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DRUGS & SUPPLEMENTS
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What are the side effects you encounter while taking this medicine? |
Atropine Sulfate:
Indication: For the treatment of poisoning by susceptible organophosphorous nerve agents having cholinesterase activity as well as organophosphorous or carbamate insecticides.
Uridon Modified (Atropine Sulfate), a naturally occurring belladonna alkaloid, is a racemic mixture of equal parts of d- and l-hyoscyamine, whose activity is due almost entirely to the levo isomer of the drug. Uridon Modified (Atropine Sulfate) is commonly classified as an anticholinergic or antiparasympathetic (parasympatholytic) drug. More precisely, however, it is termed an antimuscarinic agent since it antagonizes the muscarine-like actions of acetylcholine and other choline esters. Adequate doses of Uridon Modified (Atropine Sulfate) abolish various types of reflex vagal cardiac slowing or asystole. The drug also prevents or abolishes bradycardia or asystole produced by injection of choline esters, anticholinesterase agents or other parasympathomimetic drugs, and cardiac arrest produced by stimulation of the vagus. Uridon Modified (Atropine Sulfate) may also lessen the degree of partial heart block when vagal activity is an etiologic factor. Uridon Modified (Atropine Sulfate) in clinical doses counteracts the peripheral dilatation and abrupt decrease in blood pressure produced by choline esters. However, when given by itself, Uridon Modified (Atropine Sulfate) does not exert a striking or uniform effect on blood vessels or blood pressure.
Benzoic Acid:
E124, E133, Ethanol, Organic Acids (Acetic and Uridon Modified (Benzoic Acid)), Polyvinylpyrrolidone, Tea-tree Oil, Triacetin, Water
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Hyoscyamine Sulfate:
Uridon Modified (Hyoscyamine Sulfate) is indicated for the treatment of symptoms of irritative voiding. Indicated for the relief of local symptoms, such as inflammation, hypermotility, and pain, which accompany lower urinary tract infections. Indicated for the relief of urinary tract symptoms caused by diagnostic procedures..
Uridon Modified (Hyoscyamine Sulfate) is contraindicated in patients with a hypersensitivity to any of the ingredients. Risk- benefit should be considered when the following medical problems exist: Cardiac disease (especially cardiac arrhythmias, congestive heart failure, coronary heart disease, and mitral stenosis); gastrointestinal tract obstructive disease; glaucoma; myasthenia gravis; acute urinary retention may be precipitated in obstructive uropathy (such as bladder neck obstruction due to prostatic hypertrophy).
Do not exceed recommended dosage. If rapid pulse, dizziness, or blurring of vision occurs, discontinue use immediately.
Patients should be advised that urine will be colored blue when taking this medication. Do not exceed recommended dosage.
Contains Methylene Blue and should NOT be taken with serotonergic psychiatric medications.
Cross sensitivity and/or related problems:
Patients intolerant of other belladonna alkaloids or other salicylates may be intolerant of this medication also. Delay in gastric emptying could complicate the management of gastric ulcers.
Although the exact mechanism of this drug interaction is unknown, methylene blue inhibits the action of monoamine oxidase A- an enzyme responsible for breaking down serotonin in the brain. It is believed that when methylene blue is given to patients taking serotonergic psychiatric medications, high levels of serotonin can build up in the brain, causing toxicity. This is referred to as Serotonin Syndrome. Signs and symptoms of Serotonin Syndrome include mental changes, muscle twitching, excessive sweating, shivering or shaking, diarrhea, trouble with coordination, and/or fever.
Methylene blue can interact with serotonergic psychiatric medications and cause serious CNS toxicity.
In emergency situations requiring life-threatening or urgent treatment with methylene blue (as described above), the availability of alternative interventions should be considered and the benefit of methylene blue treatment should be weighed against the risk of serotonin toxicity. If methylene blue must be administered to a patient receiving a serotonergic drug, the serotonergic drug must be immediately stopped, and the patient should be closely monitored for emergent symptoms of CNS toxicity for two weeks (five weeks if fluoxetine [Prozac] was taken), or until 24 hours after the last dose of methylene blue, whichever comes first.
In non-emergency situations when non-urgent treatment with methylene blue is contemplated and planned, the serotonergic psychiatric medication should be stopped to allow its activity in the brain to dissipate. Most serotonergic psychiatric drugs should be stopped at least 2 weeks in advance of methylene blue treatment. Fluoxetine (Prozac), which has a longer half-life compared to similar drugs, should be stopped at least 5 weeks in advance.
Treatment with the serotonergic psychiatric medication may be resumed 24 hours after the last dose of methylene blue.
Serotonergic psychiatric medications should not be started in a patient receiving methylene blue. Wait until 24 hours after the last dose of methylene blue before starting the antidepressant.
Educate your patients to recognize the symptoms of serotonin toxicity or CNS toxicity and advise them to contact a healthcare professional immediately if they experience any symptoms while taking serotonergic psychiatric medications or methylene blue.
