Mirtazapine (Remeron) - Class, Uses, Dosage, MOA, Side effects

Mirtazapine (Remeron) is a tetracyclic antidepressant drug that is used in the treatment of unipolar major depression, anxiety with panic attacks, and chronic headache.

Mirtazapine (Remeron) Uses:

  • Major depressive disorder (unipolar):

    • Treatment of unipolar major depressive disorder (MDD)
  • Off Label Use of Mirtazapine in Adults:

    • Prophylaxis of chronic tension-type Headache
    • Panic disorder

Mirtazapine Dose in Adults:

Mirtazapine (Remeron) Dose as alternative agent  in the prophylaxis of chronic tension-type headache:

  • By mouth: Start with 15 mg once every night before bedtime. If you're doing well and can handle it, the doctor might raise it to 30 mg per day after a week.

Mirtazapine (Remeron) Dose in the treatment of unipolar major depressive disorder:

  • By mouth: Start with 15 mg once a day before bedtime.

  • The doctor may increase the dose by 15 mg at a time, but not more often than once or twice every two weeks, depending on how you're responding and tolerating the medication.

  • The most you might take in a day is 45 mg (according to the label), although in research studies, some people have taken as much as 60 mg per day.

Mirtazapine (Remeron) Dose as an alternative agent in the treatment of the Panic disorder (off-label):

Note: This medication is comparable to being used alone or as an addition to treatment for patients who don't respond well to SSRIs.

  • By mouth: Begin with 15 mg once daily at bedtime.
  • Depending on how you're doing and how well you tolerate it, the doctor may increase the dose by 15 mg each week, with the usual maximum being 45 mg taken once a day (as per the product label).
  • It's worth noting that even though doses up to 60 mg per day have been tested, the typical amount used in clinical trials was around 30 mg per day.
  • Discontinuation of therapy:

    • When you're stopping antidepressant treatment that you've been on for more than three weeks, it's advised to gradually reduce the dose over a period of 2 to 4 weeks.

    • This helps minimize withdrawal symptoms and allows for the detection of any returning symptoms.

    • If you're slowing down the reduction over 4 weeks, it's typically recommended if the medication has a short half-life (less than 24 hours), like paroxetine or venlafaxine, if you've had previous experiences of withdrawal symptoms, or if you've been on high doses of antidepressants.

    • In case withdrawal symptoms become too much to handle, it's suggested to go back to the dose you were taking before or reduce it more gradually (as mentioned in Shelton's 2001 study).

    • For certain patients, especially those with a history of discontinuation syndrome, who have been on treatment for a long time (more than 6 months), tapering over a period of more than 3 months might be beneficial.

    • However, it's important to note that there is limited evidence supporting the ideal rates for tapering.

  • Switching antidepressants:

    • There's limited research on the best ways to switch antidepressants.

    • The techniques include a "straight switch" and "cross-titration." A straight switch is when you abruptly stop the first antidepressant and start the new one at an equivalent or lower dose, gradually increasing it.

    • Cross-titration involves gradually stopping the previous antidepressant while simultaneously increasing the new one.

    • This is often recommended for most switches, except when transitioning to or from an MAOI, where the process might take 1 to 4 weeks depending on the risk of withdrawal symptoms and side effects.

    • If you're switching within the same or similar class of antidepressants (e.g., between two SSRIs), a direct switch might be suitable if the antidepressant to be discontinued has been used for less than one week or if discontinuation is due to side effects.

    • When deciding on a switch strategy, it's crucial to consider the risk of withdrawal symptoms, potential drug interactions, features of the antidepressants (like half-life, side effects, and pharmacodynamics), and the desired level of symptom control.

  • Switching to or from an MAOI:

    • To switch from an MAOI to mirtazapine, it is recommended to wait for a 14-day gap after stopping the MAOI before starting mirtazapine.

    • Similarly, if you're transitioning from mirtazapine to an MAOI, there should be a 14-day gap between stopping mirtazapine and starting the MAOI.

    • This 14-day gap is crucial to allow for the clearance of the MAOI or mirtazapine from your system and to avoid potential interactions between these medications, which could lead to adverse effects.

    • Always follow your healthcare provider's instructions when making such transitions to ensure your safety and well-being.


Use in Children:

Not indicated.


