Mycophenolate mofetil

Mycophenolate mofetil is a salt form of the immunosuppressive drug mycophenolic acid. The salt form is much better tolerated and allows good and rapid absorption by the body before it is converted to the active agent mycophenolic acid.

Mycophenolic acid acts by inhibiting lymphocyte proliferation and antibody production; hence it is used primarily in immunosuppressive regimens in solid organ transplantations. It is rather similar in action to azathioprine, but more specific.

Mycophenolate mofetil is available in both oral and intravenous preparations. The trade name in New Zealand is CellCept® and it is marketed in 250 mg capsules, 500 mg tablets and 5 ml/1 g suspension. It is currently registered for the prophylaxis of acute organ rejection in patients receiving allogeneic transplants. It is also used for other indications on specialist application, usually when corticosteroids, azathioprine and ciclosporin have failed or are unsuitable.

Use of mycophenolate for skin diseases

Mycophenolate mofetil has been used to treat various non-transplant-related conditions, including some skin disorders. It has been reported to be helpful in the following conditions.

Psoriasis
Connective tissue disorders:
- Cutaneous lupus erythematosus
- Dermatomyositis
- Cutaneous vasculitis – especially in the presence of antineutrophil cytoplasm antibodies
Dermatitis:
Blistering diseases:
Lichen planus
Pyoderma gangrenosum
Sarcoidosis
Necrobiosis lipoidica

How to use mycophenolate mofetil

For the treatment of skin diseases, mycophenolate mofetil is used either alone or in combination with other immunosuppressive agents such as ciclosporin and corticosteroids.

Because it is absorbed well, it is commonly given orally, usually in divided doses. Doses range from 1 to 1.5 g twice daily for the treatment of psoriasis and most other skin diseases (up to maximum dose of 3g daily). When the psoriasis or skin condition begins to improve, the dose can be decreased to 1g daily in divided doses.

Mycophenolate mofetil may cause anaemia, particularly if doses are greater than 3 g daily. It is important to measure complete blood count (CBC) after the first week or two of therapy. If results of several measurements are satisfactory and the patient is on a stable dosage, monthly monitoring should be continued.

Mycophenolate is classified as pregnancy category D, meaning that there is evidence of risk to the fetus. Pregnancy must be avoided when taking this medicine. Men and women should take contraceptive precautions when taking mycophenolate (warning updated to contraindication, December 2015).

Side effects of mycophenolate mofetil

Mycophenolate mofetil appears to be well tolerated and to have fewer side effects than other immunosuppressive agents. Most side effect studies have been carried out in large groups of transplant patients. Considering the doses used in transplantation are greater than those used for skin disease, mycophenolate mofetil is usually very well tolerated in patients being treated for skin disease.

The most common side effects experienced are gastrointestinal symptoms such as nausea, vomiting and diarrhoea. These are more common with dosages greater than 3 g daily but have been reported in 20% or more of patients receiving 2 g daily. Lowering the daily dose or dividing the daily dose to give smaller but more frequent doses can often minimize these side effects.

Another side effect is the slightly increased risk of viral infections including uncomplicated herpes simplex, herpes zoster and cytomegalovirus. However, this appears to be more common in transplant recipients receiving mycophenolate mofetil as part of a combination immunosuppressive regimen.

Rarely, fatalities from progressive multifocal leukoencephalopathy have been reported. This is thought due to reactivation of latent John Cunningham polyomavirus.

As with any immunosuppressive treatment, there is concern that longterm treatment might increase the risk of malignancy.

Drug interactions with mycophenolate mofetil

Mycophenolate mofetil does not seem to interact with other immunosuppressive agents. Some drugs decrease the blood levels of mycophenolate mofetil, including rifampicin, colestyramine and antacids. The coadministration of mycophenolate mofetil with aciclovir increases the blood levels of aciclovir.

Drugs such as probenecid and salicylates that interfere with renal tubular secretion and glomerular filtration can increase the blood levels of mycophenolate mofetil as these mechanisms are used for the renal removal of the drug.

Mycophenolate may occasionally reduce the concentration of other drugs including levonorgestrel – the levels of other contraceptive agents appear unchanged.