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Sunday, March 18, 2012

Ciprofloxacin Extended Release Tablets

Dosage Form: tablet, film coated, extended release

WARNING

Fluoroquinolones, including ciprofloxacin extended-release, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. (See WARNINGS.)

Fluoroquinolones, including ciprofloxacin extended-release, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid ciprofloxacin extended-release in patients with known history of myasthenia gravis. (See WARNINGS.)

Ciprofloxacin Extended Release Tablets Description

Ciprofloxacin1 extended-release tablets contain ciprofloxacin, a synthetic broad-spectrum antimicrobial agent for oral administration. Ciprofloxacin extended-release tablets are coated, bilayer tablets consisting of an immediate-release layer and an erosion-matrix type controlled release layer. The tablets contain a combination of two types of ciprofloxacin drug substance, ciprofloxacin hydrochloride, USP and ciprofloxacin, USP. Ciprofloxacin hydrochloride is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid hydrochloride. It is provided as the monohydrate. The molecular formula is C17H18FN3O3•HCl•H2O and its molecular weight is 385.8. The drug substance is faintly yellowish to light yellow crystals. The chemical structure is as follows:

Ciprofloxacin is 1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. As the anhydrous form, its molecular formula is C17H18FN3O3 and its molecular weight is 331.3. It is a white to pale yellow crystalline powder and its chemical structure is as follows:

Ciprofloxacin extended-release tablets are available in 500 mg or 1000 mg (ciprofloxacin equivalent) tablet strengths. Ciprofloxacin extended-release tablets are orange film-coated, modified capsule shaped tablets. Each ciprofloxacin extended-release 500 mg tablet contains 500 mg of ciprofloxacin as ciprofloxacin hydrochloride, USP (287.5 mg, calculated as ciprofloxacin on the dried basis) and ciprofloxacin, USP (212.6 mg, calculated on the dried basis). Each ciprofloxacin extended-release 1000 mg tablet contains 1000 mg of ciprofloxacin as ciprofloxacin hydrochloride, USP (574.9 mg, calculated as ciprofloxacin on the dried basis) and ciprofloxacin, USP (425.2 mg, calculated on the dried basis). The inactive ingredients are carnauba wax, colloidal silicon dioxide, croscarmellose sodium, dibasic calcium phosphate (anhydrous), FD&C Yellow No. 6 Aluminum Lake, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, povidone, pregelatinized starch, sodium lauryl sulfate, stearic acid, succinic acid, talc, and titanium dioxide.

1: as ciprofloxacin and ciprofloxacin hydrochloride

Ciprofloxacin Extended Release Tablets - Clinical Pharmacology

Absorption

Ciprofloxacin extended-release tablets are formulated to release drug at a slower rate compared to immediate-release tablets. Approximately 35% of the dose is contained within an immediate-release component, while the remaining 65% is contained in a slow-release matrix.

Maximum plasma ciprofloxacin concentrations are attained between 1 and 4 hours after dosing with ciprofloxacin extended-release. In comparison to the 250 mg and 500 mg ciprofloxacin immediate-release BID treatment, the Cmax of ciprofloxacin extended-release 500 mg and 1000 mg once daily are higher than the corresponding BID doses, while the AUCs over 24 hours are equivalent.

The following table compares the pharmacokinetic parameters obtained at steady-state for these four treatment regimens (500 mg QD ciprofloxacin extended-release vs. 250 mg BID ciprofloxacin immediate-release tablets and 1000 mg QD ciprofloxacin extended-release vs. 500 mg BID ciprofloxacin immediate-release).

Ciprofloxacin Pharmacokinetics (Mean ±SD) Following Ciprofloxacin Immediate-Release and Ciprofloxacin Extended-Release Administration
* median (range)
	Cmax (mg/L)	AUC0-24h (mg·h/L)	T½ (hr)	Tmax (hr)*
Ciprofloxacin Extended-Release 500 mg QD	1.59 ± 0.43	7.97 ± 1.87	6.6 ± 1.4	1.5 (1 to 2.5)
Ciprofloxacin Immediate-Release 250 mg BID	1.14 ± 0.23	8.25 ± 2.15	4.8 ± 0.6	1 (0.5 to 2.5)
Ciprofloxacin Extended-Release 1000 mg QD	3.11 ± 1.08	16.83 ± 5.65	6.31 ± 0.72	2 (1 to 4)
Ciprofloxacin Immediate-Release 500 mg BID	2.06 ± 0.41	17.04 ± 4.79	5.66 ± 0.89	2 (0.5 to 3.5)

Results of the pharmacokinetic studies demonstrate that ciprofloxacin extended-release may be administered with or without food (e.g. high-fat and low-fat meals or under fasted conditions).

Distribution

The volume of distribution calculated for intravenous ciprofloxacin is approximately 2.1 to 2.7 L/kg. Studies with the oral and intravenous forms of ciprofloxacin have demonstrated penetration of ciprofloxacin into a variety of tissues. The binding of ciprofloxacin to serum proteins is 20% to 40%, which is not likely to be high enough to cause significant protein binding interactions with other drugs. Following administration of a single dose of ciprofloxacin extended-release, ciprofloxacin concentrations in urine collected up to 4 hours after dosing averaged over 300 mg/L for both the 500 mg and 1000 mg tablets; in urine excreted from 12 to 24 hours after dosing, ciprofloxacin concentration averaged 27 mg/L for the 500 mg tablet, and 58 mg/L for the 1000 mg tablet.

Metabolism

Four metabolites of ciprofloxacin were identified in human urine. The metabolites have antimicrobial activity, but are less active than unchanged ciprofloxacin. The primary metabolites are oxociprofloxacin (M3) and sulfociprofloxacin (M2), each accounting for roughly 3% to 8% of the total dose. Other minor metabolites are desethylene ciprofloxacin (M1), and formylciprofloxacin (M4). The relative proportion of drug and metabolite in serum corresponds to the composition found in urine. Excretion of these metabolites was essentially complete by 24 hours after dosing. Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. Coadministration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the coadministered drug (see CONTRAINDICATIONS; WARNINGS; PRECAUTIONS: Drug Interactions).

Elimination

The elimination kinetics of ciprofloxacin are similar for the immediate-release and the ciprofloxacin extended-release tablet. In studies comparing the ciprofloxacin extended-release and immediate-release ciprofloxacin, approximately 35% of an orally administered dose was excreted in the urine as unchanged drug for both formulations. The urinary excretion of ciprofloxacin is virtually complete within 24 hours after dosing. The renal clearance of ciprofloxacin, which is approximately 300 mL/minute, exceeds the normal glomerular filtration rate of 120 mL/minute. Thus, active tubular secretion would seem to play a significant role in its elimination. Coadministration of probenecid with immediate-release ciprofloxacin results in about a 50% reduction in the ciprofloxacin renal clearance and a 50% increase in its concentration in the systemic circulation. Although bile concentrations of ciprofloxacin are several fold higher than serum concentrations after oral dosing with the immediate-release tablet, only a small amount of the dose administered is recovered from the bile as unchanged drug. An additional 1% to 2% of the dose is recovered from the bile in the form of metabolites. Approximately 20% to 35% of an oral dose of immediate-release ciprofloxacin is recovered from the feces within 5 days after dosing. This may arise from either biliary clearance or transintestinal elimination.

Special Populations

Pharmacokinetic studies of the immediate-release oral tablet (single-dose) and intravenous (single- and multiple-dose) forms of ciprofloxacin indicate that plasma concentrations of ciprofloxacin are higher in elderly subjects (> 65 years) as compared to young adults. Cmax is increased 16% to 40%, and mean AUC is increased approximately 30%, which can be at least partially attributed to decreased renal clearance in the elderly. Elimination half-life is only slightly (~ 20%) prolonged in the elderly. These differences are not considered clinically significant. (See PRECAUTIONS: Geriatric Use.)

Renal Impairment

In patients with reduced renal function, the half-life of ciprofloxacin is slightly prolonged. No dose adjustment is required for patients with uncomplicated urinary tract infections receiving 500 mg ciprofloxacin extended-release. For complicated urinary tract infection and acute uncomplicated pyelonephritis, where 1000 mg is the appropriate dose, the dosage of ciprofloxacin extended-release should be reduced to ciprofloxacin extended-release 500 mg q24h in patients with creatinine clearance equal to or below 30 mL/min. (See DOSAGE AND ADMINISTRATION.)

Hepatic Impairment

In studies in patients with stable chronic cirrhosis, no significant changes in ciprofloxacin pharmacokinetics have been observed. The kinetics of ciprofloxacin in patients with acute hepatic insufficiency, however, have not been fully elucidated. (See DOSAGE AND ADMINISTRATION.)

Drug-Drug Interactions

Concomitant administration with tizanidine is contraindicated. (See CONTRAINDICATIONS.) Previous studies with immediate-release ciprofloxacin have shown that concomitant administration of ciprofloxacin with theophylline decreases the clearance of theophylline resulting in elevated serum theophylline levels and increased risk of a patient developing CNS or other adverse reactions. Ciprofloxacin also decreases caffeine clearance and inhibits the formation of paraxanthine after caffeine administration. Absorption of ciprofloxacin is significantly reduced by concomitant administration of multivalent cation-containing products such as magnesium/aluminum antacids, sucralfate, Videx® (didanosine) chewable/buffered tablets or pediatric powder, or products containing calcium, iron, or zinc. (See WARNINGS, PRECAUTIONS: Drug Interactions and Information for Patients, and DOSAGE AND ADMINISTRATION.)