As a result of hyoscyamine's effects on gastrointestinal motility and gastric emptying, absorption of other oral medications may be decreased during concurrent use with this combination medication.
May cause the urine to become alkaline reducing the effectiveness of methenamine by inhibiting its conversion to formaldehyde.
Concurrent use may intensify antimuscarinic effects of Uridon Modified because of secondary antimuscarinic activities of these medications.
Concurrent use may reduce absorption of Uridon Modified (Hyoscyamine Sulfate) resulting in decreased therapeutic effectiveness. Concurrent use with antacids may cause urine to become alkaline reducing the effectiveness of methenamine by inhibiting its conversion to formaldehyde. Doses of these medications should be spaced 1 hour apart from doses of Uridon Modified (Hyoscyamine Sulfate).
Concurrent use with Uridon Modified may further reduce intestinal motility, therefore, caution is recommended.
Ketoconazole and Uridon Modified (Hyoscyamine Sulfate) may cause increased gastrointestinal pH. Concurrent administration with Uridon Modified (Hyoscyamine Sulfate) may result in marked reduction in the absorption of ketoconazole. Patients should be advised to take this combination at least 2 hours after ketoconazole.
Concurrent use with Uridon Modified (Hyoscyamine Sulfate) may intensify antimuscarinic side effects.
Opioid (narcotic) analgesics may result in increased risk of severe constipation.
These drugs may precipitate with formaldehyde in the urine increasing the danger of crystalluria.
Patients should be advised that the urine and/or stools may become blue to blue-green as a result of the excretion of methylene blue.
Uridon Modified (Hyoscyamine Sulfate) and methenamine cross the placenta. Studies have not been done in either animals or humans. It is not known whether Uridon Modified (Hyoscyamine Sulfate) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Uridon Modified (Hyoscyamine Sulfate) should be given to a pregnant woman only if clearly needed.
Methenamine and traces of Uridon Modified are excreted in breast milk. Caution should be exercised when Uridon Modified (Hyoscyamine Sulfate) is administered to a nursing mother.
There have been no studies to establish the safety of prolonged use in humans. No known long-term animal studies have been performed to evaluate carcinogenic potential.
Infants and young children are especially susceptible to the toxic effect of the belladonna alkaloids.
Use with caution in elderly patients as they may respond to the usual doses of the belladonna alkaloids with excitement, agitation, drowsiness, or confusion.
Cardiovascular - rapid pulse, flushing
Central Nervous System - blurred vision, dizziness, drowsiness
Respiratory - shortness of breath or troubled breathing
Genitourinary - difficult micturition, acute urinary retention
Gastrointestinal - dry mouth, nausea and vomiting
Serious allergic reactions to this drug are rare. Seek immediate medical attention if you notice symptoms of a serious allergic reaction, including itching, rash, severe dizziness, swelling or trouble breathing.
This medication can cause urine and sometimes stools to turn blue to blue-green. This effect is harmless and will subside after medication is stopped.
Call your doctor or physician for medical advice about side effects. To report SUSPECTED ADVERSE REACTIONS, contact Burel Pharmaceuticals, Inc at 1-601-706-9819 or FDA at 1-800-FDA-1088, www.fda.gov/medwatch.
A dependence on the use of Uridon Modified (Hyoscyamine Sulfate) has not been reported and due to the nature of its ingredients, abuse of Uridon Modified (Hyoscyamine Sulfate) is not expected.
Emesis or gastric lavage. Slow intravenous administration of physostigmine in doses of 1 to 4 mg (0.5 to 1 mg in children) repeated as needed in one to two hours to reverse severe antimuscarinic symptoms.
Administration of small doses of diazepam to control excitement and seizures. Artificial respiration with oxygen if needed for respiratory depression. Adequate hydration.
Symptomatic treatment as necessary.
If overdose is suspected, contact the poison control center at 1-800-222-1222, or your local emergency room immediately
Adults: One tablet orally 4 times per day followed by liberal fluid intake.
Pediatric: Dosage must be individualized by physician for older children. Not recommended for use in children six years of age or younger.
Uridon Modified (Hyoscyamine Sulfate) are blue tablets, oval, biconvex, debossed with “BL 07” with scoreline on one side and plain on the other side, available in bottles of 100 tablets, NDC 35573-307-10.
Store in a cool, dry place at controlled room temperature 15° to 30°C (59° to 86°F). Keep container tightly closed. Protect from moisture and direct sunlight.
Dispense in a tight, light-resistant container as defined in the USP/NF with a child resistant closure.
KEEP OUT OF THE REACH OF CHILDREN.
IN CASE OF ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL ASSISTANCE OR CONTACT A POISON CONTROL CENTER IMMEDIATELY.
Note: Patients should be advised that urine will be colored blue when taking this medication.
