Promacta

Generic Name: eltrombopag (Oral route)

el-TROM-boe-pag

Oral route(Tablet)

Eltrombopag may cause hepatotoxicity. Measure serum ALT, AST, and bilirubin before initiating eltrombopag, every 2 weeks during dose adjustment and monthly after dose is stable. Perform fractionation for elevated bilirubin. Repeat testing for abnormal serum liver values within 3 to 5 days. If abnormalities are confirmed, monitor serum liver tests weekly until abnormalities resolve, stabilize, or return to baseline levels. Discontinue eltrombopag if ALT levels increase to 3 times the upper ULN or greater and are: progressive, persistent for 4 weeks or more, accompanied by increased direct bilirubin, or accompanied by symptoms of liver injury or evidence for hepatic decompensation .

Commonly used brand name(s)

In the U.S.

• Promacta

Available Dosage Forms:

• Tablet

Therapeutic Class: Hematopoietic

Uses For Promacta

Eltrombopag is used to treat thrombocytopenia (low platelets in the blood) in patients with a blood disorder called chronic idiopathic thrombocytopenic purpura (ITP). This medicine is used after a splenectomy (surgery to remove the spleen) and other medicines, such as steroids or immunoglobulin, have not worked well enough. Platelets help clot the blood, so a person with thrombocytopenia may have bleeding problems. Eltrombopag works by stimulating the bone marrow to produce more platelets.

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

Before Using Promacta

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

Appropriate studies have not been performed on the relationship of age to the effects of eltrombopag in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of eltrombopag in the elderly. However, elderly patients are more likely to have age-related heart, kidney, or liver problems, which may require caution or an adjustment in the dose for patients receiving eltrombopag.

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 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.

• Aluminum


• Calcium


• Ciprofloxacin


• Fluvoxamine


• Gemfibrozil


• Iron


• Magnesium


• Mexiletine


• Propafenone


• Selenium


• Trimethoprim


• Zileuton


• Zinc

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.

• Atorvastatin


• Doxorubicin


• Fluvastatin


• Levothyroxine


• Methotrexate


• Nateglinide


• Penicillin G


• Pravastatin


• Repaglinide


• Rifampin


• Rosuvastatin

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. 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 is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Calcium Rich Food


• Dairy Food

Other Medical Problems

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:

• Antiphospholipid syndrome or


• ATIII deficiency or


• Factor V Leiden (blood clotting disorder) or


• Liver disease, severe—Use with caution. May increase risk for blood clotting problems (e.g., thromboembolism).

• Bleeding problems or


• Blood cancer or


• Blood clots, history of or


• Bone marrow problems (e.g., myelodysplastic syndrome) or


• Cataracts, history of—Use with caution. May make these conditions worse.

• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper Use of Promacta

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.

Tell your doctor if you have Asian relatives, such as Filipino, Chinese, Japanese, Korean, or Taiwanese. You may need a lower dose of this medicine.

This medicine comes with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

It is best to take this medicine on an empty stomach, or at least 1 hour before or 2 hours after a meal.

If you are taking antacids, multivitamins, or other products (such as dairy products or juices) that contain aluminum, calcium, iron, magnesium, selenium, or zinc, take these at least 4 hours before or 4 hours after eltrombopag.

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 oral dosage form (tablets):
  
  • For thrombocytopenia:
    
    • Adults—At first, 50 milligrams (mg) once a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 75 mg per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

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.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Promacta

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests will be needed while you are using this medicine.

Eltrombopag may cause serious liver problems. Stop taking this medicine and check with your doctor right away if you start having nausea or vomiting, dark urine, light-colored stools, right upper stomach pain, unusual tiredness, or yellow eyes or skin while you are using this medicine.

Using this medicine for a long time may cause changes in your bone marrow. These changes may lead to a serious condition called bone marrow fibrosis, where your body produces less blood cells. Your doctor will check for this unwanted effect.

Blood clotting problems may occur while you are using this medicine. Check with your doctor right away if you have pain, swelling, or tenderness in your leg, or shortness of breath and pain in your chest.

Do not stop taking this medicine without checking first with your doctor. Your doctor will check your platelet levels and progress when you stop taking the medicine.

This medicine may cause cataracts or make them worse. Check with your doctor right away if you have blurred vision, difficulty in reading, or any other change in vision while you are taking this medicine. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Promacta 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:

More common

• Body aches or pain


• chills


• cough


• difficulty with breathing


• ear congestion


• fever


• headache


• loss of voice


• nasal congestion


• runny nose


• sneezing


• sore throat


• unusual tiredness or weakness


• yellow eyes or skin

Less common

• Black, tarry stools


• bladder pain


• bleeding gums


• blindness


• blood in the urine or stools


• bloody eye


• blurred vision


• bruising


• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings


• cloudy urine


• congestion


• decreased vision


• diarrhea


• difficult, burning, or painful urination


• dryness or soreness of the throat


• frequent urge to urinate


• general feeling of discomfort or illness


• hoarseness


• joint pain


• large, flat, or blue or purplish patches in the skin


• longer or heavier menstrual periods


• loss of appetite


• lower back or side pain


• muscle aches and pains


• nausea


• pinpoint red spots on the skin


• redness of the eye


• shivering


• sweating


• tender, swollen glands in the neck


• trouble with sleeping


• trouble with swallowing


• unusual bleeding or bruising


• voice changes


• vomiting

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

• Acid or sour stomach


• back pain


• belching


• bone pain


• difficulty with moving


• dry mouth


• hair loss or thinning of the hair


• heartburn


• indigestion


• muscle aching or cramping


• muscle pains or stiffness


• rash


• stomach discomfort, upset, or pain


• swollen joints

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: Promacta 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.

More Promacta resources

• Promacta Side Effects (in more detail)
• Promacta Use in Pregnancy & Breastfeeding
• Promacta Drug Interactions
• Promacta Support Group
• 1 Review for Promacta - Add your own review/rating

• Promacta Prescribing Information (FDA)


• Promacta Consumer Overview


• Promacta Monograph (AHFS DI)


• Promacta MedFacts Consumer Leaflet (Wolters Kluwer)


• Eltrombopag Professional Patient Advice (Wolters Kluwer)

Compare Promacta with other medications

• Idiopathic Thrombocytopenic Purpura
• Thrombocytopenia Idiopathic

Stilnoct 5mg, Stilnoct 10mg

1. Name Of The Medicinal Product

Stilnoct 5mg

Stilnoct 10mg

2. Qualitative And Quantitative Composition

Stilnoct 5mg Tablets: Round white film coated tablets containing 5mg zolpidem tartrate.

Stilnoct 10mg Tablets: White to off-white film-coated oblong tablet, scored and engraved SN 10 on one side, containing 10mg zolpidem tartrate.

3. Pharmaceutical Form

Coated tablets for oral administration.

4. Clinical Particulars

4.1 Therapeutic Indications

The short-term treatment of insomnia in situations where the insomnia is debilitating or is causing severe distress for the patient.

4.2 Posology And Method Of Administration

Route of administration: Oral

Zolpidem tartrate acts rapidly and therefore should be taken immediately before retiring, or in bed.

The recommended daily dose for adults is 10 mg.

The duration of treatment should usually vary from a few days to two weeks with a maximum of four weeks including tapering off where clinically appropriate.

As with all hypnotics, long-term use is not recommended and a course of treatment should not exceed four weeks.

