Hytrin

Generic Name: Terazosin Hydrochloride
Class: alpha-Adrenergic Blocking Agents
VA Class: CV150
Chemical Name: Piperazine, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-((tetrahydro-2-furanyl-)carbonyl)-, monohydrochloride, dihydrate
CAS Number: 70024-40-7

Introduction

Postsynaptic α₁-adrenergic blocking agent; quinazoline derivative.^{1 2 3 4 5 6 7 8 9 10}

Uses for Hytrin

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).^{1 3 4 6 7 8 11 12 13 14 30 31 32 44}

Current antihypertensive and urology guidelines (e.g., JNC 7) no longer recommend α₁-blockers as preferred first-line therapy for patients with hypertension.^{62 73 74 75}

Benign Prostatic Hyperplasia (BPH)

Reduction of urinary obstruction and relief of associated manifestations in patients with symptomatic BPH.^{1 5 9 17 18 21 23 25 33}

Although drug therapy usually is not as effective as surgical therapy, it may provide adequate symptomatic relief with fewer and less serious adverse effects compared with surgery.⁵⁹

May consider combined therapy with an α₁-adrenergic blocker and 5α-reductase inhibitor for men with bothersome moderate to severe BPH and demonstrable prostatic enlargement.⁵⁹ Has been more effective than therapy with either drug alone in preventing long-term BPH symptom progression.⁵⁹ Men at risk for BPH progression are most likely to benefit from combination therapy.⁵⁹

Hytrin Dosage and Administration

Administration

Oral Administration

Administer orally once daily at bedtime.¹

Food may delay time to peak plasma concentrations by about 40 minutes but has little effect on extent of absorption.^{1 28} Manufacturer makes no specific recommendations regarding administration with meals.¹

Dosage

Available as terazosin hydrochloride; dosage expressed in terms of terazosin.¹

Individualize dosage according to patient response and tolerance.^{1 3 7 44} Initiate at low dosage to minimize frequency of postural hypotension and syncope.¹

Monitor BP 2–3 hours after dosing and at end of dosing interval to determine whether peak and trough responses are similar and to assess potential manifestations (e.g., dizziness, palpitations) of an excessive response.¹

If therapy is interrupted for several days or longer, restart using initial dosage regimen.¹

Pediatric Patients

Hypertension†

Oral

Initially, 1 mg once daily.⁷⁶ Increase dosage as necessary up to a maximum of 20 mg once daily.⁷⁶

Adults

Hypertension

Oral

Initially, 1 mg daily at bedtime.^{1 3 7 44 62} May increase dosage gradually to 5 mg daily,^{1 3 7} with further titration up to 20 mg daily if BP is not controlled.^{1 44 62}

Each increase should be delayed until BP has stabilized at a given dosage.^{1 3 7}

BPH

Oral

Initially, 1 mg daily at bedtime.^{1 9} May increase daily dosage to 2 mg and thereafter to 5 mg and 10 mg, if necessary, to reduce symptoms and/or improve urinary flow rates.^{1 9}

Prescribing Limits

Pediatric Patients

Hypertension†

Oral

Maximum 20 mg daily.⁷⁶

Adults

Hypertension

Oral

Maximum 40 mg daily.¹

BPH

Oral

Maximum 20 mg daily.¹

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations; effects on the pharmacokinetics of terazosin have not been elucidated.¹

Renal Impairment

Clinically important alterations in the pharmacokinetics of terazosin not observed to date;^{1 3 28 29} dosage adjustment not necessary.^{3 28 29 33}

Administration of supplemental doses of the drug following hemodialysis does not appear to be necessary.¹

Geriatric Patients

Use with caution; generally, increase dosage more slowly in geriatric patients than in younger adults.^{7 9}

Cautions for Hytrin

Contraindications

• 
  

  Known hypersensitivity to terazosin, quinazolines (e.g., doxazosin, prazosin), or any ingredient in the formulation.^{1 33}

  
  

Warnings/Precautions

Warnings

Postural Hypotension

Marked hypotension, especially in the upright position, can occur; may be accompanied by syncope, palpitations, and other postural effects (e.g., dizziness, lightheadedness, vertigo).^{1 2 3 4 6 7 9 13 30}

Postural effects are most common after an initial dose, shortly after dosing (e.g., within 90 minutes), when dosage is increased, or when therapy is resumed after an interruption exceeding a few days.¹

To decrease risk of excessive hypotension and syncope, initiate therapy at low dose and titrate carefully, lessen level of salt restriction, and avoid diuretics just prior to initiation of terazosin therapy.^{1 3 4 6 7 30}

Priapism

Priapism reported rarely; may lead to permanent impotence if not treated promptly.^{1 48 49} (See Advice to Patients.)

General Precautions

Prostate Cancer

Exclude possibility of prostate cancer before initiation of therapy for BPH.^{1 9}

Specific Populations

Pregnancy

Category C.¹

Lactation

Not known whether terazosin is distributed into milk.¹ Caution if used in nursing women.¹

Pediatric Use

Safety and efficacy not established in patients <21 years of age.^{1 33}

Geriatric Use

Geriatric patients may be particularly susceptible to postural effects and other adverse effects.^{7 9} (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

In the treatment of hypertension: dizziness, headache, asthenia (weakness, tiredness, lassitude, fatigue), nasal congestion, peripheral edema, somnolence, nausea, palpitation.^{1 3 4 6 7 13}

In the treatment of BPH: dizziness, asthenia, headache, postural hypotension, somnolence.^{1 9}

Interactions for Hytrin

Antihypertensive Agents

Possible rapid fall in BP and exacerbation of postural effects.^{1 7 9} Use with caution; may need to reduce and/or retitrate dosage.^{1 7}

Specific Drugs

Drug	Interaction
Acetaminophen	No interaction observed1
β-Adrenergic blocking agents (e.g., atenolol, propranolol)	No interaction observed1
Allopurinol	No interaction observed1
Antacids	No interaction observed1
Antihistamines (e.g., chlorpheniramine)	No interaction observed1
Captopril	Increased peak plasma concentrations of terazosin1
Codeine	No interaction observed1
Corticosteroids	No interaction observed1
Co-trimoxazole	No interaction observed1
Diazepam	No interaction observed1
Diuretics, thiazide (e.g., hydrochlorothiazide)	No interaction observed1
Erythromycin	No interaction observed1
Hypoglycemics	No interaction observed1
NSAIAs (e.g., aspirin, ibuprofen, indomethacin)	No interaction observed1
Sympathomimetic (adrenergic) agents (e.g., phenylephrine, pseudoephedrine)	No interaction observed1
Verapamil	Increased AUC of terazosin; decreased time to peak plasma terazosin concentrations1

Hytrin Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed from the GI tract following oral administration.^{1 2} Peak plasma concentration attained in about 1 hour.¹

Food

Food has minimal effect on extent of absorption; however, time to peak plasma concentration is delayed by about 40 minutes.^{1 28}

Distribution

Extent

Not known whether terazosin is distributed into breast milk.¹

Plasma Protein Binding

90–94%.^{1 a}

Elimination

Metabolism

Extensively metabolized in the liver,^a with minimal first-pass metabolism.¹

Elimination Route

Excreted in urine (40%) and in feces (60%).¹

Half-life

Adults: approximately 12 hours.¹

Geriatric patients: approximately 14 hours.¹

Special Populations

In geriatric patients, plasma clearance is decreased by about 30%.¹

Stability

Storage

Oral

Capsules

20–25°C.¹ Protect from light and moisture.¹

ActionsActions

• 
  

  Reduces peripheral vascular resistance and BP as a result of vasodilating effects; produces both arterial and venous dilation.^{1 3 4 6 7 10}

