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Saturday 31 March 2012

Loracarbef

Class: Carbacephems
Chemical Name: [6R-[6α,7β(R*)]]-7-[(Aminophe nylacetyl)amino]-3-chloro-8-oxo-1-azabicyclo[4.2.0]oct-2-ene-2-carbo xylic acid monohydrate
CAS Number: 121961-22-6
Brands: Lorabid

Introduction

Antibacterial; carbacephem β-lactam antibiotic.¹ ² ³

Uses for Loracarbef

Respiratory Tract Infections

Treatment of mild to moderate acute maxillary sinusitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae (non-β-lactamase-producing strains only), or Moraxella catarrhalis (including β-lactamase-producing strains).¹ Associated with lower bacteriologic eradication and clinical cure rates than some other anti-infectives (e.g., amoxicillin and clavulanate) in patient populations with high numbers of β-lactamase-producing bacteria.¹ The possibility of reduced overall efficacy should be weighed carefully against local susceptibility patterns for common pathogens encountered in these infections.¹

Treatment of secondary bacterial infections of acute bronchitis caused by susceptible S. pneumoniae, H. influenzae (including β-lactamase-producing strains), or M. catarrhalis (including β-lactamase-producing strains).¹ ²

Treatment of acute bacterial exacerbations of chronic bronchitis caused by susceptible S. pneumoniae, H. influenzae (including β-lactamase-producing strains), or M. catarrhalis (including β-lactamase-producing strains).¹ ²

Treatment of mild to moderate pneumonia caused by susceptible S. pneumoniae or H. influenzae (non-β-lactamase-producing strains only)¹ when oral therapy is considered appropriate.¹ Because of possible lack of efficacy, ATS states that loracarbef should not be used for empiric treatment of community-acquired pneumonia (CAP) if multidrug-resistant S. pneumoniae are suspected.³³

Acute Otitis Media

Treatment of acute otitis media (AOM) caused by S. pneumoniae, S. pyogenes (group A β-hemolytic streptococci), H. influenzae (including β-lactamase-producing strains), or M. catarrhalis (including β-lactamase-producing strains).¹

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci).¹ Generally effective in eradicating S. pyogenes from the nasopharynx, but efficacy in the prevention of subsequent rheumatic fever has not been established.¹

CDC, AAP, IDSA, AHA, and others recommend oral penicillin V or IM penicillin G benzathine as treatments of choice;⁹ ²⁰ ²² oral cephalosporins and oral macrolides considered alternatives.⁹ ²⁰ ²¹ ²² ²³ ²⁴ ²⁵ ²⁶ Amoxicillin sometimes used instead of penicillin V, especially for young children.²²

Skin and Skin Structure Infections

Treatment of mild to moderate uncomplicated skin and skin structure infections caused by susceptible S. aureus (including penicillinase-producing strains) or S. pyogenes;¹ abscesses usually require surgical drainage.¹

Urinary Tract Infections (UTIs)

Treatment of uncomplicated UTIs (cystitis) caused by susceptible Escherichia coli or S. saprophyticus.¹ When selecting loracarbef for UTIs, carefully weigh the lower bacterial eradication rate and lower potential for toxicity against increased eradication rates and increased potential for toxicity associated with other anti-infectives (e.g., fluoroquinolones).¹

Treatment of uncomplicated pyelonephritis caused by susceptible E. coli.¹

Loracarbef Dosage and Administration

Administration

Oral Administration

Administer orally at least 1 hour before or 2 hours after a meal.¹

Reconstitution

Reconstitute oral suspension at the time of dispensing by adding the amount of water specified on the container in 2 portions; shake well after each addition.¹

Reconstituted suspension contains 100 or 200 mg of loracarbef/5 mL.¹

Dosage

Available as loracarbef monohydrate; dosage expressed in terms of anhydrous loracarbef.¹

Pediatric Patients

Respiratory Tract Infections

Acute Sinusitis

Oral

Children 6 months to 12 years of age: 15 mg/kg every 12 hours for 10 days.¹

Children ≥13 years of age: 400 mg every 12 hours for 10 days.¹

Secondary Bacterial Infections of Acute Bronchitis

Oral

Children ≥13 years of age: 200–400 mg every 12 hours for 7 days.¹

Acute Bacterial Exacerbations of Chronic Bronchitis

Oral

Children ≥13 years of age: 400 mg every 12 hours for 7 days.¹

Pneumonia

Oral

Children ≥13 years of age: 400 mg every 12 hours for 14 days.¹

Acute Otitis Media

Oral

Children 6 months to 12 years of age: 15 mg/kg (as the oral suspension) every 12 hours for 10 days.¹ Do not use capsules for treatment of AOM.¹

Pharyngitis and Tonsillitis

Oral

Children 6 months to 12 years of age: 7.5 mg/kg every 12 hours for ≥10 days.¹

Skin and Skin Structure Infections

Oral

Children 6 months to 12 years of age: 7.5 mg/kg every 12 hours for 7 days.¹

Children ≥13 years of age: 200 mg every 12 hours for 7 days.¹

Urinary Tract Infections

Uncomplicated Cystitis

Oral

Children ≥13 years of age: 200 mg once every 24 hours for 7 days.¹

Uncomplicated Pyelonephritis

Oral

Children ≥13 years of age: 400 mg every 12 hours for 14 days.¹

Adults

Respiratory Tract Infections

Acute Sinusitis

Oral

400 mg every 12 hours for 10 days.¹

Secondary Bacterial Infections of Acute Bronchitis

Oral

200–400 mg every 12 hours for 7 days.¹

Acute Bacterial Exacerbations of Chronic Bronchitis

Oral

400 mg every 12 hours for 7 days.¹

Pneumonia

Oral

400 mg every 12 hours for 14 days.¹

Skin and Skin Structure Infections

Oral

200 mg every 12 hours for 7 days.¹

Urinary Tract Infections

Uncomplicated Cystitis

Oral

200 mg once every 24 hours for 7 days.¹

Uncomplicated Pyelonephritis

Oral

400 mg every 12 hours for 14 days.¹

Special Populations

Renal Impairment

Dosage adjustment recommended in patients with Cl_cr <50 mL/minute.¹

Patients with Cl_cr 10–49 mL/minute should receive 50% of the usual dose every 12 hours or the usual dose once every 24 hours.¹ Patients with Cl_cr <10 mL/minute should receive the usual dose once every 3–5 days.¹

Patients undergoing hemodialysis should receive a supplementary dose after the procedure.¹

Geriatric Patients

No dosage adjustments except those related to renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Cautions for Loracarbef

Contraindications

Hypersensitivity to loracarbef or any cephalosporin.¹

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible organism.¹ Careful observation of the patient is essential.¹ Institute appropriate therapy if superinfection occurs.¹

Treatment with anti-infectives may permit overgrowth of clostridia.¹ ²⁷ ²⁸ ²⁹ ³⁰ ³¹ Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.¹ ²⁷ ²⁸ ²⁹ ³⁰ ³¹

Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone.¹ ²⁷ ²⁸ ²⁹ ³⁰ ³¹ 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 ²⁷ ²⁸ ²⁹ ³⁰ ³¹

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions such as anaphylaxis, serum sickness-like reactions, Stevens-Johnson syndrome, and toxic epidermal necrolysis reported with loracarbef and other β-lactams.¹

If an allergic reaction occurs, discontinue loracarbef and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).¹

Cross-Hypersensitivity

Partial cross-allergenicity among β-lactam antibiotics, including penicillins, cephalosporins, and cephamycins.¹

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to loracarbef, cephalosporins, penicillins, or other drugs.¹ Cautious use recommended in individuals hypersensitive to penicillins;¹ contraindicated in those hypersensitive to cephalosporins.¹

General Precautions

Selection and Use of Anti-infectives

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

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.

