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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/06/10 18:05:55」(JST)
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Not to be confused with dapoxetine.
| Systematic (IUPAC) name | |
|---|---|
| (+)-(S)-N-Methyl-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propan-1-amine | |
| Clinical data | |
| Trade names | Cymbalta |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a604030 |
| Licence data | EMA:Link, US FDA:link |
| Pregnancy cat. | B3 (AU) C (US) |
| Legal status | Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US) |
| Routes | Oral |
| Pharmacokinetic data | |
| Bioavailability | ~ 50% (32% to 80%) |
| Protein binding | ~ 95% |
| Metabolism | Liver, two P450 isozymes, CYP2D6 and CYP1A2 |
| Half-life | 12.1 hours |
| Excretion | 70% in urine, 20% in feces |
| Identifiers | |
| CAS number | 116539-59-4 N (free base) 136434-34-9 (hydrochloride) |
| ATC code | N06AX21 |
| PubChem | CID 60835 |
| IUPHAR ligand | 202 |
| DrugBank | DB00476 |
| ChemSpider | 54822 Y |
| UNII | O5TNM5N07U Y |
| KEGG | D07880 Y |
| ChEBI | CHEBI:36795 Y |
| ChEMBL | CHEMBL1175 Y |
| PDB ligand ID | 29E (PDBe, RCSB PDB) |
| Chemical data | |
| Formula | C18H19NOS |
| Mol. mass | 297.41456 g/mol |
|
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InChI
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| N (what is this?) (verify) | |
Duloxetine (sold under the brand names Cymbalta, Ariclaim, Xeristar, Yentreve, Duzela, Dulane) is a serotonin-norepinephrine reuptake inhibitor (SNRI) manufactured and marketed by Eli Lilly. It is prescribed for major depressive disorder and generalized anxiety disorder (GAD). Duloxetine also has approval for use in osteoarthiritis and musculoskeletal pain. It can also relieve the symptoms of painful peripheral neuropathy, particularly diabetic neuropathy,[1][2] and it is used to control the symptoms of fibromyalgia. Duloxetine failed the US approval for stress urinary incontinence amidst concerns over liver toxicity and suicidal events; however, it was approved for this indication in Europe, where it is recommended as an add-on medication in stress urinary incontinence instead of surgery.[3]
Contents
- 1 Medical uses
- 1.1 Major depressive disorder
- 1.2 Generalized anxiety disorder
- 1.3 Diabetic peripheral neuropathy
- 1.4 Fibromyalgia and chronic pain
- 1.5 Stress urinary incontinence
- 2 Contraindications
- 3 Adverse effects
- 3.1 Postmarketing spontaneous reports
- 3.2 Discontinuation syndrome
- 3.3 Suicidality
- 4 Pharmacology
- 4.1 Mechanism of Action
- 4.2 Pharmacokinetics
- 5 History
- 6 References
- 7 External links
Medical uses
The main uses of duloxetine are in major depressive disorder, general anxiety disorder, urinary incontinence, painful peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain associated with osteoarthritis and chronic lower back pain. It is being studied for various other indications.
