rosuvastatin

roe-soo-va-STAT-in

Commonly used brand name(s)

In the U.S.

• Crestor

Available Dosage Forms:

• Tablet

Therapeutic Class: Antihyperlipidemic

Pharmacologic Class: HMG-COA Reductase Inhibitor

Uses For rosuvastatin

Rosuvastatin is used together with a proper diet to lower cholesterol and triglycerides (fats) in the blood. rosuvastatin may help prevent or slow down medical problems, like atherosclerosis (hardening of the arteries), that are caused by fats clogging the blood vessels. It may also be used to prevent certain types of heart and blood vessel problems in patients with risk factors for heart problems.

Rosuvastatin belongs to a group of medicines called HMG-CoA reductase inhibitors or "statins." It works by blocking an enzyme that is needed by the body to make cholesterol, so this reduces the amount of cholesterol in the blood.

rosuvastatin is available only with your doctor's prescription.

Before Using rosuvastatin

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 rosuvastatin, the following should be considered:

Allergies

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

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of rosuvastatin in children younger than 10 years of age. Safety and efficacy have not been established.

Geriatric

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

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	X	Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

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 rosuvastatin, 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 rosuvastatin 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


• Clarithromycin


• Cyclosporine


• Daptomycin


• Fenofibrate


• Fosamprenavir


• Gemfibrozil


• Indinavir


• Lopinavir


• Niacin

Using rosuvastatin 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.

• Acenocoumarol


• Amiodarone


• Desogestrel


• Dicumarol


• Dienogest


• Drospirenone


• Eltrombopag


• Estradiol Cypionate


• Estradiol Valerate


• Ethinyl Estradiol


• Ethynodiol Diacetate


• Etonogestrel


• Fluconazole


• Itraconazole


• Levonorgestrel


• Medroxyprogesterone Acetate


• Mestranol


• Norelgestromin


• Norethindrone


• Norgestimate


• Norgestrel


• Oat Bran


• Pectin


• Phenprocoumon


• Warfarin

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

• Alcohol abuse, or history of or


• Hypothyroidism (underactive thyroid) or


• Kidney disease, severe or


• Liver disease, history of—Use with caution. May cause side effects to become worse.

• Asian descent (having either Filipino, Chinese, Japanese, Korean, Vietnamese, or Asian-Indian origin)—May increase the amount of rosuvastatin in the body.

• Blood in the urine or


• Muscle pain or weakness, history of or


• Protein in the urine—Use with caution. May make these conditions worse.

• Convulsions (seizures), uncontrolled or


• Dehydration or


• Electrolyte deficiency or disorder or


• Hypotension (low blood pressure) or


• Infection, severe or


• Major surgery, recent or


• Major trauma, recent or


• Metabolic enzyme deficiency or disorder—Patients with these conditions may be at risk for muscle problems.

• Liver disease, active—Should not be used in patients with this condition.

Proper Use of rosuvastatin

Use rosuvastatin only as directed by your doctor. Do not use more of it, do not use it more often, or do not use it for a longer time than your doctor ordered. Also, rosuvastatin works best if there is a constant amount in the blood. To help keep this amount constant, do not miss any doses and take the medicine at the same time each day.

rosuvastatin comes with a patient information insert. Read and follow the instructions in the insert carefully. Talk to your doctor if you have any questions.

Remember that rosuvastatin will not cure your cholesterol problem, but it does help control it. You must continue to take it as directed if you expect to keep your cholesterol levels down.

Before prescribing medicine for your cholesterol problem, your doctor will probably try to control it by changing your diet. Such a diet may be low in fats, sugars, or cholesterol. Many people are able to control their cholesterol levels by carefully following a special diet and by adding exercise to their daily routine. Medicine is prescribed only when additional help is needed, and is effective only when used together with a modified diet and exercise.

Rosuvastatin may be taken with or without food.

Swallow the tablets whole.

If you need to take an antacid that contains aluminum and magnesium (e.g., Maalox®), take the antacid at least 2 hours after you take rosuvastatin.

Dosing

The dose of rosuvastatin 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 rosuvastatin. If your dose is different, do not change it unless your doctor tells you to do so.

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

• For oral dosage form (tablets):
  
  • For high cholesterol and atherosclerosis:
    
    • Adults—5 to 40 milligrams (mg) once a day.
    
    
    • Children 10 to 17 years of age—5 to 20 mg per day.
    
    
    • Children younger than 10 years of age—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of rosuvastatin, 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.

However, do not take 2 doses of rosuvastatin within 12 hours.

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

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

Precautions While Using rosuvastatin

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly to lower your cholesterol and triglyceride levels and to decide if you should continue to take it. Blood tests may be needed to check for unwanted effects.

Using rosuvastatin while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

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

Do not drink large amounts of alcohol while taking rosuvastatin. This could cause side effects on the liver.

Stop taking rosuvastatin and check with your doctor immediately if you have unexplained muscle pain, tenderness, or weakness, especially if you also have unusual tiredness or a fever. These could be symptoms of a serious muscle problem.

Do not stop or change your dose without checking first with your doctor, even if you are feeling well.

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

rosuvastatin 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:

Rare

• Dark-colored urine


• fever


• muscle cramps or spasms


• muscle pain, stiffness, tenderness, wasting, or weakness


• unusual tiredness or weakness

Incidence not known

• Abdominal or stomach pain


• clay-colored stools


• skin rash


• unpleasant breath odor


• vomiting of blood


• yellow eyes or skin

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

More common

• Body aches or pain


• congestion


• cough


• dry or sore throat


• headache


• hoarseness


• runny nose


• tender, swollen glands in the neck


• trouble with swallowing


• voice changes

Less common

• Accidental injury


• accumulation of pus, swollen, red, or tender area of infection near a tooth


• acid or sour stomach


• arm, back, or jaw pain


• back pain


• belching


• bladder pain


• bloated


• bloody or cloudy urine


• blurred vision


• bruising


• burning feeling in the chest or stomach


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


• chest pain or discomfort


• chest tightness or heaviness


• chills


• constipation


• depression


• diarrhea


• difficult or labored breathing


• difficult, burning, or painful urination


• difficulty with moving


• discouragement


• dizziness


• dry mouth


• excess air or gas in the stomach or intestines


• excessive muscle tone


• fast, irregular, pounding, or racing heartbeat or pulse


• fear


• feeling faint


• feeling of constant movement of self or surroundings


• feeling of warmth or heat


• feeling sad or empty


• flushed, dry skin


• flushing or redness of the skin especially on the face and neck


• frequent urge to urinate


• fruit-like breath odor


• full feeling


• gas in stomach


• general feeling of discomfort or illness


• heartburn


• increased hunger


• increased thirst


• increased urination


• irritability


• itching skin


• joint pain


• lack of appetite


• lack or loss of strength


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


• lightheadedness


• loss of appetite


• loss of consciousness


• loss of interest or pleasure


• lower back or side pain


• muscle tension or tightness


• nausea


• neck pain


• nerve pain


• nervousness


• noisy breathing


• pain


• pain or swelling in the arms or legs without any injury


• pain or tenderness around the eyes and cheekbones


• pain, swelling, or redness in the joints


• pale skin


• passing gas


• pounding in the ears


• sensation of spinning


• shivering


• shortness of breath


• sleeplessness


• slow heartbeat


• sneezing


• stomach pain, discomfort, tenderness, or upset


• stuffy nose


• sweating


• swelling of the hands, ankles, feet, or lower legs


• trouble with concentrating


• trouble with sleeping


• troubled breathing


• unable to sleep


• unexplained weight loss


• unusual bleeding or bruising


• vomiting


• wheezing

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: rosuvastatin side effects (in more detail)

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More rosuvastatin resources

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

• Rosuvastatin MedFacts Consumer Leaflet (Wolters Kluwer)


• Crestor Prescribing Information (FDA)


• Crestor Monograph (AHFS DI)


• Crestor Consumer Overview

Compare rosuvastatin with other medications

• Atherosclerosis
• High Cholesterol
• High Cholesterol, Familial Heterozygous
• High Cholesterol, Familial Homozygous
• Hyperlipoproteinemia
• Hyperlipoproteinemia Type IIa, Elevated LDL
• Hyperlipoproteinemia Type IIb, Elevated LDL VLDL
• Hyperlipoproteinemia Type III, Elevated beta-VLDL IDL
• Hyperlipoproteinemia Type IV, Elevated VLDL
• Prevention of Cardiovascular Disease

Raniclor

Pronunciation: SEFF-uh-klor
Generic Name: Cefaclor
Brand Name: Raniclor

Raniclor is used for:

Treating infections caused by certain bacteria.

Raniclor is a cephalosporin antibiotic. It kills sensitive bacteria by interfering with formation of the bacteria's cell wall while it is growing. This weakens the cell wall and it ruptures, resulting in the death of the bacteria.

Do NOT use Raniclor if:

• you are allergic to any ingredient in Raniclor or any other cephalosporin antibiotic (eg, cephalexin)

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

Before using Raniclor:

Some medical conditions may interact with Raniclor. 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 diarrhea, a stomach infection, or a blood clotting disorder


• if you have phenylketonuria


• if you have had a severe allergic reaction (eg, a severe rash, hives, breathing difficulties, dizziness) to a penicillin antibiotic (eg, amoxicillin) or other beta-lactam antibiotic (eg, imipenem)

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

• Probenecid because it may increase the actions and side effects of Raniclor


• Oral anticoagulants (eg, warfarin) because side effects, including risk of bleeding, may be increased by Raniclor

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

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

• Raniclor may be taken with or without food.


• Chew thoroughly before swallowing.


• To clear up your infection completely, continue using Raniclor for the full course of treatment, even if you feel better in a few days.


• Raniclor works best if it is taken at the same time(s) each day.


• If you miss a dose of Raniclor, 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 Raniclor.

Important safety information:

• Raniclor is effective only against bacteria. It is not effective for treating viral infections (eg, the common cold)


• Long-term or repeated use of Raniclor may cause a second infection. Your doctor may want to change your medicine to treat the second infection. Contact your doctor if signs of a second infection occur.


• It is important to use Raniclor for the full course of treatment. Failure to do so may decrease the effectiveness of this treatment and may increase the risk that the bacteria will no longer be sensitive to Raniclor and it will not be able to be treated by this or certain other antibiotics in the future.


• If severe diarrhea, stomach pain/cramps, or bloody stools occurs, contact your doctor immediately. This could be a symptom of a serious side effect requiring immediate medical attention. Do not treat diarrhea without consulting your doctor.


• It is important to use Raniclor for the full course of treatment. Failure to do so may decrease the effectiveness of this treatment and may increase the risk that the bacteria will no longer be sensitive to Raniclor and it will not be able to be treated by this or certain other antibiotics in the future.


• Phenylketonuria patients - Raniclor contains phenylalanine.


• Diabetes patients - Raniclor may cause false test results with some urine glucose tests. Check with your doctor before you adjust the dose of your diabetes medicine or change your diet.


• Use Raniclor with caution in the ELDERLY since they may be more sensitive to its effects.


• PREGNANCY AND BREAST-FEEDING: If you plan on becoming pregnant, discuss with your doctor the benefits and risks of using Raniclor during pregnancy. Raniclor is excreted in breast milk. If you are or will be breast-feeding while you are using Raniclor, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Raniclor:

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:

Headache; mild diarrhea; nausea; sinus infection; tiredness; vomiting.

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

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; itching); bloody stools; fever; seizures; severe diarrhea; stomach cramps/pain; urge to have a bowel movement; vaginal irritation or discharge.

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: Raniclor side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include diarrhea, nausea, stomach pain, and vomiting.

Proper storage of Raniclor:

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

General information:

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


• Raniclor 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 within a few days or if they become worse, check with your doctor.


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

This information is summary only. It does not contain all information about Raniclor. 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 Raniclor resources

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

• Raniclor Concise Consumer Information (Cerner Multum)


• cefaclor Prescribing Information (FDA)


• Cefaclor Professional Patient Advice (Wolters Kluwer)


• Cefaclor Monograph (AHFS DI)

Compare Raniclor with other medications

• Bladder Infection
• Bronchitis
• Kidney Infections
• Otitis Media
• Pneumonia
• Sinusitis
• Skin and Structure Infection
• Skin Infection
• Tonsillitis/Pharyngitis
• Upper Respiratory Tract Infection
• Urinary Tract Infection

Retrovir

Generic Name: Zidovudine
Class: Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
VA Class: AM800
Chemical Name: 3′-Azido-3′-deoxythymidine
CAS Number: 30516-87-1

Special Alerts:

[Posted 03/01/2011] ISSUE: FDA updated the public about an ongoing safety review of abacavir and a possible increased risk of heart attack. There has been conflicting information on the potential increased risk of heart attack with abacavir (Ziagen) treatment. An increased risk of heart attack (myocardial infarction or MI) has been seen in several observational studies and one randomized controlled trial (RCT) with abacavir. However, an increased risk of heart attack has not been seen in other RCTs and the safety database maintained by the drug manufacturer.

