Duloxetine Powerful Action, Uses, And Top10 Brands In Pakistan

Introduction

Duloxetine is a widely used medication in the treatment of various mental health conditions and chronic pain disorders. It belongs to a class of drugs known as serotonin-norepinephrine reuptake inhibitors (SNRIs), which work by balancing chemicals in the brain that affect mood and pain perception.

Duloxetine is a prescription medication that primarily affects the neurotransmitters serotonin and norepinephrine. These neurotransmitters play key roles in regulating mood, anxiety, and pain. By preventing their reuptake into the cells, it increases the levels of these chemicals in the brain, which helps improve mood and reduce pain sensations.

Uses of Duloxetine

The doctors prescribe duloxetine for the following health conditions:

Major Depressive Disorder (MDD)

Duloxetine is commonly prescribed for the treatment of major depressive disorder. MDD is characterized by persistent feelings of sadness, loss of interest in activities, and other symptoms that interfere with daily life. By improving the balance of neurotransmitters, it helps alleviate these symptoms and improve quality of life.

Generalized Anxiety Disorder (GAD)

Generalized anxiety disorder is another condition where duloxetine is often utilized. GAD involves excessive, uncontrollable worry about various aspects of daily life. Duloxetine helps reduce anxiety symptoms by balancing neurotransmitters involved in anxiety regulation.

Diabetic Peripheral Neuropathy

This drug is effective in treating pain caused by diabetic peripheral neuropathy, a condition resulting from nerve damage due to diabetes. This chronic pain can be debilitating, and duloxetine helps by modulating pain pathways in the nervous system.

Fibromyalgia

Fibromyalgia is a chronic condition characterized by widespread musculoskeletal pain, fatigue, and tenderness in localized areas. Duloxetine is beneficial in managing fibromyalgia symptoms by enhancing the pain-inhibitory pathways in the central nervous system.

Chronic Musculoskeletal Pain

Duloxetine is also prescribed for chronic musculoskeletal pain, which can result from conditions such as osteoarthritis and chronic back pain. By influencing pain perception in the brain, this medicine provides significant relief from chronic pain.

Off-Label Uses

In addition to its approved uses, duloxetine is sometimes prescribed off-label for other conditions. These include:

• Stress Urinary Incontinence: Duloxetine can improve symptoms by strengthening the urethral sphincter muscle.
• Chemotherapy-Induced Peripheral Neuropathy: Some studies suggest that this drug helps alleviate pain associated with nerve damage caused by chemotherapy.
• Chronic Fatigue Syndrome: It’s effects on mood and pain perception may benefit those with chronic fatigue syndrome.

Duloxetine Uses in Urdu

بڑا ڈپریشن ڈس آرڈر

یہ عام طور پر بڑے ڈپریشن ڈس آرڈر کے علاج کے لیے تجویز کیا جاتا ہے۔ ایم ڈی ڈی کی خصوصیت اداسی کے مسلسل احساسات، سرگرمیوں میں دلچسپی ختم ہونے اور روزمرہ کی زندگی میں مداخلت کرنے والی دیگر علامات سے ہوتی ہے۔ نیورو ٹرانسمیٹر کے توازن کو بہتر بنا کر، ڈولوکسیٹائن ان علامات کو کم کرنے اور معیار زندگی کو بہتر بنانے میں مدد کرتا ہے۔

عمومی تشویش کی خرابی

عمومی اضطراب کی خرابی ایک اور حالت ہے جہاں ڈولوکسیٹائن اکثر استعمال ہوتی ہے۔ عمومی تشویش کی خرابی میں روزمرہ کی زندگی کے مختلف پہلوؤں کے بارے میں ضرورت سے زیادہ، بے قابو فکر شامل ہے۔ یہ اضطراب کے ضابطے میں شامل نیورو ٹرانسمیٹر کو متوازن کرکے اضطراب کی علامات کو کم کرنے میں مدد کرتا ہے۔

ذیابیطس پردیی نیوروپتی

یہ دوا ذیابیطس کے پردیی نیوروپتی کی وجہ سے ہونے والے درد کے علاج میں موثر ہے، یہ حالت ذیابیطس کی وجہ سے اعصاب کو پہنچنے والے نقصان کے نتیجے میں ہوتی ہے۔ یہ دائمی درد کمزور ہو سکتا ہے، اور ڈولوکسیٹائن اعصابی نظام میں درد کے راستوں کو ماڈیول کر کے مدد کرتا ہے۔

Fibromyalgia

یہ ایک دائمی حالت ہے جس کی خصوصیت بڑے پیمانے پر پٹھوں میں درد، تھکاوٹ، اور مقامی علاقوں میں کوملتا ہے۔ یہ دوا مرکزی اعصابی نظام میں درد روکنے والے راستوں کو بڑھا کر فائبرومیالجیا کی علامات کو سنبھالنے میں فائدہ مند ہے۔