  
  


• 
  

  Binds to α₁-adrenergic receptors in the prostate and the bladder trigone, resulting in decreased urinary outflow resistance in men.^{5 9}

  
  


• 
  

  May improve to limited extent the serum lipid profile (e.g., small increases in HDL/total cholesterol ratio; small decreases in LDL, total cholesterol, and triglyceride concentrations).^{1 3 7 8 9 10 11 28 31 32}

  
  

Advice to Patients

• 
  

  Possible syncopal and orthostatic symptoms, especially at initiation of therapy; importance of avoiding driving or other hazardous tasks for 12 hours after first dose, a dosage increase, or when resumed after therapy interruption.^{1 9}

  
  


• 
  

  Importance of sitting or lying down when symptoms of lowered BP occur, and of rising carefully from a sitting or lying position.¹

  
  


• 
  

  Importance of informing clinician if bothersome dizziness, lightheadedness, or palpitations occur.¹

  
  


• 
  

  Possible drowsiness or somnolence; use caution when operating machinery or driving a motor vehicle until effects on individual are known.^{1 9}

  
  


• 
  

  Importance of men seeking medical treatment if painful or sustained (for hours) erection occurs.^{1 48 49}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.¹

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

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

Terazosin Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	1 mg (of terazosin)*	Hytrin (with parabens and povidone)	Abbott
		2 mg (of terazosin)*	Hytrin (with parabens and povidone)	Abbott
		5 mg (of terazosin)*	Hytrin (with parabens and povidone)	Abbott
		10 mg (of terazosin)*	Hytrin (with parabens and povidone)	Abbott

Comparative Pricing

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.

Terazosin HCl 1MG Capsules (MYLAN): 30/$14.45 or 90/$33.98

Terazosin HCl 10MG Capsules (SANDOZ): 30/$13.99 or 90/$33.99

Terazosin HCl 2MG Capsules (SANDOZ): 30/$13.99 or 90/$33.99

Terazosin HCl 5MG Capsules (SANDOZ): 30/$13.99 or 90/$33.99

Disclaimer

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 April 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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2. Babamoto KS, Hirokawa WT. Doxazosin: a new α₁-adrenergic antagonist. Clin Pharm. 1992; 11:415-27. [IDIS 294778] [PubMed 1349855]

3. Titmarsh S, Monk JP. Terazosin: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in essential hypertension. Drugs. 1987; 33:461-77. [IDIS 231489] [PubMed 2885169]

4. Khoury AF, Kaplan NM. α-Blocker therapy of hypertension. JAMA. 1991; 266:394-8. [IDIS 283041] [PubMed 1676077]

5. Monda JM, Oesterling JE. Medical treatment of benign prostatic hyperplasia: 5α-reductase inhibitors and α- adrenergic antagonists. Mayo Clin Proc. 1993; 68:670-9. [IDIS 316185] [PubMed 7688840]

6. Itskovitz HD. Alpha₁ blockers: safe, effective treatment for hypertension. Postgrad Med. 1991; 89:89-112. [IDIS 283690] [PubMed 1674822]

7. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med. 1993; 153:154-83. [IDIS 309043] [PubMed 8422206]

8. Anon. Terazosin for hypertension. Med Lett Drugs Ther. 1987; 29:112-3. [PubMed 2891021]

9. Wilde MI, Fitton A, Sorkin EM. Terazosin: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in benign prostatic hypertrophy. Drugs Aging. 1993; 3:258-77. [PubMed 7686794]

10. Kyncl JJ. Pharmacology of terazosin. Am J Med. 1986; 80(Suppl 5B):12-9. [PubMed 2872801]

11. Deger G. Effect of terazosin on serum lipids. Am J Med. 1986; 80(Suppl 5B):82-5. [IDIS 216509] [PubMed 2872813]

12. Deger G. Comparison of the safety and efficacy of once- daily terazosin versus twice-daily prazosin for the treatment of mild to moderate hypertension. Am J Med. 1986; 80(Suppl 5B):62-7. [IDIS 216505] [PubMed 2872809]

13. Cohen JD. Long-term efficacy and safety of terazosin alone and in combination with other antihypertensive agents. Am Heart J. 1991; 122:919-25. [IDIS 287852] [PubMed 1678923]

14. Ruoff G. Comparative trials of terazosin with other antihypertensive agents. Am J Med. 1986; 80(Suppl 5B):42-8. [IDIS 216502] [PubMed 2872806]

15. 1988 Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1988; 148:1023-38. [IDIS 242588] [PubMed 3365073]

16. Weber MA, Laragh JH. Hypertension: steps forward and steps backward. The Joint National Committee fifth report. Arch Intern Med. 1993; 153:149-52. [PubMed 8422205]

17. Lepor H, Meretyk S, Knapp-Maloney G. The safety, efficacy and compliance of terazosin therapy for benign prostatic hyperplasia. J Urol. 1992; 147:1554-7. [IDIS 297430] [PubMed 1375659]

18. Lepor H. The emerging role of alpha antagonists in the therapy of benign prostatic hyperplasia. J Androl. 1991; 12:389-94. [PubMed 1722795]

19. Chapple CR, Christmas TJ, Milroy EJ. A twelve-week placebo-controlled study of prazosin in the treatment of prostatic obstruction. Urol Int. 1990; 45(Suppl 1):47-55. [PubMed 1690482]

20. Kirby RS, Coppinger SW, Corcoran MO et al. Prazosin in the treatment of prostatic obstruction. A placebo-controlled study. Br J Urol. 1987; 60:136-42. [PubMed 2444306]

21. Chapple C. Medical treatment for benign prostatic hyperplasia. BMJ. 1992; 304:1198-9. [IDIS 296671] [PubMed 1381250]

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23. Lepor H. Role of long-acting selective alpha-1 blockers in the treatment of benign prostatic hyperplasia. Urol Clin North Am. 1990; 17:651-9. [PubMed 1695785]

24. Kirby RS. Alpha-adrenoceptor inhibitors in the treatment of benign prostatic hyperplasia. Am J Med. 1989; 87(Suppl 2A):26-30S.

25. Chisholm GD. Benign prostatic hyperplasia: the best treatment. BMJ. 1989; 299:215-6. [IDIS 257552] [PubMed 2475197]

26. Geller J. Nonsurgical treatment of prostatic hyperplasia. Cancer. 1992; 70(Suppl 1):339-45. [IDIS 298353] [PubMed 1376202]

27. Garraway WM, Collins GN, Lee RJ. High prevalence of benign prostatic hypertrophy in the community. Lancet. 1991; 338:469-71. [PubMed 1714529]

28. Somberg JC. Terazosin: pharmacokinetics and the effect of age and dose on the incidence of adverse events. Am Heart J. 1991; 122:901-5. [IDIS 287849] [PubMed 1678920]

29. Jungers P, Ganeval D, Pertuiset N et al. Influence of renal insufficiency on the pharmacokinetics and pharmacodynamics of terazosin. Am J Med. 1986; 80(Suppl 5B):94-9. [IDIS 216511] [PubMed 2872815]

30. Sperzel WD, Glassman HN, Jordan DC et al. Overall safety of terazosin as an antihypertensive agent. Am J Med. 1986; 80(Suppl 5B):77-81. [IDIS 216508] [PubMed 2872812]

31. Luther RR, Glassman HN, Estep CB et al. The effects of terazosin and methyclothiazide on blood pressure and serum lipids. Am Heart J. 1989; 117:842-7. [IDIS 255040] [PubMed 2564723]

32. Holtzman JL, Kaihlanen PM, Rider A et al. Concomitant administration of the terazosin and atenolol for the treatment of essential hypertension. Arch Intern Med. 1988; 148:1539-43. [PubMed 3382300]

33. Abbott Laboratories, Abbott Park, IL: Personal communication.

34. National Heart, Lung, and Blood Institute. NHLBI panel reviews safety of calcium channel blockers. Rockville, MD; 1995 Aug 31. Press release.