FDA conducted a meta-analysis of 26 randomized clinical trials that evaluated abacavir. This meta-analysis did not show an increased risk of MI associated with the use of abacavir. FDA will continue to communicate any new safety information to the public as it becomes available.

BACKGROUND: Abacavir is an antiviral medication used in combination with other antiretroviral drugs [abacavir and lamivudine (Epzicom); abacavir, lamivudine, and zidovudine (Trizivir)] for the treatment of HIV-1 infection.

RECOMMENDATION: Healthcare professionals should continue to prescribe abacavir according to the professional label. Patients should not stop taking their abacavir without first talking to their healthcare professional. For more information visit the FDA website at: and .

REMS:

FDA approved a REMS for zidovudine 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 ().

• 
  

  Hematologic toxicity reported, particularly in patients with advanced disease.^{1 231} (See Hematologic Effects under Cautions.)

  
  


• 
  

  Symptomatic myopathy reported.^{1 231} (See Musculoskeletal Effects under Cautions.)

  
  


• 
  

  Lactic acidosis and severe hepatomegaly with steatosis (including some fatalities) reported rarely in patients receiving nucleoside reverse transcriptase inhibitors (NRTIs) alone or in conjunction with other antiretrovirals.^{1 231} (See Lactic Acidosis and Severe Hepatomegaly with Steatosis under Cautions.)

  
  


• 
  

  If using Trizivir, consider that abacavir has been associated with serious and sometimes fatal hypersensitivity reactions.¹⁰

  
  

Introduction

Antiretroviral; nucleoside reverse transcriptase inhibitor (NRTI).^{1 4 7 12 16 18 29 39 47 231 260 296}

Uses for Retrovir

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.

Treatment of HIV Infection

Treatment of HIV-1 infection in conjunction with other antiretrovirals.^{1 231 279 466}

An alternative (not a preferred) NRTI for use in multiple-drug antiretroviral regimens for initial therapy in adults.²⁷⁹

Fixed-combination preparation containing zidovudine and lamivudine (Combivir) used in conjunction with other antiretrovirals.²⁷¹

Fixed-combination preparation containing zidovudine, abacavir, and lamivudine (Trizivir) used for triple NRTI treatment;¹⁰ can be used alone or in conjunction with other antiretrovirals.¹⁰ If using Trizivir, consider that data are limited regarding use of the fixed combination in patients with higher viral loads (>100,000 copies/mL) at baseline.¹⁰

Because of inferior antiretroviral activity, a triple NRTI regimen of abacavir, lamivudine, and zidovudine is not recommended for initial therapy.²⁷⁹

Prevention of Maternal-fetal Transmission of HIV

Prevention of maternal-fetal transmission of HIV.^{1 231 279 455}

A regimen that includes combination antiretroviral therapy or prophylaxis in the pregnant women, intrapartum therapy, and zidovudine prophylaxis in the newborn is recommended for the prevention of perinatal HIV transmission.⁴⁵⁵ Antiretroviral therapy or antiretroviral prophylaxis for prevention of perinatal HIV transmission during the antepartum period recommended for all pregnant HIV-infected women in the US; zidovudine should be included in the regimen when feasible.⁴⁵⁵ Intrapartum zidovudine in conjunction with other antiretroviral agents is recommended in all pregnant HIV-infected women.⁴⁵⁵ Administration of zidovudine for 6 weeks is recommended for all HIV-exposed infants.⁴⁵⁵

If intrapartum/newborn zidovudine is used for prevention of perinatal HIV transmission in women in labor who received no prior antiretroviral therapy, some clinicians would add single-dose intrapartum/newborn nevirapine (a nevirapine dose given to the mother at onset of labor and a nevirapine dose given to the neonate).⁴⁵⁵

If a single-dose nevirapine regimen in conjunction with intrapartum/newborn zidovudine is used for prevention of perinatal HIV transmission in women in labor who received no prior antiretroviral therapy, some clinicians suggest that consideration be given to adding a zidovudine and lamivudine regimen in the mother to reduce development of nevirapine resistance.⁴⁵⁵

Postexposure Prophylaxis of HIV

Postexposure prophylaxis of HIV infection† in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with risk for transmission of the virus.^{96 97 98 149 194 224 337 338 339 340 341 342 343 344 418 464 465} Used in conjunction with other antiretrovirals.⁴⁶⁴

Postexposure prophylaxis of HIV infection† in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.⁵⁰³ Used in conjunction with other antiretrovirals.⁵⁰³

Retrovir Dosage and Administration

Administration

Administer orally or by intermittent or continuous IV infusion.^{1 231} Should not be administered by rapid or bolus IV injection, IM injection, or sub-Q injection.²³¹

Oral Administration

Administer single-entity preparations (Retrovir) and fixed-combination preparations (Combivir, Trizivir) orally without regard to meals.^{1 10 271}

To reduce risk of esophageal irritation and ulceration, zidovudine capsules should be administered while the patient is in an upright position and with adequate amounts of fluid (e.g., at least 120 mL of water).¹⁸⁴

For children, zidovudine oral solution can be used.¹ Alternatively, children who can reliably swallow an intact tablet or capsule may receive zidovudine tablets or capsules.¹

Because dosage of zidovudine and lamivudine cannot be adjusted individually, the fixed-combination containing zidovudine and lamivudine (Combivir) should not be used in individuals requiring dosage adjustment, including children <12 years of age, patients with impaired renal function (i.e., Cl_cr <50 mL/minute), patients with impaired hepatic function, and patients who experience dose-limiting adverse effects.²⁷¹

Because dosage of the drugs cannot be adjusted individually, the fixed-combination containing abacavir, lamivudine, and zidovudine (Trizivir) should not be used in pediatric patients; adolescents or adults with low body weight (i.e., <40 kg); patients with impaired renal function (i.e., Cl_cr <50 mL/minute); patients with impaired hepatic function; or patients who experience dose-limiting adverse effects.¹⁰

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Oral zidovudine should replace parenteral zidovudine as soon as feasible.²³¹

Dilution

Zidovudine concentrate for IV infusion containing 10 mg/mL must be diluted prior to administration.²³¹ The appropriate dose should be withdrawn from the vial and diluted in 5% dextrose injection to provide a solution containing ≤4 mg/mL.²³¹

Rate of Administration

Intermittent IV infusions should be infused at a constant rate over 60 minutes.²³¹

In neonates, intermittent IV infusions should be infused at a constant rate over 30 minutes.²³¹

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.

