Prefest

Generic Name: conjugated estrogens and medroxyprogesterone (Oral route)

Commonly used brand name(s)

In the U.S.

• Activella


• Alesse


• Angeliq


• Estinyl


• Hemocyte


• Loestrin 1/20


• Mircette


• Ortho-Novum


• Prefest


• Premphase

Available Dosage Forms:

• Tablet


• Tablet, Chewable

Uses For Prefest

Conjugated estrogens and medroxyprogesterone are estrogen and progestin hormones. Along with other effects, estrogens help females develop sexually at puberty and regulate the menstrual cycle. Progestin lowers the effect of estrogen on the uterus and keeps estrogen-related problems from developing.

Around the time of menopause, the ovaries produce less estrogen. Estrogens are given to:

• Relieve the signs of menopause (vasomotor symptoms of menopause), such as hot flashes and unusual sweating, chills, faintness, or dizziness.


• Treat inflammation of the vagina (atrophic vaginitis) and of the genital area (atrophy of the vulva) by keeping these areas from becoming too dry, itchy, or painful.


• Prevent the loss of bone that begins at the time of menopause. Keeping bones strong decreases the chance of developing weak bones that easily break (osteoporosis). Estrogen use is most effective when it is taken for more than 7 years while you are getting regular exercise and extra calcium. Protection from bone loss can then last for many years after you stop taking the medicine.

There is no medical evidence to support the belief that the use of estrogens will keep the patient feeling young, keep the skin soft, or delay the appearance of wrinkles. Nor has it been proven that the use of estrogens during menopause will relieve emotional and nervous symptoms, unless these symptoms are related to the menopausal symptoms, such as hot flashes.

Progestins are not needed if the uterus has been removed by a surgical method called hysterectomy. In that case, it may be better to receive estrogens alone without the progestin.

Conjugated estrogens and medroxyprogesterone are available only with your doctor's prescription.

Before Using Prefest

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group 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.

Geriatric

Conjugated estrogens and medroxyprogesterone may increase your chance of having a stroke, memory problems, or breast cancer that spreads to other parts of your body.

Pregnancy

Conjugated estrogens and medroxyprogesterone are not recommended for use during pregnancy. Becoming pregnant or maintaining a pregnancy is not likely to occur around the time of menopause. Tell your doctor right away if you suspect you are pregnant.

Breast Feeding

Conjugated estrogens and medroxyprogesterone pass into the breast milk. This medicine is not recommended for use during breast-feeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking any of these medicines, 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 medicines in this class with any of the following medicines is not recommended. Your doctor may decide not to treat you with a medication in this class or change some of the other medicines you take.

• Boceprevir

Using medicines in this class 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.

• Boceprevir


• Felbamate


• Isotretinoin


• Paclitaxel


• Paclitaxel Protein-Bound


• Theophylline


• Tizanidine


• Tranexamic Acid

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of medicines in this class. Make sure you tell your doctor if you have any other medical problems, especially:

• Asthma or


• Epilepsy or


• Heart problems (congestive heart failure) or


• High blood pressure or


• Kidney problems, severe or


• Migraine headaches—Rarely, water retention caused by conjugated estrogens and medroxyprogesterone may make these conditions worse.

• Blood clotting problems, or history of with previous estrogen use or


• Breast cancer, estrogen-dependent, or history of or


• Breast cancer, or history of or


• Deep vein thrombosis (blood clot in the leg), active or history of or


• Heart attack, active or recent (within past year) or


• Liver disease, including jaundice, or history of or


• Pulmonary embolism (clot in the lung), active or history of or


• Stroke, active or recent (within past year) or


• Venous thromboembolism (clot in the veins), or history of—Conjugated estrogens and medroxyprogesterone should not be used in patients with these conditions.

• Bone cancer or


• Endometrial cancer (cancer of the uterus), active or suspected or


• Fibroid tumors of the uterus—Estrogens may interfere with the treatment of bone cancer, worsen cancer of the uterus, or increase the size of fibroid tumors.

• Changes in genital or vaginal bleeding of unknown causes—Estrogens may make these conditions worse; some irregular vaginal bleeding may be a sign that the lining of the uterus may be growing too much or is a sign of cancer of the uterus lining.

• Changes in vision—This medicine may cause changes in vision; your medicine may need to be stopped if these conditions become worse.

• Diabetes mellitus—Conjugated estrogens and medroxyprogesterone may slightly change the amount of blood sugar for some patients, but for most patients with diabetes, there is no change in blood sugar.

• Endometriosis or


• Gallbladder disease or gallstones, or history of or


• High cholesterol or triglycerides, or family history of or


• Memory loss (dementia) or


• Pancreatitis (inflammation of pancreas) or


• Porphyria (liver problem)—Conjugated estrogens and medroxyprogesterone may make these conditions worse; using estrogens can lower blood cholesterol in many patients with high cholesterol.

• Hypothyroidism (underactive thyroid)—A change in dose of thyroid medication may be needed.

• Low blood calcium, severe—Estrogens should be used with caution in patients with this condition.

Proper Use of conjugated estrogens and medroxyprogesterone

This section provides information on the proper use of a number of products that contain conjugated estrogens and medroxyprogesterone. It may not be specific to Prefest. Please read with care.

Conjugated estrogens and medroxyprogesterone usually come with patient directions. Read them carefully before taking this medicine.

Take this medicine only as directed by your doctor. Do not take more of it and do not take it for a longer period of time than your doctor ordered. The length of time you take the medicine will depend on the medical problem for which you are taking conjugated estrogens and medroxyprogesterone. Discuss with your doctor how long you will need to take these medicines.

If you are taking the estrogen or progestin hormones in a certain order (i.e., conjugated estrogens tablets followed by conjugated estrogens and medroxyprogesterone tablets), be sure you know in which order you need to take the medicines. If you have questions about this, ask your health care professional.

Nausea may occur during the first few weeks after you start taking estrogens. This effect usually disappears with continued use. If the nausea is bothersome, it can usually be prevented or reduced by taking each dose with food or immediately after food.

Dosing

The dose medicines in this class 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 these medicines. If your dose is different, do not change it unless your doctor tells you to do so.

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

• For conjugated estrogens, and conjugated estrogens and medroxyprogesterone


• For oral dosage form (tablets):
  
  • To prevent loss of bone (osteoporosis) or for treating itching or dryness of the genital area (atrophy of the vulva), inflammation of the vagina (atrophic vaginitis), or symptoms of menopause:
    
    • Adults—One tablet (containing 0.625 mg conjugated estrogens) once a day on Days 1 through 14; then, one tablet (containing 0.625 mg conjugated estrogens and 5 mg medroxyprogesterone) once a day on Days 15 through 28. Repeat cycle.
    
    
  
  

• For conjugated estrogens and medroxyprogesterone


• For oral dosage form (tablets):
  
  • To prevent loss of bone (osteoporosis) or for treating itching or dryness of the genital area (atrophy of the vulva), inflammation of the vagina (atrophic vaginitis), or symptoms of menopause:
    
    • Adults—One tablet (containing 0.3 mg conjugated estrogens and 1.5 mg medroxyprogesterone) once a day for twenty-eight days. Repeat cycle. If vaginal bleeding or spotting continues and it is undesired, your doctor may increase your dose to the next highest strength tablet (0.45 mg conjugated estrogens and 1.5 mg medroxyprogesterone). It should be taken once a day for twenty-eight days. Repeat cycle.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

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

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Prefest

It is very important that your doctor check your progress at regular visits to make sure this medicine does not cause unwanted effects. Plan on going to see your doctor every year, but some doctors require visits more often.

Although the risk for developing breast problems or breast cancer is low, it is still important that you regularly check your breasts for any unusual lumps or discharge, and report any problems to your doctor. You should also have a mammogram (x-ray pictures of the breasts) and breast examination done by your doctor whenever your doctor recommends it.

If your menstrual periods have stopped, they may start again once you begin taking this medicine. This effect will continue for as long as the medicine is taken. However, if taking the continuous treatment (0.625 mg conjugated estrogens and 2.5 mg medroxyprogesterone once a day), monthly bleeding usually stops within 10 months.

Also, vaginal bleeding between your regular menstrual periods may occur during the first 3 months of use. Do not stop taking your medicine. Check with your doctor if bleeding continues for an unusually long time, if your period has not started within 45 days of your last period, or if you think you are pregnant.

