Kelfer/L1

Kelfer

Deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one) alias L1

The world's first oral iron chelator

What is Kelfer ?
Kelfer (deferiprone) is a iron chelator administered in the form of capsules to patients of thalassaemia major. It is being sold in India since March 1995 commercially.

How does Kelfer act ?
Kelfer acts by combining with the excess iron in the body to form a complex which is excreted in the urine. This over a period of time leads to reduction in the iron overload in the body.

What is the usual dose of Kelfer ?
Studies have found that the optimum dose of Kelfer is 75 mg/kg/day in 2-4 divided doses taken with or without food. In some patients doses upto 100 mg/kg/day may be administered while in others lower doses of 50 mg/kg/day may be sufficient.

What are the side effects of Kelfer ?
In about 20% of patients, joint pains involve knees, hips, elbows or other joints. The pain may be accompanied by swelling in a few cases. This effect is completely reversible on discontinuation of the drug.

In about 12%, Kelfer can reduce white cell counts. This can be dangerous and may predispose the patients to infections. In such situations, the patient may develop fever sore throat etc. The drug should be immediately stopped, the treating physician consulted and appropriate therapy instituted. In some cases, hospitalization may be required till the counts come back to normal.

What are the precautions to be observed while taking Kelfer?
Patients taking Kelfer should be regularly monitored for their blood counts and joint pains. If the total white blood cells falls below 3000/cc of blood or absolute neutrophil counts to below 1500/cc, Kelfer should be immediately discontinued. If the patient develops fever or sore throat, the drug should be discontinued, a blood should be immediately done and if the counts are low (as mentioned above), the physician should be seen immediately.

How is Kelfer available to patients ?
Kelfer is manufactured by Cipla Ltd and is available to patients through Cipla sales offices all over India under certain guidelines. Physicians have to fil up special prescription and patient consent forms prior to initiating therapy with Kelfer. The drug is supplied for a period of 13 months. Subsequently, everytime Kelfer is purchased, a fresh prescription order form has to be filled.

What is the cost of Kelfer therapy ?
For the patients in India the monthly cost of Kelfer therapy works out to Rs.2,000/- on an average with one 250 mg capsule costing Rs.9.75 and one 500 mg capsule costing Rs.16.00

How has Kelfer helped patients of thalassaemia in India ?
The introduction of Kelfer has led to more number of patients taking chelation therapy due to its excellent compliance and low cost. More than 1000 patients have taken Kelfer with good results. Overall, this has led to a better quality of life for thalassaemic patients.

Journey through the years

Study finds Deferiprone (Kelfer/L1/Ferriprox) provides significantly greater cardiac protection

My story

Introduction
I am the only son of my parents.

I was born with a genetic blood disorder known as Thalassaemia Major (TM). A person suffering from TM does not make enough haemoglobin or Red Blood Corpuscles (RBC’s). I have this because both my parents have half a defective gene for Thalassaemia, i.e. they are both Thalassaemia Minor. That does not mean they are sick or have an illness, except that they are slightly anaemic.

I was diagnosed as TM when I was 8 months old. In those days, no one knew anything about Thalassaemia. Even doctors knew very little, therefore it was very tough on my parents to face the facts of my condition and learn to cope with it. As it is with all Indians, my parents accepted it as their fate and perhaps it is a suffering caused by their own karma or a curse carried on from a previous life.

Treatment
My early childhood was just like that of every other child. Only my parents were somewhat overprotective. I grew up with TM without really knowing that I was seriously sick. As treatment for my illness, I was being given a blood transfusion once every six weeks.

Over the years, because I have grown and my body volume has increased, the transfusion regimen has reached a weekly frequency. This frequency is necessary because in our country we encounter many problems, such as non-availability of donor blood, quality and haemoglobin level of the blood, the restricted hours of the transfusion centre, etc. In the Government and NGO facilities, even a weekly frequency is often stretched to 12-13 days due to shortage of blood and other administrative hassles. I have no choice but to put up with all this because the expenses involved are affordable at about Rs. 150/- (US$ 3.5) per transfusion.

If I were to avail of the services offered by private blood banks or nursing homes, I would not only have to bring my own donor for blood, but also spend about Rs. 1500/- (US$ 35) per transfusion. This appears to be quite cheap compared to the expenses for similar services in the UK or USA. However, one must not lose sight of the fact that my father earns about Rs. 8000/- (US$ 225per month). If I receive four transfusions a month, the expenses would take away a large part of my dad’s earnings. My family can be included in the upper middle class income group. Consider what would be the plight of people belonging to middle and lower income groups.

Respectively taking all this blood transfusions leads to another problem i.e. from overload.

