Consumer medicine information

Methylene Blue Injection 50 mg in 5 mL

Methylene blue trihydrate

BRAND INFORMATION

Brand name

Methylene Blue Injection

Active ingredient

Methylene blue trihydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Methylene Blue Injection 50 mg in 5 mL.

SUMMARY CMI

Methylene Blue Injection

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why is Methylene Blue Injection being used?

Methylene Blue Injection contains the active ingredient methylene blue. Methylene Blue Injection helps with problems related to abnormal blood pigment levels, which can cause trouble in blood carrying oxygen effectively around the body.

For more information, see Section 1. Why is Methylene Blue Injection being used? in the full CMI.

2. What should I know before Methylene Blue Injection is given?

You should not be given Methylene Blue Injection if you have ever had an allergic reaction to methylene blue any other dyes, or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or are breastfeeding.

For more information, see Section 2. What should I know before Methylene Blue Injection is given? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Methylene Blue Injection and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How is Methylene Blue Injection given?

  • Methylene Blue Injection must only be given by a doctor or nurse.
  • Your doctor will decide what dose of Methylene Blue Injection you will receive and for how long you will receive it.

More information can be found in Section 4. How is Methylene Blue Injection given? in the full CMI.

5. What should I know while Methylene Blue Injection is being given?

Things you should do
  • Remind any doctor, dentist, or pharmacist you visit that you are using Methylene Blue Injection
  • Keep all of your doctor's appointments
  • Call your doctor straight away if you become pregnant while being given this medicine
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how Methylene Blue Injection affects you
  • Methylene Blue Injection may cause dizziness in some people
Drinking alcohol
  • Tell your doctor if you drink alcohol
Looking after your medicine
  • Methylene Blue Injection will be stored in the surgery, pharmacy or ward of a hospital
  • The injection is kept in a cool, dry place where the temperature is below 25°C

For more information, see Section 5. What should I know while Methylene Blue Injection is being given? in the full CMI.

6. Are there any side effects?

Methylene Blue Injection will cause a blue colour in your urine or bowel motions. Other common side effects include nausea, vomiting, diarrhoea, headaches, dizziness, redness or swelling at the injection site, change in the colour of your skin and/or saliva, increased sensitivity to the sun or light, dilated pupils and pain when passing urine. You may need urgent medical attention if you experience any of the following serious side effects: chest pain, fast or irregular heartbeat, problems with speaking, writing or reading, allergic reaction, low blood pressure, anaemia.

This is not a full list of side effects. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Methylene Blue Injection

Active ingredient: 50 mg/5 mL methylene blue


Consumer Medicine Information (CMI)

This leaflet provides important information about using Methylene Blue Injection. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Methylene Blue Injection.

Where to find information in this leaflet:

1. Why is Methylene Blue Injection being used?
2. What should I know before Methylene Blue Injection is given?
3. What if I am taking other medicines?
4. How is Methylene Blue Injection given?
5. What should I know while Methylene Blue Injection is being given?
6. Are there any side effects?
7. Product details

1. Why is Methylene Blue Injection being used?

Methylene Blue Injection contains the active ingredient methylene blue. Methylene Blue Injection belongs to a group of medicines called dyes.

Methylene Blue Injection helps with problems related to abnormal blood pigment levels, which can cause trouble in blood carrying oxygen effectively around the body.

Methylene Blue Injection is also used:

  • to stain bacteria to make them easier to see
  • as a visible dye to help in the diagnosis of a number of conditions
  • as a stain to dye certain body tissues during surgery

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

2. What should I know before Methylene Blue Injection is given?

Warnings

You should not be given Methylene Blue Injection if:

  • you are allergic to methylene blue, or any of the ingredients listed at the end of this leaflet
  • you are allergic to any other dyes
  • you have severe renal impairment
  • you have an inherited condition called glucose-6-phosphate dehydrogenase deficiency
  • you have cyanide poisoning
  • you have chlorate poisoning

Tell your doctor if you:

  • have any other allergies
  • have any medical conditions, such as:
    - kidney problems
    - diabetes. Methylene Blue Injection may need to be diluted with glucose solution. The amount of glucose may affect your blood glucose levels
  • take any medicines for any other condition
  • have aniline poisoning

Methylene Blue Injection is not recommended for long-term use.

