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Gantovir®
(Ganciclovir)
(Ganciclovir sodium) injection, powder, lyophilized, for solution
FOR INTRAVENOUS INFUSION ONLY
Gantovir® (Ganciclovir) is the brand name for Ganciclovir sodium for injection.
Gantovir® (Ganciclovir) is available as sterile lyophilized powder in strength of 250 mg per vial for intravenous administration only. Each vial of Gantovir® (Ganciclovir) contains the equivalent of 250 mg Ganciclovir as the sodium salt (46 mg sodium). Reconstitution with 10 ml of Sterile Water for Injection, USP, yields a solution with pH 11 and a Gantovir® (Ganciclovir) concentration of approximately 25 mg/ml. Further dilution in an appropriate intravenous solution must be performed before infusion.
Mechanism of Action:
Gantovir® (Ganciclovir) is an acyclic nucleoside analogue of 2'-deoxyguanosine that inhibits replication of herpes viruses. Gantovir® (Ganciclovir) has been shown to be active against cytomegalovirus (CMV) and herpes simplex virus (HSV) in human clinical studies.
To achieve anti-CMV activity, Gantovir® (Ganciclovir) is phosphorylated first to the monophosphate form by a CMV-encoded (UL97 gene) protein kinase homologue, then to the di- and triphosphate forms by cellular kinases. Gantovir® (Ganciclovir) triphosphate concentrations may be 100-fold greater in CMV-infected than in uninfected cells, indicating preferential phosphorylation in infected cells. Ganciclovir triphosphate, once formed, persists for days in the CMV-infected cell. Gantovir® (Ganciclovir) triphosphate is believed to inhibit viral DNA synthesis by (1) competitive inhibition of viral DNA polymerases; and (2) incorporation into viral DNA, resulting in eventual termination of viral DNA elongation.
Antiviral Activity:
The median concentration of Gantovir® (Ganciclovir) that inhibits CMV replication (IC50) in vitro (laboratory strains or clinical isolates) has ranged from 0.02 to 3.48 µg/mL. Gantovir® (Ganciclovir) inhibits mammalian cell proliferation (CIC50) in vitro at higher concentrations ranging from 30 to 725 µg/mL. Bone marrow-derived colony-forming cells are more sensitive (CIC50 0.028 to 0.7 µg/mL). The relationship of in vitro sensitivity of CMV to Gantovir® (Ganciclovir) and clinical response has not been established.
Renal Impairment:
The pharmacokinetics following intravenous administration of Gantovir® (Ganciclovir) solution were evaluated in 10 immunocompromised patients with renal impairment who received doses ranging from 1.25 to 5.0 mg/kg.
Pharmacokinetics of Patients with Renal Impairment
Estimated Creatinine Clearance Clearance Half-life
Dose (mL/min) (hours)
(mL/min) n Mean + SD Mean + SD
50-79 4 3.2-5 mg/kg 128 +} 63 4.6 +} 1.4
25-49 3 3-5 mg/kg 57 + 8 4.4 +} 0.4
<25 3 1.25-5 mg/kg 30 + 13 10.7 +} 5.7
Based on these observations, it is necessary to modify the dosage of Gantovir® (Ganciclovir) in patients with renal impairment Hemodialysis reduces plasma concentrations of Gantovir® (Ganciclovir) by about 50% after intravenous administration.
Indication and Usage:
Gantovir® (Ganciclovir) is indicated for the treatment of CMV retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS). Gantovir® (Ganciclovir) is also indicated for the prevention of CMV disease in transplant recipients at risk for CMV disease.
Contraindication:
Gantovir® (Ganciclovir) is contraindicated in patients with hypersensitivity to Gantovir® (Ganciclovir) or acyclovir.
Dosage and Administration:
CAUTION - Do not administer Gantovir® (Ganciclovir) solution by rapid or bolus intravenous injection. The toxicity of Gantovir® (Ganciclovir) injection may be increased as a result of excessive plasma levels.
CAUTION - Intramuscular or subcutaneous injection of reconstituted Gantovir® (Ganciclovir) solution may result in severe tissue irritation due to high PH (11).
Dosage:
The recommended dose for Gantovir® (Ganciclovir) solution should not exceed the recommended infusion rate.
For Treatment of CMV Retinitis in Patients With Normal Renal Function:
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.
Maintenance Treatment:
Following induction treatment, the recommended maintenance dosage of Gantovir® (Ganciclovir) 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.
For patients who experience progression of CMV retinitis while receiving maintenance treatment with Gantovir® (Ganciclovir), reinduction treatment is recommended.
1. Reconstituted Solution:
1. Reconstitute lyophilized Gantovir® (Ganciclovir) by injecting 5 mL of Sterile Water for Injection, USP, into the vial.
Do not use bacteriostatic water for injection containing parabens. It is incompatible with Gantovir® (Ganciclovir) and may cause precipitation.
2. Shake the vial to dissolve the drug.
3. 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.
4. 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 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 Gantovir® (Ganciclovir) solution: 0.9% Sodium Chloride, 5% Dextrose, Ringer's Injection and Lactated Ringer's Injection, USP.
Gantovir® (Ganciclovir), when reconstituted with sterile water for injection, further diluted with 0.9% sodium chloride injection, and stored refrigerated at 5OC in polyvinyl chloride (PVC) bags, remains physically chemically stable for 14 days.
However, because Gantovir® (Ganciclovir) 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.
How supplied:
Gantovir® (Ganciclovir) sodium for injection 250 mg lyophilised powder for solution for reconstitution.
Available at all leading pharmacies in Pakistan on prescription only.
For further queries.
Tel: +92 21 34123535, 34123636, 0346-3636201
UAN: +92 21 111-graton (472-866)
Fax: +92 21 34937304
Email: info@gratonpharma.com
Web: www.gratonpharma.com |
