Spectracef

Contraindications

Documented hypersensitivity to drug, penicillin, related compounds, or milk protein sodium caseinate; carnitine deficiency or inborn errors of metabolism that may result in clinically significant carnitine deficiency

Cautions

May cause diarrhea, nausea, and vaginal moniliasis (yeast infection); pseudomembranous colitis may occur; clinical manifestations of carnitine deficiency may occur with prolonged use; prolonged use may result in emergence and overgrowth of resistant organisms; caution in breastfeeding

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

Take this medication with a full glass of water.

Your body will best absorb cefditoren if you take it with food.

Take this medication for the entire length of time prescribed by your doctor. Your symptoms may get better before the infection is completely treated. Cefditoren will not treat a viral infection such as the common cold or flu.

This medication can cause you to have false results with certain medical tests, including urine glucose (sugar) tests. Tell any doctor who treats you that you are using cefditoren.

Store cefditoren at room temperature away from moisture, heat, and light.

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include nausea, vomiting, diarrhea, stomach pain, and seizure (convulsions).

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

Cefditoren is in a group of drugs called cephalosporin (SEF a low spor in) antibiotics. It works by fighting bacteria in your body.

Cefditoren is used to treat many different types of bacterial infections that can cause bronchitis, tonsillitis, pneumonia, or skin infection.

Cefditoren may also be used for other purposes not listed in this medication guide.

Your pharmacist can provide more information about cefditoren.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Spectracef, there are no specific foods that you must exclude from your diet when receiving this medication.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Absorption

Bioavailability

Cefditoren pivoxil is a prodrug that is absorbed from the GI tract and hydrolyzed by esterases to the active metabolite, cefditoren.1

Absolute bioavailability only 14% when given without food;1 peak plasma concentrations of cefditoren attained within 1.5–3 hours.1

Food

Administration with a moderate- or high-fat meal increases the rate and extent of absorption.1

Distribution

Extent

Distributed into tonsils and skin blister fluid.1

Distributed into milk in rats.1

Plasma Protein Binding

88%;1 binding is independent of concentration.1

Binds principally to albumin; 3.3–8.1% bound to α-1-acid glycoprotein.1

Elimination

Metabolism

Cefditoren pivoxil is a prodrug and has little, if any, antibacterial activity until hydrolyzed in vivo by esterases to cefditoren.1 Hydrolysis of the drug also results in the formation of pivalate, which is absorbed and excreted as pivaloylcarnitine in urine.1

Cefditoren is not appreciably metabolized.1

Elimination Route

Principally eliminated in urine by renal tubular excretion and glomerular filtration.1

Half-life

Terminal elimination half-life is 1.6 hours in adults with normal renal function.1

Special Populations

AUC only slightly increased in adults with mild or moderate hepatic impairment (Child-Pugh class A or B).1 Pharmacokinetics have not been studied in patients with severe hepatic impairment (Child-Pugh class C).1

Clearance of the drug reduced in those with renal impairment.1

If your symptoms do not improve within a few days or if they become worse, check with your doctor.

In some patients, cefditoren may cause diarrhea:

• Severe diarrhea may be a sign of a serious side effect. Do not take any diarrhea medicine without first checking with your doctor . Diarrhea medicines may make your diarrhea worse or make it last longer.
• If you have any questions about this or if mild diarrhea continues or gets worse, check with your health care professional.

• It is used to treat bacterial infections.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Any unexplained bruising or bleeding.
• Fever or chills.
• Sore throat.
• Feeling very tired or weak.
• Not able to pass urine or change in how much urine is passed.
• Seizures.
• Vaginal itching or discharge.
• It is common to have diarrhea when taking this medicine. Rarely, a very bad form of diarrhea called Clostridium difficile (C diff)–associated diarrhea (CDAD) may occur. Sometimes, this has led to a deadly bowel problem (colitis). CDAD may happen while you are taking Spectracef (cefditoren) or within a few months after you stop taking it. Call your doctor right away if you have stomach pain or cramps, very loose or watery stools, or bloody stools. Do not try to treat loose stools without first checking with your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Spectracef or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Spectracef. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Spectracef® (cefditoren pivoxil) Tablets 200 mg and 400 mg

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Spectracef® and other antibacterial drugs, Spectracef® should be used only to treat infections that are proven or strongly suspected to be caused by bacteria.

Spectracef® is contraindicated in patients with known allergy to the cephalosporin class of antibiotics or any of its components.

Spectracef® is contraindicated in patients with carnitine deficiency or inborn errors of metabolism that may result in clinically significant carnitine deficiency, because use of Spectracef® causes renal excretion of carnitine. (See PRECAUTIONS, General.)

Spectracef® tablets contain sodium caseinate, a milk protein. Patients with milk protein hypersensitivity (not lactose intolerance) should not be administered Spectracef®.

General

Prescribing Spectracef® 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.

Spectracef® is not recommended when prolonged antibiotic treatment is necessary, since other pivalate-containing compounds have caused clinical manifestations of carnitine deficiency when used over a period of months. No clinical effects of carnitine decrease have been associated with short-term treatment. The effects on carnitine concentrations of repeat short-term courses of Spectracef® are not known.

