Micardis

Generic Name: Telmisartan
Class: Angiotensin II Receptor Antagonists
VA Class: CV805
Chemical Name: 4′ - [1(1,4′ - Dimethyl - 2′ - propyl[2,6′ - bi - 1H - benzimidazol] - 1′ - yl)methyl] - [1,1′ - biphenyl] - 2 - carboxylic acid
Molecular Formula: C₃₃H₃₀N₄O₂
CAS Number: 144701-48-4

• 
  

  May cause fetal and neonatal morbidity and mortality if used during pregnancy.^{1 2 49 50} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  


• 
  

  If pregnancy is detected, discontinue as soon as possible.^{1 2 50}

  
  

Introduction

Angiotensin II receptor (AT₁) antagonist.^{1 2 3 16}

Uses for Micardis

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).^{1 2 3 17 19}

One of several preferred initial therapies in hypertensive patients with chronic kidney disease, diabetes mellitus, or heart failure.⁴³

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.⁴³

Diabetic Nephropathy

A first-line agent in the treatment of diabetic nephropathy† in hypertensive patients with type 2 diabetes mellitus.

CHF

A second-line agent in the treatment of CHF†; should be used only in those intolerant of ACE inhibitors.

Micardis Dosage and Administration

General

Hypertension

• 
  

  Fixed-combination telmisartan/hydrochlorothiazide tablets should not be used for initial treatment of hypertension.²

  
  

Administration

Oral Administration

Administer orally once daily without regard to meals.^{1 2}

Dosage

Adults

Hypertension

Monotherapy

Oral

Initially, 40 mg once daily in adults without intravascular volume depletion.¹ Adjust dosage at approximately monthly intervals (more aggressively in high-risk patients) to achieve BP control.⁴³

Usual dosage: 20–80 mg once daily; no additional therapeutic benefit with higher dosages.¹

Combination Therapy

Oral

If BP is not adequately controlled by monotherapy with telmisartan 80 mg daily, can switch to fixed-combination tablets (telmisartan 80 mg and hydrochlorothiazide 12.5 mg; then telmisartan 160 mg and hydrochlorothiazide 25 mg), administered once daily.²

If BP is not adequately controlled by monotherapy with hydrochlorothiazide 25 mg or if BP is controlled but hypokalemia is problematic at this dosage, can use fixed-combination tablets containing telmisartan 80 mg and hydrochlorothiazide 12.5 mg, administered once daily.² Can increase dosage to telmisartan 160 mg and hydrochlorothiazide 25 mg, if needed, to control BP.²

Special Populations

Hepatic Impairment

Initiate therapy under close medical supervision in patients with obstructive biliary disease or hepatic impairment.¹

If fixed-combination tablets are used in patients with obstructive biliary disease or hepatic impairment, recommended initial dosage is telmisartan 40 mg and hydrochlorothiazide 12.5 mg daily.² Use of fixed combination not recommended in those with severe hepatic impairment.²

Renal Impairment

No initial dosage adjustments necessary in patients with Cl_cr >30 mL/minute.^{1 2} Manufacturer makes no specific recommendations regarding telmisartan monotherapy in those with Cl_cr ≤30 mL/minute.¹

Telmisartan/hydrochlorothiazide fixed combination not recommended in patients with Cl_cr <30 mL/minute.²

Geriatric Patients

No initial dosage adjustments necessary.^{1 2}

Volume- and/or Salt-Depleted Patients

Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy under close medical supervision using lower initial dosage.^{1 2}

Cautions for Micardis

Contraindications

• 
  

  Known hypersensitivity to telmisartan or any ingredient in the formulation.^{1 2 7}

  
  

Warnings/Precautions

Warnings

Hypotension

Possible symptomatic hypotension, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics or undergoing dialysis).^{1 2} (See Volume- and/or Salt-Depleted Patients under Dosage and Administration.)

Transient hypotension is not a contraindication to additional doses; may reinstate therapy cautiously after BP is stabilized (e.g., with volume expansion).^{1 2}

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.^{1 2 50} (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.⁵⁰

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.^{49 50}

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.^{49 50} Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.¹³

Malignancies

In July 2010, FDA initiated a safety review of angiotensin II receptor antagonists after a published meta-analysis found a modest but statistically significant increase in risk of new cancer occurrence in patients receiving an angiotensin II receptor antagonist compared with control.^{120 121 123 126} However, subsequent studies, including a larger meta-analysis conducted by FDA, have not shown such risk.^{126 127 128 129} Based on currently available data, FDA has concluded that angiotensin II receptor antagonists do not increase the risk of cancer.¹²⁶

Sensitivity Reactions

Anaphylactoid reactions and/or angioedema possible;^{1 2 7 14} not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitor or angiotensin II receptor antagonist therapy.^b

General Precautions

Renal Effects

Possible oliguria, progressive azotemia and, rarely, acute renal failure and/or death in patients with severe CHF.^{1 2}

Increases in BUN and S_cr possible in patients with unilateral or bilateral renal artery stenosis.^{1 2}

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.²

Specific Populations

Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters).^{1 2} (See Boxed Warning.)

Lactation

Distributed into milk in rats; not known whether distributed into human milk.^{1 2} Discontinue nursing or the drug.^{1 2}

Pediatric Use

Safety and efficacy not established in children <18 years of age.^{1 2 21}

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults, but increased sensitivity cannot be ruled out.^{1 2}

Hepatic Impairment

Plasma telmisartan concentrations may be increased in patients with obstructive biliary disease or hepatic impairment.^{1 2} (See Special Populations under Absorption, in Pharmacokinetics.) Dosage adjustments may be necessary.² (See Hepatic Impairment under Dosage and Administration.)

Use of telmisartan in fixed combination with hydrochlorothiazide is not recommended in patients with severe hepatic impairment.²

Renal Impairment

Deterioration of renal function may occur.^{1 2} (See Renal Effects under Cautions.)