Tell the doctor in charge that you are taking this medicine before having any laboratory test, because some test results may be affected.

You may need to stop taking this medicine before having some kinds of surgery or while your doctor has ordered a long period of bedrest. Talk with your doctor about this.

Prefest Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Healthy women rarely have severe side effects from taking conjugated estrogens or medroxyprogesterone to replace estrogen.

Check with your doctor immediately if any of the following side effects occur:

More common

• Itching of the vagina or genital area


• menstrual periods beginning again, including changing menstrual bleeding pattern for up to 6 months (spotting, breakthrough bleeding, prolonged or heavier vaginal bleeding, or vaginal bleeding completely stopping by 10 months)


• pain during sexual intercourse


• thick, white vaginal discharge

Less common

• Blurred vision


• breast lumps


• chest pain


• discharge from breast


• dizziness


• feeling faint, dizzy, or light-headed


• feeling of warmth or heat


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


• headache


• heavy nonmenstrual vaginal bleeding


• pounding in the ears


• severe cramping of the uterus


• slow or fast heartbeat


• sweating

Rare

• Change in vaginal discharge


• pain or feeling of pressure in pelvis


• pain or tenderness in stomach, side, or abdomen


• yellow eyes or skin

Incidence not known

• Abdominal bloating


• acid or sour stomach


• belching


• backache


• full or bloated feeling or pressure in the stomach


• heartburn


• indigestion


• loss of appetite


• pelvic pain


• stomach discomfort, upset or pain


• stomach pain


• swelling of abdominal or stomach are

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

More common

• Abdominal cramps


• back pain


• body aches or pain


• breast pain or tenderness


• congestion


• chills


• cough


• crying


• depersonalization


• diarrhea


• dryness or soreness of throat


• dysphoria


• enlarged breasts


• euphoria


• feeling faint, dizzy, or light-headedness


• feeling of warmth or heat


• fever


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


• general feeling of discomfort or illness


• headache, severe and throbbing


• hoarseness


• increase in amount of clear vaginal discharge


• itching


• joint pain


• lack or loss of strength


• mental depression


• muscle aches and pains


• nausea


• pain


• pain or tenderness around eyes and cheekbones


• painful menstrual periods


• painful or difficult urination


• paranoia


• passing of gas


• quick to react or overreact emotionally


• rapidly changing moods


• runny nose


• shivering


• shortness of breath or troubled breathing


• sneezing


• sore throat


• stuffy nose


• stomach discomfort following meals


• tender, swollen glands in neck


• tightness of chest or wheezing


• trouble sleeping


• trouble in swallowing


• unusual tiredness


• voice changes


• vomiting

Less common

• Acne


• bloating or swelling of face, ankles, or feet


• cervix disorder


• crying


• depersonalization


• dysphoria


• euphoria


• increase in sexual desire


• leg cramps


• mental depression


• paranoia


• quick to react or overreact emotionally


• rapidly changing moods


• sleeplessness


• tense muscles


• trouble sleeping


• unable to sleep


• unusual weight gain or loss

Incidence not known

• Abdominal cramping


• bloody or cloudy urine


• bloody vaginal discharge


• difficult, burning, or painful urination


• frequent urge to urinate


• light vaginal bleeding between periods and after intercourse

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: Prefest side effects (in more detail)

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

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Prefest resources

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

• Prefest Prescribing Information (FDA)


• Prefest Concise Consumer Information (Cerner Multum)


• Prefest MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Prefest with other medications

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• Atrophic Vaginitis
• Oophorectomy
• Osteoporosis
• Postmenopausal Symptoms
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Septrin for infusion 16 mg / 80mg per ml

1. Name Of The Medicinal Product

Septrin 16 mg/80 mg per ml for Infusion

2. Qualitative And Quantitative Composition

Each 5 ml of Septrin 16 mg/80 mg per ml for Infusion contains 80 mg Trimethoprim and 400 mg Sulfamethoxazole.

Excipients:

This product contains 1.7 mmoles of sodium and 13.2 vol % ethanol (alcohol) per 5 ml.

For a full list of excipients, see Section 6.1

3. Pharmaceutical Form

Solution for Infusion

A clear liquid.

4. Clinical Particulars

4.1 Therapeutic Indications

Septrin for Infusion is indicated for the treatment of the following infections when owing to sensitive organisms (see section 5.1):

Acute uncomplicated urinary tract infection.

It is recommended that initial episodes of uncomplicated urinary tract infections be treated with a single effective antibacterial agent rather than a combination such as Septrin for Infusion.

Treatment and prevention of Pneumocystis jiroveci pneumonitis (previously known as Pneumocystis carinii pneumonia or “PCP”)

Treatment and prophylaxis of toxoplasmosis.

Treatment of nocardiosis.

In general, the indications for the use of Septrin for Infusion are the same as those for oral presentations.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology And Method Of Administration

Method of Administration: Septrin for Infusion is for administration only by the intravenous route and must be diluted before administration.

It is intended that Septrin for Infusion should be used only during such a period as the patient is unable to accept oral therapy, where initiation of treatment is particularly urgent or for convenience if the patient is already receiving intravenous fluids. Although Septrin for Infusion is useful in critically ill patients, there may be no therapeutic advantage over the oral preparation.

For instructions on dilution of the product before administration, see section 6.6.

Standard dosage recommendations for acute infections

Adults and children over 12 years:

2 ampoules (10 ml) every 12 hours.

Children aged 12 years and under:

The recommended dosage is approximately 6 mg trimethoprim and 30 mg sulfamethoxazole per kg bodyweight per 24 hours, given in two equally divided doses. As a guide the following schedules may be used diluted as described above.

6 weeks to 5 months:	1.25 ml every 12 hours
6 months to 5 years:	2.5 ml every 12 hours
6 to 12 years:	5.0 ml every 12 hours

For severe infections in all age groups, dosage may be increased by 50%.

Treatment should be continued until the patient has been symptom free for two days; the majority will require treatment for at least 5 days.

The elderly:

See Special Warnings and Precautions for Use.

Impaired hepatic function:

No data are available relating to dosage in patients with impaired hepatic function.

Special Dosage Recommendations

(Standard dosage applies unless otherwise specified)

Impaired renal function:

Adults and children over 12 years (no information is available for children under 12 years of age):

Creatinine Clearance (ml/min)	Recommended Dosage
More than 30	STANDARD DOSAGE
15-30	Half the STANDARD DOSAGE
Less than 15	Not recommended

Measurements of plasma concentrations of sulfamethoxazole at intervals of 2 to 3 days are recommended in samples obtained 12 hours after administration of Septrin 16 mg/80 mg per ml for Infusion. If the concentration of total sulfamethoxazole exceeds 150 micrograms/ml then treatment should be interrupted until the value falls below 120 micrograms/ml.

Pneumocystis jiroveci (P. carinii) pneumonitis:

Treatment

20 mg trimethoprim and 100 mg sulfamethoxazole per kg of bodyweight per day in two or more divided doses. Therapy should be changed to the oral route as soon as possible and continued for a total treatment period of two weeks. The aim is to obtain peak plasma or serum levels of trimethoprim of greater than or equal to 5 microgram/ml (verified in patients receiving 1-hour infusions of intravenous Septrin). (See 4.8 Undesirable Effects)

Prevention

Standard dosage for the duration of the period at risk.

Nocardiosis: There is no consensus on the most appropriate dosage. Adult doses of 6 to 8 tablets daily for up to 3 months have been used (one tablet contains 400 mg sulfamethoxazole and 80 mg trimethoprim).

Toxoplasmosis: There is no consensus on the most appropriate dosage for the treatment or prophylaxis of this condition. The decision should be based on clinical experience. For prophylaxis, however, the dosages suggested for prevention of Pneumocystis jiroveci pneumonitis may be appropriate.

4.3 Contraindications

Septrin 16 mg/80 mg per ml for Infusion should not be given to patients with a history of hypersensitivity to sulphonamides, trimethoprim, co-trimoxazole or any excipients of Septrin.

Septrin 16 mg/80 mg per ml for Infusion is contra-indicated in patients showing marked liver parenchymal damage.

Septrin 16 mg/80 mg per ml for Infusion is contra-indicated in severe renal insufficiency where repeated measurements of the plasma concentration cannot be performed.

