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Pharmacologic class: Folic acid antagonist
Therapeutic class: Antineoplastic, antimetabolite
Pregnancy risk category D
Disrupts folate-dependent metabolic processes essential for cell replication
Powder for injection: 500 mg sterile lyophilized powder in single-use vials
⊘Indications and dosages
➣ Malignant pleural mesothelioma in patients whose disease is unresectable or who otherwise aren't eligible for curative surgery (given with cisplatin)
Adults: 500 mg/m2 as an I.V. infusion over 10 minutes on day 1 of each 21-day cycle. The recommended dose of cisplatin is 75 mg/m2 infused over 2 hours starting approximately 30 minutes after pemetrexed administration ends.
➣ Nonsquamous non-small-cell lung cancer
Adults: 500 mg/m2 I.V. infusion over 10 minutes on day 1 of each 21-day cycle for single-agent use, or in combination with cisplatin infused over 2 hours starting approximately 30 minutes after pemetrexed administration ends
• Hematologic toxicities, based on nadir absolute neutrophil and platelet counts
• Grade 2 to 4 neurotoxicity
• Grade 3 or higher nonhematologic toxicities (except neurotoxicity)
• Grade 3 or 4 diarrhea or any diarrhea requiring hospitalization
• Creatinine clearance below 45 ml/minute
• Severe hypersensitivity reaction to drug or its components
Use cautiously in:
• hepatic or renal impairment, neurotoxicity
• pregnant or breastfeeding patients
• children (safety and efficacy not established).
• Reconstitute 500-mg vial with 20 ml preservative-free normal saline solution injection, yielding 25 mg/ml. Gently swirl vial until powder dissolves completely.
• Further dilute appropriate volume of reconstituted solution to 100 ml with preservative-free normal saline solution injection; administer I.V. over 10 minutes.
• Know that drug is physically incompatible with diluents containing calcium, including Ringer's and lactated Ringer's solutions. Administration with other drugs and diluents isn't recommended.
• Administer I.V. only.
• As ordered, pretreat with dexamethasone (or equivalent) 4 mg P.O. twice daily on day before, day of, and day after pemetrexed administration to minimize cutaneous reactions.
• When administering with cisplatin, hydrate patient with 1 to 2 L fluid infused over 8 to 12 hours before and after cisplatin administration. Maintain adequate hydration and urine output for 24 hours.
• To reduce toxicity, ensure that patient receives at least five daily doses of low-dose folic acid or multivitamin with folic acid within 7 days before first pemetrexed dose. Folic acid therapy should continue throughout course of therapy and for 21 days after final dose. Patient also must receive one I.M. injection of vitamin B12 during week before first pemetrexed dose and every three cycles thereafter.
• Discontinue drug if creatinine clearance is below 45 ml/minute or patient has hematologic or nonhematologic Grade 3 or 4 toxicity after two dosage reductions (except Grade 3 transaminase elevation).
• Withdraw drug immediately in patients with Grade 3 or 4 neurotoxicity.
CNS: fatigue, sensory neuropathy, altered mood, depression
CV: thrombosis, embolism
GI: nausea, vomiting, constipation, diarrhea without colostomy, dysphagia, esophagitis, pain on swallowing, stomatitis, anorexia
GU: renal failure
Hematologic: neutropenia, leukopenia, anemia, thrombocytopenia, febrile neutropenia
Hepatic: abnormal liver function
Musculoskeletal: myalgia, arthralgia
Skin: rash, desquamation, alopecia
Other: fever, dehydration, noncardiac chest pain, infection without neutropenia or with Grade 3 or Grade 4 neutropenia, edema, other constitutional symptoms, allergic reaction, hypersensitivity reaction
Drug-drug.Ibuprofen: decreased pemetrexed clearance and increased concentration
Nephrotoxic agents: possible decrease in pemetrexed clearance
Drug-diagnostic tests.Alanine aminotransferase, aspartate aminotransferase, serum creatinine: increased
Creatinine clearance, hematocrit, hemoglobin, platelets, WBCs: decreased
• Monitor CBC and platelet counts frequently.
• Monitor renal and liver function tests and blood chemistry results (especially serum creatinine) periodically.
