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Dear Readers! I started this blog when my daughter was in the NICU. She had ventriculitis. Her CSF report grew E.coli. But, she was injected Teicoplanin directly into her brain. The doctors made two errors here:

Teicoplanin is for gram-positive bacteria only. It does not treat E.coli.
Teicoplanin is not for intraventricular use. The manufacturer strongly discourage injecting Teicoplanin into the brain.

My daughter bled into the brain. She lived for another two years and ultimately died.

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Milnacipran (Savella) - Uses, Dose, MOA, Brands, Side effects

A norepinephrine and serotonin reuptake inhibitor called milnacipran (Savella) is used to treat fibromyalgia patients.

Fibromyalgia:
- It is recommended for treating fibromyalgia.

Milnacipran (Savella) Dose in the treatment of Fibromyalgia:

By mouth, take 50 milligrams two times a day.
Start with 5 mg on the first day, then take 12.5 mg two times a day for the next three days.
After that, take 25 mg two times a day for the next four days.
Finally, take 50 mg two times a day for the rest of the days.
If your body reacts well, the doctor might increase the dose to 100 mg two times a day.
They haven't studied doses higher than 200 mg a day.
Discontinuation of therapy:
- Stopping antidepressants suddenly after using them for more than three weeks can lead to withdrawal symptoms and the return of the original symptoms.
- To reduce these effects, it's recommended to gradually decrease the dose over 2-4 weeks.
- If someone is taking a medication with a short half-life (like paroxetine or venlafaxine), has a history of withdrawal symptoms, or is on a high dose, they should slowly adjust the dose, perhaps over four weeks.
- If withdrawal symptoms become too difficult, going back to the previous dose or decreasing the dose more slowly are the best choices.
- There's not a lot of evidence to guide the ideal speed for tapering off antidepressants.
Switching antidepressants:
- There isn't much evidence on the best ways to switch antidepressants, but there are a couple of strategies:
- Cross-titration: This involves gradually stopping the first antidepressant while, at the same time, slowly increasing the new antidepressant.
- This is the usual approach for most switches, except for MAOIs (Monoamine oxidase inhibitors).
- Straight switch: This means abruptly stopping the first antidepressant and then starting the new one at an equivalent dose or lower, gradually increasing it.
- However, this method is not recommended for MAOIs.
- In certain situations, a direct switch is preferable. For example:
- When transitioning between two SSRIs (Selective Serotonin Reuptake Inhibitors), especially if the antidepressant being stopped has been taken for less than a week.
- When deciding on a switch strategy, consider factors like the likelihood of withdrawal symptoms, potential medication interactions, features of each antidepressant (such as half-life, side effects, and how they work), and the level of symptom control needed.
Switching to or from an MAOI:
- Wait at least 14 days after you stop taking MAOI before you start using milnacipran.
- Also, wait for 5 days after stopping milnacipran before starting MAOI.

Use in Children:

Not indicated.

Pregnancy Risk Factor C

- Research on animal reproduction indicates potential risks.
- If a newborn is exposed to SSRI/SNRI in the last three months of the third trimester, it might not cause birth defects, but adverse events can occur.
- These may include respiratory symptoms like crying, respiratory distress, and apnea.
- Seizures, abnormal muscle tone (hyper or hypotonia), hyperreflexia, and jitteriness are also possible.
- Other symptoms such as vomiting, feeding difficulties, hypoglycemia, constant crying, and irritability may arise.
- These symptoms could be linked to toxicity, discontinuation syndrome, or serotonin disorder associated with SSRI treatment.
- The long-term effects of these changes on the newborn are not well understood.
Milnacipran can be used during breastfeeding
- It comes out in breast milk, so it's advised that breastfeeding mothers avoid using it.

Dose in Kidney Disease:

For mild kidney issues, no change in dosage is needed.
If there's moderate impairment, be cautious.
In severe cases (when kidney function is significantly reduced), decrease the dose to 25-50 mg twice a day based on individual tolerance.
However, it's not recommended for use in end-stage renal disease (ESRD).

