INDICATIONS
AND USAGE: CYTOVENE-IV is indicated for the treatment
of CMV retinitis in immunocompromised patients, including
patients with acquired immunodeficiency syndrome (AIDS).
CYTOVENE-IV is also indicated for the prevention of CMV
disease in transplant recipients at risk for CMV disease
(see CLINICAL TRIALS).
CYTOVENE capsules are indicated for the prevention of
CMV disease in solid organ transplant recipients and in
individuals with advanced HIV infection at risk for developing
CMV disease. CYTOVENE capsules are also indicated as an
alternative to the intravenous formulation for maintenance
treatment of CMV retinitis in immunocompromised patients,
including patients with AIDS, in whom retinitis is stable
following appropriate induction therapy and for whom the
risk of more rapid progression is balanced by the benefit
associated with avoiding daily IV infusions (see CLINICAL
TRIALS).
SAFETY AND EFFICACY OF CYTOVENE-IV AND CYTOVENE HAVE
NOT BEEN ESTABLISHED FOR CONGENITAL OR NEONATAL CMV DISEASE;
NOR FOR THE TREATMENT OF ESTABLISHED CMV DISEASE OTHER
THAN RETINITIS; NOR FOR USE IN NON-IMMUNOCOMPROMISED INDIVIDUALS.
THE SAFETY AND EFFICACY OF CYTOVENE CAPSULES HAVE NOT
BEEN ESTABLISHED FOR TREATING ANY MANIFESTATION OF CMV
DISEASE OTHER THAN MAINTENANCE TREATMENT OF CMV RETINITIS.
CLINICAL TRIALS:
1. Treatment of CMV Retinitis
The diagnosis of CMV retinitis should be made by indirect
ophthalmoscopy. Other conditions in the differential diagnosis
of CMV retinitis include candidiasis, toxoplasmosis, histoplasmosis,
retinal scars and cotton wool spots, any of which may
produce a retinal appearance similar to CMV. For this
reason it is essential that the diagnosis of CMV be established
by an ophthalmologist familiar with the retinal presentation
of these conditions. The diagnosis of CMV retinitis may
be supported by culture of CMV from urine, blood, throat
or other sites, but a negative CMV culture does not rule
out CMV retinitis.
Studies With CYTOVENE-IV: In
a retrospective, non-randomized, single-center analysis
of 41 patients with AIDS and CMV retinitis diagnosed by
ophthalmologic examination between August 1983 and April
1988, treatment with CYTOVENE-IV solution resulted in
a significant delay in mean (median) time to first retinitis
progression compared to untreated controls [105 (71) days
from diagnosis vs 35 (29) days from diagnosis]. Patients
in this series received induction treatment of CYTOVENE-IV
5 mg/kg bid for 14 to 21 days followed by maintenance
treatment with either 5 mg/kg once daily, 7 days per week
or 6 mg/kg once daily, 5 days per week (see DOSAGE AND
ADMINISTRATION).
In a controlled, randomized study conducted between February
1989 and December 1990,1 immediate treatment with CYTOVENE-IV
was compared to delayed treatment in 42 patients with
AIDS and peripheral CMV retinitis; 35 of 42 patients (13
in the immediate-treatment group and 22 in the delayed-treatment
group) were included in the analysis of time to retinitis
progression. Based on masked assessment of fundus photographs,
the mean [95% CI] and median [95% CI] times to progression
of retinitis were 66 days [39, 94] and 50 days [40, 84],
respectively, in the immediate-treatment group compared
to 19 days [11, 27] and 13.5 days [8, 18], respectively,
in the delayed-treatment group.
