Clinical Trial of Ferastral® in Iron-deficient, Non-pregnant Patients in Ibadan, Nigeria

Scand J Haematol (1977) Suppl. 32, 322-325

Clinical Trial of FerastraP in Iron-deficient, Non-pregnant Patients in Ibadan, Nigeria G. J. F. ESAN,0.A. OLUBOYEDE, L. A. SALAKO & E. 0.AKANDE De#artments of Haematology, Pharmacology and Obstetrics, and Gynaecology, University College Hospital, Ibadan, Nigeria

Fifteen patients with proven iron-deficiency anaemia treated with intramuscular injections of Ferastrale, iron-poly (sorbitol-gluconic acid) complex, have been studied. Fourteen showed a satisfactory rise in haematocrit. No local or systemic complications were observed. One patient with iron-deficiency anaemia due to a bleeding malignant lesion did not achieve a satidactory haematocrit level although the bone marrow showed iron repletion following the injection. I t is concluded that Ferastral is an effective drug in the treatment of iron-deficiency anaemia. Key-words : Iron deficiency anaemia - FerastralQ - haematocrit - haematological response

The prevalence of iron-deficiency anaemia has not been exactly determined in Western Nigeria, although it has been surmised that the incidence is relatively low because of the high intake of iron in the diet, estimated to be between 21 and 60 mg daily (Nicol 1952). However, because the majority of the population are peasant farmers who work barefooted, hookworm infection is widespread and has been reported to be the commonest cause of iron-deficiency in men (Gilles et al. 1964). The treatment of iron deficiency anaemia consists of administration of iron and dealing with the underlying cause of the negative iron balance. I n our community where default in taking oral iron frequently occurs, parenteral iron is often of value in giving

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a satisfactory course of therapy, which may be achieved in a relatively short time with an assured response. We report here a trial of iron-poly (sorbitol-gluconic acid) complex (FerastralQ) in the treatment of iron-deficient subjects seen a t the University College Hospital, Ibadan, and its associated clinics. METHODS AND PATIENTS

Patients for the trial were selected on the basis of anaemia, hypochromic microcytic blood film, low serum-iron, high iron binding capacity and the absence of stainable iron in bone marrow smears. Approximately 25 % of subjects screened were found to fulfil these criteria. Subjects with megaloblastosis have been excluded.

CLINICAL TRIAL OF FERASTRAL I N NIGERIA

The 15 subjects admitted to the trial consisted of 9 females and 6 males. One patient was withdrawn because she was found to have a malignant disease. Five of the patients were followed at the Ibarapa Division, about 60 miles from Ibadan, the others attended the University College Hospital, Ibadan. Hookworm infection was the most frequent cause of iron-deficiency in this study and was found in eight patients. Of the remainder, two had postabortal bleeding, two menorrhagia and one bleeding from an oral lesion. One patient, a food fad, had iron-deficiency due to longstanding lack of food iron and bleeding from a peptic ulcer. One patient had iron-deficiency due to poor nutrition. Single doses of 500 mg of iron were given at weekly intervals. Two injections of 5 ml solution equivalent to 250 mg of iron were given intramuscularly, one in each buttock. This weekly dosage regime was found to be convenient, particularly for patients in the Ibarapa Division, which is visited weekly by the doctor. The total dose given was calculated from the initial haemoglobin concentration and varied from 750 mg to 2000 mg iron. Thus, only four attendancies were required at the most in these cases. Haematocrit (PCV) and haemoglobin concentrations were estimated before treatment, and then at weekly intervals for a period of eight weeks. Liver and kidney function tests were carried out initially and then at monthly intervals. Serum creatinine estimation, and examination of urine for protein and deposit in a midstream specimen were also done monthly. Haematological methods were performed by standard techniques (Dacie & Lewis 1968). Serum-iron and iron binding capacity were determined by the one-tube method of Williams & Conrad (1966). Biochemical

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estimations were made by standard methods based mainly on those published by Varley ( 1967). RESULTS

Initial data and final follow-up are shown in Table I. All 14 patients who were followed for over four weeks showed a satisfactory response to treatment. One patient (no. 12) was withdrawn from the trial because a bleeding parotid lesion was found to be malignant. Repeat bone marrow examination showed iron repletion, but the haematocrit did not rise to normal. Table I1 summarizes the responses obtained subdivided into two main groups; those initial PCV were equal to or less than 20 % and those greater than 20 %. Side-effects

No side-effects were reported or seen in the patients studied. The injections were well tolerated both locally and generally. No abnormalities in liver function tests or renal function were observed.

DISCUSSION

The results of this trial show that Ferastral is an effective drug in the treatment of irondeficiency anaemia. Although follow-up of all patients for the whole period was not achieved, all who completed the trial, i. e. were observed for eight weeks or more, achieved normal haematocrit levels. One patient suffering from a malignant parotid tumour, who was followed for seven weeks, showed a twofold increase in haematocrit value within the first six weeks (from 12 % to 24 %) after which it remained static. A repeat bone marrow aspiration showed

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G. J. F. ESAN &

Table I Summary of Pat. no. 1 2 3 4 5 6

7

al.

cases.

