Mycophenolate mofetil

What it is

Mycophenolate mofetil is a manufactured prescription immunosuppressant. It is a prodrug: after it is swallowed or infused it is hydrolysed to mycophenolic acid, which is the active substance. Mycophenolic acid blocks inosine monophosphate dehydrogenase, the enzyme lymphocytes depend on to make new guanosine nucleotides, so it damps down the T and B cell proliferation that drives transplant rejection and autoimmune inflammation. It comes as capsules, tablets, an oral suspension and an intravenous powder.

What the research says

Its approved job is preventing rejection after a kidney, heart or liver transplant, and in kidney transplantation two large blinded trials showed clear reductions in treatment failure and biopsy-proven rejection against azathioprine. Off-label it is used widely in autoimmune disease, where the record is uneven: better than azathioprine for keeping lupus nephritis in remission, no better than intravenous cyclophosphamide for inducing remission, no better than cyclophosphamide for scleroderma lung disease, and no better than prednisone alone in myasthenia gravis. It carries a boxed warning for pregnancy loss and malformations, cancer and serious infection, and these are not small risks.

Evidence grade: Well established.

How it works

Drug class: Inosine monophosphate dehydrogenase (IMPDH) inhibitor; antimetabolite immunosuppressant

Mycophenolate mofetil is absorbed and then converted to mycophenolic acid, its active metabolite. Mycophenolic acid selectively and uncompetitively inhibits both isoforms of inosine monophosphate dehydrogenase, which blocks the de novo route lymphocytes use to make guanosine nucleotides and therefore blocks DNA synthesis. The practical result is that T and B lymphocytes cannot multiply in response to a transplanted organ or an autoimmune trigger. The label adds that the effect is cytostatic and reversible. (Source 1)

Boxed warning

WARNING: EMBRYOFETAL TOXICITY, MALIGNANCIES and SERIOUS INFECTIONS Use during pregnancy is associated with increased risks of first trimester pregnancy loss and congenital malformations. Avoid if safer treatment options are available. Females of reproductive potential must be counseled regarding pregnancy prevention and planning [see Warnings and Precautions (5.1) , Use in Special Populations (8.1 , 8.3) ]. Increased risk of development of lymphoma and other malignancies, particularly of the skin [see Warnings and Precautions (5.2) ]. Increased susceptibility to bacterial, viral, fungal and protozoal infections, including opportunistic infections and viral reactivation of hepatitis B and C, which may lead to hospitalizations and fatal outcomes [see Warnings and Precautions (5.3) ].

(Source 2)

What it is used for

• Two large blinded randomised trials against azathioprine found consistent benefit. In the Tricontinental trial of 503 patients, treatment failure at 6 months was 50.% with azathioprine versus 34.8% with 3 g of mycophenolate mofetil and 38.2% with 2 g, and biopsy-proven rejection was 35.5% versus 15.9% and 19.7%. In the US trial of 499 patients the corresponding treatment-failure figures were 47.6% versus 31.1% and 31.3%. Graft and patient survival were similar across groups at 6 to 12 months. Evidence: established. (Source 3)
• Approved in combination with other immunosuppressants for recipients 3 months of age and older. The pivotal cardiac trial is referred to in the label but I did not reach its primary publication, so no effect size is reported here; the approval is recorded as a regulatory position with its date. Evidence: limited. (Source 4)
• Approved in combination with other immunosuppressants for recipients 3 months of age and older. As with the cardiac indication, the pivotal hepatic trial is referred to in the label but I did not reach its primary publication, so no effect size is reported here. Evidence: limited. (Source 4)
• The ALMS trial randomised 370 patients and found response in 104 of 185 (56.2%) on mycophenolate mofetil versus 98 of 185 (53.0%) on intravenous cyclophosphamide; it did not meet its primary objective of showing superiority. A Cochrane review rates the comparison as low certainty, with a risk ratio for complete remission of 1.17 (95% CI 0.97 to 1.42), a range that includes no difference. What the Cochrane review does find with moderate certainty is a different side-effect profile: less alopecia, more diarrhoea. Evidence: disputed. (Source 5)
• The ALMS maintenance trial randomised 227 responders and found treatment failure in 16.4% on mycophenolate mofetil versus 32.4% on azathioprine, hazard ratio 0.44 (95% CI 0.25 to 0.77; P = 0.003). The Cochrane review agrees with moderate certainty, putting relapse on azathioprine at a risk ratio of 1.75 (95% CI 1.20 to 2.55), which it translates to 114 more relapses per 1000 people. Evidence: established. (Source 6)
• Scleroderma Lung Study II randomised 142 patients to 24 months of mycophenolate mofetil or 12 months of oral cyclophosphamide. Lung function improved in both arms but the courses did not differ significantly (p=0·24), so the trial was negative for its primary endpoint. Mycophenolate mofetil was better tolerated: leucopenia in 4 patients versus 30 on cyclophosphamide. Evidence: limited. (Source 7)
• Eighty immunosuppression naive patients were randomised to mycophenolate mofetil 2.5 g/day plus prednisone 20 mg/day or placebo plus the same prednisone for 12 weeks. The change in quantitative myasthenia gravis score was -4.4 with the drug and -3.6 with placebo (p = 0.71). The trial demonstrated no benefit. Evidence: not-supported. (Source 8)

