Healthcare Provider

Study Objectives:

The Cymbalta Pregnancy Registry is a prospective, observational study that enrolls pregnant women prescribed Cymbalta by their health care provider and follows maternal, fetal, and infant outcomes following exposure to Cymbalta during pregnancy. Data collected from this study will be shared with the Food and Drug Administration and may be added to Cymbalta labeling to provide prescribers with additional prescribing and consulting information.

The objective is to estimate the risk of major congenital anomalies among pregnancies exposed to Cymbalta, as well as recognized spontaneous abortions, stillbirths, elective terminations, minor congenital anomalies, and any serious adverse pregnancy outcomes; the potential impact while breast-feeding is also examined.

Healthcare Provider Participation Steps:

Step 1: Inform patient of Registry so patient can provide consent to initiate enrollment.
  • Click on the Contact Us link for how to contact the Registry by phone or e-mail
Step 2: Fill out registration forms to complete enrollment.
  • To be eligible for this Registry, the patient must be at least 18 years old, a U.S. resident, pregnant and have been treated with Cymbalta during pregnancy, and provide consent
  • A woman who has taken one or more doses of Cymbalta while pregnant is eligible. Sufficient evidence is needed to confirm that Cymbalta exposure occurred during pregnancy
  • No study medication will be given and participation in the registry will not influence or interfere with the treatment plan recommended by the patient’s healthcare provider
  • Registry enrollment is voluntary and initiated by pregnant patients for women exposed to Cymbalta at any time during pregnancy beginning on or after the first day of their last menstrual period. Enrollment should occur as early in pregnancy as possible, preferably before any prenatal testing has occurred
  • Enrollment in the Registry is strictly voluntary. The patient can initiate the enrollment process by calling the Registry and providing verbal consent for participation and for contacting her healthcare provider(s). Once the patient provides her verbal consent, data can be collected for enrollment. The patient's obstetric healthcare provider is then contacted to confirm his or her willingness to provide follow up regarding the patient's pregnancy. Alternatively, the healthcare provider can initiate enrollment with a conversation about the Registry with the patient. The healthcare provider has access to the Registry forms and may consent the patient in his or her office and send the completed forms to the Registry. Subsequent follow-ups with the healthcare provider and/or patient will be initiated from the Registry
  • Healthcare professionals can obtain registration forms via the Registry website or by calling the Registry Coordinating Center. All of the Registry forms are in English and Spanish. Forms can be mailed or faxed to the Registry Coordinating Center or the data may be provided over the telephone
Step 3: Fill out outcome data forms at specified intervals and provide to Registry.
  • The Registry collects information from the patient at enrollment and confirms it with the healthcare provider
  • Follow-up information is requested from the obstetrical healthcare provider at the end of the second trimester and the end of the pregnancy
  • If a live birth is reported, the Registry conducts follow-up with the infant’s pediatric healthcare provider at outcome, 4 months, and 12 months of age
    • if a birth defect is indicated, the Registry requests additional targeted follow-up information from the healthcare provider
  • If the mother is breast-feeding, a breast-feeding questionnaire is administered to the mother at 3, 6, 9, and 12 months postpartum while breast-feeding continues
  • For details, click on the Information Collected and Data Forms links
Indications
  • Cymbalta is indicated for the treatment of Major Depressive Disorder (MDD). The efficacy of Cymbalta was established in 4 short-term trials and 1 maintenance trial in adults
  • Cymbalta is indicated for the treatment of Generalized Anxiety Disorder (GAD). The efficacy of Cymbalta was established in 3 short-term trials and 1 maintenance trial in adults
  • Cymbalta is indicated for the management of chronic musculoskeletal pain. This has been established in studies in patients with chronic low back pain (CLBP) and chronic pain due to osteoarthritis
  • Cymbalta is indicated for the management of neuropathic pain (DPNP) associated with diabetic peripheral neuropathy
  • Cymbalta is indicated for the management of fibromyalgia (FM)
Important Safety Information About Cymbalta ®

Warning: Suicidal Thoughts and Behaviors—Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. Cymbalta is not approved for use in pediatric patients.

Contraindications

  • The use of MAOIs intended to treat psychiatric disorders with Cymbalta or within 5 days of stopping treatment with Cymbalta is contraindicated because of an increased risk of serotonin syndrome. The use of Cymbalta within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated. Starting Cymbalta in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome.
  • Cymbalta was associated with an increased risk of mydriasis; therefore, it should not be used in patients with uncontrolled narrow-angle glaucoma and used cautiously in patients with controlled narrow-angle glaucoma.

Warnings and Precautions

  • Suicidal Thoughts and Behaviors in Adolescents and Young Adults
    All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially within the first few months of treatment and when changing the dose. Consider changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or includes symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, or suicidality that are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. If discontinuing treatment, the medication should be tapered. Families and caregivers of patients being treated with antidepressants for any indication should be alerted about the need to monitor patients. Prescriptions for Cymbalta should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose.
     
