Pharmacy

Antifungal

Fungizone ®

Indications

• Progressive and potentially systemic fungal infections, including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, leishmaniasis, mucormycosis and sporotrichosis.

Administration

• Consider premedication if patient previously experienced an infusion-related reaction; refer to Potential Administration Hazards section.
• Consider prehydration with NS and sodium repletion to reduce nephrotoxicity; refer to Potential 
  Administration Hazards and Dosage sections.
• Reconstitute 50 mg vial with 10 mL of SWFI without preservatives for a concentration of 5 mg/mL. Shake vial until complete dissolution.
• Intermittent IV infusion: dilute in D5W (with a pH of greater than 4.2) to a maximum concentration of 0.1 mg/mL (i.e., 50 mg or less in 500 mL) when infused into a peripheral vein or to a maximum concentration of 0.25 mg/mL when infused via a central line. Flush the line with D5W before and after administration. Recommended infusion time is 2-6 hours; however, infusion times of 1 to 2 hours have been used in adults and older children with normal renal function. The preferred method of infusion is with an infusion pump.
• Use of an in-line membrane filter during infusion is optional; however, the pore size should be 1 micron or greater. 

Potential Administration Hazards

• Hypersensitivity: anaphylactic and anaphylactoid reactions, rash, pruritus, skin exfoliation, toxic epidermal necrolysis, Stevens-Johnson syndrome.
• Infusion-related reactions: occur within 1-3 hours of starting the infusion, especially with the first few doses; fever, shaking chills, headache, anorexia, nausea, vomiting, hypotension, dyspnea, tachypnea. Rapid IV infusion (over less than 60 minutes) is associated with a more severe reaction consisting of hypotension, bronchospasm, hyperkalemia or hypokalemia, arrhythmias and shock, particularly in patients with renal impairment. In case of reaction, reduce rate of infusion and administer antihistamines and/or corticosteroids. Meperidine may be given for chills. Consider premedication with an antipyretic (ibuprofen, acetaminophen or ASA), antiemetic, diphenhydramine, hydrocortisone or meperidine 25-50 mg IV given 30 to 60 minutes prior to infusion.
• Cardiovascular: flushing, hypotension, hypertension.
• GI: anorexia, diarrhea, dyspepsia, epigastric pain, nausea, vomiting, stomach cramping.
• Electrolyte disturbances: hypokalemia, hypomagnesemia, hypocalcemia.
• Musculoskeletal: myalgia, arthralgia.
• Renal: tubular necrosis, decreased glomerular filtration rate, azotemia, nephrocalcinosis. Permanent renal damage possible when cumulative dose exceeds 5 g. Prehydration and sodium repletion can minimize nephrotoxicity.
• Local reactions: venous pain at injection site with or without phlebitis and thrombophlebitis (use pediatric scalpvein needles, decrease infusion concentration, change injection site, switch to alternate day therapy, add heparin 500-1000 units or 1 unit/mL to the infusion); extravasation can cause chemical irritation. 

Dosage

Adults:

• Consider prehydration with 500-1000 mL of NS and sodium repletion prior to administration of amphotericin B to reduce risk of nephrotoxicity.
• A test dose of 1 mg IV (1 mg in 20 mL of D5W) over 20-30 minutes is sometimes recommended followed by a 2-4 hour observation period.
• Initial dose: 0.25-0.3 mg/kg IV q24h OR 5-10 mg/day in patients with impaired cardiac or renal function or in those who reacted to test dose. Gradually increase in increments of 5-10 mg/day as tolerance permits, up to a maximum of 1.5 mg/kg IV q24h. Alternate day therapy of up to 1.5 mg/kg IV every other day is also possible.
• If therapy is interrupted for longer than 7 days, restart at 25 mg/kg/day and increase dose gradually.  

Pediatrics:

• A test dose of 1 mg/kg (maximum 1 mg) IV (in 20 mL of D5W) over 20-60 minutes is sometimes recommended.
• Initial dose: 0.25-0.5 mg/kg IV q24h, increase gradually in increments of 0.25-0.5 mg/kg/day IV until the desired dose is achieved; maximum of 1.5 mg/kg/day IV.
• Maintenance dose: 0.25-1 mg/kg IV q24h OR 1-1.5 mg/kg/day IV every other day. Rapidly progressing disease may require short-term doses of up to 1.5 mg/kg/day IV.
• Dosage in renal impairment: If CrCl is less than 10 mL/min, give full dose q24-36h; if renal impairment is due to amphotericin B, may decrease dose by 50% or give every other day. 