Septrin 16 mg/80 mg per ml for Infusion should not be given to premature babies nor to full-term infants during the first six weeks of life except for the treatment/prophylaxis of PCP in infants 4 weeks of age or greater.

4.4 Special Warnings And Precautions For Use

Fatalities, although very rare, have occurred due to severe reactions including Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis), fulminant hepatic necrosis, agranulocytosis, aplastic anaemia, other blood dyscrasias and hypersensitivity of the respiratory tract.

Septrin 16 mg/80 mg per ml for Infusion should be discontinued at the first appearance of a skin rash (see 4.8 Undesirable Effects).

Fluid overload is possible, especially when very high doses are being administered to patients with underlying cardiopulmonary disease.

An adequate urinary output should be maintained at all times. Evidence of crystalluria in vivo is rare, although sulphonamide crystals have been noted in cooled urine from treated patients. In patients suffering from malnutrition the risk may be increased.

For patients with known renal impairment special measures should be adopted (See 4.2 Posology and Method of Administration).

Regular monthly blood counts are advisable when Septrin is given for long periods, or to folate deficient patients or to the elderly since there exists a possibility of asymptomatic changes in haematological laboratory indices due to lack of available folate. These changes may be reversed by administration of folinic acid (5 to 10 mg/day) without interfering with the antibacterial activity.

Particular care is always advisable when treating elderly patients because, as a group, they are more susceptible to adverse reactions and more likely to suffer serious side effects as a result, particularly when complicating conditions exist, e.g. impaired kidney and/or liver function and/or concomitant drugs.

In glucose-6-phosphate dehydrogenase-deficient (G-6-PD) patients, haemolysis may occur.

Septrin should be given with caution to patients with severe allergy or bronchial asthma.

Septrin should not be used in the treatment of streptococcal pharyngitis due to Group A beta-haemolytic streptococci. Eradication of these organisms from the oropharynx is less effective than with penicillin.

Trimethoprim has been noted to impair phenylalanine metabolism but this is of no significance in phenylketonuric patients on appropriate dietary restriction.

The administration of Septrin to patients known or suspected to be at risk of acute porphyria should be avoided. Both trimethoprim and sulphonamides (although not specifically sulfamethoxazole) have been associated with clinical exacerbation of porphyria.

Close monitoring of serum potassium and sodium is warranted in patients at risk of hyperkalaemia and hyponatraemia.

This medicinal product contains 13.2 vol% ethanol (alcohol), i.e. up to 521 mg per dose. This is equivalent to 2.64 ml of beer, or 1.1 ml of wine. Harmful for those suffering from alcoholism. To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease, or epilepsy.

This medicinal product contains sodium metabisulphite, which may rarely cause severe hypersensitivity reaction and bronchospasm.

This medicinal product contains 1.7 mmoles (or 38.87 mg) of sodium. To be taken into consideration by patients on a sodium controlled diet.

Except under careful supervision Septrin for Infusion should not be given to patients with serious haematological disorders (see 4.8 Undesirable Effects). Septrin has been given to patients receiving cytotoxic therapy with little or no additional effect on the bone marrow or peripheral blood.

The combination of the antibiotics in Septrin for Infusion should only be used where, in the judgement of the physician, the benefits of treatment outweigh any possible risks; consideration should be given to the use of a single effective antibacterial agent.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Trimethoprim may interfere with the estimation of serum/plasma creatinine when the alkaline picrate reaction is used. This may result in overestimation of serum/plasma creatinine of the order of 10%. The creatinine clearance is reduced: the renal tubular secretion of creatinine is decreased from 23% to 9% whilst the glomerular filtration remains unchanged.

In some situations, concomitant treatment with zidovudine may increase the risk of haematological adverse reactions to co-trimoxazole. If concomitant treatment is necessary, consideration should be given to monitoring of haematological parameters.

Reversible deterioration in renal function has been observed in patients treated with co-trimoxazole and ciclosporin following renal transplantation.

Concurrent use of rifampicin and Septrin results in a shortening of the plasma half-life of trimethoprim after a period of about one week. This is not thought to be of clinical significance.

When trimethoprim is administered simultaneously with drugs that form cations at physiological pH, and are also partly excreted by active renal secretion (e.g. procainamide, amantadine), there is the possibility of competitive inhibition of this process which may lead to an increase in plasma concentration of one or both of the drugs.

In elderly patients concurrently receiving diuretics, mainly thiazides, there appears to be an increased risk of thrombocytopenia with or without purpura.

Occasional reports suggest that patients receiving pyrimethamine as malarial prophylaxis at doses in excess of 25 mg weekly may develop megaloblastic anaemia should co-trimoxazole be prescribed concurrently.

Co-trimoxazole has been shown to potentiate the anticoagulant activity of warfarin via stereo-selective inhibition of its metabolism. Sulfamethoxazole may displace warfarin from plasma-albumin protein-binding sites in vitro. Careful control of the anticoagulant therapy during treatment with Septrin is advisable.

Co-trimoxazole prolongs the half-life of phenytoin and if co-administered the prescriber should be alert for excessive phenytoin effect. Close monitoring of the patient's condition and serum phenytoin levels is advisable.

Concomitant use of trimethoprim with digoxin has been shown to increase plasma digoxin levels in a proportion of elderly patients.

Co-trimoxazole may increase the free plasma levels of methotrexate.

Trimethoprim interferes with assays for serum methotrexate when dihydrofolate reductase from Lactobacillus casei is used in the assay. No interference occurs if methotrexate is measured by radioimmuno assay.

Administration of trimethoprim/sulfamethoxazole 160mg/800mg (co-trimoxazole) causes a 40% increase in lamivudine exposure because of the trimethoprim component. Lamivudine has no effect on the pharmacokinetics of trimethoprim or sulfamethoxazole.

Interaction with sulphonylurea hypoglycaemic agents is uncommon but potentiation has been reported.

Caution should be exercised in patients taking any other drugs that can cause hyperkalaemia.

If Septrin is considered appropriate therapy in patients receiving other anti-folate drugs such as methotrexate, a folate supplement should be considered.

4.6 Pregnancy And Lactation

Pregnancy

There are not any adequate data from the use of Septrin for Infusion in pregnant women. Case-control studies have shown that there may be an association between exposure to folate antagonists and birth defects in humans.

Trimethoprim is a folate antagonist and, in animal studies, both agents have been shown to cause foetal abnormalities (see 5.3 Preclinical Safety Data).

Septrin for Infusion should not be used in pregnancy, particularly in the first trimester, unless clearly necessary. Folate supplementation should be considered if Septrin for Infusion is used in pregnancy.

Sulfamethoxazole competes with bilirubin for binding to plasma albumin. As significantly maternally derived drug levels persist for several days in the newborn, there may be a risk of precipitating or exacerbating neonatal hyperbilirubinaemia, with an associated theoretical risk of kernicterus, when Septrin for Infusion is administered to the mother near the time of delivery. This theoretical risk is particularly relevant in infants at increased risk of hyperbilirubinaemia, such as those who are preterm and those with glucose-6-phosphate dehydrogenase deficiency.

Lactation

The components of Septrin for Infusion (trimethoprim and sulfamethoxazole) are excreted in breast milk. Administration of Septrin for Infusion should be avoided in late pregnancy and in lactating mothers where the mother or infant has, or is at particular risk of developing, hyperbilirubinaemia. Additionally, administration of Septrin for Infusion should be avoided in infants younger than eight weeks in view of the predisposition of young infants to hyperbilirubinaemia.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

As co-trimoxazole contains trimethoprim and a sulphonamide the type and frequency of adverse reactions associated with such compounds are expected to be consistent with extensive historical experience.

Data from large published clinical trials were used to determine the frequency of very common to rare adverse events. Very rare adverse events were primarily determined from post-marketing experience data and therefore refer to reporting rate rather than a "true" frequency. In addition, adverse events may vary in their incidence depending on the indication.