Major depressive disorder
Duloxetine was approved for the treatment of major depression in 2004. While duloxetine has demonstrated improvement in depression-related symptoms compared to placebo, trials comparing duloxetine to other antidepressant medications have been less successful. A 2012 Cochrane Review failed to demonstrate improved efficacy of duloxetine compared to SSRIs and newer antidepressants. Additionally, the review found evidence that duloxetine has increased side effects and reduced tolerability compared to other antidepressants. It thus did not recommend duloxetine as a first line treatment for major depressive disorder, given the high cost of duloxetine compared to off-patent antidepressants and lack of increased efficacy.[4]
Generalized anxiety disorder
Duloxetine is more effective than placebo in the treatment of generalized anxiety disorder (GAD).[5] Major guidelines such as Maudsley Prescribing Guidelines,[6] and Canadian Psychiatric Association Guidelines[7] do not list duloxetine among the recommended treatment options. However, a review from the Annals of Internal Medicine lists duloxetine among the first line drug treatments, along with citalopram, escitalopram, sertraline, paroxetine, and venlafaxine. Cognitive behavioral therapy remains the first line nonpharmacologic treatment for generalized anxiety disorder.[8]
Diabetic peripheral neuropathy
Duloxetine was approved for the pain associated with diabetic peripheral neuropathy (DPN), based on the positive results of two clinical trials. The average daily pain was measured using an 11-point scale, and duloxetine treatment resulted in an additional 1–1.7 points decrease of pain as compared with placebo.[9][10][11] At least 50% pain relief was achieved in 40–45% of the duloxetine patients vs. 20–22% of placebo patients. Pain decreased by more than 90%, in 9–14% of duloxetine patients vs. 2–4% of placebo patients. Most of the response was achieved in the first two weeks on the medication. Duloxetine slightly increased the fasting serum glucose; however this effect was deemed to be of "minimal clinical significance".[9]
Duloxetine was not effective for the numbness or tingling associated with diabetic neuropathy, nor for the other complications of diabetes. It reduced the pain without treating the underlying nerve damage.[12] Only tight glycemic control was unequivocally demonstrated to slow the progression of neuropathy.[13][14] Benfotiamine, alpha-lipoic acid, and ranirestat have also shown some promise.[14]
The comparative efficacy of duloxetine and established pain-relief medications for DPN is unclear. An independent systematic review in BMJ noted that tricyclic antidepressants (imipramine and amitriptyline), traditional anticonvulsants and opioids have better efficacy than duloxetine. Duloxetine, tricyclic antidepressants and anticonvulsants have similar tolerability while the opioids caused more side effects.[13] A review in Drug and Therapeutic Bulletin saw no place for duloxetine in the treatment of DPN, based on its high cost and insufficient evidence of the comparative efficacy with tricyclic antidepressants.[15] Another independent review in Prescrire International, considered the moderate pain relief achieved with duloxetine to be clinically insignificant and the results of the clinical trials—unconvincing. The reviewer saw no reason to prescribe duloxetine in practice.[16] The comparative data collected by reviewers in BMC Neurology indicated that amitriptyline, other tricyclic antidepressants and venlafaxine may be more effective. However, the authors noted that the evidence in favor of duloxetine is much more solid.[17]
Fibromyalgia and chronic pain
A review of duloxetine found that it reduced pain and fatigue, and improved physical and mental performance compared to placebo.[18]
The Food and Drug Administration regulators approved the drug for the treatment of fibromyalgia in June 2008.[19]
Evidence also supports its use in chronic pain from osteoarthritis.[20]
On November 4, 2010, the U.S. Food and Drug Administration approved duloxetine to treat chronic musculoskeletal pain, including discomfort from osteoarthritis and chronic lower back pain.[21]
Stress urinary incontinence
Duloxetine was first reported to improve outcomes in stress urinary incontinence (SUI) in 1998.[22] The safety and utility of duloxetine in the treatment of incontinence has been evaluated in a series of meta analyses and practice guidelines.
- A 2013 meta analysis coverying ten trials with 5738 subjects concluded that duloxetine decreased incontinence episodes significantly more than placebo. Duloxetine-treated patients were about 56% more likely than placebo-treated patients to experience a 50% decrease in episodes. Adverse effects were experienced by 83% of duloxetine-treated subjects and by 45% of placebo-treated subjects.[23]
- A 2012 review and practice guideline published by the European Association of Urology concluded that the clinical trial data provides Grade 1a evidence that duloxetine improves but does not cure urinary incontinence, but that it causes a high rate of gastrointestinal side effects (mainly nausea and vomiting) leading to a high rate of treatment discontiuation.[24]
- The National Institute for Clinical and Health Excellence recommends (as of September 2013) that duloxetine not be routinely offered as first line treatment, and that it only be offered as second line therapy in women wishing to avoid therapy. The guideline further states that women should be counseled regarding the drug's side effects.[25]
Contraindications
The following contraindications are listed by the manufacturer:[26]
- Hypersensitivity - duloxetine is contraindicated in patients with a known hypersensitivity to duloxetine or any of the inactive ingredients.
