Gengraf Oral Solution

Last updated on RxList: 2/1/2021
Gengraf Oral Solution Side Effects Center

What Is Gengraf Oral Solution?

Gengraf Oral Solution (cyclosporine) is an immunosuppressive drug used to prevent organ rejection after a kidney, liver, or heart transplant. Gengraf Oral Solution is also used to treat severe psoriasis or severe rheumatoid arthritis. Gengraf Oral Solution is available in generic form.

What Are Side Effects of Gengraf Oral Solution?

Common side effects of Gengraf Oral Solution include:

Dosage for Gengraf Oral Solution

The initial dose of Gengraf varies depending on the transplanted organ and the other immunosuppressive agents included in the immunosuppressive protocol.

What Drugs, Substances, or Supplements Interact with Gengraf Oral Solution?

Gengraf Oral Solution may interact with "live" vaccines, grapefruit, etoposide, lithium, methotrexate, nefazodone, repaglinide, St. John's wort, ACE inhibitors, heart or blood pressure medications, medicines used to treat ulcerative colitis, other medicines used to prevent organ transplant rejection, pain or arthritis medicines, IV antibiotics, antiviral medicines, or cancer medicines. Tell your doctor all medications and supplements you use and all vaccines you recently received.

Gengraf Oral Solution During Pregnancy and Breastfeeding

It is unknown if Gengraf Oral Solution is harmful to a fetus. Before taking this medication, tell your doctor if you are pregnant or plan to become pregnant during treatment. This drug can pass into breast milk and may harm a nursing baby. Consult your doctor before breastfeeding.

Additional Information

Our Gengraf Oral Solution (cyclosporine) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

Psoriasis causes the top layer of skin cells to become inflamed and grow too quickly and flake off. See Answer
Gengraf Oral Solution Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • problems with speech, thought, vision, or muscle movement (may start gradually and get worse quickly);
  • a seizure;
  • severe headache, blurred vision, pounding in your neck or ears;
  • pale skin, easy bruising, unusual bleeding;
  • high potassium level--nausea, weakness, tingly feeling, chest pain, irregular heartbeats, loss of movement;
  • kidney problems--little or no urination, swelling in your feet or ankles, feeling tired or short of breath;
  • liver problems--loss of appetite, stomach pain (upper right side), jaundice (yellowing of the skin or eyes); or
  • signs of infection--fever, chills, flu symptoms, mouth sores, skin sores, sore throat, cough, trouble breathing.

Common side effects may include:

  • tremors or shaking;
  • acne, increased growth of facial or body hair;
  • increased blood pressure;
  • nausea, diarrhea; or
  • swollen or painful gums.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Gengraf Oral Solution (Cyclosporine Oral Solution)

SLIDESHOW

Types of Psoriasis: Medical Pictures and Treatments See Slideshow
Gengraf Oral Solution Professional Information

SIDE EFFECTS

Kidney, Liver, And Heart Transplantation

The principal adverse reactions of cyclosporine therapy are renal dysfunction, tremor, hirsutism, hypertension, and gum hyperplasia.

Hypertension

Hypertension, which is usually mild to moderate, may occur in approximately 50% of patients following renal transplantation and in most cardiac transplant patients.

Glomerular Capillary Thrombosis

Glomerular capillary thrombosis has been found in patients treated with cyclosporine and may progress to graft failure. The pathologic changes resembled those seen in the hemolytic-uremic syndrome and included thrombosis of the renal microvasculature, with platelet-fibrin thrombi occluding glomerular capillaries and afferent arterioles, microangiopathic hemolytic anemia, thrombocytopenia, and decreased renal function. Similar findings have been observed when other immunosuppressives have been employed post-transplantation.

Hypomagnesemia

Hypomagnesemia has been reported in some, but not all, patients exhibiting convulsions while on cyclosporine therapy. Although magnesiumdepletion studies in normal subjects suggest that hypomagnesemia is associated with neurologic disorders, multiple factors, including hypertension, high dose methylprednisolone, hypocholesterolemia, and nephrotoxicity associated with high plasma concentrations of cyclosporine appear to be related to the neurological manifestations of cyclosporine toxicity.

