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Fedorchenko Olga Valeryevna 、薬局による医学的評価、 最終更新日:13.03.2022
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Deflox is indicated for the treatment of the pain of osteoarthritis of the knee(s).
General Dosing Instructions
Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
For relief of the pain of osteoarthritis (OA) of the knee(s), the recommended dose is 40 mg of diclofenac sodium (2 pump actuations) on each painful knee, 2 times a day.
Apply Deflox to clean, dry skin.
The pump must be primed before first use. Instruct patients to fully depress the pump mechanism (actuation) 4 times while holding the bottle in an upright position. This portion should be discarded to ensure proper priming of the pump. No further priming of the bottle should be required.
After the priming procedure, Deflox is properly dispensed by completely depressing the pump 2 times to achieve the prescribed dosage for one knee. Deliver the product directly into the palm of the hand and then apply evenly around front, back, and sides of the knee.
Application of Deflox in an amount exceeding or less than the recommended dose has not been studied and is therefore not recommended.
Special Precautions
- Avoid showering/bathing for at least 30 minutes after the application of Deflox to the treated knee.
- Wash and dry hands after use.
- Do not apply Deflox to open wounds.
- Avoid contact of Deflox with eyes and mucous membranes.
- Do not apply external heat and/or occlusive dressings to treated knees.
- Avoid wearing clothing over the Deflox-treated knee(s) until the treated knee is dry.
- Protect the treated knee(s) from natural and artificial sunlight.
- Wait until the treated area is dry before applying sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medication to the same knee you have just treated with Deflox.
- Until the treated knee(s) is completely dry, avoid skin-to-skin contact between other people and the treated knee(s).
- Do not use combination therapy with Deflox and an oral NSAID unless the benefit outweighs the risk and conduct periodic laboratory evaluations.
Deflox is contraindicated in the following patients:
- Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product
- History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients
- In the setting of coronary artery bypass graft (CABG) surgery
WARNINGS
Included as part of the PRECAUTIONS section.
PRECAUTIONS
Cardiovascular Thrombotic Events
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.
To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as diclofenac, increases the risk of serious gastrointestinal (GI) events.
Status Post Coronary Artery Bypass Graft (CABG) Surgery
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG.
Post-MI Patients
Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.
Avoid the use of Deflox in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Deflox is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.
Gastrointestinal Bleeding, Ulceration, And Perforation
NSAIDs, including diclofenac, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in approximately 1% of patients treated for 3-6 months, and in about 2%-4% of patients treated for one year. However, even short-term NSAID therapy is not without risk.
Risk Factors For GI Bleeding, Ulceration, And Perforation
Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.
Strategies to Minimize the GI Risks in NSAID-treated patients:
- Use the lowest effective dosage for the shortest possible duration.
- Avoid administration of more than one NSAID at a time.
- Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For  such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs.
- Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy.
- If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue Deflox until a serious GI adverse event is ruled out.
- In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding.
Hepatotoxicity
In clinical trials of oral diclofenac containing products, meaningful elevations (i.e., more than 3 times the ULN) of AST (SGOT) occurred in about 2% of approximately 5,700 patients at some time during diclofenac treatment (ALT was not measured in all studies).
In a large, open-label, controlled trial of 3,700 patients treated with oral diclofenac for 2 - 6 months, patients were monitored first at 8 weeks and 1,200 patients were monitored again at 24 weeks. Meaningful elevations of ALT and/or AST occurred in about 4% of 3,700 patients and included marked elevations (greater than 8 times the ULN) in about 1% of the 3,700 patients. In that open-label study, a higher incidence of borderline (less than 3 times the ULN), moderate (3 to 8 times the ULN), and marked (greater than 8 times the ULN) elevations of ALT or AST was observed in patients receiving diclofenac when compared to other NSAIDs. Elevations in transaminases were seen more frequently in patients with osteoarthritis than in those with rheumatoid arthritis.
Almost all meaningful elevations in transaminases were detected before patients became symptomatic. Abnormal tests occurred during the first 2 months of therapy with oral diclofenac in 42 of the 51 patients in all trials who developed marked transaminase elevations.
In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of NSAID therapy, but can occur at any time during treatment with diclofenac.
Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.
In a European retrospective population-based, case-controlled study, 10 cases of oral diclofenac associated drug-induced liver injury with current use compared with non-use of diclofenac were associated with a statistically significant 4-fold adjusted odds ratio of liver injury. In this particular study, based on an overall number of 10 cases of liver injury associated with diclofenac, the adjusted odds ratio increased further with female gender, doses of 150 mg or more, and duration of use for more than 90 days.
