clavulanate


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Related to clavulanate: clavulanic acid, amoxicillin and clavulanate potassium

clavulanate

 [klav´u-lah-nāt]
a β-lactamase inhibitor used as the potassium salt in combination with penicillins in treating infections caused by β-lactamase–producing organisms.

amoxicillin/clavulanate

(a-mox-i-sill-in/klav-yoo-lan -ate) ,

Augmentin

(trade name),

Augmentin ES

(trade name),

Augmentin XR

(trade name),

Clavulin

(trade name)

Classification

Therapeutic: anti infectives
Pharmacologic: aminopenicillins beta lactamase inhibitors
Pregnancy Category: B

Indications

Treatment of a variety of infections including:
  • Skin and skin structure infections,
  • Otitis media,
  • Sinusitis,
  • Respiratory tract infections,
  • Genitourinary tract infections.

Action

Binds to bacterial cell wall, causing cell death; spectrum of amoxicillin is broader than penicillin. Clavulanate resists action of beta-lactamase, an enzyme produced by bacteria that is capable of inactivating some penicillins.

Therapeutic effects

Bactericidal action against susceptible bacteria.
Active against:
  • Streptococci,
  • Pneumococci,
  • Enterococci,
  • Haemophilus influenzae,
  • Escherichia coli,
  • Proteus mirabilis,
  • Neisseria meningitidis,
  • N. gonorrhoeae,
  • Staphylococcus aureus,
  • Klebsiella pneumoniae,
  • Shigella,
  • Salmonella,
  • Moraxella catarrhalis.

Pharmacokinetics

Absorption: Well absorbed from the duodenum (75–90%). More resistant to acid inactivation than other penicillins.
Distribution: Diffuses readily into most body tissues and fluids. Does not readily enter brain/CSF; CSF penetration is ↑ in the presence of inflamed meninges. Crosses the placenta and enters breast milk in small amounts.
Metabolism and Excretion: 70% excreted unchanged in the urine; 30% metabolized by the liver.
Half-life: 1–1.3 hr.

Time/action profile (peak blood levels)

ROUTEONSETPEAKDURATION
PO30 min1–2 hr8–12 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity to penicillins or clavulanate;Suspension and chewable tablets contain aspartame and should be avoided in phenylketonurics;History of amoxicillin/clavulanate-associated cholestatic jaundice.
Use Cautiously in: Severe renal insufficiency (dose ↓ necessary);Infectious mononucleosis (↑ risk of rash);Hepatic impairment (dose cautiously, monitor liver function).

Adverse Reactions/Side Effects

Central nervous system

  • seizures (high doses) (life-threatening)

Gastrointestinal

  • pseudomembranous colitis (life-threatening)
  • diarrhea (most frequent)
  • hepatic dysfunction
  • nausea
  • vomiting

Genitourinary

  • vaginal candidiasis

Dermatologic

  • rash (most frequent)
  • urticaria

Hematologic

  • blood dyscrasias

Miscellaneous

  • allergic reactions including anaphylaxis and serum sickness (life-threatening)
  • superinfection

Interactions

Drug-Drug interaction

Probenecid ↓ renal excretion and ↑ blood levels of amoxicillin—therapy may be combined for this purpose.May ↑ the effect of warfarin.Concurrent allopurinol therapy ↑ risk of rash.May ↓ the effectiveness of hormonal contraceptives.Clavulanate absorption is ↓ by a high fat meal.

Route/Dosage

Most Infections (Dosing based on amoxicillin component)
Oral (Adults and Children >40 kg) 250 mg q 8 hr or 500 mg q 12 hr.
Serious Infections and Respiratory Tract Infections
Oral (Adults and Children >40 kg) 875 mg q 12 hr or 500 mg q 8 hr; Acute bacterial sinusitis—2000 mg q 12 hr for 10 days as extended release (XR) product; Community-acquired pneumonia—2000 mg every 12 hr for 7–10 days as extended release (XR) product.
Recurrent/persistent acute otitis media due to Multidrug-resistant Streptococcus pneumonia, H. influenzae, or M. catarrhalis
Oral (Children <40 kg) 80–90 mg/kg/day in divided doses q 12 hr for 10 days (as ES formulation only).