Sex Diagnosis

F F M M F F F

Menorrhagia Hookworm Hookworm Hookworm Hookworm Hookworm Bloodloss, abortion

Total dose mg Fe

Initial PCV Hb g/lOO ml

1065 1500 2000 1250 750 1500

25 21 16 29 35 24

8.2 5.9 4.7 7.7 11.7 6.2

2000 2000 2000 2000 1500 1500

18 15 12 13 13 12

4.6 4.3 4.3 3.7 2.3 4.2

8 9 10 11 12

>, F F Hookworm M Fibroids M Hookworm F Haemorrhagia

13 14 15

M Chronic D.U.

1500 2000

26 27

8.9 7.7

M Nutritional deficiency

1500

20

5.0

M Hookworm

iron repletion and the peripheral blood film showed a transformation from a hypochromic microcytic to a macrocytic picture. Failure to achieve normal haemoglobin levels was clearly due to the presence of malignant disease (Haurani et al. 1963). The haemoglobin concentrations of all defaulting patients were increasing at the time of their last attendance. I t is likely that their failure to return for follow-up was due to the fact that they felt much better and did not trouble to return to hospital for follow-up. This conclusion is reinforced by the knowledge that one of the defaulters (patient no. 3 ) was a farmer who had been treated on two previous occasions for hookworm anaemia. On both occasions he stopped attending when the haematocrit reached between 34 % and

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PCV

Final Remarks (weeks) Completed Completed Defaulted Completed Completed Completed Defaulted Defaulted Completed Defaulted Defaulted Withdrawn from trial for diagnosis of malignant tumour Completed Completed

32

( 3)

Defaulted

38 % and was not seen again until about three years later when his anaemia had recurred from reinfection by hookworm. I t is also common knowledge among doctors in this population that the vast majority of patients who fail to attend for follow-up consider themselves well (even when they only have a partial amelioration of their illness) whereas very few default because of the impression that their cases are hopeless or not improving fast enough. These factors emphasize the special problems of our community at the present time. A common complaint of parenteral administration of drugs, including iron preparations, is local inflammation and pain. None of our patients complained although specifically questioned about it. Although it is

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Table 11 Patients treated with Ferastral subdivided into two groups according to initial packed cell volume 20 %. PCV mean values (ini( P C V ) 2 20 or tial, final, and increase) are shown together with ranges for the respective groups.

>

~

~

~

Group I Initial values 2 20 (n=8) hfcan Range

% Final

Group I1

Increase

Initial values 20 % Final (n=7)

>

Increase

14.9

33.6

18.7

26.7

39.0

12.3

12-20

24-42

12-30

21-35

33-42

6-17

possible that our patients have come to accept such side-effects as a natural consequence of injections which are frequently administered by unqualified practitioners, we observed no clinical signs of inflammation in the patients treated with Ferastral and who were observed weekly. Tests of liver and kidney function performed in the subjects in this trial showed no abnormality. At the dosage used and for the duration of observation, no toxic damage to these tissues had been caused by the preparation. Since most of the iron given had been utilized for haemoglobin synthesis (as shown by the increase in haematocrit levels) or otherwise excreted, the possibility of toxicity after the period of observation must be extremely small. Thus, we conclude that Ferastral is a safe and effective preparation for use in iron-deficiency anaemia.

estimations and Mr. M. A. Olatunji for typing the manuscript.

REFERENCES Dacie J V & Lewis S M (1968) Practical Haematology, 4th Edition, Churchill, London. Gilles H M, Watson-Williams E J & Ball P A J (1964) Hookworm infection and anaemia: an epidemiological clinical and laboratory study. Q J M e d N S 33, 1-24. Haurani F I, Young K & Tocantins L M (1963) Reutilization of iron in anaemia complicating malignant neoplasms. Blood 22, 73-81. Nicol B M (1952) The nutrition of Nigerian peasants with special reference to the effects of deficiencies of the vitamin B complex, vitamin A and animal protein. Br J Nutr 6, 34-55. Varley H (1967) Practical Clinical Biochemistry, 4th Edition. ELBS and Heinemann Medical Books Ltd., London. Williams H L & Conrad M E (1966). A one-tube method for measuring the serum-iron concentration and unsaturated iron binding capacity. J Lab Clin M e d 67, 171-176.

4CKNOWLEDGEMENTS

We are grateful to Messrs. I. Saliu, F. A. Fasuan and E. 0 Soyode of the Department of Haemato!ogy for their technical assistance; Professor B. 0. Osunkoya of the Department of Chemical Pathology for the biochemical

Ccrrespondence to Professor G. J. F. Esan Department of Haematology University College Hospital Ibadan Nigeria

Ferastral: Proceedings

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