Eprazinone Hydrochloride may be available in the countries listed below.
Eprazinone Hydrochloride (JAN) is also known as Eprazinone (Rec.INN)
International Drug Name Search
Glossary
| JAN | Japanese Accepted Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Treating certain stomach, intestinal, and bladder conditions, including spasms. It is used to control stomach secretions and cramps. It is used to relieve the symptoms of colic, runny nose, and Parkinson-like problems. It is used to treat excessive sweating or saliva production. It may also be used for other conditions as determined by your doctor.
Spasdel Elixir is an anticholinergic agent. It works by decreasing the motion of muscles in the stomach, intestines, and bladder. It also decreases the production of stomach acid.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Spasdel Elixir. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Spasdel Elixir. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Spasdel Elixir 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.
Use Spasdel Elixir as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Spasdel Elixir.
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:
Bloated feeling; blurred vision; constipation; decreased sweating; dizziness; drowsiness; dry mouth; enlarged pupils; excitability; headache; nausea; nervousness; trouble sleeping; weakness.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); agitation; behavior changes; confusion; decreased sexual ability; diarrhea; difficulty focusing eyes; disorientation; exaggerated sense of well-being; fast or irregular heartbeat; hallucinations; loss of consciousness; loss of coordination; memory loss; mental or mood changes; severe or persistent trouble sleeping; speech changes; taste changes or loss; trouble urinating; unusual tiredness or weakness; vision changes; vomiting.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Spasdel side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include disorientation; excessive thirst or excitability; fever; hot, dry skin; seizures; severe dry mouth; severe or persistent blurred vision, dizziness, headache, nausea, or vomiting; trouble breathing or swallowing.
Store Spasdel Elixir at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Spasdel Elixir out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Spasdel Elixir. 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.
Etretinato may be available in the countries listed below.
Etretinato (DCIT) is known as Etretinate in the US.
International Drug Name Search
Glossary
| DCIT | Denominazione Comune Italiana |
Laxyl may be available in the countries listed below.
Bromazepam is reported as an ingredient of Laxyl in the following countries:
International Drug Name Search
Cylence may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Cyfluthrin is reported as an ingredient of Cylence in the following countries:
Piperonyl Butoxide is reported as an ingredient of Cylence in the following countries:
International Drug Name Search
Epogam may be available in the countries listed below.
Gamolenic Acid is reported as an ingredient of Epogam in the following countries:
International Drug Name Search
Generic Name: cefpodoxime (Oral route)
sef-poe-DOX-eem PROX-e-til
In the U.S.
Available Dosage Forms:
Therapeutic Class: Antibiotic
Pharmacologic Class: 3rd Generation Cephalosporin
Cefpodoxime is used to treat bacterial infections in many different parts of the body. It belongs to the class of medicines known as cephalosporin antibiotics. It works by killing bacteria or preventing their growth. However, this medicine will not work for colds, flu, or other virus infections.
This medicine is available only with your doctor's prescription.
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of cefpodoxime in children. However, safety and efficacy have not been established in infants younger than 2 months of age.
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of cefpodoxime in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution and an adjustment in the dose for patients receiving cefpodoxime.
| Pregnancy Category | Explanation | |
|---|---|---|
| All Trimesters | B | Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus. |
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.
You or your child must take the tablets with food, while the oral liquid may be taken with or without food.
Shake the oral liquid well before each use. Measure the medicine with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.
Keep using this medicine for the full treatment time, even if you or your child feel better after the first few doses. Your infection may not clear up if you stop using the medicine too soon.
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
Store the tablets in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Store the oral liquid in the refrigerator. Throw away any unused medicine after 14 days.
If your symptoms or your child's symptoms do not improve within a few days, or if they become worse, check with your doctor.
Cefpodoxime may cause diarrhea, and in some cases it can be severe. Do not take any medicine or give medicine to your child to treat diarrhea without first checking with your doctor. Diarrhea medicines may make the diarrhea worse or make it last longer. If you have any questions about this or if mild diarrhea continues or gets worse, check with your doctor.
Before you or your child have any medical tests, tell the medical doctor in charge that you are using this medicine. The results of some tests may be affected by this medicine.
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
See also: Vantin side effects (in more detail)
The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.
The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.
Rec.INN
0128326-82-9
C18-H14-Cl2-N2
329
Antifungal agent for topical use
International Drug Name Search
Glossary
| IS | Inofficial Synonym |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Harmogen may be available in the countries listed below.
UK matches:
Estropipate is reported as an ingredient of Harmogen in the following countries:
International Drug Name Search
Glossary
| SPC | Summary of Product Characteristics (UK) |
Etamzilats may be available in the countries listed below.