History of GI Disease

Use with caution in patients with a history of GI disease, particularly colitis.¹ (See Superinfection/Clostridium difficile-associated Colitis under Cautions.)

Specific Populations

Pregnancy

Category B.¹

Lactation

Not known whether distributed into milk.¹ Use with caution.¹

Pediatric Use

Safety and efficacy not established in children <6 months of age.¹

Pediatric patients have higher incidence of GI effects (diarrhea, vomiting, anorexia), rhinitis, somnolence, and rash compared with adults.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.¹

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function.¹ Assess renal function periodically since geriatric patients are more likely to have renal impairment.¹

No dosage adjustments except those related to renal function.¹ (See Renal Impairment under Dosage and Administration.)

Renal Impairment

Use with caution in patients with known or suspected renal impairment.¹ Closely monitor and perform appropriate laboratory studies prior to and during therapy.¹

Dosage adjustments recommended in patients with Cl_cr <50 mL/minute and in those undergoing hemodialysis or peritoneal dialysis.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea, nausea, vomiting, abdominal pain, anorexia); headache; rash.¹

Interactions for Loracarbef

Specific Drugs

Drug	Interaction	Comments
Diuretics	Possible adverse effects on renal function¹	Use with caution¹
Probenecid	Decreased renal tubular secretion of loracarbef; increased loracarbef concentrations and AUC and prolonged half-life¹

Loracarbef Pharmacokinetics

Absorption

Bioavailability

90% of a dose absorbed from GI tract.¹

In fasting adults, peak plasma concentrations attained within 1.2 hours after capsules and within 0.8 hours after oral suspension. In children, peak plasma concentrations attained within 1 hour after oral suspension.¹

Capsules and oral suspension are not bioequivalent; concentrations are higher and attained more quickly with oral suspension.¹

Food

Food decreases rate and extent of absorption of capsules; effect of food on oral suspension not studied to date.¹

Distribution

Extent

Distributed into middle ear fluid and blister fluid.¹

Plasma Protein Binding

Approximately 25%.¹

Elimination

Metabolism

Does not appear to be metabolized.¹

Elimination Route

Substantially eliminated in urine.¹

Half-life

1 hour in adults with normal renal function.¹

Special Populations

Half-life and AUC in geriatric adults with normal renal function similar to younger adults.¹

Half-life prolonged in patients with renal impairment.¹ Approximately 5.6 hours in adults with moderate renal impairment (Cl_cr 10–50 mL/minute per 1.73 m²) and approximately 32 hours in those with severe renal impairment (Cl_cr <10 mL/minute per 1.73 m²).¹

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).¹ Protect from heat.¹

For Suspension

25°C (may be exposed to 15–30°C).¹ After reconstitution, 15–30°C in tight container; discard after 14 days.¹

Actions and SpectrumActions

Carbacephem structurally and pharmacologically related to cephalosporins;¹ ² ³ the carba analog of cefaclor.³

Usually bactericidal.¹

Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.¹

Spectrum of activity includes many gram-positive aerobic bacteria, some gram-negative aerobic bacteria, and a few anaerobic bacteria.¹

Gram-positive aerobes: active in vitro and in clinical infections against Staphylococcus aureus (including penicillinase-producing strains), S. saprophyticus, Streptococcus pneumoniae, and S. pyogenes (group A β-hemolytic streptococci).¹ Also active in vitro against S. epidermidis, S. agalactiae (group B streptococci), S. bovis, groups C, F, and G streptococci, and viridans streptococci.¹ Oxacillin-resistant (methicillin-resistant) staphylococci are resistant.¹

Gram-negative aerobes: active in vitro and in clinical infections against Escherichia coli, Haemophilus influenzae (including β-lactamase-producing strains), and Moraxella catarrhalis (including β-lactamase-producing strains).¹ Also active in vitro against Citrobacter diversus, H. parainfluenzae, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pasteurella multocida, Proteus mirabilis, Salmonella, Shigella, and Yersinia enterocolitica.¹ Inactive against most Acinetobacter, Enterobacter, Morganella, P. vulgaris, Providencia, Pseudomonas, and Serratia.¹

Anaerobes: although clinical importance unclear, active in vitro against Clostridium perfringens, Fusobacterium necrophorum, Peptococcus niger, Peptostreptococcus intermedius, and Propionibacterium acnes.¹

Advice to Patients

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

Importance of completing full course of therapy, even if feeling better after a few days.

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 loracarbef or other antibacterials in the future.

Importance of taking loracarbef at least 1 hour before or at least 2 hours after eating.¹

Importance of discontinuing therapy and informing clinician if an allergic reaction occurs.¹

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

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

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

Preparations

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

Loracarbef
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	200 mg (of anhydrous loracarbef)	Lorabid Pulvules	Monarch
		400 mg (of anhydrous loracarbef)	Lorabid Pulvules	Monarch
	For suspension	100 mg (of anhydrous loracarbef) per 5 mL	Lorabid (with parabens)	Monarch
		200 mg (of anhydrous loracarbef) per 5 mL	Lorabid (with parabens)	Monarch

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 August 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

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2. Cooper RDG. The carbacephems: a new beta-lactam antibiotic class. Am J Med. 1992; 92(Suppl 6A):2-6S.

3. Blaszczak LC, Brown RF, Cook GK et al. Comparative reactivity of 1-carba-1-dethiacephalosporins with cephalosporins. J Med Chem. 1990; 33:1656-62. [PubMed 2342058]

4. Doern GV, Vautour R, Parker D et al. In vitro activity of loracarbef (LY163892), a new oral carbacephem antimicrobial agent, against respiratory isolates of Haemophilus influenza and Moraxella catarrhalis. Antimicrob Agents Chemother. 1991; 35:1504-7. [IDIS 284990] [PubMed 1929318]

5. Doern G. In vitro activity of loracarbef and effects of susceptibility test methods. Am J Med. 1992; 92(Suppl 6A):7-15S. [PubMed 1731513]

6. DeSante KA, Zeckel ML. Pharmacokinetic profile of loracarbef. Am J Med. 1992; 92(Suppl 6A):16-19S.

7. Pasini CE, Indelicato JM. Pharmaceutical properties of loracarbef: the remarkable solution stability of an oral 1-carba-1-dethiacephalosporin antibiotic. Pharm Res. 1992; 9:250-4. [PubMed 1553350]

8. Kovach PM, Lantz RJ, Brier G. High-performance liquid chromatographic determination of loracarbef, a potential metabolite, cefaclor and cephalexin in human plasma, serum and urine. J Chromatogr. 1991; 567:129-39. [PubMed 1918240]

9. Cooper RJ, Hoffman JR, Bartlett JG et al. Principles of appropriate antibiotic use for acute pharyngitis in adults: background. Ann Intern Med. 2001; 134:509-17. [IDIS 460578] [PubMed 11255530]

10. Lilly Research Laboratories. Lorabid (loracarbef) product summary. Indianapolis, IN; 1991 Dec.

11. Therasse DG. The safety profile of loracarbef: clinical trials in respiratory, skin, and urinary tract infections. Am J Med. 1992; 92(Suppl 6A):20-5S.

12. Foshee WS, Qvarnberg Y. Comparative United States and European trials of loracarbef in the treatment of acute otitis media. Pediatr Inf Dis J. 1992; 11(8 Suppl):S12-9.

13. McCarty J. Loracarbef versus penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis in an adult population. Am J Med. 1992; 92(Suppl 6A):74-9S.

