Doxycycline Hyclaat may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Doxycycline hyclate (a derivative of Doxycycline) is reported as an ingredient of Doxycycline Hyclaat in the following countries:
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Aciclovir Cinfa may be available in the countries listed below.
Aciclovir is reported as an ingredient of Aciclovir Cinfa in the following countries:
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Symanastrol may be available in the countries listed below.
Anastrozole is reported as an ingredient of Symanastrol in the following countries:
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In some countries, this medicine may only be approved for veterinary use.
Rec.INN
0003615-24-5
C14-H19-N3-O
245
Analgesic, antipyretic and anti-inflammatory agent
Non-steroidal anti-inflammatory drug, NSAID
3H-Pyrazol-3-one, 1,2-dihydro-1,5-dimethyl-4-[(1-methylethyl)amino]-2-phenyl-
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Glossary
| IS | Inofficial Synonym |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Mebaxol may be available in the countries listed below.
Ornidazole is reported as an ingredient of Mebaxol in the following countries:
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Biogelat Biotin may be available in the countries listed below.
Biotin is reported as an ingredient of Biogelat Biotin in the following countries:
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Valepil may be available in the countries listed below.
Valproic Acid sodium (a derivative of Valproic Acid) is reported as an ingredient of Valepil in the following countries:
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Fluconazol Generis may be available in the countries listed below.
Fluconazole is reported as an ingredient of Fluconazol Generis in the following countries:
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Bromhexina La Santé may be available in the countries listed below.
Bromhexine is reported as an ingredient of Bromhexina La Santé in the following countries:
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Carvedilolo Mylan may be available in the countries listed below.
Carvedilol is reported as an ingredient of Carvedilolo Mylan in the following countries:
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Citalopram ecosol may be available in the countries listed below.
Citalopram hydrobromide (a derivative of Citalopram) is reported as an ingredient of Citalopram ecosol in the following countries:
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Comtan is a brand name of entacapone, approved by the FDA in the following formulation(s):
No. There is currently no therapeutically equivalent version of Comtan available.
Note: Fraudulent online pharmacies may attempt to sell an illegal generic version of Comtan. These medications may be counterfeit and potentially unsafe. If you purchase medications online, be sure you are buying from a reputable and valid online pharmacy. Ask your health care provider for advice if you are unsure about the online purchase of any medication.
See also: About generic drugs.
Patents are granted by the U.S. Patent and Trademark Office at any time during a drug's development and may include a wide range of claims.
Class: Other Nonsteroidal Anti-inflammatory Agents
Chemical Name: 2′,4′-Difluoro-4- hydroxy-[1,1′-biphenyl]-3-carboxylic acid
Molecular Formula: C13H8F2O3
CAS Number: 22494-42-4
Brands: Dolobid
Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).1 Risk may increase with duration of use.1 Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.1 (See Cardiovascular Effects under Cautions.)
Contraindicated for the treatment of pain in the setting of CABG surgery.1
Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).1 Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.1 Geriatric individuals are at greater risk for serious GI events.1 (See GI Effects under Cautions.)
Prototypical NSAIA; a difluorophenyl derivative of salicylic acid.1 2 3
Consider potential benefits and risks of diflunisal therapy as well as alternative therapies before initiating therapy with the drug.1 Use lowest effective dosage and shortest duration of therapy consistent with the patient's treatment goals.1
Relief of mild to moderate pain.1 2
Symptomatic relief of postoperative,2 9 10 postpartum, and orthopedic pain (e.g., musculoskeletal sprains or strains) and visceral pain associated with cancer.2
Symptomatic treatment of rheumatoid arthritis1 17 18 32 36 and osteoarthritis.1 12
Consider potential benefits and risks of diflunisal therapy as well as alternative therapies before initiating therapy with the drug.1
Administer orally.1 75 If GI disturbances occur, administer with meals or milk.1 75
Do not break, crush, or chew diflunisal tablets.1 75 Swallow intact.1 75
To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient's treatment goals.1 Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.1
Exhibits concentration-dependent pharmacokinetics.1 75 Plasma diflunisal concentrations increase more than proportionally with increasing and/or multiple doses; use caution when adjusting doses.1 75
Mild to moderate pain: Initially, 1 g, followed by 500 mg every 12 hours.1 75 Some patients may require 500 mg every 8 hours.1 75
Patients with lower dosage requirements (less severe pain, heightened response, low body weight): Initially, 500 mg, followed by 250 mg every 8–12 hours.1
500 mg–1 g daily in 2 divided doses.1 75
Maximum 1.5 g daily.1 75 b
Select dosage with caution because of age-related decreases in renal function.1
Initially, 500 mg, followed by 250 mg every 8–12 hours.1
Known hypersensitivity to diflunisal or any ingredient in the formulation.1
History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.1 48 49 50 51 52
Treatment of perioperative pain in the setting of CABG surgery.1
Selective COX-2 inhibitors have been associated with increased risk of cardiovascular events (e.g., MI, stroke) in certain situations.94 Several prototypical NSAIAs also have been associated with increased risk of cardiovascular events.97 98 99 Current data insufficient to assess risk associated with diflunisal.97 98 99
Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events), and at the lowest effective dosage for the shortest duration necessary.1
Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).94
No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.1 94 (See Specific Drugs under Interactions.)
Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.1 Use with caution in patients with hypertension; monitor BP.1 Impaired response to certain diuretics may occur.1 (See Specific Drugs under Interactions.)
Fluid retention and edema reported.1 Caution in patients with fluid retention or heart failure.1
Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.1 82 84 91
For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol;29 64 82 83 alternatively, consider concomitant use of a proton-pump inhibitor (e.g., lansoprazole, omeprazole) or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).29 64 82
Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.1
Potential for overt renal decompensation.1 38 40 41 42 43 44 45 Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in patients with volume depletion, in geriatric patients, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.1 39 41 (See Renal Impairment under Cautions.)
