Telithromycin

Class: Ketolides
VA Class: AM200
Chemical Name: Erythromycin, 3de[(2,6 - dideoxy - 3 - C - methyl - 3 - O - methyl - α - L - ribo - hexopyranosyn)] - 11,12 - dideoxy - 6 - O - methyl - 3 - oxo - 12,11 - [oxy - carbonyl{[4 - [4 - (3 - pyridinyl) - 1H - imidazol - 1 - yl]butyl]imino}]
Molecular Formula: C₄₃H₆₅N₅O₁₀
CAS Number: 173838-31-8
Brands: Ketek

• 
  

  Contraindicated in patients with myasthenia gravis.¹ Fatal or life-threatening acute respiratory failure reported.¹ (See Myasthenia Gravis Patients under Cautions.)

  
  

REMS:

FDA approved a REMS for telithromycin to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antibacterial; ketolide.^{1 14 23}

Uses for Telithromycin

Respiratory Tract Infections

Treatment of mild to moderate community-acquired pneumonia (CAP) caused by susceptible Streptococcus pneumoniae (including multidrug-resistant strains [MDRSP]), Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae (Chlamydia pneumoniae), or Mycoplasma pneumoniae.^{1 2 3 4 5}

Although initially approved by FDA for treatment of acute bacterial exacerbations of chronic bronchitis, acute bacterial sinusitis, and CAP in 2004,³² approval for treatment of acute bacterial exacerbations of chronic bronchitis and acute bacterial sinusitis was withdrawn in 2007 because of safety concerns.³⁴

Telithromycin Dosage and Administration

Administration

Oral Administration

Administer orally once daily without regard to meals.¹

Dosage

Adults

Respiratory Tract Infections

Community-acquired Pneumonia

Oral

800 mg once daily for 7–10 days.¹

Special Populations

Hepatic Impairment

Hepatic impairment: Dosage adjustment not required.^{1 14 15} (See Hepatic Effects under Cautions.)

Hepatic impairment with coexisting severe renal impairment (Cl_cr <30 mL/minute or undergoing hemodialysis): Use reduced dosage of 400 mg once daily.¹ (See Hepatic Effects under Cautions.)

Renal Impairment

Mild to moderate renal impairment: Dosage adjustment not required.^{2 14 16}

Severe renal impairment (Cl_cr <30 mL/minute or undergoing hemodialysis): Use reduced dosage of 600 mg once daily.¹ On dialysis days, administer daily dose after dialysis session.¹

Severe renal impairment (Cl_cr <30 mL/minute or undergoing hemodialysis) with coexisting hepatic impairment: Use reduced dosage of 400 mg once daily.¹ (See Hepatic Effects under Cautions.)

Geriatric Patients

Routine dosage adjustment based on age not required.¹

Cautions for Telithromycin

Contraindications

• 
  

  Myasthenia gravis.¹ (See Myasthenia Gravis Patients under Cautions.)

  
  


• 
  

  Known hypersensitivity to telithromycin, any macrolide, or any ingredient in the formulation.¹

  
  


• 
  

  History of hepatitis and/or jaundice associated with use of telithromycin or any macrolide.¹

  
  


• 
  

  Concomitant use with cisapride or pimozide.¹ (See Specific Drugs and Foods under Interactions.)

  
  

Warnings/Precautions

Warnings

Myasthenia Gravis Patients

Exacerbation of myasthenia gravis reported.^{1 29 30 31} Exacerbations have occurred within a few hours of the first dose and have included rapid-onset, fatal or life-threatening, acute respiratory failure.^{1 29 30 31} (See Contraindications under Cautions.)

Hepatic Effects

Acute hepatic failure and severe liver injury (in some cases fatal) reported.^{1 24} Reactions include fulminant hepatitis and hepatic necrosis requiring liver transplant.¹ Liver injury may progress rapidly and occur after administration of a few doses.¹

Monitor closely for signs and symptoms of hepatic impairment (i.e., fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness, hepatomegaly).¹ Advise patients to immediately discontinue the drug and contact their clinician if they experience signs and symptoms of hepatic injury.¹

Do not reinitiate therapy in patients with a history of telithromycin- or macrolide-associated hepatitis and/or jaundice.¹

Less severe hepatic dysfunction, including increased liver enzyme concentrations and hepatitis (with or without jaundice), reported; events were reversible.^{1 24}

Prolongation of QT Interval

Potential for prolonged QT interval.¹

Avoid use in patients with congenital or known prolongation of the QT_c interval, those with ongoing proarrhythmic conditions (e.g., uncorrected hypokalemia or hypomagnesemia) or clinically important bradycardia, and those receiving class IA (e.g., quinidine, procainamide) or class III (e.g., dofetilide) antiarrhythmic agents.¹

Ocular Effects

Visual disturbances (blurred vision, diplopia, difficulty focusing) reported, particularly slowed ability to accommodate or release accommodation.¹

Visual disturbances usually occur after first or second dose, but can occur after any dose; problems last several hours and may reoccur with subsequent doses.¹

Usually mild to moderate in severity, but may be severe.¹

Reported most frequently in women and patients <40 years of age.¹

Patients should be cautioned to minimize activities such as driving a motor vehicle, operating heavy machinery, or performing other hazardous activities during treatment and to avoid such activities if they experience visual disturbances.¹

Syncope

Syncope, sometimes associated with vagal syndrome, reported during postmarketing surveillance.¹

Patients should be cautioned to minimize activities such as driving a motor vehicle, operating heavy machinery, or performing other hazardous activities during treatment and to avoid such activities if they experience loss of consciousness.¹

Superinfection/Clostridium difficile-associated Diarrhea

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.¹

Treatment with anti-infectives may permit overgrowth of Clostridium difficile.^{1 35 36 37 38 39 40 41 42 43 44 45} C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported in patients receiving telithromycin.¹ Consider CDAD if diarrhea develops and manage accordingly.^{1 35 36 37 38 39 42 43 44}

Some mild cases of CDAD may respond to discontinuance alone.^{1 35 36 37 38 39 43} Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.^{1 35 36 37 38 39 43}

General Precautions

Provide the medication guide for telithromycin to the patient when the drug is dispensed.¹

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of telithromycin and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.¹

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹ In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Distributed into milk in rats; may be distributed into human milk.¹ Use with caution.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹

Has been investigated in children <13 years of age† for treatment of community-acquired pneumonia.¹⁰

Geriatric Use

Safety and efficacy in those ≥65 years of age similar to that in younger adults, but possibility exists of greater sensitivity to the drug in some geriatric individuals.¹

Hepatic Impairment

Contraindicated in patients with a history of telithromycin-associated hepatitis and/or jaundice.¹ (See Hepatic Effects and see Contraindications under Cautions.)

Reduced dosage required in patients with hepatic impairment and coexisting severe renal impairment.¹ (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Reduced dosage required in patients with severe renal impairment (Cl_cr <30 mL/minute or undergoing dialysis).¹ Further dosage reduction required in patients with severe renal impairment and coexisting hepatic impairment.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Diarrhea/loose stools, nausea, vomiting, headache, dizziness.^{1 14}

Interactions for Telithromycin

Induces and is metabolized by CYP3A4.^{1 11}

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A4 with possible alteration in metabolism of telithromycin and/or the other drug.¹

Drugs That Prolong QT Interval

Potential pharmacologic interactions (additive effect on QT interval prolongation).¹ Avoid concomitant use with class 1A or class III antiarrhythmic agents.¹ (See Prolongation of QT Interval under Cautions.)