Mirtazapine (Remeron) Pregnancy Risk Category: C

  • Mirtazapine can pass through the placenta during pregnancy.
  • While there hasn't been a notable rise in major birth defects with mirtazapine exposure, the available information is limited.
  • When it comes to treating depression during pregnancy, the approach should be personalized.
  • Some women might find psychotherapy or other non-medication therapies helpful.
  • However, for pregnant women dealing with moderate to severe major depression, considering antidepressant medication is a valid option.
  • In cases where treatment for Major Depressive Disorder (MDD) begins during pregnancy, healthcare providers may consider alternatives to mirtazapine.
  • The American College of Obstetricians and Gynecologists (ACOG) and the American Psychiatric Association (APA) have created treatment guidelines for women experiencing depression before and during pregnancy.
  • It's essential for pregnant women to discuss their individual circumstances and preferences with their healthcare providers to make informed decisions about the best course of action.

Use Mirtazapine while breastfeeding:

  • Mirtazapine and its active metabolite can be found in breast milk.

  • The highest reported relative infant dose (RID) of mirtazapine is 4.4%, determined after a mother took 22.5mg/day of mirtazapine 6 weeks postpartum.

  • However, researchers did not assess metabolite concentrations.

  • Breast milk was tested for 4 hours after the maternal dose, and desmethylmirtazapine can also be present.

  • Typically, if the RID falls below 10%, breastfeeding is generally considered acceptable.

  • Some sources suggest considering breastfeeding only if the RID for psychotropic drugs is less than 5%.

  • Mirtazapine has been detected in the serum of breastfed infants, but no adverse reactions have been commonly reported.

  • In one case, there were mentions of possible sedation or weight gain.

  • Mothers using psychotropic medication should monitor their infants daily for any changes in sleep, feeding, behavior, or neurodevelopment.

  • When starting an antidepressant, especially for breastfeeding females, they might prefer an agent other than mirtazapine.

  • Manufacturers advise caution in breastfeeding females.

  • It's crucial for mothers to discuss with their healthcare providers to make informed decisions about breastfeeding while taking mirtazapine.


Mirtazapine (Remeron) Dose in Kidney Disease:

The manufacturer's labeling does not include specific adjustments for dosage.

However, it's important to note that clearance of the medication is reduced in cases of moderate and severe renal impairment.

Therefore, caution should be exercised when using this medication in individuals with impaired kidney function.

Healthcare providers should carefully consider the potential impact of renal impairment on drug clearance and adjust the dosage accordingly to ensure safe and effective use.

Mirtazapine (Remeron) Dose in Liver disease:

 

The manufacturer's labeling does not provide information on dosage modifications, and it's worth noting that hepatic impairment (issues with the liver) can lead to a decrease in drug clearance.

Therefore, caution should be exercised when using the medication in individuals with liver problems.

Healthcare providers should be careful and consider the potential impact of hepatic impairment on drug metabolism, even if specific dosage adjustments are not mentioned in the labeling, to ensure the medication is used safely and effectively.


Common Side Effects of Mirtazapine (Remeron):

  • Central nervous system:

    • Drowsiness
  • Endocrine & metabolic:

    • Increased serum cholesterol
    • Weight gain
  • Gastrointestinal:

    • Increased appetite
    • Constipation
    • Xerostomia

Less Common Side Effects of Mirtazapine (Remeron):

  • Cardiovascular:

    • Hypertension
    • Edema
    • Vasodilation
    • Peripheral Edema
  • Central Nervous System:

    • Twitching
    • Abnormal Dreams
    • Malaise
    • Confusion
    • Depression
    • Amnesia
    • Apathy
    • Hypoesthesia
    • Agitation
    • Myasthenia
    • Abnormality In Thinking
    • Paresthesia
    • Anxiety
    • Vertigo
    • Dizziness
  • Dermatologic:

    • Skin Rash
    • Pruritus
  • Endocrine & Metabolic:

    • Increased Thirst
    • Increased Serum Triglycerides
  • Gastrointestinal:

    • Anorexia
    • Acute Abdominal Condition
    • Vomiting
    • Abdominal Pain
  • Genitourinary:

    • Urinary Tract Infection
    • Urinary Frequency
  • Hepatic:

    • Increased Serum Alanine Aminotransferase
  • Neuromuscular & Skeletal:

    • Hyperkinetic Muscle Activity
    • Back Pain
    • Tremor
    • Myalgia
    • Arthralgia
    • Hypokinesia
    • Asthenia
  • Respiratory:

    • Increased Cough
    • Dyspnea
    • Sinusitis
    • Flu-Like Symptoms

Rare Side effect of Mirtazapine (Remeron):

  • Cardiovascular:

    • Orthostatic hypotension

Contraindications to Mirtazapine (Remeron):

  • If someone is hypersensitive to mirtazapine or any ingredient in the formulation, they should avoid using this medication.

  • Monoamine oxidase inhibitors (MAO inhibitors) are medications used to treat psychiatric disorders.

  • They can be used concurrently with mirtazapine or within 14 days of stopping mirtazapine.