Studies Comparing CYTOVENE Capsules to CYTOVENE-IV:
|
Population
Characteristics in Studies ICM 1653, ICM 1774 and
AVI 034 |
| |
ICM
1653
(n=121) |
ICM
1774
(n=225) |
AVI
034
(n=159) |
Median
age (years)
Range |
38
24-62 |
37
22-56 |
39
23-62 |
| Sex |
Males |
116
(96%) |
222
(99%) |
148
(93%) |
| Females |
5
(4%) |
3
(1%) |
10
(6%) |
| Ethnicity |
Asian |
3
(3%) |
5
(2%) |
7
(4%) |
| Black |
11
(9%) |
9
(4%) |
3
(2%) |
| Caucasian |
98
(81%) |
186
(83%) |
140
(88%) |
| Other |
9
(7%) |
25
(11%) |
8
(5%) |
Median
CD4 Count
Range |
9.5
0-141 |
7.0
0-80 |
10.0
0-320 |
Mean
(SD)
Observation Time (days) |
107.9 (43.0) |
97.6 (42.5) |
80.9 (47.0) |
ICM 1653: In this randomized, open-label, parallel group
trial, conducted between March 1991 and November 1992, patients
with AIDS and newly diagnosed CMV retinitis received a 3-week
induction course of CYTOVENE-IV solution, 5 mg/kg bid for
14 days followed by 5 mg/kg once daily for 1 additional
week.2 Following the 21-day intravenous induction course,
patients with stable CMV retinitis were randomized to receive
20 weeks of maintenance treatment with either CYTOVENE-IV
solution, 5 mg/kg once daily, or CYTOVENE capsules, 500
mg 6 times daily (3000 mg/day). The study showed that the
mean [95% CI] and median [95% CI] times to progression of
CMV retinitis, as assessed by masked reading of fundus photographs,
were 57 days [44, 70] and 29 days [28, 43], respectively,
for patients on oral therapy compared to 62 days [50, 73]
and 49 days [29, 61], respectively, for patients on intravenous
therapy. The difference [95% CI] in the mean time to progression
between the oral and intravenous therapies (oral - IV) was
-5 days [-22, 12].
ICM 1774: In this three-arm, randomized, open-label,
parallel group trial, conducted between June 1991 and
August 1993, patients with AIDS and stable CMV retinitis
following from 4 weeks to 4 months of treatment with CYTOVENE-IV
solution were randomized to receive maintenance treatment
with CYTOVENE-IV solution, 5 mg/kg once daily, CYTOVENE
capsules, 500 mg 6 times daily, or CYTOVENE capsules,
1000 mg tid for 20 weeks. The study showed that the mean
[95% CI] and median [95% CI] times to progression of CMV
retinitis, as assessed by masked reading of fundus photographs,
were 54 days [48, 60] and 42 days [31, 54], respectively,
for patients on oral therapy compared to 66 days [56,
76] and 54 days [41, 69], respectively, for patients on
intravenous therapy. The difference [95% CI] in the mean
time to progression between the oral and intravenous therapies
(oral - IV) was -12 days [-24, 0].
AVI 034: In this randomized, open-label, parallel group
trial, conducted between June 1991 and February 1993,
patients with AIDS and newly diagnosed (81%) or previously
treated (19%) CMV retinitis who had tolerated 10 to 21
days of induction treatment with CYTOVENE-IV, 5 mg/kg
twice daily, were randomized to receive 20 weeks of maintenance
treatment with either CYTOVENE capsules, 500 mg 6 times
daily or CYTOVENE-IV solution, 5 mg/kg/day.3 The mean
[95% CI] and median [95% CI] times to progression of CMV
retinitis, as assessed by masked reading of fundus photographs,
were 51 days [44, 57] and 41 days [31, 45], respectively,
for patients on oral therapy compared to 62 days [52,
72] and 60 days [42, 83], respectively, for patients on
intravenous therapy. The difference [95% CI] in the mean
time to progression between the oral and intravenous therapies
(oral - IV) was -11 days [-24, 1].
Comparison of other CMV retinitis outcomes between oral
and IV formulations (development of bilateral retinitis,
progression into Zone 1, and deterioration of visual acuity),
while not definitive, showed no marked differences between
treatment groups in these studies. Because of low event
rates among these endpoints, these studies are underpowered
to rule out significant differences in these endpoints.