Interactions

• Magnesium or aluminium hydroxide antacids (pharmacokinetic study): Taken together, an antacid containing magnesium or aluminium hydroxide cuts how much mycophenolic acid gets into the blood. The label therefore tells people to leave a gap after their mycophenolate dose. (Source 9)
• Proton pump inhibitors (lansoprazole, pantoprazole) (pharmacokinetic study): Acid-suppressing drugs raise stomach pH, mycophenolate dissolves less well, and blood levels of the active metabolite drop by a quarter to a third of the total exposure. (Source 10)
• Iron supplements (pharmacokinetic study): Disputed. One crossover study concluded that taking iron tablets at the same time markedly reduced absorption; a later crossover trial in 16 healthy men found no interaction at all. Because the two studies disagree, this is recorded as unresolved rather than established. (Source 11)
• Bile acid sequestrants such as cholestyramine (label): These bind the recirculating metabolite in the gut and increase its excretion, which lowers mycophenolic acid exposure. The same property is why they are mentioned as a way to remove the drug. (Source 12)

Stopping it

• Stopping maintenance treatment in lupus nephritis has been tested directly. In the WIN-Lupus trial, discontinuing after two to three years was not shown to be non-inferior to carrying on, and severe lupus flares were more common in those who stopped. The trial was stopped early at 96 of 200 planned patients, so it is inconclusive rather than a demonstration either way on renal relapse. (Source 13)
• Treatment is interrupted or reduced for low neutrophils rather than tapered for withdrawal; no withdrawal syndrome is described. The label sets a numeric trigger for interrupting the dose. (Source 14)
• Where pregnancy is planned, the teratology literature advises stopping well in advance rather than at conception. (Source 15)

What goes wrong

Gastrointestinal toxicity, tissue-invasive CMV infection and malignancies were more common on the higher 3 g dose in kidney transplant. (Source 3)

• Randomized trial, Moderate certainty.
• Size: 503 patients.
• Who: Cadaveric renal graft recipients on cyclosporine and corticosteroids.
• How long: 12 months.
• Result: Noncutaneous malignancies in six patients on MMF 3 g, three on MMF 2 g and four on azathioprine; lymphoproliferative disorders in two patients per MMF group versus one on azathioprine.
• Funding: not stated.

Gastrointestinal toxicity and tissue-invasive cytomegalovirus infection were more common in the MMF 3 g group. Noncutaneous malignancies occurred in six patients on MMF 3 g, three patients on MMF 2 g, and four patients on AZA.

Adverse events were near-universal in both arms of the lupus nephritis maintenance trial, most often minor infections and gastrointestinal upset. (Source 6)

• Randomized trial, High certainty.
• Size: 227 patients.
• Who: Lupus nephritis responders on maintenance therapy.
• How long: 36 months.
• Result: Adverse events in more than 95% of patients in both groups (P = 0.68). Serious adverse events in 23.5% on MMF versus 33.3% on azathioprine (P = 0.11); withdrawal for adverse events 25.2% versus 39.6% (P = 0.02)
• Funding: industry-funded (Vifor Pharma, formerly Aspreva)

Adverse events, most commonly minor infections and gastrointestinal disorders, occurred in more than 95% of the patients in both groups (P = 0.68).

In a cohort built from US insurance claims, first-trimester mycophenolate exposure was associated with about twice the risk of pregnancy loss compared with azathioprine (adjusted relative risk 1.9). (Source 16)

• Cohort study, Low certainty.
• Size: 111 pregnancies exposed to mycophenolate and 471 to azathioprine.
• Who: US insurance-claims cohort (IBM MarketScan, 2005-2015) with a first-trimester prescription claim.
• How long: Pregnancy; outcome spontaneous abortion or stillbirth.
• Result: Pregnancy loss in 55 of 111 (49.5%) mycophenolate-exposed pregnancies versus 113 of 471 (24.0%) azathioprine-exposed; unadjusted relative risk 2.0 (95% CI 1.6, 2.6), adjusted relative risk 1.9 (95% CI, 1.6, 2.3)
• Funding: not stated.

