pemetrexed


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pemetrexed

Alimta

Pharmacologic class: Folic acid antagonist

Therapeutic class: Antineoplastic, antimetabolite

Pregnancy risk category D

Action

Disrupts folate-dependent metabolic processes essential for cell replication

Availability

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

Dosage adjustment

• 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

Contraindications

• Severe hypersensitivity reaction to drug or its components

Precautions

Use cautiously in:
• hepatic or renal impairment, neurotoxicity
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• 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.

Adverse reactions

CNS: fatigue, sensory neuropathy, altered mood, depression

CV: thrombosis, embolism

EENT: pharyngitis

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

Respiratory: dyspnea

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

Interactions

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

Patient monitoring

• 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).

Patient teaching

• 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.

PEMEtrexed

(pe-me-trex-ed) ,

Alimta

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: antimetabolites
Pregnancy Category: D

Indications

Malignant pleural mesothelioma (with cisplatin) when tumor is unresectable or patient is not a candidate for surgery.Local advanced or metastatic nonsquamous non–small cell lung cancer as initial therapy (with cisplatin), in previously treated patients (as monotherapy), or as maintenance treatment in patients whose disease has not progressed after 4 cycles of platinum-based chemotherapy.

Action

Disrupts folate dependent metabolic processes involved in thymidine and purine synthesis. Converted intracellularly to polyglutamate form which increases duration of action.

Therapeutic effects

Decreases growth and spread of mesothelioma.
Improved survival in patients with nonsquamous non–small cell lung cancer.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Minimal metabolism; 70–90% excreted unchanged in urine.
Half-life: 3.5 hr (normal renal function).

Time/action profile (hematologic effects)

ROUTEONSETPEAKDURATION
IVunknown8–15 days21 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity;CCr <45 mL/min; Obstetric / Lactation: Pregnancy, lactation.
Use Cautiously in: Concurrent use of NSAIDs in patients with CCr 45–79 mL/min (avoid those with short half-lives);3rd space fluid accumulation (ascites, pleural effusions); consider drainage prior to therapy;Hepatic impairment (dose alteration recommended); Pediatric: Safety not established.

Adverse Reactions/Side Effects

Respiratory

  • pharyngitis (most frequent)

Cardiovascular

  • chest pain

Gastrointestinal

  • constipation (most frequent)
  • nausea (most frequent)
  • stomatitis (most frequent)
  • vomiting (most frequent)
  • anorexia
  • diarrhea
  • esophagitis
  • mouth pain

Dermatologic

  • desquamation (most frequent)
  • rash (most frequent)

Hematologic

  • anemia
  • hemolytic anemia
  • leukopenia
  • thrombocytopenia

Neurologic

  • neuropathy

Miscellaneous

  • fever (most frequent)
  • infection (most frequent)

Interactions

Drug-Drug interaction

NSAIDs, 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.

Route/Dosage

Intravenous (Adults) Mesothelioma and non–small cell lung cancer (with cisplatin)500—mg/m2 on day 1 of each 21-day cycle (with cisplatin); concurrent hydration, folic acid, and vitamin B12 therapy, and pretreatment with dexamethasone required. Non–small cell lung cancer (as monotherapy)—500 mg/m2 on day 1 of each 21-day cycle (concurrent folic acid, and vitamin B12 therapy, and pretreatment with dexamethasone required).

Availability

Lyophilized powder for IV infusion: 100 mg/vial, 500 mg/vial

Nursing implications

Nursing assessment

  • 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 Diagnoses

Risk for injury (Adverse Reactions)

Implementation

  • 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.
  • Intravenous 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.

Patient/Family Teaching

  • 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.

Evaluation/Desired Outcomes

  • Decreased growth and spread of mesothelioma or non–small cell lung cancer.

pemetrexed

an antineoplastic-antimetabolite.
indications This drug is used in combination with cisplatin in the treatment of malignant pleural mesothelioma and as a single agent in the treatment of non-small cell lung cancer.
contraindications Pregnancy, an absolute neutrophil count less than 1500 cells/mm3, a creatinine clearance count of less than 45 mL/min, thrombocytopenia (less than 100,000/mm3), anemia, and known hypersensitivity to this drug prohibit its use.
adverse effects Adverse effects of this drug include creatinine elevation. Life-threatening effects include thrombosis and embolism, renal failure, neutropenia, leukopenia, thrombocytopenia, myelosuppression, anemia, and infection with or without neutropenia. Common side effects include fatigue, fever, mood alteration, neuropathy, chest pain, nausea, vomiting, anorexia, diarrhea, ulcerative stomatitis, constipation, dysphagia, dehydration, rash, desquamation, and dyspnea.
References in periodicals archive ?
pemetrexed) would not be infringed by a generic competitor that has stated an intent to market certain alternative salt forms of pemetrexed in several European countries upon expiry of the Alimta compound patents in 2015.
Retrospective Analysis of a Phase III Trial of Pemetrexed vs Docetaxel in
Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients with Non-Small Cell Lung Cancer Previously Treated with Chemotherapy.
The second 400-patient trial, evaluating the combination of talabostat with pemetrexed versus placebo and pemetrexed opened to enrollment in February 2006.
decrease pemetrexed elimination and increase the occurrence of adverse events.
Pemetrexed Docetaxel p-value (n=265) (n=276) Median Survival Time 8.
Contract notice: Product delivery leczniczego- used in chemotherapy chemical name pemetrexed dose of 500 mg, 100 mg, character - vials trade name ,, .
So far pemetrexed (brand name ""Alimta"") has been approved to more than 60 countries worldwide.
One patient who previously failed pemetrexed (Alimta(R)) has received 7 cycles of Talotrexin therapy.
The medicines to be supplied under this contract are Bortezomib, Carboplatin, Cetuximab, Cisplatin, Cyclophosphamide, Cytarabine, Docetaxel,Doxorubicin, Epirubicin, Fluorouracil, Gemcitabine,Irinotecan, Methotrexate, Oxaliplatin, Paclitaxel, Pemetrexed and Vincristine in a range of doses.
Researchers demonstrated that the drugs pemetrexed and gemcitabine killed cells from mouse and human brain tumors, called group 3 medulloblastoma, growing in the laboratory.
Lately gefitinib, pemetrexed and erlotinib have entered the market and are initially used in second or third-line treatments.