Helixate NexGen 250 IU

Helixate NexGen 250 IU powder and solvent for solution for injection

Recombinant coagulation factor VIII (octocog alfa)

Read all of this leaflet carefully before you start using this medicine.

• Keep this leaflet. You may need to read it again.


• If you have any further questions, ask your doctor or your pharmacist.


• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.


• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

• 1. What Helixate NexGen 250 IU is and what it is used for


• 2. Before you use Helixate NexGen 250 IU


• 3. How to use Helixate NexGen 250 IU


• 4. Possible side effects


• 5. How to store Helixate NexGen 250 IU


• 6. Further information

WHAT Helixate NexGen 250 IU IS AND WHAT IT IS USED FOR

Helixate NexGen 250 IU belongs to a pharmacotherapeutic group called blood coagulation Factor VIII (ATC-Code B02B D02).

Treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency).

This preparation does not contain von Willebrand factor and is therefore not indicated in von Willebrand's disease.

One vial with powder for solution for injection nominally contains 250 IU octocog alfa (IU equals International Units). After reconstitution with the appropriate volume of solvent (water for injections), each vial contains octocog alfa 100 IU/ml.

BEFORE YOU USE Helixate NexGen 250 IU

Do not use Helixate NexGen 250 IU if you are allergic (hypersensitive) to octocog alfa, to mouse or hamster protein or to any of the other ingredients of Helixate NexGen 250 IU.

If you are unsure about this, ask your doctor.

Take special care with Helixate NexGen 250 IU as there is a rare chance that you may experience an anaphylactic reaction (a severe, sudden allergic reaction). If you experience tightness in the chest, feeling dizzy, feeling sick or faint, or experience dizziness on standing, you may be experiencing an allergic reaction to Helixate NexGen 250 IU. If this occurs, stop administering the product
immediately and seek medical advice.

Your doctor may wish to carry out tests to ensure that your current dose of Helixate NexGen 250 IU is sufficient to reach and maintain adequate factor VIII levels.

If your bleeding is not being controlled with Helixate NexGen 250 IU, consult your doctor immediately. You may have developed factor VIII inhibitors and your doctor may wish to carry out tests to confirm this. Factor VIII inhibitors are antibodies in the blood which block the factor VIII you are using. This makes factor VIII less effective in controlling bleeding.

If you have previously developed a factor VIII inhibitor and you switch factor VIII products, you may be at risk of your inhibitor coming back.

Using other medicines

Interactions with other medicines are not known. However, please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

Based on the rare occurrence of haemophilia A in women, experience regarding the use of Helixate NexGen 250 IU during pregnancy and breast-feeding is not available. Therefore, if you are pregnant or breast-feeding consult your doctor before using this product.

Driving and using machines

No effects on the ability to drive or use machines have been observed.

Important information about some of the ingredients of Helixate NexGen 250 IU

This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially “sodium-free”.

HOW TO USE Helixate NexGen 250 IU

Helixate NexGen 250 IU is intended for intravenous administration only and must be administered immediately after reconstitution. Aseptic conditions (meaning clean and germ free) are required during reconstitution and administration. Use only the medical devices for reconstitution and administration provided with each package of Helixate NexGen 250 IU. Helixate NexGen 250 IU must not be mixed with other infusion solutions. Do not use solutions containing visible particles or that are cloudy.

Follow the directions given by your doctor closely and use the instructions below as a guide:

• 1. Wash hands thoroughly using soap and warm water.


• 2. Warm both unopened vials in your hands to a comfortable temperature (do not exceed 37 °C).


• 3. Ensure product and solvent vial flip caps are removed and the stoppers are treated with an aseptic solution and allowed to dry prior to opening the Mix2Vial package.

• 4. Open the Mix2Vial package by peeling away the lid. Do not remove the Mix2Vial from the blister package!

• 5. Place the solvent vial on an even, clean surface and hold the vial tight. Take the Mix2Vial together with the blister package and push the spike of the blue adapter end straight down through the solvent vial stopper.

• 6. Carefully remove the blister package from the Mix2Vial set by holding at the rim, and pulling vertically upwards. Make sure that you only pull away the blister package and not the Mix2Vial set.

• 7. Place the product vial on an even and firm surface. Invert the solvent vial with the Mix2Vial set attached and push the spike of the transparent adapter end straight down through the product vial stopper. The solvent will automatically flow into the product vial.

• 8. With one hand grasp the product-side of the Mix2Vial set and with the other hand grasp the solvent-side and unscrew the set carefully into two pieces. Discard the solvent vial with the blue Mix2Vial adapter attached.

• 9. Gently swirl the product vial with the transparent adapter attached until the substance is fully dissolved. Do not shake.

• 10. Draw air into an empty, sterile syringe. While the product vial is upright, connect the syringe to the Mix2Vial´s Luer Lock fitting. Inject air into the product vial.

• 11. While keeping the syringe plunger pressed, invert the system upside down and draw the solution into the syringe by pulling the plunger back slowly.

• 12. Now that the solution has been transferred into the syringe, firmly hold on to the barrel of the syringe (keeping the syringe plunger facing down) and disconnect the transparent Mix2Vial adapter from the syringe. Hold the syringe upright and push the plunger until no air is left in the syringe.


• 13. Apply a tourniquet.


• 14. Determine the point of injection and prepare antiseptically.


• 15. Puncture the vein and secure the venipuncture set with a plaster.


• 16 Let blood flow back to the open end of the venipuncture set and then attach the syringe with the solution. Make sure that no blood enters the syringe.


• 17. Remove tourniquet.


• 18. Inject the solution intravenously over several minutes, keeping an eye on the position of the needle. The rate of administration should be determined by the patient’s comfort (maximum rate of infusion: 2 ml/min).


• 19. If a further dose needs to be administered, use a new syringe with product reconstituted as described above.


• 20. If no further dose is required, remove the venipuncture set and syringe. Hold a swab firmly over the injection site on the outstretched arm for approx. 2 minutes. Finally, apply a small pressure dressing to the wound.

The amount of Helixate NexGen 250 IU you should use and how often you use it depends on many factors such as your weight, the severity of your haemophilia, the site and extent of bleeding, the amount of factor VIII inhibitors that you may have and the factor VIII level required.

Your doctor will calculate the dose of Helixate NexGen 250 IU and how frequently you should use it to get the necessary level of factor VIII activity in your blood. He will do this according to your particular needs using the formulae below.

I. Required IU = body weight (kg) × desired factor VIII rise as % of normal × 0.5

II. Expected factor VIII rise as % of normal = 2 × administered IU ÷ bodyweight in kg

The following table provides a guide for factor VIII minimum blood levels. In the case of the haemorrhagic events listed, the factor VIII activity should not fall below the given level (in % of normal) in the corresponding period:

Degree of haemorrhage : Factor VIII level required (% or IU/dl) : Frequency of doses in hours; duration of therapy in days

Early haemathrosis, muscle bleed or oral bleed : 20 to 40 : Repeat every 12 to 24 hours. At least 1 day, until the bleeding episode as indicated by pain is resolved or healing is achieved.

More extensive haemathrosis, muscle bleed or haematoma : 30 to 60 : Repeat infusion every 12 to 24 hours for 3 to 4 days or more until pain and disability are resolved.

Life-threatening bleeds such as intracranial bleed, throat bleed, severe abdominal bleed : 60 to 100 : Repeat infusion every 8 to 24 hours until threat is resolved.

Type of surgical procedure : Factor VIII level required (% or IU/dl) : Frequency of doses in hours; duration of therapy in days

Minor, including tooth extraction : 30 to 60 : Every 24 hours for at least 1 day until healing is achieved.

Major : 80 to 100 (pre-and post-operatively) : a) By bolus infusions. Repeat infusion every 8 to 24 hours until adequate wound healing occurs, then continue with therapy for at least another 7 days to maintain a factor VIII activity of 30 to 60 %. b) By continuous infusion. Raise factor VIII activity pre-surgery with an initial bolus infusion and immediately follow with continuous infusion (in IU/kg/h) adjusting according to patient’s daily clearance and desired factor VIII levels for at least 7 days.

Your doctor should always adapt the amount of Helixate NexGen 250 IU to be administered and the frequency of administration according to the clinical effectiveness in your individual case. Under certain circumstances larger amounts than those calculated may be required, especially in the case of the initial dose.

If you are using Helixate NexGen 250 IU to prevent bleeding (prophylaxis), your doctor will calculate the dose for you. This will usually be in the range of 20 to 60 IU of octocog alfa per kg of body weight, administered at intervals of 2 to 3 days. However, in some cases, especially younger patients, shorter dose intervals or higher doses may be necessary.

Although dosage can be estimated by the calculations presented above, it is strongly recommended that appropriate laboratory tests be performed on your plasma at suitable intervals to ensure that adequate factor VIII levels have been reached and are maintained. In the case of major surgical interventions in particular, a precise monitoring of the substitution therapy by means of coagulation analysis is indispensable.