Anaphylactoid reactions reported.1
Immediate medical intervention and discontinuance for anaphylaxis.1
Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.1
Potentially life-threatening, apparent hypersensitivity syndrome reported;1 53 includes constitutional manifestations (e.g., fever, chills) and dermatologic effects (e.g., rash), and also may involve major organs (e.g., liver function abnormalities, jaundice, leukopenia, thrombocytopenia, eosinophilia, disseminated intravascular coagulation, renal impairment) and include less specific findings (e.g., adenitis, arthralgia, myalgia, arthritis, malaise, anorexia, disorientation).1 53 If hypersensitivity reaction occurs, discontinue therapy and institute appropriate therapy as indicated.1 53
Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) can occur without warning.1 Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).1
Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.1
Elevations of serum ALT or AST reported.1
Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.1 Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur or if liver function test abnormalities persist or worsen.1
Anemia reported rarely.1 Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.1
May inhibit platelet aggregation and prolong bleeding time.1
Visual disturbances reported; ophthalmic evaluation recommended if visual changes occur.1
Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.1
May mask certain signs of infection.1
Obtain CBC and chemistry profile periodically during long-term use.1
Category C.1 Avoid use in third trimester because of possible premature closure of the ductus arteriosus.1 75
Distributed into milk; discontinue nursing or the drug.1
Safety and efficacy not established in children <12 years of age.1
Use in children with varicella infections or influenza-type illnesses may be associated with an increased risk of developing Reye’s syndrome.1
Geriatric patients appear to tolerate GI ulceration and bleeding less well than other individuals.1 Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.1
Select dosage with caution because of age-related decreases in renal function.1 May be useful to monitor renal function.1
Use with caution in patients with renal impairment.1 Use not recommended in patients with severe renal impairment; close monitoring of renal function if used.1
Drug and its metabolites eliminated principally via the kidney.1
Nausea, vomiting, dyspepsia, GI pain, diarrhea, constipation, flatulence, somnolence, insomnia, dizziness, tinnitus, rash, headache, fatigue/tiredness.1
Potential for diflunisal to be displaced from binding sites by, or to displace from binding sites, other protein-bound drugs.1 2 5 Observe for adverse effects if used with other protein-bound drugs.b
Drug | Interaction | Comments |
|---|---|---|
ACE inhibitors | Reduced BP response to ACE inhibitor1 Possible deterioration of renal function in individuals with renal impairment1 | Monitor BP1 |
Acetaminophen | Increased plasma acetaminophen concentrations1 Possible increased GI toxicity1 | Use concomitantly with caution; closely monitor hepatic function1 |
Angiotensin II receptor antagonists | Reduced BP response to angiotensin II receptor antagonist1 Possible deterioration of renal function in individuals with renal impairment1 | Monitor BP1 |
Antacids | Possible decreased plasma diflunisal concentrations1 | |
Anticoagulants (warfarin) | Possible bleeding complications and increases in PT1 | Monitor PT during and for several days following concomitant therapy1 Adjust anticoagulant dosage as needed1 |
Aspirin | Possible decreased plasma diflunisal concentrations1 5 Increased risk of GI ulceration and other complications1 No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs94 | Manufacturers state that concomitant use not recommended1 |
Corticosteroids | Increased risk of GI ulceration69 73 | Use concomitantly with caution69 73 |
Cyclosporine | Increased nephrotoxic effects of cyclosporine1 | Caution advised; closely monitor renal function1 |
Diuretics (furosemide, thiazides) | Increased risk of developing renal failure1 Possible reduced natriuretic effects1 Increased plasma hydrochlorothiazide concentrations 1 Potential for decreased hyperuricemic effects of hydrochlorothiazide1 | Monitor for diuretic efficacy and renal failure1 |
Lithium | Increased plasma lithium concentrations1 | Monitor for lithium toxicity1 |
Methotrexate | Possible toxicity associated with increased plasma methotrexate concentrations56 57 58 59 60 61 62 | Use concomitantly with caution1 |
NSAIAs | Possible additive adverse GI effects1 | Concomitant use not recommended1 75 |
Thrombolytic agents (streptokinase) | Possible increased risk of bleeding complications28 | Use concomitantly with caution 28 |
Tolbutamide | Concomitant use does not appear to affect the hypoglycemic response or plasma tolbutamide concentrations1 |
Well absorbed following oral administration; peak plasma concentrations usually attained within 2–3 hours.1 2 5
Analgesic effect occurs within 1 hour; maximum analgesic effect occurs within 2–3 hours.1
Food slightly decreases the rate but not the extent of absorption.5
Distributed into CSF and crosses the placenta in small amounts in animals.1 Distributed into human milk.1
Approximately 98–99%.1 2 5
Metabolized in the liver to glucuronide conjugates.1 2 8
Excreted in urine (90%) mainly as glucuronide conjugates and in feces (<5%).1 2 5 8
8–12 hours.1 7
In patients with severe renal impairment (i.e., Clcr<2 mL/minute), terminal half-life is approximately 68–138 hours.7
<40°C; preferably 15–30°C.34
Inhibits cyclooxygenase-1 (COX-1) and COX-2.76 77 78 79 80 81
Pharmacologic actions similar to those of other prototypical NSAIAs;2 5 exhibits anti-inflammatory, analgesic, and antipyretic activity.1 2
Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.1
Risk of serious cardiovascular events with long-term use.1
Risk of GI bleeding and ulceration.1
Risk of serious skin reactions.1 Risk of anaphylactoid and other sensitivity reactions.1
Risk of hepatotoxicity.1
Importance of notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.1
Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.1
Importance of discontinuing therapy and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.1 Importance of seeking immediate medical attention if an anaphylactic reaction occurs.1
Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Importance of avoiding diflunisal in late pregnancy (third trimester).1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 250 mg* | Dolobid | Merck |
500 mg* | Diflunisal Tablets | Sandoz, Teva, Watson | ||
Dolobid | Merck |
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Diflunisal 500MG Tablets (TEVA PHARMACEUTICALS USA): 60/$69.99 or 180/$189.98
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
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76. Hawkey CJ. COX-2 inhibitors. Lancet. 1999; 353:307-14. [IDIS 418284] [PubMed 9929039]
77. Kurumbail RG, Stevens AM, Gierse JK et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature. 1996; 384:644-8. [PubMed 8967954]
78. Riendeau D, Charleson S, Cromlish W et al. Comparison of the cyclooxygenase-1 inhibitory properties of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, using sensitive microsomal and platelet assays. Can J Phsiol Pharmacol. 1997; 75:1088-95.