- MAOIs - concomitant use in patients taking MAOIs is contraindicated.
- Uncontrolled narrow-angle glaucoma - in clinical trials, Cymbalta use was associated with an increased risk of mydriasis (dilation of the pupil); therefore, its use should be avoided in patients with uncontrolled narrow-angle glaucoma, in which mydriasis can cause sudden worsening.
- CNS acting drugs - given the primary central nervous system (CNS) effects of duloxetine, it should be used with caution when it is taken in combination with or substituted for other centrally acting drugs, including those with a similar mechanism of action.
- Duloxetine and thioridazine should not be co-administered.
In addition, the FDA has reported on life-threatening drug interactions that may be possible when co-administered with any CNS stimulant, such as phentermine, diethylpropion, amphetamine, sibutramine, methylphenidate, methamphetamine, or cocaine, leading to increased risk for serotonin syndrome.[27]
Adverse effects
Nausea, somnolence, insomnia, and dizziness are the main side effects, reported by about 10% to 20% of patients.[28]
In a trial for major depressive disorder (MDD), the most commonly reported treatment-emergent adverse events among duloxetine-treated patients were nausea (34.7%), dry mouth (22.7%), headache (20.0%) and dizziness (18.7%), and except for headache, these were reported significantly more often than in the placebo group.[29] In a long-term study of fibromyalgia patients receiving duloxetine, frequency and type of adverse effects was similar to that reported in the MDD above. Side effects tended to be mild-to-moderate, and tended to decrease in intenstity over time.[30]
Sexual dysfunction is often a side effect of drugs that inhibit serotonin reuptake. Specifically, common side effects include difficulty becoming aroused, lack of interest in sex, and anorgasmia (trouble achieving orgasm). Loss of or decreased response to sexual stimuli and ejaculatory anhedonia are also possible. Frequency of treatment-emergent sexual dysfunction in long-term treatment has been found to be similar for duloxetine and SSRIs when compared in clinical trials,[31][32] while there is some evidence that duloxetine is associated with less sexual dysfunction than escitalopram when measured at 4 and 8 weeks of treatment.[32]
Postmarketing spontaneous reports
Reported adverse events which were temporally correlated to duloxetine therapy include rash, reported rarely, and the following adverse events, reported very rarely: alanine aminotransferase increased, alkaline phosphatase increased, anaphylactic reaction, angioneurotic edema, aspartate aminotransferase increased, bilirubin increased, glaucoma, hepatitis, hyponatremia, jaundice, orthostatic hypotension (especially at the initiation of treatment), Stevens–Johnson syndrome, syncope (especially at initiation of treatment), and urticaria.[33]
Discontinuation syndrome
Further information: SSRI discontinuation syndrome
During marketing of other SSRIs and SNRIs, there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. The withdrawal syndrome from duloxetine resembles the SSRI discontinuation syndrome.
When discontinuing treatment with duloxetine, the manufacturer recommends a gradual reduction in the dose, rather than abrupt cessation, whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate. The use of a liquid form of the drug may facilitate more gradual tapering."[34]
In placebo-controlled clinical trials of up to nine weeks' duration of patients with MDD,a systematic evaluation of discontinuation symptoms in patients taking duloxetine following abrupt discontinuation found the following symptoms occurring at a rate greater than or equal to 2% and at a significantly higher rate in duloxetine-treated patients compared to those discontinuing from placebo: dizziness, nausea, headache, paresthesia, vomiting, irritability, and nightmare.[35]
Suicidality
The FDA requires all antidepressants, including duloxetine, to carry a black box warning stating that antidepressants may increase the risk of suicide in persons younger than 25. This warning is based on statistical analyses conducted by two independent groups of the FDA experts that found a 2-fold increase of the suicidal ideation and behavior in children and adolescents, and 1.5-fold increase of suicidality in the 18–24 age group.[36][37][38]
To obtain statistically significant results the FDA had to combine the results of 295 trials of 11 antidepressants for psychiatric indications. As suicidal ideation and behavior in clinical trials are rare, the results for any drug taken separately usually do not reach statistical significance.
