Indever may be available in the countries listed below.
Propranolol hydrochloride (a derivative of Propranolol) is reported as an ingredient of Indever in the following countries:
International Drug Name Search
Generic Name: oxaliplatin (ox AL i PLA tin)
Brand Names: Eloxatin
Oxaliplatin is a cancer medication that interferes with the growth of cancer cells and slows their growth and spread in the body.
Oxaliplatin is used together with other cancer medications to treat colon and rectal cancer.
Oxaliplatin may also be used for other purposes not listed in this medication guide.
Before receiving oxaliplatin, tell your doctor if you are allergic to any drugs, or if you have liver disease, asthma, or a nerve problem.
Receiving oxaliplatin can make you more sensitive to cold. This includes exposure to cold temperature and coming into contact with cold objects. To prevent discomfort avoid breathing in cold air, cover your skin in cold weather, wear gloves when handling cold objects, avoid air conditioning, and do not use ice or drink cold beverages.
Do not eat ice chips to ease mouth sores or nausea because you will be more sensitive to cold. Talk to your doctor about other ways to treat nausea or mouth sores.
Oxaliplatin can lower blood cells that help your body fight infections. This can make it easier for you to bleed or get sick. Avoid being around others who are ill. Your blood will need to be tested on a regular basis. Your kidney and liver function may also need to be tested. Do not miss any scheduled appointments.
If you have any of these other conditions, you may need a dose adjustment or special tests to safely receive oxaliplatin:
liver disease;
asthma or other breathing disorder; or
a nerve problem.
Oxaliplatin is given as an injection through a needle placed into a vein. You will receive this injection in a clinic or hospital setting. The medicine must be given slowly through an IV infusion, and can take up at least 2 hours to complete.
Oxaliplatin is usually given as part of a 2-day treatment every 2 weeks. Follow your doctor's instructions.
do not inhale deeply when you are exposed to cold air;
cover your skin, head, and face when you are outside in cold temperatures;
wear gloves when handling cold objects or refrigerated foods;
do not run an air conditioner at very cool temperature in your home or car (even during hot weather);
do not drink cold drinks or use ice cubes in drinks;
do not put ice packs on your body.
Chemotherapy often causes nausea or mouth sores. Do not eat ice chips to ease these discomforts because you will be more sensitive to cold. Talk to your doctor about other ways to treat nausea or mouth sores. You may be given other medications to prevent nausea or vomiting while you are receiving oxaliplatin.
Oxaliplatin can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. To be sure your blood cells do not get too low, your blood will need to be tested on a regular basis. Your kidney and liver function may also need to be tested. Do not miss any scheduled appointments.
Contact your doctor if you miss an appointment for your oxaliplatin injection.
Overdose symptoms may include easy bruising or bleeding, unusual weakness, severe vomiting or diarrhea, numbness or tingling, flu symptoms, wheezing, trouble breathing, chest pain, slow heart rate, weak or shallow breathing (breathing may stop).
Avoid cold temperatures and cold objects, including ice, cold drinks, and skin exposure to cold temperatures.
Avoid being near people who have colds, the flu, or other contagious illnesses. Contact your doctor at once if you develop signs of infection.
numbness or tingly feeling in your hands, feet, throat, and around your mouth;
numbness or burning pain that interferes with daily activities;
increased sensitivity to cold temperatures and cold objects;
jaw or chest tightness, eye pain, strange feeling in your tongue, problems with speech or swallowing;
fever, diarrhea, vomiting, chills, body aches, flu symptoms, sudden cough;
increased thirst, dry mouth, urinating less than usual;
decreased vision;;
easy bruising or bleeding, unusual weakness; or
white patches or sores inside your mouth or on your lips.
Less serious side effects may include:
nausea, stomach pain, loss of appetite;
constipation;
tired feeling;
hair loss;
decreased taste sensation;
muscle pain;
headache;
sleep problems (insomnia);
swelling; or
back pain.
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.
Before you receive oxaliplatin, tell your doctor if you also take a blood thinner such as warfarin (Coumadin).
There may be other drugs that can interact with oxaliplatin. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.
See also: Eloxatin side effects (in more detail)
Generic Name: moxifloxacin (Intravenous route)
mox-i-FLOX-a-sin hye-droe-KLOR-ide
Fluoroquinolones, including moxifloxacin hydrochloride, are associated with an increased risk of tendinitis and tendon rupture in all ages. Risk further increases with age over 60 years, concomitant steroid therapy, and kidney, heart, or lung transplants. Fluoroquinolones may exacerbate muscle weakness in persons with myasthenia gravis. Avoid in patients with known history of myasthenia gravis .
In the U.S.
Available Dosage Forms:
Therapeutic Class: Antibiotic
Chemical Class: Moxifloxacin
Moxifloxacin injection is used to treat bacterial infections in many different parts of the body.
Moxifloxacin injection belongs to the class of medicines known as fluoroquinolone 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 have not been performed on the relationship of age to the effects of moxifloxacin injection in the pediatric population. Safety and efficacy have not been established.
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of moxifloxacin injection in the elderly. However, elderly patients are more likely to have age-related heart problems, or develop severe tendon problems (including tendon rupture), which may require caution in patients receiving moxifloxacin injection.
| Pregnancy Category | Explanation | |
|---|---|---|
| All Trimesters | C | Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women. |
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 receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
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:
A nurse or other trained health professional will give you this medicine. This medicine is given through a needle placed in one of your veins.
Your doctor may give you a few doses of this medicine until your condition improves, and then you may be switched to an oral medicine that works the same way. If you have any concerns about this, talk to your doctor.
This medicine comes with a Medication Guide. It is very important that you read and understand this information. Be sure to ask your doctor about anything you do not understand.
It is very important that your doctor check your progress while you are receiving this medicine. This will allow your doctor to see if the medicine is working properly and to check for any unwanted effects.
If you have low potassium levels in the blood, moxifloxacin may increase your risk of having a fast, slow or irregular heartbeat; loss of consciousness; or fainting spells. If these symptoms occur, tell your doctor right away.
This medicine may cause serious allergic reactions, including anaphylaxis, which can be life-threatening and require immediate medical attention. Call your doctor right away if you have itching; hives; hoarseness; shortness of breath; trouble breathing; trouble swallowing; or any swelling of your hands, face, or mouth after you receive this medicine.
Moxifloxacin may cause diarrhea, and in some cases it can be severe. It may occur 2 months or more after you stop using this medicine. Do not take any medicine 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.
Tell your doctor right away if you start having numbness, tingling, or burning pain in your hands, arms, legs, or feet. These may be symptoms of a condition called peripheral neuropathy.
Moxifloxacin may rarely cause inflammation (tendinitis) or tearing of a tendon (the cord that attaches muscles to bones). This can occur while you are using the medicine or after you finish using it. The risk of having tendon problems may be increased if you are over 60 years of age, are using steroid medicines (eg, dexamethasone, prednisolone, prednisone, or Medrol®), have severe kidney problems, have a history of tendon problems (eg, rheumatoid arthritis), or if you have received an organ transplant (eg, heart, kidney, or lung). Stop using this medicine and check with your doctor right away if you have sudden pain or swelling in a tendon after exercise (eg, ankle, back of the knee or leg, shoulder, elbow, or wrist), bruise more easily after an injury, or are unable to bear weight or move the affected area. Refrain from exercise until your doctor says otherwise.