    Screening patients for bipolar disorder: Prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. Cymbalta is not approved for use in treating bipolar depression.
  • Hepatic failure, sometimes fatal, has been reported in patients treated with Cymbalta. Cymbalta should be discontinued in patients who develop jaundice or other evidence of clinically significant liver dysfunction and should not be resumed unless another cause can be established.
  • Because it is possible that Cymbalta and alcohol may interact to cause liver injury or that Cymbalta may aggravate pre-existing liver disease, Cymbalta should not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease.
  • Orthostatic hypotension and syncope have been reported with therapeutic doses of Cymbalta. This tends to occur within the first week of therapy but can occur at any time during Cymbalta treatment, particularly after dose increases. Consideration should be given to discontinuing Cymbalta in patients who experience symptomatic orthostatic hypotension and/or syncope.
  • Development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including Cymbalta, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Monitor patients for the emergence of serotonin syndrome. The concomitant use of Cymbalta with MAOIs intended to treat psychiatric disorders is contraindicated. Cymbalta should also not be started in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Cymbalta, discontinue Cymbalta before initiating treatment with the MAOI. If concomitant use of Cymbalta with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases. Discontinue treatment with Cymbalta and any concomitant serotonergic agents immediately if the above events occur and initiate supportive symptomatic treatment.
  • SSRIs and SNRIs, including Cymbalta, may increase the risk of bleeding events. Patients should be cautioned about the risk of bleeding associated with concomitant use of Cymbalta and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation.
  • Severe skin reactions, including erythema multiforme and Stevens-Johnson Syndrome, can occur with Cymbalta. Cymbalta should be discontinued at the first appearance of blisters, peeling rash, mucosal erosions, or any other sign of hypersensitivity, if no other etiology can be identified.
  • On abrupt or tapered discontinuation, spontaneous reports of adverse events, some of which may be serious, have been reported during the marketing of SSRIs and SNRIs. A gradual reduction in dose rather than abrupt cessation is recommended when possible.
  • Cymbalta should be used cautiously in patients with a history of mania or with a history of a seizure disorder.
  • In clinical trials across indications relative to placebo, treatment with Cymbalta was associated with mean increases of 0.5 mm Hg in systolic blood pressure and 0.8 mm Hg in diastolic blood pressure compared to mean decreases of 0.6 mm Hg systolic and 0.3 mm Hg diastolic in placebo-treated patients. There was no significant difference in the frequency of sustained (3 consecutive visits) elevated blood pressure. Blood pressure should be measured prior to initiating treatment and periodically measured throughout treatment.
  • Co-administration of Cymbalta with potent CYP1A2 inhibitors or thioridazine should be avoided.
  • SSRIs and SNRIs, including Cymbalta, have been associated with cases of clinically significant hyponatremia that appeared to be reversible when Cymbalta was discontinued. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs.
  • The effect that alterations in gastric motility may have on the stability of the enteric coating of Cymbalta is unknown. As duloxetine is rapidly hydrolyzed in acidic media to naphthol, caution is advised in using Cymbalta in patients with conditions that may slow gastric emptying (e.g., some diabetics).
  • Cymbalta should ordinarily not be administered to patients with any hepatic insufficiency or patients with end-stage renal disease (requiring dialysis) or severe renal impairment (creatinine clearance <30 mL/min).
  • As observed in DPNP trials, Cymbalta treatment worsens glycemic control in some patients with diabetes. In the extension phases (up to 52 weeks) of the DPNP studies, an increase in HbA1c in both the Cymbalta (0.5%) and the routine care groups (0.2%) was noted.
  • Cymbalta is in a class of drugs known to affect urethral resistance. If symptoms of urinary hesitation develop during Cymbalta treatment, this effect may be drug-related. In postmarketing experience, urinary retention has been observed.

Use in Specific Populations

  • Pregnancy and Nursing Mothers: Use only if the potential benefit justifies the potential risk to the fetus or child.
  • Geriatric Use: In patients 65 years of age and older from all placebo-controlled trials, 1.1% of patients treated with Cymbalta reported one or more falls (some with serious consequences), compared with 0.4% of patients treated with placebo.

Most Common Adverse Events

  • The most commonly reported adverse events (≥5% and at least twice placebo) for Cymbalta vs placebo in controlled clinical trials were: nausea* (23% vs 8%), dry mouth (13% vs 5%), somnolence (10% vs 3%), constipation* (9% vs 4%), decreased appetite* (7% vs 2%), and increased sweating* (6% vs 1%).

    * Events for which there was a significant dose-dependent relationship in fixed-dose studies, excluding three MDD studies that did not have a placebo lead-in period or dose titration.
     
  • In placebo-controlled clinical trials, the overall discontinuation rates due to adverse events were: MDD: 8% vs 5%; GAD: 14% vs 5%; DPNP: 13% vs 5%; FM: 18% vs 10%; OA: 16% vs 7%; CLBP: 17% vs 6%.
     
    The common adverse events reported as a reason for discontinuation and considered to be drug related were: MDD: nausea (1.1% vs 0.4%). GAD: nausea (3.3% vs 0.4%), dizziness (1.3% vs 0.4%). DPNP: nausea (3.5% vs 0.7%), dizziness (1.2% vs 0.4%), somnolence (1.1% vs 0%). FM: nausea (2.0% vs 0.5%), headache (1.2% vs 0.3%), somnolence (1.1% vs 0%), fatigue (1.1% vs 0.1%). OA: nausea (2.2% vs 1.0%). CLBP: nausea (3.0% vs 0.7%), somnolence (1.0% vs 0%).

See Prescribing Information, including Boxed Warning about antidepressants and suicidality, and Medication Guide.

DD HCP ISI 31OCT2012