Currently, thalidomide plus dexamethasone is one of the standard treatments for newly diagnosed myeloma patients. However, this treatment is associated with a high rate of blood clotting in the deep veins and negative effects on stem cell mobilization.

In their study, the researchers evaluated the patients’ response to CTD therapy. They also tested whether autologous stem cell transplantation following CTD treatment enhanced response and survival.

The researchers recruited 68 newly diagnosed myeloma patients under the age of 70 years. The median age of the participants was 62.6 years.

Patients received cyclophosphamide (150 mg/m² orally on days 1-4), thalidomide (400 mg orally on days 1-5 and 15-19), and dexamethasone (20 mg/m² intravenously on days 1-5 and 15-19) in 28-day treatment cycles. The median number of cycles administered was 5.7, ranging from 1 to 8 cycles.

After four cycles of therapy, 32.3 percent of patients achieved a complete response, 15.4 percent achieved a very good partial response, and 40 percent achieved a partial response, for an overall response rate of 87.7 percent. Three patients were not evaluated because they died during the third cycle of treatment.

Patients who responded well after four or more cycles of treatment, continued on to ASCT; 48.3 percent of patients experienced a complete response, and 20.7 percent of patients experienced a very good response. The overall response rate increased to 96.6 percent after ASCT. Overall survival and the time to progression were better for the patients who underwent ASCT than those who did not.

Severe side effects included low platelet count (13 percent), low white blood cell count (10 percent), and low red blood cell count (4 percent). The most common non-blood related side effects were nerve damage to the limbs (14 percent) and infections (10 percent).

The authors of the study concluded that the CTD regimen was effective and well tolerated as first-line therapy in newly diagnosed myeloma patients, resulting in a high success rate of stem cell mobilization and prolonged survival for patients who underwent ASCT.

For more information, see the study in the journal Clinical Lymphoma, Myeloma & Leukemia or the clinical trial listing from ClinicalTrials.gov.

According to CyDex’s press release, the advantages of the new treatment are its one-vial packaging, gentler formula, and increased stability at room temperature. “These advantages have the potential to enable doctors to safely achieve a higher dose intensity of pre-transplant chemotherapy, which could lead to better therapeutic outcomes,” said Dr. Parameswaran Hari, clinical director of the Adult Bone Marrow Transplant Program and an associate professor at the Medical College of Wisconsin.

CyDex’s first Phase 2 trial will start this August with 24 study subjects, but is not yet open to recruiting participants according to the National Institutes of Health’s ClinicalTrials.gov. CyDex estimated that it will finish its tests in December 2010.

In December 2008, the FDA gave orphan drug designation to CyDex’s Proylene Glycol-Free Melphalan HCL as a preparatory treatment for stem cell transplants. This “orphan status,” as the FDA calls it, gives companies tax credits and marketing incentives to make products for diseases that affect less than 200,000 people in the United States. CyDex will have exclusive marketing rights to its new melphalan for seven years.

For more information, please see the CyDex Pharmaceuticals press release (pdf) and the ClinicalTrials.gov document on CyDex’s upcoming Phase 2 trial.

The majority of cancer patients who undergo chemotherapy are given drugs, called 5-HT3 antiemetics, to prevent vomiting and nausea caused by the therapy. Most patients report the most severe nausea on the first day of chemotherapy. Some doctors use spice ginger to treat the symptoms of nausea.

Dr. Julie Ryan and the research team conducted a multi-site, Phase 2/3 randomized, placebo controlled, double blind clinical trial at the University of Rochester Community Clinical Oncology Program to see how well ginger treats nausea that is induced by chemotherapy.

The study found that a dose of one-half to one gram of ginger daily significantly reduced the nausea during the first day of chemotherapy. When asked about the treatment during an interview with The Myeloma Beacon, Dr. Ryan said that, for best results, “ginger must be given before the chemotherapy.”

In the study, 644 patients participated, with 66 percent suffering from breast cancer, 6.5 percent alimentary, and 6.1 percent lung cancer. Only patients who experienced nausea following chemotherapy and those who were scheduled to receive three cycles of chemotherapy were included in the study. Ninety percent of the patients were female with the average age of 53.

The patients were randomized into one of four groups: placebo, 0.5 gram ginger, 1.0 gram ginger, or 1.5 gram ginger. All patients were given three 250 milligram capsules of ginger or placebo twice a day. The dose was given for six days starting three days before the second and third cycles.

