Top 6 Benefits of Methylene Blue + Dosage & Side Effects

Anti-Aging Potentials of Methylene Blue for Human Skin Longevity

Top 6 Benefits of Methylene Blue + Dosage & Side Effects

Oxidative stress is the major cause of skin aging that includes wrinkles, pigmentation, and weakened wound healing ability. Application of antioxidants in skin care is well accepted as an effective approach to delay the skin aging process.

Methylene blue (MB), a traditional mitochondrial-targeting antioxidant, showed a potent ROS scavenging efficacy in cultured human skin fibroblasts derived from healthy donors and from patients with progeria, a genetic premature aging disease.

In comparison with other widely used general and mitochondrial-targeting antioxidants, we found that MB was more effective in stimulating skin fibroblast proliferation and delaying cellular senescence.

The skin irritation test, performed on an in vitro reconstructed 3D human skin model, indicated that MB was safe for long-term use, and did not cause irritation even at high concentrations.

Application of MB to this 3D skin model further demonstrated that MB improved skin viability, promoted wound healing and increased skin hydration and dermis thickness. Gene expression analysis showed that MB treatment altered the expression of a subset of extracellular matrix proteins in the skin, including upregulation of elastin and collagen 2A1, two essential components for healthy skin. Altogether, our study suggests that MB has a great potential for skin care.

Skin is the largest and the most visible organ of the human body. Aged skin is biologically characterized by the flattening of the dermal-epidermal junction and a general atrophy of the extracellular matrix (ECM) with disorganized and reduced collagen and elastin1, 2.

There are two different types of skin aging, intrinsic and extrinsic, caused by physiological and environmental factors, respectively1,2,3. The intrinsic skin aging reflects the naturally occurring changes in the skin as we age, and is clinically manifested as fine wrinkles on the dry skin.

Extrinsic skin aging is an accelerated form due to exposure of the skin to sunlight and/or air pollution and is phenotypically demonstrated as dry, rough, pigmented and abraded skin especially in the face and hands.

Although they present with different clinical features, both types of skin aging are due in part to the oxidative damage caused by free radicals.

By balancing free radical production and antioxidant neutralization, cells normally keep reactive oxygen species (ROS) at low levels4.

As we age, a combination of the accumulation of ROS and the reduced ROS scavenging capacity leads to increased oxidative stress that results in the damages of macromolecules in organs.

When the skin is routinely exposed to stressful factors from the environment, such as UV radiation, smoke, and pollutants, an elevated number of free radicals will be produced which accelerate skin aging2.

The over-abundance of ROS decreases collagen synthesis and increases collagen breakdown by stimulating matrix metalloproteinase (MMP) expression, eventually causing the alterations of the dermal matrix5, 6. this ROS theory, an effective approach to delay skin aging is to externally supply antioxidants through skincare products to either suppress the production or neutralize the excess free radicals6.

Methylene blue (MB), a century-old drug first synthesized in 1876, has been used in clinical medicine for treatment of diverse aliments, e.g. methemoglobinemia, malaria, vasoplegia, septic shock, cancer chemotherapy, and Alzheimer’s disease7,8,9.

MB is a diaminophenothiazine with a low redox potential of 11 mV. This property allows for efficient cycling between the oxidized form MB and the reduced form MBH2, which facilitates electron transport in the mitochondria and reduces mitochondrial superoxide production.

It also induces the expression of mitochondrial complexes II & IV9, 10.

Additionally, MB is highly permeable in biological membranes because of its solubility in both water and organic solvent, which permits it to freely enter the intracellular compartments mitochondria, lysosomes and the nucleus10,11,12.

MB has recently drawn attention not only for its neuroprotective effects on treating Alzheimer’s disease7, 9 but also for its anti-aging properties10, 13, 14. Previous studies have shown that upon the treatment with MB, normal fibroblasts have displayed increased cellular lifespan, improved cell proliferation and reduced expression of p16, a biomarker of physiological aging9, 10.