79. DeWitt DL, Bhattacharyya D, Lecomte M et al. The differential susceptibility of prostaglandin endoperoxide H synthases-1 and -2 to nonsteroidal anti-inflammatory drugs: aspirin derivatives as selective inhibitors. Med Chem Res. 1995; 5:325-43.
80. Cryer B, Dubois A. The advent of highly selective inhibitors of cyclooxygenase— a review. Prostaglandins Other Lipid Mediators. 1998; 56:341-61. [PubMed 9990677]
81. Simon LS. Role and regulation of cyclooxygenase-2 during inflammation. Am J Med. 1999; 106(Suppl 5B):37-42S.
82. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999; 340:1888-99. [IDIS 426864] [PubMed 10369853]
83. Lanza FL, and the members of the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. A guideline for the treatment and prevention of NSAID-induced ulcers. Am J Gastroenterol. 1998; 93:2037-46. [IDIS 417402] [PubMed 9820370]
84. Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol. 1999; 26(suppl 56):18-24.
85. in’t Veld BA, Ruitenberg A, Hofman A et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N Engl J Med. 2001; 345:1515-21. [PubMed 11794217]
86. Breitner JCS, Zandi PP. Do nonsteroidal antiinflammatory drugs reduce the risk of Alzheimer’s disease? N Engl J Med. 2001; 345:1567-8. Editorial.
87. McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology. 1996; 47:425-32. [IDIS 371394] [PubMed 8757015]
88. Beard CM, Waring SC, O’sBrien PC et al. Nonsteroidal anti-inflammatory drug use and Alzheimer’s disease : a case-control study in Rochester, Minnesota, 1980 through 1984. Mayo Clin Proc. 1998; 73:951-5. [IDIS 416502] [PubMed 9787743]
89. in’t Veld BA, Launer LJ, Hoes AW et al. NSAIDs and incident Alzheimer’s disease: the Rotterdam Study. Neurobiol Aging. 1998; 19:607-11. [PubMed 10192221]
90. Stewart WF, Kawas C, Corrada M et al. Risk of Alzheimer’s disease and duration of NSAID use. Neurology. 1997; 48:626-32. [IDIS 383303] [PubMed 9065537]
91. Pharmacia. Daypro (oxaprozin) caplets prescribing information. Chicago, IL; 2002 May.
92. Chan FKL, Hung LCT, Suen BY et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med. 2002; 347:2104-10. [IDIS 490812] [PubMed 12501222]
93. Graham DY. NSAIDs, Helicobacter pylori, and Pandora’s box. N Engl J Med. 2002; 347:2162-4. [IDIS 490815] [PubMed 12501230]
94. Food and Drug Administration. Analysis and recommendations for agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk. 2005 Apr 6.
95. Cush JJ. The safety of COX-2 inhibitors: deliberations from the February 16-18, 2005, FDA meeting. From the American College of Rheumatology website (). Accessed 2005 Oct 12.
96. Novartis Pharmaceuticals. Diovan (valsartan) capsules prescribing information (dated 1997 Apr). In: Physicians’ desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:2013-5.
97. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006; 296: 1633-44. [PubMed 16968831]
98. Kearney PM, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006; 332: 1302-5. [PubMed 16740558]
99. Graham DJ. COX-2 inhibitors, other NSAIDs, and cardiovascular risk; the seduction of common sense. JAMA. 2006; 296:1653-6. [PubMed 16968830]
100. Chou R, Helfand M, Peterson K et al. Comparative effectiveness and safety of analgesics for osteoarthritis. Comparative effectiveness review no. 4. (Prepared by the Oregon evidence-based practice center under contract no. 290-02-0024.) . Rockville, MD: Agency for Healthcare Research and Quality. 2006 Sep. Available at: .
b. AHFS drug information 2006. McEvoy GK, ed. Diflunisal. Bethesda, MD: American Society of Health-System Pharmacists; 2006:2022-2026.
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Rec.INN
0001336-80-7
C11-H24-Fe-N-O11
402
Antianemic agent
Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, (OC-6-44)-triaqua[2-hydroxy-1,2,3-propanetricarboxylato(4-)]ferrate(1-)
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| IS | Inofficial Synonym |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
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Treatment of patients with Droxia may be complicated by severe, sometimes life-threatening, adverse effects. Droxia should be administered under the supervision of a physician experienced in the use of this medication for the treatment of sickle cell anemia.
Hydroxyurea is mutagenic and clastogenic, and causes cellular transformation to a tumorigenic phenotype. Hydroxyurea is thus unequivocally genotoxic and a presumed transspecies carcinogen which implies a carcinogenic risk to humans. In patients receiving long-term hydroxyurea for myeloproliferative disorders, such as polycythemia vera and thrombocythemia, secondary leukemias have been reported. It is unknown whether this leukemogenic effect is secondary to hydroxyurea or is associated with the patient’s underlying disease. The physician and patient must very carefully consider the potential benefits of Droxia relative to the undefined risk of developing secondary malignancies.