Moxifloxacin may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert. If these reactions are especially bothersome, check with your doctor.
Some people who receive moxifloxacin may become more sensitive to sunlight than normal. Exposure to sunlight, even for brief periods of time, may cause severe sunburn, or skin rash, redness, itching, or discoloration. When you begin receiving this medicine:
If you have a severe reaction from the sun, check with your doctor.
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 or nurse 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: Avelox I.V. 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.
Class: Anthelmintics
VA Class: AP200
CAS Number: 22204-24-6
Brands: Ascarel, Pin-X, Reese’s Pinworm Medicine
Anthelmintic; pyrimidine-derivative.a
Treatment of enterobiasis caused by Enterobius vermicularis (pinworm infection).102 105 106 108 109 May be used for self-medication.100 103 108 109 Drugs of choice for enterobiasis are pyrantel, mebendazole, or albendazole.102 105
Has been used for treatment of ascariasis† caused by Ascaris lumbricoides.106 Drugs of choice for ascariasis are albendazole, ivermectin, or mebendazole.102 105
Treatment of intestinal hookworm infections caused by Ancylostoma duodenale† or Necator americanus†.102 105 Drugs of choice for intestinal hookworm infections are albendazole, mebendazole, or pyrantel.102 105
Treatment of eosinophilic enterocolitis† caused by Ancylostoma caninum (dog hookworm).102 Drugs of choice are albendazole, mebendazole, or pyrantel.102 When indicated, endoscopic worm extraction also is considered a treatment of choice for eosinophilic enterocolitis.102
Treatment of trichostrongyliasis† caused by Trichostrongylus†.102 Pyrantel is the drug of choice; albendazole and mebendazole are alternatives.102
May be effective for treatment of oesophagostomiasis† caused by Oesophagostomum bifurcum.102 Albendazole is an alternative.102
Treatment of infections caused by Moniliformis moniliformis† (thorny-headed worm).102
Administer orally.108 109 May be taken without regard to meals;108 109 may be taken or mixed with milk or fruit juice.102 108 109
Shake oral suspension well before using.108
Special diet, fasting, or purgation prior to administration not necessary.a 108 109
Presence of pinworms should be confirmed visually before initiating self-medication.100 108 109
Available as pyrantel pamoate; dosage expressed in terms of pyrantel.108 109
11 mg/kg administered as a single dose; repeat dose after 2 weeks.102
Self-medication in children ≥2 years of age: 11 mg/kg administered as a single dose.108 109 Do not repeat treatment unless directed by a clinician.100 108 109
Treatment of all household contacts may be warranted when multiple or repeated symptomatic infections occur.102 105
11 mg/kg once daily for 3 days.102
Perform a repeat stool examination 2 weeks after treatment; repeat dosing regimen if results are positive.105
11 mg/kg once daily for 3 days.102
11 mg/kg administered as a single dose.102
11 mg/kg administered as a single dose; repeat dose twice at 2-week intervals for a total of 3 doses.102
11 mg/kg administered as a single dose; repeat dose after 2 weeks.102
Self-medication: 11 mg/kg administered as a single dose.108 109 Do not repeat treatment unless directed by a clinician.100 108 109
Treatment of all household contacts may be warranted when multiple or repeated symptomatic infections occur.102 105
11 mg/kg once daily for 3 days.102
Perform a repeat stool examination 2 weeks after treatment; repeat dosing regimen if results are positive.105
11 mg/kg once daily for 3 days.102
11 mg/kg administered as a single dose.102
11 mg/kg administered as a single dose; repeat dose twice at 2-week intervals for a total of 3 doses.102
Maximum single dose 1 g.102
Maximum single dose 1 g.102
No special population dosage recommendations at this time.a
Known hypersensitivity to pyrantel or any ingredient in the formulation.a
Use caution in patients with severe malnutrition or anemia.a Ideally, anemic, dehydrated, or malnourished patients should receive supportive therapy prior to administration of pyrantel.a
Category C.107
Use during pregnancy only if benefits justify risks to the fetus and only when no alternative management is appropriate. a
Pregnant women considering self-medication for treatment of enterobiasis should do so only under the direction of a clinician.100 108 109
Safety and efficacy not established in children <2 years of age;a use in this age group only when potential benefits justify possible risks.a
Use with caution in patients with preexisting liver dysfunction.100
Individuals with liver disease considering self-medication for treatment of enterobiasis should do so only under direction of a clinician.108 109
GI disturbances (nausea,108 109 vomiting,108 109 tenesmus,a anorexia,a diarrhea,108 109 abdominal cramps,108 109 gastralgia), headache,108 109 dizziness. 108 109
Drug | Interaction | Comments |
|---|---|---|
Piperazine (no longer commercially available in the US) | Decreased efficacy of pyrantel and piperazinea | Do not administer concomitantlya |
Poorly absorbed from GI tract.a Peak serum concentrations occur 1–3 hours after a dose.a
Partially metabolized in the liver.a
Approximately 50% of an oral dose is excreted unchanged in feces; 7% excreted in urine as unchanged drug and metabolites.a
<30°C, tight, light-resistant container.a
Pyrimidine-derivative anthelmintic agent.a
Depolarizing neuromuscular blocking agent.a Paralyzes worms which are then expelled from the GI tract by peristalsis.a
Active against Enterobius vermicularis (pinworm), Ascaris lumbricoides (roundworm), Ancylostoma duodenale (hookworm), Necator americanus (hookworm), and Trichostrongylus orientalis (hairworm).a
For self-medication of enterobiasis (pinworm infection), importance of providing patient a copy of manufacturer’s patient information.100
When using to treat enterobiasis, importance of treating all household members and importance of taking hygienic precautions to minimize reinfection, including wearing tight underpants both day and night, cleaning the bedroom floor by vacuuming or damp mopping for several days after treatment, washing and not shaking bed linens and night clothes after treatment, and keeping toilet seats clean.108 109 a
Importance of informing clinician if symptoms of enterobiasis persist after treatment.100 Importance of informing clinician if worms other than pinworms are present before or after therapy.100 108 109
Importance of informing clinician if abdominal disturbances (nausea, vomiting, diarrhea), headache, or dizziness persist or become bothersome after use of the drug.100 108 109
Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., anemia, hepatic disease).a
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.a
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Powder* | |||
Suspension | 250 mg (of pyrantel) per 5 mL* | Ascarel | Pfeiffer | |
Pin-X | Effcon | |||
Pyrantel Pamoate Suspension | ||||
Reese’s Pinworm Medicine | Reese | |||
Tablets | 62.5 mg (of pyrantel) | Reese’s Pinworm Caplets | Reese |
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 August 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
100. Food and Drug Administration. Anthelmintic drug products for over-the-counter human use; final monograph. Fed Regist. 1986; 51:27756-60.
101. Food and Drug Administration. Anthelmintic drug products for over-the-counter human use; establishment of a monograph. Fed Regist. 1980; 45:59540-8.
