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Cytovene (Ganciclovir) - Side Effects and Adverse Reactions

 
 



ADVERSE EVENTS

Adverse events that occurred during clinical trials of CYTOVENE-IV solution and CYTOVENE capsules are summarized below, according to the participating study subject population.

Subjects With AIDS:    Three controlled, randomized, phase 3 trials comparing CYTOVENE-IV and CYTOVENE capsules for maintenance treatment of CMV retinitis have been completed. During these trials, CYTOVENE-IV or CYTOVENE capsules were prematurely discontinued in 9% of subjects because of adverse events. In a placebo-controlled, randomized, phase 3 trial of CYTOVENE capsules for prevention of CMV disease in AIDS, treatment was prematurely discontinued because of adverse events, new or worsening intercurrent illness, or laboratory abnormalities in 19.5% of subjects treated with CYTOVENE capsules and 16% of subjects receiving placebo. Laboratory data and adverse events reported during the conduct of these controlled trials are summarized below.

Laboratory Data:
Selected Laboratory Abnormalities in Trials for
Treatment of CMV Retinitis and Prevention of CMV Diseases
  CMV Retinitis Treatment * CMV Disease Prevention §
Treatment CYTOVENE
Capsules #
3000 mg/day
  
CYTOVENE-IV &
5 mg/kg/day
CYTOVENE
Capsules ll
3000 mg/day
  
Placebo ¶
Subjects, number 320 175 478 234
Neutropenia:
 <500 ANC/µL
18% 25% 10% 6%
  500 - <749 17% 14% 16% 7%
  750 - <1000 19% 26% 22% 16%
Anemia:
Hemoglobin:
 <6.5 g/dL
2% 5% 1% <1%
  6.5 - <8.0 10% 16% 5% 3%
  8.0 - <9.5 25% 26% 15% 16%
Maximum Serum Creatinine:
 >/=2.5 mg/dL
1% 2% 1% 2%
 >/=1.5 - <2.5 12% 14% 19% 11%
* Pooled data from Treatment Studies, ICM 1653. Study ICM 1774 and Study AVI 034
# Mean time on therapy = 91 days, including allowed reinduction treatment periods
& Mean time on therapy = 103 days, including allowed reinduction treatment periods
§ Data from Prevention Study, ICM 1654
ll Mean time on ganciclovir = 269 days
¶ Mean time on placebo = 240 days
(See discussion of clinical trials under INDICATIONS AND USAGE.)

Adverse Events:    The following table shows selected adverse events reported in 5% or more of the subjects in three controlled clinical trials during treatment with either CYTOVENE-IV solution (5 mg/kg/day) or CYTOVENE capsules (3000 mg/day), and in one controlled clinical trial in which CYTOVENE capsules (3000 mg/day) were compared to placebo for the prevention of CMV disease.

Selected Adverse Events Reported >/=5% of Subjects
in Three Randomized Phase 3 Studies Comparing CYTOVENE Capsules to
CYTOVENE-IV Solution for Maintenance Treatment of CMV Retinitis
and in One Phase 3 Randomized Study Comparing Cytovene Capsules to Placebo for Prevention of CMV Disease
    Maintenance Treatment
Studies
Prevention Study
Body System Adverse Event Capsules
(n=326)
IV
(n=179)
Capsules
(n=478)
Placebo
(n=234)
Body as a Whole Fever 38% 48% 35% 33%
Infection 9% 13% 8% 4%
Chills 7% 10% 7% 4%
Sepsis 4% 15% 3% 2%
Digestive System Diarrhea 41% 44% 48% 42%
Anorexia 15% 14% 19% 16%
Vomiting 13% 13% 14% 11%
Hemic and Lymphatic System Leukopenia 29% 41% 17% 9%
Anemia 19% 25% 9% 7%
Thrombocytopenia 6% 6% 3% 1%
Nervous System Neuropathy 8% 9% 21% 15%
Other Sweating 11% 12% 14% 12%
Pruritus 6% 5% 10% 9%
Catheter Related * Total Catheter Events 6% 22% - -
  Catheter Infection 4% 9% - -
  Catheter Sepsis 1% 8% - -
* Some of these events also appear under other body systems.

The following events were frequently observed in clinical trials but occurred with equal or greater frequency in placebo-treated subjects: abdominal pain, nausea, flatulence, pneumonia, paresthesia, rash.

Retinal Detachment:    Retinal detachment has been observed in subjects with CMV retinitis both before and after initiation of therapy with ganciclovir. Its relationship to therapy with ganciclovir is unknown. Retinal detachment occurred in 11% of patients treated with CYTOVENE-IV solution and in 8% of patients treated with CYTOVENE capsules. Patients with CMV retinitis should have frequent ophthalmologic evaluations to monitor the status of their retinitis and to detect any other retinal pathology.

Transplant Recipients:    There have been three controlled clinical trials of CYTOVENE-IV solution and one controlled clinical trial of CYTOVENE capsules for the prevention of CMV disease in transplant recipients. Laboratory data and adverse events reported during these trials are summarized below.