Special Populations

Children

Safety and effectiveness of zolpidem in paediatric patients under the age of 18 years have not been established. Therefore, zolpidem should not be prescribed in this population (see Section 4.4 Special warnings and precautions for use).

Elderly

Elderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate therefore a 5mg dose is recommended. These recommended doses should not be exceeded.

Hepatic impairment

As clearance and metabolism of zolpidem tartrate is reduced in hepatic impairment, dosage should begin at 5mg in these patients with particular caution being exercised in elderly patients. In adults (under 65 years) dosage may be increased to 10mg only where the clinical response is inadequate and the drug is well tolerated.

4.3 Contraindications

Zolpidem tartrate is contraindicated in patients with a hypersensitivity to zolpidem tartrate or any of the inactive ingredients, obstructive sleep apnoea, myasthenia gravis, severe hepatic insufficiency, acute and/or severe respiratory depression. In the absence of data, zolpidem tartrate should not be prescribed for children or patients with psychotic illness.

4.4 Special Warnings And Precautions For Use

Respiratory Insufficiency

As hypnotics have the capacity to depress respiratory drive, precautions should be observed if zolpidem is prescribed to patients with compromised respiratory function.

Hepatic Insufficiency: See section 4.2.

The cause of insomnia should be identified wherever possible and the underlying factors treated before a hypnotic is prescribed. The failure of insomnia to remit after a 7-14 day course of treatment may indicate the presence of a primary psychiatric or physical disorder, and the patient should be carefully re-evaluated at regular intervals.

Elderly: See dose recommendations.

Paediatric Patients:

Safety and effectiveness of zolpidem have not been established in patients below the age of 18 years. In an 8-week study in paediatric patients (aged 6-17 years) with insomnia associated with attention-deficit/hyperactivity disorder (ADHD), psychiatric and nervous system disorders comprised the most frequent treatment emergent adverse events observed with zolpidem versus placebo and included dizziness (23.5% vs. 1.5%), headache (12.5% vs. 9.2%), and hallucinations (7.4% vs. 0%). (See Section 4.2 Posology and method of administration).

Depression:

As with other sedative/hypnotic drugs, zolpidem tartrate should be administered with caution in patients exhibiting symptoms of depression. Suicidal tendencies may be present therefore the least amount of zolpidem that is feasible should be supplied to these patients to avoid the possibility of intentional overdosage by the patient. Pre-existing depression may be unmasked during use of zolpidem. Since insomnia may be a symptom of depression, the patient should be re-evaluated if insomnia persists.

Use in patients with a history of drug or alcohol abuse: Extreme caution should be exercised when prescribing for patients with a history of drug or alcohol abuse. These patients should be under careful surveillance when receiving zolpidem tartrate or any other hypnotic, since they are at risk of habituation and psychological dependence.

General information relating to effects seen following administration of benzodiazepines and other hypnotic agents which should be taken into account by the prescribing physician are described below.

Tolerance: Some loss of efficacy to the hypnotic effects of short-acting benzodiazepines and benzodiazepine-like agents like zolpidem may develop after repeated use for a few weeks

Dependence

Use of benzodiazepines or benzodiazepine-like agents like zolpidem may lead to the development of physical and psychological dependence. The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a history of psychiatric disorders and/or alcohol or drug abuse.

These patients should be under careful surveillance when receiving hypnotics.

Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headaches or muscle pain, extreme anxiety and tension, restlessness, confusion and irritability. In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures.

Rebound insomnia

A transient syndrome whereby the symptoms that led to treatment with a benzodiazepine or benzodiazepine-like agent recur in an enhanced form, may occur on withdrawal of hypnotic treatment. It may be accompanied by other reactions including mood changes, anxiety and restlessness.

It is important that the patient should be aware of the possibility of rebound phenomena, thereby minimising anxiety over such symptoms should they occur when the medicinal product is discontinued. Since the risk of withdrawal phenomena or rebound has been shown to be greater after abrupt discontinuation of treatment, it is recommended that the dosage is decreased gradually where clinically appropriate.

There are indications that, in the case of benzodiazepines and benzodiazepine-like agents with a short duration of action, withdrawal phenomena can become manifest within the dosage interval, especially when the dosage is high.

Amnesia

Benzodiazepines or benzodiazepine-like agents such as zolpidem may induce anterograde amnesia. The condition occurs most often several hours after ingesting the product and therefore to reduce the risk patients should ensure that they will be able to have an uninterrupted sleep of 7-8 hours.

Other psychiatric and "paradoxical" reactions

Other psychiatric and paradoxical reactions like restlessness, exacerbated insomnia, agitation, irritability, aggression, delusion, anger, nightmares, hallucinations, psychosis, abnormal behaviour and other adverse behavioural effects are known to occur when using benzodiazepines or benzodiazepine-like agents. Should this occur, use of the product should be discontinued. These reactions are more likely to occur in the elderly.

Somnambulism and associated behaviours:

Sleep walking and other associated behaviours such as “sleep driving”, preparing and eating food, making phone calls or having sex, with amnesia for the event, have been reported in patients who had taken zolpidem and were not fully awake. The use of alcohol and other CNS-depressants with zolpidem appears to increase the risk of such behaviours, as does the use of zolpidem at doses exceeding the maximum recommended dose. Discontinuation of zolpidem should be strongly considered for patients who report such behaviours (for example, sleep driving), due to the risk to patients and others (See Section 4.5 Interactions with other medicinal products and other forms of interaction; and Section 4.8 Undesirable effects).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

- Not recommended : Concomitant intake with alcohol.

The sedative effect may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machines.

- Take into account: Combination with CNS depressants.

Enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, antiepileptic drugs, anaesthetics and sedative antihistamines.

Zolpidem tartrate appears to interact with sertraline. This interaction may cause increased drowsiness. Also, isolated cases of visual hallucinations were reported

In the case of narcotic analgesics enhancement of euphoria may also occur leading to an increase in psychological dependence.

CYP450 Inhibitors

Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines and benzodiazepine-like agents.

Zolpidem tartrate is metabolised via several hepatic cytochrome P450 enzymes, the main enzyme being CYP3A4 with the contribution of CYP1A2. The pharmacodynamic effect of zolpidem tartrate is decreased when it is administered with rifampicin (a CYP3A4 inducer).

However when zolpidem tartrate was administered with itraconazole (a CYP3A4 inhibitor) its pharmacokinetics and pharmacodynamics were not significantly modified. The clinical relevance of these results is unknown.

Co-administration of Zolpidem with ketocanazole (200mg twice daily), a potent CYP3A4 inhibitor, prolonged zolpidem elimination half-life, increased total AUC, and decreased apparent oral clearance when compared to zolpidem plus placebo. The total AUC for zolpidem, when co-administered with ketoconazole, increased by a factor of 1.83 when compared with zolpidem alone. A routine dosage adjustment of zolpidem is not considered necessary, but patients should be advised that use of zolpidem with ketoconazole may enhance the sedative effects.

Since CYP3A4 plays an important role in zolpidem tartrate metabolism, possible interactions with drugs that are substrates or inducers of CYP3A4 should be considered.

Other drugs:

When zolpidem tartrate was administered with ranitidine or cimetidine, no significant pharmacokinetic interactions were observed.