Etamsylate is reported as an ingredient of Etamzilats in the following countries:
International Drug Name Search
Etec 1000 may be available in the countries listed below.
Tocopherol, α- is reported as an ingredient of Etec 1000 in the following countries:
International Drug Name Search
AGGRASTAT ® * (50 micrograms/ml) solution for Infusion
1 ml solution for infusion contains 56 micrograms of tirofiban hydrochloride monohydrate which is equivalent to 50 micrograms of tirofiban.
For excipients, see section 6.1.
Solution for infusion (250 ml bag).
A clear colourless solution.
'Aggrastat' is indicated for the prevention of early myocardial infarction in patients presenting with unstable angina or non-Q-wave myocardial infarction with the last episode of chest pain occurring within 12 hours and with ECG changes and/or elevated cardiac enzymes.
Patients most likely to benefit from 'Aggrastat' treatment are those at high risk of developing myocardial infarction within the first 3-4 days after onset of acute angina symptoms including for instance those that are likely to undergo an early PTCA (see also 4.2 'Posology and method of administration' and 5.1 'Pharmacodynamic properties').
'Aggrastat' is intended for use with acetylsalicylic acid (ASA) and unfractionated heparin.
This product is for hospital use only, by specialist physicians experienced in the management of acute coronary syndromes.
'Aggrastat' is given intravenously at an initial infusion rate of 0.4 microgram/kg/min for 30 minutes. At the end of the initial infusion, 'Aggrastat' should be continued at a maintenance infusion rate of 0.1 microgram/kg/min. 'Aggrastat' should be given with unfractionated heparin (usually an intravenous bolus of 5,000 units [U] simultaneously with the start of 'Aggrastat' therapy, then approximately 1,000 U per hour, titrated on the basis of the activated thromboplastin time [APTT], which should be about twice the normal value) and ASA, (see 5.1 'Pharmacodynamic properties' PRISM-PLUS study) unless contra-indicated.
No dosage adjustment is necessary for the elderly (see also 4.4 'Special warnings and special precautions for use').
Patients with severe kidney failure
In severe kidney failure (creatinine clearance <30 ml/min) the dosage of 'Aggrastat' should be reduced by 50% (see also 4.4 'Special warnings and precautions for use' and 5.2 'Pharmacokinetic properties').
The following table is provided as a guide to dosage adjustment by weight.
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Start and duration of therapy with 'Aggrastat'
'Aggrastat' optimally should be initiated within 12 hours after the last anginal episode. The recommended duration should be at least 48 hours. Infusion of 'Aggrastat' and unfractionated heparin may be continued during coronary angiography and should be maintained for at least 12 hours and not more than 24 hours after angioplasty/atherectomy. Once a patient is clinically stable and no coronary intervention procedure is planned by the treating physician, the infusion should be discontinued. The entire duration of treatment should not exceed 108 hours.
Concurrent therapy (unfractionated heparin, ASA)
Treatment with unfractionated heparin is initiated with an i.v. bolus of 5,000 U and then continued with a maintenance infusion of 1,000 U per hour. The heparin dosage is titrated to maintain an APTT of approximately twice the normal value.
Unless contra-indicated, all patients should receive ASA orally before the start of 'Aggrastat' (see 5.1 'Pharmacodynamic properties' PRISM-PLUS study). This medication should be continued at least for the duration of the infusion of 'Aggrastat'.
If angioplasty (PTCA) is required, heparin should be stopped after PTCA, and the sheaths should be withdrawn once coagulation has returned to normal, e.g. when the activated clotting time (ACT) is less than 180 seconds (usually 2-6 hours after discontinuation of heparin).
Instructions for use
Do not withdraw solution directly from the container with a syringe.
Directions for use of IntraVia ™† containers
To open: Tear foil overpouch or plastic dust cover down side at slit and remove IntraVia™ container. Some opacity of the plastic due to moisture absorption during the sterilisation process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution as sterility may be impaired.
Do not use unless solution is clear and seal is intact.
Do not add supplementary medication or withdraw solution directly from the bag with a syringe.
CAUTION: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is completed.
Preparation for administration
1. Suspend container from eyelet support.
2. Remove plastic protector from outlet port at bottom of container.
3. Attach administration set. Refer to complete directions accompanying set.
Use according to the dosage table above.
Where the solution and container permit, parenteral drugs should be inspected for visible particles or discoloration before use.
'Aggrastat' should only be given intravenously and may be administered with unfractionated heparin through the same infusion tube.
