Loading…
MAR-CIDOFOVIR is a brand name for Cidofovir, supplied as a solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Mar-Cidofovir is indicated for the treatment of cytomegalovirus (CMV) retinitis in adult patients having acquired immunodeficiency syndrome (AIDS). 1.1 Pediatrics Pediatrics (< 18 years of age): The safety and efficacy of Mar-Cidofovir has not been established in these patients. Use is not recommended in pediatric…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations Before each administration of Mar-Cidofovir, serum creatinine and urine protein levels must be determined to confirm adequate renal function. The recommended dosage, frequency, or infusion rate of Mar-Cidofovir must not be exceeded.
9% (normal) saline prior to administration. Serious Warnings and Precautions Renal impairment is the major toxicity of Mar-Cidofovir. Cases of acute renal failure resulting in need for dialysis and/or contributing to death have occurred with as few as one or two doses of cidofovir.
To reduce possible nephrotoxicity, intravenous pre-hydration with normal saline and administration of probenecid must be used with each Mar-Cidofovir infusion. Renal function (serum creatinine and urine protein) must be determined within 48 hours prior to administration of every dose of Mar-Cidofovir.
The dose of Mar- Cidofovir to be given should be modified for changes in renal function, as appropriate (see DOSAGE AND ADMINISTRATION). Mar-Cidofovir is contraindicated in patients who are receiving other nephrotoxic agents. Neutropenia has been observed in association with cidofovir treatment.
Therefore, neutrophil counts should be monitored during Mar-Cidofovir therapy. Mar-Cidofovir is indicated only for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). In animal studies, cidofovir was carcinogenic, teratogenic and caused hypospermia (see WARNINGS AND PRECAUTIONS, Carcinogenesis and Mutagenesis, and Sexual Health/Reproduction).
Mar-Cidofovir Marcan Pharmaceuticals Inc. 2 Recommended Dose and Dosage Adjustment). Mar-Cidofovir is indicated for use in adults only. 2 Recommended Dose and Dosage Adjustment The recommended induction dose of Mar-Cidofovir for adult patients having a creatinine clearance > 55 mL/min, without ≥ 2+ proteinuria (≥ 100 mg/dL), is 5 mg/kg of cidofovir, given as an intravenous infusion at a constant rate over 1 hour, to be administered once weekly for two consecutive weeks (see Table 1).
85 72 X [serum creatinine (mg/dL)] Starting two weeks after completion of induction treatment, the recommended maintenance dose of Mar-Cidofovir is 5 mg/kg of cidofovir once every two weeks, given as an intravenous infusion at a constant rate over 1 hour.
Probenecid:
1 Adverse Reaction Overview Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be Mar-Cidofovir Marcan Pharmaceuticals Inc.
Page 10 of 28 compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. The following are the major noted adverse reactions to have occurred with cidofovir, when given intravenously.
4 mg/dL, or decrease creatinine clearance ≤ 55 mL/min, occurred in 79 of 135 (59%) patients receiving cidofovir at a maintenance dose of 5 mg/kg intravenously every other week, and in 56 of 112 (50%) patients receiving cidofovir intravenously at a maintenance dose of 3 mg/kg every other week.
Maintenance dose reductions from 5 mg/kg to 3 mg/kg, due to proteinuria or serum creatinine elevation, were made in 12 of 41 (29%) patients who had not received prior therapy for CMV retinitis (Study 106), and in 19 of 74 (26%) patients who had received prior therapy for CMV retinitis (Study 107).
Prior foscarnet use has been associated with an increased risk of nephrotoxicity. Such patients must be monitored closely.
Neutropenia:
In clinical trials, at the 5 mg/kg maintenance dose, a decrease in absolute neutrophil count to ≤ 500 cells/mm3 occurred in 24% of patients. Granulocyte Colony Stimulating Factor (GCSF) was used in 39% of patients. At the 3 mg/kg maintenance dose, a decrease in absolute neutrophil count to ≤ 500 cells/mm3 occurred in 25% of patients.