  • However, caution is advised, and it's essential to follow medical guidance closely.

  • Intravenous or linezolid methylene blue can be initiated in patients already on mirtazapine.

  • This suggests that certain intravenous medications, like linezolid or methylene blue, may be used in conjunction with mirtazapine, but it's important to follow specific guidelines and recommendations from healthcare professionals to avoid potential interactions or adverse effects.

Warnings and precautions

  • Akathisia/psychomotor Restlessness

    • Most of these symptoms will appear within the initial weeks of treatment.
    • However, it may be detrimental for patients experiencing these symptoms to increase their dosage.
  • Anticholinergic effects

    • It can lead to anticholinergic effects, including constipation, dry mouth (xerostomia), and blurred vision.

    • Caution is advised for patients with conditions such as reduced gastrointestinal motility, paralytic ileus, urinary retention, benign prostatic hyperplasia (BPH), xerostomia, and visual impairments.

    • It's important to note that compared to other antidepressants, this agent has a lower degree of anticholinergic blocking.

  • Arrhythmias

    • QT prolongation, Torsade de Pointes, and Ventricular Fibrillation have occasionally been reported, with the majority of incidents linked to the misuse of mirtazapine.

    • However, in a series of 84 patients who had single-agent mirtazapine overdoses, no instances of QT prolongation were found.

    • Patients with cardiovascular disease, a history of QT prolongation, or those taking drugs known to prolong QT should exercise caution when using mirtazapine.

    • Monitoring and close attention to the potential risk factors are important in such cases.

  • Blood dyscrasias

    • If you observe any signs or symptoms indicative of neutropenia or agranulocytosis, it is crucial to discontinue the medication immediately.
    • Neutropenia and agranulocytosis are serious conditions characterized by a low count of certain white blood cells, which can compromise the body's ability to fight infections.
    • Stopping the medication promptly is a necessary precaution to address and manage these potentially severe side effects.
    • Additionally, seeking medical attention for a thorough evaluation and appropriate guidance is important in such cases.
  • Depression in the CNS:

    • CNS depression may occur, potentially affecting mental and physical abilities.
    • Patients should exercise caution when engaging in activities that demand mental alertness, such as driving or operating machinery.
    • In comparison to other antidepressants, the level of sedation experienced with this medication is considered to be moderate to high.
  • Dizziness

    • Dizziness is a possible side effect, but it's not clear whether tolerance to this effect can develop over time.
  • Fractures

    • Antidepressant treatment has been employed in the management of bone fractures

    • . If an individual undergoing antidepressant therapy experiences persistent bone pain, tenderness, swelling, or bruising that remains unresolved, it is important to seek medical attention for a thorough evaluation and appropriate intervention.

    • These symptoms could be indicative of underlying issues related to the bone or may require further investigation to determine the cause and ensure proper care.

  • Hyperlipidemia

    • As a consequence of treatment, triglyceride and serum cholesterol levels may increase.

    • Regular monitoring of these lipid levels is advisable to assess and manage any potential changes associated with the medication.

  • Hyponatremia

    • Hyponatremia, a condition characterized by low sodium levels, may occur.
    • Individuals at high risk, such as the elderly and those using medications that can lead to hyponatremia, should avoid receiving this treatment.
    • Caution and careful consideration of individual risk factors are essential when prescribing this medication to such patient populations.
  • Ocular effects

    • The medication may cause a mild dilation of the pupils, potentially leading to narrow-angle glaucoma in certain situations.
    • It is important to evaluate patients for risk factors associated with narrow-angle glaucoma, particularly those who have not undergone an irisectomy.
    • Assessing these risk factors is crucial to determine the appropriateness of the medication for each individual and to take necessary precautions in those at higher risk.
  • Orthostatic hypotension

    • In patients at high risk or those who cannot tolerate brief episodes of low blood pressure, there is a possibility of developing orthostatic hypotension.
    • It's worth noting that the risk of orthostatic hypotension with this medication is relatively minimal compared to some other antidepressants.
    • Monitoring blood pressure and assessing individual tolerance are important considerations for those who may be at an increased risk of experiencing this side effect.
  • Serotonin syndrome

    • Serotonin Syndrome is a potentially fatal side effect that can occur with certain serotonergic medications, including SSRIs (Selective Serotonin Reuptake Inhibitors) and SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors).

    • These medications are often used in conjunction with other serotonergic drugs like buspirone, fentanyl, tramadol, triptans, TCAs, and MAO inhibitors.

    • Close monitoring is crucial for patients using these medications to watch for symptoms of Serotonin Syndrome.

