PENICILLINSAND BETA-LACTAMASE INHIBITORS (Systemic)

Some commonly used brand names are:

In the U.S.?

• Augmentin ¹
• Timentin ⁴
• Unasyn ²
• Zosyn ³

In Canada?

• Clavulin-250 ¹
• Clavulin-125F ¹
• Clavulin-250F ¹
• Clavulin-500F ¹
• Tazocin ³
• Timentin ⁴

Category

• Antibacterial, systemic?Amoxicillin and Clavulanate; Ampicillinand Sulbactam; Piperacillin and Tazobactam; Ticarcillin and Clavulanate

Description

Penicillinsand beta-lactamase inhibitors are used to treat infections caused by bacteria.They work by killing the bacteria or preventing their growth. The beta-lactamaseinhibitor is added to the penicillin to protect the penicillin from certainsubstances (enzymes) that will destroy the penicillin before it can kill thebacteria.

There are several different kinds of penicillins. Each is used to treatdifferent kinds of infections. One kind of penicillin usually may not be usedin place of another. In addition, penicillins are used to treat bacterialinfections in many different parts of the body. They are sometimes given withother antibacterial medicines. Some of the penicillins may also be used forother problems as determined by your doctor. However, none of the penicillinswill work for colds, flu, or other virus infections.

Penicillins are available only with your doctor's prescription, in thefollowing dosage forms:

Oral
• Amoxicillin and Clavulanate
  • Oral suspension (U.S. and Canada)
  • Tablets (U.S. and Canada)
  • Chewable tablets (U.S.)

Parenteral
• Ampicillin and Sulbactam
  • Injection (U.S.)
• Piperacillin and Tazobactam
  • Injection (U.S. and Canada)
• Ticarcillin and Clavulanate
  • Injection (U.S. and Canada)

Before Using This Medicine

In deciding to use a medicine,the risks of taking the medicine must be weighed against the good it willdo. This is a decision you and your doctor will make. For penicillins, thefollowing should be considered:

Allergies?Tell your doctor if you have ever had any unusual orallergic reaction to any of the penicillins, cephalosporins, or beta-lactamaseinhibitors. Also tell your health care professional if you are allergic toany other substances, such as foods, preservatives, or dyes.

Diet?Tell your doctor if you are on a low-sodium(low-salt) diet. Some of these medicines contain enough sodium to cause problemsin some people.

Pregnancy?Penicillins and beta-lactamase inhibitors have notbeen studied in pregnant women. However, penicillins have not been shown tocause birth defects or other problems in animal studies.

Breast-feeding?Penicillins and sulbactam, a beta-lactamase inhibitor,pass into the breast milk. Even though only small amounts may pass into breastmilk, allergic reactions, diarrhea, fungus infections, and skin rash may occurin nursing babies.

Children?Penicillins and beta-lactamase inhibitors have beenused in children and, in effective doses, are not expected to cause differentside effects or problems in children than they do in adults.

Some strengths of the chewable tablets and oral suspensions of amoxicillinand clavulanate combination contain aspartame, which is changed by the bodyto phenylalanine, a substance that is harmful to patients with phenylketonuria.

Older adults?Penicillins and beta-lactamase inhibitors have beenused in the elderly and have not been shown to cause different side effectsor problems in older people than they do in younger adults.

Other medicines?Although certain medicines should not be usedtogether at all, in other cases two different medicines may be used togethereven if an interaction might occur. In these cases, your doctor may want tochange the dose, or other precautions may be necessary. When you are takinga penicillin and beta-lactamase inhibitor combination, it is especially importantthat your health care professional know if you are taking any of the following:

• Anticoagulants (blood thinners) or
• Dipyridamole (e.g., Persantine) or
• Divalproex (e.g., Depakote) or
• Heparin (e.g., Panheprin) or
• Inflammation or pain medicine (except narcotics) or
• Pentoxifylline (e.g., Trental) or
• Plicamycin (e.g., Mithracin) or
• Sulfinpyrazone (e.g., Anturane) or
• Valproic acid (e.g., Depakene)?Use of these medicines withpiperacillin and tazobactam combination or with ticarcillin and clavulanatecombination may increase the chance of bleeding

• Oral contraceptives (birth control pills)?Use of penicillinsand beta-lactamase inhibitors may prevent oral contraceptives from workingproperly, increasing the chance for pregnancy

• Probenecid (e.g., Benemid)?Probenecid causes penicillins, sulbactam,and tazobactam to build up in the blood. This may increase the chance of sideeffects. However, your doctor may want to give you probenecid with a penicillinand beta-lactamase inhibitor combination to treat some infections

Other medical problems?The presence of other medicalproblems may affect the use of penicillin and beta-lactamase inhibitor combinations.Make sure you tell your doctor if you have any other medical problems, especially:

• Allergies or a history of allergies, such as asthma, eczema, hayfever, or hives?Patients with a history of allergies may be more likelyto have a severe allergic reaction to a penicillin and beta-lactamase inhibitorcombination

• Bleeding problems, history of?Patients with a history of bleedingproblems may be more likely to have bleeding when receiving piperacillin andtazobactam combination or ticarcillin and clavulanate combination

