Dosing and uses of Alimta (pemetrexed)
Adult dosage forms and strengths
powder for injection
- 500mg/vial
Malignant Pleural Mesothelioma
Indicated for mesothelioma in combination with cisplatin in patients whose disease is unresectable or are not candidates for curative surgery
Combination use with cisplatin: 500 mg/m² IV over 10 minutes on Day 1 of each 21-day cycle; administer cisplatin (75 mg/m² IV over 2 hr) 30 minutes after end of premetrexed infusion
Nonsquamous Non-Small Cell Lung Carcinoma
Indications
- Initial treatment: In combination with cisplatin for initial treatment with locally advanced or metastatic nonsquamous NSCLC
- Maintenance: Locally advanced or metastatic nonsquamous NSCLC in patients whose disease has not progressed after 4 cycles of platinum-based first-line chemotherapy
- After prior chemotherapy: As a single agent of locally advanced or metastatic nonsquamous NSCLC after prior chemotherapy
Single-agent use: 500 mg/m² IV infusion over 10 minutes on Day 1 of each 21-day cycle
Combination use with cisplatin: 500 mg/m² IV over 10 minutes on Day 1 of each 21-day cycle; administer cisplatin (75 mg/m² IV over 2 hr) 30 minutes after end of premetrexed infusion
Premedication Regimen
Folic acid: 400-1000 mcg PO qDay beginning 7 days before first pemetrexed dose; continue during the full course of therapy and for 21 days after the last dose
Vitamin B12: 1 mg IM beginning 1 week before first pemetrexed dose and repeat every 3 cycles thereafter; subsequent doses may be administered on the same day as pemetrexed
Do not substitute PO B12 for IM (see Cautions)
Dexamethasone: 4 mg PO BID on the day before, day of, and day after pemetrexed administration treatment to help prevent skin rash
Dosage modifications
If nadir ANC <500/mm³ & nadir platelets ≥50,000/mm³
- Adjust to 75% of previous dose (both drugs)
If nadir platelets <50,000/mm³ regardless of nadir ANC
- Adjust to 50% of previous dose (both drugs)
Any Grade 3 or 4 toxicities except mucositis
- Adjust to 75% of previous dose (both drugs)
Any diarrhea requiring hospitalization
- Adjust to 75% of previous dose (both drugs)
Grade 3 or 4 mucositis
- Adjust Alimta to 50% of previous dose
CTC Grade 2
- Adjust Cisplatin to 50% of previous dose
Monitor
CBC, platelet counts, and CrCl for nadir and recovery before each cycle
Periodic hepatic monitoring
Requirements to begin new cycle
- ANC >1500 cells/mm³
- Platelets >100,000 cells/mm³
- CrCl ≥45 mL/min
Pediatric dosage forms and strengths
Safety and efficacy not established
Alimta (pemetrexed) adverse (side) effects
>10%
Nausea (84%)
Fatigue (80%)
Pulmonary dyspnea (66%)
Neutropenia (58%)
Vomiting (58%)
Leukopenia (55%)
Constipation (44%)
Chest pain (40%)
Anorexia (35%)
Anemia (33%)
Pharyngitis (28%)
Stomatitis (28%)
Thrombocytopenia (27%)
Diarrhea without colostomy (26%)
Rash/desquamation (22%)
Fever (17%)
Neuropathy/sensory (17%)
Creatinine elevation (16%)
Mood alteration/depression (14%)
Infection without neutropenia (11%)
1-10%
Dehydration, thrombosis/embolism (7%)
Dysphagia/esophagitis/odynophagia (6%)
Infection with Grade 3 or Grade 4 neutropenia (6%)
Neutropenia-other (3%)
Allergic reaction/hypersensitivity (2%)
Renal failure (2%)
Febrile neutropenia (1%)
<1%
Esophagitis
Arrhythmia
Motor neuropathy
Febrile neutropenia
Erythema multiforme
Postmarketing Reports
Gastrointestinal: Colitis, pancreatitis
Blood and lymphatic system: Immune-mediated hemolytic anemia
General: Edema
Injury, poisoning, and procedural complications: Radiation recall has been reported in patients who have previously received radiotherapy
Respiratory: Interstitial pneumonitis
Skin: Bullous conditions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (some cases were fatal)
Warnings
Contraindications
Hypersensitivity
Cautions
Premedication required with folic acid PO and vitamin B12 IM to reduce severity of hematologic and GI toxicities; do not substitute PO vitamin B12 for IM to assure adequate absorption
Renal impairment, bone marrow suppression (dose-limiting toxicity)
Obtain a complete blood count and renal function tests at the beginning of each cycle and as needed; do not initiate a cycle of treatment unless the ANC is ≥1500 cells/mm³, the platelet count is ≥100,000 cells/mm³, and creatinine clearance is ≥45 mL/min
Coadministration of NSAIDS with mild-to-moderate renal insufficiency; NSAIDs can decrease pemetrexed renal clearance
Avoid pregnancy
Pregnancy and lactation
Pregnancy category: d
Lactation: not safe
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Alimta (pemetrexed)
Mechanism of action
Antifolate antineoplastic agent
Disrupts folate-dependent metabolic processes essential for cell replication
Distribution
Vdss: 16.1 L
Protein Bound: 81%
Metabolism
Metabolites: polyglutamate forms
Enzymes inhibited
- Thymidylate synthase
- Dihydrofolate reductase
- Glycinamide ribonucleotide formyltransferase
- All folate-dependent enzymes involved in de novo biosynthesis of thymidine and purine nucleotides
Elimination
Total Body Clearance: 91.8 mL/min
Half-Life, Elimination: 3.5 hr
Excretion: urine
Administration
IV Incompatibilities
Solution: diluents containing calcium, including LR & Ringer's
Coadministration not recommended
IV Compatibilities
Solution: 0.9% NaCL
IV Preparation
Aseptically reconstitute with 20 mL of 0.9% NaCl (preservative free) to give a 25 mg/mL solution
Gently swirl until completely dissolved; resulting solution is clear and ranges in color from colorless to yellow/green-yellow without adversely affecting quality
Aseptically dilute required dose to 100 mL with 0.9% NaCl (preservative free)
Reconstituted and infusion soln stable for 24 hr at room temperature and fridgerator
IV Administration
Infuse over 10 min
Storage
Store vials at 25°C (77°F)