Clinical Studies

In controlled studies, the nature, severity, and incidence of the adverse events that were observed in 493 transplanted patients treated with cyclosporine (MODIFIED) were comparable with those observed in 208 transplanted patients who received Sandimmune® in these same studies when the dosage of the two drugs was adjusted to achieve the same cyclosporine blood trough concentrations.

Based on the historical experience with Sandimmune® , the following reactions occurred in 3% or greater of 892 patients involved in clinical trials of kidney, heart, and liver transplants.

Body SystemAdverse ReactionsRandomized Kidney PatientsCyclosporine Patients
(Sandimmune®)
Sandimmune®
(N=227) %
Azathioprine
(N=228) %
Kidney
(N=705) %
Heart
(N=112) %
Liver
(N=75) %
Genitourinary
Renal Dysfunction326253837
Cardiovascular
Hypertension2618135327
Cramps4<12<10
Skin
Hirsutism21<1212845
Acne68221
Central Nervous System
Tremor120213155
Convulsions31145
Headache2<12154
Gastrointestinal
Gum Hyperplasia409516
Diarrhea3<1348
Nausea/Vomiting2<14104
Hepatotoxicity<1<1474
Abdominal Discomfort<10<170
Autonomic Nervous System
Paresthesia30121
Flushing<10404
Hematopoietic
Leukopenia219<160
Lymphoma<10161
Respiratory
Sinusitis<10437
Miscellaneous
Gynecomastia<10<143

Among 705 kidney transplant patients treated with cyclosporine oral solution (Sandimmune® ) in clinical trials, the reason for treatment discontinuation was renal toxicity in 5.4%, infection in 0.9%, lack of efficacy in 1.4%, acute tubular necrosis in 1.0%, lymphoproliferative disorders in 0.3%, hypertension in 0.3%, and other reasons in 0.7% of the patients.

The following reactions occurred in 2% or less of cyclosporine-treated patients: allergic reactions, anemia, anorexia, confusion, conjunctivitis, edema, fever, brittle fingernails, gastritis, hearing loss, hiccups, hyperglycemia, migraine (Gengraf® ), muscle pain, peptic ulcer, thrombocytopenia, tinnitus.

The following reactions occurred rarely: anxiety, chest pain, constipation, depression, hair breaking, hematuria, joint pain, lethargy, mouth sores, myocardial infarction, night sweats, pancreatitis, pruritus, swallowing difficulty, tingling, upper GI bleeding, visual disturbance, weakness, weight loss.

Patients receiving immunosuppressive therapies, including cyclosporine and cyclosporine-containing regimens, are at increased risk of infections (viral, bacterial, fungal, parasitic). Both generalized and localized infections can occur. Pre-existing infections may also be aggravated. Fatal outcomes have been reported. (See WARNINGS)

Infectious Complications in Historical Randomized Studies in Renal Transplant Patients Using Sandimmune®

ComplicationCyclosporine Treatment
(N=227)
% of Complications
Azathioprine with Steroids*
(N=228)
% of Complications
Septicemia5.34.8
Abscesses4.45.3
Systemic Fungal Infection2.23.9
Local Fungal Infection7.59.6
Cytomegalovirus4.812.3
Other Viral Infections15.918.4
Urinary Tract Infections21.120.2
Wound and Skin Infections7.010.1
Pneumonia6.29.2
*Some patients also received ALG.

Postmarketing Experience, Kidney, Liver And Heart Transplantation

Hepatotoxicity

Cases of hepatotoxicity and liver injury including cholestasis, jaundice, hepatitis and liver failure; serious and/or fatal outcomes have been reported. (See WARNINGS, Hepatotoxicity)

Increased Risk Of Infections

Cases of JC virus-associated progressive multifocal leukoencephalopathy (PML), sometimes fatal; and polyoma virus-associated nephropathy (PVAN), especially BK virus resulting in graft loss have been reported. (See WARNINGS, Polyoma Virus Infection)

Headache, Including Migraine

Cases of migraine have been reported. In some cases, patients have been unable to continue cyclosporine, however, the final decision on treatment discontinuation should be made by the treating physician following the careful assessment of benefits versus risks.