Several commentators noted that the data FDA used in their analysis of duloxetine-associated suicidality may have been incomplete. According to Arif Khan, the Summary Basis of Approval used by the FDA to approve duloxetine for depression contained only the mention of two completed suicides out of 3490 patients, and the rest of the data was not sufficient to "conduct any meaningful analysis."[39] Jeanne Lenzer wrote in The Independent and Slate Magazine, and this fact was also confirmed by a Lilly spokesman, that another two completed suicides, which occurred in the depression studies ran by the Lilly's Japanese partner Shionogi, have not been reported to the FDA.[40][41] According to Lenzer, four completed suicides also occurred in the trials of duloxetine for stress urinary incontinence (SUI). As these trials failed, the FDA initially insisted that any information about them is a commercial secret and cannot be released.[41] Later, in a short statement the FDA acknowledged that in SUI trials eleven suicide attempts occurred in persons taking duloxetine vs none in the placebo group.[42]
A series of four cases of duloxetine-associated suicidality has been reported. In all four cases depressed patients began having suicidal thoughts after starting on duloxetine or increasing its dose. These thoughts stopped, and the patients returned to normal after duloxetine was discontinued, and they were switched to another antidepressant.[43]
A suicide of 19-year-old Traci Johnson, a healthy volunteer in a duloxetine clinical pharmacology study, was highly publicized. For about a month she had been given high doses of duloxetine, and then she was switched to placebo. Four days after the switch, she hanged herself in the bathroom of Lilly Laboratory for Clinical Research.[44][45] The New York Times article mentioned a withdrawal syndrome as a possible reason for this suicide.[45]
Pharmacology
Mechanism of Action
Duloxetine inhibits the reuptake of serotonin and norepinephrine in the central nervous system. Duloxetine is also considered a less potent inhibitor of dopamine reuptake. However, duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors and can therefore be considered to be a selective reuptake inhibitor at the 5-HT and NA transporters. Duloxetine undergoes extensive metabolism, but the major circulating metabolites do not contribute significantly to the pharmacologic activity.[46][47]
Major depressive disorder is believed to be due in part to an increase in pro-inflammatory cytokines within the central nervous system. Antidepressants including ones with a similar mechanism of action as duloxetine, i.e. serotonin metabolism inhibition, cause a decrease in proinflammatory cytokine activity and an increase in anti-inflammatory cytokines; this mechanism may apply to duloxetine in its effect on depression but research on cytokines specific to duloxetine therapy is lacking.[48]
The analgesic properties of duloxetine in the treatment of diabetic neuropathy and central pain syndromes such as fibromyalgia are believed to be due to sodium ion channel blockade.[49]
Pharmacokinetics
Absorption: Duloxetine is acid labile, and is formulated with enteric coating to prevent degradation in the stomach. Duloxetine has good oral bioavailability, averaging 50% after one 60 mg dose. There is an average 2-hour lag until absorption begins with maximum plasma concentrations occurring about 6 hours post dose. Food does not affect the Cmax of duloxetine, but delays the time to reach peak concentration from 6 to 10 hours.[47]
Distribution: Duloxetine is highly bound (>90%) to proteins in human plasma, binding primarily to albumin and α1-acid glycoprotein. Volume of distribution is 1640L.[50]
Metabolism: Duloxetime undergoes predominately hepatic metabolism via two cytochrome P450 isozymes, CYP2D6 and CYP1A2. Circulating metabolites are pharmacologically inactive.[50]
