Gengraf Oral Solution
Gengraf Oral Solution Side Effects Center
Medical Editor: John P. Cunha, DO, FACOEP
Gengraf Oral Solution (cyclosporine) is an immunosuppressive drug used to prevent organ rejection after a kidney, liver, or heart transplant. It is also used to treat severe psoriasis or severe rheumatoid arthritis. This medication is available in generic form. Common side effects include tremors or shaking, increased hair growth, headache or body pain, diarrhea, constipation, vomiting, numbness, or tingly feeling.
The initial dose of Gengraf varies depending on the transplanted organ and the other immunosuppressive agents included in the immunosuppressive protocol. 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. 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.
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.
What is Patient Information in Detail?
Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have a serious side effect such as:
- fever, sweating, chills, body aches, flu symptoms, sores in your mouth and throat, weight loss;
- change in your mental state, problems with speech or walking, decreased vision (may start gradually and get worse quickly);
- easy bruising or bleeding, pale skin, confusion or weakness;
- feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
- pain in the lower back or side, blood in your urine, pain or burning when you urinate;
- urinating less than usual or not at all, rapid weight gain;
- swelling, warmth, redness, or oozing of the skin;
- vomiting and bloody diarrhea;
- seizure (convulsions);
- high potassium (slow heart rate, weak pulse, muscle weakness, tingly feeling);
- nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
- dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, chest pain, shortness of breath, uneven heartbeats).
Less serious side effects may include:
- swollen or painful gums;
- mild headache;
- stomach pain, constipation, mild diarrhea; or
- tremors or shaking, muscle spasm, numbness or tingly feeling.
Read the entire detailed patient monograph for Gengraf Oral Solution (Cyclosporine Oral Solution) »
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Gengraf Oral Solution FDA Prescribing Information: Side Effects
Kidney, Liver, and Heart Transplantation
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 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 include 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 has been reported in some, but not all, patients exhibiting convulsions while on cyclosporine therapy. Although magnesium-depletion 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.
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 System||Adverse Reactions||Randomized Kidney Patients||Cyclosporine Patients Sandimmune®|
|Cramps||4||< 1||2||< 1||0|
|Central Nervous System||Tremor||12||0||21||31||55|
|Hepatotoxicity||< 1||< 1||4||7||4|
|Abdominal Discomfort||< 1||0||< 1||7||0|
|Autonomic Nervous System||Paresthesia||3||0||1||2||1|
|Miscellaneous||Gynecomastia||< 1||0||< 1||4||3|
Among 705 kidney transplant patients treated with cyclosporine oral solution 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 Sandimmune®-treated patients: allergic reactions, anemia, anorexia, confusion, conjunctivitis, edema, fever, brittle fingernails, gastritis, hearing loss, hiccups, hyperglycemia, 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.
Infectious Complications in Historical Randomized Studies in Renal Transplant Patients Using Sandimmune®
|Azathioprine with Steroids*
|Systemic Fungal Infection||2.2||3.9|
|Local Fungal Infection||7.5||9.6|
|Other Viral Infections||15.9||18.4|
|Urinary Tract Infections||21.1||20.2|
|Wound and Skin Infections||7.0||10.1|
|* Some patients also received ALG.|
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) /Sandimune® Rheumatoid Arthritis Percentage of Patients with Adverse Events ≥ 3% in any
Cyclosporine Treated Group
|Body System||Preferred Term||Studies
|Study 302||Study 654||Study 654||Study 302||Studies
|Autonomic Nervous System Disorders|
|Body As A Whole - General Disorders|
|Edema NOS*||5%||14%||12%||4%||10%||< 1%|
|Influenza-like symptoms||< 1%||6%||1%||0%||3%||2%|
|Central and Peripheral Nervous System Disorders|
|Gastrointestinal System Disorders|
|Gastrointestinal Disorder NOS*||0%||2%||1%||4%||4%||0%|
|Hearing and Vestibular Disorders|
|Ear Disorders NOS*||0%||5%||0%||0%||1%||0%|
|Metabolic and Nutritional Disorders|
|Musculoskeletal System Disorders|
|Leg Cramps/Involuntary Muscle Contractions||2%||11%||11%||3%||12%||1%|
|Creatinine elevations ≥ 30%||43%||39%||55%||19%||48%||13%|
|Creatinine elevations ≥ 50%||24%||18%||26%||8%||18%||3%|
|Reproductive Disorders, Female|
|Respiratory System Disorders|
|Upper Respiratory Tract||0%||14%||23%||15%||13%||0%|
|Skin and Appendages Disorders|
|Urinary System Disorders|
|Urinary Tract Infection||0%||3%||5%||4%||3%||0%|
|Vascular (Extracardiac) Disorders|
|† 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;
Cardiovascular:abnormal heart sounds, cardiac failure, myocardial infarction, peripheral ischemia;
Gastrointestinal: constipation, dysphagia, enanthema, eructation, esophagitis, gastric ulcer, gastritis, gastroenteritus, gingival bleeding, glossitis, peptic ulcer, salivary gland enlargement, tongue disorder, tooth disorder;
Liver and Biliary System: bilirubinemia;
Neoplasms: breast fibroadenosis, carcinoma;
Reproductive (Female): breast pain, uterine hemorrhage;
Respiratory System: abnormal chest sounds, bronchospasm;
*NOS = Not Otherwise Specified.
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, influenzalike symptoms, nausea/vomiting, diarrhea, abdominal discomfort, lethargy, and musculoskeletal or joint pain.
In psoriasis patients treated in U.S. 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 Term||Cyclosporine (MODIFIED)
|Infection or Potential Infection||24.7%||24.3%|
|Upper Respiratory Tract Infections||7.7%||11.3%|
|Central and Peripheral Nervous System||26.4%||20.5%|
|Body As a Whole - General||29.1%||22.2%|
|Metabolic and Nutritional||9.3%||9.7%|
|Reproductive, Female||8.5% (4 of 47 females)||11.5% (6 of 52 females)|
|Skin and Appendages||17.6%||15.1%|
|Bronchospasm, Coughing, Dyspnea, Rhinitis||5.0%||4.9%|
|White cell and RES||4.4%||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.
Read the entire FDA prescribing information for Gengraf Oral Solution (Cyclosporine Oral Solution) »
Additional Gengraf Oral Solution Information
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