Physicians should measure transaminases at baseline and periodically in patients receiving long-term therapy with diclofenac, because severe hepatotoxicity may develop without a prodrome of distinguishing symptoms. The optimum times for making the first and subsequent transaminase measurements are not known. Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with diclofenac. However, severe hepatic reactions can occur at any time during treatment with diclofenac.
If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, abdominal pain, diarrhea, dark urine, etc.), Deflox should be discontinued immediately.
Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue Deflox immediately, and perform a clinical evaluation of the patient.
To minimize the potential risk for an adverse liver-related event in patients treated with Deflox, use the lowest effective dose for the shortest duration possible. Exercise caution when prescribing Deflox with concomitant drugs that are known to be potentially hepatotoxic (e.g., acetaminophen, antibiotics, antiepileptics).
Hypertension
NSAIDs, including Deflox, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs.
Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.
Heart Failure And Edema
The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.
Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of diclofenac may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]).
Avoid the use of Deflox in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Deflox is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.
Renal Toxicity And Hyperkalemia
Renal Toxicity
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.
Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
No information is available from controlled clinical studies regarding the use of Deflox in patients with advanced renal disease. The renal effects of Deflox may hasten the progression of renal dysfunction in patients with preexisting renal disease.
Correct volume status in dehydrated or hypovolemic patients prior to initiating Deflox. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of Deflox. Avoid the use of Deflox in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. If Deflox is used in patients with advanced renal disease, monitor patients for signs of worsening renal function.
Hyperkalemia
Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.
Anaphylactic Reactions
Diclofenac has been associated with anaphylactic reactions in patients with and without known hypersensitivity to diclofenac and in patients with aspirin-sensitive asthma.
Seek emergency help if an anaphylactic reaction occurs.
Exacerbation Of Asthma Related To Aspirin Sensitivity
A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, Deflox is contraindicated in patients with this form of aspirin sensitivity. When Deflox is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.
Serious Skin Reactions
NSAIDs, including diclofenac, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of Deflox at the first appearance of skin rash or any other sign of hypersensitivity. Deflox is contraindicated in patients with previous serious skin reactions to NSAIDs.
Do not apply Deflox to open skin wounds, infections, inflammations, or exfoliative dermatitis, as it may affect absorption and tolerability of the drug.
Premature Closure Of Fetal Ductus Arteriosus
Diclofenac may cause premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Deflox, in pregnant women starting at 30 weeks of gestation (third trimester).
Hematologic Toxicity
Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with Deflox has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.
NSAIDs, including Deflox, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding.
Masking Of Inflammation And Fever
The pharmacological activity of Deflox in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.
Laboratory Monitoring
Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically.
Sun Exposure
Instruct patients to avoid exposure to natural or artificial sunlight on treated knee(s) because studies in animals indicated topical diclofenac treatment resulted in an earlier onset of ultraviolet light-induced skin tumors. The potential effects of Deflox on skin response to ultraviolet damage in humans are not known.
Eye Exposure
Avoid contact of Deflox with eyes and mucosa. Advise patients that if eye contact occurs, immediately wash out the eye with water or saline and consult a physician if irritation persists for more than an hour.
Oral Nonsteroidal Anti-Inflammatory Drugs
Concomitant use of oral NSAIDs with Deflox 1.5% resulted in a higher rate of rectal hemorrhage, more frequent abnormal creatinine, urea and hemoglobin. Therefore, do not use combination therapy with Deflox and an oral NSAID unless the benefit outweighs the risk and conduct periodic laboratory evaluations.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide) that accompanies each prescription dispensed. Inform patients, families, or their caregivers of the following information before initiating therapy with Deflox and periodically during the course of ongoing therapy.
Cardiovascular Thrombotic Events
Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately.
Gastrointestinal Bleeding, Ulceration, And Perforation
Advise patients to report symptoms of ulceration and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their health care provider. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of the increased risk for and the signs and symptoms of GI bleeding.
Hepatotoxicity
Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, instruct patients to stop Deflox and seek immediate medical therapy.
Heart Failure And Edema
Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur.
Anaphylactic Reactions
Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Instruct patients to seek immediate emergency help if these occur.
Serious Skin Reactions
Advise patients to stop Deflox immediately if they develop any type of rash and contact their health care provider as soon as possible.