Dose in Liver Disease:

For mild-to-moderate liver issues, there's no need to adjust the dosage.
In cases of severe liver impairment, no dosage adjustment is required, but it's advisable to use the medication cautiously.

Common Side Effects of Milnacipran (Savella):

Central nervous system:
- Insomnia
- Headache
Endocrine & metabolic:
- Hot flash
Gastrointestinal:
- Nausea
- Constipation

Less Common Side Effects of Milnacipran (Savella):

Cardiovascular:
- Palpitations
- Increased Heart Rate
- Hypertension
- Flushing
- Increased Blood Pressure
- Tachycardia
- Peripheral Edema
Central Nervous System:
- Dizziness
- Migraine
- Chills
- Depression
- Drowsiness
- Falling
- Fatigue
- Irritability
Dermatologic:
- Hyperhidrosis
- Skin Rash
- Night Sweats
Endocrine & Metabolic:
- Decreased Libido
- Hypercholesterolemia
- Weight Changes
Gastrointestinal:
- Vomiting
- Xerostomia
- Flatulence
- Decreased Appetite
- Dysgeusia
- Abdominal Distension
- Dyspepsia
- Gastroesophageal Reflux Disease
- Diarrhea
- Abdominal Pain
Genitourinary:
- Cystitis
- Dysuria
- Urinary Hesitancy
- Ejaculatory Disorder
- Urethral Pain
- Prostatitis
- Testicular Pain
- Erectile Dysfunction
- Testicular Swelling
- Scrotal Pain
- Urinary Retention
- Ejaculation Failure
- Urinary Tract Infection
- Decreased Urine Output
Neuromuscular & Skeletal:
- Tremor
Ophthalmic:
- Blurred Vision
Respiratory:
- Dyspnea
Miscellaneous:
- Fever

Contraindications to Milnacipran (Savella):

- - MAOIs are employed for treating psychiatric disorders.
  - However, be cautious not to use them at the same time as milnacipran or within five days of stopping milnacipran.
  - Also, avoid initiating milnacipran within two weeks after discontinuing MAOIs.
  - Additionally, if a patient has recently received intravenous linezolid or Methylene Blue, the initiation of milnacipran should be approached carefully.