Tell your doctor if you have been given methylene blue before and for how long.

The use of methylene blue in infants under 4 months of age is not recommended. Your doctor will discuss the use of this medicine in infants younger than 4 months if needed.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

You should not be given this medicine if you are pregnant or plan to become pregnant.

It may affect your developing baby if you are given Methylene Blue Injection during pregnancy.

Tell your doctor if you are breastfeeding. Your doctor can discuss with you the risks and benefits involved.

Light exposure

Methylene Blue Injection can cause a photosensitivity reaction in the skin (sunburn-like reaction) when exposed to strong light sources, such as lights in operating rooms. Protective measures against light exposure should be taken.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with Methylene Blue

Injection and affect how it works. These include:

  • serotonin reuptake inhibitors (SRIs): medicines used to treat depression, including Prozac, Zoloft and Aropax and others
  • opioids: medicines used to treat pain, including tramadol, pethidine, and dextromethorphan
  • dapsone – a medicine used to treat bacterial infections

These medicines may be affected by Methylene Blue Injection or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while being given this medicine.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Methylene Blue Injection.

4. How is Methylene Blue Injection given?

How much is given

  • Your doctor will decide how much Methylene Blue you will receive.
  • This depends on your medical condition and other factors such as your weight.
  • Sometimes only a single dose of Methylene Blue Injection is required.

When Methylene Blue Injection is given

  • Your doctor will decide when and for how long you will receive Methylene Blue Injection.

How Methylene Blue Injection is given

  • Methylene Blue Injection must only be given by a doctor or nurse.
  • Methylene Blue Injection can be given in two ways depending upon what it is being used for. It can be given as an injection into a vein or by mouth.

If Methylene Blue Injection is missed

Methylene Blue Injection should be given by your doctor or nurse. If you miss the appointment for your dose, speak with your doctor or nurse.

If you are given too much Methylene Blue Injection

As Methylene Blue Injection is always given to you in a hospital under the supervision of a doctor, it is unlikely that you will receive an overdose.

Symptoms of an overdose are the same as side effects but may be more severe. The symptoms of a side effect are listed under section 6. Are there any side effects?

You should immediately:

  • phone the Poisons Information Centre (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while MethyleneBlue Injection is being given?

Things you should do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you have been given Methylene Blue Injection.

Tell any other doctors, dentists, and pharmacists who treat you that you have been given this medicine. If you become pregnant while being given this medicine, tell you doctor immediately.

If you are about to have any blood tests, tell your doctor that you have been given this medicine. It may interfere with the results of some tests.

Keep all your doctor's appointments so that your progress can be checked.

Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly. Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Methylene Blue Injection affects you.

This medicine may cause dizziness in some people. If you feel dizzy do not drive, operate machinery, or do anything else that could be dangerous.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

  • Methylene Blue Injection will be stored in the surgery, pharmacy or ward of a hospital.
  • The injection is kept in a cool, dry place where the temperature is below 25°C.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Methylene Blue Injection will cause a blue colour in urine or bowel motions.

Common side effects

Common side effectsWhat to do
Gastrointestinal and Urinary:
  • nausea, vomiting, diarrhoea
  • pain when passing urine
Nervous System:
  • headaches, dizziness
  • mental confusion, anxiety, agitation
  • tremor
Skin:
  • redness or swelling at the injection site
  • change in the colour of your skin, saliva, urine and/or faeces to blue or blue/green
Eyes:
  • dilated pupils (increase in the size of the black part of the eyes)
Taste:
  • taste disturbance or loss of taste
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Low blood pressure:
  • loss of consciousness
  • severe fatigue
  • feeling lightheaded
  • buzzing or ringing in the ear
  • blurring or loss of vision
Anaemia:
  • tiredness and shortness of breath when exercising
  • dizziness
  • pale appearance
Allergic reaction:
  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash
  • itching or hives on the skin
Heart:
  • chest pain
  • fast or irregular heartbeat
General body:
  • stomach pain
  • pain at the injection site
  • high temperature
  • sweating more than normal
Nervous system:
  • having problems with speaking, writing or reading
Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed above may also occur in some people.

