Ampicillin Sodium

Drug overview for AMPICILLIN SODIUM (ampicillin sodium):

Generic name: AMPICILLIN SODIUM (AM-pi-SIL-in)
Drug class: Beta-Lactams
Therapeutic class: Anti-Infective Agents

Ampicillin is an aminopenicillin antibiotic.

Ampicillin shares the uses of other aminopenicillins and is used principally for the treatment of infections caused by susceptible gram-negative bacteria (e.g., Haemophilus influenzae, Escherichia coli, Proteus mirabilis, Salmonella). Ampicillin also is used for the treatment of infections caused by susceptible gram-positive bacteria (e.g., Streptococcus pneumoniae, enterococci, nonpenicillinase-producing staphylococci, Listeria); however, like other aminopenicillins, ampicillin generally should not be used for the treatment of streptococcal or staphylococcal infections when a natural penicillin would be effective. Orally administered ampicillin should not be used for the initial treatment of severe, life-threatening infections, but may be used as follow-up therapy after parenteral ampicillin therapy.

For specific information on the uses of ampicillin, see Uses in the Aminopenicillins General Statement 8:12.16.08.

DRUG IMAGES

AMPICILLIN 250 MG VIAL
AMPICILLIN 500 MG VIAL
AMPICILLIN 10 GM VIAL
AMPICILLIN 2 GM VIAL
AMPICILLIN 1 GM VIAL

The following indications for AMPICILLIN SODIUM (ampicillin sodium) have been approved by the FDA:

Indications:
Acute epiglottitis
Acute streptococcal epiglottitis
Bacterial endocarditis
Bacterial meningitis
Bacterial pneumonia
Bacterial sepsis
Bacterial urinary tract infection
Cesarean section infection prevention
Chronic bronchitis with bacterial exacerbation
E. coli septicemia
Enterococcal endocarditis
Enterococcus septicemia
Escherichia coli meningitis
Gastroenteritis due to Salmonella
Gastroenteritis due to Shigella
Genitourinary tract infections
Haemophilus influenzae pneumonia
Infection prevention for GI surgery
Meningococcal meningitis
Neonatal group B streptococcal septicemia
Pneumococcal meningitis
Proteus septicemia
Salmonella septicemia
Skin and skin structure infection
Staphylococcal pneumonia
Staphylococcus aureus septicemia
Streptococcal endocarditis
Streptococcal pneumonia
Streptococcal septicemia
Tonsillitis due to Streptococcus pyogenes
Typhoid fever
Vaginal hysterectomy infection prevention

Professional Synonyms:
Acute bacterial exacerbation of chronic bronchitis
Acute epiglottiditis
Bacillary dysentery from Shigella spp.
Bacteremia with sepsis
Bacterial exacerbation of chronic bronchitis
Bacterial septicemia
E. coli sepsis
Endocarditis due to enterococcus
Endocarditis due to Streptococcus
Escherichia coli sepsis
Escherichia coli septicemia
Gastroenteritis due to Salmonella spp.
Gastroenteritis due to Shigella species
Genitourinary infection
Genitourinary tract infection
H. flu pneumonia
H. influenzae pneumonia
Hemophilus influenzae pneumonia
Infection of skin and/or subcutaneous tissue
Infection prophylaxis for C-section
Infection prophylaxis for cesarean section
Infection prophylaxis for gastrointestinal surgery
Infection prophylaxis for vaginal hysterectomy
Influenza Bacillus pneumonia
Intestinal Shigella infection
Neonatal group B streptococcal sepsis
Pfeiffer's Bacillus pneumonia
Pneumonia due to Haemophilus influenzae
Pneumonia due to Staphylococcus species
Pneumonia due to Staphylococcus spp.
Pneumonia due to Streptococcus species
Pneumonia due to Streptococcus spp.
Salmonella food poisoning
Salmonella gastroenteritis
Salmonella sepsis
Sepsis due to Enterococcus
Sepsis due to Proteus species
Sepsis due to Staphylococcus aureus
Septicemia due to Enterococcus
Septicemia due to Proteus species
Septicemia due to Proteus spp.
Septicemia due to Staph aureus
Septicemia due to Staphylococcus aureus
Shigellosis
Skin and soft tissue skin infection
Streptococcal epiglottiditis
Streptococcal sepsis
Streptococcus pneumoniae meningitis
Streptococcus pyogenes tonsillitis

The following dosing information is available for AMPICILLIN SODIUM (ampicillin sodium):

Dosing
Administration
Dosing Information
Generic

Dosage of ampicillin sodium and ampicillin trihydrate is expressed in terms of ampicillin.

The manufacturers' dosage recommendations for adults usually are the same for both parenteral and oral routes; however, higher serum concentrations usually are attained parenterally, and this route is used for severe infections.

The usual adult dosage of ampicillin for the treatment of respiratory tract or skin and skin structure infections is 250-500 mg every 6 hours. For the treatment of GI or urinary tract infections, the usual adult dosage is 500 mg every 6 hours. For severe infections, larger doses may be required.

The usual adult dosage of ampicillin for the treatment of septicemia or bacterial meningitis is 8-14 g or 150-200 mg/kg daily given parenterally in equally divided doses every 3-4 hours. For the initial treatment of septicemia or meningitis, ampicillin should be given IV for at least 3 days but may then be given IM.

For oral therapy, most manufacturers state that children weighing more than 20 kg may receive the usual adult dosage of ampicillin. For parenteral therapy, some manufacturers recommend that the usual adult dosage be used in children weighing more than 20 kg, whereas other manufacturers and many clinicians recommend that the usual adult dosage be used in those weighing more than 40 kg. Pediatric dosage should not exceed dosage recommended for similar infections in adults.