The following convention has been used for the classification of adverse events in terms of frequency:- Very common

Infections and Infestations
Common:	Monilial overgrowth
Blood and lymphatic system disorders
Very rare:	Leucopenia, neutropenia, thrombocytopenia, agranulocytosis, megaloblastic anaemia, aplastic anaemia, haemolytic anaemia, methaemoglobinaemia, eosinophilia, purpura, haemolysis in certain susceptible G-6-PD deficient patients
Immune system disorders
Very rare:	Serum sickness, anaphylaxis, allergic myocarditis, angioedema, drug fever, allergic vasculitis resembling Henoch-Schoenlein purpura, periarteritis nodosa, systemic lupus erythematosus
Metabolism and nutrition disorders
Very common:	Hyperkalaemia
Very rare:	Hypoglycaemia, hyponatraemia, anorexia
Psychiatric disorders
Very rare:	Depression, hallucinations
Nervous system disorders
Common:	Headache
Very rare:	Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, dizziness
Aseptic meningitis was rapidly reversible on withdrawal of the drug, but recurred in a number of cases on re-exposure to either co-trimoxazole or to trimethoprim alone.
Respiratory, thoracic and mediastinal disorders
Very rare:	Cough, shortness of breath, pulmonary infiltrates
Cough, shortness of breath and pulmonary infiltrates may be early indicators of respiratory hypersensitivity which, while very rare, has been fatal.
Gastrointestinal disorders
Common:	Nausea, diarrhoea
Uncommon:	Vomiting
Very rare:	Glossitis, stomatitis, pseudomembranous colitis, pancreatitis
Eye Disorders
Very rare:	Uveitis
Hepatobiliary disorders
Very rare:	Elevation of serum transaminases, elevation of bilirubin levels, cholestatic jaundice, hepatic necrosis
Cholestatic jaundice and hepatic necrosis may be fatal.
Skin and subcutaneous tissue disorders
Common:	Skin rashes
Very rare:	Photosensitivity, exfoliative dermatitis, fixed drug eruption, erythema multiforme, Stevens-Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis)
Lyell’s syndrome carries a high mortality.
Musculoskeletal and connective tissue disorders
Very rare:	Arthralgia, myalgia
Renal and urinary disorders
Very rare:	Impaired renal function (sometimes reported as renal failure), interstitial nephritis
Effects associated with Pneumocystis jiroveci (P.carinii) Pneumonitis (PCP) management
Very rare:	Severe hypersensitivity reactions, rash, fever, neutropenia, thrombocytopenia, raised liver enzymes, hyperkalaemia, hyponatraemia, rhabdomyolysis.

At the high dosages used for PCP management severe hypersensitivity reactions have been reported, necessitating cessation of therapy. If signs of bone marrow depression occur, the patient should be given calcium folinate supplementation (5-10 mg/day). Severe hypersensitivity reactions have been reported in PCP patients on re-exposure to co-trimoxazole, sometimes after a dosage interval of a few days. Rhabdomyolysis has been reported in HIV positive patients receiving co-trimoxazole for prophylaxis or treatment of PCP.

4.9 Overdose

The maximum tolerated dose in humans is unknown.

Nausea, vomiting, dizziness and confusion are likely symptoms of overdosage. Bone marrow depression has been reported in acute trimethoprim overdosage.

In cases of known, suspected or accidental overdosage, stop therapy.

Dependent on the status of renal function, administration of fluids is recommended if urine output is low.

Both trimethoprim and active sulfamethoxazole are dialysable by renal dialysis. Peritoneal dialysis is not effective.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Combinations of sulfonamides and trimethoprim, incl. derivatives; ATC code: J01EE01

Mode of Action

Septrin is an antibacterial drug composed of two active principles, sulfamethoxazole and trimethoprim. Sulfamethoxazole is a competitive inhibitor of dihydropteroate synthetase enzyme. Sulfamethoxazole competitively inhibits the utilisation of para-aminobenzoic acid (PABA) in the synthesis of dihydrofolate by the bacterial cell resulting in bacteriostasis. Trimethoprim binds to and reversibly inhibits bacterial dihydrofolate reductase (DHFR) and blocks the production of tetrahydrofolate. Depending on the conditions the effect may be bactericidal. Thus trimethoprim and sulfamethoxazole block two consecutive steps in the biosynthesis of purines and therefore nucleic acids essential to many bacteria. This action produces marked potentiation of activity in vitro between the two agents.

Mechanism of resistance

In vitro studies have shown that bacterial resistance can develop more slowly with both sulfamethoxazole and trimethoprim in combination that with either sulfamethoxazole or trimethoprim alone.

Resistance to sulfamethoxazole may occur by different mechanisms. Bacterial mutations cause an increase the concentration of PABA and thereby out-compete with sulfamethoxazole resulting in a reduction of the inhibitory effect on dihydropteroate synthetase enzyme. Another resistance mechanism is plasmid-mediated and results from production of an altered dihydropteroate synthetase enzyme, with reduced affinity for sulfamethoxazole compared to the wild-type enzyme.

Resistance to trimethoprim occurs through a plasmid-mediated mutation which results in production of an altered dihydrofolate reductase enzyme having a reduced affinity for trimethoprim compared to the wild-type enzyme.

Trimethoprim binds to plasmodial DHFR but less tightly than to bacterial enzyme. Its affinity for mammalian DHFR is some 50,000 times less than for the corresponding bacterial enzyme.

Many common pathogenic bacteria are susceptible in vitro to trimethoprim and sulfamethoxazole at concentrations well below those reached in blood, tissue fluids and urine after the administration of recommended doses. In common with other antibiotics, however, in vitro activity does not necessarily imply that clinical efficacy has been demonstrated and it must be noted that satisfactory susceptibility testing is achieved only with recommended media free from inhibitory substances, especially thymidine and thymine.

Breakpoints

EUCAST

Enterobacteriaceae: S

S. maltophilia: S

Acinetobacter: S

Staphylococcus: S

Enterococcus: S

Streptococcus ABCG: S

Streptococcus pneumoniae: S

Hemophilus influenza: S

Moraxella catarrhalis: S

Psuedomonas aeruginosa and other non-enterobacteriaceae: S

S = susceptible, R = resistant. *These are CLSI breakpoints since no EUCAST breakpoints are currently available for these organisms.

Trimethoprim: sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as trimethoprim concentration.

Antibacterial Spectrum

The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. This information gives only an approximate guidance on probabilities whether microorganisms will be susceptible to trimethoprim/sulfamethoxazole or not.

Trimethoprim/sulfamethoxazole susceptibility against a number of bacteria are shown in the table below:

Commonly susceptible species:

Gram-positive aerobes: Staphylococcus aureus Staphylococcus saprophyticus Streptococcus pyogenes

Gram-negative aerobes: Enterobacter cloacae Haemophilus influenzae Klebsiella oxytoca Moraxella catarrhalis Salmonella spp. Stenotrophomonas maltophilia Yersinia spp.

Species for which acquired resistance may be a problem:

Gram-positive aerobes: Enterococcus faecalis Enterococcus faecium Nocardia spp. Staphylococcus epidermidis Streptococcus pneumoniae

Gram-negative aerobes: Citrobacter spp. Enterobacter aerogenes Escherichia coli Klebsiella pneumoniae Klebsiella pneumonia Proteus mirabilis Proteus vulgaris Providencia spp. Serratia marcesans

Inherently resistant organisms:

Gram-negative aerobes: Pseudomonas aeruginosa Shigella spp. Vibrio cholera

5.2 Pharmacokinetic Properties

Peak plasma levels of trimethoprim and sulfamethoxazole are higher and achieved more rapidly after one hour of intravenous infusion of Septrin 16 mg/80 mg per ml for Infusion than after oral administration of an equivalent dose of a Septrin oral presentation. Plasma concentrations, elimination half-life and urinary excretion rates show no significant differences following either the oral or intravenous route of administration.

Trimethoprim is a weak base with a pKa of 7.3. It is lipophilic. Tissue levels of trimethoprim are generally higher than corresponding plasma levels, the lungs and kidneys showing especially high concentrations. Trimethoprim concentrations exceed those in plasma in the case of bile, prostatic fluid and tissue, sputum, and vaginal secretions. Levels in the aqueous humor, breast milk, cerebrospinal fluid, middle ear fluid, synovial fluid and tissue (interstitial) fluid are adequate for antibacterial activity. Trimethoprim passes into amniotic fluid and fetal tissues reaching concentrations approximating those of maternal serum.

Approximately 50% of trimethoprim in the plasma is protein bound. The half-life in man is in the range 8.6 to 17 hours in the presence of normal renal function. It is increased by a factor of 1.5 to 3.0 when the creatinine clearance is less than 10 ml/minute. There appears to be no significant difference in the elderly compared with young patients.

The principal route of excretion of trimethoprim is renal and approximately 50% of the dose is excreted in the urine within 24 hours as unchanged drug. Several metabolites have been identified in the urine. Urinary concentrations of trimethoprim vary widely.