Some of these side effects (for example, changes in blood pressure) can only be found when your doctor does tests from time to time to check your progress.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Methylene Blue Injection contains

Active ingredient
(main ingredient)
50 mg/ 5 mL methylene blue
Other ingredients
(inactive ingredients)
Water for injections
Hydrochloric acid and/or sodium hydroxide
Potential allergensNot applicable

Do not take this medicine if you are allergic to any of these ingredients.

What Methylene Blue Injection looks like

Methylene Blue Injection is a clear, blue solution in a clear glass vial sealed with a rubber stopper and aluminium seal with a plastic flip off cap. It is available in a 5 mL vial.

(AUST R 223583)

Who distributes Methylene Blue Injection

Methylene Blue Injection is made in Australia by:
Phebra Pty Ltd
19 Orion Road
Lane Cove West, NSW 2066
Australia
Ph 1800 720 020

This leaflet was updated in September 2023.

Phebra and the Phi symbol are trademarks of Phebra Pty Ltd,
19 Orion Road, Lane Cove West, NSW 2066, Australia.

Published by MIMS October 2023

BRAND INFORMATION

Brand name

Methylene Blue Injection

Active ingredient

Methylene blue trihydrate

Schedule

S4

 

1 Name of Medicine

Methylene blue (also known as methylthioninium chloride).

2 Qualitative and Quantitative Composition

Methylene blue is a dark blue or dark green crystalline powder with a metallic sheen. It is soluble in water, alcohol and chloroform. Methylene Blue Injection is a sterile solution of methylene blue trihydrate 50 mg.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Methylene Blue Injection is a sterile solution for oral/intravenous use. The pH of the solution ranges between 3.0 and 4.5.

4 Clinical Particulars

4.1 Therapeutic Indications

Methylene Blue Injection is indicated:
for the treatment of drug induced methaemoglobinaemia;
for the treatment of idiopathic methaemoglobinaemia (in which a structural abnormality of haemoglobin is not present);
as a bacteriological stain;
as a dye in diagnostic procedures such as fistula detection;
for the delineation of certain body tissues during surgery.

4.2 Dose and Method of Administration

Methylene Blue Injection may be administered orally or by intravenous injection. In the treatment of acute methaemoglobinaemia, the intravenous route of administration is usually preferred because it provides a more rapid onset of effect.

Adults and children.

In the treatment of methaemoglobinaemia, methylene blue is administered intravenously as a 1% solution in doses of 1 mg to 2 mg per kg bodyweight injected over a period of several minutes. A repeat dose may be given after one hour if required. A maximum dose of 7 mg/kg bodyweight is recommended. The use of methylene blue is not recommended in infants under 4 months of age.
A dose of 5 mg/kg diluted in 500 mL of glucose 5% infused over 1 hour has been used successfully to stain and identify the parathyroid glands.
Methylene Blue Injection should not be diluted with sodium chloride 0.9% (saline) as precipitation may occur (due to presence of chloride ions which have been shown to reduce the solubility of methylene blue).
A suitable dilution for oral dosing would be 5-10 mL of the 1% solution diluted to 100-200 mL with water for injections. The high volume is suggested to reduce the degree of gastrointestinal disturbances and dysuria.
The dosage of methylene blue should be calculated on the basis of lean bodyweight.
Use immediately following dilution.