14. Hyslop DL. Efficacy and safety of loracarbef in the treatment of pneumonia. Am J Med. 1992; 92(Suppl 6A):65-9S.

15. Gan VN, Kusmiesz H, Shelton S et al. Comparative evaluation of loracarbef and amoxicillin-clavulanate for acute otitis media. Antimicrob Agents Chemother. 1991; 35:967-71. [IDIS 281927] [PubMed 1854178]

16. Force RW, Nahata MC. Loracarbef: a new orally administered carbacephem antibiotic. Ann Pharmacother. 1993; 27:321-7. [IDIS 312703] [PubMed 8453172]

17. Nord CE, Grahnen A, Eckernas SA. Effect of loracarbef on the normal oropharyngeal and intestinal microflora. Scand J Infect Dis. 1991; 23:255-60. [PubMed 1853174]

18. Thieme RE, Caldwell SA, Lum GM. Acute interstitial nephritis associated with loracarbef therapy. J Pediatr. 1995; 127:997-1000. [IDIS 358538] [PubMed 8523206]

19. Disney FA, Hanfling MJ, Hausinger SA. Loracarbef (LY163892) vs. penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis. Pediatr Infect Dis J. 1992; 11:S20-6.

20. Dajani A, Taubert K, Ferrieri P et al and the American Heart Association Committee on Rheumatic Fever et al. Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals. Pediatrics. 1995; 96:758-64. [IDIS 355409] [PubMed 7567345]

21. Klein JO. Selection of oral antimicrobial agents for otitis media and pharyngitis. Infect Dis Clin Pract. 1995; 4(Suppl 2):S88-94.

22. Bisno AL, Gerber MA, Gwaltney JM et al. Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Clin Infect Dis. 2002; 35:113-25. [IDIS 484228] [PubMed 12087516]

23. Klein JO. Management of streptococcal pharyngitis. Pediatr Infect Dis J. 1994; 13:572-5. [IDIS 331902] [PubMed 8078757]

24. Pichichero ME, Cohen R. Shortened course of antibiotic therapy for acute otitis media, sinusitis and tonsillopharyngitis. Pediatr Infect Dis J. 1997; 16:680-95. [IDIS 390075] [PubMed 9239773]

25. Committee on Infectious Diseases, American Academy of Pediatrics. 2000 Red book: report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2000: 526-36.

26. Anon. The choice of antibacterial drugs. Med Lett Drugs Ther. 2001; 43:69-78. [PubMed 11518876]

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

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

29. 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) [IDIS 386628] [PubMed 9149180]

30. 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]

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

32. Anon. Drugs for the treatment of otitis media in children. Med Lett Drugs Ther. 1994; 36:19-21. [PubMed 8107649]

33. American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001; 163:1730-54. [IDIS 466552] [PubMed 11401897]

34. Giebink GS, Canafax DM, Kempthorne J. Antimicrobial treatment of acute otitis media. J Pediatr. 1991; 119:495-500. [IDIS 293135] [PubMed 1880671]

35. Pichichero ME. Assessing the treatment of alternatives for acute otitis media. Pediatr Infect Dis J. 1994; 13:S27-34.

36. Klein JO. Selection of oral antimicrobial agents for otitis media and pharyngitis. Infect Dis Clin Pract. 1995; 4(Suppl 2):S88-94.

37. Pichichero ME, Cohen R. Shortened course of antibiotic therapy for acute otitis media, sinusitis and tonsillopharyngitis. Pediatr Infect Dis J. 1997; 16:680-95. [IDIS 390075] [PubMed 9239773]

38. McCracken GH. Treatment of acute otitis media in an era of increasing microbial resistance. Pediatr Infect Dis J. 1998; 17:576-9. [IDIS 408842] [PubMed 9655564]

39. Klein JO. Otitis Media. Clin Infect Dis J. 1994; 19:823-33.

40. Klein JO. Clinical implications of antibiotic resistance for management of acute otitis media. Pediatr Infect Dis J. 1998; 17:1084-9. [IDIS 417362] [PubMed 9850003]

41. Gooch WM, Philips A, Rhoades R et al. Comparison of the efficacy, safety and acceptability of cefixime and amoxicillin/clavulanate in acute otitis media. Pediatr Infect Dis J. 1997; 16(Suppl):21-4.

42. Kafetzis DA. Multi-investigator evaluation of the efficacy and safety of cefprozil, amoxicillin-clavulanate, cefixime and cefaclor in the treatment of acute otitis media, Eur J Clin Microbiol Infect Dis. 1994; 13:857-65.

43. Adler M, McDonald PJ, Trostmann U et al. Cefdinir versus amoxicillin/clavulanic acid in the treatment of suppurative acute otitis media in children. Eur J Clin Microbiol Infect Dis. 1997; 16:214-9. [PubMed 9131324]

44. Gooch WM, Adelglass J, Kelsey DK et al. Loracarbef versus clarithromycin in children with acute otitis media with effusion. Clin Ther. 1999; 21:711-21. [IDIS 428166] [PubMed 10363736]

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47. Dowell SF, Butler JC, Giebink GS et al. Acute otitis media: management and surveillance in an era of pneumococcal resistance—a report from the drug-resistant Streptococcal pneumoniae Therapeutic Working Group. Pediatr Infect Dis J. 1999; 18:1-9. [IDIS 421864] [PubMed 9951971]

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More Loracarbef resources

Loracarbef Side Effects (in more detail)
Loracarbef Use in Pregnancy & Breastfeeding
Loracarbef Drug Interactions
Loracarbef Support Group
1 Review for Loracarbef - Add your own review/rating

Loracarbef MedFacts Consumer Leaflet (Wolters Kluwer)

loracarbef Concise Consumer Information (Cerner Multum)

loracarbef Advanced Consumer (Micromedex) - Includes Dosage Information

Lorabid Prescribing Information (FDA)

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Friday 30 March 2012

Gastrinex

Pronunciation: a-mah-LASE/LYE-pase/PRO-tee-ase/SEL-ue-lase/HYE-oh-SYE-a-meen/fen-il-tole-OX-a-meen
Generic Name: Amylase/Lipase/Protease/Cellulase/Hyoscyamine/Phenyltoloxamine
Brand Name: Examples include Digex and Gastrinex

Gastrinex is used for:

Relieving symptoms of indigestion (eg, feeling of fullness, gas, bloating) that occur after meals.

Gastrinex is a digestive enzyme and anticholinergic combination. It works by helping the body to digest protein, starch, and fat. It also decreases bowel spasms.

Do NOT use Gastrinex if:

you are allergic to any ingredient in Gastrinex or to pork protein

you have inflammation of the pancreas (pancreatitis) or a flare-up of long-term pancreas problems

you have severe esophagus problems (eg, irritation, narrowing); a blockage of the stomach, bowel, or bladder; bowel motility problems; or severe bowel problems (eg, severe ulcerative colitis, toxic megacolon)

you have glaucoma, myasthenia gravis, or heart problems caused by severe bleeding

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

Before using Gastrinex:

Some medical conditions may interact with Gastrinex. 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 a history of pancreas problems, stomach or bowel problems (eg, blockage, short bowel syndrome), or cystic fibrosis

if you have nerve problems, prostate problems, esophagus problems (eg, reflux), heart or blood vessel problems (eg, fast or irregular heartbeat, heart failure, coronary heart disease), hiatal hernia, kidney problems, an overactive thyroid, high blood pressure, urinary problems, paralysis, or brain damage, or if you are at risk for glaucoma

if you have diarrhea or fever, have been very ill, or are in poor health

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

Amantadine, antihistamines (eg, diphenhydramine), haloperidol, monoamine oxidase inhibitors (MAOIs) (eg, phenelzine), other anticholinergics (eg, scopolamine), phenothiazines (eg, thioridazine), or tricyclic antidepressants (eg, amitriptyline) because they may increase the risk of Gastrinex's side effects

Narcotic pain medicines (eg, codeine) or potassium chloride because the risk of their side effects may be increased by Gastrinex

Ketoconazole or metoclopramide because their effectiveness may be decreased by Gastrinex

This may not be a complete list of all interactions that may occur. Ask your health care provider if Gastrinex 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 Gastrinex:

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

Take Gastrinex by mouth with each meal or snack as directed by your doctor.