102. Anon. Drugs for parasitic infections. From the Medical Letter website (). 2008 Aug.
103. Food and Drug Administration. Over-the-counter drug products; final monographs for antiemetic, antitussive, bronchodilator, and antihelmintic drug products; updating and technical changes; final rule. Fed Regist. 1988; 53:35808-10.
105. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.
106. Liu LX. Strongyloidiasis and other intestinal nematode infections. Infect Dis Clin North Am. 1993; 7:655-82. [PubMed 8254165]
107. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 8th ed. Baltimore, MD: Williams & Wilkins; 2008:1559.
108. Reese. Reese’s pinworm medicine (pyrantel pamoate) prescribing information. Cleveland, OH.
109. Reese. Reese’s pinworm caplets (pyrantel pamoate) prescribing information. Cleveland, OH.
a. AHFS drug information 2009. McEvoy GK, ed. Pyrantel. Bethesda, MD: American Society of Health-System Pharmacists; 2009:62-3.
GLYCERYL TRINITRATE TABLETS BP 600 micrograms
Each tablet contains 600 micrograms Glyceryl Trinitrate BP.
White uncoated tablets.
White, circular, biconvex uncoated tablets, impressed “C” on one face and the identifying letters “GS” on reverse.
As a short-acting vasodilator in the:
1. Relief of angina pectoris
2. Prophylaxis of angina pectoris
3. Relief of acute spontaneous coronary artery spasm
Posology
1-2 tablets (0.6-1.2mg) should be placed under the tongue and allowed to dissolve slowly; this dose should be repeated as required. If pain persists after a total of 3 doses in 15minutes the patient should be advised to seek medical attention.
Dosage should be adjusted according to the response obtained by the individual patient and the severity of the anginal pain.
NB Tolerance may develop with daily use, but withdrawal for a week re-establishes the original sensitivity.
Method of Administration
For sublingual administration
Known hypersensitivity to nitrates and other ingredients in the tablets. Patients with rare hereditary problems of galactose intolerence, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Marked anaemia, raised intercranial pressure including that caused by head trauma, cerebral haemorrhage, closed angle glaucoma, hypotensive conditions, hypovolaemia, obstructive hypertrophic cardiomyopathy, aortic stenosis, mitral stenosis, cardiac tamponade, obstructive heart failure and constrictive pericarditis.
Phosphodiesterase type-5 inhibitors (eg sildenafil, tadalafil, vardenafil) have been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates, and their co-administration with nitrates or nitric oxide donors is therefore contra-indicated.
Caution is necessary in patients with severe hepatic or renal impairment, hypothyroidism, hypoxaemia, hypothermia or a recent history of myocardial infaraction and malnutrition.
Some effects of glyceryl trinitrate are enhanced by alcohol. The hypotensive effects of nitrates are potentiated by concurrent administration of phosphodiestrase type-5 inhibitors (eg sildenafil, tadalafil, vardenafil).
Glyceryl trinitrate may potentiate the effects of anti-hypertensive drugs (such as vasodilators, beta-blockers, calcium-channel blockers, diuretics).
There is a potential for drugs that cause dry mouth (eg anticholinergic, antimuscarinics, tricyclic antidepressants) to reduce the effectiveness of sublingual nitrates.
There have been some reports that the anticoagulant effects of heparin may be reduced by the concurrent use of nitrates. The effects of heparin should be monitored and dose adjusted as necessary.
An enhanced hypotensive effect with sublingual apomorphine may occur as a result of concomitant administration with glyceryl trinitrate.
Ergot alkaloids may oppose the coronary vasodilatation of nitrates. Ergot alkaloids can precipitate angina and glyceryl trinitrate can reduce the first pass hepatic metabolism of dihydroergotamine.
There is no, or inadequate, evidence of safety of nitrates in human pregnancy or lactation; nitrates should not be administered in pregnancy or lactation unless considered essential.
As Glyceryl trinitrate can cause dizziness patients should make sure they are not affected before driving or operating machinery. This effect appears to be accentuated by alcohol.
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Toxic effects of glyceryl trinitrate include vomiting, restlessness, hypotension, syncope, cyanosis and methaemoglobinaemia; impairment of respiration, hypoxia, bradycardia and psychosis may ensue.
Overdosage should be treated with gastric lavage, followed by charcoal administration if necessary in case that nitrates were ingested, attention to any respiratory and circulatory symptoms. Oxygen may prove additionally useful.
Effects of hypotension may be minimised by treating the patient in the recumbent position with the head lowered or raised legs.
Methaemoglobinaemia may be treated with methylene blue intravenously 1-4mg/kg body-weight. The circulation may be maintained with infusions of plasma or suitable electrolyte solutions.
ATC Code: CO1D AO2 Organic nitrates
Glyceryl trinitrate is a vasodilator and is used for angina of effort. Vasodilation is achieved by the releasing of free redical nitric oxide which activates guanylate cyclase and increases synthesis of guanosine 3′ and 5′-monophosphate with resultant effects on the phosphorylation of proteins in smooth muscle. If taken in excess, its vasodilatory effect can cause headache.
Glyceryl trinitrate is readily absorbed from the oral mucosa, but rapidly metabolised so that it only has a fleeting duration of action.
Glyceryl trinitrate is also readily absorbed from the gastrointestinal tract, but owing to extensive first-pass metabolism in the liver its bioavailability is reduced (short plasma half-life).
Glyceryl trinitrate is metabolised by hydrolysis to dinitrates and the mononitrate, which is the main urinary metabolite.
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
The tablets also contain: acacia (E414), colloidal silica, lactose, magnesium stearate, mannitol (E421), stearic acid and water.
None known.
Shelf-life
Two years from the date of manufacture.
Shelf-life after dilution/reconstitution
Not applicable.
Shelf-life after first opening
Discard 8 weeks after first opening.
Store in a dry place below 25°C. Protect from light.
The product is supplied in amber glass bottles with screw caps lined with aluminium foil.
Pack sizes: 56s, 60s, 84s, 90s, 100s, 112s, 120s, 168s, 180s, 200s, 1000s
Product may also be supplied in bulk packs, for reassembly purposes only, in amber glass containers with screw caps lined with aluminium foil, filled with aluminium foil as a cushioning material.
Maximum size of bulk packs: 5,000
• Your Glyceryl Trinitrate tablets will be presented in a glass airtight container with a foil-lined cap. Keep them in this.
• After use reclose the bottle cap tightly.
• Do not put cotton wool, other drugs, or anything else in the bottle with the tablets.
• Store the tablets below 25oC in a dry place, protected from light. If you need to carry them with you DO NOT carry them close to your body, rather in a purse, wallet or handbag.
• If you do not use the tablets within 8 weeks of first opening the bottle obtain a fresh supply and return the old tablets to your pharmacist. (A fresh tablets should produce a slight burning sensation when placed under the tongue; if this does not occur, obtain a fresh supply). In any event do not use the tablets after the expiry date shown.