Droxia® (hydroxyurea capsules, USP) is available for oral use as capsules providing 200 mg, 300 mg, and 400 mg hydroxyurea. Inactive ingredients: citric acid, gelatin, lactose, magnesium stearate, sodium phosphate, titanium dioxide, and capsule colorants; FD&C Blue #1 and FD&C Green #3 (200 mg capsules); D&C Red #28, D&C Red #33, and FD&C Blue #1 (300 mg capsules); D&C Red #28, D&C Red #33, and D&C Yellow #10 (400 mg capsules).
Hydroxyurea is an essentially tasteless, white crystalline powder. Its structural formula is:
The precise mechanism by which hydroxyurea produces its cytotoxic and cytoreductive effects is not known. However, various studies support the hypothesis that hydroxyurea causes an immediate inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or of protein.
The mechanisms by which Droxia produces its beneficial effects in patients with sickle cell anemia (SCA) are uncertain. Known pharmacologic effects of Droxia that may contribute to its beneficial effects include increasing hemoglobin F levels in RBCs, decreasing neutrophils, increasing the water content of RBCs, increasing deformability of sickled cells, and altering the adhesion of RBCs to endothelium.
Hydroxyurea is readily absorbed after oral administration. Peak plasma levels are reached in 1 to 4 hours after an oral dose. With increasing doses, disproportionately greater mean peak plasma concentrations and AUCs are observed.
There are no data on the effect of food on the absorption of hydroxyurea.
Hydroxyurea distributes rapidly and widely in the body with an estimated volume of distribution approximating total body water.
Plasma to ascites fluid ratios range from 2:1 to 7.5:1. Hydroxyurea concentrates in leukocytes and erythrocytes.
Up to 60% of an oral dose undergoes conversion through metabolic pathways that are not fully characterized. One pathway is probably saturable hepatic metabolism. Another minor pathway may be degradation by urease found in intestinal bacteria. Acetohydroxamic acid was found in the serum of three leukemic patients receiving hydroxyurea and may be formed from hydroxylamine resulting from action of urease on hydroxyurea.
Excretion of hydroxyurea in humans is likely a linear first-order renal process. In adults with SCA, mean cumulative urinary recovery of hydroxyurea was about 40% of the administered dose.
No information is available regarding pharmacokinetic differences due to age, gender, or race.
No pharmacokinetic data are available in pediatric patients treated with hydroxyurea for SCA.
As renal excretion is a pathway of elimination, consideration should be given to decreasing the dosage of hydroxyurea in patients with renal impairment. In adult patients with sickle cell disease, an open-label, non-randomized, single-dose, multicenter study was conducted to assess the influence of renal function on the pharmacokinetics of hydroxyurea. Patients in the study with normal renal function (creatinine clearance [CrCl] >80 mL/min), mild (CrCl 50-80 mL/min), moderate (CrCl = 30-<50 mL/min), or severe (<30 mL/min) renal impairment received hydroxyurea as a single oral dose of 15 mg/kg, achieved by using combinations of the 200 mg, 300 mg, or 400 mg capsules. Patients with end-stage renal disease (ESRD) received two doses of 15 mg/kg separated by 7 days, the first was given following a 4-hour hemodialysis session, the second prior to hemodialysis. In this study, the mean exposure (AUC) in patients whose creatinine clearance was <60 mL/min (or ESRD) was approximately 64% higher than in patients with normal renal function. The results suggest that the initial dose of hydroxyurea should be reduced when used to treat patients with renal impairment. (See PRECAUTIONS and DOSAGE AND ADMINISTRATION.) The table below describes the recommended dosage modification.
| *On dialysis days, hydroxyurea should be administered to patients with ESRD following hemodialysis. | |
| Creatinine Clearance (mL/min) | Recommended Droxia Initial Dose (mg/kg daily) |
| ≥60 | 15 |
| <60 or ESRD* | 7.5 |
Close monitoring of hematologic parameters is advised in these patients.
There are no data that support specific guidance for dosage adjustment in patients with hepatic impairment. Close monitoring of hematologic parameters is advised in these patients.
There are no data on concomitant use of hydroxyurea with other drugs in humans.
The efficacy of hydroxyurea in sickle cell anemia was assessed in a large clinical study (Multicenter Study of Hydroxyurea in Sickle Cell Anemia).1
The study was a randomized, double-blind, placebo-controlled trial that evaluated 299 adult patients (≥18 years) with moderate to severe disease (≥3 painful crises yearly). The trial was stopped by the Data Safety Monitoring Committee, after accrual was completed but before the scheduled 24 months of follow-up was completed in all patients, based on observations of fewer painful crises among patients receiving hydroxyurea.
Compared to placebo treatment, treatment with hydroxyurea resulted in a significant decrease in the yearly rate of painful crises, the yearly rate of painful crises requiring hospitalization, the incidence of chest syndrome, the number of patients transfused, and units of blood transfused. Hydroxyurea treatment significantly increased the median time to both first and second painful crises.
Although patients with 3 or more painful crises during the preceding 12 months were eligible for the study, most of the benefit in crisis reduction was seen in the patients with 6 or more painful crises during the preceding 12 months.