Sulfamethoxazole is a weak acid with a pKa of 6.0. The concentration of active sulfamethoxazole in amniotic fluid, aqueous humor, bile, cerebrospinal fluid, middle ear fluid, sputum, synovial fluid and tissue (interstitial) fluid is of the order of 20 to 50% of the plasma concentration. Approximately 66% of sulfamethoxazole in the plasma is protein bound. The half-life in man is approximately 9 to 11 hours in the presence of normal renal function. There is no change in the half-life of active sulfamethoxazole with a reduction in renal function but there is prolongation of the half-life of the major, acetylated metabolite when the creatinine clearance is below 25 ml/minute.

The principal route of excretion of sulfamethoxazole is renal; between 15% and 30% of the dose recovered in the urine is in the active form. In elderly patients there is a reduced renal clearance of sulfamethoxazole.

5.3 Preclinical Safety Data

Reproductive toxicology: At doses in excess of recommended human therapeutic dose, trimethoprim and sulfamethoxazole have been reported to cause cleft palate and other foetal abnormalities in rats, findings typical of a folate antagonist. Effects with trimethoprim were preventable by administration of dietary folate. In rabbits, foetal loss was seen at doses of trimethoprim in excess of human therapeutic doses.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Propylene Glycol (E1520)

Tromethamine

Sodium Hydroxide (E524)

Sodium Metabisulphite (E223)

Ethanol

Water for Injections

6.2 Incompatibilities

None known.

6.3 Shelf Life

36 months

6.4 Special Precautions For Storage

Store below 30°C. Protect from light.

6.5 Nature And Contents Of Container

Neutral glass ampoules (5ml nominal fill volume)

Pack size: 10 x 5ml ampoules

6.6 Special Precautions For Disposal And Other Handling

Septrin for Infusion must be diluted before administration.

Dilution should be carried out immediately before use. After adding Septrin 16 mg/80 mg per ml for Infusion to the infusion solution, shake thoroughly to ensure complete mixing. If visible turbidity or crystallisation appears at any time before or during an infusion, the mixture should be discarded.

It is recommended that Septrin16 mg/80 mg per ml for Infusion is diluted according to the following schedules:

One ampoule (5 ml) to 125 ml infusion solution.

Two ampoules (10 ml) to 250 ml infusion solution.

Three ampoules (15 ml) to 500 ml infusion solution.

Septrin 16 mg/80 mg per ml for Infusion is known to be compatible, when diluted as recommended above, with the following fluids:

Glucose Intravenous Infusion BP (5% w/v and 10% w/v).

Sodium Chloride Intravenous Infusion BP (0.9% w/v).

Sodium Chloride (0.18% w/v) and Glucose (4% w/v) Intravenous Infusion BP.

Dextran 70 Injection BP (6% w/v) in glucose (5% w/v) or normal saline.

Dextran 40 Injection BP (10% w/v) in glucose (5% w/v) or normal saline.

Ringer's Solution for Injection BPC 1959.

No other substance should be mixed with the infusion.

The duration of the infusion should be approximately one to one and a half hours, but this should be balanced against the fluid requirements of the patient.

When fluid restriction is necessary, Septrin 16 mg/80 mg per ml for Infusion may be administered at a higher concentration, 5 ml diluted with 75 ml of glucose 5% w/v in water. The resultant solution, whilst being clear to the naked eye, may on occasion exceed the BP limits set for particulate matter in large volume parenterals. The solution should be infused over a period not exceeding one hour. Discard any unused solution.

7. Marketing Authorisation Holder

Laboratoires GENOPHARM

ZI de l'Esplanade

2, rue Niels Bohr

F – 77400 Saint-Thibault-des-Vignes

8. Marketing Authorisation Number(S)

PL 26946/0009

9. Date Of First Authorisation/Renewal Of The Authorisation

17 October 2006

10. Date Of Revision Of The Text

September 2010

Indometacin-Biosyntez

Indometacin-Biosyntez may be available in the countries listed below.

Ingredient matches for Indometacin-Biosyntez

Indometacin

Indometacin is reported as an ingredient of Indometacin-Biosyntez in the following countries:

• Russian Federation

International Drug Name Search

Pediacare

Generic Name: dextromethorphan (Oral route)

dex-troe-meth-OR-fan

Commonly used brand name(s)

In the U.S.

• Babee Cof Syrup


• Benylin Pediatric Formula


• Children's Pedia Care


• Creomulsion


• Creo-Terpin


• Delsym


• Dexalone


• ElixSure Cough Children's


• Father John's Medicine


• Miltuss


• Nycoff


• Pediacare


• Pediacare Long-Acting Cough


• Robafen Cough


• Robitussin


• Silphen DM


• Simply Cough


• St. Joseph


• Vicks 44 Cough Relief

Available Dosage Forms:

• Suspension, Extended Release


• Solution


• Capsule


• Syrup


• Lozenge/Troche


• Elixir


• Liquid


• Tablet


• Capsule, Liquid Filled


• Suspension

Therapeutic Class: Antitussive

Uses For Pediacare

Dextromethorphan is used to relieve coughs due to colds or influenza (flu). It should not be used for chronic cough that occurs with smoking, asthma, or emphysema or when there is an unusually large amount of mucus or phlegm (flem) with the cough.

Dextromethorphan relieves cough by acting directly on the cough center in the brain.

This medicine is available without a prescription.

Do not give any over-the-counter (OTC) cough and cold medicine to a baby or child under 4 years of age. Using these medicines in very young children might cause serious or possibly life-threatening side effects .

Before Using Pediacare

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

Allergies

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

Pediatric

Although there is no specific information comparing use of dextromethorphan in children with use in other age groups, this medicine is not expected to cause different side effects or problems in children 4 years of age and older than it does in adults.

Do not give any over-the-counter (OTC) cough and cold medicine to a baby or child under 4 years of age. Using these medicines in very young children might cause serious or possibly life-threatening side effects .

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of dextromethorphan in the elderly with use in other age groups.

Breast Feeding

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

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Clorgyline


• Iproniazid


• Isocarboxazid


• Moclobemide


• Nialamide


• Pargyline


• Phenelzine


• Procarbazine


• Rasagiline


• Selegiline


• Toloxatone


• Tranylcypromine

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.

• Abiraterone


• Amitriptyline


• Amoxapine


• Citalopram


• Clomipramine


• Desipramine


• Desvenlafaxine


• Doxepin


• Duloxetine


• Escitalopram


• Fluoxetine


• Fluvoxamine


• Imipramine


• Linezolid


• Milnacipran


• Nortriptyline


• Paroxetine


• Protriptyline


• Sertraline


• Sibutramine


• Trimipramine


• Venlafaxine

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.

• Clobazam


• Haloperidol


• Quinidine


• Vemurafenib

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Asthma—Since dextromethorphan decreases coughing, it makes it difficult to get rid of the mucus that collects in the lungs and airways during asthma

• Diabetes (sugar diabetes)—Some products contain sugar and may affect control of blood glucose monitoring

• Liver disease—Dextromethorphan may build up in the body and cause unwanted effects

• Chronic bronchitis or


• Emphysema or


• Mucus or phlegm with cough—Since dextromethorphan decreases coughing, it makes it difficult to get rid of the mucus that may collect in the lungs and airways with some diseases

• Slowed breathing—Dextromethorphan may slow the rate of breathing even further

Proper Use of dextromethorphan

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

Make certain your health care professional knows if you are on a low-sodium, low-sugar, or any other special diet. Most medicines contain more than their active ingredient, and many liquid medicines contain alcohol.

Use this medicine only as directed by your doctor or the directions on the label. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor or the label says. Although this effect has happened only rarely, dextromethorphan has become habit-forming (causing mental or physical dependence) in some persons who used too much for a long time.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

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

• For lozenge dosage form:
  
  • For cough:
    
    • Adults and children 12 years of age and older—5 to 15 mg every two to four hours, as needed.
    
    
    • Children 6 to 12 years of age—5 to 15 mg every two to six hours, as needed.
    
    
    • Children 4 to 6 years of age—5 mg every four hours, as needed.
    
    
    • Children and infants up to 4 years of age—Use is not recommended .
    
    
  
  


• For syrup dosage form:
  
  • For cough:
    
    • Adults and children 12 years of age and older—30 mg every six to eight hours, as needed.
    