In addition, MB extended the life span of female mice by 6% when included in food14.

Recently we have shown that MB at nanomolar concentration rescued abnormal nuclear and mitochondrial phenotypes, stimulated cell proliferation and delayed senescence in skin fibroblasts from patients with Hutchinson-Gilford progeria syndrome (HGPS, progeria), a rare genetic disorder of accelerated aging13.

these observations, we speculate that MB may effectively protect skin from oxidative stress and delay skin aging. To test this idea, here, we investigated the anti-aging effects of MB in human skin using 2D primary dermal fibroblasts and reconstructed 3D human skin models.

To evaluate the effectiveness of MB as an antioxidant, we first compared the effects of MB treatment with the effects of three other popular ROS scavengers, specifically, N-Acetyl-L-cysteine (NAC), MitoQ, and MitoTEMPO (mTEM). (Supplemental Tables 1 and 2).

NAC is a widely used, general ROS scavenger that acts as a precursor of glutathione synthesis and stimulates certain enzymes involved in glutathione regeneration15. MitoQ is a modified coenzyme Q10 with a selective accumulation in mitochondria16.

mTEM is a mitochondrial-targeting superoxide dismutase mimetic that possesses superoxide and alkyl radical scavenging properties17, 18. In order to evaluate the effects of each antioxidant, primary skin fibroblasts from a middle-aged normal individual and an HGPS patient were treated for 4 weeks.

Mitochondrial ROS (indicated by MitoSOX), the main resource of the total cellular ROS, was then measured through FACS analysis. HGPS cells were used as an accelerated model for normal aging since they share many features in common with physiological aging19 (Supplemental Tables 1 and 2).

NAC was supplemented in the culture medium at a concentration of 100 μM according to a previous publication20. In contrast to the anti-aging effects of MB, long-term treatment with NAC did not reduce mitochondrial ROS level and appeared to delay cell proliferation in both normal and HGPS cells (Fig. 1A and B).

To our surprise, treatment with MitoQ at 100 nM, as suggested by previous studies16, 21, did not reduce but drastically increased mitochondrial ROS level (Fig. 1C). Additionally, MitoQ treatment did not promote but inhibited cell proliferation in both normal and HGPS cells (Fig. 1D).

Treatment of mTEM at 100 nM showed moderate ROS scavenging effects on HGPS cells (Fig. 1E). It also moderately promoted normal cell proliferation but failed to stimulate HGPS cells (Fig. 1F).

Amongst all four tested anti-oxidants, MB was the most effective in reducing mitochondrial ROS and promoting skin cell proliferation (Fig. 1A–F, Supplemental Table 2).

Figure 1

MB is a more potent ROS scavenger than NAC, MitoQ and mTEM. (A) Comparison of mitochondrial specific superoxide (MitoSOX) levels in normal and HGPS fibroblasts treated with vehicle, 100 nM MB or 100 μM NAC for four weeks.

(B) Growth curves of normal and HGPS fibroblasts during the four-week treatment with vehicle, 100 nM MB or 100 μM NAC. (C) Comparison of MitoSox levels in normal and HGPS fibroblasts treated with vehicle, 100 nM MB or 100 nM MitoQ for four weeks.

(D) Growth curves of normal and HGPS fibroblasts during the four-week treatment with vehicle, 100 nM MB or 100 nM MitoQ. (E) Comparison of MitoSox levels in normal and HGPS fibroblasts treated with vehicle, 100 nM MB or 100 nM mTEM for four weeks.

(F) Growth curves of normal and HGPS fibroblasts during the four-week treatment with vehicle, 100 nM MB or 100 nM mTEM. (*p

Source: https://www.nature.com/articles/s41598-017-02419-3

Top 6 Benefits of Methylene Blue + Dosage & Side Effects

Top 6 Benefits of Methylene Blue + Dosage & Side Effects

Methylene blue, a compound used to treat a blood disorder called methemoglobinemia, has a reputation for being a cognitive and mitochondrial enhancer. But how good is the evidence for these secondary benefits? Learn more here.

