Keppra

Generic Name: Levetiracetam
Class: Anticonvulsants, Miscellaneous
VA Class: CN400
Molecular Formula: C₈H₁₄N₂O₂
CAS Number: 102767-28-2

Special Alerts:

[UPDATE 05/05/2009] FDA notified healthcare professionals that it approved updated labeling for antiepileptic drugs used to treat epilepsy, psychiatric disorders, and other conditions (e.g., migraine and neuropathic pain syndromes). FDA also required development of a medication guide, to be issued to patients each time the product is dispensed. Since issuing safety alerts on December 16, 2008 and January 31, 2008, FDA has been working with the manufacturers of drugs in this class to better understand the suicidality risk. Eleven antiepileptic drugs were included in a pooled analysis of placebo-controlled clinical studies in which these drugs were used to treat epilepsy as well as psychiatric disorders and other conditions. The increased risk of suicidal thoughts or behavior was generally consistent among the eleven drugs, with varying mechanisms of action and across a range of indications. This observation suggests that the risk applies to all antiepileptic drugs used for any indication.

The drugs included in the analyses include (some of these drugs are also available in generic form):

• 
  

  Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)

  
  


• 
  

  Felbamate (marketed as Felbatol)

  
  


• 
  

  Gabapentin (marketed as Neurontin)

  
  


• 
  

  Lamotrigine (marketed as Lamictal)

  
  


• 
  

  Levetiracetam (marketed as Keppra)

  
  


• 
  

  Oxcarbazepine (marketed as Trileptal)

  
  


• 
  

  Pregabalin (marketed as Lyrica)

  
  


• 
  

  Tiagabine (marketed as Gabitril)

  
  


• 
  

  Topiramate (marketed as Topamax)

  
  


• 
  

  Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)

  
  


• 
  

  Zonisamide (marketed as Zonegran)

  
  

For more information visit the FDA website at: and .

[UPDATE 12/16/2008] The FDA has completed its analysis of reports of suicidality (suicidal behavior or ideation [thoughts]) from placebo-controlled clinical trials of drugs used to treat epilepsy, psychiatric disorders, and other conditions. Based on the outcome of this review, FDA is requiring that all manufacturers of drugs in this class include a Warning in their labeling and develop a Medication Guide to be provided to patients prescribed these drugs to inform them of the risks of suicidal thoughts or actions.

For more information visit the FDA website at: and .

[Posted 01/31/2008] FDA informed healthcare professionals that the Agency has analyzed reports of suicidality (suicidal behavior or ideation) from placebo-controlled clinical studies of eleven drugs used to treat epilepsy as well as psychiatric disorders, and other conditions. In the FDA’s analysis, patients receiving antiepileptic drugs had approximately twice the risk of suicidal behavior or ideation (0.43%) compared to patients receiving placebo (0.22%). The increased risk of suicidal behavior and suicidal ideation was observed as early as one week after starting the antiepileptic drug and continued through 24 weeks. The results were generally consistent among the eleven drugs. The relative risk for suicidality was higher in patients with epilepsy compared to patients who were given one of the drugs in the class for psychiatric or other conditions.

Healthcare professionals should closely monitor all patients currently taking or starting any antiepileptic drug for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.

The drugs included in the analyses include (some of these drugs are also available in generic form):

• 
  

  Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)

  
  


• 
  

  Felbamate (marketed as Felbatol)

  
  


• 
  

  Gabapentin (marketed as Neurontin)

  
  


• 
  

  Lamotrigine (marketed as Lamictal)

  
  


• 
  

  Levetiracetam (marketed as Keppra)

  
  


• 
  

  Oxcarbazepine (marketed as Trileptal)

  
  


• 
  

  Pregabalin (marketed as Lyrica)

  
  


• 
  

  Tiagabine (marketed as Gabitril)

  
  


• 
  

  Topiramate (marketed as Topamax)

  
  


• 
  

  Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)

  
  


• 
  

  Zonisamide (marketed as Zonegran)

  
  

Although the 11 drugs listed above were the ones included in the analysis, FDA expects that the increased risk of suicidality is shared by all antiepileptic drugs and anticipates that the class labeling changes will be applied broadly. For more information visit the FDA website at: and .

REMS:

FDA approved a REMS for levetiracetam to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Anticonvulsant; a pyrrolidine derivative.^{1 2 3 5}

Uses for Keppra

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Seizure Disorders

Management (in combination with other anticonvulsants) of partial seizures in adults with epilepsy.^{1 2 3}

Keppra Dosage and Administration

Administration

Oral Administration

Administer orally twice daily without regard to meals.¹

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Adults

Seizure Disorders

Partial Seizures

Oral

Initially, 500 mg twice daily.^{1 2 3}

If response is inadequate, dosage may be increased by 1 g daily at 2-week intervals.^{1 2}

Some clinicians reportedly initiate therapy with dosages of 2–4 g daily.³

Dosages >3 g daily may not be associated with increased therapeutic benefit.^{1 2}

Do not discontinue abruptly;¹ withdraw gradually by reducing dosage by 1 g daily at 2-week intervals.⁵ (See Discontinuance of Levetiracetam under Cautions.)

Prescribing Limits

Adults

Seizure Disorders

Partial Seizures

Oral

Maximum 3 g daily recommended by the manufacturer.¹

Special Populations

Renal Impairment

Modify dosage according to the degree of impairment based on patient’s measured or estimated Cl_cr.^{1 2} (See Table 1.)

Table 1. Recommended Dosage Based on Clcr1

Renal Function	Clcr (mL/minute)	Dosage
Normal	>80	500–1500 mg every 12 hours
Mild	50–80	500–1000 mg every 12 hours
Moderate	30–50	250–750 mg every 12 hours
Severe	<30	250–500 mg every 12 hours
ESRD patients using dialysis	–	500–1000 mg every 24 hours; following dialysis, a 250- to 500-mg supplemental dose is recommended

Geriatric Patients

Select dosage carefully^{1 2} and consider monitoring renal function during therapy.¹

Cautions for Keppra

Contraindications

• 
  

  Known hypersensitivity to levetiracetam or any ingredient in the formulation.^{1 2}

  
  

Warnings/Precautions

Warnings

Nervous System Effects

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Possible adverse neuropsychiatric effects are classified into 3 categories: somnolence and fatigue; coordination difficulties; behavioral changes.^{1 2}

Somnolence, asthenia, and coordination difficulties occur most frequently within first 4 weeks of treatment.^{1 2}

Psychotic manifestations and hallucinations reported rarely.^{1 2}

Possible behavioral symptoms (e.g., agitation, hostility, anxiety, apathy, emotional lability, depersonalization, depression, aggression, anger, irritability).¹

Discontinuance of Levetiracetam

Abrupt withdrawal may result in increased seizure frequency or status epilepticus.^{1 2} (See Partial Seizures under Dosage and Administration.)