For the treatment of respiratory tract or skin and skin structure infections, the usual dosage of ampicillin for children weighing 40 kg or less is 25-50 mg/kg daily administered in equally divided doses every 6 hours. For the treatment of GI or urinary tract infections, the usual dosage for children weighing 40 kg or less is 50-100 mg/kg daily given in equally divided doses every 6 hours.

For the treatment of septicemia or CNS infections, the usual pediatric dosage recommended by the manufacturers is 100-200 mg/kg daily given in divided doses every 3-4 hours, starting with IV administration for 3 days and continuing with IM administration. For empiric treatment of bacterial meningitis in neonates and children younger than 2 months of age, many clinicians recommend that an IV ampicillin dosage of 100-300 mg/kg daily be given in divided doses in conjunction with IM gentamicin pending results of in vitro susceptibility tests. For the empiric treatment of bacterial meningitis in children 2 months to 12 years of age, many clinicians recommend that an IV ampicillin dosage of 200-400 mg/kg daily be given in divided doses every 4-6 hours in conjunction with IV chloramphenicol.

If bacterial susceptibility data are not available and clinical and bacteriologic response is unsatisfactory after 24-48 hours, other appropriate anti-infective therapy should be substituted.

When IM or IV ampicillin is used in neonates younger than 7 days of age, the American Academy of Pediatrics (AAP) recommends a dosage of 50 mg/kg every 12 hours in those weighing 2 kg or less or 50 mg/kg every 8 hours in those weighing more than 2 kg. For neonates 8-28 days of age, AAP recommends an IM or IV dosage of 50 mg/kg every 8 hours in those weighing 2 kg or less or 50 mg/kg every 6 hours in those weighing more than 2 kg. AAP states that higher ampicillin dosage may be necessary for the treatment of meningitis in neonates.

For the treatment of meningitis caused by Streptococcus agalactiae (group B streptococci; GBS), some experts recommend that neonates 28 days of age or younger receive IV ampicillin in a dosage of 75 mg/kg every 6 hours, regardless of weight; others recommend a dosage of 200-300 mg/kg daily given IV in 3 divided doses in neonates 7 days of age or younger or a dosage of 300 mg/kg daily given IV in 4 divided doses in neonates older than 7 days of age. AAP states that a dosage of 100 mg/kg every 12 hours is acceptable for the treatment of early-onset group B streptococcal septicemia without meningitis in neonates 7 days of age or younger.

When IM or IV ampicillin is used in pediatric patients beyond the neonatal period, AAP recommends a dosage of 100-150 mg/kg daily given in 4 divided doses for the treatment of mild to moderate infections or a dosage of 200-400 mg/kg daily given in 4 divided doses for the treatment of severe infections. The highest dosage should be used for the treatment of CNS infections. When oral ampicillin is used in pediatric patients beyond the neonatal period, AAP recommends a dosage of 50-100 mg/kg daily in 4 divided doses.

AAP states that oral ampicillin is inappropriate for the treatment of severe infections.

In patients with renal impairment, doses and/or frequency of administration of ampicillin should be modified in response to the degree of renal impairment, severity of the infection, and susceptibility of the causative organism. Some clinicians suggest that adults with glomerular filtration rates of 10-50 mL/minute receive the usual dose of ampicillin every 6-12 hours and that adults with glomerular filtration rates less than 10 mL/minute receive the usual dose every 12-16 hours. Alternatively, some clinicians suggest that modification of usual dosage of ampicillin is unnecessary in adults with creatinine clearances of 30 mL/minute or greater, but adults with creatinine clearances of 10 mL/minute or less should receive the usual dose of the drug every 8 hours.

Patients undergoing hemodialysis should receive a supplemental dose of ampicillin after each dialysis period.

No enhanced Administration information available for this drug.

No dosing information available.

No generic dosing information available.

The following drug interaction information is available for AMPICILLIN SODIUM (ampicillin sodium):

Contraindicated
Severe
Moderate

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Live Typhoid Vaccine/Antimicrobials SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1) CLINICAL EFFECTS: Vaccination may be ineffective. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3) DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)	VIVOTIF

