Sodium ferric gluconate complex in sucrose is indicated for the treatment of iron deficiency anemia in receiving supplemental erythropoietin therapy. The administration of erythropoeitin increases the ability of hemodialysis patients to produce red blood cells and to use iron more efficiently. Sodium ferric gluconate complex is an intravenous iron supplement that can be administered to this patient population to increase the patient’s hemoglobin/hematocrit ratio and/or decrease their erythropoietin dosage requirements.

Sodium ferric gluconate complex in sucrose should be dosed as follows: Test Dose: 2 ml (25 mg of elemental iron) diluted in 50 ml 0.9% NaCl, administered over 60 minutes. Recommended dosage for repletion treatment of iron deficiency in hemodialysis patients 10 ml (125 mg elemental iron) diluted in 100 ml of 0.9% NaCl. Administered over 1 hour. Do not exceed rate of administration of 2.1 mg/min. Product has been administered during dialysis session itself. Most patients will require a minimum cumulative dose of 1.0 gm of elemental iron administered over 8 sessions at sequential dialysis treatments. The product, sodium ferric gluconate complex in sucrose, contains benzyl alcohol, therefore, it should not be used in neonates. The safety and efficacy of sodium ferric gluconate complex in pediatric patients has not been established. There were not sufficient numbers of geriatric patients enrolled in the trials to assess efficacy and safety in this patient population. A general recommendation is to start the doses low in the elderly and titrate to optimal iron supplementation levels in the patient. Sodium ferric gluconate complex is contraindicated in patients with non-iron deficiency anemia or hypersensitivity to the product or any of its inactive ingredients. Hypersensitivity can lead to a potentially fatal reaction. Rapid intravenous administration of iron has been associated with flushing, lightheadedness, malaise, weakness or pain in the chest, back, flanks and groin. These symptoms have been noted to typically resolve with one to two hours of administration.

Sodium ferric gluconate complex has not been studied in an adequate and well-controlled fashion in pregnant women. It has a FDA Category B, but should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Caution should be used when sodium ferric gluconate complex is administered to a nursing woman, since it is not known whether this drug is excreted in human milk.

One of the major issues surrounding the use of intravenous iron therapy is the risk of anaphylactic reactions with the currently available products. Iron dextran injection (Infed) has a black box warning stating that intravenous use of complexes of iron and carbohydrates has resulted in anaphylactic-type reactions and deaths. The calculated rate of serious systemic allergic reactions to iron dextran in several studies has been between 20-29% of patients or 8.7 reports of allergic reaction per million doses. The immunogenic component of the product is thought to be an iron-carbohydrate or iron-dextran complex. It is felt that the sodium ferric gluconate complex in sucrose does not share the same antigenic properties as the iron dextran products. The calculated reporting rate of allergic reaction for sodium ferric gluconate complex in sucrose was 3.3 per million doses.

Serious hypotensive incidences with flushing have been reported in 3 (1.3%) of 226 dialysis patients receiving sodium ferric gluconate complex. All cases resolved within 1 hour. Other more frequent adverese reactions reported in greater than 1% of patients receiving sodium ferric gluconate complex in sucrose, which may be related to hemodialysis or chronic renal failure, were as follows: injection site reaction, pain, chest pain, asthenia, cramps, dizziness, dyspnea, coughing, hypotension, hypertension, syncope, tachycardia, bradycardia, nausea, vomiting, diarrhea, myalgia, pruritus, hyperkalemia, generalized edema, abnormal erythrocytes, anemia.

Indocyanine green (ICG) angiography is an imaging agent that is indicated for use in cardiac, hepatic and ophthalmologic studies. ICG is rapidly bound to plasma protein, principally to albumin. It is secreted entirely in the bile. When biliary obstruction occurs, ICG appears in the hepatic lymph, independently of the bile, which suggests that the biliary mucosa is able to prevent diffusion of dye but allowing bilirubin to diffuse. This makes it useful as an index of hepatic function. In ophthalmologic studies, ICG is injected in the antecubital vein where it is protein bound. ICG extravasation does not occur in the highly fenestrated choroidal vasculature, therefore, making it useful in absorption and fluorescence infrared angiography when using appropriate filters and film in the fundus camera.

The dosage range for ICG is 20 to 40 mg of the dye dissolved in 2 to 4 ml of aqueous solvent. Following reconstitution with aqueous solvent, the solution must be used within 10 hours. A 5-ml bolus of normal saline should be administered immediately after injection of ICG in the antecubital vein. A qualified physician should supervise the use of ICG dye. Caution should be exercised when using ICG in patients with a history of allergy to shellfish and iodides. ICG is a Pregnancy Category C. Caution should be used when administering ICG to nursing mothers. It is unknown whether ICG is excreted in human milk.