Pain Of lower Extremities

Isolated cases of pain of lower extremities have been reported in association with cyclosporine. Pain of lower extremities has also been noted as part of Calcineurin-Inhibitor Induced Pain Syndrome (CIPS) as described in the literature.

Rheumatoid Arthritis

The principal adverse reactions associated with the use of cyclosporine in rheumatoid arthritis are renal dysfunction (See WARNINGS), hypertension (See PRECAUTIONS), headache, gastrointestinal disturbances, and hirsutism/hypertrichosis.

In rheumatoid arthritis patients treated in clinical trials within the recommended dose range, cyclosporine therapy was discontinued in 5.3% of the patients because of hypertension and in 7% of the patients because of increased creatinine. These changes are usually reversible with timely dose decrease or drug discontinuation. The frequency and severity of serum creatinine elevations increase with dose and duration of cyclosporine therapy. These elevations are likely to become more pronounced without dose reduction or discontinuation.

The following adverse events occurred in controlled clinical trials:

Cyclosporine (MODIFIED)/Sandimmune® Rheumatoid Arthritis Percentage of Patients with Adverse Events ≥3% in any Cyclosporine Treated Group

Body System Preferred
Term
Studies
651+652+2008
Study 302Study 654Study 654Study 302Studies
651+652 + 2008
Sandimmune®
(N=269)
Sandimmune®
(N=155)
Methotrexate
&
Sandimmune®
(N=74)
Methotrexate
&
Placebo
(N=73)
Cyclosporine
(MODIFIED)
(N=143)
Placebo
(N=201)
Autonomic Nervous System Disorders
  Flushing2%2%3%0%5%2%
Body As A Whole - General Disorders
  Accidental Trauma0%1%10%4%4%0%
  Edema NOS*5%14%12%4%10%<1%
  Fatigue6%3%8%12%3%7%
  Fever2%3%0%0%2%4%
  Influenza-like symptoms<1%6%1%0%3%2%
  Pain6%9%10%15%13%4%
  Rigors1%1%4%0%3%1%
Cardiovascular Disorders
  Arrhythmia2%5%5%6%2%1%
  Chest Pain4%5%1%1%6%1%
  Hypertension8%26%16%12%25%2%
Central and Peripheral Nervous System Disorders
  Dizziness8%6%7%3%8%3%
  Headache17%23%22%11%25%9%
  Migraine2%3%0%0%3%1%
  Paresthesia8%7%8%4%11%1%
  Tremor8%7%7%3%13%4%
Gastrointestinal System Disorders
  Abdominal Pain15%15%15%7%15%10%
  Anorexia3%3%1%0%3%3%
  Diarrhea12%12%18%15%13%8%
  Dyspepsia12%12%10%8%8%4%
  Flatulence5%5%5%4%4%1%
  Gastrointestinal Disorder NOS*0%2%1%4%4%0%
  Gingivitis4%3%0%0%0%1%
  Gum Hyperplasia2%4%1%3%4%1%
  Nausea Rectal23%14%24%15%18%14%
  Rectal
Hemorrhage
0%3%0%0%1%1%
  Stomatitis7%5%16%12%6%8%
  Vomiting9%8%14%7%6%5%
Hearing and Vestibular Disorders
  Ear Disorder NOS*0%5%0%0%1%0%
Metabolic and Nutritional Disorders
  Hypomagnesemia0%4%0%0%6%0%
Musculoskeletal System Disorders
  Arthropathy0%5%0%1%4%0%
  Leg Cramps /
Involuntary
2%11%11%3%12%1%
Muscle Contractions
Psychiatric Disorders
  Depression3%6%3%1%1%2%
  Insomnia4%1%1%0%3%2%
Renal
  Creatinine elevations ≥30%43%39%55%19%48%13%
  Creatinine
elevations ≥50%
24%18%26%8%18%3%
Reproductive Disorders, Female
  Leukorrhea Menstrual1%0%4%0%1%0%
  Menstrual Disorder3%2%1%0%1%1%
Respiratory System Disorders
  Bronchitis1%3%1%0%1%3%
  Coughing5%3%5%7%4%4%
  Dyspnea5%1%3%3%1%2%
  Infection NOS*9%5%0%7%3%10%
  Pharyngitis3%5%5%6%4%4%
  Pneumonia1%0%4%0%1%1%
  Rhinitis0%3%11%10%1%0%
  Sinusitis4%4%8%4%3%3%
  Upper
Respiratory Tract
0%14%23%15%13%0%
Skin and Appendages Disorders
  Alopecia3%0%1%1%4%4%
  Bullous Eruption1%0%4%1%1%1%
  Hypertrichosis19%17%12%0%15%3%
  Rash7%12%10%7%8%10%
  Skin Ulceration1%1%3%4%0%2%
Urinary System Disorders
  Dysuria0%0%11%3%1%2%
  Micturition Frequency2%4%3%1%2%2%
  NPN, Increased0%19%12%0%18%0%
  Urinary Tract
Infection
0%3%5%4%3%0%
Vascular (Extracardiac) Disorders
  Purpura3%4%1%1%2%0%
Includes patients in 2.5 mg/kg/day dose group only.
*NOS=Not Otherwise Specified.

