Serious and occasionally fatal hypersensitivity (anaphylactic shock with collapse) reactions have occurred in patients receiving penicillin. The incidence of anaphylactic shock in all penicillin-treated patients is between 0.015 and 0.04 percent. Anaphylactic shock resulting in death has occurred in approximately 0.002 percent of the patients treated. Although anaphylaxis is more frequent following a parenteral administration, it has occurred in patients receiving oral penicillins.
When penicillin therapy is indicated, it should be initiated only after a comprehensive patient drug and allergy history has been obtained. If an allergic reaction occurs, the drug should be discontinued and the patient should receive supportive treatment, eg, artificial maintenance of ventilation, pressor amines, antihistamines, and corticosteroids. Individuals with a history of penicillin hypersensitivity may also experience allergic reactions when treated with a cephalosporin.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, and may range from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antimicrobial agents. After the diagnosis has been established, therapeutic measures should be initiated.
The use of antibiotics may result in overgrowth of nonsusceptible organisms. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin product by Clostridium difficile is one primary cause of "antibiotic-associated colitis." After the diagnosis of pseudomembranous colitis has been established therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with antibacterial drug clinically effective against C. difficile colitis.
Penicillinase-resistant penicillins should generally not be administered to patients with a history of sensitivity to any penicillin.
Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma. There is clinical and laboratory evidence of partial cross-allergenicity among penicillins and other β-lactam antibiotics including cephalosporins, cephamycins, and other 1-oxa-β-lactams. Whenever allergic reactions occur, penicillin should be withdrawn unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to penicillin therapy.
The oral route of administration should not be relied upon in patients with severe illness, or with nausea, vomiting, gastric dilation, cardiospasm, or intestinal hypermotility. Occasionally patients will not absorb therapeutic amounts of orally administered penicillin.
Prescribing dicloxacillin sodium capsules in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Information for the Patient
Patients receiving penicillins should be given the following information and instructions by the physician:
- Patients should be told that penicillin is an antibacterial agent which will work with the body's natural defenses to control certain types of infections. They should be told that the drug should not be taken if they have had an allergic reaction to any form of penicillin previously, and to inform the physician of any allergies or previous allergic reactions to any drugs they may have had (see WARNINGS).
- Patients who have previously experienced an anaphylactic reaction to penicillin should be instructed to wear a medical identification tag or bracelet.
- Because most antibacterial drugs taken by mouth are best absorbed on an empty stomach, patients should be directed, unless circumstances warrant otherwise, to take penicillin one hour before meals or two hours after eating (see CLINICAL PHARMACOLOGY–Pharmacokinetics).
- Patients should be told to take the entire course of therapy prescribed, even if fever and other symptoms have stopped (see PRECAUTIONS–General).
- If any of the following reactions occur, stop taking your prescription and notify the physician: shortness of breath, wheezing, skin rash, mouth irritation, black tongue, sore throat, nausea, vomiting, diarrhea, fever, swollen joints, or any unusual bleeding or bruising (see ADVERSE REACTIONS).
- Do not take any additional medications without physician approval, including non-prescription drugs such as antacids, laxatives, or vitamins.
Patients should be counseled that antibacterial drugs including dicloxacillin sodium capsules should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When dicloxacillin sodium capsules are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by dicloxacillin sodium capsules or other antibacterial drugs in the future.
Bacteriologic studies to determine the causative organisms and their susceptibility to the penicillinase-resistant penicillins should be performed (see CLINICAL PHARMACOLOGY-Microbiology). In the treatment of suspected staphylococcal infections, therapy should be changed to another active agent if culture tests fail to demonstrate the presence of staphylococci.
Periodic assessment of organ system function including renal, hepatic, and hematopoietic should be made during prolonged therapy with the penicillinase-resistant penicillins.
Blood cultures, white blood cell, and differential cell counts should be obtained prior to initiation of therapy and at least weekly during therapy with penicillinase-resistant penicillins.
Periodic urinalysis, blood urea nitrogen, and creatinine determinations should be performed during therapy with the penicillinase-resistant penicillins and dosage alterations should be considered if these values become elevated. If any impairment of renal function is suspected or known to exist, a reduction in the total dosage should be considered and blood levels monitored to avoid possible neurotoxic reactions (see DOSAGE AND ADMINISTRATION).
AST (SGOT) and ALT (SGPT) values should be obtained periodically during therapy to monitor for possible liver function abnormalities.
Tetracycline, a bacteriostatic antibiotic, may antagonize the bactericidal effect of penicillin and concurrent use of these drugs should be avoided.
Probenecid administered concomitantly with penicillins increases and prolongs serum penicillin levels (see DOSAGE AND ADMINISTRATION).
Penicillinase-resistant penicillins, like other penicillins, are physically and/or chemically incompatible with aminoglycosides and can inactivate the drugs in vitro. In vitro mixing of penicillins and aminoglycosides should be avoided during concomitant therapy and the drugs should be administered separately. Penicillins can inactivate aminoglycosides in vitro in serum samples from patients receiving both drugs, which could produce falsely decreased results in serum aminoglycoside assays of the serum samples.
Dicloxacillin may reduce the anticoagulant response to dicumarol and warfarin. Careful monitoring of prothrombin times is suggested during concomitant therapy, and dosage of the anticoagulant should be adjusted as required. The mechanism of this possible interaction is unclear, but may be due to hepatic enzyme induction.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term animal studies have been conducted with these drugs.
Studies on reproduction (nafcillin) in rats and rabbits reveal no fetal or maternal abnormalities before conception and continuously through weaning (one generation).
Pregnancy Category B
Reproduction studies performed in the mouse, rat, and rabbit have revealed no evidence of impaired fertility or harm to the fetus due to the penicillinase-resistant penicillins. Human experience with the penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. There are, however, no adequate or well-controlled studies in pregnant women showing conclusively that harmful effects of these drugs on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Penicillins are excreted in breast milk. Caution should be exercised when penicillins are administered to a nursing woman.
Because of incompletely developed renal function in newborns, penicillinase-resistant penicillins (especially methicillin) may not be completely excreted, with abnormally high blood levels resulting. Frequent blood levels are advisable in this group with dosage adjustments when necessary. All newborns treated with penicillin should be monitored closely for clinical and laboratory evidence of toxic or adverse effects (see DOSAGE AND ADMINISTRATION). Experience in the neonatal period is limited. Therefore a dose for the newborn is not recommended.
Clinical studies of dicloxacillin sodium capsules did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Rare reports have been received during postmarketing surveillance of esophageal burning, esophagitis, and esophageal ulceration, particularly after ingestion of dicloxacillin capsules with an insufficient quantity of water and/or before going to bed. To minimize the risk of developing such events, dicloxacillin should be taken with at least 4 fluid ounces (120 mL) of water and dicloxacillin should NOT be taken in the supine position or immediately before going to bed.