Tasmar

tolcapone

Dosage Form: tablet, film coated
Tasmar®

(tolcapone)

TABLETS

Before prescribing Tasmar, the physician should be thoroughly familiar with the details of this prescribing information.

Tasmar SHOULD NOT BE USED BY PATIENTS UNTIL THERE HAS BEEN A COMPLETE DISCUSSION OF THE RISKS AND THE PATIENT HAS PROVIDED WRITTEN ACKNOWLEDGEMENT THAT THE RISKS HAVE BEEN EXPLAINED (SEE PATIENT ACKNOWLEDGEMENT OF RISKS SECTION).

Warning

Because of the risk of potentially fatal, acute fulminant liver failure, Tasmar (tolcapone) should ordinarily be used in patients with Parkinson's disease on l-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to or are not appropriate candidates for other adjunctive therapies (see INDICATIONS and DOSAGE AND ADMINISTRATION sections).

Because of the risk of liver injury and because Tasmar, when it is effective, provides an observable symptomatic benefit, the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment, should be withdrawn from Tasmar.

Tasmar therapy should not be initiated if the patient exhibits clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than the upper limit of normal. Patients with severe dyskinesia or dystonia should be treated with caution (see PRECAUTIONS: Rhabdomyolysis).

Patients who develop evidence of hepatocellular injury while on Tasmar and are withdrawn from the drug for any reason may be at increased risk for liver injury if Tasmar is reintroduced. Accordingly, such patients should not ordinarily be considered for retreatment.

Cases of severe hepatocellular injury, including fulminant liver failure resulting in death, have been reported in postmarketing use. As of May 2005, 3 cases of fatal fulminant hepatic failure have been reported from more than 40,000 patient years of worldwide use. This incidence may be 10- to 100-fold higher than the background incidence in the general population. Underreporting of cases may lead to significant underestimation of the increased risk associated with the use of Tasmar. All 3 cases were reported within the first six months of initiation of treatment with Tasmar. Analysis of the laboratory monitoring data in over 3,400 Tasmar-treated patients participating in clinical trials indicated that increases in SGPT/ALT or SGOT/AST, when present, generally occurred within the first 6 months of treatment with Tasmar.

A prescriber who elects to use Tasmar in face of the increased risk of liver injury is strongly advised to monitor patients for evidence of emergent liver injury. Patients should be advised of the need for self-monitoring for both the classical signs of liver disease (eg, clay colored stools, jaundice) and the nonspecific ones (eg, fatigue, loss of appetite, lethargy).

Although a program of periodic laboratory monitoring for evidence of hepatocellular injury is recommended, it is not clear that periodic monitoring of liver enzymes will prevent the occurrence of fulminant liver failure. However, it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery. Accordingly, the following liver monitoring program is recommended.

Before starting treatment with Tasmar, the physician should conduct appropriate tests to exclude the presence of liver disease. In patients determined to be appropriate candidates for treatment with Tasmar, serum glutamic-pyruvic transaminase (SGPT/ALT) and serum glutamic-oxaloacetic transaminase (SGOT/AST) levels should be determined at baseline and periodically (i.e. every 2 to 4 weeks) for the first 6 months of therapy. After the first six months, periodic monitoring is recommended at intervals deemed clinically relevant. Although more frequent monitoring increases the chances of early detection, the precise schedule for monitoring is a matter of clinical judgement. If the dose is increased to 200 mg tid (see DOSAGE AND ADMINISTRATION section), liver enzyme monitoring should take place before increasing the dose and then be conducted every 2 to 4 weeks for the following 6 months of therapy. After six months, periodic monitoring is recommended at intervals deemed clinically relevant.

Tasmar should be discontinued if SGPT/ALT or SGOT/AST levels exceed 2 times the upper limit of normal or if clinical signs and symptoms suggest the onset of hepatic dysfunction (persistent nausea, fatigue, lethargy, anorexia, jaundice, dark urine, pruritus, and right upper quadrant tenderness).

