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Dr Rahul Seewal

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A:72B)428:! Duloxetine is a serotonin and noradrenalin reuptake inhibitor (SNRI). It can be useful in Major depressive illness, generalised anxiety, diabetic neuropathic pain and musculoskeletal pain &85.!-B*.7+,.! Duloxetine is started at a dose of 60 mg once a day. In generalised anxiety, the dose can be increased to a maximum of 120 mg / day. If there is intolerance, than dose can be divided as 30 - 60 mg twice a day.

Day of treatment
1 4 8 14 (not routinely required)

Daily dose 30mg 60mg 60mg 120mg

The table for dose adjustment is for guidance only. The dose increment can be done over a longer period of time or more gradually. Please contact us if you have any doubts or are experiencing side effects. Commonly seen side effects Nausea, dry mouth, somnolence, fatigue, constipation, decreased appetite, and hyperhidrosis (excessive body hair). Potential side effects Fluctuation in psychiatric symptoms and depression - Duloxetine can cause suicide ideation and behaviour. Patients and caregivers should always be warned to watch for agitation, irritability, change in behaviour, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, insomnia, mania, hypomania and akathisia (restlessness). Duloxetine dose should be reduced or discontinued in consultation with treating physician. Liver dysfunction - Duloxetine can cause liver dysfunction including fulminant hepatic failure. The transaminase levels can raise as much as 20 times normal limits. Anyone experiencing abdominal pain, jaundice or liver enlargement should not be re started on Duloxetine unless another cause has been established. Caution is necessary in prescribing patients with alcoholic hepatitis. Orthostatic hypotension and syncope - These symptoms are more common in the first week of therapy but can occur at any time during treatment, particularly after dose increases. The risk of blood pressure decreases may be greater in patients taking concomitant medications that induce orthostatic hypotension (such as antihypertensive) or are potent CYP1A2 inhibitors and in patients taking Duloxetine at doses above 60 mg daily.

! Dr Rahul Seewal 2013. All rights reserved

Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions - These symptoms are seen with concomitant use of serotonergic drugs (including triptans), with drugs which impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Serotonin syndrome, in its most severe form can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Abnormal Bleeding - Patients should be cautioned about the risk of bleeding associated with the concomitant use of duloxetine and NSAIDs, aspirin, or other drugs that affect coagulation. Bleeding events related to SSRIs and SNRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages. Discontinuation of Treatment with duloxetine - Sudden discontinuation can result in dizziness, nausea, headache, paresthesia, fatigue, vomiting, irritability, insomnia, diarrhea, anxiety, and hyperhidrosis. Dring clinical trials, these symptoms are seen in 1% of patients. dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. Although these events are generally self-limiting, some have been reported to be severe. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. Hyponatremia - This appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Serum sodium can become lower than 110 mmol/L but is reversible when Duloxetine treatment is discontinued. Elderly patients and those in diuretic therapy may be at greater risk Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. More severe and/or acute cases have been associated with hallucination, syncope, seizure, coma, respiratory arrest, and death. Effects on Male and Female Sexual Function - The Arizona Sexual Experience Scale (ASEX), a validated measure designed to identify sexual side is used in controlled trials with Duloxetine. This reveals a significantly greater chance of sexual dysfunction in males on treatment with Duloxetine. The signs are reduced sexual drive, arousal, ability to maintain erection, ease of reaching orgasm and satisfaction of orgasm. No change in sexual function is seen in women. Physicians should routinely inquire about possible sexual side effects. Urinary Hesitation and Retention - urinary retention requiring catheterization can develop during Duloxetine treatment

Treatment duration Most of the trials and scientific evidence is for treatment duration of around 3 months

! Dr Rahul Seewal 2013. All rights reserved

Medical Stuff Pharmacokinetics Duloxetine is well absorbed after oral administration. There is a 2-hour lag before absorption, after oral administration and peak plasma concentration is 6 hours post oral intake. It is highly bound to plasma proteins (mainly # - 1 acid glycoprotein) hence its free drug concentration can increase if given along with other highly protein bound drugs. It is extensively metabolised in liver by CP1A2 and CYP 2D6. It is converted to inactive metabolites that are excreted in urine (80%) and faeces (20%). Mechanism of action - Duloxetine works by inhibiting the uptake of stimulatory neurotransmitters noradrenalin and serotonin in the nervous system. This increases their concentration and reverses the imbalance which probably is the cause of altered nervous system function. The significant drug interactions with Amitriptyline are as follows Drug CYP1A2 inhibitors (fluvoxamine, cimetidine, quinolone antibiotics like ciprofloxacin) CYP2D6 inhibitors (peroxetine, flouxetine, Quinidine) Antiplatelet drugs like NSAIDS, aspirin, clopidigrel Other serotonergic drugs like triptans, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, tramadol, or St. John's Wort. Interaction Increased level of duloxatine, more likelihood of side effects. Reduce the levels of Amitriptyline and increase carbamezapine levels (possibility of toxicity) Increase risk of bleeding Potential to cause serotonergic syndrome - concomitant use not recommended

Use in pregnancy Use of duloxetine in pregnancy is not recommended. In animal studies, it has caused both teratogenic and non teratogenic (low birth weight, bleeding and respiratory distress).

! Dr Rahul Seewal 2013. All rights reserved