Methylene blue is a synthetic chemical compound with a deep blue or greenish-blue color. It has a variety of uses and applications in medicine, biology, chemistry, and other fields.
Methylene Blue Dye inhibits nitric oxide and guanylate cyclase. It is used in the treatment of methemoglobinemia. It is also used as a staining dye used in mapping sentinel node in females with breast cancer and as a diagnostic aid in chromoendoscopy.
Methylene blue Uses:
- Acquired Methemoglobinemia (Provayblue only):
- Used in the treatment of pediatric and adult patients with acquired methemoglobinemia
- Drug-induced Methemoglobinemia (generic only):
- Used in the treatment of drug-induced methemoglobinemia
- Off Label Use of Methylene blue in Adults:
- Used in chromoendoscopy (diagnostic aid);
- Used in ifosfamide-induced encephalopathy (treatment and prevention)
- Used in sentinel lymph node mapping in breast cancer surgery
- Used in toenail onychomycosis
- Used in vasoplegia syndrome associated with cardiac surgery
Methylene Blue Dose in Adults:
Methylene Blue Dose in the treatment of Acquired Methemoglobinemia:
- Inject it into a vein.
- Use 1 mg of the drug for every kg of the patient's weight.
- Inject it slowly, over a period of 5 to 30 minutes.
- If the patient still has high methemoglobin levels (above 30%) or feels unwell after 1 hour, give the same dose again.
- If after 2 doses the problem isn't fixed, think about trying a different treatment.
Methylene Blue Dose in the treatment of Drug-induced Methemoglobinemia:
- Inject Methylene blue into a vein.
- Use 1 to 2 mg of the drug for every kg of the patient's weight, or 25 to 50 mg for every square meter of the patient's body surface area.
- Inject it over a few minutes.
- If needed, you can give the same dose again after waiting 1 hour.
Methylene Blue Dose in the treatment of Chromoendoscopy (off label):
- Use Methylene blue as a liquid solution with a strength between 0.1% and 1%.
- During the procedure, spray this solution through a tube or apply it directly onto the inside lining of the stomach or intestines.
Methylene Blue Dose in the of Ifosfamide-induced encephalopathy (off-label): Oral, IV:
Note: Sometimes, the patient might get better on their own without treatment.
Prevention:
- Take 50 mg of Methylene blue every 6 to 8 hours.
- More research might be needed to understand how well Methylene blue works for this purpose.
Treatment:
- Take 50 mg of Methylene blue once or every 4 to 8 hours. Keep taking until the symptoms go away.
Methylene Blue Dose in the treatment of Toenails Onychomycosis (off-label):
- Apply a liquid with 2% Methylene blue to the toenail with fungus.
- Put it on every 15 days, and keep doing this for 6 months.
- This treatment should be paired with a special light treatment called photodynamic therapy.
Methylene Blue Dose in the treatment of Sentinel node mapping in breast cancer surgery (off-label):
- Inject 5 mL of a 1% Methylene blue solution into the breast tissue.
- Do this one time during the surgery.
Methylene Blue Dose in the treatment of Vasoplegia syndrome associated with cardiac surgery (off-label):
- Inject 1.5 to 2 mg of Methylene blue for every kg of the patient's weight into a vein.
- Do this slowly, over a period of 20 to 60 minutes, and only do it once.
Note:
- After using Methylene blue, patients often show improvement in their Vasoplegia symptoms within 1 to 2 hours. This can be seen as the body better controlling blood flow and needing less medication to help with blood pressure.
- Some doctors give a steady, small amount (0.5 to 1 mg/kg/hour) of Methylene blue after the initial big dose. But, more studies are needed to see if this way of giving the drug is a good idea.
Methylene Blue Dose in Childrens:
Warning: Methylene blue comes in different strengths, like 0.5% and 1%. Be very careful when figuring out how much to use.
Methylene Blue Dose in the treatment of acquired Methemoglobinemia (including drug-induced):
For treating Methemoglobinemia in babies, kids, and teenagers (even if it's caused by drugs):
- Give 1 to 2 mg of Methylene blue for every kg of the patient's weight. This can be injected directly into the vein (IV) or into the bone (I.O.).
- If needed (like if the methemoglobin level is still high, above 30%, or if the patient still has symptoms), you can give the same dose again after waiting 30 to 60 minutes.
