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Side Effects > Gengraf

Gengraf Side Effects

Generic Name: Cyclosporine

Please note - some side effects for Gengraf may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).


For the consumer

For the professional

Side Effects of Gengraf - for the consumer


Gengraf

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Gengraf:

Acne; burning sensation; coughing; dizziness; flushing; increased hair growth; headache; nausea; runny nose; sleeplessness; stomach discomfort; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Gengraf:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); black, tarry stool; blood in the urine; chest pain; chills; confusion; dark urine; diarrhea; fast or irregular heartbeat; fever; gum disease or overgrowth; increased or decreased urination; infection; loss of coordination; mental or mood changes; muscle cramps; numbness or tingling of the skin; seizures; severe or persistent headache or dizziness; shortness of breath; sore throat; tremors; unusual bleeding or bruising; unusual lumps; unusual thickening or lesion of the skin; unusual tiredness or weakness; vision changes; wheezing; yellowing of the skin or eyes.


Gengraf Solution

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Gengraf Solution:

Acne; burning sensation; coughing; dizziness; flushing; increased hair growth; headache; nausea; runny nose; sleeplessness; stomach discomfort; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Gengraf Solution:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); black, tarry stool; blood in the urine; chest pain; chills; confusion; dark urine; diarrhea; fast or irregular heartbeat; fever; gum disease or overgrowth; increased or decreased urination; infection; loss of coordination; mental or mood changes; muscle cramps; numbness or tingling of the skin; seizures; severe or persistent headache or dizziness; shortness of breath; sore throat; tremors; unusual bleeding or bruising; unusual lumps; unusual thickening or lesion of the skin; unusual tiredness or weakness; vision changes; wheezing; yellowing of the skin or eyes.

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For the professional


Gengraf

Kidney, Liver, and Heart Transplantation

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

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.

Randomized Kidney Patients Cyclosporine Patients
Sandimmune®
Body System Adverse Reactions
Sandimmune®
(N = 227) %
Azathioprine
(N = 228) %
Kidney
(N = 705) %
Heart
(N = 112) %
Liver
(N = 75) %
Genitourinary
Renal Dysfunction 32 6 25 38 37
Cardiovascular
Hypertension 26 18 13 53 27
Cramps 4 < 1 2 < 1 0
Skin
Hirsutism 21 < 1 21 28 45
Acne 6 8 2 2 1
Central Nervous System
Tremor 12 0 21 31 55
Convulsions 3 1 1 4 5
Headache 2 <1 2 15 4
Gastrointestinal
Gum Hyperplasia 4 0 9 5 16
Diarrhea 3 < 1 3 4 8
Nausea/Vomiting 2 < 1 4 10 4
Hepatotoxicity < 1 < 1 4 7 4
Abdominal Discomfort < 1 0 <1 7 0
Autonomic Nervous System
Paresthesia 3 0 1 2 1
Flushing < 1 0 4 0 4
Hematopoietic
Leukopenia 2 19 < 1 6 0
Lymphoma < 1 0 1 6 1
Respiratory
Sinusitis < 1 0 4 3 7
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®
Complication Cyclosporine Treatment
(N = 227)
% of Complications
Azathioprine with Steroids*
(N = 228)
% of Complications

* Some patients also received ALG.

Septicemia 5.3 4.8
Abscesses 4.4 5.3
Systemic Fungal Infection 2.2 3.9
Local Fungal Infection 7.5 9.6
Cytomegalovirus 4.8 12.3
Other Viral Infections 15.9 18.4
Urinary Tract Infections 21.1 20.2
Wound and Skin Infections 7.0 10.1
Pneumonia 6.2 9.2

Rheumatoid Arthritis

The principal adverse reactions associated with the use of cyclosporine in rheumatoid arthritis are renal dysfunction, hypertension, 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
Studies
651+652+2008
Study
302
Study
654
Study
654
Study
302
Studies
651+652
+2008
Body
System
Preferred Term Sandimmune®
(N = 269)
Sandimmune®
(N = 155)
Methotrexate
& Sandimmune®

(N = 74)
Methotrexate
& Placebo
(N = 73)
Cyclosporine
(MODIFIED)
(N = 143)
Placebo
(N = 201)

† Includes patients in 2.5 mg/kg/day dose group only.

* NOS = Not Otherwise Specified.