Actavis UK Limited
(Trading style: Actavis)
Whiddon Valley
BARNSTAPLE
N Devon EX32 8NS
PL 0142/6297 R
February 1986
March 1994, March 1999
16/04/2010
Generic Name: lavender (LAH ven der)
Brand Names:
The use of lavender in cultural and traditional settings may differ from concepts accepted by current Western medicine. When considering the use of herbal supplements, consultation with a primary health care professional is advisable. Additionally, consultation with a practitioner trained in the uses of herbal/health supplements may be beneficial, and coordination of treatment among all health care providers involved may be advantageous.
Lavender is also known as Lavandula angustifolia, aspic, lavandin, spike lavender, and true lavender.
Lavender has been used for many purposes including loss of appetite, nervousness, insomnia, acne, headaches, diabetes, rheumatic pain, nerve pain, and colds.
Lavender has not been evaluated by the FDA for safety, effectiveness, or purity. All potential risks and/or advantages of lavender may not be known. Additionally, there are no regulated manufacturing standards in place for these compounds. There have been instances where herbal/health supplements have been sold which were contaminated with toxic metals or other drugs. Herbal/health supplements should be purchased from a reliable source to minimize the risk of contamination.
Lavender may also have uses other than those listed in this product guide.
At higher doses, lavender may increase the effects of other drugs that cause drowsiness, including antidepressants, alcohol, antihistamines, sedatives (used to treat insomnia), pain relievers, anxiety medicines, seizure medicines, and muscle relaxants. Do not take lavender with other medications that may also cause drowsiness.
Lavender has not been evaluated by the FDA for safety, effectiveness, or purity. All potential risks and/or advantages of lavender may not be known. Additionally, there are no regulated manufacturing standards in place for these compounds. There have been instances where herbal/health supplements have been sold which were contaminated with toxic metals or other drugs. Herbal/health supplements should be purchased from a reliable source to minimize the risk of contamination.
Before taking lavender, talk to your doctor, pharmacist, or health care professional if you have allergies (especially to plants), have any medical condition, or if you take other medicines or other herbal/health supplements. Lavender may not be recommended in some situations.
The use of lavender in cultural and traditional settings may differ from concepts accepted by current Western medicine. When considering the use of herbal supplements, consultation with a primary health care professional is advisable. Additionally, consultation with a practitioner trained in the uses of herbal/health supplements may be beneficial, and coordination of treatment among all health care providers involved may be advantageous.
If you choose to take lavender, use it as directed on the package or as directed by your doctor, pharmacist, or other health care provider.
Standardized extracts, tinctures, and solid formulations of herbal/health supplements may provide a more reliable dose of the product.
To ensure the correct dose, measure the liquid forms of lavender with a dropper or a dose-measuring spoon or cup.
Some forms of lavender can be brewed to form a tea for drinking.
Store lavender as directed on the package. In general, lavender should be protected from light.
Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra lavender to make up the missed dose.
At higher doses, lavender may increase the effects of other drugs that cause drowsiness, including antidepressants, alcohol, antihistamines, sedatives (used to treat insomnia), pain relievers, anxiety medicines, seizure medicines, and muscle relaxants. Do not take lavender with other medications that may also cause drowsiness.
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.
At higher doses, lavender may increase the effects of other drugs that cause drowsiness, including antidepressants, alcohol, antihistamines, sedatives (used to treat insomnia), pain relievers, anxiety medicines, seizure medicines, and muscle relaxants. Do not take lavender with other medications that may also cause drowsiness.
Interactions between lavender and other prescription or over-the-counter medicines or herbal/health supplements may also occur. Talk to your doctor, pharmacist, or health care professional before taking lavender if you are taking any other medicines or supplements.
This drug should be administered only by adequately trained individuals familiar with its actions, characteristics, and hazards.
Nuromax (doxacurium chloride) is a long-acting, nondepolarizing skeletal muscle relaxant for intravenous administration. Doxacurium chloride is [1α,2β(1'S*,2'R*)] - 2,2' - [(1,4 - dioxo - 1,4 - butanediyl)bis(oxy - 3,1 - propanediyl)]bis[1,2,3,4 - tetrahydro - 6,7,8 - trimethoxy - 2 - methyl-1-[(3,4,5-trimethoxyphenyl)methyl]isoquinolinium] dichloride (meso form). The molecular formula is C56H78CI2N2O16 and the molecular weight is 1106.14. The compound does not partition into the 1-octanol phase of a distilled water/ 1-octanol system, i.e., the n-octanol:water partition coefficient is 0.
Doxacurium chloride is a mixture of three trans, trans stereoisomers, a dl pair [(1R,1'R,2S,2'S) and (1S,1'S,2R,2'R)] and a meso form (1R,1'S,2S,2'R). The meso form is illustrated below:
Nuromax Injection is a sterile, nonpyrogenic aqueous solution (pH 3.9 to 5.0) containing doxacurium chloride equivalent to 1 mg/mL doxacurium in Water for Injection. Hydrochloric acid may have been added to adjust pH. Nuromax Injection contains 0.9% w/v benzyl alcohol.
Nuromax binds competitively to cholinergic receptors on the motor end-plate to antagonize the action of acetylcholine, resulting in a block of neuromuscular transmission. This action is antagonized by acetylcholinesterase inhibitors, such as neostigmine.
Nuromax is approximately 2.5 to 3 times more potent than pancuronium and 10 to 12 times more potent than metocurine. Nuromax in doses of 1.5 to 2 × ED95 has a clinical duration of action (range and variability) similar to that of equipotent doses of pancuronium and metocurine (historic data and limited comparison). The average ED95 (dose required to produce 95% suppression of the adductor pollicis muscle twitch response to ulnar nerve stimulation) of Nuromax is 0.025 mg/kg (range: 0.020 to 0.033) in adults receiving balanced anesthesia.
The onset and clinically effective duration (time from injection to 25% recovery) of Nuromax administered alone or after succinylcholine during stable balanced anesthesia are shown in Table 1.
| Initial Dose of Nuromax (mg/kg) | |||
* Values shown are means (range). † Nuromax administered after 10% to 100% recovery from an intubating dose of succinylcholine. | |||
| 0.025† (n = 34) | 0.05 (n = 27) | 0.08 (n = 9) | |
| Time to Maximum Block (min) | 9.3 (5.4-16) | 5.2 (2.5-13) | 3.5 (2.4-5) |
| Clinical Duration (min) (Time to 25% Recovery) | 55 (9-145) | 100 (39-232) | 160 (110-338) |
Initial doses of 0.05 mg/kg (2 × ED95) and 0.08 mg/kg (3 × ED95) Nuromax administered during the induction of thiopental-narcotic anesthesia produced good-to-excellent conditions for tracheal intubation in 5 minutes (13 of 15 cases studied) and 4 minutes (eight of nine cases studied) (which are before maximum block), respectively.