Specifically, the placebo group was given three 250 milligram pills of placebo two times a day for a total of 1.5 gram placebo. Similarly, the 1.0 gram ginger group was given one 250 milligram placebo with two 250 milligram ginger, twice a day for a total of 1.0 gram ginger.

Additionally, patients took Kytril or Zofran, a class of 5-HT3 antiemetics, on the first day of all chemotherapy cycles in addition to ginger.

Patients reported their sensation of nausea on a seven-point scale for days one to four of each cycle.

According to the researchers’ statistics, all doses of ginger reduced nausea significantly. Dr. Ryan found that “the optimal amounts were the lower doses” of 0.5 and one gram of ginger. They also found that there was a significant decrease of nausea after 24 hours of ginger therapy.

While the exact mechanism of how ginger therapy reduces nausea is unknown, Dr. Ryan stated that she and her colleagues “are pretty sure it has to do with the absorption of ginger in the gut. One gram must be the actual amount that can be absorbed…and has been effective in other studies.”

While no adverse side effects were reported in the study, patients who take blood thinners should talk to their doctors before taking ginger supplements because ginger can also act as a blood thinner. Moreover, patients should note that ginger was taken in combination with standard medications given for nausea.

For more information about the use of ginger to decrease nausea after chemotherapy, please see abstract 9511 at the ASCO 2009 meeting Web site.

Kidney failure is a relatively common complication in multiple myeloma patients and can lead to life-threatening health issues. Hemodialysis clinically removes toxic waste substances from the blood, performing the same function as a healthy kidney.

Previous to this study, researchers had predicted that chemotherapy in combination with the new procedure, called high cutoff hemodialysis, might improve the condition of multiple myeloma patients. High cutoff dialysis removes immunological proteins that may cause kidney damage, preventing further damage to the organs.

This new study, conducted under Dr. Colin Hutchison of the University Hospital Birmingham (England), evaluated 19 multiple myeloma patients who were treated with both chemotherapy and high cutoff hemodialysis. Thirteen successfully completed the hemodialysis regimen, and all 13 showed reduced immunological proteins and restored kidney function. Seventy percent of the patients showed no further need for dialysis procedures, “which is greatly above the rate expected,” according to Dr. Hutchinson. These patients’ kidneys were restored to a point where they were functioning healthfully.

“High cutoff hemodialysis is exciting because it offers a novel way of treating this group of patients who have historically done very poorly,” added Dr. Hutchinson.

Because this was an uncontrolled pilot study, the results should not be used to impact medical practice. High cutoff dialysis is being further evaluated in a randomized controlled trial, the EuLITE trail (European trial of free light chain removal by extended hemodialysis).

For more information, see either the related press release at the American Society of Nephrology (pdf) or the full text of the relevant journal article at the Clinical Journal of the American Society of Nephrology.

In a recent clinical trial involving Total Treatment 3 (TT3), 80% of patients who received up-front chemotherapy, transplantation, thalidomide, and Velcade achieved nearly complete remission. Of those, 90% have not relapsed four years later.

In addition, there are even promising new drugs, such as carfilzomib, in clinical trials for relapsing patients.

Despite the treatment advances of the past decade and promising news from recent clinical trials, multiple myeloma still carries a five-year survival rate of only 34%. Physicians hope that in the future they will be able to manage the disease indefinitely in patients, much like diabetes or hypertension, but achieving this goal will require more detailed study and clinical trials.

In particular, physicians highlight a lack of information about the most effective combinations and sequences of different treatments. “Naturally, as the permutations are vast and robust data on new agent combination outcomes beyond three to four years are lacking, clear directions are only now beginning to emerge,” explained Bart Bologie, MD, PhD, director of the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences, Little Rock.

Additionally, testing the genetic instabilities and mutations in each patient’s myeloma cells could help physicians to predict each individual’s risk level more accurately and to determine the most appropriate, tailored treatments. Evaluating this information in clinical trials could also help explain why only some individuals respond to a given therapy. Already, rapidly advancing technology in the field of microgene arrays is helping accomplish this objective.