    
    • Children 6 to 12 years of age—7 mg every four hours or 15 mg every six to eight hours, as needed.
    
    
    • Children 4 to 6 years of age—3.5 mg every four hours or 7.5 mg every six to eight hours, as needed.
    
    
    • Children and infants up to 4 years of age—Use is not recommended .
    
    
  
  


• For extended-release oral suspension dosage form :
  
  • For cough:
    
    • Adults and children 12 years of age and older—60 mg every twelve hours, as needed.
    
    
    • Children 6 to 12 years of age—30 mg every twelve hours, as needed.
    
    
    • Children 4 to 6 years of age—15 mg every twelve hours, as needed.
    
    
    • Children and infants up to 4 years of age—Use is not recommended .
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Pediacare

If your cough has not improved after 7 days, if sore throat has not improved after 2 days, if you have a high fever, skin rash, or continuing headache with the cough, or if asthma or high blood pressure is present, check with your doctor. These signs may mean that you have other medical problems.

Dissolve lozenges in the mouth with caution, to lessen the risk of choking.

Pediacare Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

Symptoms of overdose

• Blurred vision


• confusion


• difficulty in urination


• drowsiness or dizziness


• nausea or vomiting (severe)


• shakiness and unsteady walk


• slowed breathing


• unusual excitement, nervousness, restlessness, or irritability (severe)

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

Less common or rare

• Confusion


• constipation


• dizziness (mild)


• drowsiness (mild)


• headache


• nausea or vomiting


• stomach pain

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: Pediacare side effects (in more detail)

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

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Pediacare resources

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

• Pediacare Concise Consumer Information (Cerner Multum)


• Delsym Extended-Release Liquid MedFacts Consumer Leaflet (Wolters Kluwer)


• DexAlone MedFacts Consumer Leaflet (Wolters Kluwer)


• Dextromethorphan Hydrobromide Monograph (AHFS DI)


• ElixSure Cough Gel Syrup MedFacts Consumer Leaflet (Wolters Kluwer)


• Robitussin Maximum Strength Liquid MedFacts Consumer Leaflet (Wolters Kluwer)


• Triaminic Long Acting Cough Orally Disintegrating Strips MedFacts Consumer Leaflet (Wolters Kluwer)


• Tussin Pediatric Elixir MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Pediacare with other medications

• Cough

Allopurinol

Class: Antigout Agents
VA Class: MS400
CAS Number: 315-30-0
Brands: Aloprim, Zyloprim

Introduction

Xanthine oxidase inhibitor; structural isomer of hypoxanthine.^{152 156}

Uses for Allopurinol

Gout

Reduction of serum and urinary uric acid concentrations in primary and secondary gout.¹⁵⁶ In early uncomplicated gout, preferred over uricosurics in patients with urinary uric acid excretion >900 mg daily and in those with gouty nephropathy, urinary tract stones or obstruction, or azotemia.^a

Management of gout when uricosuric agents cannot be used because of adverse effects, allergy, or inadequate response; when there are visible tophi or radiographic evidence of uric acid deposits and stones; or when serum urate concentrations exceed 8.5–9 mg/dL and patient has family history of tophi and low urate excretion.^a

Management of primary or secondary gouty nephropathy with or without secondary oliguria.^a

Not recommended for management of asymptomatic hyperuricemia;¹⁵⁶ however, some clinicians have suggested that therapy be initiated when serum urate concentrations exceed 9 mg/dL (by colorimetric method) because these concentrations often are associated with increased joint changes and renal complications.^a

Of no value in the treatment of acute gout attacks (due to lack of analgesic or anti-inflammatory activity).^a

Chemotherapy-induced Hyperuricemia

A component of therapy (with urinary alkalinization and IV hydration)¹⁶⁰ in patients with leukemia, lymphoma, and solid tumor malignancies who are undergoing cancer therapy expected to result in tumor lysis and subsequent elevations of serum and urinary uric acid concentrations.^{152 153 156}

Oral allopurinol may be slower and less effective in decreasing plasma uric acid concentrations than IV rasburicase.^{157 158 159 160 161}

Recurrent Renal Calculi

Management of recurrent calcium oxalate renal calculi in males and females whose urinary urate excretion exceeds 800 and 750 mg daily, respectively.¹⁵⁶

Prevention of uric acid renal calculi in patients with history of recurrent stone formation.^a

Other Uses

Has been used to reduce hyperuricemia secondary to glucose-6-phosphate dehydrogenase deficiency†, Lesch-Nyhan syndrome†, polycythemia vera†, or sarcoidosis† or secondary to administration of thiazides† or ethambutol†.^a

Allopurinol Dosage and Administration

General

• 
  

  Maintain fluid intake to yield daily urine output of ≥2 L.^{152 156} Maintain neutral or, preferably, alkaline urine.^{152 156}

  
  

Gout

• 
  

  Transition period of several months may be required when allopurinol is added to regimen of colchicine, uricosuric agents, and/or anti-inflammatory agents.^{156 a} During transition period, administer drugs concomitantly, adjusting allopurinol dosage to achieve normal serum urate concentrations and freedom from acute gouty attacks for several months.^{156 a} Withdraw uricosuric agent gradually over several weeks.^{156 a}

  
  

Chemotherapy-induced Hyperuricemia

• 
  

  For prevention of acute uric acid nephropathy in patients undergoing chemotherapy, begin allopurinol treatment 24–48 hours before initiating chemotherapy.^{152 a}

  
  

Administration

Administer orally¹⁵⁶ or by IV infusion.¹⁵²

Oral Administration

Usually administered orally once daily, preferably after meals.¹⁵⁶ If oral dose >300 mg, administer in divided doses.¹⁵⁶

IV Infusion

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

Reconstitution

Reconstitute vial containing allopurinol sodium equivalent to 500 mg of allopurinol with 25 mL of sterile water for injection to provide a solution containing 20 mg/mL of allopurinol.¹⁵² Should be diluted further before IV administration.¹⁵²

Dilution

Dilute concentrate containing allopurinol 20 mg/mL with a compatible IV solution (see Solution Compatibility under Stability) to a final concentration of ≤6 mg/mL.¹⁵² Do not use diluent containing sodium bicarbonate.¹⁵²

Rate of Administration

Administer daily dosage by continuous infusion or in equally divided intermittent IV infusions at 6-, 8-, or 12-hour intervals.¹⁵² Infusion rate depends on volume of infusate.¹⁵²

Dosage

Available as allopurinol (oral) or allopurinol sodium (for IV use); dosage is expressed in terms of allopurinol.^{152 156}

Pediatric Patients

Chemotherapy-induced Hyperuricemia

Oral

Children <6 years of age: Initially, 150 mg daily.¹⁵⁶

Children 6–10 years of age: Initially, 300 mg daily.¹⁵⁶

Adjust dosage after about 48 hours according to patient response.¹⁵⁶

IV

Children ≤10 years of age: Initial dosage of 200 mg/m² daily.^{152 a}

Children >10 years of age: 200–400 mg/m² daily.^{152 162}

Adults

Gout

Oral

Initially, 100 mg daily.¹⁵⁶ May increase dosage by 100 mg weekly until serum urate concentration falls to ≤6 mg/dL or until maximum recommended dosage of 800 mg daily is reached.¹⁵⁶ Usual dosage is 200–300 mg daily in patients with mild gout and 400–600 mg daily in those with moderately severe tophaceous gout.¹⁵⁶

After serum urate concentrations are controlled, dosage reduction may be possible; average maintenance dosage is 300 mg daily, and minimum effective dosage is 100–200 mg daily.¹⁵⁶

Chemotherapy-induced Hyperuricemia

Oral

600–800 mg daily for 2–3 days.¹⁵⁶

IV

200–400 mg/m² daily.¹⁵²

Recurrent Calcium Oxalate Renal Calculi

Oral

Initially, 200–300 mg daily.¹⁵⁶ Titrate dosage based on 24-hour urinary urate determinations.¹⁵⁶

Prescribing Limits

Pediatric Patients

IV

Children >10 years of age: Maximum 600 mg daily.¹⁵²

Adults

Oral

Maximum 800 mg daily.¹⁵⁶

IV

Maximum 600 mg daily.¹⁵²

Special Populations

Renal Impairment

Oral

Initial Oral Dosage in Patients with Renal Impairment

Clcr (mL/min)	Initial Dosage
10–20	200 mg daily156
<10	≤100 mg daily156
<3	Increase dosage interval (e.g., 300 mg twice weekly)156 a

