Penicillin V (phenoxymethyl penicillin) is a naturally derived antibiotic. It is primarily used for the treatment of group A beta-hemolytic streptococcal (GAS) pharyngitis (primary rheumatic fever prophylaxis) and tonsillitis and mild to moderate streptococcal and staphylococcal skin infections. Penicillin V is also used for pneumococcal prophylaxis in patients with anatomical or functional asplenia or bone marrow transplant recipients. The most common adverse reactions to oral penicillin are gastrointestinal-related and include nausea, vomiting, epigastric distress, and diarrhea.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-May be administered with meals; however, serum concentrations are slightly higher when given on an empty stomach.
Oral Liquid Formulations
Reconstitution
-Review the reconstitution instructions for the particular product and package size, as the amount of water required for reconstitution varies from manufacturer to manufacturer.
-Prior to reconstitution, tap the bottle several times to loosen the powder.
-Add approximately half of the total amount of water and shake well. Add the remaining water and shake well. Final concentration should be either 125 or 250 mg/5 mL depending on which bottle is used.
-Storage: Store under refrigeration for up to 14 days. Discard any unused portion 14 days after reconstitution.
Hypersensitivity reactions are among the most frequently reported adverse reactions to the penicillins. Penicillin allergy has been reported in up to 20% of patients; however, around 90% of reported allergies are incorrectly reported and patients lack penicillin-specific IgE antibodies. The actual prevalence of penicillin allergy is likely no greater than 5%. These adverse effects range from rash to anaphylactoid reactions including laryngeal edema and anaphylactic shock. Contact dermatitis and rash may occur in 4% to 8% of patients receiving penicillins and may be idiopathic in nature. Patients with a history of anaphylaxis to a beta-lactam antibiotic should not receive penicillin. Interstitial nephritis, a hypersensitivity reaction, with renal tubular necrosis and nephrotic syndrome has been reported with large doses of IV penicillin. Fever and eosinophilia may frequently be the only hypersensitivity reaction observed. Other dermatologic reactions related to allergic reactions include maculopapular rash, urticaria, and exfoliative dermatitis. Angioedema has also been reported with penicillins.
Oral penicillins have been associated with a serum sickness-like reaction (SSLR).
Reported adverse reactions to penicillin therapy include hematologic effects such as hemolytic anemia, leukopenia, and thrombocytopenia.
Penicillin antibiotics have been associated with acute generalized exanthematous pustulosis (AGEP). The nonfollicular, pustular, erythematous rash starts suddenly and is associated with a fever above 38 degrees C. Typically, the first episode of AGEP appears 2 to 3 weeks after exposure to the inciting drug; however, unintentional reexposure may cause a second episode within 2 days.
Gastrointestinal adverse events may occur in 2% to 5% of patients receiving penicillins. Nausea, vomiting, epigastric distress, diarrhea, and a black hairy tongue (tongue discoloration) are the most commonly reported gastrointestinal side effects of penicillin V. Diarrhea has been reported in 2% to 5% of patients receiving penicillins.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with penicillin V. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate.
Reported adverse reactions to penicillin therapy include peripheral neuropathy and nephropathy.
Penicillin V is contraindicated for use in patients with penicillin hypersensitivity. Penicillin V should also be used cautiously in patients with cephalosporin hypersensitivity or carbapenem hypersensitivity. These patients are more susceptible to cross-hypersensitivity reactions. Penicillin can cause a variety of hypersensitivity reactions ranging from mild rash to fatal anaphylaxis. Patients with allergies or allergic conditions including asthma may have a greater risk for hypersensitivity reactions to penicillins.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including penicillin V, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Use of penicillins in human pregnancy has not shown any evidence of harmful effects on the fetus. Animal data have also not demonstrated any evidence of impaired fertility or harmful fetal effects. However, there are no adequate and well-controlled studies during pregnancy showing conclusively that harmful effects of penicillins on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, penicillin V should be used during pregnancy only if clearly needed.