As with other long-acting agents, the clinical duration of neuromuscular block associated with Nuromax shows considerable interpatient variability. An analysis of 390 cases in US clinical trials utilizing a variety of premedications, varying lengths of surgery, and various anesthetic agents, indicates that approximately two thirds of the patients had clinical durations within 30 minutes of the duration predicted by dose (based on mg/kg actual body weight). Patients ≥ 60 years old are approximately twice as likely to experience prolonged clinical duration (30 minutes longer than predicted) than patients < 60 years old; thus, care should be used in older patients when prolonged recovery is undesirable (see PRECAUTIONS -Geriatric Use and CLINICAL PHARMACOLOGY - Individualization of Dosages subsection). In addition, obese patients (patients weighing ≥ 30% more than ideal body weight for height) were almost twice as likely to experience prolonged clinical duration than non-obese patients; therefore, dosing should be based on ideal body weight (IBW) for obese patients (see CLINICAL PHARMACOLOGY - Individualization of Dosages subsection).
The mean time for spontaneous T1 recovery from 25% to 50% of control following initial doses of Nuromax is approximately 26 minutes (range: 7 to 104, n = 253) during balanced anesthesia. The mean time for spontaneous T1 recovery from 25% to 75% is 54 minutes (range: 14 to 184, n = 184).
Most patients receiving Nuromax in clinical trials required pharmacologic reversal prior to full spontaneous recovery from neuromuscular block (see OVERDOSAGE - Antagonism of Neuromuscular Block); therefore, relatively few data are available on the time from injection to 95% spontaneous recovery of the twitch response. As with other long-acting neuromuscular blocking agents, Nuromax may be associated with prolonged times to full spontaneous recovery. Following an initial dose of 0.025 mg/kg Nuromax, some patients may require as long as 4 hours to exhibit full spontaneous recovery.
Cumulative neuromuscular blocking effects are not associated with repeated administration of maintenance doses of Nuromax at 25% T1 recovery. As with initial doses, however, the duration of action following maintenance doses of Nuromax may vary considerably among patients.
The Nuromax ED95 for children 2 to 12 years of age receiving halothane anesthesia is approximately 0.03 mg/kg. Children require higher doses of Nuromax on a mg/kg basis than adults to achieve comparable levels of block. The onset time and duration of block are shorter in children than adults. During halothane anesthesia, doses of 0.03 mg/kg and 0.05 mg/kg Nuromax produce maximum block in approximately 7 and 4 minutes, respectively. The duration of clinically effective block is approximately 30 minutes after an initial dose of 0.03 mg/kg and approximately 45 minutes after 0.05 mg/kg. Nuromax has not been studied in pediatric patients below the age of 2 years.
The neuromuscular block produced by Nuromax may be antagonized by anticholinesterase agents. As with other nondepolarizing neuromuscular blocking agents, the more profound the neuromuscular block at reversal, the longer the time and the greater the dose of anticholinesterase required for recovery of neuromuscular function.
Administration of doses of Nuromax up to and including 0.08 mg/kg (~3 × ED95) over 5 to 15 seconds to healthy adult patients during stable-state balanced anesthesia and to patients with serious cardiovascular disease undergoing coronary artery bypass grafting, cardiac valvular repair, or vascular repair produced no dose-related effects on mean arterial blood pressure (MAP) or heart rate (HR).
No dose-related changes in MAP and HR were observed following administration of up to 0.05 mg/kg Nuromax over 5 to 15 seconds in 2- to 12-year-old children receiving halothane anesthesia.
Doses of 0.03 to 0.08 mg/kg (1.2 to 3 × ED95) were not associated with dose-dependent changes in mean plasma histamine concentration. Clinical experience with more than 1000 patients indicates that adverse experiences typically associated with histamine release (e.g., bronchospasm, hypotension, tachycardia, cutaneous flushing, urticaria, etc.) are very rare following the administration of Nuromax (see ADVERSE REACTIONS).
Pharmacokinetic and pharmacodynamic results from a study of 24 healthy young adult patients and eight healthy elderly patients are summarized in Table 2. The pharmacokinetics are linear over the dosage range tested (i.e., plasma concentrations are approximately proportional to dose).
| Healthy Young Adult Patients (22 to 49 yrs) | Healthy Elderly Patients (67 to 72 yrs) | |||
* Values shown are means (range). † Time from injection to 25% recovery of the control twitch height. | ||||
| Parameter | 0.025 mg/kg (n = 8) | 0.05 mg/kg (n = 8) | 0.08 mg/kg (n = 8) | 0.025 mg/kg (n = 8) |
| t½ elimination (min) | 86 (25-171) | 123 (61-163) | 98 (47-163) | 96 (50-114) |
| Volume of Distribution at Steady State (L/kg) | 0.15 (0.10-0.21) | 0.24 (0.13-0.30) | 0.22 (0.16-0.33) | 0.22 (0.14-0.40) |
| Plasma Clearance (mL/min per kg) | 2.22 (1.02-3.95) | 2.62 (1.21-5.70) | 2.53 (1.88-3.38) | 2.47 (1.58-3.60) |
| Maximum Block (%) | 97 (88-100) | 100 (100-100) | 100 (100-100) | 96 (90-100) |
| Clinically Effective Duration of Block† (min) | 68 (35-90) | 91 (47-132) | 177 (74-268) | 97 (36-179) |
This study showed that the pharmacokinetics of Nuromax were similar in healthy young adult and elderly patients. Some healthy elderly patients tended to be more sensitive to the neuromuscular blocking effects of Nuromax than healthy young adult patients receiving the same dose. The time to maximum block was longer in elderly patients than in young adult patients (11.2 minutes versus 7.7 minutes at 0.025 mg/kg Nuromax). In addition, the clinically effective duration of block was more variable and tended to be longer in healthy elderly patients than in healthy young adult patients receiving the same dose. In contrast, a second study evaluated the pharmacokinetics and pharmacodynamics of doxacurium and showed that the plasma clearance was lower (1.75 ± 0.16 vs. 2.54 ± 0.24, respectively) and the half-life was longer (120 ± 10 vs. 75.9 ± 4.4 minutes, respectively) in 9 elderly patients (70 to 83 years of age) than in 9 younger patients (19 to 39 years of age) receiving a single intravenous dose of Nuromax 0.03 mg/kg. In addition, the time to maximum block was slower (12.9 versus 8.9 minutes, respectively) and the time to 25% T1 recovery was longer (113.4 ± 17.0 vs. 48.1 ± 5.2 minutes, respectively) in elderly patients than in younger patients. Overall, these studies showed that there may be differences in the pharmacokinetics of doxacurium in individual elderly patients and that the onset is slower and the duration of action is likely to be more variable and may be longer in elderly patients.
