Duloxetine is the generic name of Cymbalta. It is a potent selective reuptake inhibitor of serotonin and norepinephrine. Other medicines belonging to the SNRI class of medicines include venlafaxine (Effexor), desvenlafaxine (Pristiq), and milnacipran (Savella).

 

Duloxetine (Cymbalta) Uses:

Cymbalta (duloxetine) is commonly used in the treatment of the following conditions:

• Fibromyalgia

• Generalized anxiety disorder (GAD)

• Major Unipolar depression

• Chronic musculoskeletal pain including chronic low back pain and osteoarthritis.

• Neuropathic pain in individuals with diabetes mellitus

• Peripheral neuropathy caused by chemotherapy

• Stress urinary incontinence in men and women.

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Duloxetine (Cymbalta) for fibromyalgia:

Fibromyalgia is a disease of unknown etiology. It is characterized by pain and tenderness in multiple areas of the body. It is usually associated with other systemic symptoms such as fatigue, lethargy, mood fluctuations, irritability, mood, and sleep disturbances. Duloxetine has been studied in fibromyalgia.

It acts as a double-edged sword in these patients. It treats depressive symptoms and simultaneously has analgesic effects. Since more than 60 - 80% of the patients diagnosed with fibromyalgia have depressive symptoms, some studies have attributed its pain-relieving effects to improvement in depression scores.

It is important to note that lower doses of the drug (20 mg, 30 mg, and 40 mg) are effective in relieving the symptoms of pain and fatigue, while higher doses (40 mg, 60 mg, and 120 mg) have antidepressant effects. However, studies have used higher doses of duloxetine for the treatment of patients with fibromyalgia (with or without depression). Doses of 60 mg two times a day were used and found effective in reducing tender points and pain without significant side effects [Ref].

In another study, compared to milnacipran, duloxetine and pregabalin were superior in reducing the symptoms of pain and disturbed sleep. Duloxetine was superior to milnacipran and pregabalin in patients with depression [Ref]. Duloxetine was studied in female patients with fibromyalgia.

The study concluded that the drug was safe and effective in relieving the symptoms of pain and improved functional impairment and the quality of life [Ref]. Compared to tricyclic antidepressants, it has fewer adverse effects and similar efficacy in relieving somatic symptoms along with psychological benefits. Fibromyalgia is one of the two major indications in our clinical practice that responds to Cymbalta (duloxetine) and to a lesser extent to the other SSRIs.

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Cymbalta for back pain:

Lower back pain may be due to neurogenic causes, muscular causes, or problems in the joints and bones. Most of the patients with lower back pain respond temporarily to NSAIDs and other pain-relieving medicines. However, the effect of these drugs wanes off after sometimes.

Before quoting important clinical trials, I would like to share my personal experience with the use of duloxetine in chronic lower back pain. I have used this drug in many patients with lower back pain with most patients responding very well, however, three of them need to be mentioned here. The first is a young female who was receiving pain medicines (Celebrex, tramadol) for the past six months.

She responded initially but then her pain worsened and she was advised surgery for spinal stenosis and disc problems. When she was started on duloxetine 30 mg, she responded partially. However, her pain completely disappeared after 2 weeks when she was started on duloxetine 60 mg. She refused to undergo surgery then. Another patient was brought in a bed-bound status because of severe low back pain. He was already scheduled for surgery in a month's time. However, I advised him a combination of duloxetine 60 mg and pregabalin 100 mg as a temporary measurement for the relief of pain. After 2 weeks, he came walking to my clinic. He went to his surgeon but the surgeon refused to operate as he was currently asymptomatic. Lastly, my father had a sudden onset of lower back pain that radiated to his left leg.

He developed numbness and tingling sensations in the foot but could bear weight on his leg. His posture suddenly changed from erect to stooped one (90 degrees) and could not walk. His MR of the spine showed osteophytes and multi-levels disc degenerative changes. He was started on Cymbalta 60 mg and pregabalin75 mg along with active physiotherapy. After three months, his pain disappeared and he could walk normally without the support and without any discomfort. The efficacy of duloxetine in the treatment of chronic low backache has been proved in various studies [Ref] and it has been approved for the treatment of chronic low back pain [Ref].

Some studies have found it to be effective only from 3rd week onwards to the 11th and 12th week of initiating the treatment [Ref]. It is important to initiate aggressive physiotherapy during the 3rd to 11th week when the duloxetine is more effective. Another study evaluated the long term efficacy of duloxetine in patients with chronic low back pain. Unlike opioid analgesics that may result in hyperalgesia when the treatment is discontinued and NSAIDs that may be associated with a blunting in the response to the treatment (tachyphylaxis), duloxetine can be safely given for longer periods.