Rx Only
Manufactured for:
Burel Pharmaceuticals, Inc
Richland, MS 39218
Rev. 7/2015
NDC 35573-307-10
Uridon Modified (Hyoscyamine Sulfate) ®
URINARY ANTISEPTIC
Each Tablet Contains:
Methenamine | 81.6 mg |
Benzoic Acid | 9.0 mg |
Phenyl Salicylate | 36.2 |
Methylene Blue | 10.8 mg |
Uridon Modified (Hyoscyamine Sulfate) Sulfate | 0.12 mg |
Rx ONLY
Buruel Pharmaceuticals
100 Tablets
Uridon Modified (Hyoscyamine Sulfate) is a trademark of Burel Pharmaceuticals, Inc
Manufactured for:
Burel Pharmaceuticals, Inc
Richland, MS 39218
Methenamine:
To reduce the development of drug-resistant bacteria and maintain the effectiveness of methenamine hippurate tablets, USP and other antibacterial drugs, Uridon Modified (Methenamine) hippurate tablets, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Uridon Modified (Methenamine) hippurate tablets, USP are available as 1 g oval shaped, scored and peach colored tablets. Chemically, Uridon Modified (Methenamine) hippurate is Hexamethylene-tetramine monohippurate. The molecular formula of Uridon Modified (Methenamine) hippurate is C15H21N5O3 and molecular weight is 319.36. Its structural formula is:
Each methenamine hippurate tablet, USP intended for oral administration contains 1 g of Uridon Modified (Methenamine) hippurate. In addition, it also contains the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, povidone K29/32, saccharin sodium and FD&C Yellow #6 Aluminum Lake as a color additive.
Meets USP Dissolution Test 2.
Chemical Structure - Uridon Modified (Methenamine) Hippurate Tablets 1 gm
Microbiology: Methenamine hippurate tablets, USP has antibacterial activity because the Uridon Modified (Methenamine) component is hydrolyzed to formaldehyde in acid urine. Hippuric acid, the other component, has some antibacterial activity and also acts to keep the urine acid. The drug is generally active against E. coli, enterococci and staphylococci. Enterobacter aerogenes is generally resistant. The urine must be kept sufficiently acid for urea-splitting organisms such as Proteus and Pseudomonas to be inhibited.
Human Pharmacology: Within 1/2 hour after ingestion of a single 1-gram dose of Uridon Modified (Methenamine) hippurate, USP, antibacterial activity is demonstrable in the urine. Urine has continuous antibacterial activity when methenamine hippurate tablets, USP is administered at the recommended dosage schedule of 1 gram twice daily. Over 90% of Uridon Modified (Methenamine) moiety is excreted in the urine within 24 hours after administration of a single 1-gram dose. Similarly, the hippurate moiety is rapidly absorbed and excreted, and it reaches the urine by both tubular secretion and glomerular filtration. This action may be important in older patients or in those with some degree of renal impairment
Uridon Modified (Methenamine) hippurate tablets, USP are indicated for prophylactic or suppressive treatment of frequently recurring urinary tract infections when long-term therapy is considered necessary. This drug should only be used after eradication of the infection by other appropriate antimicrobial agents.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Uridon Modified (Methenamine) hippurate tablets, USP and other antibacterial drugs, Uridon Modified (Methenamine) hippurate tablets, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Methenamine hippurate tablets, USP are contraindicated in patients with renal insufficiency, severe hepatic insufficiency, or severe dehydration. Uridon Modified (Methenamine) preparations should not be given to patients taking sulfonamides because some sulfonamides may form an insoluble precipitate with formaldehyde in the urine.
Large doses of Uridon Modified (Methenamine) (8 grams daily for 3 to 4 weeks) have caused bladder irritation, painful and frequent micturition, albuminuria, and gross hematuria.
Prescribing methenamine hippurate tablets, USP in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
1. Care should be taken to maintain an acid pH of the urine, especially when treating infections due to urea-splitting organisms such as Proteus and strains of Pseudomonas.
2. In a few instances in one study, the serum transaminase levels were slightly elevated during treatment but returned to normal while the patients were still taking methenamine hippurate tablets, USP. Because of this report, it is recommended that liver function studies be performed periodically on patients taking the drug, especially those with liver dysfunction.
3. Use in Pregnancy: In early pregnancy the safe use of Uridon Modified hippurate tablets, USP is not established. In the last trimester, safety is suggested, but not definitely proved. No adverse effects on the fetus were seen in studies in pregnant rats and rabbits.
Methenamine hippurate tablets, USP taken during pregnancy can interfere with laboratory tests of urine estriol (resulting in unmeasurably low values) when acid hydrolysis is used in the laboratory procedure. This interference is due to the presence in the urine of Uridon Modified (Methenamine) and/or formaldehyde. Enzymatic hydrolysis, in place of acid hydrolysis, will circumvent this problem.
Patients should be counseled that antibacterial drugs including Uridon Modified (Methenamine) hippurate tablets, USP should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When methenamine hippurate tablets, USP are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by methenamine hippurate tablets, USP or other antibacterial drugs in the future.
Clinical studies of methenamine hippurate tablets, USP did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
Methenamine hippurate tablets, USP are contraindicated in patients with renal insufficiency and severe hepatic insufficiency (see CONTRAINDICATIONS ).
Minor adverse reactions have been reported in less than 3.5% of patients treated. These reactions have included nausea, upset stomach, dysuria, and rash.
