Password recovery. FDA approves first generic versions of Cymbalta. December 11, Author s :. Previous article Study: Low vitamin B12 increases fracture risk in older men. Home Page Recent Articles.
Innovating during a pandemic November 9, In DPN placebo-controlled clinical trials, patients treated with Cymbalta for up to weeks experienced a mean weight loss of approximately 1.
In fibromyalgia studies, patients treated with Cymbalta for up to 26 weeks experienced a mean weight loss of approximately 0. In one long-term fibromyalgia week uncontrolled study, duloxetine patients had a mean weight increase of 0. Cymbalta treatment in placebo-controlled clinical trials, was associated with small mean increases from baseline to endpoint in ALT, AST, CPK, and alkaline phosphatase; infrequent, modest, transient, abnormal values were observed for these analytes in Cymbalta-treated patients when compared with placebo-treated patients [see Warnings and Precautions 5.
Electrocardiograms were obtained from duloxetine-treated patients and placebo-treated patients in clinical trials lasting up to 13 weeks. There were no differences in clinically meaningful QTcF elevations between duloxetine and placebo. In a positive-controlled study in healthy volunteers using duloxetine up to mg twice daily, no prolongation of the corrected QT interval was observed. Following is a list of treatment-emergent adverse reactions reported by patients treated with duloxetine in clinical trials.
In clinical trials of all indications, 27, patients were treated with duloxetine. The following listing is not intended to include reactions 1 already listed in previous tables or elsewhere in labeling, 2 for which a drug cause was remote, 3 which were so general as to be uninformative, 4 which were not considered to have significant clinical implications, or 5 which occurred at a rate equal to or less than placebo.
Cardiac Disorders — Frequent: palpitations; Infrequent: myocardial infarction and tachycardia. Ear and Labyrinth Disorders — Frequent: vertigo; Infrequent: ear pain and tinnitus. Endocrine Disorders — Infrequent: hypothyroidism.
Eye Disorders — Frequent: vision blurred; Infrequent: diplopia and visual disturbance. Gastrointestinal Disorders — Frequent: flatulence; Infrequent: eructation, gastritis, halitosis, and stomatitis; Rare: gastric ulcer, hematochezia, and melena. Infections and Infestations — Infrequent: gastroenteritis and laryngitis.
Investigations — Frequent: weight increased; Infrequent: blood cholesterol increased. Metabolism and Nutrition Disorders — Infrequent: dehydration and hyperlipidemia; Rare: dyslipidemia. Musculoskeletal and Connective Tissue Disorders — Frequent: musculoskeletal pain; Infrequent: muscle tightness and muscle twitching.
Renal and Urinary Disorders — Infrequent: dysuria, micturition urgency, nocturia, polyuria, and urine odor abnormal. Skin and Subcutaneous Tissue Disorders — Infrequent: cold sweat, dermatitis contact, erythema, increased tendency to bruise, night sweats, and photosensitivity reaction; Rare: ecchymosis. Vascular Disorders — Frequent: hot flush; Infrequent: flushing, orthostatic hypotension, and peripheral coldness.
The following adverse reactions have been identified during postapproval use of Cymbalta. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Adverse reactions reported since market introduction that were temporally related to duloxetine therapy and not mentioned elsewhere in labeling include: anaphylactic reaction, aggression and anger particularly early in treatment or after treatment discontinuation , angioneurotic edema, erythema multiforme, extrapyramidal disorder, glaucoma, gynecological bleeding, hallucinations, hyperglycemia, hypersensitivity, hypertensive crisis, muscle spasm, rash, restless legs syndrome, seizures upon treatment discontinuation, supraventricular arrhythmia, tinnitus upon treatment discontinuation , trismus, and urticaria.
Other drugs that inhibit CYP1A2 metabolism include cimetidine and quinolone antimicrobials such as ciprofloxacin and enoxacin [see Warnings and Precautions 5.
Similar effects would be expected with other potent CYP2D6 inhibitors e. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding.
Patients receiving warfarin therapy should be carefully monitored when duloxetine is initiated or discontinued [see Warnings and Precautions 5. Under steady-state conditions for duloxetine 60 mg Q 12 hours and lorazepam 2 mg Q 12 hours , the pharmacokinetics of duloxetine were not affected by co-administration.
Under steady-state conditions for duloxetine 20 mg qhs and temazepam 30 mg qhs , the pharmacokinetics of duloxetine were not affected by co-administration. Cymbalta has an enteric coating that resists dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5. Drugs that raise the gastrointestinal pH may lead to an earlier release of duloxetine.