• Congestive heart failure (CHF) or
• High blood pressure?Large doses of ticarcillin and clavulanatecombination may make these conditions worse, because this medicine containsa large amount of salt

• Cystic fibrosis?Patients with cystic fibrosis may have an increasedchance of fever and skin rash when receiving piperacillin and tazobactam combination

• Kidney disease?Patients with kidney disease may have an increasedchance of side effects

• Liver disease (active or a history of)?Penicillins and beta-lactamaseinhibitor combinations may cause this condition to recur or become worse

• Mononucleosis (?mono?)?Patients with mononucleosismay have an increased chance of skin rash when receiving ampicillin and sulbactamcombination

• Phenylketonuria?Some strengths of the amoxicillin and clavulanatecombination chewable tablets and oral suspension contain aspartame, whichis changed by the body to phenylalanine.

• Stomach or intestinal disease, history of (especially colitis, includingcolitis caused by antibiotics)?Patients with a history of stomach orintestinal disease may be more likely to develop colitis while taking penicillinsand beta-lactamase inhibitors

Proper Use of This Medicine

Amoxicillinand clavulanate combination may be taken on a full or empty stomach. Takingamoxicillin and clavulanate combination with food may decrease the chanceof diarrhea, nausea, and vomiting.

For patients taking the oral liquid form of amoxicillinand clavulanate combination:

• Use a specially marked measuring spoon or other device to measureeach dose accurately. The average household teaspoon may not hold the rightamount of liquid.
• Do not use after the expiration date on the label. The medicine maynot work properly after that date. If you have any questions about this, checkwith your pharmacist.

For patients taking the chewable tablet form of amoxicillinand clavulanate combination:

• Tablets should be chewed or crushed before they are swallowed.

To help clear up your infection completely, keep takingthis medicine for the full time of treatment, even if you begin tofeel better after a few days.

This medicine works best when there is a constant amount in the blood orurine. To help keep the amount constant, do not missany doses. Also, it is best to take the doses at evenly spaced times, dayand night. For example, if you are to take four doses a day, the dosesshould be spaced about 6 hours apart. If this interferes with your sleep orother daily activities, or if you need help in planning the best times totake your medicine, check with your health care professional.

Dosing?The dose of these medicines will be differentfor different patients. Follow your doctor's orders orthe directions on the label. The following information includes onlythe average doses of these medicines. If your dose isdifferent, do not change it unless your doctor tells you to do so.

The number of tablets or teaspoonfuls of suspension that you take dependson the strength of the medicine. Also, the number ofdoses you take each day, the time allowed between doses, and the length oftime you take the medicine depend on the medical problem for which you aretaking a penicillin and beta-lactamase inhibitor combination.

For amoxicillin and clavulanate combination
• For bacterial infections:
  • For oral dosage forms (chewable tabletsand suspension):
    • Adults, teenagers, and children weighing more than 40 kilograms (kg)(88 pounds)?250 to 500 milligrams (mg) of amoxicillin, in combinationwith 125 mg of clavulanate, every eight hours or 500 to 875 mg of amoxicillin,in combination with 125 mg of clavulanate, every twelve hours.
    • Neonates and infants up to 12 weeks (3 months) of age?Doseis based on body weight and must be determined by your doctor. The usual doseis 15 mg of amoxicillin per kg (6.8 mg per pound) of body weight every twelvehours.
    • Infants 3 months of age and older and children weighing up to 40kg (88 pounds)?6.7 to 22.5 mg of amoxicillin per kg (3 to 10.2 mg perpound) of body weight, in combination with 1.7 to 3.2 mg of clavulanate perkg (0.8 to 1.5 mg per pound) of body weight, every eight or twelve hours.
  • For oral dosage form (tablets):
    • Adults, teenagers, and children weighing more than 40 kg (88 pounds)?250to 500 mg of amoxicillin, in combination with 125 mg of clavulanate, everyeight hours or 500 to 875 mg of amoxicillin, in combination with 125 mg ofclavulanate, every twelve hours.
    • Infants and children weighing up to 40 kg (88 pounds)?The amoxicillinand clavulanate combination tablets are too strong for childrenweighing less than 40 kg (88 pounds). The chewable tablets or oral suspensionare used in these children.

For ampicillin and sulbactam combination
• For bacterial infections:
  • For injection dosage form:
    • Adults and teenagers?1 to 2 grams of ampicillin, in combinationwith 500 milligrams (mg) to 1 gram of sulbactam, injected into a vein or amuscle every six hours.
    • Children 1 to 12 years of age?Dose must be determined by yourdoctor.
    • Children up to 1 year of age?Use and dose must be determinedby your doctor.

For piperacillin and tazobactam combination
• For bacterial infections:
  • For injection dosage form:
    • Adults and teenagers?3 to 4 grams of piperacillin, in combinationwith 0.375 to 0.5 grams of tazobactam, injected into a vein every six to eighthours for seven to ten days.
    • Children up to 12 years of age?Dose must be determined by yourdoctor.