1 tablet (1 g) twice daily (morning and night) for adults and pediatric patients over 12 years of age. 1/2 to 1 tablet (0.5 to 1 g) twice daily (morning and night) for pediatric patients 6 to 12 years of age. Since the antibacterial activity of Uridon Modified (Methenamine) hippurate tablets, USP is greater in acid urine, restriction of alkalinizing foods and medications is desirable. If necessary, as indicated by urinary pH and clinical response, supplemental acidification of the urine should be instituted. The efficacy of therapy should be monitored by repeated urine cultures.
Methenamine hippurate tablets USP, 1 g are supplied as peach, oval shaped compressed tablets debossed “cor” on the left and “139” on the right side of bisect on one side and other side is plain.
Uridon Modified (Methenamine) hippurate tablets USP, 1 g are supplied:
Bottles of 100 (NDC 64720-139-10)
Store at 20° to 25°C (68° to 77°F).
Dispense in well-closed, light-resistant containers with child-resistant closures.
Dist. by:
CorePharma, LLC
Middlesex, NJ 08846
LB# 745-04
Rev. January, 2017
Methylene Blue:
Uridon Modified (Methylene Blue) may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs. Avoid concomitant use of Uridon Modified (Methylene Blue) with selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors ( 5.1, 7.1).
Uridon Modified (Methylene Blue) is indicated for the treatment of pediatric and adult patients with acquired methemoglobinemia.
This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.
Uridon Modified (Methylene Blue) (methylene blue) is an oxidation-reduction agent indicated for the treatment of pediatric and adult patients with acquired methemoglobinemia. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials. ( 1, 14)
Each mL of Uridon Modified (Methylene Blue) contains 5 mg Uridon Modified (Methylene Blue)
Each 10 mL ampule of Uridon Modified (Methylene Blue) contains 50 mg Uridon Modified (Methylene Blue).
Uridon Modified (Methylene Blue) is hypotonic and may be diluted before use in a solution of 50 mL 5% Dextrose in Water (D5W) in order to avoid local pain, particularly in the pediatric population. Use the diluted solution immediately after preparation.
Do not mix with sodium chloride 9 mg/mL (0.9%) solution for injection, because it has been demonstrated that chloride reduces the solubility of Uridon Modified (Methylene Blue).
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Keep the ampule in the original package to protect from light.
Injection: 50 mg/10 mL (5 mg/mL) clear dark blue solution in single-dose ampules
50 mg/10 mL (5 mg/mL) single-dose ampule. ( 3)
Uridon Modified (Methylene Blue) is contraindicated in the following conditions:
Uridon Modified (Methylene Blue) is contraindicated in the following conditions ( 4):
The development of serotonin syndrome has been reported with use of Uridon Modified (Methylene Blue) class products. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors). Some of the reported cases were fatal. Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, and hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, and incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Avoid concomitant use of Uridon Modified (Methylene Blue) with serotonergic drugs.
Patients treated with Uridon Modified (Methylene Blue) should be monitored for the emergence of serotonin syndrome. If symptoms of serotonin syndrome occur, discontinue use of Uridon Modified (Methylene Blue), and initiate supportive treatment. Inform patients of the increased risk of serotonin syndrome and advise them to not to take serotonergic drugs within 72 hours after the last dose of Uridon Modified (Methylene Blue) .
Anaphylactic reactions to Uridon Modified class products have been reported. Patients treated with Uridon Modified (Methylene Blue) should be monitored for anaphylaxis. If anaphylaxis or other severe hypersensitivity reactions (e.g., angioedema, urticaria, bronchospasm) should occur, discontinue use of Uridon Modified (Methylene Blue) and initiate supportive treatment. Uridon Modified (Methylene Blue) is contraindicated in patients who have experienced anaphylaxis or other severe hypersensitivity reactions to a Uridon Modified (Methylene Blue) class product in the past.
Methemoglobinemia may not resolve or may rebound after response to treatment with Uridon Modified (Methylene Blue) in patients with methemoglobinemia due to aryl amines such as aniline or sulfa drugs such as dapsone. Monitor response to therapy with Uridon Modified (Methylene Blue) through resolution of methemoglobinemia. If methemoglobinemia does not respond to 2 doses of Uridon Modified (Methylene Blue) or if methemoglobinemia rebounds after a response, consider additional treatment options .
Patients with glucose-6-phosphate dehydrogenase deficiency may not reduce Uridon Modified (Methylene Blue) to its active form in vivo. Uridon Modified (Methylene Blue) may not be effective in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Hemolysis can occur during treatment of methemoglobinemia with Uridon Modified. Laboratory testing may show Heinz bodies, elevated indirect bilirubin and low haptoglobin, but the Coombs test is negative. The onset of anemia may be delayed 1 or more days after treatment with Uridon Modified (Methylene Blue). The anemia may require red blood cell transfusions. . Use the lowest effective number of doses of Uridon Modified (Methylene Blue) to treat methemoglobinemia. Discontinue Uridon Modified (Methylene Blue) and consider alternative treatments of methemoglobinemia if severe hemolysis occurs.