Antacids

When ciprofloxacin extended-release given as a single 1000 mg dose was administered 2 hours before, or 4 hours after a magnesium/aluminum-containing antacid (900 mg aluminum hydroxide and 600 mg magnesium hydroxide as a single oral dose) to 18 healthy volunteers, there was a 4% and 19% reduction, respectively, in the mean Cmax of ciprofloxacin. The reduction in the mean AUC was 24% and 26%, respectively. Ciprofloxacin extended-release should be administered at least 2 hours before or 6 hours after antacids containing magnesium or aluminum, as well as sucralfate, Videx® (didanosine) chewable/buffered tablets or pediatric powder, other highly buffered drugs, metal cations such as iron, and multivitamin preparations with zinc. Although ciprofloxacin extended-release may be taken with meals that include milk, concomitant administration with dairy products or with calcium-fortified juices alone should be avoided, since decreased absorption is possible. (See PRECAUTIONS: Information for Patients and Drug Interactions, and DOSAGE AND ADMINISTRATION.)

Omeprazole

When ciprofloxacin extended-release was administered as a single 1000 mg dose concomitantly with omeprazole (40 mg once daily for 3 days) to 18 healthy volunteers, the mean AUC and Cmax of ciprofloxacin were reduced by 20% and 23%, respectively. The clinical significance of this interaction has not been determined. (See PRECAUTIONS: Drug Interactions.)

MICROBIOLOGY

Mechanism of Action

The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination.

Mechanism of Resistance

The mechanism of action of fluoroquinolones, including ciprofloxacin, is different from that of other antimicrobial agents such as beta-lactams, macrolides, tetracyclines, or aminoglycosides; therefore, microorganisms resistant to these classes of drugs may be susceptible to ciprofloxacin. Resistance to fluoroquinolones occurs primarily by either mutations in the DNA gyrases, decreased outer membrane permeability, or drug efflux. In vitro resistance to ciprofloxacin develops slowly by multiple step mutations. Resistance to ciprofloxacin due to spontaneous mutations occurs at a general frequency of between < 10-9 to 1 × 10-6.

Cross Resistance

There is no known cross-resistance between ciprofloxacin and other classes of antimicrobials.

Ciprofloxacin has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section of the package insert for ciprofloxacin extended-release tablets.

Gram-positive bacteria

Enterococcus faecalis

Staphylococcus saprophyticus

Gram-negative bacteria

Escherichia coli

Klebsiella pneumoniae

Proteus mirabilis

Pseudomonas aeruginosa

The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ciprofloxacin (< 1 mcg/mL). However, the efficacy of ciprofloxacin in treating clinical infections due to these bacteria has not been established in adequate and well controlled clinical trials.

Gram-negative bacteria

Citrobacter koseri

Citrobacter freundii

Edwardsiella tarda

Enterobacter aerogenes

Enterobacter cloacae

Klebsiella oxytoca

Morganella morganii

Proteus vulgaris

Providencia rettgeri

Providencia stuartii

Serratia marcescens

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.

Dilution Techniques: Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method (broth or agar)1. The MIC values should be interpreted according to criteria provided in Table 1.

Diffusion Techniques: Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method.2 This procedure uses paper disks impregnated with 5 mcg ciprofloxacin to test the susceptibility of bacteria to ciprofloxacin. The disc diffusion interpretive criteria are provided in Table 1.

Table 1: Susceptibility Test Interpretive Criteria for Ciprofloxacin
S = Susceptible, I = Intermediate and R = Resistant.
Species	MIC (mcg/mL)			Zone Diameter (mm)
Species	S	I	R	S	I	R
Enterobacteriaceae	≤ 1	2	≥ 4	≥ 21	16 to 20	≤ 15
Enterococcus faecalis	≤ 1	2	≥ 4	≥ 21	16 to 20	≤ 15
Pseudomonas aeruginosa	≤ 1	2	≥ 4	≥ 21	16 to 20	≤ 15
Staphylococcus saprophyticus	≤ 1	2	≥ 4	≥ 21	16 to 20	≤ 15

A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Quality Control: Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.1,2 For dilution technique, standard ciprofloxacin powder should provide the MIC values according to criteria outlined in Table 2. For diffusion technique, the 5 mcg ciprofloxacin disk should provide the zone diameters outlined in Table 2.

Table 2: Quality Control for Susceptibility Testing of Ciprofloxacin
Strains	MIC Range (mcg/mL)	Zone Diameter (mm)
Enterococcus faecalis ATCC 29212	0.25 to 2	-
Escherichia coli ATCC 25922	0.004 to 0.015	30 to 40
Pseudomonas aeruginosa ATCC 27853	0.25 to 1	25 to 33
Staphylococcus aureus ATCC 29213	0.12 to 0.5	-
Staphylococcus aureus ATCC 25923	-	22 to 30

Indications and Usage for Ciprofloxacin Extended Release Tablets

Ciprofloxacin extended-release tablets are indicated only for the treatment of urinary tract infections, including acute uncomplicated pyelonephritis, caused by susceptible strains of the designated microorganisms as listed below. Ciprofloxacin extended-release tablets and ciprofloxacin immediate-release tablets are not interchangeable. Please see DOSAGE AND ADMINISTRATION for specific recommendations.

Uncomplicated Urinary Tract Infections (Acute Cystitis): Caused by Escherichia coli, Proteus mirabilis, Enterococcus faecalis, or Staphylococcus saprophyticus2.

Complicated Urinary Tract Infections: Caused by Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Proteus mirabilis, or Pseudomonas aeruginosa2.

Acute Uncomplicated Pyelonephritis: Caused by Escherichia coli.

THE SAFETY AND EFFICACY OF CIPROFLOXACIN EXTENDED-RELEASE TABLETS IN TREATING INFECTIONS OTHER THAN URINARY TRACT INFECTIONS HAS NOT BEEN DEMONSTRATED. Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to ciprofloxacin. Therapy with ciprofloxacin extended-release tablets may be initiated before results of these tests are known; once results become available appropriate therapy should be continued. Culture and susceptibility testing performed periodically during therapy will provide information not only on the therapeutic effect of the antimicrobial agent but also on the possible emergence of bacterial resistance.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ciprofloxacin extended-release tablets and other antibacterial drugs, ciprofloxacin extended-release tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

2: Treatment of infections due to this organism in the organ system was studied in fewer than 10 patients.

Contraindications

Ciprofloxacin extended-release tablets are contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components.

Concomitant administration with tizanidine is contraindicated. (See PRECAUTIONS: Drug Interactions.)

Warnings

Tendinopathy and Tendon Rupture

Fluoroquinolones, including ciprofloxacin extended-release, are associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and rupture of the Achilles tendon may require surgical repair. Tendinitis and tendon rupture in the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendon sites have also been reported. The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Factors, in addition to age and corticosteroid use, that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who do not have the above risk factors. Tendon rupture can occur during or after completion of therapy; cases occurring up to several months after completion of therapy have been reported. Ciprofloxacin extended-release should be discontinued if the patient experiences pain, swelling, inflammation or rupture of a tendon. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non-quinolone antimicrobial drug.

Exacerbation of Myasthenia Gravis

Fluoroquinolones, including ciprofloxacin extended-release, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Post-marketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid ciprofloxacin extended-release in patients with known history of myasthenia gravis. (See PRECAUTIONS: Information for Patients and ADVERSE REACTIONS: Post-Marketing Adverse Event Reports.)

Pregnant Women

THE SAFETY AND EFFECTIVENESS OF CIPROFLOXACIN EXTENDED-RELEASE IN PREGNANT AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED. (See PRECAUTIONS: Pregnancy and Nursing Mothers subsections.)

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving quinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Only a few patients had a history of hypersensitivity reactions. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous fluids, intravenous steroids, and airway management, should be administered as indicated.

Other Serious and Sometimes Fatal Reactions

Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with quinolones, including ciprofloxacin. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following:

fever, rash, or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson Syndrome);

vasculitis; arthralgia; myalgia; serum sickness;

allergic pneumonitis;

interstitial nephritis; acute renal insufficiency or failure;

hepatitis; jaundice; acute hepatic necrosis or failure;

anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities.

The drug should be discontinued immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted. (See PRECAUTIONS: Information for Patients and ADVERSE REACTIONS.)

Theophylline

SERIOUS AND FATAL REACTIONS HAVE BEEN REPORTED IN PATIENTS RECEIVING CONCURRENT INTRAVENOUS ADMINISTRATION OF CIPROFLOXACIN AND THEOPHYLLINE. These reactions have included cardiac arrest, seizure, status epilepticus, and respiratory failure. Although similar serious adverse effects have been reported in patients receiving theophylline alone, the possibility that these reactions may be potentiated by ciprofloxacin cannot be eliminated. If concomitant use cannot be avoided, serum levels of theophylline should be monitored and dosage adjustments made as appropriate.