    • These symptoms may include altered mental status (such as agitation, hallucinations, and delirium), coma, autonomic instability (like tachycardia, labile blood pressure, diaphoresis), neuromuscular changes (such as tremor, rigidity, and myoclonus), and gastrointestinal symptoms (like nausea, vomiting, and diarrhea).

    • Seizures can also occur.

    • If any symptoms or signs of Serotonin Syndrome appear, the treatment should be halted immediately, along with any serotonergic agents.

    • This condition requires prompt medical attention to ensure the patient's safety.

  • Sexual dysfunction

    • Mirtazapine is associated with a lower incidence of sexual dysfunction compared to SSRIs (Selective Serotonin Reuptake Inhibitors).
    • Sexual dysfunction is a common side effect of many antidepressant medications, including SSRIs, and it may manifest as reduced libido, difficulty achieving or maintaining an erection (in men), or delayed orgasm.
    • Mirtazapine, with its distinct mechanism of action, tends to have a more favorable profile in terms of sexual side effects for many individuals.
    • However, it's important to note that the impact on sexual function can vary from person to person, and individual responses to medications may differ.
    • Always consult with a healthcare professional for personalized advice based on your specific situation.
  • Weight loss

    • Mirtazapine is known for its appetite-stimulating effect, and it is associated with weight gain in some individuals.
    • This side effect can be beneficial for people who have experienced appetite loss or weight loss due to depression or other conditions.
    • The increase in appetite and weight is often considered a positive outcome for those who need to regain lost weight or maintain a healthy weight.
    • However, it's important for individuals to be aware of potential changes in appetite and weight and discuss any concerns with their healthcare provider.
    • Monitoring weight and overall health is essential during antidepressant treatment.
  • Hepatic impairment

    • Patients with hepatic impairment should exercise caution when using mirtazapine.

    • Clinically significant elevations in transaminase levels (indicators of liver function) have been observed in some cases.

    • Regular monitoring of liver function is advisable for individuals with pre-existing liver conditions or those at risk of hepatic impairment.

    • Any signs of liver problems, such as jaundice (yellowing of the skin or eyes), dark urine, or persistent nausea, should be promptly reported to a healthcare professional.

    • Adjustments to the treatment plan may be necessary based on the severity of hepatic impairment and individual patient characteristics.

    • Always consult with a healthcare provider for personalized guidance regarding the use of mirtazapine in patients with liver issues.

  • Hypomania/mania:

    • The use of mirtazapine in patients with bipolar disorder requires caution, as it could potentially lead to hypomania or mania.

    • It is generally recommended that mirtazapine not be used as monotherapy in individuals with bipolar disorder.

    • Before prescribing mirtazapine or any antidepressant to patients with depressive symptoms, thorough testing for bipolar disorder is crucial.

    • The assessment should include a detailed examination of family history, any history of suicide attempts, bipolar disorder, depression, and other mental health issues.

    • It's important to note that mirtazapine has not been approved by the FDA for the treatment of bipolar disorder.

    • Treatment decisions for individuals with bipolar disorder should be made in consultation with a healthcare professional who can consider the specific characteristics and needs of the patient.

  • Renal impairment

    • In cases of moderate and severe renal impairment, the clearance of mirtazapine is decreased.

    • Therefore, patients with renal impairment should exercise caution when using this medication.

    • It is advisable to closely monitor these individuals for any adverse effects and adjust the dosage as needed based on their renal function.

    • Additionally, healthcare providers should consider the overall health and renal status of the patient when prescribing mirtazapine and make individualized treatment decisions to ensure safety and efficacy.

    • Regular communication with a healthcare professional is important for patients with renal impairment using mirtazapine.

  • Seizure disorder

    • Mirtazapine should be used with caution in patients who are at high risk of seizures.

    • Seizures are listed as a potential side effect of mirtazapine, and individuals with a history of seizures or other factors that may increase the risk of seizures should be closely monitored during treatment.

    • The decision to use mirtazapine in such cases should be made carefully, considering the potential benefits and risks, and in consultation with a healthcare professional.

    • If any signs of seizures or unusual neurological symptoms occur, prompt medical attention is advised.

    • Regular communication between patients and healthcare providers is crucial for monitoring and managing potential side effects during mirtazapine treatment.


Mirtazapine: 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)

Alizapride

CNS depressants may have an enhanced CNS depressant impact. Perhaps makes serotonergic agents more effective (High Risk). 

Almotriptan

Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of serotonin syndrome or serotonin poisoning, such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.

Alosetron

Makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out for  any signs and symptoms of serotonin syndrome  or serotonin poisoning, such as hyperreflexia,  clonus, hyperthermia, diaphoresis, tremor, autonomic instability,  and changes in  mental status.