35. National Heart, Lung, and Blood Institute. New analysis regarding the safety of calcium-channel blockers: a statement for health professionals from the National Heart, Lung, and Blood Institute. Rockville, MD; 1995 Sep 1.

36. Psaty BM, Heckbert SR, Koepsell TD et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA. 1995; 274:620-5. [IDIS 352203] [PubMed 7637142]

37. Yusuf S. Calcium antagonists in coronary artery disease and hypertension: time for reevaluation? Circulation. 1995; 92:1079-82. Editorial.

38. Pfizer Roerig. Cardura (doxazosin mesylate) tablets prescribing information. New York, NY; 1994 Dec.

39. Bruskewitz RC. Benign prostatic hyperplasia: drug and nondrug therapies. Geriatrics. 1992; 47:39-45. [IDIS 306255] [PubMed 1280242]

40. Oesterling JE. Benign prostatic hyperplasia: medical and minimally invasive treatment options. N Engl J Med. 1995; 332:99-109. [IDIS 340651] [PubMed 7527494]

41. Hill SJ, Lawrence SL, Lepor H. New use for alpha blockers: benign prostatic hyperplasia. Am Fam Physician. 1994; 49:1885-8. [IDIS 330970] [PubMed 7515555]

42. Roberts RG. Novel idea in BPH guideline: the patient as decision maker. Am Fam Physician. 1994; 49:1044-51. [PubMed 7512307]

43. Bostwick DG, Cooner WH, Denis L et al. The association of benign prostatic hyperplasia and cancer of the prostate. Cancer. 1992; 70(Suppl 1):291-301. [PubMed 1376199]

44. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)

45. Kaplan NM. Choice of initail therapy for hypertension. JAMA. 1996; 275:1577-80. [IDIS 365188] [PubMed 8622249]

46. Psaty BM, Smith NL, Siscovich DS et al. Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. JAMA. 1997; 277:739-45. [IDIS 380501] [PubMed 9042847]

47. Whelton PK, Appel LJ, Espeland MA et al. for the TONE Collaborative Research Group. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). JAMA. 1998; 279:839-46. [PubMed 9515998]

48. Upjohn Company. Caverject (alprostadil) injection for intracavernosal use prescribing information. Kalamazoo, MI; 1995 Jul.

49. Krane RJ, Goldstein I, Saenz de Tejada I. Impotence. N Engl J Med. 1989; 321:1648-59. [PubMed 2685600]

50. The ALLHAT collaborative research group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT). JAMA. 2000; 283:1967-75. [IDIS 444771] [PubMed 10789664]

51. Lasagna L. Diuretics vs α-blockers for treatment of hypertension: lessons from ALLHAT. JAMA. 2000; 283:2013-4. [IDIS 444774] [PubMed 10789671]

52. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. [PubMed 10818056]

53. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. [PubMed 10818055]

54. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61. [IDIS 452007] [PubMed 10977801]

55. Associated Press (American Diabetes Association). Diabetics urged: drop blood pressure. Chicago, IL; 2000 Aug 29. Press Release from web site.

56. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-60. [IDIS 490723] [PubMed 12479770]

57. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. [IDIS 490721] [PubMed 12479763]

58. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT). JAMA. 2002; 288:2998-3007. [IDIS 490722] [PubMed 12479764]

59. American Urological Association. Guideline on the management of benign prostatic hyperplasia (BPH)(2003/updated 2006). Available from website. Accessed 2006 Aug 10.

60. Kaplan NM. Initial treatment of adult patients with essential hypertension. Part 2: alternating monotherapy is the preferred treatment. Pharmacotherapy. 1985; 5:195-200. [IDIS 394161] [PubMed 4034407]

61. Bauer JH. Stepped-care approach to the treatment of hypertension: is it obsolete? (unpublished observations)

62. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) Express. Bethesda, MD: May 14 2003. From NIH website. (Also published in JAMA. 2003; 289.

63. Neal B, MacMahon S, Chapman N. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs. Lancet. 2000;356:1955-64.

64. Cushman WC, Ford CE, Cutler JA, et al. Success and predictors of blood pressure control in diverse North American settings: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens (Greenwich). 2002;4:393-404.

65. Black HR, Elliott WJ, Neaton JD et al. Baseline characteristics and elderly blood pressure control in the CONVINCE trial. Hypertension. 2001; 37:12-18. [PubMed 11208750]

66. Black HR, Elliott WJ, Grandits G, et al. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA. 2003;289:2073-2082.

67. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE). Lancet. 2002;359:995-1003.

68. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342:145-153.

69. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358:1033-41.

70. Wing LMH, Reid CM, Ryan P, et al, for Second Australian National Blood Pressure Study Group. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med. 2003;348:583-92.

71. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003; 26(Suppl 1):S80-2.

72. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult. J Am Coll Cardiol. 2001;38:2101-2113.

73. Guidelines Committee. 2003 European Society of Hypertension–European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertension. 2003; 21:1011-53.

74. The Guidelines Subcommittee of the WHO/ISH Mild Hypertension Liaison Committee. 1999 guidelines for the management of hypertension. J Hypertension. 1999; 17:392-403.

75. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) Complete Version. Bethesda, MD: 2003 Nov 5. Hypertension. 2003; 42:1206-52. [PubMed 14656957]

76. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114(Suppl 2):555-76. [PubMed 15286277]

a. Sonders RC. Pharmacokinetics of terazosin. Am J Med. 1986; 80:20-24. [PubMed 2872802]

More Hytrin resources

• Hytrin Side Effects (in more detail)
• Hytrin Use in Pregnancy & Breastfeeding
• Drug Images
• Hytrin Drug Interactions
• Hytrin Support Group
• 11 Reviews for Hytrin - Add your own review/rating

• Hytrin Prescribing Information (FDA)


• Hytrin Consumer Overview


• Hytrin Advanced Consumer (Micromedex) - Includes Dosage Information


• Hytrin MedFacts Consumer Leaflet (Wolters Kluwer)


• Terazosin Prescribing Information (FDA)


• Terazosin Professional Patient Advice (Wolters Kluwer)

Compare Hytrin with other medications

• Benign Prostatic Hyperplasia
• High Blood Pressure
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Zantac

ranitidine hydrochloride

Dosage Form: tablet, film coated; effervescent tablets; syrup
Zantac® 150

(ranitidine hydrochloride)

Tablets, USP

Zantac® 300

(ranitidine hydrochloride)

Tablets, USP

Zantac® 25

(ranitidine hydrochloride effervescent)

EFFERdose® Tablets

Zantac®

(ranitidine hydrochloride)

Syrup, USP

Zantac Description

The active ingredient in Zantac 150 Tablets, Zantac 300 Tablets, Zantac 25 EFFERdose Tablets, and Zantac Syrup is ranitidine hydrochloride (HCl), USP, a histamine H2-receptor antagonist. Chemically it is N[2 - [[[5 - [(dimethylamino)methyl] - 2 - furanyl]methyl]thio]ethyl] - N′ - methyl - 2 - nitro - 1,1 - ethenediamine, HCl. It has the following structure:

The empirical formula is C13H22N4O3S•HCl, representing a molecular weight of 350.87.