Renal Impairment

Oral (Adults) CCr 10–30 mL/min—250–500 mg q 12 hr (do not use 875 mg tablet); CCr <10 mL/min—250–500 mg q 24 hr.
Otitis Media, Sinusitis, Lower Respiratory Tract Infections, Serious Infections
Oral (Children ≥3 mo) 200 mg/5 mL or 400 mg/5 mL suspension—45 mg/kg/day divided q 12 hr; 125 mg/5 mL or 250 mg/5 mL suspension—40 mg/kg/day divided q 8 hr.
Less Serious Infections
Oral (Children ≥3 mo) 200 mg/5 mL or 400 mg/5 mL suspension—25 mg/kg/day divided q 12 hr or 20 mg/kg/day divided q 8 hr (as 125 mg/5 mL or 250 mg/5 mL suspension).
Oral (Children <3 mo) 15 mg/kg q 12 hr (125 mg/mL suspension recommended).

Availability (generic available)

Tablets: 250 mg amoxicillin with 125 mg clavulanate, 500 mg amoxicillin with 125 mg clavulanate, 875 mg amoxicillin with 125 mg clavulanate Cost: Generic — 500 mg $18.98 / 20, 875 mg $23.46 / 30
Chewable tabletscherry-banana flavor: 200 mg amoxicillin with 28.5 mg clavulanate, 400 mg amoxicillin with 57 mg clavulanate Cost: Generic — 200 mg $36.17 / 20, 400 mg $68.93 / 20
Extended-release tablets (scored): 1000 mg amoxicillin with 62.5 mg clavulanate Cost: Generic — $108.62 / 28
Powder for oral suspension 125 mg/5 mL is banana flavor; 200 mg/5ml is fruit flavor; 250 mg/5 mL is orange flavor; 400 mg/5 mL is fruit flavor; 600 mg/5 mL is orange or strawberry-creme flavor: 125 mg amoxicillin with 31.25 mg clavulanate/5 mL, 200 mg amoxicillin with 28.5 mg clavulanate/5 mL, 250 mg amoxicillin with 62.5 mg clavulanate/5 mL, 400 mg amoxicillin with 57 mg clavulanate/5 mL, 600 mg amoxicillin with 42.9 mg clavulanate/5 mL (ES formulation) Cost: Generic — 200 mg $36.17 / 100 mL, 250 mg $86.43 / 100 mL, 400 mg $68.93 / 100 mL, 600 mg $83.03 / 125 mL

Nursing implications

Nursing assessment

  • Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy.
  • Obtain a history before initiating therapy to determine previous use of and reactions to penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response.
  • Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Notify health care professional immediately if these occur.
  • Obtain specimens for culture and sensitivity prior to therapy. First dose may be given before receiving results.
  • Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of pseudomembranous colitis. May begin up to several weeks following cessation of therapy.
  • Lab Test Considerations: May cause ↑ serum alkaline phosphatase, LDH, AST, and ALT concentrations. Elderly men and patients receiving prolonged treatment are at ↑ risk for hepatic dysfunction.
    • May cause false-positive direct Coombs’ test result.

Potential Nursing Diagnoses

Risk for infection (Indications,  Side Effects)
Noncompliance (Patient/Family Teaching)

Implementation

  • Oral: Administer around the clock. Administer at the start of a meal to enhance absorption and to decrease GI side effects. Do not administer with high fat meals; clavulanate absorption is decreased. XR tablet is scored and can be broken for ease of administration. Capsule contents may be emptied and swallowed with liquids. Chewable tablets should be crushed or chewed before swallowing with liquids. Shake oral suspension before administering. Refrigerated reconstituted suspension should be discarded after 10 days.
    • Two 250-mg tablets are not bioequivalent to one 500-mg tablet; 250-mg tablets and 250-mg chewable tablets are also not interchangeable. Two 500-mg tablets are not interchangeable with one 1000-mg XR tablet; amounts of clavulanic acid and durations of action are different. Augmentin ES 600 (600 mg/5 mL) does not contain the same amount of clavulanic acid as any of the other Augmentin suspensions. Suspensions are not interchangeable.
    • Pediatric: Do not administer 250-mg chewable tablets to children <40 kg due to clavulanate content. Children <3 mo should receive the 125-mg/5 mL oral solution.