Use of telmisartan in fixed combination with hydrochlorothiazide is not recommended in patients with Cl_cr <30 mL/minute.²

Blacks

BP reduction may be smaller in black patients compared with non-black patients; use in combination with a diuretic.^{1 43}

Common Adverse Effects

Upper respiratory tract infection, sinusitis, pharyngitis, back pain, diarrhea.¹

Interactions for Micardis

Not metabolized by CYP isoenzymes; has no effect on CYP isoenzymes except for some inhibition of CYP2C19 in vitro.^{1 2}

Specific Drugs

Drug	Interaction	Comment
Acetaminophen	Interactions unlikely1 2
Amlodipine	Interactions unlikely1 2
Digoxin	Increased plasma digoxin concentrations1 2	Monitor serum digoxin concentrations when telmisartan therapy is initiated, adjusted, or discontinued in patients stabilized on digoxin1 2 3 21
Glyburide	Interactions unlikely1 2
Hydrochlorothiazide	Additive hypotensive effects1 2
Ibuprofen	Interactions unlikely1 2
Simvastatin	Interactions unlikely1 2
Warfarin	Possible decreased plasma warfarin concentrations; INR not affected1 2

Micardis Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is dose dependent: 42% at 40 mg, 58% at 160 mg.^{1 2}

Peak plasma concentration generally reached at 0.5–1 hour following oral administration.^{1 2}

Onset

Antihypertensive effect evident within 2 weeks, with maximum BP reduction after 4 weeks.¹

Food

Food slightly reduces bioavailability.^{1 2}

Special Populations

In patients with hepatic insufficiency, plasma telmisartan concentrations are increased and absolute bioavailability approaches 100%.^{1 2}

Distribution

Extent

Crosses the placenta and is distributed in the fetus in animals.^{1 2}

Distributed into milk in rats; not known whether distributed into human milk.^{1 2}

Plasma Protein Binding

>99.5% (principally albumin and α₁-acid glycoprotein).^{1 2}

Elimination

Metabolism

Metabolized in liver (via conjugation) to inactive metabolite.^{1 2}

Not metabolized by CYP isoenzymes.^{1 2}

Elimination Route

Eliminated mainly (>97%) as unchanged drug in feces (via bile); small amounts (<1%) eliminated in urine.^{1 2}

Half-life

Biphasic; terminal half-life is approximately 24 hours.^{1 2}

Special Populations

Not removed from blood by hemofiltration.^{1 2}

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).^{1 2} Do not remove tablets from blisters until immediately before administration.^{1 2}

Actions

• 
  

  Blocks the physiologic actions of angiotensin II, including vasoconstrictor and aldosterone-secreting effects.^{1 2}

  
  


• 
  

  Does not interfere with response to bradykinins and substance P.^{1 2}

  
  

• 
  

  Does not share the ACE inhibitor common adverse effect of dry cough.^{1 2 33}

  
  

Advice to Patients

• 
  

  Risks of use during pregnancy.^{1 2 49 50}

  
  


• 
  

  Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^{1 2}

  
  

• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{1 2}

  
  

• 
  

  Importance of informing patients of other important precautionary information.^{1 2} (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Telmisartan

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	20 mg	Micardis (with povidone)	Boehringer Ingelheim, (also promoted by Abbott)
		40 mg	Micardis (with povidone)	Boehringer Ingelheim, (also promoted by Abbott)
		80 mg	Micardis (with povidone)	Boehringer Ingelheim, (also promoted by Abbott)

Telmisartan Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	40 mg with Hydrochlorothiazide 12.5 mg	Micardis HCT (with povidone)	Boehringer Ingelheim, (also promoted by Abbott)
		80 mg with Hydrochlorothiazide 12.5 mg	Micardis HCT (with povidone)	Boehringer Ingelheim, (also promoted by Abbott)
		80 mg with Hydrochlorothiazide 25 mg	Micardis HCT (with povidone)	Boehringer Ingelheim, (also promoted by Abbott)

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 01/2012. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Micardis 20MG Tablets (BOEHRINGER INGELHEIM): 30/$123.19 or 90/$337.09

Micardis 40MG Tablets (BOEHRINGER INGELHEIM): 30/$123.99 or 90/$355.97

Micardis 80MG Tablets (BOEHRINGER INGELHEIM): 30/$122.99 or 90/$325.95

Micardis HCT 40-12.5MG Tablets (BOEHRINGER INGELHEIM): 30/$123.99 or 90/$339.96

Micardis HCT 80-12.5MG Tablets (BOEHRINGER INGELHEIM): 30/$122.00 or 90/$331.99

Micardis HCT 80-25MG Tablets (BOEHRINGER INGELHEIM): 30/$123.99 or 90/$349.97

Twynsta 80-5MG Tablets (BOEHRINGER INGELHEIM): 30/$129.99 or 90/$365.98

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, 1959-2012, Selected Revisions December 23, 2011. 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

1. Boehringer Ingelheim. Micardis (telmisartan) tablets prescribing information. Ridgefield, CT; 2004 Mar 5.

2. Boehringer Ingelheim. Micardis HCT (telmisartan and hydrochlorothiazide) tablets prescribing information. Ridgefield, CT; 2004 Apr 19.

3. McClellan KJ, Markham A. Telmisartan. Drugs. 1998; 56:1039-44. [PubMed 9878991]

4. 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.)

5. Anon. Drugs for hypertension. Med Lett Drugs Ther. 2001; 43:17-22. [PubMed 11242494]

6. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: approaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9-38A.

7. Warner KK, Visconti JA, Tschampel MM. Angiotensin II receptor blockers in patients with ACE inhibitor-induced angioedema. Ann Pharmacother. 2000; 34:526-8. [IDIS 443518] [PubMed 10772441]

8. Anon. Telmisartan tablets, Micardis: Summary basis of approval equivalent NDA number: 20-850. Rockville, MD: US Food and Drug Administration; 1998. (IDIS 453559)

9. Unger T. Significance of angiotensin type 1 receptor blockade: why are angiotensin II receptor blockers different? Am J Cardiol. 1999; 84:9-15S.

10. Martineau P, Goulet J. New competition in the realm of renin-angiotensin axis inhibition; the angiotensin II receptor antagonists in congestive heart failure. Ann Pharmacother. 2001; 35:71-84. [IDIS 457649] [PubMed 11197588]

11. 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]

12. Parker AB, Azevedo ER, Baird MG et al. ARCTIC: assessment of haemodynamic response in patients with congestive heart failure to telmisartan: a multicentre dose-ranging study in Canada. Am Heart J. 1999; 138:843-8. [IDIS 438270] [PubMed 10539814]

13. US Food and Drug Administration. Dangers of ACE inhibitors during second and third trimesters of pregnancy. FDA Med Bull. 1992; 22:2.

