Stelazine 1mg Tablets

1. Name Of The Medicinal Product

Stelazine 1mg Tablets or Trifluoperazine 1mg Tablets

2. Qualitative And Quantitative Composition

Trifluoperazine Hydrochloride 1mg BP

3. Pharmaceutical Form

Tablet

Blue aqueous film coated tablets marked 'STE 1mg' or 'FW231'.

4. Clinical Particulars

4.1 Therapeutic Indications

Low dosage: 'Stelazine' is indicated as an adjunct in the short-term management of anxiety states, depressive symptoms secondary to anxiety, and agitation. It is also indicated in the symptomatic treatment of nausea and vomiting.

High dosage: Treatment of symptoms and prevention of relapse in schizophrenia and in other psychoses, especially of the paranoid type, but not in depressive psychoses. It may also be used as an adjunct in the short-term management of severe psychomotor agitation and of dangerously impulsive behaviour in, for example, mental subnormality.

4.2 Posology And Method Of Administration

Dosage:

Adults: Low dosage: 2-4 mg a day, given in divided doses, according to the severity of the patient's condition. If necessary, dosage may be increased to 6 mg a day, but above this level extrapyramidal symptoms are more likely to occur in some patients.

High dosage: The recommended starting dose for physically fit adults is 5 mg twice a day; after a week this may be increased to 15 mg a day. If necessary, further increases of 5 mg may be made at three-day intervals, but not more often. When satisfactory control has been achieved, dosage should be reduced gradually until an effective maintenance level has been established.

As with all major tranquillisers clinical improvement may not be evident for several weeks after starting treatment, and there may also be delay before recurrence of symptoms after stopping treatment. Gradual withdrawal from high-dosage treatment is advisable.

Children: Low dosage: For children aged 6-12 years, up to a maximum of 4 mg a day given in divided doses.

High dosage: For children aged under 12 years, the initial oral dosage should not exceed 5mg a day, given in divided doses. Any subsequent increase should be made with caution, at intervals of not less than three days, and taking into account age, body weight and severity of symptoms.

Elderly: The starting dose for elderly or frail patients should be reduced by at least half.

Administration:

Oral

4.3 Contraindications

Do not use 'Stelazine' in comatose patients, particularly is associated with other central nervous system depressants. Do not use 'Stelazine' in those patients with existing blood dyscrasias or known liver damage, or in those hypersensitive to trifluoperazine, related compounds, or any of the excipients. Patients with uncontrolled cardiac decompensation should not be given 'Stelazine'.

4.4 Special Warnings And Precautions For Use

'Stelazine' should be discontinued at the first sign of clinical symptoms of tardive dyskinesia and Neuroleptic Malignant Syndrome.

Patients on long-term phenothiazine therapy require regular and careful surveillance with particular attention to tardive dyskinesia and possible eye changes, blood dyscrasias, liver dysfunction and myocardial conduction defects, particularly if other concurrently administered drugs have potential effects in these systems.

Care should be taken when treating elderly patients, and the initial dosage should be reduced. Such patients can be especially sensitive, particularly to extrapyramidal and hypotensive effects. Patients with cardiovascular disease including arrhythmias should also be treated with caution. Because 'Stelazine' may increase activity, care should be taken in patients with angina pectoris. If an increase in pain is noted, the drug should be discontinued. Patients who have demonstrated bone marrow suppression or jaundice with a phenothiazine should not be re-exposed to 'Stelazine (or any trifluoperazine) unless in the judgement of the physician the potential benefits of treatment outweigh the possible hazard.

In patients with Parkinson's disease, symptoms may be worsened, and the effects of levodopa reversed. Since phenothiazines may lower the convulsive threshold, patients with epilepsy should be treated with caution, and metrizamide avoided. Although 'Stelazine' has minimal anticholinergic activity, this should be borne in mind when treating patients with narrow angle glaucoma, myasthenia gravis or prostatic hypertrophy.

Nausea and vomiting as a sign of organic disease may be masked by the antiemetic action of 'Stelazine'.

An approximately 3-fold increased risk of cerebrovascular adverse events have been seen in randomised placebo controlled clinical trials in the dementia population with some atypical antipsychotics. The mechanism for this increased risk is not known. Stelazine should be used with caution in patients with risk factors for stroke

Caution should be used in patients with cardiovascular disease or family history of QT prolongation. Concomitant use of neuroleptics should be avoided.

Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Stelazine and preventive measures undertaken

Acute withdrawal symptoms including nausea, vomiting and insomnia have been described after abrupt cessation of high doses of antipsychotic drugs. Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported. Therefore, a gradual withdrawal is advisable.

Phenothiazines should be used with care in extremes of temperature since they may affect body temperature control.

Increased Mortality in Elderly people with Dementia

Data from two large observational studies showed that elderly people with dementia who are treated with antipsychotics are at a small increased risk of death compared with those who are not treated. There are insufficient data to give a firm estimate of the precise magnitude of the risk and the cause of the increased risk is not known.

Stelazine is not licensed for the treatment of dementia-related behavioural disturbances.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Potentiation may occur if antipsychotic drugs are combined with CNS depressants such as alcohol, hypnotics, anaesthetics and strong analgesics, or with antihypertensives or other drugs with hypotensive activity, anticholinergics or antidepressants. Phenothiazines may antagonise the action of levodopa. Avoid drugs that depress leucopoiesis.

Serum levels of phenothiazine can be reduced to non-therapeutic concentrations by concurrent administration of lithium.

Desferrioxamine should not be used in combination with 'Stelazine', since prolonged unconsciousness has occurred after combination with the related prochlorperazine.

Trifluoperazine may diminish the effect of oral anticoagulants.

Severe extrapyramidal side-effects or neurotoxicity have been observed in patients concurrently treated with lithium and trifluoperazine. Sleep walking has been described in some patients taking phenothiazines and lithium.

Antacids can reduce the absorption of phenothiazines.

Phenothiazines increase the risk of ventricular arrhythmias when given with drugs which prolong the Q-T interval, drugs causing electrolyte imbalances.

4.6 Pregnancy And Lactation

'Stelazine' has been available since 1958. There are some animal studies that indicate a teratogenic effect, but results are conflicting. There is no clinical evidence (including follow-up surveys in over 800 women who had taken low-dosage 'Stelazine' during pregnancy) to indicate that trifluoperazine has a teratogenic effect in man. Nevertheless, drug treatment should be avoided in pregnancy unless essential, especially during the first trimester.

Trifluoperazine crosses the placenta and passes into the milk of lactating dogs; breast feeding should only be allowed at the discretion of the physician.

4.7 Effects On Ability To Drive And Use Machines

Stelazine may cause side effects including drowsiness, dizziness and visual disturbances which interfere with the ability to drive and operate machinery. Do not drive or use machines when you first start to take this medicine until you are certain that you are not getting these side effects

4.8 Undesirable Effects

Lassitude, drowsiness, dizziness, transient restlessness, insomnia, dry mouth, blurred vision, muscular weakness, anorexia, mild postural hypotension, skin reactions including photosensitivity reactions, weight gain, oedema and confusion may occasionally occur. Tachycardia, constipation, urinary hesitancy and retention, and hyperpyrexia have been reported very rarely. Adverse reactions tend to be dose-related and to disappear.

Hyperprolactinaemia may occur at higher dosages with associated effects such as galactorrhoea, amenorrhoea or gynaecomastia; certain hormone-dependent breast neoplasms may be affected. Phenothiazines can produce ECG changes with prolongation of the QT interval and T-wave changes; ventricular arrhythmias( VF,VT(rare)), sudden unexplained deaths; cardiac arrest and Torsades de pointes have been reported. Such effects are rare with 'Stelazine'.

In some patients, especially non-psychotic patients, 'Stelazine' even at low dosage may cause unpleasant symptoms of being dulled or, paradoxically, of being agitated.