If you miss a dose of Gastrinex, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once or take a dose without a snack or a meal.

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

Important safety information:

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

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

Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor.

If you open the capsule, do not breathe in the powder. Some patients may experience an asthma attack or severe allergic reaction (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue) from breathing in the powder.

Do not become overheated or dehydrated in hot weather or while you are being active; heatstroke may occur.

Drink plenty of fluids, maintain good oral hygiene, and suck on sugarless hard candy to relieve dry mouth.

Proper dental care is important while you are taking Gastrinex. Brush and floss your teeth and visit the dentist regularly.

Gastrinex may make your eyes more sensitive to sunlight. It may help to wear sunglasses.

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

Contact your doctor if you have loose stools while you take Gastrinex. Your doctor may need to decrease your dose.

Use Gastrinex with caution in the ELDERLY; they may be more sensitive to its effects, especially constipation, trouble urinating, dry mouth, drowsiness, agitation, confusion, excitability, or memory problems.

Caution is advised when using Gastrinex in CHILDREN; they may be more sensitive to its effects, especially excitability.

PREGNANCY and BREAST-FEEDING: It is not known if Gastrinex can cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Gastrinex while you are pregnant. Gastrinex is found in breast milk. If you are or will be breast-feeding while you use Gastrinex, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Gastrinex:

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:

Blurred vision; constipation; decreased sweating; dizziness; drowsiness; dry mouth; enlarged pupils; excitability; headache; nausea; nervousness; trouble sleeping; weakness.

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); agitation; behavior changes; confusion; decreased sexual ability; difficulty focusing eyes; disorientation; exaggerated sense of well-being; fast or irregular heartbeat; hallucinations; loss of consciousness; loss of coordination; memory loss; mental or mood changes; severe or persistent loose stools or diarrhea; severe or persistent stomach pain; severe or persistent trouble sleeping; speech changes; taste changes or loss; trouble urinating; unusual tiredness or weakness; vision changes; vomiting.

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: Gastrinex 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 diarrhea; disorientation; excessive thirst or excitability; fever; hot, dry skin; seizures; severe dry mouth; severe or persistent blurred vision, dizziness, headache, nausea, or vomiting; trouble breathing or swallowing.

Proper storage of Gastrinex:

Store Gastrinex at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Gastrinex out of the reach of children and away from pets.

General information:

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

Gastrinex 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 a summary only. It does not contain all information about Gastrinex. 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

More Gastrinex resources

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

Compare Gastrinex with other medications

Functional Gastric Disorder

Friday 23 March 2012

Liqui-Dual Citra

Generic Name: citric acid and sodium citrate (SIT rik AS id and SOE dee um SIT rayt)

Brand Names: Bicitra, Cytra-2, Liqui-Dual Citra, Oracit

What is Liqui-Dual Citra (citric acid and sodium citrate)?

Citric acid and sodium citrate are both alkalinizing agents that make the urine less acidic.

The combination of citric acid and sodium citrate is used to prevent gout or kidney stones, or metabolic acidosis in people with kidney problems.

Citric acid and sodium citrate may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Liqui-Dual Citra (citric acid and sodium citrate)?

You should not use this medication if you have kidney failure, severe heart damage (such as from a prior heart attack), Addison's disease (an adrenal gland disorder), high levels of potassium in your blood (hyperkalemia), or if you are severely dehydrated or have heat cramps.

Before you take citric acid and sodium citrate, tell your doctor about all your medical conditions, especially kidney disease, heart disease, high blood pressure, a history of heart attack, urinary problems, swelling (edema), or chronic diarrhea (such as ulcerative colitis, Crohn's disease).

Also tell your doctor about all other medications you use, including over-the-counter medications and household remedies.

Citric acid and sodium citrate should be taken after meals to help prevent stomach or intestinal side effects.

The liquid medicine should be mixed with water or juice. Drink plenty of liquids while you are taking citric acid and sodium citrate. Your treatment may include a special diet. You should become very familiar with the list of foods you should eat or avoid to help control your condition.

Avoid using antacids without your doctor's advice, including household baking soda (sodium bicarbonate). Antacids that contain aluminum or sodium can interact with citric acid and sodium citrate, causing a serious electrolyte imbalance or aluminum toxicity.

Avoid eating foods that are high in salt, or using extra table salt on your meals.

To be sure citric acid and sodium citrate is helping your condition, your blood and urine may need to be tested often. Follow your doctor's instructions carefully and do not miss any scheduled appointments.

Serious side effects of citric acid and sodium citrate include muscle twitching or cramps, swelling or weight gain, weakness, mood changes, rapid and shallow breathing, fast heart rate, restless feeling, black or bloody stools, severe diarrhea, or seizure (convulsions).

What should I discuss with my healthcare provider before taking Liqui-Dual Citra (citric acid and sodium citrate)?

You should not use this medication if you are allergic to it, or if you have:

kidney failure;

severe heart damage (such as from a prior heart attack);

Addison's disease (an adrenal gland disorder);

high levels of potassium in your blood (hyperkalemia); or

if you are severely dehydrated or have heat cramps.

If you have certain conditions, you may need a dose adjustment or special tests to safely take this medication. Before you take citric acid and sodium citrate, tell your doctor if you have:

kidney disease;

congestive heart failure, enlarged heart, or history of heart attack;

other heart disease or high blood pressure;

low levels of calcium in your blood (hypocalcemia);

a urinary tract infection;

toxemia of pregnancy;

urination problems (or if you are unable to urinate);

swelling of your hands or feet, or in your lungs (pulmonary edema); or

chronic diarrhea (such as ulcerative colitis, Crohn's disease).

It is not known whether this medication is harmful to an unborn baby. Before taking citric acid and sodium citrate, Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether citric acid and sodium citrate passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Liqui-Dual Citra (citric acid and sodium citrate)?

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.

Citric acid and sodium citrate should be taken after meals to help prevent stomach or intestinal side effects. You may also need to take the medicine at bedtime. Follow your doctor's instructions.

Shake the oral solution (liquid) well just before you measure a dose. To be sure you get the correct dose, measure the liquid with a marked measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one. The liquid medicine should be mixed with at lease 4 ounces of water or juice. Drink this mixture slowly and then add a little more water to the same glass, swirl gently and drink right away. You may chill the mixed medicine to make it taste better, but do not allow it to freeze.

Drink plenty of liquids while you are taking citric acid and sodium citrate.

Your treatment may include a special diet. It is very important to follow the diet plan created for you by your doctor or nutrition counselor. You should become very familiar with the list of foods you should eat or avoid to help control your condition.

Store citric acid and sodium citrate at room temperature away from moisture, heat, or freezing. Keep the medication in a closed container.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If you are more than 2 hours late in taking your medicine, wait until your next regularly scheduled time to take the medicine and skip the missed dose. 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.

Overdose symptoms may include muscle spasms or seizure (convulsions).

What should I avoid while taking Liqui-Dual Citra (citric acid and sodium citrate)?

Avoid eating foods that are high in salt, or using extra table salt on your meals.

It is very important to follow any diet plan created for you by your doctor or nutrition counselor. You should become very familiar with the list of foods you should eat or avoid to help control your condition.