Amphetamines

Makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out  for any signs and symptoms of serotonin syndrome  or serotonin poisoning, such as hyperreflexia,  clonus, hyperthermia, diaphoresis, tremor, autonomic instability, and changes  in mental status.

Antiemetics (5HT3 Antagonists) Makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out for  any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, and changes in  mental status. Alosetron, Ondansetron, and Ramosetron are exceptions.
Antipsychotic Agents

Antipsychotic Agents' negative or toxic effects may be exacerbated by Serotonergic Agents (High Risk). Particularly,  serotonergic drugs may intensify the effects of dopamine blocking, thus raising the danger of neuroleptic  malignant  syndrome. Serotonergic agents' serotonergic action may be enhanced by antipsychotic drugs (High Risk). Serotonin  syndrome might occur from this.

Aprepitant May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Bosentan May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Brexanolone

Brexanolone's CNS depressing effects may be amplified by other CNS depressants. CNS depressants may have an enhanced  CNS depressant impact.

Brimonidine (Topical)

Makes serotonergic agents more effective (High Risk). 

Bromopride Makes serotonergic agents more effective (High Risk). 
BusPIRone Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out for  any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in  mental status. Alosetron, Ondansetron, and Ramosetron  are exceptions.
Cannabidiol CNS depressants may have an enhanced CNS depressant impact.
Cannabis CNS depressants may have an enhanced CNS depressant impact.
Chlorphenesin Carbamate

CNS depressants' harmful or toxic effects could be increased. Could raise the serum level of mirtazapine.

Cimetidine May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Clofazimine Other CNS depressants' harmful or toxic effects might be exacerbated.
CNS Depressants Makes serotonergic agents more effective (High Risk).
Cyclobenzaprine

Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.

CYP3A4 Inducers (Moderate) May lower the serum level of CYP3A4 substrates (High risk with Inducers).
CYP3A4 Inducers (Strong) May lower the level of mirtazapine in the serum.
CYP3A4 Inhibitors (Moderate) May slow down CYP3A4 substrate metabolism (High risk with Inhibitors).
CYP3A4 Inhibitors (Strong) Could raise the serum level of mirtazapine. Nefazodone is an exception.
Deferasirox May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Dexmethylphenidate-Methylphenidate Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.
Dextromethorphan Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.
Dimethindene (Topical) CNS depressants may have an enhanced CNS depressant impact.
Doxylamine May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.
Dronabinol CNS depressants may have an enhanced CNS depressant impact.
Duvelisib May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Eletriptan Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.
Erdafitinib May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Erdafitinib May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Ergot Derivatives  Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status. Exceptions: Nicergoline.
Esketamine CNS depressants may have an enhanced CNS depressant impact.
Fosaprepitant May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Fosnetupitant May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Haloperidol QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTcprolonging effect of Haloperidol.
HydrOXYzine CNS depressants may have an enhanced CNS depressant impact.
Ivosidenib May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Kava Kava May enhance the adverse/toxic effect of CNS Depressants.
Larotrectinib May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Lasmiditan Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.
Lorcaserin Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.
Magnesium Sulfate CNS depressants may have an enhanced CNS depressant impact.
Metaxalone Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.
MetyroSINE The sedative effects of metyroSINE may be strengthened by CNS depressants.
Minocycline (Systemic) CNS depressants may have an enhanced CNS depressant impact.
Nabilone CNS depressants may have an enhanced CNS depressant impact.
Nefazodone Mirtazapine may enhance the serotonergic effect of Nefazodone. Serotonin syndrome might occur from this. When these  medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin  poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.
Netupitant May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Ondansetron Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.
Oxitriptan The serotonergic impact of oxitriptan may be enhanced by serotonergic agents (high risk).
Palbociclib May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Piribedil Piribedil's CNS depressing effects may be enhanced by other CNS depressants.
Pramipexole The sedative effects of pramipexole might be enhanced by CNS depressants.
QT-prolonging Agents (Highest Risk)

The QTc-prolonging action of QT-prolonging Agents may be enhanced by QT-prolonging Agents (Indeterminate Risk - Caution)  (Highest Risk). When using these medications together, watch out for cardiac arrhythmias and a prolonged QTc interval.  Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Ramosetron Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.V
ROPINIRole The sedative effects of CNS depressants may increase those of ROPINIRole.
Rotigotine Rotigotine's sedative effects may be boosted by CNS depressants.
Rufinamide

CNS depressants' harmful or toxic effects could be increased. Particularly, drowsiness and lightheadedness could be worsened.