Specific Drugs and Foods

Drug or Food	Interaction	Comments
β-Adrenergic blocking agents (metoprolol, sotalol)	Metoprolol: Increased metoprolol concentrations and AUC; no change in telithromycin exposure with a single metoprolol dose1 Sotalol: Decreased sotalol peak plasma concentrations and AUC1	Metoprolol: Interaction may be clinically important in patients receiving the drug for heart failure; caution advised in heart failure patients1
Antacids (aluminum- and magnesium-containing)	Pharmacokinetic interactions unlikely1
Antiarrhythmic agents	Potential additive effect on QT interval prolongation1	Avoid concomitant use with class 1A (e.g., quinidine, procainamide) or class III (e.g., dofetilide) antiarrhythmics1
Anticoagulants, oral	Potential for enhanced effect of the oral anticoagulant1 11	Monitor PT or INR1 11
Anticonvulsants	Carbamazepine, phenobarbital, or phenytoin: Potential for decreased telithromycin concentrations and/or increased anticonvulsant concentrations1
Antifungals, azoles	Itraconazole or ketoconazole: Increased telithromycin peak plasma concentrations and AUC 1
Antimycobacterials	Rifampin: Decreased telithromycin peak plasma concentrations and AUC1	Rifampin: Avoid concomitant use1
Benzodiazepines (midazolam, triazolam)	Midazolam: Increased midazolam AUC1 Possible pharmacokinetic interactions with other benzodiazepines metabolized by CYP3A and undergoing high first-pass metabolism (e.g., triazolam)1	Midazolam: Monitor patient; consider decreasing midazolam dosage or avoiding concomitant use1 12 Other benzodiazepines (e.g., triazolam): Use concomitantly with caution
Cisapride	Increased cisapride concentrations; increases in QTc interval1	Concomitant use contraindicated1
Digoxin	Increased digoxin concentrations; no evidence of clinically important changes in ECG parameters or digoxin toxicity1	Consider monitoring digoxin concentrations or toxicity1
Ergot alkaloids (dihydroergotamine, ergotamine)	Possible pharmacokinetic interactions; potential for peripheral vasospasm, dysesthesia, acute ergot toxicity1 12	Concomitant use not recommended1
Grapefruit juice	Pharmacokinetic interactions unlikely with 240 mL of juice1
HMG-CoA reductase inhibitors	Possible increased concentrations of atorvastatin, lovastatin, or simvastatin; increased risk of myopathy1 Pharmacokinetic interactions unlikely with fluvastatin or pravastatin1	Avoid concomitant use with atorvastatin, lovastatin, or simvastatin; temporarily suspend therapy with these HMG-CoA reductase inhibitors during telithromycin therapy1
Hormonal contraceptives	Increased levonorgestrel AUC; no change in ethinyl estradiol AUC	No interference with the antiovulatory effect of the oral contraceptive1
Immunosuppressive agents	Potential for increased concentrations of cyclosporine, sirolimus, or tacrolimus1
Paroxetine	Pharmacokinetic interactions unlikely1
Pimozide	Possible increased pimozide concentrations1	Concomitant use contraindicated1
Ranitidine	Pharmacokinetic interactions unlikely1
Repaglinide	Increased plasma concentrations and AUC of repaglinide; increased risk of hypoglycemia26	Consider increased risk of hypoglycemia26
Theophylline	Small increase in theophylline AUC; increased GI effects (nausea, vomiting), especially in women1	Administer telithromycin and theophylline at least 1 hour apart to minimize GI effects1

Telithromycin Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration; peak plasma concentrations usually attained within 1 hour.¹

Absolute bioavailability is 57%.¹

Steady-state plasma concentrations attained within 2–3 days with once-daily dosing.¹

Food

Does not affect rate or extent of absorption.^{1 13 14}

Special Populations

Mild to hepatic impairment (Child-Pugh class A, B, or C): Peak plasma concentrations and AUC similar to those in age- and sex-matched healthy individuals.^{1 15}

Severe renal impairment (Cl_cr <30 mL/minute): Increased peak plasma concentrations and AUC.^{1 16}

Geriatric patients ≥65 years of age: AUC 1–2 times higher than in younger adults.¹

Distribution

Extent

Distributed into bronchial mucosa, epithelial lining fluid, alveolar macrophages, sinus tissue, and WBCs.^{1 10}

Plasma Protein Binding

Approximately 60–70% (mainly albumin).¹

Special Populations

Protein binding not altered in geriatric individuals or in those with hepatic impairment.¹

Elimination

Metabolism

70% (33% presystemic and 37% systemic) of a dose metabolized to 1 active metabolite and 3 inactive metabolites.^{1 13 14}

Approximately 50% of metabolism mediated by CYP3A4; remaining 50% does not depend on CYP isoenzymes.^{1 13}

Elimination Route

Eliminated by multiple pathways: 7% eliminated unchanged in feces by biliary and/or intestinal secretion and 13% eliminated unchanged in urine by renal excretion.^{1 10 12 13 14}

Half-life

10 hours.¹

Special Populations

Mild to severe hepatic impairment (Child-Pugh class A, B, or C): Half-life similar to that in age- and sex-matched healthy individuals.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

Actions

• 
  

  A ketolide antibiotic.^{1 2 12 13 14} Semisynthetic derivative of erythromycin A, but differs structurally from conventional macrolides.¹⁰

  
  


• 
  

  May be bacteriostatic or bactericidal.¹⁴

  
  


• 
  

  Like conventional macrolide antibacterials, inhibits protein synthesis in susceptible organisms by binding to 50S ribosomal subunit.^{1 12 13 14 17} Has higher affinity for some ribosomal targets than conventional macrolides.^{1 10 12 13 17}

  
  


• 
  

  Gram-positive aerobes: Active in vitro and in clinical infections against Streptococcus pneumoniae (including many multidrug-resistant strains [MDRSP]).^{1 14 18 19 21 22} Also active in vitro against Staphylococcus aureus (oxacillin- and erythromycin-susceptible strains),^{1 14 18} S. pyogenes (group A β-hemolytic streptococci),^{1 14 18 21} S. agalactiae (group B streptococci),¹⁴ and groups C and G streptococci.^{1 14}

  
  


• 
  

  Gram-negative aerobes: Active in vitro and in clinical infections against Haemophilus influenzae ^{1 14 18} and Moraxella catarrhalis.^{1 14 18}

  
  


• 
  

  Other organisms: Active in vitro and in clinical infections against Chlamydophila pneumoniae(Chlamydia pneumoniae)^{1 14 20} and Mycoplasma pneumoniae.^{1 14} Also active against Legionella pneumophila.¹

  
  


• 
  

  Active against some S. pneumoniae resistant to penicillin and/or erythromycin,¹⁸ but S. pneumoniae with reduced susceptibility or resistance to telithromycin have been reported rarely.^{18 46 47}

  
  


• 
  

  Some, but not all, erythromycin-resistant S. pyogenes may be susceptible to telithromycin.^{14 18 21} S. aureus resistant to erythromycin usually also resistant to telithromycin.¹⁴

  
  

Advice to Patients

• 
  

  Advise patients that antibacterials (including telithromycin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).¹

  
  


• 
  

  Importance of completing full course of therapy, even if feeling better after a few days.¹ Importance of reporting resistant or worsening symptoms of infections.¹

  
  


• 
  

  Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with telithromycin or other antibacterials in the future.¹

  
  