Reactions reported during use of ICG include anaphylactic or urticarial reactions in patients with or without a history of allergy to iodides. Appropriate treatment measures should be available when ICG is administered.

ICG should only be reconstituted with the aqueous solvent provided by the manufacturer. Incompatibilities with alternative Water for injection products have been noted. The sodium bisulfite in heparin preparations reduces the absorption peak of ICG in the blood. Radioactive iodine uptake studies should not be performed for at least a week following ICG use

An intravitreal implant with 4.5 mg of ganciclovir is designed to release ganciclovir over a 5 to 8 month period control CMV retinitis. The implant may be removed and replaced after the ganciclovir is depleted.

No adequate or well-controlled studies in pregnant women on the effects of the implant, therefore, the intravitreal insert should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is unknown whether ganciclovir from the intravitreal insert is excreted in human milk. Since carcinogenicity and teratogenicity effects occurred in animals treated with ganciclovir, mothers should be instructed to discontinue nursing prior to implantation of intravitreal inserts with ganciclovir.

Adverse events noted most frequently following implantation of intravitreal inserts with ganciclovir were ocular in nature. Within two months following implantation, approximately 10-20% of patients reported visual acuity loss, vitreous hemorrhage, and retinal detachment. Approximately 1-5% of the patients noted cataract formation/lens opacities, macular abnormalities, intraocular pressure spikes, optic disk/nerve changes, hyphemas and uveitis.

Sirolimus is a macrolide immunosuppressive agent indicated for rejection prophylaxis following renal transplantation. Like cyclosporine and tacrolimus, sirolimus inhibits T lymphocyte activation and proliferation but by a pathway unique form previous agents. It is recommended that sirolimus be used in a regimen with cyclosporine and corticosteroids so that a lower dosage of each agent may be used, resulting in improved side effect profiles with fewer overlapping toxicities, and improved rejection prophylaxis.

Sirolimus is contraindicated in patients with a know hypersensitivity to the medication or any component of the product. Immunosuppressant therapy increases the susceptibility to infection and lymphoma. Sirolimus therapy should be initiated as soon as possible after renal transplantation with a loading dose of 6mg (three times the maintenance dosage). As part of a treatment regimen including cyclosporine and corticosteroids, the maintenance dose of (2mg daily) should be administered the following day. The dosage should be mixed in a glass or plastic container with 60mls of water or orange juice (no grapefruit juice) and consumed immediately. An additional 120mls of water or juice should be refilled into the glass, mixed, and consumed immediately. Sirolimus may be given with or without food but should be consistent. The dosage should be adjusted to (1mg/m²/day) in patients 13 years of age or below (trials in pediatric dialysis patients age 5-18 years), and patients weighing less than 40 kg. In renal impairment, no dosage adjustments are needed. In hepatic impairment, the loading dose remains unchanged (6mg), but the maintenance dosage should be approximately one-third the standard dosage. Antimicrobial prophylaxis for cytomegalovirus and pneumocystis carinii should be prescribed for 3 months and 1 year post-transplant respectively.

As with tacrolimus and cyclosporine, sirolimus is mainly metabolized by cytochrome P450 and is a substrate for the enzyme cytochrome P450 III-A4 (CYP3A4). This is of great significance for medication regimens in transplant patients due to the number of medications that induce (decease substrate levels), inhibit (increase substrate levels), or are substrates (potentially compete for metabolism) for the CYP3A4 system. Careful screenings of all medication changes are advisable to prevent potential toxicity or acute rejection due to sirolimus blood level changes caused by drug interactions. The following chart contains a list of inducers, inhibitors, and substrates for the CYP3A4 system. The agents in bold are those specifically tested by the manufacturer. The dosing adjustments recommended in those cases are presented following the chart. This is not an all-inclusive list. It is always advisable to review medications for potential drug interactions.

The most frequently cited (>20%) adverse reactions in clinical trials included: hypercholesterolemia, hyperlipidemia, hypertension, and rash. In higher dosing regimens (5 mg/day), adverse reactions included anemia, arthralgia, diarrhea, hypokalemia, and thrombocytopenia. Another frequent adverse reaction that was noted in the (2 mg/kg) trials was acne.

2 Sirolimus should be monitored and adjusted if needed (C_Max, AUC, & T_Max of sirolimus were

elevated when given with diltiazem)

3 Do not administer ketoconazole with sirolimus

4 Do not administer rifampin with sirolimus

5 No dosage adjustments are needed for glyburide or sirolimus

6 No dosage adjustments are needed for nifedipine or sirolimus

7 No dosage adjustments are needed for Lo/Ovralâ (norgestrel/ethinyl estradiol) or sirolimus

8 Do not administer sirolimus with grapefruit juice