Ampicillin

Pronunciation (am pi SIL in)

• Antibiotic Treatment of Adults With Infective Endocarditis
• Antimicrobial Drugs of Choice
• Desensitization Protocols
• Prevention of Bacterial Endocarditis
• Skin Tests
• Wound Management - Animal and Human Bites

U.S. Brand Names Marcillin®; Principen®

Synonyms Aminobenzylpenicillin; Ampicillin Sodium; Ampicillin Trihydrate

Generic Available Yes

Canadian Brand Names Apo®-Ampi; Novo-Ampicillin; Nu-Ampi

Pharmacologic Category Antibiotic, Penicillin

Use Treatment of susceptible bacterial infections (nonbeta-lactamase-producing organisms); susceptible bacterial infections caused by streptococci, pneumococci, nonpenicillinase-producing staphylococci, Listeria, meningococci; some strains of H. influenzae, Salmonella, Shigella, E. coli, Enterobacter, and Klebsiella

Use - Dental Alternate antibiotic for the prevention of bacterial endocarditis in patients undergoing dental procedures. I.M., I.V. is used in those patients unable to take oral medications.

Pregnancy Risk Factor B

Lactation Enters breast milk/compatible

Contraindications Hypersensitivity to ampicillin, any component of the formulation, or other penicillins

Warnings/Precautions Dosage adjustment may be necessary in patients with renal impairment; a low incidence of cross-allergy with other beta-lactams exists; high percentage of patients with infectious mononucleosis have developed rash during therapy with ampicillin. Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction. Ampicillin rash occurs in 5% to 10% of children receiving ampicillin and is a generalized dull red, maculopapular rash, generally appearing 3-14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees.

>10%: Local: Pain at injection site

1% to 10%:

<1%: Penicillin encephalopathy, seizures (with large I.V. doses or patients with renal dysfunction), anemia, hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, granulocytopenia, decreased lymphocytes, interstitial nephritis (rare)

Overdosage/Toxicology Symptoms of penicillin overdose include neuromuscular hypersensitivity (eg, agitation, hallucinations, asterixis, encephalopathy, confusion, and seizures). Electrolyte imbalance may occur if the preparation contains potassium or sodium salts, especially in renal failure. Hemodialysis may be helpful to aid in removal of the drug from blood; otherwise, treatment is supportive or symptom-directed.

Allopurinol: Theoretically has an additive potential for ampicillin/amoxicillin rash

Aminoglycosides: May be synergistic against selected organisms

Oral contraceptives: Anecdotal reports suggesting decreased contraceptive efficacy with penicillins have been refuted by more rigorous scientific and clinical data.

Probenecid, disulfiram: May increase levels of penicillins (ampicillin)

Warfarin: Effects of warfarin may be increased

Ethanol/Nutrition/Herb Interactions Food: Food decreases ampicillin absorption rate; may decrease ampicillin serum concentration.

Stability Oral suspension is stable for 7 days at room temperature or for 14 days under refrigeration; solutions for I.M. or direct I.V. should be used within 1 hour; solutions for I.V. infusion will be inactivated by dextrose at room temperature; if dextrose-containing solutions are to be used, the resultant solution will only be stable for 2 hours versus 8 hours in the 0.9% sodium chloride injection. D₅W has limited stability.

Minimum volume: Concentration should not exceed 30 mg/mL due to concentration-dependent stability restrictions. Manufacturer may supply as either the anhydrous or the trihydrate form.