Limit of this finding: The authors' own conclusion rounds this to "a 2-fold increase", while the adjusted figure two sentences earlier in the same abstract is a relative risk of 1.9 (95% CI 1.6 to 2.3). Treat 1.9, not 2, as the estimate. This is a study of prescription claims and not a trial: women prescribed mycophenolate differ from women prescribed azathioprine in how severe their disease is, so some of the difference may come from the illness rather than the drug. It should not be read as proof of cause, which is also why the drug carries a boxed warning rather than this study alone.

Among 111 pregnancies exposed to MPA, 55 resulted in pregnancy loss (49.5%). Among 471 pregnancies exposed to AZA, 113 had pregnancy loss (24.0%).

A recognisable pattern of birth defects follows mycophenolate exposure in pregnancy, centred on the external ear, lip, palate and eye. (Source 15)

• Expert review, not systematic, Low certainty.
• Size: Not applicable; expert summary of in vitro work, single clinical observations and a European teratogen information service study.
• Who: Infants exposed to mycophenolate mofetil in utero.
• How long: First-trimester exposure.
• Result: No rate is given. The described pattern is external ear anomalies from hypoplastic pinna to anotia, cleft lip with or without cleft palate, and iris or chorioretinal coloboma and anophthalmia or microphthalmia, with less frequent heart, limb, oesophageal, vertebral, diaphragmatic, kidney and nervous system anomalies.
• Funding: not stated.

The typical malformative pattern of MMF embryopathy includes external ear anomalies ranging from hypoplastic pinna (microtia) to complete absence of pinna (anotia); cleft lip, with or without cleft palate, and ocular anomalies as iris or chorioretinal coloboma and anophthalmia/microphthalmia.

Post-transplant lymphoproliferative disorder occurred in 0.4% to 1% of patients on mycophenolate mofetil in the controlled transplant trials. (Source 17)

• Official position, Certainty not rated.
• Size: Patients in the controlled kidney, heart and liver transplant trials.
• Who: Kidney, heart and liver transplant patients on CellCept 2 g or 3 g with other immunosuppressants.
• How long: Controlled clinical trials.
• Result: PTLD in 0.4% to 1%; the label attributes most cases to Epstein Barr Virus infection and says risk is greatest in those who are EBV seronegative, a group that includes many young children.
• Funding: not applicable.

Post-transplant lymphoproliferative disorder (PTLD) developed in 0.4% to 1% of patients receiving CELLCEPT (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients

Serious and sometimes fatal infections, including BK virus nephropathy and JC virus PML, are a recognised hazard of mycophenolate mofetil. (Source 18)

• Official position, Certainty not rated.
• Size: Not applicable; regulatory warning text drawn from trials and postmarketing reports.
• Who: Patients receiving immunosuppressants including CellCept.
• How long: Throughout treatment.
• Result: No rates are given in this section. Named serious viral infections are polyomavirus-associated nephropathy especially BK virus, JC virus-associated progressive multifocal leukoencephalopathy, cytomegalovirus, hepatitis B and C reactivation and COVID-19.
• Funding: not applicable.

Patients receiving immunosuppressants, including CELLCEPT, are at increased risk of developing bacterial, fungal, protozoal and new or reactivated viral infections, including opportunistic infections.

Severe neutropenia developed on the 3 g daily dose, most often between 31 and 180 days after transplant. (Source 14)

• Official position, Certainty not rated.
• Size: Not applicable; regulatory warning text.
• Who: Transplant patients receiving CellCept 3 g daily.
• How long: Most frequent from 31 to 180 days post-transplant.
• Result: Severe neutropenia is defined in the label as an absolute neutrophil count below 0.5 x 10(3)/microlitre. The label says dosing should be interrupted or the dose reduced if the count falls below 1.3 x 10(3)/microlitre, and says to consider monitoring with complete blood counts weekly for the first month, twice monthly for the second and third months, and monthly for the remainder of the first year.
• Funding: not applicable.

Neutropenia has been observed most frequently in the period from 31 to 180 days post-transplant in patients treated for prevention of kidney, heart and liver rejection.

Stopping maintenance immunosuppression after two to three years of lupus nephritis treatment was not shown to be non-inferior to continuing it. (Source 13)

• Randomized trial, Low certainty.
• Size: 96 patients randomised out of 200 planned (48 per group)
• Who: Patients on maintenance azathioprine or mycophenolate mofetil for 2-3 years plus hydroxychloroquine, for proliferative lupus nephritis.
• How long: 24 months after randomisation; recruitment 2011 to 2016.
• Result: Relapse of proliferative lupus nephritis in 5/40 (12.5%) continuing versus 12/44 (27.3%) discontinuing (difference 14.8%, 95% CI -1.9 to 31.5); non-inferiority not demonstrated. Severe SLE flares 5/40 versus 14/44 (p=0.035)
• Funding: investigator-initiated.