Drug Interaction

Drug Names

Live Typhoid Vaccine/Antimicrobials

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

VIVOTIF

There are 3 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Methotrexate/Penicillins SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Penicillins may compete with the renal tubular secretion of methotrexate. CLINICAL EFFECTS: The concurrent use of methotrexate and penicillins may result in elevated levels of methotrexate and methotrexate toxicity, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression. PREDISPOSING FACTORS: Risk factors for methotrexate toxicity include: - High-dose oncology regimens - Impaired renal function, ascites, or pleural effusions PATIENT MANAGEMENT: Patients receiving concurrent therapy with methotrexate and penicillins should be monitored closely for elevated methotrexate levels and methotrexate toxicity. The dose and duration of leucovorin rescue therapy may need to be increased. DISCUSSION: Elevated methotrexate levels, signs of methotrexate toxicity, and death have been reported following the concurrent use of methotrexate (both low dose and high dose) and penicillin derivatives. In a patient being treated with high-dose methotrexate (8 G/m2), the concurrent use of amoxicillin resulted in a 56% decrease in the clearance of methotrexate and signs of methotrexate toxicity.(1) There are two cases of methotrexate toxicity following the addition of amoxicillin to low-dose methotrexate therapy (7.5 mg-10 mg weekly) for psoriasis. In another case, a patient was found to have a toxic methotrexate level 12 days after her last dose of weekly methotrexate (7.5 mg). The patient had been treated with amoxicillin followed by flucloxacillin.(2) In a case report, dicloxacillin decreased methotrexate clearance 93%.(4) Flucloxacillin was shown to increase the area-under-curve (AUC) of methotrexate by 7.3% in a study in 10 subjects.(5) In a case report, a patient on low-dose methotrexate (5 mg) developed methotrexate pneumonia following the addition of flucloxacillin to his regimen.(5) In a patient being treated with high-dose methotrexate (12 G/m2), the concurrent use of mezlocillin increased the half-life of methotrexate from 10.1 to 27.2 hours.(6) In a case report, a patient developed methotrexate toxicity following the addition of penicillin V potassium to his methotrexate (50 mg weekly).(7) In a case report, penicillin decreased methotrexate clearance 36%.(4) In one report, leucovorin rescue therapy had to be continued for 192 hours following the concurrent use of methotrexate (3 G/m2) and piperacillin. During cycles without concurrent piperacillin, leucovorin rescue therapy was only required for 72 hours.(8) There are two reports of neutropenia and death following the concurrent use of piperacillin and low-dose methotrexate (2.5 mg three times weekly in one patient, 5 mg weekly in another) for psoriasis. One of these patients also received flucloxacillin. (3) In another case report, the concurrent use of piperacillin decreased methotrexate clearance by 67%.(4) In a case report, ticarcillin decreased methotrexate clearance by 60%.(4)	JYLAMVO, METHOTREXATE, METHOTREXATE SODIUM, OTREXUP, RASUVO, TREXALL, XATMEP
Cholera Vaccine Live/Selected Antibiotics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Antibiotics with activity against Vibrio cholerae may attenuate the immunization response to the live cholera vaccine.(1) CLINICAL EFFECTS: Concurrent or recent antibiotic use may make the cholera vaccine ineffective.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of live cholera vaccine states that it should not be administered to patients who have received antibiotics within 14 days prior to vaccination.(1) If antimalarial prophylaxis with chloroquine is required, administer the live cholera vaccine at least 10 days before beginning chloroquine.(1) Antibiotics linked to this monograph are: macrolides, quinolones, tetracyclines, ampicillin, cefprozil, chloramphenicol, furazolidone, sulfamethoxazole-trimethoprim, and sulfametrole-trimethoprim.(2,3) DISCUSSION: Antibiotics with activity against Vibrio cholerae may attenuate the immunization response to the live cholera vaccine, rendering the vaccine ineffective.	VAXCHORA ACTIVE COMPONENT, VAXCHORA VACCINE
Fecal Microbiota Spores/Antibiotics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1) CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1) DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.	VOWST