Elimination: Duloxetine has an elimination half-life of about 12 hours (range 8 to 17 hours) and its pharmacokinetics are dose proportional over the therapeutic range. Steady-state is usually achieved after 3 days. Only trace amounts (<1%) of unchanged duloxetine are present in the urine and most of the dose (approx. 70%) appears in the urine as metabolites of duloxetine with about 20% excreted in the feces.[50]
History
Cymbalta (duloxetine) 60mg
Duloxetine was created by Lilly researchers. David Robertson, David Wong, a co-discoverer of fluoxetine, and Joseph Krushinski are listed as inventors on the patent application filed in 1986 and granted in 1990.[51] The first publication on the discovery of the racemic form of duloxetine known as LY227942, was made in 1988.[52] The (+)-enantiomer of LY227942, assigned LY248686, was chosen for further studies, because it inhibited serotonin reuptake in rat synaptosomes to twice the degreee as the (–)-enantiomer. This molecule was subsequently named duloxetine.[53]
Initial trials conducted in patients using regimens of 20 mg/day or less did not convincingly demonstrate its efficacy[54] and the dose was increased to as high as 120 mg in subsequent clinical trials.[55]
In 2001 Lilly filed a New Drug Application (NDA) for duloxetine with the US Food and Drug Administration (FDA). However, in 2003 the FDA "recommended this application as not approvable from the manufacturing and control standpoint" because of "significant cGMP (current Good Manufacturing Practice) violations at the finished product manufacturing facility" of Eli Lilly in Indianapolis. Additionally, "potential liver toxicity" and QTc interval prolongation appeared as a concern. The FDA experts concluded that "duloxetine can cause hepatotoxicity in the form of transaminase elevations. It may also be a factor in causing more severe liver injury, but there are no cases in the NDA database that clearly demonstrate this. Use of duloxetine in the presence of ethanol may potentiate the deleterious effect of ethanol on the liver." The FDA also recommended "routine blood pressure monitoring" at the new highest recommended dose of 120 mg, "where 24% patients had one or more blood pressure readings of 140/90 vs. 9% of placebo patients."[56]
After the manufacturing issues were resolved, the liver toxicity warning included in the prescribing information, and the follow-up studies showed that duloxetine does not cause QTc interval prolongation, duloxetine was approved by the FDA for depression and diabetic neuropathy in 2004.[57] In 2007 Health Canada approved duloxetine for the treatment of depression and diabetic peripheral neuropathic pain.[58]
Duloxetine was approved for use of stress urinary incontinence (SUI) in the EU in 2004. In 2005, Lilly withdrew the duloxetine application for stress urinary incontinence (SUI) in the U.S., stating that discussions with the FDA indicated "the agency is not prepared at this time to grant approval ... based on the data package submitted." A year later Lilly abandoned the pursuit of this indication in the U.S. market.[59][60]
The FDA approved duloxetine for the treatment of generalized anxiety disorder in February 2007.[61]
Cymbalta is Eli Lilly's top selling drug. It brought in just shy of $5 billion in 2012 with $4 billion of that in the U.S., but its patent protection terminated January 1, 2014. Lilly received a six month extension beyond June 30, 2013 after testing for the treatment of depression in adolescents, which may produce $1.5 billion in added sales.[62][63]
The first generic duloxetine was marketed by Dr. Reddy.[64]
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- ^ a b Bymaster, FP; Lee, Knadler (2005). "The dual transporter inhibitor duloxetine: a review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression". Curr Pharm Des 11 (12).
- ^ De Berardis D, Conti CM, Serroni N, Moschetta FS, Olivieri L, Carano A, Salerno RM, Cavuto M, Farina B, Alessandrini M, Janiri L, Pozzi G, Di Giannantonio M (2010). "The effect of newer serotonin-noradrenalin antidepressants on cytokine production: a review of the current literature". Int J Immunopathol Pharmacol 23 (2): 417–22. PMID 20646337.