Penicillins are excreted in breast milk. Use caution when administering penicillin V during breast-feeding. Unless the child is allergic to penicillins, breast-feeding is generally safe during maternal penicillin V therapy. Breast milk concentrations range from 0.15 to 0.6 mcg/mL with a milk to plasma ratio of 0.51 to 0.87. Concentrations of penicillin V in breast milk were assessed in 12 patients receiving the drug for the treatment of mastitis and 4 healthy volunteers after a single oral dose of 1,320 mg. Based on the concentrations in breast milk, it was estimated that an exclusively breastfed child would receive between 20 and 90 mcg/kg/day of penicillin V. Of the 12 infants in the study exposed to penicillin V in breast milk, 3 had loose stools and 1 had a rash. One infant had blood in the stool, but blood in the stool had also occurred once prior to maternal penicillin use. Penicillins may cause diarrhea, candidiasis, and skin rash in breast-feeding infants and children. Monitor the child for potential effects.
Reported clinical experience with penicillin V has not identified differences in responses between geriatric and younger adult patients. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.
Administration of penicillin V may result in laboratory test interference. A false-positive reaction for glucose in the urine has been observed in patients receiving penicillins and using Benedict's solution, Fehling's solution, or Clinitest tablets for urine glucose testing. However, this reaction has not been observed with Tes-tape (glucose Enzymatic Test Strip, USP, Lilly) or Clinistix. Patients with diabetes who test their urine for glucose should use glucose tests based on enzymatic glucose oxidase reactions while on penicillin treatment.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Actinomyces israelii, Bacillus anthracis, Clostridium sp., Corynebacterium diphtheriae, Leptospira sp., Listeria monocytogenes, Neisseria gonorrhoeae, Staphylococcus sp., Streptobacillus moniliformis, Streptococcus dysgalactiae, Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Treponema pallidum, Viridans streptococci
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: Borrelia burgdorferi, Pasteurella multocida, Spirillum minus
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of group A beta-hemolytic streptococcal (GAS) pharyngitis (primary rheumatic fever prophylaxis) and tonsillitis:
-for the treatment of group A beta-hemolytic streptococcal (GAS) pharyngitis (primary rheumatic fever prophylaxis) and tonsillitis:
Oral dosage:
Adults: 500 mg PO 2 to 3 times daily or 250 mg PO 4 times daily for 10 days. The FDA-approved dose is 125 to 250 mg PO every 6 to 8 hours.
Children and Adolescents 12 to 17 years: 500 mg PO 2 to 3 times daily or 250 mg PO 4 times daily for 10 days. The FDA-approved dose is 125 to 250 mg PO every 6 to 8 hours.
Children 1 to 11 years weighing more than 27 kg*: 500 mg PO 2 to 3 times daily or 250 mg PO 3 to 4 times daily for 10 days.
Infants* and Children 1 to 11 years weighing 27 kg or less*: 250 mg PO 2 to 3 times daily for 10 days.
-for secondary prophylaxis of rheumatic fever or chorea:
Oral dosage:
Adults: 250 mg PO 2 times daily. Guidelines recommend secondary prophylaxis for 10 years or until age 40 years (whichever is longer) for patients who have experienced rheumatic fever with carditis and have residual heart disease (persistent valvular disease). For patients who have experienced rheumatic fever with carditis but have no residual heart disease, prophylaxis is recommended for 10 years or until age 21 years (whichever is longer). For patients who have experienced rheumatic fever without carditis, prophylaxis is recommended for 5 years or until age 21 years (whichever is longer).
Children and Adolescents 12 to 17 years: 250 mg PO 2 times daily. Guidelines recommend secondary prophylaxis for 10 years or until age 40 years (whichever is longer) for patients who have experienced rheumatic fever with carditis and have residual heart disease (persistent valvular disease). For patients who have experienced rheumatic fever with carditis but have no residual heart disease, prophylaxis is recommended for 10 years or until age 21 years (whichever is longer). For patients who have experienced rheumatic fever without carditis, prophylaxis is recommended for 5 years or until age 21 years (whichever is longer).