In addition, the following adverse events have been reported in 1% to <3% of the rheumatoid arthritis patients in the cyclosporine treatment group in controlled clinical trials.

Autonomic Nervous System: dry mouth, increased sweating

Body as a Whole: allergy, asthenia, hot flushes, malaise, overdose, procedure NOS*, tumor NOS*, weight decrease, weight increase

Cardiovascular: abnormal heart sounds, cardiac failure, myocardial infarction, peripheral ischemia

Central and Peripheral Nervous System: hypoesthesia, neuropathy, vertigo

Endocrine: goiter

Gastrointestinal: constipation, dysphagia, enanthema, eructation, esophagitis, gastric ulcer, gastritis, gastroenteritis, gingival bleeding, glossitis, peptic ulcer, salivary gland enlargement, tongue disorder, tooth disorder

Infection: abscess, bacterial infection, cellulitis, folliculitis, fungal infection, herpes simplex, herpes zoster, renal abscess, moniliasis, tonsillitis, viral infection

Hematologic: anemia, epistaxis, leukopenia, lymphadenopathy

Liver and Biliary System: bilirubinemia

Metabolic and Nutritional: diabetes mellitus, hyperkalemia, hyperuricemia, hypoglycemia

Musculoskeletal System: arthralgia, bone fracture, bursitis, joint dislocation, myalgia, stiffness, synovial cyst, tendon disorder

Neoplasms: breast fibroadenosis, carcinoma

Psychiatric: anxiety, confusion, decreased libido, emotional lability, impaired concentration, increased libido, nervousness, paroniria, somnolence

Reproductive (Female): breast pain, uterine hemorrhage

Respiratory System: abnormal chest sounds, bronchospasm

Skin and Appendages: abnormal pigmentation, angioedema, dermatitis, dry skin, eczema, nail disorder, pruritus, skin disorder, urticaria

Special Senses: abnormal vision, cataract, conjunctivitis, deafness, eye pain, taste perversion, tinnitus, vestibular disorder

Urinary System: abnormal urine, hematuria, increased BUN, micturition urgency, nocturia, polyuria, pyelonephritis, urinary incontinence

*NOS=Not Otherwise Specified

Psoriasis

The principal adverse reactions associated with the use of cyclosporine in patients with psoriasis are renal dysfunction, headache, hypertension, hypertriglyceridemia, hirsutism/hypertrichosis, paresthesia or hyperesthesia, influenza-like symptoms, nausea/vomiting, diarrhea, abdominal discomfort, lethargy, and musculoskeletal or joint pain.