- ^ Wang SY, Calderon J, Kuo Wang G (September 2010). "Block of neuronal Na+ channels by antidepressant duloxetine in a state-dependent manner". Anesthesiology 113 (3): 655–65. doi:10.1097/ALN.0b013e3181e89a93. PMID 20693878.
- ^ a b c "Cymbalta product insert".
- ^ Robertson DW, Wong DT, Krushinski JH (1990-09-11). "United States Patent 4,956,388: 3-Aryloxy-3-substituted propanamines". USPTO. Retrieved 2008-05-17.
- ^ Wong DT, Robertson DW, Bymaster FP, Krushinski JH, Reid LR (1988). "LY227942, an inhibitor of serotonin and norepinephrine uptake: biochemical pharmacology of a potential antidepressant drug". Life Sci. 43 (24): 2049–57. doi:10.1016/0024-3205(88)90579-6. PMID 2850421.
- ^ Bymaster FP, Beedle EE, Findlay J, et al. (December 2003). "Duloxetine (Cymbalta), a dual inhibitor of serotonin and norepinephrine reuptake". Bioorg. Med. Chem. Lett. 13 (24): 4477–80. doi:10.1016/j.bmcl.2003.08.079. PMID 14643350.
- ^ Turcotte JE, Debonnel G, de Montigny C, Hébert C, Blier P (May 2001). "Assessment of the serotonin and norepinephrine reuptake blocking properties of duloxetine in healthy subjects". Neuropsychopharmacology 24 (5): 511–21. doi:10.1016/S0893-133X(00)00220-7. PMID 11282251.
- ^ For example, see: Goldstein DJ, Mallinckrodt C, Lu Y, Demitrack MA (March 2002). "Duloxetine in the treatment a double-blind clinical trial". J Clin Psychiatry 63 (3): 225–31. doi:10.4088/jcp.v63n0309. PMID 11926722.
- ^ "Approval package for: application number NDA 721-427. Administrative/Correspondence #2" (PDF). The FDA Center for Drug Evaluation and Research. 2003. Retrieved 2008-05-18. [dead link]
- ^ FDA news
- ^ Health Canada Notice of Compliance Database - duloxetine. November 1, 2007, retrieved November 24, 2007.
- ^ Steyer R (2006-02-15). "Lilly Won't Pursue Yentreve for U.S.". TheStreet.com. Retrieved 2008-05-18.
- ^ Lenzer J (2005). "FDA warns that antidepressants may increase suicidality in adults". BMJ 331 (7508): 70. doi:10.1136/bmj.331.7508.70-b. PMC 558648. PMID 16002878. edit
- ^ "FDA approves antidepressant Cymbalta (duloxetine HCl) for treatment of generalized anxiety disorder". News-Medical.Net. Retrieved 25 December 2013.
- ^ Staton, Tracy (July 9, 2012). "Lilly could net $1.5B-plus from Cymbalta extension". FiercePharma. Retrieved 25 December 2013.
- ^ Palmer, Eric (April 11, 2013). "Eli Lilly to lay off hundreds in sales as Cymbalta nears edge of patent cliff". FiercePharma. Retrieved 25 December 2013.
- ^ Anson, Pat (December 12, 2013). "Generic Cheaper Versions of Cymbalta Approved". National Pain Report. Retrieved January 2, 2014.
External links
- Manufacturer website
- Eli Lilly Cymbalta Prescribing Guide
- U.S. National Library of Medicine: Drug Information Portal - Duloxetine
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UpToDate Contents
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- 1. 成人における初期治療の効果がない線維筋痛症の治療 treatment of fibromyalgia in adults not responsive to initial therapies
- 2. 慢性疼痛の治療の概要 overview of the treatment of chronic pain
- 3. Serotonin-norepinephrine reuptake inhibitors (SNRIs): Pharmacology, administration, and side effects
- 4. 成人における抗うつ剤：薬剤の変更および投与中止 antidepressant medication in adults switching and discontinuing medication
- 5. 成人における線維筋痛症の初期治療 initial treatment of fibromyalgia in adults
English Journal
- Efficacy and Safety of Duloxetine 30 mg/d in Patients With Fibromyalgia: A Randomized, Double-blind, Placebo-controlled Study.