It is recommended that 'Aggrastat' be administered with a calibrated infusion set using sterile equipment.
Care should be taken to ensure that no prolongation of the infusion of the initial dose occurs and that miscalculation of the infusion rates for the maintenance dose on the basis of the patient's weight is avoided.
'Aggrastat' is contra-indicated in patients who are hypersensitive to the active substance or to any of the excipients of the preparation or who developed thrombocytopenia during earlier use of a GP IIb/IIIa receptor antagonist.
Since inhibition of platelet aggregation increases the bleeding risk, 'Aggrastat' is contra-indicated in patients with:
• History of stroke within 30 days or any history of haemorrhagic stroke
• Known history of intracranial disease (e.g. neoplasm, arteriovenous malformation, aneurysm)
• Active or recent (within the previous 30 days of treatment) clinically relevant bleeding (e.g. gastro-intestinal bleeding)
• Malignant hypertension
• Relevant trauma or major surgical intervention within the past six weeks
• Thrombocytopenia (platelet count <100,000/mm3), disorders of platelet function
• Clotting disturbances (e.g. prothrombin time>1.3 times normal or INR [International Normalised Ratio]>1.5)
• Severe liver failure.
The administration of 'Aggrastat' alone without unfractionated heparin is not recommended.
There is limited experience with concomitant administration of 'Aggrastat' with enoxaparin (see also 5.1 'Pharmacodynamic properties' and 5.2 'Pharmacokinetic properties'). The concomitant administration of 'Aggrastat' with enoxaparin is associated with a higher frequency of cutaneous and oral bleeding events, but not in TIMI bleeds***, when compared with the concomitant administration of 'Aggrastat' and unfractionated heparin. An increased risk of serious bleeding events associated with the concomitant administration of 'Aggrastat' and enoxaparin cannot be excluded, particularly in patients given additional unfractionated heparin in conjunction with angiography and/or PCI. The efficacy of 'Aggrastat' in combination with enoxaparin has not been established. The safety and efficacy of 'Aggrastat' with other low molecular weight heparins has not been investigated.
There is insufficient experience with the use of tirofiban hydrochloride in the following diseases and conditions, however, an increased risk of bleeding is suspected. Therefore, tirofiban hydrochloride is not recommended in:
• Traumatic or protracted cardiopulmonary resuscitation, organ biopsy or lithotripsy within the past two weeks
• Severe trauma or major surgery>6 weeks but <3 months previously
• Active peptic ulcer within the past three months
• Uncontrolled hypertension (>180/110 mm Hg)
• Acute pericarditis
• Active or a known history of vasculitis
• Suspected aortic dissection
• Haemorrhagic retinopathy
• Occult blood in the stool or haematuria
• Thrombolytic therapy (see 4.5 'Interaction with other medicinal products and other forms of interaction').
• Concurrent use of drugs that increase the risk of bleeding to a relevant degree (see 4.5 'Interaction with other medicinal products and other forms of interaction').
There is no therapeutic experience with tirofiban hydrochloride in patients for whom thrombolytic therapy is indicated (e.g. acute transmural myocardial infarction with new pathological Q-waves or elevated ST-segments or left bundle-branch block in the ECG). Consequently, the use of tirofiban hydrochloride is not recommended in these circumstances.
'Aggrastat' infusion should be stopped immediately if circumstances arise that necessitate thrombolytic therapy (including acute occlusion during PTCA) or if the patient must undergo an emergency coronary artery bypass graft (CABG) operation or requires an intra-aortic balloon pump.
There are limited efficacy data in patients immediately undergoing PTCA.
There is no therapeutic experience with 'Aggrastat' in children, thus, the use of 'Aggrastat' is not recommended in these patients.
Other precautionary notes and measures
There are insufficient data regarding the re-administration of 'Aggrastat'.
Patients should be carefully monitored for bleeding during treatment with 'Aggrastat'. If treatment of haemorrhage is necessary, discontinuation of 'Aggrastat' should be considered (see also 4.9 'Overdose'). In cases of major or uncontrollable bleeding, tirofiban hydrochloride should be discontinued immediately.
'Aggrastat' should be used with special caution in the following conditions and patient groups:
• Recent clinically relevant bleeding (less than one year)
• Puncture of a non-compressible vessel within 24 hours before administration of 'Aggrastat'
• Recent epidural procedure (including lumbar puncture and spinal anaesthesia)
• Severe acute or chronic heart failure
• Cardiogenic shock
• Mild to moderate liver insufficiency
• Platelet count <150,000/mm3, known history of coagulopathy or platelet function disturbance or thrombocytopenia
• Haemoglobin concentration less than 11 g/dl or haematocrit <34%.