By obtaining better information about treatment sequencing and combinations, as well as patients’ individual risk profiles, “disease control is definitely a realistic goal, and in many cases we are already there,” stated Melissa Alsina, MD, associate professor and myeloma specialist in the Blood and Marrow Transplant Program at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida.

Beyond simply managing multiple myeloma, researchers are also striving for the ultimate goal: a cure. As Bologie emphasizes, “The cure is no longer an elusive goal in myeloma.”

“However, we have now come as far as we can go with available treatments,” states Guido Tricot, MD, PhD, director of the Utah Blood/Marrow Transplant and Myeloma Program at the University of Utah School of Medicine. To ultimately cure myeloma, researchers agree that they need to better understand the make-up of drug-resistant myeloma cells and to develop therapies directly targeted at the mutated myeloma stem cell.

“Until we can eradicate the myeloma stem cell, it will be difficult to cure the disease,” explains David Vesole, MD, PhD, FACP, director of Loyola University Health System’s Blood and Marrow Transplant program. Yet, he believes that physicians could provide “operational cures” in the near future, where they can adequately extend remission and survival rates to a decade and beyond.

Vesole concludes, “The future is promising these goals will come to fruition within the next 10 years.”

The full article can be found in the November 25 issue of HemOnc Today.

Chemotherapy aims to suppress multiple myeloma by targeting cancer cells which characteristically grow at uncontrollable rates. Chemotherapy is toxic to cancer cells and takes effect as the cells multiply. However, chemotherapy can also eliminate healthy cells – especially ones that divide rapidly in the body. For example, cells in the lining of the gastrointestinal tract, hair follicles, and bone marrow, which naturally grow at high rates, are inadvertently targeted by chemotherapy.

Patients should consult their doctors before deciding what preparations and combinations are appropriate for their chemotherapy treatment.

Chemotherapy Drugs Used for Multiple Myeloma
Cyclophosphamide (Cytoxan)
Dexamethasone (Decadron), may be used alone
Doxorubicin (Adriamycin)
Melphalan (Alkeran)
Prednisone
Vincristine (Oncovin)

Chemotherapy Combinations

Combination chemotherapy uses multiple drugs to improve efficacy and to decrease the chances of developing cancer cells that are resistant to one agent. The different drugs can be used simultaneously at an optimal dose, without severe side effects. Patients with advanced stages of cancer, who are not suitable for other treatments like radiation therapy and surgery, often turn to combination chemotherapy.

MP
Melphalan (Alkeran)
Prednisone

MP, a combination of an immunosuppressant and a chemotherapy agent, is a standard combination for multiple myeloma patients who are not candidates for high-dose therapy and stem cell support. Although MP is used frequently and various studies show a response rate of 50 percent with a median overall survival of three years, researchers are continually searching for other combinations with melphalan and prednisone. Currently, studies are being conducted with other drugs such as thalidomide (Thalomid) , Velcade (bortezomib), Revlimid (lenalidomide), and more.

VAD
Vincristine (Oncovin)
Doxorubicin (Adriamycin), given by IV, continuous infusion
Dexamethasone (Decadron), taken by mouth

VAD is a common combination for patients who have previously been untreated for multiple myeloma. This type of chemotherapy treatment, which is referred to as an induction therapy, is used in an effort to reduce tumors before patients undergo a stem cell transplant. VAD showed varying response rates from approximately 50 to 70 percent in different studies.

Administration
Oral or intravenous; dosing varies by purpose and route of administration as well as patient weight.

Side effects
Common side effects include:
Nausea and vomiting
Bone marrow suppression, including
Decreased white blood cell count causing increased risk of infection
Decreased platelet count causing increased risk of bleeding

Less common side effects include:
Severe allergic reactions
Scarring of lung tissue (usually only with prolonged use)
Hair loss
Rash
Itching

Source: Wikipedia, Melphalan, http://en.wikipedia.org/wiki/Melphalan (as of August 8, 2008).

The drug is administered by injection. It may be sold under the brand names Adriamycin PFS, Adriamycin RDF, or Rubex. Doxil is a liposome-encapsulated dosage form of doxorubicin made by Ben Venue Laboratories for Johnson & Johnson. The main benefits of this form are a reduction in cardiotoxicity. It is photosensitive and it is often covered by an aluminum bag to prevent light from affecting it.