Female Fertility
Advise females of reproductive potential who desire pregnancy that NSAIDs, including Deflox, may be associated with a reversible delay in ovulation
Fetal Toxicity
Inform pregnant women to avoid use of Deflox and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus.
Avoid Concomitant Use Of NSAIDs
Inform patients that the concomitant use of Deflox with other NSAIDs or salicylates (e.g.,diflunisal, salsalate) is not recommended due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy. Alert patients that NSAIDs may be present in “over the counter” medications for treatment of colds, fever, or insomnia.
Use of NSAIDs And Low-Dose Aspirin
Inform patients not to use low-dose aspirin concomitantly with Deflox until they talk to their healthcare provider.
Eye Exposure
Instruct patients to avoid contact of Deflox with the eyes and mucosa. Advise patients that if eye contact occurs, immediately wash out the eye with water or saline and consult a physician if irritation persists for more than an hour.
Prevention Of Secondary Exposure
Instruct patients to avoid skin-to-skin contact between other people and the knee(s) to which Deflox was applied until the knee(s) is completely dry.
Special Application Instructions
Instruct patients not to apply Deflox to open skin wounds, infections, inflammations, or exfoliative dermatitis, as it may affect absorption and reduce tolerability of the drug.
Instruct patients to wait until the area treated with Deflox is completely dry before applying sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medication.
Instruct patients to minimize or avoid exposure of treated knee(s) to natural or artificial sunlight.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenesis
In a dermal carcinogenicity study conducted in albino mice, daily topical applications of diclofenac sodium for two years at concentrations up to 0.035% diclofenac sodium (a 57-fold lower diclofenac sodium concentration than present in Deflox) did not increase neoplasm incidence.
In a photococarcinogenicity study conducted in hairless mice, topical application of diclofenac sodium at doses up to 0.035% diclofenac sodium (a 57-fold lower diclofenac sodium concentration than present in Deflox) resulted in an earlier median time of onset of tumors.
Mutagenesis
Diclofenac was not mutagenic or clastogenic in a battery of genotoxicity tests that included the bacterial reverse mutation assay, in vitro mouse lymphoma point mutation assay, chromosomal aberration studies in Chinese hamster ovarian cells in vitro, and in vivo rat chromosomal aberration assay of bone marrow cells.
Impairment Of Fertility
Fertility studies have not been conducted with Deflox. Diclofenac sodium administered to male and female rats at doses up to 4 mg/kg/day (approximately 3.4 times the MRHD of Deflox based on apparent bioavailability and body surface area comparison) did not affect fertility. Studies conducted in rats found no effect of dermally applied DMSO on fertility, reproductive performance, or offspring performance.
Use In Specific Populations
Pregnancy
Pregnancy Category C prior to 30 weeks gestation; Category D starting 30 weeks gestation
Risk Summary
Use of NSAIDs, including Deflox, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Deflox, in pregnant women starting at 30 weeks of gestation (third trimester).
There are no adequate and well-controlled studies of Deflox in pregnant women. Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In the general U.S. population, all clinically recognized pregnancies, regardless of drug exposure, have a background rate of 2-4% for major malformations, and 15-20% for pregnancy loss. Published reproductive and developmental studies of dimethyl sulfoxide (DMSO, the solvent used in Deflox) are equivocal as to potential teratogenicity. In animal reproduction studies, no evidence of teratogenicity was observed in mice, rats, or rabbits given diclofenac during the period of organogenesis at doses up to approximately 0.6, 0.6, and 1.3 times, respectively, the maximum recommended human dose (MRHD) of Deflox, despite the presence of maternal and fetal toxicity at these doses. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as diclofenac resulted in increased pre- and post-implantation loss.
Clinical Considerations
Labor or Delivery
There are no studies on the effects of Deflox during labor or delivery. In animal studies, NSAIDs, including diclofenac inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth.
Data
Animal data
Reproductive and developmental studies in animals demonstrated that diclofenac sodium administration during organogenesis did not produce teratogenicity despite the induction of maternal toxicity and fetal toxicity in mice at oral doses up to 20 mg/kg/day (approximately 0.6 times the maximum recommended human dose [MRHD] of Deflox, 162 mg/day, based on body surface area (BSA) comparison), and in rats and rabbits at oral doses up to 10 mg/kg/day (approximately 0.6 and 1.3-times, respectively, the MRHD based on BSA comparison). Published reproductive and developmental studies of dimethyl sulfoxide (DMSO, the solvent used in Deflox) are equivocal as to potential teratogenicity. In rats, maternally toxic doses of diclofenac were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival.