Central Nervous System Effects

Convulsions, increased intracranial pressure (including pseudotumor cerebri) and toxic psychosis have been reported in patients receiving fluoroquinolones, including ciprofloxacin. Ciprofloxacin may also cause central nervous system (CNS) events including: dizziness, confusion, tremors, hallucinations, depression, and, rarely, suicidal thoughts or acts. These reactions may occur following the first dose. If these reactions occur in patients receiving ciprofloxacin, the drug should be discontinued and appropriate measures instituted. As with all fluoroquinolones, ciprofloxacin should be used with caution in patients with known or suspected CNS disorders that may predispose to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy), or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold (e.g., certain drug therapy, renal dysfunction). (See PRECAUTIONS: General, Information for Patients, Drug Interactions and ADVERSE REACTIONS.)

Clostridium difficile Associated Diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ciprofloxacin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Peripheral Neuropathy

Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving quinolones, including ciprofloxacin. Ciprofloxacin should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness, and/or weakness, or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength in order to prevent the development of an irreversible condition.

Musculoskeletal Disorders in Pediatric Patients and Arthropathic Effects in Animals

Ciprofloxacin should be used in pediatric patients (less than 18 years of age) only for infections listed in the INDICATIONS AND USAGE section. An increased incidence of adverse events compared to controls, including events related to joints and/or surrounding tissues, has been observed. (See ADVERSE REACTIONS.)

The oral administration of ciprofloxacin caused lameness in immature dogs. Histopathological examination of the weight-bearing joints of these dogs revealed permanent lesions of the cartilage. Related quinolone-class drugs also produce erosions of cartilage of weight-bearing joints and other signs of arthropathy in immature animals of various species. (See ANIMAL PHARMACOLOGY.)

Prolongation of the QT Interval

Some fluoroquinolones, including ciprofloxacin, have been associated with prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia. Rare cases of Torsades de pointes have been spontaneously reported during post-marketing surveillance in patients receiving fluoroquinolones, including ciprofloxacin. Ciprofloxacin should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, and patients receiving Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval (See PRECAUTIONS: Drug Interactions and Geriatric Use).

Cytochrome P450 (CYP450)

Ciprofloxacin is an inhibitor of the hepatic CYP1A2 enzyme pathway. Coadministration of ciprofloxacin and other drugs primarily metabolized by CYP1A2 (e.g. theophylline, methylxanthines, tizanidine) results in increased plasma concentrations of the coadministered drug and could lead to clinically significant pharmacodynamic side effects of the coadministered drug. (See PRECAUTIONS: Drug Interactions.)

Precautions

General

Crystals of ciprofloxacin have been observed rarely in the urine of human subjects but more frequently in the urine of laboratory animals, which is usually alkaline. (See ANIMAL PHARMACOLOGY.) Crystalluria related to ciprofloxacin has been reported only rarely in humans because human urine is usually acidic. Alkalinity of the urine should be avoided in patients receiving ciprofloxacin. Patients should be well hydrated to prevent the formation of highly concentrated urine.

Quinolones, including ciprofloxacin, may also cause central nervous system (CNS) events, including: nervousness, agitation, insomnia, anxiety, nightmares or paranoia. (See WARNINGS: Information for Patients, and Drug Interactions.)

Photosensitivity/Phototoxicity

Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of quinolones after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if phototoxicity occurs. (See ADVERSE REACTIONS.)

Prescribing ciprofloxacin extended-release 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 Patients

Patients should be advised:

to contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue ciprofloxacin extended-release treatment. The risk of severe tendon disorder with fluoroquinolones is higher in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants.

that fluoroquinolones like ciprofloxacin extended-release may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Patients should call their healthcare provider right away if they have any worsening muscle weakness or breathing problems.

that antibacterial drugs including ciprofloxacin extended-release should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When ciprofloxacin extended-release 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 ciprofloxacin extended-release or other antibacterial drugs in the future.

that ciprofloxacin extended-release may be taken with or without meals and to drink fluids liberally. As with other quinolones, concurrent administration with magnesium/aluminum antacids, polymeric phosphate binders (e.g., sevelamer, lanthanum carbonate) or sucralfate, Videx® (didanosine) chewable/buffered tablets or pediatric powder, other highly buffered drugs, or with other products containing calcium, iron, or zinc should be avoided. Ciprofloxacin extended-release may be taken 2 hours before or 6 hours after taking these products. (See CLINICAL PHARMACOLOGY: Drug-Drug Interactions, DOSAGE AND ADMINISTRATION, and PRECAUTIONS: Drug Interactions.) Ciprofloxacin extended-release should not be taken with dairy products (like milk or yogurt) or calcium-fortified juices alone since absorption of ciprofloxacin may be significantly reduced; however, ciprofloxacin extended-release may be taken with a meal that contains these products. (See CLINICAL PHARMACOLOGY: Drug-Drug Interactions, DOSAGE AND ADMINISTRATION, and PRECAUTIONS: Drug Interactions.)

if the patient should forget to take ciprofloxacin extended-release at the usual time, he/she may take the dose later in the day. Do not take more than one ciprofloxacin extended-release tablet per day even if a patient misses a dose. Swallow the ciprofloxacin extended-release tablet whole. DO NOT SPLIT, CRUSH, OR CHEW THE TABLET.

that ciprofloxacin may be associated with hypersensitivity reactions, even following a single dose, and to discontinue ciprofloxacin extended-release at the first sign of a skin rash or other allergic reaction.

that photosensitivity/phototoxicity has been reported in patients receiving quinolones. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients need to be outdoors while using quinolones, they should wear loose fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. If a sunburn-like reaction or skin eruption occurs, patients should contact their physician.

that peripheral neuropathies have been associated with ciprofloxacin use. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness and/or weakness develop, they should discontinue treatment and contact their physicians.

that ciprofloxacin extended-release may cause dizziness and light-headedness; therefore, patients should know how they react to this drug before they operate an automobile or machinery or engage in activities requiring mental alertness or coordination.

that ciprofloxacin increases the effects of tizanidine (Zanaflex® ). Patients should not use ciprofloxacin if they are already taking tizanidine.

that ciprofloxacin extended-release may increase the effects of theophylline and caffeine. There is a possibility of caffeine accumulation when products containing caffeine are consumed while taking quinolones.

that convulsions have been reported in patients receiving quinolones, including ciprofloxacin, and to notify their physician before taking ciprofloxacin extended-release if there is a history of this condition.

that diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Drug Interactions

Tizanidine

In a pharmacokinetic study, systemic exposure of tizanidine (4 mg single- dose) was significantly increased (Cmax 7-fold, AUC 10-fold) when the drug was given concomitantly with ciprofloxacin (500 mg bid for 3 days). The hypotensive and sedative effects of tizanidine were also potentiated. Concomitant administration of tizanidine and ciprofloxacin is contraindicated. (See CONTRAINDICATIONS.)

Theophylline

As with some other quinolones, concurrent administration of ciprofloxacin with theophylline may lead to elevated serum concentrations of theophylline and prolongation of its elimination half-life. This may result in increased risk of theophylline-related adverse reactions. (See WARNINGS.) If concomitant use cannot be avoided, serum levels of theophylline should be monitored and dosage adjustments made as appropriate.

Other Xanthine Derivatives

Some quinolones, including ciprofloxacin, have also been shown to interfere with the metabolism of caffeine. This may lead to reduced clearance of caffeine and a prolongation of its serum half-life. On concurrent administration of ciprofloxacin and caffeine or pentoxifylline (oxpentifylline) containing products, elevated serum concentrations of these xanthine derivatives were reported.

Chelation Complex Formation

Concurrent administration of a quinolone, including ciprofloxacin, with multivalent cation-containing products such as magnesium/aluminum antacids, sucralfate, Videx® (didanosine) chewable/buffered tablets or pediatric powder, other highly buffered drugs, or products containing calcium, iron, or zinc may substantially interfere w

Triotann-S Pediatric

Generic Name: chlorpheniramine, pyrilamine, and phenylephrine (KLOR fe NEER a meen, pir IL a meen, FEN il EFF rin)

Brand Names: AllerTan, Chlorex-A 12, Conal, MyHist-PD, Nalex A 12, Phena-Plus, Phena-S, Poly Hist PD, R-Tannate, Ru-Hist Forte, Tri-Hist Pediatric, Triotann-S Pediatric, Triple Tannate Pediatric, Triplex AD

What is chlorpheniramine, phenylephrine, and pyrilamine?

Chlorpheniramine and pyrilamine are antihistamines that reduce the effects of natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Phenylephrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

The combination of chlorpheniramine, phenylephrine, and pyrilamine is used to treat runny or stuffy nose, sneezing, itching, watery eyes, and sinus congestion caused by allergies, the common cold, or the flu.

Chlorpheniramine, phenylephrine, and pyrilamine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about chlorpheniramine, phenylephrine, and pyrilamine?

Do not use this medicine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects. Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Ask a doctor or pharmacist before using any other cold, cough, allergy, or pain medicine. Antihistamines and decongestants are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains an antihistamine or decongestant. This medication may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly. Drinking alcohol can increase drowsiness caused by chlorpheniramine, phenylephrine, and pyrilamine. Before using chlorpheniramine, phenylephrine, and pyrilamine, tell your doctor if you regularly use other medicines that make you sleepy (such as sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by chlorpheniramine and pyrilamine.

