Loxotop

Loxoprofen sodium hydrate.

A patch containing 113.4 mg (100 mg as anhydride) of loxoprofen sodium hydrate in 10 g of ointment (a sheet of 140 cm²).
Patch preparation comprising ointment, uniformly spread over a support with the surface of the ointment covered by a liner. The ointment surface is white to pale yellow in color. The ointment has a fragrance of mentha oil.
Loxoprofen sodium hydrate occurs as a white to yellowish white, crystal or crystalline powder. It is very soluble in water and in methanol, freely soluble in ethanol (95), and practically insoluble in diethyl ether. A solution of loxoprofen sodium hydrate (1 in 20) does not show optical rotation.
Chemical Name: Monosodium 2-{4-[(2-oxocyclopentyl) methyl]phenyl} propanoate dihydrate.
Molecular Formula: C₁₅H₁₇NaO_3·2H₂O.
Molecular Weight: 304.31.
Excipients/Inactive Ingredients: Mentha oil, polysorbate 80, titanium oxide, tartaric acid, disodium edetate hydrate, concentrated glycerin, carmellose sodium, talc, dried aluminum hydroxide gel, crotamiton, partially neutralized polyacrylate, starch grafted acrylate 300, emulsion of methyl acrylate and 2-ethylhexyl acrylate copolymer.

Pharmacology: Pharmacodynamics: Mechanism of Action: After being absorbed transdermally, loxoprofen sodium hydrate is biotransformed into an active metabolite trans-OH form (SRS coordination) to exert its anti-inflammatory and analgesic effects in acute inflammations, chronic inflammations and pain.
Anti-inflammatory effects: LOXOTOP PAP 100 mg Patch has been demonstrated significant anti-inflammatory effects on both acute inflammations such as carrageenan-induced edema (rat) and chronic inflammations such as adjuvant arthritis (rat).
Analgesic effects: LOXOTOP PAP 100 mg Patch has been demonstrated to show the analgesic effect in the Randall-Selitto test (inflamed paw pressuring method: rat), and in the chronic adjuvant arthritis pain test (rat).
Pharmacokinetics: Plasma Concentration: Each of 14 Japanese healthy male adult volunteers was subjected to repeated administration of two LOXOTOP PAP 100 mg Patch on the back once a day for five days, showing detection of loxoprofen and its trans-OH form (active metabolite) in the plasma immediately after the start of the administration with their plasma concentrations gradually increasing over the period of the administration before reaching steady state in four or five days after the administration at low levels compared to those achieved by the equivalent oral dose of the same drug until, upon the discontinuation of the administration, they rapidly disappeared from the plasma to concentrations below the limit of quantitative determination (LQD).
Tissue Penetration: Administration of 3.5 cm² of the LOXOTOP PAP 100 mg Patch (containing ¹⁴C-loxoprofen) to the rat dorsal skin for a time period of 24 hours showed that the concentration of radioactivity in the skeletal muscle immediately under the patch administered area of the skin was 3.6- to 24-fold higher than that in the skeletal muscle under the patch non-administered area of the skin, confirming the formation of the trans-OH form of ¹⁴C-loxoprofen as its active metabolite.
Metabolism: An in vitro test of loxoprofen sodium hydrate for metabolism inhibition using human hepatic microsome showed that the drug did not inhibit the metabolism of substrates for cytochrome P450 enzymes (CYP1A1/2, 2A6, 2B6, 2C8/9, 2C19, 2D6, 2E1 and 3A4) even at a concentration of 200 μM equivalent to 1,000 times or more than the maximum plasma concentration observed by administration of LOXOTOP PAP 100 mg Patch in a dose of one patch a day.
Urinary Excretion: Each of 14 Japanese healthy male adult volunteers was subjected to repeated administration of two LOXOTOP PAP 100 mg Patch on the back once a day for five days, showing that the daily urinary excretion of loxoprofen, its trans-OH form (active metabolite) and cis-OH form remained almost constant after the elapse of 24 hours following the administration with the total cumulative excretion rate of 2.67% from the start of the administration until 48 hours after the discontinuation of the administration.

LOXOTOP PAP 100 mg Patch is indicated for anti-inflammation and pain relief in the following diseases and symptoms: Osteoarthritis, myalgia, posttraumatic swelling and pain.

LOXOTOP PAP 100 mg Patch should be applied once daily to the affected area.