Extrapyramidal symptoms are rare at oral daily dosages of 6 mg or less; they are considerably more common at higher dosage levels. These symptoms include parkinsonism; akathisia, with motor restlessness and difficulty in sitting still; and acute dystonia or dyskinesia, which may occur early in treatment and may present with torticollis, facial grimacing, trismus, tongue protrusion and abnormal eye movements including oculogyric crises. These effects are likely to be particularly severe in children. Such reactions may often be controlled by reducing the dosage or by stopping medication. In more severe dystonic reactions, an anticholinergic antiparkinsonism drug should be given.

Tardive dyskinesia of the facial muscles, sometimes with involuntary movements of the extremities, has occurred in some patients on long-term, high-dosage and, more rarely, low-dosage phenothiazine therapy, including 'Stelazine'. Symptoms may appear for the first time either during or after a course of treatment; they may become worse when treatment is stopped. The symptoms may persist for many months or even years, and while they gradually disappear in some patients, they appear to be permanent in others.

Patients have most commonly been elderly, female or with organic brain damage. Particular caution should be observed in treating such patients.

Periodic gradual reduction of dosage to reveal persisting dyskinesia has been suggested, so that treatment may be stopped if necessary.

Anticholinergic antiparkinsonism agents may aggravate the condition. Since the occurrence of tardive dyskinesia may be related to length of treatment and dosage, Trifluoperazine should be given for as short a time and at as low a dosage as possible

The neuroleptic malignant syndrome is a rare but occasionally fatal complication of treatment with neuroleptic drugs, and is characterised by hyperpyrexia, muscle rigidity, altered consciousness and autonomic instability. Intensive symptomatic treatment, following discontinuation of 'Stelazine', should include cooling. Intravenous dantrolene has been suggested for muscle rigidity.

Mild cholestatic jaundice and blood dyscrasias such as agranulocytosis, pancytopenia, leucopenia and thrombocytopenia have been reported very rarely.

Signs of persistent infection should be investigated.

Very rare cases of skin pigmentation and lenticular opacities have been reported with Stelazine'. Withdrawal reactions have been reported in association with antipyschotic drugs(see 4.4)..

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs- Frequency unknown.

4.9 Overdose

Signs and symptoms will be predominantly extrapyramidal; hypotension may occur. Absorption of trifluoperazine from the 'Spansule' capsule is likely to be prolonged and this should be borne in mind. Treatment consists of gastric lavage together with supportive and symptomatic measures. Do not induce vomiting. Extrapyramidal symptoms may be treated with an anticholinergic antiparkinsonism drug. Treat hypotension with fluid replacement; if severe or persistent, noradrenaline may be considered. Adrenaline is contra-indicated.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

'Stelazine' is a Piperazine Phenothiazine tranquiliser with potent anti-psychotic, anxiolytic and antiemetic activity, and a pharmacological profile of moderate sedative and hypotensive properties, and fairly pronounced tendency to cause extrapyramidal reactions.

5.2 Pharmacokinetic Properties

Trifluoperazine is well absorbed but undergoes extensive first pass metabolism. Distribution is wide and elimination occurs in the bile and urine. Inactive ingredients in the tablets include sucrose.

5.3 Preclinical Safety Data

Not applicable.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Calcium Sulphate

Icing sugar(Sucrose)

Maize Starch

Gelatin

Talc

Stearic acid

Coating

Opadry Blue OY -4492

Carnauba wax

Purified water

6.2 Incompatibilities

None known.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Do not store above 25°C. Protect from light and moisture.

6.5 Nature And Contents Of Container

In opaque blister packs of 100 (4 x 25), 28, 56, 100, 112.

In securitainers of 28, 56, 100, 112, 1000, 5000.

6.6 Special Precautions For Disposal And Other Handling

Not applicable

7. Marketing Authorisation Holder

Goldshield Pharmaceuticals Ltd

NLA Tower

12-16 Addiscombe Road

Croydon CR0 OXT

United Kingdom.

8. Marketing Authorisation Number(S)

PL 12762/0030

9. Date Of First Authorisation/Renewal Of The Authorisation

01.08.98

10. Date Of Revision Of The Text

30/11/2010

SymPak DM

Pronunciation: FEN-il-EF-rin/gwye-FEN-e-sin/DEX-troe-meth-OR-fan and KLOR-fen-IR-a-meen/FEN-il-EF-rin/METH-skoe-POL-a-meen
Generic Name: Phenylephrine/Guaifenesin/Dextromethorphan
Brand Name: SymPak DM

SymPak DM is used for:

Relieving nasal and chest congestion, sneezing, runny nose, and itchy, watery eyes due to colds, flu, or allergies. It is also used to reduce coughing and to make a dry cough more productive and less frequent. It may also be used for other conditions as determined by your doctor.

SymPak DM is a combination pack containing a morning dose and an evening dose. The morning dose has a decongestant, expectorant, and cough suppressant. The evening dose has an antihistamine, decongestant, and anticholinergic. The decongestant works by shrinking swollen tissue in the nose. The expectorant works by thinning mucus in the lungs. The cough suppressant works in the brain to reduce coughing. The antihistamine works by blocking histamine, a substance in the body that causes sneezing, runny nose, and watery eyes. The anticholinergic works by drying mucous membranes in the nose and chest.

Do NOT use SymPak DM if:

• you are allergic to any ingredient in SymPak DM


• you are pregnant or breast-feeding


• you are taking droxidopa, furazolidone, sodium oxybate (GHB), or a monoamine oxidase inhibitor (MAOI) (eg, phenelzine), or if you have taken an MAOI within the past 14 days


• you have severe heart blood vessel problems, severe high blood pressure, narrow-angle glaucoma, difficulty urinating due to enlarged prostate, peptic ulcer, or uncontrolled bleeding


• you are having an asthma attack

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

Before using SymPak DM:

Some medical conditions may interact with SymPak DM. 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 bladder blockage, blood vessel problems (eg, hardening of the arteries), diabetes, an enlarged prostate, glaucoma or increased pressure in the eye, heart problems (eg, irregular heartbeat, heart failure), heart blood vessel problems, high blood pressure, inflammation of the esophagus from reflux disease, kidney problems, a hiatal hernia, an adrenal gland tumor (pheochromocytoma), myasthenia gravis (muscle weakness), stomach or bowel problems (eg, constipation, inflammation, motility problems, blockage), trouble sleeping, or an overactive thyroid


• if you have chronic cough, chronic bronchitis, or any lung or breathing problems, such as asthma, emphysema, sleep apnea, or chronic obstructive pulmonary disease (COPD)


• if you have a history of alcohol abuse


• if you take potassium chloride tablets

Some MEDICINES MAY INTERACT with SymPak DM. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Droxidopa or sodium oxybate ( GHB) because the risk of severe drowsiness, breathing problems, seizures, irregular heartbeat, or heart attack may be increased


• Beta-blockers (eg, propranolol), catechol-O-methyltransferase (COMT) inhibitors (eg, tolcapone), furazolidone, MAOIs (eg, phenelzine), selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine), or tricyclic antidepressants (eg, amitriptyline) because they may increase the risk of SymPak DM's side effects


• Bromocriptine because the risk of its side effects may be increased by SymPak DM


• Guanadrel, guanethidine, mecamylamine, methyldopa, reserpine, or other medicine for high blood pressure because their effectiveness may be decreased by SymPak DM

This may not be a complete list of all interactions that may occur. Ask your health care provider if SymPak DM 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 SymPak DM:

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

• Take SymPak DM by mouth with or without food.


• Swallow SymPak DM whole. Do not break, crush, or chew before swallowing. Some brands of SymPak DM may be broken in half before taking. If you have difficulty swallowing the whole tablet, ask your pharmacist if your brand of medicine may be broken in half.


• This product contains 2 different tablets; one for the morning and one for the evening. Be sure you understand how to take SymPak DM. Check with your doctor or pharmacist if you are not sure which tablet to take in the morning or in the evening.


• If you miss a dose of SymPak DM and you are taking it regularly, take 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 take 2 doses at once.

Ask your health care provider any questions you may have about how to use SymPak DM.

Important safety information:

• SymPak DM may cause drowsiness, dizziness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use SymPak DM with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do not drink alcohol or use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using SymPak DM; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• The risk of dizziness, nervousness, and trouble sleeping may be greater if you take SymPak DM in high doses or for a long time. Do NOT take more than the recommended dose without checking with your doctor.