Warnings and precautions

- Bleeding Risk:
  - Due to its impact on platelet aggregation, there is a higher likelihood of bleeding.
  - This risk becomes more significant when combined with aspirin and NSAIDs.
  - While the evidence is inconclusive, there is a suggestion that SNRIs, when used with anticoagulants, may increase the risk of bleeding.
  - The use of SNRIs can lead to bleeding of varying severity, ranging from nosebleeds or minor bruising to potentially life-threatening hemorrhage.
- Cardiovascular effects
  - The treatment may raise blood pressure and heart rate.
  - It's crucial to evaluate these factors before starting the therapy and monitor them regularly.
  - If there's a condition of rapid heart rate (tachycardia) or sustained high blood pressure, it's important to either decrease the dosage or gradually stop using the treatment.
  - Before initiating any therapy, it's essential to address any existing heart disease.
  - Patients with preexisting heart conditions should receive treatment with caution.
- Fractures
  - Antidepressants have been associated with an increased risk of bone fractures.
  - If someone using antidepressants or similar medications experiences unexplained bone pain, it's essential to seek medical attention.
  - This pain might be accompanied by specific signs like point tenderness, swelling, or bruising.
- Hepatotoxicity
  - The use of this medication may lead to liver injury, including severe conditions like fulminant liver disease and an elevation in liver enzymes.
  - If a patient is experiencing high levels of alcohol intake, chronic liver disease (CLD), or other liver problems, it's advisable to avoid using this medication.
  - If any signs of liver dysfunction are observed, it's crucial to stop the therapy immediately.
  - Restarting the medication should only be considered after identifying and addressing any other potential causes or sources of the hepatic issues.
- Ocular effects
  - Using this medication could lead to a slight dilation of the pupils, and in rare instances, it may cause narrow-angle glaucoma.
  - It's important to assess for risk factors associated with narrow-angle glaucoma before starting the treatment.
- Serotonin syndrome
  - Serotonin syndrome can occur with drugs that affect serotonin levels (like SSRIs, SNRIs).
  - This risk increases when these drugs are used with other serotonergic medications (such as triptans, TCAs, fentanyls, lithium, tramadols, buspirones, St John's wort, and tryptophan), as well as substances that affect serotonin metabolism (like linezolid or IV methylene blue).
  - Watch out for signs of serotonin syndrome, including mental status changes (agitation, hallucinations, delirium, coma), autonomic instability (rapid heart rate, unstable blood pressure, dizziness, sweating, flushing, high body temperature, and incoordination), neuromuscular changes (tremor, rigidity, myoclonus, hyperreflexia, and coordination issues), GI symptoms (nausea, vomiting, diarrhea), and seizures.
  - If any of these signs or symptoms appear, it's crucial to stop the treatment immediately.
- SIADH and Hyponatremia
  - Both SSRIs and SNRIs can potentially cause SIADH (syndrome of inappropriate antidiuretic hormone secretion).
  - In rare cases, there have been reports of severe hyponatremia, with levels as low as 110 mg/L.
  - This risk is particularly prevalent in older patients.
  - The likelihood of this condition increases if there is volume depletion or concurrent use of diuretics.
  - It's important to be cautious in such situations to minimize the risk of severe hyponatremia.
- Urinary hesitancy
  - The medication may lead to increased resistance in urine flow.
  - It's important to advise the patient to inform you if they notice any symptoms of urgency or difficulty in urination.
  - If the patient is already experiencing symptoms related to prostatism or any other lower urinary tract disorder, caution should be exercised in the use of this medication.
- Hypomania/mania:
  - Individuals with mood disorders or those taking similar medications may experience episodes of mania.
  - The use of this medication might worsen psychosis in some patients or trigger mania and hypomania in individuals with bipolar disorder.
  - It's crucial to note that bipolar disorder should not be treated with this medication alone.
  - Testing for bipolar disorder should be conducted on patients exhibiting symptoms of depression.
  - It's important to emphasize that milnacipran has not been approved by the FDA for the treatment of bipolar disorder.
- Seizure disorders
  - Exercise caution if there is a history or condition that could potentially lead to seizures, such as a history of brain damage or addiction.