Decreased intraocular pressure/ocular hypotony:
Please see the Serious Warnings and Precautions Box at the beginning of Part I:
Health Professional Information.
Please see Contraindications at the beginning of Part I:
Health Professional Information. General Due to dose-dependent nephrotoxicity related to cidofovir, doses greater than the recommended dose of Mar-Cidofovir must not be administered and the frequency or rate of administration must not be exceeded (see DOSAGE AND ADMINISTRATION).
Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Intravenous 75 mg/mL cidofovir (as cidofovir dihydrate); 375 mg cidofovir (as cidofovir dihydrate)/vial water for injection and sodium hydroxide and hydrochloric acid Mar-Cidofovir Marcan Pharmaceuticals Inc.
Page 8 of 28 Carcinogenesis and Mutagenesis In animal studies, cidofovir was carcinogenic (rat), teratogenic (rat and rabbit), and caused hypospermia. In light of these pre-clinical safety data, Mar-Cidofovir should be considered a potential human carcinogen.
Endocrine and Metabolism Decreased serum bicarbonate associated with proximal tubule injury and renal wasting syndrome (including Fanconi's syndrome) have been reported in patients receiving cidofovir. Fatal cases of metabolic acidosis in association with liver dysfunction and pancreatitis have been reported in patients receiving cidofovir.
Hematologic Neutropenia has been observed in patients receiving cidofovir. Neutrophil count should be monitored while receiving Mar-Cidofovir therapy. Monitoring and Laboratory Tests See DOSAGE AND ADMINISTRATION Ophthalmologic Uveitis/iritis was reported in clinical trials and during post-marketing in patients receiving cidofovir.
Treatment with topical corticosteroids, with or without topical cycloplegic agents, may be considered. Patients should be monitored for signs and symptoms of uveitis or iritis during Mar-Cidofovir therapy. Decreased intraocular pressure has been reported during cidofovir therapy, and in some instances, has been associated with decreased visual acuity.
Mar-Cidofovir is contraindicated in patients with renal impairment having a creatinine clearance ≤ 55 mL/min, or having proteinuria ≥ 2+ proteinuria (≥ 100 mg/dL). Mar-Cidofovir must be used concomitantly with probenecid to diminish its nephrotoxic effects.
Patients must be well hydrated during Mar-Cidofovir administration (see DOSAGE AND ADMINISTRATION). Mar-Cidofovir is contraindicated in patients unable to receive probenecid because of clinically significant hypersensitivity to the drug or to other sulpha-containing medications.
Concomitant administration of Mar-Cidofovir with potentially nephrotoxic agents is contraindicated. Patients must discontinue such agents at least 7 days before starting treatment with Mar-Cidofovir (see SERIOUS WARNINGS AND PRECAUTIONS BOX).
Direct intraocular injection of Mar-Cidofovir is contraindicated. Direct injection may be associated with significant decreases in intraocular pressure and impairment of vision. Mar-Cidofovir is contraindicated in patients who are hypersensitive to cidofovir or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see Dosage Forms, Strengths, Composition and Packaging. Mar-Cidofovir Marcan Pharmaceuticals Inc. Page 4 of 28
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Know a brand we are missing in Canada? Suggest a brand →
Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
Probenecid must be given orally with each dose of Mar-Cidofovir. Administer 2 grams probenecid 3 hours before each Mar-Cidofovir infusion. Administer an additional 1 gram at 2 hours and 1 gram at 8 hours after completion of the 1-hour Mar-Cidofovir infusion, for a total of 4 grams.
Based on experience in clinical trials, ingestion of food prior to each dose of probenecid may reduce drug-related nausea and vomiting. The use of an antiemetic may also be necessary. , rash, fever, chills, the prophylactic or therapeutic use of an appropriate antihistamine and/or acetaminophen should be considered.
