reboxetine

Action and Spectrum

Actions and Spectrum: 

reboxetine is a medication that belongs to a class of drugs known as norepinephrine reuptake inhibitors (NRI). Its primary action is to increase norepinephrine (noradrenaline) levels in the brain through inhibiting its reuptake into the nerve cells.  

Action: 

• reboxetine blocks the reuptake of norepinephrine at nerve cell synapses. This means that it prevents norepinephrine from being taken back into the nerve cells after being released. 
• By inhibiting norepinephrine reuptake, reboxetine increases norepinephrine concentration in the synaptic cleft, enhancing norepinephrine neurotransmission. 
• The net effect of this mechanism is an increase in norepinephrine signaling in the brain, which can have various effects on mood and also in behavior. 

Spectrum: 

• reboxetine is primarily used as an antidepressant medication. It is indicated for the therapy of major depressive disorder (MDD). 
• Its selective action on norepinephrine reuptake sets it apart from other antidepressant classes, such as selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors (SNRIs), which primarily target serotonin or both serotonin and norepinephrine reuptake. 
• reboxetine may be considered in cases where other antidepressants are ineffective or have caused intolerable side effects. However, it is not typically considered a first-line treatment for depression. 
• It is essential to note that reboxetine may take several weeks to exert its full therapeutic effect, similar to other antidepressant medications. 

Drug Interaction

Adverse Reaction

Frequency not defined 

History of urinary retention or prostatic hypertrophy 

Bipolar disorder 

Hypertension 

History of suicide-related events or previously exhibiting suicidal ideation 

Hyperthyroidism 

Predisposition to hypotension (e.g. Dehydration, hypovolaemia) 

Cerebrovascular conditions 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity: reboxetine should not be used in individuals with a known hypersensitivity or allergy to reboxetine or any ingredient. Allergic reactions can be severe and life-threatening. 
• Concurrent Use of Monoamine Oxidase Inhibitors (MAOIs): reboxetine should not be used within two weeks before or after taking a monoamine oxidase inhibitor (MAOI). Concurrent use of these drugs may lead to a potentially life-threatening condition called as serotonin syndrome, characterized by agitation, confusion, rapid heart rate, high blood pressure, tremors, and fever. 
• Severe Cardiovascular Conditions: reboxetine should be used cautiously or avoided in individuals with severe cardiovascular conditions, such as recent myocardial infarction (heart attack), unstable angina, congestive heart failure, or severe arrhythmias. It can increase heart rate and blood pressure, potentially exacerbating these conditions. 
• Liver Impairment: reboxetine should be used cautiously in individuals with liver impairment. Dose adjustments may be necessary in such cases, and the medication should be used under close medical supervision. 
• Pheochromocytoma: reboxetine is contraindicated in individuals with pheochromocytoma, an infrequent tumor of the adrenal glands that can cause excessive release of norepinephrine. Using reboxetine in such individuals can lead to a dangerous increase in norepinephrine levels. 
• Epilepsy: reboxetine should be used cautiously in individuals with epilepsy, as it may lower the seizure threshold. Seizures have been reported in some patients taking reboxetine. 
• Pediatric Use: reboxetine is not approved for use in children and adolescents under 18 due to insufficient data regarding its safety and efficacy in this population. 