Milnacipran: Drug Interaction

Risk Factor C (Monitor therapy)
Acalabrutinib	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)	Other agents with antiplatelet properties may have an enhanced antiplatelet impact.
Almotriptan	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	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.
Alpha2-Agonists	The antihypertensive action of Alpha2-Agonists may be diminished by Serotonin/Norepinephrine Reuptake Inhibitors.Exceptions: Apraclonidine.
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.
Anticoagulants	The anticoagulant impact of anticoagulants may be strengthened by agents with antiplatelet properties.Exceptions: Bemiparin; Enoxaparin; Heparin.
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.Exceptions: Alosetron; Ondansetron; Ramosetron.
Antipsychotic Agents	Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome.
Apixaban	Antiplatelet agents may intensify the toxic/unfavorable effects of apixaban. In particular, there may be an elevated risk of bleeding. Management: Carefully weigh the advantages and disadvantages of this pairing, and keep a tight eye on things.
Aspirin	Serotonin/Norepinephrine Reuptake Inhibitors may improve aspirin's ability to reduce blood clots.
Brexanolone	Serotonin/Norepinephrine Reuptake Inhibitors may increase Brexanolone's ability to depress the central nervous system.
BusPIRone	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.
Cephalothin	Agents having antiplatelet properties may intensify cephalothin's harmful or hazardous effects. In particular, there may be an elevated risk of bleeding.
Collagenase (Systemic)	Collagenase's harmful or toxic effects may be enhanced by substances with antiplatelet properties (Systemic). In particular, there may be an increased risk of bruising and/or bleeding at the injection site.
Cyclobenzaprine	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.
Dabigatran Etexilate	Dabigatran Etexilate's anticoagulant activity may be strengthened by substances with antiplatelet properties. Dabigatran Etexilate's serum levels may rise in response to substances with antiplatelet properties. The drug clopidogrel is especially covered by this mechanism. Management: Carefully weigh the advantages and disadvantages of this combination, and keep a tight eye on things; Canadian labelling advises against using prasugrel or ticagrelor.
Dasatinib	Agents having antiplatelet properties may strengthen their anticoagulant effects. Management: Separate drug interaction monographs go into further detail about the medications indicated as exceptions to this book.
Deoxycholic Acid	Deoxycholic Acid's harmful or toxic effects may be increased by substances with antiplatelet properties. In particular, there may be a higher chance of bleeding or bruising in the treatment region.
Dexmethylphenidate-Methylphenidate	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.
Dextromethorphan	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.
Edoxaban	Antiplatelet agents may intensify the toxic/unfavorable effects of edoxaban. In particular, there may be an elevated risk of bleeding.
Eletriptan	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.
Ergot Derivatives	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. Exceptions: Nicergoline.
Fat Emulsion (Fish Oil Based)	Agents with poisonous or harmful effects may intensify their negative or hazardous effects.
FentaNYL	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.
Glucosamine	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Ibritumomab Tiuxetan	Antiplatelet agents may intensify the toxic/unfavorable effects of ibritumomab tiuxetan. Both substances may raise the risk of bleeding and compromise platelet function.
Ibrutinib	Agents with poisonous or harmful effects may intensify their negative or hazardous effects.
Inotersen	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Ioflupane I 123	Ioflupane I 123's ability to serve as a diagnostic tool may be diminished by serotonin/norepinephrine reuptake inhibitors.
Lasmiditan	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.
Limaprost	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Lorcaserin	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.
Meperidine	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.
Metaxalone	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.
Mirtazapine	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.
Multivitamins/Fluoride (with ADE)	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Multivitamins/Minerals (with ADEK, Folate, Iron)	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Multivitamins/Minerals (with AE, No Iron)	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Nefazodone	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..
Nonsteroidal Anti-Inflammatory Agents (Nonselective)	Nonsteroidal Anti-Inflammatory Drugs may have a stronger antiplatelet impact when used with Serotonin/Norepinephrine Reuptake Inhibitors (Nonselective).
Obinutuzumab	Agents with antiplatelet properties may intensify Obinutuzumab's toxic/unfavorable effects. In particular, there may be an increased risk of life-threatening bleeding-related incidents.
Omega-3 Fatty Acids	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Ondansetron	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.
Opioid Agonists	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. Exceptions: FentaNYL; Meperidine; TraMADol.
Oxitriptan	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.
Pentosan Polysulfate Sodium	Agents with poisonous or harmful effects may intensify their negative or hazardous effects. In particular, the concurrent use of several drugs may raise the risk of bleeding.
Pentoxifylline	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Prostacyclin Analogues	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Ramosetron	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.
Rivaroxaban	Rivaroxaban's anticoagulant impact may be increased by substances with antiplatelet properties. Management: Carefully weigh the advantages and disadvantages of this combination, and keep tight eye on things; Canadian labelling advises against using prasugrel or ticagrelor.