Due to biological reasons excess iron starts accumulating in the body and interferes with the functioning of the various organs in the body. To remove this excess iron, I started taking Desferal as early as 1977. Perhaps I was the first Thalassaemia in India to do so. Of course, the drug was not available locally and had to be imported. My father’s cousins and friends, whenever they travelled to London or Rome, used to bring a couple of boxes of Desferal with them. The first time I took one vial of Deferral in 5ml of distilled water is something I remember very well. Dr. Asha veer, a Haematologist, injected the whole syringe in one go into my bum. I could not sit straight for two days. She was a good doctor. Unfortunately, she expired due to cancer some years later. She was the type of doctor who was dedicated to her work and hence I think I should her in this write up.

After some years, we came to know that for Desferal to be effective it has to be administered subcutaneously and over 8-10 hours of slow infusion with the help of an electronic pump as small as a pencil box. My parents purchased this pump in 1982 for a princely sum of Rs. 8000/- (US$225) at a time when my dad was earning approximately Rs. 1500/- (US$35) per month. In 1982, Desferal became locally available. If I were to take the doctor’s recommended dosage it would cost me Rs. 20000/- (US$ 520) per month. After taking Desferal for seven years my serum ferritin level reached a figure of 8000, a level which ultimately took a toll on my heart and liver. Then in 1989 a wonderful thing happened which was the end of Desferal for me.

A new oral iron chelating drug called Deferiprone (Kelfer) came on the scene. I started with one capsule of 500mg per day, reaching up to a peak of 12 capsules per day, the highest dose ever given to anyone on the trial. After me, two others got a similar dose later. Regardless of the side effects of the new drug, about which I have heard, the pill definitely works for me. Today my dosage is 7 capsules per day and my serum ferritin level is 1400, the lowest ever it has been in my entire life and the biggest benefit of all is the freedom from daily injections.

After the trials were over, the pill was made commercially available in 1995. Until then, I was getting the pill free of cost, but now I have to buy it. The cost is quite cheap compared to Desferal. I spend about Rs. 3500 (US$ 100) per month. According to the procedure prescribed by the FDA, I have to get my CBC done every month and a serum ferritin every six months. This way my doctor keeps a tab on signs of any side effects. I have not touched Desferal since about 8 years now and my iron overload has only improved dramatically for the better, thanks to Deferiprone.

Deferiprone in India is available through CIPLA a pharmaceutical company who carried on the tests for long years and then introduced Kelfer in the market. I hope all Thalassemic’s out there read this and be assured that we have reached a stage where the treatment is not all that cumbersome or expensive.

With the quality of my life improving I have started to look up to other aspects. I keep in touch with latest developments in and for Thalassemia through International meets and participation in local parent-patient organisation

I thank you kindly for taking your precious time out for reading this.

Update Early 2000
Things are really looking up now, I am presently employed in the IT industry, coming out of recession, have just started saving some money finally. This is really a short update, I know I will add another paragraph to this page after all the above was written in 1998, its 2000 now. Wow I made it to the minllenium.

Update May 2002
30 years old, 8 years on desferal and 12 years on Kelfer wow!!
I need to really keep a diary for everyday I live, for sure its gonna make juicy reading. I thought millenium was big now I am targeting 2005 WOW thats like the future. I dont know whats in store but its the first time I am looking to the future instead of sulking on whats past. BTW how do you like my domain!

What is thalassaemia?

Thalassemia consists of a group of inherited diseases of the blood. About 100,000 babies worldwide are born with severe forms of the disease each year. Thalassemia occurs most frequently in people of Italian, Greek, Middle Eastern, Southern Asian and African ancestry

What Are the Different Kinds of Thalassemia?
Thalassemia includes a number of different forms of anemia (red blood cell deficiency). The two main types are called alpha and beta thalassemias, depending on which part of an oxygen-carrying protein (called hemoglobin) is lacking in the red blood cells.

The most severe form of alpha thalassemia, which affects mainly individuals of Southeast Asian, Chinese and Filipino ancestry, results in fetal or newborn death. Most individuals with alpha thalassemia have milder forms of the disease, with varying degrees of anemia.

The remainder of this information sheet focuses on beta thalassemias, which range from very severe to having no effect on health.

Thalassemia major, the most severe form, is also called Cooley's anemia, named after the doctor who first described it in 1925.

Thalassemia intermedia is a mild Cooley's anemia.

Thalassemia minor (also called thalassemia trait) may cause no symptoms, but changes in the blood do occur.

How Does Thalassemia Affect a Child?
Most children with thalassemia major appear healthy at birth, but during the first year or two of life they become pale, listless and fussy, and have a poor appetite. They grow slowly and often develop jaundice (yellowing of the skin).