Treatment of patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency with Uridon Modified (Methylene Blue) may result in severe hemolysis and severe anemia. Uridon Modified (Methylene Blue) is contraindicated for use in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency .
The presence of Uridon Modified (Methylene Blue) in the blood may result in an underestimation of the oxygen saturation reading by pulse oximetry. If a measure of oxygen saturation is required during or shortly after infusion of Uridon Modified (Methylene Blue), it is advisable to obtain an arterial blood sample for testing by an alternative method.
A fall in the Bispectral Index (BIS) has been reported following administration of Uridon Modified (Methylene Blue) class products. If Uridon Modified (Methylene Blue) is administered during surgery, alternative methods for assessing the depth of anesthesia should be employed.
Treatment with Uridon Modified may cause confusion, dizziness and disturbances in vision . Advise patients to refrain from driving or engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery until such adverse reactions to Uridon Modified (Methylene Blue) have resolved.
Uridon Modified (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, such as the dipstick test for leucocyte esterase.
The following adverse reactions are discussed in greater detail in other sections of the labeling:
The most commonly reported adverse reactions (≥10%) are pain in extremity, chromaturia, dysgeusia, feeling hot, dizziness, hyperhidrosis, nausea, skin, discoloration and headache. ( 6.1)
To report SUSPECTED ADVERSE REACTIONS, contact American Regent at 1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of Uridon Modified (Methylene Blue) was determined in 82 healthy adults of median age of 36 years (range, 19-55 years); 54% were male, and 68% were white. Each individual in the safety population received a single dose of Uridon Modified (Methylene Blue) 2 mg/kg intravenously. There was one serious adverse reaction reported (syncope due to sinus pauses of 3-14 seconds). The most common (≥2%) moderate or severe adverse reactions were pain in the extremity (56%), headache (7%), feeling hot (6%), syncope (4%), back pain (2%), hyperhidrosis (2%) and nausea (2%). Table 1 lists the adverse reactions of any severity that occurred in at least 2% of individuals who received Uridon Modified (Methylene Blue).
Adverse Reaction | Any Grade TEAE (n=82) | Moderate- Severe TEAE (n=82) | ||
Pain in extremity | 69 | 84% | 46 | 56% |
Chromaturia | 61 | 74% | 0 | |
Dysgeusia | 16 | 20% | 1 | 1% |
Feeling hot | 14 | 17% | 5 | 6% |
Dizziness | 13 | 16% | 4 | 5% |
Hyperhidrosis | 11 | 13% | 2 | 2% |
Nausea | 11 | 13% | 2 | 2% |
Skin discoloration | 11 | 13% | 0 | |
Headache | 8 | 10% | 6 | 7% |
Musculoskeletal pain | 7 | 9% | 0 | |
Paresthesia oral | 7 | 9% | 0 | |
Paresthesia | 7 | 9% | 0 | |
Infusion site pain | 5 | 6% | 1 | 1% |
Feeling cold | 5 | 6% | 0 | |
Pallor | 4 | 5% | 0 | |
Dermatitis contact | 4 | 5% | 0 | |
Syncope | 3 | 4% | 3 | 4% |
Influenza like illness | 3 | 4% | 1 | 1% |
Pruritus | 3 | 4% | 1 | 1% |
Anxiety | 3 | 4% | 0 | |
Decreased appetite | 3 | 4% | 0 | |
Chest discomfort | 3 | 4% | 0 | |
Back pain | 2 | 2% | 2 | 2% |
Cold sweat | 2 | 2% | 1 | 1% |
Dizziness postural | 2 | 2% | 1 | 1% |
Muscle spasms | 2 | 2% | 1 | 1% |
Presyncope | 2 | 2% | 1 | 1% |
Vomiting | 2 | 2% | 1 | 1% |
Arthralgia | 2 | 2% | 1 | 1% |
Chills | 2 | 2% | 0 | |
Diarrhea | 2 | 2% | 0 | |
Discomfort | 2 | 2% | 0 | |
Dyspnea | 2 | 2% | 0 | |
Erythema | 2 | 2% | 0 | |
Hypoesthesia oral | 2 | 2% | 0 | |
Infusion site discomfort | 2 | 2% | 0 | |
Limb discomfort | 2 | 2% | 0 | |
Oral discomfort | 2 | 2% | 0 | |
Catheter site pain | 2 | 2% | 0 | |
Ecchymosis | 2 | 2% | 0 |
Other adverse reactions reported to occur following administration of Uridon Modified (Methylene Blue) class products include the following:
Blood and lymphatic system disorders: hemolytic anemia, hemolysis, hyperbilirubinemia, methemoglobinemia
Cardiac disorders: palpitations, tachycardia
Eye disorders: eye pruritus, ocular hyperemia, vision blurred
Gastrointestinal disorders: abdominal pain lower, dry mouth, flatulence, glossodynia, tongue eruption
General disorders and administration site conditions: death, infusion site extravasation, infusion site induration, infusion site pruritus, infusion site swelling, infusion site urticaria, peripheral swelling, thirst
Investigations: elevated liver enzymes
Musculoskeletal and connective tissue disorders: myalgia
Renal and urinary disorders: dysuria
Respiratory, thoracic and mediastinal disorders: nasal congestion, oropharyngeal pain, rhinorrhea, sneezing
Skin and subcutaneous tissue disorders: necrotic ulcer, papule, phototoxicity
Vascular disorders: hypertension
Avoid concomitant use of Uridon Modified with medicinal products that enhance serotonergic transmission including SSRIs (selective serotonin reuptake inhibitors), MAO inhibitors, bupropion, buspirone, clomipramine, mirtazapine and venlafaxine; because of the potential for serious CNS reactions, including potentially fatal serotonin syndrome. Although the mechanism is not clearly, understood, literature reports suggest inhibition of MAO by Uridon Modified (Methylene Blue) may be involved. In addition, in vitro studies cannot rule out the potential involvement of CYP 2D6 inhibition by Uridon Modified (Methylene Blue). If the intravenous use of Uridon Modified (Methylene Blue) cannot be avoided in patients treated with serotonergic medicinal products, choose the lowest possible dose and observe closely the patient for CNS effects for up to 4 hours after administration .