For ticarcillin and clavulanate combination
• For bacterial infections:
  • For injection dosage form:
    • Adults and teenagers weighing 60 kilograms (kg) (132 pounds) or more?3grams of ticarcillin, in combination with 100 milligrams (mg) of clavulanate,injected into a vein every four to six hours.
    • Adults and teenagers weighing less than 60 kg (132 pounds)?50mg of ticarcillin per kg (22.7 mg per pound) of body weight, in combinationwith 1.7 mg of clavulanate per kg (0.8 mg per pound) of body weight, injectedinto a vein every four to six hours.
    • Infants and children 1 month to 12 years of age?50 mg of ticarcillinper kg (22.7 mg per pound) of body weight, in combination with 1.7 mg of clavulanateper kg (0.8 mg per pound) of body weight, injected into a vein every fourto six hours.
    • Infants up to 1 month of age?Use and dose must be determinedby your doctor.

Missed dose?If you miss a dose of this medicine, take it assoon as possible. This will help to keep a constant amount of medicine inthe blood or urine. However, if it is almost time for your next dose, skipthe missed dose and go back to your regular dosing schedule. Do not doubledoses.

Storage?To store this medicine:

• Keep out of the reach of children.
• Store away from heat and direct light.
• Do not store tablets in the bathroom, near the kitchen sink, or inother damp places. Heat or moisture may cause the medicine to break down.
• Store the oral liquid form of penicillins in the refrigerator becauseheat will cause this medicine to break down. However, keep the medicine fromfreezing. Follow the directions on the label.
• Do not keep outdated medicine or medicine no longer needed. Be surethat any discarded medicine is out of the reach of children.

Precautions While Using This Medicine

If yoursymptoms do not improve within a few days, or if they become worse, checkwith your doctor.

Penicillins may cause diarrhea in some patients.

• Check with your doctor if severe diarrhea occurs. Severe diarrhea may be a sign of a serious side effect. Do not take any diarrhea medicine. Diarrhea medicines may make yourdiarrhea worse or make it last longer.
• For mild diarrhea, diarrhea medicine containing kaolin or attapulgite(e.g., Kaopectate tablets, Diasorb) may be taken. However, other kinds ofdiarrhea medicine should not be taken. They may make your diarrhea worse ormake it last longer.
• If you have any questions about this or if mild diarrhea continuesor gets worse, check with your health care professional.

For patients with diabetes:

• Penicillin and beta-lactamase inhibitor combinationsmay cause false test results with some urine sugar tests. Check withyour doctor before changing your diet or the dosage of your diabetes medicine.

Before you have any medical tests, tell the doctor in charge that you aretaking this medicine. The results of some tests may be affected by this medicine.

Side Effects of This Medicine

Along with its needed effects, a medicine may cause some unwanted effects.Although not all of these side effects may occur, if they do occur they mayneed medical attention.

Stop taking this medicineand get emergency help immediately if any of the following side effectsoccur:

Less common

Cough; fast or irregular breathing; fever; joint pain; lightheadedness or fainting (sudden); pain, redness,or swelling at site of injection; puffiness or swellingaround the face; red, irritated eyes ; shortness of breath; skin rash, hives,itching; sore mouth or tongue; unusual tiredness or weakness; vaginal itching anddischarge; white patches in mouth and/or on tongue

In addition to the side effects mentioned above, check with your doctor immediately if any of the following side effectsoccur:

Rare

Abdominal or stomach cramps and pain (severe); blistering, peeling, or loosening of skin and mucous membranes; chest pain; cloudy urine; convulsions (seizures); diarrhea (wateryand severe), which may also be bloody; general feelingof illness or discomfort; nausea or vomiting; redness, soreness, or swelling of tongue; red skin lesions, often with a purple center; sorethroat; swelling of face, fingers, lower legs, orfeet; trouble in urinating; unusual bleeding or bruising; weight gain; yellow eyes or skin

Note:

Some of the above side effects (severe abdominal or stomach crampsand pain, and watery and severe diarrhea, which may also be bloody) may alsooccur up to several weeks after you stop taking any of these medicines.

Other side effects may occur that usually do not need medical attention.These side effects may go away during treatment as your body adjusts to themedicine. However, check with your doctor if any of the following side effectscontinue or are bothersome:

More common

Diarrhea (mild); gas; headache; stomach pain; swelling of abdomen

Less common or rare

Chills; nosebleed; long-lasting muscle relaxation (with piperacillin and tazobactam combination); unusual tiredness or weakness

Other side effects not listed above may also occur insome patients. If you notice any other effects, check with your doctor.

Additional Information

Once a medicine has been approvedfor marketing for a certain use, experience may show that it is also usefulfor other medical problems. Although these uses are not included in productlabeling, penicillins and beta-lactamase inhibitor combinations are used incertain patients with the following medical conditions:

Amoxicillin and clavulanate combination
• Bronchitis
• Chancroid

Ampicillin and sulbactam combination
• Gonorrhea

Ticarcillin and clavulanate combination
• Certain surgeries, such as colorectal surgery, abdominal hysterectomy,and high-risk cesarean section: This medicine is sometimes used to preventinfection from these surgical procedures.

Other than the above information, there is no additional information relatingto proper use, precautions, or side effects for these uses.