Icavex may be available in the countries listed below.
Moxisylyte hydrochloride (a derivative of Moxisylyte) is reported as an ingredient of Icavex in the following countries:
International Drug Name Search
Generic Name: hydrocortisone, neomycin, and polymyxin B otic (HYE droe KOR ti sone, NEE oh MYE sin, POL ee MIX in B)
Brand names: Cort-Biotic, Cortatrigen, Cortatrigen Modified, Cortisporin Otic, Cortomycin, Oti-Sone, Pediotic, ...show all 15 brand names.
Hydrocortisone is a steroid. It reduces the actions of chemicals in the body that cause inflammation, redness, and swelling.
Neomycin and polymyxin B are antibiotics that fight bacteria.
The combination of hydrocortisone, neomycin, and polymyxin B otic (for the ears) is used to treat ear infections caused by bacteria.
This medication will not treat a viral infection such as herpes or shingles.
Hydrocortisone, neomycin, and polymyxin B otic may also be used for other purposes not listed in this medication guide.
Before using this medication, tell your doctor if you have herpes (simplex or zoster), chickenpox or small pox, any ear infection that causes blistering, asthma or sulfite allergy, or if you are allergic to an antibiotic similar to neomycin, such as amikacin (Amikin), gentamicin (Garamycin), kanamycin (Kantrex), netilmicin (Netromycin), paromomycin (Humatin, Paromycin), streptomycin, or tobramycin (Nebcin, Tobi).
Use this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Talk with your doctor if your symptoms do not improve after 1 week of using this medication.
a ruptured ear drum; or
an ear infection caused by chickenpox, or herpes infection (simplex or zoster).
If you have any of these other conditions, you may need a dose adjustment or special tests to safely use this medication:
herpes (simplex or zoster);
chickenpox or small pox;
any ear infection that causes blistering;
asthma or sulfite allergy; or
if you are allergic to an antibiotic similar to neomycin, such as amikacin (Amikin), gentamicin (Garamycin), kanamycin (Kantrex), netilmicin (Netromycin), paromomycin (Humatin, Paromycin), streptomycin, or tobramycin (Nebcin, Tobi).
Use this medication exactly as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended. Follow the directions on your prescription label.
Before using this medication, clean and dry your ear canal with sterile cotton.
This medication is usually given as 4 to 5 drops into the affected ear every 6 to 8 hours. Children may need to use fewer drops. Follow your doctor's instructions about how much medication you should use and how often.
To use the ear drops, first remove the cap from the dropper bottle. Lie down or tilt your head with your ear facing upward. Pull back on your ear gently to open up the ear canal. If giving this medicine to a child, pull down on the earlobe to open the ear canal. Hold the dropper upside down over the ear canal and drop the correct number of drops into the ear.
Do not place the dropper tip into your ear or allow the tip to touch any surface. It may become contaminated.
After using the ear drops, stay lying down or with your head tilted for at least 5 minutes.
As an alternative to dropping the medicine into your ear, you may insert a small piece of cotton into the ear canal and then drop the medicine directly onto the cotton to soak it. Leave the cotton in the ear and keep it moist by adding more of the medication every 4 to 8 hours. Replace the cotton at least every 24 hours. Follow your doctor's instructions about the use of cotton with this medication.
Wipe the ear dropper tip with a clean tissue. Do not wash the tip with water or soap.
Use this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Talk with your doctor if your symptoms do not improve after 1 week of using this medication.
Use the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up the missed dose.
Overdose symptoms may include hearing problems, or urinating less than usual.
skin rash, redness, swelling, itching, dryness, scaling, or other irritation in or around the ear;
severe burning, stinging, or other irritation when using the medication;
new signs of infection;
hearing loss; or
urinating less than usual or not at all.
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.
Usual Adult Dose for Otitis Externa:
Solution or suspension: Instill 4 drops into the affected ear(s) 3 to 4 times daily for up to 10 days.
Usual Adult Dose for Otitis Media:
Mastoidectomy infection and fenestration cavity infection:
Suspension: Instill 4 drops into the affected ear(s) 3 to 4 times daily for up to 10 days.
Usual Pediatric Dose for Otitis Externa:
Children:
Solution or suspension: Instill 3 drops into the affected ear(s) 3 to 4 times daily for up to 10 days.
Usual Pediatric Dose for Otitis Media:
Children:
Mastoidectomy infection and fenestration cavity infection:
Suspension: Instill 3 drops into the affected ear(s) 3 to 4 times daily for up to 10 days.
It is not likely that other drugs you take orally or inject will have an effect on hydrocortisone, neomycin, and polymyxin B used in the ears. But many drugs can interact with each other. 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.
There are currently no drugs listed for "Anemia Associated with Chronic Disease". See Anemia.
Generic Name: nicotine (Oral route, Transdermal route)
NIK-oh-teen
In the U.S.
In Canada
Available Dosage Forms:
Therapeutic Class: Smoking Cessation Agent
Pharmacologic Class: Cholinergic
Nicotine, in a flavored chewing gum, a lozenge, or a skin patch, is used to help you stop smoking. It is used for up to 12 weeks as part of a stop-smoking program. This program may include education, counseling, and psychological support.
As you chew nicotine gum or suck on the nicotine lozenge, nicotine passes through the lining of your mouth and into your blood stream. When you wear a nicotine patch, nicotine passes through your skin into your blood stream. This nicotine takes the place of nicotine that you would otherwise get from smoking. In this way, the withdrawal effects of not smoking are less severe. Then, as your body adjusts to not smoking, the use of the nicotine gum is decreased gradually until use is stopped altogether. For most brands of patches, the strength of the patch you use will be decreased over a few weeks until use is stopped. If you are using the brand of patch that is available in only one strength, use is stopped after the treatment period indicated on the label.
Children, pregnant women, and nonsmokers should not use nicotine gum or patches because of harmful effects.
Nicotine transdermal patches, gum, and lozenges are available without a prescription.
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:
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.
Small amounts of nicotine can cause serious harm in children. Even nicotine patches that have been used still contain enough nicotine to cause problems in children. Although there is no specific information comparing use of nicotine in teenagers with use in other age groups, this medicine is not expected to cause different side effects or problems in nicotine-dependent teenagers than it does in adults.
Nicotine gum, lozenges, and patches have been used in a limited number of patients 60 years of age or older, and have not been shown to cause different side effects or problems in older people than in younger adults.
| Pregnancy Category | Explanation | |
|---|---|---|
| All Trimesters | D | Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk. |
Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.
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 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.
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.
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
This section provides information on the proper use of a number of products that contain nicotine. It may not be specific to Nicoderm. Please read with care.
For patients using the chewing gum:
For patients using the lozenge:
For patients using the transdermal system (skin patch):
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.
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.
Ask your healthcare professional how you should dispose of any medicine you do not use.
Do not smoke during treatment with nicotine gum, lozenges, or patches because of the risk of nicotine overdose.
Nicotine should not be used in pregnancy. If there is a possibility you might become pregnant, you may want to use some type of birth control. If you think you may have become pregnant, stop using this medicine immediately and check with your doctor.
Nicotine products must be kept out of the reach of children and pets. Even nicotine patches that have been used still contain enough nicotine to cause problems in children. If a child chews or swallows one or more pieces of nicotine gum or lozenges, contact your doctor or poison control center at once. If a child puts on a nicotine patch or plays with a patch that is out of the sealed pouch, take it away from the child and contact your doctor or poison control center at once.