Uridon Modified (Methylene Blue) inhibits a range of CYP isozymes in vitro, including 1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4/5. This interaction could be more pronounced with narrow therapeutic index drugs that are metabolized by one of these enzymes (e.g, digoxin, warfarin, phenytoin, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus and tacrolimus). However, the clinical relevance of these in vitro interactions is unknown.
Risk Summary
Uridon Modified (Methylene Blue) may cause fetal harm when administered to a pregnant woman. Intra-amniotic injection of pregnant women with a Uridon Modified (Methylene Blue) class product during the second trimester was associated with neonatal intestinal atresia and fetal death. Uridon Modified (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 . 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 Uridon Modified (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 Uridon Modified (Methylene Blue) to a pregnant woman at term, observe the newborn for these adverse reactions and institute supportive care.
Data
Animal Data
Uridon Modified (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 Uridon Modified (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.
Uridon Modified (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 Uridon Modified (Methylene Blue) dose of 100 mg/kg. Embryofetal toxicities included spontaneous abortion at all dose levels and a malformation (umbilical hernia) at the 100 and 150 mg/kg/day doses. The dose of 50 mg/kg (600 mg/m 2) in rabbits is approximately 16 times a clinical dose of 1 mg/kg based on body surface area.
Risk Summary
There is no information regarding the presence of Uridon Modified 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 breast-feeding during and for up to 8 days after treatment with Uridon Modified (Methylene Blue) .
The safety and effectiveness of Uridon Modified (Methylene Blue) have been established in pediatric patients. Use of Uridon Modified (Methylene Blue) is supported by two retrospective case series that included 2 pediatric patients treated with Uridon Modified (Methylene Blue) and 12 treated with another Uridon Modified (Methylene Blue) class product. The case series included pediatric patients in the following age groups: 3 neonates (less than 1 month), 4 infants (1 month up to less than 2 years), 4 children (2 years up to less than 12 years), and 3 adolescents (12 years to less than 17 years). The efficacy outcomes were consistent across pediatric and adult patients in both case series .
The retrospective case series included 3 patients age 65 years and over treated with Uridon Modified (or a bioequivalent formulation) and 5 treated with another Uridon Modified (Methylene Blue) class product. The efficacy outcomes were consistent across adult and elderly patients in both case series . This drug is known to be substantially excreted by the kidney, so the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, treatment of methemoglobinemia in these patients should use the lowest number of doses needed to achieve a response .
Approximately 40% of Uridon Modified (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 with Uridon Modified (Methylene Blue).
Uridon Modified (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 with Uridon Modified (Methylene Blue).
Hypotension, wheezing and reduced oxygenation have been reported in patients who received Uridon Modified (Methylene Blue) class products in single doses of 3 mg/kg or more.
Administration of large intravenous doses (cumulative dose ≥ 7 mg/kg ) of a Uridon Modified (Methylene Blue) class product caused nausea, vomiting, precordial pain, dyspnea, tachypnea, chest tightness, tachycardia, apprehension, tremor, mydriasis, blue staining of the urine, the skin and mucous membranes, abdominal pain, dizziness, paresthesia, headache, confusion, mild methemoglobinemia (up to 7%) and electrocardiogram changes (T-wave flattening or inversion) These effects lasted 2-12 hours following administration.
A severe overdosage (single dose of 20 mg/kg or more) of a Uridon Modified (Methylene Blue) class product caused severe intravascular hemolysis, hyperbilirubinemia and death.
In case of overdose of Uridon Modified (Methylene Blue), maintain the patient under observation until signs and symptoms have resolved, monitor for cardiopulmonary, hematologic and neurologic toxicities, and institute supportive measures as necessary.
