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  • CLASSES

    Penicillin and Beta-Lactamase Inhibitor Combination Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Ticarcillin is a parenteral, semisynthetic extended-spectrum penicillin; clavulanic acid is a beta-lactamase inhibitor; combination extends the spectrum of ticarcillin to include many beta-lactamase-producing organisms.

    COMMON BRAND NAMES

    Timentin

    DOSAGE & INDICATIONS

    For the treatment of lower respiratory tract infections, including pneumonia.
    Intravenous dosage
    Adults weighing 60 kg or more

    3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) IV every 4 to 6 hours.

    Adults weighing less than 60 kg

    200 to 300 mg/kg/day (ticarcillin component) IV in divided doses every 4 to 6 hours.

    Infants 3 months and older, Children, and Adolescents

    50 mg/kg/dose (ticarcillin component) IV every 6 hours (Max: 3 g ticarcillin/dose [3.1 g ticarcillin; clavulanate]) for mild to moderate infections and 50 mg/kg/dose (ticarcillin component) IV every 4 hours (Max: 3 g ticarcillin/dose) for severe infections.

    Infants 1 to 2 months†

    50 mg/kg/dose IV (ticarcillin component) administered every 6 hours for moderate infections and every 4 hours for severe infections has been recommended by the American Academy of Pediatrics (AAP). Based on pharmacokinetic/pharmacodynamic data, a dose of approximately 80 mg/kg/dose every 8 hours has been suggested to be sufficient for the majority of infections.

    Term Neonates†

    75 mg/kg/dose (ticarcillin component) IV every 12 hours for neonates 7 days postnatal age or younger and 75 mg/kg/dose (ticarcillin component) IV every 8 hours for neonates 8 to 28 days postnatal age is recommended by the American Academy of Pediatrics (AAP). Doses of 80 to 100 mg/kg/dose (ticarcillin component) IV every 8 hours have also been reported.

    Premature Neonates†

    50 mg/kg/dose (ticarcillin component) IV every 6 hours has been suggested. Other studies have used 80 to 100 mg/kg/dose (ticarcillin component) IV every 12 hours. The American Academy of Pediatrics (AAP) recommends 75 mg/kg/dose (ticarcillin component) IV every 12 hours for neonates 7 days postnatal age or younger and 75 mg/kg/dose IV every 8 hours for neonates 8 to 28 days postnatal age.

    For the treatment of moderate to severe infection including bacteremia, sepsis, skin and skin structure infections, pericarditis†, intraabdominal infections (e.g., peritonitis), urinary tract infection (UTI), bone and joint infections, gynecologic infections (e.g., endometritis) due to susceptible bacteria.
    Intravenous dosage
    Adults weighing 60 kg or more

    3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) IV every 4 to 6 hours. For mild to moderate gynecological infections, 200 mg/kg/day (ticarcillin component) IV in divided doses every 6 hours. For severe gynecological infections, 300 mg/kg/day (ticarcillin component) IV in divided doses every 4 hours.

    Adults weighing less than 60 kg

    200 to 300 mg/kg/day (ticarcillin component) IV in divided doses every 4 to 6 hours. For mild to moderate gynecological infections, 200 mg/kg/day (ticarcillin component) IV in divided doses every 6 hours. For severe gynecological infections, 300 mg/kg/day (ticarcillin component) IV in divided doses every 4 hours.

    Children and Adolescents weighing 60 kg or more

    For mild to moderate infections, 3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) IV every 6 hours. For severe infections 3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) IV every 4 hours.

    Infants 3 months and older, Children, and Adolescents weighing less than 60 kg

    For mild to moderate infections, 200 mg/kg/day (ticarcillin component) IV in divided doses every 6 hours. For severe infections, 300 mg/kg/day (ticarcillin component) IV in divided doses every 4 hours.