There are 3 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Oral Contraceptives/Penicillins SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Estrogens and progesterones are extensively excreted in bile, principally as glycuronide conjugates. Subsequently, they undergo enterohepatic circulation where bacterial hydrolysis occurs, allowing for reabsorption of the oral contraceptives through the bowel wall and eventual urinary excretion. Treatment with antibiotics destroys the gut flora and prevents steroid reabsorption, resulting in lower than normal concentrations of the contraceptive and excretion via the feces rather than the urine. CLINICAL EFFECTS: May observe reduced pharmacologic effects of oral contraceptives with resultant breakthrough bleeding and pregnancy. Reduced effects may be seen for several days after discontinuation of antibiotic therapy. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Current guidelines suggest that additional precautions are not necessary when non-enzyme inducing antibiotics are used concurrently with hormonal contraceptives; however, some patients may still prefer to use an additional method of contraception. DISCUSSION: Evidence for this interaction is limited and conflicting; however, the CDC and the Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit no longer recommend use of a backup contraceptive method during use of a non-enzyme inducing antibiotic. Reports of breakthrough bleeding and loss of contraceptive protection leading to unwanted pregnancies have occurred in women taking oral contraceptive agents who received concurrent ampicillin, amoxicillin, penicillin G, or oxacillin. Several studies have shown that the administration of ampicillin or penicillin to pregnant and nonpregnant women resulted in lowered urinary estrogen excretion, in some women as soon as three days after ampicillin therapy began. However in one small prospective study, plasma ethinyl estradiol concentrations showed a tendency to decrease during ampicillin administration on the third, fourth, and fifth morning of ampicillin administration, but were never lower than pretreatment values. In another small prospective study of women taking low dose combination contraceptives, concurrent ampicillin therapy neither altered the plasma levels nor the AUC of norethisterone and ethinyl estradiol. In addition, progesterone levels were in an anovulatory range. In another prospective study of 13 women taking long term oral contraceptive steroids, concurrent ampicillin was not associated with any significant changes in plasma concentrations of ethinyl estradiol, levonorgestrel, follicle stimulating hormone or progesterone, although lower concentrations of ethinyl estradiol were noted in two women.	2-METHOXYESTRADIOL, AFIRMELLE, ALTAVERA, ALYACEN, AMETHIA, AMETHYST, APRI, ARANELLE, ASHLYNA, AUBRA, AUBRA EQ, AUROVELA, AUROVELA 24 FE, AUROVELA FE, AVIANE, AYUNA, AZURETTE, BALCOLTRA, BALZIVA, BEYAZ, BLISOVI 24 FE, BLISOVI FE, BRIELLYN, CAMILA, CAMRESE, CAMRESE LO, CAZIANT, CHARLOTTE 24 FE, CHATEAL EQ, CRYSELLE, CYRED, CYRED EQ, DASETTA, DAYSEE, DEBLITANE, DESOGESTR-ETH ESTRAD ETH ESTRA, DIETHYLSTILBESTROL, DOLISHALE, DROSPIRENONE-ETH ESTRA-LEVOMEF, DROSPIRENONE-ETHINYL ESTRADIOL, ELINEST, ELLA, EMZAHH, ENPRESSE, ENSKYCE, ERRIN, ESTARYLLA, ESTRADIOL, ESTRADIOL BENZOATE, ESTRADIOL CYPIONATE, ESTRADIOL HEMIHYDRATE, ESTRADIOL HEMIHYDRATE MICRO, ESTRADIOL MICRONIZED, ESTRADIOL VALERATE, ESTRIOL, ESTRIOL MICRONIZED, ESTRONE, ETHINYL ESTRADIOL, ETHYNODIOL-ETHINYL ESTRADIOL, FALMINA, FEIRZA, FEMLYV, FINZALA, GEMMILY, HAILEY, HAILEY 24 FE, HAILEY FE, HEATHER, ICLEVIA, INCASSIA, ISIBLOOM, JAIMIESS, JASMIEL, JENCYCLA, JOLESSA, JOYEAUX, JULEBER, JUNEL, JUNEL FE, JUNEL FE 24, KAITLIB FE, KALLIGA, KARIVA, KELNOR 1-35, KELNOR 1-50, KURVELO, LARIN, LARIN 24 FE, LARIN FE, LAYOLIS FE, LEENA, LESSINA, LEVONEST, LEVONORG-ETH ESTRAD ETH ESTRAD, LEVONORG-ETH ESTRAD-FE BISGLYC, LEVONORGESTREL-ETH ESTRADIOL, LEVORA-28, LO LOESTRIN FE, LO-ZUMANDIMINE, LOESTRIN, LOESTRIN FE, LOJAIMIESS, LORYNA, LOW-OGESTREL, LUTERA, LYLEQ, LYZA, MARLISSA, MERZEE, MIBELAS 24 FE, MICROGESTIN, MICROGESTIN FE, MILI, MINZOYA, MONO-LINYAH, NATAZIA, NECON, NEXTSTELLIS, NIKKI, NORA-BE, NORETHIN-ETH ESTRA-FERROUS FUM, NORETHINDRON-ETHINYL ESTRADIOL, NORETHINDRONE, NORETHINDRONE-E.ESTRADIOL-IRON, NORGESTIMATE-ETHINYL ESTRADIOL, NORTREL, NYLIA, OCELLA, ORTHO TRI-CYCLEN, ORTHO-NOVUM, PHILITH, PIMTREA, PORTIA, RECLIPSEN, RIVELSA, SAFYRAL, SETLAKIN, SHAROBEL, SIMLIYA, SIMPESSE, SLYND, SPRINTEC, SRONYX, SYEDA, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TAYTULLA, TILIA FE, TRI-ESTARYLLA, TRI-LEGEST FE, TRI-LINYAH, TRI-LO-ESTARYLLA, TRI-LO-MARZIA, TRI-LO-MILI, TRI-LO-SPRINTEC, TRI-MILI, TRI-SPRINTEC, TRI-VYLIBRA, TRI-VYLIBRA LO, TRIVORA-28, TULANA, TURQOZ, TYBLUME, VALTYA, VELIVET, VESTURA, VIENVA, VIORELE, VOLNEA, VYFEMLA, VYLIBRA, WERA, WYMZYA FE, XARAH FE, XELRIA FE, YASMIN 28, YAZ, ZARAH, ZOVIA 1-35, ZUMANDIMINE