4.6 Pregnancy And Lactation

Although animal studies have shown no teratogenic or embryotoxic effects, safety in pregnancy has not been established. As with all drugs zolpidem tartrate should be avoided in pregnancy particularly during the first trimester.

If the product is prescribed to a woman of childbearing potential, she should be warned to contact her physician about stopping the product if she intends to become or suspects that she is pregnant.

If, for compelling medical reasons, zolpidem tartrate is administered during the late phase of pregnancy, or during labour, effects on the neonate, such as hypothermia, hypotonia and moderate respiratory depression, can be expected due to the pharmacological action of the product. Cases of severe neonatal respiratory depression have been reported when zolpidem tartrate was used with other CNS depressants at the end of pregnancy.

Infants born to mothers who took benzodiazepines or benzodiazepine-like agents chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk of developing withdrawal symptoms in the postnatal period.

Small quantities of zolpidem tartrate appear in breast milk. The use of zolpidem tartrate in nursing mothers is therefore not recommended.

4.7 Effects On Ability To Drive And Use Machines

Vehicle drivers and machine operators should be warned that, as with other hypnotics, there may be a possible risk of drowsiness the morning after therapy. In order to minimise this risk a resting period of 7 to 8 hours is recommended between taking zolpidem tartrate and driving.

4.8 Undesirable Effects

The following CIOMS frequency rating is used, when applicable:

Very common

Common

Uncommon

Rare

Very rare < 0.01%

Not known: cannot be estimated based on available data.

There is evidence of a dose-relationship for adverse effects associated with zolpidem tartrate use, particularly for certain CNS and gastrointestinal events. As recommended in section 4.2, they should in theory be less if zolpidem tartrate is taken immediately before retiring, or in bed. They occur most frequently in elderly patients.

Immune system disorders

Not known: angioneurotic oedema

Psychiatric disorders

Common: hallucination, agitation, nightmare

Uncommon: confusional state, irritability

Not known: restlessness, aggression, delusion, anger, psychosis, abnormal behaviour, somnambulism (See Section 4.4), dependence (withdrawal symptoms, or rebound effects may occur after treatment discontinuation), libido disorder

Most of these psychiatric undesirable effects are related to paradoxical reactions

Nervous system disorders:

Common: somnolence, headache, dizziness, exacerbated insomnia, anterograde amnesia: (amnestic effects may be associated with inappropriate behaviour)

Not known: depressed level of consciousness

Eye disorders

Uncommon: diplopia

Gastro-intestinal Disorders

Common: diarrhoea

Hepatobiliary disorders

Not known: Liver enzymes elevated

Skin and subcutaneous tissue disorders

Not known: rash, pruritus, urticaria

Musculoskeletal and connective tissue disorders

Not known: muscular weakness

General disorders and administration site conditions

Common: fatigue

Not known: gait disturbance, drug tolerance, fall (predominantly in elderly patients and when zolpidem was not taken in accordance with prescribing recommendation)

4.9 Overdose

Signs and Symptoms:

In cases of overdose involving zolpidem tartrate alone or with other CNS-depressant agents (including alcohol), impairment of consciousness ranging from somnolence to coma and including fatal outcomes have been reported.

Management:

General symptomatic and supportive measures should be used. If there is no advantage in emptying the stomach, activated charcoal should be given to reduce absorption. Sedating drugs should be withheld even if excitation occurs.

Use of flumazenil may be considered where serious symptoms are observed.

Flumazenil is reported to have an elimination half-life of about 40 to 80 minutes. Patients should be kept under close observation because of this short duration of action; further doses of flumazenil may be necessary. However, flumazenil administration may contribute to the appearance of neurological symptoms (convulsions).

The value of dialysis in the treatment of an overdose has not been determined. Dialysis in patients with renal failure receiving therapeutic doses of zolpidem have demonstrated no reduction in levels of zolpidem.

In the management of overdose with any medicinal product, it should be borne in mind that multiple agents may have been taken.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

(GABA-A receptor modulator selective for omega-1 receptor subtype hypnotic agent).

Zolpidem tartrate is an imidazopyridine which preferentially binds the omega-1 receptor subtype (also known as the benzodiazepine-1 subtype) which corresponds to GABA-A receptors containing the alpha-1 sub-unit, whereas benzodiazepines non-selectively bind both omega-1 and omega-2 subtypes. The modulation of the chloride anion channel via this receptor leads to the specific sedative effects demonstrated by zolpidem tartrate. These effects are reversed by the benzodiazepine antagonist flumazenil.

In animals: The selective binding of zolpidem tartrate to omega-1 receptors may explain the virtual absence at hypnotic doses of myorelaxant and anti-convulsant effects in animals which are normally exhibited by benzodiazepines which are not selective for omega-1 sites.

In man: zolpidem tartrate decreases sleep latency and the number of awakenings, and increases sleep duration and sleep quality. These effects are associated with a characteristic EEG profile, different from that of the benzodiazepines. In studies that measured the percentage of time spent in each sleep stage, zolpidem tartrate has generally been shown to preserve sleep stages. At the recommended dose, zolpidem tartrate has no influence on the paradoxical sleep duration (REM). The preservation of deep sleep (stages 3 and 4 - slow-wave sleep) may be explained by the selective omega-1 binding by zolpidem tartrate. All identified effects of zolpidem tartrate are reversed by the benzodiazepine antagonist flumazenil.

5.2 Pharmacokinetic Properties

Zolpidem tartrate has both a rapid absorption and onset of hypnotic action. Bioavailability is 70% following oral administration and demonstrates linear kinetics in the therapeutic dose range. Peak plasma concentration is reached at between 0.5 and 3 hours.

The elimination half-life is short, with a mean of 2.4 hours (± 0.2 h) and a duration of action of up to 6 hours.

Protein binding amounts to 92.5% ± 0.1%. First pass metabolism by the liver amounts to approximately 35%. Repeated administration has been shown not to modify protein binding indicating a lack of competition between zolpidem tartrate and its metabolites for binding sites.

The distribution volume in adults is 0.54 ± 0.02 L/kg and decreases to 0.34 ± 0.05 L/kg in the very elderly.

All metabolites are pharmacologically inactive and are eliminated in the urine (56%) and in the faeces (37%).

Zolpidem tartrate has been shown in trials to be non-dialysable.

Plasma concentrations in elderly subjects and those with hepatic impairment are increased. In patients with renal insufficiency, whether dialysed or not, there is a moderate reduction in clearance. The other pharmacokinetic parameters are unaffected.

Zolpidem tartrate is metabolised via several hepatic cytochrome P450 enzymes, the main enzyme being CYP3A4 with the contribution of CYP1A2. Since CYP3A4 plays an important role in zolpidem tartrate metabolism, possible interactions with drugs that are substrates or inducers of CYP3A4 should be considered.

5.3 Preclinical Safety Data

No data of therapeutic relevance.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Tablet core:	Lactose monohydrate, Microcrystalline cellulose, Hypromellose, Sodium starch glycollate, Magnesium stearate.
Film coating:	Hypromellose, Titanium dioxide (E171), Macrogol 400 (Stilnoct 10mg only), Polyethylene glycol 400 (Stilnoct 5mg only).

6.2 Incompatibilities

None known

6.3 Shelf Life

Stilnoct 5mg:	3 years
Stilnoct 10mg:	4 years

6.4 Special Precautions For Storage

Stilnoct 5mg:	Store in a dry place below 30°C
Stilnoct 10mg:	No special precautions

6.5 Nature And Contents Of Container

Stilnoct 5mg:	Cartons of 28 tablets in PVC/foil blister strips.
Stilnoct 10mg:	Cartons of 28 tablets in PVC/foil blister strips.

6.6 Special Precautions For Disposal And Other Handling

Please consult the package insert before use. Do not use after the stated expiry date on the carton and blister.

KEEP OUT OF THE REACH OF CHILDREN

7. Marketing Authorisation Holder

sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

8. Marketing Authorisation Number(S)

Stilnoct 5mg: PL 04425/0618

Stilnoct 10mg: PL 04425/0619

9. Date Of First Authorisation/Renewal Of The Authorisation

Stilnoct 5mg: 3rd December 2009

Stilnoct 10mg: 27th January 2009

10. Date Of Revision Of The Text

Stilnoct 5mg: 3^rd December 2009

Stilnoct 10mg 27 October 2009

Legal Category: POM

Liquid Polibar oral and rectal

Generic Name: barium sulfate (oral and rectal) (BER ee um SUL fate)

Brand Names: Anatrast, Bar-Test, Baricon, Baro-Cat, Barosperse, Bear-E-Yum GI, CheeTah, CheeTah Butterscotch, CheeTah Chocolaty-Fudge, CheeTah Orange, CheeTah Raspberry, Digibar 190, E-Z AC, E-Z Disk, E-Z Dose Kit with Polibar Plus, E-Z Paste, E-Z-Cat, E-Z-Cat Dry, E-Z-HD, E-Z-Paque, Enecat, Eneset 2, Enhancer, Entero VU, Entero-H, Entrobar, Esopho-Cat, Intropaste, Liqui-Coat HD, Liquid Barosperse, Liquid E-Z Paque, Liquid Polibar, Liquid Polibar Plus, Maxibar, Medebar Plus, Medebar Super 250, Polibar ACB, Readi-Cat, Readi-Cat 2, Scan C, Sitzmarks, Smoothie Readi-Cat 2, Sol-O-Pake, Tagitol V, Tonojug, Tonopaque, Varibar Honey, Varibar Nectar, Varibar Pudding, Varibar Thin, Varibar Thin Honey, Volumen

What is barium sulfate?

Barium sulfate is in a group of drugs called contrast agents. Barium sulfate works by coating the inside of your esophagus, stomach, or intestines which allows them to be seen more clearly on a CT scan or other radiologic (x-ray) examination.

Barium sulfate is used to help diagnose certain disorders of the esophagus, stomach, or intestines.

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

What is the most important information I should know about barium sulfate?

You should not use this medication if you are allergic to barium sulfate. Tell your doctor if you have ever had an allergic reaction to a contrast agent.

Before you use barium sulfate, tell your doctor if you have any allergies, or if you have asthma, cystic fibrosis, heart disease or high blood pressure, rectal cancer, a colostomy, a blockage in your stomach or intestines, a condition called pseudotumor cerebri, or if you have recently had a rectal biopsy or surgery on your esophagus, stomach, or intestines.

Tell your doctor if you are pregnant or breast-feeding before your medical test.

Carefully follow your doctor's instructions about what to eat or drink within the 24-hour period before your test.

Serious side effects of barium sulfate may include severe stomach pain, sweating, ringing in your ears, pale skin, weakness, or severe cramping, diarrhea, or constipation

What should I discuss with my health care provider before using barium sulfate?

You should not use barium sulfate if you are allergic to it. Tell your doctor if you have ever had an allergic reaction to a contrast agent.

To make sure you can safely use barium sulfate, tell your doctor if you have any of these other conditions:

• 
  

  asthma, eczema, or allergies;

  
  


• 
  

  a blockage in your stomach or intestines;

  
  


• 
  

  cystic fibrosis;

  
  


• 
  

  a colostomy;

  
  


• 
  

  rectal cancer;

  
  


• 
  

  heart disease or high blood pressure;

  
  


• 
  

  Hirschsprung's disease (a disorder of the intestines);

  
  


• 
  

  a condition called pseudotumor cerebri (high pressure inside the skull that may cause headaches, vision loss, or other symptoms);

  
  


• 
  

  a recent history of surgery on your esophagus, stomach, or intestines;

  
  


• 
  

  a history of perforation (a hole or tear) in your esophagus, stomach, or intestines;

  
  


• 
  

  if you have recently had a rectal biopsy;

  
  


• 
  

  if you have ever choked on food by accidentally inhaling it into your lungs;

  
  


• 
  

  if you are allergic to simethicone (Gas-X, Phazyme, and others); or

  
  


• 
  

  if you are allergic to latex rubber.

  
  

It is not known whether barium sulfate will harm an unborn baby, but the radiation used in x-rays and CT scans may be harmful. Before your medical test, tell your doctor if you are pregnant. Barium sulfate may pass into breast milk and could harm a nursing baby. Before your medical test, tell your doctor if you are breast-feeding a baby.

How should I use barium sulfate?

Use this medication exactly as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended.

Barium sulfate comes in tablets, paste, cream, or liquid forms.

In some cases, barium sulfate is taken by mouth. The liquid form may also be used as a rectal enema.

You may need to begin using this medication at home a day before your medical test. Follow your doctor's instructions about how much of the medication to use and how often.

If you are receiving barium sulfate as a rectal enema, a healthcare professional will give you the medication at the clinic or hospital where your testing will take place.

Do not crush, chew, or break a barium sulfate tablet. Swallow the pill whole.

Dissolve the barium sulfate powder in a small amount of water. Stir this mixture and drink all of it right away. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.

If you receive the medication as a liquid to take by mouth, shake the liquid well just before you measure a dose. To be sure you get the correct dose, measure the liquid with a marked measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Carefully follow your doctor's instructions about what to eat or drink within the 24-hour period before your test.

Store at room temperature away from heat and moisture. Keep the bottle tightly closed when not in use.

What happens if I miss a dose?

If you are using barium sulfate at home, call your doctor for instructions if you miss a 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 severe stomach pain, ongoing diarrhea, confusion, or weakness.

What should I avoid before or after using barium sulfate?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Barium sulfate 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 stomach pain;

  
  


• 
  

  severe cramping, diarrhea, or constipation;

  
  


• 
  

  sweating;

  
  


• 
  

  ringing in your ears;

  
  


• 
  

  confusion, fast heart rate; or

  
  


• 
  

  pale skin, weakness.

  
  

Less serious side effects may include:

• 
  

  mild stomach cramps;

  
  


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  nausea, vomiting;

  
  


• 
  

  loose stools or mild constipation.

  
  

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 barium sulfate?

There may be other drugs that can interact with barium sulfate. 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.

More Liquid Polibar resources

• Liquid Polibar Side Effects (in more detail)
• Liquid Polibar Use in Pregnancy & Breastfeeding
• Liquid Polibar Support Group
• 0 Reviews for Liquid Polibar - Add your own review/rating

Compare Liquid Polibar with other medications

• Computed Tomography

Where can I get more information?

• Your doctor or pharmacist can provide more information about barium sulfate.

See also: Liquid Polibar side effects (in more detail)

miconazole vaginal

Generic Name: miconazole vaginal (my CAW nah zole)

Brand Names: M-Zole Dual Pack, Micon 7, Monistat 3, Monistat 5, Monistat 7

What is miconazole vaginal?

Miconazole is an antifungal medication. It prevents fungus from growing.

Miconazole vaginal is used to treat vaginal candida (yeast) infections.

Miconazole vaginal may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about miconazole vaginal?

Use this medication for the full amount of time prescribed by your doctor or recommended in the package even if you begin to feel better. The symptoms may improve before the infection is completely healed.

Avoid wearing tight-fitting, synthetic clothing (e.g., panty hose) that does not allow air circulation. Wear loose-fitting clothing made of cotton and other natural fibers until the infection is healed.

Avoid getting this medication in the eyes, nose, or mouth.

What should I discuss with my healthcare provider before using miconazole vaginal?

If this is the first time that you have ever had symptoms of a vaginal yeast infection, consult your doctor before using this medication.

Do not use miconazole vaginal if you have ever had an allergic reaction to it.

Before using miconazole vaginal, talk to your doctor if you have

• 
  

  a fever,

  
  


• 
  

  abdominal pain,

  
  


• 
  

  foul-smelling discharge,

  
  


• 
  

  diabetes, or

  
  


• 
  

  HIV or AIDS.

  
  

You may not be able to use miconazole vaginal, or you may require special monitoring during treatment if you have any of the conditions listed above.

Do not use miconazole vaginal without first talking to your doctor if you are pregnant. Do not use miconazole vaginal without first talking to your doctor if you are breast-feeding a baby.

How should I use miconazole vaginal?

Use miconazole vaginal exactly as directed by your doctor or follow the directions that accompany the package. If you do not understand these instructions, ask your pharmacist, nurse, or doctor to explain them to you.

Wash your hands before and after using the medication.

Insert the tablet, suppository, or cream into the vagina using the applicator as directed.

Use this medication for the full amount of time prescribed by your doctor or recommended in the package even if you begin to feel better. The symptoms may improve before the infection is completely healed.

Use this medication continuously, even during your menstrual period.

You can use a sanitary napkin to prevent the medication from staining your clothing but do not use a tampon.

If the infection does not clear up after you have finished one course of therapy, or if it appears to get worse, see your doctor. You may have another type of infection.

Avoid getting this medication in the eyes, nose, or mouth. Store miconazole vaginal at room temperature away from moisture and heat.

What happens if I miss a dose?

Apply the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the dose you missed and apply only the next regularly scheduled dose. Do not use a double dose of this medication.

What happens if I overdose?

An overdose of miconazole vaginal is unlikely. If you do suspect that a much larger than normal dose has been used or that miconazole vaginal has been ingested, contact an emergency room or a poison control center.

What should I avoid while using miconazole vaginal?

Avoid wearing tight-fitting, synthetic clothing (e.g., panty hose) that does not allow air circulation. Wear loose-fitting clothing made of cotton and other natural fibers until the infection is healed.

Miconazole may damage a condom or diaphragm. Use another form of birth control while using miconazole vaginal.

Miconazole vaginal side effects

Stop using miconazole vaginal and seek emergency medical attention if you experience an allergic reaction (shortness of breath; closing of your throat; swelling of your lips, face, or tongue; or hives).

Other, less serious side effects may be more likely to occur. These include burning, itching, irritation of the skin, and an increased need to urinate.

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.

Miconazole vaginal Dosing Information

Usual Adult Dose for Vaginal Candidiasis:

Suppository -
1 day therapy: Insert 1200 mg suppository intravaginally at bedtime for 1 day
7 day therapy: Insert 100 mg suppository intravaginally at bedtime for 7 days.
3 day therapy: Insert 200 mg suppository intravaginally at bedtime for 3 days.

Cream:
Intravaginal 2% cream: Insert one applicatorful at bedtime for 3 to 7 days.
Intravaginal 4% cream: Insert one applicatorful at bedtime for 3 days.

Topical: Apply twice daily for up to 7 days or as needed to external vulvar area.

Usual Adult Dose for Cutaneous Candidiasis:

Apply a thin layer to affected areas twice a day.

Usual Adult Dose for Tinea Corporis:

Apply a thin layer to affected areas twice a day.

Usual Adult Dose for Tinea Cruris:

Apply a thin layer to affected areas twice a day.

Usual Adult Dose for Tinea Pedis:

Apply a thin layer to affected areas twice a day.

Usual Adult Dose for Tinea Versicolor:

Apply a thin layer to affected areas once a day.

What other drugs will affect miconazole vaginal?

Do not use miconazole vaginal without first talking to your doctor if you are taking warfarin (Coumadin). Special monitoring or a dosage adjustment may be necessary.

Avoid using other vaginal creams or douches at the same time as miconazole vaginal unless otherwise directed by your doctor.

Drugs other than those listed here may also interact with miconazole vaginal. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including herbal products.

More miconazole vaginal resources

• Miconazole vaginal Use in Pregnancy & Breastfeeding
• Miconazole vaginal Drug Interactions
• Miconazole vaginal Support Group
• 8 Reviews for Miconazole - Add your own review/rating

Compare miconazole vaginal with other medications

• Cutaneous Candidiasis
• Oral Thrush
• Tinea Corporis
• Tinea Cruris
• Tinea Pedis
• Tinea Versicolor
• Vaginal Yeast Infection

Where can I get more information?

• Your pharmacist has additional information about miconazole vaginal written for health professionals that you may read.

Lexuss 210 Liquid

codeine phosphate and chlorpheniramine maleate

Dosage Form: liquid
Lexuss 210 Liquid

CV

Drug Facts

Active Ingredients

Each 5 mL (1 teaspoonful) of vanilla cream flavored liquid for oral administration contains:

 

10 mg Codeine Phosphate

 

  2 mg Chlorpheniramine Maleate

Purpose

• Cough Suppressant


• Antihistamine

Codeine is one of the naturally occurring phenanthrene alkaloids of opium derived from the opium poppy, it is classified pharmacologically as a narcotic analgesic. Codeine phosphate may be chemically designated as 7.8-Didehydro-4, 5α-epoxy-3-methoxy-17-methylmorphinan-6-α-ol phosphate (1:1)(salt)hemihydrate. The phosphate salt of codeine occurs as white, needle-shaped crystals or white crystalline powder. Codeine phosphate is freely soluble in water and slightly soluble in alcohol and has the following chemical structure:

C18H21NO3 • H3PO4 • ½H2O          M.W. 406.37

Chlorpheniramine Maleate is an antihistamine having the chemical name: 2-Pyridinepropanamine, γ-(4-chlorophenyl)-N,N-dimethyl-, (Z)-2-butenedioate (1:1), and has the following chemical structure:

C16H19ClN2 • C4H4O4              M.W. 390.86

Lexuss 210 Liquid - Clinical Pharmacology

Codeine

Narcotic analgesics, including codeine, exert their primary effects on the central nervous system and gastrointestinal tract. The analgesic effects of codeine are due to its central action; however, the precise sites of action have not been determined, and the mechanisms involved appear to be quite complex. Codeine resembles morphine both structurally and pharmacologically, but its actions at the doses of codeine used therapeutically are milder, with less sedation, respiratory depression, and gastrointestinal, urinary, and pupilary effects. Codeine produces an increase in biliary tract pressure, but less than morphine or meperidine. Codeine is less constipating than morphine. Codeine has good antitussive activity, although less than that of morphine at equal doses. It is used in preference to morphine, because side effects are infrequent at the usual antitussive dose of codeine. Codeine in oral therapeutic dosage does not usually exert major effects on the cardiovascular system. Narcotic analgesics may cause nausea and vomiting by stimulating the chemoreceptor trigger zone (CTZ); however, they also depress the vomiting center, so that subsequent doses are unlikely to produce vomiting. Nausea is minimal after usual oral doses of codeine. Narcotic analgesics cause histamine release, which appears to be responsible for wheals or urticaria sometimes seen at the site of injection on parenteral administration. Histamine release may also produce dilation of cutaneous blood vessels, with resultant flushing of the face and neck, pruritus, and sweating.

Codeine and its salts are well absorbed following both oral and parenteral administration. Codeine is about 2/3 as effective orally as parenterally. Codeine is metabolized primarily in the liver by enzymes of the endoplasmic reticulum, where it undergoes 0-demethylation, N-demethylation, and partial conjugation with glucuronic acid. The drug is excreted primarily in the urine, largely as inactive metabolites and small amounts of free and conjugated morphine. Negligible amounts of codeine and its metabolites are found in the feces. Following oral or subcutaneous administration of codeine, the onset of analgesia occurs within 15 to 30 minutes and lasts for four to six hours. The cough-depressing action, in animal studies, was observed to occur 15 minutes after oral administration of codeine, peak action at 45 to 60 minutes after ingestion. The duration of action, which is dose-dependent, usually did not exceed 3 hours.

Chlorpheniramine

Chlorpheniramine Maleate is an alkylamine-type antihistamine that possesses anticholinergic and sedative effects. Antihistamines competitively antagonize histamine at the H1 receptor site. Thus, activation of H1 receptors by released histamine which results in increased vascular permeability, increased mucus production, pruritis and sneezing is prevented.

INDICATIONS

Temporarily relieves runny nose and alleviates sneezing, itching of the nose or throat, and itchy watery eyes due to hay fever or allergic rhinitis; for the temporary control of cough due to minor throat and bronchial irritation associated with the common cold or inhaled irritants; calms the cough control center and relieves coughing.

Contraindications

Codeine is contraindicated in patients with a known hypersensitivity to the drug. Antihistamines and codeine are both contraindicated for use in the treatment of lower respiratory tract symptoms, including asthma. Antihistamines and anticholinergics are contraindicated in patients with narrow-angle glaucoma, urinary retention, peptic ulcer and during an asthma attack. Contraindicated in breast-feeding mothers.

Warnings

Do not exceed recommended dosage. If nervousness, dizziness, or sleeplessness occur, discontinue use and consult a doctor. When using this product, Lexuss 210 Liquid may cause marked drowsiness.

A persistent cough may be a sign of a serious condition. If cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash, or persistent headache, consult a doctor.

Do not take this product for persistent or chronic cough such as occurs with smoking, asthma, chronic bronchitis, or emphysema, or where cough is accompanied by excessive phlegm (mucus) unless directed by a physician.

Adults and children who have a chronic pulmonary disease or shortness of breath, or children who are taking other drugs, should not take this product unless directed by a physician.

Dosage of codeine SHOULD NOT BE INCREASED if cough fails to respond; an unresponsive cough should be reevaluated in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease.

Codeine may cause or aggravate constipation.

Respiratory depression leading to arrest, coma, and death has occurred with the use of codeine antitussive in young children, particularly in the under-one-year infants whose ability to deactivate the drug is not fully developed.

Administration of codeine may be accomplished by histamine release and should be used with caution in atopic children.

Head Injury and Increased Intracranial Pressure

The respiratory depressant effects of narcotic analgesics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, intracranial lesions, or a reexisting increase in intracranial pressure. Narcotics may produce adverse reactions which may obscure the clinical course of patients with head injuries.

Asthma and Other Respiratory Conditions

Narcotic analgesics or cough suppressants, including codeine, should not be used in asthmatic patients. Nor should they be used in acute febrile illness associated with productive cough or in chronic respiratory disease where interference with ability to clear the tracheobronchial tree of secretions would have a deleterious effect on the patient's respiratory function.

Hypotensive Effect

Codeine may produce orthostatic hypotension in ambulatory patients.

Antihistamines may cause excitability especially in children. Do not take this product, unless directed by a physician, if you have a breathing problem such as emphysema or chronic bronchitis, or if you have glaucoma or difficulty in urination due to enlargement of the prostate gland. May cause drowsiness; alcohol, sedatives, and tranquilizers may increase the drowsiness effect. Avoid alcoholic beverages while taking this product. Do not take this product if you are taking sedatives or tranquilizers, without first consulting your doctor. Use caution when driving a motor vehicle or operating machinery.

Precautions

General

Before prescribing medication to suppress or modify cough, it is important that the underlying cause of cough is identified, that modification of cough does not increase the risk of clinical or physiological complications, and that appropriate therapy for the primary disease is instituted.

Narcotic analgesics, including codeine, should be administered with caution and the initial dose reduced in patients with acute abdominal conditions, convulsive disorders, significant hepatic or renal impairment, fever, hypothyroidism, Addison's disease, ulcerative colitis, prostatic hypertrophy, in patients with recent gastrointestinal or urinary tract surgery, and in the very young or elderly or debilitated patients.

Ultra-rapid Metabolizers of Codeine

Some individuals may be ultra-rapid metabolizers due to a specific CYP2D6*2x2 genotype. These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels. Even at labeled dosage regiments, individuals who are ultra-rapid metabolizers may experience overdose symptoms such as extreme sleepiness, confusion or shallow breathing.

The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese and Japanese, 0.5 to 1% in Hispanics, 1-10% in Caucasians, 3% in African Americans, and 16-28% in North Africans, Ethiopians and Arabs. Data is not available for other ethnic groups.

When physicians prescribe codeine-containing drugs, they should choose the lowest effective dose for the shortest period of time and should inform their patients about these risks and the signs of morphine overdose.

Drug/Laboratory Test Interactions

In patients receiving MAO inhibitors, an initial small test dose is advisable to allow observation of any excessive narcotic effects or MAOI interaction.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No data are available on the long-term potential for carcinogenesis, mutagenesis, or impairment of fertility in animals or humans.

Pregnancy

Pregnancy Category C

A study in rats and rabbits reported no teratogenic effect of codeine administered during the period of organogenesis in doses ranging from 5 to 120 mg/kg. In the rat, doses at the 120-mg/kg level, in the toxic range for the adult animal were associated with an increase in embryo resorption at the time of implantation. In another study a single 100-mg/kg dose of codeine administered to pregnant mice reportedly resulted in delayed ossification in the offspring. There are no studies in humans, and the significance of these findings to humans, if any, is not known. Do not use during third trimester.

Labor and Delivery

Narcotic analgesics cross the placental barrier. The closer to delivery and the larger the dose used, the greater the possibility of respiratory depression in the newborn. Narcotic analgesics should be avoided during labor if delivery of a premature infant is anticipated. If the mother has received narcotic analgesics during labor, newborn infants should be observed closely for signs of respiratory depression. Resuscitation may be required.

Nursing Mothers

Codeine is secreted into human milk. In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent. Despite the common use of codeine products to manage postpartum pain, reports of adverse events in infants are rare. However, some women are ultra-rapid metabolizers of codeine. These women achieve higher-than-expected serum levels of codeine's active metabolite, morphine, leading to higher-than-expected levels of morphine in breast milk and potentially dangerously high serum morphine levels in their breastfed infants. Therefore, maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants.

The risk of infant exposure to codeine and morphine through breast milk should be weighed against the benefits of breastfeeding for both the mother and baby. Caution should be exercised when codeine is administered to a nursing woman. If a codeine containing product is selected, the lowest dose should be prescribed for the shortest period of time to achieve the desired clinical effect. Mothers using codeine should be informed about when to seek immediate medical care and how to identify the signs and symptoms of neonatal toxicity, such as drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone in their baby. Nursing mothers who are ultra-rapid metabolizers may also experience overdose symptoms such as extreme sleepiness, confusion or shallow breathing. Prescribers should closely monitor mother-infant pairs and notify treating pediatricians about the use of codeine during breastfeeding.

Information for Patients

Codeine may cause marked drowsiness or may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. Ambulatory patients should be told to avoid engaging in such activities until it is known that they do not become drowsy or dizzy from codeine therapy.

The concomitant use of alcohol or other central nervous system depressants, including narcotic analgesics, sedatives, hypnotics, and tranquilizers, may have an additive effect and should be avoided or their dosage reduced.

Patients should be advised to report any involuntary muscle movements. Avoid prolonged exposure to the sun. Codeine, like other narcotic analgesics, may produce orthostatic hypotension in some ambulatory patients. Patients should be cautioned accordingly. Caution patients that some people have a variation in a liver enzyme and change codeine into morphine more rapidly and completely than other people. These people are ultra-rapid metabolizers and are more likely to have higher-than-normal levels of morphine in their blood after taking codeine which can result in overdose symptoms such as extreme sleepiness, confusion, or shallow breathing. In most cases, it is unknown if someone is an ultra-rapid codeine metabolizer. Nursing mothers taking codeine can also have higher morphine levels in their breast milk if they are ultra-rapid metabolizers. These higher levels of morphine in breast milk may lead to life-threatening or fatal side effects in nursing babies. Instruct nursing mothers to watch for signs of morphine toxicity in their infants including increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness. Instruct nursing mothers to talk to the baby's doctor immediately if they notice these signs and, if they cannot reach the doctor right away, to take the baby to an emergency room or call 911 (or local emergency services).

Caution patient using Chlorpheniramine that each product has specific dosing instructions and to read package label before using and not to exceed dose or frequency of administration instructions. Advise patient to take each dose without regard to meals, but to take with food if stomach upset occurs. Advise patient or caregiver using oral syrup to measure and administer prescribed dose using dosing syringe, dosing spoon, or dosing cup. Advise patient that if a dose is missed, to take it as soon as possible unless it is nearing time for the next scheduled dose. If it is nearing time for next scheduled dose, advise patient to skip the missed dose and take the next dose at the regularly scheduled time. Caution patient not to double the dose to catch up. Advise patient that if allergy symptoms are not controlled, not to increase the dose of medication or frequency of use but to inform health care provider. Caution patient that larger doses or more frequent dosing does not increase efficacy and may cause excessive drowsiness or other adverse reactions. Instruct patient to stop taking drug and immediately report any of these symptoms to health care provider: persistent dizziness; excessive drowsiness; severe dry mouth, nose, or throat; flushing; unexplained shortness of breath or difficulty breathing; unusual tiredness or weakness; sore throat, fever, or other signs of infection; bleeding or unusual bruising; fast or irregular heartbeat; excitability, confusion, or changes in thinking or behavior; chest tightness; difficulty with urination. Advise patient medication may cause drowsiness or dizziness and not to drive or perform other activities requiring mental alertness until tolerance is determined. Advise patient to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs. Caution patient alcohol and other CNS depressants (e.g., sedatives) will have additional sedative effects if taken with Chlorpheniramine. Caution patient not to take any other OTC antihistamines while taking this medication unless advised by health care provider. Caution patient that medication may cause sensitivity to sunlight and to avoid excessive exposure to the sun or UV light (e.g., tanning booths) and to wear protective clothing and use sunscreens until tolerance is determined. If patient is to have allergy skin testing, advise patient not to take the medication for at least 4 days before the skin testing.

Use in the Elderly

Use with caution, usually starting at the low end of the dosage range because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Adverse Reactions

Phenylephrine HCl

Codeine

Nervous System - CNS depression, particularly respiratory depression, and to a lesser extent circulatory depression; light-headedness, dizziness, sedation, euphoria, dysphoria, headache, transient hallucination, disorientation, visual disturbances, and convulsions.

Cardiovascular – Tachycardia, bradycardia, palpitation, faintness, syncope, orthostatic hypotension (common to narcotic analgesics).

Gastrointestinal – Nausea, vomiting, constipation, and biliary tract spasm. Patients with chronic ulcerative colitis may experience increased colonic motility; in patients with acute ulcerative colitis, toxic dilation has been reported.

Genitourinary – Oliguria, urinary retention, antidiuretic effect has been reported (common to narcotic analgesics).

Allergic – Infrequent pruritus, giant urticaria, angioneurotic edema, and laryngeal edema.

Other – Flushing of the face, sweating and pruritus (due to opiate-induced histamine release); weakness.

Drug Abuse and Dependence

Lexuss 210 Liquid is subject to Federal Controlled Substances Act (Schedule V).

Abuse

Codeine is known to be subject to abuse; however, the abuse potential of oral codeine appears to be quite low. Even parenteral codeine does not appear to offer the psychic effects sought by addicts to the same degree as heroin or morphine. However, codeine must be administered only under close supervision to patients with a history of drug abuse or dependence.

Dependence

Psychological dependence, physical dependence, and tolerance are known to occur with codeine.

Overdosage

Serious overdose with codeine is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. The triad of coma, pinpoint pupils, and respiratory depression is strongly suggestive of opiate poisoning. In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur. It is difficult to determine what constitutes a standard toxic or lethal dose. However, the lethal oral dose of codeine in an adult is reported to be in the range of 0.5 to 1 gram. Infants and children are believed to be relatively more sensitive to opiates on a body-weight basis. Elderly patients are also comparatively intolerant to opiates. Treatment of overdosage with codeine is essentially symptomatic and supportive. Only in cases of extreme overdosage or individual sensitivity do vital signs including respiration, pulse, blood pressure, temperature, and EKG need to be monitored. Activated charcoal orally or by lavage may be given, or sodium or magnesium sulfate orally as a cathartic. Attention should be given to the reestablishment of adequate respiratory exchange through provision of a patient airway and institution of assisted or controlled ventilation. The narcotic antagonist, naloxone hydrochloride, may be administered when significant respiratory depression occurs with codeine; Severe hypotension usually responds to the administration of norepinephrine or Phenylephrine. EPINEPHRINE SHOULD NOT BE USED, since its use in a patient with partial adrenergic blockade may further lower the blood pressure. Limited experience with dialysis indicates that it is not helpful. Overdosage with Chlorpheniramine may cause hallucinations, convulsions, and death. Antihistamines may diminish mental alertness. In young children, they may produce paradoxical excitation.

DOSAGE AND ADMINISTRATION1

Adults and children 12 years of age and over: 1 to 2 teaspoonfuls (5-10 mL) every 4 to 6 hours. Not to exceed 8 teaspoonfuls in a 24 hour period.

Children 6 to under 12 years of age: 1/2 to 1 teaspoonful (2.5 - 5 mL) every 4 to 6 hours. Not to exceed 4 teaspoonfuls in a 24 hour period.

Also contains the following inactive ingredients (in alphabetical order): Citric Acid, Methyl Paraben, Potassium Citrate, Potassium Sorbate, Propyl Paraben, Propylene Glycol, Purified Water, Sorbitol Solution 70%, Sucralose, Vanilla Ice Cream Flavor

1

In mild cases or in particularly sensitive patients, less frequent or reduced doses may be appropriate and adequate. Shake liquid well before use.

How is Lexuss 210 Liquid Supplied

Lexuss 210 Liquid is a clear solution with a vanilla aroma which contains 10 mg Codeine Phosphate and 2 mg Chlorpheniramine Maleate, available in 16 fl oz (473 mL) bottles.

NDC 23359-016-16

WARNING

KEEP THIS AND ALL MEDICATION OUT OF THE REACH OF CHILDREN. IN CASE OF ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL ASSISTANCE OR CONTACT A POISON CONTROL CENTER IMMEDIATELY.

Rx Only

Dispense in a tight, light-resistant container as defined in USP/NF with a child-resistant closure.

Store at controlled room temperature 15°-30°C (59°-86°F).

Manufactured for:

Centurion Labs, LLC

Birmingham, AL 35243

Manufactured by:

TG United Liquid, Inc.

Brooksville, FL 34604

Rev. 03/09

PRINCIPAL DISPLAY PANEL - 473 mL Label

NDC 23359-016-16

LEXUSS 210

Liquid

COUGH SUPPRESSANT

ANTIHISTAMINE

• Sugar Free

EACH TEASPOONFUL (5 mL)

CONTAINS:

Codeine Phosphate             10 mg

Chlorpheniramine Maleate     2 mg

Vanilla Cream Flavor

Alcohol Content 0.1%

CV

16 fl oz (473 mL)

Rx Only

LEXUSS 210  codeine phosphate and chlorpheniramine maleate  liquid

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 23359-016 Route of Administration ORAL DEA Schedule CV

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Codeine Phosphate (Codeine) Codeine Phosphate 10 mg  in 5 mL Chlorpheniramine Maleate (Chlorpheniramine) Chlorpheniramine Maleate 2 mg  in 5 mL

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color      Score      Shape Size Flavor VANILLA Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 23359-016-16 473 mL In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
Unapproved drug other		04/15/2009

Labeler - Centurion Labs (806756461)

Revised: 01/2010Centurion Labs

More Lexuss 210 Liquid resources

• Lexuss 210 Liquid Side Effects (in more detail)
• Lexuss 210 Liquid Dosage
• Lexuss 210 Liquid Use in Pregnancy & Breastfeeding
• Lexuss 210 Liquid Drug Interactions
• 0 Reviews for Lexuss 210 - Add your own review/rating

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LoKara Lotion

Pronunciation: DES-oh-nide
Generic Name: Desonide
Brand Name: Examples include DesOwen and LoKara

LoKara Lotion is used for:

Treating mild to moderate itching, redness, and swelling caused by certain skin conditions.

LoKara Lotion is a topical corticosteroid. It works by reducing skin inflammation (redness, swelling, itching, and irritation).

Do NOT use LoKara Lotion if:

• you are allergic to any ingredient in LoKara Lotion

Contact your doctor or health care provider right away if any of these apply to you.

Before using LoKara Lotion:

Some medical conditions may interact with LoKara Lotion. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have any kind of skin infection, cuts, scrapes, or lessened blood flow to your skin


• if you have measles, tuberculosis (TB), chicken pox, or shingles, a positive TB skin test, or if you have recently had a vaccination


• if you are taking an oral corticosteroid (eg, prednisone)

Some MEDICINES MAY INTERACT with LoKara Lotion. Because little, if any, of LoKara Lotion is absorbed into the blood, the risk of it interacting with another medicine is low.

Ask your health care provider if LoKara Lotion may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use LoKara Lotion:

Use LoKara Lotion as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Shake well before each use.


• Apply a small amount of LoKara Lotion to the affected area(s). Gently rub the medicine in until it is evenly distributed.


• Wash your hands immediately after applying LoKara Lotion, unless your hands are part of the treated area.


• Do not cover the treated area(s) with bandages or other dressings unless advised to do so by your health care provider.


• If you miss a dose of LoKara Lotion, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use LoKara Lotion.

Important safety information:

• LoKara Lotion is for external use only. Do not get it in your eyes, nose, or mouth. If you get it any of these areas, rinse right away with cool tap water.


• Do NOT use more than the recommended dose or use for longer than 2 weeks without checking with your doctor.


• If your symptoms do not get better within 2 weeks or if they get worse, check with your doctor.


• Talk with your doctor before you use any other medicines or cleansers on your skin.


• Do not apply LoKara Lotion over large areas of the body, to open wounds, or to scraped, infected, or burned skin without first checking with your doctor.


• Do not use LoKara Lotion for other skin conditions at a later time.


• Overuse of topical products may worsen your condition.


• If LoKara Lotion was prescribed to treat the diaper area, avoid using tight-fitting undergarments or plastic pants.


• Check with your doctor before you receive any vaccine while you are using LoKara Lotion.


• LoKara Lotion has a corticosteroid in it. Before you start any new medicine, check the label to see if it has a corticosteroid in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• Tell your doctor or dentist that you take LoKara Lotion before you receive any medical or dental care, emergency care, or surgery.


• Contact your doctor if you have a cut or sore that does not heal.


• Serious side effects may occur if too much of LoKara Lotion is absorbed through the skin. This may be more likely to occur if you use LoKara Lotion over a larger area of the body. It may also be more likely if you wrap or bandage the area after you apply LoKara Lotion. The risk is greater in children. Do not use more than the prescribed dose. Contact your doctor right away if you develop unusual weight gain (especially in the face), muscle weakness, increased thirst or urination, confusion, unusual drowsiness, severe or persistent headache, or vision changes. Discuss any questions or concerns with your doctor.


• LoKara Lotion should be used with extreme caution in CHILDREN younger than 3 months old; safety and effectiveness in these children have not been confirmed.


• Corticosteroids may affect growth rate in CHILDREN and teenagers in some cases. They may need regular growth checks while they use LoKara Lotion.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using LoKara Lotion while you are pregnant. It is not known if LoKara Lotion is found in breast milk after topical use. If you are or will be breast-feeding while you use LoKara Lotion, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of LoKara Lotion:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Mild, temporary stinging or burning when first applied.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); acne-like rash; inflamed hair follicles; inflammation around the mouth; severe or persistent burning, irritation, redness, or swelling of the skin; thinning, softening, or discoloration of the skin.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: LoKara side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include blurred vision or other vision changes; muscle weakness; severe or persistent headache; symptoms of high blood sugar (eg, increased thirst or urination, confusion, unusual drowsiness); unusual weight gain, especially in the face.

Proper storage of LoKara Lotion:

Store LoKara Lotion between 36 and 86 degrees F (2 and 30 degrees C). Store in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep LoKara Lotion out of the reach of children and away from pets.

General information:

• If you have any questions about LoKara Lotion, please talk with your doctor, pharmacist, or other health care provider.


• LoKara Lotion is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about LoKara Lotion. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More LoKara resources

• LoKara Side Effects (in more detail)
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• Atopic Dermatitis
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