Patient/Family Teaching

  • Instruct patients to take medication around the clock and to finish the drug completely as directed, even if feeling better. Advise patients that sharing of this medication may be dangerous.
  • Pediatric: Teach parents or caregivers to calculate and measure doses accurately. Reinforce importance of using measuring device supplied by pharmacy or with product, not household items.
  • Advise patient to report the signs of superinfection (furry overgrowth on the tongue, vaginal itching or discharge, loose or foul-smelling stools) and allergy.
  • Instruct patient to notify health care professional immediately if diarrhea, abdominal cramping, fever, or bloody stools occur and not to treat with antidiarrheals without consulting health care professionals.
  • Instruct the patient to notify health care professional if symptoms do not improve or if nausea or diarrhea persists when drug is administered with food.
  • Instruct female patients taking oral contraceptives to use an alternate or additional method of contraception during therapy and until next menstrual period; may decrease effectiveness of hormonal contraceptives.

Evaluation/Desired Outcomes

  • Resolution of the signs and symptoms of infection. Length of time for complete resolution depends on the organism and site of infection.

ticarcillin/clavulanate

(tye-kar-sil-in/klav-yoo-la-nate) ,

Timentin

(trade name)

Classification

Therapeutic: anti infectives
Pharmacologic: extended spectrum penicillins
Pregnancy Category: B

Indications

Treatment of:
  • Skin and skin structure infections,
  • Bone and joint infections,
  • Septicemia,
  • Lower respiratory tract infections,
  • Intra-abdominal, gynecologic, and urinary tract infections.

Action

Binds to bacterial cell wall membrane, causing cell death.
Addition of clavulanate enhances resistance to beta-lactamase, an enzyme that can inactivate penicillins.

Therapeutic effects

Bactericidal action.
Similar to penicillin but extended to include several gram-negative aerobic pathogens, notably:
  • Pseudomonas aeruginosa,
  • Escherichia coli,
  • Citrobacter,
  • Enterobacter,
  • Haemophilus influenzae,
  • Klebsiella,
  • Serratia marcescens.
Active against some anaerobic bacteria, including bacteroides.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Widely distributed. Enters CSF well when meninges are inflamed. Crosses the placenta; enters breast milk in low concentrations.
Metabolism and Excretion: 10% of ticarcillin is metabolized by the liver; 90% excreted unchanged by the kidneys. Clavulanate is metabolized by the liver.
Half-life: Ticarcillin—1.1 hr (↑ in renal impairment); clavulanate—1.1 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
IVrapidend of infusion4–6 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity to penicillins (cross-sensitivity with cephalosporins may occur).
Use Cautiously in: Renal impairment (dose ↓ and/or ↑ interval required if CCr <60 mL/min);HF (due to high sodium content); Obstetric / Lactation: Safety not established; Pediatric: Children <3 mo (safety not established).

Adverse Reactions/Side Effects

Central nervous system

  • seizures (high doses) (life-threatening)
  • confusion
  • lethargy

Cardiovascular

  • chf (life-threatening)
  • arrhythmias

Gastrointestinal

  • pseudomembranous colitis (life-threatening)
  • diarrhea (most frequent)
  • nausea

Genitourinary

  • hematuria (children only)
  • hemorrhagic cystitis

Dermatologic

  • rash (most frequent)
  • urticaria

Fluid and Electrolyte

  • hypokalemia (most frequent)
  • hypernatremia

Hematologic

  • bleeding
  • blood dyscrasias
  • ↑ bleeding time

Local

  • phlebitis (most frequent)

Metabolic

  • metabolic alkalosis

Miscellaneous

  • hypersensitivity reactions including anaphylaxis (life-threatening)
  • superinfection

Interactions

Drug-Drug interaction

Probenecid ↓ renal excretion and ↑ blood levels.

