levothyroxine (Synthroid, Levoxyl, Levothroid, Unithroid, Levolet, Novothyrox, Thyrotab)
Jump to navigation
Jump to search
[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]
Introduction
Tradenames: Synthroid, Levoxyl, Levothroid, Unithroid, Levolet, Novothyrox, Thyrotab.[9]
* Generic equally effective as brand name[27]
Epidemiology
- <10% of new levothyroxine prescriptions are for overt hypothyroidism
Indications
- thyroid replacement (hypothyroidism)
- thyroid carcinoma
- goiter
- Hashimoto's thyroiditis[21]
Contraindications
Caution
- patients over 65
- patients with heart disease
- patients with borderline adrenal function (may precipitate adrenal insufficiency)
- subclinical hypothyroidism with serum TSH < 10 mIU/L[28]
Dosage
- hypothyroidism
- start: 50 ug PO QD; 25 ug QD cautious replacement
- 25 ug QD dose increases every 6 weeks
- max 300 ug/day
- administer on empty stomach, delay eating
- in morning on empty stomach at least 30-60 min before food[14][15]
- absorption is best when taken at least an hour before breakfast or coffee, after overnight fasting[5][16]
- absorption is best when taken before bedtime[18]
- delay iron supplement > 4 hours to minimize interaction resulting in diminished absorption[5]
- myxedema coma: load 400 ug IV, then 100-200 ug QD
- higher doses likely needed during pregnancy, on average 30-50%
- consider gastrointestinal disorder if levothyroxine doose requirement higher than expected
- celiac disease can inhibit levothyroxine absorption[3]
(replacement dose averages 1.7 ug/kg/day)
switching generics does not require dose adjustment[31]
Tabs: 25, 50, 75, 88, 100, 112, 125, 137, 150, 175, 200, 300 mg.
Powder for injection: 0.2 mg (10 mL), 0.5 mL (10 mL)
Pharmacokinetics
- oral absorption is variable
- FDA-approved brands equivalent[8]
- impaired gastric acid secretion diminishes absorption[12][13]
- highly protein bound, thyroid-binding globulin increases in parallel with estrogen (i.e. during pregnancy)
- slow onset of action
- prolonged duration of action
- peak effect occurs in 3-4 weeks
elimination via liver
Monitor
- serum TSH
- baseline then every 6-8 weeks until normal, then every 6-12 months[17]
- every 6 weeks to 3 months after change is dose or product
- change in patient health
- including positive pregnancy test[5]
- every 4-6 weeks patients > 50 years with cardiac disease
- every 2-4 weeks patients < 50 years with severe hypothyroidism
Adverse effects
- most adverse reactions are dose-related & can be minimized by increasing the dose slowly
- uncommon (< 1%)
- nervousness, tremors, hand tremors, clumsiness, insomnia, headache
- palpitations, tachycardia, cardiac arrhythmias, chest pain, shortness of breath
- weight loss, increased appetite, diarrhea, constipation, abdominal cramps
- changes in menstrual cycle, muscle aches
- fever, sweating, hair loss
- signs of overdose
- headache
- palpitations
- chest pain (angina pectoris)
- sweating
- leg cramps
- heat intolerance
- weight loss
- diarrhea
- onset of signs & symptoms of toxicity may be delayed 3-10 days, due to delay of metabolism of T4 to the more active T3[30]
- TSH suppression may predispose patients to osteoporosis
- dose-related increased risk of fractures in the elderly[19]
Drug interactions
- inducers of cyt P450 increase catabolism of thyroxine thus increase thyroxine requirements
- phenytoin, carbamazepine, rifampin, phenobarbital
- sertraline allegedly increases catabolism of thyroxine[5], but it is an inhibitor rather than inducer of cyt P450s
- thyroxine may alter concentrations of warfarin, digoxin, insulin
- drugs that decrease absorption of thyroxine
- dietary fiber & bile acid sequestrants (psyllium, cholestyramine)
- ferrous sulfate (see dosage)
- sucralfate
- aluminum hydroxide
- calcium carbonate[26]
- proton pump inhibitors may inhibit absorption of levothyroxine in tablet form[23]
- switching to oral solution corrects impaired absorption
- soybean oil
- coffee (caffeinated or decaffeinated)
- increased thyroxine-binding globulin (TBG), thus diminishing free T4[7]
- decreased thyroxine-binding globulin (TBG), thus increasing free T4[7]
- propranolol & glucocorticoids may inhibit conversion of T3 to T4[10]
- statins in combination may diminish serum TSH (5 mIU/L in 3.7% of patients)[24]
- separate levothyroxine dose from interfering medication by 4 hours[3]
- drug interaction(s) of levothyroxine with proton pump inhibitors
- drug interaction(s) of beta-adrenergic receptor antagonists with thyroid hormone
- drug interaction(s) of raloxifene with levothyroxine
Mechanism of action
- synthetic hormone identical to thyroxine (T4)
- thyroid hormones increase metabolic rate of tissues
- involved in regulation of growth & differentiation
More general terms
Additional terms
Component of
- levothyroxine/triiodothyronine
- desiccated thyroid (Armour, Niva, Apur)
- thyroxine/triiodothyronine (Euthroid, Thyrolar)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 Department of Veterans Affairs, VA National Formulary
- ↑ 3.0 3.1 3.2 Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 275
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 5.0 5.1 5.2 5.3 5.4 Medical Knowledge Self Assessment Program (MKSAP) 11, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2015, 2018, 2023.
- ↑ Journal Watch 20(14): 114, 2000 Singh N et al Effect of calcium carbonate on the absorption of levothyroxine. JAMA 283:2822, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10838651
- ↑ 7.0 7.1 7.2 Journal Watch 21(13):106, 2001 Arafah BM et al Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med 344:1743, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11396440
- ↑ 8.0 8.1 Prescriber's Letter 10(8):44 2003
- ↑ 9.0 9.1 Prescriber's Letter 11(10): 2004 Levothyroxine Sustitution Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=201013&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 10.0 10.1 Prescriber's Letter 12(5): 2005 Combination Liothyronine (T3) and Levothyroxine (T4) Supplementation for Hypothyroidism Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210512&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Roos A, Linn-Rasker SP, van Domburg RT, Tijssen JP, Berghout A. The starting dose of levothyroxine in primary hypothyroidism treatment: a prospective, randomized, double-blind trial. Arch Intern Med. 2005 Aug 8-22;165(15):1714-20. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16087818
- ↑ 12.0 12.1 Centanni M et al, Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N Engl J Med 2006; 354:1787 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16641395
- ↑ 13.0 13.1 Prescriber's Letter 13(5): 2006 Levothyroxine Absorption in Patients with Reduced Gastric Acid Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220613&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 14.0 14.1 Lexi-Comp IncTHYROXINE
- ↑ 15.0 15.1 Prescriber's Letter 15(12): 2008 Drugs and Substances that Reduce Absorption of Levothyroxine Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=241209&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 16.0 16.1 Bach-Huynh T-G et al Timing of levothyroxine administration affects serum thyrotropin concentration. J Clin Endocrinol Metab 2009 Oct; 94:3905. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19584184
- ↑ 17.0 17.1 Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260704&pb=PRL (subscription needed) http://www.prescribersletter.com18)
- ↑ 18.0 18.1 Bolk N et al Effects of Evening vs Morning Levothyroxine Intake A Randomized Double-blind Crossover Trial Arch Intern Med. 2010;170(22):1996-2003 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21149757 <Internet> http://archinte.ama-assn.org/cgi/content/abstract/170/22/1996
- ↑ 19.0 19.1 Turner MR et al Levothyroxine dose and risk of fractures in older adults: nested case-control study BMJ 2011; 342:d2238 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21527461 <Internet> http://www.bmj.com/content/342/bmj.d2238.full
Leese GP and Flynn RV Levothyroxine dose and fractures in older adults BMJ 2011; 342:d2250 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21527462 <Internet> http://www.bmj.com/content/342/bmj.d2250 - ↑ Prescriber's Letter 19(11): 2012 Helping Patients Take Levothyroxine Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=281112&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 21.0 21.1 Deprecated Reference
- ↑ 22.0 22.1 Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
- ↑ 23.0 23.1 Vita R et al. Switching levothyroxine from the tablet to the oral solution formulation corrects the impaired absorption of levothyroxine induced by proton-pump inhibitors. J Clin Endocrinol Metab 2014 Dec; 99:4481 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25259910 <Internet> http://press.endocrine.org/doi/abs/10.1210/jc.2014-2684
- ↑ 24.0 24.1 Irving SA et al Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS). Clin Endocrinol. 2015;82(1):136-141. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25040647
- ↑ Tahboub R, Arafah BM. Sex steroids and the thyroid. Best Pract Res Clin Endocrinol Metab. 2009 Dec;23(6):769-80. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19942152
- ↑ 26.0 26.1 Zamfirescu I, Carlson HE. Absorption of levothyroxine when coadministered with various calcium formulations. Thyroid. 2011 May;21(5):483-6. doi:http://dx.doi.org/ 10.1089/thy.2010.0296. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21595516 Free PMC Article
- ↑ 27.0 27.1 Brito JP et al. Comparative effectiveness of generic vs brand-name levothyroxine in achieving normal thyrotropin levels. JAMA Netw Open 2020 Sep 30; 3:e2017645 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32997127 PMCID: PMC7527873 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2771041
- ↑ 28.0 28.1 Brito JP, Ross JS, El Kawkgi OM et al Levothyroxine Use in the United States, 2008-2018. JAMA Intern Med. Published online June 21, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34152370 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2781311
Silverstein WK, Grady D Overuse of Levothyroxine in Patients With Subclinical Hypothyroidism. Time to "Leve"-Out-Thyroxine. JAMA Intern Med. Published online June 21, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34152358 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2781314 - ↑ 29.0 29.1 Brito JP et al. Levothyroxine use in the United States, 2008-2018. JAMA Intern Med 2021 Jun 21; PMID: https://www.ncbi.nlm.nih.gov/pubmed/34152370 PMCID: PMC8218227 (available on 2022-06-21) https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2781311
- ↑ 30.0 30.1 Windle ML Fast Five Quiz: Levothyroxine Medscape. October 7, 2021 https://reference.medscape.com/viewarticle/960226
- ↑ 31.0 31.1 Brito JP, Deng Y, Ross JS et al. Association between generic-to-generic levothyroxine switching and thyrotropin levels among US adults. JAMA Intern Med 2022 Feb 28; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35226058 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2789278
- ↑ Medscape: Levothyroxine https://reference.medscape.com/drug/synthroid-levoxyl-levothyroxine-342732