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Cymbalta and Effexor (Venlafaxine):

Cymbalta and Effexor (Venlafaxine extended-release) have been used to treat generalized anxiety disorders. Compared to a placebo medicine, these drugs resulted in greater improvement in the somatic symptoms as well [Ref]. Effexor (Venlafaxine) XR 150 mg and Duloxetine (Cymbalta) 60 mg were found in one study to be equally effective in the management of major depression [Ref]. Venlafaxine and duloxetine have been compared in meta-analysis with SSRIs and TCAs.

The authors conclude that although these drugs (Cymbalta and Effexor) are equally effective in the treatment of major depression, they should be used as the second line of treatment because of the low tolerability. Although minor differences exist between duloxetine and venlafaxine, most experts favor venlafaxine over duloxetine for the treatment of major depression. For the treatment of depression with predominantly physical symptoms such as fatigue, pain, and tenderness, duloxetine is considered more efficacious.

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Cymbalta and Celebrex (Celecoxib) for the treatment of Osteoarthritis and skeletal pains:

Cymbalta and Celebrex (Celecoxib) have synergistic effects when used to treat patients with degenerative arthritis and chronic low back pain. One study compared Celebrex and Cymbalta in patients with osteoarthritis. The study concluded that patients in the duloxetine were more likely to adhere to long-term treatment compared to Celecoxib. Furthermore, patients in the duloxetine group were less likely to take an opioid analgesic for pain relief compared to Celecoxib [Ref].

Another meta-analysis evaluated the efficacy of duloxetine and other first-line therapies in patients with osteoarthritis. The study did not find any statistical differences between duloxetine and the other first-line treatments. However, etoricoxib was found to be superior to duloxetine. Duloxetine, on the other hand, was superior to tramadol and hydromorphone [Ref].

Cymbalta for Rheumatoid Arthritis (RA):

Cymbalta has not been evaluated in patients with rheumatoid arthritis since the primary goal of treatment in patients with rheumatoid arthritis is to control inflammation. Cymbalta (Duloxetine) does not have any effect on inflammation. Furthermore, more effective therapies are available for Rheumatoid arthritis. It may, however, be used in patients with rheumatoid arthritis if concomitant neuropathy, fibromyalgia, or depression is present.

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Rexulti and Cymbalta:

Rexulti is the brand name of Bexpiprazole. It has been approved in 2015 for the treatment of schizophrenia and as adjunctive therapy for major depression. Rexulti has been studied in patients taking duloxetine for major depression. Rexulti added to Cymbalta appeared more effective for the treatment of major depression [Ref]

Cymbalta and Abilify (Aripiprazole):

Cymbalta and Abilify in low doses have the same effects as Rexulti when used in patients with major depression. Abilify in one case report was used to treat patients with duloxetine-induced hyperprolactinemia.

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Duloxetine and sexual dysfunction:

Treatment-emergent sexual dysfunction is a common side effect of all psychotherapeutic drugs including Cymbalta (Duloxetine). Compared to placebo, duloxetine was associated with sexual dysfunction in one study. However, in the same study, the incidence of duloxetine-induced sexual dysfunction was significantly lower in patients treated with paroxetine [Ref].

Another study evaluated the changes in sexual functions associated with escitalopram and duloxetine. A higher incidence of sexual dysfunction was found in the escitalopram treated patients compared to duloxetine [Ref]. One case series of patients noticed better results and clinical improvement in sexual dysfunction when mirtazapine and duloxetine were given to patients with treatment-resistant depression [Ref].

Treatment of duloxetine induced sexual dysfunction may include reducing the dose or totally discontinuing the drug. Patients may need to be switched to other antidepressants like bupropion and mirtazapine. Drugs that inhibit the phosphodiesterases like sildenafil (Viagra), Tadalafil (Cialis), and Vardenafil ( Levitra) may temporarily improve the erectile dysfunction in these patients. 

 

Duloxetine Dose in Adults:

Cymbalta 30 mg - Dose as off-label use in the Chemotherapy-induced peripheral neuropathy:

• 30 mg orally once a day for one week
• Increase the dose after one week to 60 mg if required.

Duloxetine dose in the treatment of Fibromyalgia:

• 30 mg orally once a day for one week.
• The dose is then increased to 60 mg once a day after one week if tolerated.
• Smaller increments in the dose may be tolerated better.
• An initial dose of 20 mg is titrated upward at weekly intervals by 20 mg to the maximum dose of 60 mg once a day.
• Doses of up to 120 mg have been used but may not have additional benefits.