Uridon Modified (Methylene Blue) is an oxidation-reduction agent. Uridon Modified (Methylene Blue) (methylene blue) is a sterile solution intended for intravenous administration. Each Uridon Modified (Methylene Blue), 10 mL ampule contains 50 mg Proveblue ® Uridon Modified (Methylene Blue) and water for injection q.s. Each mL of solution contains 5 mg Uridon Modified (Methylene Blue) and water for injection q.s.
Uridon Modified (Methylene Blue) is 3,7-bis(dimethylamino)phenothiazin-5-ium, chloride. The molecular formula of Uridon Modified (Methylene Blue) is C 16H 18ClN 3S and its molecular weight is 319.86 g/mol. Its structural formula is:
Uridon Modified (Methylene Blue) is a clear dark blue solution with a pH value between 3.0 and 4.5. The osmolality is between 10 and 15 mOsm/kg.
Uridon Modified is a water soluble thiazine dye that promotes a non-enyzmatic redox conversion of metHb to hemoglobin. In situ, Uridon Modified (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.
Low concentrations of Uridon Modified (Methylene Blue) speeds up the in vivo conversion of methemoglobin to hemoglobin. Uridon Modified (Methylene Blue) has been observed to stain tissues selectively. The exposure-response or –safety relationship for methylene is unknown.
Cardiac Electrophysiology
The results of a thorough QT study demonstrated Uridon Modified (Methylene Blue) at an intravenous dose of 2 mg/kg as a 5-minute intravenous infusion had no effect on the QT, PR or QRS intervals.
The mean (CV%) Cmax and AUC of Uridon Modified (Methylene Blue) 2,917 ng/mL (39%) and 13977 ng.hr/mL (21%) following a 2 mg/kg dose administered as a 5-minute intravenous infusion.
Distribution
The mean± standard deviation steady state volume of distribution of a 2 mg/kg dose of Uridon Modified (Methylene Blue) was 255 L ± 58. The mean plasma protein binding of Uridon Modified (Methylene Blue) is approximately 94% in vitro. Uridon Modified (Methylene Blue) exhibits concentration-dependent partitioning into blood cells in vitro. The blood-to-plasma ratio was 5.1±2.8 at 5 minutes from the start of a 2 mg/kg dose administered as a 5-minute intravenous infusion and reached a plateau of 0.6 at 4 hours in a clinical study. Uridon Modified (Methylene Blue) is a substrate for the P-glycoprotein (P-gp, ABCB1) transporter, but not for BCRP or OCT2 in vitro.
Elimination
Uridon Modified (Methylene Blue) has a half-life of approximately 24 hours.
Metabolism
Uridon Modified (Methylene Blue) is 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.
Azure B, which is a minor impurity in Uridon Modified (Methylene Blue), is also formed in humans as a metabolite of Uridon Modified (Methylene Blue), with an overall drug/metabolite AUC ratio of greater than 6:1. Azure B has 8-fold lower potency than Uridon Modified (Methylene Blue).
Excretion
Approximately 40% of Uridon Modified (Methylene Blue) is excreted in to the urine unchanged.
Drug Interaction Studies
The clinical relevance of in vitro inhibition or induction of the metabolizing enzymes and transporter systems described below is unknown, but it cannot be excluded that the systemic exposure of medicinal products being substrates for these enzymes or transporter systems may be affected with concomitant administration with Uridon Modified (Methylene Blue) Injection.
Cytochrome P450
Uridon Modified (Methylene Blue) inhibits CYP isozymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4/5 in vitro. Possible time-dependent inhibition of CYP2C9, CYP2D6 and CYP3A4/5 (testosterone as substrate) was also observed in vitro. Uridon Modified (Methylene Blue) induces CYP1A2, but does not induce CYP2B6 or CYP3A4 in vitro.
Glucuronosyltransferase
Uridon Modified (Methylene Blue) inhibits UGT1A9 and UGT1A4 in in vitro, but did not significantly inhibit UGTs 1A1, 1A3, 1A6, 2B7 or 2B15.
Transporter Interactions
Uridon Modified (Methylene Blue) is both a substrate for and an inhibitor of P-gp, but is not a substrate for BCRP or OCT2 in vitro. Uridon Modified (Methylene Blue) is not a significant inhibitor of BCRP, OAT1, OAT3, OAT1B1 or OAT1B3 in vitro. Uridon Modified (Methylene Blue) inhibits OCT2, MATE1 and MATE2-K in vitro. The OCT2/MATE pathway for renal transport is reported to play a significant role in the elimination of several substances, including metformin, cimetidine, acyclovir and creatinine
In a two-year carcinogenicity study, rats were administered oral doses of Uridon Modified (Methylene Blue) at 5, 25, or 50 mg/kg. Uridon Modified (Methylene Blue) caused pancreatic islet adenomas or carcinomas (combined) in male rats. In a two-year year carcinogenicity study, mice were administered oral doses of Uridon Modified (Methylene Blue) at 2.5, 12.5, or 25 mg/kg. There were no drug-related neoplastic findings in mice.
