Brand names: Provayblue
Route: Intravenous
FDA Black Box Warning
WARNING: SEROTONIN SYNDROME WITH CONCOMITANT USE OF SEROTONERGIC DRUGS AND OPIOIDS PROVAYBLUE may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids. Avoid concomitant use of PROVAYBLUE 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 )]. WARNING: SEROTONIN SYNDROME WITH CONCOMITANT USE OF SEROTONERGIC DRUGS AND OPIOIDS See full prescribing information for complete boxed warning. PROVAYBLUE may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids. Avoid concomitant use of PROVAYBLUE with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs) and opioids. ( 5.1 , 7.1 )
Contraindications
4 CONTRAINDICATIONS PROVAYBLUE 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 )]. PROVAYBLUE 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
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary PROVAYBLUE 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. Methylene blue produced adverse developmental outcomes in rats and rabbits when administered orally during organogenesis at doses at least 32 and 16 times, respectively, the clinical dose of 1 mg/kg (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively. Clinical Considerations Fetal/neonatal adverse reactions Intra-amniotic injection of a methylene blue class product hours to days prior to birth can result hyperbilirubinemia, hemolytic anemia, skin staining, methemoglobinemia, respiratory distress and photosensitivity in the newborn. Following administration of PROVAYBLUE to a pregnant woman at term, observe the newborn for these adverse reactions and institute supportive care. Data Animal Data Methylene blue was administered orally to pregnant rats at doses of 50 to 350 mg/kg/day, during the period of organogenesis. Maternal and embryofetal toxicities were observed at all doses of methylene blue and were most evident at the 200 and 350 mg/kg/day doses. Maternal toxicity consisted of increased spleen weight. Embryo-fetal toxicities included reduced fetal weight, post-implantation loss, edema, and malformations including enlarged lateral ventricles. The dose of 200 mg/kg (1200 mg/m 2 ) in rats is approximately 32 times a clinical dose of 1 mg/kg based on body surface area. Methylene blue was administered orally to pregnant rabbits at doses of 50, 100, or 150 mg/kg/day, during the period of organogenesis. Maternal death was observed at the methylene blue dose of 100 mg/kg. Embryofetal toxicities included spontaneous a
48 interactions on record
Concomitant use contraindicated. Serious, sometimes fatal reactions including hyperthermia, rigidity, myoclonus, and autonomic instability reported with MAOIs like IV methylene blue.
Source: NLP:atomoxetine hydrochloride
Intravenous methylene blue (reversible MAOI); starting buspirone is contraindicated due to increased risk of serotonin syndrome.
Source: NLP:buspirone hydrochloride
Concomitant use increases risk of serotonin syndrome. Citalopram is contraindicated in patients taking intravenous methylene blue.
Source: NLP:citalopram
Concomitant use increases risk of serotonin syndrome. Citalopram is contraindicated in patients taking intravenous methylene blue.
Source: NLP:citalopram hydrobromide
Intravenous methylene blue is contraindicated due to risk of serotonin syndrome.
Source: NLP:desvenlafaxine
Concomitant use increases risk of serotonin syndrome. Contraindicated with intravenous methylene blue.
Source: NLP:desvenlafaxine er
Concomitant intravenous methylene blue is contraindicated due to increased risk of serotonin syndrome.
Source: NLP:desvenlafaxine succinate
Concomitant use can cause hypertensive crisis with potential outcomes including death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure.
Source: NLP:dexmethylphenidate hydrochloride
MAOI that potentiates amphetamine effects; concomitant use can cause hypertensive crisis with potentially fatal outcomes including stroke, MI, aortic dissection.
Source: NLP:dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, and amphetamine sulfate
Intravenous methylene blue is an MAOI. Concomitant use with doxepin hydrochloride increases risk of serotonin syndrome. Use within 14 days of discontinuation is contraindicated.
Source: NLP:doxepin hydrochloride
MAOI with potential to increase serotonin syndrome risk. Escitalopram is contraindicated in patients taking intravenous methylene blue.
Source: NLP:escitalopram
Concomitant use increases risk of serotonin syndrome. Escitalopram oxalate is contraindicated in patients taking intravenous methylene blue.
Source: NLP:escitalopram oxalate
Concomitant use increases risk of serotonin syndrome. GEPIRONE is contraindicated in patients taking intravenous methylene blue or within 14 days of stopping.
Source: NLP:gepirone
Not recommended for patients taking MAOIs or within 14 days of stopping. May manifest as serotonin syndrome or opioid toxicity.
Source: NLP:hydromorphone hydrochloride
MAOI-like compound that increases risk of serotonin syndrome when used intravenously with levomilnacipran. Contraindicated use.
Source: NLP:levomilnacipran hydrochloride
Concomitant use can cause hypertensive crisis with potential outcomes including death, stroke, myocardial infarction, and other serious complications.
