Alimta® (Pemetrexed)

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Pemetrexed: Concurrent Use With NSAIDs

Ibuprofen increased the risk of pemetrexed toxicity in patients with a CrCl of 45-79 mL/min. Dosage modification of ibuprofen is recommended for these patients.

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Detailed Information

Ibuprofen increases exposure (AUC) of pemetrexed.1

NSAID Use in Patients With Normal Renal Function

Moderate doses of NSAIDs can be administered with pemetrexed to patients with normal renal function (CrCl ≥80 mL/min).2 

Dosage Modification of Ibuprofen in Patients With Mild to Moderate Renal Impairment Receiving Pemetrexed

Increased Risk of Toxicity With Ibuprofen in Patients With Renal Impairment

Exposure to pemetrexed is increased in patients with mild to moderate renal impairment who take concomitant ibuprofen, increasing the risks of adverse reactions of pemetrexed.1

In patients with creatinine clearances between 45 mL/min and 79 mL/min, avoid administration of ibuprofen for

  • 2 days before
  • the day of, and
  • 2 days following administration of pemetrexed.1

If concomitant ibuprofen use cannot be avoided, monitor patients more frequently for pemetrexed adverse reactions, including myelosuppression, renal, and GI toxicity.1

Drug Interaction Studies

Drugs Inhibiting OAT3 Transporter

Ibuprofen, an OAT3 inhibitor, administered at 400 mg four times a day decreased the clearance of pemetrexed and increased its exposure (AUC) by approximately 20% in patients with normal renal function (CrCl >80 mL/min).1

In Vitro Studies

Pemetrexed is a substrate for OAT3. Ibuprofen, an OAT3 inhibitor, inhibited the uptake of pemetrexed in OAT3-expressing cell cultures with an average [Iu]/IC50 ratio of 0.38. In vitro data predict that at clinically relevant concentrations, other NSAIDs (naproxen, diclofenac, celocoxib) would not inhibit the uptake of pemetrexed by OAT3 and would not increase the AUC of pemetrexed to a clinically significant extent.1

Pemetrexed is a substrate for OAT4. In vitro, ibuprofen and other NSAIDs (naproxen, diclofenac, celocoxib) are not inhibitors of OAT4 at clinically relevant concentrations.1

Aspirin

Aspirin, administered in low to moderate doses (325 mg every 6 hours), does not affect the pharmacokinetics of pemetrexed.1

References

1[DO NOT USE] -- Alimta [package insert]. Indianapolis, IN: Eli Lilly and Company; 2018. http://uspl.lilly.com/alimta/alimta.html

2Data on file, Eli Lilly and Company and/or one of its subsidiaries.

Glossary

AUC = area under the curve

CrCl = creatinine clearance

GI = gastrointestinal

IC50 = half maximal inhibitory concentration 

NSAID = nonsteroidal anti-inflammatory drug

OAT = organic anion transporter

Fecha de la última revisión: 2018 M08 01


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