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 (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)]
  .

Mycophenolate Mofetil is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogenic kidney

• Mycophenolate Mofetil for Injection 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 for injection should not be used without the supervision of a physician with experience in immunosuppressive therapy.

  Mycophenolate Mofetil for Injection

  Mycophenolate mofetil for injection is recommended for patients unable to take oral mycophenolate mofetil. Mycophenolate mofetil for injection should be administered within 24 hours following transplant. Mycophenolate mofetil for injection 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.

  Mycophenolate mofetil for injection must be reconstituted before use

  [see Dosage and Administration (2.6)]

  . Mycophenolate mofetil for injection is incompatible with other intravenous infusion solutions and should not be mixed or administered concurrently via the same infusion catheter with other intravenous drugs or infusion admixtures.

  Mycophenolate mofetil for injection must not be administered as a bolus. Following reconstitution, mycophenolate mofetil for injection must be administered by slow intravenous infusion over a period of no less than 2 hours by either peripheral or central vein, as rapid infusion increases the risk of local adverse reactions such as phlebitis and thrombosis

  [see Adverse Reactions (6.1)]

  .
  )
• 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 (12.3)]

  . 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 (12.3)].

  Neutropenia

  If neutropenia develops (ANC <1.3 x 10³/μL), 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 (6.1)].
  )
• 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 (12.3)]

  . 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 (12.3)].

  Neutropenia

  If neutropenia develops (ANC <1.3 x 10³/μL), 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 (6.1)].
  ), preparation of IV solution. (
  2.6 Preparation Instructions of Intravenous 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 (5.1), Adverse Reactions (6.2), Use in Specific Populations (8.1 , 8.3), How Supplied/Storage and Handling (16.1)]

  .

  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.

  Mycophenolate Mofetil for Injection

  Before proceeding with the preparation steps for mycophenolate mofetil for injection read the general preparation instructions

  [see General Preparation Instructions Before Handling the Formulations]

  and note the following:

  • Mycophenolate mofetil for injection does not contain an antibacterial preservative; therefore, reconstitution and dilution of the product must be performed under aseptic conditions.
  • This product is sealed under vacuum and should retain a vacuum throughout its shelf life. If a lack of vacuum in the vial is noted while adding the diluent, the vial should not be used.

  Mycophenolate mofetil for injection must be reconstituted and further diluted. A detailed description of the preparation is given below.

  Table 4 Preparation Instructions of Mycophenolate Mofetil for Injection for Pharmacists
  Preparation of the 1g dose	Reconstitute two (2) vials of mycophenolate mofetil for injection by injecting 14 mL of 5% Dextrose Injection USP into each vial. Gently shake the vial to dissolve the drug. Inspect the resulting slightly yellow solution for particulate matter and discoloration prior to further dilution. Discard the vials if particulate matter or discoloration is observed. Dilute the contents of the two reconstituted vials (approximately 2 x 15 mL) into 140 mL of 5% Dextrose Injection USP. Inspect the resulting infusion solution and discard if particulate matter or discoloration is observed.
  Preparation of the 1.5 g dose	Reconstitute three (3) vials of mycophenolate mofetil for injection by injecting 14 mL of 5% Dextrose Injection USP into each vial. Gently shake the vial to dissolve the drug. Inspect the resulting slightly yellow solution for particulate matter and discoloration prior to further dilution. Discard the vials if particulate matter or discoloration is observed. Dilute the contents of the three reconstituted vials (approximately 3 x 15 mL) into 210 mL of 5% Dextrose Injection USP. Inspect the resulting infusion solution and discard if particulate matter or discoloration is observed.

  The administration of the infusion should be initiated within 4 hours of reconstitution and dilution of the drug product. Keep solutions at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F). Discard unused portion of the reconstituted solutions.

  Mycophenolate mofetil for injection should not be mixed or administered concurrently via the same infusion catheter with other intravenous drugs or infusion admixtures.
  )

Mycophenolate Mofetil for Injection, USP 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 (7.2)].

  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 (8.1), Nonclinical Toxicology (13.1), P atient Counseling Information (17.9)]

  .
  )