• If your cough or other symptoms persist for more than 1 week, come back, or if you also have fever, rash, or persistent headache, check with your doctor.


• SymPak DM may interfere with certain lab test results. Be sure your doctors and laboratory personnel know that you are taking SymPak DM.


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


• SymPak DM may cause dry mouth. To relieve dry mouth, suck on sugarless hard candy or ice chips, chew sugarless gum, drink water, or use a saliva substitute.


• SymPak DM may reduce sweating. Do not become overheated in hot weather or during exercise or other activities because heatstroke may occur.


• SymPak DM has phenylephrine, chlorpheniramine, and dextromethorphan in it. Before you start any new medicine, check the label to see if it has phenylephrine, chlorpheniramine, and dextromethorphan in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• Do not take diet or appetite control medicines while you are taking SymPak DM without checking with your doctor.


• Diabetes patients - SymPak DM may affect your blood sugar. Check blood sugar levels closely and ask your doctor before adjusting the dose of your diabetes medicine.


• Use SymPak DM with caution in the ELDERLY; they may be more sensitive to its effects.


• SymPak DM should be used with extreme caution in CHILDREN younger than 6 years old; safety and effectiveness in these children have not been confirmed.


• Caution is advised when using SymPak DM in CHILDREN; they may be more sensitive to its effects, especially excitability.


• PREGNANCY and BREAST-FEEDING: It is not known if SymPak DM can cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using SymPak DM while you are pregnant. SymPak DM is found in breast milk. Do not breast-feed while taking SymPak DM.

Possible side effects of SymPak DM:

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:

Blurred vision; dizziness; drowsiness; dry mouth, nose, or throat; excitability or irritability (especially in children); giddiness; headache; lightheadedness; nausea; nervousness; trouble sleeping; unusual tiredness or weakness.

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); fast or irregular heartbeat; flushing; hallucinations; mental or mood changes; seizures severe drowsiness; tremor; vomiting.

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: SymPak DM 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.

Proper storage of SymPak DM:

Store SymPak DM in a tightly closed container between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep SymPak DM out of the reach of children and away from pets.

General information:

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


• SymPak DM 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 SymPak DM. 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 SymPak DM resources

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

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• Cough and Nasal Congestion

Mucinex Full Force

Generic Name: oxymetazoline (Nasal route)

ox-i-me-TAZ-oh-leen

Commonly used brand name(s)

In the U.S.

• 4-Way Long Lasting


• Afrin


• Duramist Plus


• Duration


• Genasal


• Mucinex Full Force


• Mucinex Moisture Smart


• Nasacon


• Nasin


• Neo-Synephrine 12 Hour


• Nostrilla


• NRS-Nasal Relief


• Sinarest Nasal


• Vicks Sinex 12 Hour

Available Dosage Forms:

• Solution


• Spray

Therapeutic Class: Decongestant

Chemical Class: Imidazoline

Uses For Mucinex Full Force

Oxymetazoline is used for the temporary relief of nasal (of the nose) congestion or stuffiness caused by hay fever or other allergies, colds, or sinus trouble.

This medicine may also be used for other conditions as determined by your doctor.

This medicine is available without a prescription.

Before Using Mucinex Full Force

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

Children may be especially sensitive to the effects of oxymetazoline. This may increase the chance of side effects during treatment.

Geriatric

Many medicines have not been tested in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information about the use of oxymetazoline in the elderly.

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. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

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

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:

• Type 2 diabetes mellitus

• Dry membranes in nose

• Enlarged prostate—Difficulty urinating may worsen

• Glaucoma

• Heart or blood vessel disease or


• High blood pressure—Oxymetazoline may make the condition worse

• Overactive thyroid

Proper Use of oxymetazoline

This section provides information on the proper use of a number of products that contain oxymetazoline. It may not be specific to Mucinex Full Force. Please read with care.

To use the nose drops:

• Blow your nose gently. Tilt the head back while standing or sitting up, or lie down on a bed and hang the head over the side. Place the drops into each nostril and keep the head tilted back for a few minutes to allow the medicine to spread throughout the nose.


• Rinse the dropper with hot water and dry with a clean tissue. Replace the cap right after use.


• To avoid spreading the infection, do not use the container for more than one person.

To use the nose spray:

• Blow your nose gently. With the head upright, spray the medicine into each nostril. Sniff briskly while squeezing the bottle quickly and firmly. For best results, spray once into each nostril, wait 3 to 5 minutes to allow the medicine to work, then blow the nose gently and thoroughly. Repeat until the complete dose is used.


• Rinse the tip of the spray bottle with hot water, taking care not to suck water into the bottle, and dry with a clean tissue. Replace the cap right after use.


• To avoid spreading the infection, do not use the container for more than one person.

Use this medicine only as directed. Do not use more of it, do not use it more often, and do not use it for longer than 3 days without first checking with your doctor. To do so may make your runny or stuffy nose worse and may also increase the chance of side effects.

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 nasal dosage form (nose drops or spray):
  
  • For nasal congestion or stuffiness:
    
    • Adults and children 6 years of age and older—Use 2 or 3 drops or sprays of 0.05% solution in each nostril every ten to twelve hours. Do not use more than two times in twenty four hours.
    
    
    • Children up to 6 years of age—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.

Mucinex Full Force 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 as soon as possible if any of the following side effects occur:

Symptoms of too much medicine being absorbed into the body

• Blurred vision


• fast, irregular, or pounding heartbeat


• headache, dizziness, drowsiness, or lightheadedness


• high blood pressure


• nervousness


• trembling


• trouble in sleeping


• weakness.

• Increase in runny or stuffy nose

The above side effects are more likely to occur in children because there is a greater chance in children that too much of this medicine may be absorbed into the body.

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:

• Burning, dryness, or stinging inside of nose


• increase in nasal discharge


• sneezing

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: Mucinex Full Force 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 Mucinex Full Force resources

• Mucinex Full Force Side Effects (in more detail)
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• Mucinex Full Force Drug Interactions
• Mucinex Full Force Support Group
• 0 Reviews for Mucinex Full Force - Add your own review/rating

• Afrin Concise Consumer Information (Cerner Multum)


• Afrin Solution MedFacts Consumer Leaflet (Wolters Kluwer)

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• Nasal Congestion

Cardene 20 and 30mg

1. Name Of The Medicinal Product

Cardene 20 mg

Cardene 30 mg

2. Qualitative And Quantitative Composition

Nicardipine hydrochloride 20 mg

Nicardipine hydrochloride 30 mg

3. Pharmaceutical Form

Capsules

4. Clinical Particulars

4.1 Therapeutic Indications

Cardene is indicated for the prophylaxis of patients with chronic stable angina. For the treatment of hypertension considered to be mild to moderate in severity.

4.2 Posology And Method Of Administration

Nicardipine should be taken with a little water.

Prophylaxis of chronic stable angina:

Starting dose: 20 mg every 8 hours titrating upwards as required.

Usual effective dose: 30 mg every 8 hours (range of total dose 60 mg - 120 mg per day).

Allow at least 3 days before increasing the dose of Cardene to ensure steady state plasma levels have been achieved.

Hypertension:

Starting dose: 20 mg every 8 hours titrating upwards as required.

Usual effective dose: 30 mg every 8 hours (range of total dose 60 mg - 120 mg per day).

Use in elderly:

Starting dose is 20 mg 3 times a day. Titrate upwards with care as nicardipine may lower systolic pressure more than diastolic pressure in these patients.

Children:

Cardene is not recommended in patients under the age of 18.

Cardene capsules are for oral administration.

4.3 Contraindications

(1) Pregnancy and lactation.

(2) Hypersensitivity to nicardipine hydrochloride or other dihydropyridines because of the theoretical risk of cross reactivity.

(3) Because part of the effect of nicardipine is secondary to reduced afterload, the drug should not be given to patients with advanced aortic stenosis. Reduction of diastolic pressure in these patients may worsen rather than improve myocardial infarction.

(4) Cardene should not be used in cardiogenic shock, clinically significant aortic stenosis, unstable angina, and during or within one month of a myocardial infarction.

(5) Cardene should not be used for acute attacks of angina.

(6) Cardene should not be used for secondary prevention of myocardial infarction.

4.4 Special Warnings And Precautions For Use

If used in combination with diuretics or beta-blockers, careful titration of Cardene is advised to avoid excessive reduction in blood pressure.

If switching from beta-blockers to Cardene, gradually reduce the beta-blocker dose (preferably over 8 - 10 days) since nicardipine gives no protection against the dangers of abrupt beta-blocker withdrawal.

Stop Cardene in patients experiencing ischaemic pain within 30 minutes of starting therapy or after increasing the dose.

Use in patients with congestive heart failure or poor cardiac reserve:

Haemodynamic studies in patients with heart failure have shown that nicardipine reduces afterload and improves overall haemodynamics. In one study, intravenous nicardipine reduced myocardial contractility in patients with severe heart failure despite increases in cardiac index and ejection fraction noted in the same patients.

Since nicardipine has not been extensively studied in patients with severe left ventricular dysfunction and cardiac failure one must consider that worsening of cardiac failure may occur.

Use in patients with impaired hepatic or renal function:

Since Cardene is subject to first-pass metabolism, use with caution in patients with impaired liver function or reduced hepatic blood flow. Patients with severe liver disease showed elevated blood levels and the half-life of nicardipine was prolonged. Cardene blood levels may also be elevated in some renally impaired patients. Therefore the lowest starting dose and extending the dosing interval should be individually considered in these patients.

Use in patients following a stroke (infarction or haemorrhage):

Avoid inducing systemic hypotension when administering Cardene to these patients.

Laboratory tests:

Transient elevations of alkaline phosphatase, serum bilirubin, SGPT, SGOT and glucose, have been observed. BUN and creatinine may also become elevated. While out-of-range values were seen in T₃, T₄ and TSH, the lack of consistent alterations suggest that any changes were not drug-related.

Treatment with short acting nicardipine may induce an exaggerated fall in blood pressure and reflex tachycardia which can cause cardiovascular complications such as myocardial and cerebrovascular ischaemia.

There has been some concern about increased mortality and morbidity in the treatment of ischaemic heart disease using higher than recommended doses of some other short-acting dihydropyridines.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Digoxin

Careful monitoring of serum digoxin levels is advised in patients also receiving Cardene as levels may be increased.

Propanolol, Dipyridamole, Warfarin, Quinidine, Naproxen:

Therapeutic concentrations of these drugs does not change the in vitro plasma protein binding of nicardipine.

Cimetidine:

Cimetidine increases nicardipine plasma levels. Carefully monitor patients receiving both drugs.

Fentanyl Anaesthesia:

Severe hypotension has been reported during fentanyl anaesthesia with concomitant use of a beta-blocker and calcium blockade. Even though such interactions have not been seen in clinical trials, such hypotensive episodes should be vigorously treated with conventional therapy such as intravenous fluids.

Cyclosporin:

Monitor cyclosporin plasma levels and reduce dosage accordingly in patients concomitantly receiving nicardipine as elevated cyclosporin levels have been reported.

Rifampicin:

Rifampicin can interact with other dihydropyridines to substantially reduce their plasma levels and so rifampicin and nicardipine should be used together with caution.

As with other dihydropyridines, nicardipine should not be taken with grapefruit juice because bioavailability may be increased.

Cardene may be used in combination with beta-blocking and other anti-hypertensive drugs but the possibility of an additive effect resulting in postural hypotension should be considered.

4.6 Pregnancy And Lactation

See contra-indications.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Majority are not serious and are expected consequences of the vasodilator effects of Cardene.

The most frequent side-effects reported are headache, pedal oedema, heat sensation and/or flushing, palpitations, nausea and dizziness.

Other side-effects noted in clinical trials include the following:

Cardiovascular System: As with the use of other short-acting dihydropyridines in patients with ischaemic heart disease, exacerbation of angina pectoris may occur frequently at the start of treatment with nicardipine capsules. The occurrence of myocardial infarction has been reported although it is not possible to distinguish such an event from the natural course of ischaemic heart disease.

Central nervous system: Drowsiness, insomnia, tinnitus, paraesthesia, functional disorders.

Skin: Itching, rashes.

Hepato-Renal: Impairment, frequency of micturition.

Dyspnoea, gastro-intestinal upset and, rarely, depression, impotence and thrombocytopenia, have also been reported.

4.9 Overdose

Symptoms may include marked hypotension, bradycardia, palpitations, flushing, drowsiness, confusion and slurred speech. In laboratory animals, overdosage also resulted in reversible hepatic function abnormalities, sporadic focal hepatic necrosis and progressive atrioventricular conduction block.

For treatment of overdose, standard measures including monitoring of cardiac and respiratory functions should be implemented. The patient should be positioned so as to avoid cerebral anoxia. Frequent blood pressure determinations are essential. Vasopressors are clinically indicated for patients exhibiting profound hypotension. Intravenous calcium gluconate may help reverse the effects of calcium entry blockade.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Cardene is a potent calcium antagonist. Pharmacological studies demonstrate its preferential high selectivity for the peripheral vasculature over the myocardium which accounts for its minimal negative inotropic effects. Cardene produces smooth muscle relaxation and marked peripheral vasodilatation.

In man Cardene produces a significant decrease in systemic vascular resistance, the degree of vasodilatation being more predominant in hypertensive patients than in normotensive subjects. Haemodynamic studies in patients with coronary artery disease and normal left ventricular function have shown significant increases in cardiac index and coronary blood flow, with little if any increase in left ventricular end-diastolic pressure.

Electrophysiologic effects: Electrophysiological studies in man show that Cardene does not depress sinus node function or atrial or ventricular conduction in patients with either normal or decreased electrical conduction systems. Refractory periods of the His-Purkinje system were actually shortened slightly by nicardipine and SA conduction time was improved.

5.2 Pharmacokinetic Properties

Pharmacokinetics and metabolism: Nicardipine is rapidly and completely absorbed with plasma levels detectable 20 minutes following an oral dose. Maximal plasma levels are observed within 30 minutes to two hours (mean T_max = 1 hour). When given with a high fat meal peak plasma levels are reduced by 30%. Nicardipine is subject to saturable first-pass metabolism and the bioavailability is about 35% following a 30 mg oral dose at steady state.

The pharmacokinetics of Cardene are non-linear due to saturable hepatic first pass metabolism.

Steady state plasma levels are achieved after about 3 days of dosing at 20 and 30 mg tds and remain relatively constant over 28 days of dosing at 30 mg tds. Considerable intersubject variability in plasma levels is observed. Following dosing to steady state using doses of 30 and 40 mg (tds), the terminal plasma half-life of nicardipine averaged 8.6 hours. Nicardipine is highly protein-bound (>99%) in human plasma over a wide concentration range.

Nicardipine does not induce its own metabolism and does not induce hepatic microsomal enzymes.

5.3 Preclinical Safety Data

Please refer to section 4.6 Pregnancy and Lactation.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Starch, Pregelatinised

Magnesium Stearate

Cardene 20mg

Capsule shell body

Titanium Dioxide E171

Gelatin

Cardene 30mg

Capsule shell body

Indigotine E132

Titanium Dioxide E171

Gelatin

Cardene 20mg and 30mg

Capsule shell cap

Indigotine E132

Titanium Dioxide E171

Gelatin

6.2 Incompatibilities

None known.

6.3 Shelf Life

Cardene 20mg

Securitainer: 60 months.

Blister packs of 21, 100 and 200 capsules: 60 months.

Blister packs of 56 and 84 capsules: 36 months.

Cardene 30mg

Securitainer: 60 months

Blister packs of 21, 56, 60, 100 and 200 capsules: 60 months.

Blister packs of 84 capsules: 36 months.

6.4 Special Precautions For Storage

Do not store above 25°C.

6.5 Nature And Contents Of Container

Cardene 20mg

Securitainer packs of 50 and 100.

PVC/aluminium foil blister strips of 21, 56, 84,100 and 200 capsules.

Cardene 30mg

Securitainer packs of 50 and 100.

PVC/aluminium foil blister strips of 21, 56, 60, 84,100 and 200 capsules.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

Administrative Data

7. Marketing Authorisation Holder

Astellas Pharma Limited

Lovett House

Lovett Road

Staines

TW18 3AZ

United Kingdom

8. Marketing Authorisation Number(S)

Cardene 20mg - PL 00166/0181

Cardene 30mg - PL 00166/0182

9. Date Of First Authorisation/Renewal Of The Authorisation

15 May 1998/ 15 July 2002

10. Date Of Revision Of The Text

4 November 2005

11. Legal category

POM

Urso

Generic Name: ursodiol (ur so DY all)

Brand Names: Actigall, Urso, Urso Forte

What is Urso (ursodiol)?

Ursodiol is a bile acid that decreases the amount of cholesterol produced by the liver and absorbed by the intestines. Ursodiol helps break down cholesterol that has formed into stones in the gallbladder. Ursodiol also increases bile flow in patients with primary biliary cirrhosis.

Ursodiol is used to treat small gallstones in people who cannot have gallbladder surgery, and to prevent gallstones in overweight patients undergoing rapid weight loss. Ursodiol is also used to treat primary biliary cirrhosis.

Ursodiol is not for treating gallstones that are calcified.

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

What is the most important information I should know about Urso (ursodiol)?

Before taking ursodiol, tell your doctor if you are also taking cholestyramine (Questran), colestipol (Colestid), or estrogens (birth control pills or hormone replacement).

Avoid using antacids without your doctor's advice. Use only the specific type of antacid your doctor recommends. Antacids contain different medicines and some types can make it harder for your body to absorb ursodiol.

To treat gallstones, you may have to take ursodiol for several months, and not all gallstones may completely dissolve. Many people who use this medicine will develop gallstones again within 5 years after treatment with ursodiol. Talk to your doctor about your specific risks for repeated gallstones.

To be sure this medication is helping your condition, your doctor may perform ultrasound examinations of your gallbladder on a regular basis. Your liver function may also need to be tested. Do not miss any scheduled visits to your doctor.

What should I discuss with my healthcare provider before taking Urso (ursodiol)?

Before using this medication, tell your doctor if you are allergic to any drugs, or if you have liver disease.

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether ursodiol passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

To treat gallstones, you may have to take ursodiol for several months, and not all gallstones may completely dissolve. Many people who use this medicine will develop gallstones again within 5 years after treatment with ursodiol. Talk to your doctor about your specific risks for repeated gallstones.

How should I take Urso (ursodiol)?

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

Take each dose with a full glass of water. The medication can be taken with meals unless your doctor tells you otherwise.

To be sure this medication is helping your condition, your doctor may perform ultrasound examinations of your gallbladder on a regular basis. Your liver function may also need to be tested. Do not miss any scheduled visits to your doctor.

It may take several months of taking ursodiol before your gallstones dissolve. Take this medication for the entire length of time prescribed by your doctor.

It is important to take ursodiol regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

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

What happens if I miss a dose?

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

What happens if I overdose?

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

An overdose of ursodiol is likely to cause diarrhea.

What should I avoid while taking Urso (ursodiol)?

Avoid using antacids without your doctor's advice. Use only the specific type of antacid your doctor recommends. Antacids contain different medicines and some types can make it harder for your body to absorb ursodiol.

Urso (ursodiol) 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.

Other less serious side effects are more likely to occur, such as:

• 
  

  fever, chills, body aches, flu symptoms;

  
  


• 
  

  stomach pain, nausea, diarrhea, constipation;

  
  


• 
  

  dizziness, tired feeling;

  
  


• 
  

  back pain;

  
  


• 
  

  runny or stuffy nose, cold symptoms; or

  
  


• 
  

  headache.

  
  

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.

What other drugs will affect Urso (ursodiol)?

Before taking ursodiol, tell your doctor if you are using any of the following drugs:

• 
  

  cholestyramine (Questran);

  
  


• 
  

  colestipol (Colestid);

  
  


• 
  

  estrogens (birth control pills or hormone replacement); or

  
  


• 
  

  antacids that contain aluminum, such as Rolaids, Mylanta, or Maalox).

  
  

If you are using any of these drugs, you may not be able to use ursodiol or you may need dosage adjustments or special tests during treatment.

There may be other drugs not listed that can affect ursodiol. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Urso resources

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

• Urso MedFacts Consumer Leaflet (Wolters Kluwer)


• Urso Advanced Consumer (Micromedex) - Includes Dosage Information


• Urso Prescribing Information (FDA)


• Ursodiol Prescribing Information (FDA)


• Ursodiol Professional Patient Advice (Wolters Kluwer)


• Ursodiol Monograph (AHFS DI)


• Actigall Prescribing Information (FDA)

Compare Urso with other medications

• Biliary Cirrhosis
• Gallbladder Disease
• Nonalcoholic Fatty Liver Disease

Where can I get more information?

• Your pharmacist has more information about ursodiol written for health professionals that you may read.

See also: Urso side effects (in more detail)

Nicardipine Injection

Dosage Form: injection - powder, for solution

Nicardipine Injection Description

Nicardipine hydrochloride is a calcium ion influx inhibitor (slow channel blocker or calcium channel blocker). Nicardipine hydrochloride for intravenous administration contains 2.5 mg/mL of nicardipine hydrochloride. Nicardipine hydrochloride is a dihydropyridine derivative with IUPAC (International Union of Pure and Applied Chemistry) chemical name (±)-2-(benzyl-methyl amino) ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate monohydrochloride and has the following structure:

Nicardipine hydrochloride is a greenish-yellow, odorless, crystalline powder that melts at about 169ºC. It is freely soluble in chloroform, methanol, and glacial acetic acid, sparingly soluble in anhydrous ethanol, slightly soluble in n-butanol, water, 0.01 M potassium dihydrogen phosphate, acetone, and dioxane, very slightly soluble in ethyl acetate, and practically insoluble in benzene, ether, and hexane. It has a molecular weight of 515.99. Nicardipine hydrochloride injection is available as a sterile, non-pyrogenic, clear, yellow solution in 10 mL vials for intravenous infusion after dilution. Each mL contains 2.5 mg nicardipine hydrochloride in water for injection, USP with 48 mg sorbitol, NF, buffered to pH 3.5 with 0.525 mg citric acid monohydrate, USP and 0.09 mg sodium hydroxide, NF. Additional citric acid and/or sodium hydroxide may have been added to adjust pH.

Nicardipine Injection - Clinical Pharmacology

Mechanism of Action

Nicardipine inhibits the transmembrane influx of calcium ions into cardiac muscle and smooth muscle without changing serum calcium concentrations. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. The effects of nicardipine are more selective to vascular smooth muscle than cardiac muscle. In animal models, nicardipine produced relaxation of coronary vascular smooth muscle at drug levels which cause little or no negative inotropic effect.

Pharmacokinetics and Metabolism

Following infusion, nicardipine plasma concentrations decline tri-exponentially, with a rapid early distribution phase (α-half-life of 2.7 minutes), an intermediate phase (β-half-life of 44.8 minutes), and a slow terminal phase (γ-half-life of 14.4 hours) that can only be detected after long-term infusions. Total plasma clearance (Cl) is 0.4 L/hr•kg, and the apparent volume of distribution (Vd) using a non-compartment model is 8.3 L/kg. The pharmacokinetics of nicardipine hydrochloride injection are linear over the dosage range of 0.5 to 40 mg/hr.

Rapid dose-related increases in nicardipine plasma concentrations are seen during the first two hours after the start of an infusion of nicardipine hydrochloride injection. Plasma concentrations increase at a much slower rate after the first few hours, and approach steady state at 24 to 48 hours. On termination of the infusion, nicardipine concentrations decrease rapidly, with at least a 50% decrease during the first two hours post-infusion. The effects of nicardipine on blood pressure significantly correlate with plasma concentrations.

Nicardipine is highly protein bound (> 95%) in human plasma over a wide concentration range.

Nicardipine hydrochloride injection has been shown to be rapidly and extensively metabolized by the liver. After coadministration of a radioactive intravenous dose of nicardipine hydrochloride injection with an oral 30 mg dose given every 8 hours, 49% of the radioactivity was recovered in the urine and 43% in the feces within 96 hours. None of the dose was recovered as unchanged nicardipine.

Nicardipine does not induce or inhibit its own metabolism and does not induce or inhibit hepatic microsomal enzymes. The steady-state pharmacokinetics of nicardipine are similar in elderly hypertensive patients (> 65 years) and young healthy adults.

Hemodynamics

Nicardipine hydrochloride injection produces significant decreases in systemic vascular resistance. In a study of intra-arterially administered nicardipine hydrochloride injection, the degree of vasodilation and the resultant decrease in blood pressure were more prominent in hypertensive patients than in normotensive volunteers. Administration of nicardipine hydrochloride injection to normotensive volunteers at dosages of 0.25 to 3 mg/hr for eight hours produced changes of < 5 mmHg in systolic blood pressure and < 3 mmHg in diastolic blood pressure.

An increase in heart rate is a normal response to vasodilation and decrease in blood pressure; in some patients these increases in heart rate may be pronounced. In placebo-controlled trials, the mean increases in heart rate were 7 ± 1 bpm in postoperative patients and 8 ± 1 bpm in patients with severe hypertension at the end of the maintenance period. Hemodynamic studies following intravenous dosing in patients with coronary artery disease and normal or moderately abnormal left ventricular function have shown significant increases in ejection fraction and cardiac output with no significant change, or a small decrease, in left ventricular end-diastolic pressure (LVEDP). There is evidence that nicardipine hydrochloride increases blood flow. Coronary dilatation induced by nicardipine hydrochloride injection improves perfusion and aerobic metabolism in areas with chronic ischemia, resulting in reduced lactate production and augmented oxygen consumption. In patients with coronary artery disease, nicardipine hydrochloride injection, administered after beta-blockade, significantly improved systolic and diastolic left ventricular function. In congestive heart failure patients with impaired left ventricular function, nicardipine hydrochloride injection increased cardiac output both at rest and during exercise. Decreases in left ventricular end-diastolic pressure were also observed. However, in some patients with severe left ventricular dysfunction, it may have a negative inotropic effect and could lead to worsened failure.

“Coronary steal” has not been observed during treatment with nicardipine hydrochloride injection. (Coronary steal is the detrimental redistribution of coronary blood flow in patients with coronary artery disease from underperfused areas toward better perfused areas.) Nicardipine hydrochloride injection has been shown to improve systolic shortening in both normal and hypokinetic segments of myocardial muscle. Radionuclide angiography has confirmed that wall motion remained improved during increased oxygen demand. (Occasional patients have developed increased angina upon receiving oral nicardipine. Whether this represents coronary steal in these patients, or is the result of increased heart rate and decreased diastolic pressure, is not clear.)

In patients with coronary artery disease, nicardipine hydrochloride injection improves left ventricular diastolic distensibility during the early filling phase, probably due to a faster rate of myocardial relaxation in previously underperfused areas. There is little or no effect on normal myocardium, suggesting the improvement is mainly by indirect mechanisms such as afterload reduction and reduced ischemia. Nicardipine hydrochloride injection has no negative effect on myocardial relaxation at therapeutic doses. The clinical benefits of these properties have not yet been demonstrated.

Electrophysiologic Effects

In general, no detrimental effects on the cardiac conduction system have been seen with nicardipine hydrochloride injection. During acute electrophysiologic studies, it increased heart rate and prolonged the corrected QT interval to a minor degree. It did not affect sinus node recovery or SA conduction times. The PA, AH, and HV intervals* or the functional and effective refractory periods of the atrium were not prolonged. The relative and effective refractory periods of the His-Purkinje system were slightly shortened.

*PA = conduction time from high to low right atrium; AH = conduction time from low right atrium to His bundle deflection, or AV nodal conduction time; HV = conduction time through the His bundle and the bundle branch-Purkinje system.

Hepatic Function

Because the liver extensively metabolizes nicardipine, plasma concentrations are influenced by changes in hepatic function. In a clinical study with oral nicardipine in patients with severe liver disease, plasma concentrations were elevated and the half-life was prolonged (see PRECAUTIONS). Similar results were obtained in patients with hepatic disease when nicardipine hydrochloride injection was administered for 24 hours at 0.6 mg/hr.

Renal Function

When nicardipine hydrochloride injection was given to mild to moderate hypertensive patients with moderate degrees of renal impairment, significant reduction in glomerular filtration rate (GFR) and effective renal plasma flow (RPF) was observed. No significant differences in liver blood flow were observed in these patients. A significantly lower systemic clearance and higher area under the curve (AUC) were observed.

When oral nicardipine (20 mg or 30 mg TID) were given to hypertensive patients with impaired renal function, mean plasma concentrations, AUC, and Cmax were approximately 2-fold higher than in healthy controls. There is a transient increase in electrolyte excretion, including sodium (see PRECAUTIONS).

Acute bolus administration of nicardipine hydrochloride injection (2.5 mg) in healthy volunteers decreased mean arterial pressure and renal vascular resistance; glomerular filtration rate (GFR), renal plasma flow (RPF), and the filtration fraction were unchanged. In healthy patients undergoing abdominal surgery, nicardipine hydrochloride injection (10 mg over 20 minutes) increased GFR with no change in RPF when compared with placebo. In hypertensive type II diabetic patients with nephropathy, oral nicardipine (20 mg TID) did not change RPF and GFR, but reduced renal vascular resistance.

Pulmonary Function

In two well controlled studies of patients with obstructive airway disease treated with oral nicardipine, no evidence of increased bronchospasm was seen. In one of the studies, oral nicardipine improved forced expiratory volume 1 second (FEV1) and forced vital capacity (FVC) in comparison with metoprolol. Adverse experiences reported in a limited number of patients with asthma, reactive airway disease, or obstructive airway disease are similar to all patients treated with oral nicardipine.

Effects in Hypertension

In patients with mild to moderate chronic stable essential hypertension, nicardipine hydrochloride injection (0.5 to 4 mg/hr) produced dose dependent decreases in blood pressure, although only the decreases at 4 mg/hr were statistically different from placebo. At the end of a 48-hour infusion at 4 mg/hr, the decreases were 26 mmHg (17%) in systolic blood pressure and 20.7 mmHg (20%) in diastolic blood pressure. In other settings (e.g., patients with severe or postoperative hypertension), nicardipine hydrochloride injection (5 to 15 mg/hr) produced dose dependent decreases in blood pressure. Higher infusion rates produced therapeutic responses more rapidly. The mean time to therapeutic response for severe hypertension, defined as diastolic blood pressure ≤ 95 mmHg or ≥ 25 mmHg decrease and systolic blood pressure ≤ 160 mmHg, was 77 ± 5.2 minutes. The average maintenance dose was 8 mg/hr. The mean time to therapeutic response for postoperative hypertension, defined as ≥ 15% reduction in diastolic or systolic blood pressure, was 11.5 ± 0.8 minutes. The average maintenance dose was 3 mg/hr.

Indications and Usage for Nicardipine Injection

Nicardipine hydrochloride injection is indicated for the short-term treatment of hypertension when oral therapy is not feasible or not desirable. For prolonged control of blood pressure, transfer patients to oral medication as soon as their clinical condition permits (see DOSAGE AND ADMINISTRATION).

Contraindications

Nicardipine hydrochloride injection is contraindicated in patients with advanced aortic stenosis because part of the effect of nicardipine hydrochloride injection is secondary to reduced afterload. Reduction of diastolic pressure in these patients may worsen rather than improve myocardial oxygen balance.

Warnings

Use in Patients with Angina

Increases in frequency, duration, or severity of angina have been seen in chronic oral therapy with oral nicardipine. Induction or exacerbation of angina has been seen in less than 1% of coronary artery disease patients treated with nicardipine hydrochloride injection. The mechanism of this effect has not been established.

Use in Patients with Heart Failure

Titrate slowly when using nicardipine hydrochloride injection, particularly in combination with a beta-blocker, in patients with heart failure or significant left ventricular dysfunction because of possible negative inotropic effects.

Intravenous Infusion Site

To reduce the possibility of venous thrombosis, phlebitis, local irritation, swelling, extravasation, and the occurrence of vascular impairment, administer drug through large peripheral veins or central veins rather than arteries or small peripheral veins, such as those on the dorsum of the hand or wrist. To minimize the risk of peripheral venous irritation, change the site of the drug infusion every 12 hours.

Precautions

General

Blood Pressure

In administering nicardipine, close monitoring of blood pressure and heart rate is required. Nicardipine may occasionally produce symptomatic hypotension or tachycardia. Avoid systemic hypotension when administering the drug to patients who have sustained an acute cerebral infarction or hemorrhage.

Use in Patients with Impaired Hepatic Function

Since nicardipine is metabolized in the liver, consider lower dosages and closely monitor responses in patients with impaired liver function or reduced hepatic blood flow.

Use in Patients with Impaired Renal Function

When nicardipine hydrochloride injection was given to mild to moderate hypertensive patients with moderate renal impairment, a significantly lower systemic clearance and higher area under the curve (AUC) was observed. These results are consistent with those seen after oral administration of nicardipine. Titrate gradually in patients with renal impairment.

Drug Interactions

Beta-Blockers

In most patients, nicardipine hydrochloride injection can safely be used concomitantly with beta-blockers. However, titrate slowly when using nicardipine hydrochloride injection in combination with a beta-blocker in heart failure patients (see WARNINGS).

Cimetidine

Cimetidine has been shown to increase nicardipine plasma concentrations with oral nicardipine administration. Frequently monitor response in patients receiving both drugs. Data with other histamine-2 antagonists are not available.

Cyclosporine

Concomitant administration of oral nicardipine and cyclosporine results in elevated plasma cyclosporine levels. Closely monitor plasma concentrations of cyclosporine during nicardipine hydrochloride injection administration, and reduce the dose of cyclosporine accordingly.

In Vitro Interaction

The plasma protein binding of nicardipine was not altered when therapeutic concentrations of furosemide, propranolol, dipyridamole, warfarin, quinidine, or naproxen were added to human plasma in vitro.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Rats treated with nicardipine in the diet (at concentrations calculated to provide daily dosage levels of 5, 15, or 45 mg/kg/day) for two years showed a dose-dependent increase in thyroid hyperplasia and neoplasia (follicular adenoma/carcinoma). One- and three-month studies in the rat have suggested that these results are linked to a nicardipine-induced reduction in plasma thyroxine (T4) levels with a consequent increase in plasma levels of thyroid stimulating hormone (TSH). Chronic elevation of TSH is known to cause hyperstimulation of the thyroid. In rats on an iodine deficient diet, nicardipine administration for one month was associated with thyroid hyperplasia that was prevented by T4 supplementation. Mice treated with nicardipine in the diet (at concentrations calculated to provide daily dosage levels of up to 100 mg/kg/day) for up to 18 months showed no evidence of neoplasia of any tissue and no evidence of thyroid changes. There was no evidence of thyroid pathology in dogs treated with up to 25 mg nicardipine/kg/day for one year and no evidence of effects of nicardipine on thyroid function (plasma T4 and TSH) in man. There was no evidence of a mutagenic potential of nicardipine in a battery of genotoxicity tests conducted on microbial indicator organisms, in micronucleus tests in mice and hamsters, or in a sister chromatid exchange study in hamsters. No impairment of fertility was seen in male or female rats administered nicardipine at oral doses as high as 100 mg/kg/day (human equivalent dose about 16 mg/kg/day, 8 times the maximum recommended oral dose).

Pregnancy

Teratogenic Effects. Pregnancy Category C

There are no adequate and well controlled studies of nicardipine use in pregnant women. However, limited human data in pregnant women with preeclampsia or pre-term labor are available. In animal studies, no embryotoxicity occurred in rats with oral doses 8 times the maximum recommended human dose (MRHD) based on body surface area (mg/m2), but did occur in rabbits with oral doses at 24 times the maximum recommended human dose (MRHD) based on body surface area (mg/m2). Nicardipine hydrochloride injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Hypotension, reflex tachycardia, postpartum hemorrhage, tocolysis, headache, nausea, dizziness, and flushing have been reported in pregnant women who were treated with intravenous nicardipine for hypertension during pregnancy. Fetal safety results ranged from transient fetal heart rate decelerations to no adverse events. Neonatal safety data ranged from hypotension to no adverse events.

Adverse events in women treated with intravenous nicardipine during pre-term labor include pulmonary edema, dyspnea, hypoxia, hypotension, tachycardia, headache, and phlebitis at site of injection. Neonatal adverse events include acidosis (pH < 7.25).

In embryofetal toxicity studies, nicardipine was administered intravenously to pregnant rats and rabbits during organogenesis at doses up to 0.14 times the MRHD based on body surface area (mg/m2) (5 mg/kg/day) (rats) and 0.03 times the MRHD based on body surface area (mg/m2) (0.5 mg/kg/day) (rabbits). No embryotoxicity or teratogenicity was seen at these doses. Embryotoxicity, but not teratogenicity was seen at 0.27 times the MRHD based on body surface area (mg/m2) (10 mg/kg/day) in rats and at 0.05 times the MRHD based on body surface area (mg/m2) (1 mg/kg/day) in rabbits.

In other animal studies, pregnant Japanese White rabbits received oral nicardipine during organogenesis, at doses 8 and 24 times the MRHD based on body surface area (mg/m2) (50 and 150 mg/kg/day). Embryotoxicity occurred at the high dose along with signs of maternal toxicity (marked maternal weight gain suppression). New Zealand albino rabbits received oral nicardipine during organogenesis at doses up to 16 times the MRHD based on body surface area (mg/m2) (100 mg nicardipine/kg/day). While significant maternal mortality occurred, no adverse effects on the fetus were observed. Pregnant rats received oral nicardipine from day 6 through day 15 of gestation at doses up to 8 times the MRHD based on body surface area (mg/m2) (100 mg/kg/day). There was no evidence of embryotoxicity or teratogenicity; however, dystocia, reduced birth weights, reduced neonatal survival, and reduced neonatal weight gain were noted.

Nursing Mothers

Nicardipine is minimally excreted into human milk. Among 18 infants exposed to nicardipine through breast milk in the postpartum period, calculated daily infant dose was less than 0.3 mcg and there were no adverse events observed. Consider the possibility of infant exposure when using nicardipine in nursing mothers.

In a study of 11 women who received oral nicardipine 4 to 14 days postpartum, four women received immediate-release nicardipine 40 mg to 80 mg daily, six received sustained-release nicardipine 100 mg to 150 mg daily, and one received intravenous nicardipine 120 mg daily. The peak milk concentration was 7.3 mcg/L (range 1.9 to 18.8), and the mean milk concentration was 4.4 mcg/L (range 1.3 to 13.8). Infants received an average of 0.073% of the weight-adjusted maternal oral dose and 0.14% of the weight-adjusted maternal intravenous dose.

In another study of seven women who received intravenous nicardipine for an average of 1.9 days in the immediate postpartum period as therapy for preeclampsia, 34 milk samples were obtained at unspecified times and nicardipine was undetectable (< 5 mcg/L) in 82% of the samples. Four women who received 1 to 6.5 mg/hour of nicardipine had six milk samples with detectable nicardipine levels (range 5.1 to 18.5 mcg/L). The highest concentration of 18.5 mcg/L was found in a woman who received 5.5 mg/hour of nicardipine. The estimated maximum dose in a breastfed infant was < 0.3 mcg daily or between 0.015% to 0.004% of the therapeutic dose in a 1 kg infant.

Pediatric Use

Safety and efficacy in patients under the age of 18 have not been established.

Use in the Elderly

The steady-state pharmacokinetics of nicardipine are similar in elderly hypertensive patients (> 65 years) and young healthy adults.

Clinical studies of nicardipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, use low initial doses in elderly patients, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE EXPERIENCES

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials doses, however, provides a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Two hundred forty-four patients participated in two multicenter, double-blind, placebo-controlled trials of nicardipine hydrochloride injection. Adverse experiences were generally not serious and most were expected consequences of vasodilation. Adverse experiences occasionally required dosage adjustment. Therapy was discontinued in approximately 12% of patients, mainly due to hypotension, headache, and tachycardia.