For patients using the chewing gum:
For patients using the lozenges:
For patients using the transdermal system (skin patch) :
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 as soon as possible if any of the following side effects occur:
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:
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: Nicoderm 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.
The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.
Resolor 2 mg film-coated tablets
Each film-coated tablet contains 2 mg prucalopride (as prucalopride succinate).
Excipients: Each film-coated tablet contains 165 mg lactose monohydrate.
For a full list of excipients, see section 6.1.
Film-coated tablet (tablet).
Pink, round, biconvex tablets marked “PRU 2” on one side.
Resolor is indicated for symptomatic treatment of chronic constipation in women in whom laxatives fail to provide adequate relief.
Posology
Women: 2 mg once daily.
Men: The safety and efficacy of Resolor for use in men has not been established in controlled clinical trials therefore Resolor is not recommended for use in men until further data becomes available.
Elderly (>65 years): Start with one 1 mg once daily (see section 5.2); if needed the dose can be increased to 2 mg once daily.
Children and adolescents: Resolor is not recommended in children and adolescents younger than 18 years until further data become available. Currently available data are described in section 5.2.
Patients with renal impairment: The dose for patients with severe renal impairment (GFR < 30 ml/min/1.73 m2) is 1 mg once daily (see sections 4.3 and 5.2). No dose adjustment is required for patients with mild to moderate renal impairment.
Patients with hepatic impairment: The dose for patients with severe hepatic impairment (Child-Pugh class C) is 1 mg once daily (see sections 4.4 and 5.2). No dose adjustment is required for patients with mild to moderate hepatic impairment.
Due to the specific mode of action of prucalopride (stimulation of propulsive motility) exceeding the daily dose of 2 mg is not expected to increase efficacy.
If the intake of once daily prucalopride is not effective after 4 weeks of treatment, the patient should be re-examined and the benefit of continuing treatment reconsidered.
The efficacy of prucalopride has been established in double blind placebo controlled studies for up to 3 months. In case of prolonged treatment the benefit should be reassessed at regular intervals.
Method of administration
Resolor film-coated tablets are for oral use and can be taken with or without food, at any time of the day.
- Hypersensitivity to the active substance or to any of the excipients.
- Renal impairment requiring dialysis.
- Intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the intestinal tract, such as Crohn's disease, and ulcerative colitis and toxic megacolon/megarectum.
Renal excretion is the main route of elimination of prucalopride (see section 5.2). A dose of 1 mg is recommended in subjects with severe renal impairment (see section 4.2).
Patients with severe and clinically unstable concomitant disease (e.g. liver, cardiovascular or lung disease, neurological or psychiatric disorders, cancer or AIDS and other endocrine disorders) have not been studied. Caution should be exercised when prescribing Resolor to patients with these conditions. In particular Resolor should be used with caution in patients with a history of arrhythmias or ischaemic cardiovascular disease.
In case of severe diarrhoea, the efficacy of oral contraceptives may be reduced and the use of an additional contraceptive method is recommended to prevent possible failure of oral contraception (see the prescribing information of the oral contraceptive).
It is unlikely that hepatic impairment will affect prucalopride metabolism and exposure in man to a clinically relevant extent. No data are available in patients with mild, moderate or severe hepatic impairment, and therefore a lower dose is recommended for patients with severe hepatic impairment (see section 4.2).
Men: The safety and efficacy of Resolor for use in men has not been established in controlled clinical trials therefore Resolor is not recommended for use in men until further data becomes available.
The tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption must not take this medicinal product.
In vitro data indicate that prucalopride has a low interaction potential, and therapeutic concentrations of prucalopride are not expected to affect the CYP-mediated metabolism of co-medicated medicinal products. Although prucalopride may be a weak substrate for P-glycoprotein (P-gp), it is not an inhibitor of P-gp at clinically relevant concentrations.
Ketoconazole (200 mg b.i.d.), a potent inhibitor of CYP3A4 and of P-gp, increased the area under the curve (AUC) of prucalopride by approximately 40%. This effect is too small to be clinically relevant and is likely attributable to inhibition of P-gp mediated renal transport. Interactions of similar magnitude as observed with ketoconazole may also occur with other potent inhibitors of P-gp such as verapamil, cyclosporine A and quinidine. Prucalopride is likely also secreted via another renal transporter(s). Inhibition of all transporters involved in the active secretion of prucalopride (including P-gp) may theoretically increase the exposure by up to 75%.
Studies in healthy subjects showed that there were no clinically relevant effects of prucalopride on the pharmacokinetics of warfarin, digoxin, alcohol and paroxetine. A 30% increase in the plasma concentrations of erythromycin was found during prucalopride co-treatment. The mechanism for this interaction is not fully known, but the available data support that this is the consequence of the high intrinsic variability in erythromycin kinetics, rather than a direct effect of prucalopride.
Therapeutic doses of probenecid, cimetidine, erythromycin and paroxetine did not affect the pharmacokinetics of prucalopride.
Resolor should be used with caution in patients receiving concomitant drugs known to cause QTc prolongation.
Because of the mechanism of action, the use of atropine-like substances may reduce the 5-HT4 receptor mediated effects of prucalopride.
Interactions with food have not been observed.
Pregnancy
Experience with prucalopride during pregnancy is limited. Cases of spontaneous abortion have been observed during clinical studies, although, in the presence of other risk factors, the relationship to prucalopride is unknown. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). Resolor is not recommended during pregnancy. Women of childbearing potential should use effective contraception during treatment with prucalopride.
Lactation
Prucalopride is excreted in breast milk. However, at therapeutic doses of Resolor no effects on the breastfed newborns/infants are anticipated. In the absence of human data, it is not recommended to use Resolor during breast-feeding.
Fertility
Animal studies indicate that there is no effect on male or female fertility.
No studies on the effects of prucalopride on the ability to drive and use machines have been performed. Resolor has been associated with dizziness and fatigue particularly during the first day of treatment which may have an effect on driving and using machines (see section 4.8).
Resolor has been given orally to approximately 2,700 patients with chronic constipation in controlled clinical studies. Of these patients, almost 1,000 patients received Resolor at the recommended dose of 2 mg per day, while about 1,300 patients were treated with 4 mg prucalopride daily. Total exposure in the clinical development plan exceeded 2,600 patient years. The most frequently reported adverse reactions associated with Resolor therapy are headache and gastrointestinal symptoms (abdominal pain, nausea or diarrhoea) occurring in approximately 20% of patients each. The adverse reactions occur predominantly at the start of therapy and usually disappear within a few days with continued treatment. Other adverse reactions have been reported occasionally. The majority of adverse events were mild to moderate in intensity.
The following adverse reactions were reported in controlled clinical studies at the recommended dose of 2 mg with frequencies corresponding to Very common (
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After the first day of treatment, the most common adverse reactions were reported in similar frequencies (incidence less than 1% different between prucalopride and placebo) during Resolor therapy as during placebo, with the exception of nausea and diarrhoea that still occurred more frequently during Resolor therapy, but less pronounced (difference in incidence between prucalopride and placebo between 1 and 3%).
