FDA Label for Mycophenolate Mofetil

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)].

1 Indications And Usage

Mycophenolate (MMF) is indicated for the prophylaxis of organ rejection, in recipients of allogeneic kidney [see Clinical Studies (14.1)], heart [see Clinical Studies (14.2)] or liver transplants [see Clinical Studies (14.3)], in combination with other immunosuppressants.

2.1 Important Administration Instructions

Mycophenolate mofetil should not be used without the supervision of a physician with experience in immunosuppressive therapy.

2.3 Dosing For Heart Transplant Patients: Adults

The recommended dose of mycophenolate mofetil for adult heart transplant patients is 1.5 g orally or intravenously infused over no less than 2 hours administered twice daily (daily dose of 3 g).

2.4 Dosing For Liver Transplant Patients: Adults

The recommended dose of mycophenolate mofetil for adult liver transplant patients is 1.5 g administered orally twice daily (daily dose of 3 g) or 1 g infused intravenously over no less than 2 hours, twice daily (daily dose of 2 g).

3 Dosage Forms And Strengths

Mycophenolate Mofetil for Oral Suspension, USP is available in the following dosage form and strength:

For oral suspension: 35 g mycophenolate mofetil white or almost white powder, 200 mg/mL upon reconstitution.

4 Contraindications

Allergic reactions to mycophenolate mofetil have been observed; therefore, mycophenolate mofetil is contraindicated in patients with a hypersensitivity to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product.

5.1 Embryofetal Toxicity

Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney and nervous system. Females of reproductive potential must be made aware of these risks and must be counseled regarding pregnancy prevention and planning. Avoid use of MMF during pregnancy if safer treatment options are available [see Use in Specific Populations (8.1, 8.3)].

5.2 Lymphoma And Other Malignancies

Patients receiving immunosuppressants, including mycophenolate mofetil, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Adverse Reactions (6.1)]. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. For patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen with a high protection factor.

Post-transplant lymphoproliferative disorder (PTLD) developed in 0.4% to 1% of patients receiving mycophenolate mofetil (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients [see Adverse Reactions (6.1)]. The majority of PTLD cases appear to be related to Epstein Barr Virus (EBV) infection. The risk of PTLD appears greatest in those individuals who are EBV seronegative, a population which includes many young children. In pediatric patients, no other malignancies besides PTLD were observed in clinical trials [see Adverse Reactions (6.1)].

5.3 Serious Infections

Patients receiving immunosuppressants, including mycophenolate mofetil, are at increased risk of developing bacterial, fungal, protozoal and new or reactivated viral infections, including opportunistic infections. The risk increases with the total immunosuppressive load. These infections may lead to serious outcomes, including hospitalizations and death [see Adverse Reactions (6.1), (6.2)].

Serious viral infections reported include:

• Polyomavirus-associated nephropathy (PVAN), especially due to BK virus infection
• JC virus-associated progressive multifocal leukoencephalopathy (PML), and
• Cytomegalovirus (CMV) infections: CMV seronegative transplant patients who receive an organ from a CMV seropositive donor are at highest risk of CMV viremia and CMV disease.
• Viral reactivation in patients infected with Hepatitis B and C

Consider reducing immunosuppression in patients who develop new infections or reactivate viral infections, weighing the risk that reduced immunosuppression represents to the functioning allograft.

PVAN, especially due to BK virus infection, is associated with serious outcomes, including deteriorating renal function and renal graft loss [see Adverse Reactions (6.2)]. Patient monitoring may help detect patients at risk for PVAN.

PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia [see Adverse Reactions (6.2)]. In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms.

The risk of CMV viremia and CMV disease is highest among transplant recipients seronegative for CMV at time of transplant who receive a graft from a CMV seropositive donor. Therapeutic approaches to limiting CMV disease exist and should be routinely provided. Patient monitoring may help detect patients at risk for CMV disease.

Viral reactivation has been reported in patients infected with HBV or HCV. Monitoring infected patients for clinical and laboratory signs of active HBV or HCV infection is recommended.

5.4 Blood Dyscrasias: Neutropenia And Pure Red Cell Aplasia (Prca)

Severe neutropenia [absolute neutrophil count (ANC) <0.5 × 10³/μL] developed in transplant patients receiving mycophenolate mofetil 3 g daily [see Adverse Reactions (6.1)]. Patients receiving mycophenolate mofetil should be monitored for neutropenia. 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. The development of neutropenia may be related to mycophenolate mofetil itself, concomitant medications, viral infections, or a combination of these causes. If neutropenia develops (ANC <1.3 × 10³/μL), dosing with mycophenolate mofetil should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Dosage and Administration (2.5)].