2. Prevention of CMV Disease in Subjects
With AIDS
ICM 1654: In a double-blind study conducted between November
1992 and July 1994, 725 subjects with AIDS, who were CMV
seropositive and/or culture positive, were randomized to
receive CYTOVENE capsules, 1000 mg, every 8 hours, or placebo.4
The study population had a median age of 38 years (range:
21 to 69); were 99% male; were 82% Caucasian, 10% Hispanic,
7% African-American and 1% Asian; and had a median CD4 count
of 21 (range: 0 to 100). The mean observation time was 351
days (range: 5 to 621). As shown in the following table,
significantly more placebo recipients developed CMV disease.
|
Incidence
of CMV Disease at 6, 12 and 18 Months After Enrollment
(Kaplan-Meier Estimates) |
| |
Incidence
(Number Still at Risk) |
| |
CMV
Disease |
| |
Ganciclovir
|
Placebo
|
| 6
months |
8%
(397) |
11%
(190) |
| 12
months |
14%
(225) |
26%
(92) |
| 18
months |
20%
(27) |
39%
(9) |
3. Prevention of CMV Disease in Transplant Recipients
CYTOVENE-IV: CYTOVENE-IV was evaluated
in three randomized, controlled trials of prevention of
CMV disease in organ transplant recipients.
ICM 1496: In a randomized, double-blind, placebo-controlled
study of 149 heart transplant recipients5 at risk for
CMV infection (CMV seropositive or a seronegative recipient
of an organ from a CMV seropositive donor), there was
a statistically significant reduction in the overall incidence
of CMV disease in patients treated with CYTOVENE-IV. Immediately
posttransplant, patients received CYTOVENE-IV solution
5 mg/kg bid for 14 days followed by 6 mg/kg qd for 5 days/week
for an additional 14 days. Twelve of the 76 (16%) patients
treated with CYTOVENE-IV vs 31 of the 73 (43%) placebo-treated
patients developed CMV disease during the 120-day posttransplant
observation period. No significant differences in hematologic
toxicities were seen between the two treatment groups
(refer to table in ADVERSE EVENTS).
ICM 1689: In a randomized, double-blind, placebo-controlled
study of 72 bone marrow transplant recipients6 with asymptomatic
CMV infection (CMV positive culture of urine, throat or
blood) there was a statistically significant reduction
in the incidence of CMV disease in patients treated with
CYTOVENE-IV following successful hematopoietic engraftment.
Patients with virologic evidence of CMV infection received
CYTOVENE-IV solution 5 mg/kg bid for 7 days followed by
5 mg/kg qd through day 100 posttransplant. One of the
37 (3%) patients treated with CYTOVENE-IV vs 15 of the
35 (43%) placebo-treated patients developed CMV disease
during the study. At 6 months posttransplant, there continued
to be a statistically significant reduction in the incidence
of CMV disease in patients treated with CYTOVENE-IV. Six
of 37 (16%) patients treated with CYTOVENE-IV vs 15 of
the 35 (43%) placebo-treated patients developed disease
through 6 months posttransplant. The overall rate of survival
was statistically significantly higher in the group treated
with CYTOVENE-IV, both at day 100 and day 180 posttransplant.
Although the differences in hematologic toxicities were
not statistically significant, the incidence of neutropenia
was higher in the group treated with CYTOVENE-IV (refer
to table in ADVERSE EVENTS).
ICM 1570: A second, randomized, unblinded study evaluated
40 allogeneic bone marrow transplant recipients at risk
for CMV disease.7 Patients underwent bronchoscopy and
bronchoalveolar lavage (BAL) on day 35 posttransplant.
Patients with histologic, immunologic or virologic evidence
of CMV infection in the lung were then randomized to observation
or treatment with CYTOVENE-IV solution (5 mg/kg bid for
14 days followed by 5 mg/kg qd 5 days/week until day 120).