Lactation
Risk Summary
Based on available data, diclofenac may be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for CATAFLAM and any potential adverse effects on the breastfed infant from the CATAFLAM or from the underlying maternal condition.
Data
One woman treated orally with a diclofenac salt, 150 mg/day, had a milk diclofenac level of 100 mcg/L, equivalent to an infant dose of about 0.03 mg/kg/day. Diclofenac was not detectable in breast milk in 12 women using diclofenac (after either 100 mg/day orally for 7 days or a single 50 mg intramuscular dose administered in the immediate postpartum period).
Females And Males Of Reproductive Potential
Infertility
Females
Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including Deflox, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including Deflox, in women who have difficulties conceiving or who are undergoing investigation of infertility.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects.
Of the 911 patients treated with Deflox 1.5% in seven controlled, Phase 3 clinical trials, 444 subjects were 65 years of age and over. There was no age-related difference in the incidence of adverse events. Of the 793 patients treated with Deflox 1.5% in one open-labeled safety trial, 334 subjects were 65 years of age and over including 107 subjects 75 and over. There was no difference in the incidence of adverse events with long-term exposure to Deflox 1.5% for this elderly population.
NSAIDを服用した後、めまい、損傷、疲労、視覚障害などの望ましくない影響が生じる可能性があります。. 影響を受ける場合、患者は機械を運転または操作してはなりません。.
以下の副作用については、ラベル表示の他のセクションで詳しく説明します。
- 心血管血栓性イベント。
- GI出血、 ⁇ 瘍、 ⁇ 孔。
- 肝毒性。
- 高血圧。
- 心不全と浮腫。
- 腎毒性および高カリウム血症。
- アナフィラキシー反応。
- 深刻な皮膚反応。
- 血液毒性。
臨床試験の経験。
臨床試験はさまざまな条件下で行われるため、薬物の臨床試験で観察された副作用率は、他の薬物の臨床試験の率と直接比較することはできず、実際に観察された率を反映しない場合があります。.
以下に説明するデータは、1つの第2相対照試験で4週間(平均期間28日)治療された130人の患者のDefloxへの曝露を反映しています。. この人口の平均年齢は約60歳で、患者の85%は白人、65%は女性、すべての患者は原発性変形性関節症でした。. Defloxの最も一般的な有害事象は、塗布部位の皮膚反応でした。. これらの出来事は、研究から撤退する最も一般的な理由でした。.
アプリケーションサイトの反応。
この対照試験では、適用部位の反応は、乾燥(22%)、角質除去(7%)、紅斑(4%)、 ⁇ 性(2%)、痛み(2%)、硬結( 2%)、発疹(2%)、かさぶた。.
その他の一般的な副作用。
表1は、変形性関節症の患者を対象に実施された対照研究からの、デフロックス群の割合が車両を超えた、デフロックスを投与された患者の1%以上で発生したすべての副作用を示しています。.
表1:変形性関節症の被験者の1%以上でDefloxを使用している有害反応の発生率、およびOAの被験者よりも車両制御(プール)を使用している頻度が高い。
副作用。 | Deflox。 N = 130。 n(%)。 | 車両制御。 N = 129。 n(%)。 |
二次管感染症。 | 4(3%)。 | 1(<1%)。 |
アプリケーションサイトの硬結。 | 2(2%)。 | 1(<1%)。 |
概念。 | 2(2%)。 | 1(<1%)。 |
副鼻腔の混雑。 | 2(2%)。 | 1(<1%)。 |
吐き気。 | 2(2%)。 | 0 |
Deflox 1.5%。
Deflox 2%の安全性は、Deflox 1.5%の以前の経験に一部基づいています。. 以下に説明するデータは、4〜12週間治療された911人の患者のDeflox 1.5%への曝露を反映しています。 (49日間の平均期間。) 7つのフェーズ3対照試験。, オープンラベル研究で治療された793人の患者の曝露と同様に。, 少なくとも6か月間治療された463人の患者を含む。, 144人の患者が少なくとも12か月間治療されました。. 人口の平均年齢は約60歳で、患者の89%は白人、64%は女性、すべての患者は原発性変形性関節症でした。. Deflox 1.5%の最も一般的な有害事象は、塗布部位の皮膚反応でした。. これらの出来事は、研究から撤退する最も一般的な理由でした。.