Palpitations were reported in 0.7% of the placebo patients, 1.0% of the 1 mg prucalopride patients, 0.7% of the 2 mg prucalopride patients and 1.9% of the 4 mg prucalopride patients. The majority of patients continued using prucalopride. As with any new symptom, patients should discuss the new onset of palpitations with their physician.
In a study in healthy volunteers treatment with prucalopride was well tolerated when given in an up-titrating scheme up to 20 mg once daily (10 times the recommended therapeutic dose). An overdose may result in symptoms resulting from an exaggeration of the medicinal product's known pharmacodynamic effects and include headache, nausea and diarrhoea. Specific treatment is not available for Resolor overdose. Should an overdose occur, the patient should be treated symptomatically and supportive measures instituted, as required. Extensive fluid loss by diarrhoea or vomiting may require correction of electrolyte disturbances.
Pharmacotherapeutic group: Drugs acting on serotonin receptors, ATC code: A03AE04.
Mechanism of action
Prucalopride is a dihydrobenzofurancarboxamide with enterokinetic activities. Prucalopride is a selective, high affinity serotonin (5-HT4) receptor agonist, which is likely to explain its enterokinetic effects. In vitro, only at concentrations exceeding its 5-HT4 receptor affinity by at least 150-fold, affinity for other receptors was detected. In rats prucalopride in vivo at doses above 5 mg/kg (at and above 30-70 times the clinical exposure) induced hyperprolactinaemia caused by an antagonistic action at the D2 receptor.
In dogs, prucalopride alters colonic motility patterns via serotonin 5-HT4 receptor stimulation: it stimulates proximal colonic motility, enhances gastroduodenal motility and accelerates delayed gastric emptying. Furthermore, giant migrating contractions are induced by prucalopride. These are equivalent to the colonic mass movements in humans, and provide the main propulsive force to defecation. In dogs, the effects observed in the gastrointestinal tract are sensitive to blockade with selective 5-HT4 receptor antagonists illustrating that the observed effects are exerted via selective action on 5-HT4 receptors.
Clinical experience
The efficacy of prucalopride was established in three multicentre, randomised, double-blind, 12-week placebo-controlled studies in subjects with chronic constipation (n=1,279 on prucalopride, 1,124 females, 155 males). The prucalopride doses studied in each of these three studies included 2 mg and 4 mg once daily. The primary efficacy endpoint was the proportion (%) of subjects that reached normalisation of bowel movements defined as an average of three or more spontaneous, complete bowel movements (SCBM) per week over the 12-week treatment period. Both doses were statistically superior (p<0.001) to placebo at the primary endpoint in each of the three studies, with no incremental benefit of the 4 mg over the 2 mg dose. The proportion of patients treated with the recommended dose of 2 mg prucalopride that reached an average of
In all three studies, treatment with prucalopride also resulted in significant improvements in a validated and disease specific set of symptom measures (PAC SYM), including abdominal, stool and rectal symptoms, determined at week 4 and week 12. A significant benefit on a number of Quality of Life measures, such as degree of satisfaction with treatment and with bowel habits, physical and psychosocial discomfort and worries and concerns, was also observed at both the 4 and 12 week assessment time points.
Prucalopride has been shown not to cause rebound phenomena, nor to induce dependency.
A thorough QT study was performed to evaluate the effects of prucalopride on the QT interval at therapeutic (2 mg) and supratherapeutic doses (10 mg) and compared with the effects of placebo and a positive control. This study did not show significant differences between prucalopride and placebo at either dose, based on mean QT measurements and outlier analysis. This confirmed the results of two placebo controlled QT studies. In double blind clinical studies, the incidence of QT-related adverse events and ventricular arrhythmias was low and comparable to placebo.
Data from open label studies up to 2.6 years offer some evidence for longer-term safety and efficacy; however, no placebo controlled efficacy data for treatments longer than 12 weeks duration are available.
Absorption
Prucalopride is rapidly absorbed; after a single oral dose of 2 mg Cmax was attained in 2-3 hours. The absolute oral bioavailability is >90%. Concomitant intake of food does not influence the oral bioavailability of prucalopride.
Distribution
Prucalopride is extensively distributed, and has a steady-state volume of distribution (Vdss) of 567 litre. The plasma protein binding of prucalopride is about 30%.
Metabolism
Metabolism is not the major route of elimination of prucalopride. In vitro, human liver metabolism is very slow and only minor amounts of metabolites are found. In an oral dose study with radiolabelled prucalopride in man small amounts of eight metabolites were recovered in urine and faeces. The major metabolite (R107504, formed by O-demethylation and oxidation of the resulting alcohol function to a carboxylic acid) accounted for less than 4% of the dose. Unchanged active substance made up about 85% of the total radioactivity in plasma and only R107504 was a minor plasma metabolite.
Elimination
A large fraction of the active substance is excreted unchanged (about 60% of the administered dose in urine and at least 6% in faeces). Renal excretion of unchanged prucalopride involves both passive filtration and active secretion. The plasma clearance of prucalopride averages 317 ml/min. Its terminal half-life is about one day. Steady-state is reached within three to four days. On once daily treatment with 2 mg prucalopride steady-state plasma concentrations fluctuate between trough and peak values of 2.5 and 7 ng/ml, respectively. The accumulation ratio after once daily dosing ranged from 1.9 to 2.3. The pharmacokinetics of prucalopride is dose-proportional within and beyond the therapeutic range (tested up to 20 mg). Prucalopride o.d. displays time-independent kinetics during prolonged treatment.
Special populations
Population pharmacokinetics
A population pharmacokinetic analysis showed that the apparent total clearance of prucalopride was correlated with creatinine clearance, but that age, body weight, sex or race had no influence.
Elderly
After once daily dosing of 1 mg, peak plasma concentrations and AUC of prucalopride in elderly subjects were 26% to 28% higher than in young adults. This effect can be attributed to a diminished renal function in elderly.
Renal impairment
Compared to subjects with normal renal function, plasma concentrations of prucalopride after a single 2 mg dose were on average 25% and 51% higher in subjects with mild (ClCR 50-79 ml/min) and moderate (ClCR 25-49 ml/min) renal impairment, respectively. In subjects with severe renal impairment (ClCR
Hepatic impairment
Non-renal elimination contributes to about 35% of total elimination, and hepatic impairment is unlikely to affect the pharmacokinetics of prucalopride to a clinically relevant extent (see section 4.2 and 4.4).
Paediatric population
After a single oral dose of 0.03 mg/kg in paediatric patients aged between 4 and 12 years , Cmax of prucalopride was comparable to the Cmax in adults after a single 2 mg dose, while unbound AUC was 30-40% lower than after 2 mg in adults. Unbound exposure was similar over the whole age-range (4-12 years).The average terminal half life in the paediatric subjects was about 19 hours (range 11.6 to 26.8 hours) (see section 4.2).
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction and development. An extended series of safety pharmacology studies with special emphasis on cardiovascular parameters showed no relevant changes in haemodynamic and ECG derived parameters (QTc) with the exception of a modest increase in heart rate and blood pressure observed in anaesthesized pigs after intravenous administration, and an increase in blood pressure in conscious dogs after bolus intravenous administration, which was not observed either in anaesthetized dogs or after oral administration in dogs reaching similar plasma levels.
Tablet core
Lactose monohydrate
Microcrystalline cellulose
Colloidal silicon dioxide
Magnesium stearate
Coating
Hypromellose
Lactose monohydrate
Triacetin
Titanium dioxide (E171)
Macrogol
Iron oxide red (E172)
Iron oxide yellow (E172)
Indigo carmine aluminium lake (E132)
Not applicable.