Duloxetine 60 mg dose in the treatment of Generalized anxiety disorder:

• 60 mg once a day orally.
• Some patients may require lower doses of 30 mg which are then increased after a week to 60 mg once a day.
• The usual maintenance dose is 60 mg once a day.
• Doses of up to 120 mg have been used but rarely may be more beneficial.

Duloxetine dose in the treatment of major unipolar depressive disorder:

• It is given as 40 - 60 mg once daily or in two divided doses.
• Some patients may benefit from initiating a lower dose of 30 mg daily.
• The usual maintenance dose is 60 mg once daily, however, doses of up to 120 mg per day have been used.

Duloxetine (Cymbalta) dose in the treatment of chronic Musculoskeletal pain:

• Duloxetine dose in chronic low back pain (alternative agent):

  • It is used as an adjunct to the treatment when the pain does not adequately respond to NSAIDs and nonpharmacologic therapy.
  • A starting dose of 30 mg is initiated once a day for one week that is then increased to the usual maintenance dose of 60 mg once a day.

• Osteoarthritis of the knee (alternative agent):

  • It is used in patients with moderate to severe disease when the response to NSAIDs and nonpharmacologic interventions is inadequate.
  • A dose of 30 mg once a day for one week is used that can be increased to 60 mg once a day.
  • The maximum dose according to the manufacturer is 60 mg once a day.
  • However, some patients may require doses up to 120 mg per day.

Duloxetine (Cymbalta) Dose in the treatment of Neuropathic pain associated with diabetes mellitus:

• Duloxetine 60 mg orally once a day initially.
• Lower doses may be used in some patients.
• The usual maximum dose is 60 mg once a day.
• Some patients may require higher doses of 120 mg per day.

Duloxetine dose in the treatment of stress urinary incontinence in women and men (off-label):

Note: It should be used when the patients have comorbid depression or the response to nonpharmacologic interventions is inadequate.

• It is started at a dose of 40 mg twice daily orally.
• Lower initial doses may be used in some patients who do not tolerate it well.
• 20 mg two times a day is given for 2 weeks and then the dose is increased to 40 mg twice daily.

How to discontinue Duloxetine (Cymbalta)?

• Discontinuation should be slow if it has been used for more than 3 weeks.
• The dose should be tapered off over 2 - 4 weeks to avoid withdrawal symptoms.
• Patients who develop any withdrawal symptoms should be reinitiated with the last dose that was well tolerated.
• The dose should then be tapered off more slowly.
• Patients who have been using it for more than 6 months and those who experience withdrawal symptoms should taper off the drug over a period of 3 months.

How to switch to another antidepressant?

Although data regarding switching strategies from one antidepressant to another antidepressant is limited, some of the important points are listed here:

• Cross-titration:

  • This method is usually followed especially when duloxetine or the other antidepressant has been used for more than 2 - 4 weeks.
  • One drug is gradually tapered while the dose of the other drug is increased gradually at the same time.

• Direct switch:

  • The direct switch is the abrupt discontinuation of one drug and initiating the other drug at an equivalent dose.
  • This method may be appropriate in cases where the drug has been used for less than 1 - 2 weeks or when the drug is discontinued because of the adverse effects.
• Switching to or from an MAOI:

At least a 14 days drug-free interval should be allowed when switching from an MAOI to duloxetine.

Switching from an MAOI, a gap of at least five days should be kept. Cross titration is contraindicated when switching from an MAOI to an SSRI and vice versa.

Dose in children:

Duloxetine dose in children with Generalized anxiety disorder:

• Children and Adolescents 7 - 17 years:

  • 30 mg orally once a day initially
  • The dose may be increased to 60 mg once a day after one week if it is tolerated.
  • The dose should not be increased by more than 30 mg increments.
  • The maximum dose is 120 mg once a day.

• Discontinuation of therapy:

  • See adult dose.

• Switching antidepressants:

  • See adult dose.

Duloxetine Pregnancy Risk Factor C

• It crosses the placental boundary.
• It may have nonteratogenic effects on the newborn if it is used in the third trimester. These effects could include:
  • Respiratory distress
  • Cyanosis
  • Apnea
  • Seizures
  • Temperature instability
  • Feeding difficulties
  • Vomiting
  • Hypoglycemia
  • Hypertonia
  • Hypotonia
  • Hyperreflexia
  • Jotteriness
  • Irritability
  • You cry incessantly.
  • Tremor.
• These symptoms could be caused by discontinuation syndrome, or duloxetine.
• ACOG recommends a personalized approach to treating depression during pregnancy.
• American Psychiatric Association recommends that you weigh the risks for the fetus against the benefits for the mother.
• It may be possible to restart the medication after delivery if it is stopped during pregnancy for women who are at high risk of developing postpartum depression.