If the factor VIII level of your plasma fails to reach expected levels, or if bleeding is not controlled after apparently adequate dosage, the presence of factor VIII inhibitors should be suspected. By appropriate laboratory procedures, the presence of factor VIII inhibitors must be checked and quantified by an experienced doctor.

If you have the impression that the effect of Helixate NexGen 250 IU is too strong or too weak, talk to your doctor.

Patients with inhibitors

If you have been informed by your doctor that you have developed factor VIII inhibitors you will possibly be required to use a larger amount of Helixate NexGen than previously to control a bleeding. If this dose does not control your bleeding your doctor may consider the use of an additional product, factor VIIa concentrate or (activated) prothrombin complex concentrate. Do not increase the dose of Helixate NexGen you use to control your bleeding without consulting your doctor. Speak to your doctor if you would like further information on this.

These therapies should be directed by doctors with experience in the care of patients with haemophilia A.

Helixate NexGen 250 IU should be injected intravenously over several minutes. The rate of administration should be determined by the patient’s comfort level (maximal rate of infusion: 2 ml/min).

Your doctor will tell you, how often and at what intervals Helixate NexGen 250 IU is to be administered.

Usually, the substitution therapy with Helixate NexGen 250 IU is a life-time treatment.

If you use more Helixate NexGen 250 IU than you should

No symptoms of overdosage with recombinant coagulation factor VIII have been reported.

If you have used more Helixate NexGen 250 IU than you should, please inform your doctor.

If you forget to use Helixate NexGen 250 IU

• Proceed with the next administration immediately and continue at regular intervals as advised by your doctor.


• Do not take a double dose to make up for a forgotten dose.

If you stop using Helixate NexGen 250 IU

Do not stop using Helixate NexGen 250 IU without consulting your doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Possible Side Effects

Like all medicines, Helixate NexGen 250 IU can cause side effects, although not everybody gets them.

The frequency of possible side effects listed below is defined using the following convention:

very common (affects more than 1 user in 10)

common (affects 1 to 10 users in 100)

uncommon (affects 1 to 10 users in 1,000)

rare (affects 1 to 10 users in 10,000)

very rare (affects less than 1 user in 10,000)

not known (frequency cannot be estimated from the available data).

Side effects where frequency is common:

You may notice any of the following side effects after administration of Helixate NexGen 250 IU:

• rash/itchy rash


• local reactions at the injection site (e.g. burning sensation, temporary redness)

Side effects where frequency is rare:

You may notice any of the following side effects after administration of Helixate NexGen 250 IU:

• hypersensitivity reactions (e.g. tightness of the chest/general feeling of being unwell, dizziness and nausea and mildly reduced blood pressure, which may make you feel faint upon standing)


• fever.

Furthermore, the possibility of an anaphylactic shock cannot be completely excluded. If you notice any of the following symptoms during injection/infusion:

• chest tightness/general feeling of being unwell


• dizziness


• mild hypotension (mildly reduced blood pressure, which may make you feel faint upon standing)


• nausea

this can constitute an early warning for hypersensitivity and anaphylactic reactions. If allergic or anaphylactic reactions occur, the injection/infusion should be stopped immediately. Please consult your doctor immediately.

During studies, no patient developed clinically relevant antibody titres against the trace amounts of mouse protein and hamster protein present in the preparation. However, the possibility of allergic reactions to constituents, e.g. trace amounts of mouse and hamster protein in the preparation exists in certain predisposed patients.

The formation of neutralising antibodies to factor VIII (inhibitors) is a known complication in the management of individuals with haemophilia A. In studies with recombinant factor VIII preparations, development of inhibitors is predominantly observed in previously untreated haemophiliacs.

You should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests.

In clinical studies, Helixate NexGen has been used in the treatment of bleeding episodes in 37 previously untreated patients (PUPs) and 23 minimally treated pediatric patients (MTPs, defined as having equal to or less than 4 exposure days). Five out of 37 (14%) PUP and 4 out of 23 (17%) MTP patients treated with Helixate NexGen developed inhibitors: Overall 6 out of 60 (10%) with a titre above 10 BU and 3 out of 60 (5%) with a titre below 10 BU. The median number of exposure days at the time of inhibitor detection in these patients was 9 days (range 3 - 18 days).

The median number of exposure days in the clinical studies was 114 (range: 4-478). Four of the five patients, who had not achieved 20 exposure days at the end of the study, ultimately achieved more than 20 exposure days in post-study follow-up and one of them developed a low titre inhibitor. The fifth patient was lost to follow-up.

In clinical studies with 73 previously treated patients (PTP, defined as having more than 100 exposure days), followed over four years, no de-novo inhibitors were observed.

In extensive post-registration studies with Helixate NexGen, involving more than 1000 patients the following was observed: Less than 0.2% PTP developed de-novo inhibitors. In a subset defined as having less than 20 exposure days at study entry, less than 11% developed de-novo inhibitors.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

HOW TO STORE Helixate NexGen 250 IU

Keep out of the reach and sight of children.

Store in a refrigerator (2°C - 8°C). Do not freeze. Keep the vials in the outer carton in order to protect from light.

You may store the product when kept in its outer carton at ambient room temperature (up to 25°C) for a single period of up to 3 months. In this case, the product expires at the end of this 3-month period; you must note the new expiry date on the top of the outer carton.

Do not refrigerate the solution after reconstitution. The reconstituted solution should be used immediately. This product is for single use only. Any unused solution must be discarded.

Do not use Helixate NexGen 250 IU after the expiry date which is stated on labels and cartons. The expiry date refers to the last day of that month.

Do not use Helixate NexGen 250 IU if you notice any particles or the solution is cloudy.

Further Information

What Helixate NexGen 250 IU contains

Powder:

The active substance is recombinant coagulation factor VIII (octocog alfa).

The other ingredients are glycine, sodium chloride, calcium chloride, histidine, polysorbate 80, and sucrose.

Solvent:

Water for injections.

What Helixate NexGen 250 IU looks like and content of the pack

Helixate NexGen 250 IU is provided as a powder and solvent for solution for injection and is a dry white to slightly yellow powder or cake. After reconstitution the solution is clear. Medical devices for reconstitution and administration are provided with each package of Helixate NexGen 250 IU.

Marketing Authorisation Holder:

Bayer Schering Pharma AG

13342 Berlin

Germany

Manufacturer:

Bayer HealthCare Manufacturing S.r.l.

Via delle Groane 126

20024 Garbagnate Milanese (MI)

Italy

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

United Kingdom

CSL Behring UK Limited

Tel:+44-(0)1444 447400

This leaflet was last approved in 03/2010

Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http://www.emea.europa.eu.

Adrenaclick Auto-Injector

Pronunciation: EP-i-NEF-rin
Generic Name: Epinephrine
Brand Name: Adrenaclick or Twinject

Adrenaclick Auto-Injector is used for:

Treating severe allergic reactions (eg, difficulty breathing; rash; hives; itching; tightness in the chest; swelling of the mouth, lips, or tongue) caused by insect stings or bites, foods, drugs, or other causes. It may also be used for other conditions as determined by your doctor.

Adrenaclick Auto-Injector is a sympathomimetic. It works on different receptors in the body to relax the smooth muscle of the lungs, which improves breathing.

Do NOT use Adrenaclick Auto-Injector if:

• you are allergic to any ingredient in Adrenaclick Auto-Injector, unless your doctor tells you otherwise

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

Before using Adrenaclick Auto-Injector:

Some medical conditions may interact with Adrenaclick Auto-Injector. 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 (eg, sulfites)


• if you have glaucoma, heart disease, chest pain, high blood pressure, blood vessel problems, diabetes, Parkinson disease, thyroid problems, mood or mental disorders, depression, asthma, or an irregular heartbeat

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

• Alpha-blockers (eg, prazosin), beta-blockers (eg, propanolol), droxidopa, ergot alkaloids (eg, ergotamine), or phenothiazines (eg, chlorpromazine) because the risk of high or low blood pressure and fast or slow heartbeat may be increased


• Bromocriptine, furazolidone, linezolid, or tricyclic antidepressants (eg, amitriptyline) because the risk of side effects, such as headache, high temperature, and high blood pressure, may be increased


• Antihistamines (eg, diphenhydramine), catechol-O-methyltransferase (COMT) inhibitors (eg, entacapone), digoxin, diuretics (eg, furosemide, hydrochlorothiazide), levothyroxine, monoamine oxidase inhibitors (MAOIs) (eg, phenelzine), or medicines for irregular heartbeat (eg, quinidine) because they may increase the risk of Adrenaclick Auto-Injector's side effects


• Guanethidine because its effectiveness may be decreased by Adrenaclick Auto-Injector

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

Use Adrenaclick Auto-Injector as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Adrenaclick Auto-Injector. Talk to your pharmacist if you have questions about this information.


• Adrenaclick Auto-Injector may be given as an injection at your doctor's office, hospital, or clinic. If you will be using Adrenaclick Auto-Injector at home, a health care provider will teach you how to use it. Be sure you understand how to use Adrenaclick Auto-Injector. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.