14. Mazzolai L, Burnier M. Comparative safety and tolerability of angiotensin II receptor antagonists. Drug Safety. 1999; 21:23-33. [PubMed 10433351]

15. Kirk JK. Therapy with angiotensin II receptor antagonists. Clin Geriatrics. From the MultiMedia Health Care website ().

16. Stangier J, Su CPF, Schöndorfer G et al. Pharmacokinetics and safety of intravenous and oral telmisartan 20 mg and 120 mg in subjects with hepatic impairment compared with healthy volunteers. J Clin Pharmacol. 2000; 40:1355-64. [IDIS 455811] [PubMed 11185634]

17. Neutel JM, Smith DHG. Dose response and antihypertensive efficacy of the AT1 receptor antagonist telmisartan in patients with mild to moderate hypertension. Adv Ther. 1998;15:206-17.

18. Elliott HL. The efficacy and safety of telmisartan compared to atenolol and placebo in patients with hypertension. Am J Hypertens. 1998; 11(Part 2): 124A.

19. Smith DHG, Neutel JM, Morgenstern P. Once-daily telmisartan compared with enalapril in the treatment of hypertension. Adv Ther. 1998; 15:229-40.

20. Littlejohn T, Mroczek W, Marbury T et al. A prospective, randomized, open-label trial comparing telmisartan 80 mg with valsartan 80 mg in patients with mild to moderate hypertension using ambulatory blood pressure monitoring. Can J Cardiol. 2000; 16:1123-32. [PubMed 11021956]

21. Boehringer Ingelheim, Ridgefield, CT: Personal communication.

22. AstraZeneca, Wayne, PA: Personal communication on candesartan.

23. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2002; 25:134-47. [IDIS 479088] [PubMed 11772914]

24. Brenner BM, Cooper ME, de Zeeuw D et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001; 345:861-9. [IDIS 469607] [PubMed 11565518]

25. Lewis EJ, Hunsicker LG, Claarke WR et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001; 345:851-60. [IDIS 469606] [PubMed 11565517]

26. Sica DA, Bakris GL. Type 2 diabetes: RENAAL and IDNT—the emergence of new treatment options. J Clin Hypertens (Greenwich). 2002; 4:52-7. [PubMed 11821641]

27. Parving HH, Brenner BM, Cooper ME et al. [Effect of losartan on renal and cardiovascular complications of patients with type 2 diabetes and nephropathy.] (Danish; with English abstract.) Ugeskr Laeger. 2001; 163:5514-9.

28. Weekers L, Krzesinski JM. [Clinical study of the month. Nephroprotective role of angiotensin II receptor antagonists in type 2 diabetes: results of IDNT and RENAAL trials.] (French with English abstract.) Rev Med Liege. 2001; 56:723-6.

29. Parving HH, Lehnert H, Brochner-Mortensen J et al and the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001; 345:870-8. [IDIS 469608] [PubMed 11565519]

30. Walser M. Angiotensin-receptor blockers, type 2 diabetes, and renoprotection. N Engl J Med. 2002; 346:706.

31. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2002; 25(Suppl 1):S33-43.

32. American Diabetes Association. Clinical Practice Recommendations 2002. Position Statement. Diabetic nephropathy. Diabetes Care. 2002; 25(Suppl 1):S85-9.

33. Hunt SA, Baker DW, Chin MH et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). 2001. Available at: . Accessed July 25, 2002.

34. Lewis EJ, Hunsicker LG, Bain RP et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993; 329:1456-62. [IDIS 321612] [PubMed 8413456]

35. Remuzzi G. Slowing the progression of diabetic nephropathy. N Engl J Med. 1993; 329:1496-7. [PubMed 8413463]

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

37. Viberti G, Mogensen CE, Groop LC et al. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. JAMA. 1994; 271:275-9. [IDIS 324307] [PubMed 8295285]

38. Joint National Committee on Detection, Evaluation. The 1984 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1984; 144:1045-57. [IDIS 184763] [PubMed 6143542]

39. Joint National Committee on Detection, Evaluation. 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]

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

42. 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]

43. 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.

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

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

46. 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]

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

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

49. Cooper WO, Hernandez-Diaz S, Arbogast PG et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006; 354:2443-51. [PubMed 16760444]

50. Food and Drug Administration. FDA public health advisory: angiotensin-converting enzyme inhibitor (ACE inhibitor) drugs and pregnancy. From FDA website.

120. Food and Drug Administration. FDA drug safety communication: ongoing safety review of the angiotensin receptor blockers and cancer. Rockville, MD; 2010 Jul 15. From FDA website.

121. Sipahi I, Debanne SM, Rowland DY et al. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. 2010; 11:627-36. [PubMed 20542468]

122. Nissen SE. Angiotensin-receptor blockers and cancer: urgent regulatory review needed. Lancet Oncol. 2010; 11:605-6. [PubMed 20542469]

123. Sica DA. Angiotensin receptor blockers and the risk of malignancy: a note of caution. Drug Saf. 2010; 33:709-12. [PubMed 20701404]

126. Food and Drug Administration. FDA drug safety communication: No increase in risk of cancer with certain blood pressure drugs-angiotensin receptor blockers (ARBs). Rockville, MD; 2011 Jun 2. Available from FDA website. Accessed 2011 Jun 15.

127. Bangalore S, Kumar S, Kjeldsen SE et al. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials. Lancet Oncol. 2011; 12:65-82. [PubMed 21123111]

128. ARB Trialists Collaboration. Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals. J Hypertens. 2011; 29:623-35. [PubMed 21358417]

129. Pasternak B, Svanström H, Callréus T et al. Use of angiotensin receptor blockers and the risk of cancer. Circulation. 2011; 123:1729-36. [PubMed 21482967]

130. Volpe M, Morganti A. 2010 Position Paper of the Italian Society of Hypertension (SIIA): Angiotensin Receptor Blockers and Risk of Cancer. High Blood Press Cardiovasc Prev. 2011; 18:37-40. [PubMed 21612311]

131. Siragy HM. A current evaluation of the safety of angiotensin receptor blockers and direct renin inhibitors. Vasc Health Risk Manag. 2011; 7:297-313. [PubMed 21633727]

b. Howes LG, Tran D. Can angiotensin receptor antagonists be used safely in patients with previous ACE inhibitor-induced angioedema? Drug Saf. 2002; 25:73-6.

