Provayblue 50mg/10ml Inj, 10ml

Methylene blue is a redox agent. In methemoglobinemia, it acts as an electron acceptor, being reduced to leukomethylene blue by NADPH-dependent methemoglobin reductase (NADPH-diaphorase). Leukomethylene blue then reduces the ferric iron (Fe3+) of methemoglobin to the ferrous iron (Fe2+) of hemoglobin, restoring oxygen-carrying capacity. At higher concentrations, it can oxidize hemoglobin to methemoglobin. It is also a weak monoamine oxidase inhibitor (MAOI) and can inhibit guanylate cyclase.

Serious Side Effects: Seek Medical Help Immediately

Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention right away:

Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of electrolyte problems, including:
+ Mood changes
+ Confusion
+ Muscle pain, cramps, or spasms
+ Weakness
+ Shakiness
+ Change in balance
+ Abnormal heartbeat
+ Seizures
+ Loss of appetite
+ Severe upset stomach or vomiting
Dizziness or fainting
Confusion
Changes in vision
Feeling extremely tired or weak
Pale skin
Dark urine or yellowing of the skin or eyes
Seizures

Other Possible Side Effects

Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms, contact your doctor for advice:

Urine or stool turning blue or green (this is a normal and harmless effect)
Skin turning blue-green
Pain, redness, or swelling at the injection site
Diarrhea or stomach upset
Headache

Reporting Side Effects

This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, don't hesitate to contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have a condition called G6PD deficiency.
If you are pregnant or think you might be pregnant. This medication may pose a risk to your unborn baby, so it is crucial to discuss the potential benefits and risks with your doctor to determine if this medication is suitable for you.
If you are breastfeeding. You should not breastfeed while taking this medication or for 8 days after your last dose.

Additionally, this medication may interact with other medications or health conditions. Therefore, it is vital to:

Inform your doctor and pharmacist about all the medications you are taking, including prescription and over-the-counter medications, natural products, and vitamins.
Share information about any health problems you have.
Verify with your doctor that it is safe to take this medication with your other medications and health conditions.
Never start, stop, or change the dose of any medication without first consulting your doctor.

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular monitoring is crucial, so be sure to undergo blood work, other laboratory tests, blood pressure checks, and heart rate assessments as directed by your doctor. Additionally, you will need to have your heart rhythm checked with an electrocardiogram (ECG) as scheduled.

Please note that this medication may interfere with certain laboratory tests. Therefore, it is vital to disclose that you are taking this drug to all your healthcare providers and laboratory personnel.

When starting this medication, exercise caution when engaging in activities that require alertness, such as driving, until you understand how it affects you. You may also be more susceptible to sunburn, so it is recommended to avoid excessive sun exposure, sunlamps, and tanning beds. To protect yourself from the sun, use sunscreen and wear protective clothing and eyewear.

• Patients with G6PD deficiency (risk of severe hemolytic anemia)
• Patients with known hypersensitivity to methylene blue or any component of the formulation
• Patients receiving serotonergic drugs (e.g., SSRIs, SNRIs, MAOIs, tricyclic antidepressants, bupropion, buspirone, fentanyl, tramadol, triptans, St. John's Wort) due to risk of serotonin syndrome
• Patients with severe renal insufficiency (eGFR <30 mL/min/1.73m2) for diagnostic use (e.g., cystoscopy)

• Serotonergic drugs (SSRIs, SNRIs, MAOIs, TCAs, etc.) - increased risk of serotonin syndrome
• Drugs that cause methemoglobinemia (e.g., dapsone, nitrates, nitrites, local anesthetics like prilocaine, sulfonamides) - additive effect, increased risk of methemoglobinemia
• Drugs metabolized by CYP2D6 (e.g., desipramine, fluoxetine, paroxetine) - methylene blue is a potent CYP2D6 inhibitor, increasing exposure to these drugs
• Drugs metabolized by CYP3A4 (e.g., midazolam, simvastatin) - methylene blue is a moderate CYP3A4 inhibitor, increasing exposure to these drugs

• Drugs metabolized by CYP1A2, CYP2B6, CYP2C9, CYP2C19 (methylene blue is a weak inhibitor of these enzymes) - potential for increased exposure to co-administered drugs
• Anticoagulants (e.g., warfarin) - theoretical risk of increased bleeding due to potential effect on platelet function or coagulation factors (monitor INR)

• Not specifically listed, but general caution with drugs that may affect renal or hepatic function.