• Check Adrenaclick Auto-Injector regularly. Replace the injector unit if it contains particles, is discolored (pink or brown), or is cracked or damaged in any way.


• Inject Adrenaclick Auto-Injector only into the outer thigh. Do not inject into the buttocks or into a vein.


• Immediately after use, go to the nearest hospital emergency room. You may need further medical attention. Tell the doctor or health care provider that you have received an injection of epinephrine. Show the thigh where the injection was given to the doctor. Give your used auto-injector to the doctor for inspection and proper disposal.


• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.


• Adrenaclick Auto-Injector is usually given as a one-time dose in an emergency situation. If you are unable to use Adrenaclick Auto-Injector, seek medical attention immediately.


• If you miss a dose of Adrenaclick Auto-Injector, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Adrenaclick Auto-Injector.

Important safety information:

• Never put your thumb, fingers, or hand over the tip of the auto-injector. Do NOT remove the cap until ready to use.


• Only inject Adrenaclick Auto-Injector into the outer thigh. Never inject Adrenaclick Auto-Injector into hands, fingers, feet, or toes. Doing so may cause a loss of blood flow and result in tissue damage to these areas. If you accidentally inject Adrenaclick Auto-Injector into any of these areas, seek immediate emergency medical attention.


• It may be helpful to train others how to give Adrenaclick Auto-Injector in case you are unable to give it to yourself during a reaction.


• Diabetes patients - Adrenaclick Auto-Injector may raise your blood sugar. High blood sugar may make you feel confused, drowsy, or thirsty. It can also make you flush, breathe faster, or have a fruit-like breath odor. If these symptoms occur, tell your doctor right away.


• Patients with Parkinson disease may notice a temporary worsening of symptoms (eg, uncontrolled muscle movements). If these symptoms persist, contact your doctor.


• Use Adrenaclick Auto-Injector with caution in the ELDERLY; they may be more sensitive to its effects.


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

Possible side effects of Adrenaclick Auto-Injector:

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:

Anxiety; difficulty sleeping; dizziness; fearfulness; headache; nausea; nervousness; paleness; sweating; tremors; vomiting; weakness.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; fast or irregular heartbeat; wheezing.

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: Adrenaclick 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 chest pain; extreme paleness or coldness of the skin; fast or irregular heartbeat; one-sided weakness; severe headache or dizziness; trouble breathing.

Proper storage of Adrenaclick Auto-Injector:

Store Adrenaclick Auto-Injector at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store in the carrying case provided. Do not refrigerate or freeze. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Adrenaclick Auto-Injector out of the reach of children and away from pets.

General information:

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


• Adrenaclick Auto-Injector is to be used only by the patient for whom it is prescribed. Do not share it with other people.


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


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

This information is a summary only. It does not contain all information about Adrenaclick Auto-Injector. 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 Adrenaclick resources

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

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esterified estrogens

Generic Name: esterified estrogens (ess TER ih fied ESS troe jenz)

Brand Names: Estratab, Menest

What are esterified estrogens?

Estrogen is a female sex hormone necessary for many processes in the body.

Esterified estrogens are naturally occurring female sex hormones that are used to treat symptoms of menopause; deficiency in ovary function (including underdevelopment of female sexual characteristics and some types of infertility); some types of breast cancer in men and in postmenopausal women; degeneration of the vagina; and urethra and prostate cancer. In addition, esterified estrogens are used to prevent osteoporosis.

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

What is the most important information I should know about esterified estrogens?

Esterified estrogens increase the risk of developing a condition (endometrial hyperplasia) that may lead to cancer of the lining of the uterus. Taking progestins, another hormone drug, with esterified estrogens lowers the risk of developing this condition. Therefore, if your uterus has not been removed, your doctor may prescribe a progestin for you to take together with the estrogen. Visit your doctor regularly and report any unusual vaginal bleeding right away.

Have yearly physical exams and examine your breasts for lumps on a monthly basis while taking esterified estrogens.

Do not take esterified estrogens if you are pregnant.

Who should not take esterified estrogens?

Do not take esterified estrogens without first talking to your doctor if you have

• 
  

  a circulation, bleeding, or blood-clotting disorder;

  
  


• 
  

  undiagnosed, abnormal vaginal bleeding; or

  
  


• 
  

  any type of breast, uterine, or hormone-dependent cancer.

  
  

Taking esterified estrogens may be dangerous in some cases if you have any of the conditions listed above.

Before taking esterified estrogens, tell your doctor if you have

• 
  

  high blood pressure, angina, or heart disease;

  
  


• 
  

  high levels of cholesterol or triglycerides in your blood;

  
  


• liver disease;


• kidney disease;


• 
  

  asthma;

  
  


• 
  

  epilepsy;

  
  


• 
  

  migraines;

  
  


• 
  

  diabetes;

  
  


• 
  

  depression;

  
  


• 
  

  gallbladder disease;

  
  


• 
  

  uterine fibroids; or

  
  


• 
  

  had a hysterectomy (uterus removed).

  
  

You may not be able to take esterified estrogens, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

Esterified estrogens are in the FDA pregnancy category X. This means that esterified estrogens will cause birth defects in an unborn baby. Do not take this medication if you are pregnant or are planning a pregnancy. Esterified estrogens may decrease milk flow and have other effects on milk composition. Do not use this medication without first talking to your doctor if you are breast-feeding a baby.

How should I take esterified estrogens?

Take this medication exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each dose with a full glass of water. Take esterified estrogens with food or milk to lessen stomach upset.

Try to take every dose at the same time each day. You may be taking it every day, or you may be taking it every day for 3 weeks with 1 week off each month to mimic your body's natural cycle. Follow the directions on your prescription label.

If you are taking esterified estrogens to treat cancer, you may be taking it several times a day in very large doses.

Have yearly physical exams and examine your breasts for lumps on a monthly basis while taking esterified estrogens.

Store esterified estrogens at room temperature away from moisture and heat.

See also: Esterified estrogens dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember. Do not take a double dose of this medication unless otherwise directed by your doctor.

What happens if I overdose?

An overdose of this medication is unlikely to threaten life. Consult an emergency room or poison control center for advice.

Symptoms of an overdose of esterified estrogens include nausea, vomiting, and breakthrough bleeding in females.

What should I avoid while taking esterified estrogens?

There are no restrictions on food, beverages, or activity while taking esterified estrogens unless your doctor directs otherwise.

Esterified estrogens side effects

If you experience any of the following serious side effects, stop taking esterified estrogens and seek emergency medical attention:

• 
  

  an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives);

  
  


• 
  

  a blood clot (pain, redness, and swelling in an arm or leg, shortness of breath, chest pain, headache, blurred vision, or confusion);

  
  


• 
  

  a lump in a breast; or

  
  


• 
  

  liver damage (yellowing of the skin or eyes, nausea, abdominal pain or discomfort, unusual bleeding or bruising, severe fatigue).

  
  

Other, less serious side effects may be more likely to occur. Continue to take esterified estrogens and talk to your doctor if you experience

• 
  

  decreased appetite, nausea, or vomiting;

  
  


• 
  

  swollen or tender breasts;

  
  


• 
  

  acne or skin color changes;

  
  


• 
  

  decreased sex drive;

  
  


• 
  

  migraine headaches or dizziness;

  
  


• 
  

  water retention (swollen hands, feet, or ankles);

  
  


• 
  

  problems with wearing contact lenses;

  
  


• 
  

  depression; or

  
  


• 
  

  changes in your menstrual cycle or breakthrough bleeding.

  
  

Esterified estrogens increase the risk of developing a condition (endometrial hyperplasia) that may lead to cancer of the lining of the uterus. Taking progestins, another hormone drug, with esterified estrogens lowers the risk of developing this condition. Therefore, if your uterus has not been removed, your doctor may prescribe a progestin for you to take together with the estrogen. Visit your doctor regularly and report any unusual vaginal bleeding right away.

It is unclear to what extent estrogen treatments may affect the risk of breast cancer.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

Esterified estrogens Dosing Information

Usual Adult Dose for Osteoporosis:

0.3 mg orally once a day.

In addition to hormonal therapy, adequate calcium intake is important for postmenopausal women who require treatment or prevention of osteoporosis. The average diet of older American women contains 400 to 600 mg of calcium per day. A suggested optimal intake is 1500 mg per day. If dietary intake is insufficient to achieve 1500 mg per day, supplementation may be useful in women who have no contraindication to calcium supplementation.

Long-term therapy (for more than 5 years) is generally necessary in order to obtain substantive benefits in reducing the risk of bone fracture. Maximal benefits are obtained if estrogen therapy is initiated as soon after menopause as possible. The optimal duration of therapy has not been definitively determined.

Usual Adult Dose for Postmenopausal Symptoms:

1.25 mg orally once a day.

In general, the duration of hormone therapy for the treatment of postmenopausal symptoms should be limited. Treatment for one to five years is generally sufficient. However, long-term therapy (for the treatment/prophylaxis of osteoporosis and for risk reduction of cardiovascular disease) may be considered during the time in which the patient is being treated for postmenopausal symptoms.

