Cytovene (Ganciclovir) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

CYTOVENE drug label information in our database does not contain a dedicated section on drug interactions. Please check subsections of WARNINGS AND PRECAUTIONS as well as other sources.

OVERDOSAGE

CYTOVENE-IV:    Overdosage with CYTOVENE-IV has been reported in 17 patients (13 adults and 4 children under 2 years of age). Five patients experienced no adverse events following overdosage at the following doses: 7 doses of 11 mg/kg over a 3-day period (adult), single dose of 3500 mg (adult), single dose of 500 mg (72.5 mg/kg) followed by 48 hours of peritoneal dialysis (4-month-old), single dose of approximately 60 mg/kg followed by exchange transfusion (18-month-old), 2 doses of 500 mg instead of 31 mg (21-month-old).

Irreversible pancytopenia developed in 1 adult with AIDS and CMV colitis after receiving 3000 mg of CYTOVENE-IV solution on each of 2 consecutive days. He experienced worsening GI symptoms and acute renal failure that required short-term dialysis. Pancytopenia developed and persisted until his death from a malignancy several months later. Other adverse events reported following overdosage included: persistent bone marrow suppression (1 adult with neutropenia and thrombocytopenia after a single dose of 6000 mg), reversible neutropenia or granulocytopenia (4 adults, overdoses ranging from 8 mg/kg daily for 4 days to a single dose of 25 mg/kg), hepatitis (1 adult receiving 10 mg/kg daily, and one 2 kg infant after a single 40 mg dose), renal toxicity (1 adult with transient worsening of hematuria after a single 500 mg dose, and 1 adult with elevated creatinine (5.2 mg/dL) after a single 5000 to 7000 mg dose), and seizure (1 adult with known seizure disorder after 3 days of 9 mg/kg). In addition, 1 adult received 0.4 mL (instead of 0.1 mL) CYTOVENE-IV solution by intravitreal injection, and experienced temporary loss of vision and central retinal artery occlusion secondary to increased intraocular pressure related to the injected fluid volume.

CYTOVENE Capsules:    There have been no reports of overdosage with CYTOVENE capsules. Doses as high as 6000 mg/day, given either as 1000 mg 6 times daily or as 2000 mg tid, did not result in overt toxicity other than transient neutropenia. Daily doses of more than 6000 mg have not been studied.

Since ganciclovir is dialyzable, dialysis may be useful in reducing serum concentrations. Adequate hydration should be maintained. The use of hematopoietic growth factors should be considered.

CONTRAINDICATIONS

CYTOVENE-IV and CYTOVENE are contraindicated in patients with hypersensitivity to ganciclovir or acyclovir.

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.

Distributed by Roche Laboratories Inc., Nutley, NJ 07110

Revised: September 2000