• 
  

  Importance of reading the medication guide for telithromycin that is provided to the patient when the drug is dispensed.¹

  
  


• 
  

  Risk of visual disturbances (blurred vision, difficulty focusing, double vision), especially when looking quickly between objects close by and objects far away.¹ Advise patients that avoiding quick changes in viewing between distant and close objects may decrease the effects of these visual difficulties.¹

  
  


• 
  

  Risk of loss of consciousness.¹

  
  


• 
  

  Because of the potential for visual disturbances or loss of consciousness, advise patients to minimize activities such as driving a motor vehicle, operating heavy machines, or performing other hazardous activities.¹ Advise patients experiencing visual difficulties or loss of consciousness to contact their clinician before taking another dose of telithromycin.¹ Advise patients experiencing these symptoms to avoid driving a motor vehicle, operating heavy machines, or engaging in other hazardous activities.¹

  
  


• 
  

  Importance of informing clinicians if they have myasthenia gravis.¹ Telithromycin is contraindicated in patients with myasthenia gravis.¹

  
  


• 
  

  Risk of adverse hepatic effects.¹ Advise patients to immediately discontinue telithromycin and seek medical attention if they experience signs or symptoms of hepatic injury (e.g., nausea, fatigue, anorexia, jaundice, dark urine, light-colored stools, pruritus, tender abdomen).¹ Importance of not reinitiating telithromycin in patients who have experienced hepatitis or jaundice while receiving the drug.¹

  
  


• 
  

  Importance of informing clinician if they have a personal or family history of prolongation of the QT_c interval, proarrhythmic conditions (e.g., uncorrected hypokalemia), or clinically important bradycardia.¹

  
  


• 
  

  Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.¹ Especially important to report use of drugs that affect the QT interval (e.g., cisapride, pimozide), antiarrhythmic agents (class IA and III), and/or some HMG-CoA reductase inhibitors (i.e., atorvastatin, lovastatin, simvastatin).¹

  
  


• 
  

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

Telithromycin

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	300 mg	Ketek (with povidone)	Sanofi-Aventis
		400 mg	Ketek (with povidone; available in Ketek-Pak 5-day mnemonic blister cards of 10 tablets, regular packaging, and unit-dose blister packages)	Sanofi-Aventis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Ketek 400MG Tablets (SANOFI-AVENTIS U.S.): 60/$311.99 or 180/$899.99

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 October 27, 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. Sanofi-Aventis. Ketek (telithromycin) tablets prescribing information. Bridgewater, NJ; 2007 Feb.

2. Tellier G, Niederman MS, Nusrat R et al. Clinical and bacteriological efficacy and safety of 5 and 7 day regimens of telithromycin once daily compared with a 10 day regimen of clarithromycin twice daily in patients with mild to moderate community-acquired pneumonia. J Antimicrob Chemother. 2004; 54:515-23. [IDIS 523620] [PubMed 15269191]

3. Dunbar LM, Hassman J, Tellier G. Efficacy and tolerability of once-daily oral telithromycin compared with clarithromycin for the treatment of community-acquired pneumonia in adults. Clin Ther. 2004; 26:48-62. [PubMed 14996517]

4. Pullman J, Champlin J, Vrooman PS Jr. Efficacy and tolerability of once-daily oral therapy with telithromycin compared with trovafloxacin for the treatment of community-acquired pneumonia in adults. Int J Clin Pract. 2003; 57:377-84. [IDIS 499736] [PubMed 12846341]

5. Hagberg L, Torres A, van Rensburg D et al. Efficacy and tolerability of once-daily telithromycin compared with high-dose amoxicillin for treatment of community-acquired pneumonia. Infection. 2002; 30:378-86. [PubMed 12478329]

6. Zervos MJ, Heyder AM, Leroy B. Oral telithromycin 800 mg once daily for 5 days versus cefuroxime axetil 500 mg twice daily for 10 days in adults with acute exacerbations of chronic bronchitis. J Int Med Res. 2003; 31:157-69. [IDIS 517304] [PubMed 12870368]

7. Aubier M, Aldons PM, Leak A et al. Telithromycin is as effective as amoxicillin/clavulanate in acute exacerbations of chronic bronchitis. Respir Med. 2002; 96:862-71. [IDIS 517306] [PubMed 12418583]

8. Luterman M, Tellier G, Lasko B et al. Efficacy and tolerability of telithromycin for 5 or 10 days vs amoxicillin/clavulanic acid for 10 days in acute maxillary sinusitis. Ear Nose Throat J. 2003; 82:576-90. [IDIS 517305] [PubMed 14503094]

9. Buchanan PP, Stephens TA, Leroy B. A comparison of the efficacy of telithromycin versus cefuroxime axetil in the treatment of acute bacterial maxillary sinusitis. Am J Rhinol. 2003; 17:369-77. [IDIS 517307] [PubMed 14750614]

10. Aventis. American Hospital Formulary Service Fact Book: Ketek. 2004 Aug.

11. Kolilekas L, Anagnostopoulos GK, Lampaditis I, Eleftheriadis I. Potential interaction between telithromycin and warfarin. Ann Pharmacother. 2004: 38:1424-7.

12. Anon. Telithromycin (Ketek) for respiratory infections. Med Lett Drugs Ther. 2004; 46:66-8. [PubMed 15314586]

13. Wellington K, Noble S. Telithromycin. Drugs. 2004; 64:1683-94. [PubMed 15257629]

14. Zhanel GG, Walters M, Noreddin A et al. The ketolides: a critical review. Drugs. 2002; 62:1771-804. [PubMed 12149046]

15. Cantalloube C, Bhargava V, Sultan E et al. Pharmacokinetics of the ketolide telithromycin after single and repeated doses in patients with hepatic impairment. Int J Antimicrob Agents. 2003; 22:112-21. [IDIS 517308] [PubMed 12927950]

16. Shi J, Montay G, Chapel S et al. Pharmacokinetics and safety of the ketolide telithromycin in patients with renal impairment. J Clin Pharmacol. 2004; 44:234-4. [IDIS 512832] [PubMed 14973302]

17. Berisio R, Harms J, Schluenzen F et al. Structural insight into the antibiotic action of telithromycin against resistant mutants. J Bacteriol. 2003;185:4276-9.

18. Dohar J, Canton R, Cohen R et al. Activity of telithromycin and comparators against bacterial pathogens isolated from 1,336 patient with clinically diagnosed acute sinusitis. Ann Clin Microbiol Antimicrob. 2004;3:1476-07.

19. Powis J, McGeer A, Green K et al. In vitro antimicrobial susceptibilities of Streptococcus pneumoniae clinical isolates obtained in Canada in 2002. Antimicrob Agents Chemother. 2004;48:3305-11.

20. Miyashita N, Fukano H, Niki Y et al. In vitro activity of telithromycin, a new ketolide, against Chlamydia pneumoniae. J Antimicrob Chemother. 2001;48:403-5.

21. Reinert RR, Lutticken R, Bryskier A et al. Macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes in the pediatric population in Germany during 2000–2001. Antimicrob Agents Chemother. 2003;47:489-93.

22. Brown SD, Tybak MJ. Antimicrobial susceptibility of Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae collected from patients across the USA, in 2001-2002, as part of the PROTEKT US study. J Antimicrob Chemother. 2004;54 (Suppl 1):17-115.