Selected Anticoagulants (Vit K antag)/Selected Penicillins SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown. CLINICAL EFFECTS: Large doses of parenterally administered penicillins and oral amoxicillin appear to increase the risk of bleeding during concurrent administration of anticoagulants. PREDISPOSING FACTORS: Renal failure may predispose patients to penicillin-induced coagulation abnormalities. A study suggests that various inflammatory syndromes or the nature of the infection can affect INR levels. The risk for bleeding episodes may be greater in patients with additional disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Monitor patient INR for an increase in the hypoprothrombinemic response to anticoagulants during concomitant administration of penicillins. Adjust the dose of warfarin accordingly. When concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: High dose parenteral administration of penicillins and oral amoxicillin have been reported to cause an increase in the hypoprothrombinemic effects of warfarin producing bleeding. Significant clinical effects have been reported with combined administration of warfarin and either carbenicillin or penicillin G. There have been several case reports and retrospective reviews documenting increased acenocoumarol and warfarin effects, including bleeding, following the addition of amoxicillin, with and without clavulanic acid, to therapy. In a randomized controlled trial, adult ambulatory patients that had no recent and ongoing infectious or inflammatory conditions received warfarin to a target INR between 2 and 3 with amoxicillin-clavulanic acid (1 gram twice daily for seven days) or placebo. The results showed the mean maximum INR increase from baseline to day 10 did not differ between amoxicillin/clavulanic acid (0.22 +/- 0.3) and the placebo period (0.24 +/- 0.6, p = 0.94). No patient experienced an INR of greater than 3.5. No bleeding events were reported during the entire study. A prospective cross-sectional observational study in 120 patients evaluated warfarin drug interactions, particularly with high-dose amoxicillin/clavulanate. The study found that patients on amoxicillin/clavulanate had a relative risk of having an INR >=4 of 4.8 compared to patients not on amoxicillin/clavulanate (95% CI 2.1-11.3, p < 0.001). This risk was primarily driven by patients on high-dose amoxicillin/clavulanate, who were 5.8 times more likely to have INR >=4 (95% CI 3.5-9.6, p<0.001). Significantly more patients on high-dose than normal dose amoxicillin/clavulanate had an INR value >= 4 (87.5% v. 28.9%, respectively). Nine out of ten patients who experienced bleeding during hospitalization were prescribed amoxicillin/clavulanate. A large systematic review was performed on 72 warfarin drug-drug interactions studies that reported on bleeding, thromboembolic events, or death. Most studies were retrospective cohorts. A meta-analysis of 11 of those studies found a higher rate of clinically significant bleeding in patients on warfarin and antimicrobials (OR=1.63; 95% CI 1.45-1.83). Increased bleeding risk was also seen in subgroup analyses with penicillins (OR=1.59; 95% CI 1.14-2.20) and amoxicillin (OR=1.78; 95% CI 1.14-2.79). A case-control nested cohort study of Medicare beneficiaries with warfarin prescriptions was evaluated for antibiotic use and warfarin toxicity in older adults. An increased risk of bleeding was associated with penicillins with an adjusted odds ratio of 1.92. Parenteral penicillins linked to this monograph include: almecillin, amdinocillin, amoxicillin, ampicillin, azlocillin, bacampicillin, carbenicillin, cyclacillin, hetacillin, mezlocillin, penicillin, penicillin G, penicillin V, phenethicillin, piperacillin, and ticarcillin. Oral penicillins linked to this monograph include: amoxicillin and penicillin.	ANISINDIONE, DICUMAROL, JANTOVEN, WARFARIN SODIUM
Allopurinol/Amoxicillin, Ampicillin, Bendamustine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown. Allopurinol, amoxicillin, ampicillin, and bendamustine have been documented to cause cases of Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), and Drug reaction with eosinophilia and systemic symptoms (DRESS).(1) CLINICAL EFFECTS: Concurrent administration of allopurinol with amoxicillin, ampicillin or bendamustine may result in an increased incidence of rash which may be severe. PREDISPOSING FACTORS: Patients who are HLA-B*58:01 positive may be at increased risk. PATIENT MANAGEMENT: Consider an alternative to amoxicillin, ampicillin, or bendamustine in patients with a history of serious skin rashes, such as SJS, TEN, or DRESS. Discontinue allopurinol at the first appearance of skin rash or other signs which may indicate a hypersensitivity reaction when used with amoxicillin or ampicillin or bendamustine. Instruct patients to seek medical attention for any peeling skin rash or blisters.(1) DISCUSSION: In the Boston Collaborative Drug Surveillance Program, drug rash was seen in 22.4% of 67 hospitalized patients (relative risk 3.0) receiving concurrent allopurinol and ampicillin compared to 7.5% of 1257 patients receiving only ampicillin and 2.1% of 283 patients rceiving only allopurinol.(4) A hospital drug monitoring program found the observed risk of developing an exanthema with concurrent use is as follows: aminopenicillin without allopurinol 10.1%, aminopenicillin combined with allopurinol 7.2%, allopurinol without aminopenicillin 3.0%, or neither of the two drugs 1.5%.(6) A case-control study did not find a statistically significant increased risk of SJS with concurrent use of allopurinol and amoxicillin or ampicillin (allopurinol alone 4.4% vs. with amoxicillin 6.8%; allopurinol alone 0.1% vs. with ampicillin 2.7% at 1 month)(allopurinol alone 4.4% vs. with amoxicillin 5.7% or allopurinol alone 0.2% vs. with ampicillin 2.9% at 3 months).(8) In a retrospective study looking at mortality data, records were screened for administration of high risk drugs associated with SJS. Allopurinol and ampicillin was one of the drug combinations listed as contributing to mortality in patients (p = 0.049).(9)	ALLOPURINOL, ALLOPURINOL SODIUM, ALOPRIM, DUZALLO, ZYLOPRIM