Limit of this finding: This trial was stopped after 96 of the 200 patients it planned to recruit, so it was underpowered. The relapse comparison rests on the 40 and 44 patients who could be analysed, not the 48 and 48 who were randomised, and the 14.8% difference carries a confidence interval from -1.9 to 31.5 that includes no difference at all. The honest reading is that the trial could not show stopping was as safe as continuing. It is not evidence that continuing prevents relapse.

Relapse of proliferative LN occurred in 5/40 (12.5%) patients with IST continuation and in 12/44 (27.3%) patients with IST discontinuation (difference 14.8% (95% CI -1.9 to 31.5)).

Magnesium or aluminium hydroxide antacids lower mycophenolic acid exposure. (Source 9)

• Blood level study, Low certainty.
• Size: 10 rheumatoid arthritis patients.
• Who: Rheumatoid arthritis patients taking an antacid four times a day alongside a single 2 g dose of mycophenolate mofetil.
• How long: Single dose, 24-hour sampling.
• Result: Mycophenolic acid Cmax 33% lower and AUC over 24 hours 17% lower than mycophenolate mofetil alone under fasting conditions.
• Funding: not stated.

The C max and AUC(0-24h) for MPA were 33% and 17% lower, respectively, than when MMF was administered alone under fasting conditions.

Proton pump inhibitors reduce mycophenolic acid exposure substantially. (Source 10)

• Blood level study, Low certainty.
• Size: Healthy volunteers given single doses and transplant patients given multiple doses.
• Who: Healthy volunteers and transplant patients on CellCept with lansoprazole or pantoprazole.
• How long: Single and multiple dosing.
• Result: Cmax reduced by approximately 30 to 70% and AUC by 25% to 35%, attributed to lower mycophenolic acid solubility at higher gastric pH.
• Funding: not stated.

An approximate reduction of 30 to 70% in the C max and 25% to 35% in the AUC of MPA has been observed, possibly due to a decrease in MPA solubility at an increased gastric pH.

One crossover pharmacokinetic study reported a large fall in mycophenolic acid exposure when iron tablets were taken at the same time. (Source 19)

• Blood level study, Very low certainty.
• Size: Healthy volunteers in a two-phase randomised crossover design; the abstract does not state the number.
• Who: Volunteers given 1.0 g of mycophenolate mofetil alone, then with 2 tablets of iron ion preparations.
• How long: Two phases separated by a 7-day washout.
• Result: The abstract reports area under the curve 32.9 +/- 14.7 versus 2.92 +/- 0.883 mcg x h/mL and maximum concentration 20.1 +/- 9.21 versus 1.30 +/- 0.367, both P < .001. Note that the printed ordering of the two figures does not match the sentence that precedes them, so the direction should be read from the authors' conclusion rather than the number order.
• Funding: not stated.

Limit of this finding: The numbers in this abstract are printed study 1 first and study 2 second, while the sentence introducing them says study 2 was lower than study 1. So "32.9 +/- 14.7 versus 2.92 +/- 0.883" means 32.9 without iron and 2.92 with it - the opposite of the order most readers will assume, and an easy way to invert the direction of the effect. The same sentence also gives the maximum concentration in the units of an area under the curve (microg x h/mL), which cannot be right for a peak concentration. Take the direction from the authors' conclusion, not from the number order, and note that the later crossover study recorded separately in this entry found no such interaction.

This finding shows that when mycophenolate mofetil and iron ion preparations were administered concomitantly, a remarkable decrease of mycophenolate mofetil absorption was observed.

What the evidence supports

Mycophenolate mofetil cut treatment failure and biopsy-proven rejection after cadaveric kidney transplant compared with azathioprine. (Source 3)

• Randomized trial, High certainty.
• Size: 503 patients (MMF 3 g n=164, MMF 2 g n=173, azathioprine n=166)
• Who: Patients receiving a first or second cadaveric renal graft, all on cyclosporine and oral corticosteroids.
• How long: 12 months of follow-up; primary endpoint at 6 months.
• Result: Treatment failure 50.% with azathioprine versus 34.8% with MMF 3 g (P=0.0045) and 38.2% with MMF 2 g (P=0.0287). Biopsy-proven rejection 35.5% with azathioprine versus 15.9% (3 g) and 19.7% (2 g). Graft survival in the MMF groups was marginally superior but not statistically significant.
• Funding: not stated in the abstract; the drug was a new product of the sponsor.