More Micardis resources

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

• Micardis Prescribing Information (FDA)


• Micardis Consumer Overview


• Micardis Advanced Consumer (Micromedex) - Includes Dosage Information


• Micardis MedFacts Consumer Leaflet (Wolters Kluwer)


• Telmisartan Professional Patient Advice (Wolters Kluwer)

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Micronor Oral Contraceptive Tablets

1. Name Of The Medicinal Product

Micronor Oral Contraceptive Tablets

2. Qualitative And Quantitative Composition

Each tablet contains norethisterone 0.35 mg.

3. Pharmaceutical Form

Small, round, white tablet, engraved C035 on both faces.

4. Clinical Particulars

4.1 Therapeutic Indications

Oral contraceptive.

4.2 Posology And Method Of Administration

For oral administration.

4.2.1 Adults

How to take Micronor:

Tablet intake from the first pack is started on the first day of menstruation; no extra contraceptive precautions are necessary.

One tablet is taken at the same time each day, every day of the year, whether menstruation occurs or not.

Starting treatment

It is preferable that tablet intake from the first pack is started up to and including day 5 of menstruation in which case no extra contraceptive precautions are necessary.

Micronor can be started at any other time, if pregnancy can reasonably be excluded. In this case, additional contraceptive precautions must be taken for the first 48 hours of tablet taking.

If the patient is amenorrhoeic, pregnancy should be excluded prior to starting Micronor and there is no risk of conception. In this case additional contraceptive precautions must be taken for the first 48 hours of tablet taking.

Switching from another contraceptive

Combined oral Contraceptive (CoC), Progestogen-only Pill (POP), Progestogen-only implant: Micronor can be started immediately if the patient has been using the current hormonal method consistently and correctly, or if pregnancy can reasonably be excluded. There is no need to wait for the next menstruation. Additional contraceptive precautions are not required.

Progestogen-only injectable:Micronor can be started when the repeat injection would have been given, or before. Additional contraceptive precautions are not required.

IUDs: Start Micronor at least 2 days before the removal of the IUD. Additional contraceptive precautions are not required. However, if it is started at the time of removal, the patient should avoid intercourse or use another non-hormonal contraceptive (e.g. condoms) for 7 days before removal if possible and take extra contraceptive precautions for 48 hours after starting Micronor.

Levonorgesterel-releasing IUS: Micronor can be started when the IUS is removed. Additional contraceptive precautions are not required.

Post-partum administration

Following a vaginal delivery, Micronor can be started immediately. No additional contraceptive precautions are required. If post-partum administration begins more than 21 days after delivery, additional contraceptive precautions are required for the first 48 hours of tablet taking.

Use after Abortion or Miscarriage

Micronor can be started immediately. An additional method of contraception is not needed.

If tablet taking is started more than 1 day after surgical abortion, second part of medical abortion or miscarriage, additional contraceptive precautions must be taken for the first 48 hours of tablet taking.

Reduced reliability

When Micronor is taken according to the directions for use, the occurrence of pregnancy is highly unlikely. However, the reliability of oral contraceptives may be reduced under the following circumstances:

(i) Missed or late tablets

If a tablet is missed within 3 hours of the correct dosage time, then the missed tablet should be taken as soon as possible; this will ensure that contraceptive protection is maintained. If one (for longer than 3 hours) or more tablets are missed, it is recommended that the patient takes the last missed tablet as soon as possible and continues to take the rest of the tablets as usual. This may mean taking two tablets in one day. Additional means of contraception (non-hormonal) should be used for the next 48 hours.

If the patient does not have a period within 45 days of her last period, Micronor should be discontinued and pregnancy should be excluded.

(ii) Vomiting and diarrhoea

If vomiting occurs within 3 hours of taking a tablet, the patient should take another tablet as soon as possible. If vomiting and/or diarrhoea continue for more than 3 hours after taking a tablet, or if severe diarrhoea lasts for more than 24 hours, the effectiveness of the contraception may not be adequate, and an additional non-hormonal method of contraception should be used for 48 hours without interruption.

4.2.2 Children

Use of this product before menarche is not indicated.

4.2.3 Elderly

Use of this product is not indicated in post-menopausal women.

4.3 Contraindications

• Known or suspected carcinoma of the breast

• Hypersensitivity to norethisterone or to any of the excipients.

4.4 Special Warnings And Precautions For Use

There is a general opinion, based on statistical evidence, that users of combined oral contraceptives (ie oestrogen plus progestogen) experience more often than non-users various disorders of the circulation of blood, including strokes (blood clots in, and haemorrhages from, the blood vessels of the brain), heart attacks (coronary thromboses) and blood clots obstructing the arteries of the lungs (pulmonary emboli). There may not be a full recovery from such disorders and it should be realised that in a few cases they may be fatal.

To date no association between these disorders and progestogen-only oral contraceptives (such as Micronor Oral Contraceptive Tablets) has been shown. However there is a risk that the users of such progestogen-only oral contraceptives will (like users of the combined oral contraceptive) be exposed to an increased risk of suffering from these disorders.

Assessment of women prior to starting oral contraceptives (and at regular intervals thereafter) should include a personal and family medical history of each woman. Physical examination should be guided by this and by the contra-indications (Section 4.3) and warnings for this product. The frequency and nature of these assessments should be based upon relevant guidelines and should be adapted to the individual woman, but should include measurement of blood pressure and, if judged appropriate by the clinician, breast, abdominal and pelvic examination including cervical cytology.

Exclude likelihood of pregnancy before starting treatment.

In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy.

Oral contraceptives DO NOT protect against HIV infections (AIDS) or any other sexually transmitted disease.

Because of a possible increased risk of post surgery thrombo-embolic complications in oral contraceptive users, therapy should be discontinued six weeks prior to elective surgery.

When Micronor is administered during the post-partum period, the increased risk of thrombo-embolic disease associated with the post-partum period must be considered.

Conditions requiring supervision

The theoretical or proven risks usually outweigh the advantages of using POPs in the conditions listed below. Consequently the decision to prescribe the POP must be made with specialist clinical judgement and in consultation with the individual patient.

• A history of breast cancer with no evidence of disease in the last 5 years

• Severe decompensated cirrhosis

• Liver tumours (benign and malignant)

• Systemic Lupus Erythematosus (SLE) with antiphospholipid antibodies

• Current or history of ischaemic heart disease

• History of cerebrovascular accidents, including transient ischaemic attacks

• Porphyria

The worsening or first appearance of any of these conditions may indicate that Micronor should be discontinued.

