Mycophenolate Mofetil

• 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 , Use in Special Populations ]

  .

• Increased
  risk of development of lymphoma and other malignancies, particularly of the skin

  [see Warnings and Precautions ]

  .

• 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 ]

  .

Warnings and Precautions (

• Mycophenolate mofetil Intravenous is an alternative when patients cannot tolerate oral medication. Administer within 24 hours following transplantation, until patients can tolerate oral medication, up to 14 days.

  2.1 Important Administration Instructions

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

  Mycophenolate mofetil for Oral Suspension

  Mycophenolate mofetil oral dosage forms (oral suspension)

  should not be used interchangeably with mycophenolic acid delayed-release tablets without supervision of a physician with experience in immunosuppressive therapy

  because the rates of absorption following the administration of mycophenolate mofetil oral dosage forms and mycophenolic acid delayed-release tablets are not equivalent.

  Patients should avoid inhalation or contact of the skin or mucous membranes with the powder contained in mycophenolate mofetil for 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.

  The initial oral dose of mycophenolate mofetil should be given as soon as possible following kidney, heart or liver transplant. It is recommended that mycophenolate mofetil be administered on an empty stomach. In stable transplant patients, however, mycophenolate mofetil may be administered with food if necessary

  [see Clinical Pharmacology ]

  . Once reconstituted, Mycophenolate mofetil for Oral Suspension must not be mixed with any liquids prior to dose administration. If needed, Mycophenolate mofetil for Oral Suspension can be administered via a nasogastric tube with a minimum size of 8 French (minimum 1.7 mm interior diameter).

  Patients should be instructed 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.

  Mycophenolate mofetil Intravenous

  Mycophenolate mofetil Intravenous is recommended for patients unable to take oral mycophenolate mofetil. Mycophenolate mofetil Intravenous should be administered within 24 hours following transplant. Mycophenolate mofetil Intravenous can be administered for up to 14 days; however, patients should be switched to oral mycophenolate mofetil as soon as they can tolerate oral medication.
  )

• Reduce or interrupt dosing in the event of neutropenia. (

  2.5 Dosage Modifications: Patients with Renal
  Impairment, Neutropenia

  Renal Impairment

  No dosage modifications are needed in kidney transplant patients with delayed graft function postoperatively

  [see Clinical Pharmacology ]

  . In

  kidney transplant patients with severe chronic impairment of the graft

  (GFR <25 mL/min/1.73 m²), do not administer doses of mycophenolate mofetil greater than 1 g twice a day. These patients should be carefully monitored

  [see Clinical Pharmacology ].

  Neutropenia

  If neutropenia develops (ANC <1.3 x 10³/mcL), dosing with mycophenolate mofetil should be interrupted or reduced, appropriate diagnostic tests performed, and the patient managed appropriately

  [see Warnings and Precautions (5.4)

  and

  Adverse Reactions ].
  )

• See full prescribing information (FPI) for: adjustments for renal impairment and neutropenia (

  2.5 Dosage Modifications: Patients with Renal
  Impairment, Neutropenia

  Renal Impairment

  No dosage modifications are needed in kidney transplant patients with delayed graft function postoperatively

  [see Clinical Pharmacology ]

  . In

  kidney transplant patients with severe chronic impairment of the graft

  (GFR <25 mL/min/1.73 m²), do not administer doses of mycophenolate mofetil greater than 1 g twice a day. These patients should be carefully monitored

  [see Clinical Pharmacology ].

  Neutropenia

  If neutropenia develops (ANC <1.3 x 10³/mcL), dosing with mycophenolate mofetil should be interrupted or reduced, appropriate diagnostic tests performed, and the patient managed appropriately

  [see Warnings and Precautions (5.4)

  and

  Adverse Reactions ].
  ), preparation of oral suspension. (
  2.6
  Preparation Instructions of Oral Suspension for Pharmacists

  General Preparation Instructions Before Handling the Formulations

  Mycophenolate mofetil (MMF) has demonstrated teratogenic effects in humans. Follow applicable special handling and disposal procedures¹

  [see Warnings and Precautions , Adverse Reactions , Use in Specific Populations , How Supplied/Storage and Handling ].

  Care should be taken to avoid inhalation or direct contact with skin or mucous membranes of the dry powder or the constituted suspension because MMF has demonstrated teratogenic effects in humans. Wearing disposable gloves is recommended during reconstitution and when wiping the outer surface of the bottle/cap and the table surface after reconstitution. If such contact occurs, wash hands thoroughly with soap and water; rinse eyes with water.