Ranitidine HCl is a white to pale yellow, granular substance that is soluble in water. It has a slightly bitter taste and sulfurlike odor.

Each Zantac 150 Tablet for oral administration contains 168 mg of ranitidine HCl equivalent to 150 mg of ranitidine. Each tablet also contains the inactive ingredients FD&C Yellow No. 6 Aluminum Lake, hypromellose, magnesium stearate, microcrystalline cellulose, titanium dioxide, triacetin, and yellow iron oxide.

Each Zantac 300 Tablet for oral administration contains 336 mg of ranitidine HCl equivalent to 300 mg of ranitidine. Each tablet also contains the inactive ingredients croscarmellose sodium, D&C Yellow No. 10 Aluminum Lake, hypromellose, magnesium stearate, microcrystalline cellulose, titanium dioxide, and triacetin.

Zantac 25 EFFERdose Tablets for oral administration is an effervescent formulation of ranitidine that must be dissolved in water before use. Each individual tablet contains 28 mg of ranitidine HCl equivalent to 25 mg of ranitidine and the following inactive ingredients: aspartame, monosodium citrate anhydrous, povidone, and sodium bicarbonate. Each tablet also contains sodium benzoate. The total sodium content of each tablet is 30.52 mg (1.33 mEq) per 25 mg of ranitidine.

Each 1 mL of Zantac Syrup contains 16.8 mg of ranitidine HCl equivalent to 15 mg of ranitidine. Zantac Syrup also contains the inactive ingredients alcohol (7.5%), butylparaben, dibasic sodium phosphate, hypromellose, peppermint flavor, monobasic potassium phosphate, propylparaben, purified water, saccharin sodium, sodium chloride, and sorbitol.

Zantac - Clinical Pharmacology

Zantac is a competitive, reversible inhibitor of the action of histamine at the histamine H2-receptors, including receptors on the gastric cells. Zantac does not lower serum Ca++ in hypercalcemic states. Zantac is not an anticholinergic agent.

Pharmacokinetics

Absorption: Zantac is 50% absorbed after oral administration, compared to an intravenous (IV) injection with mean peak levels of 440 to 545 ng/mL occurring 2 to 3 hours after a 150-mg dose. The syrup and EFFERdose formulations are bioequivalent to the tablets. Absorption is not significantly impaired by the administration of food or antacids. Propantheline slightly delays and increases peak blood levels of ranitidine, probably by delaying gastric emptying and transit time. In one study, simultaneous administration of high-potency antacid (150 mmol) in fasting subjects has been reported to decrease the absorption of Zantac.

Distribution: The volume of distribution is about 1.4 L/kg. Serum protein binding averages 15%.Metabolism: In humans, the N-oxide is the principal metabolite in the urine; however, this amounts to <4% of the dose. Other metabolites are the S-oxide (1%) and the desmethyl ranitidine (1%). The remainder of the administered dose is found in the stool. Studies in patients with hepatic dysfunction (compensated cirrhosis) indicate that there are minor, but clinically insignificant, alterations in ranitidine half-life, distribution, clearance, and bioavailability.

Excretion: The principal route of excretion is the urine, with approximately 30% of the orally administered dose collected in the urine as unchanged drug in 24 hours. Renal clearance is about 410 mL/min, indicating active tubular excretion. The elimination half-life is 2.5 to 3 hours. Four patients with clinically significant renal function impairment (creatinine clearance 25 to 35 mL/min) administered 50 mg of ranitidine intravenously had an average plasma half-life of 4.8 hours, a ranitidine clearance of 29 mL/min, and a volume of distribution of 1.76 L/kg. In general, these parameters appear to be altered in proportion to creatinine clearance (see DOSAGE AND ADMINISTRATION).

Geriatrics: The plasma half-life is prolonged and total clearance is reduced in the elderly population due to a decrease in renal function. The elimination half-life is 3 to 4 hours. Peak levels average 526 ng/mL following a 150-mg twice-daily dose and occur in about 3 hours (see PRECAUTIONS: Geriatric Use and DOSAGE AND ADMINISTRATION: Dosage Adjustment for Patients With Impaired Renal Function).

Pediatrics: There are no significant differences in the pharmacokinetic parameter values for ranitidine in pediatric patients (from 1 month up to 16 years of age) and healthy adults when correction is made for body weight. The average bioavailability of ranitidine given orally to pediatric patients is 48%, which is comparable to the bioavailability of ranitidine in the adult population. All other pharmacokinetic parameter values (t1/2, Vd, and CL) are similar to those observed with intravenous ranitidine use in pediatric patients. Estimates of Cmax and Tmax are displayed in Table 1.

Table 1. Ranitidine Pharmacokinetics in Pediatric Patients Following Oral Dosing

Population (age)	n	Dosage Form (dose)	Cmax (ng/mL)	Tmax (hours)
Gastric or duodenal ulcer (3.5 to 16 years)	12	Tablets (1 to 2 mg/kg)	54 to 492	2.0
Otherwise healthy requiring Zantac (0.7 to 14 years, Single dose)	10	Syrup (2 mg/kg)	244	1.61
Otherwise healthy requiring Zantac (0.7 to 14 years, Multiple dose)	10	Syrup (2 mg/kg)	320	1.66

Plasma clearance measured in 2 neonatal patients (less than 1 month of age) was considerably lower (3 mL/min/kg) than children or adults and is likely due to reduced renal function observed in this population (see PRECAUTIONS: Pediatric Use and DOSAGE AND ADMINISTRATION: Pediatric Use).

Pharmacodynamics

Serum concentrations necessary to inhibit 50% of stimulated gastric acid secretion are estimated to be 36 to 94 ng/mL. Following a single oral dose of 150 mg, serum concentrations of ranitidine are in this range up to 12 hours. However, blood levels bear no consistent relationship to dose or degree of acid inhibition.

In a pharmacodynamic comparison of the EFFERdose with the Zantac Tablets, during the first hour after administration, the EFFERdose tablet formulation gave a significantly higher intragastric pH, by approximately 1 pH unit, compared to the Zantac Tablets.

Antisecretory Activity:1. Effects on Acid Secretion: Zantac inhibits both daytime and nocturnal basal gastric acid secretions as well as gastric acid secretion stimulated by food, betazole, and pentagastrin, as shown in Table 2.

Table 2. Effect of Oral Zantac on Gastric Acid Secretion

	Time After Dose, hours	% Inhibition of Gastric Acid Output by Dose, mg
		75-80	100	150	200
Basal	Up to 4		99	95
Nocturnal	Up to 13	95	96	92
Betazole	Up to 3		97	99
Pentagastrin	Up to 5	58	72	72	80
Meal	Up to 3		73	79	95

It appears that basal-, nocturnal-, and betazole-stimulated secretions are most sensitive to inhibition by Zantac, responding almost completely to doses of 100 mg or less, while pentagastrin- and food-stimulated secretions are more difficult to suppress.