Ectopic pregnancy

The incidence of ectopic pregnancies for progestogen-only oral contraceptive users is 5 per 1000 woman-years, which is higher than for women using other contraceptive methods but similar to the incidence for women not using any contraception. Up to 10% of pregnancies reported in clinical studies of progestogen-only oral contraceptive users are extrauterine. Although symptoms of ectopic pregnancy should be watched for, a history of ectopic pregnancy need not be considered a contraindication to use of this contraceptive method. Vaginal bleeding and abdominal pain are typical symptoms of an ectopic pregnancy. Women reporting these symptoms should be evaluated.

Carcinomas

Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian and cervical cancer in women using oral contraceptives.

Breast cancer

A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk of having breast cancer diagnosed in women who are currently using oral contraceptives (OCs). The observed pattern of increased risk may be due to an earlier diagnosis of breast cancer in OC users, the biological effects of OCs or a combination of both. The additional breast cancers diagnosed in current users of OCs or in women who have used OCs in the last 10 years are more likely to be localised to the breast than those in women who have never used OCs.

Breast cancer is rare among women under 40 years of age whether or not they take OCs. Whilst the background risk increases with age, the excess number of breast cancer diagnoses in current and recent progesterone-only pill (POP) users is small in relation to the overall risk of breast cancer, possibly of similar magnitude to that associated with combined OCs. However, for POPs, the evidence is based on much smaller populations of users and so is less conclusive than that for combined OCs.

The most important risk factor for breast cancer in POP users is the age women discontinue the POP; the older the age at stopping, the more breast cancers are diagnosed. Duration of use is less important and the excess risk gradually disappears during the course of the 10 years after stopping POP use, such that by 10 years there appears to be no excess.

The evidence suggests that compared with never-users, among 10,000 women who use POPs for up to five years but stop by age 20, there would be much less than one extra case of breast cancer diagnosed up to 10 years afterwards. For those stopping by age 30 after 5 years use of the POP, there would be an estimated 2-3 extra cases (additional to the 44 cases of breast cancer per 10,000 women in this age group never exposed to oral contraceptives). For those stopping by age 40 after 5 years use, there would be an estimated 10 extra cases diagnosed up to 10 years afterwards (additional to the 160 cases of breast cancer per 10,000 never-exposed women in this age group).

It is important to inform patients that users of all contraceptive pills appear to have a small increase in the risk of being diagnosed with breast cancer, compared with non-users of oral contraceptives, but that this has to be weighed against the known benefits.

Cervical cancer

Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behaviour and other factors. There is insufficient data to determine whether the use of POPs increases the risk of developing cervical intraepithelial neoplasia.

Hepatic neoplasia

Malignant hepatic tumours have been reported on rare occasions in long-term users of oral contraceptives. Benign hepatic tumours have also been associated with oral contraceptive use. A hepatic tumour should be considered in the differential diagnosis when upper abdominal pain, enlarged liver or signs of intra-abdominal haemorrhage occur.

Carbohydrate and lipid metabolism

Carbohydrate changes in healthy individuals from clinical studies are mixed. Most studies show no effect, but in some studies there is a suggestion of slight deterioration in glucose tolerance and elevation in plasma insulin concentration. From the limited data on POPs in diabetic women, no increase in insulin dose was required.

Delayed follicular atresia/ovarian cysts

If follicular development occurs, atresia of the follicle is sometimes delayed, and the follicle may continue to grow beyond the size it would attain in a normal cycle. Generally these enlarged follicles disappear spontaneously. Often they are asymptomatic; in some cases they are associated with mild abdominal pain. Rarely they may twist or rupture, requiring surgical intervention.

Bleeding irregularities

Irregular menstrual patterns are common among women using progestogen-only oral contraceptives. If genital bleeding is suggestive of infection, malignancy or other abnormal conditions, such non-pharmacologic causes should be ruled out. If prolonged amenorrhea occurs, the possibility of pregnancy should be evaluated.

Headache

The onset or exacerbation of migraine or development of headache with a new pattern, which is recurrent, persistent or severe, requires discontinuation of oral contraceptives and evaluation of the cause should be considered.

Other conditions and warnings

In the following conditions the benefit of oral contraception generally outweighs the theoretical or known risk. However, they may need to be considered before prescribing to individual patients or continuing treatment if they arise:

• Multiple risk factors for cardiovascular disease (including older age, smoking, diabetes, hypertension and obesity)

• Vascular disease (including coronary heart disease with angina, peripheral vascular disease with intermittent claudication, hypertensive retinopathy)

• History of venous thrombo-embolism (VTE) or current VTE

• Major surgery with prolonged immobilisation

• Known thrombogenic mutations (such as Factor V Leiden, Prothrombin mutation, Protein S, Protein C and Antithrombin deficiencies

• Migraine with or without focal aura at any age or a past history (

• Carriers of known gene mutations associated with breast cancer (e.g. BRCA1)

• Diabetes with or without vascular involvement (although all patients with diabetes are at increased risk of arterial disease)

• Known hyperlipidaemias. However, routine screening of women with is not considered appropriate

• Gall bladder disease

• History of cholestasis related to past COC use

• Benign liver tumour (focal nodular hyperplasia)

• Inflammatory bowel disease (including Crohn's disease and ulcerative colitis)

• Raynaud's disease secondary with Systemic Lupus Erythematosus (SLE) if lupus anticoagulant is present.

Laboratory tests

Certain endocrine and liver function tests and blood components may be affected by progestogen-only oral contraceptive use:

• Sex hormone-binding globulin (SHBG) concentrations may be decreased

• Thyroxine concentrations may be decreased, due to a decrease in thyroid binding globulin (TBG).

Excipients

The tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Potential Reduction in Contraceptive Effectiveness Associated With Co-Administration of Other Drugs:

Hepatic enzyme inducers

Drugs or herbal products that induce enzymes, especially CYP3A4, may decrease the plasma concentrations of norethisterone, and may decrease its effectiveness and/or increase breakthrough bleeding.