Compatibility, Stability

• Store vials between 2-8°C. Protect from light. Also stable for 2-4 weeks at room temp, protected from light.
• Reconstituted solution is stable for 24 hours at room temp (protected from light) and for 7 days in the fridge.
• Incompatible with NS, RL or sterile water that contains preservatives as diluents other than D5W may cause precipitation.
• Stable for 24 hours at room temp in D5W at a concentration of 0.1 mg/mL in PVC containers.
• Stable for 35 days in the fridge (protected from light) in D5W at concentrations of 0.1 mg/mL and 0.25 mg/mL in PVC containers.
• Stable for 5 days at room temp (exposed to light) or in the fridge (protected from light) in D5W at concentrations of 0.2 mg/mL, 0.5 mg/mL and 1 mg/mL in PVC containers.
• Although the manufacturer recommends light protection for aqueous solutions of amphotericin B, several reports indicate that short-term exposure to light for 8 to 24 hours results in little difference in potency compared to light protection. 

Miscellaneous

• Monitor renal function, liver function, electrolytes, blood counts and hemoglobin. 

References

1, 4, 5, 40, 95, 102, 135, 143, 182, 208, 366, 462. 

Antineoplastic

Cisplatinum, Platinol ®, Platinol-AQ ®

Indications

• Treatment of testicular, ovarian, cervical, bladder, head and neck, and lung cancers as well as in a variety of other neoplasms.

Administration

• Ensure administration of protocol-specific prehydration and medication to reduce risk or nephrotoxicity; refer to Potential Administration Hazards section.
• Emergency drugs (epinephrine, antihistamines and injectable corticosteroids) should be immediately available for the treatment of hypersensitivity reactions.
• Intermittent IV infusion: dilute dose in NS, D5-NS, D5-1/2NS or D5-1/3NS (do NOT dilute in D5W). Dilute small doses in 100-500 mL and infuse over 15 minutes to 2 hours; dilute larger doses in 1-2 L and infuse each litre over 3-4 hours; consult specific protocol.
• Continuous IV infusion: dilute dose in 1-2 L of compatible fluid (see above) and administer as a continuous infusion; consult specific protocol.
• Do NOT use needles, IV sets or equipment containing aluminum for preparation or administration; a black platinum precipitate will form if cisplatin comes in contact with aluminum and potency will decrease. 

Potential Administration Hazards

• High alert medication: consult Corporate policy ADM VIII 860 (High alert medications).
• Cytotoxic drug: consult Corporate standard operating procedure C-SOP V 250 (Cytotoxic and hazardous drug waste and spills) AND Nursing policy 01651 (Administration of chemotherapy & biotherapy).
• Hypersensitivity: anaphylaxis, anaphylactoid reactions (e.g., facial edema, flushing, bronchoconstriction, hypotension and tachycardia); rash, urticaria.
• Cardiovascular: thromboembolism, bradycardia, conduction disorder.
• GI: nausea, vomiting.
• CNS: neurotoxicity (peripheral neuropathy, leukoencephalopathy, posterior reversible encephalopathy syndrome); cumulative, may be irreversible.
• Electrolyte disturbances: hyponatremia, hypocalcemia, hypophosphatemia, hypokalemia, hypomagnesemia.
• Hematologic: myelosuppression, anemia, hemolytic anemia.
• Hepatic: elevated LTFs and bilirubin.
• Ophthalmic: optic neuritis, papilledema, cerebral blindness, blurred vision, altered colour perception.
• Otic: ototoxicity; dose related, cumulative and irreversible.
• Renal: nephrotoxicity with electrolyte disturbances (dose related, cumulative); prehydration with IV fluids (supplemented possibly with potassium chloride and magnesium sulfate) and concomitant mannitol or furosemide- induced diuresis may be used to reduce nephrotoxicity. Consult specific protocol.
• Myasthenia gravis exacerbation.
• Tumour lysis syndrome, hyperuricemia; can be minimized with allopurinol and alkalinization of urine.
• Local reactions: irritation, phlebitis at injection site.
• Extravasation hazard: irritant at concentrations up to 0.4 mg/mL; vesicant at concentrations greater than 0.4 mg/mL. Consult the extravasation section of the Nursing policy 01651 (Administration of chemotherapy & biotherapy).

Dosage

Usual dosage of 20-100 mg/m2 IV per cycle. Doses greater than 100 mg/m2 IV every 3-4 weeks are rarely used; confirmation of higher doses is advised.

Dosage in renal impairment: 

• Dosage in hepatic impairment: no dosage adjustment is required.
• Dosage adjustment due to toxicity: refer to manufacturer’s recommendations.
• Consult specific protocol. 

