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Myfortic (Mycophenolic Acid) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

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

  • Embryofetal Toxicity [see Boxed Warning, Warnings and Precautions (5.1)]
  • Lymphomas and Other Malignancies [see Boxed Warning, Warnings and Precautions (5.4)]
  • Serious Infections [see Boxed Warning, Warnings and Precautions (5.5)]
  • New or Reactivated Viral Infections [see Warnings and Precautions (5.6)]
  • Blood Dyscrasias Including Pure Red Cell Aplasia [see Warnings and Precautions (5.7)]
  • Serious GI Tract Complications [see Warnings and Precautions (5.8)]
  • Rare Hereditary Deficiencies [see Warnings and Precautions (5.10)]

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.

The data described below derive from two randomized, comparative, active-controlled, double-blind, double-dummy trials in prevention of acute rejection in de novo and converted stable kidney transplant patients.

In the de novo trial, patients were administered either Myfortic 1.44 grams per day (N=213) or MMF 2 grams per day (N=210) within 48 hours post-transplant for 12 months in combination with cyclosporine, USP MODIFIED and corticosteroids. Forty-one percent of patients also received antibody therapy as induction treatment. In the conversion trial, renal transplant patients who were at least 6 months post-transplant and receiving 2 grams per day MMF in combination with cyclosporine USP MODIFIED, with or without corticosteroids for at least two weeks prior to entry in the trial were randomized to Myfortic 1.44 grams per day (N=159) or MMF 2 grams per day (N=163) for 12 months.

The average age of patients in both studies was 47 years and 48 years (de novo study and conversion study, respectively), ranging from 22 to 75 years. Approximately 66% of patients were male; 82% were white, 12% were black, and 6% other races. About 40% of patients were from the United States and 60% from other countries.

In the de novo trial, the overall incidence of discontinuation due to adverse reactions was 18% (39/213) and 17% (35/210) in the Myfortic and MMF arms, respectively. The most common adverse reactions leading to discontinuation in the Myfortic arm were graft loss (2%), diarrhea (2%), vomiting (1%), renal impairment (1%), CMV infection (1%), and leukopenia (1%). The overall incidence of patients reporting dose reduction at least once during the 0 to 12 month study period was 59% and 60% in the Myfortic and MMF arms, respectively. The most frequent reasons for dose reduction in the Myfortic arm were adverse reactions (44%), dose reductions according to protocol guidelines (17%), dosing errors (11%) and missing data (2%).

The most common adverse reactions (≥20%) associated with the administration of Myfortic were anemia, leukopenia, constipation, nausea, diarrhea, vomiting, dyspepsia, urinary tract infection, CMV infection, insomnia, and postoperative pain.

The adverse reactions reported in ≥10% of patients in the de novo trial are presented in Table 2 below.

Table 2: Adverse Reactions (%) Reported in ≥10% of de novo Kidney Transplant Patients in Either Treatment Group
**The trial was not designed to support comparative claims for Myfortic for the adverse reactions reported in this table.
de novo Renal Trial
System organ class
Adverse drug reactions
Myfortic
1.44 grams per day
(n=213)
(%)
mycophenolate mofetil (MMF)
2 grams per day
(n=210)
(%)
Blood and Lymphatic System Disorders
     Anemia 22 22
     Leukopenia 19 21
Gastrointestinal System Disorders
     Constipation 38 40
     Nausea 29 27
     Diarrhea 24 25
     Vomiting 23 20
     Dyspepsia 23 19
     Abdominal pain upper 14 14
     Flatulence 10 13
General and Administrative Site Disorders
     Edema 17 18
     Edema lower limb 16 17
     Pyrexia 13 19
Investigations
     Increased blood creatinine 15 10
Infections and Infestations
     Urinary Tract Infection 29 33
     CMV Infection 20 18
Metabolism and Nutrition Disorders
     Hypocalcemia 11 15
     Hyperuricemia 13 13
     Hyperlipidemia 12 10
     Hypokalemia 13 9
     Hypophosphatemia 11 9
Musculoskeletal, Connective Tissue and Bone Disorders
     Back pain 12 6
     Arthralgia 7 11
Nervous System Disorder
     Insomnia 24 24
     Tremor 12 14
     Headache 13 11
Vascular Disorders
     Hypertension 18 18

Table 3 summarizes the incidence of opportunistic infections in de novo transplant patients.