Autonomic Nervous System Disorders
Flushing 2% 2% 3% 0% 5% 2%
Body As A Whole - General Disorders
Accidental Trauma 0% 1% 10% 4% 4% 0%
Edema NOS* 5% 14% 12% 4% 10% < 1%
Fatigue 6% 3% 8% 12% 3% 7%
Fever 2% 3% 0% 0% 2% 4%
Influenza-like symptoms < 1% 6% 1% 0% 3% 2%
Pain 6% 9% 10% 15% 13% 4%
Rigors 1% 1% 4% 0% 3% 1%
Cardiovascular Disorders
Arrhythmia 2% 5% 5% 6% 2% 1%
Chest Pain 4% 5% 1% 1% 6% 1%
Hypertension 8% 26% 16% 12% 25% 2%
Central and Peripheral Nervous System Disorders
Dizziness 8% 6% 7% 3% 8% 3%
Headache 17% 23% 22% 11% 25% 9%
Migraine 2% 3% 0% 0% 3% 1%
Paresthesia 8% 7% 8% 4% 11% 1%
Tremor 8% 7% 7% 3% 13% 4%
Gastrointestinal System Disorders
Abdominal Pain 15% 15% 15% 7% 15% 10%
Anorexia 3% 3% 1% 0% 3% 3%
Diarrhea 12% 12% 18% 15% 13% 8%
Dyspepsia 12% 12% 10% 8% 8% 4%
Flatulence 5% 5% 5% 4% 4% 1%
Gastrointestinal Disorder NOS* 0% 2% 1% 4% 4% 0%
Gingivitis 4% 3% 0% 0% 0% 1%
Gum Hyperplasia 2% 4% 1% 3% 4% 1%
Nausea 23% 14% 24% 15% 18% 14%
Rectal Hemorrhage 0% 3% 0% 0% 1% 1%
Stomatitis 7% 5% 16% 12% 6% 8%
Vomiting 9% 8% 14% 7% 6% 5%
Hearing and Vestibular Disorders
Ear Disorders NOS* 0% 5% 0% 0% 1% 0%
Metabolic and Nutritional Disorders
Hypomagnesemia 0% 4% 0% 0% 6% 0%
Musculoskeletal System Disorders
Arthropathy 0% 5% 0% 1% 4% 0%
Leg Cramps/Involuntary Muscle Contractions 2% 11% 11% 3% 12% 1%
Psychiatric Disorders
Depression 3% 6% 3% 1% 1% 2%
Insomnia 4% 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 1% 0% 4% 0% 1% 0%
Menstrual Disorder 3% 2% 1% 0% 1% 1%
Respiratory System Disorders
Bronchitis 1% 3% 1% 0% 1% 3%
Coughing 5% 3% 5% 7% 4% 4%
Dyspnea 5% 1% 3% 3% 1% 2%
Infection NOS* 9% 5% 0% 7% 3% 10%
Pharyngitis 3% 5% 5% 6% 4% 4%
Pneumonia 1% 0% 4% 0% 1% 1%
Rhinitis 0% 3% 11% 10% 1% 0%
Sinusitis 4% 4% 8% 4% 3% 3%
Upper Respiratory Tract 0% 14% 23% 15% 13% 0%
Skin and Appendages Disorders
Alopecia 3% 0% 1% 1% 4% 4%
Bullous Eruption 1% 0% 4% 1% 1% 1%
Hypertrichosis 19% 17% 12% 0% 15% 3%
Rash 7% 12% 10% 7% 8% 10%
Skin Ulceration 1% 1% 3% 4% 0% 2%
Urinary System Disorders
Dysuria 0% 0% 11% 3% 1% 2%
Micturition Frequency 2% 4% 3% 1% 2% 2%
NPN, Increased 0% 19% 12% 0% 18% 0%
Urinary Tract Infection 0% 3% 5% 4% 3% 0%
Vascular (Extracardiac) Disorders
Purpura 3% 4% 1% 1% 2% 0%

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 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)
(N = 182)
Cyclosporine
(N = 185)

* Total percentage of events within the system.

** Newly occurring hypertension = SBP≥ 160 mm Hg and/or DBP ≥ 90 mm Hg.

Infection or Potential Infection 24.7% 24.3%
Influenza-like Symptoms 9.9% 8.1%
Upper Respiratory Tract Infections 7.7% 11.3%
Cardiovascular System 28.0% 25.4%
Hypertension** 27.5% 25.4%
Urinary System 24.2% 16.2%
Increased Creatinine 19.8% 15.7%
Central and Peripheral Nervous System 26.4% 20.5%
Headache 15.9% 14.0%
Paresthesia 7.1% 4.8%
Musculoskeletal System 13.2% 8.7%
Arthralgia 6.0% 1.1%
Body As a Whole – General 29.1% 22.2%
Pain 4.4% 3.2%
Metabolic and Nutritional 9.3% 9.7%
Reproductive, Female 8.5% (4 of 47 females) 11.5% (6 of 52 females)
Resistance Mechanism 18.7% 21.1%
Skin and Appendages 17.6% 15.1%
Hypertrichosis 6.6% 5.4%
Respiratory System 5.0% 6.5%
Bronchospasm, Coughing, Dyspnea, Rhinitis 5.0% 4.9%
Psychiatric 5.0% 3.8%
Gastrointestinal System 19.8% 28.7%
Abdominal Pain 2.7% 6.0%
Diarrhea 5.0% 5.9%
Dyspepsia 2.2% 3.2%
Gum Hyperplasia 3.8% 6.0%
Nausea 5.5% 5.9%
White cell and RES 4.4% 2.7%

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.