Treatment failure occurred in 50.% of patients in the AZA group by 6 months after transplantation, compared with 34.8% in the MMF 3g group (P=0.0045) and 38.2 % in the MMF 2g group (P=0.0287).

A second blinded trial in primary cadaveric kidney transplant recipients replicated the reduction in rejection or treatment failure. (Source 20)

• Randomized trial, High certainty.
• Size: 499 patients randomised; 495 received study drug.
• Who: Adults receiving a primary cadaveric renal allograft as their first transplant, on cyclosporine, corticosteroids and antithymocyte globulin induction.
• How long: First 6 months after transplantation.
• Result: Biopsy-proven rejection or treatment failure 47.6% with azathioprine versus 31.1% with MMF 2 g (P = 0.0015) and 31.3% with MMF 3 g (P = 0.0021). First biopsy-proven rejection alone 38.0% versus 19.8% and 17.5%.
• Funding: not stated.

Biopsy-proven acute rejection episodes or treatment failure occurred in 47.6% of patients in the azathioprine group compared with 31.1% (P = 0.0015) and 31.3% (P = 0.0021) of patients in the MMF 2 g and 3 g treatment groups, respectively.

Mycophenolate mofetil beat azathioprine for maintaining remission of lupus nephritis. (Source 6)

• Randomized trial, High certainty.
• Size: 227 patients (116 MMF, 111 azathioprine)
• Who: Patients with lupus nephritis who met response criteria during a 6-month induction trial.
• How long: 36 months, double-blind double-dummy.
• Result: Time to treatment failure hazard ratio 0.44 (95% CI 0.25 to 0.77; P = 0.003). Observed treatment failure 19 of 116 (16.4%) on MMF versus 36 of 111 (32.4%) on azathioprine.
• Funding: industry-funded (Vifor Pharma, formerly Aspreva)

Mycophenolate mofetil was superior to azathioprine with respect to the primary end point, time to treatment failure (hazard ratio, 0.44; 95% confidence interval, 0.25 to 0.77; P = 0.003)

What the evidence does not support

Mycophenolate mofetil failed to beat intravenous cyclophosphamide for inducing remission in lupus nephritis. (Source 5)

• Randomized trial, Moderate certainty.
• Size: 370 patients (185 per arm)
• Who: Patients with class III to V lupus nephritis, international multicentre.
• How long: 24-week induction phase.
• Result: Response in 104 of 185 (56.2%) on MMF versus 98 of 185 (53.0%) on intravenous cyclophosphamide; secondary endpoints similar; nine deaths on MMF and five on cyclophosphamide.
• Funding: industry-funded (Aspreva/Vifor sponsored the ALMS programme)

Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC.

Mycophenolate mofetil added nothing to prednisone as initial immunotherapy in myasthenia gravis. (Source 8)

• Randomized trial, Moderate certainty.
• Size: Eighty subjects (41 MMF, 39 placebo) at 13 centres.
• Who: Immunosuppression-naive adults with mild to moderate generalised, acetylcholine receptor positive myasthenia gravis.
• How long: 12 weeks double-blind, then up to 24 weeks open-label.
• Result: Mean change in quantitative myasthenia gravis score -4.4 (SD 5.1) with MMF versus -3.6 (SD 5.0) with placebo (p = 0.71). Prednisone dose fell by a similar amount in both groups.
• Funding: not stated.

The mean change in QMG score was similar in the treated (-4.4 +/- 5.1) and placebo (-3.6 +/- 5.0) groups (p = 0.71).

A later crossover trial found no interaction between iron supplements and mycophenolate mofetil absorption. (Source 11)

• Blood level study, Low certainty.
• Size: 16 healthy males.
• Who: Fasting healthy male volunteers, open-label single-centre randomised crossover.
• How long: Two treatment periods, 24-hour sampling.
• Result: Mycophenolic acid AUC over 24 hours was 42.5 +/- 10.5 with mycophenolate mofetil alone and 44.7 +/- 12.4 microg per mL per hour with iron; relative bioavailability similar, 90% confidence interval 0.92, 1.19.
• Funding: not stated.

There was no interaction between mycophenolate mofetil and iron supplements administered concomitantly to healthy fasting subjects.