Sarilumab May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Selective Serotonin Reuptake Inhibitors

Selective serotonin reuptake inhibitors may have a worsened or more hazardous effect when taken with CNS depressants.  Particularly, there may be an increased risk of psychomotor impairment.

Selective Serotonin Reuptake Inhibitors Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.
Serotonergic Agents (High Risk, Miscellaneous) Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.
Serotonin 5-HT1D Receptor Agonists (Triptans) Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.Exceptions: Almotriptan; Eletriptan.
Serotonin/Norepinephrine Reuptake Inhibitors

Serotonin/Norepinephrine Reuptake Inhibitors' serotonergic effects may be strengthened by mirtazapine. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

Siltuximab May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Simeprevir May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
St John's Wort Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.
Syrian Rue Serotonin syndrome might occur from this. When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.
Tetrahydrocannabinol CNS depressants may have an enhanced CNS depressant effect.
Tetrahydrocannabinol and Cannabidiol CNS depressants may have an enhanced CNS depressant effect.
Tobacco (Smoked) May lower the level of mirtazapine in the serum.
Tocilizumab May lower the serum level of CYP3A4 substrates (High risk with Inducers).
TraZODone Could intensify mirtazapine's CNS depressive effects. The serotonergic effect of mirtazapine may be enhanced by trazonodine.
Tricyclic Antidepressants Serotonergic non-opioid CNS depressants may have an enhanced CNS depressant impact. 
Trimeprazine Tricyclic antidepressants may increase a CNS depressant's ability to do so.
Warfarin Warfarin's anticoagulant action may be strengthened by mirtazapine.

Risk Factor D (Consider therapy modification)

Alpha2-Agonists

The antihypertensive effects of Alpha2-Agonists may be lessened by mirtazapine. Management: Take into account forgoing  concurrent use. If the combination cannot be avoided, keep an eye out for either enhanced effects or decreased effects of alpha2-agonists if mirtazapine is started or dose increased.

Blonanserin CNS Depressants may enhance the CNS depressant effect of Blonanserin.
Buprenorphine CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants.
Chlormethiazole May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.
Dabrafenib May lower the serum level of CYP3A4 substrates (High risk with Inducers).Management: When possible, look for  substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the  substrate's clinical  consequences (particularly therapeutic effects).
Droperidol

CNS depressants may have an enhanced CNS depressant impact. Consider lowering the dosage of  droperidol or other CNS  drugs (such as opioids or barbiturates) when they are used concurrently. In separate drug interaction monographs,  exceptions to this monograph are covered in more detail.

Enzalutamide May lower the serum level of CYP3A4 substrates (High risk with Inducers).Treatment: Enzalutamide should not be used  concurrently  with CYP3A4 substrates that have a limited therapeutic index.Enzalutamide use, like with the use of  any other CYP3A4 substrate, should be done cautiously and under close observation.
Flunitrazepam CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.
HYDROcodone CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Lemborexant

CNS depressants may have an enhanced CNS depressant impact. Management: Due to the possibility of additive  CNS depressant effects when lemborexant and concurrent CNS depressants are administered concurrently, dosage  modifications  may be required. Effects of CNS depressants must be closely monitored.

Lorlatinib May lower the serum level of CYP3A4 substrates (High risk with Inducers).Management: Avoid taking lorlatinib at the same  time as any CYP3A4 substrates for  which even a small drop in serum levels of the  substrate could result in therapeutic failure  and negative clinical outcomes.
Methotrimeprazine

The CNS depressing action of methotrimeprazine may be enhanced by CNS depressants. The CNS depressant  action of CNS Depressants may be strengthened by methotrimeprazine. Management: Start concurrent methotrimeprazine  therapy  while reducing the adult dose of CNS depressants by 50%. Only once a clinically effective dose of methotrimeprazine has been established should  additional CNS depressant dosage modifications be made.

MiFEPRIStone May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).Management: During and  two weeks after mifepristone treatment, reduce doses of CYP3A4 substrates and keep an eye out for elevated  amounts or toxicity. Fentanyl, pimozide, quinidine, sirolimus, and tacrolimus should all be avoided. Cyclosporine should also be avoided.
Mitotane May lower the serum level of CYP3A4 substrates (High risk with Inducers).Treatment: When administered in individuals  receiving mitotane, doses of CYP3A4 substrates may need to be significantly modified.
Opioid Agonists CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
OxyCODONE CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Perampanel May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination.
Serotonergic Opioids (High Risk)

The CNS depressing impact of serotonin-dependent opioids may be enhanced by serotonin-dependent non-opioid CNS  depressants (High Risk). The serotonergic action of serotonergic opioids may be enhanced by serotonergic non-opioid  CNS depressants (High Risk). Serotonin syndrome might occur from this. Management: Take into account different  pharmacological combinations. Keep an eye out for the warning signs and symptoms of CNS depression and  serotonin syndrome, if they occur together.