2. Effects on Other Gastrointestinal Secretions:

Pepsin: Oral Zantac does not affect pepsin secretion. Total pepsin output is reduced in proportion to the decrease in volume of gastric juice.

Intrinsic Factor: Oral Zantac has no significant effect on pentagastrin-stimulated intrinsic factor secretion.

Serum Gastrin: Zantac has little or no effect on fasting or postprandial serum gastrin.

Other Pharmacologic Actions:

1. Gastric bacterial flora—increase in nitrate-reducing organisms, significance not known.


2. Prolactin levels—no effect in recommended oral or IV dosage, but small, transient, dose-related increases in serum prolactin have been reported after IV bolus injections of 100 mg or more.


3. Other pituitary hormones—no effect on serum gonadotropins, TSH, or GH. Possible impairment of vasopressin release.


4. No change in cortisol, aldosterone, androgen, or estrogen levels.


5. No antiandrogenic action.


6. No effect on count, motility, or morphology of sperm.

Pediatrics: Oral doses of 6 to 10 mg/kg/day in 2 or 3 divided doses maintain gastric pH >4 throughout most of the dosing interval.

Clinical Trials

Active Duodenal Ulcer: In a multicenter, double-blind, controlled, US study of endoscopically diagnosed duodenal ulcers, earlier healing was seen in the patients treated with Zantac as shown in Table 3.

Table 3. Duodenal Ulcer Patient Healing Rates

	Zantaca		Placeboa
	Number Entered	Healed/ Evaluable	Number Entered	Healed/ Evaluable
Outpatients
Week 2		69/182 (38%)b		31/164 (19%)
	195		188
Week 4		137/187 (73%)b		76/168 (45%)

aAll patients were permitted antacids as needed for relief of pain.

bP<0.0001.

In these studies, patients treated with Zantac reported a reduction in both daytime and nocturnal pain, and they also consumed less antacid than the placebo-treated patients.

Table 4. Mean Daily Doses of Antacid

	Ulcer Healed	Ulcer Not Healed
Zantac	0.06	0.71
Placebo	0.71	1.43

Foreign studies have shown that patients heal equally well with 150 mg twice daily and 300 mg at bedtime (85% versus 84%, respectively) during a usual 4-week course of therapy. If patients require extended therapy of 8 weeks, the healing rate may be higher for 150 mg twice daily as compared to 300 mg at bedtime (92% versus 87%, respectively).

Studies have been limited to short-term treatment of acute duodenal ulcer. Patients whose ulcers healed during therapy had recurrences of ulcers at the usual rates.

Maintenance Therapy in Duodenal Ulcer: Ranitidine has been found to be effective as maintenance therapy for patients following healing of acute duodenal ulcers. In 2 independent, double-blind, multicenter, controlled trials, the number of duodenal ulcers observed was significantly less in patients treated with Zantac (150 mg at bedtime) than in patients treated with placebo over a 12-month period.

Table 5. Duodenal Ulcer Prevalence

Double-Blind, Multicenter, Placebo-Controlled Trials
Multicenter Trial	Drug	Duodenal Ulcer Prevalence			No. of Patients
		0-4 Months	0-8 Months	0-12 Months
USA	RAN	20%a	24%	35%a	138
	PLC	44%	54%	59%	139
Foreign	RAN	12%a	21%a	28%a	174
	PLC	56%	64%	68%	165

% = Life table estimate.

a = P<0.05 (Zantac versus comparator).

RAN = ranitidine (Zantac).

PLC = placebo.

As with other H2-antagonists, the factors responsible for the significant reduction in the prevalence of duodenal ulcers include prevention of recurrence of ulcers, more rapid healing of ulcers that may occur during maintenance therapy, or both.

Gastric Ulcer: In a multicenter, double-blind, controlled, US study of endoscopically diagnosed gastric ulcers, earlier healing was seen in the patients treated with Zantac as shown in Table 6.

Table 6. Gastric Ulcer Patient Healing Rates

	Zantaca		Placeboa
	Number Entered	Healed/ Evaluable	Number Entered	Healed/ Evaluable
Outpatients
Week 2		16/83 (19%)		10/83 (12%)
	92		94
Week 6		50/73 (68%)b		35/69 (51%)

aAll patients were permitted antacids as needed for relief of pain.

bP = 0.009.

In this multicenter trial, significantly more patients treated with Zantac became pain free during therapy.

Maintenance of Healing of Gastric Ulcers: In 2 multicenter, double-blind, randomized, placebo-controlled, 12-month trials conducted in patients whose gastric ulcers had been previously healed, Zantac 150 mg at bedtime was significantly more effective than placebo in maintaining healing of gastric ulcers.

Pathological Hypersecretory Conditions (such as Zollinger-Ellison syndrome): Zantac inhibits gastric acid secretion and reduces occurrence of diarrhea, anorexia, and pain in patients with pathological hypersecretion associated with Zollinger-Ellison syndrome, systemic mastocytosis, and other pathological hypersecretory conditions (e.g., postoperative, “short-gut” syndrome, idiopathic). Use of Zantac was followed by healing of ulcers in 8 of 19 (42%) patients who were intractable to previous therapy.

Gastroesophageal Reflux Disease (GERD): In 2 multicenter, double-blind, placebo-controlled, 6-week trials performed in the United States and Europe, Zantac 150 mg twice daily was more effective than placebo for the relief of heartburn and other symptoms associated with GERD. Ranitidine-treated patients consumed significantly less antacid than did placebo-treated patients.

The US trial indicated that Zantac 150 mg twice daily significantly reduced the frequency of heartburn attacks and severity of heartburn pain within 1 to 2 weeks after starting therapy. The improvement was maintained throughout the 6-week trial period. Moreover, patient response rates demonstrated that the effect on heartburn extends through both the day and night time periods.

In 2 additional US multicenter, double-blind, placebo-controlled, 2-week trials, Zantac 150 mg twice daily was shown to provide relief of heartburn pain within 24 hours of initiating therapy and a reduction in the frequency of severity of heartburn. In these trials, Zantac EFFERdose Tablets were shown to provide heartburn relief within 45 minutes of dosing.

Erosive Esophagitis: In 2 multicenter, double-blind, randomized, placebo-controlled, 12-week trials performed in the United States, Zantac 150 mg 4 times daily was significantly more effective than placebo in healing endoscopically diagnosed erosive esophagitis and in relieving associated heartburn. The erosive esophagitis healing rates were as follows:

Table 7. Erosive Esophagitis Patient Healing Rates

	Healed/Evaluable
	Placeboa n = 229	Zantac 150 mg 4 times dailya n = 215
Week 4	43/198 (22%)	96/206 (47%)b
Week 8	63/176 (36%)	142/200 (71%)b
Week 12	92/159 (58%)	162/192 (84%)b

aAll patients were permitted antacids as needed for relief of pain.

bP<0.001 versus placebo.

No additional benefit in healing of esophagitis or in relief of heartburn was seen with a ranitidine dose of 300 mg 4 times daily.