23. Adventis Pharmaceuticals, Bridgewater, N: Personal communication.

24. Clay KD, Hanson JS, Pope SD et al. Brief communication: severe hepatotoxicity of telithromycin: three case reports and literature review. Ann Intern Med. 2006; 144:415-20. [PubMed 16481451]

25. Nenciu LM, Laberge P, Thirion DJ. Telithromycin-induced digoxin toxicity and electrocardiographic changes. Pharmacotherapy. 2006; 26:872-6. [PubMed 16716140]

26. Kajosaari LI, Niemi M, Backman JT et al. Telithromycin, but not montelukast, increases the plasma concentrations and effects of the cytochrome P450 3A4 and 2C8 substrate repaglinide. Clin Pharmacol Ther. 2006; 79:231-42. [PubMed 16513447]

27. Young D. Panel urges black-box warning for Ketek. From the American Society of Health-System Pharmacists website (.).

28. Department of Health and Human Services, Food and Drug Administration. Joint meeting of the anti-infective drugs advisory committee and the drug safety and risk management advisory committee: notice of meeting. Fed Regist. 2006; 71:66545.

29. Perrot X, Bernard N, Vial C et al. Myasthenia gravis exacerbation or unmasking associated with telithromycin treatment. Neurology. 2006; 67:2256-8. [PubMed 17065592]

30. Nieman RB, Sharma K, Edelberg H, Caffe SE. Telithromycin and myasthenia gravis. Clin Infect Dis. 2003; 37:1579. Letter. [PubMed 14614683]

31. Jennett AM, Bali D, Jasti P et al. Telithromycin and myasthenia crisis. Clin Infect Dis. 2006; 43:1621-2. Letter. [PubMed 17109301]

32. Aventis. Ketek (telithromycin) tablets prescribing information. Kansas City, MO; 2004.

33. Mandell LA, Wunderink RG, Anzueto A et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on management of community-acquired pneumonia in adults. Clin Infect Dis. 2007; 44 (suppl 2):S27-72. [PubMed 17278083]

34. Food and Drug Administration. Telithromycin (marketed as Ketek) information. 2007 Feb 12. from FDA website (.

35. Johnson S, Gerding DN. Clostridium difficile-associated diarrhea. Clin Infect Dis. 1998; 26:1027-36. [IDIS 407733] [PubMed 9597221]

36. Gerding DN, Johnson S, Peterson LR et al for the Society for Healthcare Epidemiology of America. Position paper on Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol. 1995; 16:459-77. [PubMed 7594392]

37. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. Am J Gastroenterol. 1997; 92:739-50. [IDIS 386628] [PubMed 9149180]

38. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease. Am J Health-Syst Pharm. 1998; 55:1407-11. [IDIS 407213] [PubMed 9659970]

39. Wilcox MH. Treatment of Clostridium difficile infection. J Antimicrob Chemother. 1998; 41(Suppl C):41-6. [IDIS 407246] [PubMed 9630373]

40. McDonald LC, Killgore GE, Thompson A et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005; 353:2433-41. [PubMed 16322603]

41. Loo VG, Poirier L, Miller MA et al. A predominantly clonal multi-institutional outbreak of Clostricium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005; 353:2442-9. [PubMed 16322602]

42. McDonald LC, Owings M, Jernigan DB. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis. 2006; 12:409-15. [PubMed 16704777]

43. Bartlett JG, Peri TM. The new Clostridium difficile–what does it mean? N Engl J Med. 2005; 353:2503-5.

44. Centers for Disease Control and Prevention. Severe Clostridium difficile-associated disease in populations previously at low risk–four states, 2005. MMWR Morb Mortal Wkly Rep. 2005; 54:1201-5. [PubMed 16319813]

45. Kazakova SV, Ware K, Baughman B et al. A hospital outbreak of diarrhea due to an emerging epidemic strains of Clostridium difficile. Arch Intern Med. 2006; 166:2518-24. [PubMed 17159019]

46. Al-Lahham A, Appelbaum PC, van der Linden M et al. Telithromycin-nonsusceptible clinical isolates of Streptococcus pneumoniae from Europe. Antimicrob Agents Chemother. 2006; 50:3897-900.

47. Wolter N, Smith AM, Low DE et al. High-level telithromycin resistance in a clinical isolate of Streptococcus pneumoniae. Antimicrob Agents Chemother. 2007; 51:1092-5. [PubMed 17210764]

More Telithromycin resources

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

• Telithromycin MedFacts Consumer Leaflet (Wolters Kluwer)


• Telithromycin Professional Patient Advice (Wolters Kluwer)


• telithromycin Advanced Consumer (Micromedex) - Includes Dosage Information


• Ketek Prescribing Information (FDA)


• Ketek Consumer Overview

Compare Telithromycin with other medications

• Bronchitis
• Pneumonia
• Sinusitis
• Tonsillitis/Pharyngitis

chlorpheniramine and codeine

Generic Name: chlorpheniramine and codeine (KLOR fen IR a meed and KOE deen)

Brand names: Cotab A, Cotab AX, Notuss-AC, Z-Tuss AC, Zodryl AC 25, Zodryl AC 30, Zodryl AC 35, Zodryl AC 40, Zodryl AC 50, Zodryl AC 60, Zodryl AC 80, Codeprex, Endacof-C, TL-Hist CM, Zodryl AC Adult, Codar AR

What is chlorpheniramine and codeine?

Chlorpheniramine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Codeine is a narcotic cough suppressant. It affects the signals in the brain that trigger cough reflex.

The combination of chlorpheniramine and codeine is used to treat runny or stuffy nose, sneezing, watery eyes, and cough caused by allergies or the common cold.

Chlorpheniramine and codeine will not treat a cough that is caused by smoking, asthma, or emphysema.

Chlorpheniramine and codeine may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about chlorpheniramine and codeine?

Do not take a cough and cold if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take a cough and cold medicine before the MAO inhibitor has cleared from your body. You should not take this medication if you are allergic to chlorpheniramine or codeine, or if you have severe high blood pressure or coronary artery disease, ischemic heart disease, a stomach ulcer, narrow-angle glaucoma, if you are having an asthma attack, if you are pregnant or breast-feeding, or if you are unable to urinate.

Before taking this medication, tell your doctor if you have asthma or other breathing disorder, glaucoma, heart disease, high blood pressure, seizures, a thyroid disorder, diabetes, urination problems, stomach problems, liver or kidney disease, Addison's disease, mental illness, or a history of drug or alcohol addiction.

Codeine may be habit-forming and should be used only by the person it was prescribed for. This medication should never be shared with another person, especially someone who has a history of drug abuse or addiction. Keep the medication in a secure place where others cannot get to it. Do not give this medicine to a child younger than 6 years old.

What should I discuss with my healthcare provider before taking chlorpheniramine and codeine?

Do not take a cough and cold if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take a cough and cold medicine before the MAO inhibitor has cleared from your body. You should not take this medication if you are allergic to chlorpheniramine or codeine, or if you have:

• 
  

  severe or uncontrolled high blood pressure;

  
  


• 
  

  severe coronary artery disease;

  
  


• 
  

  ischemic heart disease;

  
  


• 
  

  a stomach ulcer;

  
  


• 
  

  narrow-angle glaucoma;

  
  


• 
  

  if you are having an asthma attack;

  
  


• 
  

  if you are unable to urinate; or

  
  


• 
  

  if you are pregnant or breast-feeding.