• Know that patients with mild to moderate renal insufficiency should avoid taking nonsteroidal anti-inflammatory drugs (NSAIDs) with short elimination half-lives (such as aspirin, diclofenac, and ibuprofen) for 5 days before, on day of, and for 2 days after pemetrexed administration. If concomitant NSAID use is necessary, monitor patient closely for toxicities (especially myelosuppression and renal and GI toxicity).
• Be aware that all patients should avoid NSAIDs with long half-lives (such as diflunisal, piroxicam, and sulindac) for at least 5 days before, on day of, and for 2 days after pemetrexed administration. If concomitant NSAID use is necessary, monitor patient closely for toxicities (especially myelosuppression and renal and GI toxicity).
• Instruct patient to take folic acid and vitamin B12 before and during therapy, as prescribed.
• Advise patient to drink ten 8-oz glasses of fluid and to urinate frequently during first 24 hours after therapy that includes cisplatin.
• Teach patient to recognize signs and symptoms of anemia and to contact prescriber if temperature above 100.4 °F (38 °C) develops.
• Tell patient to consult prescriber before taking products containing ibuprofen.
• Advise female with childbearing potential to avoid pregnancy during therapy.
• Instruct breastfeeding patient to stop breastfeeding during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.
Time/action profile (hematologic effects)
|IV||unknown||8–15 days||21 days|
Adverse Reactions/Side Effects
- pharyngitis (most frequent)
- chest pain
- constipation (most frequent)
- nausea (most frequent)
- stomatitis (most frequent)
- vomiting (most frequent)
- mouth pain
- desquamation (most frequent)
- rash (most frequent)
- hemolytic anemia
- fever (most frequent)
- infection (most frequent)
Drug-Drug interactionNSAIDs, especially those with short half-lives, ↑ blood levels and risk of toxicity; avoid for 2 days before, day of, and 2 days after treatment. Probenecid ↑ blood levels.Concurrent use of nephrotoxic agents ↑ risk of nephrotoxicity.
- Monitor for rash during therapy. Pretreatment with dexamethasone 4 mg orally twice daily the day before, the day of, and the day after administration reduces incidence and severity or reaction.
- Monitor for hematologic and GI (mucositis, diarrhea) toxicities. If any Grade 3 or 4 toxicities, except mucositis or diarrhea, requiring hospitalization occur, decrease doses of pemetrexed and cisplatin by 75%. If Grade 3 or 4 mucositis occurs decrease pemetrexed dose by 50% and cisplatin by 100% of previous dose.
- Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur; monitor for increased fatigue, dyspnea, and orthostatic hypotension.
- Assess for neurotoxicity during therapy. If Grade 0–1 neurotoxicity occurs, decrease pemetrexed and cisplatin doses by 100% of previous dose. If Grade 2 neurotoxicity occurs, decrease pemetrexed dose by 100% and cisplatin dose by 50% of previous dose. If Grade 3 or 4 neurotoxicity occurs, discontinue therapy.
- Lab Test Considerations: Monitor CBC and platelet counts for nadir and recovery and renal function, before each dose and on days 8 and 15 of each cycle and chemistry for renal and liver functions periodically. May cause neutropenia, thrombocytopenia, leukopenia, and anemia. A new cycle should not be started unless the ANC is at least 1500 cells/mm3, platelet count is at least 100,000 cells/mm3, and creatinine clearance is at least 45 mL/min. If nadir of ANC is less than 500/mm3 and nadir of platelets are at least 50,000/mm3 decrease doses of pemetrexed and cisplatin by 75%. If nadir of platelets is less than 50,000/mm3 regardless of ANC nadir decrease pemetrexed and cisplatin doses by 50%.
Potential Nursing DiagnosesRisk for injury (Adverse Reactions)
- Do not confuse pemetrexed with pralatrexate.
- Pemetrexed should be administered under supervision of a physician experienced in the use of chemotherapeutic agents.
- Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in designated containers.