    Infants 1 to 2 months†

    50 mg/kg/dose IV (based on ticarcillin component) every 6 hours for moderate infections and every 4 hours for severe infections has been recommended by the American Academy of Pediatrics (AAP). Based on pharmacokinetic/pharmacodynamic data, a dose of approximately 80 mg/kg/dose every 8 hours has been suggested to be sufficient for the majority of infections.

    Term Neonates†

    75 mg/kg/dose IV every 12 hours for neonates 7 days postnatal age or younger and 75 mg/kg/dose IV every 8 hours for neonates 8 to 28 days postnatal age is recommended by the American Academy of Pediatrics (AAP). Doses of 80 to 100 mg/kg/dose IV every 8 hours have also been reported.

    Premature Neonates†

    50 mg/kg/dose IV every 6 hours has been suggested. Other studies have used 80 to 100 mg/kg/dose IV every 12 hours. The American Academy of Pediatrics (AAP) recommends 75 mg/kg/dose IV every 12 hours for neonates 7 days postnatal age or younger and 75 mg/kg/dose IV every 8 hours for neonates 8 to 28 days postnatal age.

    For the treatment of acute pulmonary exacerbations† in patients with cystic fibrosis†.
    For the treatment of of acute pulmonary exacerbations† in pediatric patients with cystic fibrosis†.
    Intravenous dosage
    Infants, Children, and Adolescents

    400—750 mg/kg/day (ticarcillin component) IV divided every 6 hours (Max: 24—30 g ticarcillin/day). High doses of ticarcillin; clavulanic acid have been safely used for pulmonary exacerbations in pediatric patients with cystic fibrosis (CF) and are recommended by the CF Foundation. Higher than standard doses have been shown to be necessary in CF patients due to lower ticarcillin concentrations and a faster elimination rate. Doses as high as 500—750 mg/kg/day (ticarcillin component) IV divided every 6 hours (Max: 30 g ticarcillin/day) are recommended by the European Consensus guidelines for acute pulmonary exacerbations in CF patients.

    For the empiric treatment of febrile neutropenia†.
    For the treatment of febrile neutropenia in adults.
    Intravenous dosage
    Adults weighing 60 kg or more

    3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) IV every 6 to 8 hours. An antipseudomonal beta-lactam is recommended by guidelines as first line therapy in neutropenic adults. The FDA-approved dosage for other labeled indications is 3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) IV every 4 to 6 hours.

    Adults weighing less than 60 kg

    Doses of 3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) IV every 6 to 8 hours have been studied. An antipseudomonal beta-lactam is recommended by guidelines as first line therapy in neutropenic adults. The FDA-approved dosage for other labeled indications is 200 to 300 mg/kg/day (ticarcillin component) IV in divided doses every 4 to 6 hours.

    For the treatment of febrile neutropenia in pediatric patients.
    Intravenous dosage
    Infants, Children, and Adolescents

    250 to 300 mg/kg/day (ticarcillin component) IV divided every 6 to 8 hours (maximum dosage, 3 g ticarcillin component per dose). In clinical studies of pediatric patients with febrile neutropenia, success rates for ticarcillin; clavulanic acid (alone or in combination with an aminoglycoside) have ranged from 71% to 88%. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, and for centers with high rates of resistant pathogens.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    60 kg and more: 18.6 g/day (18 g ticarcillin and 0.6 g clavulanic acid) IV for most indications; doses up to 750 mg/kg/day (ticarcillin component) IV (Max: 30 g/day ticarcillin) have been used off-label for pulmonary infections in patients with cystic fibrosis.
    less than 60 kg: 300 mg/kg/day (ticarcillin component) IV for most indications (Max: 18 g/day ticarcillin); doses up to 750 mg/kg/day (ticarcillin component) IV (Max: 30 g/day ticarcillin) have been used off-label for pulmonary infections in patients with cystic fibrosis.