However, co-administration of Cymbalta with aluminum- and magnesium-containing antacids 51 mEq or Cymbalta with famotidine, had no significant effect on the rate or extent of duloxetine absorption after administration of a 40 mg oral dose. It is unknown whether the concomitant administration of proton pump inhibitors affects duloxetine absorption [see Warnings and Precautions 5. In vitro drug interaction studies demonstrate that duloxetine does not induce CYP1A2 activity.
Therefore, an increase in the metabolism of CYP1A2 substrates e. Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine was administered at a dose of 60 mg twice daily in conjunction with a single 50 mg dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold [see Warnings and Precautions 5. Duloxetine does not inhibit the in vitro enzyme activity of CYP2C9.
Inhibition of the metabolism of CYP2C9 substrates is therefore not anticipated, although clinical studies have not been performed. Results of in vitro studies demonstrate that duloxetine does not inhibit or induce CYP3A activity. Therefore, an increase or decrease in the metabolism of CYP3A substrates e. Results of in vitro studies demonstrate that duloxetine does not inhibit CYP2C19 activity at therapeutic concentrations.
Inhibition of the metabolism of CYP2C19 substrates is therefore not anticipated, although clinical studies have not been performed. Based on the mechanism of action of SNRIs and SSRIs, including Cymbalta, and the potential for serotonin syndrome, caution is advised when Cymbalta is co-administered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, linezolid an antibiotic which is a reversible non-selective MAOI , lithium, tramadol, or St.
John's Wort. There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of Cymbalta with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases [see Warnings and Precautions 5. When Cymbalta and ethanol were administered several hours apart so that peak concentrations of each would coincide, Cymbalta did not increase the impairment of mental and motor skills caused by alcohol.
In the Cymbalta clinical trials database, three Cymbalta-treated patients had liver injury as manifested by ALT and total bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, and this may have contributed to the abnormalities seen [see Warnings and Precautions 5.
Because duloxetine is highly bound to plasma protein, administration of Cymbalta to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, potentially resulting in adverse reactions. Post-weaning growth and reproductive performance of the progeny were not affected adversely by maternal duloxetine treatment. There are no adequate and well-controlled studies in pregnant women; therefore, duloxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects — Neonates exposed to SSRIs or serotonin and norepinephrine reuptake inhibitors SNRIs , late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying.
It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions 5. When treating pregnant women with Cymbalta during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering Cymbalta in the third trimester [see Dosage and Administration 2. The effect of duloxetine on labor and delivery in humans is unknown.
Duloxetine should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus. Duloxetine is excreted into the milk of lactating women. Because the safety of duloxetine in infants is not known, nursing while on Cymbalta is not recommended. However, if the physician determines that the benefit of duloxetine therapy for the mother outweighs any potential risk to the infant, no dosage adjustment is required as lactation did not influence duloxetine pharmacokinetics.
The disposition of duloxetine was studied in 6 lactating women who were at least 12 weeks postpartum. Duloxetine 40 mg twice daily was given for 3. Like many other drugs, duloxetine is detected in breast milk, and steady state concentrations in breast milk are about one-fourth those in plasma. The excretion of duloxetine metabolites into breast milk was not examined. Because the safety of duloxetine in infants is not known, nursing while on Cymbalta is not recommended [see Dosage and Administration 2.
Safety and effectiveness in the pediatric population have not been established [see Boxed Warning and Warnings and Precautions 5. Anyone considering the use of Cymbalta in a child or adolescent must balance the potential risks with the clinical need.
Of the 2, patients in premarketing clinical studies of Cymbalta for MDD, 5. Of the 1, patients in FM premarketing studies, 7. Premarketing clinical studies of GAD did not include sufficient numbers of subjects age 65 or over to determine whether they respond differently from younger subjects. In the MDD, DPNP, and FM studies, no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
SSRIs and SNRIs, including Cymbalta have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [see Warnings and Precautions 5. The pharmacokinetics of duloxetine after a single dose of 40 mg were compared in healthy elderly females 65 to 77 years and healthy middle-age females 32 to 50 years.
Dosage adjustment based on the age of the patient is not necessary [see Dosage and Administration 2. Duloxetine's half-life is similar in men and women. Dosage adjustment based on gender is not necessary. Duloxetine bioavailability AUC appears to be reduced by about one-third in smokers. Dosage modifications are not recommended for smokers. Patients with clinically evident hepatic insufficiency have decreased duloxetine metabolism and elimination.
Although C max was similar to normals in the cirrhotic patients, the half-life was about 3 times longer [see Dosage and Administration 2.
Limited data are available on the effects of duloxetine in patients with end-stage renal disease ESRD. The elimination half-life, however, was similar in both groups. The AUCs of the major circulating metabolites, 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate, largely excreted in urine, were approximately 7- to 9-fold higher and would be expected to increase further with multiple dosing.