Infants and Children 1 to 11 years*: 250 mg PO 2 times daily. Guidelines recommend secondary prophylaxis for 10 years or until age 40 years (whichever is longer) for patients who have experienced rheumatic fever with carditis and have residual heart disease (persistent valvular disease). For patients who have experienced rheumatic fever with carditis but have no residual heart disease, prophylaxis is recommended for 10 years or until age 21 years (whichever is longer). For patients who have experienced rheumatic fever without carditis, prophylaxis is recommended for 5 years or until age 21 years (whichever is longer).
For the treatment of skin and skin structure infections, including cellulitis, erysipelas, erysipeloid, and animal bite wounds:
-for the treatment of nonpurulent skin infections, such as cellulitis and erysipelas, due to methicillin-sensitive S. aureus:
Oral dosage:
Adults: 250 to 500 mg PO every 6 to 8 hours for 5 to 14 days.
Children and Adolescents 12 to 17 years: 250 to 500 mg PO every 6 to 8 hours for 5 to 14 days.
Infants and Children 1 to 11 years*: 25 to 50 mg/kg/day (Max: 2 g/day) PO divided every 6 hours for 5 to 14 days.
-for the treatment of nonpurulent skin infections, such as cellulitis and erysipelas, due to Streptococcus:
Oral dosage:
Adults: 250 to 500 mg PO every 6 hours for 5 to 14 days. The FDA-approved dosage is 125 to 250 mg PO every 6 to 8 hours for 10 days.
Children and Adolescents 12 to 17 years: 250 to 500 mg PO every 6 hours for 5 to 14 days. The FDA-approved dosage is 125 to 250 mg PO every 6 to 8 hours for 10 days.
Infants and Children 1 to 11 years*: 25 to 50 mg/kg/day (Max: 2 g/day) PO divided every 6 hours for 5 to 14 days.
-for the treatment of erysipeloid:
Oral dosage:
Adults: 500 mg PO every 6 hours for 7 to 10 days.
-for the treatment of animal bite wounds:
Oral dosage:
Adults: 500 mg PO every 6 hours plus dicloxacillin. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.
For the treatment of scarlet fever due to Streptococcus pyogenes (group A beta-hemolytic streptococci):
Oral dosage:
Adults: 125 to 250 mg PO every 6 to 8 hours for 10 days.
Children and Adolescents 12 to 17 years: 125 to 250 mg PO every 6 to 8 hours for 10 days.
For the treatment of actinomycosis*:
Oral dosage:
Adults: 250 mg to 1 g PO every 6 hours for 6 to 12 months after IV therapy. Shorter courses may be appropriate for less extensive infections.
For the treatment of necrotizing ulcerative gingivitis (fusospirochetosis or Vincent's infection):
Oral dosage:
Adults: 250 to 500 mg PO every 6 to 8 hours for mild to moderate infections.
Children and Adolescents 12 to 17 years: 250 to 500 mg PO every 6 to 8 hours for mild to moderate infections.
For bacterial endocarditis prophylaxis:
Oral dosage:
Adults: Not recommended by guidelines. The FDA-approved dosage is 2 g PO given 60 minutes prior to procedure then 1 g PO 6 hours later.
Children and Adolescents 12 to 17 years weighing more than 27 kg: Not recommended by guidelines. The FDA-approved dosage is 2 g PO given 60 minutes prior to procedure then 1 g PO 6 hours later.
Children and Adolescents 12 to 17 years weighing 27 kg or less: Not recommended by guidelines. The FDA-approved dosage is 1 g PO given 60 minutes prior to procedure then 500 mg PO 6 hours later.
For the treatment of rat-bite fever* as step-down therapy:
Oral dosage:
Adults: 500 mg PO every 6 hours for 7 days after an initial treatment course with intravenous penicillin G.