Use while breastfeeding

• It is found in breastmilk, and in infant serums.
• Its use in lactating women has not been documented.
• Monitor infants breastfed while their mother takes duloxetine.
• If the mother is already taking it, and on a steady dose, she may continue breastfeeding.
• If treatment for depression is necessary while breastfeeding, you can use other preferred agents.

Renal dose:

Duloxetine dose adjustment in kidney disease:

• •  

  • CrCl greater than 30 mL/minute

    • Although the manufacturer has not suggested any adjustments to the dose, it can still be safely used in these patients.

  • CrCl less than 30mL/minute

    • It is best to avoid its use.

  • End-stage renal disease (ESRD).

    • It is best to avoid its use.

 

Duloxetine in Liver disease:

It should be avoided in patients with liver disease.

Duloxetine (Cymbalta) Side effects:

• Central Nervous System:

  • Headache
  • Drowsiness
  • Fatigue

• Gastrointestinal:

  • Nausea
  • Xerostomia
  • Abdominal Pain

• Endocrine & Metabolic:

  • Weight Loss

• Neuromuscular & Skeletal:

  • Weakness

Less common Side Effects Of Duloxetine (Cymbalta):

• Cardiovascular:

  • Flushing
  • Increased Blood Pressure
  • Palpitations

• Central Nervous System:

  • Insomnia
  • Dizziness
  • Agitation
  • Anxiety
  • Delayed Ejaculation
  • Yawning
  • Abnormal Dreams
  • Anorgasmia
  • Chills
  • Hypoesthesia
  • Lethargy
  • Paresthesia
  • Rigors
  • Sleep Disorder
  • Vertigo

• Dermatologic:

  • Diaphoresis
  • Pruritus

• Endocrine & Metabolic:

  • Decreased Libido
  • Orgasm Abnormal
  • Hot Flash
  • Weight Gain

• Gastrointestinal:

  • Constipation
  • Decreased Appetite
  • Vomiting
  • Diarrhea
  • Dyspepsia
  • Dysgeusia
  • Flatulence

• Genitourinary:

  • Erectile Dysfunction
  • Ejaculatory Disorder
  • Urinary Frequency

• Hepatic:

  • Increased Serum ALT

• Neuromuscular & Skeletal:

  • Tremor
  • Musculoskeletal Pain

• Ophthalmic:

  • Blurred Vision

• Respiratory:

  • Oropharyngeal Pain
  • Cough

 

Duloxetine Contraindications:

•  

• Allergy reactions to any drug or component of the formulations
• Concurrent MAO (monoamine-oxidase inhibitor) should be used within 14 days after discontinuing the drug
• Within 5 days of stopping duloxetine, initiate an MAO inhibitor.
• Patients who receive intravenous methyleneblue or linezolid concurrently.
• Liver disease
• End-stage renal disease (ESRD), or severe renal disease (CrCl less than 30 ml/min).
• Glaucoma with uncontrolled narrow-angle vision
• Use with potent CYP1A2 inhibitors or thioridazine in conjunction.

• Warnings and precautions

• Bleeding Risk:

  • Use of duloxetine is associated with impaired platelet accumulation.
  • The patient may be at risk of bleeding. These patients can experience bleeding from minor to severe epistaxis or rash.
  • Concomitant Aspirin and NSAIDs can cause GI bleeding in individuals.

• Depression in the CNS:

  • It is not as likely to cause cognitive or motor impairments as other SSRIs or TCAs.
  • Be aware of those who drive heavy machinery.

• Dermatologic:

  • Stevens-Johnson syndrome and erythema multiforme may be skin manifestations.
  • Patients might experience skin peeling, blisters, mucosal erosions or urticaria.
  • If hypersensitivity reactions occur, treatment must be stopped immediately.

• Fractures

  • It has been linked to fractures.
  • Bony fractures should be checked for all patients suffering from bone tenderness, pain, swelling, or bruising.

• Hepatotoxicity

  • Patients suffering from liver disease or cirrhosis and those who consume moderate to high amounts of alcohol should abstain.
  • It has been linked to acute liver failure.
  • If liver toxicities are diagnosed, treatment must be stopped immediately.
  • Monitor patients for symptoms such as abdominal pain, jaundice, hepatomegaly, or elevated liver enzymes (especially if they are greater than 20 times the normal upper limit).