Table 3: Viral and Fungal Infections (%) Reported Over 0 to 12 Months
de novo Renal Trial
Myfortic
1.44 grams per day
(n=213)
(%)
mycophenolate mofetil (MMF)
2 grams per day
(n=210)
(%)
Any Cytomegalovirus 22 21
- Cytomegalovirus Disease 5 4
Herpes Simplex 8 6
Herpes Zoster 5 4
Any Fungal Infection 11 12
- Candida NOS 6 6
- Candida albicans 2 4

Lymphoma developed in 2 de novo patients (1%), (1 diagnosed 9 days after treatment initiation) and in 2 conversion patients (1%) receiving Myfortic with other immunosuppressive agents in the 12-month controlled clinical trials.

Nonmelanoma skin carcinoma occurred in 1% de novo and 12% conversion patients. Other types of malignancy occurred in 1% de novo and 1% conversion patients [see Warnings and Precautions (5.4)].

The adverse reactions reported in <10% of de novo or conversion patients treated with Myfortic in combination with cyclosporine and corticosteroids are listed in Table 4.

Table 4: Adverse Reactions Reported in <10% of Patients Treated with Myfortic in Combination with Cyclosporine* and Corticosteroids
* USP MODIFIED
Blood and Lymphatic Disorders Lymphocele, thrombocytopenia
Cardiac Disorder Tachycardia
Eye Disorder Vision blurred
Gastrointestinal Disorders Abdominal pain, abdominal distension, gastroesophageal reflux disease, gingival hyperplasia
General Disorders and Administration Site Conditions Fatigue, peripheral edema
Infections and Infestations Nasopharyngitis, herpes simplex, upper respiratory infection, oral candidiasis, herpes zoster, sinusitis, influenza, wound infection, implant infection, pneumonia, sepsis
Investigations Hemoglobin decrease, liver function tests abnormal
Metabolism and Nutrition Disorders Hypercholesterolemia, hyperkalemia, hypomagnesemia, diabetes mellitus, hyperglycemia
Musculoskeletal and Connective Tissue Disorders Arthralgia, pain in limb, peripheral swelling, muscle cramps, myalgia
Nervous System Disorders Dizziness (excluding vertigo)
Psychiatric Disorders Anxiety
Renal and Urinary Disorders Renal tubular necrosis, renal impairment, hematuria, urinary retention
Respiratory, Thoracic and Mediastinal Disorders Cough, dyspnea, dyspnea exertional
Skin and Subcutaneous Tissue Disorders Acne, pruritus, rash
Vascular Disorders Hypertension aggravated, hypotension

The following additional adverse reactions have been associated with the exposure to mycophenolic acid (MPA) when administered as a sodium salt or as mofetil ester:

Gastrointestinal: Intestinal perforation, gastrointestinal hemorrhage, gastric ulcers, duodenal ulcers [see Warnings and Precautions (5.8)], colitis (including CMV colitis), pancreatitis, esophagitis, and ileus.

Infections: Serious life-threatening infections such as meningitis and infectious endocarditis, tuberculosis, and atypical mycobacterial infection [see Warnings and Precautions (5.5)].

Respiratory: Interstitial lung disorders, including fatal pulmonary fibrosis.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Myfortic or other MPA derivatives. 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.