Infants, Children, and Adolescents: 25 to 50 mg/kg/day (Max: 2 g/day) PO divided every 6 hours for 7 days after an initial treatment course with intravenous penicillin G.
For pneumococcal prophylaxis* in bone marrow transplant recipients with chronic graft-versus-host disease (GVHD) and persons with functional or anatomic asplenia, including those with sickle cell disease:
-for pneumococcal prophylaxis* in bone marrow transplant recipients, including stem-cell transplant recipients, with chronic graft-versus-host disease (GVHD):
Oral dosage:
Adults: 250 mg PO twice daily beginning from the time of marrow engraftment and continuing for 180 days posttransplant or for the duration of immunosuppressive therapy. Guidelines recommend prophylaxis against encapsulated organisms (including S. pneumoniae) in patients with chronic GVHD for as long as active GVHD treatment is administered.
-for pneumococcal prophylaxis* in persons with functional or anatomic asplenia, including those with sickle cell disease:
Oral dosage:
Adults: 500 mg PO once or twice daily for at least 1 to 2 years post-splenectomy. Lifelong prophylaxis may be warranted in certain populations.
Children and Adolescents 6 to 17 years: 250 mg PO twice daily for at least 1 to 2 years post-splenectomy. Lifelong prophylaxis may be warranted in certain populations.
Children 3 to 5 years: 250 mg PO twice daily until at least age 5 years and at least 1 to 2 years post-splenectomy. Lifelong prophylaxis may be warranted in certain populations.
Infants and Children 1 month to 2 years: 125 mg PO twice daily until at least age 5 years. Lifelong prophylaxis may be warranted in certain populations.
For penicillin desensitization* of patients with a positive penicillin allergy skin test who require penicillin therapy:
NOTE: Fourteen oral doses are to be administered before any parenteral administration. Oral doses listed are further diluted in approximately 30 mL of water and administered every 15 minutes. The total time elapsed for the oral desensitization protocol is 3 hours and 45 minutes with a cumulative dose of 1.3 million units. After the administration of the 14th oral dose of the desensitization protocol is complete, the patient should be observed for 30 minutes before beginning parenteral therapy. Patients must be maintained on penicillin continuously for the duration of the course of therapy.
-for doses 1 to 7 of oral desensitization protocol:
Oral dosage (as penicillin V solution diluted to 1,000 units/mL):
Adults: Dose 1: 100 units PO; Dose 2: 200 units PO; Dose 3: 400 units PO; Dose 4: 800 units PO; Dose 5: 1,600 units PO; Dose 6: 3,200 units PO; Dose 7: 6,400 units PO.
-for doses 8 to 10 of oral desensitization protocol:
Oral dosage (as penicillin V solution diluted to 10,000 units/mL):
Adults: Dose 8: 12,000 units PO; Dose 9: 24,000 units PO; Dose 10: 48,000 units PO.
-for doses 11 to 14 of oral desensitization protocol:
Oral dosage (as penicillin V solution diluted to 80,000 units/mL):
Adults: Dose 11: 80,000 units PO; Dose 12: 160,000 units PO; Dose 13: 320,000 units PO; Dose 14: 640,000 units PO.
For the treatment of acute otitis media:
Oral dosage:
Adults: 250 to 500 mg PO every 6 hours until the patient is afebrile for at least 2 days for S. pneumoniae infections and 125 to 250 mg PO every 6 to 8 hours for 10 days for infections due to other Streptococcus sp.
Children and Adolescents 12 to 17 years: Penicillin V is not recommended for the treatment of acute otitis media by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 250 to 500 mg PO every 6 hours until the patient is afebrile for at least 2 days for S. pneumoniae infections and 125 to 250 mg PO every 6 to 8 hours for 10 days for infections due to other Streptococcus sp.
For the treatment of anthrax*:
-for the treatment of cutaneous anthrax* without aerosol exposure or signs and symptoms of meningitis:
Oral dosage:
Adults: 500 mg PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met.