Patients receiving mycophenolate mofetil should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression.

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.

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate mofetil in combination with other immunosuppressive agents. In some cases, PRCA was found to be reversible with dose reduction or cessation of mycophenolate mofetil therapy. In transplant patients, however, reduced immunosuppression may place the graft at risk.

5.5 Gastrointestinal Complications

Gastrointestinal bleeding requiring hospitalization, ulceration and perforations were observed in clinical trials. Physicians should be aware of these serious adverse effects particularly when administering mycophenolate mofetil to patients with a gastrointestinal disease.

5.6 Patients With Hypoxanthine-Guanine Phosphoribosyl-Transferase Deficiency (Hgprt)

Mycophenolate mofetil is an inosine monophosphate dehydrogenase (IMPDH) inhibitor; therefore it should be avoided in patients with hereditary deficiencies of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndromes because it may cause an exacerbation of disease symptoms characterized by the overproduction and accumulation of uric acid leading to symptoms associated with gout such as acute arthritis, tophi, nephrolithiasis or urolithiasis and renal disease including renal failure.

5.7 Immunizations

During treatment with mycophenolate mofetil, the use of live attenuated vaccines should be avoided (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) and patients should be advised that vaccinations may be less effective. Advise patients to discuss with the physician before seeking any immunizations.

5.9 Risks In Patients With Phenylketonuria

Phenylalanine can be harmful to patients with phenylketonuria (PKU). Mycophenolate mofetil for oral suspension contains aspartame, a source of phenylalanine (0.56 mg phenylalanine/mL suspension). Before prescribing mycophenolate mofetil for oral suspension to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including mycophenolate mofetil.

5.10 Blood Donation

Patients should not donate blood during therapy and for at least 6 weeks following discontinuation of mycophenolate mofetil because their blood or blood products might be administered to a female of reproductive potential or a pregnant woman.

5.11 Semen Donation

Based on animal data, men should not donate semen during therapy and for 90 days following discontinuation of mycophenolate mofetil [see Use In Specific Populations (8.3)].

5.12 Effect Of Concomitant Medications On Mycophenolic Acid Concentrations

A variety of drugs have potential to alter systemic MPA exposure when co-administered with mycophenolate mofetil. Therefore, determination of MPA concentrations in plasma before and after making any changes to immunosuppressive therapy, or when adding or discontinuing concomitant medications, may be appropriate to ensure MPA concentrations remain stable.

5.13 Potential Impairment Of Ability To Drive Or Operate Machinery

Mycophenolate mofetil may impact the ability to drive and use machines. Patients should avoid driving or using machines if they experience somnolence, confusion, dizziness, tremor, or hypotension during treatment with mycophenolate mofetil [see Adverse Reactions (6.1)].

6 Adverse Reactions

The following adverse reactions are discussed in greater detail in other sections of the label:

• Embryofetal Toxicity [see Warnings and Precautions (5.1)]
• Lymphomas and Other Malignancies [see Warnings and Precautions (5.2)]
• Serious Infections [see Warnings and Precautions (5.3)]
• Blood Dyscrasias: Neutropenia, Pure Red Cell Aplasia [see Warnings and Precautions (5.4)]
• Gastrointestinal Complications [see Warnings and Precautions (5.5)]

6.1 Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

An estimated total of 1557 patients received mycophenolate mofetil during pivotal clinical trials in the prevention of acute organ rejection. Of these, 991 were included in the three renal studies, 277 were included in one hepatic study, and 289 were included in one cardiac study. Patients in all study arms also received cyclosporine and corticosteroids.

The data described below primarily derive from five randomized, active-controlled double-blind 12-month trials of mycophenolate mofetil in de novo kidney (3) heart (1) and liver (1) transplant patients [see Clinical Studies (14.1, 14.2 and 14.3)].