    Geriatric

    60 kg or more: 18.6 g/day (18 g ticarcillin and 0.6 g clavulanic acid) IV for most indications; doses up to 750 mg/kg/day (ticarcillin component) IV (Max: 30 g/day ticarcillin) have been used off-label for pulmonary infections in patients with cystic fibrosis.
    less than 60 kg: 300 mg/kg/day (ticarcillin component) IV for most indications (Max: 18 g/day ticarcillin); doses up to 750 mg/kg/day (ticarcillin component) IV (Max: 30 g/day ticarcillin) have been used off-label for pulmonary infections in patients with cystic fibrosis.

    Adolescents

    300 mg/kg/day (ticarcillin component) IV is the FDA-approved dosage (Max: 18 g/day ticarcillin [18.6 g ticarcillin; clavulanic acid]); however, doses up to 750 mg/kg/day (ticarcillin component) IV (Max: 30 g/day ticarcillin) have been used off-label for pulmonary infections in patients with cystic fibrosis.

    Children

    300 mg/kg/day (ticarcillin component) IV for most indications (Max: 18 g/day ticarcillin [18.6 g ticarcillin; clavulanic acid]); doses up to 750 mg/kg/day IV (Max: 30 g/day ticarcillin) have been used off-label for pulmonary infections in patients with cystic fibrosis.

    Infants

    3 months and older: 300 mg/kg/day (ticarcillin component) IV for most indications; doses up to 750 mg/kg/day (ticarcillin component) IV have been used off-label for pulmonary infections in patients with cystic fibrosis.
    younger than 3 months: Safety and efficacy have not been established; however, doses up to 300 mg/kg/day (ticarcillin component) IV for most indications and up to 750 mg/kg/day (ticarcillin component) IV for pulmonary infections in patients with cystic fibrosis have been used off-label.

    Neonates

    Term Neonates: Safety and efficacy have not been established; however, doses up to 300 mg/kg/day (ticarcillin component) IV have been used off-label.
    Premature Neonates: Safety and efficacy have not been established; however, doses up to 225 mg/kg/day (ticarcillin component) IV have been used off-label.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No specific dosage adjustment recommendations are available. Ticarcillin is not appreciably metabolized by the liver.

    Renal Impairment

    Adults
    CrCl more than 60 mL/min: No dosage adjustment needed.
    CrCl 30 to 60 mL/min: Loading dose of 3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) IV then, give 2 g (1.94 g ticarcillin and 0.06 g clavulanic acid) IV every 4 hours.
    CrCl 10 to 30 mL/min: Loading dose of 3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) IV then, give 2 g (1.94 g ticarcillin and 0.06 g clavulanic acid) IV every 8 hours.
    CrCl less than 10 mL/min: Loading dose of 3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) IV then, give 2 g (1.94 g ticarcillin and 0.06 g clavulanic acid) IV every 12 hours.
    CrCl less than 10 mL/min with hepatic impairment: Loading dose of 3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) IV then, give 2 g (1.94 g ticarcillin and 0.06 g clavulanic acid) IV every 24 hours.
     
    Pediatric patients
    The renal dose modifications for pediatric patients listed below are based on the usual recommended dose in children of 50 to 75 mg/kg/dose (ticarcillin component) IV every 6 hours.
    CrCl 30 mL/min or more: No dosage adjustment needed.
    CrCl 10 to 29 mL/min: 50 to 75 mg/kg/dose (ticarcillin component) IV every 8 hours.
    CrCl less than 10 mL/min: 50 to 75 mg/kg/dose (ticarcillin component) IV every 12 hours.
    CrCl less than 10 mL/min with hepatic impairment: 50 to 75 mg/kg/dose (ticarcillin component) IV every 24 hours.
     
    Intermittent hemodialysis
    For adult patients, 2 g (1.94 g ticarcillin and 0.06 g clavulanic acid) IV every 12 hours supplemented with 3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) after each dialysis session. For pediatric patients, 50 to 75 mg/kg/dose (ticarcillin component) IV every 12 hours supplemented with usual dose after each dialysis session.
     
    Peritoneal dialysis
    For adult patients, 3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) IV every 12 hours. For pediatric patients, 50 to 75 mg/kg/dose (ticarcillin component) IV every 12 hours.