Infants, Children, and Adolescents: 12.5 to 18.7 mg/kg/dose (Max 500 mg/dose) PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met.
Neonates 37 weeks gestation and older and 7 days and older: 25 mg/kg/dose PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met.
Neonates 37 weeks gestation and older and 0 to 6 days: 25 mg/kg/dose PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met.
Neonates 32 to 36 weeks gestation and 7 days and older: 25 mg/kg/dose PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met.
Neonates 32 to 36 weeks gestation and 0 to 6 days: 25 mg/kg/dose PO every 12 hours for 7 to 10 days or until clinical criteria for stability are met.
-for the treatment of cutaneous anthrax* with aerosol exposure and without signs and symptoms of meningitis:
Oral dosage:
Adults: 500 mg PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 42- to 60-day total treatment course depending on vaccine status and immunocompetence.
Infants, Children, and Adolescents: 12.5 to 18.7 mg/kg/dose (Max 500 mg/dose) PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Neonates 37 weeks gestation and older and 7 days and older: 25 mg/kg/dose PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Neonates 37 weeks gestation and older and 0 to 6 days: 25 mg/kg/dose PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Neonates 32 to 36 weeks gestation and 7 days and older: 25 mg/kg/dose PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Neonates 32 to 36 weeks gestation and 0 to 6 days: 25 mg/kg/dose PO every 12 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
For postexposure anthrax prophylaxis*:
-for postexposure anthrax prophylaxis after nonaerosol exposure (cutaneous or ingestion):
Oral dosage:
Adults: 500 mg PO every 6 hours for 7 days after exposure.
Infants, Children, and Adolescents: 12.5 to 18.7 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours for 7 days after exposure.
Neonates 37 weeks gestation and older and 7 days and older: 25 mg/kg/dose PO every 6 hours every for 7 days after exposure.
Neonates 37 weeks gestation and older and 0 to 6 days: 25 mg/kg/dose PO every 8 hours for 7 days after exposure.
Neonates 32 to 36 weeks gestation and 7 days and older: 25 mg/kg/dose PO every 8 hours for 7 days after exposure.
Neonates 32 to 36 weeks gestation and 0 to 6 days: 25 mg/kg/dose PO every 12 hours for 7 days after exposure.
-for postexposure anthrax prophylaxis* after aerosol exposure:
Oral dosage:
Adults 66 years and older: 500 mg PO every 6 hours for 60 days after exposure.
Adults 18 to 65 years: 500 mg PO every 6 hours for 60 days after exposure. For immunocompetent, nonpregnant persons who received the anthrax vaccine, may decrease duration to 42 days after first antibiotic dose or 2 weeks after the last vaccine dose, whichever occurs later.
Infants, Children, and Adolescents: 12.5 to 18.7 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours for 60 days after exposure.
Neonates 37 weeks gestation and older and 7 days and older: 25 mg/kg/dose PO every 6 hours every for 60 days after exposure.
Neonates 37 weeks gestation and older and 0 to 6 days: 25 mg/kg/dose PO every 8 hours for 60 days after exposure.
Neonates 32 to 36 weeks gestation and 7 days and older: 25 mg/kg/dose PO every 8 hours for 60 days after exposure.
Neonates 32 to 36 weeks gestation and 0 to 6 days: 25 mg/kg/dose PO every 12 hours for 7 days after exposure.
For group A streptococci chronic pharyngeal carriage eradication* in combination with oral rifampin:
Oral dosage:
Adults: 50 mg/kg/day (Max: 2 g/day) PO divided every 6 hours for 10 days. Most chronic streptococcal carriers do not need antimicrobial therapy. Treatment may be considered during a community outbreak of acute rheumatic fever, acute poststreptococcal glomerulonephritis or invasive group A streptococcal (GAS) infection; during an outbreak of GAS pharyngitis in a closed or partially closed community; in the presence of a family or personal history of acute rheumatic fever; in a family with excessive anxiety about GAS infections; or when tonsillectomy is being considered only because of carriage.