Mar-Cidofovir Marcan Pharmaceuticals Inc. 9% (normal) saline solution intra- venously with each infusion of Mar-Cidofovir. The saline solution should be infused over a 1-2 hour period immediately before Mar-Cidofovir infusion. Patients who can tolerate the additional fluid load should then receive a second liter.
If administered, the second liter of saline should be initiated either at the start of the Mar-Cidofovir infusion or immediately afterwards, and infused over a 1-3 hour period. Since patients with chronic diarrhea or AIDS-related wasting may have intravascular volume depletion, special attention should be given to repletion of fluids in these patients.
4 mg/dL) above baseline. 5 mg/dL) above baseline or for the development of ≥ 2+ proteinuria.
Pre-existing Renal Impairment:
Mar-Cidofovir is contraindicated in patients having a creatinine clearance ≤ 55 mL/min, or having proteinuria ≥ 2+ proteinuria (≥ 100 mg/dL) (see CONTRAINDICATIONS).
Patient Monitoring:
Serum creatinine and urine protein must be monitored within 48 hours prior to each dose of Mar-Cidofovir being administered. White blood cell counts with differential should also be monitored prior to each dose. In patients with proteinuria, intravenous hydration should be administered, and the test repeated.
Intraocular pressure, visual acuity and ocular symptoms should be monitored periodically. 3 Administration As with all parenteral drug products, intravenous admixtures should be inspected visually for clarity, particulate matter, precipitate, discolouration and leakage prior to administration, whenever solution and container permit.
[…]
Among the subset of patients monitored for intraocular pressure changes, a ≥ 50% decrease from baseline intraocular pressure was reported in 17 of 70 (24%) patients at the 5 mg/kg maintenance dose. At the 3 mg/kg maintenance dose, a ≥ 50% decrease from baseline intraocular pressure was reported in 12 of 83 (14%).
Severe hypotony (intraocular pressure of 0-1 mm/Hg) has been reported in 3 patients. Risk of ocular hypotony may be increased in patients with pre-existing diabetes mellitus.
Metabolic acidosis:
A diagnosis of Fanconi’s syndrome was reported in 1% of patients. Decreases in serum bicarbonate to ≤ 16 mEq/L occurred in 16% of cidofovir-treated patients. Fanconi’s syndrome and decreases in serum bicarbonate with evidence of renal tubular damage have been reported in patients receiving cidofovir.
Fatal cases of metabolic acidosis in association with liver dysfunction and pancreatitis have been reported in patients receiving cidofovir.
Anterior uveitis/iritis:
Uveitis or iritis was reported in 15 of 135 (11 %) patients receiving 5 mg/kg maintenance dose, and in 5 of 112 (4%) patients receiving 3 mg/kg maintenance dose. Treatment with topical corticosteroids, with or without topical cycloplegic agents, may be considered.
Patients should be monitored for signs and symptoms of uveitis/iritis during therapy with Mar-Cidofovir. 2 Clinical Trial Adverse Reactions Three clinical trials have been conducted with cidofovir given intravenously to evaluate treatment in patients with AIDS having cytomegalovirus retinitis (see CLINICAL TRIALS).
Mar-Cidofovir Marcan Pharmaceuticals Inc. Page 11 of 28 In clinical trials, cidofovir treatment was withdrawn due to adverse events in 39% of patients treated with 5 mg/kg every other week as maintenance therapy, and in 26% of patients receiving 3 mg/kg as maintenance dose.
The incidence of serious adverse events (SAE) in these three controlled clinical studies, regardless of presumed relationship to drug, is listed in the following table. 0 mg/dL) 16 (12) 6 (5) Pneumonia 12 (9) 12 (11) Dyspnea 11 (8) 5 (4) Nausea with vomiting 10 (7) 4 (4) * Patients receiving 5 mg/kg maintenance regimen in Studies 105, 106 and 107 § Patients receiving 3 mg/kg maintenance regimen in Studies 105 and 107 Þ Defined as decreased intraocular pressure (IOP) to ≤ 50% that at baseline.