Salicylates	The harmful or toxic effect of salicylates may be increased by substances with antiplatelet properties. Bleeding risk could rise as a result.
Selective Serotonin Reuptake Inhibitors	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. Exceptions: Dapoxetine.
Serotonergic Agents (High Risk, Miscellaneous)	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.
Serotonin 5-HT1D Receptor Agonists (Triptans)	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. Exceptions: Almotriptan; Eletriptan.
Serotonin/Norepinephrine Reuptake Inhibitors	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.In addition, monitor for signs and symptoms of bleeding.
St John's Wort	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.
Syrian Rue	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.
Thrombolytic Agents	The anticoagulant impact of thrombolytic agents may be strengthened by agents with antiplatelet properties.
Tipranavir	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
TraMADol	Serotonin/Norepinephrine Reuptake Inhibitors may enhance the adverse/toxic effect of TraMADol. 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.
TraZODone	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.
Tricyclic Antidepressants	Tricyclic Antidepressants' serotonergic effects may be strengthened by serotonin/norepinephrine reuptake inhibitors. Serotonin syndrome might occur from this. When using these drugs together, watch out for any changes in mental status and indicators of serotonin syndrome, such as hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, and autonomic instability.
Vitamin E (Systemic)	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Vitamin K Antagonists (eg, warfarin)	Milnacipran may make vitamin K antagonists more harmful or poisonous. In particular, there may be an elevated risk of bleeding.
Zanubrutinib	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Risk Factor D (Consider therapy modification)
Alcohol (Ethyl)	Tricyclic Antidepressants' serotonergic effects may be strengthened by serotonin/norepinephrine reuptake inhibitors. Serotonin syndrome might occur from this. When using these drugs together, watch out for any changes in mental status and indicators of serotonin syndrome, such as hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, and autonomic instability.
Alpha-/Beta-Agonists	The tachycardic action of beta- and alpha-agonists may be enhanced by serotonin/norepinephrine reuptake inhibitors. The vasopressor impact of alpha/beta agonists may be enhanced by serotonin/norepinephrine reuptake inhibitors.
Bemiparin	Bemiparin's anticoagulant impact may be strengthened by substances with antiplatelet properties. Management: Avoid taking bemiparin at the same time as antiplatelet medications. If concurrent use is unavoidable, keep a cautious eye out for bleeding signs and symptoms.
Digoxin	Milnacipran may intensify Digoxin's harmful or hazardous effects. Particularly when IV digoxin is used, the risk of postural hypotension and tachycardia may increase. Avoid giving IV digoxin to individuals who are taking milnacipran at the same time. When using oral digoxin and milnacipran together, proceed with caution and pay close attention for any signs of postural hypotension and tachycardia.
Enoxaparin	Enoxaparin's anticoagulant impact may be strengthened by substances with antiplatelet properties. When feasible, stop using antiplatelet medications before starting enoxaparin. If simultaneous administration must occur, keep a cautious eye out for any bleeding signs and symptoms.
Heparin	The anticoagulant effect of heparin may be strengthened by substances with antiplatelet properties. If coadministration is necessary, reduce the dose of heparin or other medications with antiplatelet characteristics.
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)	Agents with poisonous or harmful effects may intensify their negative or hazardous effects. Bleeding could happen. Management: When at all possible, avoid combining. If used, keep a closer eye out for signs of bleeding. Two weeks before any type of surgery, dental work, or invasive procedure, stop using herbal remedies that have anticoagulant or antiplatelet effects.
Metoclopramide	Tricyclic Antidepressants' serotonergic effects may be strengthened by serotonin/norepinephrine reuptake inhibitors. Serotonin syndrome might occur from this. When using these drugs together, watch out for any changes in mental status and indicators of serotonin syndrome, such as hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, and autonomic instability.
Risk Factor X (Avoid combination)
Bromopride	The negative or hazardous effects of serotonin/norepinephrine reuptake inhibitors may be increased.
Dapoxetine	Makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this. Treatment: Avoid using highrisk 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.
Iobenguane Radiopharmaceutical Products	Tricyclic Antidepressants' serotonergic effects may be strengthened by serotonin/norepinephrine reuptake inhibitors. Serotonin syndrome might occur from this. When using these drugs together, watch out for any changes in mental status and indicators of serotonin syndrome, such as hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, and autonomic instability.
Linezolid	Serotonin/Norepinephrine Reuptake Inhibitors may improve their serotonergic effects. Serotonin syndrome might occur from this.
Methylene Blue	Serotonin/Norepinephrine Reuptake Inhibitors may improve their serotonergic effects. Serotonin syndrome might occur from this.
Monoamine Oxidase Inhibitors (Antidepressant)	Serotonin/Norepinephrine Reuptake Inhibitors may improve their serotonergic effects. Serotonin syndrome might occur from this.
Rasagiline	Serotonin/Norepinephrine Reuptake Inhibitors may improve their serotonergic effects. Serotonin syndrome might occur from this.
Safinamide	Serotonin/Norepinephrine Reuptake Inhibitors may improve their serotonergic effects. Serotonin syndrome might occur from this.
Selegiline	Serotonin/Norepinephrine Reuptake Inhibitors may improve their serotonergic effects. Serotonin syndrome might occur from this.
Urokinase	Urokinase's anticoagulant impact may be strengthened by substances with antiplatelet properties.