Used in conjunction with other antiretrovirals for treatment of HIV infection or for postexposure prophylaxis of HIV;^{1 231 271} may be used alone or in conjunction with other antiretrovirals for prevention of maternal-fetal transmission of HIV.^{1 231} The fixed-combination preparation containing zidovudine, abacavir, and lamivudine may be used alone or in conjunction with other antiretrovirals.¹⁰

Dosage of Combivir and Trizivir expressed as number of tablets.^{10 271}

IV dosing regimen of 1 mg/kg every 4 hours is equivalent to an oral regimen of 100 mg every 4 hours.²³¹

Modification of zidovudine dosage is necessary in adults or pediatric patients who develop anemia and/or neutropenia.^{1 91 92 229 231 244 245 451} Substantial anemia (hemoglobin <7.5 g/dL or a reduction >25% from baseline) and/or neutropenia (granulocyte count <750/mm³ or a reduction >50% from baseline) may require dose interruption until evidence of bone marrow recovery occurs.^{1 231} If bone marrow recovery occurs following interruption of therapy, reinitiation of zidovudine therapy may be appropriate.^{1 231} (See Hematologic Effects under Cautions.)

Pediatric Patients

Treatment of HIV Infection

To avoid medication errors, use extra care in calculating the dose, transcribing the medication order, dispensing the prescription, and providing dosing instructions.¹

Oral

Premature neonates: 2 mg/kg every 12 hours; frequency of administration may be increased to every 8 hours at 2 weeks of age in neonates with ≥30 weeks gestation at birth or at 4 weeks of age in those with <30 weeks gestation at birth.^{455 466}

Neonates and infants <6 weeks of age: 2 mg/kg every 6 hours.⁴⁶⁶

Zidovudine Dosage in Pediatric Patients ≥6 Weeks of Age Who Weigh ≥4 kg 1

Body Weight (kg)	Dosage Regimen
4 to <9	12 mg/kg twice daily or 8 mg/kg 3 times daily
9 to <30	9 mg/kg twice daily or 6 mg/kg 3 times daily
≥30	300 mg twice daily or 200 mg 3 times daily

Alternatively, for pediatric patients ≥6 weeks of age, 240 mg/m² twice daily or 160 mg/m² 3 times daily.¹

Combivir: 1 tablet twice daily in adolescents ≥12 years of age.^{271 466}

Trizivir: 1 tablet twice daily in adolescents weighing ≥40 kg.^{10 466}

IV

Premature neonates: 1.5 mg/kg every 12 hours; the frequency of administration may be increased to every 8 hours at 2 weeks of age in neonates with ≥30 weeks gestation at birth or at 4 weeks of age in those with <30 weeks gestation at birth.^{455 466}

Neonates and infants <6 weeks of age: 1.5 mg/kg every 6 hours.⁴⁶⁶

Infants and children 6 weeks to 12 years of age: 120 mg/m² by intermittent IV infusion every 6 hours; alternatively, 20 mg/m² per hour by continuous IV infusion.⁴⁶⁶

Prevention of Maternal-fetal Transmission of HIV

Postexposure Prophylaxis

Oral

Premature neonates: Initiate therapy with 2 mg/kg every 12 hours; frequency of administration may be increased to every 8 hours at 2 weeks of age in neonates with >30 to <35 weeks gestation at birth or at 4 weeks of age in those with <30 weeks gestation at birth.^{455 466} Zidovudine is continued through 6 weeks of age.⁴⁵⁵

Neonates ≥35 weeks at gestation: 2 mg/kg every 6 hours starting within 6–12 hours after birth and continued through 6 weeks of age.^{1 231 455 458}

Used in conjunction with intrapartum zidovudine in the mother.⁴⁶⁶

IV

Premature neonates: Initiate therapy with 1.5 mg/kg every 12 hours; frequency of administration may be increased to every 8 hours at 2 weeks of age in neonates with ≥30 to <35 weeks gestation at birth or at 4 weeks of age in those with <30 weeks gestation at birth.^{455 466} Zidovudine is continued through 6 weeks of age.⁴⁵⁵

Neonates ≥35 weeks at gestation: 1.5 mg/kg every 6 hours starting within 6–12 hours after birth.^{1 231 455} Zidovudine is continued through 6 weeks of age.⁴⁵⁵

Used in conjunction with intrapartum zidovudine in the mother.⁴⁶⁶

Adults

Treatment of HIV Infection

Oral

600 mg daily in divided doses.^{1 3 279 466 483 484 485 486 487 488 489 490 497} Usually given in a dosage of 200 mg 3 times daily or 300 mg twice daily.^{3 279 466}

Combivir: 1 tablet twice daily.^{271 279}

Trizivir: 1 tablet twice daily.^{10 279} Patient should weigh ≥40 kg.¹⁰

IV

1 mg/kg 5 to 6 times daily (5 to 6 mg/kg daily).²³¹ Higher dosage may be associated with greater improvement of neurologic symptoms in patients with preexisting neurologic disease.²³¹

Prevention of Maternal-fetal Transmission of HIV

Oral

IV

At start of labor, 2 mg/kg over 1 hour followed by 1 mg/kg per hour given by continuous IV infusion until the umbilical cord is clamped.^{1 231 455}

Used in conjunction with a 6-week zidovudine regimen in the neonate.^{466 455}

Postexposure Prophylaxis of HIV†

Occupational Exposure†

Oral

200 mg 3 times daily or 300 mg twice daily.⁴⁶⁴

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.^{464 467 470}

Nonoccupational Exposure†

Oral

200 mg 3 times daily or 300 mg twice daily.⁵⁰³

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.⁵⁰³

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection

Oral

Children 6 weeks to 12 years of age: Maximum 200 mg every 8 hours.¹

Special Populations

Hepatic Impairment

Treatment of HIV Infection

Insufficient clinical experience to recommend dosage adjustment for patients with mild to moderate hepatic impairment or liver cirrhosis; a reduction in dosage may be necessary in these patients and frequent monitoring for hematologic toxicities advised.^{1 231}

Renal Impairment

Treatment of HIV Infection

Oral

100 mg every 6 to 8 hours for patients with end-stage renal disease maintained on hemodialysis or peritoneal dialysis.¹

IV

1 mg/kg every 6 to 8 hours for patients with end-stage renal disease maintained on hemodialysis or peritoneal dialysis.²³¹

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^{1 231}

Cautions for Retrovir

Contraindications

• 
  

  History of clinically important hypersensitivity reaction (e.g., anaphylaxis, Stevens-Johnson syndrome) to zidovudine or any ingredient in the formulation.^{1 231}

  
  

Warnings/Precautions

Warnings

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.