Caution 

• Suicidal Ideation: Like many antidepressant medications, reboxetine may be associated with an enhanced risk of suicidal thoughts or behaviors, particularly in children, adolescents, and young adults. Close monitoring is essential, especially during the early stages of treatment and when the dosage is adjusted. 
• Cardiovascular Effects: reboxetine can increase heart rate and blood pressure. Patients with pre-existing cardiovascular conditions, such as hypertension (high blood pressure), should use reboxetine with caution and under the supervision of the healthcare provider. Regular monitoring of blood pressure and heart rate is recommended during treatment. 
• Seizures: reboxetine may lower the seizure threshold, potentially increasing the risk of seizures, especially in individuals with a history of epilepsy or seizure disorders. Caution is advised when prescribing reboxetine to individuals with a history of seizures. 
• Liver Function: reboxetine is metabolized in the liver, so individuals with liver impairment should use reboxetine cautiously. Dose adjustments may be necessary in these cases, and a healthcare provider should monitor the medication closely. 
• Renal Function: Although reboxetine is primarily eliminated via the liver, individuals with severe kidney impairment should also be cautious when using this medication. Dose adjustments may be necessary, and close monitoring is recommended. 
• Withdrawal Symptoms: Abruptly discontinuing reboxetine can lead to withdrawal symptoms. It is essential to follow a healthcare provider’s guidance when discontinuing the medication to reduce the risk of withdrawal effects, which may include flu-like symptoms, dizziness, irritability, and anxiety. 
• Drug Interactions: reboxetine may interact with other medications, including monoamine oxidase inhibitors (MAOIs), other antidepressants, and drugs that affect heart rate or blood pressure. It’s key to inform your healthcare provider about all drugs, supplements, and herbal products you are taking to avoid potential interactions. 
• Pregnancy and Breastfeeding: The safety of reboxetine during pregnancy condition and breastfeeding has not been adequately studied.  
• Cognitive and Motor Skills: reboxetine may cause drowsiness or dizziness in some individuals. Caution should be exercised when operating heavy machinery/engaging in activities that generally require alertness until you know how the medication affects you. 
• Psychiatric Conditions: reboxetine should be used cautiously in individuals with a history of psychiatric conditions, such as bipolar disorder or psychosis. It may exacerbate manic episodes or psychotic symptoms. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk: Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence, these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

reboxetine is a selective norepinephrine reuptake inhibitor that exerts its pharmacological action by blocking the reuptake of norepinephrine (noradrenaline) at nerve cell synapses, leading to increased norepinephrine levels in the synaptic cleft. This results in enhanced norepinephrine neurotransmission, which is thought to play a role in its antidepressant effects.

By selectively inhibiting the reuptake of norepinephrine without significantly affecting the reuptake of serotonin or other neurotransmitters, reboxetine differs from other antidepressant classes, like selective serotonin reuptake inhibitors and also serotonin-norepinephrine reuptake inhibitors. Its ability to modulate norepinephrine levels in the brain may help regulate mood and alleviate symptoms of major depressive disorder. 

Pharmacodynamics: 

Mechanism of action: reboxetine is an antidepressant medication that primarily exerts its therapeutic effects through its mechanism of action on neurotransmitters in the brain. It belongs to a class of drugs known as norepinephrine reuptake inhibitors (NRIs). The primary mechanism of action of reboxetine involves the modulation of the neurotransmitter norepinephrine (also known as noradrenaline) in the brain.  

Inhibition of Norepinephrine Reuptake: 

reboxetine acts by selectively blocking norepinephrine reuptake at the synapses between nerve cells (neurons) in the brain. 

In standard synaptic transmission, norepinephrine is released from one neuron into the synaptic cleft, the small gap between two adjacent neurons. 

After its release, norepinephrine can bind to receptors on the receiving neuron, transmitting a nerve signal. This binding initiates various physiological responses, including mood regulation and stress response. 

Enhanced Norepinephrine Signaling: 

By inhibiting norepinephrine reuptake, reboxetine prolongs the presence of norepinephrine in the synaptic cleft. 

This extended presence of norepinephrine allows it to continue binding to its receptors on the receiving neuron, thereby enhancing and prolonging norepinephrine neurotransmission. 

Increased norepinephrine signaling is thought to positively impact mood regulation and might help alleviate the symptoms of major depressive disorder (MDD). 

Selective Action: 

reboxetine’s selectivity for norepinephrine reuptake inhibition distinguishes it from other classes of antidepressant medications, such as selective serotonin reuptake inhibitors and also serotonin-norepinephrine reuptake inhibitors, which primarily target serotonin or both serotonin and norepinephrine reuptake. 

The selective action of reboxetine on norepinephrine is believed to contribute to its specific therapeutic effects and side effect profile. 

Pharmacokinetics: 

Absorption 

reboxetine is administered orally in the form of capsules. 

After oral administration, it is absorbed from the gastrointestinal tract into the bloodstream. 

Food can influence its absorption, with some reports suggesting that taking reboxetine with a meal may reduce the risk of stomach upset. 

Distribution 

reboxetine is distributed throughout the body via the bloodstream. 