What should I discuss with my healthcare provider before taking chlorpheniramine, phenylephrine, and pyrilamine?

severe or uncontrolled high blood pressure;

severe coronary artery disease;

diabetes;

overactive thyroid; or

asthma, pneumonia, or other breathing problems.

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have:

liver disease;

kidney disease;

heart disease or high blood pressure;

glaucoma;

enlarged prostate;

bladder obstruction or other urination problems; or

a blockage in your digestive tract (stomach or intestines).

FDA pregnancy category C. It is not known whether chlorpheniramine, phenylephrine, and pyrilamine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Chlorpheniramine, phenylephrine, and pyrilamine can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using chlorpheniramine, phenylephrine, and pyrilamine.

How should I take chlorpheniramine, phenylephrine, and pyrilamine?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Cough or cold medicine is usually taken only for a short time until your symptoms clear up.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not crush, chew, or break an extended-release tablet. Swallow the pill whole. Breaking or crushing the pill may cause too much of the drug to be released at one time.

Measure liquid medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Shake the oral suspension (liquid) well just before you measure a dose. Store at room temperature away from moisture, heat, and light.

What happens if I miss a dose?

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.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include dry mouth, dilated pupils, nausea, vomiting, and warmth, redness, or tingly feeling under your skin.

What should I avoid while taking chlorpheniramine, phenylephrine, and pyrilamine?

Ask a doctor or pharmacist before using any other cold, cough, allergy, or pain medicine. Antihistamines and decongestants are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains an antihistamine or decongestant. This medication may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly. Drinking alcohol can increase certain side effects of this medication.

Avoid taking this medication if you also take diet pills, caffeine pills, or other stimulants (such as ADHD medications). Taking a stimulant together with a decongestant can increase your risk of unpleasant side effects.

Chlorpheniramine, phenylephrine, and pyrilamine side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have a serious side effect such as:

severe dizziness, anxiety, restless feeling, or nervousness;

fast, pounding, or uneven heartbeats;

confusion, hallucinations, unusual thoughts or behavior;

feeling like you might pass out;

urinating less than usual or not at all;

easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms;

increased blood pressure (severe headache, blurred vision, trouble concentrating, chest pain, numbness, seizure); or

nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

upset stomach, constipation;

dry mouth;

blurred vision;

dizziness, drowsiness;

problems with memory;

sleep problems (insomnia); or

feeling restless or excited (especially in children).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect chlorpheniramine, phenylephrine, and pyrilamine?

Cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by chlorpheniramine or pyrilamine. Tell your doctor if you regularly use any of these medicines, or any other cough and cold medications.

Tell your doctor about all other medications you use, especially:

digoxin (Lanoxin);

blood pressure medication;

an antidepressant;

a barbiturate such as phenobarbital (Solfoton) and others;

a diuretic (water pill);

medication to treat irritable bowel syndrome;

bladder or urinary medications such as oxybutynin (Ditropan, Oxytrol) or tolterodine (Detrol);

aspirin or salicylates (such as Disalcid, Doan's Pills, Dolobid, Salflex, Tricosal, and others); or

a beta-blocker such as atenolol (Tenormin), carteolol (Cartrol), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal), sotalol (Betapace), timolol (Blocadren), and others.

This list is not complete and there may be other drugs that can interact with chlorpheniramine, phenylephrine, and pyrilamine. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Triotann-S Pediatric resources

Triotann-S Pediatric Side Effects (in more detail)
Triotann-S Pediatric Use in Pregnancy & Breastfeeding
Triotann-S Pediatric Drug Interactions
Triotann-S Pediatric Support Group
0 Reviews for Triotann-S Pediatric - Add your own review/rating

Chlorpheniramine/Phenylephrine/Pyrilamine MedFacts Consumer Leaflet (Wolters Kluwer)

AllerTan Suspension MedFacts Consumer Leaflet (Wolters Kluwer)

Phena-S Liquid MedFacts Consumer Leaflet (Wolters Kluwer)

Poly Hist PD Prescribing Information (FDA)

Ru-Hist Forte Controlled-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Triotann-S Pediatric with other medications

Cold Symptoms
Hay Fever

Where can I get more information?

Your pharmacist can provide more information about chlorpheniramine, phenylephrine, and pyrilamine.

See also: Triotann-S Pediatric side effects (in more detail)

Saturday, March 17, 2012

Multaq

Generic Name: dronedarone (droe NE da rone)

Brand Names: Multaq

What is dronedarone?

Dronedarone is an antiarrhythmic medication that affects the rhythm of heartbeats.

Dronedarone helps keep the heart beating normally in people with life-threatening heart rhythm disorders of the atrium (the upper chambers of the heart that allow blood to flow into the heart) and risk factors such as diabetes, high blood pressure, a history of stroke, or being over 70 years old.

Dronedarone is used to treat certain heart rhythm disorders called atrial fibrillation or atrial flutter. Dronedarone is given to reduce the need for hospitalization due to these heart conditions.

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

What is the most important information I should know about dronedarone?

Dronedarone is used to treat intermittent or "temporary" heart rhythm disorders. In some people with "permanent" atrial fibrillation, dronedarone increased the risk of stroke, hospitalization due to heart failure, and death. Talk with your doctor about your individual risk. Do not stop taking this medication without first talking to your doctor. Stopping suddenly may make your condition worse. You should not use dronedarone if you are allergic to dronedarone, if you are pregnant or breast-feeding, or if you have severe liver disease, certain serious heart conditions, especially severe heart failure, "AV block" or sick sinus syndrome (unless you have a pacemaker), a history of slow heart beats that have caused you to faint, or if you were recently hospitalized for heart failure. There are many other medicines that can cause serious medical problems if you take them together with dronedarone. You may need to stop taking certain drugs while you are taking dronedarone. Tell your doctor about all other medications you use.

Also tell your doctor if you have kidney disease, liver disease, a history of heart failure, an electrolyte imbalance (such as low levels of potassium or magnesium in your blood), or if you have a pacemaker or defibrillator implanted in your chest.

Dronedarone can harm an unborn baby or cause birth defects. Do not use dronedarone if you are pregnant.

You may need regular medical tests to be sure this medication is not causing harmful effects. Visit your doctor regularly.

What should I discuss with my healthcare provider before taking dronedarone?

severe liver disease;

certain serious heart conditions, especially severe heart failure, "AV block" or sick sinus syndrome (unless you have a pacemaker);

a history of slow heart beats that have caused you to faint;

if you were hospitalized with severe heart failure within the past 30 days; or

if you are pregnant or breast-feeding.

There are many other medicines that can cause serious medical problems if you take them together with dronedarone. You may need to stop taking certain drugs while you are taking dronedarone. Tell your doctor about all other medications you use, especially:

heart rhythm medication;

an antibiotic or antifungal medication;

an antidepressant;

medicine to treat HIV or AIDS;

medicine to treat or prevent malaria;

medicine to treat a psychiatric disorder;

migraine headache medication;

narcotic pain medicine;

medicine to prevent or treat nausea and vomiting; or

medicine used to prevent organ transplant rejection.

To make sure you can safely take dronedarone, tell your doctor if you have any of these other conditions:

kidney disease;

liver disease;

a history of heart failure;

an electrolyte imbalance (such as low levels of potassium or magnesium in your blood); or

if you have a pacemaker or defibrillator implanted in your chest.

FDA pregnancy category X. This medication can harm an unborn baby or cause birth defects. Do not use dronedarone if you are pregnant. Tell your doctor right away if you become pregnant during treatment. Use effective birth control while you are using this medication. It is not known whether dronedarone passes into breast milk or if it could harm a nursing baby. You should not breast-feed while taking dronedarone.

How should I take dronedarone?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Dronedarone works best if you take it with your morning and evening meals.

Use dronedarone regularly even if you feel fine or have no symptoms. Get your prescription refilled before you run out of medicine completely.

To be sure this medication is not causing harmful effects, your heart function will need to be checked every 3 months using an electrocardiograph or ECG (sometimes called an EKG). An ECG measures electrical activity of the heart. This will help your doctor determine how long to treat you with dronedarone. Your liver and kidney function may also need to be tested. Visit your doctor regularly. Do not stop taking this medication without first talking to your doctor. Store at room temperature away from heat and moisture.

What happens if I miss a dose?

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.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking dronedarone?

Grapefruit and grapefruit juice may interact with dronedarone and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Dronedarone side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

severe dizziness, fainting, fast or pounding heartbeats;

slow heart rate, feeling like you might pass out;

a new or a worsening irregular heartbeat pattern;

feeling short of breath, even with mild exertion, swelling in your ankles or feet, rapid weight gain;

wheezing, cough, chest pain, trouble breathing, coughing up mucus;

nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

breathing problems while lying down trying to sleep; or

low electrolytes (confusion, jerky muscle movements, uneven heartbeats, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling).

Less serious side effects may include:

mild stomach pain, diarrhea, upset stomach;

feeling weak or tired; or

mild skin rash or redness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect dronedarone?