• Hyperglycemia

  • Patients with diabetes who use it to treat diabetic peripheral neuropathy symptoms may experience changes in their glycemic control.
  • It has been associated with mild hyperglycemia.

• Ocular effects

  • It can cause pupillary dilatation, which may lead to angle-closure glaucoma.
  • Patients at high risk of infection should not use it.

• Orthostatic hypotension, syncope

  • Patients who are hypertensive may experience an increase in their blood pressure.
  • However, syncope and postural drops in blood pressure may also occur within the first week.
  • Patients who use vasodilators, diuretics or CYP1A2 inhibits should increase their doses.
  • Patients with symptomatic conditions should have their doses reduced or tapered down gradually. Then, they should be discontinued.

• Serotonin syndrome (SS), reactions:

  • Serotonin syndrome can be life-threatening if it's used with serotonergic medications like triptans, TCAs (tricyclic Antidepressants), fentanyl and lithium.
  • It can also occur after the intake of MAO inhibitors (linezolid, methyleneblue, and other drugs that impair serotonin metabolism).
  • Duloxetine therapy patients should be closely monitored for signs and symptoms of serotonin syndrome. These include:
    • Modifications in mentation (shown as delirium and hallucination, or agitation).
    • Seizures
    • Autonomic instability can include increased heart rate, dizziness and postural drops in blood pressure.
    • Neuromuscular symptoms such as rigidity, tremor and myoclonus include tremor, rigidity and myoclonus.
    • Gastrointestinal symptoms such as nausea, vomiting, or diarrhea.
  • If any of these clinical features are present, the patient should immediately stop receiving treatment.

• Sexual dysfunction

  • All psychotherapeutic drugs, including duloxetine, can cause sexual dysfunction.

• SIADH and Hyponatremia

  • SSRIs like escitalopram have been linked to drug-induced hyponatremia secondary SIADH.
  • Patients may experience symptoms such as drowsiness or seizures when sodium levels fall below 110 mEq/l.
  • Hyponatremia is more common in elderly patients, those taking concomitant diuretics and other medications.

• Urinary hesitancy

  • Patients with impaired urination, such as patients with prostatic obstruction symptoms or diabetics, may experience symptoms of increased urinary urgency in the elderly and patients with diabetes.
  • It should be used with caution for patients at high risk of developing urinary retention.

• Gastroparesis

  • Patients with impaired gastric motility or other conditions should be cautious when using it.
  • The stability of the capsule may be affected by prolonged stomach stay.

• Hepatic impairment

  • Patients suffering from cirrhosis or chronic liver disease should not use it.

• Hypertension

  • Hypertension patients should not use it.
  • This medication can lead to a hypertensive emergency. Patients with high blood pressure should gradually reduce their intake and discontinue use.

• Hypomania and mania:

  • It has not been approved by the FDA for treatment of bipolar disorder
  • It can lead to mania and hypomania in patients suffering from bipolar disorder.
  • Monotherapy should not be used for patients with bipolar depression.

• Renal impairment

  • Patients with kidney disease should use it with caution. The dose may need adjustment.
  • Creatinine clearances below 30 ml/minute should be avoided.

• Seizure disorders

  • Be on the lookout for seizures, especially if there are any history of strokes, brain damage, infections, or alcoholics.

