Basic Introduction

Loxoprofen sodium is a prodrug-type NSAID that is available in several formulations, including 60 mg tablets, 100 mg hydrogel patches and 50 or 100 mg tape. In active comparator-controlled trials, oral loxoprofen therapy (ranging from 2 days to 6 weeks’ duration depending on the pain type) provided analgesic efficacy that generally did not significantly differ from that of celecoxib for postoperative pain or frozen shoulder, ibuprofen for knee osteoarthritis or naproxen for lumbar pain. In double-blind, double-dummy, multicentre trials, Loxoprofen sodium hydrogel patches were noninferior to oral loxoprofen with regard to rates of final overall symptomatic improvement over 1–4 weeks in patients with knee osteoarthritis, myalgia or trauma-induced swelling and pain. Loxoprofen hydrogel patches were also noninferior to other commercially available patches (ketoprofen and indometacin) over 2 or 4 weeks in patients with knee osteoarthritis or myalgia in open-label studies. Oral and topical Loxoprofen sodium were generally well tolerated in clinical trials. Thus, Loxoprofen sodium is a useful analgesic option for patients with pain and inflammation, with topical loxoprofen potentially reducing the risk of gastrointestinal, cardiovascular and renal complications associated with oral NSAID use.

Chemical synthesis route

27.5 g (0.112 mol) of Loxoprofen sodium was dissolved in 50 mL of absolute ethanol, 4.6 g (0.115 mol) of sodium hydroxide was dissolved in 50 mL of absolute ethanol, and the above sodium hydroxide ethanol solution was dropped at 50 ° C. In the ethanol solution of loxoprofen, after 1 h, the reaction was continued for 1 h. After filtration, the filter cake was dried (dried to constant weight at 100 ° C) to obtain 27.1 g of a white solid. The melting point is 199.1 to 200.3 ° C, the yield is 90.3%, and the purity is 99%. The above total yield of 2-(4-bromomethylphenyl) propionic acid esterified, enamine alkylated, and salt formed was 65.0%.[1]

Precautions for the use of Loxoprofen sodium

If you are using a product without a prescription, read all directions on the product package before using this medication. If your doctor has prescribed this medication, read the Medication Guide given by your pharmacist before you start using Loxoprofen sodium and each time you get a refill. If you have questions, ask your doctor or pharmacist. Dosage is based on your medical condition and response to treatment. To reduce the risk of stomach bleeding and other side effects, take this medication at the lowest dose for the shortest possible time. Do not increase your dose or use this medication more frequently than directed by your doctor or package label. For ongoing conditions such as arthritis, continue to take this medication as directed by your doctor. When Loxoprofen is used by children, the dosage is based on the child's weight. Read the directions to find the correct dosage for your child's weight. Consult your pharmacist or doctor if you have any questions or if you need help choosing a non-prescription product. If you are taking this medication "as needed" (not on a regular schedule), remember that it works best when it is used when the first signs of illness occur. If you wait until the pain gets worse, the medicine may not work very well.[2]

If your condition remains the same or gets worse, or if you think you may have a serious medical problem, seek medical help right away.Before using this medication, tell your doctor if you are allergic to loxoprofen, aspirin or other NSAIDs such as ketoprofen (Orudis KT, Actron) and naproxen (Aleve, Naprosyn), any other medications, or any of the inactive ingredients in Loxoprofen sodium that you plan to take. Ask the pharmacist or check the label on the package for a list of inactive ingredients. Tell your doctor or pharmacist any prescription or nonprescription drugs, vitamins, nutritional supplements, herbal products you are taking or planning to take. List the following drugs: angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon) ), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik); diuretics ('water pills'); lithium (Eskalith, Lithobid); and methotrexate (Rheumatrex). Your doctor may need to change your dose or monitor carefully for side effects. Do not take nonprescription Loxoprofen with other medicines unless directed to do so by your doctor. Tell your doctor if you have or have had some conditions such as peptic ulcers, haematological disorders, asthma, especially if you also have a runny nose or nasal polyps (swelling of the inside of the nose); swelling of the hands, arms, legs, ankles, or lower legs; lupus (a condition in which the body attacks many of its own tissues and organs, often including the skin, joints, blood, and kidneys); or liver or kidney disease. If you are giving Loxoprofen to a child, tell the pediatrician if the child has not drunk fluids or has lost large amounts of fluids due to vomiting or diarrhea. Tell your doctor if you are pregnant, especially if you are in the last few months of your pregnancy, or if you plan to become pregnant or breastfeeding. If you become pregnant while taking loxapine, call your doctor. If you have surgery, including dental surgery, tell your doctor or dentist that you are taking Loxoprofen. If you have phenylketonuria (PKU, an inherited disease in which mental retardation develops if a certain diet is not followed), read package labels carefully before taking Loxoprofen sodium recipe. Some types of non-prescription Loxoprofen sodium can be sweetened with aspartame, a source of phenylalanine.[3]