Where the evidence is mixed

A Cochrane review rates mycophenolate mofetil versus cyclophosphamide for lupus nephritis induction as low certainty, with a range that includes no difference. (Source 21)

• Systematic review, Low certainty.
• Size: 74 studies involving 5175 participants overall; Sixty-seven studies (4791 participants) for induction.
• Who: Adults and children with biopsy-proven class III, IV, V+III and V+VI lupus nephritis.
• How long: Median 12 months for induction studies (range 2.5 to 48 months)
• Result: Complete remission RR 1.17 (95% CI 0.97 to 1.42), low certainty. Alopecia RR 0.29 (95% CI 0.19 to 0.46), 170 fewer per 1000 people, moderate certainty. Diarrhoea RR 2.42 (95% CI 1.64 to 3.58), 142 more per 1000 people, moderate certainty. Major infection RR 1.02 (95% CI 0.67 to 1.54), low certainty.
• Funding: Cochrane review; funding not stated in the abstract.

Compared with intravenous (IV) cyclophosphamide, MMF may have increased complete disease remission (RR 1.17, 95% CI 0.97 to 1.42; low certainty evidence), although the range of effects includes the possibility of little or no difference.

Mycophenolate mofetil was negative for its primary endpoint against cyclophosphamide in scleroderma lung disease, but was better tolerated. (Source 7)

• Randomized trial, Moderate certainty.
• Size: 142 patients randomised (69 MMF, 73 cyclophosphamide); 126 in the primary analysis.
• Who: Patients at 14 US centres with scleroderma-related interstitial lung disease meeting dyspnoea, pulmonary function and HRCT criteria.
• How long: 24 months of MMF or 12 months of cyclophosphamide then 12 months of placebo.
• Result: Adjusted percent predicted FVC improved by 2·19 (95% CI 0·53-3·84) with MMF and 2·88 (1·19-4·58) with cyclophosphamide; the courses did not differ (p=0·24). 16 (11%) patients died, five (7%) on MMF and 11 (15%) on cyclophosphamide. Leucopenia in 4 versus 30 patients and thrombocytopenia in 0 versus 4.
• Funding: National Heart, Lung and Blood Institute, with drug supplied by Hoffmann-La Roche and Genentech.

The course of the % FVC did not differ significantly between the two treatment groups based on the prespecified primary analysis using a joint model (p=0·24), indicating that the trial was negative for the primary endpoint.

Where the research disagrees

Whether iron supplements block mycophenolate mofetil absorption

• Morii and colleagues (2000), randomised crossover pharmacokinetic study in volunteers: This finding shows that when mycophenolate mofetil and iron ion preparations were administered concomitantly, a remarkable decrease of mycophenolate mofetil absorption was observed. (Source 19)
• A later British Journal of Clinical Pharmacology crossover trial (2006), open-label randomised crossover trial in 16 healthy males: There was no interaction between mycophenolate mofetil and iron supplements administered concomitantly to healthy fasting subjects. (Source 11)

Whether mycophenolate mofetil is better than intravenous cyclophosphamide for inducing remission in lupus nephritis

• ALMS induction investigators (2009), international open-label randomised trial, 370 patients: the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis (Source 5)
• Cochrane review authors (2018), systematic review of 74 studies with GRADE certainty ratings: MMF may have increased complete disease remission (RR 1.17, 95% CI 0.97 to 1.42; low certainty evidence), although the range of effects includes the possibility of little or no difference (Source 21)

How much

• Reference intake: The dose is set by the prescriber. The US CellCept label (effective 2026-08-05) gives adult kidney transplant patients 1 g orally or intravenously over no less than 2 hours, twice daily, for a total daily dose of 2 g. Children from 3 months of age are dosed by body surface area at 600 mg/m2 twice daily. (Source 22)
• Upper limit: For the kidney transplant indication the label's ceiling is a maximum total daily dose of 2 g, or 10 mL of the oral suspension, in children dosed by body surface area; children with a body surface area of 1.5 m2 or more take capsules or tablets 1 g twice daily, again 2 g total daily. There is no consumer upper limit for this drug: it is prescription-only and the dose depends on the transplanted organ. (Source 22)
• Studied: The Tricontinental kidney transplant trial gave MMF 3 g (n=164) or MMF 2 g (n=173) daily against azathioprine 100-150 mg daily. (Source 3)
• Studied: The US kidney transplant trial gave MMF 1.0 g twice daily or MMF 1.5 g twice daily against azathioprine 1-2 mg/kg/day. (Source 20)
• Studied: The ALMS induction trial used open-label MMF at a target dosage of 3 g/d against monthly intravenous cyclophosphamide pulses. (Source 5)
• Studied: The ALMS maintenance trial used oral mycophenolate mofetil 2 g per day against azathioprine 2 mg per kilogram per day. (Source 6)
• Studied: Scleroderma Lung Study II used mycophenolate mofetil at a target dose 1500 mg twice daily for 24 months. (Source 7)
• Studied: The myasthenia gravis trial used 2.5 g/day MMF plus 20 mg/day prednisone. (Source 8)

A common belief, and what the research shows

The belief: Mycophenolate is the mild, steroid-sparing option, so it is a safe choice for a woman who might become pregnant.