Duloxetine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)
Abiraterone Acetate	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)	May enhance the antiplatelet effect of other Agents with Antiplatelet Properties.
Ajmaline	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Ajmaline.
Alpha2-Agonists	Serotonin/Norepinephrine Reuptake Inhibitors may diminish the antihypertensive effect of Alpha2-Agonists. Exceptions: Apraclonidine.
Amphetamines	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amphetamines.
Anticoagulants	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
Antiemetics (5HT3 Antagonists)	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Antipsychotic Agents	Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Apixaban	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely.
ARIPiprazole	May enhance the adverse/toxic effect of DULoxetine. ARIPiprazole may enhance the serotonergic effect of DULoxetine. This could result in serotonin syndrome. DULoxetine may increase the serum concentration of ARIPiprazole.
Aspirin	Serotonin/Norepinephrine Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin.
Blood Pressure Lowering Agents	May enhance the hypotensive effect of DULoxetine.
Brexanolone	Serotonin/Norepinephrine Reuptake Inhibitors may enhance the CNS depressant effect of Brexanolone.
Brexpiprazole	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: If brexpiprazole is to be used together with both a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor, the brexpiprazole dose should be reduced to 25% of the usual dose.
Broccoli	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
Cannabis	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
Cephalothin	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased.
CloZAPine	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of CloZAPine.
Codeine	CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine.
Collagenase (Systemic)	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased.
CYP1A2 Inducers (Moderate)	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
CYP1A2 Inhibitors (Moderate)	May decrease the metabolism of CYP1A2 Substrates (High risk with Inhibitors).
CYP2D6 Inhibitors (Strong)	May increase the serum concentration of DULoxetine.
CYP2D6 Substrates (High risk with Inhibitors)	CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Exceptions: Tamoxifen.
Cyproterone	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
Dabigatran Etexilate	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management:Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.
Dasatinib	May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Deferasirox	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Deoxycholic Acid	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.
Edoxaban	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased.
Fat Emulsion (Fish Oil Based)	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties.
Fesoterodine	CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine.
Glucosamine	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Ibritumomab Tiuxetan	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding.
Ibrutinib	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties.
Indoramin	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Indoramin.
Inotersen	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Ioflupane I 123	Serotonin/Norepinephrine Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123.
Limaprost	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Metaxalone	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Methylphenidate	May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased.
Metoprolol	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoprolol.
Multivitamins/Fluoride (with ADE)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Multivitamins/Minerals (with ADEK, Folate, Iron)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Multivitamins/Minerals (with AE, No Iron)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Nebivolol	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol.
Nonsteroidal Anti-Inflammatory Agents (Nonselective)	Serotonin/Norepinephrine Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective).
Obeticholic Acid	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Obinutuzumab	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.
Omega-3 Fatty Acids	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Opioid Agonists	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Peginterferon Alfa-2b	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Pentosan Polysulfate Sodium	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents.
Pentoxifylline	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Propafenone	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Prostacyclin Analogues	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Rivaroxaban	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.
Salicylates	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result.
Serotonin Modulators	May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid.
Tamsulosin	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin.
Tedizolid	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Teriflunomide	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
Thrombolytic Agents	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.
Tipranavir	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Tobacco (Smoked)	May decrease the serum concentration of DULoxetine.
TraMADol	CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects.
TraMADol	Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Tricyclic Antidepressants	DULoxetine may enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. DULoxetine may decrease the metabolism of Tricyclic Antidepressants.
Vitamin E (Systemic)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Risk Factor D (Consider therapy modification)
Alcohol (Ethyl)	May enhance the adverse/toxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. Specifically, risks of psychomotor impairment may be enhanced. Alcohol (Ethyl) may enhance the hepatotoxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. Particularly duloxetine and milnacipran. Management: Patients receiving serotonin/norepinephrine reuptake inhibitors (SNRIs) should be advised to avoid alcohol. Monitor for increased psychomotor impairment and hepatotoxicity in patients who consume alcohol during treatment with SNRIs.
Alpha-/Beta-Agonists	Serotonin/Norepinephrine Reuptake Inhibitors may enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists.
DOXOrubicin (Conventional)	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided.
Eliglustat	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor.
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures.
Linezolid	May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Management: Consider alternatives to this combination whenever possible, and discontinue serotonin/norepinephrine reuptake inhibitors (SNRIs) prior to administration of linezolid.
Linezolid	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely.
Metoclopramide	May enhance the adverse/toxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with serotonin/norepinephrine reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome.
PARoxetine	DULoxetine may enhance the serotonergic effect of PARoxetine. This could result in serotonin syndrome. PARoxetine may increase the serum concentration of DULoxetine. Management: Coadminister with caution. If duloxetine and paroxetine are used in combination, monitor for signs and symptoms of serotonin toxicity/serotonin syndrome, as well as other toxic effects of duloxetine.
Perhexiline	CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required.
Tamoxifen	CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible.
Vemurafenib	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs.
Risk Factor X (Avoid combination)
Bromopride	May enhance the adverse/toxic effect of Serotonin/Norepinephrine Reuptake Inhibitors.
CYP1A2 Inhibitors (Strong)	May increase the serum concentration of DULoxetine.
Dapoxetine	May enhance the adverse/toxic effect of Serotonin Modulators.
Iobenguane Radiopharmaceutical Products	Serotonin/Norepinephrine Reuptake Inhibitors may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose.
Methylene Blue	Serotonin/Norepinephrine Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome.
Methylene Blue	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Monoamine Oxidase Inhibitors	May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid.
Thioridazine	CYP2D6 Inhibitors may increase the serum concentration of Thioridazine.
Urokinase	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase.

Monitor:

• Before starting therapy, monitor blood pressure (especially for hypertensives).
• Before initiating therapy, monitor the patient's mental state, including depression and suicidal thoughts.
• Monitor your patient for signs of anxiety, mania or changes in mental state such as panic attacks, social functioning, anxiety, and panic attacks.
• Diabetes patients should monitor their plasma glucose levels and glycated haglobin levels
• Monitor creatinine, BUN and liver function.