    ADMINISTRATION

    Injectable Administration

    Ticarcillin; clavulanic acid is administered intravenously.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    Each 3.1 grams of ticarcillin; clavulanic acid corresponds to 3 grams of ticarcillin and 100 mg of clavulanic acid.

    Intravenous Administration

    Reconstitution
    Vials: Reconstitute each 3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) vial with approximately 13 mL of Sterile Water for Injection or 0.9% Sodium Chloride Injection. Shake the vial until the drug is dissolved. The resulting IV solution contains approximately 200 mg/mL of ticarcillin and 6.7 mg/mL of clavulanic acid.
    Storage: The reconstituted solution is stable for up to 6 hours at room temperature or up to 72 hours under refrigeration.
    ADD-Vantage vials: Reconstitute 3.1 g (3 g ticarcillin and 0.1 g clavulanic acid) vial with 0.9% Sodium Chloride Injection or 5% Dextrose Injection in the appropriate 50 or 100 mL flexible diluent container.
    Storage: Reconstituted ADD-Vantage vials are stable for 24 hours at room temperature in 0.9% Sodium Chloride Injection and 12 hours at room temperature in 5% Dextrose Injection.
    Pharmacy bulk packages: Reconstitute the 31 g (30 g ticarcillin and 1 g clavulanic acid) package with 76 mL of Sterile Water for Injection or 0.9% Sodium Chloride Injection. The diluent may be added in 2 parts, shaking well after each addition. The resultant IV solution contains 300 mg/mL of ticarcillin and 10 mg/mL of clavulanic acid.
    Storage: The reconstituted solution is stable for up to 6 hours at room temperature or up to 72 hours under refrigeration.
     
    Dilution
    Further dilute reconstituted solution to 10—100 mg/mL of ticarcillin with a compatible IV solution.
    Storage: Diluted solutions are stable for 24 hours at room temperature or for 3 days (5% Dextrose Injection) or 7 days (0.9% Sodium Chloride Injection or Lactated Ringer's Injection) under refrigeration. Solutions prepared with 0.9% Sodium Chloride Injection or Lactated Ringer's Injection may be stored frozen for up to 30 days. Solutions prepared with 5% Dextrose Injection may be stored frozen for up to 7 days. Thawed solutions should be used within 8 hours or discarded; do not refreeze.
    ADD-Vantage vials and frozen GALAXY bags: No further dilution is required.
     
    Thawing Frozen Pre-Mixed Bags
    Frozen GALAXY bags: Thaw at room temperature. Do not force thaw. No reconstitution necessary.
    Storage: Thawed solution is stable for 24 hours at room temperature or 7 days under refrigeration; do not refreeze.
     
    Intermittent IV Infusion
    Infuse over 15—30 minutes.

    STORAGE

    Timentin:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Product is stable for up to 6 hours at room temperature (70 to 75 degrees F) or up to 72 hours under refrigeration (40 degrees F)
    - Store unreconstituted product at or below 75 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Antibiotic therapy can result in superinfection or suprainfection with non susceptible organisms. Overgrowth of Candida can occur with ticarcillin-clavulanic acid therapy. Patients should be monitored closely during therapy.

    Viral infection

    This drug does not treat viral infection (e.g., common cold). Prescribing ticarcillin; clavulanic acid in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Patients should be told to complete the full course of treatment, even if they feel better earlier.

    Renal disease, renal failure, renal impairment

    Ticarcillin; clavulanic acid should be used with caution in patients with renal disease, renal impairment, or renal failure because the drug is eliminated via renal mechanisms. Dosage adjustments are required in patients with renal impairment (CrCl < 60 ml/min) or in those who are receiving dialysis (see Dosage).