Maintenance of Healing of Erosive Esophagitis: In 2 multicenter, double-blind, randomized, placebo-controlled, 48-week trials conducted in patients whose erosive esophagitis had been previously healed, Zantac 150 mg twice daily was significantly more effective than placebo in maintaining healing of erosive esophagitis.

Indications and Usage for Zantac

Zantac is indicated in:

1. Short-term treatment of active duodenal ulcer. Most patients heal within 4 weeks. Studies available to date have not assessed the safety of ranitidine in uncomplicated duodenal ulcer for periods of more than 8 weeks.


2. Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of acute ulcers. No placebo-controlled comparative studies have been carried out for periods of longer than 1 year.


3. The treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome and systemic mastocytosis).


4. Short-term treatment of active, benign gastric ulcer. Most patients heal within 6 weeks and the usefulness of further treatment has not been demonstrated. Studies available to date have not assessed the safety of ranitidine in uncomplicated, benign gastric ulcer for periods of more than 6 weeks.


5. Maintenance therapy for gastric ulcer patients at reduced dosage after healing of acute ulcers. Placebo-controlled studies have been carried out for 1 year.


6. Treatment of GERD. Symptomatic relief commonly occurs within 24 hours after starting therapy with Zantac 150 mg twice daily.


7. Treatment of endoscopically diagnosed erosive esophagitis. Symptomatic relief of heartburn commonly occurs within 24 hours of therapy initiation with Zantac 150 mg 4 times daily.


8. Maintenance of healing of erosive esophagitis. Placebo-controlled trials have been carried out for 48 weeks.

Concomitant antacids should be given as needed for pain relief to patients with active duodenal ulcer; active, benign gastric ulcer; hypersecretory states; GERD; and erosive esophagitis.

Contraindications

Zantac is contraindicated for patients known to have hypersensitivity to the drug or any of the ingredients (see PRECAUTIONS).

Precautions

General:

1. Symptomatic response to therapy with Zantac does not preclude the presence of gastric malignancy.


2. Since Zantac is excreted primarily by the kidney, dosage should be adjusted in patients with impaired renal function (see DOSAGE AND ADMINISTRATION). Caution should be observed in patients with hepatic dysfunction since Zantac is metabolized in the liver.


3. Rare reports suggest that Zantac may precipitate acute porphyric attacks in patients with acute porphyria. Zantac should therefore be avoided in patients with a history of acute porphyria.

Information for Patients

Phenylketonurics: Zantac 25 EFFERdose Tablets contain phenylalanine 2.81 mg per 25 mg of ranitidine. Zantac EFFERdose Tablets should not be chewed, swallowed whole, or dissolved on the tongue.

Laboratory Tests

False-positive tests for urine protein with MULTISTIX® may occur during therapy with Zantac, and therefore testing with sulfosalicylic acid is recommended.

Drug Interactions

Ranitidine has been reported to affect the bioavailability of other drugs through several different mechanisms such as competition for renal tubular secretion, alteration of gastric pH, and inhibition of cytochrome P450 enzymes.

Procainamide: Ranitidine, a substrate of the renal organic cation transport system, may affect the clearance of other drugs eliminated by this route. High doses of ranitidine (e.g., such as those used in the treatment of Zollinger-Ellison syndrome) have been shown to reduce the renal excretion of procainamide and N-acetylprocainamide resulting in increased plasma levels of these drugs. Although this interaction is unlikely to be clinically relevant at usual ranitidine doses, it may be prudent to monitor for procainamide toxicity when administered with oral ranitidine at a dose exceeding 300 mg per day.

Warfarin: There have been reports of altered prothrombin time among patients on concomitant warfarin and ranitidine therapy. Due to the narrow therapeutic index, close monitoring of increased or decreased prothrombin time is recommended during concurrent treatment with ranitidine.

Ranitidine may alter the absorption of drugs in which gastric pH is an important determinant of bioavailability. This can result in either an increase in absorption (e.g., triazolam, midazolam, glipizide) or a decrease in absorption (e.g., ketoconazole, atazanavir, delavirdine, gefitinib). Appropriate clinical monitoring is recommended.

Atazanavir: Atazanavir absorption may be impaired based on known interactions with other agents that increase gastric pH. Use with caution. See atazanavir label for specific recommendations.

Delavirdine: Delavirdine absorption may be impaired based on known interactions with other agents that increase gastric pH. Chronic use of H2-receptor antagonists with delavirdine is not recommended.

Gefitinib: Gefitinib exposure was reduced by 44% with the coadministration of ranitidine and sodium bicarbonate (dosed to maintain gastric pH above 5.0). Use with caution.

Glipizide: In diabetic patients, glipizide exposure was increased by 34% following a single 150-mg dose of oral ranitidine. Use appropriate clinical monitoring when initiating or discontinuing ranitidine.

Ketoconazole: Oral ketoconazole exposure was reduced by up to 95% when oral ranitidine was coadministered in a regimen to maintain a gastric pH of 6 or above. The degree of interaction with usual dose of ranitidine (150 mg twice daily) is unknown.

Midazolam: Oral midazolam exposure in 5 healthy volunteers was increased by up to 65% when administered with oral ranitidine at a dose of 150 mg twice daily. However, in another interaction study in 8 volunteers receiving IV midazolam, a 300 mg oral dose of ranitidine increased midazolam exposure by about 9%. Monitor patients for excessive or prolonged sedation when ranitidine is coadministered with oral midazolam.

Triazolam: Triazolam exposure in healthy volunteers was increased by approximately 30% when administered with oral ranitidine at a dose of 150 mg twice daily. Monitor patients for excessive or prolonged sedation.

Carcinogenesis, Mutagenesis, Impairment of Fertility

There was no indication of tumorigenic or carcinogenic effects in life-span studies in mice and rats at dosages up to 2,000 mg/kg/day.

Ranitidine was not mutagenic in standard bacterial tests (Salmonella, Escherichia coli) for mutagenicity at concentrations up to the maximum recommended for these assays.

In a dominant lethal assay, a single oral dose of 1,000 mg/kg to male rats was without effect on the outcome of 2 matings per week for the next 9 weeks.

Pregnancy

Teratogenic Effects: Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at doses up to 160 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Zantac. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Ranitidine is secreted in human milk. Caution should be exercised when Zantac is administered to a nursing mother.

Pediatric Use

The safety and effectiveness of Zantac have been established in the age-group of 1 month to 16 years for the treatment of duodenal and gastric ulcers, gastroesophageal reflux disease and erosive esophagitis, and the maintenance of healed duodenal and gastric ulcer. Use of Zantac in this age-group is supported by adequate and well-controlled studies in adults, as well as additional pharmacokinetic data in pediatric patients and an analysis of the published literature (see CLINICAL PHARMACOLOGY: Pediatrics and DOSAGE AND ADMINISTRATION: Pediatric Use).

Safety and effectiveness in pediatric patients for the treatment of pathological hypersecretory conditions or the maintenance of healing of erosive esophagitis have not been established.

Safety and effectiveness in neonates (less than 1 month of age) have not been established (see CLINICAL PHARMACOLOGY: Pediatrics).

Geriatric Use

Of the total number of subjects enrolled in US and foreign controlled clinical trials of oral formulations of Zantac, for which there were subgroup analyses, 4,197 were 65 and over, while 899 were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

This drug is known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, caution should be exercised in dose selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Geriatrics and DOSAGE AND ADMINISTRATION: Dosage Adjustment for Patients With Impaired Renal Function).