Hematologic Effects

Use with caution in patients who have compromised bone marrow function (i.e., hemoglobin concentration <9.5 g/dL or granulocyte count <1000/mm³).^{1 231}

Anemia and/or neutropenia reported; these events are especially important in patients with advanced symptomatic HIV disease.^{1 2 3 4 29 30 33 38 62 64 65 82 106 107 134 139 231 260 332} Pancytopenia reported; pancytopenia usually reversible following discontinuation of zidovudine.^{1 231}

Blood cell counts and indices of anemia (e.g., hemoglobin, mean corpuscular volume) should be determined prior to and monitored during zidovudine therapy.^{1 50 64 181 231 332} Patients with advanced HIV disease or low baseline blood cell counts and indices of anemia should be monitored frequently^{1 231} (at least every 2 weeks);^{181 231} periodic monitoring^{1 231} (once monthly for the first 3 months and then, if stable, once every 3 months) recommended for patients with asymptomatic or early symptomatic HIV infection.¹⁸¹

If anemia and/or neutropenia occurs, interruption of zidovudine therapy and/or dosage adjustment may be necessary.^{1 231} In patients who develop substantial anemia, interruption of zidovudine therapy does not necessarily eliminate the need for transfusions.^{1 231}

Musculoskeletal Effects

Myopathy and myositis with pathologic changes, similar to that produced by HIV disease, associated with long-term use of zidovudine.^{1 231}

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving zidovudine.^{1 271} Reported most frequently in women; obesity and long-term NRTI therapy also may be risk factors.^{1 271} Has been reported in patients with no known risk factors.^{1 271}

Use with caution in patients with known risk factors for liver disease.^{1 271}

Interrupt therapy if there are clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (e.g., hepatomegaly and steatosis even in the absence of marked increases in serum aminotransferase concentrations).^{1 271}

General Precautions

Do not use multiple zidovudine-containing preparations concomitantly.^{1 271}

Incidence of adverse effects increases with disease progression; monitor patients carefully, especially as disease progression occurs.^{1 231}

Use of Fixed Combinations

When used in fixed combination with lamivudine (Combivir), consider the cautions, precautions, and contraindications associated with lamivudine.²⁷¹

When used in fixed combination with abacavir and lamivudine (Trizivir), consider the cautions, precautions, and contraindications associated with the concomitant agents.¹⁰

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.¹

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]); this may necessitate further evaluation and treatment.¹

Specific Populations

Pregnancy

Category C.^{1 231} Antiretroviral Pregnancy Registry at 800-258-4263.^{1 231}

The preferred NRTI for use in antiretroviral regimens in pregnant women based on efficacy studies and extensive experience.²⁷⁹ Pregnancy registry data indicate no increased risk for congenital abnormalities among infants born to women who receive zidovudine during pregnancy compared with general population.^{453 455}

Lactation

Distributed into human milk.^{1 231}

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.¹

Pediatric Use

Studied in neonates perinatally exposed to HIV and in HIV-infected pediatric patients >3 months of age.^{1 231}

The major adverse effects reported in children are similar to those reported in adults^{1 91 92 114 163 244 245} and include bone marrow toxicity resulting in anemia and/or neutropenia.^{1 91 92 114 155 231 244 245}

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.^{1 231} No substantial differences in response relative to younger adults identified.^{1 231}

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^{1 231}

Hepatic Impairment

Possibility of increased risk of hematologic toxicity in patients with severe hepatic impairment.^{1 231}

Use with caution in patients with known risk factors for liver disease.^{1 231}

Renal Impairment

Dosage adjustment recommended in patients with severe renal impairment (Cl_cr <15 mL/minute).^{1 231} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Adults: Headache, malaise, anorexia, nausea, vomiting.^{1 231}

Children: Fever, cough, GI disorders.¹

Interactions for Retrovir

Specific Drugs

Drug	Interaction	Comments
Abacavir	Pharmacokinetic interactions unlikely161 In vitro evidence of synergistic antiretroviral effects161
Acetaminophen	Pharmacokinetic interactions unlikely156
Acyclovir	Increased toxicity reported;15 has been used concomitantly without increased toxicity61 181
Antifungals, azoles (fluconazole)	Increased zidovudine AUC with fluconazole1 231 457	Routine dosage adjustment not needed;1 231 monitor for zidovudine-associated adverse effects457 Consider reduction in zidovudine dosage if patient experiences severe anemia or other severe events1 231
Antimycobacterials, rifamycins (rifabutin, rifampin)	Pharmacokinetic interactions unlikely with rifabutin409 Decreased zidovudine AUC with rifampin1 150 231
Atazanavir	No change in zidovudine AUC, but possible decreased zidovudine concentrations279 In vitro evidence of additive antiretroviral effects507	Clinical importance unknown279
Atovaquone	Increased zidovudine AUC; no change in pharmacokinetics of atovaquone1 231 242 Possible increased hematologic toxicity242	Routine dosage adjustments not needed1 231
Cidofovir	No pharmacokinetic interaction with cidofovir; cidofovir must be given concomitantly with probenecid and probenecid can reduce zidovudine clearance243	Temporarily discontinue zidovudine or reduce zidovudine dosage by 50% on days that cidofovir and probenecid are given243
Co-trimoxazole	Pharmacokinetic interactions unlikely333
Cytotoxic/Myelosuppressive agents	Increased risk of hematologic toxicity1 29 176 231 332	Use with caution29 176 332
Darunavir	Ritonavir-boosted darunavir: Pharmacokinetic interaction unlikely510
Delavirdine	Pharmacokinetic interactions unlikely284 In vitro evidence of additive or synergistic antiretroviral effects1 175 284 391 406
Didanosine	Pharmacokinetic interactions unlikely279 422 In vitro evidence of synergistic antiretroviral effects281
Doxorubicin	In vitro evidence of antagonism1 227 231	Concomitant use should be avoided1 231
Efavirenz	Pharmacokinetic interactions unlikely175 In vitro evidence of synergistic antiretroviral effects1 175 284 391 406	Dosage adjustment not needed175
Emtricitabine	In vitro evidence of additive or synergistic antiretroviral effectsb
Fosamprenavir	Studies using amprenavir indicate possible increased amprenavir AUC;d possible increased zidovudine plasma concentrations and AUCd In vitro evidence of synergistic antiretroviral effectsd
Ganciclovir	No clinically important pharmacokinetic interactions279 Increased risk of hematologic toxicity196 197 201 213 278 279	Concomitant use not recommended196 197 201 213 278
Indinavir	In vitro evidence of additive or synergistic antiretroviral effects166 215 480 481 482
Interferon (interferon alfa, peginterferon alfa)	Possible increased risk of potentially fatal hepatic decompensation in patients coinfected with hepatitis C virus (HCV) and HIV who are receiving interferon alfa, ribavirin, and antiretroviral agents1 f Increased risk of hematologic toxicity (e.g., neutropenia, thrombocytopenia) and hepatic toxicity in patients receiving interferon alfa or peginterferon alfa, ribavirin, and zidovudine1 231 395 399 f In vitro evidence of synergistic antiretroviral effects34 57 351 395 396 397 398 399	Monitor for adverse effects1 231 395 399 f If zidovudine used in patients receiving interferon alfa or peginterferon alfa (with or without ribavirin), closely monitor for toxicities, especially hepatic decompensation; consider discontinuing zidovudine as appropriate; if worsening toxicities (e.g., hepatic decompensation Child-Pugh >6) are observed, consider discontinuing or reducing dosage of interferon or peginterferon alfa and/or ribavirin1 f
Lamivudine	Pharmacokinetic interactions unlikely1 231 In vitro evidence of synergistic antiretroviral effects347
Lopinavir	Possible decreased zidovudine concentrations508	Clinical importance unknown508
Megestrol acetate	Slight decrease in zidovudine AUC102	Not considered clinically important102
Methadone	Increased zidovudine AUC; no change in pharmacokinetics of methadone1 231 279 350	Routine dosage adjustment not needed; monitor for zidovudine toxicity1 231 279
Nelfinavir	Decreased zidovudine peak plasma concentrations and AUC; no effect on nelfinavir pharmacokinetics1 215 231 In vitro evidence of additive or synergistic antiretroviral effects166 215 480 481 482	Routine dosage adjustment not needed1 215 231
Nevirapine	Decreased plasma zidovudine concentrations391 In vitro evidence of synergistic antiretroviral effects1 175 284 391 406
Oxazepam	Pharmacokinetic interactions unlikely353
Phenytoin	Pharmacokinetic interactions; alteration in pharmacokinetics of both drugs reported1 231	Use with caution; monitor closely1 231
Probenecid	Increased zidovudine peak plasma concentrations and AUC1 231	Routine dosage adjustment not needed1 231
Ribavirin	Ribavirin can reduce phosphorylation of zidovudine;37 60 279 no evidence of pharmacokinetic or pharmacodynamic interaction in patients coinfected with HCV and HIV1 Possible increased risk of potentially fatal hepatic decompensation in patients coinfected with HCV and HIV who are receiving interferon alfa or peginterferon alfa, ribavirin, and antiretroviral agents1 f	Concomitant use should be avoided if possible or closely monitor virologic response and hematologic toxicities 279 If zidovudine used in patients receiving interferon alfa or peginterferon alfa (with or without ribavirin), closely monitor for toxicities, especially hepatic decompensation; consider discontinuing zidovudine as appropriate; if worsening toxicities (e.g., hepatic decompensation Child-Pugh >6) are observed, consider discontinuing or reducing dosage of interferon and/or ribavirin1 f
Ritonavir	Decreased zidovudine peak plasma concentrations and AUC; no effect on ritonavir pharmacokinetics1 231 481 In vitro evidence of additive or synergistic antiretroviral effects166 215 480 481 482	Routine dosage adjustment not needed1 231
Saquinavir	In vitro evidence of additive or synergistic antiretroviral effects166 215 480 481 482
Stavudine	In vitro evidence of antagonism1 165 231	Concomitant use not recommended1 231 279
Tipranavir	Ritonavir-boosted tipranavir: Decreased zidovudine AUC279 e In vitro evidence of additive antiretroviral effectse	Clinical importance unknowne Appropriate dosages for concomitant use with ritonavir-boosted tipranavir not established279 e
Valproic acid	Increased zidovudine AUC1 231	Routine dosage adjustment not needed; monitor for zidovudine toxicity1 231 279 Consider reduction in zidovudine dosage if patient experiences severe anemia or other severe events1 231

Retrovir Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration; peak plasma concentrations achieved within 0.5–1.5 hours.^{1 2 4 110 111 115 116 117 119} Bioavailability is 64%.¹

Commercially available tablets, capsules, and oral solution are bioequivalent.¹

Food

Extent of absorption (AUC) not affected by food.¹

Special Populations

Zidovudine AUC increased in patients with renal impairment.^{1 177 231}

Zidovudine pharmacokinetics in pediatric patients >3 months of age similar to that in adults; bioavailability is 61% in infants 14 days to 3 months of age and 65% in pediatric patients 3 months to 12 years of age.¹ Bioavailability is greater in neonates ≤14 days of age and is reported to be 89%.¹

Pharmacokinetics of zidovudine in pregnant women are similar to those reported in nonpregnant adults.^{1 231}

Distribution

Extent

Widely distributed.^{1 32 231}

Distributed into CSF; ^{1 32 67 114 148 177 231} the ratio of CSF/plasma concentrations reported in adults or children with HIV infection is 0.15–2.1.^{1 32 67 114 115 148 177 231}

Distributed into semen.^{110 145 159 160}

Rimantadine Hydrochloride

Class: Adamantanes
VA Class: AM800
Chemical Name: α-Methyl tricyclo[3.3.1.13,7]decane-1-methanamine hydrochloride
Molecular Formula: C₁₂H₂₁N•HCl
CAS Number: 1501-84-4
Brands: Flumadine

Introduction

Antiviral; adamantane derivative.^{1 3 10 15 16 40 42}

Uses for Rimantadine Hydrochloride

Treatment of Seasonal Influenza A Virus Infections

Symptomatic treatment of uncomplicated illness caused by susceptible influenza A virus.^{1 2 3 5 11 15 16 33 37 61}