History
The history of doxorubicin can be traced back to the 1950s, when an Italian research company, Farmitalia Research Laboratories, began an organized effort to find anticancer compounds from soil-based microbes. A soil sample was isolated from the area surrounding the Castel del Monte, a 13th century castle. A new strain of Streptomyces peucetius which produced a bright red pigment was isolated, and an antibiotic was produced from this bacterium that was found to have good activity against murine tumors. Since a group of French researchers discovered the same compound at about the same time, the two teams named the compound daunorubicin, combining the name Dauni, a pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word for ruby, rubis, describing the color. Clinical trials began in the 1960s, and the drug saw success in treating acute leukemia and lymphoma. However, by 1967, it was recognized that daunorubicin could produce fatal cardiac toxicity.

Researchers at Farmitalia soon discovered that changes in biological activity could be made by minor changes in the structure of the compound. A strain of Streptomyces was mutated using N-nitroso-N-methyl urethane and this new strain produced a different, red-colored antibiotic. They named this new compound Adriamycin, after the Adriatic Sea, and the name was later changed to doxorubicin to conform to the established naming convention. Doxorubicin showed better activity than daunorubicin against murine tumors, and especially solid tumors. It also showed a relatively higher therapeutic index, yet the cardiotoxicity remained.

Doxorubicin and daunorubicin together can be thought of as prototype compounds for the anthracyclines. Subsequent research by many investigators throughout the world has led to many other anthracycline antibiotics, or analogs, and today, it is estimated that there are over 2,000 known analogs of doxorubicin. By 1991, 553 of them have been evaluated in the screening program at the National Cancer Institute (NCI).

Biosynthesis
Doxorubicin (DXR) is a 14-hydroxylated version of daunorubicin, the immediate precursor of DXR in its biosynthetic pathway. Daunorubicin is more abundantly found as a natural product because it is produced by a number of different wild type strains of streptomyces. In contrast, only one known non-wild type species, streptomyces peucetius subspecies cesius ATCC 27952, was initially found to be capable of producing the more widely used doxorubicin. This strain was created by Arcamone et. al in 1969 by mutating a strain producing daunorubicin, but not DXR, at least in detectable quantities. Subsequently, Hutchinson’s group showed that under special environmental conditions, or by the introduction of genetic modifications, other strains of streptomyces can produce doxorubicin. His group has also cloned many of the genes required for DXR production, although not all of them have been fully characterized. In 1996, Strohl’s group discovered, isolated and characterized dox A, the gene encoding the enzyme that converts daunorubicin into DXR. By 1999, they produced recombinant Dox A, a Cytochrome P450 oxidase, and found that it catalyzes multiple steps in DXR biosynthesis, including steps leading to daunorubicin. This was significant because it became clear that all daunorubicin producing strains have the necessary genes to produce DXR, the much more therapeutically important of the two. Hutchinson’s group went on to develop methods to improve the yield of DXR, from the fermentation process used in its commercial production, not only by introducing Dox A encoding plasmids, but also by introducing mutations to deactivate enzymes that shunt DXR precursors to less useful products, for example baumycin-like glycosides. Some triple mutants, that also over-expressed Dox A, were able to double the yield of DXR. This is of more than academic interest because at that time DXR cost about $1.37 million per kg and current production in 1999 was 225 kg per annum. More efficient production techniques have brought the price down to $1.1 million per kg for the non-liposomal formulation. Although DXR can be produced semi-synthetically from daunorubicin, the process involves electrophilic bromination and multiple steps and the yield is poor. Since daunorubicin is produced by fermentation, it would be ideal if the bacteria could complete DXR synthesis more effectively.

Mechanism of action
The exact mechanism of action of doxorubicin is complex and still somewhat unclear, though it is thought to interact with DNA by intercalation. Doxorubicin is known to interact with DNA by intercalation and inhibition of macromolecular biosynthesis. This inhibits the progression of the enzyme topoisomerase II, which unwinds DNA for transcription. Doxorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication.

The planar aromatic chromophore portion of the molecule intercalates between two base pairs of the DNA, while the six-membered daunosamine sugar sits in the minor groove and interacts with flanking base pairs immediately adjacent to the intercalation site, as evidenced by several crystal structures.