Four of 20 (20%) patients treated with CYTOVENE-IV and
14 of 20 (70%) control patients developed interstitial
pneumonia. The incidence of CMV disease was significantly
lower in the group treated with CYTOVENE-IV, consistent
with the results observed in ICM 1689.
CYTOVENE Capsules: GAN040: CYTOVENE capsules
were evaluated in a randomized, double-blind, placebo-controlled
study of 304 orthotopic liver transplant recipients who
were CMV seropositive or recipients of an organ from a seropositive
donor. Administration of CYTOVENE capsules (1000 mg three
times daily) or matching placebo commenced as soon as patients
were able to take medication by mouth, but no later than
10 days following transplantation, and continued through
14 weeks after transplantation. Dosing was adjusted for
patients with an estimated creatinine clearance <50 mL/min.
The incidence of CMV disease at 6 months is summarized in
the table below:
|
Incidence of CMV Disease at 6
Months (Kaplan-Meier Estimates)
|
| CMV
Disease at 6 months |
| |
Ganciclovir
(n=150) |
Placebo
(n=154) |
Relative
Risk (95% Cl) |
| CMV Disease,*
N (%) |
7
(4.8%) |
29
(18.9%) |
0.22
(0.10, 0.51) |
| CMV syndrome# |
6
(4.1%) |
19
(12.4%) |
| CMV hepatitis |
1
(0.7%) |
9
(5.9%) |
| CMV GI
disease |
0
(0.0%) |
3
(2.0%) |
| CMV lung
disease |
0
(0.0%) |
4
(2.6%) |
* One or more CMV endpoints
# CMV syndrome: CMV
viremia and unexplained fever, accompanied by malaise
and/or neutropenia.
CYTOVENE capsules significantly reduced the 6-month incidence
of CMV disease in patients at increased risk of CMV disease,
including seronegative recipients of organs from seropositive
donors (15% [3/21] with CYTOVENE capsules vs 44% [11/25]
with placebo), and patients receiving antilymphocyte antibodies
(5% [2/44] with CYTOVENE capsules vs 33% [12/37] with placebo).
The incidence of HSV infection at 6 months was 4% (5/150)
in ganciclovir vs 24% (36/154) in placebo recipients (relative
risk: 0.13; 95% CI: 0.05, 0.32).
DOSAGE AND ADMINISTRATION
: CAUTION – DO NOT ADMINISTER CYTOVENE-IV SOLUTION
BY RAPID OR BOLUS INTRAVENOUS INJECTION. THE TOXICITY OF
CYTOVENE-IV MAY BE INCREASED AS A RESULT OF EXCESSIVE PLASMA
LEVELS.
CAUTION – INTRAMUSCULAR OR SUBCUTANEOUS INJECTION OF
RECONSTITUTED CYTOVENE-IV SOLUTION MAY RESULT IN SEVERE
TISSUE IRRITATION DUE TO HIGH pH (11).
Dosage: THE RECOMMENDED DOSE FOR CYTOVENE-IV
SOLUTION AND CYTOVENE CAPSULES SHOULD NOT BE EXCEEDED.
THE RECOMMENDED INFUSION RATE FOR CYTOVENE-IV SOLUTION
SHOULD NOT BE EXCEEDED.
For Treatment of CMV Retinitis in Patients With
Normal Renal Function:
1. Induction Treatment
The recommended initial dosage for patients with normal
renal function is 5 mg/kg (given intravenously at a constant
rate over 1 hour) every 12 hours for 14 to 21 days. CYTOVENE
capsules should not be used for induction treatment.
2. Maintenance Treatment
CYTOVENE-IV: Following induction treatment, the recommended
maintenance dosage of CYTOVENE-IV solution is 5 mg/kg
given as a constant-rate intravenous infusion over 1 hour
once daily, 7 days per week or 6 mg/kg once daily, 5 days
per week.