- If after 2 doses the problem isn't fixed, think about trying a different treatment.
- Giving the medicine directly into the bone has been done and is mentioned in some studies.
Pregnancy Risk Factor: X
- Some products with methylene blue may not be safe for pregnant women or those who might become pregnant. It's crucial to consider the mother's health and her chances of getting better.
- Using methylene blue during a procedure called amniocentesis has caused problems in unborn babies, like issues with the intestine. But, taking it by mouth hasn't shown the same problems.
- If methylene blue is injected into the womb near the end of pregnancy, it can cause problems in the newborn, like jaundice (yellowing of the skin and eyes), staining of the skin, and trouble breathing.
- There have been cases of blood problems, a condition where the blood can't carry oxygen well (methemoglobinemia), and skin problems in babies exposed to methylene blue while still in the womb.
- When methylene blue is used for finding lymph nodes in breast cancer, it might not expose the fetus to as much risk based on studies in women who aren't pregnant.
- However, if it's given near the end of pregnancy, it's still important to watch the baby for any problems.
Methylene blue use during breastfeeding:
- We're not sure if methylene blue passes into breast milk.
- To be safe, one company suggests moms should stop breastfeeding while taking methylene blue and for 8 days after they finish the treatment.
Dose in Kidney Disease:
- The company that makes the medicine doesn't give any specific advice on changing the dose.
- But, if someone has serious kidney problems, be careful when using methylene blue.
Dose in Liver disease:
The company that makes the medicine doesn't give any specific advice on changing the dose for people with liver problems.
Common Side Effects of Methylene blue:
- Central nervous system:
- Feeling hot
- Dizziness
- Dermatologic:
- Hyperhidrosis
- Skin discoloration
- Gastrointestinal:
- Dysgeusia
- Nausea
- Genitourinary:
- Urine discoloration
- Neuromuscular & skeletal:
- Limb pain
Less Common Side Effects of Methylene blue:
- Cardiovascular:
- Chest Discomfort
- Syncope
- Presyncope
- Central Nervous System:
- Headache
- Paresthesia
- Infusion-Site Pain
- Sensation Of Cold
- Anxiety
- Chills
- Discomfort At Injection Site
- Local Discomfort
- Malaise
- Orthostatic Dizziness
- Dermatologic:
- Contact Dermatitis
- Pallor
- Pruritus
- Diaphoresis
- Ecchymosis
- Erythema
- Gastrointestinal:
- Oral Paresthesia
- Decreased Appetite
- Diarrhea
- Oral Hypoesthesia
- Vomiting
- Local:
- Catheter Pain
- Neuromuscular & Skeletal:
- Musculoskeletal Pain
- Arthralgia
- Back Pain
- Muscle Spasm
- Oral Discomfort
- Respiratory:
- Flu-Like Symptoms
- Dyspnea
Frequency of Side effects Not Defined:
- Cardiovascular:
- Hypertension
- Palpitations
- Peripheral Edema
- Tachycardia
- Central Nervous System:
- Confusion
- Dermatologic:
- Papule
- Phototoxicity
- Skin Discoloration
- Endocrine & Metabolic:
- Increased Thirst
- Gastrointestinal:
- Abdominal Pain
- Fecal Discoloration (Blue-Green)
- Flatulence
- Glossalgia
- Lower Abdominal Pain
- Tongue Rash
- Xerostomia
- Genitourinary:
- Dysuria
- Hematologic & Oncologic:
- Hemolysis
- Hemolytic Anemia
- Methemoglobinemia
- Hepatic:
- Hyperbilirubinemia
- Increased Liver Enzymes
- Local:
- Extravasation
- Infusion Site Reaction (Pruritus, Urticaria, Swelling, And Induration)
- Neuromuscular & Skeletal:
- Myalgia
- Ophthalmic:
- Blurred Vision
- Eye Pruritus
- Ocular Hyperemia
- Respiratory:
- Nasal Congestion
- Oropharyngeal Pain
- Rhinorrhea
- Sneezing
- Miscellaneous:
- Ulcer (Necrotic)
Contraindications to Methylene blue:
Do not use methylene blue if:
- You are allergic to methylene blue or anything else in the medicine.
For the generic version of methylene blue:
- Don't use if you are pregnant or might become pregnant.
- Don't inject it into the spine or just under the skin.
For a specific brand called "Provayblue":
- Don't use if you're allergic to similar blue dyes called thiazine dyes.
- Don't use if you have a condition called G6PD deficiency.
Warnings and precautions
CNS depression:
- Methylene blue might make you feel drowsy or less alert.
- So, be careful and avoid doing things that need you to be fully alert, like driving or using heavy machinery.
Extravasation:
- Methylene blue can cause damage if it leaks out of the vein (called "extravasation").
- If giving it as a steady drip, make sure the needle or tube is in the right place before and during the treatment.
- Try to use a main vein (central line) for the treatment if you can, and always keep a close eye on the place where the IV is inserted.
Hypersensitivity
- If someone has a severe allergic reaction or a very bad reaction called anaphylaxis after taking methylene blue, stop using it immediately and start treatment to help with the allergic response.
Methemoglobinemia:
- Methylene blue can sometimes cause a problem called methemoglobinemia, especially at high doses, in people with a condition called G6PD-deficiency, or in babies.
- This problem means that the iron in the blood changes in a way that stops it from carrying oxygen properly.
- This can lead to breaking down of red blood cells, and the symptoms might not show up until a day or more later. If this happens, a person might need a blood transfusion.
- When using methylene blue, try to use the smallest amount that works. If there's a lot of breakdown of red blood cells, stop using it and think about other treatments. Keep checking the levels of methemoglobin in the blood while giving the medicine.
Serotonin Syndrome: [US Boxed Warning]
- Warning: Using methylene blue with certain other medications, like antidepressants such as SSRIs, SNRIs, and MAOIs, can lead to a severe condition called serotonin syndrome, which can be life-threatening. So, don't take methylene blue with these medications.
- Keep a close watch for signs of serotonin syndrome, like changes in mental state (like confusion or hallucinations), problems with your body's automatic functions (like a racing heart, unstable blood pressure, dizziness, sweating, feeling very hot), muscle and coordination issues (like tremors or rigidity), stomach problems (like nausea or vomiting), or seizures.
- If any of these signs appear, stop the treatment and get medical help.
Hepatic impairment
- Be careful when giving methylene blue to people with liver problems.
- Watch closely for signs that the medicine is causing harm or isn't working right.
Renal impairment
- Be careful when giving methylene blue to people with serious kidney problems.
- Watch closely for signs that the medicine might be causing harm.
Methylene blue: 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
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Risk Factor C (Monitor therapy) |
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Acetylcholinesterase Inhibitors |
May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. |
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Alosetron |
May enhance the serotonergic effect of Serotonergic Agents (High Risk). 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. |
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May enhance the anticholinergic effect of Anticholinergic Agents. |
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Amifampridine |
Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. |
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Anticholinergic Agents |
May enhance the adverse/toxic effect of other Anticholinergic Agents. |
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Antiemetics (5HT3 Antagonists) |
May enhance the serotonergic effect of Serotonergic Agents (High Risk). 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. Exceptions: Alosetron; Ondansetron; Ramosetron. |
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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. |
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Beta2-Agonists |
Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Beta2Agonists. |
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Monoamine Oxidase Inhibitors may increase the serum concentration of Betahistine. |
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Blood Glucose Lowering Agents |
Monoamine Oxidase Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
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Botulinum Toxin-Containing Products |
May enhance the anticholinergic effect of Anticholinergic Agents. |
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Brimonidine (Ophthalmic) |
Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Brimonidine (Ophthalmic). Monoamine Oxidase Inhibitors may increase the serum concentration of Brimonidine (Ophthalmic). |
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Brimonidine (Topical) |
Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Brimonidine (Topical). Monoamine Oxidase Inhibitors may increase the serum concentration of Brimonidine (Topical). |
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Cannabinoid-Containing Products |
Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. |
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Cerebrolysin |
May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. |
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Chloral Betaine |
May enhance the adverse/toxic effect of Anticholinergic Agents. |
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Chlorphenesin Carbamate |
May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. |
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Clemastine |
Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Clemastine. |
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Dihydrocodeine |
May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. |
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Domperidone |
Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Domperidone. Monoamine Oxidase Inhibitors may diminish the therapeutic effect of Domperidone. Domperidone may diminish the therapeutic effect of Monoamine Oxidase Inhibitors. |
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Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Doxapram. |
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Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Doxylamine. Management: The US manufacturer of Diclegis (doxylamine/pyridoxine) and the manufacturers of Canadian doxylamine products specifically lists use with monoamine oxidase inhibitors as contraindicated. |
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EPINEPHrine (Nasal) |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of EPINEPHrine (Nasal). |
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Epinephrine (Racemic) |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Epinephrine (Racemic). |
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EPINEPHrine (Systemic) |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of EPINEPHrine (Systemic). |
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Ergot Derivatives |
May enhance the serotonergic effect of Serotonergic Agents (High Risk). 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. Exceptions: Nicergoline. |
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May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. |
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Gastrointestinal Agents (Prokinetic |
Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). |
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Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. |
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Itopride |
Anticholinergic Agents may diminish the therapeutic effect of Itopride. |
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May enhance the serotonergic effect of Serotonergic Agents (High Risk). 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. |
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May enhance the serotonergic effect of Serotonergic Agents (High Risk). 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. |
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Metaraminol |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Metaraminol. |
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May enhance the serotonergic effect of Serotonergic Agents (High Risk). 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. |
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Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. |
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Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. |
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Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Norepinephrine. |
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May enhance the serotonergic effect of Serotonergic Agents (High Risk). 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. |
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Opioid Agonists |
Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. |
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Opioid Agonists |
May enhance the serotonergic effect of Serotonergic Agents (High Risk). 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. Exceptions: FentaNYL; Meperidine; TraMADol. |
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Oxitriptan |
Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. 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. |
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Ramosetron |
Anticholinergic Agents may enhance the constipating effect of Ramosetron. |
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Ramosetron |
May enhance the serotonergic effect of Serotonergic Agents (High Risk). 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. |
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St John's Wort |
May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). 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. |
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Syrian Rue |
May enhance the serotonergic effect of Serotonergic Agents (High Risk). 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. |
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Thiazide and Thiazide-Like Diuretics |
Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. |
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Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. |
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Risk Factor D (Consider therapy modification) |
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Benzhydrocodone |
May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: The use of benzhydrocodone is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. |
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COMT Inhibitors |
May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. |
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DOPamine |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of DOPamine. Management: Initiate dopamine at no greater than one-tenth (1/10) of the usual dose in patients who are taking (or have taken within the last 2 to 3 weeks) monoamine oxidase inhibitors. Monitor for an exaggerated hypertensive response to dopamine. |
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Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of HYDROcodone. Management: Consider alternatives to this combination when possible. |
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Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. |
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Iomeprol |
Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. |
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Iopamidol |
Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. |
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Lithium |
Methylene Blue may enhance the serotonergic effect of Lithium. This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). |
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May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. |
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Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Remifentanil. Specifically, the risk for opioid toxicity (eg, respiratory depression) may be increased. Remifentanil may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: The use of remifentanil is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. |
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Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Reserpine. Existing MAOI therapy can result in paradoxical effects of added reserpine (e.g., excitation, hypertension). Management: Monoamine oxidase inhibitors (MAOIs) should be avoided or used with great caution in patients who are also receiving reserpine. |
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Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. |
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Serotonergic Opioids (High Risk) |
Methylene Blue may enhance the serotonergic effect of Serotonergic Opioids (High Risk). This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). |
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Risk Factor X (Avoid combination) |
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Aclidinium |
May enhance the anticholinergic effect of Anticholinergic Agents. |
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Alcohol (Ethyl |
May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. |
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Alpha-/Beta-Agonists (Indirect-Acting |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. |
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Alpha1-Agonists |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Alpha1Agonists. While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. |
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Amphetamines |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. |
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Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Apraclonidine. Monoamine Oxidase Inhibitors may increase the serum concentration of Apraclonidine. |
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Monoamine Oxidase Inhibitors may enhance the neurotoxic (central) effect of AtoMOXetine. |
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Atropine (Ophthalmic) |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Atropine (Ophthalmic). |
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Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Bezafibrate. |
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May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. |
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BuPROPion |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of BuPROPion. |
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May enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. |
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May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Management: Avoid concurrent use of carbamazepine during, or within 14 days of discontinuing, treatment with a monoamine oxidase inhibitor. |
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Cimetropium |
Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. |
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Codeine |
Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Codeine. |
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Cyclobenzaprine |
May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. |
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Cyproheptadine |
Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Cyproheptadine. Cyproheptadine may diminish the serotonergic effect of Monoamine Oxidase Inhibitors. |
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Dapoxetine |
May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. |
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Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Deutetrabenazine. |
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Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Dexmethylphenidate. |
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Monoamine Oxidase Inhibitors may enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. |
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Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Diethylpropion. |
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Diphenoxylate |
May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. |
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Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Droxidopa. |
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Anticholinergic Agents may enhance the constipating effect of Eluxadoline. |