Based on 70 patients receiving 5 mg/kg maintenance dosing (Studies 105 and 107), and on 83 patients receiving 3 mg/kg maintenance regimen (Studies 105 and 107), with available baseline and follow-up IOP determinations The most frequently reported adverse events regardless of relationship to study drugs (cidofovir or probenecid) or severity are shown in the following table.
5 mg/dL) 29 (21) 15 (13) Mar-Cidofovir Marcan Pharmaceuticals Inc. 3 Less Common Clinical Trial Adverse Reactions The following additional list of adverse events or intercurrent illnesses have been observed in clinical studies of cidofovir when given intravenously, and are listed below regardless of causal relationship to cidofovir.
Evaluation of these reports was […]
Intraocular pressure should be monitored during Mar-Cidofovir therapy to exclude ocular hypotony. Renal Dose-dependent nephrotoxicity is the major dose-limiting toxicity related to administration of cidofovir intravenously. Proteinuria, as measured by urinalysis in a clinical laboratory, may be an early indicator of cidofovir-related nephrotoxicity.
Patients receiving Mar-Cidofovir must have their serum creatinine and urine protein levels determined within 48 hours prior to each Mar-Cidofovir infusion. In patients exhibiting only ≥ 2+ proteinuria, intravenous hydration should be performed and the test repeated.
If following hydration, ≥ 2+ proteinuria is still observed, Mar-Cidofovir must be discontinued. During treatment, these parameters should be investigated prior to the administration of each infusion, and treatment should be stopped in case of abnormality.
Renal function that did not return to baseline after drug discontinuation has been observed in clinical trials of cidofovir given intravenously. In case of complete recovery, the re- introduction of cidofovir has not been evaluated.
Intravenous normal saline hydration and oral probenecid must accompany each Mar-Cidofovir infusion. Probenecid is known to interact with the metabolism or renal tubular excretion of many drugs (see DRUG INTERACTIONS). An interval of at least 7 days must elapse following the administration of agents with Mar-Cidofovir Marcan Pharmaceuticals Inc.
Page 9 of 28 nephrotoxic potential prior to the initiation of therapy with Mar-Cidofovir, and must not be used during the course of therapy. , tobramycin, gentamicin, and amikacin), amphotericin B, foscarnet, intravenous pentamidine, vancomycin, adefovir, tenofovir, and nonsteroidal anti-inflammatory agents.
Sexual Health/Reproduction Male patients should be advised that cidofovir caused reduced testes weight and hypospermia in animals. Although not observed in clinical studies of intravenous cidofovir, such changes may occur in humans and may cause infertility.
Men should be advised to practice barrier contraceptive methods during and for 3 months after treatment with Mar-Cidofovir. 1 Pregnant Women Mar-Cidofovir should not be used during pregnancy, or in women of childbearing age not using contraception.
There are no studies of cidofovir in pregnant women. However, passage of drug- related compounds through the placental barrier was observed in pregnant rats, and embryotoxicity was seen in rats and rabbits. 2 Breast-feeding HIV-1-infected mothers should not breast-feed their infants to avoid risking post-natal transmission of HIV.
It is not known whether cidofovir is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for adverse reactions as well as the potential for tumorigenicity shown for cidofovir in animal studies, nursing mothers should be instructed not to breast-feed if they are receiving Mar-Cidofovir.
3 Pediatrics The safety and efficacy of cidofovir have not been established in patients less than 18 years of age. Therefore, Mar-Cidofovir is not recommended for use in children and neonates. 4 Geriatrics The safety and efficacy of Mar-Cidofovir have not been established in patients over 60 years of age.
Since elderly individuals frequently have reduced glomerular function, particular attention should be paid to assessing renal function before and during administration of Mar-Cidofovir.