Examples include:

• barbiturates

• bosentan

• carbamazepine

• griseofulvin

• some HIV protease inhibitors (e.g. darunavir/ritonavir, lopinavir/ritonavir)

• some non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine)

• phenytoin

• rifampicin and rifabutin

• St. John's Wort

Management

Women on short-term treatment with drugs and herbal products that interact with hormonal contraception and may decrease plasma levels of contraceptive hormones could have their contraceptive effectiveness reduced. They should therefore temporarily use a barrier contraceptive method (e.g. condoms, diaphragm) in addition to Micronor during the time of concomitant medicinal product administration and for 28 days after their discontinuation.

For women on long-term treatment with drugs and herbal products that interact with hormonal contraception, another reliable, non-hormonal method of contraception is recommended.

Physicians are advised to consult the labelling of concurrently-used drugs to obtain further information about interactions with hormonal contraceptives and the possible need to adjust dosages.

4.6 Pregnancy And Lactation

4.6.1. Use during pregnancy

Not indicated during pregnancy. Confirm suspected pregnancy before discontinuing treatment.

Many studies have found no effects on foetal development associated with long-term use of contraceptive doses of oral progestogens. The few studies of infant growth and development that have been conducted have not demonstrated significant adverse effects. It is nonetheless prudent to rule out suspected pregnancy before initiating any hormonal contraceptive use.

4.6.2. Use during lactation

In most women, progestogen-only contraceptives, such as Micronor, do not affect the quantity and quality of breast milk or length of lactation. However, isolated post-marketing cases of decreased milk production have been reported. Studies with various orally administered progestogen-only contraceptives have shown that small amounts of progestogens pass into the breast milk of nursing mothers resulting in detectable steroid levels in infant plasma. No adverse effects have been found on the health, growth or development of the infant.

4.7 Effects On Ability To Drive And Use Machines

Not applicable

4.8 Undesirable Effects

Side effects are usually self-limiting and of relatively short duration. Amongst the symptoms reported are:

• Headaches/migraine

• Nausea

• Vomiting

• Breast changes

• Change in weight

• Changes in libido

• Chloasma

• Breakthrough bleeding and spotting

• Rash

• Depression

• Irregular cycle length (particularly in early cycles of therapy). It is important that patients should be advised that whilst on Micronor therapy they may experience that variation in cycle length and that they should continue taking a tablet every day whether they have a period or not. However, patients should be advised to discontinue Micronor and to consult their doctor if they have gone 45 days without having a period.

4.9 Overdose

No serious ill effects have been reported following acute ingestion of large doses of oral contraceptives. Overdosage may cause nausea, vomiting and vaginal bleeding. There are no antidotes and treatment should be symptomatic.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Micronor Oral Contraceptive Tablets have a progestational effect on the endometrium and the cervical mucus.

5.2 Pharmacokinetic Properties

Norethisterone is absorbed from the gastro-intestinal tract and metabolised in the liver. To obtain maximal contraceptive effectiveness, the tablets should be taken at the same time each day, every day.

5.3 Preclinical Safety Data

No relevant information additional to that contained elsewhere in the Summary of Product Characteristics.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose

Magnesium stearate

Pregelatinised starch

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Store at room temperature (below 25°C).

Protect from light.

6.5 Nature And Contents Of Container

PVC/aluminium foil blister strips with or without a card wallet in cardboard carton, containing either 42, 2 x 42, 3 x 28, 1 x 28 or 100 x 28 tablets.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Janssen-Cilag Ltd

50 -100 Holmers Farm Way

High Wycombe

Buckinghamshire

HP12 4EG

UK

8. Marketing Authorisation Number(S)

0242/0234

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of First Authorisation: 1 October 1995

Renewal of Authorisation: 4 December 2008

10. Date Of Revision Of The Text

06 October 2011

Legal category POM

Cortagon

Cortagon may be available in the countries listed below.

Ingredient matches for Cortagon

Dihydroergotoxine

Dihydroergotoxine mesilate (a derivative of Dihydroergotoxine) is reported as an ingredient of Cortagon in the following countries:

• Japan

International Drug Name Search

Penject

Dosage Form: FOR ANIMAL USE ONLY
Drug Facts

Description

Procaine penicillin G is a potent antibacterial agent which is effective against a variety of pathogenic organisms, chiefly in the Gram-positive category. Penicillin-G Procaine is a free-flowing product prepared by combining penicillin G and procaine, molecule for molecule, with dispersing agents.

Warning

Milk taken from animals during treatment and for 48 hours (4 milkings) after the latest treatment must not be used for food. A withdrawal period has not been established for this product in preruminating calves. Do not use in calves to be processed for veal.

Discontinue use of this drug for the following time periods before treatment animals are slaughtered for food: Cattle-10 days, Sheep-9 days, Swine-7 days. Not for use in horses intended for food.

Dosage Levels

The recommended daily dosage of penicillin is 3, 000 units per pound of body weight (one mL per 100lb body weight). Continue daily treatment until recovery is apparent and for at least 1 day after Symptoms disappear, usually in 2 or 3 days. Treatment should not exceed 4 consecutive days.

Directions for Use

Penicillin-G Procaine should be administered by the intramuscular route. A thoroughly cleaned, sterile needle and syringe should be used for each injection (needles and syringes may be sterilized by boiling in water for 15 minutes). Before withdrawing the solution from the bottle, disinfect the rubber cap on the bottle with a suitable disinfectant such as 70 percent alcohol. The injection site should be similarly cleaned with the disinfectant. Needles of 16 to 18 gauge and 1 to 1½ inches long are adequate for intramuscular injection.

INTRAMUSCULAR INJECTION: In livestock, intramuscular injection should be made by directing the needle of suitable gauge and length into the fleshy part of a thick muscle such as the rump, hip, or thigh region; avoid blood vessels and major nerves. Before injecting the solution, pull back gently on the plunger. If blood appears in the syringe, a blood vessel has been entered; withdraw the needle and select a different site. No more than 10mL should be injected at any one site in adult livestock; rotate injection sites for each succeeding treatment.

Care of sick animals: The use of antibiotics in the management of disease is based on an accurate diagnosis and an adequate course of treatment. When properly used in the treatment of diseases caused by penicillin-susceptible organisms, Most animals treated with Penicillin-G Procaine show a noticeable improvement within 24 to 48 hours. I improvement does not occur within this period of time, the diagnosis and course of treatment should be re-evaluated. It is recommended that the diagnosis and treatment of animal diseases be carried out by a veterinarian. Since many diseases look alike but require different types of treatment, the use of professional veterinary and laboratory services can reduce treatment time, cost, and needless losses. Good housing, sanitation, and nutrition are important in the maintenance of healthy animals and are essential in the treatment of disease.