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EPINEPHrine (Oral Inhalation |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). |
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Glycopyrrolate (Oral Inhalation |
Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). |
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Glycopyrronium (Topical |
May enhance the anticholinergic effect of Anticholinergic Agents. |
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Guanethidine |
May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. |
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Heroin |
Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Heroin. |
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Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of HYDROmorphone. |
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Indoramin |
Monoamine Oxidase Inhibitors may enhance the hypotensive effect of Indoramin. |
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Iobenguane Radiopharmaceutical Products |
Monoamine Oxidase Inhibitors may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. |
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Ipratropium (Oral Inhalation |
May enhance the anticholinergic effect of Anticholinergic Agents. |
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Isometheptene |
Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Isometheptene. |
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Levodopa-Containing Products |
May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Of particular concern is the development of hypertensive reactions when levodopa is used with nonselective MAOI. |
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Levomethadone |
May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. |
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Levonordefrin |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Levonordefrin. |
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Levosulpiride |
Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. |
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Linezolid |
Methylene Blue may enhance the serotonergic effect of Linezolid. This could result in serotonin syndrome. |
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May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. |
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Meptazinol |
Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Meptazinol. |
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Mequitazine |
Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Mequitazine. |
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May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. |
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Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Methyldopa. |
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Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Methylphenidate. |
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May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. |
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Mianserin |
Monoamine Oxidase Inhibitors may enhance the neurotoxic effect of Mianserin. |
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Monoamine Oxidase Inhibitors (Antidepressant) |
May enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. |
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Monoamine Oxidase Inhibitors (Type B) |
May enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. |
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Morphine (Systemic) |
Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Morphine (Systemic). |
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May enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. |
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Nefopam |
Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Nefopam. |
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Normethadone |
Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Normethadone. |
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Opium |
Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Opium. |
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Oxatomide |
May enhance the anticholinergic effect of Anticholinergic Agents. |
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May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. |
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May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. |
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Pheniramine |
May enhance the anticholinergic effect of Monoamine Oxidase Inhibitors. |
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Pholcodine |
May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. |
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Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Pizotifen. |
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Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. |
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Potassium Citrate |
Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. |
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Reboxetine |
Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Reboxetine. |
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Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. |
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Selective Serotonin Reuptake Inhibitors |
May enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Exceptions: Dapoxetine. |
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Serotonergic Non-Opioid CNS Depressants |
May enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. |
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Serotonin 5-HT1D Receptor Agonists (Triptans |
May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase the serum concentration of Serotonin 5-HT1D Receptor Agonists (Triptans). |
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Serotonin/Norepinephrine Reuptake Inhibitors |
May enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. |
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Solriamfetol |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Solriamfetol. |
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May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Specifically, the risk for serotonin syndrome or opioid toxicities (eg, respiratory depression, coma) may be increased. Management: Sufentanil should not be used with monoamine oxidase (MAO) inhibitors (or within 14 days of stopping an MAO inhibitor) due to the potential for serotonin syndrome and/or excessive CNS depression. |
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Tapentadol |
May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Specifically, the additive effects of norepinephrine may lead to adverse cardiovascular effects. Tapentadol may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. |
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May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. |
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Tetrahydrozoline (Nasal |
Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Tetrahydrozoline (Nasal). |
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Tianeptine |
May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. |
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Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. |
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Tricyclic Antidepressants |
May enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. |
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Tryptophan |
May enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. |
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May enhance the anticholinergic effect of Anticholinergic Agents. |
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May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. |
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Monitoring parameters:
Blood Tests & Measurements:
- Arterial blood gases: To check oxygen and carbon dioxide levels in the blood.
- CBC (Complete Blood Count): To check overall health and detect disorders.
- Methemoglobin levels: Use co-oximetry as it gives a direct and accurate measure of these levels.
Heart & Lungs:
- Cardiac monitoring: Especially for those with existing lung or heart diseases.