Tasmar Description

Tasmar® is available as tablets containing 100 mg or 200 mg tolcapone.

Tolcapone, an inhibitor of catechol-O-methyltransferase (COMT), is used in the treatment of Parkinson's disease as an adjunct to levodopa/carbidopa therapy. It is a yellow, odorless, non-hygroscopic, crystalline compound with a relative molecular mass of 273.25. The chemical name of tolcapone is 3,4-dihydroxy-4'-methyl-5-nitrobenzophenone. Its empirical formula is C14H11NO5 and its structural formula is:

Inactive ingredients: Core: lactose monohydrate, microcrystalline cellulose, dibasic calcium phosphate anhydrous, povidone K-30, sodium starch glycolate, talc and magnesium stearate. Film coating: hydroxypropyl methylcellulose, titanium dioxide, talc, ethylcellulose, triacetin and sodium lauryl sulfate, with the following dye systems: 100 mg — yellow and red iron oxide; 200 mg — red iron oxide.

Tasmar - Clinical Pharmacology

Mechanism of Action

Tolcapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT).

In mammals, COMT is distributed throughout various organs. The highest activities are in the liver and kidney. COMT also occurs in the heart, lung, smooth and skeletal muscles, intestinal tract, reproductive organs, various glands, adipose tissue, skin, blood cells and neuronal tissues, especially in glial cells. COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include dopa, catecholamines (dopamine, norepinephrine, epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. In the presence of a decarboxylase inhibitor, COMT becomes the major metabolizing enzyme for levodopa catalyzing the metabolism to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery.

The precise mechanism of action of tolcapone is unknown, but it is believed to be related to its ability to inhibit COMT and alter the plasma pharmacokinetics of levodopa. When tolcapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that these sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson's disease in patients as well as increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa. Tolcapone enters the CNS to a minimal extent, but has been shown to inhibit central COMT activity in animals.

Pharmacodynamics

COMT Activity in Erythrocytes

Studies in healthy volunteers have shown that tolcapone reversibly inhibits human erythrocyte catechol-O-methyltransferase (COMT) activity after oral administration. The inhibition is closely related to plasma tolcapone concentrations. With a 200-mg single dose of tolcapone, maximum inhibition of erythrocyte COMT activity is on average greater than 80%. During multiple dosing with tolcapone (200 mg tid), erythrocyte COMT inhibition at trough tolcapone blood concentrations is 30% to 45%.

Effect on the Pharmacokinetics of Levodopa and its Metabolites

When tolcapone is administered together with levodopa/carbidopa, it increases the relative bioavailability (AUC) of levodopa by approximately twofold. This is due to a decrease in levodopa clearance resulting in a prolongation of the terminal elimination half-life of levodopa (from approximately 2 hours to 3.5 hours). In general, the average peak levodopa plasma concentration (Cmax) and the time of its occurrence (Tmax) are unaffected. The onset of effect occurs after the first administration and is maintained during long-term treatment. Studies in healthy volunteers and Parkinson's disease patients have confirmed that the maximal effect occurs with 100 mg to 200 mg tolcapone. Plasma levels of 3-OMD are markedly and dose-dependently decreased by tolcapone when given with levodopa/carbidopa.

Population pharmacokinetic analyses in patients with Parkinson's disease have shown the same effects of tolcapone on levodopa plasma concentrations that occur in healthy volunteers.

Pharmacokinetics of Tolcapone

Tolcapone pharmacokinetics are linear over the dose range of 50 mg to 400 mg, independent of levodopa/carbidopa coadministration. The elimination half-life of tolcapone is 2 to 3 hours and there is no significant accumulation. With tid dosing of 100 mg or 200 mg, Cmax is approximately 3 µg/mL and 6 µg/mL, respectively.