Table 3 summarizes the pharmacokinetic and pharmacodynamic results from a study of nine healthy young adult patients, eight patients with end-stage kidney disease undergoing kidney transplantation, and seven patients with end-stage liver disease undergoing liver transplantation. The results suggest that a longer t½ can be expected in patients with end-stage kidney disease; in addition, these patients may be more sensitive to the neuromuscular blocking effects of Nuromax. The time to maximum block was slightly longer and the clinically effective duration of block was prolonged in patients with end-stage kidney disease.
| Healthy Young Adult Patients | Kidney Transplant Patients | Liver Transplant Patients | |
* Values shown are means (range). | |||
| Parameter | 0.015 mg/kg (n = 9) | 0.015 mg/kg (n = 8) | 0.015 mg/kg (n = 7) |
| t½ elimination (min) | 99 (48-193) | 221 (84-592) | 115 (69-148) |
| Volume of Distribution at Steady State (L/kg) | 0.22 (0.11-0.43) | 0.27 (0.17-0.55) | 0.29 (0.17-0.35) |
| Plasma Clearance (mL/min per kg) | 2.66 (1.35-6.66) | 1.23 (0.48-2.40) | 2.30 (1.96-3.05) |
| Maximum Block (%) | 86 (59-100) | 98 (95-100) | 70 (0-100) |
| Clinically Effective Duration of Block (min) | 36 (19-80) | 80 (29-133) | 52 (20-91) |
No data are available from patients with liver disease not requiring transplantation. There are no significant alterations in the pharmacokinetics of Nuromax in liver transplant patients. Sensitivity to the neuromuscular blocking effects of Nuromax was highly variable in patients undergoing liver transplantation. Three of seven patients developed ≤ 50% block, indicating that a reduced sensitivity to Nuromax may occur in such patients. In those patients who developed > 50% neuromuscular block, the time to maximum block and the clinically effective duration tended to be longer than in healthy young adult patients (see CLINICAL PHARMACOLOGY - Individualization of Dosages subsection).
Consecutively administered maintenance doses of 0.005 mg/kg Nuromax, each given at 25% T1 recovery following the preceding dose, do not result in a progressive increase in the plasma concentration of doxacurium or a progressive increase in the depth or duration of block produced by each dose.
Nuromax is not metabolized in vitro in fresh human plasma. Plasma protein binding of Nuromax is approximately 30% in human plasma.
In vivo data from humans suggest that Nuromax is not metabolized and that the major elimination pathway is excretion of unchanged drug in urine and bile. In studies of healthy adult patients, 24% to 38% of an administered dose was recovered as parent drug in urine over 6 to 12 hours after dosing. High bile concentrations of Nuromax (relative to plasma) have been found 35 to 90 minutes after administration. The overall extent of biliary excretion is unknown. The data derived from analysis of human urine and bile are consistent with data from in vivo studies in the rat, cat, and dog, which indicate that all of an administered dose of Nuromax is recovered as parent drug in the urine and bile of these species.
In elderly patients or patients who have impaired renal function, the potential for a prolongation of block may be reduced by decreasing the initial dose of Nuromax and by titrating the dose to achieve the desired depth of block. In obese patients (patients weighing ≥ 30% more than ideal body weight for height), the dose of Nuromax should be determined using the patient's ideal body weight (IBW), according to the following formulae:
Men: IBW in kg = [106 + (6 × inches in height above 5 feet)]/2.2
Women: IBW in kg = [100 + (5 × inches in height above 5 feet)]/2.2
Dosage requirements for patients with severe liver disease are variable; some patients may require a higher than normal initial dose of Nuromax to achieve clinically effective block. Once adequate block is established, the clinical duration of block may be prolonged in such patients relative to patients with normal liver function.
As with pancuronium, metocurine, and vecuronium, resistance to Nuromax, manifested by a reduced intensity and/or shortened duration of block, must be considered when Nuromax is selected for use in patients receiving phenytoin or carbamazepine (see PRECAUTIONS - Drug Interactions).
As with other nondepolarizing neuromuscular blocking agents, a reduction in dosage of Nuromax must be considered in cachectic or debilitated patients; in patients with neuromuscular diseases, severe electrolyte abnormalities, or carcinomatosis; and in other patients in whom potentiation of neuromuscular block or difficulty with reversal is anticipated. Increased doses of Nuromax may be required in burn patients (see PRECAUTIONS).
Nuromax is a long-acting neuromuscular blocking agent, indicated to provide skeletal muscle relaxation as an adjunct to general anesthesia, for endotracheal intubation or to facilitate mechanical ventilation.
Nuromax is contraindicated in patients known to have hypersensitivity to it. Use of Nuromax from multiple-dose vials containing benzyl alcohol as a preservative is contraindicated in patients with a known hypersensitivity to benzyl alcohol.
Nuromax SHOULD BE ADMINISTERED IN CAREFULLY ADJUSTED DOSAGE BY OR UNDER THE SUPERVISION OF EXPERIENCED CLINICIANS WHO ARE FAMILIAR WITH THE DRUG'S ACTIONS AND THE POSSIBLE COMPLICATIONS OF ITS USE. THE DRUG SHOULD NOT BE ADMINISTERED UNLESS FACILITIES FOR INTUBATION, ARTIFICIAL RESPIRATION, OXYGEN THERAPY, AND AN ANTAGONIST ARE WITHIN IMMEDIATE REACH. IT IS RECOMMENDED THAT CLINICIANS ADMINISTERING LONG-ACTING NEUROMUSCULAR BLOCKING AGENTS SUCH AS Nuromax EMPLOY A PERIPHERAL NERVE STIMULATOR TO MONITOR DRUG RESPONSE, NEED FOR ADDITIONAL RELAXANTS, AND ADEQUACY OF SPONTANEOUS RECOVERY OR ANTAGONISM.
Nuromax HAS NO KNOWN EFFECT ON CONSCIOUSNESS, PAIN THRESHOLD, OR CEREBRATION. TO AVOID DISTRESS TO THE PATIENT, NEUROMUSCULAR BLOCK SHOULD NOT BE INDUCED BEFORE UNCONSCIOUSNESS.
Nuromax Injection is acidic (pH 3.9 to 5.0) and may not be compatible with alkaline solutions having a pH greater than 8.5 (e.g., barbiturate solutions).
Nuromax Injection contains benzyl alcohol. In newborn infants, benzyl alcohol has been associated with an increased incidence of neurological and other complications which are sometimes fatal (see PRECAUTIONS - Pediatric Use).
Nuromax has no clinically significant effects on heart rate; therefore, Nuromax will not counteract the bradycardia produced by many anesthetic agents or by vagal stimulation.
Neuromuscular blocking agents may have a profound effect in patients with neuromuscular diseases (e.g., myasthenia gravis and the myasthenic syndrome). In these and other conditions in which prolonged neuromuscular block is a possibility (e.g., carcinomatosis), the use of a peripheral nerve stimulator and a small test dose of Nuromax are recommended to assess the level of neuromuscular block and to monitor dosage requirements. Shorter acting muscle relaxants than Nuromax may be more suitable for these patients.
Resistance to nondepolarizing neuromuscular blocking agents may develop in patients with burns depending upon the time elapsed since the injury and the size of the burn. Nuromax has not been studied in patients with burns.
Acid-base and/or serum electrolyte abnormalities may potentiate or antagonize the action of neuromuscular blocking agents. The action of neuromuscular blocking agents may be enhanced by magnesium salts administered for the management of toxemia of pregnancy.
Nuromax has not been studied in patients with asthma.
No data are available to support the use of Nuromax by intramuscular injection.
Nuromax has been studied in patients with end-stage kidney (n = 8) or liver (n = 7) disease undergoing transplantation procedures (see CLINICAL PHARMACOLOGY). The possibility of prolonged neuromuscular block in patients undergoing renal transplantation and the possibility of a variable onset and duration of neuromuscular block in patients undergoing liver transplantation must be considered when Nuromax is used in such patients.