- Pulse oximeter: Measures oxygen in the blood but isn't accurate when methemoglobin levels are too high (>35%) or after taking methylene blue.
- Look out for symptoms of methemoglobinemia: Such as pale skin, bluish skin or lips, nausea, muscle weakness, dizziness, confusion, agitation, fast breathing, and fast heart rate.
Kidney Health:
- Renal function: To see how well the kidneys are working.
Oxygen Level:
- Transcutaneous O2 saturation: Measures the oxygen level through the skin.
General:
- Monitor the infusion site: To ensure no complications arise from the site where the medicine is injected.
How to administer Methylene blue?
For IV (Into the Vein):
- Generic: Inject directly into the vein without diluting. Do this slowly over a few minutes.
- ProvayBlue: Inject into the vein over 5 to 30 minutes. Don't inject just under the skin. You can dilute it with D5W (a type of IV fluid) before injection to reduce pain.
- Warning about Vesicant: Methylene blue can cause damage if it leaks out of the vein. Make sure the needle or tube is correctly placed.
- If it leaks (extravasation): Stop the drip, but leave the needle in place. Try to pull out the leaked drug without flushing the line. Remove the needle, lift the limb, and put warm compresses on the area.
- For damage: Put a 1-inch strip of 2% nitroglycerin ointment on the hurt area. You can do this every 8 hours if needed.
- If the infusion is long or continuous: Use a main vein (central line) because of the risk of the drug leaking out and causing harm.
For Ifosfamide-induced encephalopathy (special use):
- IV: Inject directly into the vein slowly over at least 5 minutes. You can dilute it and give it over 5 to 30 minutes. Consider giving sugar (dextrose), especially if the patient has low blood sugar.
- Oral: Can be mixed in fruit juice to hide the taste.
Topical (On the Skin or Surface):
- Diagnostic: Spray or directly apply the solution to the area being looked at. The exact method might change based on the procedure.
- For toenail fungus: Put on the affected nail, wait 3 minutes, then use light treatment (photodynamic therapy).
Intraparenchymal (Directly into Tissue, Off-Label Use):
- Inject it straight into the tissue of interest, like a lymph node.
What NOT to do:
- Do NOT inject just under the skin or into the spine.
Mechanism of action of Methylene Blue:
For Methemoglobin:
- At low amounts, methylene blue helps turn methemoglobin back into regular hemoglobin.
- But, at high amounts, it does the opposite, turning the iron in regular hemoglobin into a form that makes methemoglobin.
- When treating cyanide poisoning, methylene blue binds with cyanide to form a compound that stops cyanide from harming cells.
For Vasoplegia Syndrome (a condition where blood vessels don't tighten the way they should):
- Methylene blue might restore the normal tightness of blood vessels by directly blocking certain enzymes like eNOS and possibly iNOS. These enzymes, when active, can make blood vessels relax too much.
- The way it does this is by affecting the iron in these enzymes.
- Methylene blue also stops another process that makes blood vessels relax. It blocks the creation of a molecule called cGMP by interfering with another enzyme, guanylate cyclase. This helps reduce the relaxation of blood vessels.
Effect Timing:
- Methemoglobin Reduction: After an IV injection, it starts working in about 30 to 60 minutes.
Absorption:
- Oral: The body absorbs between 53% to 97% of the dose taken by mouth.
Distribution:
- It spreads out in the body to a volume of about 255 L ± 58 L.
Protein Binding:
- About 94% of it binds to proteins in the blood.
Metabolism:
- It likely goes through an initial metabolism or distribution process.
- It gets changed in the body to another form called leukomethylene blue.
Half-life (time taken for the drug concentration to reduce by half):
- It's not exactly clear, but it's around 5 to 6.5 hours. For the ProvayBlue brand, it's about 24 hours.
Time to Maximum Level:
- Oral: Reaches its highest level in the blood in about 1 to 2 hours.
- IV: Reaches its highest level in the blood in about 30 minutes.
Excretion (how the drug leaves the body):
- Generic: Leaves the body through bile, feces, and urine. About 33% goes out in urine as leukomethylene blue.
- ProvayBlue: About 40% leaves the body through urine unchanged.
International Brands of Methylene blue:
- ProvayBlue
- Blumet
- Proveblue
Methylene blue Brand Names in Pakistan:
Update soon.
 Injection.webp)