  
  

If you have any of these other conditions, you may need a dose adjustment or special tests to safely use this medication:

• 
  

  asthma, COPD, emphysema, or other breathing disorder;

  
  


• 
  

  glaucoma;

  
  


• 
  

  heart disease, high blood pressure;

  
  


• 
  

  a history of head injury or brain tumor;

  
  


• 
  

  epilepsy or other seizure disorder;

  
  


• 
  

  a thyroid disorder;

  
  


• 
  

  diabetes;

  
  


• 
  

  enlarged prostate or urination problems;

  
  


• 
  

  stomach or intestinal problems;

  
  


• liver or kidney disease;


• 
  

  Addison's disease;

  
  


• 
  

  mental illness; or

  
  


• 
  

  a history of drug or alcohol addiction.

  
  

FDA pregnancy category C. It is not known whether chlorpheniramine and codeine is harmful to an unborn baby. Codeine can cause breathing problems or addiction/withdrawal symptoms in a newborn. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Codeine can pass into breast milk and may harm a nursing baby. The use of codeine by some nursing mothers may lead to life-threatening side effects in the baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Older adults are more likely to have side effects from this medicine.

Do not give chlorpheniramine and codeine to a child younger than 6 years old. Codeine may be habit-forming and should be used only by the person it was prescribed for. This medication should never be shared with another person, especially someone who has a history of drug abuse or addiction. Keep the medication in a secure place where others cannot get to it.

How should I take chlorpheniramine and codeine?

Take this medication exactly as prescribed by your doctor. Do not take it in larger amounts or for longer than recommended. Follow the directions on your prescription label.

Do not take this medication more often than you doctor has prescribed. An overdose of chlorpheniramine and codeine can cause life-threatening side effects. Take chlorpheniramine and codeine with a full glass of water.

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

Chlorpheniramine and codeine can be taken with food if it upsets your stomach.

Call your doctor if your symptoms do not improve after 7 days of treatment, or if you also have a fever, headache, or skin rash.

Store chlorpheniramine and codeine at room temperature away from moisture and heat. Keep track of how much of this medicine has been used from each new bottle. Codeine is a drug of abuse and you should be aware if any person in the household is using this medicine improperly or without a prescription.

See also: Chlorpheniramine and codeine dosage (in more detail)

What happens if I miss a dose?

Cough or cold medicine is usually taken only as needed, so you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at your next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. An overdose of chlorpheniramine and codeine can be fatal, especially to a child.

Overdose symptoms may include feeling restless or nervous, sleep problems, extreme drowsiness, weak or limp feeling, confusion, hallucinations, chest pain, shortness of breath, uneven heartbeats, pinpoint pupils, cold and clammy skin, fainting, seizure (convulsions), weak pulse, shallow breathing, or breathing that stops.

What should I avoid while taking chlorpheniramine and codeine?

This medication can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Avoid drinking alcohol while using chlorpheniramine and codeine. Alcohol may increase drowsiness and dizziness.

Chlorpheniramine and codeine 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:

• 
  

  weak or shallow breathing;

  
  


• 
  

  chest tightness, fast heart rate;

  
  


• 
  

  painful urination;

  
  


• 
  

  urinating less than usual or not at all; or

  
  


• 
  

  confusion, hallucinations, or unusual behavior.

  
  

Less serious side effects may include:

• 
  

  feeling restless or excited (especially in children);

  
  


• 
  

  dizziness, drowsiness, loss of coordination;

  
  


• 
  

  ringing in your ears;

  
  


• 
  

  constipation or diarrhea;

  
  


• 
  

  nausea, vomiting, loss of appetite;

  
  


• 
  

  dry mouth, nose, or throat; or

  
  


• 
  

  mild itching or skin rash.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Chlorpheniramine and codeine Dosing Information

Usual Adult Dose for Allergic Rhinitis:

Chlorpheniramine-codeine 2 mg-10 mg/5 mL oral liquid:
5 to 10 mL orally every 4 to 6 hours not to exceed 40 mL daily.

Chlorpheniramine-codeine 2 mg-9 mg/5 mL oral liquid, or
Chlorpheniramine-codeine 2 mg-8 mg/5 mL oral liquid:
10 mL orally every 4 to 6 hours not to exceed 60 mL daily.

Chlorpheniramine-codeine 4 mg-10 mg oral tablet:
1 tablet orally every 4 to 6 hours not to exceed 6 tablets daily.

Chlorpheniramine-codeine 4 mg-15 mg/15 mL oral suspension:
15 mL orally every 4 to 6 hours not to exceed 6 doses daily.

Chlorpheniramine-codeine 4 mg-20 mg/5 mL:
10 mL orally every 12 hours not to exceed 2 doses daily.

Chlorpheniramine-codeine 4 mg-20 mg oral tablet:
1 tablet orally every 4 to 6 hours not to exceed 6 tablets daily.

Usual Adult Dose for Cough and Nasal Congestion:

Chlorpheniramine-codeine 2 mg-10 mg/5 mL oral liquid:
5 to 10 mL orally every 4 to 6 hours not to exceed 40 mL daily.

Chlorpheniramine-codeine 2 mg-9 mg/5 mL oral liquid, or
Chlorpheniramine-codeine 2 mg-8 mg/5 mL oral liquid:
10 mL orally every 4 to 6 hours not to exceed 60 mL daily.

Chlorpheniramine-codeine 4 mg-10 mg oral tablet:
1 tablet orally every 4 to 6 hours not to exceed 6 tablets daily.

Chlorpheniramine-codeine 4 mg-15 mg/15 mL oral suspension:
15 mL orally every 4 to 6 hours not to exceed 6 doses daily.

Chlorpheniramine-codeine 4 mg-20 mg/5 mL:
10 mL orally every 12 hours not to exceed 2 doses daily.

Chlorpheniramine-codeine 4 mg-20 mg oral tablet:
1 tablet orally every 4 to 6 hours not to exceed 6 tablets daily.

Usual Pediatric Dose for Allergic Rhinitis:

Chlorpheniramine-codeine 2 mg-10 mg/5 mL oral liquid:
6 to 11 years: 2.5 to 5 mL orally every 4 to 6 hours not to exceed 20 mL daily.
12 years or older: 5 to 10 mL orally every 4 to 6 hours not to exceed 40 mL daily.

Chlorpheniramine-codeine 2 mg-9 mg/5 mL oral liquid:
6 to 11 years: 5 mL orally every 4 to 6 hours not to exceed 30 mL daily.
12 years or older: 10 mL orally every 4 to 6 hours not to exceed 60 mL daily.

Chlorpheniramine-codeine 4 mg-10 mg oral tablet:
6 to 11 years: 1/2 tablet orally every 4 to 6 hours not to exceed 3 tablets daily.
12 years or older: 1 tablet orally every 4 to 6 hours not to exceed 6 tablets daily.

Chlorpheniramine-codeine 4 mg-15 mg/15 mL oral suspension:
12 years or older: 15 mL orally every 4 to 6 hours not to exceed 6 doses daily.

Chlorpheniramine-codeine 4 mg-20 mg/5 mL:
6 to 11 years: 5 mL orally every 12 hours not to exceed 2 doses daily.
12 years or older: 10 mL orally every 12 hours not to exceed 2 doses daily.

Chlorpheniramine-codeine 4 mg-20 mg oral tablet:
6 to 11 years: 1/2 tablet orally every 4 to 6 hours not to exceed 3 tablets daily
12 years or older:1 tablet orally every 4 to 6 hours not to exceed 6 tablets daily.

chlorpheniramine-codeine 1 mg-3 mg/3 mL oral suspension (AC 25):
2 to 5 years and 23 to 28 pounds:
3 mL orally every 4 to 6 hours not to exceed 12 mL in 24 hours.

chlorpheniramine-codeine 1 mg-3.5 mg/3.5 mL oral suspension(AC 30)
2 to 5 years and 29 to 32 pounds:
3.5 mL orally every 4 to 6 hours not to exceed 14 mL in 24 hours.

chlorpheniramine-codeine 1 mg-4 mg/4 mL oral suspension (AC 35)
2 to 5 years and 33 to 36 pounds:
4 mL orally every 4 to 6 hours not to exceed 16 mL in 24 hours.

chlorpheniramine-codeine 1 mg-4.5 mg/4.5 mL oral suspension (AC 40)
2 to 5 years and 37 to 41 pounds:
4.5 mL orally every 4 to 6 hours not to exceed 18 mL in 24 hours.

chlorpheniramine-codeine 2 mg-5 mg/5 mL oral suspension (AC 50):
6 to 11 years and 42 to 55 pounds:
5 mL orally every 4 to 6 hours not to exceed 30 mL in 24 hours.

chlorpheniramine-codeine 2 mg-7.5 mg/7.5 mL oral suspension (AC 60)
6 to 11 years and 56 to 69 pounds:
7.5 mL orally every 4 to 6 hours not to exceed 45 mL in 24 hours.

chlorpheniramine-codeine 2 mg-10 mg/10 mL oral suspension (AC 80)
6 to 11 years and 70 to 87 pounds:
10 mL orally every 4 to 6 hours not to exceed 60 mL in 24 hours.

chlorpheniramine-codeine 2 mg-10 mg/10 mL oral suspension (AC Adult)
12 years and older:
15 mL orally every 4 to 6 hours not to exceed 90 mL in 24 hours.

Usual Pediatric Dose for Cough and Nasal Congestion:

Chlorpheniramine-codeine 2 mg-10 mg/5 mL oral liquid:
6 to 11 years: 2.5 to 5 mL orally every 4 to 6 hours not to exceed 20 mL daily.
12 years or older: 5 to 10 mL orally every 4 to 6 hours not to exceed 40 mL daily.

Chlorpheniramine-codeine 2 mg-9 mg/5 mL oral liquid:
6 to 11 years: 5 mL orally every 4 to 6 hours not to exceed 30 mL daily.
12 years or older: 10 mL orally every 4 to 6 hours not to exceed 60 mL daily.

Chlorpheniramine-codeine 4 mg-10 mg oral tablet:
6 to 11 years: 1/2 tablet orally every 4 to 6 hours not to exceed 3 tablets daily.
12 years or older: 1 tablet orally every 4 to 6 hours not to exceed 6 tablets daily.

Chlorpheniramine-codeine 4 mg-15 mg/15 mL oral suspension:
12 years or older: 15 mL orally every 4 to 6 hours not to exceed 6 doses daily.

Chlorpheniramine-codeine 4 mg-20 mg/5 mL:
6 to 11 years: 5 mL orally every 12 hours not to exceed 2 doses daily.
12 years or older: 10 mL orally every 12 hours not to exceed 2 doses daily.

Chlorpheniramine-codeine 4 mg-20 mg oral tablet:
6 to 11 years: 1/2 tablet orally every 4 to 6 hours not to exceed 3 tablets daily
12 years or older:1 tablet orally every 4 to 6 hours not to exceed 6 tablets daily.

chlorpheniramine-codeine 1 mg-3 mg/3 mL oral suspension (AC 25):
2 to 5 years and 23 to 28 pounds:
3 mL orally every 4 to 6 hours not to exceed 12 mL in 24 hours.

chlorpheniramine-codeine 1 mg-3.5 mg/3.5 mL oral suspension(AC 30)
2 to 5 years and 29 to 32 pounds:
3.5 mL orally every 4 to 6 hours not to exceed 14 mL in 24 hours.

chlorpheniramine-codeine 1 mg-4 mg/4 mL oral suspension (AC 35)
2 to 5 years and 33 to 36 pounds:
4 mL orally every 4 to 6 hours not to exceed 16 mL in 24 hours.

chlorpheniramine-codeine 1 mg-4.5 mg/4.5 mL oral suspension (AC 40)
2 to 5 years and 37 to 41 pounds:
4.5 mL orally every 4 to 6 hours not to exceed 18 mL in 24 hours.

chlorpheniramine-codeine 2 mg-5 mg/5 mL oral suspension (AC 50):
6 to 11 years and 42 to 55 pounds:
5 mL orally every 4 to 6 hours not to exceed 30 mL in 24 hours.

chlorpheniramine-codeine 2 mg-7.5 mg/7.5 mL oral suspension (AC 60)
6 to 11 years and 56 to 69 pounds:
7.5 mL orally every 4 to 6 hours not to exceed 45 mL in 24 hours.

chlorpheniramine-codeine 2 mg-10 mg/10 mL oral suspension (AC 80)
6 to 11 years and 70 to 87 pounds:
10 mL orally every 4 to 6 hours not to exceed 60 mL in 24 hours.

chlorpheniramine-codeine 2 mg-10 mg/10 mL oral suspension (AC Adult)
12 years and older:
15 mL orally every 4 to 6 hours not to exceed 90 mL in 24 hours.

What other drugs will affect chlorpheniramine and codeine?

Narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by chlorpheniramine and codeine. Tell your doctor if you regularly use any of these medicines, or any other cold or allergy medicine.

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

• 
  

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

  
  


• 
  

  bronchodilators such as ipratroprium (Atrovent) or tiotropium (Spiriva);

  
  


• 
  

  glycopyrrolate (Robinul);

  
  


• 
  

  mepenzolate (Cantil);

  
  


• 
  

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

  
  


• 
  

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

  
  


• 
  

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

  
  

This list is not complete and there may be other drugs that can interact with chlorpheniramine and codeine. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More chlorpheniramine and codeine resources

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

Compare chlorpheniramine and codeine with other medications

• Cough and Nasal Congestion
• Hay Fever

Where can I get more information?

• Your pharmacist can provide more information about chlorpheniramine and codeine.

See also: chlorpheniramine and codeine side effects (in more detail)

Fusilev

Generic Name: levoleucovorin (Intravenous route)

lee-voe-loo-koe-VOE-rin

Commonly used brand name(s)

In the U.S.

• Fusilev

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Methotrexate Rescue

Uses For Fusilev

Levoleucovorin injection is used as an antidote to the harmful effects of methotrexate (a cancer medicine) that is given in high doses in patients with bone cancer (osteosarcoma). It is also used to treat overdosage of certain medicines. This medicine acts the same way in the body as folic acid (vitamin B9).

Levoleucovorin injection is also used in combination with 5-fluorouracil (Adrucil®) to relieve and prevent symptoms of patients with advanced metastatic (cancer that has already spread) cancer of the colon and rectum.

This medicine is to be given only by or under the direct supervision of a doctor.

Before Using Fusilev

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of levoleucovorin injection in children younger than 6 years of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies on the relationship of age to the effects of levoleucovorin injection have not been performed in geriatric patients with bone cancer. However, no geriatric-specific problems have been documented to date.

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of Fusilev® in elderly patients with advanced colorectal cancer.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Capecitabine


• Fluorouracil

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Ascites (fluid in the stomach) or


• Dehydration or


• Kidney disease, severe or


• Pleural effusion (fluid around the lungs)—Levels of methotrexate may be increased because of its slower removal from the body. The dose of levoleucovorin may not be enough to block the unwanted effects of methotrexate.

• Blood problems (e.g., anemia caused by lack of vitamin B12)—Should not be used in patients with these conditions.

Proper Use of Fusilev

A nurse or other trained health professional will give you this medicine. This medicine is given through a needle placed in one of your veins.

Precautions While Using Fusilev

It is very important that your doctor check your closely to make sure that this medicine is working properly. Blood and urine tests will be needed to check for unwanted effects.

Do not take other medicines unless they have been discussed with your doctor. This includes 5-fluorouracil (Adrucil®) and combination of trimethoprim and sulfamethoxazole (Bactrim®, Septra®). Using any of these medicines together with levoleucovorin increases your risk of serious side effects. .

Fusilev Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

More common

• Cloudy urine


• decrease in urine output or decrease in urine-concentrating ability


• difficult or labored breathing


• fever


• general feeling of discomfort or illness


• lack or loss of strength


• shortness of breath


• stomach cramps, tenderness, or pain


• tightness in the chest


• unusual tiredness or weakness


• watery or bloody diarrhea


• wheezing

Incidence not known

• Feeling unusually cold


• shivering

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Acid or sour stomach


• bad, unusual, or unpleasant (after) taste


• belching


• blistering, crusting, irritation, itching, reddening, or swelling of the skin


• burning, tingling, numbness, or pain in the hands, arms, feet, or legs


• change in taste


• cracked, dry, or scaly skin


• decreased appetite


• diarrhea


• hair loss or thinning of the hair


• heartburn


• indigestion


• loss of appetite


• mood or mental changes


• nausea


• sensation of pins and needles


• stabbing pain


• stomach discomfort or upset


• swelling or inflammation of the mouth


• vomiting


• weight loss

Incidence not known

• Rash

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Fusilev side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Fusilev resources

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

• Fusilev Prescribing Information (FDA)


• Fusilev MedFacts Consumer Leaflet (Wolters Kluwer)


• Fusilev Concise Consumer Information (Cerner Multum)


• Fusilev Monograph (AHFS DI)


• Levoleucovorin Professional Patient Advice (Wolters Kluwer)

Compare Fusilev with other medications

• Colorectal Cancer
• Methotrexate Overdosage
• Methotrexate Rescue

Voltarol Emulgel P

1. Name Of The Medicinal Product

Voltarol Emulgel^® P

2. Qualitative And Quantitative Composition

Diethylammonium-{-o-[2,6-dichlorophenyl)-amino]-phenyl}-acetate.

100g of Voltarol Emulgel P contains 1.16g of the active substance diclofenac diethylammonium, which corresponds to 1g diclofenac sodium.

For excipients, see section 6.1

3. Pharmaceutical Form

Gel for topical administration.

White to practically white, soft, homogeneous, cream-like.

4. Clinical Particulars

4.1 Therapeutic Indications

For the local symptomatic relief of pain and inflammation in:

- trauma of the tendons, ligaments, muscles and joints,

e.g. due to sprains, strains and bruises

- localised forms of soft tissue rheumatism

For the relief of pain of non-serious arthritic conditions.

4.2 Posology And Method Of Administration

Adults and children 14 years and over: Voltarol Emulgel P should be rubbed gently into the skin. Depending on the size of the affected site to be treated, 2-4g (a circular shaped mass approximately 2.0-2.5cm in diameter) should be applied 3-4 times a day. The maximum daily dose is 16g. Therefore the maximum weekly dose is 112g.

For arthritis pain it may be necessary to apply the gel for up to 7 days (to allow its effect to build up on the joint) before an improvement in pain is noticed. The gel can be used for up to 14 days under pharmacy supervision.

After application, the hands should be washed unless they are the site being treated.

If symptoms do not improve by day 7, or if they worsen within the first 7 days, a consultation with a doctor is recommended. Consultation with a doctor is recommended if more than two major joints in the body are affected. Do not use for more than 14 days unless recommended by a doctor.

Use in the elderly: The usual adult dosage may be used.

Children: There are insufficient data on efficacy and safety available for the children and adolescents below 14 years of age (see also contraindications section 4.3). In children aged 14 years and over, if this product is required for more than 7 days for pain relief or if the symptoms worsen the patient/parents of the adolescent is/are advised to consult a doctor.

4.3 Contraindications

Patients with or without chronic asthma in whom attacks of asthma, urticaria or acute rhinitis are precipitated by aspirin or other non-steroidal anti-inflammatory agents.

Hypersensitivity to diclofenac, acetylsalicylic acid or other non-steroidal anti-inflammatory drugs.

Hypersensitivity to any other ingredient of the gel.

Concomitant use of other products containing diclofenac.

Concomitant use of oral NSAIDS.

The use in children and adolescents aged less than 14 years is contraindicated.

4.4 Special Warnings And Precautions For Use

Voltarol Emulgel P should be applied only to intact, non-diseased skin and not to skin wounds or open injuries. It should not be used with occlusion. It should not be allowed to come into contact with the eyes or mucous membranes, and should never be taken by mouth.

Patients with a history of, or active, peptic ulceration.Some possibility of gastro-intestinal bleeding in those with a significant history of this condition has been reported in isolated cases.

Like other drugs that inhibit prostaglandin synthetase activity, diclofenac and other NSAIDs can precipitate bronchospasm if administered to patients suffering from or with a previous history of, bronchial asthma.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No drug interactions during treatment with Voltarol Emulgel P have been reported, but the following have been observed with oral forms of diclofenac or other NSAIDs.

Lithium and digoxin: Voltarol may increase plasma concentrations of lithium and digoxin.

Anticoagulants: Although clinical investigations do not appear to indicate that Voltarol has an influence on the effect of anticoagulants, there are isolated reports of an increased risk of haemorrhage with the combined use of diclofenac and anticoagulant therapy. Therefore, to be certain that no change in anticoagulant dosage is required, close monitoring of such patients is required. As with other non-steroidal anti-inflammatory agents, diclofenac in a high dose can reversibly inhibit platelet aggregation.

Antidiabetic agents: Clinical studies have shown that Voltarol can be given together with oral antidiabetic agents without influencing their clinical effect. However there have been isolated reports of hypoglycaemic and hyperglycaemic effects which have required adjustment to the dosage of hypoglycaemic agents.

Ciclosporin: Cases of nephrotoxicity have been reported in patients receiving concomitant cyclosporin and NSAIDs, including diclofenac. This might be mediated through combined renal antiprostaglandin effects of both the NSAID and cyclosporin.

Methotrexate: Cases of serious toxicity have been reported when methotrexate and NSAIDs are given within 24 hours of each other. This interaction is mediated through accumulation of methotrexate resulting from impairment of renal excretion in the presence of the NSAID.

Quinolone antimicrobials: Convulsions may occur due to an interaction between quinolones and NSAIDs. This may occur in patients with or without a previous history of epilepsy or convulsions. Therefore, caution should be exercised when considering the use of a quinolone in patients who are already receiving an NSAID.

Other NSAIDs and steroids: Co-administration of Voltarol with other systemic NSAIDs and steroids may increase the frequency of unwanted effects. Concomitant therapy with aspirin lowers the plasma levels of each, although no clinical significance is known.

Diuretics: Various NSAIDs are liable to inhibit the activity of diuretics. Concomitant treatment with potassium-sparing diuretics may be associated with increased serum potassium levels, hence serum potassium should be monitored.

Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effects of mifepristone.