Infants, Children, and Adolescents: 50 mg/kg/day (Max: 2 g/day) PO divided every 6 hours for 10 days. Most chronic streptococcal carriers do not need antimicrobial therapy. Treatment may be considered during a community outbreak of acute rheumatic fever, acute poststreptococcal glomerulonephritis or invasive group A streptococcal (GAS) infection; during an outbreak of GAS pharyngitis in a closed or partially closed community; in the presence of a family or personal history of acute rheumatic fever; in a family with excessive anxiety about GAS infections; or when tonsillectomy is being considered only because of carriage.
For the adjunctive treatment of diphtheria*:
Oral dosage:
Adults: 50 mg/kg/day (Max: 2 g/day) PO divided every 6 hours for 14 days as an adjunct to diphtheria antitoxin.
Infants, Children, and Adolescents: 50 mg/kg/day (Max: 2 g/day) PO divided every 6 hours for 14 days as an adjunct to diphtheria antitoxin.
For the treatment of community-acquired pneumonia*:
Oral dosage:
Infants, Children, and Adolescents 4 months to 17 years: 50 to 75 mg/kg/day (Max: 2 g/day) PO divided every 6 to 8 hours for 5 to 7 days. Penicillin V is recommended as a preferred treatment for mild infections due to Streptococcus pyogenes (group A beta-hemolytic streptococci) or as step-down therapy.
For bacterial infection prophylaxis* after tooth avulsion:
Oral dosage:
Adults: 500 mg PO every 6 hours for 7 days.
Children and Adolescents: 50 mg/kg/day (Max 2 g/day) divided every 6 hours for 7 days.
For long-term suppressive therapy of orthopedic device-related infection* (prosthetic joint infections*):
Oral dosage:
Adults: 500 mg PO every 6 to 12 hours.
Maximum Dosage Limits:
-Adults
2 g/day PO.
-Geriatric
2 g/day PO.
-Adolescents
2 g/day PO.
-Children
12 years: 2 g/day PO.
1 to 11 years: Safety and efficacy have not been established; however, doses up to 75 mg/kg/day (Max: 2 g/day) PO have been used off-label.
-Infants
Safety and efficacy have not been established; however, doses up to 75 mg/kg/day PO have been used off-label.
-Neonates
Safety and efficacy have not been established; however, doses up to 75 mg/kg/day PO have been used off-label.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; however, only about 25% of the dose is absorbed orally. Guidelines suggest no dosage adjustment is necessary in adult patients.
Intermittent hemodialysis
Dose after dialysis on dialysis days.
*non-FDA-approved indication
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Dipyridamole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Omeprazole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Oxycodone: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Caffeine; Sodium Benzoate: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Choline Salicylate; Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
Demeclocycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Desogestrel; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Dichlorphenamide: (Moderate) Use dichlorphenamide and penicillin V together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including penicillin V. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Dienogest; Estradiol valerate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Digoxin: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Doxycycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Drospirenone: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estetrol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Levonorgestrel: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norethindrone: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norgestimate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethacrynic Acid: (Minor) Ethacrynic acid may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Ethinyl Estradiol; Norelgestromin: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norgestrel: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Etonogestrel; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Furosemide: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Indomethacin: (Minor) Indomethacin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Leuprolide; Norethindrone: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Mafenide: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
Methotrexate: (Major) Avoid concomitant use of methotrexate with penicillins due to the risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions.
Minocycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Neomycin: (Minor) Oral neomycin has been shown to reduce the bioavailability of oral penicillin V.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestimate; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestrel: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Omadacycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Oral Contraceptives: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Probenecid: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Probenecid; Colchicine: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Salsalate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites or could displace other highly protein-bound drugs such as penicillins. An enhanced effect of the displaced drug may occur.
Sarecycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Sodium Benzoate; Sodium Phenylacetate: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Sulfadiazine: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfasalazine: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfonamides: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Tetracycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Tetracyclines: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Typhoid Vaccine: (Major) Antibiotics which possess bacterial activity against salmonella typhi organisms may interfere with the immunological response to the live typhoid vaccine. Allow 24 hours or more to elapse between the administration of the last dose of the antibiotic and the live typhoid vaccine.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
Penicillin V is a beta-lactam antibacterial antibiotic. It is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinsic activity of penicillin V, as well as the other penicillins, against a particular organism depends on its ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, penicillin V's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor.
Beta-lactams exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism. This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval.
The susceptibility interpretive criteria for penicillin are delineated by pathogen. The MICs are defined for non-CSF isolates of S. pneumoniae as susceptible at 0.06 mcg/mL or less, intermediate at 0.12 to 1 mcg/mL, and resistant at 2 mcg/mL or more. The MICs are defined for beta-hemolytic Streptococcus sp. as susceptible at 0.12 mcg/mL or less. The MICs are defined for Enterococcus sp. as susceptible at 8 mcg/mL or less and resistant at 16 mcg/mL or more. The MICs are defined for Staphylococcus sp. as susceptible at 0.12 mcg/mL or less and resistant at 0.25 mcg/mL or more. The MICs are defined for Streptococcus sp. Viridans group as susceptible at 0.12 mcg/mL or less, intermediate at 0.25 to 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for N. gonorrhoeae as susceptible at 0.06 mcg/mL or less, intermediate at 0.12 to 1 mcg/mL, and resistant at 2 mcg/mL or more. The MICs are defined for N. meningitidis as susceptible at 0.6 mcg/mL or less, intermediate at 0.12 to 0.25 mcg/mL, and resistant at 0.5 mcg/mL or more. The MICs are defined for anaerobes as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more. The MICs are defined for Abiotrophia sp., Granulicatella sp., Aerococcus sp., Corynebacterium sp., Gemella sp., and R. mucilaginosa as susceptible at 0.12 mcg/mL or less, intermediate at 0.25 mcg/mL to 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for Leuconostoc sp., Lactobacillus sp., and Pediococcus sp. as susceptible at 8 mcg/mL or less. The MICs are defined for L. monocytogenes as susceptible at 2 mcg/mL or less. The MICs are defined for Lactococcus sp., Aggregatibacter sp., Cardiobacter sp., E. corrodens, and Kingella sp. as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for B. anthracis as susceptible at 0.5 mcg/mL or less and resistant at 1 mcg/mL or more. The MICs are defined for Micrococcus sp. and Bacillus sp. (excluding B. anthracis) as susceptible at 0.12 mcg/mL or less and resistant at 0.25 mcg/mL or more. The MICs are defined for E. rhusiopathiae as susceptible at 0.12 mcg/mL or less. The MICs are defined for Pasteurella sp. as susceptible at 0.5 mcg/mL or less.
Penicillin V (phenoxymethyl penicillin) is administered orally. Approximately 75% to 89% of the circulating drug is protein-bound. Tissue concentrations are highest in the kidneys with lesser amounts in the liver, skin, and intestines. Small amounts are found in all other body tissues and the CSF. Penicillins are minimally metabolized and are primarily excreted by the kidneys through glomerular filtration and tubular secretion.
Affected cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Oral Route
Penicillin V is absorbed from the GI tract and shows greater acid stability than penicillin G (benzyl penicillin) because the phenoxymethyl group provides resistance to gastric acid breakdown. It is absorbed in the upper part of the small bowel and produces peak serum levels within 60 minutes after the dose. Only about 25% of the dose is absorbed. Serum concentrations are slightly higher when administered on an empty stomach.
-Special Populations
Renal Impairment
The elimination half-life of penicillin V increases as renal function declines.
Pediatrics
Neonates and Infants
Elimination of penicillin V may be delayed in neonates and young infants due to decreased renal function as compared to older patients.