ALIMTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALIMTA (ALIMTA).
Pemetrexed is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. It inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), which are key enzymes in the de novo synthesis of thymidine and purine nucleotides.
| Metabolism | Pemetrexed is minimally metabolized. It is excreted primarily unchanged in the urine (70-90% within 24 hours). Metabolism is negligible; no significant cytochrome P450 involvement. |
| Excretion | Primarily renal excretion; approximately 70-90% of the dose is eliminated unchanged in urine within 24 hours. Biliary/fecal excretion is minimal (<5%). |
| Half-life | Terminal elimination half-life is 3.5 hours (range 2.7-5.0 hours) in patients with normal renal function. In patients with moderate renal impairment (creatinine clearance 45-79 mL/min), half-life is prolonged to approximately 4.2 hours. Clinical context: Half-life does not accumulate significantly with once-weekly dosing; no dose adjustment required for mild impairment. |
| Protein binding | 81% bound to plasma proteins (primarily albumin). Binding is concentration-independent over therapeutic range. |
| Volume of Distribution | Mean steady-state volume of distribution is 16.1 L/m² (approximately 0.3-0.4 L/kg in adults). Total body water distribution indicates limited tissue binding; primarily confined to extracellular space. |
| Bioavailability | Not administered orally; bioavailability data not applicable. Only intravenous route is used. Not available as oral formulation. |
| Onset of Action | Intravenous administration: Onset of clinical effect (antitumor activity) occurs within days to weeks, typically after 2-3 cycles of treatment. Peak plasma concentrations achieved immediately after infusion. |
| Duration of Action | Duration of action is approximately 3 weeks for dosing interval (once every 21 days). Clinical note: Myelosuppression (neutropenia, thrombocytopenia) nadir occurs around 8-10 days post-dose and resolves by day 21. Antitumor effect may persist beyond treatment cycles. |
| Action Class | Antimetabolites |
| Brand Substitutes | Pemnat 500mg Injection, Pemetero 500 Injection, Mytrex 500mg Injection, Pempro 500mg Injection, Pemexar 500mg Injection, Pemxcel 100 Injection, Pemnat 100mg Injection, Antifol 100mg Injection, Pempro 100mg Injection, Mytrex 100mg Injection |
500 mg/m2 IV over 10 minutes on day 1 of each 21-day cycle, in combination with cisplatin 75 mg/m2 IV over 2 hours starting 30 minutes after pemetrexed.
| Dosage form | POWDER |
| Renal impairment | For CrCl 45-79 mL/min: no adjustment. For CrCl <45 mL/min: do not administer. CrCl calculated by Cockcroft-Gault using actual body weight. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: use with caution; efficacy and safety not established. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dosing available. |
| Geriatric use | No specific dose adjustment based on age alone; dose based on renal function. Monitor renal function and myelosuppression closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALIMTA (ALIMTA).
| Breastfeeding | Excretion into human milk unknown; M/P ratio not determined. Because of potential for serious adverse reactions in breastfed infants (e.g., myelosuppression, gastrointestinal toxicity), breastfeeding is contraindicated during therapy and for at least one week after last dose. |
| Teratogenic Risk | Pregnancy Category D. First trimester: High risk of major congenital malformations including CNS, skeletal, and visceral anomalies based on animal studies and mechanism of action (antifolate). Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and fetal demise due to cytotoxic effects on rapidly dividing cells. Pregnant women should be advised of potential fetal harm. |
■ FDA Black Box Warning
ALIMTA can cause fetal harm when administered to pregnant women. Pemetrexed is teratogenic and embryotoxic. Women of childbearing potential should be advised to avoid pregnancy during treatment.
| Serious Effects |
["History of severe hypersensitivity reaction to pemetrexed","Creatinine clearance <45 mL/min (due to risk of renal failure)","Pregnancy (fetal harm)","Lactating women (discontinue nursing or drug)"]
| Precautions | ["Myelosuppression: Dose-dependent bone marrow suppression, may require dose adjustment or delay","Renal toxicity: Increased risk with renal impairment; contraindicated in CrCl <45 mL/min","GI toxicity: Nausea, vomiting, diarrhea, and mucositis; premedicate with corticosteroids","Rash and desquamation: Requires vitamin B12 and folic acid supplementation to reduce toxicity","Hepatotoxicity: Monitor liver function tests","Radiation recall: Has been reported with prior radiotherapy","Third-space fluid: May accumulate in pleural effusions or ascites; consider drainage before treatment"] |
| Food/Dietary | Avoid folic acid supplements beyond prescribed dose. No known specific food interactions, but maintain adequate hydration. Grapefruit does not interact significantly. |
Loading safety data…
| Fetal Monitoring | Complete blood counts (CBC) with differential and platelets at baseline and before each cycle. Serum creatinine, bilirubin, and transaminases prior to each dose. Monitor for signs of myelosuppression, renal toxicity, and hepatic impairment. Fetal ultrasound to assess growth and amniotic fluid volume if exposure occurs during pregnancy. |
| Fertility Effects | Pemetrexed may impair fertility in males and females based on animal studies showing testicular degeneration and ovarian atrophy. In humans, reversible oligospermia and amenorrhea may occur. Advise patients of potential impact on future fertility. |
| Clinical Pearls | Premedicate with folic acid (350-1000 mcg daily) and vitamin B12 (1000 mcg IM every 9 weeks) starting 1 week before first dose to reduce toxicity. Administer as an IV infusion over 10 minutes. Do not use with NSAIDs in patients with renal impairment due to increased toxicity. Monitor renal function, CBC, and LFTs regularly. |
| Patient Advice | Take folic acid daily and get vitamin B12 injections as prescribed to lower side effects. · Report any signs of infection, bleeding, or unusual tiredness immediately. · Avoid ibuprofen, naproxen, and other anti-inflammatory drugs unless approved by your doctor. · Drink plenty of fluids to stay hydrated and protect kidneys. · May cause diarrhea, nausea, vomiting; take antiemetics as prescribed. · Use effective contraception during and for 3 months after treatment. · Do not breastfeed during treatment. |