General Precautions

Hematologic Effects

Minor decreases in total mean erythrocyte count, mean hemoglobin, and mean hematocrit possible.¹

Possible leukopenia, neutropenia, pancytopenia with myelosuppression in some cases, and thrombocytopenia.¹

Hepatic Effects

No meaningful changes in liver function test results in controlled studies.¹

Possible Prescribing and Dispensing Errors

Ensure accuracy of prescription; similarity in spelling of Keppra (levetiracetam) and Kaletra (fixed combination of lopinavir and ritonavir, both antiretroviral agents) may result in errors.⁷

Specific Populations

Pregnancy

Category C.¹

Keppra Pregnancy Registry at 888-537-7734 or North American Antiepileptic Drug Pregnancy Registry at 888-233-2334.¹

Lactation

Distributed into milk.¹ Discontinue nursing or the drug because of potential risk in nursing infant.¹

Pediatric Use

Safety and efficacy not established in children <16 years of age.^{1 2}

Geriatric Use

No substantial differences in safety relative to younger adults; insufficient experience in patients ≥65 years of age to determine whether efficacy is similar.^{1 2}

Renal Impairment

Dosage adjustment recommended for patients with decreased Cl_cr.^{1 2} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Somnolence, asthenia, headache, infection, dizziness, pain, pharyngitis.^{1 2}

Interactions for Keppra

Not a high-affinity substrate for or inhibitor of CYP isoenzymes.^{1 2}

Drugs Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interaction unlikely.^{1 2}

Protein-bound Drugs

Pharmacokinetic interaction unlikely.^{1 2}

Specific Drugs

Drug	Interaction	Comments
Anticonvulsants (e.g., carbamazepine, gabapentin, lamotrigine, phenobarbital, phenytoin, primidone, valproic acid)	Pharmacokinetic interaction unlikely1 2
Digoxin	Pharmacokinetic interaction unlikely1 2
Oral contraceptives	Pharmacokinetic interaction unlikely1 2
Probenecid	No effect on levetiracetam pharmacokinetics, but steady-state plasma concentrations of principal inactive metabolite of levetiracetam approximately doubled because of 60% reduction in renal clearance1 2	Clinically unimportant5
Warfarin	Pharmacokinetic interaction unlikely1 2

Keppra Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed (nearly 100% bioavailable) following oral administration, with peak plasma concentrations attained in approximately 1 hour.¹

Commercially available tablets and oral solution are bioequivalent.¹

Food

Food does not affect bioavailability but delays time to peak plasma concentration by 1.5 hours and decreases peak plasma concentration by 20%.¹

Distribution

Extent

Distributed into milk.¹

Plasma Protein Binding

<10%.¹

Elimination

Metabolism

Not extensively metabolized.¹ About 24% of an administered dose is metabolized to an inactive metabolite by hydrolysis of the acetamide group; metabolism is not dependent on CYP isoenzymes.¹

Elimination Route

Excreted principally as unchanged drug (66%) in urine.¹

Clearance is correlated with Cl_cr.¹

Half-life

6–8 hours.¹

Special Populations

In patients with renal impairment, clearance is reduced by 40, 50, and 60% in patients with mild, moderate, and severe renal impairment, respectively.¹ In patients with end-stage renal disease, clearance is reduced by about 70%; hemodialysis removes about 50% of body stores of levetiracetam.¹ (See Renal Impairment under Dosage and Administration.)

In patients with severe hepatic impairment (Child Pugh class C), total body clearance is reduced by 50%, principally due to decreased renal clearance; pharmacokinetics unchanged in patients with mild (Child Pugh class A) to moderate (Child Pugh class B) hepatic impairment.¹

In geriatric patients with Cl_cr of 30–74 mL/minute, total body clearance is reduced by 38% and half-life increased by 2.5 hours, but no pharmacokinetic differences related solely to age observed.^{1 2}

In pediatric patients 6–12 years of age, body weight-adjusted apparent clearance is approximately 40% higher than in adults.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

Solution

25°C (may be exposed to 15–30°C).¹

Actions

• 
  

  Structurally unrelated to other currently available anticonvulsants.^{1 2 3 5}

  
  


• 
  

  Mechanism of anticonvulsant action is not known.^{1 2 4}

  
  


• 
  

  Protection observed against secondarily generalized activity from focal seizures induced by 2 chemoconvulsants known to induce seizures that mimic some features of human complex partial seizures with secondary generalization.^{1 2}

  
  


• 
  

  Demonstrated inhibitory properties in the kindling model in rats, another model of human complex partial seizures.^{1 2 4}

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Provide copy of manufacturer’s patient information.¹

  
  


• 
  

  Risk of adverse neuropsychiatric effects (e.g., somnolence, fatigue, dizziness, coordination difficulties, behavioral changes), especially during the initial weeks of therapy.^{1 2}

  
  


• 
  

  Risk of drowsiness; avoid driving, operating machinery, or performing hazardous tasks until effects on individual are known.^{1 2 5}

  
  


• 
  

  Importance of adhering to prescribed directions for use.¹

  
  


• 
  

  Importance of not abruptly discontinuing therapy.^{1 2}

  
  


• 
  

  Use in combination with other anticonvulsants, not as monotherapy.^{1 2}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 2} Importance of clinicians informing women about existence of and encouraging enrollment in pregnancy registries. (See Pregnancy under Cautions.)

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary supplements, and/or herbal products, as well as any concomitant illness (e.g., renal disease).¹

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Levetiracetam

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution	100 mg/mL	Keppra Oral Solution (dye-free; with glycerin and parabens)	UCB Pharma
	Tablets, film-coated	250 mg	Keppra (scored)	UCB Pharma
		500 mg	Keppra (scored)	UCB Pharma
		750 mg	Keppra (scored)	UCB Pharma

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Keppra 100MG/ML Solution (UCB PHARMA): 473/$437.98 or 1419/$1,306.04

Keppra 1000MG Tablets (UCB PHARMA): 60/$570.02 or 180/$1,690.05

Keppra 250MG Tablets (UCB PHARMA): 10/$51.99 or 30/$129.97

Keppra 500MG Tablets (UCB PHARMA): 30/$149.99 or 90/$429.97

Keppra 750MG Tablets (UCB PHARMA): 30/$189.99 or 90/$549.95

Keppra XR 500MG 24-hr Tablets (UCB PHARMA): 60/$245.98 or 180/$699.97

Keppra XR 750MG 24-hr Tablets (UCB PHARMA): 60/$349.98 or 180/$1,019.91

Levetiracetam 100MG/ML Solution (ROXANE): 473/$259.99 or 1419/$719.96

Levetiracetam 1000MG Tablets (LUPIN PHARMACEUTICALS): 60/$209.99 or 180/$599.98

Levetiracetam 250MG Tablets (LUPIN PHARMACEUTICALS): 60/$23.99 or 120/$37.97

Levetiracetam 500MG Tablets (LUPIN PHARMACEUTICALS): 30/$29.99 or 90/$59.97

Levetiracetam 750MG Tablets (LUPIN PHARMACEUTICALS): 60/$34.99 or 120/$57.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. UCB Pharma, Inc. Keppra (levetiracetam) tablets and oral solution prescribing information. Smyrna, GA; 2004 Nov.