    Electrolyte imbalance, hypokalemia

    Ticarcillin; clavulanic acid should be used cautiously in patients with fluid and electrolyte imbalance. Timentin contains approximately 4.51 mEq of sodium per gram of ticarcillin (18.7 mEq in a 3.1 gram Galaxy container). This should be considered in patients with sodium restriction (i.e., severe congestive heart failure or hypertension). Timentin also contains 0.15 mEq of potassium per gram of ticarcillin (0.5 mEq in a 3.1 gram Galaxy container). Because ticarcillin; clavulanic acid can cause hypokalemia, it should be used with caution in patients who already have hypokalemia or who may have low potassium stores. Serum electrolytes may need to be monitored in all patients receiving the drug.

    Asthma, carbapenem hypersensitivity, cephalosporin hypersensitivity, cystic fibrosis, eczema, penicillin hypersensitivity

    Ticarcillin; clavulanic acid is contraindicated in patients with penicillin hypersensitivity. Ticarcillin should be used cautiously in patients with cephalosporin hypersensitivity or carbapenem hypersensitivity. Due to the drug's structural similarity to the cephalosporins and imipenem, these patients are more susceptible to hypersensitivity reactions. Patients with allergies or allergic conditions including asthma, eczema, hives, or hay fever may have a greater risk for hypersensitivity reactions to penicillins. Patients with cystic fibrosis also have a higher incidence of hypersensitivity reactions to the extended-spectrum penicillins. This may be due to these patients having a greater cumulative exposure to the drugs than other patients as well as a high rate of generalized immune response and atopy.

    Coagulopathy, hemophilia

    Ticarcillin is relatively contraindicated in patients with a coagulopathy (e.g., hemophilia) because the drug can inhibit platelet aggregation, and its use in these patients may increase the risk of bleeding.

    Colitis, diarrhea, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis

    Almost all antibacterial agents have been associated with pseudomembranous colitis (antibiotic-associated colitis) which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may exist when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. It is known that systemic use of antibiotics predisposes patients to development of pseudomembranous colitis. Consideration should be given to the diagnosis of pseudomembranous colitis in patients presenting with diarrhea following ticarcillin; clavulanic acid administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. In milder cases, the colitis may respond to discontinuation of the offending agent. In moderate to severe cases, fluids and electrolytes, protein supplementation, and treatment with an antibacterial effective against Clostridium difficile may be warranted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over two months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken.

    Pregnancy

    Ticarcillin; clavulanic acid is classified as FDA pregnancy risk category B. Animal studies have indicated no teratogenic effects. However, no studies have been performed in pregnant women. This drug should be used during pregnancy only if clearly needed.

    Breast-feeding

    Penicillins are excreted in breast milk in small amounts. Penicillins may cause diarrhea (due to disruption of GI flora), candidiasis, and skin rash in breast-feeding infants. Unless the infant is allergic to penicillins, breast-feeding is generally safe during maternal penicillin therapy; the infant should be observed for potential effects. The American Academy of Pediatrics (AAP) considers ticarcillin compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Diabetes mellitus

    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 mellitus who test their urine for glucose should use glucose tests based on enzymatic glucose oxidase reactions while on ticarcillin treatment. Also, ticarcillin can alter the results of urine protein tests.

    Geriatric, heart failure, sodium restriction

    Clinical trial reports and other experience with ticarcillin; clavulanic acid have not identified differences in responses between geriatric and younger adult patients. This drug product is known to be substantially excreted by the kidney; care should be taken in dose selection in the elderly and it may be useful to monitor renal function. Consider the sodium content of the injection during therapy in patients with need for sodium restriction. The product contains 103.6 mg (4.51 mEq) of sodium per gram of ticarcillin; clavulanic acid. At the usual recommended doses, patients would receive between 1,285 and 1,927 mg/day (56 and 84 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to sodium loading. This may be clinically important with regard to such diseases as congestive heart failure. 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.