How and when to take Duloxetine (Cymbalta)?

You should swallow the capsule whole. You can open it and sprinkle it on food. The manufacturer recommends not opening the capsule. You can take it without any consideration for meals. 

Duloxetine (Cymbalta) mechanism of action:

Duloxetine is one of the drugs that blocks the neuronal junction's uptake of serotonin and norepinephrine. It has a weak inhibitory impact on the dopamine reuptake, but it does not affect the muscarinic or H-1 (histaminergic) or alpha-2adrenergic activities. It does not also inhibit MAO activity.

It isIntakeIt is fully absorbed within two hours after ingestion. It is less absorbable if taken with food (about 10%), but its peak concentration doesn't change. More than 90% of the drug are available in CanadaProtein-bound (Primarily to albumin and alpha-1-acid glycoprotein It isMetabolizedthrough the liver, and then converted to multiple inactivated metabolites using the enzymes CYP1A2 or CYP2D6.

It has been aEliminating half-lifeBetween 8 and 17 hours. For elderly women, the half-life is approximately 16 hours. Time to get therePeak serum concentrationIt takes approximately 6 hours to complete and can be delayed by 2 – 4 hours if eaten with food. 70% of the drug's total value is unknown.Excreted20 percent in the urine, and 20 percent in the feces.  

Duloxetine brand names (International):

• Cymbalta
• Irenka
• AG-Duloxetine
• APO-Duloxetine
• Auro-Duloxetine
• JAMP-Duloxetine
• M-Duloxetine
• Mar-Duloxetine
• MINT-Duloxetine
• MYLAN-Duloxetine
• NRA-Duloxetine
• PMS-Duloxetine
• RAN-Duloxetine
• RIVA-Duloxetine
• SANDOZ Duloxetine
• Alacir
• Ambidext
• Andepra
• Ariclaim
• Aritavi
• Cicleno
• Cimal
• Clonia
• Cymbalta
• Cymbatex
• Dalaful
• Delok
• Deloxi
• Deuloks
• Doxet
• Dulan
• Dulonorm
• Dulopressive
• Duloprex
• Dulox
• Duloxa
• Duloxeteg
• Dulsevir
• Duroceptol
• Duseta
• Duxela
• Duxetin
• Duxetine
• Duxtin
• Inmox
• Loxentia
• Loxyt
• Lyta
• Nitidex
• Psynil
• Sebata
• Xeristar
• Xinolax DR
• Yentreve

Duloxetine Brand Names in Pakistan:

Duloxetine Hydrochloride 30 mg Tablets in Pakistan
Loxiwan	Swan Pharmaceuticals (Pvt) Ltd

 

Capsule Duloxetine Hydrochloride 20 mg in Pakistan
Dudep	Navegal Laboratories
Dulan	Hilton Pharma (Pvt) Limited
Dulexin	Shaigan Pharmaceuticals (Pvt) Ltd
Dulox	S.J. & G. Fazul Ellahie (Pvt) Ltd.
Duloxet	Gray`S Pharmaceuticals
Duron	Global Pharmaceuticals
Duzalta	Pharmevo (Pvt) Ltd.
Enlon	Opal Laboratories (Pvt) Ltd.
Eziness	Murfy Pharmaceuticals (Pvt) Ltd
Hapibar	Barrett Hodgson Pakistan (Pvt) Ltd.
Ilario	Wilshire Laboratories (Pvt) Ltd.
Lyta	Getz Pharma Pakistan (Pvt) Ltd.
Symbal	Bosch Pharmaceuticals (Pvt) Ltd.
Yentreve	Shrooq Pharmaceuticals
Zenbar	Searle Pakistan (Pvt.) Ltd.
Zuloxet	Nabiqasim Industries (Pvt) Ltd.