There is no data available on overdose.

LOXOTOP PAP 100 mg Patch is contraindicated in the following patients. Patients with a history of hypersensitivity to any ingredients of LOXOTOP PAP 100 mg Patch.
Patients with or with a history of aspirin-induced asthma (induction of asthmatic attack with nonsteroidal anti-inflammatory-analgesics, etc.). [May induce an aspirin-induced asthmatic attack.]

WARNING: Risk of GI Ulceration, Bleeding and Perforation with NSAID: Serious GI toxicity such as bleeding, ulceration and perforation can occur at any time, with or without warning symptoms, in patients treated with NSAID therapy. Although minor upper GI problems (e.g. dyspepsia) are common, usually developing early in therapy, prescribers should remain alert for ulceration and bleeding in patients treated with NSAIDs even in the absence of previous GI tract symptoms.
Studies to date have not identified any subset of patients not at risk of developing peptic ulceration and bleeding. Patients with prior history of serious GI events and other risk factors associated with peptic ulcer disease (e.g. alcoholism, smoking, and corticosteroid therapy) are at increased risk. Elderly or debilitated patients seem to tolerate ulceration or bleeding less than other individuals and account for most spontaneous reports for fatal GI events.
Careful Administration: LOXOTOP PAP 100 mg Patch should be administered with caution in the following patients: Patients with bronchial asthma (as the disease state may be exacerbated).
Important Precautions: It is important to note that treatment with anti-inflammatory-analgesic agents is a symptomatic treatment, not a causal treatment.
For treatment of skin inflammation caused by infectious disease, LOXOTOP PAP 100 mg Patch may cause a risk of masking the signs and symptoms of the infectious disease, therefore, the appropriate antibacterial and/or antifungal drugs must be administered in combination with LOXOTOP PAP 100 mg Patch to the affected part of the skin, under careful observation and caution.
Therapies other than drug treatment must also be considered in using LOXOTOP PAP 100 mg Patch in the management of chronic diseases (osteoarthritis and others). The patient's clinical condition should be closely monitored with caution against the development of adverse reactions.
Precautions Concerning Use: Site of application: Do not apply LOXOTOP PAP 100 mg Patch onto area of damaged or non-intact skin or mucosal membrane.
Do not apply LOXOTOP PAP 100 mg Patch onto area of eczema and rash.
Effects on Ability to Drive and Use Machines: There is no data available on effects on ability to drive and use machines.
Use in Children: The safety of LOXOTOP PAP 100 mg Patch in low birth weight infants, newborn infants, infants and toddlers, children and adolescents has not been established (because there has been little experience of its use in pediatric patients).
Use in the Elderly: LOXOTOP PAP 100 mg Patch should be used with careful monitoring of dermal condition of application area, in the elderly patients.

LOXOTOP PAP 100 mg Patch should be administered to women who are or are possibly pregnant only when the anticipated therapeutic benefits are considered to outweigh any potential risk. [The safety of LOXOTOP PAP 100 mg Patch in these populations has not been established.]
The following information is for reference only, the adverse reaction is not reported on the use of this product. It has been reported that constriction of the fetal ductus arteriosus is observed when woman in the late stage of pregnancy received other nonsteroidal anti-inflammatory-analgesic drugs for external use.
Renal impairment and decreased urine output in foetuses as well as accompanying oligohydramnios have been reported following use of cyclooxygenase inhibitors (oral dosage form or suppository) in pregnant women.

Clinically Significant Adverse Reactions: Shock, anaphylaxis (The incidence unknown).
Shock, anaphylaxis: Shock or anaphylaxis (decreased blood pressure, urticaria, laryngeal oedema, dyspnoea, etc.) may occur. Patients should be carefully monitored. If any abnormalities are observed, use of this drug should be discontinued immediately and appropriate measures should be taken.
Other adverse reactions: (See table.)

Click on icon to see table/diagram/image

Not applicable to both contraindications and precautions for coadministration.

Instructions for use/handling: After removing the patch from the pouch for use, be sure to close it securely by gently pressing both sides of its zip-lock portion against each other.

LOXOTOP PAP 100 mg Patch must be stored in light-proof tightly-sealed container. Do not store above 30°C.
Shelf life: 24 months.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AE - Propionic acid derivatives ; Used in the treatment of inflammation and rheumatism.

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