In animal studies, duloxetine did not demonstrate barbiturate-like depressant abuse potential. While Cymbalta has not been systematically studied in humans for its potential for abuse, there was no indication of drug-seeking behavior in the clinical trials. Consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of Cymbalta e.
In drug dependence studies, duloxetine did not demonstrate dependence-producing potential in rats. In postmarketing experience, fatal outcomes have been reported for acute overdoses, primarily with mixed overdoses, but also with duloxetine only, at doses as low as mg. Signs and symptoms of overdose duloxetine alone or with mixed drugs included somnolence, coma, serotonin syndrome, seizures, syncope, tachycardia, hypotension, hypertension, and vomiting.
In case of acute overdose, treatment should consist of those general measures employed in the management of overdose with any drug. An adequate airway, oxygenation, and ventilation should be assured, and cardiac rhythm and vital signs should be monitored.
Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients. Activated charcoal may be useful in limiting absorption of duloxetine from the gastrointestinal tract. Administration of activated charcoal has been shown to decrease AUC and C max by an average of one-third, although some subjects had a limited effect of activated charcoal.
Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be beneficial. In managing overdose, the possibility of multiple drug involvement should be considered. A specific caution involves patients who are taking or have recently taken Cymbalta and might ingest excessive quantities of a TCA.
The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Longtime Goldman Sachs drug stock analyst Jami Rubin is less optimistic. Goldman downgraded Lilly stock this fall to sell from neutral, writing, "We don't think Lilly has gone far enough to address its upcoming challenges from patent expirations.
Yet, Lilly trades at a premium valuation for a pipeline which we view as underwhelming. Recent pipeline dropouts haven't helped. A promising Alzheimer's drug candidate ran into disappointing clinical trial results, though Lilly still has high hopes for using it to treat patients with mild dementia.
Other recent clinical trial failures have tripped up a breast cancer compound and an antidepressant. Still, Lilly remains undaunted and has submitted four potential new medicines for regulatory approval this year with more anticipated next year, Derica Rice, chief financial officer, said last week.
Joseph Krushinski would also be listed on the patent as a co-inventor. It proves no more effective against depression than a placebo.
Johnson was in a Lilly trial testing duloxetine as Yentreve, a urinary stress incontinence medication, and not in an anti-depressant trial. In light of suicide risks, some critics claim that the FDA approval of duloxetine for MDD and diabetic neuropathy is irresponsible.
On the other hand, the number of participants in the SUI studies was large, and trials of duloxetine for MDD and diabetic neuropathy showed no increase in suicidality. At the time of its release in , duloxetine was by far the most promising medicine in Eli Lilly's pipeline. With Cymbalta's patents set to expire on June 11, , Lilly says it is working on at least two new antidepressants to ensure its place in the SSRI antidepressant market.
Eli Lilly originally patented duloxetine on June 11, , and has asked the U. Patent and Trademark Office for an extension on the exclusivity of the chemical compound beyond to June 11, with an official patent extension application on January 5, As of Feb. Approximately 6. On October 19 , Eli Lilly issued a press release saying they had done trials which found that Cymbalta, at 60 mg once or twice daily, significantly reduced pain in more than half of women treated for fibromyalgia FM , with and without major depression, according to week data presented at the annual meeting of the American College of Rheumatology.
Critics argue that randomized controlled trials of FM are difficult due to factors such as a lack of understanding of the pathophysiology and a heterogeneous FM patient population. In the study testing the efficacy of Cymbalta for FM, participants completed several questionnaires to measure the amount of pain and discomfort the disease caused them at the beginning of the study, and then at the end of each of the first two weeks and every second week for the remaining 12 weeks of the study.
Researchers also tested the participants for depression. Women who took Cymbalta had significantly less pain and discomfort than those who took the placebo.
For men, who made up only 11 percent of the study, there was no effect from taking the medication compared with a placebo. Reportedly, depression played no part in whether or not the drug worked to control pain. The change in the level of women's pain was particularly pronounced after a month of taking the drug, then leveled off a bit before dropping again near the end of the study.
However, in one of the primary measures of pain there was no significant difference between the two groups at the end of the week trial. Also, because the trial lasted only 12 weeks, it is impossible to tell how well the drug would control treatment for a longer period of time. Category : Serotonin-norepinephrine reuptake inhibitors. Read what you need to know about our industry portal bionity. My watch list my. My watch list My saved searches My saved topics My newsletter Register free of charge.
Keep logged in. Cookies deactivated. To use all functions of this page, please activate cookies in your browser. Login Register. Home Encyclopedia Duloxetine Duloxetine. Additional recommended knowledge. Curr Opin Investig Drugs. November 1, , retrieved November 24, Perahia1, D. Kajdasz, D. Walker, J. Raskin, A. Depression and diabetic neuropathy: too many adverse effects. Journal of Annual Toxicology. J Clin Psychopharmacol.
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