What the research shows: It carries a boxed warning that begins with pregnancy: "Use during pregnancy is associated with increased risks of first trimester pregnancy loss and congenital malformations." A claims-based cohort found pregnancy loss in 49.5% of mycophenolate-exposed pregnancies versus 24.0% of azathioprine-exposed ones, and the teratology literature describes a specific pattern of ear, lip, palate and eye malformations.

Questions and answers

What is it?

A prescription immunosuppressant tablet, capsule, suspension or infusion. It is an antimetabolite: it interferes with the building blocks immune cells need to divide. It is licensed to stop the body rejecting a transplanted kidney, heart or liver, always alongside other immunosuppressants. (Source 23)

What does it do in the body?

Once absorbed it becomes mycophenolic acid, which blocks an enzyme called inosine monophosphate dehydrogenase. Lymphocytes rely on that enzyme to make new DNA building blocks, so they stop multiplying. The effect holds the immune response back rather than killing cells outright, and the label notes it is reversible. (Source 1)

Is it good or bad for you?

Both, and the trade-off is the whole point of the drug. In kidney transplantation it clearly reduces rejection: treatment failure fell from 50.% on azathioprine to 34.8% on the 3 g dose. The price is paid in infection and cancer risk, and the harms rise with dose: gastrointestinal toxicity, tissue-invasive CMV and malignancies were all more common in the 3 g group. (Source 3)

How do you get more of it?

This question does not apply in the way it does to a nutrient. There is no food or behaviour that raises mycophenolate; the amount is whatever a prescriber writes. For an adult kidney transplant recipient the label's recommended dose is 1 g twice daily, a total of 2 g a day. (Source 22)

If it is harmful, what reduces it?

Dialysis does not clear the active metabolite to any useful degree. What does remove it is a bile acid sequestrant such as cholestyramine, which binds the recirculating metabolite in the gut and increases excretion. That is also how the drug's exposure gets accidentally cut when someone is on a sequestrant for another reason. (Source 12)

Why might someone be low in it or missing it?

Reframed for a drug: blood levels can run lower than intended because of what else is being taken. Proton pump inhibitors cut exposure by a quarter to a third, magnesium or aluminium antacids by a similar order, and bile acid sequestrants interrupt the gut recirculation the drug depends on. The label advises checking plasma levels when concomitant medicines change. (Source 24)

Which whole foods contain it or feed it?

None. Mycophenolate mofetil is a manufactured medicine, not a nutrient, so no whole food contains it or feeds it. The relevant food question runs the other way: antacids and acid-suppressing drugs taken around a dose reduce how much reaches the blood. (Source 4)

What happens if you do not have it?

For a transplant recipient, less immunosuppression means more rejection: in the blinded kidney transplant trial, 35.5% of patients on azathioprine had biopsy-proven rejection against 15.9% on the 3 g mycophenolate dose. (Source 3)

How can you test for it?

There is a blood test: mycophenolic acid plasma concentration. It is not used routinely in the way tacrolimus levels are, but the label suggests measuring it before and after any change to the immunosuppressive regimen or to concomitant medicines, because so many drugs shift exposure. Blood counts are also monitored, for neutropenia. (Source 24)