2. UCB Pharma. Keppra (levetiracetam) tablets product monograph. Smyrna, GA; 2002.

3. Anon. Two new drugs for epilepsy. Med Lett Drugs Ther. 2000; 42:33-5. [PubMed 10803174]

4. Haria M, Balfour JA. Levetiracetam. CNS Drugs. 1997; 7:159-64.

5. UCB Pharma, Smyrna, GA: Personal communication.

6. Krakow K, Walker M, Otoul C et al. Long-term continuation of levetiracetam in patients with refractory epilepsy. Neurology. 2001; 56:1772-4. [IDIS 466256] [PubMed 11425954]

7. Magnus L. Dear healthcare professional letter: Dispensing error alert. Smyrna, GA: UCB Pharma, Inc; 2003 Sep.

8. Institute for Safe Medication Practices. What’s in a name? Ways to prevent dispensing errors linked to name confusion. ISMP Medication Safety Alert!. Huntingdon Valley, PA; 2002 Jun 12.

More Keppra resources

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

• Keppra Prescribing Information (FDA)


• Keppra Consumer Overview


• Keppra Advanced Consumer (Micromedex) - Includes Dosage Information


• Keppra MedFacts Consumer Leaflet (Wolters Kluwer)


• Keppra XR Extended-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Levetiracetam Prescribing Information (FDA)


• Levetiracetam Professional Patient Advice (Wolters Kluwer)

Compare Keppra with other medications

• Bipolar Disorder
• Epilepsy
• Hyperekplexia
• Neuralgia
• New Daily Persistent Headache
• Seizures

Flovent

Generic Name: fluticasone (Inhalation route)

floo-TIK-a-sone

Commonly used brand name(s)

In the U.S.

• Flovent


• Flovent Diskus


• Flovent HFA


• Flovent Rotadisk

Available Dosage Forms:

• Powder


• Disk


• Aerosol Powder

Therapeutic Class: Anti-Inflammatory

Pharmacologic Class: Adrenal Glucocorticoid

Uses For Flovent

Fluticasone belongs to the family of medicines known as corticosteroids (cortisone-like medicines). It is used to help prevent the symptoms of asthma. When used regularly every day, inhaled fluticasone decreases the number and severity of asthma attacks. However, it will not relieve an asthma attack that has already started.

Inhaled fluticasone works by preventing certain cells in the lungs and breathing passages from releasing substances that cause asthma symptoms.

This medicine may be used with other asthma medicines, such as bronchodilators (medicines that open up narrowed breathing passages) or other corticosteroids taken by mouth.

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

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in the product labeling, fluticasone propionate is used in certain patients with the following medical conditions:

• Pulmonary disease, chronic obstructive

Before Using Flovent

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

Corticosteroids taken by mouth or injection have been shown to slow or stop growth in children and cause reduced adrenal gland function. If enough fluticasone is absorbed following inhalation, it is possible it also could cause these effects. Your doctor will want you to use the lowest possible dose of fluticasone that controls asthma. This will lessen the chance of an effect on growth or adrenal gland function. It is also important that children taking fluticasone visit their doctors regularly so that their growth rates may be monitored. Children who are taking this medicine may be more susceptible to infections, such as chickenpox or measles. Care should be taken to avoid exposure to chickenpox or measles. If the child is exposed or the disease develops, the doctor should be contacted and his or her directions should be followed carefully. Before this medicine is given to a child, you and your child's doctor should talk about the good this medicine will do as well as the risks of using it.

Geriatric

Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of inhaled fluticasone in the elderly. However, elderly patients may be more sensitive to the effects of this medicine than younger adults, which may require caution in patients receiving inhaled fluticasone.

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.

• Atazanavir


• Boceprevir


• Bupropion


• Clarithromycin


• Darunavir


• Indinavir


• Itraconazole


• Ketoconazole


• Nefazodone


• Nelfinavir


• Ritonavir


• Saquinavir


• Telaprevir


• Telithromycin


• Tipranavir

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:

• Herpes simplex (virus) infection of the eye or


• Infections (virus, bacteria, or fungus)—Inhaled fluticasone may make these infections worse.

• Tuberculosis (active or history of)—Inhaled fluticasone may cause this infection to start up again.

Proper Use of fluticasone

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

Inhaled fluticasone is used to prevent asthma attacks. It is not used to relieve an attack that has already started. For relief of an asthma attack that has already started, you should use another medicine. If you do not have another medicine to use for an attack or if you have any questions about this, check with your health care professional.

Use this medicine only as directed. Do not use more of it and do not use it more often than your doctor ordered. To do so may increase the chance of side effects. The full benefit of this medicine may take 1 to 2 weeks or longer to achieve.

In order for this medicine to help prevent asthma attacks, it must be used every day in regularly spaced doses, as ordered by your doctor.

Gargling and rinsing your mouth with water after each dose may help prevent hoarseness, throat irritation, and infection in the mouth. However, do not swallow the water after rinsing.

Inhaled fluticasone is used with a special inhaler and usually comes with patient directions. Read the directions carefully before using this medicine. If you do not understand the directions or you are not sure how to use the inhaler, ask your health care professional to show you what to do. Also, ask your health care professional to check regularly how you use the inhaler to make sure you are using it properly.

For patients using the inhalation aerosol:

• When you use the inhaler for the first time, or if you have not used it for 4 weeks or longer, it may not deliver the right amount of medicine with the first puff. Therefore, before using the inhaler, prime it by spraying the medicine into the air four times. (Spray the inhaler once into the air if it has not been used in 1 to 3 weeks.) The inhaler will now be ready to give the right amount of medicine when you use it.


• To use the inhaler:
  
  • Shake the inhaler well for 15 seconds immediately before each use.
  
  
  • Take the cap off the mouthpiece (the strap will stay attached to the actuator). Check the mouthpiece and remove any foreign objects. Make sure the canister is fully and firmly inserted into the actuator.
  
  
  • Hold the mouthpiece away from your mouth and breathe out slowly and completely.
  
  
  • Use the inhalation method recommended by your doctor.
    
    • Open-mouth method—Place the mouthpiece about 1 or 2 inches (two fingerwidths) in front of your widely opened mouth. Make sure the inhaler is aimed into your mouth so that the spray does not hit the roof of your mouth or your tongue.
    
    
    • Closed-mouth method—Place the mouthpiece in your mouth between your teeth and over your tongue, with your lips closed tightly around it. Do not block the mouthpiece with your teeth or tongue.
    
    
  
  
  • Tilt your head back a little. Start to breathe in slowly and deeply through your mouth and, at the same time, press the top of the canister one time to get one puff of the medicine. Continue to breathe in slowly for 5 to 10 seconds. Count the seconds while inhaling. It is important to press the top of the canister and breathe in slowly at the same time so the medicine is pulled into your lungs. This step may be difficult at first. If you are using the closed-mouth method and you see a fine mist coming from your mouth or nose, the inhaler is not being used correctly.
  
  
  • Hold your breath as long as you can up to 10 seconds. This gives the medicine time to settle in your airways and lungs. Take the mouthpiece away from your mouth and breathe out slowly.
  
  
  • If your doctor has told you to inhale more than one puff of medicine at each dose, wait about 30 seconds and then gently shake the inhaler again, and take the second puff following exactly the same steps you used for the first puff.
  
  
  • When you are finished, wipe off the mouthpiece and replace the cover to keep the mouthpiece clean and free of foreign objects.
  
  


• The inhaler has a dose counter that keeps track of how many more times you can use it before you need to open a new one. When the dose counter reaches "020", call your doctor or pharmacist if refill is needed .


• If the dose counter is not working correctly, do not use the inhaler and return it to your pharmacy or doctor. Do not change the numbers or remove the counter from the canister .


• Clean the inhaler and mouthpiece at least once a day to prevent buildup of medicine and blockage of the mouthpiece.
  
  • To clean the inhaler:
    
    • Remove the metal canister from the inhaler and set it aside.
    
    
    • Rinse the mouthpiece and cover and plastic case in warm, running water.
    
    
    • Shake off the excess water and let the inhaler parts air dry completely before replacing the metal canister and cover.
    
    
  
  

For patients using the powder for inhalation:

• To load the inhaler:
  
  • Make sure your hands are clean and dry.
  
  
  • Do not insert the disk until just before you are ready to use the medicine.
  
  
  • Take off the mouthpiece cover and make sure that the mouthpiece is clean.
  
  
  • Hold the corners of the white tray and pull out gently until you can see all of the plastic ridges on the sides of the tray.
  
  
  • Put your finger and thumb on the ridges, squeeze inward, and gently pull the tray out of the body of the inhaler.
  
  
  • Place a disk on the wheel with the numbers facing up, and then slide the tray back into the inhaler.
  
  
  • Hold the corners of the tray and slide the tray out and in. This will rotate the disk.
  
  
  • Continue to turn the disk in this way until the number 4 appears in the small window. Each disk has four blisters containing the medicine. The window will display how many inhalations you have left after you use it each time. For example, when you see the number 1, you have one inhalation left.
  
  
  • To replace the empty disk with a full disk, follow the same steps you used to load the inhaler. Do not throw away the wheel when you discard the empty disk.
  
  


• To use the inhaler:
  
  • Hold the inhaler flat in your hand. Lift the rear edge of the lid until it is fully upright.
  
  
  • The plastic needle on the front of the lid will break the blister containing one inhalation of medicine. When the lid is raised as far as it will go, both the upper and the lower surfaces of the blister will be pierced. Do not lift the lid if the cartridge is not in the inhaler. Doing this will break the needle and you will need a new inhaler.
  
  
  • After the blister is broken open, close the lid. Keeping the inhaler flat and well away from your mouth, breathe out to the end of a normal breath.
  
  
  • Raise the inhaler to your mouth, and place the mouthpiece in your mouth.
  
  
  • Close your lips around the mouthpiece and tilt your head slightly back. Do not bite down on the mouthpiece. Do not block the mouthpiece with your teeth or tongue. Do not cover the air holes on the side of the mouthpiece.
  
  
  • Breathe in through your mouth as steadily and as deeply as you can until you have taken a full deep breath.
  
  
  • Hold your breath and remove the mouthpiece from your mouth. Continue holding your breath as long as you can up to 10 seconds before breathing out. This gives the medicine time to settle in your airways and lungs.
  
  
  • Hold the inhaler well away from your mouth and breathe out to the end of a normal breath.
  
  
  • Prepare the cartridge for your next inhalation. Pull the cartridge out once and push it in once. The disk will turn to the next numbered dose as seen in the indicator window. Do not pierce the blister until just before the inhalation.
  
  
  • If your doctor has told you to inhale more than one puff of medicine at each dose, take the second puff following exactly the same steps you used for the first puff.
  
  
  • When you are finished, wipe off the mouthpiece and replace the cover to keep the mouthpiece clean and free of foreign objects.
  
  


• To clean the inhaler:
  
  • Remove the tray from the body of the inhaler.
  
  
  • Hold the wheel between your forefinger and thumb and pull upward to separate it from the tray.
  
  
  • Use the brush that is stored in the rear of the body of the inhaler to brush away any powder left behind on the parts of the inhaler.
  
  
  • Replace the wheel and push it down firmly until it snaps back into place.
  
  
  • Replace the tray and mouthpiece cover.
  
  
  • Separate the parts of the inhaler using the steps outlined above.
  
  
  • Rinse the parts of the inhaler with warm water and let them air dry before reassembling them as described above.
  
  
  
  The inhaler should be cleaned once a week.

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 bronchial asthma
  
  • For inhalation aerosol:
    
    • Adults and children 12 years of age and older—88 to 880 micrograms (mcg) two times a day, morning and evening.
    
    
    • Canadian labeling recommends—For adults and children 16 and older: 100 to 1000 mcg two times a day.
    
    
    • Children 4 to 11 years of age—88 mcg two times a day.
    
    
    • Canadian labeling recommends—For children 4 to 16 years of age: 50 to 100 mcg two times a day; For children up to 4 years of age: Use and dose must be determined by your doctor.
    
    
    • Children younger than 4 years of age—Use and dose must be determined by your doctor .
    
    
  
  
  • For powder for inhalation:
    
    • Adults and children older than 11 years of age—100 to 1000 mcg two times a day.
    
    
    • Children 4 to 11 years of age—50 to 100 mcg two times a day.
    
    
    • Canadian labeling recommends—For children 4 to 16 years of age: 50 to 100 mcg two times a day.
    
    
    • Children younger than 4 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.

Store the canister at room temperature, away from heat and direct light. Do not freeze. Do not keep this medicine inside a car where it could be exposed to extreme heat or cold. Do not poke holes in the canister or throw it into a fire, even if the canister is empty.

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Flovent

Check with your doctor if:

• You go through a period of unusual stress to your body, such as surgery, injury, or infection.


• You have an asthma attack that does not improve after you take a bronchodilator medicine.


• Your asthma symptoms do not improve or your condition worsens.


• You are exposed to the chickenpox or measles.

Your doctor may want you to carry a medical identification card stating that you are using this medicine and that you may need additional medicine during times of emergency, a severe asthma attack or other illness, or unusual stress.

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

Flovent 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

• White patches in mouth and throat

Less common

• Diarrhea


• ear ache


• fever


• lower abdominal pain


• nausea


• pain on passing urine


• redness or discharge of the eye, eyelid, or lining of the eye


• shortness of breath


• sore throat


• trouble in swallowing


• vaginal discharge (creamy white) and itching


• vomiting

Rare

• Blindness, blurred vision, eye pain


• large hives


• bone fractures


• diabetes mellitus [increased hunger, thirst, or urination]


• excess facial hair in women


• fullness or roundness of face, neck, and trunk


• growth reduction in children or adolescents


• heart problems


• high blood pressure


• hives and skin rash


• impotence in males


• lack of menstrual periods


• muscle wasting


• numbness and weakness of hands and feet


• weakness


• swelling of face, lips, or eyelids


• tightness in chest, troubled breathing, or wheezing

Incidence not known

• Difficulty breathing


• difficulty swallowing


• dizziness


• fast heartbeat


• growth rate decreased in children and teenagers


• itching, puffiness, or swelling of the eyelids or around the eyes, face, lips, or tongue


• noisy breathing


• swelling of the mouth or throat

Symptoms of overdose

• Darkening of skin


• fainting


• loss of appetite


• mental depression


• unusual tiredness or weakness

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:

More common

• Cough


• general aches and pains or general feeling of illness


• greenish-yellow mucus in nose


• headache


• hoarseness or other voice changes


• runny, sore, or stuffy nose

Less common

• Bloody mucus or unexplained nosebleeds


• dizziness


• eye irritation


• feeling 'faint'


• giddiness


• irregular or painful menstrual periods


• irritation due to inhalant


• joint pain


• migraines


• mouth irritation


• muscle soreness, sprain, or strain


• sneezing


• stomach pain or burning

Rare

• Aggression


• agitation


• bruising


• itching


• restlessness


• weight gain

Incidence not known

• Abdominal pain


• blurred vision


• decrease in height


• dry mouth


• fatigue


• flushed, dry skin


• fruit-like breath odor


• increased hunger


• increased thirst


• increased urination


• loss of voice


• pain in back, ribs, arms or legs


• sweating


• trouble sitting still


• unexplained weight loss

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: Flovent 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 Flovent resources

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

• Flovent Prescribing Information (FDA)


• Flovent Consumer Overview


• Flovent Monograph (AHFS DI)


• Flovent Aerosol Inhaler MedFacts Consumer Leaflet (Wolters Kluwer)


• Fluticasone Prescribing Information (FDA)


• Fluticasone Professional Patient Advice (Wolters Kluwer)


• Flovent Diskus Powder MedFacts Consumer Leaflet (Wolters Kluwer)


• Flovent HFA Aerosol Inhaler MedFacts Consumer Leaflet (Wolters Kluwer)


• Flovent Rotadisk Prescribing Information (FDA)

Compare Flovent with other medications

• Asthma, Maintenance
• Bronchopulmonary Dysplasia
• Eosinophilic Esophagitis

Trazodone 50mg Capsules (Winthrop Pharmaceuticals UK Ltd)

1. Name Of The Medicinal Product

Trazodone Hydrochloride 50mg Capsules

2. Qualitative And Quantitative Composition

Trazodone hydrochloride 50mg per capsule.

For excipients, see 6.1.

3. Pharmaceutical Form

Capsules.

4. Clinical Particulars

4.1 Therapeutic Indications

Anxiety, depression, mixed anxiety and depression.

4.2 Posology And Method Of Administration

Route of administration: Oral.

DEPRESSION:

Adults:

Initially 150mg/day in divided doses after food or as a single dose on retiring.

This may be increased up to 300mg/day in a single or divided doses. The major portion of a divided dose to be taken on retiring. The dose may be further increased to 600mg/day in divided doses in hospitalised patients.

Elderly:

For very elderly or frail patients, the recommended initial starting dose is reduced to 100mg/day given in divided doses or as a single night-time dose. This may be incrementally increased, under supervision, according to efficacy and tolerance. In general, single doses above 100mg should be avoided in these patients. It is unlikely that 300mg/day will be exceeded.

Children:

There are insufficient data on safety to recommend the use of Trazodone in children below the age of 18 years.

DEPRESSION ACCOMPANIED BY ANXIETY:

As for depression.

ANXIETY:

75mg/day increasing to 300mg/day as necessary.

A decrease in side-effects (increase of the resorption and decrease of the peak plasma concentration) can be reached by taking Trazodone after a meal.

Hepatic Impairment:

Trazodone undergoes extensive hepatic metabolism, see section 5.2, and has also been associated with hepatotoxicity, see sections 4.4 and 4.8. Therefore caution should be exercised when prescribing for patients with hepatic impairment, particularly in cases of severe hepatic impairment. Periodic monitoring of liver function may be considered.

Renal Impairment:

No dosage adjustment is usually necessary, but caution should be exercised when prescribing for patients with severe renal impairment (see also section 4.4 and 5.2).

4.3 Contraindications

Known sensitivity to trazodone or to any of the excipients.

Alcohol intoxication and intoxication with hypnotics.

Acute myocardial infarction.

4.4 Special Warnings And Precautions For Use

Use in children and adolescents under 18

Trazodone should not be used in children and adolescents under 18 years old. Suicidal behaviour (suicidal attempt and suicidal planning) and hostility (essentially aggressiveness, opposing behavior and anger) has been observed in a clinical study on children and adolescents treated with antidepressant more frequently than with placebo. Moreover, long-term safety data on children and adolescents regarding growth, maturation and cognitive and behavioral development are not available.

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which Trazodone is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

To minimise the potential risk of suicide attempts, particularly at therapy initiation, only restricted quantities of Trazodone should be prescribed at each occasion.

It is recommended that careful dosing and regular monitoring is adopted in patients with the following conditions:

• Epilepsy, specifically abrupt increases or decreases of dosage should be avoided

• Patients with hepatic or renal impairment, particulary if severe

• Patients with cardiac disease, such as angina pectoris, conduction disorders or AV blocks of different degree, recent myocardial infarction

• Hyperthyroidism

• Micturition disorders, such as prostate hypertrophy, although problems would not be anticipated as the anticholinergic effect of Trazodone is only minor

• Acute narrow angle glaucoma, raised intra-ocular pressure, although major changes would not be anticipated due to the minor anticholinergic effect of Trazodone

Should jaundice occur in a patient, Trazodone therapy must be withdrawn.

Administration of antidepressants in patients with schizophrenia or other psychotic disorders may result in a possible worsening of psychotic symptoms. Paranoid thoughts may be intensified. During therapy with Trazodone a depressive phase can change from a manic – depressive psychosis into a manic phase. In that case Trazodone must be stopped.

Interactions in terms of serotonine syndrome/malignant neuroleptic syndrome have been described in case of concomitant use of other serotonergically acting substances like other antidepressants (e.g. tricyclic antidepressants, SSRI's, SNRI's and MAO-inhibitors) and neuroleptics. Malignant neuroleptic syndromes with fatal outcome have been reported in cases of coadministration with neuroleptics, for which this syndrome is a known possible adverse drug reaction. See Sections 4.5 and 4.8 for further information.

Since agranulocytosis may clinically reveal itself with influenza-like symptoms, sore throat, and fever, in these cases it is recommended to check haematology.

Hypotension, including orthostatic hypotension and syncope, has been reported to occur in patients receiving Trazodone. Concomitant administration of antihypertensive therapy with Trazodone may require a reduction in the dose of the antihypertensive drug

Elderly patients are often more sensitive to antidepressants, in particular to orthostatic hypotension and other anticholinergic effects.

Following therapy with Trazodone, particularly for a prolonged period, an incremental dosage reduction to withdrawal is recommended, to minimise the occurrence of withdrawal syptoms, characterised by nausea, headache, and malaise.

There is no evidence that Trazodone possesses any addictive properties.

As with other antidepressant drugs, cases of QT interval prolongation have been reported with Trazodone very rarely. Caution is advised when prescribing Trazodone with medicinal products known to prolong QT interval. Trazodone should be used with caution in patients with known cardiovascular disease including those associated with prolongation of the QT interval.

Potent CYP3A4 inhibitors may lead to increases in trazodone serum levels. See section 4.5 for further information.

As with other drugs with alpha-adrenolytic activity, Trazodone has very rarely been associated with priapism. This may be treated with an intracavernosum injection of an alpha-adrenergic agent such as adrenaline or metaraminol. However there are reports of Trazodone -induced priapism which have required surgical intervention or led to permanent sexual dysfunction. Patients developing this suspected adverse reaction should cease Trazodone immediately.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

General: The sedative effects of antipsychotics, hypnotics, sedatives, anxiolytics, and antihistaminic drugs may be intensified; dosage reduction is recommended in such instances.

The metabolism of antidepressants is accelerated due to hepatic effects by oral contraceptives, phenytoin, carbamazepine and barbiturates. The metabolism of antidepressants is inhibited by cimetidine and some other antipsychotics.

In vitro drug metabolism studies suggest that there is a potential for drug interactions when Trazodone is given with potent CYP3A4 inhibitors such as erythromycin, ketoconazole, itraconazole, ritonavir, indinavir, and nefazodone. It is likely that potent CYP3A4 inhibitors may lead to substantial increases in trazodone plasma concentrations with the potential for adverse effects. Exposure to ritonavir during initiation or resumption of treatment in patients receiving Trazodone will increase the potential for excessive sedation, cardiovascular, and gastrointestinal effects. It has been confirmed in in- vivo-studies in healthy volunteers, that a ritonavir dose of 200 mg BID increased the plasma levels of Trazodone by greater than two-fold, leading to nausea, syncope and hypotension. If Trazodone is used with a potent CYP3A4 inhibitor, a lower dose of Trazodone should be considered. However, the co-administration of Trazodone and potent CYP3A4 inhibitors should be avoided where possible.

Carbamazepine reduced plasma concentrations of trazodone when coadministered. Concomitant use of carbamazepine 400 mg daily led to a decrease of plasma concentrations of trazadone and its active metabolite m-chlorophenylpiperazine of 76 % and 60 %, respectively. Patients should be closely monitored to see if there is a need for an increased dose of Trazodone when taken with carbamazepine.

, Trazodone may enhance the effects of muscle relaxants and volatile anaesthetics, and caution should be exercised in such instances. Similar considerations apply to combined administration with sedative and anti-depressant drugs, including alcohol. Trazodone intensifies the sedative effects of alcohol. Alcohol should be avoided during Trazodone therapy.

Trazodone has been well tolerated in depressed schizophrenic patients receiving standard phenothiazine therapy and also in depressed parkinsonian patients receiving therapy with levodopa. Antidepressants can accelerate the metabolism of levodopa.

Tricyclic antidepressants: Concurrent administration should be avoided due to the risk of interaction. Serotonine syndrome and cardiovascular side effects should be bewared.

Fluoxetine: Rare cases have been reported of elevated Trazodone plasma levels and adverse effects when Trazodone had been combined with fluoxetine, a CYP1A2/2D6 inhibitor. The mechanism underlying a pharmacokinetic interaction is not fully understood. A pharmacodynamic interaction (serotonine syndrome) could not be excluded.

Possible interactions with monoamine oxidase inhibitors have occasionally been reported. Although some clinicians do give both concurrently, use of Trazodone with MAOIs, or within two weeks of stopping treatment with these compounds is not recommended. The giving of MAOIs within one week of stopping Trazodone is also not recommeded.

Phenothiazines: Severe orthostatic hypotension has been observed in case of concomitant use of phenothiazines, like e.g. chlorpromazine, fluphenazine, levomepromazine, perphenazine.

Other

Concomitant use of Trazodone with drugs known to prolong the QT interval may increase the risk of ventricular arrhythmias, including torsade de pointes. Caution should be used when these drugs are coadministered with Trazodone.

Since Trazodone is only a very weak inhibitor of noradrenaline re-uptake and does not modify the blood pressure response to tyramine, interference with the hypotensive action of guanethidine-like compounds is unlikely. However, studies in laboratory animals suggest that Trazodone may inhibit most of the acute actions of clonidine. In the case of other types of antihypertensive drug, although no clinical interactions have been reported, the possibility of potentiation should be considered.

Undesirable effects may be more frequent when Trazodone is administered together with preparations containing Hypericum perforatum (St Johns wort).

There have been reports of changes in prothrombin time in patients concomitantly receiving trazodone and warfarin.

Concurrent use with Trazodone may result in elevated serum levels of digoxin or phenytoin. Monitoring of serum levels should be considered in these patients.

4.6 Pregnancy And Lactation

Pregnancy:

Data on a limited number (< 200) of exposed pregnancies indicate no adverse effects of Trazodone on pregnancy or on the health of the foetus/newborn child. To date, no other relevant epidemiological data area available. The safety of Trazodone in human pregnancy has not been established. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development at therapeutic doses. On basic principles, therefore, its use during the first trimester should be avoided.

Caution should be exercised when prescribing to pregnant women. When Trazodone is used until delivery, newborns should be monitored for the occurrence of withdrawal symptoms.

Lactation:

Limited data indicate that excretion of Trazodone in human breast milk is low, but levels of the active metabolite are not known. Due to the paucity of data, a decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Trazodone should be made taking into account the benefit of breast-feeding to the child and the benefit of Trazodone therapy to the woman.

4.7 Effects On Ability To Drive And Use Machines

Trazodone has minor or moderate influence on the ability to drive and use machines.As with all other drugs acting on the central nervous system, patients should be cautioned against the risks of driving or operating machinery until they are sure they are not affected by drowsiness, sedation, dizziness, confusional states, or blurred vision.

4.8 Undesirable Effects

Cases of suicidal ideation and suicidal behaviours have been reported during Trazodone therapy or early after treatment discontinuation (see section 4.4).

Trazodone has had no effect on arterial blood pCO₂ or pO₂ levels in patients with severe respiratory insufficiency due to chronic bronchial or pulmonary disease.

The following symptoms, some of which are commonly reported in cases of untreated depression, have also been recorded in patients receiving Trazodone therapy.

MedDRA System Organ Class	Frequency not known (cannot be estimated from the available data)
Blood and the lymphatic system disorders	Blood dyscrasias (including agranulocytosis, thrombocytopenia, eosinophilia, leucopenia and anaemia)
Immune system disorders	Allergic reactions
Endocrine disorders	Syndrome of Inappropriate Antidiuretic Hormone Secretion
Metabolism and nutrition disorders	Hyponatraemia1, weight loss, anorexia, increased appetite,
Psychiatric disorders	Suicidal ideation or suicidal behaviours2, confusional state, insomnia, disorientation, mania, anxiety, nervousness, agitation (very occasionally exacerbating to delirium), delusion, aggressive reaction, hallucinations, nightmares, libido decreased, withdrawal syndrome
Nervous system disorders	Serotonin syndrome, convulsion, neuroleptic malignant syndrome, dizziness, vertigo, headache, drowsiness3, restlessness, decreased alertness, tremor, blurred vision, memory disturbance, myoclonus, expressive aphasia, paraesthesia, dystonia, taste altered
Cardiac disorders	Cardiac arrhythmias4 (including Torsade de Pointes, palpitations, premature ventricular contractions, ventricular couplets, ventricular tachycardia), bradycardia, tachycardia, ECG abnormalities (QT prolongation)2
Vascular disorders	Ortostatic hypotension, hypertension, syncope
Respiratory, thoracic and mediastinal disorders	Nasal congestion, dyspnoea
Gastrointestinal disorders	Nausea, vomiting, dry mouth, constipation, diarrhoea, dyspepsia, stomach pain, gastroenteritis, increased salivation, paralytic ileus
Hepato-biliary disorders	Hepatic function abnormalities (including jaundice and hepatocellular damage)5 , cholestasis intrahepatic
Skin and subcutaneous tissue disorders	Skin rash, pruritus, hyperhidrosis
Musculoskeletal and connective tissue disorders	Pain in limb, back pain, myalgia, arthralgia
Renal and urinary disorders	Micturition disorderd
Reproductive system and breast disorders	Priapism6
General disorders and administration site conditions	Weakness, oedema, influenza-like symptoms, fatigue, chest pain, fever
Investigations	Elevated liver enzymes

¹ Fluid and electrolyte status should be monitored in symptomatic patients.

² See also Section 4.4.

³ Trazodone is a sedative antidepressant and drowsiness, sometimes experienced during the first days of treatment, usually disappears on continued therapy.

⁴ Studies in animals have shown that trazodone is less cardiotoxic than the tricyclic antidepressants, and clinical studies suggest that the drug may be less likely to cause cardiac arrhythmias in man. Clinical studies in patients with pre-existing cardiac disease indicate that trazodone may be arrhythmogenic in some patients in that population.

⁵ Adverse effects on hepatic function, sometimes severe, have been rarely reported. Should such effects occur, trazodone should be immediately discontinued.

⁶ See slso section 4.4.

4.9 Overdose

Features of toxicity

The most frequently reported reactions to overdose have included drowsiness, dizziness, nausea and vomiting. In more serious cases coma, tachycardia, hypotension, hyponatraemia, convulsions and respiratory failure have been reported. Cardiac features may include bradycardia, QT prolongation and torsade de pointes. Symptoms may appear 24 hours or more after overdose.

Overdoses of Trazodone in combination with other antidepressants may cause serotonin syndrome.

Management

There is no specific antidote to trazodone. Activated charcoal should be considered in adults who have ingested more than 1 g trazodone, or in children who have ingested more than 150 mg trazodone within 1 hour of presentation. Alternatively, in adults, gastric lavage may be considered within 1 hour of ingestion of a potentially life-threatening overdose.

Observe for at least 6 hours after ingestion (or 12 hours if a sustained release preparation has been taken). Monitor BP, pulse and Glasgow Coma Scale (GCS). Monitor oxygen if GCS is reduced. Cardiac monitoring is appropriate in symptomatic patients.

Single brief convulsions do not require treatment. Control frequent or prolonged convulsions with intravenous diazepam (0.1-0.3 mg/kg body weight) or lorazepam (4 mg in an adult and 0.05 mg/kg in a child). If these measures do not control the fits, an intravenous infusion of phenytoin may be useful. Give oxygen and correct acid base and metabolic disturbances as required.

Treatment should be symptomatic and supportive in the case of hypotension and excessive sedation. If severe hypotension persists consider use of inotropes, eg dopamine or dobutamine.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

ATC code: N06A X05. Other antidepressants.

Trazodone is a potent antidepressant. It also has anxiety reducing activity. Trazodone is a triazolopyridine derivative chemically unrelated to known tricyclic, tetracyclic and other antidepressant agents. It has negligible effect on noradrenaline re-uptake mechanisms. Whilst the mode of action of Trazodone is not known precisely, its antidepressant activity may concern noradrenergic potentiation by mechanisms other than uptake blockade. A central antiserotonin effect may account for the drug's anxiety reducing properties.

5.2 Pharmacokinetic Properties

Trazodone is rapidly absorbed from the gastro-intestinal tract and extensively metabolised. Paths of metabolism of trazodone include n-oxidation and hydroxylation. The metabolic m-chlorophenylpiperazine is active. trazodone is excreted in the urine almost entirely in the form of its metabolites, either in free or in conjugated form. The elimination of trazodone is biphasic, with a terminal elimination half-life of 5 to 13 hours. Trazodone is excreted in breast milk.

There was an approximate two-fold increase in terminal phase half-life and significantly higher plasma concentrations of trazodone in 10 subjects aged 65 to 74 years compared with 12 subjects aged 23 to 30 years following a 100mg dose of trazodone. It was suggested that there is an age-related reduction in the hepatic metabolism of trazodone.

In vitro studies in human liver microsomes show that trazodone is metabolised by cytochrome P4503A4 (CYP3A4) to form m-chlorophenylpiperazine. Whilst significant, the role of this pathway in the total clearance of trazodone in vivo has not been fully determined.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose

Magnesium stearate

Gelatin

Titanium dioxide E171

Erythrosine E127

Indigo Carmine E132

Yellow iron oxide E172

Ink (1028 (S-1-27794) or 1014 (SW-9008) Black)

6.2 Incompatibilities

None stated.

6.3 Shelf Life

60 months.

6.4 Special Precautions For Storage

Blister packs: Store below 30ºC in a dry place.

Glass bottles and securitainers: Store below 30ºC.