Clinical use
Doxorubicin is commonly used to treat some leukemias, Hodgkin’s lymphoma, as well as cancers of the bladder, breast, stomach, lung, ovaries, thyroid, soft tissue sarcoma, multiple myeloma, and others. Commonly used doxorubicin-containing regimens are CA (cyclophosphamide, Adriamycin), TAC (Taxotere, CA), ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine), BEACOPP, CHOP (Cyclophosphamide, Adriamycin, Vincristine, Prednisone) and FAC (5-Fluorouracil, Adriamycin, Cyclophosphamide). Doxil is used primarily for the treatment of ovarian cancer where the disease has progressed or recurred after platinum-based chemotherapy, or for the treatment of AIDS-related Kaposi’s sarcoma.

Experimental therapy
Combination therapy experiments with sirolimus (rapamycin) and doxorubicin have shown promise in treating Akt-positive lymphomas in mice.

Recent animal research coupling a murine monoclonal antibody with doxorubicin has created an immunoconjugate that was able to eliminate HIV-1 infection in mice. Current treatment with antiretroviral therapy (ART) still leaves pockets of HIV within the host. The immunoconjugate could potentially provide a complimentary treatment to ART to eradicate antigen-expressing T cells.

Side effects
Acute side-effects of doxorubicin can include nausea, vomiting, and heart arrhythmias. It can also cause neutropenia (a decrease in white blood cells), as well as complete alopecia (hair loss). When the cumulative dose of doxorubicin reaches 550 mg/m², the risks of developing cardiac side effects, including congestive heart failure, dilated cardiomyopathy, and death, dramatically increase. Doxorubicin cardiotoxicity is characterized by a dose-dependent decline in mitochondrial oxidative phosphorylation. Reactive oxygen species, generated by the interaction of doxorubicin with iron, can then damage the myocytes (heart cells), causing myofibrillar loss and cytoplasmic vacuolization. Additionally, some patients may develop Palmar plantar erythrodysesthesia, or, “Hand-Foot Syndrome,” characterized by skin eruptions on the palms of the hand or soles of the feet, characterized by swelling, pain and erythema.

Due to these side effects and its red color, doxorubicin has earned the nickname “red devil.”

Source: Wikipedia, Doxorubicin, http://en.wikipedia.org/wiki/Doxorubicin (as of August 8, 2008).

Therapeutic use

Anti-inflammatory
Dexamethasone is used to treat many inflammatory and autoimmune conditions, e.g., rheumatoid arthritis.

It is also given in small amounts (usually 5-6 tablets) before and/or after some forms of dental surgery, such as the extraction of the wisdom teeth, an operation which often leaves the patient with puffy, swollen cheeks.

It is injected into the heel when treating plantar fasciitis, sometimes in conjunction with triamcinolone acetonide.

It is useful to counteract allergic anaphylactic shock, if given in high doses. It is present in certain eye drops and as a nasal spray (trade name Dexacort).

Dexamethasone is used in transvenous screw-in cardiac pacing leads to minimize the inflammatory response of the myocardium. The steroid is released into the myocardium as soon as the screw is extended and can play a significant role in minimizing the acute pacing threshold due to the reduction of inflammatory response. The typical quantity present in a lead tip is less than 1.0 mg.

Dexamethasone is often administered before antibiotics in cases of bacterial meningitis. It then acts to reduce the inflammatory response of the body to the bacteria killed by the antibiotics (bacterial death releases pro-inflammatory mediators that can cause a response which is harmful to the patient), thus improving prognosis and outcome.

Oncologic uses
In oncology, it is given to cancer patients undergoing chemotherapy, to counteract certain side-effects of their antitumor treatment. Dexamethasone can augment the antiemetic effect of 5-HT3 receptor antagonists like ondansetron. Dexamethasone is also used in certain hematological malignancies, especially in the treatment of multiple myeloma, in which dexamethasone is given alone or together with thalidomide (thal-dex) or a combination of Adriamycin (doxorubicin) and vincristine (VAD). In brain tumours (primary or metastatic), dexamethasone is used to counteract the development of edema, which could eventually compress other brain structures. Dexamethasone is also given in cord compression where a tumor is compressing the spinal cord.