Many drugs can interact with dronedarone and some should not be used at the same time. Below is only a partial list of these drugs. Tell your doctor if you are using:

a blood thinner such as warfarin (Coumadin, Jantoven);

cyclosporine (Gengraf, Neoral, Sandimmune);

digoxin (digitalis, Lanoxin, Lanoxicaps);

sirolimus (Rapamune) or tacrolimus (Prograf);

St. John's wort;

theophylline (Elixophyllin, Theo-24, Uniphyl);

tuberculosis medications;

a beta-blocker such as atenolol (Tenormin), bisoprolol (Zebeta, Ziac), metoprolol (Lopressor, Toprol), propranolol (Inderal, InnoPran), and others;

cholesterol-lowering medicines such as cholestyramine (Prevalite, Questran), atorvastatin (Lipitor), simvastatin (Zocor), lovastatin (Mevacor), pravastatin (Pravachol), or fluvastatin (Lescol);

heart or blood pressure medication such as amlodipine (Norvasc), diltiazem (Cardizem, Dilacor, Tiazac), felodipine (Plendil), nifedipine (Procardia, Adalat), verapamil (Calan, Covera, Isoptin, Verelan), and others; or

seizure medication such as carbamazepine (Carbatrol, Equetro, Tegretol), phenytoin (Dilantin), and others.

This list is not complete and there are many other drugs that can cause serious drug interactions with dronedarone. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

More Multaq resources

Multaq Side Effects (in more detail)
Multaq Use in Pregnancy & Breastfeeding
Drug Images
Multaq Drug Interactions
Multaq Support Group
11 Reviews for Multaq - Add your own review/rating

Multaq Prescribing Information (FDA)

Multaq Monograph (AHFS DI)

Multaq Advanced Consumer (Micromedex) - Includes Dosage Information

Multaq Consumer Overview

Multaq MedFacts Consumer Leaflet (Wolters Kluwer)

Dronedarone Professional Patient Advice (Wolters Kluwer)

Compare Multaq with other medications

Atrial Fibrillation
Atrial Flutter

Where can I get more information?

Your pharmacist can provide more information about dronedarone.

See also: Multaq side effects (in more detail)

Thursday, March 15, 2012

Lonox

Generic Name: diphenoxylate and atropine (Oral route)

dye-fen-OX-i-late hye-droe-KLOR-ide, AT-roe-peen SUL-fate

Commonly used brand name(s)

In the U.S.

Lomocot

Lomotil

Lonox

Vi-Atro

Available Dosage Forms:

Solution

Tablet

Therapeutic Class: Antidiarrheal

Pharmacologic Class: Atropine

Chemical Class: Diphenoxylate

Uses For Lonox

Diphenoxylate and atropine is a combination medicine used along with other measures to treat severe diarrhea in adults. Diphenoxylate helps stop diarrhea by slowing down the movements of the intestines.

Since diphenoxylate is chemically related to some narcotics, it may be habit-forming if taken in doses that are larger than prescribed. To help prevent possible abuse, atropine (an anticholinergic) has been added. If higher than normal doses of the combination are taken, the atropine will cause unpleasant effects, making it unlikely that such doses will be taken again.

Diphenoxylate and atropine combination medicine should not be used in children. Children with diarrhea should be given solutions of carbohydrates (sugars) and important salts (electrolytes) to replace the water, sugars, and important salts that are lost from the body during diarrhea. For more information on these solutions, see the Carbohydrates and Electrolytes (Systemic) monograph.

This medicine is available only with your doctor's prescription.

Before Using Lonox

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

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

This medicine should not be used in children. Children, especially very young children, are very sensitive to the effects of diphenoxylate and atropine. This may increase the chance of side effects during treatment. Also, the fluid loss caused by diarrhea may result in a severe condition. For this reason, it is very important that a sufficient amount of liquids be given to replace the fluid lost by the body. If you have any questions about this, check with your health care professional.

Geriatric

Shortness of breath or difficulty in breathing may be especially likely to occur in elderly patients, who are usually more sensitive than younger adults to the effects of diphenoxylate. Also, the fluid loss caused by diarrhea may result in a severe condition. For this reason, elderly persons should not take this medicine without first checking with their doctor. It is also very important that a sufficient amount of liquids be taken to replace the fluid lost by the body. If you have any questions about this, check with your health care professional.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

Ambenonium

Potassium

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Clorgyline

Digoxin

Furazolidone

Iproniazid

Isocarboxazid

Moclobemide

Nialamide

Pargyline

Phenelzine

Procarbazine

Rasagiline

Selegiline

Tapentadol

Toloxatone

Tranylcypromine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Arbutamine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Proper Use of diphenoxylate and atropine

This section provides information on the proper use of a number of products that contain diphenoxylate and atropine. It may not be specific to Lonox. Please read with care.

If this medicine upsets your stomach, your doctor may want you to take it with food.

Take this medicine only as directed by your doctor . Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. If too much is taken, it may become habit-forming.

For patients taking the liquid form of this medicine:

This medicine is to be taken by mouth even if it comes in a dropper bottle. The amount to be taken is to be measured with the specially marked dropper.

Importance of diet and fluids while treating diarrhea :

In addition to using medicine for diarrhea, it is very important that you replace the fluid lost by the body and follow a proper diet. For the first 24 hours you should eat gelatin and drink plenty of caffeine-free clear liquids, such as ginger ale, decaffeinated cola, decaffeinated tea, and broth. During the next 24 hours you may eat bland foods, such as cooked cereals, bread, crackers, and applesauce. Fruits, vegetables, fried or spicy foods, bran, candy, caffeine, and alcoholic beverages may make the condition worse.

If too much fluid has been lost by the body due to the diarrhea a serious condition may develop. Check with your doctor as soon as possible if any of the following signs or symptoms of too much fluid loss occur:
- Decreased urination
- Dizziness and light-headedness
- Dryness of mouth
- Increased thirst
- Wrinkled skin

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For severe diarrhea:
- For oral dosage form (oral solution):
  - Adults and teenagers—At first, the dose is 5 milligrams (mg) (2 teaspoonfuls) three or four times a day. Then, the dose is usually 5 mg (2 teaspoonfuls) once a day, as needed.
  - Children up to 12 years of age—Use is not recommended.
- For oral dosage form (tablets):
  - Adults and teenagers—At first, the dose is 5 mg (2 tablets) three or four times a day. Then, the dose is usually 5 mg (2 tablets) once a day, as needed.
  - Children up to 12 years of age—Use is not recommended.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Lonox

Your doctor should check your progress at regular visits if you will be taking this medicine regularly for a long time.

Check with your doctor if your diarrhea does not stop after two days or if you develop a fever.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that slow down the nervous system, possibly causing drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; barbiturates; medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are taking this medicine.

If you think you or anyone else may have taken an overdose, get emergency help at once. Taking an overdose of this medicine may lead to unconsciousness and possibly death. Signs or symptoms of overdose include severe drowsiness; shortness of breath or troubled breathing; fast heartbeat; and unusual warmth, dryness, and flushing of the skin.

Before having any kind of surgery (including dental surgery) or emergency treatment, tell the medical doctor or dentist in charge that you are taking this medicine.

This medicine may cause some people to become dizzy, drowsy, or less alert than they are normally. Even if taken at bedtime, it may cause some people to feel drowsy or less alert on arising. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or are not alert.

Lonox Side Effects

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 may need medical attention.

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

Bloating

constipation

loss of appetite

stomach pain (severe) with nausea and vomiting

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

Blurred vision (continuing) or changes in near vision

drowsiness (severe)

dryness of mouth, nose, and throat (severe)

fast heartbeat

shortness of breath or troubled breathing (severe)

unusual excitement, nervousness, restlessness, or irritability

unusual warmth, dryness, and flushing of the skin

Some side effects 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:

Less common or rare

Blurred vision

confusion

difficult urination

dizziness or light-headedness

drowsiness

dryness of skin and mouth

fever

headache

increased body temperature

mental depression

numbness of hands or feet

skin rash or itching

swelling of the gums

After you stop using this medicine, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:

Rare

Increased sweating

muscle cramps

nausea or vomiting

shivering or trembling

stomach cramps

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Lonox side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

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Diarrhea

Monday, March 12, 2012

Acebutolol

Dosage Form: capsule
Acebutolol HYDROCHLORIDE CAPSULES

DESCRIPTION

Acebutolol HCl is a selective, hydrophilic beta-adrenoreceptor blocking agent with mild intrinsic sympathomimetic activity for use in treating patients with hypertension and ventricular arrhythmias. It is marketed in capsule form for oral administration. Acebutolol HCl capsules are provided in two dosage strengths which contain 200 or 400 mg of Acebutolol as the hydrochloride salt. The inactive ingredients present are D&C Red 28, D&C Yellow 10, FD&C Blue 1, FD&C Red 40, gelatin, maize starch, povidone, titanium dioxide and stearic acid.

Acebutolol HCl has the following structural formula:

C18H28N2O4•HCl M.W. 372.89

Acebutolol HCl is a white or slightly off-white powder freely soluble in water, and less soluble in alcohol. Chemically it is defined as the hydrochloride salt of (±) N-[3-Acetyl-4-[2-hydroxy-3-[(1-methylethyl) amino]propoxy]phenyl] butanamide.

CLINICAL PHARMACOLOGY

Acebutolol is a cardioselective, β-adrenoreceptor blocking agent, which possesses mild intrinsic sympathomimetic activity (ISA) in its therapeutically effective dose range.

PHARMACODYNAMICS

β1-cardioselectivity has been demonstrated in experimental animal studies. In anesthetized dogs and cats, Acebutolol is more potent in antagonizing isoproterenol-induced tachycardia (β1) than in antagonizing isoproterenolinduced vasodilatation (β2). In guinea pigs and cats, it is more potent in antagonizing this tachycardia than in antagonizing isoproterenol-induced bronchodilatation (β2). ISA of Acebutolol has been demonstrated in catecholamine-depleted rats by tachycardia induced by intravenous administration of this agent. A membrane-stabilizing effect has been detected in animals, but only with high concentrations of Acebutolol.

Clinical studies have demonstrated β1-blocking activity at the recommended doses by: a) reduction in the resting heart rate and decrease in exerciseinduced tachycardia; b) reduction in cardiac output at rest and after exercise; c) reduction of systolic and diastolic blood pressures at rest and postexercise; d) inhibition of isoproterenol-induced tachycardia.

The β1-selectivity of Acebutolol has also been demonstrated on the basis of the following vascular and bronchial effects:

Vascular Effects: Acebutolol has less antagonistic effects on peripheral vascular β2receptors at rest and after epinephrine stimulation than nonselective β-antagonists.

Bronchial Effects: In single-dose studies in asthmatics examining effects of various beta-blockers on pulmonary function, low doses of Acebutolol produce less evidence of bronchoconstriction and less reduction of beta2 agonist, bronchodilating effects, than nonselective agents like propranolol but more than atenolol.

ISA has been observed with Acebutolol in man, as shown by a slightly smaller (about 3 beats per minute) decrease in resting heart rate when compared to equivalent β-blocking doses of propranolol, metoprolol or atenolol. Chronic therapy with Acebutolol induced no significant alteration in the blood lipid profile.

Acebutolol has been shown to delay AV conduction time and to increase the refractoriness of the AV node without significantly affecting sinus node recovery time, atrial refractory period, or the HV conduction time. The membrane-stabilizing effect of Acebutolol is not manifest at the doses used clinically.

Significant reductions in resting and exercise heart rates and systolic blood pressures have been observed 1.5 hours after Acebutolol administration with maximal effects occurring between 3 and 8 hours postdosing in normal volunteers. Acebutolol has demonstrated a significant effect on exerciseinduced tachycardia 24 to 30 hours after drug administration.

There are significant correlations between plasma levels of Acebutolol and both the reduction in resting heart rate and the percent of β-blockade of exercise-induced tachycardia.

The antihypertensive effect of Acebutolol has been shown in double-blind controlled studies to be superior to placebo and similar to propranolol and hydrochlorothiazide. In addition, patients responding to Acebutolol administered twice daily had a similar response whether the dosage regimen was changed to once daily administration or continued on a b.i.d. regimen.

Most patients responded to 400 to 800 mg per day in divided doses.

The antiarrhythmic effect of Acebutolol was compared with placebo, propranolol, and quinidine. Compared with placebo, Acebutolol significantly reduced mean total ventricular ectopic beats (VEB), paired VEB, multiform VEB, R-on-T beats, and ventricular tachycardia (VT). Both Acebutolol and propranolol significantly reduced mean total and paired VEB and VT.

Acebutolol and quinidine significantly reduced resting total and complex VEB; the antiarrhythmic efficacy of Acebutolol was also observed during exercise.

PHARMACOKINETICS and METABOLISM

Acebutolol is well absorbed from the GI tract. It is subject to extensive firstpass hepatic biotransformation, with an absolute bioavailability of approximately 40% for the parent compound. The major metabolite, an Nacetyl derivative (diacetolol), is pharmacologically active. This metabolite is equipotent to Acebutolol and in cats is more cardioselective than Acebutolol;

therefore, this first-pass phenomenon does not attenuate the therapeutic effect of Acebutolol. Food intake does not have a significant effect on the area under the plasma concentration-time curve (AUC) of Acebutolol although the rate of absorption and peak concentration decreased slightly.

The plasma elimination half-life of Acebutolol is approximately 3 to 4 hours, while that of its metabolite, diacetolol, is 8 to 13 hours.The time to reach peak concentration for Acebutolol is 2.5 hours and for diacetolol, after oral administration of Acebutolol, 3.5 hours.

Within the single oral dose range of 200 to 400 mg, the kinetics are dose proportional. However, this linearity is not seen at higher doses, probably due to saturation of hepatic biotransformation sites. In addition, after multiple dosing the lack of linearity is also seen by AUC increases of approximately 100% as compared to single oral dosing. Elimination via renal excretion is

approximately 30% to 40% and by nonrenal mechanisms 50% to 60%, which includes excretion into the bile and direct passage through the intestinal wall.

Acebutolol has a low binding affinity for plasma proteins (about 26%). Acebutolol and its metabolite, diacetolol, are relatively hydrophilic and, therefore, only minimal quantities have been detected in the cerebrospinal fluid (CSF). Drug interaction studies with tolbutamide and warfarin indicated no influence on the therapeutic effects of these compounds. Digoxin and hydrochlorothiazide plasma levels were not affected by concomitant Acebutolol administration. The kinetics of Acebutolol were not significantly altered by concomitant administration of hydrochlorothiazide, hydralazine, sulfinpyrazone, or oral contraceptives.

In patients with renal impairment, there is no effect on the elimination half-life of Acebutolol, but there is decreased elimination of the metabolite, diacetolol, resulting in a two- to three-fold increase in its half-life. For this reason, the drug should be administered with caution in patients with renal insufficiency (see Precautions). Acebutolol and its major metabolite are dialyzable.

Acebutolol crosses the placental barrier and is secreted in breast milk.

In geriatric patients, the bioavailability of Acebutolol and its metabolite is increased, approximately two-fold, probably due to decreases in the first-pass metabolism and renal function in the elderly.

INDICATIONS & USAGE

HYPERTENSION: Acebutolol hydrochloride capsules are indicated for the management of hypertension in adults. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

VENTRICULAR ARRHYTHMIAS: Acebutolol hydrochloride capsules are indicated in the management of ventricular premature beats; it reduces the total number of premature beats, as well as the number of paired and multiform ventricular ectopic beats, and R-on-T beats.

CONTRAINDICATIONS

Acebutolol HCl is contraindicated in: 1) persistently severe bradycardia; 2) second-and third-degree hear t block; 3) over t cardiac failure; and 4) cardiogenic shock. (See Warnings.)

WARNINGS

CARDIAC FAILURE: Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by β-adrenergic receptor blockade may precipitate more severe failure. Although β-blockers should be avoided in overt cardiac failure, Acebutolol can be used with caution in patients with a history of heart failure who are controlled with digitalis and/or diuretics. Both digitalis and Acebutolol impair AV conduction. If cardiac failure persists, therapy with Acebutolol should be withdrawn.

IN PATIENTSWITHOUT A HISTORY OF CARDIAC FAILURE: In patients with aortic or mitral valve disease or compromised left ventricular function, continued depression of the myocardium with β-blocking agents over a period of time may lead to cardiac failure. At the first signs of failure, patients should be digitalized and/or be given a diuretic and the response observed closely. If cardiac failure continues despite adequate digitalization and/or diuretic, Acebutolol therapy should be withdrawn.

EXACERBATION OF ISCHEMIC HEART DISEASE FOLLOWING ABRUPT WITHDRAWAL: Following abrupt cessation of therapy with certain β-blocking agents in patients with coronary artery disease, exacerbation of angina pectoris and, in some cases, myocardial infarction and death have been reported. Therefore, such patients should be cautioned against interruption of therapy without a physician’s advice. Even in the absence of overt ischemic heart disease, when discontinuation of Acebutolol is planned, the patient should be carefully observed, and should be advised to limit physical activity to a minimum while Acebutolol is gradually withdrawn over a period of about two weeks. (If therapy with an alternative β-blocker is desired, the patient may be transferred directly to comparable doses of another agent without interruption of β-blocking therapy.) If an exacerbation of angina pectoris occurs, antianginal therapy should be restarted immediately in full doses and the patient hospitalized until his condition stabilizes.

PERIPHERAL VASCULAR DISEASE: Treatment with β-antagonists reduces cardiac output and can precipitate or aggravate the symptoms of arterial insufficiency in patients with peripheral or mesenteric vascular disease. Caution should be exercised with such patients, and they should be observed closely for evidence of progression of arterial obstruction.

BRONCHOSPASTIC DISEASES: PATIENTS WITH BRONCHOSPASTIC DISEASE SHOULD, IN GENERAL, NOT RECEIVE A β-BLOCKER. Because of its relative β1-selectivity, however, low doses of Acebutolol may be used with caution in patients with bronchospastic disease who do not respond to, or who cannot tolerate, alternative treatment. Since β1-selectivity is not absolute and is dose-dependent, the lowest possible dose of Acebutolol should be used initially, preferably in divided doses to avoid the higher plasma levels associated with the longer dose-interval. A bronchodilator, such as theophylline or a β2-stimulant, should be made available in advance with instructions concerning its use.

ANESTHESIA AND MAJOR SURGERY: The necessity, or desirability, of withdrawal of a β-blocking therapy prior to major surgery is controversial. β-adrenergic receptor blockade impairs the ability of the heart to respond to β-adrenergically mediated reflex stimuli. While this might be of benefit in preventing arrhythmic response, the risk of excessive myocardial depression during general anesthesia may be enhanced and difficulty in restarting and maintaining the heart beat has been reported with beta-blockers. If treatment is continued, particular care should be taken when using anesthetic agents which depress the myocardium, such as ether, cyclopropane, and trichlorethylene, and it is prudent to use the lowest possible dose of Acebutolol.

Acebutolol, like other β-blockers, is a competitive inhibitor of β-receptor agonists, and its effect on the hear t can be reversed by cautious administration of such agents (e.g., dobutamine or isoproterenol – see Overdosage).

Manifestations of excessive vagal tone (e.g., profound bradycardia, hypotension) may be corrected with atropine 1 to 3 mg IV in divided doses.

DIABETES AND HYPOGLYCEMIA: β-blockers may potentiate insulin-induced hypoglycemia and mask some of its manifestations such as tachycardia; however, dizziness and sweating are usually not significantly affected. Diabetic patients should be warned of the possibility of masked hypoglycemia.

THYROTOXICOSIS: β-adrenergic blockade may mask certain clinical signs (tachycardia) of hyperthyroidism. Abrupt withdrawal of β-blockade may precipitate a thyroid storm; therefore, patients suspected of developing thyrotoxicosis from whom Acebutolol therapy is to be withdrawn should be monitored closely.

PRECAUTIONS

RISK OF ANAPHYLACTIC REACTION: While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenged, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

IMPAIRED RENAL OR HEPATIC FUNCTION: Studies on the effect of Acebutolol in patients with renal insufficiency have not been performed in the U.S. Foreign published experience shows that Acebutolol has been used successfully in chronic renal insufficiency. Acebutolol is excreted through the GI tract, but the active metabolite, diacetolol, is eliminated predominantly by the kidney. There is a linear relationship between renal clearance of diacetolol and creatinine clearance. Therefore, the daily dose of Acebutolol should be reduced by 50% when the creatinine clearance is less than 50 mL/min and by 75% when it is less than 25 mL/min. Acebutolol should be used cautiously in patients with impaired hepatic function.

Acebutolol has been used successfully and without problems in elderly patients in the U.S. clinical trials without specific adjustment of dosage. However, elderly patients may require lower maintenance doses because the bioavailability of both Acebutolol and its metabolite are approximately doubled in this age group.

INFORMATION FOR PATIENTS: Patients, especially those with evidence of coronary ar tery disease, should be warned against interruption or discontinuation of Acebutolol therapy without a physician’s supervision. Although cardiac failure rarely occurs in properly selected patients, those being treated with β-adrenergic blocking agents should be advised to consult a physician if they develop signs or symptoms suggestive of impending CHF, or unexplained respiratory symptoms.

Patients should also be warned of possible severe hypertensive reactions from concomitant use of α-adrenergic stimulants, such as the nasal decongestants commonly used in OTC cold preparations and nasal drops.

CLINICAL LABORATORY FINDINGS: Acebutolol, like other β-blockers, has been associated with the development of antinuclear antibodies (ANA). In prospective clinical trials, patients receiving Acebutolol had a dose-dependent increase in the development of positive ANA titers, and the overall incidence was higher than that observed with propranolol. Symptoms (generally persistent arthralgias and myalgias) related to this laboratory abnormality were infrequent (less than 1% with both drugs). Symptoms and ANA titers were reversible upon discontinuation of treatment.

DRUG INTERACTIONS: Catecholamine-depleting drugs, such as reserpine, may have an additive effect when given with β-blocking agents. Patients treated with Acebutolol plus catecholamine depletors should, therefore, be observed closely for evidence of marked bradycardia or hypotension which may present as vertigo, syncope/presyncope, or orthostatic changes in blood pressure without compensatory tachycardia. Exaggerated hypertensive responses have been reported from the combined use of β-adrenergic antagonists and α-adrenergic stimulants, including those contained in proprietary cold remedies and vasoconstrictive nasal drops. Patients receiving β-blockers should be warned of this potential hazard.

Blunting of the antihypertensive effect of beta-adrenoreceptor blocking agents by nonsteroidal anti-inflammatory drugs has been reported.

No significant interactions with digoxin, hydrochlorothiazide, hydralazine, sulfinpyrazone, oral contraceptives, tolbutamide, or warfarin have been observed.

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY: Chronic oral toxicity studies in rats and mice, employing dose levels as high as 300 mg/kg/day, which is equivalent to 15 times the maximum recommended (60 kg) human dose, did not indicate a carcinogenic potential for Acebutolol. Diacetolol, the major metabolite of Acebutolol in man, was without carcinogenic potential in rats when tested at doses as high as 1800 mg/kg/day. Acebutolol and diacetolol were also shown to be devoid of mutagenic potential in the Ames Test. Acebutolol, administered orally to two generations of male and female rats at doses of up to 240 mg/kg/day (equivalent to 12 times the maximum recommended therapeutic dose in a 60-kg human) and diacetolol, administered to two generations of male and female rats at doses of up to 1000 mg/kg/day, had no significant impact on reproductive performance or fertility.

PREGNANCY:

Teratogenic Effects:

Pregnancy Category B: Reproduction studies have been performed with Acebutolol in rats (up to 630 mg/kg/day) and rabbits (up to 135 mg/kg/day). These doses are equivalent to approximately 31.5 and 6.8 times the maximum recommended therapeutic dose in a 60-kg human, respectively. The compound was not teratogenic in either species. In the rabbit, however, doses of 135 mg/kg/day caused slight fetal growth retardation; this effect was considered to be a result of maternal toxicity, as evidenced by reduced food intake, a lowered rate of body weight gain, and mortality. Studies have also been performed in these species with diacetolol (at doses of up to 450 mg/kg/day in rabbits and up to 1800 mg/kg/day in rats). Other than a significant elevation in post-implantation loss with 450 mg/kg/day diacetolol, a level at which food consumption and body weight gain were reduced in rabbit dams and a nonstatistically significant increase in incidence of bilateral cataract in rat fetuses from dams treated with 1800 mg/kg/day diacetolol, there was no evidence of harm to the fetus. There are no adequate and wellcontrolled trials in pregnant women. Because animal teratology studies are not always predictive of the human response, Acebutolol should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

Nonteratogenic Effects:

Studies in humans have shown that both Acebutolol and diacetolol cross the placenta. Neonates of mothers who have received Acebutolol during pregnancy have reduced birth weight, decreased blood pressure, and decreased heart rate. In the newborn the elimination half-life of Acebutolol was 6 to 14 hours, while the half-life of diacetolol was 24 to 30 hours for the first 24 hours after birth, followed by a half-life of 12 to 16 hours. Adequate facilities for monitoring these infants at birth should be available.

LABOR AND DELIVERY: The effect of Acebutolol on labor and delivery in pregnant women is unknown. Studies in animals have not shown any effect of Acebutolol on the usual course of labor and delivery.

NURSING MOTHERS: Acebutolol and diacetolol also appear in breast milk with a milk:plasma ratio of 7.1 and 12.2, respectively. Use in nursing mothers is not recommended.

PEDIATRIC USE: Safety and effectiveness in pediatric patients have not been established.

GERIATRIC USE: Clinical studies of Acebutolol and other reported clinical experience is inadequate to determine whether there are differences in safety or effectiveness between patients above or below age 65. Elderly subjects evidence greater bioavailability of Acebutolol (see Clinical Pharmacology - PHARMACOKINETICS AND METABOLISM), presumably because of age related reduction in first-pass metabolism and renal function. Therefore, it may be appropriate to start elderly patients at the low end of the dosing range (see Dosage and Administration - USE IN OLDER PATIENTS).

ADVERSE REACTIONS

Acebutolol is well tolerated in properly selected patients. Most adverse reactions have been mild, not required discontinuation of therapy, and tended to decrease as duration of treatment increases.

The following table shows the frequency of treatment-related side effects derived from controlled clinical trials in patients with hypertension, angina pectoris, and arrhythmia. These patients received Acebutolol, propranolol, or hydrochlorothiazide as monotherapy, or placebo.

The following selected (potentially important) side effects were seen in up to 2% of Acebutolol patients:

Cardiovascular: hypotension, bradycardia, heart failure.

Central Nervous System: anxiety, hyper/hypoesthesia, impotence.

Dermatological: pruritus.

Gastrointestinal: vomiting, abdominal pain.

Genitourinary: dysuria, nocturia.

Liver and Biliary System: A small number of cases of liver abnormalities (increased SGOT, SGPT, LDH) have been reported in association with Acebutolol therapy. In some cases increased bilirubin or alkaline phosphatase, fever, malaise, dark urine, anorexia, nausea, headache, and/or other symptoms have been reported. In some of the reported cases, the symptoms and signs were confirmed by rechallenge with Acebutolol. The abnormalities were reversible upon cessation of Acebutolol therapy.

Musculoskeletal: back pain, joint pain.

Respiratory: pharyngitis, wheezing.

Special Senses: conjunctivitis, dry eye, eye pain.

Autoimmune: In extremely rare instances, systemic lupus erythematosus has been reported.