In community-acquired pneumonia patients (N=192, mean age 50.3 ± 17.2 years) given a 200 mg BID regimen for 14 days, the mean decrease in serum concentrations of total carnitine while on therapy was 13.8 ± 10.8 nmole/mL, representing a 30% decrease in serum carnitine concentrations. In community-acquired pneumonia patients (N=192, mean age 51.3 ± 17.8 years) given a 400 mg BID regimen for 14 days, the mean decrease in serum concentrations of total carnitine while on therapy was 21.5 ± 13.1 mole/mL, representing a 46% decrease in serum carnitine concentrations. Plasma concentrations of carnitine returned to the normal control range within 7 days after discontinuation of cefditoren pivoxil. Comparable decreases in carnitine were observed in healthy volunteers (mean age 33.6 ± 7.4 years) following a 200 mg or 400 mg BID regimen. (See CLINICAL PHARMACOLOGY.) Community-acquired pneumonia clinical trials demonstrated no adverse events attributable to decreases in serum carnitine concentrations.

However, some sub-populations (e.g., patients with renal impairment, patients with decreased muscle mass) may be at increased risk for reductions in serum carnitine concentrations during cefditoren pivoxil therapy. Furthermore, the appropriate dose in patients with end-stage renal disease has not been determined. (See DOSAGE AND ADMINISTRATION, Patients with Renal Insufficiency).

As with other antibiotics, prolonged treatment may result in the possible emergence and overgrowth of resistant organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate alternative therapy should be administered.

Cephalosporins may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment, or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated. In clinical trials, there was no difference between cefditoren and comparator cephalosporins in the incidence of increased prothrombin time.

Information for Patients

Patients should be counseled that antibacterial drugs including Spectracef® should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Spectracef® is 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 Spectracef® or other antibacterial drugs in the future.

Spectracef® (cefditoren pivoxil) should be taken with meals to enhance absorption.

Spectracef® may be taken concomitantly with oral contraceptives.

It is not recommended that Spectracef® be taken concomitantly with antacids or other drugs taken to reduce stomach acids. (See PRECAUTIONS, Drug Interactions.)

Spectracef® tablets contain sodium caseinate, a milk protein. Patients with milk protein hypersensitivity (not lactose intolerance) should not be administered Spectracef®.

Drug Interactions

Multiple doses of cefditoren pivoxil had no effect on the pharmacokinetics of ethinyl estradiol, the estrogenic component in most oral contraceptives.

Co-administration of a single dose of an antacid which contained both magnesium (800 mg) and aluminum (900 mg) hydroxides reduced the oral absorption of a single 400 mg dose of cefditoren pivoxil administered following a meal, as evidenced by a 14% decrease in mean Cmax and an 11% decrease in mean AUC. Although the clinical significance is not known, it is not recommended that cefditoren pivoxil be taken concomitantly with antacids.

Co-administration of a single dose of intravenously administered famotidine (20 mg) reduced the oral absorption of a single 400 mg dose of cefditoren pivoxil administered following a meal, as evidenced by a 27% decrease in mean Cmax and a 22% decrease in mean AUC. Although the clinical significance is not known, it is not recommended that cefditoren pivoxil be taken concomitantly with H2 receptor antagonists.

As with other ß-lactam antibiotics, co-administration of probenecid with cefditoren pivoxil resulted in an increase in the plasma exposure of cefditoren, with a 49% increase in mean Cmax, a 122% increase in mean AUC, and a 53% increase in t1/2.

Drug/Laboratory Test Interactions

Cephalosporins are known to occasionally induce a positive direct Coombs’ test. A false-positive reaction for glucose in the urine may occur with copper reduction tests (Benedict’s or Fehling’s solution or with CLINITEST® tablets), but not with enzyme-based tests for glycosuria (e.g., CLINISTIX®, TES-TAPE®). As a false-negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase method be used to determine blood/plasma glucose levels in patients receiving cefditoren pivoxil.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term animal carcinogenicity studies have been conducted with cefditoren pivoxil. Cefditoren pivoxil was not mutagenic in the Ames bacterial reverse mutation assay, or in the mouse lymphoma mutation assay at the hypoxanthineguanine phosphoribosyltransferase locus. In Chinese hamster lung cells, chromosomal aberrations were produced by cefditoren pivoxil, but not by cefditoren. Subsequent studies showed that the chromosome aberrations were due to the release of formaldehyde from the pivoxil ester moiety in the in vitro assay system. Neither cefditoren nor cefditoren pivoxil produced chromosomal aberrations when tested in an in vitro human peripheral blood lymphocyte assay, or in the in vivo mouse micronucleus assay. Cefditoren pivoxil did not induce unscheduled DNA syntheses when tested. In rats, fertility and reproduction were not affected by cefditoren pivoxil at oral doses up to 1000 mg/kg/day, approximately 24 times a human dose of 200 mg BID based on mg/m2/day.