CYTOVENE Capsules: Following induction treatment, the
recommended maintenance dosage of CYTOVENE capsules is
1000 mg tid with food. Alternatively, the dosing regimen
of 500 mg 6 times daily every 3 hours with food, during
waking hours, may be used.
For patients who experience progression of CMV retinitis
while receiving maintenance treatment with either formulation
of ganciclovir, reinduction treatment is recommended.
For the Prevention of CMV Disease in Patients
With Advanced HIV Infection and Normal Renal Function:
CYTOVENE Capsules: The recommended prophylactic dose
of CYTOVENE capsules is 1000 mg tid with food.
For the Prevention of CMV Disease in Transplant
Recipients With Normal Renal Function:
CYTOVENE-IV: The recommended initial dosage of CYTOVENE-IV
solution for patients with normal renal function is 5
mg/kg (given intravenously at a constant rate over 1 hour)
every 12 hours for 7 to 14 days, followed by 5 mg/kg once
daily, 7 days per week or 6 mg/kg once daily, 5 days per
week.
CYTOVENE Capsules: The recommended prophylactic dosage
of CYTOVENE capsules is 1000 mg tid with food.
The duration of treatment with CYTOVENE-IV solution and
CYTOVENE capsules in transplant recipients is dependent
upon the duration and degree of immunosuppression. In
controlled clinical trials in bone marrow allograft recipients,
treatment with CYTOVENE-IV was continued until day 100
to 120 posttransplantation. CMV disease occurred in several
patients who discontinued treatment with CYTOVENE-IV solution
prematurely. In heart allograft recipients, the onset
of newly diagnosed CMV disease occurred after treatment
with CYTOVENE-IV was stopped at day 28 posttransplant,
suggesting that continued dosing may be necessary to prevent
late occurrence of CMV disease in this patient population.
In a controlled clinical trial of liver allograft recipients,
treatment with CYTOVENE capsules was continued through
week 14 posttransplantation (see
INDICATIONS
AND USAGE section for a more detailed discussion).
Renal Impairment:
CYTOVENE-IV: For patients with impairment of renal function,
refer to the table below for recommended doses of CYTOVENE-IV
solution and adjust the dosing interval as indicated:
|
Creatinine
Clearance*
(mL/min) |
CYTOVENE-IV
Induction
Dose (mg/kg) |
Dosing
Interval
(hours) |
CYTOVENE-IV
Maintenance
Dose (mg/kg) |
Dosing
Interval
(hours) |
|
>70
50-69
25-49
10-24
<10 |
5.0
2.5
2.5
1.25
1.25 |
12
12
24
24
3 times per week,
following hemodialysis |
5.0
2.5
1.25
0.625
0.625 |
24
24
24
24
3 times per week,
following hemodialysis |
|
*Creatinine clearance can be related to serum creatinine
by the formulas given below.
Dosing for patients undergoing hemodialysis should not
exceed 1.25 mg/kg 3 times per week, following each hemodialysis
session. CYTOVENE-IV should be given shortly after completion
of the hemodialysis session, since hemodialysis has been
shown to reduce plasma levels by approximately 50%.
CYTOVENE Capsules: In patients with renal impairment, the
dose of CYTOVENE capsules should be modified as shown below:
|
Creatinine Clearance*
mL/min |
CYTOVENE
Capsule Doses |
|
|
>70
50-69
25-49
10-24
<10 |
1000 mg tid or 500
mg q3h, 6x/day
1500 mg qd or 500
mg tid
1000 mg qd or 500
mg bid
500 mg qd
500 mg 3 times per week, following hemodialysis |
|
Creatinine clearance can be related to serum creatinine
by the following formulas:
| Creatinine clearance for males
= |
(140 age [yrs]) (body wt [kg])
————————————
(72) (serum creatinine [mg/dL]) |
Creatinine clearance for females = 0.85 x male value
Patient Monitoring: Due to the frequency of granulocytopenia,
anemia and thrombocytopenia in patients receiving ganciclovir
(see ADVERSE EVENTS), it is recommended that complete
blood counts and platelet counts be performed frequently,
especially in patients in whom ganciclovir or other nucleoside
analogues have previously resulted in cytopenia, or in
whom neutrophil counts are less than 1000 cells/µL
at the beginning of treatment. Patients should have serum
creatinine or creatinine clearance values followed carefully
to allow for dosage adjustments in renally impaired patients
(see
DOSAGE AND ADMINISTRATION
).
Reduction of Dose: Dosage reductions in renally impaired
patients are required for CYTOVENE-IV and should be considered
for CYTOVENE capsules (see Renal Impairment). Dosage reductions
should also be considered for those with neutropenia,
anemia and/or thrombocytopenia (see ADVERSE EVENTS). Ganciclovir
should not be administered in patients with severe neutropenia
(ANC less than 500/µL) or severe thrombocytopenia
(platelets less than 25,000/µL).
Method of Preparation of CYTOVENE-IV Solution: Each 10 mL
clear glass vial contains ganciclovir sodium equivalent
to 500 mg of ganciclovir and 46 mg of sodium. The contents
of the vial should be prepared for administration in the
following manner:
|
|
a.
|
Reconstitute
lyophilized CYTOVENE-IV by injecting 10 mL of Sterile
Water for Injection, USP, into the vial. |
|
|
DO NOT USE BACTERIOSTATIC
WATER FOR INJECTION CONTAINING PARABENS. IT IS INCOMPATIBLE
WITH CYTOVENE-IV AND MAY CAUSE PRECIPITATION. |
|
|
b.
|
Shake
the vial to dissolve the drug. |
| |
c. |
Visually inspect the reconstituted
solution for particulate matter and discoloration
prior to proceeding with infusion solution. Discard
the vial if particulate matter or discoloration is
observed. |
|
|
d.
|
Reconstituted
solution in the vial is stable at room temperature
for 12 hours. It should not be refrigerated. |
2. Infusion Solution:
Based on patient weight, the appropriate volume of the
reconstituted solution (ganciclovir concentration 50 mg/mL)
should be removed from the vial and added to an acceptable
(see below) infusion fluid (typically 100 mL) for delivery
over the course of 1 hour. Infusion concentrations greater
than 10 mg/mL are not recommended. The following infusion
fluids have been determined to be chemically and physically
compatible with CYTOVENE-IV solution: 0.9% Sodium Chloride,
5% Dextrose, Ringer’s Injection and Lactated Ringer’s
Injection, USP.
CYTOVENE-IV, when reconstituted with sterile water for injection,
further diluted with 0.9% sodium chloride injection, and
stored refrigerated at 5°C in polyvinyl chloride (PVC)
bags, remains physically and chemically stable for 14 days.
However, because CYTOVENE-IV is reconstituted with nonbacteriostatic
sterile water, it is recommended that the infusion solution
be used within 24 hours of dilution to reduce the risk
of bacterial contamination. The infusion should be refrigerated.
Freezing is not recommended.
Handling and Disposal: Caution
should be exercised in the handling and preparation of solutions
of CYTOVENE-IV and in the handling of CYTOVENE capsules.
Solutions of CYTOVENE-IV are alkaline (pH 11). Avoid direct
contact with the skin or mucous membranes of the powder
contained in CYTOVENE capsules or of CYTOVENE-IV solutions.
If such contact occurs, wash thoroughly with soap and water;
rinse eyes thoroughly with plain water. CYTOVENE capsules
should not be opened or crushed.
Because ganciclovir shares some of the properties of
antitumor agents (ie, carcinogenicity and mutagenicity),
consideration should be given to handling and disposal
according to guidelines issued for antineoplastic drugs.