Contains

Each mL contains 300,000 units of procaine penicillin G and approximately: 0.08% sodium citrate, 0.15% sodium carboxymethylcellulose; 25% sorbitol solution U.S.P; 0.06% povidone; 0.6%lecithin; 0.1% methylparaben; 0.01% propylparaben; 0.25% phenol.

Store between 2°-8°C (36°-46°F)

Restricted Drug (California)-

Use Only As Directed

Not For Human Use

Refer to label insert for complete directions SHAKE WELL BEFORE USING.

Manufactured By Teva Animal Health, Inc. Fort Dodge, IA 50501

NADA 65-110

Penject

Penicillin-G Procaine

In Aqueous Suspension

For Use In Cattle, Sheep, Swine and Horses

READ ENTIRE BROCHURE CAREFULLY BEFORE USING THIS PRODUCT

FOR INTRAMUSCULAR USE ONLY

Indications

Penject is recommended for treatment of bacterial pneumonia (shipping fever) caused by Pasteurella multocida in cattle and sheep, erysipelas caused by Erysipelothrix insidiosa in swine, and strangles caused by streptococcus equi in horses.

Precautions

Exceeding the highest recommended daily dosage of 3,000 units per pound of body weight, administering at recommended levels for more than 4 consecutive days, and/or exceeding 10mL intramuscularly per injection site may result in antibiotic residues beyond the withdrawal time.

Penicillin-G Procaine should be injected deep within the fleshy muscles of the hip, rump, round, or thigh. Do not inject this material subcutaneously (under the skin), into a blood vessel, or near a major nerve.

Procaine penicillin G is a substance of low toxicity. However, side effects, or so-called allergic or anaphylactic reactions-sometimes fatal, have been known to occur in animals hypersensitive to penicillin and procaine. Such reactions can occur unpredictably with varying intensity. Animals administered Penicillin-G Procaine should be kept under close observation for at least one-half hour. Should allergic or anaphylactic reactions occur, discontinue use of the product and immediately administer epinephrine following manufacturer’s recommendations; call a veterinarian. As with all antibiotic preparations, use of this drug may result in overgrowth of non-susceptible organisms, including fungi. A lack of response by the treated animal, or the development of new signs or symptoms suggest that an overgrowth of non-susceptible organisms has occurred. In such instances, consult your veterinarian. Since bactericidal drugs may interfere with the bacteriostatic action of tetracyclines, it is advisable to avoid giving penicillin in conjunction with tetracyclines. Penicillin-G should be stored between 2-8°C (36-46°F). Warm to room temperature and shake before using.

Directions For Use

Penject should be administered by the intramuscular route. A thoroughly cleaned, sterile needle and syringe should be used for each injection (needles and syringes may be sterilized by boiling in later for 15 minutes). Before withdrawing the solution from the bottle, disinfect the rubber cap on the bottle with a suitable disinfectant, such as 70 percent alcohol. The injection site should be similarly cleaned with the disinfectant. Needles of 14 to 16 gauge and not more than 1 inch long are adequate for injections.

SHAKE WELL BEFORE USING

FOR ANIMAL USE ONLY

RESTRICTED DRUG (CALIFORNIA)

USE ONLY AS DIRECTED

NOT FOR HUMAN USE

Storage

Penject should be stored between 2°-8°C (36°-46°F) warm to room temperature and shake before using.

Trademark of Butler Animal Health Supply, LLC.

Manufactured By Teva Animal Health, Inc. Fort Dodge, IA 50501

7600021

Package Information

Penicillin-G is available in vials of 100mL and 250mL with each mL containing 300,000 units of procaine penicillin G.

FOR ANIMAL USE ONLY

RESTRICTED DRUG (California)

USE ONLY AS DIRECTED.

NOT FOR HUMAN USE.

Principle Display Panel

Principle Display Panel

Penject  penicillin g procaine  injection, suspension

Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 11695-3600 Route of Administration INTRAMUSCULAR DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PENICILLIN G PROCAINE (PENICILLIN G) PENICILLIN G PROCAINE 300000 ug  in 1 mL

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 11695-3600-1 100 mL In 1 BOTTLE, GLASS None 2 11695-3600-2 250 mL In 1 BOTTLE, GLASS None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA65110	08/17/2006	07/31/2009

Labeler - Butler Animal Health Supply (017880659)

Registrant - Teva Animal Health, Inc. (625254461)

Revised: 02/2010Butler Animal Health Supply

Cloviran

Cloviran may be available in the countries listed below.

Ingredient matches for Cloviran

Acyclovir

Aciclovir is reported as an ingredient of Cloviran in the following countries:

• Chile

International Drug Name Search

Vilazodone

Pronunciation: vil-AZ-oh-done
Generic Name: Vilazodone
Brand Name: Viibryd

Antidepressants may increase the risk of suicidal thoughts or actions in children, teenagers, and young adults. However, depression and certain other mental problems may also increase the risk of suicide. Talk with the patient's doctor to be sure that the benefits of using Vilazodone outweigh the risks.

Families and caregivers must closely watch patients who take Vilazodone. It is important to keep in close contact with the patient's doctor. Tell the doctor right away if the patient has symptoms like worsened depression, suicidal thoughts, or changes in behavior. Discuss any questions with the patient's doctor.

Vilazodone is used for:

Treating depression. It may also be used for other conditions as determined by your doctor.

Vilazodone is an antidepressant. It is thought to work by increasing the activity of one of the brain chemicals (serotonin), which helps elevate mood.

Do NOT use Vilazodone if:

• you are allergic to any ingredient in Vilazodone or to nefazodone


• you are taking rasagiline or tryptophan


• you are taking or have taken linezolid, methylene blue, a monoamine oxidase inhibitor (MAOI) (eg, phenelzine), or St. John's wort within the last 14 days

Contact your doctor or health care provider right away if any of these apply to you.

Video: Treatment for Depression

Treatments for depression are getting better everyday and there are things you can start doing right away.