Adverse Reactions

The following have been reported as events in clinical trials or in the routine management of patients treated with Zantac. The relationship to therapy with Zantac has been unclear in many cases. Headache, sometimes severe, seems to be related to administration of Zantac.

Central Nervous System

Rarely, malaise, dizziness, somnolence, insomnia, and vertigo. Rare cases of reversible mental confusion, agitation, depression, and hallucinations have been reported, predominantly in severely ill elderly patients. Rare cases of reversible blurred vision suggestive of a change in accommodation have been reported. Rare reports of reversible involuntary motor disturbances have been received.

Cardiovascular

As with other H2-blockers, rare reports of arrhythmias such as tachycardia, bradycardia, atrioventricular block, and premature ventricular beats.

Gastrointestinal

Constipation, diarrhea, nausea/vomiting, abdominal discomfort/pain, and rare reports of pancreatitis.

Hepatic

There have been occasional reports of hepatocellular, cholestatic, or mixed hepatitis, with or without jaundice. In such circumstances, ranitidine should be immediately discontinued. These events are usually reversible, but in rare circumstances death has occurred. Rare cases of hepatic failure have also been reported. In normal volunteers, SGPT values were increased to at least twice the pretreatment levels in 6 of 12 subjects receiving 100 mg intravenously 4 times daily for 7 days, and in 4 of 24 subjects receiving 50 mg intravenously 4 times daily for 5 days.

Musculoskeletal

Rare reports of arthralgias and myalgias.

Hematologic

Blood count changes (leukopenia, granulocytopenia, and thrombocytopenia) have occurred in a few patients. These were usually reversible. Rare cases of agranulocytosis, pancytopenia, sometimes with marrow hypoplasia, and aplastic anemia and exceedingly rare cases of acquired immune hemolytic anemia have been reported.

Endocrine

Controlled studies in animals and man have shown no stimulation of any pituitary hormone by Zantac and no antiandrogenic activity, and cimetidine-induced gynecomastia and impotence in hypersecretory patients have resolved when Zantac has been substituted. However, occasional cases of impotence and loss of libido have been reported in male patients receiving Zantac, but the incidence did not differ from that in the general population. Rare cases of breast symptoms and conditions, including galactorrhea and gynecomastia, have been reported in both males and females.

Integumentary

Rash, including rare cases of erythema multiforme. Rare cases of alopecia and vasculitis.

Respiratory

A large epidemiological study suggested an increased risk of developing pneumonia in current users of histamine-2-receptor antagonists (H2RAs) compared to patients who had stopped H2RA treatment, with an observed adjusted relative risk of 1.63 (95% CI, 1.07–2.48). However, a causal relationship between use of H2RAs and pneumonia has not been established.

Other

Rare cases of hypersensitivity reactions (e.g., bronchospasm, fever, rash, eosinophilia), anaphylaxis, angioneurotic edema, acute interstitial nephritis, and small increases in serum creatinine.

Overdosage

There has been limited experience with overdosage. Reported acute ingestions of up to 18 g orally have been associated with transient adverse effects similar to those encountered in normal clinical experience (see ADVERSE REACTIONS). In addition, abnormalities of gait and hypotension have been reported.

When overdosage occurs, the usual measures to remove unabsorbed material from the gastrointestinal tract, clinical monitoring, and supportive therapy should be employed.

Studies in dogs receiving dosages of Zantac in excess of 225 mg/kg/day have shown muscular tremors, vomiting, and rapid respiration. Single oral doses of 1,000 mg/kg in mice and rats were not lethal. Intravenous LD50 values in mice and rats were 77 and 83 mg/kg, respectively.

Zantac Dosage and Administration

Active Duodenal Ulcer

The current recommended adult oral dosage of Zantac for duodenal ulcer is 150 mg or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to 150 mg of ranitidine) twice daily. An alternative dosage of 300 mg or 20 mL of syrup (4 teaspoonfuls of syrup equivalent to 300 mg of ranitidine) once daily after the evening meal or at bedtime can be used for patients in whom dosing convenience is important. The advantages of one treatment regimen compared to the other in a particular patient population have yet to be demonstrated (see Clinical Trials: Active Duodenal Ulcer). Smaller doses have been shown to be equally effective in inhibiting gastric acid secretion in US studies, and several foreign trials have shown that 100 mg twice daily is as effective as the 150-mg dose.

Antacid should be given as needed for relief of pain (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

Maintenance of Healing of Duodenal Ulcers

The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to 150 mg of ranitidine) at bedtime.

Pathological Hypersecretory Conditions (such as Zollinger-Ellison syndrome)

The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to 150 mg of ranitidine) twice daily. In some patients it may be necessary to administer Zantac 150-mg doses more frequently. Dosages should be adjusted to individual patient needs, and should continue as long as clinically indicated. Dosages up to 6 g/day have been employed in patients with severe disease.

Benign Gastric Ulcer

The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to 150 mg of ranitidine) twice daily.

Maintenance of Healing of Gastric Ulcers

The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to 150 mg of ranitidine) at bedtime.

GERD

The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to 150 mg of ranitidine) twice daily.

Erosive Esophagitis

The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to 150 mg of ranitidine) 4 times daily.

Maintenance of Healing of Erosive Esophagitis

The current recommended adult oral dosage is 150 mg or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to 150 mg of ranitidine) twice daily.

Pediatric Use

The safety and effectiveness of Zantac have been established in the age-group of 1 month to 16 years. There is insufficient information about the pharmacokinetics of Zantac in neonatal patients (less than 1 month of age) to make dosing recommendations.

The following 3 subsections provide dosing information for each of the pediatric indications. Also, see the subsection on Preparation of Zantac 25 EFFERdose Tablets, below.

Treatment of Duodenal and Gastric Ulcers: The recommended oral dose for the treatment of active duodenal and gastric ulcers is 2 to 4 mg/kg twice daily to a maximum of 300 mg/day. This recommendation is derived from adult clinical studies and pharmacokinetic data in pediatric patients.

Maintenance of Healing of Duodenal and Gastric Ulcers: The recommended oral dose for the maintenance of healing of duodenal and gastric ulcers is 2 to 4 mg/kg once daily to a maximum of 150 mg/day. This recommendation is derived from adult clinical studies and pharmacokinetic data in pediatric patients.

Treatment of GERD and Erosive Esophagitis: Although limited data exist for these conditions in pediatric patients, published literature supports a dosage of 5 to 10 mg/kg/day, usually given as 2 divided doses.

Dosage Adjustment for Patients With Impaired Renal Function

On the basis of experience with a group of subjects with severely impaired renal function treated with Zantac, the recommended dosage in patients with a creatinine clearance <50 mL/min is 150 mg or 10 mL of syrup (2 teaspoonfuls of syrup equivalent to 150 mg of ranitidine) every 24 hours. Should the patient's condition require, the frequency of dosing may be increased to every 12 hours or even further with caution. Hemodialysis reduces the level of circulating ranitidine. Ideally, the dosing schedule should be adjusted so that the timing of a scheduled dose coincides with the end of hemodialysis.

Elderly patients are more likely to have decreased renal function, therefore caution should be exercised in dose selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Geriatrics and PRECAUTIONS: Geriatric Use).