Special caution should be used during concurrent administration of ticlopidine, clopidogrel, adenosine, dipyridamole, sulfinpyrazone, and prostacyclin.
Elderly patients, female patients, and patients with low body weight
Elderly and/or female patients had a higher incidence of bleeding complications than younger or male patients, respectively. Patients with a low body weight had a higher incidence of bleeding than patients with a higher body weight. For these reasons 'Aggrastat' should be used with caution in these patients and the heparin effect should be carefully monitored.
Impaired renal function
There is evidence from clinical studies that the risk of bleeding increases with decreasing creatinine clearance and hence also reduced plasma clearance of tirofiban. Patients with decreased renal function (creatinine clearance <60 ml/min) should therefore be carefully monitored for bleeding during treatment with 'Aggrastat' and the heparin effect should be carefully monitored. In severe kidney failure the 'Aggrastat' dosage should be reduced (see also 4.2 'Posology and method of administration').
Femoral artery line
During treatment with 'Aggrastat' there is a significant increase in bleeding rates, especially in the femoral artery area, where the catheter sheath is introduced. Care should be taken to ensure that only the anterior wall of the femoral artery is punctured. Arterial sheaths may be removed when coagulation has returned to normal, e.g. when activated clotting time (ACT) is less than 180 seconds, (usually 2–6 hours after discontinuation of heparin).
After removal of the introducer sheath, careful haemostasis should be ensured under close observation.
General nursing care
The number of vascular punctures, and intramuscular injections should be minimised during the treatment with 'Aggrastat'. I.V. access should only be obtained at compressible sites of the body. All vascular puncture sites should be documented and closely monitored. The use of urinary catheters, nasotracheal intubation and nasogastric tubes should be critically considered.
Monitoring of laboratory values
Platelet count, haemoglobin and haematocrit levels should be determined before treatment with 'Aggrastat' as well as within 2-6 hours after start of therapy with 'Aggrastat' and at least once daily thereafter while on therapy (or more often if there is evidence of a marked decrease). In patients who have previously received GP IIb/IIIa receptor antagonists (cross reactivity can occur), the platelet count should be monitored immediately e.g., within the first hour of administration after re-exposure (see also 4.8 'Undesirable effects'). If the platelet count falls below 90,000/mm3, further platelet counts should be carried out in order to rule out pseudothrombocytopenia. If thrombocytopenia is confirmed, 'Aggrastat' and heparin should be discontinued. Patients should be monitored for bleeding and treated if necessary (see also 4.9 'Overdose').
In addition, activated thromboplastin time (APTT) should be determined before treatment and the anticoagulant effects of heparin should be carefully monitored by repeated determinations of APTT and the dose should be adjusted accordingly (see also 4.2 'Posology and method of administration'). Potentially life-threatening bleeding may occur especially when heparin is administered with other products affecting haemostasis, such as GP IIb/IIIa receptor antagonists.
The use of several platelet aggregation inhibitors increases the risk of bleeding, likewise their combination with heparin, warfarin and thrombolytics. Clinical and biological parameters of haemostasis should be regularly monitored.
The concomitant administration of 'Aggrastat' and ASA (acetylsalicyclic acid or aspirin) increases the inhibition of platelet aggregation to a greater extent than aspirin alone, as m,easured by the ex vivo ADP-induced platelet aggregation test. The concomitant administration of 'Aggrastat' and unfractionated heparin increases the prolongation of the bleeding time to a greater extent as compared to unfractionated heparin alone.
With the concurrent use of 'Aggrastat' and unfractionated heparin and ASA there was a higher incidence of bleeding than when only unfractionated heparin and ASA were used together (see also 4.4 'Special warnings and precautions for use' and 4.8 'Undesirable effects').
'Aggrastat' prolonged bleeding time, however, the combined administration of 'Aggrastat' and ticlopidine did not additionally affect bleeding time.
Concomitant use of warfarin with 'Aggrastat' plus heparin was associated with an increased risk of bleeding.
'Aggrastat' is not recommended in thrombolytic therapy - concurrent or less than 48 hours before administration of tirofiban hydrochloride or concurrent use of drugs that increase the risk of bleeding to a relevant degree (e.g. oral anticoagulants, other parenteral GP IIb/IIIa inhibitors, dextran solutions). There is insufficient experience with the use of tirofiban hydrochloride in these conditions; however, an increased risk of bleeding is suspected.