Endocrine
Dexamethasone can be used in the context of congenital adrenal hyperplasia, to prevent virilisation of a female fetus. If one or both parents are carriers of mutations to the CYP21A gene, the mother may start dexamethasone treatment within 7 weeks of conception. At the 12th week, a chorionic villus sample will determine whether the fetus is male (in which case the dexamethasone is stopped) or female. Subsequent DNA analysis can then reveal whether the female fetus is a carrier of the mutation, in which case dexamethasone treatment must continue until birth. The side-effects for the mother can be severe and the long-term impact on the child is not clear.

Obstetrics
Dexamethasone may be given to women at risk of delivering prematurely in order to promote maturation of the fetus’ lungs. This has been associated with low birth weight, although not with increased rates of neonatal death.

High altitude illnesses
Dexamethasone is used in the treatment of high altitude cerebral edema as well as pulmonary edema. It is commonly carried on mountain climbing expeditions to help climbers deal with altitude sickness.

Diagnostic use
Dexamethasone is also used in a diagnostic context, namely in its property to suppress the natural pituitary-adrenal axis. Patients presenting with clinical signs of glucocorticoid excess (Cushing’s syndrome) are generally diagnosed by a 24-hour urine collection for cortisol or by a dexamethasone suppression test. During the latter, the response of the body to a high dose of glucocorticoids is monitored. Various forms are performed. In the most common form, a patient takes a nighttime dose of either 1 or 4 mg of dexamethasone, and the serum cortisol levels are measured in the morning. If the levels are relatively high (over 5 µg/dl or 150 nmol/l), then the test is positive and the patient has an autonomous source of either cortisol or ACTH, indicating Cushing’s syndrome where the tumor does not have a feedback mechanism. If ACTH levels are lowered by at least 50%, this would indicate Cushing’s Disease, since the pituitary adenoma has a feedback mechanism that has been reset to a higher level of cortisol. Longer versions rely on urine collections on oral dexamethasone over various days.

Veterinary use
Combined with marbofloxacin and clotrimazole, dexamethasone is available under the name Aurizon , CAS number 115550-35-1, and used to treat difficult ear infections, especially in dogs. It can also be combined with Trichlormethiazide to treat horses with swelling of distal limbs and general bruising.

Contraindications
Some of these contraindications are relative:

Existing gastrointestinal ulceration
Cushing’s syndrome
Severe forms of heart insufficiency
Severe hypertension
Uncontrolled diabetes mellitus
Systemic tuberculosis
Severe systemic viral, bacterial, and fungal infections
Preexisting wide angle glaucoma
Osteoporosis

Side effects
If dexamethasone is given orally or by injection (parenteral) over a period of more than a few days, side-effects common to systemic glucocorticoids may occur. These may include:

Stomach upset, increased sensitivity to stomach acid to the point of ulceration of esophagus, stomach, and duodenum
Increased appetite leading to significant weight gain
A latent diabetes mellitus often becomes manifest. Glucose intolerance is worsened in patients with preexisting diabetes.
Immunsuppressant action, particularly if given together with other immunosuppressants such as ciclosporine. Bacterial, viral, and fungal disease may progress more easily and can become life-threatening. Fever as a warning symptom is often suppressed.
Psychiatric disturbances, including personality changes, irritability, euphoria, mania
Osteoporosis under long term treatment, pathologic fractures (e.g., hip)
Muscle atrophy, negative protein balance (catabolism)
Elevated liver enzymes, fatty liver degeneration (usually reversible)
Cushingoid (syndrome resembling hyperactive adrenal cortex with increase in adiposity, hypertension, bone demineralization, etc.)
Depression of the adrenal gland is usually seen, if more than 1.5 mg daily are given for more than three weeks to a month.
Hypertension, fluid and sodium retention, edema, worsening of heart insufficiency (due to mineral corticoid activity)
Dependence with withdrawal syndrome is frequently seen.
Increased intraocular pressure, certain types of glaucoma, cataract (serious clouding of eye lenses)
Dermatologic: Acne, allergic dermatitis, dry scaly skin, ecchymoses and petechiae, erythema, impaired wound-healing, increased sweating, rash, striae, suppression of reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria.
Allergic reactions (though infrequently): Anaphylactoid reaction, anaphylaxis, angioedema. (Highly unlikely, since dexamethasone is given to prevent anaphylactoid reactions.)
Other side-effects have been noted, and should cause concern if they are more than mild.

The short time treatment for allergic reaction, shock, and diagnostic purposes usually does not cause serious side effects.

Interactions
NSAIDs and alcohol: increased risk of gastrointestinal ulceration
Mineralocorticoids: increased risk of hypertension, edema and heart problems
Oral antidiabetic drugs and insulin: antidiabetic therapy may have to be adjusted
Other interactions (with certain antibiotics, estrogens, ephedrine, digoxin) are known.

Dosage
Shock: 4 to 8 mg intravenously initially, repeat if necessary to a total dose of 24 mg.
Autoimmune diseases and inflammations: longterm therapy with 0.5 to 1.5 mg oral per day. Avoid more than 1.5 mg daily, because serious side effects are more frequently encountered with higher doses.
Adjuvant to or part of chemotherapy: individual schedule
Diagnostic purposes: special schedule

Sports doping
In 2005, Polish cross country skier Justyna Kowalczyk was disqualified from the Under 23 (U23) OPA (Alpine nations) Intercontinential Competition in Germany and issued a 2-year suspension for her doping offenses on dexamethasone. This was eventually reduced to one year during 2005 and later rescinded by the Court of Arbitration for Sport in December 2005. She would later earn a bronze in the women’s 30 km freestyle mass start at the 2006 Winter Olympics in Turin.

Source: Wikipedia, Dexamethasone, http://en.wikipedia.org/wiki/Dexamethasone (as of August 8, 2008).

Uses
Prednisone is particularly effective as an immunosuppressant, and affects virtually all of the immune system. It can, therefore, be used in autoimmune diseases, inflammatory diseases (such as severe asthma, severe allergies, severe poison ivy dermatitis, systemic lupus erythematosus, ulcerative colitis, rheumatoid arthritis, Bell’s Palsy, Crohn’s disease, pemphigus and sarcoidosis), uveitis, various kidney diseases including nephrotic syndrome, and to prevent and treat rejection in organ transplantation. This medicine may also reduce the sex drive. Prednisone has also been used in the treatment of migraine headaches and cluster headaches.

Furthermore, the pharmaceutical industry uses prednisone tablets for the calibration of dissolution testing equipment according to the United States Pharmacopeia (USP).

Intravenous application may be employed for cerebral inflammation, as in the period attacks caused by multiple sclerosis.

History
Prednisone was invented in the early 1950s when Arthur Nobile at Schering demonstrated that the side-effects of cortisone, such as water retention, high blood pressure and muscle weakness, could be removed by oxidisation of the drug through exposure to microbes. The drug was introduced by Schering in the mid-1960s.

Dependency
Adrenal suppression occurs if prednisone is taken for longer than 7 days, a condition wherein the body is unable to synthesize natural corticosteroids and becomes dependent on the prednisone taken by the patient. For this reason, prednisone should not be stopped abruptly if taken for longer than seven days; rather the dosage must be reduced slowly. This reduction may be over a few days if the course of prednisone was short, but may take weeks or months if the patient had been on long-term treatment. Abrupt withdrawal may lead to an Addisonian crisis, which may be life-threatening. For those on chronic therapy, alternate-day dosing may preserve adrenal function, thereby reducing side-effects.

Side-effects
Short-term side-effects, as with all glucocorticoids, include high blood glucose levels, especially in patients that already have diabetes mellitus or are on other medications that increase blood glucose (such as tacrolimus), and mineralocorticoid effects such as fluid retention (although it is worth noting, however, that the mineralocorticoid effects of prednisone are very minor; this is why it is not used in the management of adrenal insufficiency unless a more potent mineralocorticoid is administered concomitantly). Additional short-term side-effects include insomnia, euphoria, and, rarely, mania. Long-term side-effects include Cushing’s syndrome, weight gain, osteoporosis, glaucoma, type II diabetes mellitus, and depression upon withdrawal.

Major
increased blood sugar for diabetics
weight gain
facial swelling
depression, mania, or other psychiatric symptoms
unusual fatigue or weakness
mental confusion / indecisiveness
blurred vision
abdominal pain
peptic ulcer
infections
painful hips or shoulders
osteoporosis
insomnia
severe joint pain
cataracts
osteonecrosis
anxiety
black, tarry stools
stomach pain or bloating
severe swelling
mouth sores or dry mouth

Minor
stretch marks
nervousness
acne
rash
increased appetite
hyperactivity
frequent urination
diarrhea
removes intestinal flora