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Gengraf Capsules

Kidney, Liver, and Heart Transplantation

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

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® (cyclosporine capsules) 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.

Randomized Kidney Patients Cyclosporine Patients
(Sandimmune® )
Body System Adverse Reactions
Sandimmune®
(N = 227) %
Azathioprine
(N = 228) %
Kidney
(N = 705) %
Heart
(N = 112) %
Liver
(N = 75) %
Genitourinary
Renal Dysfunction 32 6 25 38 37
Cardiovascular
Hypertension 26 18 13 53 27
Cramps 4 < 1 2 < 1 0
Skin
Hirsutism 21 < 1 21 28 45
Acne 6 8 2 2 1
Central Nervous System
Tremor 12 0 21 31 55
Convulsions 3 1 1 4 5
Headache 2 <1 2 15 4
Gastrointestinal
Gum Hyperplasia 4 0 9 5 16
Diarrhea 3 < 1 3 4 8
Nausea/Vomiting 2 < 1 4 10 4
Hepatotoxicity < 1 < 1 4 7 4
Abdominal Discomfort < 1 0 <1 7 0
Autonomic Nervous System
Paresthesia 3 0 1 2 1
Flushing < 1 0 4 0 4
Hematopoietic
Leukopenia 2 19 < 1 6 0
Lymphoma < 1 0 1 6 1
Respiratory
Sinusitis < 1 0 4 3 7
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®
Complication Cyclosporine Treatment
(N = 227)
% of Complications
Azathioprine with Steroids*
(N = 228)
% of Complications

* Some patients also received ALG.

Septicemia 5.3 4.8
Abscesses 4.4 5.3
Systemic Fungal Infection 2.2 3.9
Local Fungal Infection 7.5 9.6
Cytomegalovirus 4.8 12.3
Other Viral Infections 15.9 18.4
Urinary Tract Infections 21.1 20.2
Wound and Skin Infections 7.0 10.1
Pneumonia 6.2 9.2

Rheumatoid Arthritis

The principal adverse reactions associated with the use of cyclosporine in rheumatoid arthritis are renal dysfunction, hypertension, 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
Studies
651+652+2008
Study
302
Study
654
Study
654
Study
302
Studies
651+652
+2008
Body
System
Preferred Term Sandimmune®
(N = 269)
Sandimmune®
(N = 155)
Methotrexate
& Sandimmune®
(N = 74)
Methotrexate
& Placebo
(N = 73)
Cyclosporine
(MODIFIED)
(N = 143)
Placebo
(N = 201)

† Includes patients in 2.5 mg/kg/day dose group only.

* NOS = Not Otherwise Specified.