Pregnancy
For tirofiban hydrochloride, no clinical data on exposed pregnancies are available. Animal studies provide limited information with respect to effects on pregnancy, embryonal/foetal development, parturation, and postnatal development. 'Aggrastat' should not be used during pregnancy unless clearly necessary.
Lactation
It is not known whether 'Aggrastat' is excreted in human milk, but it is known to be excreted in rat milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
No data are available on whether 'Aggrastat' impairs the ability to drive or operate machinery.
Bleeding
The adverse event causally related to 'Aggrastat' therapy (used concurrently with unfractionated heparin and ASA) most commonly reported was bleeding, which was usually of a milder nature.
In the PRISM-PLUS study, the overall incidence of major bleeding using the TIMI criteria (defined as a haemoglobin drop of>50 g/l with or without an identified site, intracranial haemorrhage, or cardiac tamponade) in patients treated with 'Aggrastat' in combination with heparin was not significantly higher than in the control group. The incidence of major bleeding using the TIMI criteria was 1.4% for 'Aggrastat' in combination with heparin and 0.8% for the control group (which received heparin). The incidence of minor bleeding using the TIMI criteria (defined as a haemoglobin drop of>30 g/l with bleeding from a known site, spontaneous gross haematuria, haematemesis or haemoptysis) was 10.5% for 'Aggrastat' in combination with heparin and 8.0% for the control group. There were no reports of intracranial bleeding for 'Aggrastat' in combination with heparin or in the control group. The incidence of retroperitoneal bleeding reported for 'Aggrastat' in combination with heparin was 0.0% and 0.1% for the control group. The percentage of patients who received a transfusion (including packed red blood cells, fresh frozen plasma, whole blood cryoprecipitates and platelets) was 4.0% for 'Aggrastat' and 2.8% for the control group.
'Aggrastat' given with unfractionated heparin and ASA was associated with gastro-intestinal, haemorrhoidal and post-operative bleeding, epistaxis, gum bleeds and surface dermatorrhagia as well as oozing haemorrhage (haematoma) in the area of intravascular puncture sites (e.g. in cardiac catheter examinations) significantly more often than was unfractionated heparin and ASA alone.
Non-bleeding-associated adverse reactions
The most common adverse drug reactions (incidence over 1%) associated with 'Aggrastat' given concurrently with heparin, apart from bleeding, were nausea (1.7%), fever (1.5%) and headache (1.1%); nausea, fever and headache occurred with incidences of 1.4%, 1.1% and 1.2%, respectively, in the control group.
The incidence of adverse non-bleeding-related events was higher in women (compared to men) and older patients (compared to younger patients). However, the incidences of non-bleeding-related adverse events in these patients were comparable for the ' “Aggrastat” with heparin' group and the 'heparin alone' group.
[Common: (>1/100, <1/10)]
Nervous system and psychiatric disorders:
Common: headache
Gastrointestinal disorders:
Common: nausea
General disorders and administration site conditions:
Common: fever
Investigations
The most common changes of laboratory parameters associated with 'Aggrastat' related to bleeding: reduction of haemoglobin and haematocrit levels and an increased occurrence of occult blood in urine and faeces.
Occasionally during 'Aggrastat' therapy an acute fall in the platelet count or thrombocytopenia occurred. The percentage of patients in whom the platelet count fell to below 90,000/mm3 was 1.5%. The percentage of patients in whom the platelet count fell to less than 50,000/mm3 was 0.3%. These decreases were reversible upon discontinuation of 'Aggrastat'. Acute and severe platelet decreases have been observed in patients with no prior history of thrombocytopenia upon re-administration of GP IIb/IIIa receptor antagonists.
The following additional adverse reactions have been reported infrequently in post-marketing experience; they are derived from spontaneous reports for which precise incidences cannot be determined:
Blood and lymphatic system disorders:
Intracranial bleeding, retroperitoneal bleeding, haemopericardium, pulmonary (alveolar) haemorrhage, and epidural haematoma in the spinal region. Fatal bleedings have been reported rarely.
Acute and/or severe (<20,000/mm3) decreases in platelet counts which may be associated with chills, low-grade fever or bleeding complications (see Investigations above)
Immune system disorders:
Severe allergic reactions (e.g., bronchospasm, urticaria) including anaphylactic reactions. The reported cases have occurred during initial treatment (also on the first day) and during readministration of tirofiban. Some cases have been associated with severe thrombocytopenia (platelet counts <10,000/mm3).