    ADVERSE REACTIONS

    Severe

    serum sickness / Delayed / 1.0-10.0
    anaphylactoid reactions / Rapid / 0-1.0
    anaphylactic shock / Rapid / 0-1.0
    Stevens-Johnson syndrome / Delayed / 0-1.0
    toxic epidermal necrolysis / Delayed / 0-1.0
    erythema multiforme / Delayed / 0-1.0
    angioedema / Rapid / 0-1.0
    hemorrhagic cystitis / Delayed / 0-1.0
    thrombosis / Delayed / Incidence not known
    seizures / Delayed / Incidence not known

    Moderate

    pseudomembranous colitis / Delayed / 1.0-10.0
    superinfection / Delayed / 1.0-10.0
    stomatitis / Delayed / 2.0-5.0
    hemolysis / Early / 0-1.0
    bleeding / Early / 0-1.0
    hypokalemia / Delayed / 0-1.0
    hepatitis / Delayed / 0-1.0
    cholestasis / Delayed / 0-1.0
    jaundice / Delayed / 0-1.0
    phlebitis / Rapid / Incidence not known
    prolonged bleeding time / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    platelet dysfunction / Delayed / Incidence not known
    hypernatremia / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known

    Mild

    chills / Rapid / 1.0-10.0
    arthralgia / Delayed / 1.0-10.0
    malaise / Early / 1.0-10.0
    fever / Early / 1.0-10.0
    pruritus / Rapid / 1.0-10.0
    rash (unspecified) / Early / 1.0-10.0
    urticaria / Rapid / 1.0-10.0
    myalgia / Early / 1.0-10.0
    dysgeusia / Early / 2.0-5.0
    nausea / Early / 2.0-5.0
    diarrhea / Early / 2.0-5.0
    vomiting / Early / 2.0-5.0
    abdominal pain / Early / 2.0-5.0
    flatulence / Early / 2.0-5.0
    injection site reaction / Rapid / Incidence not known
    headache / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: 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; Caffeine; Magnesium Salicylate; Phenyltoloxamine: 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.
    Anticoagulants: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Antithrombin III: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Apixaban: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Argatroban: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Aspirin, ASA: 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: 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; Codeine: 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; Dihydrocodeine: 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: 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: 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: 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: 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: 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; Pravastatin: 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.
    Bivalirudin: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Choline Salicylate; Magnesium Salicylate: 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.
    Dabigatran: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Dalteparin: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Danaparoid: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Desirudin: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Dichlorphenamide: Use dichlorphenamide and penicillins together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including penicillins. 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: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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: 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.
    Drospirenone; Estradiol: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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.
    Edoxaban: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Enoxaparin: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Erythromycin; Sulfisoxazole: Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. These combinations should be used with caution and patients monitored for increased side effects.
    Estradiol; Levonorgestrel: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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: 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: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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; Desogestrel: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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; Ethynodiol Diacetate: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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; Etonogestrel: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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; Levonorgestrel: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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; Levonorgestrel; Folic Acid; Levomefolate: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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; Norelgestromin: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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; Ferrous fumarate: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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; Ferrous fumarate: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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; Norgestimate: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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.
    Fondaparinux: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Furosemide: 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.
    Heparin: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Ibuprofen lysine: Use caution in combining ibuprofen lysine with renally eliminated medications like penicillins, as ibuprofen may reduce renal blood flow.
    Indomethacin: 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.
    Lepirudin: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Leuprolide; Norethindrone: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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.
    Magnesium Salicylate: 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.
    Mestranol; Norethindrone: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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.
    Methotrexate: Penicillins may reduce the renal clearance of methotrexate. Increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with concurrent administration of high or low doses of methotrexate and penicillins. Patients should be carefully monitored while receiving this combination.
    Norethindrone: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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.
    Oral Contraceptives: It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in 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 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 concentrations of OCs. 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 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 penicillin 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 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.
    Pentosan: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Phenytoin: Penicillin G is 60% bound to albumin or moderately protein bound. Displacement of penicillins from plasma protein binding sites by highly protein bound drugs (e.g., phenytoin, fosphenytoin) 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.
    Probenecid: 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.
    Pyrimethamine; Sulfadoxine: Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. These combinations should be used with caution and patients monitored for increased side effects.
    Rivaroxaban: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Salsalate: 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.
    Sodium Benzoate; Sodium Phenylacetate: 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: 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: Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. These combinations should be used with caution and patients monitored for increased side effects.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. These combinations should be used with caution and patients monitored for increased side effects.
    Sulfasalazine: Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. These combinations should be used with caution and patients monitored for increased side effects.
    Sulfisoxazole: Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. These combinations should be used with caution and patients monitored for increased side effects.
    Sulfonamides: Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. These combinations should be used with caution and patients monitored for increased side effects.
    Tinzaparin: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.
    Typhoid Vaccine: 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: Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. 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 in patients receiving warfarin.