Anti-hypertensives: Concomitant use of NSAIDs with antihypertensive drugs (i.e. beta-blockers, angiotensin converting enzyme (ACE) inhibitors, diuretics) may cause a decrease in their antihypertensive effect via inhibition of vasodilatory prostaglandin synthesis.

4.6 Pregnancy And Lactation

Since no experience has been acquired with Voltarol Emulgel P in pregnancy or lactation, it is not recommended for use in these circumstances.

During the last trimester of pregnancy the use of prostaglandin synthetase inhibitors may result in premature closure of the ductus arteriosus, or in uterine inertia.

Animal data has shown an increased incidence of dystonia and delayed parturition when drug administration is continued into late pregnancy.

Following oral doses of 50mg diclofenac administered every 8 hours, diclofenac passes into breast milk in quantities so small that no undesirable effects on the infant are to be expected.

4.7 Effects On Ability To Drive And Use Machines

Voltarol Emulgel P has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable Effects

Local:

Voltarol Emulgel P is usually well tolerated. Local irritation, erythema, pruritus or dermatitis may occasionally occur. Skin photosensitivity, desquamation, discoloration and bullous or vesicular eruptions have been reported in isolated cases. Patients should be warned against excessive exposure to sunlight in order to reduce the incidence of photosensitivity.

General:

Systemic absorption of Voltarol Emulgel P is low compared with plasma levels obtained following oral forms of diclofenac. However, where Voltarol Emulgel P is applied to a relatively large area of skin and over a prolonged period, the possibility of systemic side effects cannot be completely excluded.

Asthma has been rarely reported in patients using topical NSAID preparations.

The following additional side-effects have been observed with oral forms of diclofenac.

Gastro-intestinal tract

Occasional: Epigastric pain, other gastro-intestinal disorders (e.g. nausea, vomiting, diarrhoea, abdominal cramps, dyspepsia, flatulence, anorexia).

Rare: Gastro-intestinal bleeding, peptic ulcer (with or without bleeding or perforation), bloody diarrhoea.

In isolated cases: Lower gut disorders (e.g. non-specific haemorrhagic colitis and exacerbations of ulcerative colitis or Crohn's proctocolitis, colonic damage and stricture formation), pancreatitis, aphthous stomatitis, glossitis, oesophageal lesions, constipation.

Central Nervous System:

Occasional: Headache, dizziness, or vertigo.

Rare: Drowsiness, tiredness.

In isolated cases: Disturbances of sensation, paraesthesia, memory disturbance, disorientation, disturbance of vision (blurred vision, diplopia), impaired hearing. Tinnitus, insomnia, irritability, convulsions, depression, anxiety, nightmares, tremor, psychotic reactions. Taste alteration disorders.

Skin:

Occasional: Rashes or skin eruptions.

Rare: Urticaria.

In isolated cases: Eczema, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome, (acute toxic epidermolysis), photosensitivity reactions, erythroderma (exfoliative dermatitis), loss of hair, purpura including allergic purpura.

Kidney:

In isolated cases: Acute renal failure, urinary abnormalities (e.g. haematuria, proteinuria), interstitial nephritis, nephrotic syndrome, papillary necrosis.

Liver:

Occasional: Elevation of serum aminotransferase enzymes (ALT, AST).

Rare: Liver function disorders including hepatitis (in isolated cases fulminant) with or without jaundice.

Blood:

In isolated cases: Thrombocytopenia, leucopenia, agranulocytosis, haemolytic anaemia, aplastic anaemia.

Hypersensitivity:

Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of rare cases of anaphylactic/anaphylactoid systemic reactions including hypotension, and respiratory tract reactivity comprising

asthma, aggravated asthma, bronchospasm or dyspnoea. (See also “Skin”).

Other organ systems:

Rare: Oedema

Isolated cases: Impotence (association with diclofenac is doubtful), palpitation, chest pain, hypertension.

4.9 Overdose

Signs and symptoms

The low systemic absorption of topical diclofenac renders overdosage extremely unlikely. In the event of accidental ingestion, resulting in significant systemic side-effects, general therapeutic measures normally adopted to treat poisoning with non-steroidal anti-inflammatory drugs should be used.

Treatment

Management of overdosage with NSAIDs essentially consists of supportive and symptomatic measures. There is no typical clinical picture resulting from diclofenac overdosage. Supportive and symptomatic treatment should be given for complications such as hypotension, renal failure, convulsions, gastro-intestinal irritation, and respiratory depression; specific therapies such as forced diuresis, dialysis or haemoperfusion are probably of no help in eliminating NSAIDs due to their high rate of protein binding and extensive metabolism.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Voltarol Emulgel P is an anti-inflammatory and analgesic preparation designed for external application. Due to an aqueous-alcoholic base the gel exerts a soothing and cooling effect.

5.2 Pharmacokinetic Properties

When Voltarol Emulgel P is applied locally, the active substance is absorbed through the skin. In healthy volunteers approximately 6% of the dose applied is absorbed when determined by urinary excretion of diclofenac and its hydroxylated metabolites. Findings in patients confirm that diclofenac penetrates inflamed areas following local application of Emulgel P.

Synovial fluid and tissue levels of diclofenac are higher than those detected in plasma.

5.3 Preclinical Safety Data

None known.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Diethylamine, carbomers, macrogol cetostearyl ether, cocoyl caprylocaprate, isopropyl alcohol, liquid paraffin, perfume creme 45, propylene glycol, purified water.

6.2 Incompatibilities

None stated.

6.3 Shelf Life

Three years.

6.4 Special Precautions For Storage

All presentations: Do not store above 30°C.

Pump dispenser presentation: The pump dispenser is a pressurised container. It should be protected from direct sunlight and must not be pierced or burned even when empty.

Voltarol Emulgel P should be kept out of reach of children.

6.5 Nature And Contents Of Container

Sealed aluminium tubes with protective inner coating, closed with a polypropylene screw cap, available in packs of 10g, 30g, 50g and 100g.

Aluminium laminated tube (low density polyethylene / aluminium / high density polyethylene (internal layer)) fitted with a high density polyethylene shoulder and closed by a moulded seal. The tube is closed with a polypropylene screw cap in white or blue, with two alternate shapes of cap and thread, incorporating a moulded feature used to insert, twist and remove the seal before first use. Available in packs of 30g, 50g and 100g.

Pump dispenser with aluminium can, valve (high density polyethylene, reinforced with titanium dioxide) with multi-layer pouch (low density polyethylene), mounted with a protective cap. Available in packs of 75ml.

6.6 Special Precautions For Disposal And Other Handling

None

Administrative Data

7. Marketing Authorisation Holder

Novartis Consumer Health UK Ltd.

Trading as Novartis Consumer Health

Wimblehurst Road

Horsham

West Sussex

RH12 5AB

UK

8. Marketing Authorisation Number(S)

PL 00030/0174

9. Date Of First Authorisation/Renewal Of The Authorisation

1 April 2000

10. Date Of Revision Of The Text

17 March 2011.

Legal Category: P

Renal Osteodystrophy Medications

Definition of Renal Osteodystrophy: Rickets is a childhood disorder involving softening and weakening of the bones, primarily caused by lack of vitamin D, calcium, and/or phosphate.

Drugs associated with Renal Osteodystrophy

The following drugs and medications are in some way related to, or used in the treatment of Renal Osteodystrophy. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Drug List:

Calcidol

Calciferol-Solution

Calcijex-Solution

Dht

Dht-Intensol

Drisdol

Hytakerol

Rocaltrol

Vitamin-D2