Stability of parenteral admixture in NS at room temperature (25°C): 8 hours

Stability of parenteral admixture in NS at refrigeration temperature (4°C): 2 days

Standard diluent: 500 mg/50 mL NS; 1 g/50 mL NS; 2 g/100 mL NS

Compatibility Incompatible in D₅W, D₅NS, D₁₀W, fat emulsion 10%, hetastarch 6%, LR; variable compatibility (consult detailed reference) in NS

Y-site administration: Compatible: Acyclovir, amifostine, aztreonam, clarithromycin, cyclophosphamide, docetaxel, doxorubicin liposome, enalaprilat, esmolol, etoposide, famotidine, filgrastim, fludarabine, foscarnet, gatifloxacin, gemcitabine, granisetron, heparin, heparin with hydrocortisone sodium succinate, insulin (regular), labetalol, levofloxacin, linezolid, magnesium sulfate, melphalan, meperidine, morphine, multivitamins, ofloxacin, perphenazine, phytonadione, potassium chloride, propofol, remifentanil, tacrolimus, teniposide, theophylline, thiotepa, tolazoline, vitamin B complex with C. Incompatible: Amphotericin B cholesteryl sulfate complex, epinephrine, fluconazole, hydralazine, midazolam, ondansetron, sargramostim, verapamil, vinorelbine. Variable (consult detailed reference): Calcium gluconate, cisatracurium, diltiazem, hetastarch, hydromorphone, vancomycin

Compatibility in syringe: Compatible: Chloramphenicol, colistimethate, diatrizoate meglumine 52%, diatrizoate sodium 8%, diatrizoate sodium 60%, heparin, iohexol, iopamidol, iothalamate meglumine 60%, ioxaglate meglumine 39.3%, ioxaglate 19.6%, procaine. Incompatible: Erythromycin lactobionate, gentamicin, hydromorphone, kanamycin, lincomycin, metoclopramide. Variable (consult detailed reference): Lidocaine, polymyxin B sulfate, streptomycin

Compatibility when admixed: Compatible: Clindamycin, erythromycin lactobionate, floxacillin, furosemide. Incompatible: Amikacin, chlorpromazine, dopamine, gentamicin, hydralazine, prochlorperazine. Variable (consult detailed reference): Aztreonam, cefepime, cimetidine, heparin, hydrocortisone sodium succinate, metronidazole, metronidazole with sodium bicarbonate, ranitidine, sodium bicarbonate, verapamil

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

Absorption: Oral: 50%

Distribution: Bile, blister, and tissue fluids; penetration into CSF occurs with inflamed meninges only, good only with inflammation (exceeds usual MICs)

Protein binding: 15% to 25%

Half-life elimination:

Time to peak: Oral: Within 1-2 hours

Excretion: Urine (~90% as unchanged drug) within 24 hours

Neonates: I.M., I.V.:

Infants and Children: I.M., I.V.: 100-400 mg/kg/day in doses divided every 4-6 hours

Children: Oral: 50-100 mg/kg/day in doses divided every 6 hours; maximum dose: 2-3 g/day

Adults:

Dosing interval in renal impairment:

Hemodialysis: Moderately dialyzable (20% to 50%); administer dose after dialysis

Peritoneal dialysis: Moderately dialyzable (20% to 50%)

Continuous arteriovenous or venovenous hemofiltration effects: Dose as for Cl_cr 10-50 mL/minute; ~50 mg of ampicillin per liter of filtrate is removed

Administration Administer orally on an empty stomach (ie, 1 hour prior to, or 2 hours after meals) to increase total absorption

Monitoring Parameters With prolonged therapy monitor renal, hepatic, and hematologic function periodically; observe signs and symptoms of anaphylaxis during first dose

Test Interactions May interfere with urinary glucose tests using cupric sulfate (Benedict's solution, Clinitest®); may inactivate aminoglycosides in vitro

Dietary Considerations Take on an empty stomach 1 hour before or 2 hours after meals.

Patient Information Take entire prescription, even if you are feeling better. Take at equal intervals around-the-clock; preferably on an empty stomach with a full glass of water (1 hour before or 2 hours after meals). Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience nausea or vomiting (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). If diabetic, drug may cause false tests with Clinitest® urine glucose monitoring; use of glucose oxidase methods (Clinistix®) or serum glucose monitoring is preferable. Report rash; unusual diarrhea; unusual vaginal discharge, itching, burning, or pain; mouth sores; unresolved vomiting or constipation; fever or chills; unusual bruising or bleeding; or if condition being treated worsens or does not improve by the time prescription is completed.