What is Methylene Blue?

Methylene blue (MB), also known as methylthioninium chloride, is a bioactive substance and a blue dye.

Some researchers believe that it can directly improve cellular and mitochondrial function and decrease the production of proteins linked to Alzheimer’s. It is also being studied for its potential to inhibit monoamine oxidase (MAO), nitric oxide (NO) synthase, and guanylate cyclase [1, 2].

Proponents:

  • Used to treat methemoglobinemia
  • Improves mitochondrial function
  • Improves memory consolidation
  • Protects nerve function
  • Anti-microbial

Skeptics:

  • Possible negative impact on the gut microbiome at large doses
  • May interact with monoamine oxidase inhibitors (MAOIs)
  • Increases blood pressure
  • Poor tasting

Mitochondrial Mechanisms

At low doses, methylene blue (MB) has been shown to protect the brain from disease by acting as an electron donor to complex I-IV of the mitochondria which increases adenosine triphosphate (ATP) production. ATP is the currency of life and the energy that powers humans. If our production of ATP declines, our physical and mental performance declines. Even healthy individuals can benefit from a boost in ATP production [1].

More specifically, MB can donate electrons to coenzyme Q and possibly to cytochrome C, thus increasing cytochrome oxidase (complex IV) activity and oxygen consumption. MB also increases heme synthesis [3].

MB is also able to stimulate glucose metabolism in conditions without oxygen and increase the amount of NAD+ produced by mitochondria [4, 5].

Low dose MB also acts as an antioxidant in mitochondria.

MB interacts with oxygen to form water, which would decrease the superoxide radicals produced during the process of oxidative phosphorylation.

MB can also trap leaking electrons produced by mitochondrial inhibitors and preserve the metabolic rate by bypassing blocked points of electron flow, thus improving mitochondrial respiration [1].

However, at high concentrations, MB can promoteoxidative stress. Therefore, it is expected that low MB doses or concentrations will be, in general, more effective than large ones at facilitating physiological effects within mitochondria.

In fact, at high local concentrations, MB can potentially “steal” electrons away from the electron transport chain complexes, disrupting the redox balance and acting as a pro-oxidant.

This is thought to a result of excess electrons saturating the electron transport chain, producing reactive oxygen species (ROS) [1, 2].

In a rat model of cerebral ischemia, MB was able to speed up the removal of damaged mitochondria from a cell prior to cell death (mitophagy) [6].

MB is also capable of reducing the mitochondrial damaging effects of amyloid beta in animal models [7].

1) Methemoglobinemia

Methemoglobinemia is a blood disorder where an abnormal amount of methemoglobin is produced. Methemoglobin is an oxidized type of hemoglobin (carries oxygen throughout the body) that does not release oxygen efficiently [8].

This condition can cause troublesome symptoms blue skin, shortness of breath, weakness, headache, and psychological changes. Severe, untreated cases can cause changes in heart rhythm, coma, and death [9].

Methylene blue (MB) binds to methemoglobin and converts it to a more efficient form, thereby improving the symptoms of methemoglobinemia [10].

A doctor may administer methylene blue intravenously to patients with methemoglobinemia. Do not under any circumstances attempt this treatment yourself. If you have symptoms of methemoglobinemia, seek medical attention immediately.

2) Septic Shock

During septic shock, blood pressure can drop dangerously low. Methylene blue has been found to restore blood pressure and heart function during these dangerous episodes. While methylene blue may prevent hypotension on its own, some researchers believe that it is most promising as a complement to other medications used to treat septic shock [11, 12, 13].

The evidence for methylene blue’s effectiveness against the hypotension and heart problems associated with septic shock is quite strong. However, it has not been approved by the FDA for this purpose, and clinical trials are still ongoing [14].