Pregnancy-Teratogenic Effects

Cefditoren pivoxil was not teratogenic up to the highest doses tested in rats and rabbits. In rats, this dose was 1000 mg/kg/day, which is approximately 24 times a human dose of 200 mg BID based on mg/m2/day. In rabbits, the highest dose tested was 90 mg/kg/day, which is approximately four times a human dose of 200 mg BID based on mg/m2/day. This dose produced severe maternal toxicity and resulted in fetal toxicity and abortions.

In a postnatal development study in rats, cefditoren pivoxil produced no adverse effects on postnatal survival, physical and behavioral development, learning abilities, and reproductive capability at sexual maturity when tested at doses of up to 750 mg/kg/day, the highest dose tested. This is approximately 18 times a human dose of 200 mg BID based on mg/m2/day.

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Labor and Delivery

Cefditoren pivoxil has not been studied for use during labor and delivery.

Nursing Mothers

Cefditoren was detected in the breast milk of lactating rats. Because many drugs are excreted in human breast milk, caution should be exercised when cefditoren pivoxil is administered to nursing women.

Pediatric Use

Use of cefditoren pivoxil is not recommended for pediatric patients less than 12 years of age. The safety and efficacy of cefditoren pivoxil tablets in this population, including any effects of altered carnitine concentration, have not been established. (See PRECAUTIONS, General.)

Geriatric Use

Of the 2675 patients in clinical studies who received cefditoren pivoxil 200 mg BID, 308 (12%) were >65 years of age. Of the 2159 patients in clinical studies who received cefditoren pivoxil 400 mg BID, 307 (14%) were >65 years of age. No clinically significant differences in effectiveness or safety were observed between older and younger patients. No dose adjustments are necessary in geriatric patients with normal (for their age) renal function. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See DOSAGE AND ADMINISTRATION.)

Common side effects of Spectracef include: diarrhea. Other side effects include: vulvovaginal candidiasis and nausea. See below for a comprehensive list of adverse effects.

Applies to cefditoren: oral tablet

Along with its needed effects, cefditoren (the active ingredient contained in Spectracef) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking cefditoren:

• Allergic reaction, such as, itching, pain, redness, or swelling of eye or eyelid, watering of eyes, troubled breathing or wheezing, severe skin rash or hives, flushing, headache, fever, chills, runny nose, increased sensitivity to sunlight, joint pain, swollen glands
• leukopenia, such as, black, tarry stools, chest pain, chills, cough, fever, painful or difficult urination, shortness of breath, sore throat, sores, ulcers, or white spots on lips or in mouth, swollen glands, unusual bleeding or bruising, unusual tiredness, or weakness
• pseudomembranous colitis, such as, abdominal or stomach cramps, pain, bloating, abdominal tenderness, diarrhea, watery and severe, which may also be bloody, fever, increased thirst, nausea or vomiting, unusual tiredness or weakness, or unusual weight loss
• or thrombocythemia, such as, pain, warmth or burning in fingers, toes, and legs, dizziness, problems with vision or hearing

Some side effects of cefditoren may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea
• nausea
• or vaginal moniliasis, such as, thick whitish discharge from the vagina or cervical canal

• Abdominal pain
• Dyspepsia, such as, acid or sour stomach, belching, heartburn, indigestion, or stomach discomfort, upset or pain
• or headache

• Abnormal dreams
• anorexia, such as, loss of appetite
• asthenia, such as, lack or loss of strength
• constipation
• dizziness
• dry mouth
• dysgeusia, such as, taste perversion
• eructation, such as, belching, bloated full feeling, excess air or gas in stomach
• fever
• flatulence, such as, passing of gas
• fungal infection
• gastritis, such as, burning feeling in chest or stomach, tenderness in stomach area, stomach upset, or indigestion
• headache
• hyperglycemia, such as, blurred vision, dry mouth, fatigue, flushed, dry skin, fruit-like breath odor, increased hunger, increased thirst, increased urination, loss of consciousness, nausea, stomachache, sweating, troubled breathing, unexplained weight loss, vomiting
• increased appetite
• insomnia, such as, sleeplessness
• leukorrhea, such as, increase in amount of clear vaginal discharge, white vaginal discharge
• mouth ulceration
• myalgia, such as, muscle pain
• nervousness
• oral moniliasis, such as, sore mouth or tongue, white patches in mouth, tongue, or throat
• pain
• peripheral edema, such as, bloating or swelling of face, arms, hands, lower legs, or feet, rapid weight gain, tingling of hands or feet, unusual weight gain or loss
• pharyngitis, such as, body aches or pain, congestion, cough, dryness or soreness of throat, fever, hoarseness, runny nose, tender, swollen glands in neck, trouble in swallowing, or voice changes
• pruritus, such as, itching skin
• rash
• rhinitis, such as, stuffy nose, runny nose, or sneezing
• sinusitis, such as, pain or tenderness around eyes and cheekbones, fever, stuffy or runny nose, headache, cough, shortness of breath or troubled breathing, tightness of chest or wheezing
• somnolence, such as, sleepiness or unusual drowsiness
• stomatitis, such as, swelling or inflammation of the mouth
• sweating
• urinary frequency
• urticaria, such as, hives or welts, itching, redness of skin, or rash
• vaginitis
• vomiting
• or weight loss