References

1. DailyMed (US National Library of Medicine) / Genentech, Inc.. CELLCEPT (mycophenolate mofetil) tablets, capsules, oral suspension and CELLCEPT Intravenous - Full Prescribing Information (section quoted below) - section: moa [label effective date 2026-08-05]. 2026. Read the source
2. DailyMed (US National Library of Medicine) / Genentech, Inc.. CELLCEPT (mycophenolate mofetil) tablets, capsules, oral suspension and CELLCEPT Intravenous - Full Prescribing Information (section quoted below) - section: boxed [label effective date 2026-08-05]. 2026. Read the source
3. Transplantation. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group.. 1996. PMID 8623181. Read the source
4. DailyMed (US National Library of Medicine) / Genentech, Inc.. CELLCEPT (mycophenolate mofetil) tablets, capsules, oral suspension and CELLCEPT Intravenous - Full Prescribing Information (section quoted below) - section: 1 INDICATIONS AND USAGE [label effective date 2026-08-05]. 2026. Read the source
5. Journal of the American Society of Nephrology : JASN. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis.. 2009. PMID 19369404, DOI 10.1681/asn.2008101028. Read the source
6. The New England journal of medicine. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis.. 2011. PMID 22087680, DOI 10.1056/nejmoa1014460. Read the source
7. The Lancet. Respiratory medicine. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial.. 2016. PMID 27469583, DOI 10.1016/s2213-2600(16)30152-7. Read the source
8. Neurology. A trial of mycophenolate mofetil with prednisone as initial immunotherapy in myasthenia gravis.. 2008. PMID 18434639, DOI 10.1212/01.wnl.0000312373.67493.7f. Read the source
9. DailyMed (US National Library of Medicine) / Genentech, Inc.. CELLCEPT (mycophenolate mofetil) tablets, capsules, oral suspension and CELLCEPT Intravenous - Full Prescribing Information (section quoted below) - section: antacid [label effective date 2026-08-05]. 2026. Read the source
10. DailyMed (US National Library of Medicine) / Genentech, Inc.. CELLCEPT (mycophenolate mofetil) tablets, capsules, oral suspension and CELLCEPT Intravenous - Full Prescribing Information (section quoted below) - section: ppi [label effective date 2026-08-05]. 2026. Read the source
11. British journal of clinical pharmacology. Absence of an interaction between iron and mycophenolate mofetil absorption.. 2006. PMID 16995871, DOI 10.1111/j.1365-2125.2005.02541.x. Read the source
12. DailyMed (US National Library of Medicine) / Genentech, Inc.. CELLCEPT (mycophenolate mofetil) tablets, capsules, oral suspension and CELLCEPT Intravenous - Full Prescribing Information (section quoted below) - section: overdose [label effective date 2026-08-05]. 2026. Read the source
13. Annals of the rheumatic diseases. Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial.. 2022. PMID 35725295, DOI 10.1136/annrheumdis-2022-222435. Read the source
14. DailyMed (US National Library of Medicine) / Genentech, Inc.. CELLCEPT (mycophenolate mofetil) tablets, capsules, oral suspension and CELLCEPT Intravenous - Full Prescribing Information (section quoted below) - section: 5.4 Blood Dyscrasias: Neutropenia and Pure Red Cell Aplasia (PRCA) [label effective date 2026-08-05]. 2026. Read the source
15. European journal of medical genetics. Mycophenolate mofetil embryopathy: A newly recognized teratogenic syndrome.. 2017. PMID 27639443, DOI 10.1016/j.ejmg.2016.09.014. Read the source
16. Pharmacoepidemiology and drug safety. Risk of pregnancy loss in patients exposed to mycophenolate compared to azathioprine: A retrospective cohort study.. 2020. PMID 32347619, DOI 10.1002/pds.5017. Read the source
17. DailyMed (US National Library of Medicine) / Genentech, Inc.. CELLCEPT (mycophenolate mofetil) tablets, capsules, oral suspension and CELLCEPT Intravenous - Full Prescribing Information (section quoted below) - section: malig [label effective date 2026-08-05]. 2026. Read the source
18. DailyMed (US National Library of Medicine) / Genentech, Inc.. CELLCEPT (mycophenolate mofetil) tablets, capsules, oral suspension and CELLCEPT Intravenous - Full Prescribing Information (section quoted below) - section: 5.3 Serious Infections [label effective date 2026-08-05]. 2026. Read the source
19. Clinical pharmacology and therapeutics. Impairment of mycophenolate mofetil absorption by iron ion.. 2000. PMID 11180021, DOI 10.1067/mcp.2000.111480. Read the source
20. Transplantation. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. U.S. Renal Transplant Mycophenolate Mofetil Study Group.. 1995. PMID 7645033, DOI 10.1097/00007890-199508000-00003. Read the source
21. The Cochrane database of systematic reviews. Immunosuppressive treatment for proliferative lupus nephritis. — abstract, Main results. 2018. PMID 29957821, DOI 10.1002/14651858.cd002922.pub4. Read the source
22. DailyMed (US National Library of Medicine) / Genentech, Inc.. CELLCEPT (mycophenolate mofetil) tablets, capsules, oral suspension and CELLCEPT Intravenous - Full Prescribing Information (section quoted below) - section: dose [label effective date 2026-08-05]. 2026. Read the source
23. DailyMed (US National Library of Medicine) / Genentech, Inc.. CELLCEPT (mycophenolate mofetil) tablets, capsules, oral suspension and CELLCEPT Intravenous - Highlights of Prescribing Information (section quoted below) - section: INDICATIONS AND USAGE [label effective date 2026-08-05]. 2026. Read the source
24. DailyMed (US National Library of Medicine) / Genentech, Inc.. CELLCEPT (mycophenolate mofetil) tablets, capsules, oral suspension and CELLCEPT Intravenous - Full Prescribing Information (section quoted below) - section: tdm [label effective date 2026-08-05]. 2026. Read the source