Without treatment, the spleen, liver, and heart soon become greatly enlarged. Bones become thin and brittle; face bones become distorted, and children with thalassemia often look alike. Heart failure and infection are the leading causes of death among children with untreated thalassemia major.

Children with thalassemia intermedia may develop some of the same complications, although in most cases, the course of the disease is mild for the first two decades of life.

What Is the Treatment?
The use of frequent blood transfusions and antibiotics has improved the outlook for children with thalassemia major. Children with thalassemia intermedia usually do not require transfusions, although they may be recommended if complications start to develop.

When children with thalassemia major are treated with frequent transfusions (generally every 3 to 4 weeks) aimed at keeping their hemoglobin level near normal, many of the complications of thalassemia can be prevented. This form of treatment, referred to as "hypertransfusion," enhances the child's growth and well-being, and usually prevents heart failure and bone deformities.

Unfortunately, repeated blood transfusions lead to a buildup of iron in the body, which can damage the heart, liver and other organs. A drug referred to as an iron chelator, an iron binding agent, can help rid the body of excess iron, preventing or delaying problems related to iron overload. The drug is usually administered daily via a mechanical pump that pumps the drug underneath the skin while the child is sleeping.

Children with thalassemia major who are treated with frequent blood transfusions and iron chelation live 20 to 30 years or longer. Since intensive chelation treatment was introduced only in the 1960s, continuing studies may show that treated individuals are living even longer.

Thalassemia has been cured using bone marrow transplants. However, this form of treatment is possible only for a small minority of patients who have a suitable bone marrow donor, and the transplant procedure is still risky and can result in death.

How Is the Disease Transmitted?
All forms of thalassemia are transmitted only through heredity. It cannot be caught from another child who has it. The disease is passed on through parents who carry the thalassemia gene in their cells. A "carrier" has one normal gene and one thalassemia gene in all body cells, a state sometimes called "thalassemia trait." Most carriers lead completely normal, healthy lives.

When two carriers become parents, there is a one-in-four chance that any child they have will inherit a thalassemia gene from each parent and have a severe form of the disease. There is a two-in-four chance that the child will inherit one of each kind of gene and become a carrier like its parents; and a one-in-four chance that the child will inherit two normal genes from its parents and be completely free of the disease or carrier state. These odds are the same for each pregnancy when both parents are carriers.

Is There a Test for Thalassemia?
Yes. Blood tests and family genetic studies can show whether an individual has thalassemia or is a carrier. In addition, prenatal testing using chorionic villus sampling (CVS) or amniocentesis can detect or rule out thalassemia in the fetus. Early diagnosis is important so that treatment can prevent as many complications as possible.

Can Thalassemia Be Prevented?
The disease can't be prevented at this time, but a program of health education, testing for the trait, genetic counseling, and prenatal diagnosis can provide families with full medical information to help them have healthy children.

People who think they may have or carry thalassemia can go to a genetic services center or clinic for the latest information and for testing. Individuals can be tested to find out if they are carriers. Genetic counselors then can help them make plans about future families.

What Research on Thalassemia Is Taking Place
Scientists are working on better ways to remove excess iron from the body in order to prevent or delay iron overload. They are developing and testing the effectiveness of oral iron-chelating drugs, which could greatly simplify treatment of this disease. March of Dimes grantees are among the many scientists seeking to develop an effective form of gene therapy that may someday offer a cure for thalassemia. Gene therapy may involve inserting a normal beta globin gene (the gene that is abnormal in this disease) into the patient's stem cells, the immature bone marrow cells that are the precursors of all other cells in the blood. Another form of gene therapy may involve using drugs or other methods to reactivate the patient's genes for fetal hemoglobin. All humans produce a fetal form of hemoglobin before birth; after birth, natural genetic switches "turn off" production of fetal hemoglobin and "turn on" production of adult hemoglobin. Scientists are seeking ways to activate these genetic switches so that they can make the blood cells of patients with thalassemia produce more fetal hemoglobin to compensate for their deficiency of adult hemoglobin. Initial studies of rare individuals with genetic traits that allow them to produce only fetal hemoglobin show that they are generally healthy, demonstrating that fetal hemoglobin can be a fine substitute for adult hemoglobin.

In addition, improved bone marrow transplantation methods may lead to wider use of the technique as a treatment for thalassemia. Bone marrow transplants have cured some cases of thalassemia but they are not widely used for the reasons discussed earlier.

Other Frequently Asked Questions about Thalassaemia

This article is the official text on thalassaemia taken from the
Thalassaemia International Federation Website