 

Capsule Duloxetine 30 mg in Pakistan
Ambalta	Amarant Pharmaceuticals (Pvt)
C-Yalta	Obs
Delores	Fassgen Pharmaceuticals
Deloxt Dr	Prays Pharmaceuticals
Depfree	Glitz Pharma
Dostax	Scotmann Pharmaceuticals
Dulact	Cellgene Pharmaceuticals International
Dulan	Hilton Pharma (Pvt) Limited
Dulcap	Benson Pharamceuticals.
Dulex	Caylex Pharmaceuticals (Pvt) Ltd.
Dulexin	Shaigan Pharmaceuticals (Pvt) Ltd
Dulosoft	Mcolson Research Laboratories
Dulox	S.J. & G. Fazul Ellahie (Pvt) Ltd.
Duloxe	Amarant Pharmaceuticals (Pvt)
Dulset	Max Pharmaceuticals
Duron	Global Pharmaceuticals
Duxafit	Wns Field Pharmaceuticals
Duxet	Medera Pharmaceuticals (Pvt) Ltd.
Enlon	Opal Laboratories (Pvt) Ltd.
Eziness	Murfy Pharmaceuticals (Pvt) Ltd
Hapibar	Barrett Hodgson Pakistan (Pvt) Ltd.
Ilario	Wilshire Laboratories (Pvt) Ltd.
Loxetine	Saffron Pharmaceutical Company
Lyta	Getz Pharma Pakistan (Pvt) Ltd.
Oxcym Dr	Atco Laboratories Limited
Rexa	Noa Hemis Pharmaceuticals
Rexa	Noa Hemis Pharmaceuticals
Rexa	Noa Hemis Pharmaceuticals
Rexa	Noa Hemis Pharmaceuticals
Swenta	Martin Dow Pharmaceuticals (Pak) Ltd.
Symbal	Bosch Pharmaceuticals (Pvt) Ltd.
Synap	Genome Pharmaceuticals (Pvt) Ltd
Worth	Werrick Pharmaceuticals
Zenbar	Searle Pakistan (Pvt.) Ltd.
Zuloxet	Nabiqasim Industries (Pvt) Ltd.

 

Duloxetine 40 mg Capsules in Pakistan
Dulan	Hilton Pharma (Pvt) Limited
Duloxet	Gray`S Pharmaceuticals
Duzela	S.J. & G. Fazul Ellahie (Pvt) Ltd.
Worth	Werrick Pharmaceuticals

 

Duloxetine 60 mg Capsules in Pakistan
C-Yalta	Obs
Cymbalta	Eli Lilly Pakistan (Pvt) Ltd.
Delores	Fassgen Pharmaceuticals
Depfree	Glitz Pharma
Dulact	Cellgene Pharmaceuticals International
Dulan	Hilton Pharma (Pvt) Limited
Dulan	Hilton Pharma (Pvt) Limited
Dulcap	Benson Pharamceuticals.
Dulcap	Benson Pharamceuticals.
Dulcap	Benson Pharamceuticals.
Dulex	Caylex Pharmaceuticals (Pvt) Ltd.
Dulexin	Shaigan Pharmaceuticals (Pvt) Ltd
Dulosoft	Mcolson Research Laboratories
Dulox	S.J. & G. Fazul Ellahie (Pvt) Ltd.
Dulox	Panacea Pharmaceuticals
Dulox	Panacea Pharmaceuticals
Dulox	Panacea Pharmaceuticals
Dulox Dr	Linear Pharma
Duloxet	Gray`S Pharmaceuticals
Dulset	Max Pharmaceuticals
Durole	Pharmix Laboratories (Private) Limited.
Duron	Global Pharmaceuticals
Duron	Global Pharmaceuticals
Duxafit	Wns Field Pharmaceuticals
Duxet	Medera Pharmaceuticals (Pvt) Ltd.
Duzalta	Pharmevo (Pvt) Ltd.
Eziness	Murfy Pharmaceuticals (Pvt) Ltd
Hapibar	Barrett Hodgson Pakistan (Pvt) Ltd.
Ilario	Wilshire Laboratories (Pvt) Ltd.
Loxetine	Saffron Pharmaceutical Company
Lyta	Getz Pharma Pakistan (Pvt) Ltd.
Oxcym Dr	Atco Laboratories Limited
Rexa D	Noa Hemis Pharmaceuticals
Rexa D	Noa Hemis Pharmaceuticals
Rexa D	Noa Hemis Pharmaceuticals
Rexa D	Noa Hemis Pharmaceuticals
Swenta	Martin Dow Pharmaceuticals (Pak) Ltd.
Symbal	Bosch Pharmaceuticals (Pvt) Ltd.
Synap	Genome Pharmaceuticals (Pvt) Ltd
Worth	Werrick Pharmaceuticals
Yentreve	Shrooq Pharmaceuticals
Zenbar	Searle Pakistan (Pvt.) Ltd.
Zepril	Rotex Medica Pakistan (Pvt) Ltd
Zuloxet	Nabiqasim Industries (Pvt) Ltd.

 

Duloxetine 90 mg Capsules in Pakistan
C-Yalta	OBS
Dulan	Hilton Pharma (Pvt) Limited
Dulan	Hilton Pharma (Pvt) Limited