Compatibility, Stability

(Consult NAPRA compounding standards; information provided below refers to physical/chemical stability and not to sterility)

• Store vials between 15-25°C. Protect from light. Do not put in fridge or freezer as precipitate may form; however, the precipitate should dissolve at room temp without loss of Do not use if precipitate remains. Do not heat vials to speed up redissolution.
• Precipitation occurs in diluted solutions at concentrations of 0.6 mg/mL or greater when stored in the fridge. More dilute solutions may be refrigerated for up to 72 hours. Discard any diluted solution with precipitate; it should not be warmed for redissolution.
• Minimize exposure of solution to light.
• Stable for 28 days at room temp, protected from light, in NS at concentrations of 0.1 mg/mL and 0.4 mg/mL in PVC containers.
• Stable for 14 days at 30°C, protected from light, in NS at a concentration of 167 mg/mL in PVC, polyethylene and polypropylene bags.
• Stable for 23 hours at room temp, exposed to light, in D5-1/2NS at a concentration of 0.3 mg/mL in PVC containers.
• Stable for 9 days at room temp, protected from light, in NS at a concentration of 0.6 mg/mL in PVC containers.

Miscellaneous

References

1, 4, 5, 6, 40, 129, 135, 165, 208

Immunosuppressant

Cyclosporine A, Neoral ®, Sandimmune ®

Indications

• Prophylaxis and treatment of graft rejection after solid organ transplantation or bone marrow
• Prevention of graft-versus-host disease (GVHD).
• For patients unable to take the oral solution pre- or postoperatively.

Administration

• Emergency drugs (e.g., epinephrine) and oxygen should be immediately available for the treatment of hypersensitivity reactions.
• Intermittent IV infusion, Continuous IV infusion: dilute each 50 mg (1 mL from ampoule) with 20 to 100 mL (i.e., dilute each 5 mL ampoule with 100 to 500 mL) of D5W or NS and infuse over 2 to 6 hours or continuously over 24 hours.
• Glass or non-PVC containers are preferred over PVC bags for infusion. Use non-PVC IV administration sets.
• Observe patient for at least 30 minutes after the start of infusion and frequently thereafter for signs of hypersensitivity. 

Potential Administration Hazards

• Non-cytotoxic hazardous drug: consult Corporate standard operating procedure C-SOP V 250 (Cytotoxic and hazardous drug waste and spills) AND Nursing policy 01651 (Administration of chemotherapy & biotherapy).
• Hypersensitivity: Anaphylactoid reactions, consisting of flushing of face and upper thorax, pulmonary edema, acute respiratory distress with dyspnea, wheezing, BP changes, tachycardia, due to Cremophor EL (polyoxyethylated castor oil); prophylaxis with an antihistamine and an H2 antagonist has been administered to minimize anaphylactoid reactions.
• Cardiovascular: hypertension.
• GI: nausea, vomiting, diarrhea, anorexia, abdominal discomfort.
• CNS: tremor, headache, convulsions, paresthesias.
• Hepatic: increase in serum bilirubin and liver enzymes.
• Renal: dose-related nephrotoxicity. 

Dosage

• The initial dose should be given 4-12 hours prior to transplantation.
• Transplantation: initiate with 3 to 6 mg/kg/day Protocols vary based on institution. Adjust dose to the desired blood or plasma concentration.
• For patients unable to take the oral formulation: treat with IV at one-third of the oral dose.
• Dosage in hepatic impairment: dose reductions may be required in patients with severe liver disease.

Compatibility, Stability

(Consult NAPRA compounding standards; information provided below refers to physical/chemical stability and not to sterility)

• Store ampoules between 15-30°C. Protect from Do not freeze.
• Cremophor EL causes significant leaching of DEHP plasticizer from PVC containers and PVC administration
• Cyclosporine is subject to significant sorption to PVC containers and PVC administration Sorption is higher with dilutions in NS than with D5W.
• Stable for 48 hours at room temp or in the fridge in D5W at a concentration of 2 mg/mL in glass.
• Stable 14 days at room temp in D5W and NS at concentrations of 0.2 mg/mL and 2.5 mg/mL in polypropylene- polyolefin bags.
• Stable for 14 days at room temp in NS and D5W at a concentration of 2.5 mg/mL in EVA bags.
• Stable for 7 days at room temp in NS and D5W at a concentration of 0.2 mg/mL in EVA bags
• Short term (less than 10 minutes) use of polypropylene syringes for preparation is considered safe. Cyclosporine should not be stored in plastic syringes due to leaching of rubber components from rubber tips of plungers.

Miscellaneous

• Contains ethanol 34.4% v/v.

References

1, 4, 5, 6, 40, 95, 135, 143