6.5 Nature And Contents Of Container

i) Amber glass bottles with jay-cap closures: contents 100 capsules.

ii) PVdC coated 250μm PVC blisters sealed with 20μm aluminium foil: contents 84 and 100 capsules.

iii) Securitainers: contents 1000 capsules.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

8. Marketing Authorisation Number(S)

PL 04425/0609

9. Date Of First Authorisation/Renewal Of The Authorisation

26 August 2009

10. Date Of Revision Of The Text

27/09/2010

LEGAL STATUS

POM

Vivotif

Generic Name: typhoid vaccine, live (Oral route)

TYE-foid VAX-een, lyve

Commonly used brand name(s)

In the U.S.

• Vivotif

Available Dosage Forms:

• Capsule, Delayed Release


• Capsule

Therapeutic Class: Vaccine

Uses For Vivotif

Typhoid fever is a serious disease that can cause death. It is caused by a germ called Salmonella typhi, and is spread most often through infected food or water. Typhoid may also be spread by close person-to-person contact with infected persons (such as occurs with persons living in the same household). Some infected persons do not appear to be sick, but they can still spread the germ to others.

Typhoid fever is very rare in the United States (U.S.) and other areas of the world that have good water and sewage (waste) systems. However, it is a problem in parts of the world that do not have such systems. If you are traveling to certain countries or remote areas, typhoid vaccine will help protect you from typhoid fever. The U.S. CDC recommends caution in the following areas of the world:

• Africa


• Asia


• Latin America

Typhoid vaccine taken by mouth helps prevent typhoid fever, but does not provide 100% protection. Therefore, it is very important to avoid infected persons and food and water that may be infected, even if you have taken the vaccine.

To get the best possible protection against typhoid, you should complete the vaccine dosing schedule (all 4 doses of the vaccine) at least 1 week before travel to areas where you may be exposed to typhoid.

If you will be traveling regularly to parts of the world where typhoid is a problem, you should get a booster (repeat) dose of the vaccine every 5 years.

Typhoid vaccine is available only from a health care professional.

Before Using Vivotif

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

Typhoid vaccine is not recommended for infants and children up to 6 years of age. Although there is no specific information comparing use of typhoid vaccine in children 6 years of age and over with use in other age groups, this vaccine is not expected to cause different side effects or problems in these children than it does in adults.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of typhoid vaccine in the elderly with use in other age groups, this vaccine is not expected to cause different side effects or problems in older people than it does in younger adults.

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

Studies in women suggest that this medication poses minimal risk to the infant when used during 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 receiving this vaccine, 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.

Receiving this vaccine 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.

• Aclarubicin


• Adalimumab


• Aldesleukin


• Altretamine


• Amonafide


• Amsacrine


• Asparaginase


• Azacitidine


• Azathioprine


• Bleomycin


• Broxuridine


• Busulfan


• Capecitabine


• Carboplatin


• Carmustine


• Certolizumab Pegol


• Chlorambucil


• Cisplatin


• Cladribine


• Cyclophosphamide


• Cytarabine


• Cytarabine Liposome


• Dacarbazine


• Dactinomycin


• Daunorubicin


• Daunorubicin Citrate Liposome


• Decitabine


• Docetaxel


• Doxifluridine


• Doxorubicin Hydrochloride


• Doxorubicin Hydrochloride Liposome


• Edatrexate


• Eflornithine


• Epirubicin


• Estramustine


• Etanercept


• Etoposide


• Everolimus


• Fingolimod


• Floxuridine


• Fludarabine


• Fluorouracil


• Fotemustine


• Gallium Nitrate


• Gemcitabine


• Golimumab


• Hydroxyurea


• Idarubicin


• Ifosfamide


• Irinotecan


• Lomustine


• Mechlorethamine


• Melphalan


• Mercaptopurine


• Methotrexate


• Mitolactol


• Mitomycin


• Mitotane


• Mitoxantrone


• Mycophenolic Acid


• Oxaliplatin


• Paclitaxel


• Pegaspargase


• Pentostatin


• Pipobroman


• Pirarubicin


• Plicamycin


• Procarbazine


• Raltitrexed


• Rilonacept


• Rituximab


• Sirolimus


• Streptozocin


• Tacrolimus


• Teceleukin


• Tegafur


• Temsirolimus


• Teniposide


• Thioguanine


• Thiotepa


• Topotecan


• Treosulfan


• Trimetrexate


• Trofosfamide


• Uracil Mustard


• Ustekinumab


• Vinblastine


• Vincristine


• Vincristine Liposome


• Vindesine


• Vinorelbine

Receiving this vaccine 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.

• Abatacept


• Cytomegalovirus Immune Globulin, Human


• Leflunomide


• Vaccinia Immune Globulin, Human

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 vaccine. Make sure you tell your doctor if you have any other medical problems, especially:

• Diarrhea or


• Fever or


• Other illness (severe) or


• Stomach or intestinal illness (severe) or


• Vomiting—These conditions may reduce the useful effect of the vaccine.

• Immune deficiency condition, including HIV or AIDS—May increase the chance of side effects from the vaccine.

Proper Use of Vivotif

It is important that all 4 doses of the vaccine be taken exactly as directed. If all the doses are not taken or if doses are not taken at the correct times, the vaccine may not work properly.

The vaccine capsules are meant to dissolve in the intestines. Therefore, they should be inspected to make sure that they are not broken or cracked when you take them. If any are broken or cracked, you will need to replace them.

Typhoid vaccine must be stored in the refrigerator at a temperature between 2 and 8 degrees C (35.6 and 46.4 degrees F) at all times. If the vaccine is left at room temperature, it will lose its effectiveness. Therefore, remember to replace unused vaccine in the refrigerator between doses.

Each dose of the vaccine should be taken approximately 1 hour before a meal. Take with a cold or lukewarm drink that has a temperature that does not exceed body temperature (eg, 37 degrees C or 98.6 degrees F).

Swallow the capsule whole. Do not chew it before swallowing. Also swallow the capsule as soon as possible after you place it in your mouth.

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.

• Take 1 capsule by mouth every other day for a total of 4 doses.

Missed Dose

Call your doctor or pharmacist for instructions.

If you do not remember the missed dose until the next day, take the missed dose at that time and reschedule your every-other-day doses from then. It is important that this vaccine be taken exactly as directed so it can give you the most protection against typhoid fever.

Storage

Store in the refrigerator. Do not freeze.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Vivotif

Tell all of your doctors that you have taken this vaccine if you plan to receive any other live vaccines within 1 month after the last dose.

If you are receiving this vaccine, do not take proguanil (Paludrine(R)) as a single medicine (not available in the United States) for at least 10 days after your last dose.

Vivotif 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:

• Difficulty with breathing or swallowing


• hives


• itching, especially of the feet or hands


• reddening of the skin, especially around the ears


• swelling of the eyes, face, or inside of the nose


• unusual tiredness or weakness that is sudden and severe

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

Less common or rare

• Diarrhea


• fever


• nausea


• skin rash


• stomach cramps or pain


• vomiting

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: Vivotif side effects (in more detail)

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

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More Vivotif resources

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

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