4.3 Contraindications

Methylene Blue Injection is contraindicated in the following circumstances:
known hypersensitivity to the drug or to any other thiazide dyes;
patients with severe renal impairment;
patients with glucose-6-phosphate dehydrogenase deficiency;
methaemoglobinaemia due to chlorate poisoning;
methaemoglobinaemia during treatment of cyanide poisoning.
Intrathecal and subcutaneous injection of methylene blue are also contraindicated, as they can result in neural damage (intrathecal administration) and necrotic abscess (subcutaneous administration).

4.4 Special Warnings and Precautions for Use

Long-term administration of methylene blue may result in marked anaemia due to accelerated destruction of erythrocytes; haemoglobin concentrations should be checked frequently.
If methylene blue is injected subcutaneously or if extravasation occurs, necrotic abscesses may result (see Section 4.3 Contraindications). Slow injection rates are recommended to prevent high local concentration of the compound.
Methylene blue imparts a blue green colour to urine, faeces and a blue colour to skin which may hinder a diagnosis of cyanosis.
Caution should be exercised in the course of treating aniline induced methaemoglobinaemia. The repeated doses, that may be required, may exacerbate Heinz body formation and haemolytic anaemia. Lower doses should be considered.
Exacerbation of dapsone induced haemolytic anaemia has been reported as a result of the formation of the dapsone reactive metabolite hydroxylamine which oxidises haemoglobin. It is recommended not to exceed a cumulative dose for the course of treatment of 4 mg/kg in patients with dapsone induced methaemoglobinaemia.
Anaesthesiologists should be vigilant for methaemoglobinaemia in patients receiving dapsone therapy and for BIS (bispectral index) interference.
Failure to respond to methylene blue suggests cytochrome b5 reductase deficiency, glucose-6-phosphate dehydrogenase deficiency or sulfhaemoglobinemia. Alternative treatment options should be considered.
Patients with hyperglycaemia or diabetes mellitus: if diluted in glucose 5% (50 mg/mL) solution for injection, Methylene Blue Injection must be used with caution in patients with hyperglycaemia or diabetes mellitus, as these conditions may be exacerbated by the glucose solution.

Patient monitoring.

Full blood count, including reticulocyte count should be undertaken to ensure haemolysis has not occurred.
Due to the potential risk of cardiac arrhythmia and hypotension, electrocardiographs (ECG) and blood pressure should be monitored during and after treatment with methylene blue.
Long-term administration of methylene blue may result in anaemia. Haemoglobin levels should be monitored during long-term therapy.
Methaemoglobin levels should be monitored throughout therapy.

Potent monoamine oxidase inhibition and serotonin syndrome.

Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause serious or fatal serotonin toxicity (serotoninergic syndrome) when combined with serotonergic drugs. Avoid concomitant use of methylthioninium chloride with selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors. If methylene blue is judged to be indicated, serotonin reuptake inhibitors (SRIs) must be ceased prior to treatment/procedure/surgery.
Patients treated with methylene blue in combination with serotonergic drugs should be monitored for the emergence of serotonin syndrome. If symptoms of serotonin syndrome occur, discontinue use of methylene blue, and initiate supportive treatment (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Photosensitivity.

Methylene blue may cause a cutaneous photosensitivity reaction when exposed to strong light sources, such as phototherapy, those found in operating theatres or locally from illuminating devices such as pulse oximeters.
Advise patients to take protective measures against exposure to light, because photosensitivity may occur after administration of methylene blue.

Use in renal impairment.

Methylene blue is excreted mainly via the urine, primarily as leucomethylene blue. Methylene Blue Injection is contraindicated in patients with severe renal impairment. Caution should be exercised when administering methylene blue to patients with mild to moderate renal impairment.

Use in the elderly.

No data available.

Paediatric use.

Safety and efficacy of methylene blue in infants have not been established. It has been reported that the metabolism of methylene blue to leucomethylene blue is likely to be less efficient in neonates, due to reduced efficacy of NADP-diaphorase in this age group. The use of Methylene Blue Injection in infants up to 4 months of age is not recommended.
Extreme caution should be exercised when administering to the newborns and infants below the age of 3 months due to lower concentrations of NADPH-methaemoglobin reductase necessary for reducing methaemoglobin to haemoglobin, making these infants more susceptible to methaemoglobinaemia produced by high doses of methylene blue.