It has a relatively small volume of distribution, meaning it tends to stay mainly within the blood and does not extensively distribute into tissues. 

reboxetine does not readily cross the blood-brain barrier, which is believed to contribute to its selective action on norepinephrine reuptake in the brain. 

Metabolism 

reboxetine is primarily metabolized in the liver by the cytochrome P450 enzyme system, particularly CYP3A4 and CYP2D6 enzymes. 

The primary metabolite formed in this process is desethylreboxetine, which is pharmacologically active but less potent than the parent compound. 

Other minor metabolites may also be produced. 

Elimination and Excretion 

reboxetine and its metabolites are excreted mainly through the kidneys as urine. 

The elimination half-life of reboxetine can vary among individuals but is generally 10 to 12 hours. This means it takes about this amount of time for half of the drug to be eliminated. 

Renal impairment can affect the clearance of reboxetine, potentially leading to the accumulation of the drug in the body. Dose adjustments may be necessary for individuals with impaired kidney function. 

Adminstartion

Administration: 

reboxetine is typically administered as an oral medication in the form of capsules.  

Dosage: The appropriate dosage of reboxetine varies from person to person and depends on the individual’s medical condition and response to the medication. Your healthcare provider will generally determine the correct dosage for you. It is crucial to take the prescribed dose and not exceed it. 

Timing: reboxetine is usually taken once daily. Your healthcare provider will specify whether it should be taken in the morning or evening.  

With or Without Food: reboxetine can be taken with or without food. However, taking it with a meal may help reduce the likelihood of stomach upset in some individuals. 

Swallow Whole: reboxetine capsules should be swallowed whole with a glass of water. Do not crush, chew, or open the capsules, as this can affect the release of the drug and might lead to an enhanced risk of side effects. 

Consistency: To ensure the medication works effectively, it is essential to take it regularly as prescribed, even if you start to feel better. Abruptly discontinuing reboxetine without your healthcare provider’s guidance can leads to withdrawal symptoms or a recurrence of your condition. 

Follow-Up: Regularly follow up with the healthcare provider during treatment to monitor your progress, discuss any side effects, and make necessary adjustments to your treatment plan if needed. 

Duration: The duration of reboxetine treatment will vary depending on your condition and how you respond to the medication. It is essential to continue taking reboxetine as directed by the healthcare provider, even if your symptoms improve. Stopping the medication prematurely may lead to a relapse of your condition. 

Missed Dose: If a dose is missed, taking it as soon as possible is generally recommended. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is key to avoid taking a double dose of the drug in order to compensate for the missed dose. 

Storage: Store reboxetine capsules at room temperature, away from moisture and direct sunlight. Keep the medication out of the reach of children and pets. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: reboxetine 

Why do we use reboxetine? 

reboxetine is a medication primarily used to treat major depressive disorder (MDD) in adults. Its primary mechanism of action is to increase the levels of norepinephrine (noradrenaline) in the brain by inhibiting its reuptake into nerve cells. This action can have antidepressant effects.  

Major Depressive Disorder (MDD): reboxetine is approved for treating major depressive disorder, a common and severe mood disorder characterized by persistent and pervasive sadness, hopelessness, and a lack of interest/pleasure in activities. It can be used as a treatment option for adults diagnosed with MDD. 

Treatment-Resistant Depression: In some cases, reboxetine may be considered as a treatment option when other antidepressant medications have not been effective/have caused intolerable side effects. It is generally not considered a first-line therapy for depression but may be used when other options have been exhausted. 

Off-Label Uses: While reboxetine’s primary approved use is for MDD, it may be prescribed off-label by healthcare providers for other conditions, such as: 

• Generalized Anxiety Disorder (GAD): reboxetine has been studied for its potential efficacy in treating generalized anxiety disorder, although it is not a first-line treatment. 
• Social Anxiety Disorder (Social Phobia): Some studies have explored reboxetine’s use in social anxiety disorder, but more research is needed. 
• Attention-Deficit/Hyperactivity Disorder (ADHD): reboxetine is not a first-line treatment for ADHD, but it has been investigated for its potential use in managing ADHD symptoms, particularly in adults. 
• Neuropathic Pain: In some cases, reboxetine may be prescribed off-label to manage neuropathic pain, although its use is less daily than other medications.