Maintenance Oral Dosage in Patients with Renal Impairment150

Clcr (mL/min)	Maintenance Dosage
80	250 mg daily
60	200 mg daily
40	150 mg daily
20	100 mg daily
10	100 mg every 2 days
0	100 mg every 3 days

IV

Maintenance IV Dosage in Patients with Renal Impairment152

Clcr (mL/min)	Maintenance Dosage
10–20	200 mg daily
3–10	100 mg daily
<3	100 mg at extended intervals

Cautions for Allopurinol

Contraindications

• 
  

  Known hypersensitivity to allopurinol or previous serious reaction.^{152 156}

  
  

Warnings/Precautions

Warnings

Hepatic Effects

Hepatotoxic reactions and elevations of serum transaminase or alkaline phosphatase concentrations reported.^{152 156}

Perform liver function tests (especially in patients with preexisting liver disease) before and periodically during therapy, particularly during initial months of therapy.^{152 156 a}

If anorexia, weight loss, or pruritus develops, assess liver function.^{152 156}

CNS Effects

Drowsiness may occur; performance of activities requiring mental alertness may be impaired.¹⁵²

Sensitivity Reactions

Hypersensitivity Reactions

Severe hypersensitivity reactions (including fatalities) have been reported following appearance of rash.^{152 156} Discontinue at first appearance of rash or any sign that may indicate hypersensitivity reaction.^{152 156}

Hypersensitivity reactions may occur more frequently in patients with renal impairment receiving allopurinol and thiazide diuretics; use these drugs with caution and careful monitoring in this population.^{152 156}

General Precautions

Acute Gout

Allopurinol is of no value in the treatment of acute gout attacks; will prolong and exacerbate inflammation during the acute phase.¹⁵⁶

May increase frequency of acute attacks during the first 6–12 months of therapy; therefore, administer prophylactic doses of colchicine concurrently during the first 3–6 months of therapy.^{156 a}

Hydration

Maintain sufficient fluid intake and a neutral or slightly alkaline urine to avoid possible formation of xanthine calculi and to prevent renal precipitation of urates in patients receiving concomitant uricosuric agents.^{152 156}

Adequate Laboratory Monitoring

Perform liver and renal function tests and complete blood cell counts before and periodically during therapy (particularly during initial months of therapy).^{152 156 a}

Specific Populations

Pregnancy

Category C.^{152 156}

Lactation

Allopurinol and oxypurinol distribute into milk; use with caution in nursing women.^{152 156}

Pediatric Use

Rarely indicated in children except in those with hyperuricemia secondary to neoplastic disease, cancer chemotherapy, or genetic disorders of purine metabolism.^{156 a}

Safety and efficacy profile for allopurinol sodium for injection in children is similar to that in adults.¹⁵²

Geriatric Use

Select dosage carefully due to age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^{152 154} Elimination may be prolonged due to age-related changes in renal function.¹⁵⁴

Numbers of geriatric patients in clinical studies of IV allopurinol sodium insufficient to determine whether they respond differently than younger adults; other clinical experience identified no difference in response.¹⁵²

Renal Impairment

Increased half-life.¹⁵² Reduce dosage.^{150 152 153 156} (See Renal Impairment under Dosage and Administration.)

Monitor closely; if deterioration in renal function occurs and persists, reduce dosage or discontinue drug.^{152 156}

Possible increased risk of rash.^a

Concomitant therapy with a thiazide diuretic in patients with renal impairment may increase risk of allopurinol-induced hypersensitivity reactions; use with caution in such patients and observe closely.¹⁵² (See Specific Drugs under Interactions.)

Common Adverse Effects

Oral therapy: pruritic maculopapular rash.¹⁵⁶

IV therapy: rash, renal failure/impairment, nausea, vomiting.¹⁵²

Interactions for Allopurinol

Does not inhibit hepatic microsomal enzymes.^a

Specific Drugs

Drug	Interaction	Comments
Alcohol	Potential for increased serum urate concentrations156 a	May need to increase allopurinol dosage156 a
Ampicillin and Amoxicillin	Increased incidence of rash in patients with hyperuricemia152 156 a	Clinical importance not determined; avoid concomitant use, if possiblea
Anticoagulants (e.g., dicumarol, warfarin)	Inhibition of dicumarol metabolism;a 152 156 not shown to substantially potentiate anticoagulant effect of warfarina	In patients receiving dicumarol and allopurinol, monitor PT and observe patient for increased anticoagulant effects152 156 a
Azathioprine	Inhibition of azathioprine metabolism; possible increase in toxic effects (including bone marrow depression)152 156	Decrease azathioprine dosage initially by 66–75%; base subsequent dosage adjustments on patient response and toxic effects152 156
Chlorpropamide	Potential for adverse hepatorenal reactions;a competition with chlorpropamide for renal tubular secretion152 156	Observe for signs of excessive hypoglycemia, especially in patients with renal impairment152 156
Co-trimoxazole	Rare cases of thrombocytopeniaa
Cyclophosphamide	Potential for bone marrow depression; mechanism not known152 156 a
Cyclosporine	Increased blood concentrations of cyclosporine152 156	Monitor blood concentration and consider dosage adjustments of cyclosporine152 156
Diazoxide	Potential for increased serum urate concentrations156 a	May need to increase allopurinol dosage156 a
Diuretics (e.g., thiazides, ethacrynic acid)	Potential for increased serum urate concentrations; potential for increased serum oxypurinol concentrations and increased risk of allopurinol toxicity, including hypersensitivity reactions, particularly in patients with renal impairment152 156 a	Monitor renal function; adjust dosage of allopurinol if necessary152 156 a
Mercaptopurine	Inhibition of mercaptopurine metabolism; possible increase in toxic effects (including bone marrow depression)152 156	Decrease mercaptopurine dosage initially by 66–75%; base subsequent dosage adjustments on patient response and toxic effects152 156
Pyrazinamide	Potential for increased serum urate concentrations156 a	May need to increase allopurinol dosage156 a
Uricosurics	Increased uric acid excretion; possible reduction in inhibition of xanthine oxidase by oxypurinol; possible renal precipitation of oxypurines152 156 a	May use smaller doses of each druga

Allopurinol Pharmacokinetics

Absorption

Bioavailability

About 80–90% absorbed following oral administration;^{156 a} peak plasma concentrations of allopurinol and oxypurinol are reached in 1.5 and 4.5 hours, respectively.¹⁵⁶

Following IV infusion over 30 minutes, peak plasma concentrations of allopurinol and oxypurinol are reached in about 30 minutes and 4 hours, respectively.¹⁵²

Onset

In patients with gout, serum urate concentrations begin to decrease slowly within 24–48 hours; minimum concentrations may not be reached for about 1–3 weeks.^{156 a} Because of continued mobilization of urate deposits, substantial reduction of uric acid may be delayed 6–12 months or may not occur in some patients.^{156 a}

Duration

After discontinuance of therapy, serum urate concentrations return to pretreatment levels within 1–2 weeks.^{a 156}

Special Populations

In geriatric patients (71–93 years of age), peak plasma concentrations and AUC of oxypurinol following oral allopurinol dose are 50–60% higher than in younger adults (24–35 years of age); apparently related to changes in renal function in older population.¹⁵⁴

Distribution

Extent

Uniformly distributed in total tissue water, except in the brain where concentrations are approximately 50% of those in other tissues.^a Allopurinol and oxypurinol are distributed into milk.^{152 156}

Plasma Protein Binding

Allopurinol and oxypurinol are not bound to plasma proteins.^a

Elimination

Metabolism

Rapidly metabolized by xanthine oxidase; metabolized principally to an active metabolite, oxypurinol.^{152 156}

Elimination Route

Excreted in urine as oxypurinol (about 70%) and in feces as unchanged drug (about 20%) within 48–72 hours.^{152 156 a}

Allopurinol and oxypurinol are dialyzable.¹⁵⁶

Half-life

1–3 and 18–30 hours for allopurinol and oxypurinol, respectively.^{152 156 a}

Special Populations

In patients with severe renal impairment or decreased urate clearance, plasma half-life of oxypurinol is greatly prolonged.^{152 156}

Patients genetically deficient in xanthine oxidase are unable to convert allopurinol to oxypurinol.^a

Stability

Storage

Oral

Tablets

15–25°C in dry place; protect from light.¹⁵⁶

Parenteral

Powder for Injection

25°C (may be exposed to 15–30°C).¹⁵²

Store diluted allopurinol sodium solutions containing ≤6 mg/mL of allopurinol at 20–25°C; use within 10 hours of reconstitution.¹⁵² Do not refrigerate reconstituted and/or diluted solutions.¹⁵²

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility¹⁵²

Compatible
Dextrose 5% in water
Sodium chloride 0.9%

Drug Compatibility

Y-Site Compatibilityb

Compatible
Acyclovir sodium
Aminophylline
Aztreonam
Bleomycin sulfate
Bumetanide
Buprenorphine HCl
Butorphanol tartrate
Calcium gluconate
Carboplatin
Cefazolin sodium
Cefotetan disodium
Ceftazidime
Ceftizoxime sodium
Ceftriaxone sodium
Cefuroxime sodium
Cisplatin
Co-trimoxazole
Cyclophosphamide
Dactinomycin
Dexamethasone sodium phosphate
Doxorubicin HCl liposome injection
Enalaprilat
Etoposide
Famotidine
Fluconazole
Fludarabine phosphate
Fluorouracil
Furosemide
Ganciclovir sodium
Granisetron HCl
Heparin sodium
Hydrocortisone sodium phosphate
Hydrocortisone sodium succinate
Hydromorphone HCl
Ifosfamide
Lorazepam
Mannitol
Mesna
Methotrexate sodium
Metronidazole
Mitoxantrone HCl
Morphine sulfate
Plicamycin
Potassium chloride
Ranitidine HCl
Teniposide
Thiotepa
Ticarcillin disodium
Ticarcillin disodium–clavulanate potassium
Vancomycin HCl
Vinblastine sulfate
Vincristine sulfate
Zidovudine
Incompatible
Amikacin sulfate
Amphotericin B
Carmustine
Cefotaxime sodium
Chlorpromazine HCl
Cimetidine HCl
Clindamycin phosphate
Cytarabine
Dacarbazine
Daunorubicin HCl
Diphenhydramine HCl
Doxorubicin HCl
Doxycycline hyclate
Droperidol
Floxuridine
Gentamicin sulfate
Haloperidol lactate
Hydroxyzine HCl
Idarubicin HCl
Imipenem–cilastatin sodium
Mechlorethamine HCl
Meperidine HCl
Methylprednisolone sodium succinate
Metoclopramide HCl
Minocycline HCl
Nalbuphine HCl
Ondansetron HCl
Prochlorperazine edisylate
Promethazine HCl
Sodium bicarbonate
Streptozocin
Tobramycin sulfate
Vinorelbine tartrate

ActionsActions

• 
  

  Allopurinol and its active metabolite, oxypurinol, inhibit xanthine oxidase.^{152 156} Inhibition of xanthine oxidase blocks conversion of oxypurines (hypoxanthine, xanthine) to uric acid, resulting in decreases in serum and urine uric acid concentrations and increases in serum and urine concentrations of hypoxanthine and xanthine.^{152 156}

  
  


• 
  

  Decreases de novo purine biosynthesis by indirectly increasing oxypurine and allopurinol ribonucleotide concentrations and decreasing phosphoribosylpyrophosphate concentrations.^a Also decreases serum uric acid concentrations by increasing incorporation of hypoxanthine and xanthine into DNA and RNA.^{152 a}

  
  


• 
  

  Has no analgesic, anti-inflammatory, or uricosuric activity.¹⁵³

  
  

Advice to Patients

• 
  

  Importance of discontinuing drug and consulting clinician at first sign of rash, painful urination, blood in urine, irritation of eyes, or swelling of lips or mouth.^{152 156}

  
  


• 
  

  Importance of maintaining fluid intake sufficient to yield daily urine output of ≥2 L.^{152 156}

  
  


• 
  

  Administering drug after meals may minimize gastric irritation.¹⁵⁶

  
  


• 
  

  Importance of continuing allopurinol therapy as prescribed for gout; optimal benefit may be delayed for 2–6 weeks.¹⁵⁶

  
  


• 
  

  Potential for drug to cause drowsiness and impair mental alertness; use caution when operating machinery or performing hazardous tasks until effects on individual are known.^{152 156}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{152 156}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.^{152 156}

  
  


• 
  

  Importance of informing patients of other important precautionary information.^{152 156} (See Cautions.)

  
  

Preparations

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

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

Allopurinol

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	100 mg*	Zyloprim (with povidone; scored)	Prometheus
		300 mg*	Zyloprim (with povidone; scored)	Prometheus

Allopurinol Sodium

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IV infustion only	500 mg (of allopurinol)	Aloprim	Nabi

Comparative Pricing

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

Allopurinol 100MG Tablets (WATSON LABS): 100/$13.99 or 300/$33.96

Allopurinol 300MG Tablets (WATSON LABS): 100/$22.99 or 300/$54.99

Zyloprim 100MG Tablets (PROMETHEUS): 30/$39.99 or 90/$79.97

Zyloprim 300MG Tablets (PROMETHEUS): 30/$79.99 or 90/$195.99

Disclaimer

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

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

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions May 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

150. Hande KR, Noone RM, Stone WJ. Severe allopurinol toxicity: description and guidelines for prevention in patients with renal insufficiency. Am J Med. 1984; 76:47-56. [IDIS 180407] [PubMed 6691361]

151. Ettinger B, Tang A, Citron JT et al. Randomized trial of allopurinol in the prevention of calcium oxalate calculi. N Engl J Med. 1986; 315:1386-9. [IDIS 223014] [PubMed 3534570]

152. Nabi. Aloprim (allopurinol sodium) for injection prescribing information. Boca Raton, FL; 2003 Feb.

153. Smalley RV, Guaspari A, Haase-Statz S et al. Allopurinol: intravenous use for prevention and treatment of hyperuricemia. J Clin Oncol. 2000; 18:1758-63. [IDIS 447152] [PubMed 10764437]

154. Turnheim K, Krivanek P, Oberbauer R. Pharmacokinetics and pharmacodynamics of allopurinol in elderly and young subjects. Br J Clin Pharmacol. 1999; 48:501-9. [IDIS 437123] [PubMed 10583019]

155. Newton DW. Introduction: physicochemical determinants of incompatibility and instability of drugs for injection and infusion. In: Trissel LA. Handbook of injectable drugs. 3rd ed. Bethesda, MD: American Society of Health-System Pharmacists, Inc., Inc.; 1983:xi-xxi.

156. Prometheus. Zyloprim (allopurinol) tablets prescribing information. San Diego, CA; 2003 Oct.

157. Sanofi-Synthelabo Inc. Elitek (rasburicase) injection for intravenous use prescribing information. New York, NY; 2002 Jul 22.

158. Goldman SC, Holcenberg JS, Finklestein JZ et al. A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis. Blood. 2001; 97:2998-3003. [IDIS 463743] [PubMed 11342423]

159. Easton J, Noble S, Jarvis B. Rasburicase. Pediatr Drugs. 2001; 3:433-9

160. Anon. Rasburicase (Elitek) for hyperuricemia. Med Letter Drug Ther. 2002; 44:96-7.

161. Lohr LK. Rasburicase, a new, recombinate form of urate oxidase, treats hyperuricemia in tumor lysis syndrome. Hem/Onc Today. October 2002. From the Hem/Onc Today website. Accessed 2003 Jan 23.

162. Nabi, Boca Raton, FL: Personal communication.

a. AHFS Drug Information 2003. McEvoy GK, ed. Allopurinol. American Society of Health-System Pharmacists; 2003: page 3546-50.

b. Trissel LA. Handbook on injectable drugs. 13th ed; Bethesda, MD: American Society of Health-System Pharmacists; 2005:23-29.

More Allopurinol resources

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

• Allopurinol Prescribing Information (FDA)


• Allopurinol MedFacts Consumer Leaflet (Wolters Kluwer)


• Allopurinol Professional Patient Advice (Wolters Kluwer)


• allopurinol Concise Consumer Information (Cerner Multum)


• allopurinol Intravenous Advanced Consumer (Micromedex) - Includes Dosage Information


• Aloprim Prescribing Information (FDA)


• Zyloprim Prescribing Information (FDA)

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