The incidence of drug-related adverse effects (volunteered and solicited) according to Acebutolol dose is shown below. (Data from 266 hypertensive patients treated for 3 months on a constant dose.)

POTENTIAL ADVERSE EFFECTS

In addition, certain adverse effects not listed above have been reported with other β-blocking agents and should also be considered as potential adverse effects of Acebutolol.

Central Nervous System: Reversible mental depression progressing to catatonia (an acute syndrome characterized by disorientation for time and place), short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance (neuropsychometrics).

Cardiovascular: Intensification of AV block (see Contraindications).

Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm, and respiratory distress.

Hematologic: Agranulocytosis, nonthrombocytopenic, and thrombocytopenic purpura.

Gastrointestinal: Mesenteric arterial thrombosis and ischemic colitis.

Miscellaneous: Reversible alopecia and Peyronie’s disease. The oculomucocutaneous syndrome associated with the β-blocker practolol has not been reported with Acebutolol during investigational use and extensive foreign clinical experience.

OVERDOSAGE

No specific information on emergency treatment of overdosage is available for Acebutolol.

However, overdosage with other β-blocking agents has been accompanied by extreme bradycardia, advanced atrioventricular block, intraventricular conduction defects, hypotension, severe congestive heart failure, seizures, and in susceptible patients, bronchospasm and hypoglycemia. Although specific information on the emergency treatment of Acebutolol overdose is not available on the basis of the pharmacological actions and the observations in treating overdoses with other β-blockers, the following general measures should be considered:

1. Empty stomach by emesis or lavage.

2. Bradycardia: IV atropine (1 to 3 mg in divided doses). If antivagal response is inadequate, administer isoproterenol cautiously since larger than usual doses of isoproterenol may be required.

3. Persistent hypotension in spite of correction of bradycardia: Administer vasopressor (e.g., epinephrine, norepinephrine, dopamine, or dobutamine) with frequent monitoring of blood pressure and pulse rate.

4. Bronchospasm: A theophylline derivative, such as aminophylline and/or parenteral β2-stimulant, such as terbutaline.

5. Cardiac failure: Digitalize the patient and/or administer a diuretic. It has been reported that glucagon is useful in this situation.

Acebutolol is dialyzable.

DOSAGE & ADMINISTRATION

HYPERTENSION: The initial dosage of Acebutolol in uncomplicated mild-to-moderate hypertension is 400 mg. This can be given as a single daily dose, but in occasional patients twice daily dosing may be required for adequate 24-hour blood-pressure control. An optimal response is usually achieved with dosages of 400 to 800 mg per day, although some patients have been maintained on as little as 200 mg per day. Patients with more severe hypertension or who have demonstrated inadequate control may respond to a total of 1200 mg daily (administered b.i.d.), or to the addition of a second antihypertensive agent. Beta-1 selectivity diminishes as dosage is increased.

VENTRICULAR ARRHYTHMIA: The usual initial dose of Acebutolol is 400 mg daily given as 200 mg b.i.d. Dosage should be increased gradually until an optimal clinical response is obtained, generally at 600 to 1200 mg per day. If treatment is to be discontinued, the dosage should be reduced gradually over a period of about two weeks.

USE IN OLDER PATIENTS: Older patients have an approximately 2-fold increase in bioavailability and may require lower maintenance doses. Doses above 800 mg/day should be avoided in the elderly.

HOW SUPPLIED

Acebutolol hydrochloride capsules are available as follows:

200 mg: Size “2” hard gelatin capsules with bright orange opaque body printed radially “669” with black ink and lavender opaque cap printed radially “Amneal” with black ink.

Bottles of 100 NDC 65162-669-10

Bottles of 500 NDC 65162-669-50

400 mg: Size “2” hard gelatin capsules with bright orange opaque body printed radially “670” with black ink and lavender opaque cap printed radially “Amneal” with black ink.

Bottles of 30 NDC 65162-670-03

Bottles of 100 NDC 65162-670-10

Bottles of 500 NDC 65162-670-50

Store at 20° to 25°C (68° to 77°F) (See USP Controlled Room Temperature).

Protect from light. Keep tightly closed. Dispense in a light resistant, tight container.

Manufactured by:

Amneal Pharmaceuticals of NY

Hauppauge, NY 11788

Distributed by:

Amneal Pharmaceuticals

Glasgow, KY 42164

Rev. 09-2010

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Acebutolol HYDROCHLORIDE
Acebutolol hydrochloride capsule

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	NDC Product Code (Source)	65162-669
Route of Administration	ORAL	DEA Schedule

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
Acebutolol HYDROCHLORIDE (Acebutolol)	Acebutolol HYDROCHLORIDE	200 mg

Inactive Ingredients
Ingredient Name	Strength
FD&C BLUE NO. 1

Product Characteristics
Color	PURPLE (Lavender Opaque) , ORANGE (Bright Orange Opaque)	Score	no score
Shape	CAPSULE (Hard Gelatin)	Size	18mm
Flavor		Imprint Code	Amneal;669
Contains

Packaging
#	NDC	Package Description	Multilevel Packaging
1	65162-669-10	100 CAPSULE In 1 BOTTLE	None
2	65162-669-50	500 CAPSULE In 1 BOTTLE	None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA075047	12/01/2009

Acebutolol HYDROCHLORIDE
Acebutolol hydrochloride capsule

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	NDC Product Code (Source)	65162-670
Route of Administration	ORAL	DEA Schedule

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
Acebutolol HYDROCHLORIDE (Acebutolol)	Acebutolol HYDROCHLORIDE	400 mg

Inactive Ingredients
Ingredient Name	Strength
FD&C BLUE NO. 1

Product Characteristics
Color	PURPLE (Lavender Opaque) , ORANGE (Bring Orange Opaque)	Score	no score
Shape	CAPSULE (Hard Gelatin)	Size	23mm
Flavor		Imprint Code	Amneal;670
Contains

Packaging
#	NDC	Package Description	Multilevel Packaging
1	65162-670-03	30 CAPSULE In 1 BOTTLE	None
2	65162-670-10	100 CAPSULE In 1 BOTTLE	None
3	65162-670-50	500 CAPSULE In 1 BOTTLE	None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA075047	12/01/2009

Labeler - Amneal Pharmaceuticals, LLC (123797875)

Registrant - Amneal Pharmaceuticals (123797875)

Establishment
Name	Address	ID/FEI	Operations
Amneal Pharmaceuticals		831227801	ANALYSIS, MANUFACTURE, LABEL, PACK

Establishment
Name	Address	ID/FEI	Operations
Amneal Pharmaceuticals		831227777	ANALYSIS, MANUFACTURE, LABEL, PACK

Revised: 12/2010Amneal Pharmaceuticals, LLC

More Acebutolol resources

Acebutolol Side Effects (in more detail)
Acebutolol Dosage
Acebutolol Use in Pregnancy & Breastfeeding
Drug Images
Acebutolol Drug Interactions
Acebutolol Support Group
0 Reviews for Acebutolol - Add your own review/rating

Acebutolol MedFacts Consumer Leaflet (Wolters Kluwer)

acebutolol Concise Consumer Information (Cerner Multum)

acebutolol Advanced Consumer (Micromedex) - Includes Dosage Information

Acebutolol Hydrochloride Monograph (AHFS DI)

Compare Acebutolol with other medications

High Blood Pressure
Premature Ventricular Depolarizations
Ventricular Tachycardia

Sunday, March 18, 2012

Ciprofloxacin Extended Release Tablets

WARNING

Ciprofloxacin Extended Release Tablets - Clinical Pharmacology

Absorption

Distribution

Metabolism

Elimination

Special Populations

Drug-Drug Interactions

MICROBIOLOGY

Mechanism of Action

Mechanism of Resistance

Cross Resistance

Susceptibility Test Methods

Indications and Usage for Ciprofloxacin Extended Release Tablets

Contraindications

Warnings

Tendinopathy and Tendon Rupture

Exacerbation of Myasthenia Gravis

Pregnant Women

Hypersensitivity Reactions

Theophylline

Central Nervous System Effects

Clostridium difficile Associated Diarrhea

Peripheral Neuropathy

Musculoskeletal Disorders in Pediatric Patients and Arthropathic Effects in Animals

Prolongation of the QT Interval

Cytochrome P450 (CYP450)

Precautions

General

Photosensitivity/Phototoxicity

Information for Patients

Drug Interactions

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What other drugs will affect chlorpheniramine, phenylephrine, and pyrilamine?

More Triotann-S Pediatric resources

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Saturday, March 17, 2012

Multaq

What is dronedarone?

What is the most important information I should know about dronedarone?

What should I discuss with my healthcare provider before taking dronedarone?

How should I take dronedarone?

What happens if I miss a dose?

What happens if I overdose?

What should I avoid while taking dronedarone?

Dronedarone side effects

What other drugs will affect dronedarone?

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Thursday, March 15, 2012

Lonox

Commonly used brand name(s)

Uses For Lonox

Before Using Lonox

Allergies

Pediatric

Geriatric

Pregnancy

Breast Feeding

Interactions with Medicines

Interactions with Food/Tobacco/Alcohol

Other Medical Problems

Proper Use of diphenoxylate and atropine

Dosing

Missed Dose

Storage

Precautions While Using Lonox

Lonox Side Effects