4 years.
Store in the original blister in order to protect from moisture.
Aluminium/aluminium perforated unit dose blisters (calendar marked) containing 7 tablets. Each pack contains 7 x 1, 14 x 1, 28 x 1 or 84 x 1 film-coated tablet.
Not all pack sizes may be marketed.
No special requirements.
Shire-Movetis NV
Veedijk 58
B-2300 Turnhout
Belgium
Tel.: 008006683 8470
EU/1/09/581/002 (28 tablets)
EU/1/09/581/004 (7 tablets)
EU/1/09/581/006 (14 tablets)
EU/1/09/581/008 (84 tablets)
15/10/09
October 2011
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http://www.emea.europa.eu/.
Generic Name: hydrocortisone topical (hye droe KOR ti sone)
Brand Names: Ala-Cort, Ala-Scalp HP, Aquanil HC, Beta HC, Caldecort, Cortaid, Cortaid Intensive Therapy, Cortaid Maximum Strength, Cortaid with Aloe, Cortalo with Aloe, Corticaine, Cortizone for Kids, Cortizone-10, Cortizone-10 Intensive Healing Formula, Cortizone-10 Plus, Cortizone-5, Dermarest Dricort, Dermarest Eczema Medicated, Dermarest Plus Anti-Itch, Dermtex HC, Genasone/Aloe, Gly-Cort, Gynecort Maximum Strength, Hycort, Hydrocortisone 1% In Absorbase, Hydrocortisone with Aloe, Hydrocortisone-Aloe, Hytone, Instacort, Itch-X Lotion, Locoid, Locoid Lipocream, Locoid Lotion, Massengill Medicated Soft Cloth, MD Hydrocortisone, Neutrogena T-Scalp, NuCort with Aloe, NuZon, Pandel, Recort Plus, Rederm, Sarnol-HC, Scalacort, Texacort, U-Cort, Westcort
Hydrocortisone is a topical steroid. It reduces the actions of chemicals in the body that cause inflammation, redness, and swelling.
Hydrocortisone topical is used to treat inflammation of the skin caused by a number of conditions such as allergic reactions, eczema, or psoriasis.
Hydrocortisone topical may also be used for other purposes not listed in this medication guide.
There are many brands and forms of hydrocortisone topical available and not all brands are listed on this leaflet.
Use this medication exactly as directed on the label, or as it has been prescribed by your doctor. Do not use the medication in larger amounts or for longer than recommended.
Avoid using this medication on your face, near your eyes, or on body areas where you have skin folds or thin skin.
Hydrocortisone topical will not treat a bacterial, fungal, or viral skin infection.
Hydrocortisone topical will not treat a bacterial, fungal, or viral skin infection.
Use this medication exactly as directed on the label, or as it has been prescribed by your doctor. Do not use the medication in larger or smaller amounts, or use it for longer than recommended.
Hydrocortisone topical will not treat a bacterial, fungal, or viral skin infection.
Wash your hands before and after each application, unless you are using hydrocortisone topical to treat a hand condition.
Apply a small amount to the affected area and rub it gently into the skin.
Avoid using this medication on your face, near your eyes or mouth, or on body areas where you have skin folds or thin skin.
Use the medication as soon as you remember. If it is almost time for the next dose, skip the missed dose and use the medicine at the next regularly scheduled time. Do not use extra medicine to make up the missed dose.
Avoid using skin products that can cause irritation, such as harsh soaps or shampoos or skin cleansers, hair coloring or permanent chemicals, hair removers or waxes, or skin products with alcohol, spices, astringents, or lime. Do not use other medicated skin products unless your doctor has told you to.
blurred vision, or seeing halos around lights;
uneven heartbeats;
sleep problems (insomnia);
weight gain, puffiness in your face; or
feeling tired.
Less serious side effects may include:
skin redness, burning, itching, or peeling;
thinning of your skin;
blistering skin; or
stretch marks.
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.
Usual Adult Dose for Dermatitis:
Topical cream, ointment, solution, gel, or lotion:
Apply to the affected area 2 to 4 times a day.
For treatment of resistant dermatoses, hydrocortisone may be used with occlusive dressings.
Butyrate cream, ointment or solution:
Apply to the affected area once or twice a day.
Usual Adult Dose for Eczema:
Topical cream, ointment, solution, gel, or lotion:
Apply to the affected area 2 to 4 times a day.
For treatment of resistant dermatoses, hydrocortisone may be used with occlusive dressings.
Butyrate cream, ointment or solution:
Apply to the affected area once or twice a day.
Usual Adult Dose for Psoriasis:
Topical cream, ointment, solution, gel, or lotion:
Apply to the affected area 2 to 4 times a day.
For treatment of resistant dermatoses, hydrocortisone may be used with occlusive dressings.
Butyrate cream, ointment or solution:
Apply to the affected area once or twice a day.
Usual Adult Dose for Ulcerative Colitis -- Active:
Hydrocortisone is recommended for use in patients whose ulcerative colitis presents with proctitis or distal colitis. The rectal enema reaches the splenic flexure whereas the rectal foam penetrates just to the rectum and sigmoid colon.
Rectal solution:
60 mL (100 mg) by rectal enema once a day at bedtime. Hydrocortisone enema should be retained for at least 1 to 3 hours and preferably all night. Sedatives and/or antidiarrheal medications may aid in extending enema retention time.
-or-
Rectal foam (10%):
one applicatorful (80 mg) of rectal foam rectally once or twice daily.
-or-
Rectal suppository:
one suppository (25 mg) inserted rectally twice daily.
Therapy should be continued for approximately 3 weeks or until ulcerative colitis remission.
Usual Adult Dose for Gingivitis:
dental paste (0.5%):
Apply paste to the oral mucosa 2 to 3 times a day following meals and at bedtime. Usually a small amount (1/4 inch) should be applied to the lesion without rubbing in, which will form a smooth film over the area. The manufacturer recommends that if improvement is not seen within 7 days, treatment should be reevaluated.
Usual Adult Dose for Aphthous Stomatitis -- Recurrent:
dental paste (0.5%):
Apply paste to the oral mucosa 2 to 3 times a day following meals and at bedtime. Usually a small amount (1/4 inch) should be applied to the lesion without rubbing in, which will form a smooth film over the area. The manufacturer recommends that if improvement is not seen within 7 days, treatment should be reevaluated.
Usual Adult Dose for Seborrheic Dermatitis:
Topical Solution:
Apply to affected area once a day.
-or-
Topical Lotion:
Apply to affected area once a day.
The manufacturer recommends that if improvement is not seen within 7 days, treatment should be reevaluated.
Usual Adult Dose for Hemorrhoids:
Rectal Suppository:
25 mg inserted rectally once or twice a day. The dose may be increased to 75 mg or 100 mg a day as needed.
Cream or lotion:
Apply 1 to 2 times a day as needed.
Therapy should be continued for approximately 3 days to 4 weeks, depending on the nature and severity of the condition.
Usual Adult Dose for Proctitis:
Rectal Suppository:
25 mg inserted rectally 2 times a day (once in the morning and once at night). The dose may be increased to 75 mg or 100 mg a day as needed.
-or-
Rectal foam:
one applicatorful (80 mg) rectally once or twice a day.
Therapy should be continued for approximately 2 weeks, but may require up to 8 weeks depending on the nature of the condition.
Usual Adult Dose for Pruritus:
Relief of minor feminine itching associated with external vaginal area:
Topical Pad:
Apply not more than 4 times a day.
Usual Pediatric Dose for Dermatitis:
> 1 year:
Topical cream, ointment, solution or lotion:
Apply to the affected area 2 to 4 times a day.
Butyrate cream, ointment or solution:
Apply to the affected area once or twice a day.
Usual Pediatric Dose for Eczema:
> 1 year:
Topical cream, ointment, solution or lotion:
Apply to the affected area 2 to 4 times a day.
Butyrate cream, ointment or solution:
Apply to the affected area once or twice a day.
Usual Pediatric Dose for Psoriasis:
> 1 year:
Topical cream, ointment, solution or lotion:
Apply to the affected area 2 to 4 times a day.
Butyrate cream, ointment or solution:
Apply to the affected area once or twice a day.
Usual Pediatric Dose for Pruritus:
Relief of minor feminine itching associated with external vaginal area:
Topical Pad
> 2 years: Apply not more than 4 times a day.
Rectal cream and ointment:
>= 13 years: 1 to 2 applicatorsful per day.
It is not likely that other drugs you take orally or inject will have an effect on topically applied hydrocortisone. But many drugs can interact with each other. 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.
Generic Name: tolnaftate topical (toll NAF tate)
Brand Names: Absorbine Athletes Foot, Absorbine Jr. Antifungal, Aftate For Athletes Foot, Blis-To-Sol, Desenex Spray, Fungatin, Fungi-Guard, Genaspor, Hongos, NP 27, Podactin, T-Athlete, Tinactin, Tinaspore, Ting
Tolnaftate topical is an antifungal medication. Tolnaftate topical prevents fungus from growing on the skin.
Tolnaftate topical is used to treat skin infections such as athlete's foot, jock itch, and ringworm infections. Tolnaftate is also used, along with other antifungals, to treat infections of the nails, scalp, palms, and soles of the feet. The powder and powder aerosol may be used to prevent athlete's foot.
Tolnaftate topical may also be used for purposes other than those listed in this medication guide.
Do not use bandages or dressings that do not allow air to circulate to the affected area (occlusive dressings) unless otherwise directed by your doctor. Wear loose-fitting clothing (preferably cotton).
Do not use tolnaftate topical if you have had an allergic reaction to it in the past.
Wash your hands before and after using this medication.
Clean and dry the affected area. Apply the gel, cream, lotion, spray, or powder twice daily as directed for 2 to 6 weeks.
If the infection does not clear up in 10 days or if it appears to get worse, see your doctor.
Do not use bandages or dressings that do not allow air circulation over the affected area (occlusive dressings) unless otherwise directed by your doctor. A light cotton-gauze dressing may be used to protect clothing.
Apply the missed dose as soon as you remember. However, if it is almost time for the next regularly scheduled dose, skip the dose you missed and apply only the regular amount of tolnaftate topical. Do not use a double dose unless otherwise directed by your doctor.
An overdose of tolnaftate topical is unlikely to occur. If you do suspect that a much larger than normal dose has been used or that tolnaftate topical has been ingested, contact an emergency room or a poison control center.
Avoid wearing tight-fitting, synthetic clothing that doesn't allow air circulation. Wear loose-fitting clothing made of cotton and other natural fibers until the infection is healed.
Serious side effects of tolnaftate topical use are not expected to occur. Stop using tolnaftate topical and see your doctor if you experience unusual or severe blistering, itching, redness, peeling, dryness, or irritation of the skin.
Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.
Other skin medications may affect the absorption or effectiveness of tolnaftate topical. Avoid using other topicals at the same time except under the direction of a doctor.
See also: Hongos side effects (in more detail)
A drug may be classified by the chemical type of the active ingredient or by the way it is used to treat a particular condition. Each drug can be classified into one or more drug classes.
Medical conditions associated with vaccine combinations:
Fluoroquinolones, including Proquin XR, are associated with an increased risk of tendinitis and tendon rupture in all ages. The risk is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart and lung transplant recipients (See WARNINGS).
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Proquin XR and other antibacterial drugs, Proquin XR should be used only to treat uncomplicated urinary tract infections that are strongly suspected to be caused by bacteria.
Proquin XR (ciprofloxacin hydrochloride) extended-release tablets contain ciprofloxacin hydrochloride, a synthetic broad-spectrum fluoroquinolone antimicrobial agent for oral administration.
Ciprofloxacin hydrochloride is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid hydrochloride. The molecular weight of the monohydrate is 385.82. It is a faintly yellowish to light yellow crystalline substance and its chemical structure is as follows:
Proquin XR is available as 500 mg (ciprofloxacin equivalent) tablets, utilizing AcuForm™ delivery technology. Proquin XR tablets are blue film-coated and oval-shaped. The inactive ingredients are povidone, magnesium stearate, polyethylene oxide, and film coating (Opadry® Blue).
When Proquin XR is administered with food, approximately 87% of ciprofloxacin is gradually released from the tablet over a 6-hour period. When administered following a meal maximum plasma ciprofloxacin concentrations are attained approximately 4.5-7 hours after dosing with Proquin XR tablets. Proquin XR should be administered with a main meal of the day, preferably the evening meal; if Proquin XR is given while fasting, the bioavailability will be lowered substantially. Administration of Proquin XR with a standardized meal (1000 calories, 50% fat) increased the Cmax and AUC0-24h by approximately 120% and 170%, respectively, compared to administration under fasting conditions; the mean Tmax was prolonged from 2.3 hours to 4.5 hours. The following table presents the pharmacokinetic parameters obtained at steady state for Proquin XR 500 mg qd versus CIPRO 250 mg bid.
| Pharmacokinetic Parameters | Proquin XR 500 mg Tablets (qd) (n=27) | CIPRO 250 mg Tablets (bid) (n=27) |
|---|---|---|
| a both treatments were administered following a standardized meal (approximately 1000 calories, 50% fat). b Cmax1 = peak concentration after the evening dose of CIPRO bid. Cmax2 = peak concentration after the morning dose of CIPRO bid. c Tmax1 = time of peak concentration after the evening dose CIPRO bid. Tmax2 = time of peak concentration after the morning dose CIPRO bid. | ||
| Mean (%CV) | ||
| AUC0-24h (mcg.hr/mL) | 7.67 (25) | 7.83 (16) |
| Cmax (mcg/mL) | 0.82 (28) | Cmax1 0.57 (25)b Cmax2 0.93 (27) |
| Cmin (mcg/mL) | 0.06 (42) | 0.14 (29) |
| Mean ± SD | ||
| Tmax (hr) | 6.1 ± 2.6 | Tmax1 2.5 ± 1.2c Tmax2 2.5 ± 1.4 |
The in vitro binding of ciprofloxacin to plasma proteins over a concentration ranging from 0.9 to 30 micromolar is 9.9% to 36.6%, which is not likely to cause clinically significant protein binding interactions with other drugs.
Four metabolites of ciprofloxacin have been identified in human urine and feces. The metabolites have antimicrobial activity, but are less active than unchanged ciprofloxacin. The metabolites are desethyleneciprofloxacin (M1), sulfociprofloxacin (M2), oxociprofloxacin (M3), and formylciprofloxacin (M4), which account for approximately 11% of the total dose.
The plasma elimination half-life of ciprofloxacin in healthy volunteers following a Proquin XR 500 mg dose was approximately 4.5 hours. Following a 500 mg oral dose of Proquin XR, 26.9% was excreted in the urine over 24 hours as unchanged drug for both formulations.
Following administration of a single 500 mg dose of Proquin XR, approximately 41% of the oral dose was excreted into the urine over 96 hours as unchanged drug and metabolites. The urinary excretion of ciprofloxacin was virtually complete within 24 hours after dosing. Urinary excretion is a main route of elimination of ciprofloxacin and its urinary concentrations relative to the MICs of the bacterial species may be important to understanding the efficacy of ciprofloxacin for the treatment of urinary tract infections. The mean urinary ciprofloxacin concentration after dosing with Proquin XR 500 mg qd and CIPRO 250 mg bid are shown in the following table:
| Treatment | Day | Mean (%CV) urinary ciprofloxacin concentration over 24 hours (mcg/mL) |
|---|---|---|
| Proquin XR 500 mg once daily | 1 | 71 (41) |
| 3 | 67 (28) | |
| CIPRO 250 mg twice daily | 1 | 79 (32) |
| 3 | 75 (24) |
The renal clearance of ciprofloxacin following administration of Proquin XR, which is approximately 304-383 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.
Approximately 43% of the oral dose of Proquin XR is recovered from the feces as unchanged drug and metabolites within 7 days after dosing. This may arise from either biliary clearance or transintestinal elimination.
Antacids: The interaction of Proquin XR (administered as a single 1000 mg [2 x 500 mg] dose) and magnesium/aluminum-containing antacids (900 mg aluminum hydroxide and 600 mg magnesium hydroxide administered as a single oral dose) was evaluated in healthy volunteers. When Proquin XR was given 2 hours after antacids and 6 hours before antacids, the Cmax values were similar to those when Proquin XR was given alone and AUC values were reduced by approximately 10%. When Proquin XR was given 4 hours before antacids, Cmax was reduced by approximately 11% and AUC was reduced by approximately 22%. Thus, to minimize the effect of antacids on the absorption of ciprofloxacin, Proquin XR should be given either 2 hours after or at least 4 hours before antacids (see PRECAUTIONS: Drug Interactions, and Information for Patients).
Caffeine: Some quinolones, including ciprofloxacin also decrease caffeine clearance and inhibit the formation of paraxanthine after caffeine administration. (See PRECAUTIONS: Drug Interactions)
Calcium-containing beverages: Concomitant administration of ciprofloxacin with milk products or calcium-fortified juices alone should be avoided since decreased absorption is possible. (See PRECAUTIONS: Drug Interactions and Information for Patients, and DOSAGE AND ADMINISTRATION)
Histamine H2-receptor antagonists: Histamine H2-receptor antagonists appear to have no significant effect on the bioavailability of ciprofloxacin.
Metronidazole: The serum concentrations of ciprofloxacin and metronidazole were not altered when these two drugs were given concomitantly.
Multivalent cation-containing products: Concomitant administration of ciprofloxacin with sucralfate, VIDEX® (didanosine) chewable/buffered tablets, metal cations such as iron and calcium, and multivitamin preparations with zinc should be avoided. (See PRECAUTIONS: Drug Interactions and Information for Patients)
Omeprazole: When Proquin XR was administered following a meal as a single 1000 mg dose (2 x 500 mg), 2 hours after the third dose of omeprazole (given 40 mg once daily for three days) to 27 healthy volunteers, the mean AUC and Cmax of ciprofloxacin were bioequivalent to the mean AUC and Cmax values when Proquin XR was administered alone. Omeprazole should be taken as directed and Proquin XR should be taken with a main meal of the day, preferably the evening meal. (See PRECAUTIONS: Drug Interactions and Information for Patients)
Probenecid: Co-administration of probenecid with fluoroquinolones results in a reduction in the renal clearance and an increase in their concentrations in the systemic circulation.
Theophylline: Previous studies with quinolones, including ciprofloxacin, have shown that concomitant administration of these drugs with theophylline decreases the clearance of theophylline resulting in elevated serum theophylline levels and increased risk of a patient developing central nervous system (CNS) or other adverse reactions. (See WARNINGS, PRECAUTIONS: Drug Interactions)
Warfarin: Ciprofloxacin and other quinolones have been reported to enhance the effects of the oral anticoagulant, warfarin, or its derivatives. When these products are administered concomitantly, prothrombin time or other suitable coagulation tests should be closely monitored. The co-administration of single doses of Proquin XR and Coumadin® (7.5 mg) did not result in significant changes in the pharmacokinetics of ciprofloxacin nor did it significantly affect the pharmacodynamics of S-warfarin and R-warfarin. Although the Cmax and AUC of the two warfarin enantiomers and the elimination half-life of S-warfarin were not significantly altered by ciprofloxacin co-administration, the half-life of R-warfarin was statistically significantly prolonged (P=0.029). (See PRECAUTIONS: Drug Interactions)
Elderly: When a single 500 mg dose of Proquin XR was administered to elderly subjects (>65 years) Cmax and AUC values were increased by approximately 24% and 20% respectively, compared to younger subjects from a reference study. This can be at least partially attributed to decreased renal clearance in the elderly. However, in elderly subjects, the percentage of the ciprofloxacin dose excreted in the urine was 11% lower as compared to younger subjects. The elimination half-life was not significantly prolonged in elderly subjects (4.9 hours) compared to healthy young subjects (4.5 hours). These differences are not considered clinically significant. (See PRECAUTIONS: Geriatric Use)
Renal Impairment: After receiving a single dose of Proquin XR 500 mg, the ciprofloxacin AUC0-24h in subjects with mild renal impairment (CLcr = 51-80 mL/min; n=10) and moderate renal impairment (CLcr = 30-50 mL/min; n=10) were 42% and 54% greater, respectively, compared to subjects with normal renal function (CLcr >80 mL/min; n=10). The elimination half-life of ciprofloxacin in patients with mild and moderate renal impairment was approximately 1.7 times longer as compared to the control group (7.8-7.5 hours versus 4.5 hours). In patients with end-stage renal disease (CLcr <10 mL/min), the half-life of ciprofloxacin is approximately doubled compared to subjects with normal renal function. No dose adjustment of Proquin XR is required for patients with uUTI and mild to moderate renal impairment. The efficacy of Proquin XR has not been studied in patients with severe renal impairment. (See DOSAGE AND ADMINISTRATION)
Altered Liver Function: In studies in patients with stable chronic cirrhosis, no significant changes in ciprofloxacin pharmacokinetics have been observed. The pharmacokinetics of ciprofloxacin in patients with acute hepatic insufficiency, however, has not been fully elucidated. (See DOSAGE AND ADMINISTRATION)
Pediatrics: The pharmacokinetics of Proquin XR have not been studied in pediatric populations.
Ciprofloxacin has in vitro activity against a wide range of gram-negative and gram-positive organisms. The bactericidal action of ciprofloxacin results from inhibition of topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases) which are required for bacterial DNA replication, transcription, repair and recombination. The mechanism of action of quinolones, including ciprofloxacin, is different from that of other antimicrobial agents such as beta-lactams, macrolides, tetracyclines, or aminoglycosides; therefore, organisms resistant to these drugs may be susceptible to ciprofloxacin. There is no known cross-resistance between ciprofloxacin and other classes of antimicrobials. Resistance to ciprofloxacin in vitro develops slowly (multiple step mutation). Resistance to ciprofloxacin due to spontaneous mutations occurs at a general frequency of between <10-9 to 1x10-6.
Ciprofloxacin is less active when tested at acidic pH. The inoculum size has little effect when tested in vitro. The minimal bactericidal concentration (MBC) generally does not exceed the MIC by more than a factor of 2.
Ciprofloxacin has been shown to be active against most strains of the following organisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.
Aerobic gram-negative microorganisms
Escherichia coli
Klebsiella pneumoniae
The following in vitro data are available, but their clinical significance is unknown.
Ciprofloxacin exhibits in vitro MICs of 1 mcg/mL or less against most (>90%) strains of the following microorganisms; however, the safety and effectiveness of Proquin XR in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.
Aerobic gram-negative microorganisms
Proteus mirabilis
Interpretive criteria for urinary isolates have not been established for Proquin XR. Interpretive criteria established based on systemic drug levels may not be appropriate for uncomplicated urinary tract infections.
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 procedure. Standardized procedures are based on a dilution method1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of ciprofloxacin powder. The MIC values should be interpreted according to the following criteria:
For testing Enterobacteriaceae:
| MIC (mcg/mL) | Interpretation |
| ≤ 1 | Susceptible (S) |
| 2 | Intermediate (I) |
| ≥ 4 | Resistant (R) |
A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentration 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 concentration usually achievable; other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard ciprofloxacin powder should provide the following MIC values:
| Microorganism | MIC Range (mcg/mL) | |
| Escherichia coli | ATCC 25922 | 0.004-0.015 |
| Staphylococcus aureus | ATCC 29213 | 0.12-0.5 |
Diffusion Techniques: Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 5-mcg ciprofloxacin to test the susceptibility of microorganisms to ciprofloxacin.
Reports from the laboratory providing results of the standard single-disk susceptibility test with a 5-mcg ciprofloxacin disk should be interpreted according to the following criteria:
For testing Enterobacteriaceae:
| Zone Diameter (mm) | Interpretation |
| ≥ 21 | Susceptible (S) |
| 16-20 | Intermediate (I) |
| ≤ 15 | Resistant (R) |
Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for ciprofloxacin.
As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 5-mcg ciprofloxacin disk should provide the following zone diameters in these laboratory quality control strains:
| Microorganism | Zone Diameter (mm) | |
| Escherichia coli | ATCC 25922 | 30-40 |
| Staphylococcus aureus | ATCC 25923 | 22-30 |
Proquin XR is indicated only for the treatment of uncomplicated urinary tract infections (acute cystitis) caused by susceptible strains of the designated microorganisms listed below. Proquin XR is not interchangeable with other ciprofloxacin extended-release or immediate release oral formulations. See DOSAGE AND ADMINISTRATION for specific recommendations.
Uncomplicated urinary tract infections (acute cystitis) caused by Escherichia coli and Klebsiella pneumoniae.
THE SAFETY AND EFFICACY OF Proquin XR IN TREATING PYELONEPHRITIS, COMPLICATED URINARY TRACT INFECTIONS, AND INFECTIONS OTHER THAN UNCOMPLICATED URINARY TRACT INFECTIONS HAVE NOT BEEN DEMONSTRATED. Alternative therapy should be considered for patients who remain symptomatic or develop fever and back pain while on treatment with Proquin XR.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Proquin XR and other antibacterial drugs, Proquin XR should only be used to treat uncomplicated urinary tract infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and sensitivity 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.
Proquin XR is contraindicated in persons with a history of hypersensitivity to ciprofloxacin or any member of the quinolone class of antimicrobial agents, or any of the product components.
Tendinopathy and Tendon Rupture: Fluoroquinolones, including Proquin XR, 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. Proquin XR 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.
THE SAFETY AND EFFECTIVENESS OF Proquin XR IN PEDIATRIC PATIENTS AND ADOLESCENTS (LESS THAN 18 YEARS OF AGE), PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED. (See PRECAUTIONS: Pediatric Use, Pregnancy, and Nursing Mothers subsections)
Ciprofloxacin, as with other members of the quinolone class, causes arthropathy and/or chondroplasia in immature dogs. Related quinolone-class drugs also produce erosions of cartilage of weight-bearing joints and other signs of arthropathy in immature animals of various species. The relevance of these findings to the clinical use of ciprofloxacin is unknown. (See ANIMAL PHARMACOLOGY)
Central Nervous System: Convulsions, increased intracranial pressure, and toxic psychosis have been reported in patients receiving quinolones, including ciprofloxacin. Ciprofloxacin may also cause CNS events including: dizziness, confusion, tremors, hallucinations, depression, and, rarely, suicidal thoughts or acts. The 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 quinolones, 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)
Theophylline: SERIOUS AND FATAL REACTIONS HAVE BEEN REPORTED IN PATIENTS RECEIVING CONCURRENT ADMINISTRATION OF FLUOROQUINOLONES, INCLUDING CIPROFLOXACIN, AND THEOPHYLLINE. These reactions have included cardiac arrest, seizure, status epilepticus, and respiratory failure. Although similar adverse effects have been reported in patients receiving theophylline alone, the possibility that these reactions may be potentiated by Proquin XR cannot be eliminated. If concomitant use cannot be avoided, serum levels of theophylline should be monitored and dosage adjustments made as appropriate.
Hypersensitivity 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:
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).
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Proquin XR, 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 represent with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two 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, dyesthesias, 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.
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 CNS events, including nervousness, agitation, insomnia, anxiety, nightmares, or paranoia. (See WARNINGS)
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 quinolone antibiotics 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 and ADVERSE REACTIONS/ Post-Marketing Adverse Events).
Prescribing Proquin XR in the absence of a strongly suspected bacterial infection is unlikely to benefit the patient and increases the risk of the development of drug-resistant bacteria.
Patients should be advised:
Caffeine: 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.
Cyclosporine: Some quinolones, including ciprofloxacin, have been associated with transient elevations in serum creatinine in patients receiving cyclosporine concomitantly.
Glyburide: The concomitant administration of ciprofloxacin with the sulfonylurea glyburide has, on rare occasions, resulted in severe hypoglycemia.
Histamine H2-receptor antagonists: Histamine H2-receptor antagonists appear to have no significant effect on the bioavailability of ciprofloxacin.
Methotrexate: Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin, potentially leading to increased plasma levels of methotrexate. This might increase the risk of methotrexate toxic reactions. Therefore, patients under methotrexate therapy should be carefully monitored when concomitant ciprofloxacin therapy is indicated.
Multivalent cation-containing products: Concurrent administration of a quinolone, including ciprofloxacin, with multivalent cation-containing products such as magnesium or aluminum antacids, sucralfate, VIDEX® chewable/buffered tablets or pediatric powder, or products containing calcium, iron, or zinc may substantially decrease the absorption of ciprofloxacin, resulting in serum and urine levels considerably lower than desired. Proquin XR should be administered at least 4 hours before or 2 hours after these products. This time window is different than for other oral formulations of ciprofloxacin, which are usually administered 2 hours before or 6 hours after antacids. (See CLINICAL PHARMACOLOGY: Drug Interactions, PRECAUTIONS: Information for Patients, and DOSAGE AND ADMINISTRATION)
Non-steroidal anti-inflammatory drugs (but not aspirin): These drugs in combination with very high doses of quinolones have been shown to provoke convulsions in pre-clinical studies.