Sodium Oxybate

CNS depressants may have an enhanced CNS depressant impact. Management: Take into account substitutes for combined use.  Reduce the doses of one or more medications when simultaneous use is necessary. It is not advised to use  sodium oxybate with alcoholic beverages or hypnotic sedatives.

Stiripentol May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: Due to the increased  potential for side effects and toxicity, stiripentol should not be used with CYP3A4 substrates that are thought  to have a narrow therapeutic index. Any CYP3A4 substrate administered with stiripentol requires greater monitoring.
Suvorexant

Suvorexant's CNS depressing effects may be amplified by other CNS depressants. Treatment: Suvorexant and/or  any other CNS depressant dosage reduction may be required. Suvorexant shouldn't be taken with alcohol,  and it shouldn't  be taken for sleeplessness with any other medication either.

Tapentadol

CNS depressants may have an enhanced CNS depressant impact. Treatment: When feasible, refrain from using  tapentadol and benzodiazepines or other CNS depressants simultaneously. Only in the event that other treatment choices are insufficient should these medications be combined. Limit the duration and dosage of each medicine  when used together.

Zolpidem CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.

Risk Factor X (Avoid combination)

Alcohol (Ethyl) May enhance the CNS depressant effect of Mirtazapine.
Azelastine (Nasal) CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Bromperidol May enhance the CNS depressant effect of CNS Depressants.
Conivaptan May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Dapoxetine

Makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this. Treatment: Avoid using high-risk serotonergic medications with dapoxetine or within 7 days after stopping them. Within 14 days of using a monoamine  oxidase inhibitor, do not take dapoxetine. This combination is listed on the labelling for dapoxetine as being harmful.

Fusidic Acid (Systemic) May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Idelalisib Could intensify the serotonergic effects of non-opioid serotonergic CNS  depressants.
Linezolid

Serotonin syndrome might occur from this.

Methylene Blue

The serotonergic impact of Methylene Blue may be strengthened by serotonergic non-opioid CNS depressants. Serotonin  syndrome might occur from this.

Monoamine Oxidase Inhibitors (Antidepressant)

The serotonergic impact of monoamine oxidase inhibitors may be enhanced by serotonergic non-opioid CNS  depressants (Antidepressant). Serotonin syndrome might occur from this.

Orphenadrine CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxomemazine May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
Pitolisant Mirtazapine may diminish the therapeutic effect of Pitolisant.
Rasagiline .Could intensify the serotonergic effects of non-opioid serotonergic CNS depressants.
Safinamide Could intensify the serotonergic effects of non-opioid serotonergic CNS depressants.
Selegiline Could intensify the serotonergic effects of non-opioid serotonergic CNS depressants.
Thalidomide This might cause serotonin syndrome.

 

Monitoring parameters:

  • Patients taking mirtazapine should be regularly monitored for various factors to ensure their well-being and manage potential side effects.

  • Monitoring should include:

  • Agranulocytosis or Severe Neutropenia Symptoms: Keep an eye out for symptoms such as a sore throat, stomatitis, or other infection-related symptoms, as well as monitoring the white blood cell count (WBC).

  • Renal Function: Regular assessments of renal function are important, especially in patients with pre-existing renal conditions.

  • Hepatic Function: Monitoring liver function is crucial, as mirtazapine may impact the liver. Any signs of liver problems, such as jaundice or dark urine, should be promptly addressed.

  • Mental Health: Regular check-ins on mental health are essential to assess the effectiveness of the treatment and address any emerging concerns.

  • Lipid Profile: Given the potential for mirtazapine to affect lipid levels, monitoring the lipid profile can help manage any changes.

  • Serotonin Syndrome: Watch for symptoms of serotonin syndrome, such as altered mental status, autonomic instability, and neuromuscular changes.

  • Weight Gain: As mirtazapine is known to stimulate appetite and potentially lead to weight gain, monitoring weight changes is advised.

  • These routine checks contribute to the overall safety and effectiveness of mirtazapine treatment and help healthcare providers make informed decisions about the ongoing care of the patient.

  • Always consult with a healthcare professional for personalized advice based on individual health conditions and treatment needs.


How to administer Mirtazapine (Remeron)?

Mirtazapine is administered orally without any specific requirement regarding meals.

It can be taken with or without food, making it more flexible for patients to incorporate into their daily routine.

The lack of a strict meal-related requirement simplifies the administration of the medication, providing convenience for individuals taking mirtazapine.