3) Antimicrobial Action

Methylene blue (MB) was first used in 1891 to treat malaria, and it is considered safe and effective. Current studies have been investigating whether MB treatment alongside other antiparasitic drugs could prevent the parasites from developing drug resistance [15].

Photodynamic therapy using the light-activated antimicrobial agent, MB kills methicillin-resistant Staphylococcus aureus (MRSA) in superficial and deep excisional wounds [12].

MB in combination with light also inactivates viral nucleic acid of hepatitis-C and human immunodeficiency virus (HIV-1) and treats cases of resistant plaque psoriasis [12].

MB is an antifungal agent and may inhibit candida by causing mitochondrial dysfunction in this species [16].

Potential Benefits (Possibly Effective)

Methylene blue has not been approved by the FDA for the purpose of cognitive enhancement, neuroprotection, or any medical purpose other than methemoglobinemia.

Despite promising early results, existing clinical studies have not been large or powerful enough to determine effectiveness for any of the potential benefits in this section.

Talk to your doctor before attempting to use methylene blue.

Cognitive Performance

A clinical trial of twenty-six adults was conducted to investigate whether low doses (0.5 – 4.0 mg/kg) of methylene blue (MB) could increase brain activity and improve performance in memory tasks [17].

In this randomized study, low-dose MB increased functional MR imaging activity during sustained attention and short-term memory tasks and potentiated memory retrieval [17].

Compared with control subjects, oral administration MB increased functional MR imaging response during the encoding, maintenance, and retrieval components of a short-term memory task in multiple clusters in the prefrontal, parietal, and occipital cortex. MB was also associated with a 7% increase in correct responses during memory retrieval [17].

In rat hippocampal slices, glutamate-mediated synaptic transmission is abolished by relatively high concentrations (5 – 50 mM) of MB [18].

Neurodegeneration

Methylene blue (MB) has been investigated in people with Alzheimer’s dementia, Some researchers believe that it could affect neurodegeneration via the inhibition of tau protein aggregation and amyloid formation [19, 20, 21].

Early studies have also begun to investigate methylene blue in models of Parkinson’s and Huntington’s diseases. However, these have not produced clinical evidence so far [22, 23].

Phobias

Adult participants displaying marked claustrophobic fear were randomly assigned to double-blind administration of 260 mg of MB or administration of placebo immediately following six 5-minute extinction trials in an enclosed chamber [24].

The study concluded that MB enhances memory and the retention of fear extinction when administered after a successful exposure session but may have a deleterious effect on extinction when administered after an unsuccessful exposure session [24].

It is unclear whether these findings can be repeated in people with other types of phobias. Further clinical trials are needed.

Early Cell Studies (Lacking Evidence)

No clinical evidence supports the use of methylene blue for any of the conditions listed in this section. Below is a summary of the existing cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit. As always, talk to your doctor before using methylene blue.

5) Depression

Methylene Blue (MB) was a potent monoamine oxidase inhibitor (MAOI) in a laboratory study [25].

MB inhibited MAO-A more than MAO-B, but it inhibited both at large doses. The researchers cautioned that MB should therefore not be combined with antidepressants. At doses exceeding 5 mg/kg, it may cause serious serotonin toxicity/serotonin syndrome, if combined with any SSRIs or other serotonin reuptake inhibitor [25, 26].

Because this study was undertaken via direct exposure in a glass dish, it is currently unclear whether MB could work as an antidepressant on its own. Future clinical studies will clarify. For the time being, we do not recommend using methylene blue for the purposes of improving depression. If you have depressive symptoms, talk to your doctor about better-studied solutions.

6) Skin Aging

A study showed MB to be an effective antioxidant in connective tissue cells. This was true whether the cells were taken from healthy donors or from patients with a premature aging disease [27].

MB was more effective at building connective tissue and delaying cell death than other common mitochondrial-targeting antioxidants [27].

MB treatment changed the expression of some of the proteins in the skin. For example, the expression of elastin and collagen, essential elements of healthy skin, was increased [27].

These effects have only been observed in cell and tissue studies so far. Animal and human trials will determine whether topical application or oral doses could have the same effect.

Dosage

The FDA has only approved methylene blue for the treatment of methemoglobinemia, and this treatment can only be carried out by a medical professional. There is no safe and effective dose for any other purpose because no sufficiently powerful study has been undertaken to find one. That being said, we can look at the doses which have provided benefits in clinical studies.

Various studies have used between 1 and 4 mg/kg, depending on the source [18].

Most side effects of MB appear to be dose-dependent and have not occurred with doses of less than 2 mg/ kg, a dose range that is widely used in clinical trials [18].

Side Effects

Methylene blue (MB) is contraindicated in patients who have developed hypersensitivity reactions to it and in severe renal insufficiency. It is relatively contraindicated in G6PD deficient patients as it can cause severe hemolysis and also in patients with Heinz body anemia [12].

As mentioned, it should not be taken with an SSRI or serotonin increasing drug, if you’re taking a high dosage [12].

Babies are particularly prone to the adverse effects of MB. It causes hyperbilirubinemia, meth-Hemoglobin formation, hemolytic anemia, respiratory distress, pulmonary edema, phototoxicity and bluish discoloration of tracheal secretions and urine [12].

MB also interferes with the pulse oximeter’s light emission resulting in falsely depressed oxygen saturation reading [12].

It may also cause higher blood pressure [12].

Safety Notes

Even pharmaceutical (USP) grade methylene blue may contain impurities such as arsenic, aluminum, cadmium, mercury, and lead. At higher doses, some researchers have warned of the danger of these contaminants accumulating in the patient’s tissues [3].

Industrial-grade and chemical-grade MB sold as a dye or stain can consist of more than 8% or 11% of various contaminants (NTP, 2008, Sigma Chemical Co, St. Louis, MO) and should not be administered to humans or animals [3].

For example, commercial chemical suppliers routinely warn that their non-USP MB products are of a chemical grade not suitable for use in living applications [3].

When combined with rivastigmine, a cholinesterase inhibitor, the effect of MB was potentiated. To avoid unexpected interactions, talk to your doctor before using methylene blue [18].

Source: https://selfhacked.com/blog/methylene-blue-the-cheapest-cognitive-enhancer/

Methylene Blue: Revisited

Top 6 Benefits of Methylene Blue + Dosage & Side Effects

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Side Effects of Methylene Blue (Methylene Blue Injection), Warnings, Uses

Top 6 Benefits of Methylene Blue + Dosage & Side Effects

Methylene Blue Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 11/18/2016

Methylene Blue (methylene blue) injection is a form of hemoglobin, a substance in blood, used to treat methemoglobinemia. Methylene Blue oral is used to treat methemoglobinemia and urinary tract infections.

Methylene Blue is also used as a dye or staining agent to make certain body fluids and tissues easier to view during surgery or on an x-ray or other diagnostic exam. Methylene Blue is available in generic form.

Common side effects of Methylene Blue include abnormal urine or stool color. Less frequent side effects of Methylene Blue include:

  • mild bladder irritation,
  • dizziness,
  • headache,
  • increased sweating,
  • nausea,
  • vomiting,
  • abdominal pain,
  • diarrhea,
  • upset stomach,
  • frequent urination, or
  • stomach cramps.

Side effects of large doses of Methylene Blue include chest pain and confusion.

Methylene Blue is dosed 0.045 to 0.09 mL per pound of body weight. Methylene Blue may interact with acetazolamide, antacids, sodium bicarbonate, or diuretics (water pills). Tell your doctor all medications you are taking.

Methylene blue may cause harm to a fetus, but the medication may sometimes be used during pregnancy. Your doctor will determine whether or not this medication is safe. Tell your doctor if you are pregnant.

It is not known whether Methylene Blue passes into breast milk or if it could harm a nursing baby. Consult your doctor before breastfeeding.