• Cyanosis (especially of lips, nail beds, skin)
• Dyspnea or shortness of breath
• Headache
• Dizziness
• Fatigue
• Confusion or altered mental status
• Chest pain
• Palpitations
• Nausea, vomiting, abdominal pain
• Diaphoresis (sweating)
• Dark blue or green discoloration of urine and stool
• Skin discoloration (blue-green tint)
• Signs of hemolysis (jaundice, dark urine, pallor)

Methylene blue is not recommended for use during pregnancy, especially near term. While human data are limited, animal studies show adverse effects. There is a theoretical risk of hemolytic anemia in the fetus, particularly if the fetus has G6PD deficiency. The decision to use should weigh the potential benefits against the risks to the fetus.

Methylene blue is excreted into breast milk. Due to the potential for serious adverse reactions in breastfed infants (e.g., hemolytic anemia, hyperbilirubinemia), breastfeeding is not recommended during treatment and for up to 5 days after the last dose.

Use with caution, especially in neonates and infants, due to increased risk of hyperbilirubinemia and hemolytic anemia. G6PD deficiency is more common in neonates. Dosing for methemoglobinemia is generally 1 mg/kg, similar to adults, but careful monitoring is crucial.

No specific dose adjustments are generally required based on age alone. However, geriatric patients may have age-related decreases in renal and hepatic function, and may be more susceptible to adverse effects. Use with caution and monitor closely.

• Always confirm G6PD status before administering methylene blue, as it is contraindicated in G6PD deficient patients due to the risk of severe, life-threatening hemolytic anemia.
• Methylene blue can cause a blue or green discoloration of urine, stool, and skin. Inform patients about this expected side effect.
• Pulse oximetry readings may be falsely lowered by methylene blue due to its absorption characteristics. Co-oximetry is required for accurate methemoglobin level measurement.
• Avoid concomitant use with serotonergic drugs due to the significant risk of serotonin syndrome. A washout period may be necessary for patients on such medications.
• If a second dose is needed for methemoglobinemia, wait at least one hour after the initial dose and re-evaluate methemoglobin levels and clinical response. Do not exceed a total cumulative dose of 2 mg/kg.
• Methylene blue is ineffective in treating sulfhemoglobinemia and may worsen the condition.

• Supportive care (e.g., oxygen therapy, blood transfusion for severe anemia)
• Exchange transfusion (for severe methemoglobinemia unresponsive to methylene blue or in G6PD deficient patients)
• Ascorbic acid (Vitamin C) - a slower-acting reducing agent, sometimes used in mild cases or as an adjunct, but less effective than methylene blue for acute, severe methemoglobinemia.

If your symptoms or health problems do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. To ensure safe and effective treatment, never share your medication with others, and do not take medication prescribed to someone else.

Store all medications in a secure location, out of the reach of children and pets, to prevent accidental ingestion. Properly dispose of unused or expired medications by checking with your pharmacist for guidance on the best disposal method. Unless instructed to do so, avoid flushing medications down the toilet or pouring them down the drain, as this can harm the environment. Many communities have drug take-back programs, which your pharmacist can help you locate.

Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, consult with your doctor, nurse, pharmacist, or other healthcare provider.

In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. Be prepared to provide critical information, including the name of the medication, the amount taken, and the time it was taken, to ensure prompt and effective treatment.