Administration of Nuromax on the basis of actual body weight is associated with a prolonged duration of action in obese patients (patients weighing ≥ 30% more than ideal body weight for height) (see CLINICAL PHARMACOLOGY). Therefore, the dose of Nuromax should be based upon ideal body weight in obese patients (see CLINICAL PHARMACOLOGY - Individualization of Dosages).
In a study of MH-susceptible pigs, Nuromax did not trigger MH. Nuromax has not been studied in MH-susceptible patients. Since MH can develop in the absence of established triggering agents, the clinician should be prepared to recognize and treat MH in any patient scheduled for general anesthesia.
Information on the use of Nuromax in the ICU is limited. In a double-blind, randomized study, 17 patients received Nuromax by intermittent bolus injection for a mean of 2.7 ± 0.5 days (range: 0.8 to 6.8 days) to facilitate mechanical ventilation. No evidence of tachyphylaxis, accumulation, or prolonged recovery was observed. The adverse experiences in patients receiving Nuromax were consistent in type, severity, and frequency to those expected in a critically ill patient population. Since many ICU patients have hepatic and/or renal failure, a prolonged duration of block should be anticipated in these patients after administration of Nuromax.
WHENEVER THE USE OF Nuromax OR ANY NEUROMUSCULAR BLOCKING AGENT IS CONTEMPLATED IN THE ICU, IT IS RECOMMENDED THAT NEUROMUSCULAR TRANSMISSION BE MONITORED CONTINUOUSLY DURING ADMINISTRATION WITH THE HELP OF A NERVE STIMULATOR. ADDITIONAL DOSES OF Nuromax OR ANY OTHER NEUROMUSCULAR BLOCKING AGENT SHOULD NOT BE GIVEN BEFORE THERE IS A DEFINITE RESPONSE TO T1, OR TO THE FIRST TWITCH. IF NO RESPONSE IS ELICITED, BOLUS ADMINISTRATION SHOULD BE DELAYED UNTIL A RESPONSE RETURNS.
Prior administration of succinylcholine has no clinically important effect on the neuromuscular blocking action of Nuromax.
The use of Nuromax before succinylcholine to attenuate some of the side effects of succinylcholine has not been studied.
There are no clinical data on concomitant use of Nuromax and other nondepolarizing neuromuscular blocking agents.
Isoflurane, enflurane, and halothane decrease the ED50 of Nuromax by 30% to 45%. These agents may also prolong the clinically effective duration of action by up to 25%.
Other drugs which may enhance the neuromuscular blocking action of nondepolarizing agents such as Nuromax include certain antibiotics (e.g., aminoglycosides, tetracyclines, bacitracin, polymyxins, lincomycin, clindamycin, colistin, and sodium colistimethate), magnesium salts, lithium, local anesthetics, procainamide, and quinidine.
As with some other nondepolarizing neuromuscular blocking agents, the time of onset of neuromuscular block induced by Nuromax is lengthened and the duration of block is shortened in patients receiving phenytoin or carbamazepine.
Carcinogenesis and fertility studies have not been performed. Nuromax was evaluated in a battery of four short-term mutagenicity tests. It was nonmutagenic in the Ames Salmonella assay, in the mouse lymphoma assay, and in the human lymphocyte assay. In the in vivo rat bone marrow cytogenetic assay, statistically significant increases in the incidence of structural abnormalities, relative to vehicle controls, were observed in male rats dosed with 0.1 mg/kg (0.625 mg/m2) Nuromax and sacrificed at 6 hours, but not at 24 or 48 hours, and in female rats dosed with 0.2 mg/kg (1.25 mg/m2) Nuromax and sacrificed at 24 hours, but not at 6 or 48 hours. There was no increase in structural abnormalities in either male or female rats given 0.3 mg/kg (1.875 mg/m2) Nuromax and sacrificed at 6, 24, or 48 hours. Thus, the incidence of abnormalities in the in vivo rat bone marrow cytogenetic assay was not dose-dependent and, therefore, the likelihood that the observed abnormalities were treatment-related or clinically significant is low.
Teratology testing in nonventilated, pregnant rats and mice treated subcutaneously with maximum subparalyzing doses of Nuromax revealed no maternal or fetal toxicity or teratogenic effects. There are no adequate and well-controlled studies of Nuromax in pregnant women. Because animal studies are not always predictive of human response and the doses used were subparalyzing, Nuromax should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
The use of Nuromax during labor, vaginal delivery, or cesarean section has not been studied. It is not known whether Nuromax administered to the mother has immediate or delayed effects on the fetus. The duration of action of Nuromax exceeds the usual duration of operative obstetrics (cesarean section). Therefore, Nuromax is not recommended for use in patients undergoing C-section.
It is not known whether Nuromax is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised following administration of Nuromax to a nursing woman.
Nuromax has not been studied in pediatric patients below the age of 2 years. See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION for clinical experience and recommendations for use in children 2 to 12 years of age.
Of the total number of subjects in the clinical studies of Nuromax, 134 were 60 years of age and over while 37 were 70 years of age and over. The geriatric population included a subset of patients with significant cardiovascular disease. The clearance of doxacurium may be reduced and the half-life may be prolonged in elderly patients. In addition, the onset of maximum block is slower and the duration of neuromuscular block produced by Nuromax is more variable and, in some cases, longer than in young adult patients (see CLINICAL PHARMACOLOGY - Pharmacodynamics and Individualization of Dosages).
This drug is known to be excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.
The most frequent adverse effect of nondepolarizing blocking agents as a class consists of an extension of the pharmacological action beyond the time needed for surgery and anesthesia. This effect may vary from skeletal muscle weakness to profound and prolonged skeletal muscle paralysis resulting in respiratory insufficiency and apnea which require manual or mechanical ventilation until recovery is judged to be clinically adequate (see OVERDOSAGE). Inadequate reversal of neuromuscular block from Nuromax is possible, as with all nondepolarizing agents. Prolonged neuromuscular block and inadequate reversal may lead to postoperative complications.
Adverse experiences were uncommon among the 1034 surgical patients and volunteers who received Nuromax and other drugs in US clinical studies in the course of a wide variety of procedures conducted during balanced or inhalational anesthesia. The following adverse experiences were reported in patients administered Nuromax (all events judged by investigators during the clinical trials to have a possible causal relationship):
None
| Cardiovascular:* | Hypotension,† flushing,† ventricular fibrillation, myocardial infarction |
* Reports of ventricular fibrillation (n = 1) and myocardial infarction (n = 1) were limited to ASA Class 3-4 patients undergoing cardiac surgery (n = 142). † 0.3% incidence. All other reactions unmarked were ≤ 0.1%. | |
| Respiratory: | Bronchospasm, wheezing |
| Dermatological: | Urticaria, injection site reaction |
| Special Senses: | Diplopia |
| Nonspecific: | Difficult neuromuscular block reversal, prolonged drug effect, fever |
Overdosage with neuromuscular blocking agents may result in neuromuscular block beyond the time needed for surgery and anesthesia. The primary treatment is maintenance of a patent airway and controlled ventilation until recovery of normal neuromuscular function is assured. Once evidence of recovery from neuromuscular block is observed, further recovery may be facilitated by administration of an anticholinesterase agent (e.g., neostigmine, edrophonium) in conjunction with an appropriate anticholinergic agent (see Antagonism of Neuromuscular Block below).