Our Methylene Blue (methylene blue injection) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

About how much does an adult human brain weigh? See Answer Methylene Blue Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers right away if you have:

  • confusion or weakness;
  • pale or yellowed skin;
  • dark colored urine;
  • fever; or
  • high levels of serotonin in the body–agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting.

Common side effects may include:

  • pain in your arms or legs;
  • blue or green urine;
  • altered sense of taste;
  • headache, dizziness;
  • sweating, skin discoloration;
  • nausea; or
  • feeling hot.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Methylene Blue (Methylene Blue Injection)

Digestive Disorders: Common Misconceptions See Slideshow Related Resources for Methylene Blue

© Methylene Blue Patient Information is supplied by Cerner Multum, Inc. and Methylene Blue Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

About how much does an adult human brain weigh? See Answer

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Source: https://www.rxlist.com/methylene-blue-side-effects-drug-center.htm

Provayblue (methylene blue) dosing, indications, interactions, adverse effects, and more

Top 6 Benefits of Methylene Blue + Dosage & Side Effects

  • 5mg/mL (50mg/10mL) single-dose ampule

1 mg/kg IV over 5-30 minutes  

If methemoglobin level remains >30% or if clinical symptoms persist, repeat dose up to 1 mg/kg 1 hr after the first dose

Ifosfamide-induced Encephalopathy (Off-Label)

Prevention: 50 mg IVq6-8hr

Treatment: 50 mg once or q4-8hr until symptoms resolve

Dosing Considerations

Methemoglobinemia indication is approved under accelerated approval

Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials

Minor

All Interactions Sort By: SeverityName

Pain in extremity (84%)

Chromaturia (74%)

Dysgeusia (20%)

Feeling hot (17%)

Dizziness (16%)

Hyperhidrosis (13%)

Nausea (13%)

Skin discoloration (13%)

1-10%

Headache (10%)

Musculoskeletal pain (9%)

Paresthesia oral (9%)

Paresthesia (9%)

Infusion site pain (6%)

Feeling cold (6%)

Pallor (5%)

Contact dermatitis (5%)

Syncope (4%)

Pruritus (4%)

Anxiety (4%)

Decreased appetite (4%)

Chest discomfort (4%)

Back pain (2%)

Cold sweat (2%)

Dizziness postural (2%)

Muscle spasms (2%)

Presyncope (2%)

Arthralgia (2%)

Chills (2%)

Diarrhea (2%)

Discomfort (2%)

Dyspnea (2%)

Erythema (2%)

Hypoesthesia oral (2%)

Infusion site discomfort (2%)

Limb discomfort (2%)

Oral discomfort (2%)

Catheter site pain (2%)

Ecchymosis (2%)

Severe hypersensitivity reactions to methylene blue or any other thiazine dye

Patients with glucose-6-phosphate dehydrogenase deficiency (G6PD) due to the risk of hemolytic anemia

Cautions

Hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria, bronchospasm) reported; monitor vital signs and ECG during treatment; if severe hypersensitivity occurs, discontinue drug and initiate supportive treatment (see Administration and Contraindications)

Methemoglobinemia may not resolve or may rebound after response to treatment due to aryl amines (eg, aniline, sulfa drugs [dapsone]); monitor response to therapy with through resolution of methemoglobinemia

Patients with G6PD deficiency may not reduce methylene blue to its active form in vivo and thereby be ineffective (see Contraindications)

Hemolysis can occur during treatment of methemoglobinemia with methylene blue and anemia may occur; hemolytic anemia may not be apparent until ≥1 day after

The presence of methylene blue in the blood may result in an underestimation of the oxygen saturation reading by pulse oximetry

A fall in the Bispectral Index (BIS) has been reported following administration of methylene blue class products; if methylene blue is administered during surgery, alternative methods for assessing the depth of anesthesia should be employed

May cause confusion, dizziness and disturbances in vision; patients should refrain from driving or engaging in hazardous occupations or activities