  Alert patients that they and others should also avoid inhalation or contact of the skin or mucous membranes with the oral suspension. Advise them to wash the area thoroughly with soap and water if such contact occurs; if ocular contact occurs, rinse eyes with plain water.

  Mycophenolate mofetil for Oral Suspension

  Mycophenolate mofetil for Oral Suspension must be reconstituted by the pharmacist prior to dispensing to the patient. Mycophenolate mofetil for Oral Suspension should not be mixed with any other medication. After reconstitution, the oral suspension contains 200 mg/mL MMF.

  Before proceeding with the reconstitution steps read the general preparation instructions above

  [see General Preparation Instructions Before Handling the Formulations]

  . The following are the steps for reconstitution:

  • Tap the closed bottle several times to loosen the powder.

  • Measure 91 mL of water in a graduated cylinder.

  • Add approximately half the total amount of water for reconstitution to the bottle and shake the closed bottle well for about 1 minute.

  • Add the remainder of water and shake the closed bottle well for about 1 minute.

  • Remove the child-resistant cap and push bottle adapter into neck of bottle.

  • Close bottle with child-resistant cap tightly. This will assure the proper seating of the bottle adapter in the bottle and child-resistant status of the cap.

  • Write the date of expiration of the constituted suspension on the bottle label. (The shelf-life of the constituted suspension is 60 days.)

  • Dispense with the “Instruction for Use” and oral dispensers. Alert patients to read the important handling information described in the instructions for use.

  Store reconstituted suspension at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Storage in a refrigerator at 2°C to 8°C (36°F to 46°F) is acceptable. Do not freeze. Discard any unused portion 60 days after constitution.
  )

Mycophenolate mofetil is available in the following dosage form and strength:

• Male Patients: Sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment (

  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.

  Pregnancy Planning

  For patients who are considering pregnancy, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible. Risks and benefits of mycophenolate mofetil should be discussed with the patient.

  Pregnancy Testing

  To prevent unplanned exposure during pregnancy, all females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL immediately before starting mycophenolate mofetil. Another pregnancy test with the same sensitivity should be done 8 to 10 days later. Repeat pregnancy tests should be performed during routine follow-up visits. Results of all pregnancy tests should be discussed with the patient. In the event of a positive pregnancy test, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible.

  Contraception

  Female Patients

  Females of reproductive potential taking mycophenolate mofetil must receive contraceptive counseling and use acceptable contraception (see

  Table 9

  for acceptable contraception methods). Patients must use acceptable birth control during the entire mycophenolate mofetil therapy, and for 6 weeks after stopping mycophenolate mofetil, unless the patient chooses abstinence.

  Patients should be aware that mycophenolate mofetil reduces blood levels of the hormones from the oral contraceptive pill and could theoretically reduce its effectiveness

  [see Drug Interactions ].

  Table 9  Acceptable Contraception Methods for Females of Reproductive Potential

  Pick from the following birth control options:

  Option 1
  Methods to Use Alone	Intrauterine devices (IUDs) Tubal sterilization Patient’s partner vasectomy

  OR

  Option 2	Hormone Methods choose 1		Barrier Methods choose 1
  Choose One Hormone Method AND One Barrier Method	Estrogen and Progesterone Oral Contraceptive Pill Transdermal patch Vaginal ring Progesterone-only Injection Implant	AND	Diaphragm with spermicide Cervical cap with spermicide Contraceptive sponge Male condom Female condom

  OR

  Option 3	Barrier Methods choose 1		Barrier Methods choose 1
  Choose One Barrier Method from each column (must choose two methods)	Diaphragm with spermicide Cervical cap with spermicide Contraceptive sponge	AND	Male condom Female condom

  Male Patients

  Genotoxic effects have been observed in animal studies at exposures exceeding the human therapeutic exposures by approximately 1.25 times. Thus, the risk of genotoxic effects on sperm cells cannot be excluded. Based on this potential risk, sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment. Also, based on the potential risk of genotoxic effects, male patients should not donate sperm during treatment with mycophenolate mofetil and for at least 90 days after cessation of treatment

  [see Use in Special Populations , Nonclinical Toxicology , Patient Counseling Information ]

  .
  ).