Severe List
Clostridioides difficile infection

The following adverse reaction information is available for AMPICILLIN SODIUM (ampicillin sodium):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 36 severe adverse reactions.

More Frequent	Less Frequent
None.	Anaphylaxis Dyspnea Exfoliative dermatitis Hypotension Kounis syndrome Serum sickness

Rare/Very Rare
Abnormal desquamation Abnormal hepatic function tests Acute generalized exanthematous pustulosis Agranulocytosis Altered mental status Angioedema Cholestasis Clostridioides difficile infection Crystalluria DRESS syndrome Eosinophilia Facial edema Hemolytic anemia Hepatitis Hyperreflexia Hypokalemia Increased risk of bleeding due to coagulation disorder Interstitial nephritis Laryngismus Leukopenia Myoclonus Neutropenic disorder Pancytopenia Phlebitis after infusion Renal failure Seizure disorder Stevens-johnson syndrome Thrombocytopenic disorder Thrombophlebitis Toxic epidermal necrolysis

Rare/Very Rare

Abnormal desquamation
Abnormal hepatic function tests
Acute generalized exanthematous pustulosis
Agranulocytosis
Altered mental status
Angioedema
Cholestasis
Clostridioides difficile infection
Crystalluria
DRESS syndrome
Eosinophilia
Facial edema
Hemolytic anemia
Hepatitis
Hyperreflexia
Hypokalemia
Increased risk of bleeding due to coagulation disorder
Interstitial nephritis
Laryngismus
Leukopenia
Myoclonus
Neutropenic disorder
Pancytopenia
Phlebitis after infusion
Renal failure
Seizure disorder
Stevens-johnson syndrome
Thrombocytopenic disorder
Thrombophlebitis
Toxic epidermal necrolysis

There are 12 less severe adverse reactions.

More Frequent	Less Frequent
Diarrhea Headache disorder Nausea Oral candidiasis Vomiting Vulvovaginal candidiasis	Pruritus of skin Skin rash Stomatitis

Rare/Very Rare
Fever Injection site sequelae Urticaria

The following precautions are available for AMPICILLIN SODIUM (ampicillin sodium):

Pediatric
Pregnant
Lactation
Geriatric

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Safe use of ampicillin during pregnancy has not been established. There are no adequate or controlled studies using ampicillin in pregnant women, and the drug should be used during pregnancy only when clearly needed. However, ampicillin has been administered to pregnant women, especially in the treatment of urinary tract infections, without evidence of adverse effects to the fetus.