EVENT | HYDROXYUREA (N=152) | PLACEBO (N=147) | PERCENT CHANGE VS PLACEBO | P-VALUE |
|---|---|---|---|---|
| * A painful crisis was defined in the study as acute sickling-related pain that resulted in a visit to a medical facility, that lasted more than 4 hours, and that required treatment with a parenteral narcotic or NSAID. Chest syndrome, priapism, and hepatic sequestration were also included in this definition. | ||||
| Median yearly rate of painful crises* | 2.5 | 4.6 | −46 | =0.001 |
| Median yearly rate of painful crises requiring hospitalization | 1.0 | 2.5 | −60 | =0.0027 |
| Median time to first painful crisis (months) | 2.76 | 1.35 | +104 | =0.014 |
| Median time to second painful crisis (months) | 6.58 | 4.13 | +59 | =0.0024 |
| Incidence of chest syndrome (# episodes) | 56 | 101 | −45 | =0.003 |
| Number of patients transfused | 55 | 79 | −30 | =0.002 |
| Number of units of blood transfused | 423 | 670 | −37 | =0.003 |
No deaths were attributed to treatment with hydroxyurea, and none of the patients developed neoplastic disorders during the study. Treatment was permanently stopped for medical reasons in 14 hydroxyurea-treated (2 patients with myelotoxicity) and 6 placebo-treated patients. (See ADVERSE REACTIONS.)
In patients with SCA treated with hydroxyurea, fetal hemoglobin (HbF) increases 4 to 12 weeks after initiation of treatment. In general, average HbF levels correlate with dose and plasma level with possible plateauing at higher dosages.
A clear relation between reduction in crisis frequency and increased HbF or F-cell levels has not been demonstrated. The dose-related cytoreductive effects of hydroxyurea, particularly on neutrophils, was the factor most strongly correlated with reduced crisis frequency.
Droxia (hydroxyurea capsules, USP) is indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in adult patients with sickle cell anemia with recurrent moderate to severe painful crises (generally at least 3 during the preceding 12 months).
Droxia is contraindicated in patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation.
Droxia is a cytotoxic and myelosuppressive agent. Droxia should not be given if bone marrow function is markedly depressed, as indicated by neutrophils below 2000 cells/mm3; a platelet count below 80,000/mm3; a hemoglobin level below 4.5 g/dL; or reticulocytes below 80,000/mm3 when the hemoglobin concentration is below 9 g/dL. Neutropenia is generally the first and most common manifestation of hematologic suppression. (See DOSAGE AND ADMINISTRATION.) Thrombocytopenia and anemia occur less often, and are seldom seen without a preceding leukopenia. Recovery from myelosuppression is usually rapid when therapy is interrupted. Droxia causes macrocytosis, which may mask the incidental development of folic acid deficiency. Prophylactic administration of folic acid is recommended.
In HIV-infected patients during therapy with hydroxyurea and didanosine, with or without stavudine, fatal and nonfatal pancreatitis have occurred. Hepatotoxicity and hepatic failure resulting in death have been reported during postmarketing surveillance in HIV-infected patients treated with hydroxyurea and other antiretroviral agents. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine. This combination should be avoided.
Peripheral neuropathy, which was severe in some cases, has been reported in HIV-infected patients receiving hydroxyurea in combination with antiretroviral agents, including didanosine, with or without stavudine.
Cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene, have occurred in patients with myeloproliferative disorders during therapy with hydroxyurea. These vasculitic toxicities were reported most often in patients with a history of, or currently receiving, interferon therapy. Due to potentially severe clinical outcomes for the cutaneous vasculitic ulcers reported in patients with myeloproliferative disease, hydroxyurea should be discontinued if cutaneous vasculitic ulcerations develop.
(See BOXED WARNING.)
Hydroxyurea is genotoxic in a wide range of test systems and is thus presumed to be a human carcinogen. In patients receiving long-term hydroxyurea for myeloproliferative disorders, such as polycythemia vera and thrombocythemia, secondary leukemia has been reported. It is unknown whether this leukemogenic effect is secondary to hydroxyurea or is associated with the patient’s underlying disease. Skin cancer has also been reported in patients receiving long-term hydroxyurea.
Conventional long-term studies to evaluate the carcinogenic potential of Droxia have not been performed. However, intraperitoneal administration of 125 to 250 mg/kg hydroxyurea (about 0.6-1.2 times the maximum recommended human oral daily dose on a mg/m2 basis) thrice weekly for 6 months to female rats increased the incidence of mammary tumors in rats surviving to 18 months compared to control. Hydroxyurea is mutagenic in vitro to bacteria, fungi, protozoa, and mammalian cells. Hydroxyurea is clastogenic in vitro (hamster cells, human lymphoblasts) and in vivo (SCE assay in rodents, mouse micronucleus assay). Hydroxyurea causes the transformation of rodent embryo cells to a tumorigenic phenotype.
Droxia can cause fetal harm when administered to a pregnant woman. Hydroxyurea has been demonstrated to be a potent teratogen in a wide variety of animal models, including mice, hamsters, cats, miniature swine, dogs, and monkeys at doses within 1-fold of the human dose given on a mg/m2 basis. Hydroxyurea is embryotoxic and causes fetal malformations (partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, missing lumbar vertebrae) at 180 mg/kg/day (about 0.8 times the maximum recommended human daily dose on a mg/m2 basis) in rats and at 30 mg/kg/day (about 0.3 times the maximum recommended human daily dose on a mg/m2 basis) in rabbits. Embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays. Hydroxyurea crosses the placenta. Single doses of ≥375 mg/kg (about 1.7 times the maximum recommended human daily dose on a mg/m2 basis) to rats caused growth retardation and impaired learning ability. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.
Therapy with Droxia requires close supervision. Some patients treated at the recommended initial dose of 15 mg/kg/day have experienced severe or life-threatening myelosuppression, requiring interruption of treatment and dose reduction. The hematologic status of the patient, as well as kidney and liver function should be determined prior to, and repeatedly during treatment. Treatment should be interrupted if neutrophil levels fall to <2000/mm3; platelets fall to <80,000/mm3; hemoglobin declines to less than 4.5 g/dL; or if reticulocytes fall below 80,000/mm3 when the hemoglobin concentration is below 9 g/dL. Following recovery, treatment may be resumed at lower doses (see DOSAGE AND ADMINISTRATION).
