hydroxyurea; hydroxycarbamide (Hydrea, Droxia)
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Indications
- sickle cell anemia
- increases hemoglobin F
- reduces frequency of acute chest syndrome, painful crises, hospitalizations, & blood transfusions[9]
- underutilized[9]
- polycythemia vera
- essential thrombocytosis
- psoriasis
- AIDS
- malignant neoplasms
- melanoma
- granulocytic leukemia (CML)
- ovarian carcinomas
- trophoblastic neoplasm
- squamous cell carcinoma of the head & neck
- used in association with radiation therapy
Contraindications
- severe anemia
- WBC < 2500/mm3
- platelets < 100,000/mm3
- pregnancy
- stop at least 3 months prior to conception[5]
Dosage
- solid tumor: 80 mg/kg PO as single dose or every 3rd day
- CML: 30-30 mg/kg daily
- sickle cell & polycythemia: 500 mg PO QD
- 15-20 mg/kg daily, increase PRN
Capsules: 500 mg.
Pharmacokinetics
- well abosorbed orally
- 50% metabolized by liver to inactive metabolites
- 50% eliminated in the urine unchanged
- 1/2life 2-4 hours
elimination via kidney
elimination via liver
1/2life = 2-4 hours
Adverse effects
- common (> 10%)
- less common (1-10%)
- skin changes: hyperpigmentation, erythema of hands & face, maculopapular rash, dry skin
- alopecia
- increased creatinine & BUN
- abnormal LFTs
- carcinogenic potential
- uncommon (< 1%)
- neurotoxicity, renal tubular impairment, hyperuricemia, dizziness, disorientation, hallucination, seizures, headache, dysuria
- other
- vasculitis, resulting in ulcerations & gangrene[4]
- decreased sperm count
- macrocytosis & macrocytic anemia[5]
Drug interactions
- 5-fluorouracil
- interferon therapy may increase risk of vasculitis[4]
Test interactions
increases serum K+
Mechanism of action
- antimetabolite
- inhibits the incorporation of thymidine into DNA
- directly damages DNA
- S-phase inhibitor
- urease inhibitor
- induces fetal hemoglobin synthesis
- inhibits ribonucleotide reductase Mechanism of drug resistance:
- alteration in target enzyme ribonucleotide reductase
More general terms
Additional terms
References
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529, 533
- ↑ 4.0 4.1 4.2 FDA Medwatch http://www.fda.gov/medwatch/safety/2006/safety06.htm#Hydrea
- ↑ 5.0 5.1 5.2 5.3 5.4 Medical Knowledge Self Assessment Program (MKSAP) 16, 17. American College of Physicians, Philadelphia 2012, 2015
- ↑ Burns ER, Reed LJ, Wenz B. Volumetric erythrocyte macrocytosis induced by hydroxyurea. Am J Clin Pathol. 1986 Mar;85(3):337-41. PMID: https://www.ncbi.nlm.nih.gov/pubmed/3790210
- ↑ Platt OS. Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med. 2008 Mar 27;358(13):1362-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18367739
- ↑ Voskaridou E, Christoulas D, Bilalis A et al The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial (LaSHS). Blood. 2010 Mar 25;115(12):2354-63. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19903897
- ↑ 9.0 9.1 9.2 Stettler N et al. Proportion of adults with sickle cell anemia and pain crises receiving hydroxyurea. JAMA 2015 Apr 28; 313:1671 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25919532
- ↑ Nevitt SJ et al Hydroxyurea (hydroxycarbamide) for sickle cell disease. Cochrane Database Syst Rev 2017 Apr 20; 4:CD002202 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28426137 PMCID: PMC6478259 Free PMC article