- To reduce toxicity, 0.4–1 mg of folic acid must be taken daily for 7 days preceding first dose of pemetrexed and should continue during and for 21 days after last dose. Patients must also receive an injection of vitamin B12 1 mg IM during the week preceding first dose of pemetrexed and every 3 cycles thereafter. Subsequent doses of vitamin B12 may be given on same day as pemetrexed. Also administer dexamethasone 4 mg twice daily the day before, the day of, and the day after pemetrexed administration.
- Intermittent Infusion: Calculate number of pemetrexed 500-mg vials needed; vials contain excess to facilitate delivery. Reconstitute 500 mg with 20 mL of preservative–free 0.9% NaCl. Concentration: 25 mg/mL. Swirl gently until powder is completely dissolved. Solution is clear and colorless to yellow or green-yellow. Do not administer if discolored or containing particulate matterDiluent: Dilute further to 100 mL with preservative–free 0.9% NaCl. Solution is stable at room temperature or if refrigerated for up to 24 hr.
- Rate: Administer over 10 min.
- Y-Site Compatibility: acyclovir, alfentanil, allopurinol, amifostine, amikacin, aminocaproic acid, aminophylline, amiodarone, amphotericin B lipid complex, amphotericin B liposome, ampicillin, amipicillin/sulbactam, atracurium, azithromycin, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, carboplatin, carmustine, ceftriaxone, cefuroxime, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dactinomycin, daptomycin, dexamethasone sodium phosphate, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, docetaxel, dolasetron, dopamine, doxacurium, doxorubicin liposome, enalaprilat, ephedrine, epinephrine, eptifibitide, ertapenem, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, fluorouracil, foscarnet, fosphenytoin, furosemide, ganciclovir, glycopyrrolate, granisetron, haloperidol, heparin, hydrocortisone sodium succinate, hydromorphone, ifosfamide, imipenem/cilastatin, insulin, isoproterenol, ketorolac, labetalol, leucovorin, levofloxacin, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, meperidine, meropenem, mesna, methyldopate, methylprednisolone sodium succinate, metoclopramide, metoprolol, midazolam, milrinone, mitomycin, morphine, moxifloxacin, nafcillin, naloxone, nesiritide, nitroglycerin, norepinephrine, octreotide, oxaliplatin, paclitaxel, pamidronate, pancuronium, pentobarbital, phenobarbital, phentolamine, piperacillin/tazobactam, potassium acetate, potassium chloride, potassium phosphates, procainamide, promethazine, propranolol, ranitidine, remifentanil, rocuronium, sodium acetate, sodium bicarbonate, sodium phosphates, succinylcholine, sufentanil, tacrolimus, theophylline, thiopental, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, trimethoprim/sulfamethoxazole, vancomycin, vecuronium, verapamil, vinblastine, vincristine, vinorelbine, zidovudine, zoledronic acid
- Y-Site Incompatibility: amphotericin B colloidal, anidulafungin, calcium acetate, calcium chloride, calcium gluconate, caspofungin, cefazolin, cefepime, cefotaxime, cefotetan, cefoxitin, ceftazidime, chloramphenicol, chlorpromazine, ciprofloxacin, dacarbazine, dantrolene, daunorubicin hydrochloride, diazepam, dobutamine, doxorubicin, doxycycline, droperidol, epirubicin, erythromycin, gemcitabine, gentamicin, hydralazine, idarubicin, irinotecan, metronidazole, mitoxantrone, nalbuphine, nicardipine, nitroprusside, ondansetron, pantoprazole, pentamidine, pentazocine, phenytoin, prochlorperazine, quinupristin/dalfopristin, tobramycin, topotecan, vasopressin
- Additive Incompatibility: Solutions containing calcium, including Lactated Ringer's and Ringer's solution.
- Emphasize the importance of taking prophylactic folic acid and vitamin B12 to reduce treatment-related hematologic and GI toxicity.
- Advise patient to notify health care professional immediately if signs and symptoms of infection (fever, sore throat), anemia, or neurotoxicity occur.
- Instruct patients to notify health care professional if persistent vomiting, diarrhea, or signs of dehydration appear.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially NSAIDs and to avoid alcohol during therapy.
- Advise patient to avoid becoming pregnant during therapy. If pregnancy is planned or suspected, notify health care professional promptly.
- Decreased growth and spread of mesothelioma or non–small cell lung cancer.