Hydroxyurea should be used with caution in patients with renal dysfunction. Data from a single-dose study of the pharmacokinetics of hydroxyurea in patients with sickle cell anemia suggest that the initial dose of hydroxyurea should be reduced in patients with renal impairment. (See CLINICAL PHARMACOLOGY: Special Populations and DOSAGE AND ADMINISTRATION.)
Patients must be able to follow directions regarding drug administration and their monitoring and care.
Hydroxyurea is not indicated for the treatment of HIV infection; however, if HIV-infected patients are treated with hydroxyurea, and in particular, in combination with didanosine and/or stavudine, close monitoring for signs and symptoms of pancreatitis is recommended. Patients who develop signs and symptoms of pancreatitis should permanently discontinue therapy with hydroxyurea. (See WARNINGS and ADVERSE REACTIONS.)
An increased risk of hepatotoxicity, which may be fatal, may occur in patients treated with hydroxyurea, and in particular, in combination with didanosine and stavudine. This combination should be avoided.
See WARNINGS and BOXED WARNING for Carcinogenesis and Mutagenesis information.
Impairment of Fertility: Hydroxyurea administered to male rats at 60 mg/kg/day (about 0.3 times the maximum recommended human daily dose on a mg/m2 basis) produced testicular atrophy, decreased spermatogenesis, and significantly reduced their ability to impregnate females.
Pregnancy Category D. (See WARNINGS.)
Hydroxyurea is excreted in human milk. Because of the potential for serious adverse reactions with hydroxyurea, a decision should be made either to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in pediatric patients have not been established.
Prospective studies on the potential for hydroxyurea to interact with other drugs have not been performed.
Studies have shown that there is an analytical interference of hydroxyurea with the enzymes (urease, uricase, and lactic dehydrogenase) used in the determination of urea, uric acid and lactic acid, rendering falsely elevated results of these in patients treated with hydroxyurea.
(See Patient Information at end of labeling.)
Patients should be reminded that this medication must be handled with care. People who are not taking Droxia should not be exposed to it. To decrease the risk of exposure, wear disposable gloves when handling Droxia or bottles containing Droxia. Anyone handling Droxia should wash their hands before and after contact with the bottle or capsules. If the powder from the capsule is spilled, it should be wiped up immediately with a damp disposable towel and discarded in a closed container, such as a plastic bag. The medication should be kept away from children and pets. Contact your doctor for instructions on how to dispose of outdated capsules.
The necessity of monitoring blood counts every two weeks, throughout the duration of therapy, should be emphasized. For additional information, see the accompanying Patient Information leaflet.
In patients treated for sickle cell anemia in the Multicenter Study of Hydroxyurea in Sickle Cell Anemia,1 the most common adverse reactions were hematologic, with neutropenia, and low reticulocyte and platelet levels necessitating temporary cessation in almost all patients. Hematologic recovery usually occurred in two weeks.
Non-hematologic events that possibly were associated with treatment include hair loss, skin rash, fever, gastrointestinal disturbances, weight gain, bleeding, and parvovirus B-19 infection; however, these non-hematologic events occurred with similar frequencies in the hydroxyurea and placebo treatment groups. Melanonychia has also been reported in patients receiving Droxia for SCA.
Adverse events associated with the use of hydroxyurea in the treatment of neoplastic diseases, in addition to hematologic effects include: gastrointestinal symptoms (stomatitis, anorexia, nausea, vomiting, diarrhea, and constipation), and dermatological reactions such as maculopapular rash, skin ulceration, dermatomyositis-like skin changes, peripheral erythema, and facial erythema. Hyperpigmentation, atrophy of skin and nails, scaling, and violet papules have been observed in some patients after several years of long-term daily maintenance therapy with hydroxyurea. Skin cancer has been reported. Cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene, have occurred in patients with myeloproliferative disorders during therapy with hydroxyurea. These vasculitic toxicities were reported most often in patients with a history of, or currently receiving, interferon therapy (see WARNINGS). Dysuria and alopecia have been reported. Large doses may produce drowsiness. Neurological disturbances have occurred and were limited to headache, dizziness, disorientation, hallucinations, and convulsions. Hydroxyurea may cause temporary impairment of renal tubular function accompanied by elevations in serum uric acid, blood urea nitrogen (BUN), and creatinine levels. Abnormal bromsulphalein (BSP) retention has been reported. Fever, chills, malaise, edema, asthenia, and elevation of hepatic enzymes have also been reported.
The association of hydroxyurea with the development of acute pulmonary reactions consisting of diffuse pulmonary infiltrates, fever, and dyspnea has been reported. Pulmonary fibrosis also has been reported.
In HIV-infected patients who received hydroxyurea in combination with antiretroviral agents, in particular, didanosine plus stavudine, fatal and nonfatal pancreatitis and hepatotoxicity, and severe peripheral neuropathy have been reported. Patients treated with hydroxyurea in combination with didanosine, stavudine, and indinavir in Study ACTG 5025 showed a median decline in CD4 cells of approximately 100/mm3. (SeeWARNINGS and PRECAUTIONS.)
Acute mucocutaneous toxicity has been reported in patients receiving hydroxyurea at dosages several times the therapeutic dose. Soreness, violet erythema, edema on palms and soles followed by scaling of hands and feet, severe generalized hyperpigmentation of the skin, and stomatitis have been observed.
Procedures for proper handling and disposal of cytotoxic drugs should be considered. Several guidelines on this subject have been published.2-5
To minimize the risk of dermal exposure, always wear impervious gloves when handling bottles containing Droxia capsules. Droxia capsules should not be opened. Personnel should avoid exposure to crushed or opened capsules. If contact with crushed or opened capsules occurs, wash immediately and thoroughly. More information is available in the references listed below.