In psoriasis patients treated in US controlled clinical studies within the recommended dose range, cyclosporine therapy was discontinued in 1.0% of the patients because of hypertension and in 5.4% of the patients because of increased creatinine. In the majority of cases, these changes were reversible after dose reduction or discontinuation of cyclosporine.

There has been one reported death associated with the use of cyclosporine in psoriasis. A 27-year-old male developed renal deterioration and was continued on cyclosporine. He had progressive renal failure leading to death.

Frequency and severity of serum creatinine increases with dose and duration of cyclosporine therapy. These elevations are likely to become more pronounced and may result in irreversible renal damage without dose reduction or discontinuation.

Adverse Events Occurring in 3% or More of Psoriasis Patients in Controlled Clinical Trials

Body System*Preferred TermCyclosporine
(MODIFIED)
(N=182)
Sandimmune®
(N=185)
Infection or Potential Infection24.7%24.3%
Influenza-Like Symptoms9.9%8.1%
Upper Respiratory Tract Infections7.7%11.3%
Cardiovascular System28.0%25.4%
Hypertension**27.5%25.4%
Urinary System24.2%16.2%
Increased Creatinine19.8%15.7%
Central and Peripheral Nervous System26.4%20.5%
Headache15.9%14.0%
Paresthesia7.1%4.8%
Musculoskeletal System13.2%8.7%
Arthralgia6.0%1.1%
Body As a Whole– General29.1%22.2%
Pain4.4%3.2%
Metabolic and Nutritional9.3%9.7%
Reproductive, Female8.5% (4 of 47 females)11.5% (6 of 52 females)
Resistance Mechanism18.7%21.1%
Skin and Appendages17.6%15.1%
Hypertrichosis6.6%5.4%
Respiratory System5.0%6.5%
Bronchospasm, Coughing, Dyspnea, Rhinitis5.0%4.9%
Psychiatric Gastrointestinal5.0%3.8%
System19.8%28.7%
Abdominal Pain2.7%6.0%
Diarrhea5.0%5.9%
Dyspepsia2.2%3.2%
Gum Hyperplasia3.8%6.0%
Nausea5.5%5.9%
White cell and RES4.4%2.7%
*Total percentage of events within the system
**Newly occurring hypertension=SBP ≥160 mm Hg and/or DBP ≥90 mm Hg

The following events occurred in 1% to less than 3% of psoriasis patients treated with cyclosporine:

Body as a Whole: fever, flushes, hot flushes

Cardiovascular: chest pain

Central and Peripheral Nervous System: appetite increased, insomnia, dizziness, nervousness, vertigo

Gastrointestinal: abdominal distention, constipation, gingival bleeding

Liver and Biliary System: hyperbilirubinemia

Neoplasms: skin malignancies [squamous cell (0.9%) and basal cell (0.4%) carcinomas]

Reticuloendothelial: platelet, bleeding, and clotting disorders, red blood cell disorder

Respiratory: infection, viral and other infection

Skin and Appendages: acne, folliculitis, keratosis, pruritus, rash, dry skin

Urinary System: micturition frequency

Vision: abnormal vision

Mild hypomagnesemia and hyperkalemia may occur but are asymptomatic. Increases in uric acid may occur and attacks of gout have been rarely reported. A minor and dose related hyperbilirubinemia has been observed in the absence of hepatocellular damage. Cyclosporine therapy may be associated with a modest increase of serum triglycerides or cholesterol. Elevations of triglycerides (>750 mg/dL) occur in about 15% of psoriasis patients; elevations of cholesterol (>300 mg/dL) are observed in less than 3% of psoriasis patients. Generally these laboratory abnormalities are reversible upon dose reduction or discontinuation of cyclosporine.

Postmarketing Experience, Psoriasis

Cases of transformation to erythrodermic psoriasis or generalized pustular psoriasis upon either withdrawal or reduction of cyclosporine in patients with chronic plaque psoriasis have been reported.

Read the entire FDA prescribing information for Gengraf Oral Solution (Cyclosporine Oral Solution)

© Gengraf Oral Solution Patient Information is supplied by Cerner Multum, Inc. and Gengraf Oral Solution Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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