Usual Adult Dose for Atrophic Urethritis:

0.3 mg to 1.25 mg orally once a day.

In general, the duration of hormone therapy for the treatment of postmenopausal symptoms like atrophic vaginitis, kraurosis vulvae, or atrophic urethritis should be limited. Treatment for one to five years is generally sufficient.

Usual Adult Dose for Atrophic Vaginitis:

0.3 mg to 1.25 mg orally once a day.

In general, the duration of hormone therapy for the treatment of postmenopausal symptoms like atrophic vaginitis, kraurosis vulvae, or atrophic urethritis should be limited. Treatment for one to five years is generally sufficient.

Usual Adult Dose for Hypoestrogenism:

2.5 mg to 7.5 mg orally once a day in divided doses for 21 days followed by a 10 day rest period. This schedule is repeated as necessary to product bleeding.

Usual Adult Dose for Oophorectomy:

1.25 mg orally once a day.

Usual Adult Dose for Primary Ovarian Failure:

1.25 mg orally once a day.

Usual Adult Dose for Breast Cancer:

10 mg orally three times a day for at least three months.

Estrogen therapy for breast cancer should be considered only for palliation in the treatment of metastatic disease in postmenopausal women and select male patients.

Usual Adult Dose for Prostate Cancer:

1.25 mg to 2.5 mg orally three times a day.

Estrogen therapy for prostate cancer should be considered only for palliation in the treatment of metastatic disease in select patients.

What other drugs will affect esterified estrogens?

Before taking esterified estrogens, tell your doctor if you are taking any of the following medicines:

• 
  

  an anticoagulant (blood thinner) such as warfarin (Coumadin);

  
  


• 
  

  a thyroid medication such as Synthroid, Levoxyl, Levothroid, and others;

  
  


• 
  

  insulin or an oral diabetes medicine such as glipizide (Glucotrol) or glyburide (Diabeta, Micronase);

  
  


• 
  

  tamoxifen (Nolvadex);

  
  


• 
  

  didanosine (Videx);

  
  


• 
  

  phenytoin (Dilantin) or ethotoin (Peganone);

  
  


• 
  

  carbamazepine (Tegretol);

  
  


• 
  

  phenobarbital (Solfoton, Luminal);

  
  


• 
  

  primidone (Mysoline); or

  
  


• 
  

  rifampin (Rifadin).

  
  

A dosage adjustment or special monitoring may be required during treatment if you are taking any of the medicines listed above.

Drugs other than those listed here may also interact with esterified estrogens. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.

More esterified estrogens resources

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

• Esterified Estrogens MedFacts Consumer Leaflet (Wolters Kluwer)


• Menest Prescribing Information (FDA)


• Menest Advanced Consumer (Micromedex) - Includes Dosage Information

Compare esterified estrogens with other medications

• Atrophic Urethritis
• Atrophic Vaginitis
• Breast Cancer
• Breast Cancer, Palliative
• Hypoestrogenism
• Oophorectomy
• Osteoporosis
• Postmenopausal Symptoms
• Primary Ovarian Failure
• Prostate Cancer

Where can I get more information?

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

See also: esterified estrogens side effects (in more detail)

Levo-Dromoran

Generic Name: Levorphanol Tartrate
Class: Opiate Agonists
VA Class: CN101
CAS Number: 5985-38-6

Introduction

Opiate agonist; phenanthrene derivative.^{a b c}

Uses for Levo-Dromoran

Pain

Relief of moderate to severe pain.^{a b}

Usually, temporary relief of moderate to severe pain such as that associated with acute and some chronic medical disorders including renal or biliary colic, acute trauma, postoperative pain, and cancer.^c

Consider around-the-clock dosing of analgesics in the initial stages of acute pain to avoid wide swings in pain and sedation often associated with as-needed dosing regimens.^c

In the management of chronic pain associated with a terminal illness such as cancer, the principal goal of analgesic therapy is to make the patient relatively pain-free while maintaining as good a quality of life as possible.^c

Analgesic therapy must be individualized and titrated according to patient response and tolerance.^c

Levo-Dromoran Dosage and Administration

Administration

Administer orally.^b

Dosage

Available as levorphanol tartrate; dosage expressed in terms of the salt.^b

Give the smallest effective dose as infrequently as possible to minimize the development of tolerance and physical dependence.^a

Individualize dosage according to clinical status of the patient, desired therapeutic effect, degree of existing opiate tolerance, and age and weight; assess dosage at periodic intervals.^b

Reduce dosage in poor-risk patients, in geriatric patients, in patients receiving other CNS depressants.^{a b}

Reduce initial dose ≥50% in patients with compromised respiratory function and in those receiving other drugs that depress respiration.^b (See Specific Drugs under Interactions.)

Reduce initial dose in patients with hypothyroidism, Addison's disease, toxic psychosis, prostatic hypertrophy, urethral strictures, acute alcoholism, or delirium tremens.^b

In patients who are tolerant to opiate agonists and who require high dosages (e.g., patients with severe chronic pain associated with cancer), individualize dosage of highly potent preparations based on response and tolerance.^b

Avoid abrupt withdrawal from relatively high dosages (e.g., in chronic pain patients) since precipitation of severe abstinence syndrome is likely.^b

Assess patients for signs of hypoventilation or excessive sedation during therapy.^b

Adults

Pain

Oral

Usually, initiate with 2 mg every 6–8 hours as needed.^b May increase to 3 mg every 6–8 hours.^b Adjust according to response and tolerance.^b

Initial dosages >6–12 mg in 24 hours not recommended in non-opiate-tolerant patients; lower dosages may be appropriate.^b

If a patient is placed on an “around-the-clock” dosing regimen, allow at least 72 hours to elapse between dosage adjustments; this is needed to avoid excessive sedation.^b (See Half-life under Pharmacokinetics.)

Switching from Morphine to Levorphanol

Oral

The manufacturer states that the initial total daily dose of oral levorphanol should be 1/15 to 1/12 of the total daily dose of oral morphine; adjust subsequent dosage based on clinical response.^b

Prescribing Limits

Adults

Pain

Oral

Maximum initial daily dose in non-opiate-tolerant patients: 6–12 mg in 24 hours.^b

Special Populations

Hepatic Impairment

Reduce initial dose in patients with severe hepatic impairment.^b

Renal Impairment

Reduce initial dose in patients with severe renal impairment.^b

Geriatric Patients

Reduce initial dose by ≥50% in debilitated geriatric patients.^b

Respiratory Impairment

Reduce initial dose by ≥50% in patients with any condition affecting respiratory reserve.^b Titrate subsequent doses according to patient's response.^b

Cautions for Levo-Dromoran

Contraindications

• 
  

  Known hypersensitivity to levorphanol or any ingredient in the formulation.^b

  
  

Warnings/Precautions

Warnings

Respiratory Depression

Causes dose-related respiratory depression.^b

Occurs most frequently in debilitated patients and following large and/or frequent doses.^b

Use with extreme caution in patients with impaired respiratory reserve or respiratory depression (e.g., individuals with uremia, severe infection, obstructive respiratory conditions, restrictive respiratory diseases, intrapulmonary shunting, or chronic asthma).^b

Use not recommended in patients with acute or severe asthma.^b

Dependence and Abuse

Physical and psychologic dependence and tolerance may develop with repeated administration; abuse potential exists.^b Use with caution.^b

Use with careful surveillance in patients with a history of drug or alcohol dependence or abuse.^b

Abrupt cessation of therapy or sudden reduction in dosage after prolonged use may result in withdrawal symptoms.^b After prolonged exposure to opiate analgesics, if withdrawal is necessary, it must be undertaken gradually.^b

Head Injury and Increased Intracranial Pressure

Respiratory depressant effects of levorphanol (with CO₂ retention and secondary elevation of CSF pressure) may be markedly exaggerated in the presence of head injury, other intracranial lesions, or preexisting increase in intracranial pressure.^b

Adverse effects of opiates may obscure the existence, extent, or course of intracranial pathology.^b

Hypotensive Effects

Possible severe hypotension in individuals whose ability to maintain their BP is compromised by depleted blood volume or concomitant drugs that compromise vasculature tone (e.g., phenothiazines, general anesthetics).^b

May produce orthostatic hypotension in ambulatory patients.^b

Cardiovascular Effects

Limit use in patients with acute MI, myocardial dysfunction, or coronary insufficiency.^b Manufacturer states effect of levorphanol on the cardiac function unknown.^b

Biliary Tract Surgery

Moderate to marked increases in biliary tract pressure reported.^b Use not recommended in patients undergoing biliary tract surgery.^b

General Precautions

Acute Abdominal Conditions

May obscure diagnosis or clinical course of patients with acute abdominal conditions.^b

Debilitated and Special-Risk Patients.

Use with caution in debilitated patients or in patients with hypothyroidism, Addison’s disease, prostatic hypertrophy, urethral stricture, toxic psychosis, acute alcoholism, or delirium tremens.^b

Specific Populations

Pregnancy

Category C.^b

Use not recommended during labor and delivery.^b

Infants born to women regularly taking opiates during pregnancy may be physically dependent.^b

Lactation

Not known whether levorphanol is distributed into human milk.^b Discontinue nursing or the drug.^b

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years age.^b

Geriatric Use

Use with caution.^b Dosage adjustment recommended in debilitated geriatric patients.^b (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution.^b Extensive liver disease may predispose to excessive sedation, probably due to increased pharmacodynamic sensitivity or decreased hepatic metabolism of the drug.^b Reduce initial dose in patients with severe hepatic impairment.^b

Renal Impairment

Use with caution in patients with severe renal impairment; reduce initial dose in these patients.^b

Common Adverse Effects

Nausea, vomiting, altered mood/mentation, flushing, urinary retention, pruritus, constipation, biliary spasm.^b

Interactions for Levo-Dromoran

Specific Drugs

Drug	Interaction	Comments
CNS depressants (e.g., opiate agonists, general anesthetics, tricyclic antidepressants, antihistamines, tranquilizers, phenothiazines, sedatives/hypnotics, alcohol)	Additive CNS effectsb	Reduce dosage of one or both agentsb
MAO inhibitors		Concomitant use not recommendedb
Opiate partial agonists (butorphanol, buprenorphine, nalbuphine, pentazocine)	Possible reduced analgesic effect and/or withdrawal symptomsb	Avoid concomitant useb
Respiratory depressants	Additive depressant effects on respirationb	Reduce initial dose of levorphanol by ≥50%b
Skeletal muscle relaxants	May enhance the neuromuscular-blocking action of skeletal muscle relaxantsc Additive CNS effectsb	Reduce dosage of one or both agentsb

Levo-Dromoran Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tract.^{a b} Following oral administration, peak plasma concentration achieved in about 1 hour.^b Steady-state plasma concentrations expected to be achieved by the third day of continuous dosing.^b

Duration

6–8 hours.^a

Distribution

Plasma Protein Binding

40%.^b

Elimination

Metabolism

Extensively metabolized in the liver; undergoes conjugation with glucuronic acid.^{a b}

Elimination Route

Primarily in urine as the glucuronide conjugate.^{a b}

Half-life

IV administration: 11–16 hours.^b

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 15–30°C.^{a b}

ActionsActions

• 
  

  A potent analgesic; shares actions of the opiate agonists.^b

  
  


• 
  

  Precise mechanism of action has not been fully elucidated; opiate agonists act at several CNS sites, involving several neurotransmitter systems to produce analgesia.^c

  
  


• 
  

  Pain perception is altered in the spinal cord and higher CNS levels (e.g., substantia gelatinosa, spinal trigeminal nucleus, periaqueductal gray, periventricular gray, medullary raphe nuclei, hypothalamus).^c

  
  


• 
  

  Opiate agonists do not alter the threshold or responsiveness of afferent nerve endings to noxious stimuli, nor peripheral nerve impulse conduction.^c

  
  


• 
  

  Opiate agonists act at specific receptor binding sites in the CNS and other tissues; opiate receptors are concentrated in the limbic system, thalamus, striatum, hypothalamus, midbrain, and spinal cord.^c

  
  


• 
  

  Agonist activity at the opiate μ- or κ-receptor can result in analgesia, miosis, and/or decreased body temperature.^c

  
  


• 
  

  Agonist activity at the μ-receptor also can result in suppression of opiate withdrawal (and antagonist activity can result in precipitation of withdrawal).^c

  
  


• 
  

  Respiratory depression may be mediated by μ-receptors, possibly μ₂-receptors (which may be distinct from μ₁-receptors involved in analgesia); κ- and δ-receptors may also be involved in respiratory depression.^c

  
  

Advice to Patients

• 
  

  Importance of informing patients that levorphanol may impair mental and/or physical ability required for performance of potentially hazardous tasks; avoid driving or operating heavy machinery until effects on individual are known.^b

  
  


• 
  

  Advise patients that levorphanol should not be combined with alcohol or other CNS depressants (e.g., sleep medications, tranquilizers).^b

  
  


• 
  

  Risk of hypotension, dizziness, and syncope.^b

  
  


• 
  

  Importance of informing patients that this is a drug of potential abuse and should be protected from theft.^b

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^b

  
  


• 
  

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

  
  


• 
  

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

  
  

Preparations

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

Levorphanol tartrate is subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.

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

Levorphanol Tartrate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	2 mg*	Levo-Dromoran (C-II; scored)	Valeant
			Levorphanol Tartrate Tablets (C-II; scored)	Roxane

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 September 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

a. AHFS drug information 2007. McEvoy GK, ed. Levorphanol. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2137.

b. Roxane Laboratories. Levorphanol tartrate tablets prescribing information. Columbus, OH; 2004 Dec.

c. AHFS drug information 2007. McEvoy GK, ed. Opiod Agonists General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2123-8.

More Levo-Dromoran resources

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

• Levo-Dromoran Prescribing Information (FDA)


• Levo-Dromoran MedFacts Consumer Leaflet (Wolters Kluwer)


• Levo-Dromoran Concise Consumer Information (Cerner Multum)


• Levo-Dromoran Advanced Consumer (Micromedex) - Includes Dosage Information


• Levorphanol Prescribing Information (FDA)

Compare Levo-Dromoran with other medications

• Light Sedation
• Pain

Venomous Scorpion Bite Medications

Drugs associated with Venomous Scorpion Bite

The following drugs and medications are in some way related to, or used in the treatment of Venomous Scorpion Bite. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Drug List:

Anascorp

Zaditor

Generic Name: ketotifen ophthalmic (kee toe TYE fen off THAL mik)

Brand Names: Alaway, Zaditor

What is Zaditor (ketotifen ophthalmic)?

Ketotifen is an antihistamine that inhibits the body's release of a chemical called histamine. Histamine can produce allergy symptoms such as sneezing, runny nose, and watery eyes.

Ketotifen ophthalmic is used to treat itching of the eyes caused by allergy to dust, pollen, animals, or other allergens.

Ketotifen ophthalmic may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Zaditor (ketotifen ophthalmic)?

Do not use this medication if you are allergic to ketotifen, or if you have an untreated eye infection. Ketotifen ophthalmic should not be used to treat eye irritation caused by wearing contact lenses.

Use this medication exactly as directed on the label, or as it has been prescribed by your doctor. Do not use the medication in larger amounts, or use it for longer than recommended.

If you wear contact lenses, remove them before applying ketotifen ophthalmic. This medication may contain a preservative (benzalkonium chloride) that may cause discoloration of contact lenses. Wait at least 10 minutes after using in the eye drops before putting contact lenses into your eyes.

Do not allow the medicine dropper tip to touch any surface, including the eyes or hands. If the dropper becomes contaminated it could cause an infection in your eye, which can lead to vision loss or serious damage to the eye.

What should I discuss with my healthcare provider before using Zaditor (ketotifen ophthalmic)?

Do not use this medication if you are allergic to ketotifen, or if you have an untreated eye infection. Ketotifen ophthalmic should not be used to treat eye irritation caused by wearing contact lenses. FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether ketotifen passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Do not use this medication in a child younger than 3 years old without the advice of a doctor.

How should I use Zaditor (ketotifen ophthalmic)?

Use this medication exactly as directed on the label, or as it has been prescribed by your doctor. Do not use the medication in larger amounts, or use it for longer than recommended.

Wash your hands before using the eye drops.

If you wear contact lenses, remove them before applying ketotifen ophthalmic. This medication may contain a preservative (benzalkonium chloride) that may cause discoloration of contact lenses.

To apply the eye drops:

• 
  

  Tilt your head back slightly and pull down your lower eyelid. Hold the dropper above the eye with the dropper tip down. Look up and away from the dropper as you squeeze out a drop, then close your eye. Gently press your finger to the inside corner of the eye (near your nose) for about 1 minute to keep the liquid from draining into your tear duct. If you use more than one drop in the same eye, wait about 5 minutes before putting in the next drop.

  
  

Do not allow the dropper tip to touch any surface, including the eyes or hands. If the dropper becomes contaminated it could cause an infection in your eye, which can lead to vision loss or serious damage to the eye.

After using the eyedrops, wait at least 10 minutes before putting contact lenses into your eyes.

Do not use the eye drops if the liquid has changed colors or has particles in it. Call your doctor for a new prescription. Store the drops at room temperature away from heat and moisture. Keep the bottle tightly closed when not in use.

What happens if I miss a dose?

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

What happens if I overdose?

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

An overdose of ketotifen ophthalmic is not expected to produce life-threatening symptoms.

What should I avoid while using Zaditor (ketotifen ophthalmic)?

Avoid using other medications in your eyes during treatment with ketotifen ophthalmic unless your doctor has told you to.

