Overview
11 DESCRIPTION Methylene blue is an oxidation-reduction agent. Its chemical name is 3,7-bis(dimethylamino)phenothiazin-5-ium, chloride hydrate. The molecular formula of methylene blue is C 16 H 18 ClN 3 S•xH 2 O and its molecular weight of 319.85 g/mol for the anhydrous form. The structural formula of methylene blue is: Methylene Blue Injection, USP is a sterile solution intended for intravenous...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Methylene blue is a water soluble thiazine dye that promotes a non-enzymatic 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. 12.2 Pharmacodynamics Low concentrations of methylene blue speeds up the in vivo conversion of methemoglobin to hemoglobin. Methylene blue has been observed to stain tissues selectively. The exposure-response or –safety relationship for methylene is unknown.
Indications
- 1 INDICATIONS AND USAGE Methylene Blue Injection is indicated for the treatment of pediatric and adult patients with acquired methemoglobinemia. Methylene Blue Injection is an oxidation-reduction agent indicated for the treatment of pediatric and adult patients with acquired methemoglobinemia.
Common Doses
- 1 mg
- 59 mL
- 50 mL
Dosage
2 DOSAGE AND ADMINISTRATION Administer 1 mg/kg intravenously over 5-30 minutes. ( 2.1 ) If methemoglobin level remains above 30% or if clinical symptoms persist, give a repeat dose of up to 1 mg/kg one hour after the first dose. ( 2.1 ) Administer a single dose of 1 mg/kg in patients with moderate or severe renal impairment. ( 2.2 ) 2.1 Dosage and Administration Ensure patent venous access prior to administration of methylene blue injection. Do not administer methylene blue injection subcutaneously. Administer methylene blue injection 1 mg/kg intravenously over 5-30 minutes.
Black Box Warning
WARNING: SEROTONIN SYNDROME WITH CONCOMITANT USE OF SEROTONERGIC DRUGS AND OPIOIDS Methylene blue injection may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids. Avoid concomitant use of methylene blue injection with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs) and opioids [see Warnings and Precautions (5.1) and Drug Interactions (7.1) ] .
Contraindications
- 4 CONTRAINDICATIONS Methylene blue injection is contraindicated in the following conditions: Severe hypersensitivity reactions to methylene blue or any other thiazine dye [see Warnings and Precautions (5.2) ] . Patients with glucose-6-phosphate dehydrogenase deficiency (G6PD) due to the risk of hemolytic anemia [see Warnings and Precautions (5.3 , 5.4 )] . Methylene blue injection is contraindicated in the following conditions ( 4 ): Severe hypersensitivity to methylene blue Patients with glucose-6-phosphate dehydrogenase deficiency (G6PD) due to the risk of hemolytic anemia
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Serotonin Syndrome with Concomitant Use of Serotonergic Drugs [see Warnings and Precautions (5.1) ] Anaphylaxis [see Warnings and Precautions (5.2) ] Lack of Effectiveness [see Warnings and Precautions (5.3) ] Hemolytic Anemia [see Warnings and Precautions (5.4) ] Interference with In Vivo Monitoring Devices [see Warnings and Precautions (5.5) ] Effects on Ability to Drive and Operate Machinery [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Clinically significant drug interactions with methylene blue injection are described below: The concomitant use of methylene blue injection with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Although the mechanism is not clearly understood, literature reports suggest methylene blue is a potent reversible inhibitor of monoamine oxidase. Avoid concomitant use of methylene blue injection with medicinal products that enhance serotonergic transmission including antidepressants like SSRIs (selective serotonin reuptake...