Interaction with other medicinal products and other forms of interaction

Coumarin-Type Anticoagulants: Several short-term controlled studies failed to wshow that ibuprofen significantly affected prothrombin times or a variety of other clotting factors when administered to individuals on coumarin-type anticoagulants. However, because bleeding has been reported when ibuprofen and other nonsteroidal anti-inflammatory agents have been administered to patients on coumarin-type anticoagulants, the physician should be cautious when administering ibuprofen to patients on anticoagulants.[4]

Aspirin: Animal studies wshow that aspirin given with nonsteroidal anti-inflammatory agents, including ibuprofen, yields a net decrease in anti-inflammatory activity with lowered blood levels of the non-aspirin drug. Single dose bioavailability studies in normal volunteers have failed to wshow an effect of aspirin on ibuprofen blood levels. Correlative clinical studies have not been performed.

Methotrexate: Loxoprofen Sodium, as well as other nonsteroidal anti-inflammatory drugs, probably reduces the tubular secretion of methotrexate based on in vitro studies in rabbit kidney slices. This may indicate that ibuprofen could enhance the toxicity of methotrexate. Caution should be used if ibuprofen is administered concomitantly with methotrexate.

H-2 Antagonists: In studies with human volunteers, co-administration of cimetidine or ranitidine with ibuprofen had no substantive effect on ibuprofen serum concentrations.

Furosemide: Clinical studies, as well as random observations, have shown that ibuprofen can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with ibuprofen, the patient should be observed closely for signs of renal failure, as well as to assure diuretic efficacy.

Lithium: Loxoprofen Sodium produced an elevation of plasma lithium levels and a reduction in renal lithium clearance in a study of eleven normal volunteers. The mean minimum lithium concentration increased 15% and the renal clearance of lithium was decreased by 19% during this period of concomitant drug administration.This effect has been attributed to inhibition of renal prostaglandin synthesis by ibuprofen. Thus, when ibuprofen and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. (Read circulars for lithium preparation before use of such concurrent therapy).

Certain drugs should not be used with meals or around meals at certain foods or foods because drug interactions can occur. Consuming alcohol or tobacco with certain drugs can also cause interactions to occur. Discuss your use of drugs with food, alcohol, or tobacco with your health care provider.

References

[1] ZHEJIANG UNIVERSITY - CN109776300, 2019, A

[2] Masahiro Noguchi, et al. "Enzymologic and pharmacologic profile of loxoprofen sodium and its metabolites." Biol Pharm Bull. 2005 Nov;28(11):2075-9.

[3] Kang, J., Li, X., Liang, K., Qi, P., Hu, X., Li, C., Yang, R., & Wang, Q. (2023). Enhancing effect of phosphoric acid on release of loxoprofen sodium in hot-melt pressure-sensitive adhesives based on polystyrene-isoprene-styrene. Journal of Drug Delivery Science and Technology, 88, 104946.

[4] Cao, S., Fu, Y., Jiang, B., Ge, X., Wu, Q., Tao, Y., Zhao, P., & Wang, Z. (2023). Simultaneous stereoisomeric separation of loxoprofen sodium and its alcohol metabolites: Application to a stereoselective pharmacokinetic study. Arabian Journal of Chemistry, 16(8), 104942