دائمی  درد(Musculoskeletal)

یہ دوا اس حالت کے لیے بھی تجویز کی جاتی ہے جس کا نتیجہ آسٹیو ارتھرائٹس اور کمر میں دائمی درد جیسی حالتوں سے ہو سکتا ہے۔ دماغ میں درد کے ادراک کو متاثر کرکے، ڈولوکسیٹائن دائمی درد سے اہم ریلیف فراہم کر سکتا ہے۔

Mechanism of Action

Duloxetine works by inhibiting the reuptake of serotonin and norepinephrine, two neurotransmitters involved in regulating mood and pain. By preventing their reabsorption, this drug increases their levels in the brain, which can enhance mood and reduce pain signals. This dual action on both serotonin and norepinephrine makes duloxetine a versatile medication for both mental health and pain conditions.

Dosage and Administration

Starting Dosage

The starting dosage of duloxetine varies depending on the condition being treated. For major depressive disorder and generalized anxiety disorder, the typical starting dose is 30 mg once daily, which may be increased to 60 mg daily after a week. For diabetic peripheral neuropathy and chronic musculoskeletal pain, the initial dose is usually 60 mg once daily.

Dosage Adjustments

Dosage adjustments may be necessary based on the patient’s response to the medication and the presence of any side effects. It is crucial to follow the prescribing physician’s instructions and not to adjust the dose without medical advice.

How to Take Duloxetine

It is available in delayed-release capsules and should be taken whole, without crushing or chewing. It can be taken with or without food. Consistency in the timing of doses is important to maintain stable levels of the medication in the body.

Potential Side Effects

Like all medications, duloxetine can cause side effects. These vary from person to person and can range from mild to severe.

Common Side Effects

Some of the common side effects of duloxetine include:

• Nausea
• Dry mouth
• Drowsiness
• Fatigue
• Dizziness
• Insomnia
• Constipation
• Increased sweating

These side effects are often temporary and may improve as the body adjusts to the medication.

Serious Side Effects

Serious side effects are less common but require immediate medical attention. These include:

• Severe skin reactions
• Liver damage (symptoms include yellowing of the skin or eyes, dark urine, and severe abdominal pain)
• Serotonin syndrome (symptoms include agitation, hallucinations, rapid heart rate, and severe dizziness)
• Suicidal thoughts or behaviors (particularly in young adults and children)
• sexual problems in males; decreased sex drive, delayed ejaculation, or inability to get or keep an erection
• sexual problems in females; decreased sex drive, unable to have an orgasm, or delayed orgasm.

Long-Term Effects

Long-term use of duloxetine can lead to additional considerations, such as the potential for liver damage and the need for periodic monitoring by a healthcare provider. It is important to have regular follow-ups to ensure the medication is still appropriate and to adjust the dosage if necessary.

Pharmacokinetics of Duloxetine

Absorption

Duloxetine is acid labile and is formulated with an enteric coating to prevent degradation in the stomach. It 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.

Distribution

Duloxetine is highly bound (>90%) to proteins in human plasma, binding primarily to albumin and α1-acid glycoprotein. The volume of distribution is 1640L, indicating extensive distribution throughout the body.

Metabolism

Duloxetine undergoes predominantly hepatic metabolism via two cytochrome P450 isozymes, CYP2D6 and CYP1A2. Circulating metabolites are pharmacologically inactive. Duloxetine is a moderate CYP2D6 inhibitor, which can influence the metabolism of other drugs metabolized by this enzyme.

Elimination

When administered to healthy young male subjects at doses between 20 and 40 mg twice a day, duloxetine has a half-life of 12.5 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 (approximately 70%) appears in the urine as metabolites, with about 20% excreted in the feces.

Interactions with Other Medications

Duloxetine can interact with various medications, potentially altering their effects or increasing side effects. Inform your doctor and pharmacist about all prescription, and nonprescription medications, and vitamins you are taking or plan to take, especially:

• Amphetamines: such as amphetamine (in Adderall), dextroamphetamine (Dexedrine), and methamphetamine (Desoxyn)
• Anticoagulants (‘blood thinners’): such as warfarin (Coumadin, Jantoven)
• Antidepressants: including amitriptyline (Elavil), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Adapin, Sinequan), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), trimipramine (Surmontil)
• Aspirin and NSAIDs: such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn)
• Buspirone
• Cimetidine (Tagamet)
• Ciprofloxacin (Cipro)
• Diuretics (‘water pills’)
• Fentanyl: (Abstral, Actiq, Fentora, Onsolis)
• Medications for irregular heartbeat: such as amiodarone (Cordarone), flecainide (Tambocor), moricizine (Ethmozine), propafenone (Rythmol), quinidine (Nuedexta)
• Medications for anxiety, high blood pressure, mental illness, pain, and nausea
• Medications for migraine headaches: such as almotriptan, eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, Onzetra, Tosymra, Treximet), zolmitriptan (Zomig)
• Lithium (Lithobid)
• Proton pump inhibitors: such as lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), rabeprazole (Aciphex)
• Sedatives
• Certain SSRIs: such as fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil)
• Sleeping pills
• Theophylline (Theo-24, Theochron)
• Tramadol (Ultram)
• Tranquillizers

Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may interact with duloxetine, so ensure your healthcare provider is fully informed about all substances you are taking.

Special Considerations

Pregnancy and Breastfeeding

The safety of duloxetine during pregnancy and breastfeeding is not fully established. It should be used during pregnancy only if the potential benefits justify the potential risks to the fetus. Duloxetine can pass into breast milk, so breastfeeding while on this medication should be discussed with a healthcare provider.

Use in Older Adults

Older adults may be more sensitive to the side effects of duloxetine, particularly dizziness and dry mouth. Lower starting doses and careful monitoring are often recommended for this population.

Liver and Kidney Function

Patients with impaired liver or kidney function may require dosage adjustments or additional monitoring while taking duloxetine. Severe liver impairment is a contraindication for duloxetine use.

Managing Side Effects

If you experience side effects from duloxetine, several strategies can help manage them:

• Nausea: Taking duloxetine with food or a small snack can help reduce nausea.
• Dry Mouth: Chewing sugar-free gum or sucking on sugar-free candies can help alleviate dry mouth.
• Drowsiness or Fatigue: Taking duloxetine at bedtime may help if drowsiness is problematic during the day.
• Insomnia: If duloxetine causes insomnia, taking it in the morning may be more suitable.

History of Duloxetine

Discovery and Development

Duloxetine was created by researchers at Eli Lilly and Company, with David Robertson, David Wong (a co-discoverer of fluoxetine), and Joseph Krushinski listed as inventors on the patent application filed in 1986 and granted in 1990. The first publication on the discovery of the racemic form of duloxetine, known as LY227942, was made in 1988. The (+)-enantiomer, assigned LY248686, was chosen for further studies because it inhibited serotonin reuptake in rat synaptosomes to twice the degree of the (–)-enantiomer. This molecule was subsequently named duloxetine.

Regulatory Approval

In 2001, Eli 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 due to significant current Good Manufacturing Practice (cGMP) violations at the finished product manufacturing facility in Indianapolis. Concerns regarding potential liver toxicity and QTc interval prolongation were also raised.

After resolving manufacturing issues, including liver toxicity warnings in the prescribing information, and follow-up studies showing no QTc interval prolongation, duloxetine was approved by the FDA for depression and diabetic neuropathy in 2004. Health Canada approved duloxetine for the treatment of depression and diabetic peripheral neuropathic pain in 2007.

Market Approval and Use

This drug was approved for use in stress urinary incontinence (SUI) in the EU in 2004. However, in 2005, Eli Lilly withdrew the duloxetine application for SUI in the U.S. after discussions with the FDA indicated the agency was not prepared to grant approval based on the submitted data. In 2007, the FDA approved duloxetine for the treatment of generalized anxiety disorder.

Market Impact

Duloxetine is sold under the brand name Cymbalta generated nearly US$5 billion in sales in 2012, with US$4 billion of that in the U.S. Its patent protection terminated on January 1, 2014, with Eli Lilly receiving a six-month extension beyond June 30, 2013, after testing for the treatment of depression in adolescents, potentially producing an additional US$1.5 billion in sales. The first generic duloxetine was marketed by Indian pharmaceutical company Dr. Reddy’s Laboratories.

Duloxetine Brands in Pakistan

Duloxetine is sold under various brand names some popular brands include:

• Symbal is manufactured by Bosch Pharmaceuticals
• Hapibar is manufactured by Barrett Hodgson Pakistan (Pvt) Ltd.
• Dulan is manufactured by Hilton Pharma (Pvt) Limited.
• Cymbalta is manufactured by Eli Lilly Pakistan (Pvt) Ltd.
• Duzalta is manufactured by PharmEvo (Pvt) Ltd.
• Enlon is manufactured by Opal Laboratories (Pvt) Ltd.
• Zenbar is manufactured by Searle Pakistan (Pvt.) Ltd.
• Zuloxet is manufactured by NabiQasim Industries (Pvt) Ltd.
• Dulosoft is manufactured by Mcolson Research Laboratories
• Lyta is manufactured by Getz Pharma Pakistan (Pvt) Ltd.