No

Antineoplastic Agent, Natural Source (Plant) Derivative

Treatment of metastatic carcinoma of the ovary in combination with cisplatin; treatment of metastatic breast cancer

D

History of hypersensitivity to any component

Severe hypersensitivity reactions have been reported with the first or later infusions. Current evidence indicates that prolongation of the infusion (to greater than or equal to 6 hours) plus premedication may minimize this effect.

Irritant chemotherapy

Cardiovascular: Hypotension, abnormal EKG

Dermatologic: Alopecia

Gastrointestinal: Nausea, vomiting, diarrhea, mucositis

Hematologic: Bleeding, neutropenia, leukopenia, thrombocytopenia, anemia, neutropenia is increased with longer infusions

Hepatic: Abnormal LFTs

Neuromuscular & skeletal: Peripheral neuropathy, myalgia

Miscellaneous: Hypersensitivity reactions, infections

1% to 10%: Cardiovascular: Bradycardia, severe cardiovascular events

<1%: Rare reports of radiation pneumonitis have been received in patients receiving concurrent radiotherapy; rare reports of skin abnormalities related to radiation recall as well as reports of maculopapular rash and pruritus have been received

CYP2C8 and 3A3/4 substrate

In phase I trials, myelosuppression was more profound when given after cisplatin than with alternative sequence; pharmacokinetic data demonstrates a decrease in clearance of ~33% when administered following cisplatin

Possibility of an inhibition of metabolism in patients treated with ketoconazole

Store intact vials at room temperature or refrigeration (2°C to 36°C/36°F to 77°F)

Paclitaxel should be administered in either glass or Excel™/PAB™ containers. Should also use nonpolyvinyl (non-PVC) tubing (eg, polyethylene) to minimize leaching. Formulated in a vehicle known as Cremophor® EL (polyoxyethylated castor oil). Cremophor® EL has been found to leach the plasticizer DEHP from polyvinyl chloride infusion bags or administration sets. Contact of the undiluted concentrate with plasticized polyvinyl chloride (PVC) equipment or devices is not recommended. Administer through I.V. tubing containing an in-line (NOT >0.22 m) filter; administration through IVEX-2® filters (which incorporate short inlet and outlet polyvinyl chloride-coated tubing) has not resulted in significant leaching of DEHP.

Visually compatible via Y-site: Acyclovir, amikacin, bleomycin, calcium chloride, carboplatin, ceftazidime, ceftriaxone, cimetidine, cisplatin, cyclophosphamide, cytarabine, dexamethasone sodium phosphate, diphenhydramine hydrochloride, doxorubicin, etoposide, famotidine, fluconazole, fluorouracil, ganciclovir, gentamicin, haloperidol lactate, heparin, hydrocortisone sodium succinate, hydrocortisone phosphate hydromorphone, lorazepam, magnesium sulfate, mannitol, meperidine, mesna, methotrexate sodium, metoclopramide hydrochloride, morphine sulfate, ondansetron, potassium chloride, prochlorperazine edisylate, ranitidine hydrochloride, sodium bicarbonate, vancomycin hydrochloride

Visually/chemically incompatible via Y-site: amphotericin B, chlorpromazine, hydroxyzine, methylprednisolone, mitoxantrone

Standard I.V. dilution: IVPB: Dose/500-1,000 mL D₅W or NS

Solutions are stable for 27 hours at room temperature (25°C)

Paclitaxel exerts its effects on microtubules and their protein subunits, tubulin dimers. Microtubules serve as facilitators of intracellular transport and maintain the integrity and function of cells. Paclitaxel promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly. Maintaining microtubule assembly inhibits mitosis and cell death. The G₂- and M-phases of the cell cycle are affected. In addition, the drug can distort mitotic spindles, resulting in the breakage of chromosomes.

Administered by I.V. infusion and exhibits a biphasic decline in plasma concentrations

Protein binding: 89% to 98% bound to human serum proteins at concentrations of 0.1-50 mcg/mL

Metabolism: In the liver in animals and evidence suggests hepatic metabolism in humans

Half-life, mean, terminal: 5.3-17.4 hours after 1- and 6-hour infusions at dosing levels of 15-275 mg/m²

Elimination: Urinary recovery of unchanged drug: 1.3% to 12.6% following 1-, 6-, and 24-hour infusions of 15-275 mg/m²

Mean total body clearance range:

After 1- and 6-hour infusions: 5.8-16.3 L/hour/m²

After 24-hour infusions: 14.2-17.2 L/hour/m²

Premedication with dexamethasone (20 mg orally or I.V. at 12 and 6 hours or 14 and 7 hours before the dose), diphenhydramine (50 mg I.V. 30-60 minutes prior to the dose), and cimetidine, famotidine or ranitidine (I.V. 30-60 minutes prior to the dose) is recommended

Ovarian carcinoma: 135-175 mg/m² over 1-24 hours administered every 3 weeks

Metastatic breast cancer: Treatment is still undergoing investigation; most protocols have used doses of 175-250 mg/m² over 1-24 hours every 3 weeks

Hemodialysis: Significant drug removal is unlikely based on physiochemical characteristics

Peritoneal dialysis: Significant drug removal is unlikely based on physiochemical characteristics

Dosage adjustment in hepatic impairment:

Total bilirubin less than or equal to 1.5 mg/dL and AST >2 X normal limits: Total dose <135 mg/m²

Total bilirubin 1.6-3.0 mg/dL: Total dose less than or equal to 75 mg/m²

Total bilirubin greater than or equal to 3.1 mg/dL: Total dose less than or equal to 50 mg/m²

Monitor for hypersensitivity reactions

Mean maximum serum concentrations: 435-802 ng/mL following 24-hour infusions of 200-275 mg/m² and were approximately 10% to 30% of those following 6-hour infusions of equivalent doses

None reported

May cause neutropenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This medication can only be administered by infusion, usually on a cyclic basis. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) and nutrition (small frequent meals will help). You will most likely lose your hair (will grow back after therapy); experience some nausea or vomiting (request antiemetic); feel weak or lethargic (use caution when driving or engaging in tasks that require alertness until response to drug is known). Use good oral care to reduce incidence of mouth sores. You will be more susceptible to infection; avoid crowds or exposure to infection. Report numbness or tingling in fingers or toes (use care to prevent injury); signs of infection (fever, chills, sore throat, burning urination, fatigue); unusual bleeding (tarry stools, easy bruising, or blood in stool, urine, or mouth); unresolved mouth sores; nausea or vomiting; or skin rash or itching. Pregnancy/breast-feeding precautions: Do not get pregnant or breast-feed.

Injection: 6 mg/mL (5 mL, 16.7 mL)

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