Laboratory Data:   The following table shows the frequency of granulocytopenia (neutropenia) and thrombocytopenia observed:

Controlled Trials - Transplant Recipients
  CYTOVENE-IV CYTOVENE Capsules
  Heart Allograft * Bone Marrow Allograft # Liver Allograft &
  CYTOVENE-IV
  
(n=76)
Placebo
  
(n=73)
CYTOVENE-IV
  
(n=57)
Control
  
(n=55)
CYTOVENE
Capsules
(n=150)
Placebo
  
(n=154)
Neutropenia            
Minimum ANC
 <500/µL
4% 3% 12% 6% 3% 1%
Minimum ANC
  500-1000/µL
3% 8% 29% 17% 3% 2%
TOTAL ANC
 </=1000/µL
7% 11% 41% 23% 6% 3%
Thrombocytopenia            
Platelet count
 <25,000/µL
3% 1% 32% 28% 0% 3%
Platelet count
  25,000-50,000/µL
5% 3% 25% 37% 5% 3%
TOTAL Platelet
 </=50,000/µL
8% 4% 57% 65% 5% 6%
*Study ICM 1496. Mean duration of treatment = 28 days
# Study ICM 1570 and ICM 1689. Mean duration of treatment = 45 days
& Study GAN040. Mean duration of ganciclovir treatment = 82 days
(See discussion of clinical trials under INDICATIONS AND USAGE.)

The following table shows the frequency of elevated serum creatinine values in these controlled clinical trials:

Controlled Trials - Transplant Recipients
  CYTOVENE-IV CYTOVENE Capsules
  Heart Allograft
ICM 1496
Bone Marrow Allograft
ICM 1570
Bone Marrow Allograft
ICM 1689
Liver Allograft
Study 040
Maximum
  Serum
  Creatinine
  Levels
  
CYTOVENE-IV
  
(n=76)
  
Placebo
  
(n=73)
  
CYTOVENE-IV
  
(n=20)
  
Control
  
(n=20)
  
CYTOVENE-IV
  
(n=37)
  
Placebo
  
(n=35)
  
CYTOVENE
Capsules
(n=150)
  
Placebo
  
(n=154)
Serum
  Creatinine
 >/=2.5 mg/dL
18% 4% 20% 0% 0% 0% 16% 10%
Serum
  Creatinine
 >/=1.5 -<2.5 mg/dL
58% 69% 50% 35% 43% 44% 39% 42%

In 3 out of 4 trials, patients receiving either CYTOVENE-IV solution or CYTOVENE capsules had elevated serum creatinine levels when compared to those receiving placebo. Most patients in these studies also received cyclosporine. The mechanism of impairment of renal function is not known. However, careful monitoring of renal function during therapy with CYTOVENE-IV solution or CYTOVENE capsules is essential, especially for those patients receiving concomitant agents that may cause nephrotoxicity.

General:    Other adverse events that were thought to be "probably" or "possibly" related to CYTOVENE-IV solution or CYTOVENE capsules in controlled clinical studies in either subjects with AIDS or transplant recipients are listed below. These events all occurred in at least 3 subjects.

Body as a Whole:    abdomen enlarged, asthenia, chest pain, edema, headache, injection site inflammation, malaise, pain

Digestive System:    abnormal liver function test, aphthous stomatitis, constipation, dyspepsia, eructation

Hemic and Lymphatic System:    pancytopenia

Respiratory System:    cough increased, dyspnea

Nervous System:    abnormal dreams, anxiety, confusion, depression, dizziness, dry mouth, insomnia, seizures, somnolence, thinking abnormal, tremor

Skin and Appendages:    alopecia, dry skin

Special Senses:    abnormal vision, taste perversion, tinnitus, vitreous disorder

Metabolic and Nutritional Disorders:    creatinine increased, SGOT increased, SGPT increased, weight loss

Cardiovascular System:    hypertension, phlebitis, vasodilatation

Urogenital System:    creatinine clearance decreased, kidney failure, kidney function abnormal, urinary frequency

Musculoskeletal System:    arthralgia, leg cramps, myalgia, myasthenia

The following adverse events reported in patients receiving ganciclovir may be potentially fatal: gastrointestinal perforation, multiple organ failure, pancreatitis and sepsis.

Adverse Events Reported During Postmarketing Experience With CYTOVENE-IV and CYTOVENE Capsules: The following events have been identified during post-approval use of the drug. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either the seriousness, frequency of reporting, the apparent causal connection or a combination of these factors:

acidosis, allergic reaction, anaphylactic reaction, arthritis, bronchospasm, cardiac arrest, cardiac conduction abnormality, cataracts, cholelithiasis, cholestasis, congenital anomaly, dry eyes, dysesthesia, dysphasia, elevated triglyceride levels, encephalopathy, exfoliative dermatitis, extrapyramidal reaction, facial palsy, hallucinations, hemolytic anemia, hemolytic uremic syndrome, hepatic failure, hepatitis, hypercalcemia, hyponatremia, inappropriate serum ADH, infertility, intestinal ulceration, intracranial hypertension, irritability, loss of memory, loss of sense of smell, myelopathy, oculomotor nerve paralysis, peripheral ischemia, pulmonary fibrosis, renal tubular disorder, rhabdomyolysis, Stevens-Johnson syndrome, stroke, testicular hypotrophy, Torsades de Pointes, vasculitis, ventricular tachycardia



REPORTS OF SUSPECTED CYTOVENE SIDE EFFECTS / ADVERSE REACTIONS

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

Possible Cytovene side effects / adverse reactions in 8 year old female

Reported by a physician from United States on 2012-04-05

Patient: 8 year old female

Reactions: Hepatic Function Abnormal, Cholangitis Sclerosing, Diarrhoea, Cytomegalovirus Chorioretinitis, BK Virus Infection, Treatment Failure, Device Occlusion

Suspect drug(s):
Valcyte
    Indication: Cytomegalovirus Chorioretinitis

Cytovene
    Indication: Cytomegalovirus Chorioretinitis



See index of all Cytovene side effect reports >>

Drug label data at the top of this Page last updated: 2006-02-26

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