The table below shows percentage of patients with adverse events where the rate is > 3% more common on nicardipine hydrochloride injection than placebo.

Adverse Experience	Nicardipine Hydrochloride Injection (n = 144)	Placebo (n = 100)
Body as a Whole
Headache (%, n)	21 (15)	2 (2)
Cardiovascular
Hypotension (%, n)	8 (6)	1 (1)
Tachycardia (%, n)	5 (4)	0
Digestive
Nausea/vomiting (%, n)	7 (5)	1 (1)

 

Other adverse events have been reported in clinical trials or in the literature in association with the use of intravenously administered nicardipine.

Body as a Whole: fever, neck pain

Cardiovascular: angina pectoris, atrioventricular block, ST segment depression, inverted T wave, deep-vein thrombophlebitis

Digestive: dyspepsia

Hemic and Lymphatic: thrombocytopenia

Metabolic and Nutritional: hypophosphatemia, peripheral edema

Nervous: confusion, hypertonia

Respiratory: respiratory disorder

Special Senses: conjunctivitis, ear disorder, tinnitus

Urogenital: urinary frequency

Sinus node dysfunction and myocardial infarction, which may be due to disease progression, have been seen in patients on chronic therapy with orally administered nicardipine.

Overdosage

Several overdosages with orally administered nicardipine have been reported. One adult patient allegedly ingested 600 mg of nicardipine [standard (immediate-release) capsules], and another patient, 2160 mg of the sustained-release formulation of nicardipine. Symptoms included marked hypotension, bradycardia, palpitations, flushing, drowsiness, confusion and slurred speech. All symptoms resolved without sequelae. An overdosage occurred in a one-year-old child who ingested half of the powder in a 30 mg nicardipine standard capsule. The child remained asymptomatic.

Based on results obtained in laboratory animals, lethal overdose may cause systemic hypotension, bradycardia (following initial tachycardia) and progressive atrioventricular conduction block. Reversible hepatic function abnormalities and sporadic focal hepatic necrosis were noted in some animal species receiving very large doses of nicardipine.

For treatment of overdosage, implement standard measures including monitoring of cardiac and respiratory functions. Position the patient so as to avoid cerebral anoxia. Use vasopressors for patients exhibiting profound hypotension.

Nicardipine Injection Dosage and Administration

Nicardipine hydrochloride injection is intended for intravenous use. Titrate dose to achieve the desired blood pressure reduction. Individualize dosage depending on the blood pressure to be obtained and the response of the patient.

The time course of blood pressure decrease is dependent on the initial rate of infusion and the frequency of dosage adjustment. With constant infusion, blood pressure begins to fall within minutes. It reaches about 50% of its ultimate decrease in about 45 minutes.

Preparation

WARNING: VIALS MUST BE DILUTED BEFORE INFUSION.

Dilution

Nicardipine hydrochloride injection is administered by slow continuous infusion at a CONCENTRATION OF 0.1 mg/mL. Each vial (25 mg) should be diluted with 240 mL of compatible intravenous fluid (see below), resulting in 250 mL of solution at a concentration of 0.1 mg/mL.

Nicardipine hydrochloride injection has been found to be compatible and stable in glass or polyvinyl chloride containers for 24 hours at controlled room temperature with:

Dextrose (5%) Injection, USP

Dextrose (5%) and Sodium Chloride (0.45%) Injection, USP

Dextrose (5%) and Sodium Chloride (0.9%) Injection, USP

Dextrose (5%) with 40 mEq Potassium, USP

Sodium Chloride (0.45%) Injection, USP

Sodium Chloride (0.9%) Injection, USP

Nicardipine hydrochloride injection is NOT compatible with Sodium Bicarbonate (5%) Injection, USP or Lactated Ringer’s Injection, USP.

THE DILUTED SOLUTION IS STABLE FOR 24 HOURS AT ROOM TEMPERATURE.

Inspection

As with all parenteral drugs, nicardipine hydrochloride injection should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Nicardipine hydrochloride injection is normally light yellow in color.

Dosage

Dosage as a Substitute for Oral Nicardipine Therapy

The intravenous infusion rate required to produce an average plasma concentration equivalent to a given oral dose at steady state is shown in the following table:

Oral Nicardipine Dose	Equivalent I.V. Infusion Rate
20 mg q8h	0.5 mg/hr = 5 mL/hr
30 mg q8h	1.2 mg/hr = 12 mL/hr
40 mg q8h	2.2 mg/hr = 22 mL/hr

Dosage for Initiation of Therapy in a Patient Not Receiving Oral Nicardipine

Initiate therapy at 50 mL/hr (5 mg/hr). If desired blood pressure reduction is not achieved at this dose, the infusion rate may be increased by 25 mL/hr (2.5 mg/hr) every 5 minutes (for rapid titration) to 15 minutes (for gradual titration) up to a maximum of 150 mL/hr (15 mg/hr), until desired blood pressure reduction is achieved. Following achievement of the blood pressure goal utilizing rapid titration, decrease the infusion rate to 30 mL/hr (3 mg/hr).

Drug Discontinuation and Transfer to Oral Antihypertensive Agents

Discontinuation of infusion is followed by a 50% offset action in about 30 minutes.

If treatment includes transfer to an oral antihypertensive agent other than oral nicardipine, initiate therapy upon discontinuation of nicardipine hydrochloride injection.

If oral nicardipine is to be used, administer the first dose one hour prior to discontinuation of the infusion.

How is Nicardipine Injection Supplied

Nicardipine Hydrochloride Injection, 25 mg/10 mL (2.5 mg/mL) is available as:

NDC 67457-224-10

25 mg of nicardipine hydrochloride in a 10 mL single dose vial; in cartons containing 10 vials

Store at 20º to 25ºC (68º to 77ºF). [See USP Controlled Room Temperature.]

Freezing does not adversely affect the product, but exposure to elevated temperatures should be avoided.

Protect from light. Store vials in carton until used.

Manufactured for:

Mylan Institutional LLC

Rockford, IL 61103 U.S.A.

Manufactured by:

Gland Pharma Ltd

Hyderabad 500 043

India

M.L.: 103/AP/RR/97/F/R

JULY 2011

MI:NICAIJ:R1

  

PRINCIPAL DISPLAY PANEL - 25 mg/10 mL

NDC 67457-224-10

For Intravenous Infusion Only

NICARdipine

Hydrochloride

Injection

25 mg/10 mL

(2.5 mg/mL)

WARNING: MUST BE DILUTED BEFORE INFUSION

Rx only      10 x 10 mL Single Dose Vials

Sterile.

Each 10 mL vial contains: 25 mg nicardipine

hydrochloride in water for injection, USP, with 480 mg

sorbitol, NF. Buffered with 5.25 mg citric acid

monohydrate, USP, and 0.9 mg sodium hydroxide, NF.

Additional citric acid and/or sodium hydroxide may have

been added to adjust pH.

Usual Dosage: See accompanying prescribing

information.

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

Room Temperature.]

Protect from light.

Store in carton until time of use.

Manufactured for:

Mylan Institutional LLC

Rockford, IL 61103 U.S.A.

Made in India

M.L.: 103/AP/RR/97/F/R

MI:224:10C:R1

NICARDIPINE HYDROCHLORIDE  nicardipine  powder, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 67457-224 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength NICARDIPINE HYDROCHLORIDE (NICARDIPINE) NICARDIPINE HYDROCHLORIDE 2.5 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength WATER   CITRIC ACID MONOHYDRATE 0.525 mg  in 1 mL SORBITOL 48 mg  in 1 mL SODIUM HYDROXIDE 0.09 mg  in 1 mL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 67457-224-10 10  In 1 CARTON contains a VIAL 1 10 mL In 1 VIAL This package is contained within the CARTON (67457-224-10)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA090664	12/13/2011

Labeler - Mylan Institutional LLC (790384502)

Revised: 07/2011Mylan Institutional LLC