Dosage should be based on the patient’s actual or ideal weight, whichever is less. The initial dose of Droxia is 15 mg/kg/day as a single dose. The patient’s blood count must be monitored every two weeks. (See WARNINGS.)
If blood counts are in an acceptable range*, the dose may be increased by 5 mg/kg/day every 12 weeks until a maximum tolerated dose (the highest dose that does not produce toxic** blood counts over 24 consecutive weeks), or 35 mg/kg/day, is reached.
If blood counts are between the acceptable range* and toxic**, the dose is not increased.
If blood counts are considered toxic**, Droxia should be discontinued until hematologic recovery. Treatment may then be resumed after reducing the dose by 2.5 mg/kg/day from the dose associated with hematologic toxicity. Droxia may then be titrated up or down, every 12 weeks in 2.5 mg/kg/day increments, until the patient is at a stable dose that does not result in hematologic toxicity for 24 weeks. Any dosage on which a patient develops hematologic toxicity twice should not be tried again.
*acceptable range =
neutrophils ≥2500 cells/mm3,
platelets ≥95,000/mm3,
hemoglobin >5.3 g/dL and
reticulocytes ≥95,000/mm3 if the hemoglobin concentration <9 g/dL.
**toxic =
neutrophils <2000 cells/mm3,
platelets <80,000/mm3,
hemoglobin <4.5 g/dL and
reticulocytes <80,000/mm3 if the hemoglobin concentration <9 g/dL.
As renal excretion is a pathway of elimination, consideration should be given to decreasing the dosage of Droxia in patients with renal impairment. The results of a single-dose study of the influence of renal function on the pharmacokinetics of hydroxyurea in adults with sickle cell disease suggest that the initial dose of hydroxyurea should be reduced by 50%, to 7.5 mg/kg/day, when used to treat patients with renal impairment. (See PRECAUTIONS and CLINICAL PHARMACOLOGY.) Close monitoring of hematologic parameters is advised in these patients.
| *On dialysis days, hydroxyurea should be administered to patients with ESRD following hemodialysis. | |
| Creatinine Clearance (mL/min) | Recommended Droxia Initial Dose (mg/kg daily) |
| ≥60 | 15 |
| <60 or ESRD* | 7.5 |
There are no data that support specific guidance for dosage adjustment in patients with hepatic impairment. Close monitoring of hematologic parameters is advised in these patients.
Droxia® (hydroxyurea capsules, USP).
200 mg capsules packaged in HDPE bottles of 60 with a plastic safety screw cap. (NDC 0003-6335-17). The cap and body are opaque blue-green. The capsule is marked in black ink on both the cap and body with “Droxia” and “6335”.
300 mg capsules packaged in HDPE bottles of 60 with a plastic safety screw cap. (NDC 0003-6336-17). The cap and body are opaque purple. The capsule is marked in black ink on both the cap and body with “Droxia” and “6336”.
400 mg capsules packaged in HDPE bottles of 60 with a plastic safety screw cap. (NDC 0003-6337-17). The cap and body are opaque reddish-orange. The capsule is marked in black ink on both the cap and body with “Droxia” and “6337”.
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Keep tightly closed.
Manufactured for:
Bristol-Myers Squibb Company
Princeton, New Jersey 08543 USA
Made in Italy
1053547A7
Rev July 2011
Patient Information About
Droxia® Capsules
(generic name = hydroxyurea)
What is the most important information I should know about Droxia?
Droxia (pronounced drock-SEE-yuh) capsules are used to treat sickle cell anemia in adults. Droxia reduces the frequency of painful crises and reduces the need for blood transfusions.
What is Droxia?
Droxia (hydroxyurea capsules, USP) is a prescription medicine that is used to reduce the frequency of painful crises and reduce the need for blood transfusions in adults with sickle cell anemia. How Droxia works is not certain but it may work by reducing the number of white blood cells and/or increasing red blood cells that carry fetal hemoglobin (HbF). Fetal hemoglobin may prevent sickling.
What is Sickle Cell Anemia?
Sickle cell anemia is an inherited disorder of the red blood cells. Red blood cells carry oxygen to all parts of the body by using a protein called hemoglobin. Normal red blood cells contain only normal hemoglobin and are shaped like indented disks. These cells are very flexible and move easily through small blood vessels.
In sickle cell anemia, the red blood cells contain sickle hemoglobin, which causes them to change to a rigid, spiked shape (sickle shape) after oxygen is released. Sickled cells get stuck and form plugs in small blood vessels. These plugs restrict blood flow, causing damage to surrounding tissues resulting in a painful crisis.
Because there are blood vessels in all parts of the body, painful crises can occur anywhere in your body. In addition, sickle cells are trapped and destroyed in the liver and spleen. This results in a shortage of red blood cells (anemia).
Will Droxia cure my Sickle Cell Anemia?
No. However, Droxia may help you better control your sickle cell anemia, but it is important to follow your doctor’s instructions carefully.
In a study of adults taking recommended doses, daily treatment with Droxia resulted in fewer painful crises, fewer patients with “acute chest syndrome” (a pneumonia-like condition that leads to difficulty in breathing) and less need for blood transfusions.
Who should not take Droxia capsules?
Do not take Droxia capsules if you are allergic to any of the ingredients. Besides the active ingredient hydroxyurea, Droxia capsules contain the following inactive ingredients: citric acid, gelatin, lactose, magnesium stearate, sodium phosphate, titanium dioxide, and capsule colorants. Tell your doctor if you think you have ever had an allergic reaction.
If you get pregnant, Droxia may harm or cause death to your unborn child. You should not become pregnant while taking Droxia. Make sure you use a contraceptive method. Tell your doctor if you become pregnant or plan to become pregnant while taking Droxia.
How do I take Droxia capsules?