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of mycophenolate mofetil. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

• Embryo-Fetal Toxicity: Congenital malformations and spontaneous abortions, mainly in the first trimester, have been reported following exposure to mycophenolate mofetil (MMF) in combination with other immunosuppressants during pregnancy [see Warnings and Precautions (5.1), and Use in Specific Populations (8.1), (8.3)]. Congenital malformations include:
  • Facial malformations: cleft lip, cleft palate, micrognathia, hypertelorism of the orbits
  • Abnormalities of the ear and eye: abnormally formed or absent external/middle ear, coloboma, microphthalmos
  • Malformations of the fingers: polydactyly, syndactyly, brachydactyly
  • Cardiac abnormalities: atrial and ventricular septal defects
  • Esophageal malformations: esophageal atresia
  • Nervous system malformations: such as spina bifida.
  • Cardiovascular: Venous thrombosis has been reported in patients treated with mycophenolate mofetil administered intravenously.
  • Digestive: Colitis, pancreatitis
  • Hematologic and Lymphatic: Bone marrow failure, cases of pure red cell aplasia (PRCA) and hypogammaglobulinemia have been reported in patients treated with mycophenolate mofetil in combination with other immunosuppressive agents [see Warnings and Precautions (5.4)].
  • Immune: Hypersensitivity, hypogammaglobinemia.
  • Infections: Meningitis, infectious endocarditis, tuberculosis, atypical mycobacterial infection, progressive multifocal leukoencephalopathy, BK virus infection, viral reactivation of hepatitis B and hepatitis C, protozoal infections [see Warnings and Precautions (5.3)].
  • Respiratory: Bronchiectasis, interstitial lung disease, fatal pulmonary fibrosis, have been reported rarely and should be considered in the differential diagnosis of pulmonary symptoms ranging from dyspnea to respiratory failure in post-transplant patients receiving mycophenolate mofetil.
  • Vascular: Lymphocele
  
  

7.1 Effect Of Other Drugs On Mycophenolate Mofetil

7.2 Effect Of Mycophenolate Mofetil On Other Drugs

8.3 Females And Males Of Reproductive Potential

Females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning.

8.4 Pediatric Use

Safety and effectiveness of mycophenolate mofetil have been established in pediatric patients 3 months and older for the prophylaxis of kidney rejection after allogeneic kidney transplant. Use of mycophenolate mofetil in this population is supported by evidence from adequate and well-controlled studies mycophenolate mofetil in adults with additional data from one open-label, pharmacokinetic and safety study of mycophenolate mofetil in pediatric patients after receiving allogeneic kidney transplant [see Dosage and Administration (2.2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.1)].

Safety and effectiveness in pediatric patients receiving allogeneic heart or liver transplants have not been established.

8.5 Geriatric Use

Clinical studies of mycophenolate mofetil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should take into consideration the presence of decreased hepatic, renal or cardiac function and of concomitant drug therapies [see Adverse Reactions (6.1), Drug Interactions (7)].

10 Overdosage

Possible signs and symptoms of acute overdose include hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, and dyspepsia.

The experience with overdose of mycophenolate mofetil in humans is limited. The reported effects associated with overdose fall within the known safety profile of the drug. The highest dose administered to kidney transplant patients in clinical trials has been 4 g/day. In limited experience with heart and liver transplant patients in clinical trials, the highest doses used were 4 g/day or 5 g/day. At doses of 4 g/day or 5 g/day, there appears to be a higher rate, compared to the use of 3 g/day or less, of gastrointestinal intolerance (nausea, vomiting, and/or diarrhea), and occasional hematologic abnormalities, particularly neutropenia [see Warnings and Precautions (5.4)].

11 Description

Mycophenolate mofetil is an antimetabolite immunosuppressant. It is the 2- morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor.

The chemical name for mycophenolate mofetil (MMF) is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate. It has an empirical formula of C₂₃H₃₁NO₇, a molecular weight of 433.49 g/mole, and the following structural formula:

Structure - mycophenolate mofetil for oral suspension usp 1

MMF is a white to off-white crystalline powder. It is slightly soluble in water (43 μg/mL at pH 7.4); the solubility increases in acidic medium (4.27 mg/mL at pH 3.6). It is freely soluble in acetone, soluble in methanol, and sparingly soluble in ethanol. The apparent partition coefficient in 1-octanol/water (pH 7.4) buffer solution is 238. The pKa values for MMF are 5.6 for the morpholino group and 8.5 for the phenolic group.

Mycophenolate mofetil is available for oral administration as a powder for oral suspension which, when reconstituted, contains 200 mg/mL of MMF.

Inactive ingredients in Mycophenolate Mofetil for Oral Suspension, USP include aspartame, citric acid anhydrous, colloidal silicon dioxide, methylparaben, sodium citrate dihydrate, sorbitol, de-oiled soy lecithin, tutti-frutti flavor, and xanthan gum.

12.1 Mechanism Of Action

Mycophenolate mofetil (MMF) is absorbed following oral administration and hydrolyzed to mycophenolic acid (MPA), the active metabolite. MPA is a selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Because T- and B-lymphocytes are critically dependent for their proliferation on de novo synthesis of purines, whereas other cell types can utilize salvage pathways, MPA has potent cytostatic effects on lymphocytes. MPA inhibits proliferative responses of T- and B-lymphocytes to both mitogenic and allospecific stimulation. Addition of guanosine or deoxyguanosine reverses the cytostatic effects of MPA on lymphocytes. MPA also suppresses antibody formation by B-lymphocytes. MPA prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection. MMF did not inhibit early events in the activation of human peripheral blood mononuclear cells, such as the production of interleukin-1 (IL-1) and interleukin-2 (IL-2), but did block the coupling of these events to DNA synthesis and proliferation.

12.2 Pharmacodynamics

There is a lack of information regarding the pharmacodynamic effects of MMF.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

In a 104-week oral carcinogenicity study in mice, MMF in daily doses up to 180 mg/kg was not tumorigenic. The highest dose tested was 0.4 times the recommended clinical dose (2 g/day) in renal transplant patients and 0.3 times the recommended clinical dose (3 g/day) in cardiac transplant patients when corrected for differences in body surface area (BSA). In a 104-week oral carcinogenicity study in rats, MMF in daily doses up to 15 mg/kg was not tumorigenic. The highest dose was 0.07 times the recommended clinical dose in kidney transplant patients and 0.05 times the recommended clinical dose in heart transplant patients when corrected for BSA. While these animal doses were lower than those given to patients, they were maximal in those species and were considered adequate to evaluate the potential for human risk [see Warnings and Precautions (5.2)].

The genotoxic potential of MMF was determined in five assays. MMF was genotoxic in the mouse lymphoma/thymidine kinase assay and the in vivo mouse micronucleus assay. MMF was not genotoxic in the bacterial mutation assay, the yeast mitotic gene conversion assay or the Chinese hamster ovary cell chromosomal aberration assay.

MMF had no effect on fertility of male rats at oral doses up to 20 mg/kg/day. This dose represents 0.1 times the recommended clinical dose in renal transplant patients and 0.06 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. In a female fertility and reproduction study conducted in rats, oral doses of 4.5 mg/kg/day caused malformations (principally of the head and eyes) in the first generation offspring in the absence of maternal toxicity. This dose was 0.02 times the recommended clinical dose in renal transplant patients and 0.01 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. No effects on fertility or reproductive parameters were evident in the dams or in the subsequent generation.

14.2 Heart Transplantation

A double-blind, randomized, comparative, parallel-group, multicenter study in primary de novo heart transplant recipients was performed at centers in the United States (20), in Canada (1), in Europe (5) and in Australia (2). The total number of patients enrolled (ITT population) was 650; 72 never received study drug and 578 received study drug (Safety Population). Patients received mycophenolate mofetil 1.5 g twice daily (n=289) or AZA 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune^® or Neoral^®) and corticosteroids as maintenance immunosuppressive therapy. The two primary efficacy endpoints were: (1) the proportion of patients who, after transplantation, had at least one endomyocardial biopsy-proven rejection with hemodynamic compromise, or were re-transplanted or died, within the first 6 months, and (2) the proportion of patients who died or were re-transplanted during the first 12 months following transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection for up to 6 months and for the occurrence of death for 1 year.

The analyses of the endpoints showed:

• Rejection: No difference was established between mycophenolate mofetil and AZA with respect to biopsy-proven rejection with hemodynamic compromise.
• Survival: Mycophenolate mofetil was shown to be at least as effective as AZA in preventing death or re-transplantation at 1 year (see Table 13).