Consider viral surveillance data available from local and state health departments and the CDC when selecting an antiviral for treatment of seasonal influenza.^{116 137 149} Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve,^{116 144} and emergence of rimantadine-resistant influenza virus may decrease effectiveness of the drug.¹

Beginning in the 2005–2006 influenza season, most influenza A (H3N2) strains circulating in the US were resistant to adamantanes (amantadine, rimantadine),^{29 77 116 121} and resistance to the drugs among seasonal influenza A (H3N2) isolates has remained high during subsequent influenza seasons.^{29 117 162} In addition, the 2009 pandemic influenza A (H1N1) virus was resistant to amantadine and rimantadine,^{52 117 151 162} and this strain is expected to continue to circulate during the 2010–2011 influenza season.^{144 162}

Amantadine and rimantadine have little or no activity against influenza B.^{1 11 15 16 35 42}

CDC recommends that adamantanes (amantadine, rimantadine) not be used for the treatment of influenza in the US until susceptibility to these antiviral agents has been reestablished in circulating influenza A viruses.⁷⁷

CDC issues recommendations concerning the use of antiviral agents for the treatment of influenza, and these recommendations are updated as needed during each influenza season.¹⁴⁴ Information regarding influenza surveillance and updated recommendations for treatment of seasonal influenza are available from CDC at .

Prevention of Seasonal Influenza A Virus Infections

Prophylaxis of influenza infection caused by susceptible influenza A when timely vaccination with influenza virus vaccine is not feasible, contraindicated, or not available.^{1 3 4 7 8 16 47}

Annual vaccination with seasonal influenza virus vaccine, as recommended by the US Public Health Service Advisory Committee on Immunization Practices (ACIP), is the primary means of preventing seasonal influenza and its severe complications.^{1 29 116 144 149 161} Prophylaxis with an appropriate antiviral active against circulating influenza strains is considered an adjunct to vaccination for control and prevention of influenza in certain individuals.^{1 29 116 144 149 161}

Consider viral surveillance data available from local and state health departments and the CDC when selecting an antiviral for the prophylaxis of influenza.^{116 137 149} The most appropriate antiviral for prevention of influenza is selected based on information regarding the likelihood that the influenza strain is susceptible and the known adverse effects of the drug.^{137 144} Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve,^{137 144} and emergence of rimantadine-resistant influenza virus may decrease effectiveness of the drug.¹

CDC recommends that adamantanes (amantadine, rimantadine) not be used for prevention of influenza in the US until susceptibility to these antiviral agents has been reestablished in circulating influenza A viruses.⁷⁷

CDC issues recommendations concerning the use of antiviral agents for prophylaxis of influenza, and these recommendations are updated as needed during each influenza season.¹⁴⁴ Information regarding influenza surveillance and updated recommendations for prevention of seasonal influenza are available from CDC at .

Avian Influenza A Virus Infections

May be used for treatment or prophylaxis of avian influenza A virus infections† in certain situations.^{94 104}

The WHO recommends use of a neuraminidase inhibitor (i.e., oseltamivir) for the treatment of avian influenza A infections.^{94 104}

Concomitant use of a neuraminidase inhibitor (i.e., oseltamivir) and an adamantane (amantadine, rimantadine) can be considered in a patient with pneumonic disease or clinical progression if local surveillance data indicate the H5N1 virus is known or likely to be susceptible to an adamantane.¹⁰⁴

Should not be used alone for treatment of avian influenza A if a neuraminidase inhibitor is available.^{94 104}

Rimantadine Hydrochloride Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals.^{1 14}

Dosages <150 mg daily can be given as a single dose; dosages of 200 mg daily can be given in 2 divided doses.^{1 23} Dividing dosages >100 mg daily into 2 doses may minimize adverse effects.⁶³

Dosage

Available as rimantadine hydrochloride; dosage expressed in terms of rimantadine hydrochloride.¹

Pediatric Patients

Treatment of Seasonal Influenza A Virus Infections

Oral

Children ≥13 years of age†: 100 mg twice daily.²⁹

Initiate rimantadine treatment as soon as possible, preferably within 24–48 hours after onset of symptoms and continue for up to 5 days or 24–48 hours after symptoms disappear.¹

Prevention of Seasonal Influenza A Virus Infections

Oral

Children 1–9 years of age: 5 mg/kg (maximum 150 mg) once daily.^{1 29}

Children ≥10 years of age: 100 mg twice daily.¹ AAP recommends 5 mg/kg daily in 2 divided doses in those weighing <40 kg or 100 mg twice daily in those weighing ≥40 kg.²⁹

Individualize duration of prophylaxis. For maximum effectiveness, must be taken every day during influenza activity in the community. Manufacturer states that safety and efficacy for >6 weeks not established.¹

Adults

Treatment of Seasonal Influenza A Virus Infections

Oral

100 mg twice daily.^{1 28}

Initiate rimantadine treatment as soon as possible, preferably within 24–48 hours after onset of symptoms and continue for up to 5 days or 24–48 hours after symptoms disappear.¹

Prevention of Seasonal Influenza A Virus Infections

Oral

100 mg twice daily.^{1 28}

Duration of antiviral prophylaxis should be individualized. For maximum effectiveness, the antiviral agent must be taken every day during influenza activity in the community. Manufacturer states that safety and efficacy for >6 weeks not established.¹

For prophylaxis in conjunction with influenza virus vaccine (see Specific Drugs under Interactions), rimantadine should be administered for 2 weeks after vaccine administration.¹

Prescribing Limits

Pediatric Patients

Prevention of Seasonal Influenza A Virus Infections

Oral

Children 1–9 years of age: Maximum 150 mg daily.^{1 29}

Special Populations

Hepatic Impairment

Treatment or Prevention of Seasonal Influenza A Virus Infections

100 mg daily in patients with severe hepatic impairment.¹

Renal Impairment

Treatment or Prevention of Seasonal Influenza A Virus Infections

100 mg daily in patients with severe renal impairment (Cl_cr ≤10 mL/minute).¹ Further dosage adjustments may be needed.¹

Geriatric Patients

≥65 years of age: 100 mg daily recommended by the manufacturer;¹ ACIP and others recommend 100 mg daily in those who experienced adverse effects with the usual adult dosage.²⁸

Geriatric individuals residing in nursing homes: 100 mg daily.¹

Cautions for Rimantadine Hydrochloride

Contraindications

• 
  

  Known hypersensitivity to adamantane derivatives (rimantadine, amantadine) or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

CNS Effects

Patients with a history of seizure disorders should be observed closely for possible increased seizure activity.¹ Discontinue if seizures occur.¹

General Precautions

Other Viral or Bacterial Infections

Not effective for treatment or prophylaxis of viral respiratory tract illnesses other than those due to influenza A virus.¹

Serious bacterial infections may present with influenza-like symptoms, coexist with influenza, or occur during influenza.^{25 73}

Prescribing and Dispensing Errors.