- Arnold LM, Zhang S, Pangallo BA.Source*Department of Psychiatry and Behavioral Neuroscience, Women's Health Research Program, University of Cincinnati College of Medicine, Cincinnati, OH †Eli Lilly and Company, Indianapolis, IN.
- The Clinical journal of pain.Clin J Pain.2012 Nov;28(9):775-81. doi: 10.1097/AJP.0b013e3182510295.
- OBJECTIVES: : To evaluate the efficacy and safety of duloxetine 30 mg/d in adults with fibromyalgia.METHODS: : This 12-week, randomized, double-blind, placebo-controlled study was conducted in the United States, Mexico, Argentina, and Israel and enrolled patients meeting the criteria for primary fib
- PMID 22971669
- Automated measurement of spontaneous pain-associated limb movement and drug efficacy evaluation in a rat model of neuropathic pain.
- Kawasaki-Yatsugi S, Nagakura Y, Ogino S, Sekizawa T, Kiso T, Takahashi M, Ishikawa G, Ito H, Shimizu Y.SourcePharmacology Research Labs, Drug Discovery Research, Astellas Pharma Inc, Ibaraki, Japan.
- European journal of pain (London, England).Eur J Pain.2012 Nov;16(10):1426-36. doi: 10.1002/j.1532-2149.2012.00142.x. Epub 2012 Mar 27.
- BACKGROUND: The withdrawal response elicited by a nociceptive stimulus, i.e., evoked pain measure, is commonly used as an efficacy endpoint in neuropathic pain animal models. It, however, has several limitations, which highlight the importance of examining spontaneous pain. The present study describ
- PMID 22451419
Japanese Journal
- 大うつ病性障害を併存した身体症状症にduloxetineが著効した1例
- 精神医学 58(5), 443-446, 2016-05
- NAID 40020825050
- 線維筋痛症のマネジメント
- 心身医学 56(5), 427-432, 2016
- NAID 130005149625
- 有痛性化学療法誘発性末梢神経障害に対し高用量デュロキセチンが著効した1例
- 日本ペインクリニック学会誌 23(1), 29-32, 2016
- NAID 130005131933
Related Pictures
★リンクテーブル★
| リンク元 | 「デュロキセチン」 |
| 拡張検索 | 「duloxetine hydrochloride」 |
「デュロキセチン」
- 英
- duloxetine
- 化
- 塩酸デュロキセチン duloxetine hydrochloride
- 商
- サインバルタ Cymbalta, Yentreve
- 関
- 抗精神病薬、抗うつ薬、セロトニン・ノルアドレナリン再取り込み阻害薬 SNRI
特徴
構造
