Desferal in patients with acute iron intoxication, and also in thalassaemic patients (see section 4.8 Undesirable effects). The recommended daily doses should therefore not be exceeded.

It should be noted that desferrioxamine will affect aluminium levels and may necessitate some dosage adjustment of erythropoietin if co-prescribed.

Oral administration of vitamin C (up to a maximum of 200 mg daily, given in divided doses) may serve to enhance excretion of the iron complex in response to Desferal; larger doses of vitamin C fail to produce an additional effect. Monitoring of cardiac function is indicated during such combined therapy. Vitamin C should be given only if the patient is receiving Desferal regularly and should not be administered within the first month of Desferal therapy. In patients with severe chronic iron-storage disease undergoing combined treatment with Desferal and high doses of vitamin C (more than 500 mg daily) impairment of cardiac function has been encountered; this proved reversible when the vitamin C was withdrawn. Vitamin C supplements should not, therefore, be given to patients with cardiac failure.

Desferal should not be used in combination with prochlorperazine (a phenothiazine derivative) since prolonged unconsciousness may result.

Gallium⁶⁷ imaging results may be distorted because of the rapid urinary excretion of Desferal-bound radiolabel. Discontinuation of Desferal 48 hours prior to scintigraphy is advised.

Women of child-bearing potential

In women of child-bearing potential, each case the benefits for the mother must be weighed against the risks for the child.

Pregnancy

There is a limited amount of data on the use of desferrioxamine in pregnant patients. Studies in animals (rabbits) have shown reproductive toxicity/teratogenicity (see section 5.3 Preclinical safety data). The risk to the foetus/mother is unknown.

Desferal should be used during pregnancy only if the expected benefits to the mother outweigh the potential risk to the foetus.

Breastfeeding

It is not known whether Desferal is excreted into the breast milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse drug reactions in breast-fed newborns/infants, a decision should be made whether to abstain from breast-feeding or to abstain from using the medicinal product, taking into account the importance of the medicinal product to the mother.

Patients experiencing CNS effects such as dizziness or impaired vision or hearing should be warned against driving or operating machinery.

Adverse reactions (Table 1) are ranked under heading 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) including isolated reports; not known (cannot be estimated from the available data).

Some signs and symptoms reported as adverse effects may also be manifestations of the underlying disease (iron and/or aluminium overload).

Table 1:

Special remarks

At the injection site pain, swelling, infiltration, erythema, pruritus and eschar/crust are very common; vesicles, local oedema and burning are uncommon reactions. The local manifestations may be accompanied by systemic reactions like arthralgia/myalgia (very common), headache (common), urticaria (common), nausea (common), pyrexia (common), vomiting (uncommon), or abdominal pain (uncommon) or asthma (uncommon).

Excretion of the iron complex may cause reddish-brown discoloration of the urine.

Convulsion has been mainly reported in dialysed patients with aluminium overload.

Patients treated for chronic aluminum overload

Desferal chelation therapy aluminum overload may result in hypocalcemia and aggravation of hyperparathyroidism (see section 4.4 Special warnings and precautions for use).

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

None known.