Zaditor (ketotifen ophthalmic) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using ketotifen ophthalmic and call your doctor at once if you have any of these serious side effects:

• 
  

  redness, drainage, eyelid swelling, or other signs of infection;

  
  


• 
  

  eye pain;

  
  


• 
  

  vision changes; or

  
  


• 
  

  severe itching of the eyes worse than before using the medication.

  
  

Less serious side effects may include:

• 
  

  mild burning, stinging, or eye irritation;

  
  


• 
  

  dryness of the eyes; or

  
  


• 
  

  increased sensitivity to light.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Zaditor (ketotifen ophthalmic)?

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

More Zaditor resources

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

• Zaditor Prescribing Information (FDA)


• Zaditor Drops MedFacts Consumer Leaflet (Wolters Kluwer)


• Zaditor Monograph (AHFS DI)


• Zaditor Advanced Consumer (Micromedex) - Includes Dosage Information


• Zyrtec Itchy Eye Prescribing Information (FDA)

Compare Zaditor with other medications

• Conjunctivitis, Allergic

Where can I get more information?

• Your pharmacist can provide more information about ketotifen ophthalmic.

See also: Zaditor side effects (in more detail)

Genaphed

Generic Name: pseudoephedrine (SOO doe ee FED rin)

Brand Names: Chlor Trimeton Nasal Decongestant, Contac Cold, Drixoral Decongestant Non-Drowsy, Elixsure Decongestant, Entex, Genaphed, Kid Kare Drops, Nasofed, Seudotabs, Silfedrine, Sudafed, Sudafed 12-Hour, Sudafed 24-Hour, Sudafed Children's Nasal Decongestant, Sudodrin, SudoGest, SudoGest 12 Hour, Suphedrin, Triaminic Softchews Allergy Congestion, Unifed

What is Genaphed (pseudoephedrine)?

Pseudoephedrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

Pseudoephedrine is used to treat nasal and sinus congestion, or congestion of the tubes that drain fluid from your inner ears, called the eustachian (yoo-STAY-shun) tubes.

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

What is the most important information I should know about Genaphed (pseudoephedrine)?

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Ask a doctor or pharmacist before using any other cough or cold medicine. Pseudoephedrine or other decongestants are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains pseudoephedrine or a decongestant. Do not use pseudoephedrine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

What should I discuss with my healthcare provider before taking Genaphed (pseudoephedrine)?

Do not use pseudoephedrine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects. Do not use this medication if you are allergic to pseudoephedrine or to other decongestants, diet pills, stimulants, or ADHD medications.

Ask a doctor or pharmacist if it is safe for you to take pseudoephedrine if you have:

• 
  

  heart disease or high blood pressure;

  
  


• 
  

  diabetes; or

  
  


• 
  

  a thyroid disorder.

  
  

FDA pregnancy category C. It is not known whether pseudoephedrine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Pseudoephedrine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Artificially sweetened liquid cold medicine may contain phenylalanine. If you have phenylketonuria (PKU), check the medication label to see if the product contains phenylalanine.

How should I take Genaphed (pseudoephedrine)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Cold medicine is usually taken only for a short time until your symptoms clear up.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Take this medicine with a full glass of water. Do not crush, chew, or break an extended-release tablet. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time. You may need to shake the oral suspension (liquid) well just before you measure a dose. Measure the liquid with a special dose measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose measuring device, ask your pharmacist for one. Do not take pseudoephedrine for longer than 7 days in a row. Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash. If you need surgery, tell the surgeon ahead of time that you are using pseudoephedrine. You may need to stop using the medicine for a short time. Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Since pseudoephedrine is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include feeling restless or nervous.

What should I avoid while taking Genaphed (pseudoephedrine)?

Avoid taking this medication if you also take diet pills, caffeine pills, or other stimulants (such as ADHD medications). Taking a stimulant together with a decongestant can increase your risk of unpleasant side effects.

Ask a doctor or pharmacist before using any other cough or cold medicine. Pseudoephedrine or other decongestants are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains pseudoephedrine or a decongestant.

Genaphed (pseudoephedrine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using pseudoephedrine and call your doctor at once if you have a serious side effect such as:

• 
  

  fast, pounding, or uneven heartbeat;

  
  


• 
  

  severe dizziness or anxiety;

  
  


• 
  

  easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms; or

  
  


• 
  

  dangerously high blood pressure (severe headache, blurred vision, ringing in your ears, anxiety, confusion, chest pain, trouble breathing, uneven heart rate, seizure).

  
  

Less serious side effects may include:

• 
  

  loss of appetite;

  
  


• 
  

  warmth, tingling, or redness under your skin;

  
  


• 
  

  feeling restless or excited (especially in children);

  
  


• 
  

  sleep problems (insomnia); or

  
  


• 
  

  skin rash or itching.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Genaphed (pseudoephedrine)?

Tell your doctor about all other medicines you use, especially:

• 
  

  blood pressure medications;

  
  


• 
  

  a beta blocker such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Dutoprol, Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others; or

  
  


• 
  

  an antidepressant such as amitriptyline (Elavil, Vanatrip, Limbitrol), doxepin (Sinequan), nortriptyline (Pamelor), and others.

  
  

This list is not complete and other drugs may interact with pseudoephedrine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Genaphed resources

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

• Genaphed Advanced Consumer (Micromedex) - Includes Dosage Information


• Pseudoephedrine MedFacts Consumer Leaflet (Wolters Kluwer)


• Pseudoephedrine Monograph (AHFS DI)


• Dimetapp Decongestant Drops MedFacts Consumer Leaflet (Wolters Kluwer)


• Drixoral Non-Drowsy Sustained-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)


• Entex Liquid MedFacts Consumer Leaflet (Wolters Kluwer)


• Entex Consumer Overview


• Sudafed Consumer Overview


• Tylenol Simply Stuffy Liquid MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Genaphed with other medications

• Nasal Congestion

Where can I get more information?

• Your pharmacist can provide more information about pseudoephedrine.

See also: Genaphed side effects (in more detail)

Mirapex

Generic Name: Pramipexole Dihydrochloride
Class: Nonergot-derivative Dopamine Receptor Agonists
VA Class: CN500
Chemical Name: (S)-4,5,6,7-Tetrahydro-N6-propyl,2,6-benzothiazolediamine
Molecular Formula: C₁₀H₁₇N₃S
CAS Number: 104632-26-0

Introduction

Nonergot-derivative dopamine receptor agonist.^{1 2 3 6 7 8 9 15 16 17 18 19}

Uses for Mirapex

Parkinsonian Syndrome

Symptomatic management of idiopathic parkinsonian syndrome.^{1 2 6 7 8 9 10 13 14 15 16 17 18 19}

Used as an adjunct to levodopa for the symptomatic management of parkinsonian syndrome in patients with advanced disease.^{23 24}

Also used as monotherapy for the initial symptomatic management of parkinsonian syndrome.²³ Most clinicians would use levodopa for initial therapy in individuals >70 years of age (less likely than younger individuals to develop levodopa-related motor complications and because of concerns about cognitive dysfunction), in patients with cognitive impairment, and in those with severe disease.²³ A dopamine receptor agonist may be preferred for initial therapy in patients ≤70 years of age.²³

Mirapex Dosage and Administration

Administration

Oral Administration

Administer orally, usually in 3 equally divided doses daily.¹

May be administered without regard to meals;²⁰ however, taking the drug with food may reduce the occurrence of nausea.¹

Dosage

Available as pramipexole dihydrochloride; dosage expressed in terms of the monohydrated form of this salt.¹

Adults

Parkinsonian Syndrome

Oral

Initiate at a low dosage and increase slowly (at intervals of ≥5–7 days) until the maximum therapeutic response is achieved.¹

Table 1. Usual Initial Dosage of Pramipexole Dihydrochloride for the Treatment of Parkinsonian Syndrome1

Week of Therapy	Daily Dosage Schedule	Total Daily Dose
1	0.125 mg 3 times daily	0.375 mg daily
2	0.25 mg 3 times daily	0.75 mg daily
3	0.5 mg 3 times daily	1.5 mg daily
4	0.75 mg 3 times daily	2.25 mg daily
5	1 mg 3 times daily	3 mg daily
6	1.25 mg 3 times daily	3.75 mg daily
7	1.5 mg 3 times daily	4.5 mg daily

Continually reevaluate and adjust the dosage according to the needs of the patient in an effort to find a dosage schedule that provides maximum relief of symptoms with minimum adverse effects.^{1 17}

In a fixed-dose study in patients with early parkinsonian syndrome, dosages >1.5 mg daily (i.e., 3, 4.5, or 6 mg daily) were not associated with additional therapeutic benefit.¹ As the dosage increased over the range from 1.5 mg to 6 mg daily, the incidence of postural hypotension, nausea, constipation, somnolence, and amnesia increased.¹

When pramipexole is used as an adjunct to levodopa, consider reducing the levodopa dosage.¹

Discontine pramipexole therapy gradually over a period of 1 week.¹ (See Nervous System and Muscular Effects under Cautions.)