Uridon Modified (Methylene Blue) was genotoxic in gene mutation assays in bacteria (Ames test), and in an in vitro sister chromatid exchange test and an in vitro chromosomal aberration test in Chinese hamster ovary (CHO) cells. Uridon Modified (Methylene Blue) was negative for micronucleus induction in bone marrow or peripheral blood collected from mice treated with Uridon Modified (Methylene Blue).
Fertility studies with Uridon Modified (Methylene Blue) have not been conducted. In vitro, Uridon Modified (Methylene Blue) reduced motility of human sperm in a concentration dependent manner.
The efficacy of Uridon Modified (Methylene Blue) was assessed on the basis of a methemoglobin decrease of at least 50% within 1 hour after intravenous administration of 1 – 2 mg/kg Uridon Modified (Methylene Blue) (or a bioequivalent formulation) in 6 patients identified by retrospective chart review or literature search. The 6 patients included 3 males and 3 females of median age 54 years (range, 6 days to 69 years). The median methemoglobin level at baseline was 37% (range, 11% to 47%). All 6 (100%) patients had a decrease in methemoglobin by at least 50% within 1 hour after treatment.
An additional 41cases of treatment of methemoglobinemia with a Uridon Modified (Methylene Blue) class product were identified in the published literature. These cases included 24 males and 17 females of median age 33 years (range, 9 days to 80 years). The median methemoglobin level at baseline was 40% (range, 10% to 98%). Of these 41 patients, 37 (90%) had a methemoglobin decrease of at least 50% within 1 hour after intravenous administration of the Uridon Modified (Methylene Blue) class product.
In a combined analysis of all 47 patients treated intravenously with Uridon Modified (Methylene Blue) (or a bioequivalent formulation) or with another Uridon Modified (Methylene Blue) class product, there was no difference in response rate by dose. The methemoglobin decreased by at least 50% within 1 hour of infusion for 15/17 (88%) of patients treated with 1 mg/kg, 12/13 (92%) treated with 2 mg/kg and 16/17 (94%) treated with a different dose or for those whose dose was not reported.
Uridon Modified (Methylene Blue) is supplied in 10 mL single-dose ampules. Each 10 mL ampule contains 50 mg of Uridon Modified (Methylene Blue) as a clear dark blue solution. A box contains five ampules placed in a tray.
Box of 5 ampules: NDC 0517-0374-05
Storage:
Store at 20°C to 25°C (68°F to 77°F).
Any unused product or waste material should be disposed of in accordance with local practice.
Do not refrigerate or freeze.
Keep the ampule in the original package to protect from light.
Serotonin Syndrome
Advise patients of the possibility of serotonin syndrome, especially with concomitant use of serotonergic agents such as medications to treat depression and migraines. Advise patients to seek immediate medical attention if the following symptoms occur after treatment with Uridon Modified (Methylene Blue) : changes in mental status, autonomic instability, or neuromuscular symptoms with or without gastrointestinal symptoms .
Pregnancy
Advise pregnant women of the potential risk to the fetus with the use of Uridon Modified (Methylene Blue) during pregnancy .
Breastfeeding
Advise patients to discontinue breast-feeding for up to 8 days after treatment with Uridon Modified (Methylene Blue) .
Driving and Using Machines
Advise patients to avoid driving and use of machines during treatment with Uridon Modified (Methylene Blue). Driving can be affected as a result of a confusional state, dizziness and possible eye disturbances .
Phototoxicity
Advise patients to take protective measures against exposure to light, because phototoxicity may occur after administration of Uridon Modified (Methylene Blue) .
Skin and Body Fluid Blue Discoloration
Advise patients that Uridon Modified (Methylene Blue) may cause a blue discoloration of the skin and body fluids .
Manufactured for:
PROVEPHARM SAS
22 rue Marc Donadille
13013 Marseille, France
Manufactured by:
CENEXI
52 rue Marcel et Jacques Gaucher
94120 Fontenay sous Bois, FRANCE
Distributed by:
American Regent
Shirley, NY
Questions? : 1-800-734-9236
4/2016
[controlled part number code]
Principal Display Panel - 5 mg Ampule Label
NDC 0517-0374-01 28039135 Rev 4/16
Uridon Modified (Methylene Blue)
(methylene blue) Injection, 0.5%
50 mg/10 mL (5 mg/mL)
Intravenous use only
Single dose ampule - RX only
Discard unused portion
Manufacturer by:
CENEXI
Distributed by:
AMERICAN REGENT, INC
Shirley, NY 19967
Principal Display Panel - 5 mg Carton Label
NDC 0517-0374-05 5 ampules
Uridon Modified (Methylene Blue)
(methylene blue) Injection, 0.5%
50 mg/10 mL (5 mg/mL)
Intravenous use only - For slow intravenous injection.
10 mL - Single dose ampule -
Discard unused portion
Rx only
Distributed by:
AMERICAN
REGENT
Shirley, NY 11967
Patented: US 8,765,942; US 9,227,945
Depending on the reaction of the Uridon Modified after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Uridon Modified not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Uridon Modified addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology