Mycophenolate Mofetil

Evidence Level: L2

Predicted Indications: 10

Mycophenolate Mofetil

Pharmacist Assessment Report

Mycophenolate Mofetil: From Transplant Immunosuppression to HIV Infectious Disease

One-Sentence Summary

Mycophenolate mofetil (MMF) is an immunosuppressant marketed in Canada under many licences. It is predicted by the TxGNN model to be effective for HIV infectious disease, with 4 registered clinical trials and 20 publications in the data compiled for this report. Most of these trials are small, withdrawn, or only tangentially related, so the evidence is limited.

Quick Overview

Item	Content
Original Indication	Not stated in the data compiled for this report (no approved indication text was available for any Canadian licence)
Predicted New Indication	HIV infectious disease
TxGNN Prediction Score	0.9986
Evidence Level	L2 (as assigned in the compiled data; note that the only Phase 2 HIV trial of MMF was withdrawn, so the supporting evidence is weaker than this label suggests)
Canada Market Status	Marketed (marketed DINs: 15 of 15)
Number of DINs	15 (marketed: 15)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data for MMF were not available in the compiled data. The following rationale comes from the repurposing analysis. Its active form, mycophenolic acid, inhibits inosine monophosphate dehydrogenase (IMPDH), which depletes intracellular guanosine nucleotide pools. This has two effects relevant to HIV:

It limits T-cell proliferation, and HIV disease progression is linked to chronic immune activation.
It can lower HIV replication and potentiate nucleoside analogues such as abacavir and didanosine by shifting dNTP pool ratios.

Published work supports this link. A small series reported that adding MMF to an abacavir-containing regimen was associated with depletion of intracellular dGTP and a fall in plasma HIV-1 RNA. A randomised study (PMID 15353978) examined HAART with or without MMF in treatment-naive patients.

Clinical data are limited to small trials with mixed virologic benefit. Immunosuppression in people with HIV also carries a safety risk. The prediction is therefore mechanistically plausible but not clinically established.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00021489	Phase 2	Withdrawn	0	Safety and antiretroviral activity of MMF added to abacavir in treatment-experienced HIV patients. Directly relevant, but no participants were enrolled, so there are no data.
NCT00038272	Phase 2	Completed	56	Placebo-controlled study of DAPD versus DAPD plus MMF added to anti-HIV regimens. The study evaluates a different agent, so it is only partial evidence for MMF.
NCT01288131	Phase 3	Terminated	8	Cyclosporine plus MMF versus cyclophosphamide plus prednisolone for anti-erythropoietin-associated pure red cell aplasia. The HIV link is tangential.
NCT00112593	Not applicable	Completed	5	Stem cell transplantation in HIV-positive patients. MMF is used for post-transplant immunosuppression, not as anti-HIV therapy.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
15353978	2004	RCT	AIDS	Studied the effect of MMF on HIV-1 RNA decay and the latent cellular reservoir in treatment-naive patients starting antiretroviral therapy.
15871638	2005	Clinical PK/PD study	Clin Pharmacokinet	Pharmacokinetics and pharmacodynamics of low-dose MMF in HIV patients on abacavir, efavirenz and nelfinavir.
12352149	2002	Case series	J Acquir Immune Defic Syndr	Adding MMF to abacavir-containing regimens in 5 patients was associated with dGTP depletion and lower plasma HIV-1 RNA.
16379601	2005	Short communication	AIDS Res Hum Retroviruses	MMF plus HAART showed no detrimental immunological effects on T-cell reconstitution in treatment-naive patients.
17017956	2006	Review	Curr Top Med Chem	Immunosuppressive drugs in HIV disease, targeting immune activation alongside HAART.
16515490	2006	Review	Curr Pharm Des	Virostatics as a way to target HIV infection.
20840478	2010	Retrospective study	Am J Transplant	Kidney transplantation in 27 HIV-infected patients on regimens that included MMF.
23622672	2013	Cohort/Review	Transplant Proc	Renal transplantation experience in HIV-infected patients in Spain, with literature review.
39396546	2025	Case report	Trop Doct	IgA vasculitis in an HIV patient with a complete renal response to steroid plus MMF.
41118390	2025	Preclinical	J Clin Invest	Selective targeting of HIV-infected clones with antiproliferative drugs.

Canada Market Information

Health Canada lists 15 valid single-ingredient licences. Dosage form, manufacturer and approved indication text were not available for any of them. The main authorizations are:

DIN	Product Name	Dosage Form	Approved Indication
02192748	CELLCEPT	Not available	Not available
02237484	CELLCEPT	Not available	Not available
02242145	CELLCEPT	Not available	Not available
02240347	CELLCEPT I.V.	Not available	Not available
02444836	MYCOPHENOLATE MOFETIL FOR INJECTION, USP	Not available	Not available

The remaining 10 licences cover generic products (Sandoz, Teva, ACH, JAMP, Mar and others).

Cytotoxicity

MMF is not a conventional anticancer drug, but it is an antiproliferative immunosuppressant, so the relevant haematological risks are summarised below.

Item	Content
Cytotoxicity Classification	Antimetabolite immunosuppressant (IMPDH inhibitor), not a conventional cytotoxic chemotherapy
Myelosuppression Risk	Please refer to the package insert warnings and precautions. The knowledge graph lists neutropenia, agranulocytosis and aplastic anaemia among contraindication-related conditions.
Emetogenicity Classification	Please refer to the package insert warnings and precautions
Monitoring Items	Complete blood count with differential, liver and renal function
Handling Protection	Please refer to the package insert warnings and precautions

Safety Considerations

Contraindication-related conditions from the knowledge graph (these come from drug-disease relationship data, not from label text):

Haematological: neutropenia, agranulocytosis, aplastic anaemia (including inherited forms), Fanconi anaemia, Diamond-Blackfan anaemia
Infections: cytomegalovirus infection, herpes simplex, herpes zoster, progressive multifocal leukoencephalopathy
Malignancy: cancer, lymphoma, primary CNS lymphoma, skin cancer
Organ conditions: liver disease, gallbladder disease, active peptic ulcer disease

Drug interactions: 92 interactions were identified. Examples include:

Major: activated charcoal
Moderate: proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, rabeprazole, dexlansoprazole), antibiotics (amoxicillin, clarithromycin, doxycycline, minocycline, tetracycline, vancomycin, kanamycin, paromomycin), and antacids (aluminium hydroxide, calcium carbonate, magnesium oxide)
Minor: zinc sulfate, zinc acetate, iron

Immunosuppression in HIV-infected patients carries an additional infection risk. Please refer to the package insert for the official warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: The mechanism is plausible and there is early clinical work, but the only directly relevant Phase 2 HIV trial was withdrawn with no participants. The remaining evidence is small studies with mixed virologic benefit, and immunosuppression adds risk in HIV. The data also lack Health Canada label warnings and the original indication, so safety screening cannot proceed.

To proceed, the following is needed:

Health Canada package insert warnings, contraindications and approved indication text
Detailed mechanism-of-action data
A properly powered randomised trial of MMF in HIV, or a clear justification for such a study
A safety plan for infection risk and myelosuppression in HIV-infected patients

Other predictions: Multiple sclerosis (score 0.9954, L2) has the most developed supporting evidence after HIV, including small Phase 2 MMF trials and a Cochrane review, but efficacy remains uncertain. Hemosiderosis has only indirect review-level support (L4). The other predictions (a rare neurodevelopmental disorder, Paget disease of bone, simian and feline immunodeficiency, Heiner syndrome, African iron overload, neonatal hemochromatosis) rest on model scores alone (L5) and should be held.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.