Nursing Implications Ampicillin and gentamicin should not be mixed in the same I.V. tubing or administered concurrently

Sodium content of 5 mL suspension (250 mg/5 mL): 10 mg (0.4 mEq)

Sodium content of 1 g: 66.7 mg (3 mEq)

Dental Health: Effects on Dental Treatment Prolonged use of penicillins may lead to development of oral candidiasis.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions No information available to require special precautions

Mental Health: Effects on Mental Status Large I.V. doses may rarely produce encephalopathy; penicillins have been reported to cause apprehension, illusions, agitation, insomnia, depersonalization, and encephalopathy

Mental Health: Effects on Psychiatric Treatment Rarely may cause bone marrow suppression; use caution with clozapine and carbamazepine

Capsule: 250 mg, 500 mg

Injection, powder for reconstitution, as sodium: 125 mg, 250 mg, 500 mg, 1 g, 2 g, 10 g

Powder for oral suspension (Principen®): 125 mg/5 mL (100 mL, 200 mL); 250 mg/5 mL (100 mL, 200 mL)

Boguniewicz M and Leung DY, "Hypersensitivity Reactions to Antibiotics Commonly Used in Children,"Pediatr Infect Dis J, 1995, 14(3):221-31.

Brown RD, Campoli-Richards DM, "Antimicrobial Therapy in Neonates, Infants, and Children,"Clin Pharmacokinet, 1989, 17(Suppl 1):105-15.

Dajani AS, Taubert KA, Wilson W, et al, "Prevention of Bacterial Endocarditis Recommendations by the American Heart Association,"JAMA 1997, 277(22):1794-801.

Donowitz GR and Mandell GL, "Beta-Lactam Antibiotics,"N Engl J Med, 1988, 318(7):419-26 and 318(8):490-500.

Tenenbein M, Cohen S, and Sitar DS, "Whole Bowel Irrigation as a Decontamination Procedure After Acute Drug Overdose,"Arch Intern Med, 1987, 147(5):905-7.

Triggs EJ, Johnson JM, and Learoyd B, "Absorption and Disposition of Ampicillin in the Elderly,"Eur J Clin Pharmacol, 1980, 18(2):195-8.

Wright AJ, "The Penicillins,"Mayo Clin Proc, 1999, 74(3):290-307.