Route/Dosage

Ticarcillin/clavulanate contains 4.51 mEq sodium/g and 0.15 mEq potassium/g of ticarcillin/clavulanate. 3 g ticarcillin plus 100 mg clavulanate labeled as 3.1 g combined potency. Dosing is based on ticarcillin component.
Intravenous (Adults and Children >16 yr) 3 g ticarcillin q 4–6 hr.
Intravenous (Children 3 mo–16 yr) <60 kg—Mild to moderate infection: 50 mg ticarcillin/kg q 6 hr; severe infection: 50 mg ticarcillin/kg q 4 hr. ≥60 kg—Mild to moderate infection: 3 g ticarcillin q 6 hr; severe infection: 3 g ticarcillin q 4 hr.

Renal Impairment

Intravenous (Adults) Give loading dose of 3 g ticarcillin × 1 dose, followed by maintenance dose based on CCr. CCr 30–60 mL/min—2 g ticarcillin q 4 hr; 10–30 mL/min—2 g ticarcillin q 8 hr; CCr <10 mL/min—2 g ticarcillin q 12 hr; CCr <10mL/min with hepatic dysfunction—2 g ticarcillin q 24 hr; Peritoneal dialysis—3 g ticarcillin q 12 hr; Hemodialysis—2 g ticarcillin q 12 hr supplemented with 3 g ticarcillin after each dialysis session.

Availability

Powder for injection: 3.1 g/vial, 31 g/vial
Premixed infusion: 3.1 g/100 mL

Nursing implications

Nursing assessment

  • Assess patient for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy.
  • Obtain a history before initiating therapy to determine use of and reactions to penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response.
  • Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
  • Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue drug and notify physician immediately if these problems occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of anaphylactic reaction.
  • Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of pseudomembranous colitis. May begin up to several weeks following cessation of therapy.
  • Lab Test Considerations: Evaluate renal and hepatic function, CBC, serum potassium, and bleeding times prior to and routinely throughout therapy.
    • May cause false-positive urine protein testing and increased BUN, creatinine, AST, ALT, serum bilirubin, alkaline phosphatase, LDH, and uric acid levels. May also cause ↑ bleeding time.
    • May cause hypernatremia and hypokalemia with high doses.

Potential Nursing Diagnoses

Risk for infection (Indications,  Side Effects)