Monitoring Parameters:

Monitoring parameters for individuals on this therapy include:
Blood pressure and heart rate: Regularly check and monitor blood pressure and heart rate to ensure they are within the acceptable range.
Renal function: Monitor renal function to assess the health of the kidneys and ensure they are functioning properly.
Mental status: Keep a close eye on the patient's mental status, particularly for signs of suicidal ideation or tendencies. This is especially important at the beginning of therapy or with any changes in dosage.
Intraocular pressure: If the patient has a history of glaucoma, measure baseline intraocular pressure as it may already be elevated. Regular monitoring can help detect any changes.
Regular and thorough monitoring of these parameters is essential for the overall well-being of the patient during the course of the therapy.

How to administer Milnacipran (Savella)?

This medication can be taken orally, and it can be taken with or without food.

Mechanism of action of Milnacipran (Savella):

This medication is a strong inhibitor of norepinephrine reuptake and serotonin metabolism (in a ratio of 3:1).

Importantly, it does not possess properties that inhibit MAO (monoamine oxidase). Here are some details about its pharmacokinetics:

Absorption: It is well absorbed when taken orally.
Protein Binding: Approximately 13% of the drug binds to proteins.
Metabolism: The liver metabolizes it into inactive forms.
Bioavailability: The medication has a bioavailability of 85% to 90%.
Half-life Elimination: It has an elimination half-life of 6-8 hours.
Time to Peak in Plasma: When taken orally, it reaches peak plasma levels in 2-4 hours.
Excretion: The primary route of elimination is through urine, with 55% being excreted as the unchanged drug.

International Brand Names of Milnacipran:

Savella
Savella Titration Pack
Dalcipran
Ixel
Joncia
Milnacip
Milran
Misulvan
Mydonia
Neocipran
Tivanyl
Xian Wei Ning

Milnacipran Brand Names in Pakistan:

No Brands Available in Pakistan.

Milnacipran (Savella) - Uses, Dose, MOA, Brands, Side effects

Milnacipran (Savella) Dose in the treatment of Fibromyalgia:

Discontinuation of therapy:

Switching antidepressants:

Switching to or from an MAOI:

Use in Children:

Pregnancy Risk Factor C

Milnacipran can be used during breastfeeding

Dose in Kidney Disease:

Dose in Liver Disease:

Common Side Effects of Milnacipran (Savella):

Less Common Side Effects of Milnacipran (Savella):

Contraindications to Milnacipran (Savella):

Warnings and precautions

Bleeding Risk:

Cardiovascular effects

Fractures

Hepatotoxicity

Ocular effects

Serotonin syndrome

SIADH and Hyponatremia

Urinary hesitancy

Hypomania/mania:

Seizure disorders

Monitoring Parameters:

How to administer Milnacipran (Savella)?

Mechanism of action of Milnacipran (Savella):

International Brand Names of Milnacipran:

Milnacipran Brand Names in Pakistan:

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