Effects on laboratory tests.

Phenolsulfonphthalein excretion test.

Methylene blue may cause false positive results.

Pulse oximetry.

Methylene blue may result in an underestimation of oxygen saturation reading. It is advisable to check the oxygen saturation by co-oximetry when available since pulse oximetry may provide a false estimation of oxygen saturation during administration of methylene blue.

Bispectral index (BIS).

Methylene blue may interfere with BIS values.

4.5 Interactions with Other Medicines and Other Forms of Interactions

An in vitro study showed that methylene blue is a potential inhibitor of CYP450 1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4/5. The clinical relevance of this finding is unknown, but it cannot be excluded that the systemic exposure of medical products being substrates for these isozymes may be increased on concomitant administration with methylene blue.
The administration of methylene blue has the potential to transiently increase or decrease the clearance of drugs that are primarily metabolised by these enzymes. The clinical consequences are however considered minimal since methylene blue is used often only once and in an acute emergency setting.
Methylene blue is a potent inhibitor of the transporters OCT2, MATE1 and MATE2-K. The clinical consequences of the inhibition are not known. The administration of methylene blue has the potential to transiently increase the exposure of drugs primarily cleared by renal transport involving the OCT2/MATE pathway, including cimetidine, metformin, and acyclovir.
Methylene blue is a substrate of P-glycoprotein (P-gp). The clinical consequences are considered likely to be minimal due to the transient and single dose use that normally occurs in the emergency setting.

Serotonin reuptake inhibitor.

Methylene Blue Injection may interact with any drug that acts as an SRI including, amongst others, SSRIs such as fluvoxamine, fluoxetine, paroxetine, sertraline, escitalopram and citalopram, and SNRIs like venlafaxine and duloxetine. Such combinations have the consequence of potential serious CNS reactions, including potentially fatal serotonin toxicity (serotonin syndrome). Methylene blue should not be co-administered with any drug that acts as an SRI (see Section 4.4 Special Warnings and Precautions for Use).

Serotonin syndrome.

Spontaneous reports of serotonin syndrome associated with the co-administration of methylene blue and serotonergic agents, including antidepressants such as SSRIs have been reported. Co-administration of methylene blue and serotonergic agents is therefore not recommended except where administration of methylene blue and concomitant serotonergic agents is essential. In those cases, the lowest possible dose should be used, and patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia, clonus and incoordination. If signs or symptoms occur physicians should consider discontinuing either one or both agents; if the concomitant serotonergic agent is withdrawn, discontinuation symptoms can occur. Opioids, for example tramadol, pethidine, and dextromethorphan, may also increase the risk of developing serotonin syndrome when used in combination with methylene blue.
Methylene blue has been demonstrated to be a potent MAOI and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with SRIs (see Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In vitro, methylene blue has been shown to reduce motility of human sperm. It has also been shown to inhibit the growth of cultured two cell mouse embryos and the production of progesterone in cultured human luteal cells. In vivo effects on fertility and reproduction are not known.
(Category D)
Methylene Blue Injection caused ileal abnormalities including fetal intestinal atresia.
Methylene blue should not be administered to pregnant women.
Australian categorisation definition of category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.
There is no information on whether or not methylene blue crosses into the breast milk. Safety in the newborn has not been established, and hence it is recommended that breastfeeding is discontinued prior to administration of Methylene Blue Injection.

4.7 Effects on Ability to Drive and Use Machines

Driving can be affected due to confusional state, dizziness and possibly eye disturbances. However, the risk is limited as the medical product is intended for acute administration only in emergency situations at hospital.

