Brand names are Sandimmune and Neoral by Novartis
Neoral has been available since 1995 to prevent organ rejection. In 1998, the FDA approved SangCya - an oral equivalent - by SangStat Medical Corporation. The FDA declared it to be a direct substitute for Neoral. In February of 1999, Novartis sued the FDA, claiming incorrect FDA procedures. Novartis also sued Sangstat for patent infringement.
May 16, 2000 - The FDA approved generic immunosuppressant Gengraf capsules, made by Abbott Laboratories and its partner SangStat, to prevent organ rejection in heart transplants. The cyclosporine capsules are based on Novartis' Neoral capsules. Gengraf's AB rating means that the FDA considers it interchangeable with Neoral. State pharmacy and Medicaid laws allow (and in certain cases require) that an AB-rated generic drug be used instead of the brand name drug. Gengraf is not equivalent to Sandimmune, and the 2 products may not be used interchangeably without a doctor's supervision.
Abbott and SangStat are launching their generic cyclosporine against only one competitor: Eon Laboratories, which won FDA approval in January. Gengraf may have one added advantage besides lower cost. In a "panel assessment" by 101 healthy volunteers, 94% preferred Gengraf's "aroma," according to an Abbott press release. (Source: Reuters Health)
July 11, 2000 - Patients may not absorb enough of "SangCya oral solution" if they swallow it with apple juice. The FDA started a nationwide recall of SangCya - a generic version of liquid cyclosporine - Monday. The brand-name version - Neoral - is not affected; neither are cyclosporine capsules. FDA officials urge patients not to change how they take SangCya until contacting their transplant cardiologist for advice.
This is the latest controversy over SangCya. Neoral manufacturer Novartis already sued the FDA, claiming the government improperly approved the generic drug, and said Monday's recall strengthens that argument. SangCya's instructions suggest that patients mix it in apple juice or orange juice to disguise the bad taste. However, a study found that volunteers who took SangCya mixed in apple juice absorbed about 20 to 30% less of the drug than people absorb when taking Neoral with orange juice. Generic drug actions are supposed to be identical to the brand-name drugs they imitate.
Manufacturer SangStat Medical Corporation completed the study before the FDA approved SangCya's sale in 1998, but didn't tell the agency about the results until last week. A SangStat spokeswoman said the FDA required only one study showing SangCya was equivalent to Neoral and the company had already submitted a positive study before this one was complete.
The product in question is SangCya Cyclosporine Oral Solution, 100mg/mL, 50 mL bottle. More info on the recall can be found here.
Cyclosporine suppresses the immune system's T-cells. Both the T-helper cell and the T-suppressor cell may be affected. Cyclosporine also inhibits interleukins. The drug comes in 3 forms:
Sandimmune is a soft-gel capsule form of cyclosporine. Absorption from the intestinal tract can vary a lot and is incomplete. Children often require larger doses than adults. Levels of Sandimmune in your blood peak about 3 1/2 hours after you take a dose. Food may delay and reduce drug absorption, more so than with Neoral. The drug is removed from your system by your liver. Sandimmune has been used in children as young as 6 months with side effects no different than those seen in adults. When you open the blister pack to remove the pill, you'll notice a peculiar smell. This is normal and does not mean something is wrong with the capsule. Swallow capsules whole.
Neoral or SangCya is a suspension form of cyclosporine, meaning it is tiny particles of the drug suspended in an oily liquid. Neoral is absorbed and used by the body more easily than Sandimmune. For that reason, Sandimmune and Neoral are not equivalent and cannot be used interchangeably without close supervision by your transplant cardiologist. Food lowers the amount of drug that is absorbed but less so than with Sandimmune. Neoral is always taken twice a day.
You take Neoral by measuring a dose out with the dropper that comes with the prescription. You mix it with milk, orange juice, or apple juice. Do not use grapefruit juice. Stir well just before drinking it. The dropper should not touch the juice. If you clean the syringe, do not rinse it; just wipe the outside with a dry tissue. After drinking the mixture, rinse the cup with a little more juice or milk and drink that. Neoral is sensitive to light and temperature, so do not let it sit in direct sunlight and do not refrigerate it.
Neoral should be used within 2 months. Studies have shown no significant differences between Sandimmune and Neoral in terms of kidney safety, serious side effects, or lab tests like blood pressure, creatinine clearance, uric acid levels, potassium, cholesterol or triglycerides.
This is highly individual and depends in part on how close a match your new heart is to your own body. Adults and children usually start at a 15 mg/kg dose given in 2 divided doses before transplant surgery. There is a trend towards use of a lower initial dose of 10 to 14 mg/kg/day. This is continued after surgery for 1 to 2 weeks, followed by a 5% decrease in dose per week until a maintenance dose of anywhere from 2 to 10 mg/kg/day is reached. Neoral may allow lower maintenance doses than Sandimmune.
Sandimmune and Neoral are not interchangeable at equal doses. If converting from Sandimmune to Neoral, you will usually start with the same dose; then the Neoral dose will be adjusted until you reach the proper cyclosporine blood level. Until this level is reached, your cyclosporine blood level will be checked at least once every 4 to 7 days. Neoral is taken twice a day.
You will not get all, or even most, of these side effects, but they are possible. This is not a complete list. The most common side effects are signs of kidney dysfunction such as less output when urinating and swollen hands or feet; nervous system effects such as tremors (shaky hands); excessive growth of body hair, swollen or bleeding gums, and headache.
Taking cyclosporine may change the results of the following lab tests. You will be closely monitored through blood testing to keep your cyclosporine levels in that narrow range between effectiveness and poison. Don't get too scared by this - remember that many of the drugs you probably took for heart failure had the potential to really mess you up but you took them and survived okay.
After your transplant surgery, your blood will be tested at least every 2 to 3 days. After you go home, your cyclosporine levels will be measured at each clinic visit, which is usually twice a week for the first 2 months, once a week for 2 more months, and once a month for the remainder of your first year.
The blood test to measure cyclosporine levels is called "Cyclosprine Level/Whole Blood HPLC." A high level means increased risk of infection and side effects. A low level invites organ rejection. The normal range is 150 to 300 ng/ml. Do not take cyclosporine the morning of your clinic visit. See this page for info on some of these blood tests.
I do not include drugs which may alter your blood levels of cyclosporine. This is not a complete list. Drug interactions are no joke for heart transplant recipients. You must never take any drug or over the counter medicine without checking first with your transplant cardiologist. Period.
Cyclosporine is transformed in your body into about 15 metabolites. The drug is eliminated through your liver. Only 0.1% of a dose is lost unchanged through urination. Cyclosporine's half-life is about 18 hours. This is radically different from one patient to the next, though. For example, the half-life ranged from 6.3 hours in healthy volunteers to 20.4 hours in patients with severe liver disease.
Sex and pregnancy Getting pregnant while on cyclosporine is generally considered a bad idea, but oral contraceptives (birth control pills) are also a bad idea due to possibly serious side effects. Frankly, I don't know how this contradiction is handled in women with heart transplants. Mothers taking cyclosporine should not breast feed their infant(s). Men treated with cyclosporine have fathered normal children. Experience in children is almost entirely based on Sandimmune, not Neoral. In several studies, children needed higher doses of Sandimmune per pound of body weight.
Kidney changes Cyclosporine may increase blood levels of creatinine and uric acid, as a result of reduced glomerular filtration rate (GFR). This is not fully understood. These changes sometimes disappear when the dose is reduced. Less often, patients have structural changes in their kidney (interstitial fibrosis) during long-term treatment. Although these kidney changes are less common, they may be irreversible.
Liver, blood pressure, cholesterol, vaccines The drug may increase liver enzymes. Liver function should be closely monitored. Many patients develop high blood pressure. Great care is needed in choosing a drug to lower high blood pressure. Diuretics may interact with cyclosporine. Calcium channel blockers - which do not interfere with cyclosporine - are recommended. Most transplant patients develop high cholesterol levels and all recipients develop coronary artery disease. A low-fat diet is strongly recommended. Lovastatin is not to be used due to the risk of myocyte necrosis. Live vaccines must not be used.
Overdose Documented cases include both single and multiple overdoses of Sandimmune capsules and oral solution, to a maximum overdose of 25,000mg. High cyclosporine levels cause acute poisoning symptoms such as nausea, headache, acute sensitivity of the skin, flushing, gum pain and bleeding, and a sensation of increased stomach size. High levels may cause liver or kidney failure but this is temporary and no permanent failure is known.
Material taken from manuals given to potential transplant recipients at transplant centers in the USA, online drug monographs, medical dictionaries, and from heart transplant recipients - Updated April 24, 2002
All information on this site is opinion only. All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor. Use the reference information at the end of each article to search MedLine for more complete and accurate information. All original copyrights apply. No information on this page should be used by any person to affect their medical, legal, educational, social, or psychological treatment in any way. I am not a doctor. This web site and all its pages, graphics, and content copyright © 1997, 1998, 1999, 2000, 2001, 2002, 2003, 2004 Jon C.