アプリケーションサイトの反応。
対照試験では、適用部位の反応は、乾燥、紅斑、硬結、小胞、感覚異常、 ⁇ 、血管拡張、にきび、じんま疹の1つ以上によって特徴付けられました。. これらの反応の中で最も頻繁に見られたのは、乾燥肌(32%)、皮膚紅斑と硬結を特徴とする接触性皮膚炎(9%)、小胞(2%)と真 ⁇ (4%)の接触性皮膚炎でした。. 1つの対照試験では、Deflox 1.5%と経口ジクロフェナクの組み合わせによる152人の被験者の治療後に、小胞とのより高い接触皮膚炎(4%)が観察されました。. オープンラベルの制御されていない長期安全性研究では、接触皮膚炎が13%で発生し、 ⁇ との接触皮膚炎が患者の10%で発生しました。これは、一般的に曝露の最初の6か月以内であり、申請サイトイベントの離脱率は14でした。 %。.
その他の一般的な副作用。
対照試験では、Deflox 1.5%で治療された被験者は、プラセボを使用している被験者よりもNSAIDクラスに関連するいくつかの有害事象を経験しました(便秘、下 ⁇ 、消化不良、吐き気、 ⁇ 腸、腹痛、浮腫;表2を参照)。. Deflox 1.5%と経口ジクロフェナクの組み合わせは、経口ジクロフェナクのみと比較して、直腸出血の発生率が高くなりました(3%vs. 1%未満)、より頻繁な異常なクレアチニン(12%対. 7%)、尿素(20%vs. 12%)、およびヘモグロビン(13%vs. 9%)、しかし肝トランスアミナーゼの上昇に違いはありません。.
表2は、変形性関節症の患者を対象に実施された7つの対照研究から、デフロックス1.5%を投与された患者の1%以上で発生したすべての副作用を示しています。. これらの試験は期間が異なるため、これらのパーセンテージは累積発生率をキャプチャしません。.
表2:プラセボおよび経口ジクロフェナク対照試験でDeflox 1.5%の局所溶液で治療された患者の1%以上で発生する副作用。
治療グループ:。 | Deflox 1.5%。 N = 911。 | 局所プラセボ。 N = 332。 |
副作用。 | N(%)。 | N(%)。 |
乾燥肌(アプリケーションサイト)。 | 292(32)。 | 17(5)。 |
皮膚炎(申請サイト)に連絡してください。 | 83(9)。 | 6(2)。 |
消化不良。 | 72(8)。 | 13(4)。 |
腹痛。 | 54(6)。 | 10(3)。 |
⁇ 腸。 | 35(4)。 | 1(<1)。 |
Pruitus(申請サイト)。 | 34(4)。 | 7(2)。 |
下 ⁇ 。 | 33(4)。 | 7(2)。 |
吐き気。 | 33(4)。 | 3(1)。 |
⁇ 頭炎。 | 40(4)。 | 13(4)。 |
便秘。 | 29(3)。 | 1(<1)。 |
浮腫。 | 26(3)。 | 0 |
発疹(非適用サイト)。 | 25(3)。 | 5(2)。 |
感染。 | 25(3)。 | 8(2)。 |
斑状出血。 | 19(2)。 | 1(<1)。 |
乾燥肌(非適用サイト)。 | 19(2)。 | 1(<1)。 |
接触皮膚炎、小胞(適用部位)。 | 18(2)。 | 0 |
感覚異常(非適用サイト)。 | 14(2)。 | 3(<1)。 |
偶発的な傷害。 | 22(2)。 | 7(2)。 |
Pruitus(非申請サイト)。 | 15(2)。 | 2(<1)。 |
副鼻腔炎。 | 10(1)。 | 2(<1)。 |
口臭。 | 11(1)。 | 1(<1)。 |
申請サイトの反応(特に指定のない)。 | 11(1)。 | 3(<1)。 |
市販後の経験。
市販後調査では、Deflox 1.5%の承認後の使用中に以下の副作用が報告されています。. これらの反応は不確実なサイズの集団から自発的に報告されるため、その頻度を確実に推定したり、薬物曝露との因果関係を確立したりすることは常に可能ではありません。.