Source: NLP:methylphenidate hydrochloride
Concomitant use can cause hypertensive crisis with potential outcomes including death, stroke, myocardial infarction, aortic dissection, and renal failure.
Source: NLP:methylphenidate hydrochloride extended release
Do not initiate SAVELLA in patients being treated with intravenous methylene blue. Discontinue SAVELLA before initiating intravenous methylene blue treatment.
Source: NLP:milnacipran hydrochloride
Intravenous methylene blue increases risk of serotonin syndrome. Mirtazapine is contraindicated in patients taking this MAOI.
Source: NLP:mirtazapine
Do not use morphine sulfate with intravenous methylene blue. MAOI interaction may manifest as serotonin syndrome or opioid toxicity.
Source: NLP:morphine sulfate
Intravenous methylene blue with paroxetine increases risk of serotonin syndrome. Paroxetine is contraindicated in patients taking methylene blue.
Source: NLP:paroxetine
Concomitant use of SSRIs including paroxetine and MAOIs increases the risk of serotonin syndrome.
Source: NLP:paroxetine hydrochloride
Concomitant use is contraindicated due to MAOI properties and risk of serotonin syndrome.
Source: NLP:paroxetine hydrochloride hemihydrate
Concomitant use increases risk of serotonin syndrome. Sertraline is contraindicated in patients taking intravenous methylene blue.
Source: NLP:sertraline
Concomitant use of intravenous methylene blue with sertraline hydrochloride increases risk of serotonin syndrome.
Source: NLP:sertraline hydrochloride
MAOI activity may cause serotonin syndrome or opioid toxicity when given intravenously.
Source: NLP:tapentadol hydrochloride
Intravenous methylene blue is contraindicated; emergency use only with close monitoring and immediate discontinuation of tranylcypromine if necessary.
Source: NLP:tranylcypromine
Intravenous methylene blue is contraindicated. If emergency treatment necessary, discontinue tranylcypromine immediately and monitor closely.
Source: NLP:tranylcypromine sulfate
Intravenous methylene blue concomitant use increases risk of serotonin syndrome. Trazodone is contraindicated.
Source: NLP:trazodone hydrochloride
Concomitant use with intravenous methylene blue (an MAOI) increases the risk of serotonin syndrome and is contraindicated.
Source: NLP:venlafaxine
MAOI with properties that increase risk of serotonin syndrome when used with venlafaxine. Contraindicated.
Source: NLP:venlafaxine hcl er
Concomitant use with intravenous methylene blue (MAOI) increases risk of serotonin syndrome. Contraindicated in patients taking intravenous methylene blue.
Source: NLP:venlafaxine hydrochloride
Intravenous MAOI that increases risk of serotonin syndrome when combined with vilazodone hydrochloride.
Source: NLP:vilazodone hydrochloride
Concomitant intravenous use increases risk of serotonin syndrome. Contraindicated with IV methylene blue or within 21 days of stopping vortioxetine.
Source: NLP:vortioxetine
Intravenous methylene blue has MAOI-like properties that may result in serotonin syndrome when combined with opioids.
Source: NLP:atropa belladonna and opium
Concomitant use may result in serotonin syndrome with serious CNS reactions, potentially fatal.
Source: NLP:methylene blue
Concomitant use may result in serotonin syndrome with serious CNS reactions, potentially fatal.
Source: NLP:methylene blue
Concomitant use may result in serotonin syndrome with serious CNS reactions, potentially fatal.
Source: NLP:methylene blue
Concomitant use may result in serotonin syndrome with serious CNS reactions, potentially fatal.
Source: NLP:methylene blue
Concomitant use has resulted in serotonin syndrome.
Source: NLP:levorphanol tartrate
Concomitant use may result in serotonin syndrome with serious CNS reactions, potentially fatal.
Source: NLP:methylene blue
Concomitant use may result in serotonin syndrome. Carefully observe patient during treatment initiation and dosage modification; discontinue metaxalone if serotonin syndrome occurs.
Source: NLP:metaxalone
Concomitant use may result in serotonin syndrome with serious CNS reactions, potentially fatal.
Source: NLP:methylene blue
MAOI-like interaction may manifest as serotonin syndrome.
Source: NLP:nalbuphine hydrochloride
MAOI that can manifest as serotonin syndrome or opioid toxicity including respiratory depression and coma.
Source: NLP:oxymorphone hydrochloride
Concomitant use has resulted in serotonin syndrome. Carefully observe patient during treatment initiation and dose adjustment.
Source: NLP:pentazocine and naloxone
MAOI activity may result in serotonin syndrome or opioid toxicity.
Source: NLP:remifentanil hydrochloride
Concomitant use may result in serotonin syndrome with serious CNS reactions, potentially fatal.
Source: NLP:methylene blue