Ensure accuracy of prescription; similar spelling of Flumadine (rimantadine) and flutamide may result in errors.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Distributed into milk in rats; adverse effects noted in the offspring of rats given the drug during the perinatal and postnatal period.¹ Use not recommended.¹

Pediatric Use

Used in children ≥1 year of age for prophylaxis of influenza A;¹ has not been evaluated for prophylaxis in infants <1 year of age.¹

Safety and efficacy for treatment of influenza A virus infection not established in children.¹ Has been used for the treatment of influenza A infection in children 1–15 years of age; safety and efficacy similar to that in adults.^{37 59 61}

Geriatric Use

Frequency and severity of adverse effects, including adverse CNS effects, in individuals >65 years of age receiving rimantadine hydrochloride 100 mg twice daily higher than in younger adults and children.^{1 47}

Consider age-related decreases in renal function when selecting dosage.¹ (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Caution in patients with hepatic impairment.¹ (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Caution in patients with renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Nausea,^{1 3 9 37 47 53} insomnia,^{1 3 40 47 53} dizziness.^{1 3 19 25 40 47 53}

Interactions for Rimantadine Hydrochloride

Specific Drugs

Drug	Interaction	Comments
Acetaminophen	Slightly decreased rimantadine peak plasma concentrations and AUC1
Aspirin	Slightly decreased rimantadine peak plasma concentrations and AUC1
Cimetidine	Decreased rimantadine clearance with single dose of cimetidine1	Effect of long-term administration not evaluated1
Influenza virus vaccines	Influenza virus vaccine inactivated: Rimantadine does not interfere with the antibody response to the vaccine1 Influenza virus vaccine live intranasal: Potential interference with antibody response to the live vaccine; no specific studies1 144	Influenza virus vaccine inactivated: May be used concomitantly with or at any interval before or after rimantadine1 144 Influenza virus vaccine live intranasal: Do not administer the live intranasal vaccine until at least 48 hours after rimantadine is discontinued; do not administer rimantadine until at least 2 weeks after administration of the live intranasal vaccine;1 144 repeat vaccination if influenza antiviral is given 2 days before to 14 days after the vaccine144

Rimantadine Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract; peak plasma concentrations usually attained within 6 hours.^{1 14 40 49 51}

Commercially available tablets and oral solution are bioequivalent.^{1 56 60}

Food

Food does not appear to affect absorption.^{1 14}

Distribution

Extent

Not fully characterized.¹ Distributed into nasal secretions.^{40 51 54}

Crosses the placenta in rats; distributed into milk in rats.¹ Not known whether rimantadine crosses the placenta or is distributed into human milk.¹

Plasma Protein Binding

40%.^{1 40}

Elimination

Metabolism

Extensively metabolized in the liver.^{1 40 55}

Elimination Route

Principally excreted in urine (74%) as metabolites and unchanged drug (25%).^{1 40 55}

Not removed by hemodialysis.¹

Half-life

25–38 hours in adults and children.^{1 40 49 51 54 60}

Special Populations

No change in pharmacokinetics in patients with chronic liver disease (mainly stabilized cirrhosis).¹ Clearance reduced and half-life increased twofold in patients with severe hepatic impairment.¹

In patients with renal impairment, half-life prolonged and clearance decreased.^{1 20}

Stability

Storage

Oral

Tablets

15–30°C.¹

Oral Solution

15–30°C.¹

ActionsActions and Spectrum

• 
  

  Adamantane-derivative (a symmetric tricyclic amine);^{1 3 10 15 16 40 42} structurally related to amantadine.^{2 3 4 5 8 10 15 16 17 40 42}

  
  


• 
  

  Has antiviral activity against some strains of influenza A, including some strains of H1N1, H2N2, and H3N2.^{1 4 5 11 12 16 42 45}

  
  


• 
  

  Has little or no activity against influenza B.^{1 11 15 16 35 42}

  
  


• 
  

  Worldwide incidence of influenza A viruses resistant to adamantanes (amantadine, rimantadine) has increased over the last several years.^{84 92 121}

  
  


• 
  

  Beginning in the 2005–2006 influenza season, most influenza A (H3N2) strains circulating in the US were resistant to amantadine and rimantadine.^{77 121} Resistance to amantadine and rimantadine among seasonal influenza A (H3N2) isolates has remained high during subsequent influenza seasons.^{29 93 117 162}

  
  


• 
  

  Although amantadine and rimantadine were active against most seasonal influenza A (H1N1) viruses circulating in the US during the 2008–2009 and 2009–2010 influenza seasons,^{133 139 162} the 2009 pandemic influenza A (H1N1) virus is resistant to amantadine and rimantadine.^{52 117 151 162}

  
  


• 
  

  Some strains of avian influenza A (H5N1) have been susceptible to rimantadine;^{38 39} other strains, including influenza A (H5N1) isolated from patients in Asia during 2004 and 2005, have been resistant.⁷⁶

  
  


• 
  

  Rimantadine inhibits viral replication by interfering with the influenza A virus M2 protein, an integral membrane protein.^{1 11 15 16 41 42 46}

  
  


• 
  

  Strains of influenza A virus with reduced susceptibility to rimantadine have been produced in vitro and have emerged during therapy with the drug.^{1 6 8 9 10 11 12 24 25 41 42 43 46}

  
  


• 
  

  Rimantadine-resistant influenza A viruses also are resistant to amantadine.^{9 10 16 25 41 42 43 46 48}

  
  

Advice to Patients

• 
  

  Importance of not getting up suddenly from a sitting or lying position; notify clinician if dizziness or lightheadedness occur.¹

  
  


• 
  

  Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, as well as any concomitant illnesses.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of advising 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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Rimantadine Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution	50 mg/5 mL	Flumadine Syrup	Forest
	Tablets, film-coated	100 mg*	Flumadine	Forest
			Rimantadine Hydrochloride Tablets

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Flumadine 100MG Tablets (CARACO): 14/$43.99 or 42/$109.97

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 December 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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