Several guidelines on this subject have been published.8-10
There is no general agreement that all of the procedures
recommended in the guidelines are necessary or appropriate.
HOW SUPPLIED: CYTOVENE®-IV (ganciclovir
sodium for injection) is supplied in 10 mL sterile vials,
each containing ganciclovir sodium equivalent to 500 mg
of ganciclovir, in cartons of 25 (NDC 0004-6940-03).
Store vials at temperatures below 40°C (104°F).
CYTOVENE® (ganciclovir capsules) 250 mg are two-pieced,
size No. 1, opaque green hard gelatin capsules with ROCHE
and CYTOVENE 250 mg imprinted on the capsules in dark
blue ink and with two blue lines partially encircling
the capsule body. Each capsule contains 250 mg of ganciclovir
as a white to off-white powder. CYTOVENE capsules are
supplied as follows: Bottles of 180 capsules (NDC 0004-0269-48).
CYTOVENE® (ganciclovir capsules) 500 mg are two-pieced,
size No. 0 elongated, opaque yellow/opaque green hard
gelatin capsules with ROCHE and CYTOVENE 500 mg imprinted
on the capsules in dark blue ink and with two blue lines
partially encircling the capsule body. Each capsule contains
500 mg of ganciclovir as a white to off-white powder.
CYTOVENE capsules are supplied as follows: Bottles of
180 capsules (NDC 0004-0278-48).
Store between 5° and 25°C (41° and 77°F).
* Retrovir is a registered trademark of Glaxo Wellcome.
# Videx is a registered trademark of Bristol-Myers Squibb.
REFERENCES
1. Spector SA, Weingeis T, Pollard R,
et al. A randomized, controlled study of intravenous ganciclovir
therapy for cytomegalovirus peripheral retinitis in patients
with AIDS. J Inf Dis. 1993; 168:557-563. 2.
Drew WL, Ives D, Lalezari JP, et al. Oral ganciclovir
as maintenance treatment for cytomegalovirus retinitis
in patients with AIDS. New Engl J Med. 1995; 333:615-620.
3. The Oral Ganciclovir European and
Australian Cooperative Study Group. Intravenous vs oral
ganciclovir: European/Australian comparative study of
efficacy and safety in the prevention of cytomegalovirus
retinitis recurrence in patients with AIDS. AIDS. 1995;
9:471-477. 4. Spector SA, McKinley GF,
Lalezari JP, Samo T, et al. Oral ganciclovir for the prevention
of cytomegalovirus disease in persons with AIDS. New Engl
J Med. 1996; 334:1491-1497. 5. Merigan
TC, Renlund DG, Keay S, et al. A controlled trial of ganciclovir
to prevent cytomegalovirus disease after heart transplantation.
New Engl J Med. 1992; 326:1182-1186. 6.
Goodrich JM, Mori M, Gleaves CA, et al. Early treatment
with ganciclovir to prevent cytomegalovirus disease after
allogeneic bone marrow transplantation. New Engl J Med.
1991; 325:1601-1607. 7. Schmidt GM, Horak
DA, Niland JC, et al. The City of Hope-Stanford-Syntex
CMV Study Group. A randomized, controlled trial of prophylactic
ganciclovir for cytomegalovirus pulmonary infection in
recipients of allogeneic bone marrow transplants. New
Engl J Med. 1991; 15:1005-1011. 8. Recommendations
for the Safe Handling of Cytotoxic Drugs. US Department
of Health and Human Services, National Institutes of Health,
Bethesda, MD, September 1992. NIH Publication No. 92-2621.
9. American Society of Hospital Pharmacists technical
assistance bulletin on handling cytotoxic and hazardous
drugs. Am J Hosp Pharm. 1990; 47:1033-1049. 10.
Controlling Occupational Exposures to Hazardous Drugs.
US Department of Labor. Occupational Health and Safety
Administration. OSHA Technical Manual. Section V - Chapter
3, September 22, 1995.
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