Ospen suspension

Dosing: Pediatric

General dosing, susceptible infections:

Infants and Children <12 years: Mild to moderate infection: Oral: 25 to 75 mg/kg/day in divided doses every 6 to 8 hours (maximum daily dose: 2,000 mg/day) (Red Book[AAP 2015])

Children ≥12 years and Adolescents: Oral:

Manufacturer’s labeling (fixed dosing): 125 to 500 mg every 6 to 8 hours

Alternate dosing (weight-based): Mild to moderate infection: 25 to 75 mg/kg/day in divided doses every 6 to 8 hours (maximum daily dose: 2,000 mg/day [Red Book(AAP 2015)])

Indication-specific dosing:

Anthrax (cutaneous), community-acquired (off-label use): Infants, Children, and Adolescents: Oral: 25 to 50 mg/kg/day in divided doses 2 or 4 times daily; maximum single dose: 500 mg (Stevens 2005)

Fusospirochetosis (Vincent infection), mild to moderately severe infections: Children ≥12 years and Adolescents: Oral: Refer to adult dosing.

Tonsillopharyngitis; Group A streptococcal infection, treatment and primary prevention of rheumatic fever:

Acute treatment (Gerber 2009; Shulman 2012; WHO 2004):

Children ≤27 kg: Oral: 250 mg 2 to 3 times daily for 10 days

Children >27 kg and Adolescents: Oral: 500 mg 2 to 3 times daily for 10 days; in adolescents, 250 mg 4 times daily has also been suggested

Chronic carrier treatment (Group A streptococci) (off-label use): Children and Adolescents: 50 mg/kg/day in 4 divided doses for 10 days in combination with oral rifampin; maximum daily dose: 2,000 mg/day (Shulman 2012)

Recurrent rheumatic fever, prophylaxis (off-label): Children and Adolescents: 250 mg twice daily (Gerber 2009)

Pneumococcal infection prophylaxis for anatomic or functional asplenia (eg, sickle cell disease [SCD]) (off-label use) (AAP 2002; Kavanagh 2011; NHLBI 2014):

Infants (as soon as SCD diagnosed or asplenic) and Children <3 years: Oral: 125 mg twice daily

Children ≥3 years: Oral: 250 mg twice daily; the decision to discontinue penicillin prophylaxis after 5 years of age in children who have not experienced invasive pneumococcal infection and have received recommended pneumococcal immunizations is patient and clinician dependent

Pneumonia, community-acquired; Group A Streptococcus, mild infection or step-down therapy (off-label use): Infants ≥3 months, Children, and Adolescents: Oral: 50 to 75 mg/kg/day in 3 to 4 divided doses (Bradley 2011); maximum daily dose: 2,000 mg/day

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in manufacturer’s labeling. Use with caution; excretion is prolonged in patients with renal impairment.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer’s labeling.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Oral:

Generic: 125 mg/5 mL (100 mL, 200 mL); 250 mg/5 mL (100 mL, 200 mL)

Tablet, Oral:

Generic: 250 mg, 500 mg

Generic Equivalent Available (US)

Yes

Administration

Oral: Administer around-the-clock to promote less variation in peak and trough serum levels. Take on an empty stomach 1 hour before or 2 hours after meals, to enhance absorption.

Use

Fusospirochetosis (Vincent gingivitis and pharyngitis): Treatment of fusospirochetosis (Vincent gingivitis and pharyngitis), in conjunction with dental care for infections involving gum tissue.

Pneumococcal infections: Treatment of mild to moderately severe pneumococcal respiratory tract infections, including otitis media.

Rheumatic fever and/or chorea prophylaxis: Prophylaxis (chronic, secondary) of rheumatic fever and/or chorea.

Staphylococcal infections (penicillin G-sensitive): Treatment of mild infections of the skin and soft tissues.

Streptococcal infections (without bacteremia): Treatment of mild to moderate streptococcal infections of the upper respiratory tract, scarlet fever, and mild erysipelas.

Use: Off-Label

Actinomycosis; Bite wounds (animal); Chronic antimicrobial suppression of prosthetic joint infection; Cutaneous anthrax; Cutaneous erysipeloid; GAS chronic carrier; Pneumococcal prophylaxis in asplenia/sickle cell; Pneumonia, community-acquired (children)

Medication Safety Issues

Sound-alike/look-alike issues:

Penicillin may be confused with penicillamine

Penicillin V potassium may be confused with penicillin G potassium

Adverse Reactions

>10%: Gastrointestinal: Melanoglossia, mild diarrhea, nausea, oral candidiasis, vomiting

<1%: Acute interstitial nephritis, anaphylaxis, convulsions, exfoliative dermatitis, fever, hemolytic anemia, hypersensitivity reaction, positive direct Coombs test, serum-sickness like reaction

Contraindications

Hypersensitivity to penicillin or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactic/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity or history of sensitivity to multiple allergens.). Use with caution in asthmatic patients. If a serious reaction occurs, treatment with supportive care measures and airway protection should be instituted immediately.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: Use with caution in patients with severe renal impairment.

• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.

Concurrent drug therapy related issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

Other warnings/precautions:

• Prolonged use: Extended duration of therapy or use associated with high serum concentrations (eg, in renal insufficiency) may be associated with an increased risk for some adverse reactions (neutropenia, hemolytic anemia, serum sickness).

Metabolism/Transport Effects

None known.

Drug Interactions

(For additional information: Launch drug interactions program)

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Risk X: Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Risk C: Monitor therapy

Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy

Probenecid: May increase the serum concentration of Penicillins. Management: Avoid the routine use of penicillins and probenecid, but this combination may be used advantageously in select cases with careful monitoring. Monitor for toxic effects of penicillins if probenecid is initiated or the dose is increased. Risk D: Consider therapy modification

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Risk D: Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Food Interactions

Food decreases drug absorption rate; decreases drug serum concentration. Management: Take on an empty stomach 1 hour before or 2 hours after meals around-the-clock to promote less variation in peak and trough serum levels.

Pregnancy Implications

Penicillin crosses the placenta. Maternal use of penicillins has generally not resulted in an increased risk of adverse fetal effects. Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of penicillin V may be altered in the second and third trimester (Heikkilä 1993). If treatment for the management of Bacillus anthracis is needed in pregnant women, other agents are preferred (Meaney-Delman 2014)

Breast-Feeding Considerations

Penicillin V is excreted into breast milk and may be detected in the urine of some breast-feeding infants. Loose stools and rash have been reported in nursing infants (Matheson 1988).

Monitoring Parameters

Periodic renal and hematologic function tests during prolonged therapy; monitor for signs of anaphylaxis during first dose

Mechanism of Action

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Pharmacodynamics/Kinetics

Protein binding, plasma: 80%

Excretion: Urine (as unchanged drug and metabolites)

• Twitter
• Facebook
• Google
• Tumblr
• Pinterest