Special Populations

Renal Impairment

Parkinsonian Syndrome

Oral

Modify dosage and/or frequency of administration in response to the degree of renal impairment.^{1 17}

Table 2. Recommended Dosage of Pramipexole Dihydrochloride for Patients with Renal Impairment115

Clcr	Initial Dosage	Maximum Dosage
≥60 mL/minute	0.125 mg 3 times daily	1.5 mg 3 times daily
35–59 mL/minute	0.125 mg twice daily	1.5 mg twice daily
15–34 mL/minute	0.125 mg once daily	1.5 mg once daily
<15 mL/minute	Not adequately studied; no specific recommendation
Hemodialysis	Not adequately studied; no specific recommendation

Geriatric Patients

No dosage adjustments necessary, since therapy is initiated at a low dosage and titrated according to clinical response.¹

Cautions for Mirapex

Contraindications

• 
  

  Known hypersensitivity to pramipexole dihydrochloride or to any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Somnolence

Sudden, irresistible attacks of sleep that resemble narcolepsy have been reported in patients treated with pramipexole.^{1 20 21 22} Episodes of falling asleep while engaged in activities of daily living (e.g., business meetings, telephone calls, driving), which occasionally resulted in accidents, have been reported,^{1 20 21 22 23} in some cases as late as 1 year after initiation of pramipexole therapy.^{1 20 21 22} Some patients perceived no warning signs (e.g., excessive drowsiness) and believed that they were alert immediately prior to the event;^{1 20 21 22 23} many experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of preexisting somnolence, although patients may not give such a history.^{1 20 21 23}

Patients with a history of sleep disorders (e.g., somnolence) or those taking multiple drugs known to cause sedation may be at increased risk of experiencing sudden sleep onset.²⁰ Sleep attacks appear to occur more frequently at higher dosages but may occur at any dosage.²⁰ Somnolence is common at dosages >1.5 mg daily.^{1 20 21}

Patients should not drive or operate other machinery until effects on the individual are known.¹

Continually reassess patients for drowsiness or sleepiness.^{1 20 21 22} Patients may not acknowledge drowsiness or sleepiness until directly questioned about such adverse effects during specific activities.^{1 20 21} Ask patients about any factors that may increase the risk of somnolence (e.g., concomitant sedating drugs, the presence of sleep disorders, concomitant drugs that increase plasma pramipexole concentrations).^{1 20 21}

Pramipexole generally should be discontinued if a patient develops clinically important daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating).^{1 20 21} If the drug is continued, the patient should be advised not to drive and to avoid other potentially dangerous activities.^{1 20 21} Insufficient information to establish that dosage reduction will eliminate episodes of falling asleep while engaged in activities of daily living.^{1 20 21}

Hallucinations

Potential for hallucinations, particularly in geriatric patients.¹

Symptomatic Hypotension

Dopamine agonists appear to impair systemic regulation of BP in patients with parkinsonian syndrome; patients with parkinsonian syndrome appear to have an impaired capacity to respond to an orthostatic challenge.¹

Use of dopamine agonists in patients with parkinsonian syndrome ordinarily requires careful monitoring for manifestations of orthostatic hypotension, especially during dosage escalation.¹ Unexpectedly, the reported incidence of clinically important orthostatic hypotension with pramipexole did not differ from that with placebo in clinical trials;¹ however, a dose-dependent increase in the incidence of postural hypotension occurs over a pramipexole dihydrochloride dosage range of 1.5–6 mg daily.¹

Caution patients about rising rapidly after sitting or lying down, especially if they have been in a seated or recumbent position for prolonged periods and/or if they are just beginning pramipexole therapy.¹

General Precautions

Rhabdomyolysis

Rhabdomyolysis reported in at least 1 patient with advanced parkinsonian syndrome treated with pramipexole.¹

Nervous System and Muscular Effects

Although not reported in clinical trials with pramipexole, a symptom complex resembling neuroleptic malignant syndrome (e.g., elevated temperature, muscular rigidity, altered consciousness, autonomic instability) has been reported in association with rapid dosage reduction of, withdrawal of, or changes in antiparkinsonian therapy.¹

If pramipexole therapy is discontinued, gradual dosage reduction over a period of 1 week is recommended; in some studies, however, abrupt discontinuance was uneventful.¹

Dyskinesia

May potentiate adverse dopaminergic effects of levodopa and may cause or exacerbate preexisting dyskinesias.^{1 7 8 11 13} Reduction of levodopa dosage may ameliorate dyskinesia.¹

Fibrotic Effects

Retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, and thickening of pleura reported in patients receiving ergot-derivative dopamine receptor agonists (e.g., bromocriptine, pergolide);¹ presumably related to the ergoline structure of these agents.¹ Not known whether non-ergot-derived drugs that increase dopaminergic activity (e.g., pramipexole) may induce similar changes.¹

Ocular Effects

Retinal degeneration reported in albino rats receiving pramipexole for 2 years; similar changes not observed in albino mice, monkeys, or minipigs.¹ Clinical importance in humans not established.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Appears to be distributed into milk in rats.¹ Not known whether pramipexole is distributed into human milk.¹ Pramipexole inhibits prolactin secretion.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in children.^{1 20}

Geriatric Use

Geriatric patients are at increased risk for hallucinations.¹ No other apparent differences in efficacy or safety between geriatric patients and younger adults.¹

Renal Impairment

Use with caution.¹ Clearance is decreased.¹ Dosage adjustment recommended.^{1 15} (See Renal Impairment under Dosage and Administration.)

Safety and efficacy not evaluated systematically in patients with Cl_cr <15 mL/minute or in those undergoing hemodialysis.¹

Common Adverse Effects

Patients with early parkinsonian syndrome (without levodopa): Nausea, dizziness, somnolence, insomnia, asthenia, constipation, hallucinations, general edema, peripheral edema.¹

Patients with advanced parkinsonian syndrome (with concomitant levodopa): Postural hypotension, dyskinesia, extrapyramidal syndrome, insomnia, dizziness, hallucinations, accidental injury, dream abnormalities, confusion, asthenia, constipation, somnolence, dystonia, dry mouth, gait abnormalities, hypertonia, amnesia, urinary frequency.¹

Interactions for Mirapex

Does not inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2E1, 3A4, or 2D6 at usual plasma concentrations; is not appreciably metabolized by CYP isoenzymes.¹

Drugs Eliminated via Renal Secretion

Drugs that are secreted by the cationic transport system may decrease the oral clearance of pramipexole by about 20%; those secreted by the anionic transport system are likely to have little effect on the oral clearance of pramipexole.¹

Dopamine Antagonists

Possible pharmacodynamic interaction, resulting in diminished effectiveness of pramipexole.¹

Specific Drugs

Drug	Interaction	Comments
Amantadine	Alteration of oral clearance of pramipexole is unlikely1
Antipsychotic agents (e.g., phenothiazines, butyrophenones, thioxanthenes)	Dopamine antagonist activity of the antipsychotic agent may diminish effectiveness of pramipexole1
Cephalosporins	Effect on oral clearance of pramipexole is unlikely1
Chlorpropamide	Effect on oral clearance of pramipexole is unlikely1
Cimetidine	Cimetidine-induced inhibition of renal tubular secretion of organic bases via the cationic transport system increases the AUC and prolongs the half-life of pramipexole1
CNS depressants (e.g., alcohol, antidepressants, antipsychotics, benzodiazepines)	Possible additive sedative effects1 20 21
Diltiazem	Diltiazem is secreted by the cationic transport system and may decrease oral clearance of pramipexole1
Hydrochlorothiazide	Effect on oral clearance of pramipexole is unlikely1
Indomethacin	Effect on oral clearance of pramipexole is unlikely1
Levodopa	Additive therapeutic and/or adverse (e.g., dyskinesia) effects; peak plasma levodopa concentration may be higher and occur sooner after administration, but extent of levodopa absorption is not altered1	Consider a reduction in levodopa dosage when pramipexole is added to levodopa therapy1
Metoclopramide	Dopamine antagonist activity of metoclopramide may diminish effectiveness of pramipexole1
Penicillins	Effect on oral clearance of pramipexole is unlikely1
Probenecid	No appreciable alteration of pramipexole pharmacokinetics1
Quinidine and Quinine	Quinidine and quinine are secreted by the cationic transport system and may decrease oral clearance of pramipexole1
Ranitidine	Ranitidine is secreted by the cationic transport system and may decrease oral clearance of pramipexole1
Selegiline	Alteration of oral clearance of pramipexole is unlikely1
Triamterene	Triamterene is secreted by the cationic transport system and may decrease oral clearance of pramipexole1
Verapamil	Verapamil is secreted by the cationic transport system and may decrease oral clearance of pramipexole1

Mirapex Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed after oral administration, with peak plasma concentration attained in approximately 2 hours.¹ Absolute bioavailability is >90%.¹

Food

Food decreases the rate but not the extent of absorption; time to peak concentration is delayed by about 1 hour.^{1 12}