Inadvertent overdosage with tirofiban hydrochloride occurred in the clinical studies, up to 50 microgram/kg as a three minute bolus or 1.2 microgram/kg/min as an initial infusion. Overdosage with up to 1.47 microgram/kg/min as a maintenance infusion rate has also occurred.
a) Symptoms of overdosage
The symptom of overdosage most commonly reported was bleeding, usually mucosal bleeding and localised bleeding at the arterial puncture site for cardiac catheterisation but also single cases of intracranial haemorrhages and retroperitoneal bleedings (see also 4.4 'Special warnings and precautions for use' and 5.1 'Pharmacodynamic properties' PRISM-PLUS study).
b) Measures
Overdosage with tirofiban hydrochloride should be treated in accordance with the patient's condition and the attending physician's assessment. If treatment of hemorrhage is necessary, the 'Aggrastat' infusion should be discontinued. Transfusions of blood and/or thrombocytes should also be considered. 'Aggrastat' can be removed by haemodialysis.
ATC-Code: B01A C17
Tirofiban hydrochloride is a non-peptidal antagonist of the GP IIb/IIIa receptor, an important platelet surface receptor involved in platelet aggregation. Tirofiban hydrochloride prevents fibrinogen from binding to the GP IIb/IIIa receptor, thus blocking platelet aggregation.
Tirofiban hydrochloride leads to inhibition of platelet function, evidenced by its ability to inhibit ex vivo ADP-induced platelet aggregation and to prolong bleeding time (BT). Platelet function returns to baseline within eight hours after discontinuation.
The extent of this inhibition runs parallel to the tirofiban hydrochloride plasma concentration.
In the target population the recommended dosage of 'Aggrastat', in the presence of unfractionated heparin and ASA, produced a more than 70% (median 89%) inhibition of ex vivo ADP-induced platelet aggregation in 93% of patients and a prolongation of the bleeding time by a factor of 2.9 during infusion. Inhibition was achieved rapidly with the 30-minute loading infusion and was maintained over the duration of the infusion.
PRISM-PLUS study
The double-blind, multicentre, controlled PRISM-PLUS study compared the efficacy of tirofiban and unfractionated heparin (n=773) versus unfractionated heparin (n=797) in patients with unstable angina or acute non-Q-wave myocardial infarction (NQWMI).
Patients had to have prolonged, repetitive anginal pain, or post-infarction angina within 12 hours prior to randomisation, accompanied by new transient or persistent ST-T wave changes (ST depression or elevation
In this study, patients were randomised to either
− 'Aggrastat' (30 minute loading infusion of 0.4 microgram/kg/min followed by a maintenance infusion of 0.10 microgram/kg/min) and heparin (bolus of 5,000 units [U] followed by an infusion of 1,000 U/hr titrated to maintain an activated partial thromboplastin time [APTT] of approximately two times control),
− or heparin alone (bolus of 5,000 U followed by an infusion of 1,000 U/hr titrated to maintain an APTT of approximately two times control).
All patients received ASA unless contra-indicated; 300-325 mg orally per day were recommended for the first 48 hours and thereafter 80-325 mg orally per day (as determined by the physician). Study drug was initiated within 12 hours after the last anginal episode. Patients were treated for 48 hours, after which they underwent angiography and possibly angioplasty/atherectomy, if indicated, while tirofiban hydrochloride was continued. Tirofiban hydrochloride was infused for a mean period of 71.3 hours.
The combined primary study endpoint was the occurrence of refractory ischaemia, myocardial infarction or death at seven days after the start of tirofiban hydrochloride.
The mean age of the population was 63 years; 32% of patients were female. At baseline approximately 58% of patients had ST segment depression; 53% had T-wave inversions; 46% of patients presented with elevated cardiac enzymes. During the study approximately 90% of patients underwent coronary angiography; 30% underwent early angioplasty and 23% underwent early coronary artery bypass surgery.
At the primary end-point, there was a 32% risk reduction (RR) (12.9% vs. 17.9%) in the tirofiban hydrochloride group for the combined end-point (p=0.004): this represents approximately 50 events avoided for 1,000 patients treated. Results of the primary end-point were principally attributed to the occurrence of myocardial infarction and refractory ischaemic conditions.
After 30 days the RR for the combined end-point (death/myocardial infarction/refractory ischaemic conditions/readmissions for unstable angina) was 22% (18.5% vs. 22.3%; p=0.029).
After six months the risk of the combined end-point (death/myocardial infarction/refractory ischaemic conditions/readmissions for unstable angina) was reduced by 19% (27.7% vs. 32.1%; p=0.024).