Because ampicillin is distributed into milk, the drug should be used with caution in nursing women.

No enhanced Geriatric Use information available for this drug.

The following icd codes are available for AMPICILLIN SODIUM (ampicillin sodium)'s list of indications:

Acute epiglottitis
J05.1	Acute epiglottitis
J05.10	Acute epiglottitis without obstruction
J05.11	Acute epiglottitis with obstruction
Acute streptococcal epiglottitis
B95.0	Streptococcus, group a, as the cause of diseases classified elsewhere
B95.1	Streptococcus, group b, as the cause of diseases classified elsewhere
B95.3	Streptococcus pneumoniae as the cause of diseases classified elsewhere
B95.4	Other streptococcus as the cause of diseases classified elsewhere
B95.5	Unspecified streptococcus as the cause of diseases classified elsewhere
J05.1	Acute epiglottitis
J05.10	Acute epiglottitis without obstruction
J05.11	Acute epiglottitis with obstruction
Bacterial endocarditis
I33.0	Acute and subacute infective endocarditis
Bacterial meningitis
G00.9	Bacterial meningitis, unspecified
G01	Meningitis in bacterial diseases classified elsewhere
G04.2	Bacterial meningoencephalitis and meningomyelitis, not elsewhere classified
Bacterial pneumonia
J15.9	Unspecified bacterial pneumonia
Bacterial sepsis
A02.1	Salmonella sepsis
A20.7	Septicemic plague
A22.7	Anthrax sepsis
A26.7	Erysipelothrix sepsis
A32.7	Listerial sepsis
A40	Streptococcal sepsis
A40.0	Sepsis due to streptococcus, group A
A40.1	Sepsis due to streptococcus, group B
A40.3	Sepsis due to streptococcus pneumoniae
A40.8	Other streptococcal sepsis
A40.9	Streptococcal sepsis, unspecified
A41	Other sepsis
A41.0	Sepsis due to staphylococcus aureus
A41.01	Sepsis due to methicillin susceptible staphylococcus aureus
A41.02	Sepsis due to methicillin resistant staphylococcus aureus
A41.1	Sepsis due to other specified staphylococcus
A41.2	Sepsis due to unspecified staphylococcus
A41.3	Sepsis due to hemophilus influenzae
A41.4	Sepsis due to anaerobes
A41.5	Sepsis due to other gram-negative organisms
A41.50	Gram-negative sepsis, unspecified
A41.51	Sepsis due to escherichia coli [e. coli]
A41.52	Sepsis due to pseudomonas
A41.53	Sepsis due to serratia
A41.54	Sepsis due to acinetobacter baumannii
A41.59	Other gram-negative sepsis
A41.8	Other specified sepsis
A41.81	Sepsis due to enterococcus
A41.89	Other specified sepsis
A41.9	Sepsis, unspecified organism
A42.7	Actinomycotic sepsis
A54.86	Gonococcal sepsis
O03.37	Sepsis following incomplete spontaneous abortion
O08.82	Sepsis following ectopic and molar pregnancy
O85	Puerperal sepsis
O86.04	Sepsis following an obstetrical procedure
P36	Bacterial sepsis of newborn
P36.0	Sepsis of newborn due to streptococcus, group B
P36.1	Sepsis of newborn due to other and unspecified streptococci
P36.10	Sepsis of newborn due to unspecified streptococci
P36.19	Sepsis of newborn due to other streptococci
P36.2	Sepsis of newborn due to staphylococcus aureus
P36.3	Sepsis of newborn due to other and unspecified staphylococci
P36.30	Sepsis of newborn due to unspecified staphylococci
P36.39	Sepsis of newborn due to other staphylococci
P36.4	Sepsis of newborn due to escherichia coli
P36.5	Sepsis of newborn due to anaerobes
P36.8	Other bacterial sepsis of newborn
P36.9	Bacterial sepsis of newborn, unspecified
R65.2	Severe sepsis
T81.12	Postprocedural septic shock
T81.12xA	Postprocedural septic shock, initial encounter
T81.44	Sepsis following a procedure
T81.44xA	Sepsis following a procedure, initial encounter
Bacterial urinary tract infection
N30.0	Acute cystitis
N30.00	Acute cystitis without hematuria
N30.01	Acute cystitis with hematuria
N30.9	Cystitis, unspecified
N30.90	Cystitis, unspecified without hematuria
N30.91	Cystitis, unspecified with hematuria
N39.0	Urinary tract infection, site not specified
O23.0	Infections of kidney in pregnancy
O23.00	Infections of kidney in pregnancy, unspecified trimester
O23.01	Infections of kidney in pregnancy, first trimester
O23.02	Infections of kidney in pregnancy, second trimester
O23.03	Infections of kidney in pregnancy, third trimester
O23.1	Infections of bladder in pregnancy
O23.10	Infections of bladder in pregnancy, unspecified trimester
O23.11	Infections of bladder in pregnancy, first trimester
O23.12	Infections of bladder in pregnancy, second trimester
O23.13	Infections of bladder in pregnancy, third trimester
O23.2	Infections of urethra in pregnancy
O23.20	Infections of urethra in pregnancy, unspecified trimester
O23.21	Infections of urethra in pregnancy, first trimester
O23.22	Infections of urethra in pregnancy, second trimester
O23.23	Infections of urethra in pregnancy, third trimester
O23.3	Infections of other parts of urinary tract in pregnancy
O23.30	Infections of other parts of urinary tract in pregnancy, unspecified trimester
O23.31	Infections of other parts of urinary tract in pregnancy, first trimester
O23.32	Infections of other parts of urinary tract in pregnancy, second trimester
O23.33	Infections of other parts of urinary tract in pregnancy, third trimester
O23.4	Unspecified infection of urinary tract in pregnancy
O23.40	Unspecified infection of urinary tract in pregnancy, unspecified trimester
O23.41	Unspecified infection of urinary tract in pregnancy, first trimester
O23.42	Unspecified infection of urinary tract in pregnancy, second trimester
O23.43	Unspecified infection of urinary tract in pregnancy, third trimester
O23.90	Unspecified genitourinary tract infection in pregnancy, unspecified trimester
O23.91	Unspecified genitourinary tract infection in pregnancy, first trimester
O23.92	Unspecified genitourinary tract infection in pregnancy, second trimester
O23.93	Unspecified genitourinary tract infection in pregnancy, third trimester
P39.3	Neonatal urinary tract infection
T83	Complications of genitourinary prosthetic devices, implants and grafts
T83.5	Infection and inflammatory reaction due to prosthetic device, implant and graft in urinary system
T83.51	Infection and inflammatory reaction due to urinary catheter
T83.59	Infection and inflammatory reaction due to prosthetic device, implant and graft in urinary system
T83.6	Infection and inflammatory reaction due to prosthetic device, implant and graft in genital tract
Cesarean section infection prevention
O82	Encounter for cesarean delivery without indication
Chronic bronchitis with bacterial exacerbation
J44.0	Chronic obstructive pulmonary disease with (acute) lower respiratory infection
E. coli septicemia
A41.51	Sepsis due to escherichia coli [e. coli]
P36.4	Sepsis of newborn due to escherichia coli
Enterococcal endocarditis
B95.2	Enterococcus as the cause of diseases classified elsewhere
I33.0	Acute and subacute infective endocarditis
Enterococcus septicemia
A41.81	Sepsis due to enterococcus
Escherichia coli meningitis
B96.2	Escherichia coli [e. coli ] as the cause of diseases classified elsewhere
B96.20	Unspecified escherichia coli [e. coli] as the cause of diseases classified elsewhere
B96.29	Other escherichia coli [e. coli] as the cause of diseases classified elsewhere
G00.8	Other bacterial meningitis
G00.9	Bacterial meningitis, unspecified
Gastroenteritis due to salmonella
A02.0	Salmonella enteritis
Gastroenteritis due to shigella
A03	Shigellosis
A03.0	Shigellosis due to shigella dysenteriae
A03.1	Shigellosis due to shigella flexneri
A03.2	Shigellosis due to shigella boydii
A03.3	Shigellosis due to shigella sonnei
A03.8	Other shigellosis
A03.9	Shigellosis, unspecified
Genitourinary tract infections
N30.0	Acute cystitis
