Azathioprine
Uses and indications: Azathioprine has been in use as a drug for long-term immunosuppressive treatment. It inhibits the growth of immune system cells, especially the growth of lymphocytes. The main indication is as an adjunctive treatment for the prevention of rejection in renal homotransplantation. It is also indicated for the management of severe, active rheumatoid arthritis unresponsive to rest, aspirin or other nonsteroidal anti-inflammatory drugs. Azathioprine may also be used for other conditions as determined by your doctor.
Dosing: For Rheumatoid Arthritis, Azathioprine is usually given on a daily basis. The initial dose should be approximately 1.0 mg/kg (50 to 100 mg) given as a single dose or on a twice daily schedule. The dose may be increased, beginning at six to eight weeks and thereafter by steps at four-week intervals, if there are no serious toxicities and if initial response is unsatisfactory. Dose increments should be 0.5 mg/kg daily, up to a maximum dose of 2.5 mg/kg/day. The effect on the immune system only starts some weeks after the beginning of treatment and is maintained for several weeks after the end of treatment.
Safety: Severe leukopenia and/or thrombocytopenia may occur in patients on azathioprine. Macrocytic anemia and severe bone marrow depression may also occur. Hematologic toxicities are dose related and may be more severe in renal transplant patients whose homograft is undergoing rejection. It is suggested that patients on azathioprine have complete blood counts, including platelet counts, weekly during the first month, twice monthly for the second and third months of treatment, then monthly or more frequently if dosage alterations or other therapy changes are necessary. Delayed hematologic suppression may occur.
The principal and potentially serious toxic effects of azathioprine are hematologic and gastrointestinal (nausea and vomiting, diarrhea, fever). The risks of secondary infection and neoplasia are also significant. The frequency and severity of adverse reactions depend on the dose and duration of azathioprine as well as on the patient’s underlying disease or concomitant therapies.
Because of the inhibitory effect on cell growth, the use of azathioprine and, in fact, of all other immunosuppressive drugs is prohibited for women who are pregnant, or seeking to become pregnant. Regular monitoring of the blood count is required.
Mitoxantrone
Uses and indications: Mitoxantrone belongs to the general group of medicines known as antineoplastics. It is used to treat some forms of Multiple Sclerosis (MS). It is also used to treat some kinds of cancer like breast cancer with metastasis, and non-Hodgkin lymphoma and acute leukemia.
Dosing: The recommended dose for Multiple Sclerosis is 12mg/ m2 every three months. The cumulative dose should not exceed 100-140 mg/m2. The dose of mitoxantrone will be different for different patients. The dose that is used may depend on a number of things, including what the medicine is being used for, the patient's size, and whether or not other medicines are also being taken. It is administered by drip at regular intervals under stationary conditions (e.g. in hospital).
This drug is relatively well tolerated, and there are only rare instances of a feeling slightly unwell, sometimes associated with tiredness and exhaustion.
Safety: The main side effects of mitoxantrone are the possibility of damage to the heart (heart failure), risk of leukemia, and myelosuppression, which among other things, can lead to infections. Other common side effects include black, tarry stools; cough or shortness of breath, sores in mouth and on lips; stomach pain.
Cyclophosphamide
Uses and indications: Cyclophosphamide is a drug that strongly inhibits cell metabolism and reproduction. It is mainly used to treat cancer of the ovaries, breast, blood and lymph system, nerves (found primarily in children), retinoblastoma (a cancer of the eye found primarily in children), multiple myeloma (cancer in the bone marrow), and mycosis fungoides (tumors on the skin).
Cyclophosphamide is also used for treatment of some kinds of kidney disease.
It also inhibits the growth and multiplication of the cells of the immune system. Cyclophosphamide may also be used for other conditions as determined by your doctor.
Dosing: For the above mentioned indications in high dose interval therapy it is used in the dose of 20-40 mg/kg corporal weight or 800-1600 mg/m2 body surface. It is administered as an infusion at regular intervals under stationary conditions (e.g. in hospital). During treatment, leukocytes should be checked regularly because myelosupression can occur and in that case the dose should be adapted.
The dose of cyclophosphamide will be different for different patients. The dose that is used may depend on a number of things, including what the medicine is being used for, the patient's weight, and whether or not other medicines are also being taken.
Safety: The more common side effects are cough or hoarseness; fever or chills; lower back or side pain; missing menstrual periods; painful or difficult urination; darkening of skin and fingernails; loss of appetite; nausea or vomiting. Cyclophosphamide may cause a temporary loss of hair in some people. Nevertheless, side effects can be so considerable that cyclophosphamide should be used only in specialized centres and only in severe cases of MS while desisting from the use of other kinds of treatment. Also myelosupression, sometimes associated with infections, is a common side effect and the dose should be adapted accordingly.
Methotrexate
Uses and indications: Methotrexate belongs to the group of medicines known as antimetabolites (anti-cancer drugs). It is used to treat cancer, psoriasis and rheumatoid arthritis. It may also be used for other conditions as determined by your doctor.
Dosing: The dose of methotrexate will be different for different patients. The number of tablets that you take or doses of injection that you use depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are taking methotrexate.
Safety: Along with their desired effects, medicines like methotrexate can sometimes cause unwanted effects such as myelosuppression, sometimes associated with infections, kidney problems, stomach or liver problems, urinary problems and loss of hair. The most common side effects include diarrhea; reddening of skin; sores in mouth and on lips; stomach pain; nausea or vomiting, skin rashes, urticaria and photosensitivity. Liver toxicity may be of concern after chronic use of the drug.
Natalizumab
Uses and indications: Natalizumab is a recombinant humanized monoclonal antibody proven to show efficacy in MS.
Dosing: Natalizumab is administered by intravenous infusion of 300 mg every four weeks under stationary conditions.
Safety: Although the relationship between natalizumab and PML is not known, on February 2005 Biogen Idec and Elan Corporation suspended from the market the supply of Tysabri from commercial distribution and the drug is currently not available on the market. Tysabri was initially suspended due to two cases of PML (progressive multifocal leukoencephalopathy). Later a third case was confirmed, and a fourth case is suspected.
The U.S. Food and Drug Administration (FDA) is alerting the public that the risk of developing progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection associated with the use of Tysabri (natalizumab), increases with the number of Tysabri infusions received. This new safety information, based on reports of 31 confirmed cases of PML received by the FDA as of January 21, 2010, will now be included in the Tysabri drug label and patient Medication Guide ). The incidence of PML is still considered close to 1 in 1000 patients. However, the FDA noted that outside the U.S. the incidence rate climbs to about 2 cases per 1000 patients; the agency said that the reason for this increased rate is unknown.