    PREGNANCY AND LACTATION

    Pregnancy

    Ticarcillin; clavulanic acid is classified as FDA pregnancy risk category B. Animal studies have indicated no teratogenic effects. However, no studies have been performed in pregnant women. This drug should be used during pregnancy only if clearly needed.

    Penicillins are excreted in breast milk in small amounts. Penicillins may cause diarrhea (due to disruption of GI flora), candidiasis, and skin rash in breast-feeding infants. Unless the infant is allergic to penicillins, breast-feeding is generally safe during maternal penicillin therapy; the infant should be observed for potential effects. The American Academy of Pediatrics (AAP) considers ticarcillin compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Ticarcillin is a beta-lactam antibiotic. 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 ticarcillin, 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, ticarcillin'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.
     
    Clavulanic acid is a beta-lactam drug that acts as a competitive inhibitor of bacterial beta-lactamases. It does so by binding to the enzyme's active site, preventing the beta-lactamase from inactivating the beta-lactam antibiotic; clavulanic acid is also inactivated by this process, earning it the title "suicide" inhibitor. Clavulanic acid can bind with many plasmid- and chromosomally mediated bacterial beta-lactamases. Penetration of the cell wall allows clavulanic acid to bind both bound and extracellular beta-lactamases. Clavulanic acid does not alter the actions of the beta-lactam antibiotics.
     
    Ticarcillin; clavulanic acid is active against many gram-positive bacteria including most of the penicillinase- and nonpenicillinase-producing staphylococci and streptococci. Enterococci and methicillin-resistant staphylococci are resistant to ticarcillin; clavulanic acid. In addition to Pseudomonas, ticarcillin's gram-negative spectrum includes E. coli, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia, and N. gonorrhoeae. Some extended spectrum beta-lactamase (ESBL)-producing isolates and most carbapenemase-producing isolates are resistant to ticarcillin; clavulanic acid. The anaerobic spectrum of ticarcillin; clavulanic acid includes the Peptococcus and Peptostreptococcus species, Clostridium perfringens, Clostridium tetani, and Bacteroides including many strains of B. fragilis. Clinicians are advised to consult susceptibility data at the institution in which they practice to determine ticarcillin's activity.

    PHARMACOKINETICS

    Ticarcillin/clavulanic acid is administered parenterally. Approximately 45—65% of the circulating ticarcillin and 22—30% of circulating clavulanic acid are protein-bound. Ticarcillin is distributed into kidney, bone, bile, urine, sputum, and pleural fluids. Clavulanic acid is distributed into lungs, urine, and pleural and peritoneal fluids. Ticarcillin/clavulanic acid reaches minimal levels within the CSF when the meninges are uninflamed; these levels increase in the presence of inflammation. The drug crosses the placenta.
     
    Approximately 10—15% of ticarcillin is metabolized to inactive derivatives. Clavulanic acid appears to be extensively metabolized, although the exact mechanism is not fully established. Clavulanic acid also is cleared by the kidney via glomerular filtration. The majority of ticarcillin and its metabolites are excreted into the urine, primarily via tubular secretion and glomerular filtration. Some may be excreted in feces via biliary elimination. A small percentage of both ticarcillin and clavulanic acid is excreted in breast milk. In patients with normal renal function, the elimination half-lives of ticarcillin and clavulanic acid are 1 hour.

    Intramuscular Route

    Peak serum levels of ticarcillin occur within 30—75 minutes following an IM dose.