N30.00	Acute cystitis without hematuria
N30.01	Acute cystitis with hematuria
N30.9	Cystitis, unspecified
N30.90	Cystitis, unspecified without hematuria
N30.91	Cystitis, unspecified with hematuria
N39.0	Urinary tract infection, site not specified
O03.38	Urinary tract infection following incomplete spontaneous abortion
O03.88	Urinary tract infection following complete or unspecified spontaneous abortion
O04.88	Urinary tract infection following (induced) termination of pregnancy
O07.38	Urinary tract infection following failed attempted termination of pregnancy
O23.0	Infections of kidney in pregnancy
O23.00	Infections of kidney in pregnancy, unspecified trimester
O23.01	Infections of kidney in pregnancy, first trimester
O23.02	Infections of kidney in pregnancy, second trimester
O23.03	Infections of kidney in pregnancy, third trimester
O23.1	Infections of bladder in pregnancy
O23.10	Infections of bladder in pregnancy, unspecified trimester
O23.11	Infections of bladder in pregnancy, first trimester
O23.12	Infections of bladder in pregnancy, second trimester
O23.13	Infections of bladder in pregnancy, third trimester
O23.2	Infections of urethra in pregnancy
O23.20	Infections of urethra in pregnancy, unspecified trimester
O23.21	Infections of urethra in pregnancy, first trimester
O23.22	Infections of urethra in pregnancy, second trimester
O23.23	Infections of urethra in pregnancy, third trimester
O23.3	Infections of other parts of urinary tract in pregnancy
O23.30	Infections of other parts of urinary tract in pregnancy, unspecified trimester
O23.31	Infections of other parts of urinary tract in pregnancy, first trimester
O23.32	Infections of other parts of urinary tract in pregnancy, second trimester
O23.33	Infections of other parts of urinary tract in pregnancy, third trimester
O23.4	Unspecified infection of urinary tract in pregnancy
O23.40	Unspecified infection of urinary tract in pregnancy, unspecified trimester
O23.41	Unspecified infection of urinary tract in pregnancy, first trimester
O23.42	Unspecified infection of urinary tract in pregnancy, second trimester
O23.43	Unspecified infection of urinary tract in pregnancy, third trimester
O23.9	Unspecified genitourinary tract infection in pregnancy
O23.90	Unspecified genitourinary tract infection in pregnancy, unspecified trimester
O23.91	Unspecified genitourinary tract infection in pregnancy, first trimester
O23.92	Unspecified genitourinary tract infection in pregnancy, second trimester
O23.93	Unspecified genitourinary tract infection in pregnancy, third trimester
O86.2	Urinary tract infection following delivery
O86.20	Urinary tract infection following delivery, unspecified
O86.21	Infection of kidney following delivery
O86.22	Infection of bladder following delivery
O86.29	Other urinary tract infection following delivery
P39.3	Neonatal urinary tract infection
Haemophilus influenzae pneumonia
J14	Pneumonia due to hemophilus influenzae
Meningococcal meningitis
A39.0	Meningococcal meningitis
Neonatal group B streptococcal septicemia
P36.0	Sepsis of newborn due to streptococcus, group B
Pneumococcal meningitis
G00.1	Pneumococcal meningitis
Proteus septicemia
A41.59	Other gram-negative sepsis
Salmonella septicemia
A02.1	Salmonella sepsis
Skin and skin structure infection
H05.01	Cellulitis of orbit
H05.011	Cellulitis of right orbit
H05.012	Cellulitis of left orbit
H05.013	Cellulitis of bilateral orbits
H05.019	Cellulitis of unspecified orbit
H60.1	Cellulitis of external ear
H60.10	Cellulitis of external ear, unspecified ear
H60.11	Cellulitis of right external ear
H60.12	Cellulitis of left external ear
H60.13	Cellulitis of external ear, bilateral
K12.2	Cellulitis and abscess of mouth
L03	Cellulitis and acute lymphangitis
L03.0	Cellulitis and acute lymphangitis of finger and toe
L03.01	Cellulitis of finger
L03.011	Cellulitis of right finger
L03.012	Cellulitis of left finger
L03.019	Cellulitis of unspecified finger
L03.03	Cellulitis of toe
L03.031	Cellulitis of right toe
L03.032	Cellulitis of left toe
L03.039	Cellulitis of unspecified toe
L03.1	Cellulitis and acute lymphangitis of other parts of limb
L03.11	Cellulitis of other parts of limb
L03.111	Cellulitis of right axilla
L03.112	Cellulitis of left axilla
L03.113	Cellulitis of right upper limb
L03.114	Cellulitis of left upper limb
L03.115	Cellulitis of right lower limb
L03.116	Cellulitis of left lower limb
L03.119	Cellulitis of unspecified part of limb
L03.2	Cellulitis and acute lymphangitis of face and neck
L03.21	Cellulitis and acute lymphangitis of face
L03.211	Cellulitis of face
L03.22	Cellulitis and acute lymphangitis of neck
L03.221	Cellulitis of neck
L03.3	Cellulitis and acute lymphangitis of trunk
L03.31	Cellulitis of trunk
L03.311	Cellulitis of abdominal wall
L03.312	Cellulitis of back [any part except buttock]
L03.313	Cellulitis of chest wall
L03.314	Cellulitis of groin
L03.315	Cellulitis of perineum
L03.316	Cellulitis of umbilicus
L03.317	Cellulitis of buttock
L03.319	Cellulitis of trunk, unspecified
L03.8	Cellulitis and acute lymphangitis of other sites
L03.81	Cellulitis of other sites
L03.811	Cellulitis of head [any part, except face]
L03.818	Cellulitis of other sites
L03.9	Cellulitis and acute lymphangitis, unspecified
L03.90	Cellulitis, unspecified
L08.9	Local infection of the skin and subcutaneous tissue, unspecified
N48.22	Cellulitis of corpus cavernosum and penis
Staphylococcal pneumonia
J15.2	Pneumonia due to staphylococcus
J15.20	Pneumonia due to staphylococcus, unspecified
J15.21	Pneumonia due to staphylococcus aureus
J15.211	Pneumonia due to methicillin susceptible staphylococcus aureus
J15.212	Pneumonia due to methicillin resistant staphylococcus aureus
J15.29	Pneumonia due to other staphylococcus
Staphylococcus aureus septicemia
A41.0	Sepsis due to staphylococcus aureus
A41.01	Sepsis due to methicillin susceptible staphylococcus aureus
A41.02	Sepsis due to methicillin resistant staphylococcus aureus
P36.2	Sepsis of newborn due to staphylococcus aureus
Streptococcal endocarditis
B95.0	Streptococcus, group a, as the cause of diseases classified elsewhere
B95.1	Streptococcus, group b, as the cause of diseases classified elsewhere
B95.3	Streptococcus pneumoniae as the cause of diseases classified elsewhere
B95.4	Other streptococcus as the cause of diseases classified elsewhere
B95.5	Unspecified streptococcus as the cause of diseases classified elsewhere
I33.0	Acute and subacute infective endocarditis
Streptococcal pneumonia
J13	Pneumonia due to streptococcus pneumoniae
J15.3	Pneumonia due to streptococcus, group B
J15.4	Pneumonia due to other streptococci
Streptococcal septicemia
A40	Streptococcal sepsis
A40.0	Sepsis due to streptococcus, group A
A40.1	Sepsis due to streptococcus, group B
A40.3	Sepsis due to streptococcus pneumoniae
A40.8	Other streptococcal sepsis
A40.9	Streptococcal sepsis, unspecified
P36.0	Sepsis of newborn due to streptococcus, group B
P36.1	Sepsis of newborn due to other and unspecified streptococci
P36.10	Sepsis of newborn due to unspecified streptococci
P36.19	Sepsis of newborn due to other streptococci
Tonsillitis due to streptococcus pyogenes
J03.0	Streptococcal tonsillitis
J03.00	Acute streptococcal tonsillitis, unspecified
J03.01	Acute recurrent streptococcal tonsillitis
Typhoid fever
A01.0	Typhoid fever
A01.00	Typhoid fever, unspecified
A01.01	Typhoid meningitis
A01.02	Typhoid fever with heart involvement
A01.03	Typhoid pneumonia
A01.04	Typhoid arthritis
A01.05	Typhoid osteomyelitis
A01.09	Typhoid fever with other complications