Methylene blue is a blue dye which passes freely into the urine and may interfere with the interpretation of any urine test which relies on a blue indicator (eg, dipstick test for leucocyte esterase)

Methylene blue is extensively metabolized in the liver; monitor patients with any hepatic impairment for toxicities and potential drug interactions for an extended period of time following treatment

Approximately 40% of methylene blue is excreted by the kidneys; patients with any renal impairment should be monitored for toxicities and potential drug interactions for an extended period of time following treatment

Serotonin syndrome

  • Avoid coadministration with serotonergic psychiatric drugs (eg, SSRIs, SNRIs, TCAs, MAOIs) due to increased risk of serotonin syndrome, unless indicated for life-threatening conditions or when urgent treatment is required such as emergency treatment of methemoglobinemia, ifosfamide-induced encephalopathy, or cyanide poisoning; methylene blue may increase serotonin CNS levels by MAO-A inhibition
  • If methylene blue must be administered to a patient currently taking a serotonergic drug, stop serotonergic drug immediately and monitor for CNS toxicity; serotonergic therapy may be resumed 24 hours after the last dose of methylene blue, or after 2 weeks of monitoring (5 weeks if fluoxetine was taken), whichever comes first
  • If possible, discontinue serotonergic psychiatric medication at least 2 weeks in advance of methylene blue treatment; fluoxetine, should be stopped at least 5 weeks in advance due to longer half-life
  • Also see Black Box Warnings

May cause fetal harm when administered to a pregnant woman

Intra-amniotic injection of pregnant women with a methylene blue class product during the second trimester was associated with neonatal intestinal atresia and fetal death

Lactation

There is no information regarding the presence of methylene blue in human milk, the effects on the breastfed infant, or the effects on milk production

Because of the potential for serious adverse reactions, including genotoxicity discontinue breastfeeding during and for up to 8 days after treatment

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.

Methylene blue is a water soluble thiazine dye that promotes a nonenyzmatic redox conversion of metHb to hemoglobin

In situ, methylene blue is first converted to leucomethylene blue (LMB) via NADPH reductase; it is the LMB molecule which then reduces the ferric iron of metHb to the ferrous state of normal hemoglobin

It also combines with cyanide to form cyanmethemoglobin, which prevents the interference of cyanide with the cytochrome system

Absorption

Peak plasma concentration: 2,917 ng/mL

AUC: 13,977 ng·hr/mL

Metabolism

Metabolized by CYPs 1A2, 2C19 and 2D6 in vitro; however, the predominant in vitro pathway appears to be UGT-mediated conjugation by multiple UGT enzymes, including UGT1A4 and UGT1A9

Elimination

Half-life: 24 hr

Excretion: 40% unchanged in urine

0.9% NaCl (reduces methylene blue solubility)

Incompatible with caustic alkalis, iodides, dichromates, and oxidizing or reducing substances

IV Preparation

Solution is hypotonic and may be diluted before use in a solution of 50 mL D5W to avoid local pain, particularly in the pediatric population

Use the diluted solution immediately after preparation

Do not mix with 0.9% NaCl, because it has been demonstrated that chloride reduces the solubility of methylene blue

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit

IV Administration

Ensure patent venous access prior to administration

For IV use only, do not administer SC or IM

Administer IV slowly over 5-30 minutes

If the methemoglobin level remains >30% or if clinical signs and symptoms persist, a repeat dose of 1 mg/kg may be given 1 hr after the first dose

If methemoglobinemia does not resolve after 2 doses, consider initiating alternative interventions for treatment of methemoglobinemia

Monitor vital signs, ECG, and methemoglobin levels during treatment and through resolution of methemoglobinemia

Storage

Store at 20-25°C (68-77°F)

Do not refrigerate or freeze

Keep ampule in original container to protect from light

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

Medscape prescription drug monographs are FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.

Source: https://reference.medscape.com/drug/provayblue-methylene-blue-343739

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