Always follow your doctor’s instructions carefully when taking Droxia capsules or any prescription medication. The usual dose of Droxia may range from as few as one to several capsules per day. Droxia is usually taken once a day. You should try to take it at the same time each day. Your doctor will determine the proper starting dose of Droxia for you based on your weight and blood count. The dose will then be increased slowly to your maximum tolerated dose (maximum dose that does NOT produce severely low blood counts). Your doctor should measure your blood counts every two weeks after you begin treatment with Droxia. Depending on the results, your dosage may be adjusted or the drug may be stopped for a while.
If you accidentally take an overdose of Droxia capsules, seek medical attention immediately. Contact your doctor, local Poison Control Center, or emergency room.
How do I handle Droxia capsules safely?
Droxia is a medication that must be handled with care. People who are not taking Droxia should not be exposed to it. To decrease the risk of exposure, wear disposable gloves when handling Droxia or bottles containing Droxia. Anyone handling Droxia should wash their hands before and after contact with the bottle or capsules. If the powder from the capsule is spilled, it should be wiped up immediately with a damp disposable towel and discarded in a closed container, such as a plastic bag. Droxia should be kept out of the reach of children and pets. Contact your doctor or pharmacist for instructions on how to dispose of outdated capsules.
What if I miss a dose of Droxia capsules?
Try not to miss your dose of Droxia, but if you do, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses during the same day. If you miss more than one dose, call your doctor for instructions.
What should I avoid while taking Droxia capsules?
Some other medications can increase your risk of experiencing serious side effects from Droxia. While you are taking Droxia capsules, you should inform your doctor of all prescription and over-the-counter medicines that you are taking.
In nursing mothers, Droxia is present in breast milk. Because of the potential for side effects in the newborn, you should discontinue nursing your baby while taking Droxia.
What are the possible side effects of Droxia capsules?
As with other medicines, Droxia may cause unwanted effects, although it is not always possible to tell whether such effects are caused by Droxia, another medication you may be taking, or your sickle cell anemia. Any side effects or unusual symptoms that you experience should be reported to your doctor, particularly if they persist or are troublesome.
The most serious side effects of Droxia involve the blood, and may include severely low white blood cell counts (leukopenia, neutropenia), which can decrease your resistance to infections, severely low red blood cell counts (anemia), or severely low platelet counts (thrombocytopenia), which can cause bleeding. Almost all patients who received Droxia in clinical studies needed to have their medication stopped for a time to allow their low blood counts to return to acceptable levels.
The side effects reported most often by adults with sickle cell anemia participating in studies of Droxia included hair loss, skin rash, fever, stomach and/or bowel disturbances, weight gain, bleeding, virus infection, and discolored nails (melanonychia), but these were equally common in people getting a placebo (sugar pill).
Skin cancer and leukemia, which can be fatal, have been reported in patients receiving long-term hydroxyurea for conditions other than sickle cell anemia. In laboratory tests, Droxia causes changes in chromosomes and DNA (genetic material) that strongly suggest it can cause cancer in people, especially if it is taken for a long time.
Skin ulcers have been seen in patients taking Droxia therapy. Contact your doctor if skin ulcers develop while you are taking Droxia.
Are regular blood counts necessary while taking Droxia capsules?
Yes. Your doctor should measure your blood counts every two weeks while you are taking Droxia. Your Droxia dose will require adjustment based on these regular blood counts. Serious problems can occur if the Droxia dose is not adjusted on time.
What else should I know about Droxia capsules?
If you have kidney or liver disease, close monitoring of your blood count, kidney and liver function will be required. If you have kidney disease, your dose of Droxia may be started at a lower level and increased gradually.
Because it may not be possible to detect a deficiency of folic acid in patients taking Droxia, your doctor may prescribe a folic acid supplement for you.
What else should I do to control my sickle cell crises?
Because painful crises can be brought on by factors such as infection, dehydration, worsening anemia, emotional stress, extreme temperature exposure, or ingestion of substances such as alcohol or other recreational drugs, you should be aware of the following general guidelines that will help keep you pain-free:
What should I know if I am HIV-positive?
Because of serious, life-threatening side effects associated with Droxia used in combination with certain medications for HIV, your doctor should closely monitor your pancreas and liver function with frequent physical examinations and laboratory blood tests. The combination of Droxia, ZERIT® (stavudine) and VIDEX® (didanosine) should be avoided. Some studies have shown a decrease in the number of CD4 (T-cells) for HIV-positive patients taking Droxia. Although Droxia is approved by the U.S. Food and Drug Administration for treating sickle cell anemia, it is not approved for treating HIV infection.
This medicine was prescribed for your particular condition. Do not use Droxia capsules for another condition or give it to others.
This summary does not include everything there is to know about Droxia capsules. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. If you have questions or concerns, or want more information about Droxia capsules, your physician and pharmacist have the complete prescribing information upon which this guide is based. You may want to read it and discuss it with your doctor. Remember, no written summary can replace careful discussion with your doctor.
This Patient Information has been approved by the U.S. Food and Drug Administration.
Manufactured for:
Bristol-Myers Squibb Company
Princeton, New Jersey 08543 USA
Made in Italy
1053547A7
Rev July 2011
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REPRESENTATIVE PACKAGING
See How Supplied section for a complete list of available packages of Droxia.
60 CAPSULES
NDC 0003-6335-17
Droxia®
(hydroxyurea capsules, USP)
200 mg per capsule
Rx only
Bristol-Myers Squibb
60 CAPSULES
NDC 0003-6336-17
Droxia®
(hydroxyurea capsules, USP)
300 mg per capsule
Rx only
Bristol-Myers Squibb
60 CAPSULES
NDC 0003-6337-17
Droxia®
(hydroxyurea capsules, USP)
400 mg per capsule
Rx only
Bristol-Myers Squibb
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