Before using Vilazodone:

Some medical conditions may interact with Vilazodone. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have low blood volume, low blood pressure, or low blood sodium levels; you are dehydrated; or you are on a low-salt (sodium) diet


• if you or a family member has a history of bipolar disorder (manic-depression) or other mental or mood problems (eg, depression), suicidal thoughts or attempts, alcohol or substance abuse, or if you drink alcohol


• if you have a history of liver problems, kidney problems, bleeding problems, or seizures

Some MEDICINES MAY INTERACT with Vilazodone. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Anticoagulants (eg, warfarin), nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, ibuprofen, intranasal ketorolac), or salicylates (eg, aspirin) because the risk of bleeding may be increased


• Antipsychotics (eg, olanzapine, haloperidol), buspirone, fenfluramine or its derivatives (eg, dexfenfluramine), linezolid, MAOIs, (eg, phenelzine), methylene blue, metoclopramide, narcotic (opioid) pain medicines (eg, morphine), phenothiazines (eg, thioridazine), rasagiline, selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine), selegiline, serotonin-norepinephrine reuptake inhibitors (SNRIs) (eg, duloxetine, venlafaxine), sibutramine, St. John's wort, tramadol, "triptans" (eg, sumatriptan), or tryptophan because severe side effects, such as a reaction that may include fever, rigid muscles, blood pressure changes, mental changes, confusion, irritability, agitation, delirium, or coma, may occur


• Diuretics (eg, furosemide, hydrochlorothiazide) because the risk of low blood sodium levels may be increased


• Azole antifungals (eg, itraconazole, ketoconazole), HIV protease inhibitors (eg, indinavir, ritonavir), macrolide antibiotics (eg, clarithromycin, erythromycin), nefazodone, or telithromycin because the risk of Vilazodone's side effects may be increased


• Cyproheptadine because it may decrease Vilazodone's effectiveness


• Lithium because the risk of its side effects may be increased by Vilazodone

This may not be a complete list of all interactions that may occur. Ask your health care provider if Vilazodone may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Vilazodone:

Use Vilazodone as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Vilazodone comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Vilazodone refilled.


• Take Vilazodone by mouth with food.


• When starting Vilazodone, your doctor may slowly increase your dose to avoid side effects. Discuss any questions or concerns with your doctor.


• It may take 1 to 4 weeks for Vilazodone to work. Do not stop taking Vilazodone without checking with your doctor.


• Do not suddenly stop taking Vilazodone. You may have an increased risk of side effects. If you need to stop Vilazodone, your doctor will gradually lower your dose.


• If you miss a dose of Vilazodone, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Vilazodone.

Important safety information:

• Vilazodone may cause drowsiness, dizziness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Vilazodone with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do not drink alcohol while you are using Vilazodone.


• Check with your doctor before you use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Vilazodone; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• Be sure to keep all doctor appointments while you are taking Vilazodone.


• Children, teenagers, and young adults who take Vilazodone may be at increased risk of suicidal thoughts or actions. Watch all patients who take Vilazodone closely. Contact the doctor at once if new, worsened, or sudden symptoms, such as depressed mood; anxious, restless, or irritable behavior; panic attacks; or any unusual change in mood or behavior, occur. Contact the doctor right away if any signs of suicidal thoughts or actions occur.


• Neuroleptic malignant syndrome (NMS) is a possibly fatal syndrome that can be caused by Vilazodone. Symptoms may include fever; stiff muscles; confusion; abnormal thinking; fast or irregular heartbeat; and sweating. Contact your doctor at once if you have any of these symptoms.


• Serotonin syndrome is a possibly fatal syndrome that can be caused by Vilazodone. Your risk may be greater if you take Vilazodone with certain other medicines (eg, "triptans," MAOIs). Symptoms may include agitation; confusion; hallucinations; coma; fever; fast or irregular heartbeat; tremor; excessive sweating; and nausea, vomiting, or diarrhea. Contact your doctor at once if you have any of these symptoms.


• Tell your doctor or dentist that you take Vilazodone before you receive any medical or dental care, emergency care, or surgery.


• Use Vilazodone with caution in the ELDERLY; they may be more sensitive to its effects, especially low blood sodium levels.


• Vilazodone should not be used in CHILDREN or TEENAGERS; safety and effectiveness in children and teenagers have not been confirmed. Children and teenagers may also be more sensitive to its effects, especially the increased risk of suicidal thoughts or actions.


• PREGNANCY and BREAST-FEEDING: Vilazodone may cause harm to the fetus if taken during the third trimester of pregnancy. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Vilazodone while you are pregnant. Vilazodone is found in breast milk. If you are or will be breast-feeding while you take Vilazodone, check with your doctor. Discuss any possible risks to your baby.

Do not suddenly stop taking Vilazodone. If you do, you may have WITHDRAWAL symptoms. These may include feeling unwell or unhappy, anxious or irritable, dizzy, confused, or sluggish. You may also have nausea, unusual skin sensations, mood swings, headache, trouble sleeping, or sweating. If you need to stop Vilazodone, your doctor will lower your dose over time.

Possible side effects of Vilazodone:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Decreased sexual desire or ability; diarrhea; dizziness; drowsiness; dry mouth; nausea; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); behavior changes; black, tarry, or bloody stools; bloody or dark urine; blurred vision; decreased coordination; fainting; hallucinations; irregular heartbeat; new or worsening agitation, anxiety, depression, panic attacks, aggressiveness, impulsiveness, irritability, hostility, exaggerated feeling of well-being, restlessness, trouble sleeping, or inability to sit still; seizures; severe or persistent dizziness; suicidal thoughts or actions; symptoms of low blood sodium levels (eg, confusion, severe or persistent headache, trouble concentrating, memory problems, weakness, unsteadiness, sluggishness); tremor; unusual bruising or bleeding; vomit that looks like coffee grounds.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Vilazodone side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include agitation; confusion; disorientation; excessive sweating; fast or irregular heartbeat; fever; hallucinations; loss of consciousness or coma; nausea, vomiting, or diarrhea; restlessness; tiredness or weakness; tremor.

Proper storage of Vilazodone:

Store Vilazodone at 77 degrees F (25 degrees C) in a tight, light-resistant container. Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Vilazodone out of the reach of children and away from pets.

General information:

• If you have any questions about Vilazodone, please talk with your doctor, pharmacist, or other health care provider.


• Vilazodone is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is summary only. It does not contain all information about Vilazodone. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Vilazodone resources

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

• vilazodone Advanced Consumer (Micromedex) - Includes Dosage Information


• Viibryd Prescribing Information (FDA)


• Viibryd Consumer Overview

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