全体としての体:。 腹痛、偶発的損傷、アレルギー反応、無力症、腰痛、体臭、胸痛、浮腫、顔面浮腫、口臭、頭痛、首の硬直、痛み。
心血管:。 動 ⁇ 、心血管障害。
消化管:。 下 ⁇ 、口渇、消化不良、胃腸炎、食欲減退、唇の腫れ、口内 ⁇ 瘍、吐き気、直腸出血、 ⁇ 瘍性口内炎、舌の腫れ。
代謝と栄養:。 クレアチニンが増加しました。
筋骨格:。 脚圧着、筋肉痛。
神経質:。 適用部位でのうつ病、めまい、眠気、 ⁇ 眠、感覚異常。
呼吸:。 ⁇ 息、呼吸困難、喉頭炎、喉頭炎、 ⁇ 頭炎、喉の腫れ。
皮膚と付属物:。 アプリケーションで。
サイト :。 発疹、皮膚 ⁇ 熱感;。
その他の皮膚および付属肢の副作用:。 湿疹、皮膚の変色、じんま疹。
特別感覚:。 異常な視力、かすみ目、白内障、耳の痛み、目の障害、目の痛み、味覚異常。
血管:。 血圧の上昇、高血圧。
急性NSAIDの過剰摂取後の症状は、通常、 ⁇ 眠、損傷、吐き気、 ⁇ 吐、および心 ⁇ 部痛に限定されており、これらは一般的に支持療法で可逆的でした。. 消化管出血が発生しました。. 高血圧、急性腎不全、呼吸抑制、 ⁇ 睡が発生しましたが、まれでした。.
NSAIDの過剰摂取後の交感神経および支持療法で患者を管理します。. 特定の解毒剤はありません。. Defloxに含まれるDMSOによる吸引とその後の呼吸刺激の可能性があるため、Emesisは推奨されません。. 摂取から4時間以内に見られる症候性患者または大量の投与量のある患者(5)では、活性炭(成人では60〜100グラム、小児患者では体重1 kgあたり1〜2グラム)および/または浸透性下剤を検討してください。. 強制利尿、尿のアルカリ化、血液透析、または血液 ⁇ 流は、タンパク質結合が高いため、役に立たない場合があります。.
過剰摂取治療の詳細については、毒物管理センター(1-800-222-1222)にお問い合わせください。.
薬物療法。 グループ:。 非ステロイド性抗炎症薬(NSAID)。.
ATCコード:。 M01A B05。
デフロックスカリウム錠剤には、非ステロイド性化合物であるデフロックスのカリウム塩が含まれています。これは、明白で臨床的に実証可能な鎮痛作用、抗炎症作用、および抗発熱作用があります。.
Defloxは、プロスタグランジン生合成の強力な阻害剤であり、アラキドン酸の放出と取り込みのモジュレーターです。.
デフロックスカリウム錠剤は、作用が急速に始まるため、痛みや炎症の急性エピソードの治療に適しています。.
片頭痛発作では、Defloxカリウム錠剤が頭痛の緩和とそれに伴う吐き気の症状の改善に効果的であることが示されています。.
Deflox。 in vitro。 人間で到達した濃度と同等の濃度で軟骨中のプロテオグリカン生合成を抑制しません。.
JRA / JIA小児患者におけるDefloxの使用の臨床試験経験は限られています。. JRA / JIAを使用した3〜15歳の子供を対象としたランダム化二重盲検2週間並行群試験では、毎日の2〜3 mg / kg BW Defloxの有効性と安全性をアセチルサリチル酸と比較しました(ASS、 50-100 meb /それぞれ。. 世界的な評価では、15人のデフロックス患者のうち11人、12人のアスピリンのうち6人、15人のプラセボ患者のうち4人が改善を示し、その差は統計的に有意でした(p <0.05)。. 圧痛関節の数はDefloxとASSで減少しましたが、プラセボで増加しました。. JRA / JIAを使用した4〜15歳の子供を対象とした2回目の無作為化二重盲検6週間並行群試験では、Defloxの有効性(1日量2〜3 mg / kg BW、n = 22)は、インドメタシンのそれ(1日量2-3。.
薬物療法。 グループ:。 非ステロイド性抗炎症薬(NSAID)。.
ATCコード:。 M01A B05。
デフロキサックカリウム錠剤には、非ステロイド性化合物であるデフロキサックのカリウム塩が含まれています。.
デフロキサックは、プロスタグランジン生合成の強力な阻害剤であり、アラキドン酸の放出と取り込みのモジュレーターです。.