Omeprazole: The rate and extent of absorption of ciprofloxacin was bioequivalent when Proquin XR was given alone or when Proquin XR was given 2 hours after omeprazole at the dose that maximally suppresses gastric acid secretion. Omeprazole should be taken as directed and Proquin XR should be taken with a main meal of the day, preferably the evening meal. (See CLINICAL PHARMACOLOGY: Drug Interactions and Information for Patients).
Phenytoin: Altered serum levels of phenytoin (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin.
Probenecid: Probenecid interferes with renal tubular secretion of ciprofloxacin and produces an increase in the level of ciprofloxacin in serum.
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.
Warfarin: Quinolones have been reported to enhance the effects of the oral anticoagulant warfarin or its derivatives. When these products are administered concomitantly, prothrombin time or other suitable coagulation tests should be monitored.
Rodent carcinogenicity studies were not required. Two in vitro mutagenicity tests were conducted with ciprofloxacin:
In addition to the in vitro genotoxicity assays, an in vivo rat micronucleus study with ciprofloxacin was negative.
Fertility studies performed with male and female rats at oral doses of ciprofloxacin up to 600 mg/kg/day (approximately 10-fold the recommended 500 mg therapeutic dose based upon body surface area) revealed no evidence of impairment.
There are no adequate and well-controlled studies of Proquin XR in pregnant women. An expert review of published data on experiences with ciprofloxacin use during pregnancy by TERIS - the Teratogen Information System - concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (quantity and quality of data = fair), but the data are insufficient to state that there is no risk.
A controlled prospective observational study followed 200 women exposed to fluoroquinolones (52.5% exposed to ciprofloxacin and 68% first trimester exposures) during gestation. In utero exposure to fluoroquinolones during embryogenesis was not associated with increased risk of major malformations. The reported rates of major congenital malformations were 2.2% for the fluoroquinolone group and 2.6% for the control group (background incidence of major malformations is 1-5%). Rates of spontaneous abortions, prematurity and low birth weight did not differ between the groups and there were no clinically significant musculoskeletal dysfunctions up to one year of age in the ciprofloxacin exposed children.
Another prospective follow up study reported on 549 pregnancies with fluoroquinolone exposure (93% first trimester exposures). There were 70 ciprofloxacin exposures, all within the first trimester. The malformation rates among live-born babies exposed to ciprofloxacin and to fluoroquinolones overall were both within background incidence ranges. No specific patterns of congenital abnormalities were found. The study did not reveal any clear adverse reactions due to in utero exposure to ciprofloxacin.
No differences in the rates of prematurity, spontaneous abortions, or birth weight were seen in women exposed to ciprofloxacin during pregnancy. However, these small postmarketing epidemiology studies, of which most experience is from short term first semester exposure, are insufficient to evaluate the risk for less common defects or to permit reliable and definitive conclusions regarding the safety of ciprofloxacin in pregnant women and their developing fetuses. Ciprofloxacin should not be used during pregnancy unless the potential benefit justifies the potential risk to both fetus and mother (see WARNINGS).
Embryo/fetal developmental toxicity studies were conducted in pregnant rats and rabbits using oral doses up to 600 mg/kg/day in rats and 30 mg/kg/day in rabbits. Fetal development (skeletal variation) was affected in rats at the maternally toxic dose of 600 mg/kg/day (approximately 1.8-fold the recommended 500 mg therapeutic dose based upon plasma AUC measure of systemic exposure). The maternally toxic 30 mg/kg/day dose to pregnant rabbits resulted in abortions and body weight gain depression; embryo/fetal lethality and skeletal developmental effects were observed at this dose level (approximately 1.2-fold the recommended therapeutic dose based upon body surface area). The 10 mg/kg/day dose level, although maternally toxic, did not induce embryo/fetal developmental effects. A peri/postnatal developmental toxicity study with pregnant/lactating female rats exhibited no developmental effects to the F1 pups at the highest dose level of 600 mg/kg/day; the 300 and 600 mg/kg/day dose levels were maternally toxic to the pregnant dams based upon slight body weight gain reduction. No evidence of compound-related fetal malformation was observed in any of the reproductive toxicity studies.
Ciprofloxacin is excreted in human milk. The amount of ciprofloxacin absorbed by the nursing infant is unknown. Because of the potential for serious adverse reactions in infants nursing from mothers taking ciprofloxacin, a decision should be made whether to discontinue nursing or to discontinue ciprofloxacin taking into account the importance of the drug to the mother.
The safety and effectiveness of Proquin XR in pediatric patients and adolescents less than 18 years of age have not been established. Quinolones, including ciprofloxacin, cause arthropathy in juvenile animals. (See WARNINGS)
Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as Proquin XR. This risk is further increased in patients receiving concomitant corticosteroid therapy. Tendinitis or tendon rupture can involve the Achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported. Caution should be used when prescribing Proquin XR to elderly patients especially those on corticosteroids. Patients should be informed of this potential side effect and advised to discontinue Proquin XR and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur (See Boxed Warning, WARNINGS, and ADVERSE REACTIONS/ Post-Marketing Adverse Event Reports).
Clinical experience with Proquin XR did not include sufficient number of subjects 65 years of age or older to determine whether they respond differently than younger subjects. Reported clinical experience with other formulations of ciprofloxacin has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals on any drug therapy cannot be ruled out. Ciprofloxacin is substantially excreted by the kidney and the risk of adverse reactions may be greater in patients with impaired renal function. No alteration of dosage is necessary for patients greater than 65 years of age with normal renal function. (See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION)
In general, elderly patients may be more susceptible to drug-associated effects on the QT interval. Therefore, precaution should be taken when using Proquin XR with concomitant drugs that can result in prolongation of the QT interval (e.g. class IA or class III antiarrhythmics) or in patients with risk factors for torsades de pointes (e.g., known QT prolongation, uncorrected hypokalemia).
Two clinical trials enrolled 1,095 patients, of whom 547 patients received Proquin XR 500 mg once daily and 538 patients received CIPRO 250 mg twice daily for 3 days. The patients were followed for approximately 5 weeks after the end of study drug dosing. Most adverse events reported were described as mild to moderate in severity and required no treatment. Proquin XR was discontinued due to adverse reactions thought to be drug-related in 0.5% of patients.
The incidence of all adverse events (regardless of relationship to study drug) reported for at least 2% of patients treated with Proquin XR during the entire 5-week study period was as follows: fungal infection (2.6%), nasopharyngitis (2.6%), headache (2.4%), and micturition urgency (2.0%).
The incidence of adverse events (regardless of relationship to study drug) reported for at least 1% of patients treated with Proquin XR during study drug treatment and up to 3 days after study drug was headache (1.5%).
The incidence of adverse events, judged by investigators to be at least possibly drug-related, occurring any time during the study in at least 1% of Proquin XR-treated patients was fungal infection (1.6%).
Additional uncommon events, judged by the investigator to be at least possibly drug-related, occurring at any time during the study in less than 1% of Proquin XR-treated patients we