Table 13 De Novo Heart Transplantation Study Rejection at 6 Months/Death or Re-transplantation at 1 Year

	All Patients (ITT)		Treated Patients
	AZA N = 323	Mycophenolate Mofetil N = 327	AZA N = 289	Mycophenolate Mofetil N = 289
Biopsy-proven rejection with hemodynamic compromise at 6 months Hemodynamic compromise occurred if any of the following criteria were met: pulmonary capillary wedge pressure ≥20 mm or a 25% increase; cardiac index <2.0 L/min/m2 or a 25% decrease; ejection fraction ≤30%; pulmonary artery oxygen saturation ≤60% or a 25% decrease; presence of new S3 gallop; fractional shortening was ≤20% or a 25% decrease; inotropic support required to manage the clinical condition.	121 (38%)	120 (37%)	100 (35%)	92 (32%)
Death or re-transplantation at 1 year	49 (15.2%)	42 (12.8%)	33 (11.4%)	18 (6.2%)

14.3 Liver Transplantation

A double-blind, randomized, comparative, parallel-group, multicenter study in primary hepatic transplant recipients was performed at centers in the United States (16), in Canada (2), in Europe (4) and in Australia (1). The total number of patients enrolled was 565. Per protocol, patients received mycophenolate mofetil 1 g twice daily intravenously for up to 14 days followed by mycophenolate mofetil 1.5 g twice daily orally or AZA 1 to 2 mg/kg/day intravenously followed by AZA 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral^®) and corticosteroids as maintenance immunosuppressive therapy. The actual median oral dose of AZA on study was 1.5 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) initially and 1.26 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) at 12 months. The two primary endpoints were: (1) the proportion of patients who experienced, in the first 6 months post-transplantation, one or more episodes of biopsy-proven and treated rejection or death or re-transplantation, and (2) the proportion of patients who experienced graft loss (death or re-transplantation) during the first 12 months post-transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection and for the occurrence of graft loss (death or re-transplantation) for 1 year.

In combination with corticosteroids and cyclosporine, mycophenolate mofetil demonstrated a lower rate of acute rejection at 6 months and a similar rate of death or re-transplantation at 1 year compared to AZA (Table 14).

15 References

1. "OSHA Hazardous Drugs." OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

16.1 Handling And Disposal

Mycophenolate mofetil (MMF) has demonstrated teratogenic effects in humans [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. Wearing disposable gloves is recommended during reconstitution and when wiping the outer surface of the bottle/cap and the table after reconstitution. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in Mycophenolate Mofetil for Oral Suspension, USP (before or after constitution) [see Dosage and Administration (2.6)]. Follow applicable special handling and disposal procedures¹.

16.4 Mycophenolate Mofetil For Oral Suspension, Usp

For oral suspension: 35 g mycophenolate mofetil, white or almost white powder blend for constitution to a white or almost white tutti-frutti flavor suspension

225 mL bottle with bottle adapter and 2 oral dispensers                                                        NDC 0527-5160-82

Storage

• Store dry powder at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).
• Store constituted suspension at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) for up to 60 days. Storage in a refrigerator at 2° to 8°C (36° to 46°F) is acceptable. Do not freeze.

17.2 Development Of Lymphoma And Other Malignancies

• Inform patients that they are at increased risk of developing lymphomas and other malignancies, particularly of the skin, due to immunosuppression [see Warnings and Precautions (5.2)].
• Advise patients to limit exposure to sunlight and ultraviolet (UV) light by wearing protective clothing and use of broad-spectrum sunscreen with high protection factor.

17.3 Increased Risk Of Serious Infections

Inform patients that they are at increased risk of developing a variety of infections due to immunosuppression. Instruct them to contact their physician if they develop any of the signs and symptoms of infection explained in the Medication Guide.

17.4 Blood Dyscrasias

Inform patients that they are at increased risk for developing blood adverse effects such as anemia or low white blood cells. Advise patients to immediately contact their healthcare provider if they experience any evidence of infection, unexpected bruising, or bleeding, or any other manifestation of bone marrow suppression [see Warnings and Precautions (5.4)].

17.5 Gastrointestinal Tract Complications

Inform patients that mycophenolate mofetil can cause gastrointestinal tract complications including bleeding, intestinal perforations, and gastric or duodenal ulcers. Advise the patient to contact their healthcare provider if they have symptoms of gastrointestinal bleeding, or sudden onset or persistent abdominal pain [see Warnings and Precautions (5.5)].

17.6 Immunizations

Inform patients that mycophenolate mofetil can interfere with the usual response to immunizations. Before seeking vaccines on their own, advise patients to discuss first with their physician [see Warnings and Precautions (5.7)].

17.7 Administration Instructions

• Advise patients to avoid inhalation or contact of the skin or mucous membranes with the powder contained in the oral suspension. If such contact occurs, they must wash the area of contact thoroughly with soap and water. In case of ocular contact, rinse eyes with plain water.
  