4.8 Adverse Effects (Undesirable Effects)

The adverse effects listed in Table 1 occur in adults, children and adolescents (age 0 to 17 years old) after intravenous administration.
Oral administration may cause gastrointestinal disturbances and dysuria.
Use of methylene blue for endoscopic tattoo has been associated with vascular necrosis, mucosal ulceration, mural necrosis, extramural fat necrosis and inflammatory changes in the colon.
Injection of methylene blue into joint space has resulted in effusion in the treated joint.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

No specific information is available. However, large doses of methylene blue can produce methaemoglobinaemia. Side effects seen with high doses include chest pain, dyspnoea, restlessness, apprehension, tremors and a sense of oppression. Large doses are an irritant to the urinary tract. In addition, it can produce a mild haemolysis with moderate hyperbilirubinaemia, reticulosis and slight anaemia. Rarely, however, severe haemolytic anaemia with Heinz body formation has resulted. Methylene blue in large doses could cause a blue discolouration of the skin after methaemoglobinaemia levels have returned to normal.

Treatment of overdosage.

There is no specific antidote for methylene blue overdose. Treatment is symptomatic and supportive. In severe and refractory cases of methaemoglobinaemia, blood transfusions and even exchange transfusions and (possibly) hyperbaric oxygen may be the only alternative available.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

In patients with methaemoglobinaemia, therapeutic doses of methylene blue can lower the levels of methaemoglobin in the red blood cells. It activates a normally dormant reductase enzyme system that reduces the methylene blue to leucomethylene blue, which in turn is able to reduce methaemoglobin to haemoglobin. However, in large doses, methylene blue can itself produce methaemoglobinaemia and the methaemoglobin concentration should therefore be closely monitored during treatment. Methylene blue is not effective for the treatment of methaemoglobinaemia in patients with glucose-6-phosphate dehydrogenase deficiency as these patients have a diminished capacity to reduce methylene blue to leucomethylene blue. It is also potentially harmful as patients with glucose-6-phosphate dehydrogenase deficiency are particularly susceptible to the haemolytic anaemia induced by methylene blue.
Methylene blue also possesses weak antiseptic and bacteriological staining properties and is reported to inhibit amine oxidase in tissues. The drug appears to bind irreversibly to viral nucleic acid and cause disruption of the virus molecule upon exposure to light.
The use of methylene blue as a diagnostic aid is based on its ability to stain tissue. Any skin discolouration can be removed with hypochlorite solution.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Metabolism.

In tissues, methylene blue is rapidly reduced to leucomethylene blue, which is stabilised as an undetermined salt complex, or combination form in the urine but not in the blood.

Excretion.

About 75% of an oral dose of methylene blue is excreted in the urine, a small proportion of which is the unchanged drug, while some is excreted via the bile.

5.3 Preclinical Safety Data

Genotoxicity.

Methylene blue was positive to gene mutation assays in bacteria and mouse lymphoma cells, but was negative in the in vivo mouse micronucleus test.

Carcinogenicity.

There is no information on the carcinogenic potential of methylene blue.

6 Pharmaceutical Particulars

6.1 List of Excipients

Methylene Blue Injection contains water for injections, sodium hydroxide and/or hydrochloric acid may be used for pH adjustment.

6.2 Incompatibilities

Methylene blue is reported to be incompatible with caustic alkalis, iodides and dichromates, and oxidising and reducing substances.
Precipitation has been reported in cases where methylene blue has been diluted with sodium chloride 0.9%, saline, (due to presence of chloride ions which have been shown to reduce the solubility of methylene blue).

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG)1. The expiry date can be found on the packaging.
1AUST R 223583.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

Methylene Blue Injection is presented as 5 mL of solution in a 7 mL glass vial as a pack of 10.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

The active ingredient of Methylene Blue Injection USP is methylene blue trihydrate (3, 7- bis(dimethylamino) phenazathionium chloride trihydrate). The molecular formula of methylene blue trihydrate is C16H18ClN3S.3H2O. It has a molecular weight of 373.9.

Chemical structure.


CAS number.

7220-79-3.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes