Trough specimens should be collected less than an hour before the next dose.
Please note: Only non-gel tubes are acceptable, LIGHT GREEN tubes with gel (PST) are NOT acceptable.
0.5 mL Paediatric Plain tube x2 (Always required)
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Prophylaxis: 1 - 2 mg/L (aiming to achieve AUC24 of 40-60 mg/L*h) Treatment: 2 - 4 mg/L (aiming to achieve an AUC24 of 80-120 mg/L*h) Individual targets may vary depending on patient circumstances. |
UoM: 6%
1 - 4 days
Principle : High performance liquid chromatography with fluorescence detection
Ganciclovir is an antiviral used in patients at high risk or proven viral infection (e.g. CMV in immunosuppressed individual). This can be administered intravenously or given orally as the prodrug (Valganciclovir). The main adverse consequences are bone marrow suppression, neuropathy, liver dysfunction (abnormal LFT) and renal insufficiency. This drug binds minimally to plasma proteins, and is predominantly excreted in urine unaltered.
Use of (val)ganciclovir is complicated by toxicity, slow response to treatment and acquired resistance with breakthrough infections. Although highly variable trough levels can be obtained using standard weight and renal function-based dosing regimen (significant interindividual variability), studies have indicated mixed results for the routine use of therapeutic drug monitoring for ganciclovir. Since its action is intracellular, measurement of plasma levels is only an indirect assessment. Nevertheless, therapeutic drug monitoring is likely useful in patients with fluctuating renal function, very young or premature neonates, abnormal GI function for the oral prodrug (Valganciclovir), high clinical risk of treatment failure (e.g. resistance to ganciclovir) or to guide dosage reduction in patients with ganciclovir related adverse effects.
There are two methods for (val)ganciclovir TDM. For the majority of patients, a trough concentration at steady state (5-7 days after initiation or dose adjustments) should be taken ideally 30-60 minutes before the next dose is due. Some patients may benefit from Bayesian AUC24 monitoring instead. This requires a random ganciclovir concentration (2-6 hours post dose) to be taken instead of a trough - contact your Antimicrobial Pharmacist or Infectious Diseases team for advice.
The half-life of ganciclovir is approximately 2-4h and increases with age. In the setting of advanced renal failure, this can increase by more than 10-fold (half-life of 60 hours). As it may take 3-5 half-lives to reach a new steady state, repeat dose measurements after a dose adjustment should be taken after 7-10 days for an accurate trough level.
Very low levels (< 0.6 mg/L) are associated with a higher incidence of disease progress and treatment failure. Risk of neutropenia increases from a trough > 2.6 ug/mL. Treatment targets may vary depending of knowledge of ganciclovir resistance, (baseline) viral load, renal function (eGFR), state of immunosuppression or dose/duration of use. Higher targets may be required for life threatening infections. Please contact the infectious diseases pharmacist or another team member before dose adjustments.
References:
1. Martson AG, Edwina AE, Burgerhof JGM, Berger SP, de Joode A, Damman K, et al. Ganciclovir therapeutic drug monitoring in transplant recipients. J Antimicrob Chemother 2021;76:2356-2363.
2. Ritchie BM, Barreto JN, Barreto EF, Crow SA, Dierkhising RA, Jannetto PJ, et al. Relationship of Ganciclovir Therapeutic Drug Monitoring with Clinical Efficacy and Patient Safety. Antimicrobial Agents and Chemotherapy 2019;63:e01855-18.
3. Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, et al. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation 2018;102:900-931.
4. Stockmann C, Roberts JK, Knackstedt ED, Spigarelli MG, Sherwin CM. Clinical pharmacokinetics and pharmacodynamics of ganciclovir and valganciclovir in children with cytomegalovirus infection. Expert Opin Drug Metab Toxicol 2015;11:205-19.
5. Nguyen T, Oualha M, Briand C, Bendavid M, Beranger A, Benaboud S, et al. Population Pharmacokinetics of Intravenous Ganciclovir and Oral Valganciclovir in a Pediatric Population To Optimize Dosing Regimens. Antimicrob Agents Chemother 2021;65.
Emails to chemicalpathologist@adhb.govt.nz will receive priority attention from the on-call chemical pathologist.
If the query concerns a specific patient please include the NHI number in your email.
If email is not a suitable option, please contact the on-call chemical pathologist via Lablink (Auckland City Hospital ext. 22000 or 09-3078995).
Individual chemical pathologists may be contacted but will not be available at all times.
After-hours : contact Lablink (Auckland City Hospital ext. 22000 or 09-3078995) or hospital operator for on duty staff after hours.
Dr Samarina Musaad (Clinical Lead) : SamarinaM@adhb.govt.nz ext. 22402
Dr Cam Kyle: CampbellK@adhb.govt.nz ext 22052
Dr Weldon Chiu: WeldonC@adhb.govt.nz ext. 23427
Dr Campbell Heron: CHeron@adhb.govt.nz ext. 23427
Dr Sakunthala Jayasinghe: Sakunthala@adhb.govt.nz ext. 23427
For further information contact the laboratory or the Virology team virology@adhb.govt.nz
Plain or heparin specimen; Gel tube not acceptable
Minimum of 0.2 mL plasma is required.
Transport at 4 o C (if longer than 5 days to receipt, transport frozen at -20 o C)
Time of previous dose (or "Trough") must be documented with request.