Regarding the most commonly used double combined end-point, death or myocardial infarction, the results at 7 days, 30 days and 6 months were as follows: at 7 days for the tirofiban group there was a 43% RR (4.9% vs. 8.3%; p=0.006); at 30 days the RR was 30% (8.7% vs. 11.9%; p=0.027) and at six months the RR was 23% (12.3% vs. 15.3%; p=0.063).
The reduction in the incidence of myocardial infarctions in patients receiving 'Aggrastat' appeared early during treatment (within the first 48 hours) and this reduction was maintained through six months, without significant effect on mortality.
In the 30% of patients who underwent angioplasty/atherectomy during initial hospitalisation, there was a 46% RR (8.8% vs. 15.2%) for the primary combined end-point at 30 days as well as a 43% RR (5.9% vs. 10.2%) for 'myocardial infarction or death'.
Based on a safety study, the concomitant administration of 'Aggrastat' with enoxaparin (n=315) was compared to the concomitant administration of 'Aggrastat' with unfractionated heparin (n=210) in patients presenting with unstable angina and non-Q wave myocardial infarction. A 30 minute loading dose of tirofiban (0.4 microgram/kg/min) was followed by a maintenance infusion of 0.1 microgram/kg/min for up to 108 hours. Patients randomised to the enoxaparin group received a 1.0 microgram/kg subcutaneous injection of enoxaparin every 12 hours for a period of at least 24 hours and a maximum duration of 96 hours. Patients randomised to the unfractionated heparin group received a 5000-unit intravenous bolus of unfractionated heparin followed by a maintenance infusion of 1000 units per hour for at least 24 hours and a maximum duration of 108 hours. The total TIMI bleed rate was 3.5% for the tirofiban/enoxaparin group and 4.8% for the tirofiban/unfractionated heparin group. Cutaneous bleeds and oral bleeds occurred significantly more frequently in patients randomised to the enoxaparin group versus the unfractionated heparin group. Catheter site bleeds were more common in the enoxaparin group who subsequently required PCI were switched to unfractionated heparin peri-procedurally with the dose titrated to maintain an ACT of 250 seconds or higher. Although there was a significant difference in the rates of cutaneous bleeds between the two groups (29.2% in the enoxaparin converted to unfractionated heparin group and 15.2% in the unfractionated heparin only group), there were no TIMI major bleeds (see 4.4 'Special warnings and precautions for use') in either group. The efficacy of 'Aggrastat' in combination with enoxaparin has not been established.
Patients most likely to benefit from 'Aggrastat' treatment are those at high risk of developing myocardial infarction within the 3-4 days after onset of acute angina symptoms. According to epidemiological findings, a higher incidence of cardiovascular events has been associated with certain indicators, for instance: age, elevated heart rate or blood pressure, persistent or recurrent ischaemic cardiac pain, marked ECG changes (in particular ST-segment abnormalities), raised cardiac enzymes or markers (e.g. CK-MB, troponins) and heart failure.
Distribution
Tirofiban is not strongly bound to plasma protein, and protein binding is concentration-independent in the range of 0.01–25 microgram/ml. The unbound fraction in human plasma is 35%.
The distribution volume of tirofiban in the steady state is about 30 litres.
Biotransformation
Experiments with 14C-labelled tirofiban showed the radioactivity in urine and faeces to be emitted chiefly by unchanged tirofiban. The radioactivity in circulating plasma originates mainly from unchanged tirofiban (up to 10 hours after administration). These data suggested limited metabolisation of tirofiban.
Elimination
After intravenous administration of 14C-labelled tirofiban to healthy subjects, 66% of the radioactivity was recovered in the urine, 23% in the faeces. The total recovery of radioactivity was 91%. Renal and biliary excretion contribute significantly to the elimination of tirofiban.
In healthy subjects the plasma clearance of tirofiban is about 250 ml/min. Renal clearance is 39–69% of plasma clearance. The half-life is 1.5 hours.
Gender
The plasma clearance of tirofiban in patients with coronary heart disease is similar in men and women.
Elderly patients
The plasma clearance of tirofiban is about 25% less in elderly (> 65 years) patients with coronary heart disease in comparison to younger (
Ethnic groups
No difference was found in the plasma clearance between patients of different ethnic groups.
Coronary Artery Disease
In patients with unstable angina pectoris or NQWMI the plasma clearance was about 200 ml/min, the renal clearance 39% of the plasma clearance. The half-life is about two hours.
Impaired renal function
In clinical studies patients with decreased renal function showed a reduced plasma clearance of tirofiban depending on the degree of impairment of creatinine clearance. In patients with a creatinine clearance of less than 30 ml/min, including haemodialysis patients, the plasma clearance of tirofiban is reduced to a clinically relevant extent (over 50%) (see also 4.2 'Posology and method of administration'). Tirofiban is removed by haemodialysis.