Zydone

Generic Name: acetaminophen and hydrocodone (a SEET a MIN oh fen and hye droe KOE done)

Brand Names: Anexsia, Co-Gesic, Hycet, Liquicet, Lorcet 10/650, Lorcet Plus, Lortab 10/500, Lortab 2.5/500, Lortab 5/500, Lortab 7.5/500, Lortab Elixir, Maxidone, Norco, Polygesic, Stagesic, Vicodin, Vicodin ES, Vicodin HP, Xodol, Zamicet, Zolvit, Zydone

What is Zydone (acetaminophen and hydrocodone)?

Hydrocodone is in a group of drugs called narcotic pain relievers.

Acetaminophen is a less potent pain reliever that increases the effects of hydrocodone.

The combination of acetaminophen and hydrocodone is used to relieve moderate to severe pain.

Acetaminophen and hydrocodone may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Zydone (acetaminophen and hydrocodone)?

Tell your doctor if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take medicine that contains acetaminophen. Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death. Tell your doctor if the medicine seems to stop working as well in relieving your pain. Hydrocodone may be habit-forming and should be used only by the person it was prescribed for. Keep the medication in a secure place where others cannot get to it. Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP. This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen.

What should I discuss with my healthcare provider before taking Zydone (acetaminophen and hydrocodone)?

Do not use this medication if you are allergic to acetaminophen (Tylenol) or hydrocodone. Tell your doctor if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take medicine that contains acetaminophen.

To make sure you can safely take acetaminophen and hydrocodone, tell your doctor if you have any of these other conditions:

• 
  

  asthma, COPD, sleep apnea, or other breathing disorders;

  
  


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  liver or kidney disease;

  
  


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  a history of head injury or brain tumor;

  
  


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  low blood pressure;

  
  


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  a stomach or intestinal disorder;

  
  


• 
  

  underactive thyroid;

  
  


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  Addison's disease or other adrenal gland disorder;

  
  


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  curvature of the spine;

  
  


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  mental illness; or

  
  


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  a history of drug or alcohol addiction.

  
  

Hydrocodone may be habit forming and should be used only by the person it was prescribed for. Never share acetaminophen and hydrocodone with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it. FDA pregnancy category C. It is not known whether this medication is harmful to an unborn baby, but it could cause breathing problems or addiction/withdrawal symptoms in a newborn. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Acetaminophen and hydrocodone can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Zydone (acetaminophen and hydrocodone)?

Take exactly as prescribed. Never take acetaminophen and hydrocodone in larger amounts, or for longer than recommended by your doctor. An overdose of acetaminophen can damage your liver or cause death.

One acetaminophen and hydrocodone tablet may contain up to 750 mg of acetaminophen. Know the amount of acetaminophen in the specific product you are taking.

Follow the directions on your prescription label. Tell your doctor if the medicine seems to stop working as well in relieving your pain.

Measure liquid medicine with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Drink 6 to 8 full glasses of water daily to help prevent constipation while you are taking acetaminophen and hydrocodone. Ask your doctor about ways to increase the fiber in your diet. Do not use a stool softener (laxative) without first asking your doctor. Do not stop using this medicine suddenly after long-term use, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using acetaminophen and hydrocodone.

Acetaminophen can cause false results with certain lab tests for glucose (sugar) in the urine. Talk to your doctor if you are diabetic and you notice changes in your glucose levels during treatment.

If you need surgery, tell the surgeon ahead of time that you are using acetaminophen and hydrocodone. You may need to stop using the medicine for a short time.

Store at room temperature away from moisture and heat.

Keep track of the amount of medicine used from each new bottle. Oxycodone is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

Always check your bottle to make sure you have received the correct pills (same brand and type) of medicine prescribed by your doctor. Ask the pharmacist if you have any questions about the medicine you receive at the pharmacy.

What happens if I miss a dose?

Since acetaminophen and hydrocodone is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of acetaminophen and hydrocodone can be fatal.

The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

Overdose symptoms may also include extreme drowsiness, pinpoint pupils, cold and clammy skin, muscle weakness, fainting, weak pulse, slow heart rate, coma, blue lips, shallow breathing, or no breathing

What should I avoid while taking Zydone (acetaminophen and hydrocodone)?

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP. Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen.

Zydone (acetaminophen and hydrocodone) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have any of these serious side effects:

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  shallow breathing, slow heartbeat;

  
  


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  feeling light-headed, fainting;

  
  


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  confusion, fear, unusual thoughts or behavior;

  
  


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  seizure (convulsions);

  
  


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  problems with urination; or

  
  


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  nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

  
  

Less serious side effects may include:

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  anxiety, dizziness, drowsiness;

  
  


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  mild nausea, vomiting, upset stomach, constipation;

  
  


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  headache, mood changes;

  
  


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  blurred vision;

  
  


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  ringing in your ears; or

  
  


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  dry mouth.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Zydone (acetaminophen and hydrocodone)?

Do not take acetaminophen and hydrocodone with any other narcotic pain medications, sedatives, tranquilizers, sleeping pills, muscle relaxers, or other medicines that can make you sleepy or slow your breathing. Dangerous side effects may result.

Tell your doctor about all other medicines you use, especially:

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  an antidepressant such as amitriptyline (Elavil, Vanatrip, Limbitrol), doxepin (Sinequan), nortriptyline (Pamelor), and others;

  
  


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  an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate);

  
  


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  atropine (Donnatal, and others), benztropine (Cogentin), dimenhydrinate (Dramamine), glycopyrrolate (Robinul), mepenzolate (Cantil), methscopolamine (Pamine), or scopolamine (Transderm-Scop);

  
  


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  bladder or urinary medications such as darifenacin (Enablex), flavoxate (Urispas), oxybutynin (Ditropan, Oxytrol), tolterodine (Detrol), or solifenacin (Vesicare);

  
  


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  a bronchodilator such as ipratropium (Atrovent) or tiotropium (Spiriva); or

  
  


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  irritable bowel medications such as dicyclomine (Bentyl), hyoscyamine (Anaspaz, Cystospaz, Levsin, and others), or propantheline (Pro-Banthine).

  
  

This list is not complete and other drugs may interact with acetaminophen and hydrocodone. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Zydone resources

• Zydone Side Effects (in more detail)
• Zydone Use in Pregnancy & Breastfeeding
• Drug Images
• Zydone Drug Interactions
• Zydone Support Group
• 0 Reviews for Zydone - Add your own review/rating

• Zydone Advanced Consumer (Micromedex) - Includes Dosage Information


• Zydone Prescribing Information (FDA)


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• Hycet Prescribing Information (FDA)


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• Liquicet Prescribing Information (FDA)


• Lorcet Plus Prescribing Information (FDA)


• Lortab Prescribing Information (FDA)


• Lortab Consumer Overview


• Lortab MedFacts Consumer Leaflet (Wolters Kluwer)


• Maxidone Prescribing Information (FDA)


• Norco Consumer Overview


• Norco Prescribing Information (FDA)


• Vicodin Consumer Overview


• Vicodin Prescribing Information (FDA)


• Vicodin ES Prescribing Information (FDA)


• Vicodin HP Prescribing Information (FDA)


• Xodol Prescribing Information (FDA)


• Zolvit Prescribing Information (FDA)

Compare Zydone with other medications

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Where can I get more information?

• Your pharmacist can provide more information about acetaminophen and hydrocodone.

See also: Zydone side effects (in more detail)