  • Congenital malformations and an increased incidence of first trimester pregnancy loss have been reported following exposure to MMF during pregnancy [see Boxed Warning, Warnings and Precautions (5.1)].
  • Infections [see Warnings and Precautions (5.5, 5.6)] Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal.
  • Polyomavirus associated nephropathy (PVAN), especially due to BK virus infection, associated with serious outcomes, including deteriorating renal function and renal graft loss.
  • Viral reactivation in patients infected with HBV or HCV.
  • Cases of pure red cell aplasia (PRCA) have been reported in patients treated with MPA derivatives in combination with other immunosuppressive agents [see Warnings and Precautions (5.7)].
  • The following additional adverse reactions have been identified during postapproval use of Myfortic: agranulocytosis, asthenia, osteomyelitis, lymphadenopathy, lymphopenia, wheezing, dry mouth, gastritis, peritonitis, anorexia, alopecia, pulmonary edema, Kaposi’s sarcoma.



    REPORTS OF SUSPECTED MYFORTIC SIDE EFFECTS / ADVERSE REACTIONS

    Below is a sample of reports where side effects / adverse reactions may be related to Myfortic. The information is not vetted and should not be considered as verified clinical evidence.

    Possible Myfortic side effects / adverse reactions in 70 year old male

    Reported by a physician from Austria on 2011-10-04

    Patient: 70 year old male weighing 72.0 kg (158.4 pounds)

    Reactions: Pneumonia, Cardiac Failure, Bronchopneumonia, Circulatory Collapse, Enteritis, Septic Shock, Leukopenia

    Adverse event resulted in: death

    Suspect drug(s):
    Myfortic
        Dosage: 360 mg
        Administration route: Oral
        Indication: Immunosuppression
        Start date: 2010-11-14

    Myfortic
        Dosage: 720 mg, unk
        Administration route: Oral
        Start date: 2010-11-15
        End date: 2010-12-04

    Myfortic
        Dosage: 720 mg, unk
        Administration route: Oral
        Start date: 2011-01-07
        End date: 2011-01-09

    Myfortic
        Dosage: 360 mg, unk
        Administration route: Oral
        Start date: 2011-01-05
        End date: 2011-01-06

    Other drugs received by patient: Pantoprazole Sodium; Insulin Novo; Yomogi; CAL-D-Vita; Urosin; Prograf; Sodium Polystyrene Sulfonate; Tamsulosin HCL; Aprednislon; Lovenox



    Possible Myfortic side effects / adverse reactions in 47 year old male

    Reported by a individual with unspecified qualification from United States on 2011-10-12

    Patient: 47 year old male weighing 74.0 kg (162.8 pounds)

    Reactions: Blood Creatine Phosphokinase Increased, Vomiting, Nausea, Pancreatitis, Kidney Transplant Rejection, Gastric Ulcer

    Adverse event resulted in: hospitalization

    Suspect drug(s):
    Myfortic

    Other drugs received by patient: Wellbutrin XL; Soriatane; Zofran; Cymbalta; Prednisone; Abilify; Lamictal; Protonix; Norvasc; Adderall XR 10; Adderall 5; Diazepam; Atenolol; Temazepam; Prograf



    Possible Myfortic side effects / adverse reactions in 61 year old male

    Reported by a physician from United States on 2011-10-18

    Patient: 61 year old male weighing 84.0 kg (184.8 pounds)

    Reactions: Squamous Cell Carcinoma of Skin

    Suspect drug(s):
    Myfortic
        Dosage: 720 mg
        Administration route: Oral
        Indication: Immunosuppression
        Start date: 2009-09-16
        End date: 2009-10-06

    Study Drug
        Dosage: 10 mg
        Administration route: Oral
        Indication: Kidney Transplant Rejection
        Start date: 2009-12-18

    Prednisone
        Dosage: 5 mg
        Administration route: Oral
        Indication: Immunosuppression
        Start date: 2009-01-04

    Myfortic
        Dosage: 360 mg
        Administration route: Oral
        Start date: 2010-10-07
        End date: 2010-12-23

    Myfortic
        Dosage: 180 mg
        Administration route: Oral
        Start date: 2010-12-24

    Other drugs received by patient: Simvastatin; Norvasc; Multi-Vitamins; Lovaza; Vitamin D; Bactrim; Calcium Carbonate



    See index of all Myfortic side effect reports >>

    Drug label data at the top of this Page last updated: 2013-09-27

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