• Advise patients to take a missed dose as soon as they remember, except if it is closer than 2 hours to the next scheduled dose; in this case they should continue to take mycophenolate mofetil at the usual times.

17.8 Blood Donation

Advise patients not to donate blood during therapy and for at least 6 weeks following discontinuation of mycophenolate mofetil.

17.9 Semen Donation

Advise males of childbearing potential not to donate semen during therapy and for 90 days following discontinuation of mycophenolate mofetil.

17.10 Potential To Impair Driving And Use Of Machinery

Advise patients that mycophenolate mofetil can affect the ability to drive or operate machines. Patients should avoid driving or operating machines if they experience somnolence, confusion, dizziness, tremor or hypotension during treatment with mycophenolate mofetil.

Instructions For Usemycophenolate Mofetil[Mye-Koe-Fen-Oh-Late Moe-Fe-Til]For Oral Suspension, Usp

Be sure that you read, understand and follow these instructions carefully to ensure proper dosing of mycophenolate mofetil for oral suspension.

Important:

• Always use the oral dispenser provided with mycophenolate mofetil for oral suspension to make sure you measure the right amount of medicine.
• Call your pharmacist if your oral dispenser is lost or damaged.
• Your pharmacist will write the expiration date on your mycophenolate mofetil for oral suspension bottle label. Do not use after the expiration date.
• Ask your doctor or pharmacist if you have any questions or are unsure about how to take your dose of medicine.

To take a dose of mycophenolate mofetil for oral suspension, you will need the bottle of medicine and an oral dispenser provided with the medicine (See Figure 1). Your pharmacist will insert the bottle adapter in the mycophenolate mofetil for oral suspension bottle.

figure 1 - mycophenolate mofetil for oral suspension usp 2




Step 1:	With the child-resistant cap on the bottle, shake the bottle well for about 5 seconds before each use.
Step 2:	Open the bottle by pressing down on the child-resistant bottle cap and turning it counter-clockwise (to the left). Do not throw away the child-resistant bottle cap.
Step 3:	Before inserting the tip of the oral dispenser into the bottle adapter, push the blue plunger completely down toward the tip of the oral dispenser. Insert the tip firmly into the opening of the bottle adapter.
Step 4:	Carefully turn the bottle upside down with the oral dispenser in place. Slowly pull the blue plunger down to withdraw your prescribed dose. Do not pull the blue plunger out of the oral dispenser (See Figure 2).
Step 5:	Leave the oral dispenser in the bottle and turn the bottle to an upright position. Slowly remove the oral dispenser from the bottle.
Step 6:	Place the tip of the oral dispenser in the patient's mouth and slowly push the blue plunger down until the oral dispenser is empty. The mycophenolate mofetil for oral suspension that is in the oral dispenser should not be mixed with any type of liquids before taking the dose.
Step 7:	Put the child-resistant bottle cap back on the bottle after each use.
Step 8:	Rinse the oral dispenser under running tap water after each use: Remove the blue plunger from the oral dispenser. Rinse the oral dispenser and blue plunger with water and let them air dry. When the oral dispenser and blue plunger are dry, put the blue plunger back in the oral dispenser for the next use.

Important:

• Do not let mycophenolate mofetil for oral suspension come in contact with the skin. If this happens, wash the skin well with soap and water.
• If you spill any oral suspension, wipe it up using paper towels wet with water. Put the child-resistant bottle cap back on the bottle and wipe the outside of the bottle with wet paper towels.

How should I store Mycophenolate Mofetil for Oral Suspension?

• Store the mycophenolate mofetil for oral suspension at room temperature between 59°F to 86°F (15°C to 30°C), for up to 60 days. You can also store mycophenolate mofetil for oral suspension in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Do not freeze.

Keep Mycophenolate Mofetil for Oral Suspension and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Distributed by:
Lannett Company, Inc.
Philadelphia, PA 19136

CIB71993A
Rev. 03/2021

Principal Display Panel - 200 Mg/Ml Bottle Carton

NDC 0527-5160-82

Mycophenolate
Mofetil for Oral
Suspension, USP

200 mg/mL

Each mL contains 200 mg mycophenolate
mofetil after constitution.

Print Medication Guides at: www.lannett.com/med-guide/mycophenolate

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carton - mycophenolate mofetil for oral suspension usp 4