Liqui-Dual Citra (citric acid and sodium citrate) 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. Stop using this medication and call your doctor at once if you have any of these serious side effects:

swelling, tingling, or numbness in your hands or feet;

muscle twitching or pain, leg pain or cramps;

unusual weakness, rapid and shallow breathing, fast or slow heart rate, dizziness, confusion, or mood changes;

feeling restless, nervous, or irritable;

black, bloody, or tarry stools;

severe or ongoing diarrhea; or

seizure (convulsions).

Less serious side effects may include:

nausea, or vomiting, stomach pain;

mild or occasional diarrhea; or

mild stomach pain.

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

What other drugs will affect Liqui-Dual Citra (citric acid and sodium citrate)?

The following drugs can interact with citric acid and sodium citrate. Tell your doctor if you are using any of these:

lithium (Eskalith, LithoBid);

methenamine (Hiprex, Mandelamine, Urex),

quinidine (Quinaglute, Quinidex, Quin-Release);

cold or allergy medicine (decongestants), diet pills, ADHD medication;

a vitamin, mineral supplement, or medication that contains calcium;

salicylates such as aspirin, Backache Relief Extra Strength, Novasal, Nuprin Backache Caplet, Doan's Pills Extra Strength, Tricosal, and others; or

an antacid that contains aluminum or sodium, including Alka-Seltzer, Maalox, Mylanta, Di-Gel, Gelusil, Alamag Plus, Rulox Plus, Tempo, and others.

This list is not complete and there may be other drugs that can interact with citric acid and sodium citrate. 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 Liqui-Dual Citra resources

Liqui-Dual Citra Use in Pregnancy & Breastfeeding
Liqui-Dual Citra Drug Interactions
Liqui-Dual Citra Support Group
0 Reviews for Liqui-Dual Citra - Add your own review/rating

Bicitra MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Liqui-Dual Citra with other medications

Urinary Alkalinization
Urinary Tract Stones

Where can I get more information?

Your pharmacist can provide more information about citric acid and sodium citrate.

Thursday 22 March 2012

Viracept

Generic Name: Nelfinavir Mesylate
Class: HIV Protease Inhibitors
VA Class: AM800
Chemical Name: [3S-[2(2S*,3S*),3α,4aβ,8aβ]] -N-(1,1-dimethylethyl)decahydro-2-[2-hydroxy-3-[(3-hydroxy-2 -methylbenzoyl)amino]-4-(phenylthio)butyl]-3-isoquinolinecarboxamide monomethanesulfonate (salt)
Molecular Formula: C₃₂H₄₅N₃O₄S•CH₄O₃S
CAS Number: 159989-65-8

Introduction

Antiretroviral; HIV protease inhibitor (PI).¹ ² ³ ⁴ ⁶ ⁷ ⁸

Uses for Viracept

Treatment of HIV Infection

Treatment of HIV infection in conjunction with other antiretrovirals.¹

Because of inferior virologic efficacy, nelfinavir is not recommended for initial therapy.⁹⁵

Postexposure Prophylaxis of HIV

Postexposure prophylaxis of HIV infection† in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with risk for transmission of the virus.¹⁴⁶ Used in conjunction with other antiretrovirals.¹⁴⁶

Postexposure prophylaxis of HIV infection† in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.¹⁷⁴ Used in conjunction with other antiretrovirals.¹⁷⁴

Viracept Dosage and Administration

Administration

Oral Administration

Administer orally with a meal or light snack.¹ ⁹⁵ ¹¹⁹

Children who are able to swallow tablets may receive the appropriate number of tablets.¹ Smaller children and children unable to swallow tablets may receive nelfinavir powder for oral suspension.¹

Reconstitution

When the powder for oral suspension is used, the appropriate dose of powder should be added to a small amount of water, milk, soy milk, milk- or soy-based formula or liquid dietary supplement, pudding, or ice cream.¹ ⁸⁰ ¹¹⁹ Each level scoop (provided with the powder by the manufacturer) provides 50 mg of nelfinavir; if a teaspoon measure is used, each level teaspoon provides 200 mg of nelfinavir.¹ ⁸⁰ After mixing, the entire mixture must be consumed to provide the full dose of nelfinavir; the dose should be consumed within 6 hours of preparation.¹

For individuals unable to swallow tablets, the appropriate dose of nelfinavir tablets (whole or crushed) may be placed in a small amount of water and allowed to disperse and then this dispersion swallowed or mixed with milk or chocolate milk.¹ ⁸⁰ ¹¹⁹ ¹²⁴ Alternatively, the tablets may be crushed and mixed in a small amount of food (e.g., pudding).¹ ¹¹⁹ After being dispersed in water or mixed in food, the entire contents must be consumed within 6 hours to provide the full dose of nelfinavir.¹

Nelfinavir oral powder or tablets should not be mixed with acidic food or juice (e.g., apple juice, applesauce, orange juice) since the resultant mixture may have a bitter taste.¹ ⁸⁰ ¹¹⁹

Dosage

Available as nelfinavir mesylate; dosage expressed as nelfinavir.¹

Must be given in conjunction with other antiretrovirals.¹ If used with didanosine, lopinavir, or indinavir, adjustment in the treatment regimen may be necessary.¹ ⁸⁰ ⁹⁵ (See Specific Drugs under Interactions.)

Pediatric Patients

Treatment of HIV Infection

Oral

Neonates and children <2 years of age†: Reliably effective dosage not established.¹ High interindividual variability in drug concentrations observed when 40 mg/kg every 12 hours was evaluated in neonates and infants up to 6 weeks of age; higher dosages are being investigated.¹¹⁹

Children 2–13 years of age: 45–55 mg/kg twice daily or 25–35 mg/kg 3 times daily.¹ ¹¹⁹

Children >13 years of age: 1.25 g (five 250-mg tablets or two 625-mg tablets) twice daily or 750 mg (three 250-mg tablets) 3 times daily.¹ ⁹⁵ ¹¹⁹

Table 1. Pediatric Patients ≥2 Years of Age (Tablets)
Weight (kg)	No. of 250-mg Tablets 2 times daily (45–55 mg/kg 2 times daily)	No. of 250-mg Tablets 3 times daily (25–35 mg/kg 3 times daily)
10–12	2	1
13–18	3	2
19–20	4	2
≥21	4–5	3

Table 2. Pediatric Patients ≥2 years of Age (Oral Powder)
Weight (kg)	No. of Level 50-mg Scoops 2 times daily (45–55 mg/kg 2 times daily)	No. of Level 200-mg Teaspoons 2 times daily (45–55 mg/kg 2 times daily)	No. of Level 50-mg Scoops 3 times daily (25–35 mg/kg 3 times daily)	No. of Level 200-mg Teaspoons 3 times daily (25–35 mg/kg 3 times daily)
9 to <10.5	10	2½	6	1½
10.5 to <12	11	2¾	7	1¾
12 to <14	13	3¼	8	2
14 to <16	15	3¾	9	2¼
16 to <18	Use tablets	Use tablets	10	2½
18 to <23	Use tablets	Use tablets	12	3
≥23	Use tablets	Use tablets	15	3¾

Adults

Treatment of HIV Infection

Oral

1.25 g (five 250-mg tablets or two 625-mg tablets) twice daily or 750 mg (three 250-mg tablets) 3 times daily.¹ ⁹⁵

Postexposure Prophylaxis of HIV†

Occupational Exposure†

Oral

1.25 g twice daily.¹⁴⁶

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.¹⁴⁶

Nonoccupational Exposure†

Oral

1.25 g twice daily or 750 mg 3 times daily in conjunction with other antiretrovirals.¹⁷⁴

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.¹⁷⁴

Prescribing Limits

Pediatric Patients

Treatment of HIV

Oral

>2.5 g daily not studied in children.¹

Special Populations

Hepatic Impairment

Treatment of HIV Infection

Oral

Dosage adjustment not needed in patients with mild hepatic impairment (Child-Pugh class A).¹ Not recommended in patients with moderate or severe hepatic impairment.¹

Renal Impairment

Treatment of HIV Infection

Oral

Dosage adjustments not necessary.⁹⁵

Cautions for Viracept

Contraindications

Known hypersensitivity to nelfinavir or any ingredient in the formulation.¹

Concomitant use with drugs highly dependent on CYP3A for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., amiodarone, cisapride, ergot alkaloids, midazolam, pimozide, quinidine, triazolam).¹ ⁹⁵ (See Specific Drugs under Interactions.)

Warnings/Precautions

Warnings

Interactions

Concomitant use with certain drugs not recommended (e.g., lovastatin, simvastatin, St. John’s wort, fluticasone) or requires particular caution (e.g., sildenafil, tadalafil, vardenafil).¹ ⁹⁵ ¹¹⁹ (See Specific Drugs under Interactions.)

Phenylketonuria

Nelfinavir powder for oral suspension contains aspartame (NutraSweet), which is metabolized in the GI tract to provide 11.2 mg of phenylalanine for each 50-mg dose of nelfinavir.¹

Ethyl Methanesulfonate (EMS)

In September 2007, the manufacturer of nelfinavir informed prescribers that commercially available preparations contained EMS, an impurity from the manufacturing process.¹⁷⁸ EMS is a potential human carcinogen.¹⁷⁸ Recommendations that limited use of nelfinavir in children and pregnant women were issued at that time.¹⁶⁸ ¹⁷⁸ ¹⁷⁹ The manufacturer and FDA have agreed on a final limit for EMS in nelfinavir preparations; all nelfinavir preparations manufactured and released after March 31, 2008 meet the final limit established by FDA for all patient populations, including children and pregnant women.¹⁸⁴ Recommendations concerning use in pregnant women and children issued in 2007 no longer apply.¹ ¹⁸⁴ Nelfinavir may be used in pregnant women and for initial therapy in pediatric patients.¹⁸⁵

Hyperglycemic Effects

Hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of HIV protease inhibitors (PIs); diabetic ketoacidosis has occurred.¹ ⁸² ¹³⁰ ¹³¹ ¹³² ¹⁴⁸

Monitor blood glucose and initiate or adjust dosage of oral hypoglycemic agent or insulin as needed.¹

General Precautions

HIV Resistance

Possibility of HIV resistance to nelfinavir and possible cross-resistance to other PIs.¹ ⁹⁵ Effect of nelfinavir therapy on subsequent therapy with other PIs under investigation.¹ ⁹⁵

Hemophilia A and B

Spontaneous bleeding noted with PIs; causal relationship not established.¹ ⁷⁵ ⁷⁷ ¹²⁴ ¹⁴⁸

Caution in patients with a history of hemophilia type A or B.¹ ⁷⁵ Increased hemostatic (e.g., antihemophilic factor) therapy may be needed.¹

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]); this may necessitate further evaluation and treatment.¹

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.¹ ¹³⁷ ¹³⁸ ¹³⁹ ¹⁴⁰ ¹⁴¹ ¹⁴² ¹⁴³ ¹⁴⁴

Specific Populations

Pregnancy

Category B.¹ Antiretroviral Pregnancy Registry at 800-258-4263.¹

Some experts state that nelfinavir is an alternative PI when the regimen is given solely for perinatal prophylaxis.¹⁶⁸

Lactation

Distributed into milk in rats.¹

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.¹ ⁷⁹ ¹⁶⁸

Pediatric Use

Safety and efficacy not established in children <2 years of age.¹ Some data collected in this age group, but reliably effective dosage not established.¹ Some evidence that those <2 years of age have a lower response rate than older children.¹

Use of nelfinavir in children 2–13 years of age supported by evidence from adequate and well-controlled studies in adults and pharmacokinetic and clinical studies supporting activity in pediatric patients.¹ ⁸⁰ ¹¹⁹ ¹²⁴ ¹²⁶ ¹²⁷ ¹⁴⁷ ¹⁵² ¹⁵³ ¹⁵⁴ ¹⁶¹ Diarrhea reported less frequently in children than in adults.⁸⁰ ¹²⁴

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.¹

Hepatic Impairment

Use in patients with moderate or severe hepatic impairment not recommended.¹

Common Adverse Effects

Diarrhea, nausea.¹ ⁴ ⁸⁰

Interactions for Viracept

Metabolized by CYP3A and CYP2C19.¹ ⁸⁰ ⁸³

Inhibits CYP3A; does not inhibit CYP2D6, CYP2C9, CYP2C19, CYP2C8, CYP1A2, or CYP2E1.¹ ⁸⁰ ⁸³

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A or CYP2C19 with possible alteration in metabolism of nelfinavir and/or other drug.¹

Specific Drugs

Drug	Interaction	Comments
Abacavir	In vitro evidence of synergistic antiretroviral effects¹
Antiarrhythmic agents (amiodarone, quinidine)	Possible increased antiarrhythmic agent concentrations; potential for serious or life-threatening effects (e.g., cardiac arrhythmias)¹	Concomitant use with amiodarone or quinidine contraindicated¹
Anticonvulsants (carbamazepine, phenobarbital, phenytoin)	Decreased phenytoin concentrations and AUC; no change in nelfinavir plasma concentrations¹ Possible decreased nelfinavir concentrations with carbamazepine or phenobarbital¹ ⁹⁰	Monitor phenytoin concentrations; adjustment of phenytoin dosage may be needed ¹ Monitor anticonvulsant concentrations and virologic response; consider use of alternative anticonvulsant or monitoring nelfinavir concentrations⁹⁵
Antifungals, azoles (itraconazole, ketoconazole, voriconazole)	Itraconazole: Manufacturer states pharmacokinetic interactions unlikely;¹ some experts state possible pharmacokinetic interactions affecting both drugs⁹⁵ Ketoconazole: Increased nelfinavir concentrations and AUC¹ Voriconazole: Possible pharmacokinetic interactions; may affect both drugs⁹⁵	Itraconazole: Dosage adjustment not needed;⁸⁰ monitor itraconazole concentrations⁹⁵ Ketoconazole: Dosage adjustments not necessary¹ ⁹⁵ Voriconazole: Monitor for toxicities⁹⁵
Antimycobacterials (rifabutin, rifampin, rifapentine)	Rifabutin: Increased rifabutin concentrations; decreased nelfinavir concentrations¹ ⁹⁵ Rifampin: Decreased nelfinavir concentrations¹ ⁸⁴ ⁹⁵	Rifabutin: Reduce rifabutin dosage to 150 mg once daily or 300 mg 3 times weekly;⁹⁵ nelfinavir 1.25 g twice daily is preferred regimen when concomitant therapy is necessary¹ Rifampin: Concomitant use not recommended¹ ⁸⁵ ⁹⁵ ¹⁴⁵ Rifapentine: Concomitant use not recommended⁹⁵
Benzodiazepines	Pharmacokinetic interaction with midazolam or triazolam; potential for prolonged or increased sedation or respiratory depression¹	Manufacturer of nelfinavir states that concomitant use with midazolam or triazolam contraindicated;¹ ⁹⁵ however, some experts state a single parenteral dose of midazolam can be used with caution in a monitored situation for procedural sedation⁹⁵
Cisapride	Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)⁹⁵	Concomitant use not recommended⁹⁵
Corticosteroids (fluticasone)	Fluticasone nasal spray/oral inhalation: Possible increased plasma fluticasone concentrations¹	Fluticasone nasal spray/oral inhalation: Consider alternatives in patients receiving nelfinavir, especially when long-term corticosteroid therapy is anticipated¹
Co-trimoxazole	Interaction unlikely¹
Dapsone	Interaction unlikely¹
Darunavir		Concomitant use with ritonavir-boosted darunavir not recommended pending further accumulation of data¹⁷⁷
Delavirdine	Decreased plasma delavirdine concentrations; increased plasma nelfinavir concentrations¹ ⁸⁰ ⁹⁵ ¹³³ ¹⁷⁶ Increased toxicity (i.e., neutropenia) observed¹ ⁸⁰ ¹³³ In vitro evidence of synergistic antiretroviral effects¹	Appropriate dosages for concomitant use with respect to safety and efficacy not established ¹ ¹⁷⁶
Didanosine	No change in nelfinavir concentrations when didanosine administered 1 hour before nelfinavir¹ ⁸⁰ In vitro evidence of additive antiretroviral effects¹	Administer nelfinavir (with food) 1 hour after or 2 hours before didanosine (without food)¹ ⁸⁰
Efavirenz	Increased peak plasma concentrations and AUC of nelfinavir; decreased peak plasma concentrations and AUC of nelfinavir metabolite (M8); no change in the pharmacokinetics of efavirenz¹ ⁹⁵ ¹²² ¹⁴⁷ In vitro evidence of synergistic antiretroviral effects¹	Dosage adjustment not needed¹ ⁹³ ⁹⁵ ¹²² ¹⁴⁷
Emtricitabine	In vitro evidence of additive or synergistic antiretroviral effects¹⁸²
Ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine)	Possibility of pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., acute ergot toxicity)¹	Concomitant use contraindicated¹ ⁹⁵ If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving nelfinavir, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible¹⁶⁸
Estrogens/Progestins	Hormonal contraceptives: Decreased concentrations of ethinyl estradiol and norethindrone with oral contraceptive preparations⁹⁵	Use alternative or concomitant nonhormonal contraceptive measures¹ ⁹⁵
Etravirine	Increased nelfinavir concentrations¹⁸³	Concomitant use not recommended⁹⁵ ¹⁸³
Fosamprenavir	Studies using amprenavir indicate possible alterations in amprenavir pharmacokinetics;¹⁸¹ concomitant use of ritonavir-boosted fosamprenavir with nelfinavir not evaluated¹⁸¹ In vitro evidence of additive antiretroviral effects¹⁸¹	Appropriate dosages for concomitant use with respect to safety and efficacy not established⁹⁵ ¹⁸¹
HMG-CoA reductase inhibitors	Decreased clearance and increased concentrations of some HMG-CoA reductase inhibitors with potential for increased risk of myopathy (including rhabdomyolysis)¹	Concomitant use with lovastatin or simvastatin not recommended;¹ ⁹⁵ caution if used with other HMG-CoA reductase inhibitors metabolized by the CYP3A4 pathway¹ ⁹⁵ If used with atorvastatin or rosuvastatin, use lowest possible dosage of the HMG-CoA reductase inhibitor¹ Consider using HMG-CoA reductase inhibitors with low potential for interaction (e.g., fluvastatin, pravastatin)¹
Immunosuppressive agents	Potential for increased concentrations of cyclosporine, sirolimus, or tacrolimus¹
Indinavir	Increased AUC of both drugs¹ ⁸⁰ ⁸⁷ ⁹⁵	Appropriate dosages for concomitant use with respect to safety and efficacy not established ¹ Limited data supports use of nelfinavir 1.25 g twice daily with indinavir 1.2 g twice daily⁹⁵
Lamivudine	Increased lamivudine peak plasma concentrations and AUC¹ In vitro evidence of synergistic antiretroviral effects¹	Dosage adjustment not needed¹ ⁸⁰ ¹²⁴
Lopinavir	Decreased lopinavir concentrations and increased nelfinavir concentrations⁹⁵ ¹⁷¹	Once-daily lopinavir regimen not recommended with nelfinavir¹⁷¹ Some experts state that appropriate dosages for concomitant use of lopinavir and nelfinavir not established⁹⁵ For adults, manufacturer of lopinavir recommends 500 mg of lopinavir and 125 mg of ritonavir (as tablets) twice daily¹⁷¹ Manufacturer of lopinavir recommends that adults receive 533 mg of lopinavir and 133 mg of ritonavir (6.7 mL of the oral solution) twice daily¹⁷¹ For pediatric patients 6 months to 18 years of age, manufacturer of lopinavir recommends 300 mg/m² of lopinavir and 75 mg/m² of ritonavir twice daily (do not exceed the adult dosage)¹⁷¹
Macrolides (azithromycin)	Increased azithromycin peak plasma concentrations and AUC; no clinically important changes in nelfinavir pharmacokinetic values¹	Dosage adjustment not needed; monitor for azithromycin adverse effects (e.g., hepatic enzyme abnormalities, hearing impairment)¹ ¹⁷³
Maraviroc	Possible increased concentrations of maraviroc⁹⁵	Recommended dosage of maraviroc is 150 mg twice daily⁹⁵ ¹⁸⁶
Methadone	Decreased methadone plasma concentrations and AUC¹	Monitor and titrate methadone dose if needed; consider need to increase methadone dosage¹ ³⁰ ⁹⁵
Nevirapine	Clinically important pharmacokinetic interactions unlikely¹ ⁸⁰ ⁹⁵ In vitro evidence of synergistic antiretroviral effects¹	Dosage adjustment not needed¹ ⁹⁵
Pimozide	Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)¹	Concomitant use contraindicated¹ ⁹⁵
Proton-pump inhibitors	Omeprazole: Decreased nelfinavir concentrations and possible loss of therapeutic effect¹	Concomitant use with proton pump inhibitors not recommended¹
Ritonavir	Increased nelfinavir concentrations;¹ ⁸⁰ ⁸⁷ ⁹⁵ no change in ritonavir concentrations⁹⁵	Appropriate dosages for concomitant use with respect to safety and efficacy not established ¹
Saquinavir	Increased saquinavir concentrations and increased nelfinavir concentrations¹ ⁸⁰ ⁹⁵ Ritonavir-boosted saquinavir not studied¹⁵⁸	Manufacturer of nelfinavir states appropriate dosages for concomitant use with respect to safety and efficacy not established¹ Saquinavir 1.2 g twice daily with nelfinavir 1.25 g twice daily results in adequate plasma concentrations of both PIs¹⁵⁸
St. John’s wort (Hypericum perforatum)	Decreased nelfinavir concentrations; possible loss of virologic response and increased risk of nelfinavir resistance ⁹⁵ ¹⁶⁴ ¹⁶⁵	Concomitant use not recommended¹ ⁹⁵
Sildenafil	Increased sildenafil concentrations¹ ⁹⁵ ¹⁴⁸ ¹⁵⁷	Use caution and reduced sildenafil dosage (25 mg repeated no more frequently than every 48 hours);¹ ⁹⁵ closely monitor for adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)¹ ⁹⁵ ¹⁴⁸ ¹⁵⁷
Stavudine	Pharmacokinetic interactions unlikely¹ In vitro evidence of additive antiretroviral effects¹	Dosage adjustments not needed¹
Tadalafil	Increased tadalafil concentrations¹ ⁹⁵	Use caution and reduced tadalafil dosage (10 mg repeated no more frequently than every 72 hours); closely monitor for adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection);¹ some experts recommend initial dose of 5 mg and not maximum dosage of 10 mg once every 72 hours⁹⁵
Tenofovir	Pharmacokinetic interaction unlikely¹⁷⁶ In vitro evidence of synergistic antiretroviral effects¹
Tipranavir	Data not available to date⁹⁵	Concomitant use not recommended; appropriate dosage not established⁹⁵
Trazodone	Possible increased trazodone concentrations¹	Use with caution; consider using decreased trazodone dosage¹
Vardenafil	Possible increased vardenafil concentrations¹ ⁹⁵	Use caution and reduced vardenafil dosage (2.5 mg repeated no more frequently than every 72 hours); closely monitor for adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)¹ ⁹⁵
Zidovudine	Decreased zidovudine peak plasma concentrations and AUC¹ In vitro evidence of synergistic antiretroviral effects¹	Dosage adjustment not needed¹

Viracept Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract; peak plasma concentrations attained within 2–4 hours when administered with food.⁴ ⁸ ²⁰ ²¹ ⁸⁰

Nelfinavir 625-mg tablets are not bioequivalent to the 250-mg tablets; AUC 24% higher with the 625-mg tablets (given with food) compared with the 250-mg tablets (given with food).¹

Food

Presence of food in the GI tract substantially increases extent of absorption and decreases pharmacokinetic variability of the drug relative to the fasting state.¹ ²⁰ ⁸⁰ Peak plasma concentration and AUC reportedly are 2–5 times greater when administered with a meal (125–1000 kcal with 20–50% fat) rather than under fasting conditions.¹ ⁸⁰

Special Populations

Use in children associated with highly variable drug concentrations;¹ may be related to inconsistent food intake.¹

Plasma concentrations of nelfinavir not altered in individuals with mild hepatic impairment (Child-Pugh class A).¹ AUC increased 62% in individuals with moderate hepatic impairment (Child-Pugh class B).¹ Pharmacokinetics not investigated in individuals with severe hepatic impairment.¹

Distribution

Extent

Not fully characterized.¹

Not detected in CSF in adults.¹⁵⁰

Not known whether crosses the placenta or is distributed into human milk.¹

Plasma Protein Binding

98%.¹

Elimination

Metabolism

Metabolized by CYP3A and CYP2C19.¹ ⁸⁰

The major metabolite (M8) has in vitro antiviral activity similar to that of nelfinavir.¹

Elimination Route

Excreted principally in feces as unchanged drug and metabolites.¹

Removed by hemodialysis;⁵¹ does not appear to be removed by peritoneal dialysis.¹⁶⁰

Half-life

3.5–5 hours.¹ ⁸⁰

Special Populations

Nelfinavir clearance is 2–3 times greater in children 2–13 years of age than in adults (weight-adjusted basis).⁸⁰ ¹²⁴

Stability

Storage

Oral

Tablets

15–30°C.¹

Powder for Oral Suspension

15–30°C.¹

Actions and SpectrumActions

Pharmacologically related to other PIs (e.g., amprenavir, atazanavir, fosamprenavir, indinavir, lopinavir, ritonavir, saquinavir); differs structurally from these drugs and also differs pharmacologically and structurally from other currently available antiretrovirals.¹ ⁸⁰

Active against HIV-1 and HIV-2.¹ ⁷ ⁸ The major metabolite (M8) has antiviral activity similar to that of nelfinavir.¹

Inhibits replication of HIV-1 and HIV-2 by interfering with HIV protease.¹ ² ³ ⁴ ⁷ ⁹² ¹²⁰

HIV-1 with reduced susceptibility to nelfinavir have been selected in vitro and have emerged during therapy with the drug.¹ ⁷ ⁹ ⁸⁰

Varying degrees of cross-resistance occur among PIs; only limited data available to date regarding cross-resistance between nelfinavir and other PIs.¹ ⁴ ¹¹ ¹³ ¹⁴ ¹⁵ ¹⁹ ⁹³ ⁹⁴

Cross-resistance between nelfinavir and nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs) unlikely since the drugs have different target enzymes and mechanisms of action.¹

Advice to Patients

Critical nature of compliance with HIV therapy.¹ Importance of using nelfinavir in conjunction with other antiretrovirals—not for monotherapy.¹

Antiretroviral therapy is not a cure for HIV infection, and opportunistic infections still may occur.¹ HIV transmission via sexual contact or sharing needles is not prevented by antiretrovirals.¹

Importance of taking with food.¹

Importance of reading patient package insert from manufacturer.¹

Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.¹

Diarrhea, a frequent adverse effect, can be controlled with OTC drugs such as loperamide.¹

If using oral contraceptives, need for alternative or concomitant nonhormonal contraceptive measures¹ ⁹⁵

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products.¹

Importance of women informing clinicians 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.

Nelfinavir Mesylate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	For suspension	50 mg (of nelfinavir) per g	Viracept Oral Powder	Agouron
	Tablets, film-coated	250 mg (of nelfinavir)	Viracept	Agouron
		625 mg (of nelfinavir)	Viracept	Agouron

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Viracept 250MG Tablets (VIIV HEALTHCARE): 300/$716.02 or 900/$2110.06

Viracept 50MG/GM Powder (VIIV HEALTHCARE): 144/$72.99 or 432/$195.97

Disclaimer

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

References

1. Agouron Pharmaceuticals. Viracept (nelfinavir mesylate) tablets and oral powder prescribing information. La Jolla, CA; 2008 Sep.

2. Longer M, Shetty B, Zamansky I et al. Preformulation studies of a novel HIV protease inhibitor, AG1343. J Pharm Sci. 1995; 84:1090-3. [PubMed 8537887]

3. Kaldor SW, Kalish VJ, davies JF et al. Viracept (nelfinavir mesylate, AG13430: a potent orally bioavailable inhibitor of HIV-1 protease. J Med Chem. 1997; 40:3979-85. [PubMed 9397180]

4. Moyle G, Gazzard B. Current knowledge and future prospects for the use of HIV protease inhibitors. Drugs. 1996; 51:701-12. [PubMed 8861542]

5. Vella S. Rationale and experience with reverse transcriptase inhibitors and protease inhibitors. J Acquir Immune Defic Syndr Hum Retrovirol. 1995; 10(Suppl 1):S58-61.

6. .

7. Patick AK, Mo H, Markowitz M et al. Antiviral and resistance studies of AG1343, an orally bioavailable inhibitor of human immunodeficiency virus protease. Antimicrob Agents Chemother. 1996; 40:292-7. [PubMed 8834868]

8. Shetty BV, Kosa MB, Khalil DA et al. Preclinical pharmacokinetics and distribution to tissue of AG1343, an inhibitor of human immunodeficiency virus type 1 protease. Antimicrob Agents Chemother. 1996; 40:110-4. [PubMed 8787890]

9. Patick AK, Duran M, Cao Y et al. Genotypic and phenotypic characterization of human immunodeficiency virus type 1 variants isolated from patients treated with the protease inhibitor nelfinavir. Antimicrob Agents Chemother. 1998; 42:2637-44. [PubMed 9756769]

10. Lech WJ, Wang G, Yang YL et al. In vivo sequence diversity of the protease of human immunodeficiency virus type 1: presence of protease inhibitor-resistant variants in untreated subjects. J Virol. 1996; 70:2038-43. [PubMed 8627733]

11. Ridky T, Leis J. Development of drug resistance to HIV-1 protease inhibitors. J Biol Chem. 1995; 270:29621-3. [PubMed 8530341]

12. Montaner JSG, Hogg RS, O’Shaughnessy MV. Emerging international consensus for use of antiretroviral therapy. Lancet. 1997; 349:1042. [IDIS 383566] [PubMed 9107240]

13. Deeks SG, Smith M, Holodniy M