Implementation

  • Intravenous Administration
  • Intravenous: Change IV sites every 48 hr to prevent phlebitis.
  • Intermittent Infusion: Add 13 mL of sterile water for injection or 0.9% NaCl for injection to each 3.1-g vial, to provide a concentration of ticarcillin 200 mg/mL and clavulanic acid 6.7 mg/mL. Diluent: Further dilute in 0.9% NaCl, D5W, or LR. Reconstituted vials stable for 24 hr at room temperature or 72 hr if refrigerated. Infusion is stable for 24 hr at room temperature. If refrigerated, infusion is stable for 3 days (diluted in D5W) or 7 days (if diluted in 0.9% NaCl or LR). Concentration: 10–100 mg/mL.
  • Rate: Infuse over 30 min.
  • Y-Site Compatibility: alfentanyl, allopurinol, amifostine, amikacin, aminocaproic acid, aminophylline, amphotericin B lipid complex, amphotericin B liposome, anidulafungin, argatroban, ascorbic acid, atropine, aztreonam, benztropine, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium chloride, calcium gluconate, carboplastin, carmustine, cefazolin, cefepime, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, chloramphenicol, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dactinomycin, daptomycin, dexamethasone sodium phosphate, dexmedetomidine, digoxin, diltiazem, diphenhydramine, docetaxel, dopamine, doxorubicin hydrochloride, doxorubicin liposome, doxycycline, enalaprilat, ephedrine, epinephrine, epoetin alfa, eptifibatide, esmolol, etoposide phosphate, famotidine, fenoldopam, fentanyl, filgrastim, fluconazole, fludarabine, fluorouracil, folic acid, furosemide, gemcitabine, gentamicin, glycopyrrolate, granisetron, heparin, hydrocortisone sodium succinate, hydromorphone, ifosfamide, imipenem/cilastatin, indomethacin, insulin, irinotecan, isoproterenol, ketorolac, labetalol, levofloxacin, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitil, mechlorethamine, melphalan, meperidine, methotrexate, methyldopate, methylprednisolone sodium succinate, metoclopramide, metoprolol, metronidazole, milrinone, morphine, multivitamins, nafcillin, nalbuphine, naloxone, nitroglycerin, nitroprusside, norepinephrine, octreotide, ondansetron, oxacillin, oxaliplatin, oxytocin, paclitaxel, palonosetron, pamidronate, pancuronium, pantoprazole, pemetrexed, penicillin G, perphenazine, phenobarbital, phentolamine, phenylephrine, phytonadione, potassium acetate, potassium chloride, procainamide, prochlorperazine, propofol, propranolol, pyridoxime, ranitidine, remifentanil, rituximab, rocuronium, sargramostim, sodium acetate, sodium bicarbonate, streptokinase, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiamine, thiotepa, tigecycline, tirofiban, tobramycin, tolazoline, trastuzumab, trimetaphan, vasopressin, vecuronium, verapamil, vincristine, vinorelbine, voriconazole, zoledronic acid
  • Y-Site Incompatibility: acyclovir, alemtuzumab, amphotericin B cholesteryl, azithromycin, caspofungin, chlorpromazine, dantrolene, diazepam, diazoxide, dobutamine, epirubicin, erythromycin, ganciclovir, haloperidol, hydroxyzine, idarubicin, mitoxantrone, mycophenolate, papaverine, pentamidine, pentazocine, phenytoin, promethazine, protamine, quinupristin/dalfopristin, tranexamic acid, trimethoprim/sulfamethoxazole.If aminoglycosides and penicillins must be administered concurrently, administer in separate sites at least 1 hr apart.

Patient/Family Teaching

  • Advise patient to report signs of superinfection (black, furry overgrowth on the tongue; vaginal itching or discharge; loose or foul-smelling stools) and allergy.
  • Caution patient to notify health care professional if fever and diarrhea occur, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional. May occur up to several weeks after discontinuation of medication.

Evaluation/Desired Outcomes

  • Resolution of the signs and symptoms of infection. Length of time for complete resolution depends on the organism and site of infection.

clavulanate

/clav·u·la·nate/ (klav´u-lah-nāt) a β-lactamase inhibitor used as the potassium salt in combination with penicillins in treating infections caused by β-lactamase–producing organisms.

clavulanic acid, clavulanate

a beta-lactam product of Streptomyces spp. It binds irreversibly and inhibits β-lactamase produced by many organisms. Used commonly in combination with amoxicillin.
References in periodicals archive ?
As a last resort, the Belgian physicians decided to try clavulanate and meropenem, the combination therapy they had read about in Blanchard's Science paper.
The likely explanation is that AmpC-type [beta]-lactamases resist inhibition by clavulanate and hence obscure the synergistic effect of clavulanate and cephalosporins against ESBLs.
In DDST cefepime and cefotaxime together with the clavulanate containing disk detected most of the ESBL producing isolates.
Clinical Cure Rates in Uncomplicated Cystitis Amoxicillin- Ciprofloxacin Clavulanate 2 weeks 98% 80% 4 weeks 90% 77% 8 weeks 84% 70% 12 weeks 79% 66% Source: Dr.
A more detailed drug history obtained from the patient revealed that a similar, although less severe, episode of hepatitis had occurred approximately 3 years before, soon after she took amoxicillin/ clavulanate for an upper respiratory tract infection.
Tenders are invited for Injection Amoxycillin - 1 Gm Plus Sodium Or Potassium Clavulanate / Clavulanic Acid - 200 Mg With Diluent
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Patients could continue on the intravenous regimen, if needed, for up to 28 days, but patients who were treated for at least 5 days and met certain clinical criteria for improvement were switched to an oral regimen with amoxicillin and clavulanate.
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Prescription of quinolones increased 127% and amoxicillin plus clavulanate rose 76%.