Liver failure
There is no evidence of a clinically significant reduction of the plasma clearance of tirofiban in patients with mild to moderate liver failure. No data are available on patients with severe liver failure.
Effects of other drugs
The plasma clearance of tirofiban in patients receiving one of the following drugs was compared to that in patients not receiving that drug in a sub-set of patients (n=762) in the PRISM study. There were no substantial (>15%) effects of these drugs on the plasma clearance of tirofiban: acebutolol, alprazolam, amlodipine, aspirin preparations, atenolol, bromazepam, captopril, diazepam, digoxin, diltiazem, docusate sodium, enalapril, furosemide, glibenclamide, unfractionated heparin, insulin, isosorbide, lorazepam, lovastatin, metoclopramide, metoprolol, morphine, nifedipine, nitrate preparations, oxazepam, paracetamol, potassium chloride, propranolol, ranitidine, simvastatin, sucralfate and temazepam.
The pharmacokinetics and pharmacodynamics of 'Aggrastat' were investigated when concomitantly administered with enoxaparin (1 mg/kg subcutaneously every 12 hours) and compared with the combination of 'Aggrastat' and unfractionated heparin. There was no difference in the clearance of 'Aggrastat' between the two groups.
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.
Tirofiban crosses the placenta in rats and rabbits.
Sodium chloride, sodium citrate dihydrate, citric acid anhydrous, water for injections, hydrochloric acid and/or sodium hydroxide (for pH adjustment).
Incompatibility has been found with diazepam. Therefore, 'Aggrastat' and diazepam should not be administered in the same intravenous line.
2 years.
Do not freeze. Keep container in foil overpouch to protect from light.
250 ml IntraVia™ container (PL 2408 plastic), colourless, 3-layer polyolefine film with outlet port and PVC tube with blue top. It is packed in a preprinted foil overpouch.
Pack sizes: 1 or 3 containers with 250 ml solution for infusion. Not all pack sizes may be marketed.
No incompatibilities have been found with 'Aggrastat' and the following intravenous formulations: atropine sulfate, dobutamine, dopamine, epinephrine, HCl, furosemide, heparin, lidocaine, midazolam HCl, morphine sulfate, nitroglycerin, potassium chloride, propanolol HCl and famotidine injection.
Any unused solution should be discarded. See 4.2 'Posology and method of administration'.
Some opacity of the plastic due to moisture absorption during the sterilisation process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution as sterility may be impaired.
Do not use unless solution is clear and seal is intact.
Iroko Cardio (UK) Ltd., 201 Bishopsgate, London, EC2M 3AF, UK.
PL 35173/0002
15 July 1999.
30 September 2009
POM
* in the following 'Aggrastat' means 'Aggrastat' Solution for infusion.
* in the following 'Aggrastat' means 'Aggrastat' Solution for infusion.
† IntraVia is the tradename for the infusion bag used for 'Aggrastat' Solution. Trademark of Baxter International Inc.
***TIMI major bleeds are defined as a haemaglobin drop of>50 g/l with or without an identified site, intracranial haemorrhage, or cardiac tamponade. TIMI minor bleeds are defined as a haemoglobin drop of>30 g/l but
Azulfidine-EN may be available in the countries listed below.
Sulfasalazine is reported as an ingredient of Azulfidine-EN in the following countries:
International Drug Name Search
Treating pain, soreness, burning, and itching of the anal area due to hemorrhoids and other anorectal disorders.
Tucks Hemorrhoidal Ointment is a topical anesthetic. It works by blocking pain signals from the nerve endings in the skin, which helps relieve discomfort.
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Some MEDICINES MAY INTERACT with Tucks Hemorrhoidal Ointment. Because little, if any, of Tucks Hemorrhoidal Ointment is absorbed into the blood, the risk of it interacting with another medicine is low.
This may not be a complete list of all interactions that may occur. Ask your health care provider if Tucks Hemorrhoidal Ointment 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.
Use Tucks Hemorrhoidal Ointment as directed by your doctor. Check the label on the medicine for exact dosing instructions.
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All medicines may cause side effects, but many people have no, or minor, side effects. When used in small doses, no COMMON side effects have been reported with this product. Seek medical attention right away if any of these SEVERE side effects occur:
Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bleeding from the rectum; new or increasing redness, pain, swelling, irritation, or other symptoms.
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See also: Tucks Hemorrhoidal side effects (in more detail)
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