作用機序
薬理作用
抗菌スペクトル
動態
適応
- うつ病・うつ状態
- 下記疾患に伴う疼痛：糖尿病性神経障害、線維筋痛症、慢性腰痛症、変形性関節症
用法・用量
- 通常、成人には1日1回朝食後、デュロキセチンとして40mgを経口投与する。投与は1日20mgより開始し、1週間以上の間隔を空けて1日用量として20mgずつ増量する。
- なお、効果不十分な場合には、1日60mgまで増量することができる。
- 減量する場合には1-2週で20mgずつ減量しする。20mgまで到達したら、隔日投与、2日おき投与、3日おき投与と投与間隔を長くしていく。離脱症状（身体症状：しびれ・耳鳴り・めまい・頭痛・吐き気・だるさ。精神症状：イライラ・ソワソワ感・不安・不眠。特徴的な症状：シャンピリ感・ビリビリする）に注意する。
注意
禁忌
- 1. 本剤の成分に対し過敏症の既往歴のある患者
- 2. モノアミン酸化酵素阻害剤(MAOI)を投与中あるいは投与中止後2週間以内の患者
- 3. 高度の肝障害のある患者［肝障害が悪化することがある。また、消失半減期が延長し、本剤の血中濃度が上昇することがある。
- 4. 高度の腎障害のある患者［本剤の血中濃度が上昇することがある。
- 5. コントロール不良の閉塞隅角緑内障の患者［症状が悪化することがある。］
副作用
副作用等発現状況の概要
- うつ病・うつ状態の患者を対象とした国内臨床試験において、安全性評価対象例735例中、副作用（臨床検査値異常変動を含む）は663例（90.2％）に認められた。
- 主なものは、悪心269例（36.6％）、傾眠228例（31.0％）、口渇168例（22.9％）、頭痛154例（21.0％）、便秘102例（13.9％）、下痢87例（11.8％）、めまい80例（10.9％）、トリグリセリド上昇56例（7.6％）、腹部痛52例（7.0％）、ALT（GPT）上昇51例（6.9％）、不眠50例（6.8％）、倦怠感45例（6.1％）、AST（GOT）上昇38例（5.2％）、食欲減退38例（5.2％）であった。（承認時）
重大な副作用
- 1. セロトニン症候群（頻度不明※1）
- 不安、焦燥、興奮、錯乱、発汗、下痢、発熱、高血圧、固縮、頻脈、ミオクローヌス、自律神経不安定等があらわれることがある。セロトニン作用薬との併用時に発現する可能性が高くなるため、特に注意すること。異常が認められた場合には投与を中止し、体冷却、水分補給等の全身管理と共に適切な処置を行うこと。
- 2. 抗利尿ホルモン不適合分泌症候群（SIADH）（頻度不明※1）
- 低ナトリウム血症、低浸透圧血症、尿中ナトリウム排泄量の増加、高張尿、痙攣、意識障害等を伴う抗利尿ホルモン不適合分泌症候群（SIADH）があらわれることがあるので、異常が認められた場合には投与を中止し、水分摂取の制限等適切な処置を行うこと。
- 3. 痙攣（0.27％）、幻覚（頻度不明※1）
- 痙攣、幻覚があらわれることがあるので、異常が認められた場合には投与を中止し、適切な処置を行うこと。
- 4. 肝機能障害、肝炎、黄疸（頻度不明※1）
- AST（GOT）、ALT（GPT）、γ-GTP、総ビリルビン等の上昇を伴う肝機能障害、肝炎、黄疸があらわれることがあるので、適宜肝機能検査を行うとともに、患者の症状を十分に観察し、異常が認められた場合には、減量、休薬又は中止するなど適切な処置を行うこと。
- 5. 皮膚粘膜眼症候群（Stevens-Johnson症候群）（頻度不明※1）
- 皮膚粘膜眼症候群（Stevens-Johnson症候群）があらわれることがあるので、観察を十分に行い、異常が認められた場合には投与を中止し、適切な処置を行うこと。
- 6. アナフィラキシー反応（頻度不明※1）
- 呼吸困難、痙攣、血管浮腫、蕁麻疹等を伴うアナフィラキシー反応があらわれることがあるので、観察を十分に行い、異常が認められた場合には投与を中止し、適切な処置を行うこと。
- 7. 高血圧クリーゼ（頻度不明※1）
- 高血圧クリーゼがあらわれることがあるので、高血圧又は心疾患のある患者においては血圧の推移等に十分注意しながら投与すること。異常が認められた場合には投与を中止し、適切な処置を行うこと。
- 8. 尿閉（頻度不明※1）
- 尿閉があらわれることがあるので、症状があらわれた場合には投与を中止し、導尿を実施するなど適切な処置を行うこと。
添付文書
http://www.info.pmda.go.jp/go/pack/1179052M1022_2_03/