Distribution

Extent

Widely distributed throughout the body.¹

Plasma Protein Binding

15%.¹

Elimination

Metabolism

No metabolites have been identified in plasma or urine.¹

Elimination Route

Eliminated in urine (90%), almost entirely as unchanged drug.¹ Renal clearance of pramipexole is approximately 3 times higher than GFR.¹ Pramipexole is secreted by the renal tubules, probably by the organic cationic transport system.¹

Half-life

Terminal half-life is about 8 hours in young healthy individuals.¹

Special Populations

In individuals >65 years, total oral clearance of pramipexole is reduced by approximately 30% and the terminal half-life is about 12 hours.¹

Pharmacokinetics not evaluated to date in patients with hepatic impairment; however, hepatic impairment would not be expected to have a significant effect on pramipexole elimination, since approximately 90% of a dose is excreted in urine as unchanged drug.¹

In patients with renal impairment, clearance of pramipexole is about 75% lower in patients with Cl_cr of approximately 20 mL/minute and about 60% lower in patients with Cl_cr of approximately 40 mL/minute compared with healthy volunteers.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹ Protect from light.¹

ActionsActions

• 
  

  Exhibits high binding specificity for and intrinsic activity at dopamine D₂ receptors in vitro compared with other dopamine receptor agonists (e.g., bromocriptine, pergolide);^{3 6 7 8 9 18 19} has a higher affinity for the D₃ subtype¹³ than for the D₂ or D₄ subtypes.^{1 2 9 15 16 19}

  
  


• 
  

  Appears to act by directly stimulating postsynaptic dopamine receptors in the corpus striatum.^{1 6 9 15 16}

  
  

Advice to Patients

• 
  

  Risk of somnolence;¹ possibility of falling asleep while engaged in activities of daily living.^{1 20 21 22 23} Avoid driving or operating machinery until effects on the individual are known.¹

  
  


• 
  

  Potential for orthostatic hypotension (e.g., dizziness, nausea, syncope, sweating), especially during dosage escalation.¹ Patients should avoid rising rapidly after sitting or lying down, especially if they have been in a seated or recumbent position for prolonged periods and/or if they are just beginning pramipexole therapy.¹

  
  


• 
  

  Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs (especially CNS depressants or alcohol), as well as any concomitant illnesses.¹

  
  


• 
  

  Risk of hallucinations, particularly in geriatric patients.¹

  
  


• 
  

  Pramipexole may be taken with or without food; however, taking the drug with food may reduce the occurrence of nausea.¹

  
  


• 
  

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

  
  


• 
  

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

  
  

Preparations

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

Pramipexole Dihydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	0.125 mg	Mirapex (with povidone)	Pfizer
		0.25 mg	Mirapex (with povidone; scored)	Pfizer
		0.5 mg	Mirapex (with povidone; scored)	Pfizer
		1 mg	Mirapex (with povidone; scored)	Pfizer
		1.5 mg	Mirapex (with povidone; scored)	Pfizer

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.

Mirapex 0.125MG Tablets (BOEHRINGER INGELHEIM): 30/$130.99 or 90/$360.95

Mirapex 0.25MG Tablets (BOEHRINGER INGELHEIM): 90/$349 or 270/$1020.97

Mirapex 0.5MG Tablets (BOEHRINGER INGELHEIM): 90/$336 or 270/$985.96

Mirapex 1MG Tablets (BOEHRINGER INGELHEIM): 90/$336 or 270/$985.96

Mirapex 1.5MG Tablets (BOEHRINGER INGELHEIM): 90/$341 or 270/$974.93

Pramipexole Dihydrochloride 0.125MG Tablets (TEVA PHARMACEUTICALS USA): 30/$85.99 or 90/$239.99

Pramipexole Dihydrochloride 0.25MG Tablets (TEVA PHARMACEUTICALS USA): 90/$239.99 or 270/$679.98

Pramipexole Dihydrochloride 0.5MG Tablets (TEVA PHARMACEUTICALS USA): 90/$239.99 or 270/$679.98

Pramipexole Dihydrochloride 1MG Tablets (TEVA PHARMACEUTICALS USA): 90/$239.99 or 270/$679.98

Pramipexole Dihydrochloride 1.5MG Tablets (TEVA PHARMACEUTICALS USA): 90/$239.99 or 270/$679.98

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 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Pfizer. Mirapex (pramipexole dihydrochloride) tablets prescribing information. Kalamazoo, MI; 2003 Jun.

2. Parkinson Study Group. Safety and efficacy of pramipexole in early Parkinson disease. JAMA. 1997; 278:125-130. [IDIS 388331] [PubMed 9214527]

3. Schilling JC, Adamus WS, Palluk R. Neuroendocrine and side effect profile of pramipexole, a new dopamine receptor agonist, in humans. Clin Pharmacol Ther. 1992; 51:541-8. [IDIS 297374] [PubMed 1350237]

4. Eli Lilly and Company. Permax (pergolide mesylate) prescribing information (dated 1995 Feb 15). In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:571-3.

5. Sandoz. Parlodel SnapTabs (bromocriptine mesylate) prescribing information (dated 1996 Feb). In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:2411-3.

6. Hubble JP, Koller WC, Cutler NR et al. Pramipexole in patients with early Parkinson’s disease. Clin Neuropharmacol. 1995; 18:338-47. [PubMed 8665547]

7. Molho ES, Factor SA, Weiner WJ et al. The use of pramipexole, a novel dopamine (DA) agonist, in advanced Parkinson’s disease. J Neural Transm. 1995; 45(Suppl):225-30.

8. Rabey JM. Second generation of dopamine agonists: pros and cons. J Neural Transm. 1995; 45(Suppl):213-24.

9. Goetz CG. New strategies with dopaminergic drugs: modified formulations of levodopa and novel agonists. Exp Neurol. 1997; 144:17-20. [PubMed 9126145]

10. Shannon KM for the Pramipexole Study Group. Pramipexole monotherapy in early Parkinson’s disease: long-term follow-up and interim analysis. Paper presented at XIIth International Symposium on Parkinson’s Disease. London: World Health Organization; 1997 Mar.

11. Oertel WH, Pogarell O. Long-term follow-up of patients with advanced Parkinson’s disease. Paper presented at XIIth International Symposium on Parkinson’s Disease. London: 1997 Mar.

12. Wright CE, Sisson L, Ichhpurani AK et al. Influence of food on the bioavailability of pramipexole. J Neurol. 1997; 244(Suppl 3):S52.

13. Lieberman A, Ranhosky A, Korts D. Clinical evaluation of pramipexole in advanced Parkinson’s disease: results of a double-blind, placebo-controlled, parallel-group study. Neurology. 1997; 49:162-8. [IDIS 388119] [PubMed 9222185]

14. Wright CE, Sisson TL, Ichhpurani AK et al. Pramipexole and levodopa pharmacokinetics following concomitant administration. Neurology. 1997; 48:A185.

15. Wright CE, Sisson L, Ichhpurani AK et al. Influence of renal impairment and hemodialysis on pramipexole pharmacokinetics. Movement Disorders. 1997; 12(Suppl 1):66. [PubMed 8990056]

16. Wright CE, Sisson L, Ichhpurani AK et al. Pramipexole steady-state pharmacokinetics in healthy male and female volunteers. Movement Disorders. 1997; 12(Suppl 1):65.

17. Wright CE, Lasher Sisson T, Ichhpurani AK et al. Influence of age and gender on pramipexole pharmacokinetics. Clin Pharmacol Ther. 1996; 59:184.

18. Albani C, Popescu R, Lacher R et al. Single dose response to pramipexole in patients with Parkinson’s disease. Movement Disorders. 1992; 7(Suppl 1):98.

19. Piercey MF, Hoffmann WE, Smith MW et al. Inhibition of dopamine neuron firing by pramipexole, a dopamine D₃ receptor-preferring agonist: comparison to other dopamine receptor agonists. Eur J Pharmacol. 1996; 312:35-44. [PubMed 8891576]

20. Pharmacia & Upjohn, Kalamazoo, MI: Personal communication.

21. Gallen CC. Dear healthcare professional letter regarding pramipexole and reports of sudden sleep onset during daily activities. Kalamazoo, MI: Pharmacia & Upjohn; 1999 Aug.

22. Frucht S, Rogers JD, Greene PE et al. Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology. 1999; 52:1908-10. [IDIS 430280] [PubMed 10371546]

23. Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology. 2001; 56:S1-S88.

24. Anon. Initial treatment of Parkinson’ disease: wait just a minute. Med Lett Drugs Ther. 2001; 43:59-60. [PubMed 11445778]

More Mirapex resources

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

• Mirapex Prescribing Information (FDA)


• Mirapex Consumer Overview


• Mirapex Advanced Consumer (Micromedex) - Includes Dosage Information


• Mirapex MedFacts Consumer Leaflet (Wolters Kluwer)


• Pramipexole Prescribing Information (FDA)


• Mirapex ER Prescribing Information (FDA)


• Mirapex ER Extended-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

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