International Brand Names Acupillin (ZA); Adobacillin® (JP); Albipenal® [vet.] (AT); Albipen® [vet.] (FR, NL, CH); Alfasilin Oral Suspansiyon® (TR); Alphacin (AU); Alpovex® (AR); Amblosin (DE); Amfipen® (DE, GB, IE, NL); Amipenix® (JP); Ampen® (CA); Ampen (IT); Ampensaar® (DE); Ampicil® (BR); Ampicilina® (AR, CL); Ampicilina L.CH.® (CL); Ampicilin® (HR, YU); Ampicillat (DE); Ampicillina® (IT); Ampicilline-Eurogenerics® (LU); Ampicillin Mepha® (CH); Ampicillin-Rivopharm® (CH); Ampiciman (ES); Ampicina® (IT); Ampicin® (CA); Ampicler (BR); Ampicur (ES); Ampicyn (AU, ZA); Ampi (DE); Ampigal® (ES); Ampikel (ES); Ampilan® (IT); Ampilin® (TR); Ampilisa® (IT); Ampilux® (IT); Ampimax (ZA); Ampi Oral (ES); Ampipen® (IN); Ampiplus (ES); Ampiplus Simplex (IT); Ampi-Rol (ZA); Ampisalt (ZA); Ampisan® [vet.] (CH); Ampisil® (TR); Ampisina® (TR); Ampisint (IT); Ampispectrin® (BR); Ampi-Tablinen (DE); Ampitab® [vet.] (AT, CH); Ampitex® (IT); Ampitotal® (BR); Ampiwerfft® [vet.] (CH); Ampixyl® (CH); Ampi-Zoja (IT); Amplacilina (BR); Amplifar (PT); Amplimedix (ES); Ampliomax (ES); Amplipenyl® (IT); Ampliscocil® (IT); Amplital® (IT); Amplitor® (BR); Amplizer® (IT); Amplofen® (BR); Amprialen® (AR); Anglopen® (MX); Anhypen (DK); Antibiopen (ES); Anticyl® (IT); Apicillina® (IT); Apo-Ampi® (CA, CZ); Argocillina® (IT); Austrapen® (AU); Bacipen® (IN); Bacterinil® (BR); Bacterion® (BR); Be-Ampicil (ZA); Binotal (AT, BR, DE, MX, ES); Binotine (BR); Biocellina® (IT); Biocilin® (IN); Bonapicillin® (JP); Britacil® (PT); Britapen (ES); Britcin® (GB); Broacil® (IN); Campicilin® (IN); Ciarbiot (ES); Cimexillin® (CH); Citicil® (IT); Clonamp (IE); Co-Cillin (ZA); Copharcilin® (CH); Dhacillin® (HK); Dibacilina (MX); Doktacillin (AT, DK, NO, SE); duraampicillin (DE); Dyna-Ampcil (ZA); Electopen (ES); Espectral (ES); Espectrosira® (ES); Excillin (ZA); Fidesbiotic® (ES); Flamicina® [tabs] (MX); Fortapen® (BE); Geycillina® (IT); Gobemicina (ES); Gonocilin® (BR); Gramcilina® (BR); Gramcillina® (IT); Herpen (JP); Hexacillin (ZA); Hiperbiotico (PT); Hiperbiotico Retard (PT); Huma-Ampicillin® (HU); Ibimicyn (IT); Ikapen® (IL); Iwacillin® (JP); Jenampin (DE); Kalampi® [vet.] (FR); Lampicin (MX); Lampocillina (IT); Makrocillin® (BR); Marisilan® (JP); Marovilina® (MX); Maxicilina® (ES); M-P-Cil (ZA); NC-Cillin® (JP); Negmapen (FR); Neoflaina® (IT); Novapen® (IE); Novo-Ampicillin (CA); Nu-Ampi (CA); Nuvapen (ES); Omnipen® (MX); Panestes (ES); Penactam inj.® [+ Sulbactam] (HR); Penbisin Süspansiyon® (TR); Pen-Bristol (DE); Penbritin (AU, BE, CA, HR, HK, IE, LU, NL, NO, ZA); Penibrin® (IL); Penicline (FR); Penimaster (ES); Penimic® (JP); Penodil® (HK); Penoral® (TR); Penorsin® (ES); Penrite (ZA); Penstabil® (CZ); Penstabil (DE, HU); Pentrexyl (DK, HU, IE, IT, LU, MX, NL, NO, ES, SE, YU); Pentrex (ZA); Pentricine® (CH); Petercillin (ZA); Platocillina® (IT); Principen (IT); Probenzima (BR); Prototapen (FR); Ranamp (ZA); Resan® (ES); Rimacillin® (GB); Rosampline (FR); Semicillin® (HU); Sentapent® (TR); Servicillin® (HK, CH); Seskasilin Oral Süsp.® (TR); Silina® (TR); Sinaplin® [tabs] (MX); Sintecilina (ES); Spectracil (ZA); Standacillin (AT, HU); Statcillin (ZA); Togram (ES); Topsilin® (TR); Totalciclina® (IT); Totapen (FR); Trifacilin® (AR); Ukapen (FR); Ultrabion (ES); Valmingina (ES); Vidopen (IE); Vidopen® [inj.] (GB); Zymopen® (BR)