ANTAGONISTS (SUCH AS NEOSTIGMINE) SHOULD NOT BE ADMINISTERED PRIOR TO THE DEMONSTRATION OF SOME SPONTANEOUS RECOVERY FROM NEUROMUSCULAR BLOCK. THE USE OF A NERVE STIMULATOR TO DOCUMENT RECOVERY AND ANTAGONISM OF NEUROMUSCULAR BLOCK IS RECOMMENDED. T4/T1 SHOULD BE > ZERO BEFORE ANTAGONISM IS ATTEMPTED.
In an analysis of patients in whom antagonism of neuromuscular block was evaluated following administration of single doses of neostigmine averaging 0.06 mg/kg (range: 0.05 to 0.075) administered at approximately 25% T1 spontaneous recovery during balanced anesthesia, 71% of patients exhibited T4/T1≥ 0.7 before monitoring was discontinued. For these patients, the mean time to T4/T1≥ 0.7 was 19 minutes (range: 7 to 55). As with other long-acting nondepolarizing neuromuscular blocking agents, the time for recovery of neuromuscular function following administration of neostigmine is dependent upon the level of residual neuromuscular block at the time of attempted reversal; longer recovery times than those cited above may be anticipated when neostigmine is administered at more profound levels of block (i.e., at < 25% T1 recovery).
Patients should be evaluated for adequate clinical evidence of antagonism, e.g., 5-second head lift, and grip strength. Ventilation must be supported until no longer required. As with other neuromuscular blocking agents, physicians should be alert to the possibility that the action of the drugs used to antagonize neuromuscular block may wear off before the effects of Nuromax on the neuromuscular junction have declined sufficiently.
Antagonism may be delayed in the presence of debilitation, carcinomatosis, and the concomitant use of certain broad-spectrum antibiotics or anesthetic agents and other drugs which enhance neuromuscular block or separately cause respiratory depression (see PRECAUTIONS - Drug Interactions). Under such circumstances the management is the same as that of prolonged neuromuscular block.
In clinical trials, a dose of 1 mg/kg edrophonium was not as effective as a dose of 0.06 mg/kg neostigmine in antagonizing moderate to deep levels of neuromuscular block (i.e., < 60% T1 recovery). Therefore, the use of 1 mg/kg edrophonium is not recommended for reversal from moderate to deep levels of block. The use of pyridostigmine has not been studied.
Nuromax SHOULD ONLY BE ADMINISTERED INTRAVENOUSLY.
Nuromax, like other long-acting neuromuscular blocking agents, displays variability in the duration of its effect. The potential for a prolonged clinical duration of neuromuscular block must be considered when Nuromax is selected for administration. The dosage information provided below is intended as a guide only. Doses should be individualized (see CLINICAL PHARMACOLOGY -Individualization of Dosages). Factors that may warrant dosage adjustment include: advancing age, the presence of kidney or liver disease, or obesity (patients weighing ≥ 30% more than ideal body weight for height). The use of a peripheral nerve stimulator will permit the most advantageous use of Nuromax, minimize the possibility of overdosage or underdosage, and assist in the evaluation of recovery.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
When administered as a component of a thiopental/narcotic induction-intubation paradigm as well as for production of long-duration neuromuscular block during surgery, 0.05 mg/kg (2 × ED95) Nuromax produces good-to-excellent conditions for tracheal intubation in 5 minutes in approximately 90% of patients. Lower doses of Nuromax may result in a longer time for development of satisfactory intubation conditions. Clinically effective neuromuscular block may be expected to last approximately 100 minutes on average (range: 39 to 232) following 0.05 mg/kg Nuromax administered to patients receiving balanced anesthesia.
An initial Nuromax dose of 0.08 mg/kg (3 × ED95) should be reserved for instances in which a need for very prolonged neuromuscular block is anticipated. In approximately 90% of patients, good-to-excellent intubation conditions may be expected in 4 minutes after this dose; however, clinically effective block may be expected to persist for as long as 160 minutes or more (range: 110 to 338) (see CLINICAL PHARMACOLOGY).
If Nuromax is administered during steady-state isoflurane, enflurane, or halothane anesthesia, reduction of the dose of Nuromax by one third should be considered.
When succinylcholine is administered to facilitate tracheal intubation in patients receiving balanced anesthesia, an initial dose of 0.025 mg/kg (ED95) Nuromax provides about 60 minutes (range: 9 to 145) of clinically effective neuromuscular block for surgery. For a longer duration of action, a larger initial dose may be administered.
Maintenance dosing will generally be required about 60 minutes after an initial dose of 0.025 mg/kg Nuromax or 100 minutes after an initial dose of 0.05 mg/kg Nuromax during balanced anesthesia. Repeated maintenance doses administered at 25% T1 recovery may be expected to be required at relatively regular intervals in each patient. The interval may vary considerably between patients. Maintenance doses of 0.005 and 0.01 mg/kg Nuromax each provide an average 30 minutes (range: 9 to 57) and 45 minutes (range: 14 to 108), respectively, of additional clinically effective neuromuscular block. For shorter or longer desired durations, smaller or larger maintenance doses may be administered.
When administered during halothane anesthesia, an initial dose of 0.03 mg/kg (ED95) produces maximum neuromuscular block in about 7 minutes (range: 5 to 11) and clinically effective block for an average of 30 minutes (range: 12 to 54). Under halothane anesthesia, 0.05 mg/kg produces maximum block in about 4 minutes (range: 2 to 10) and clinically effective block for 45 minutes (range: 30 to 80). Maintenance doses are generally required more frequently in children than in adults. Because of the potentiating effect of halothane seen in adults, a higher dose of Nuromax may be required in children receiving balanced anesthesia than in children receiving halothane anesthesia to achieve a comparable onset and duration of neuromuscular block. Nuromax has not been studied in pediatric patients below the age of 2 years.
Nuromax Injection may not be compatible with alkaline solutions with a pH greater than 8.5 (e.g., barbiturate solutions).
Nuromax is compatible with:
Nuromax diluted up to 1:10 in 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP has been shown to be physically and chemically stable when stored in polypropylene syringes at 5° to 25°C (41° to 77°F), for up to 24 hours. Since dilution diminishes the preservative effectiveness of benzyl alcohol, aseptic techniques should be used to prepare the diluted product. Immediate use of the diluted product is preferred, and any unused portion of diluted Nuromax should be discarded after 8 hours.
Nuromax Injection, 1 mg doxacurium in each mL.
5-mL Multiple-dose vials containing 0.9% w/v benzyl alcohol as a preservative (see WARNINGS). Tray of 10 (List No. 4437).
Store Nuromax Injection at room temperature of 15° to 25°C (59° to 77°F). DO NOT FREEZE.
US Patent No. 4,701,460
Nuromax is a registered trademark of GlaxoSmithKline, licensed for use by Abbott Laboratories.
Manufactured for Abbott Laboratories, North Chicago, IL 60064, USA
©Abbott 2003
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