Autonomic Nervous System Disorders
Flushing 2% 2% 3% 0% 5% 2%
Body As A Whole - General Disorders
Accidental Trauma 0% 1% 10% 4% 4% 0%
Edema NOS* 5% 14% 12% 4% 10% < 1%
Fatigue 6% 3% 8% 12% 3% 7%
Fever 2% 3% 0% 0% 2% 4%
Influenza-like symptoms < 1% 6% 1% 0% 3% 2%
Pain 6% 9% 10% 15% 13% 4%
Rigors 1% 1% 4% 0% 3% 1%
Cardiovascular Disorders
Arrhythmia 2% 5% 5% 6% 2% 1%
Chest Pain 4% 5% 1% 1% 6% 1%
Hypertension 8% 26% 16% 12% 25% 2%
Central and Peripheral Nervous System Disorders
Dizziness 8% 6% 7% 3% 8% 3%
Headache 17% 23% 22% 11% 25% 9%
Migraine 2% 3% 0% 0% 3% 1%
Paresthesia 8% 7% 8% 4% 11% 1%
Tremor 8% 7% 7% 3% 13% 4%
Gastrointestinal System Disorders
Abdominal Pain 15% 15% 15% 7% 15% 10%
Anorexia 3% 3% 1% 0% 3% 3%
Diarrhea 12% 12% 18% 15% 13% 8%
Dyspepsia 12% 12% 10% 8% 8% 4%
Flatulence 5% 5% 5% 4% 4% 1%
Gastrointestinal Disorder NOS* 0% 2% 1% 4% 4% 0%
Gingivitis 4% 3% 0% 0% 0% 1%
Gum Hyperplasia 2% 4% 1% 3% 4% 1%
Nausea 23% 14% 24% 15% 18% 14%
Rectal Hemorrhage 0% 3% 0% 0% 1% 1%
Stomatitis 7% 5% 16% 12% 6% 8%
Vomiting 9% 8% 14% 7% 6% 5%
Hearing and Vestibular Disorders
Ear Disorders NOS* 0% 5% 0% 0% 1% 0%
Metabolic and Nutritional Disorders
Hypomagnesemia 0% 4% 0% 0% 6% 0%
Musculoskeletal System Disorders
Arthropathy 0% 5% 0% 1% 4% 0%
Leg Cramps/ Involuntary Muscle Contractions 2% 11% 11% 3% 12% 1%
Psychiatric Disorders
Depression 3% 6% 3% 1% 1% 2%
Insomnia 4% 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 1% 0% 4% 0% 1% 0%
Menstrual Disorder 3% 2% 1% 0% 1% 1%
Respiratory System Disorders
Bronchitis 1% 3% 1% 0% 1% 3%
Coughing 5% 3% 5% 7% 4% 4%
Dyspnea 5% 1% 3% 3% 1% 2%
Infection NOS* 9% 5% 0% 7% 3% 10%
Pharyngitis 3% 5% 5% 6% 4% 4%
Pneumonia 1% 0% 4% 0% 1% 1%
Rhinitis 0% 3% 11% 10% 1% 0%
Sinusitis 4% 4% 8% 4% 3% 3%
Upper Respiratory Tract 0% 14% 23% 15% 13% 0%
Skin and Appendages Disorders
Alopecia 3% 0% 1% 1% 4% 4%
Bullous Eruption 1% 0% 4% 1% 1% 1%
Hypertrichosis 19% 17% 12% 0% 15% 3%
Rash 7% 12% 10% 7% 8% 10%
Skin Ulceration 1% 1% 3% 4% 0% 2%
Urinary System Disorders
Dysuria 0% 0% 11% 3% 1% 2%
Micturition Frequency 2% 4% 3% 1% 2% 2%
NPN, Increased 0% 19% 12% 0% 18% 0%
Urinary Tract Infection 0% 3% 5% 4% 3% 0%
Vascular (Extracardiac) Disorders
Purpura 3% 4% 1% 1% 2% 0%

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 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)
(N = 182)
Sandimmune®
(N = 185)

* Total percentage of events within the system.

** Newly occurring hypertension = SBP≥160 mm Hg and/or DBP ≥90 mm Hg.

Infection or Potential Infection 24.7% 24.3%
Influenza-like Symptoms 9.9% 8.1%
Upper Respiratory Tract Infections 7.7% 11.3%
Cardiovascular System 28.0% 25.4%
Hypertension** 27.5% 25.4%
Urinary System 24.2% 16.2%
Increased Creatinine 19.8% 15.7%
Central and Peripheral Nervous System 26.4% 20.5%
Headache 15.9% 14.0%
Paresthesia 7.1% 4.8%
Musculoskeletal System 13.2% 8.7%
Arthralgia 6.0% 1.1%
Body As a Whole – General 29.1% 22.2%
Pain 4.4% 3.2%
Metabolic and Nutritional 9.3% 9.7%
Reproductive, Female 8.5% (4 of 47 females) 11.5% (6 of 52 females)
Resistance Mechanism 18.7% 21.1%
Skin and Appendages 17.6% 15.1%
Hypertrichosis 6.6% 5.4%
Respiratory System 5.0% 6.5%
Bronchospasm, Coughing, Dyspnea, Rhinitis 5.0% 4.9%
Psychiatric 5.0% 3.8%
Gastrointestinal System 19.8% 28.7%
Abdominal Pain 2.7% 6.0%
Diarrhea 5.0% 5.9%
Dyspepsia 2.2% 3.2%
Gum Hyperplasia 3.8% 6.0%
Nausea 5.5% 5.9%
White cell and RES 4.4% 2.7%

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.

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More resources:

Cerner Multum Gengraf

PDR Neoral

PDR Cyclosporine

MedFacts Cyclosporine

MedFacts Gengraf

Micromedex Cyclosporine - Includes detailed dosage instructions.

Micromedex Neoral - Includes detailed dosage instructions.

FDA Sandimmune

FDA Neoral

FDA Cyclosporine

FDA Gengraf

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