However, it's always advisable for patients to follow their healthcare provider's specific instructions on how to take their medication based on their individual needs and conditions.

Orally disintegrating tablet:

  • To take the tablet, place it on your tongue after opening the blister pack.

  • There is no need to split the pill as it is designed to dissolve on the tongue without the need for water.


Mechanism of action of Mirtazapine (Remeron):

  • Mirtazapine, a tetracyclic antidepressant, works by inhibiting central presynaptic beta-adrenergic receptors.

  • This inhibition leads to increased release of serotonin and norepinephrine.

  • Additionally, it acts as a potent peripheral alpha-adrenergic antagonist and muscarinic antagonist, and it competes with serotonin receptors (5-HT-2 and 5-HT-3) and histamine receptors (H).

  • It's important to note that mirtazapine does not prevent the reuptake of norepinephrine and serotonin, but rather, it influences their release through its complex interactions with various receptors in the central nervous system.

Absorption:

  • Rapid and complete

Protein binding:

  • About 85%

Metabolism:

  • It is extensively metabolized in the liver via CYP1A2, 2D6, 3A4 and via demethylation and hydroxylation

Bioavailability:

  • About 50%

Half-life elimination:

  • 20 to 40 hours;
  • increased with renal or hepatic impairment

Time to peak serum concentration:

  • About 2 hours

Excretion:

  • Urine (75%) and feces (15%) as metabolites

International Brand Names of Mirtazapine:

  • Remeron
  • Remeron SolTab
  • APO-Mirtazapine
  • Auro-Mirtazapine
  • Auro-Mirtazapine OD
  • DOM-Mirtazapine
  • JAMP-Mirtazapine
  • MYLAN-Mirtazapine
  • PMS-Mirtazapine
  • PRO-Mirtazapine
  • Remeron
  • Remeron RD
  • RIVA-Mirtazapine [DSC]
  • SANDOZ Mirtazapine
  • TEVA-Mirtazapine
  • TEVA-Mirtazapine OD
  • Afloyan
  • Aurozapine
  • Avanza
  • Avanza Soltab
  • Axit
  • Calixta
  • Ciblex
  • Comment
  • Espirtal
  • Menelat
  • Mi Er Ning
  • Mirap
  • Mirastad
  • Mirazep
  • Mirez
  • Miro
  • Mirta TD
  • Mirtapax
  • Mirtapil
  • Mirtaz
  • Mirtazon
  • Mirtel
  • Mirtimash
  • Mitrapil
  • Norset
  • Noxibel
  • Odonazin
  • Rapine
  • Reflex
  • Remergil
  • Remergon
  • Remeron
  • Remeron SolTab
  • Remeron Soltab
  • Remirta
  • Remirta OD
  • Remixil ODT
  • Resant
  • Sinmaron
  • Tazeurin
  • Trazapin
  • U-Mirtaron
  • Vastat Flas
  • Zamir
  • Zapex
  • Zapimet
  • Zismirt
  • Zispin
  • Zulin

Mirtazapine Brand Names in Pakistan:

Mirtazapine Tablets 15 mg

Elaxine Standpharm Pakistan (Pvt) Ltd.
Memron Biogen Pharma
Mirtazep Zafa Pharmaceutical Laboratories (Pvt) Ltd.
Mirton Genome Pharmaceuticals (Pvt) Ltd
Mirtz Paramount Pharmaceuticals
Notense Qintar Pharmacuticals
Ramargon Organic Pharmaceuticals.
Tizapine Amarant Pharmaceuticals (Pvt)
Tizidan Danas Pharmaceuticals (Pvt) Ltd
Tnsles Panacea Pharmaceuticals

 

Mirtazapine 30 mg Tablets

Elaxine Standpharm Pakistan (Pvt) Ltd.
Mezeron Obs
Mipine Raazee Theraputics (Pvt) Ltd.
Mirpine Global Pharmaceuticals
Mirtazep Zafa Pharmaceutical Laboratories (Pvt) Ltd.
Mirton Genome Pharmaceuticals (Pvt) Ltd
Mirtz Paramount Pharmaceuticals
Notense Qintar Pharmacuticals
Ramargon Organic Pharmaceuticals.
Remeron Obs
Tizapine Amarant Pharmaceuticals (Pvt)
Tizidan Danas Pharmaceuticals (Pvt) Ltd
Tnsles Panacea Pharmaceuticals
Valta Getz Pharma Pakistan (Pvt) Ltd.
Zemer Mass Pharma (Private) Limited
Zimar Pharma Health Pakistan (Pvt) Ltd

 

Mirtazapine Tablets 45 mg

Charmfil Wilshire Laboratories (Pvt) Ltd.