デフロキサックカリウム錠剤は、作用が急速に始まるため、痛みや炎症の急性エピソードの治療に適しています。.
片頭痛発作では、デフロキサックカリウム錠剤が頭痛の緩和とそれに伴う悪心の症状の改善に効果的であることが示されています。.
デフロキサック。 in vitro。 人間で到達した濃度と同等の濃度で軟骨中のプロテオグリカン生合成を抑制しません。.
JRA / JIA小児患者におけるデフロキサックの使用の臨床試験経験は限られています。. JRA / JIAを使用した3〜15歳の子供を対象としたランダム化二重盲検2週間並行群試験では、毎日の2〜3 mg / kg BWデフロキサックの有効性と安全性をアセチルサリチル酸(ASS、 50-100 mg /。. 世界的な評価では、デフロキサック患者15人中11人、アスピリン12人中6人、プラセボ患者15人中4人が改善を示し、差は統計的に有意でした(p <0.05)。. 圧痛関節の数は、DefloxacとASSで減少しましたが、プラセボでは増加しました。. JRA / JIAを使用した4〜15歳の子供を対象とした2回目の無作為化二重盲検6週間並行群試験では、デフロキサックの有効性(1日量2〜3 mg / kg BW、n = 22)は、インドメタシン(1日量nk。.
吸収。
Deflox局所溶液の投与後。 (12時間ごとに40 mg /膝。; 毎日の総ジクロフェナク曝露:80 mg / gnee。) 7.5日間。, 平均。 (SD。) AUC0-12と平均。 (SD。) Cmaxは77.27でした。 (49.89。) ng•h / mLおよび12.16。 (7.66。) ng / mL。, それぞれ。, 1日目。; および204.58。 (111.02。) ng•h / mLおよび25.24。 (12.95。) ng / mL。, それぞれ。, 8日目の定常状態。. Deflox 1.5%局所溶液の投与後。 (19.3 mg /膝、6時間ごと。; 毎日の総ジクロフェナク暴露77.2 mg / gnee。) 平均。 (SD。) AUC0-12と平均。 (SD。) Cmaxは27.46でした。 (23.97。) ng•h / mLおよび2.30。 (2.02。) ng / mL。, それぞれ。, 1日目。; および141.49。 (92.47。) ng•h / mLおよび04/17。 (11.28。) ng / mL。, それぞれ。, 8日目の定常状態。.
Defloxの薬物動態と効果は、熱の塗布、閉塞性包帯のオーバーレイ、または製品塗布後の運動の条件下では評価されませんでした。. したがって、これらの条件下でのDefloxの同時使用は推奨されません。.
分布。
ジクロフェナクは、主にアルブミンに、99%以上がヒト血清タンパク質に結合しています。.
ジクロフェナクは、滑液の内外で異なります。. 関節への拡散は、血漿レベルが滑液のレベルよりも高い場合に発生します。その後、プロセスが逆転し、滑液レベルが血漿レベルよりも高くなります。. 関節への拡散がジクロフェナクの有効性に役割を果たすかどうかは不明です。.
除去。
代謝。
5つのジクロフェナク代謝物がヒトの血漿と尿で確認されています。. 代謝物には、4つの「-ヒドロキシ-、5ヒドロキシ-、3'-ヒドロキシ-、4 '、5-ジヒドロキシ-および3'-ヒドロキシ-4'-メトキシジクロフェナクが含まれます。. 主要なジクロフェナク代謝物である4'ヒドロキシジクロフェナクは、薬理活性が非常に弱いです。. 4 '-ヒドロキシジクロフェナクの形成は、主にCYP2C9によって媒介されます。. ジクロフェナクとその酸化代謝物の両方がグルクロン酸抱合または硫酸化を受け、その後胆 ⁇ 排 ⁇ されます。. UGT2B7によって媒介されるアシルグルクロン酸抱合およびCYP2C8によって媒介される酸化も、ジクロフェナク代謝に役割を果たす可能性があります。. CYP3A4は、マイナーな代謝物、5-ヒドロキシおよび3'-ヒドロキシジクロフェナクの形成に関与しています。.
排 ⁇ 。
ジクロフェナクは、代謝とそれに続くグルクロニドと代謝産物の硫酸塩抱合体の尿および胆 ⁇ 排 ⁇ によって排除されます。.
変化のないジクロフェナクはほとんどまたはまったく尿中に排 ⁇ されません。.
However, we will provide data for each active ingredient