Absorption

Tolcapone is rapidly absorbed, with a Tmax of approximately 2 hours. The absolute bioavailability following oral administration is about 65%. Food given within 1 hour before and 2 hours after dosing of tolcapone decreases the relative bioavailability by 10% to 20% (see DOSAGE AND ADMINISTRATION).

Distribution

The steady-state volume of distribution of tolcapone is small (9 L). Tolcapone does not distribute widely into tissues due to its high plasma protein binding. The plasma protein binding of tolcapone is >99.9% over the concentration range of 0.32 to 210 µg/mL. In vitro experiments have shown that tolcapone binds mainly to serum albumin.

Metabolism and Elimination

Tolcapone is almost completely metabolized prior to excretion, with only a very small amount (0.5% of dose) found unchanged in urine. The main metabolic pathway of tolcapone is glucuronidation; the glucuronide conjugate is inactive. In addition, the compound is methylated by COMT to 3-O-methyl-tolcapone. Tolcapone is metabolized to a primary alcohol (hydroxylation of the methyl group), which is subsequently oxidized to the carboxylic acid. In vitro experiments suggest that the oxidation may be catalyzed by cytochrome P450 3A4 and P450 2A6. The reduction to an amine and subsequent N-acetylation occur to a minor extent. After oral administration of a 14C-labeled dose of tolcapone, 60% of labeled material is excreted in urine and 40% in feces. Tolcapone is a low-extraction-ratio drug (extraction ratio = 0.15) with a moderate systemic clearance of about 7 L/h.

Special Populations

Tolcapone pharmacokinetics are independent of sex, age, body weight, and race (Japanese, Black and Caucasian). Polymorphic metabolism is unlikely based on the metabolic pathways involved.

Hepatic Impairment

A study in patients with hepatic impairment has shown that moderate non-cirrhotic liver disease had no impact on the pharmacokinetics of tolcapone. In patients with moderate cirrhotic liver disease (Child-Pugh Class B), however, clearance and volume of distribution of unbound tolcapone was reduced by almost 50%. This reduction may increase the average concentration of unbound drug by twofold (see DOSAGE AND ADMINISTRATION). Tasmar therapy should not be initiated if the patient exhibits clinical evidence of active liver disease or two SGPT/ALT or SGOT/AST values greater than the upper limit of normal (see BOXED WARNING).

Renal Impairment

The pharmacokinetics of tolcapone have not been investigated in a specific renal impairment study. However, the relationship of renal function and tolcapone pharmacokinetics has been investigated using population pharmacokinetics during clinical trials. The data of more than 400 patients have confirmed that over a wide range of creatinine clearance values (30 mL/min to 130 mL/min) the pharmacokinetics of tolcapone are unaffected by renal function. This could be explained by the fact that only a negligible amount of unchanged tolcapone (0.5%) is excreted in the urine. The glucuronide conjugate of tolcapone is mainly excreted in the urine but is also excreted in the bile. Accumulation of this stable and inactive metabolite should not present a risk in renally impaired patients with creatinine clearance above 25 mL/min (see DOSAGE AND ADMINISTRATION). Given the very high protein binding of tolcapone, no significant removal of the drug by hemodialysis would be expected.

Drug Interactions

See PRECAUTIONS: Drug Interactions.

Clinical Studies

The effectiveness of Tasmar as an adjunct to levodopa in the treatment of Parkinson's disease was established in three multicenter randomized controlled trials of 13 to 26 weeks' duration, supported by four 6-week trials whose results were consistent with those of the longer trials. In two of the longer trials, tolcapone was evaluated in patients whose Parkinson's disease was characterized by deterioration in their response to levodopa at the end of a dosing interval (so-called fluctuating patients with wearing-off phenomena). In the remaining trial, tolcapone was evaluated in patients whose response to levodopa was relatively stable (so-called non-fluctuators).

Fluctuating Patients

In two 3-month trials, patients with documented episodes of wearing-off phenomena, despite optimum levodopa therapy, were randomized to receive placebo, tolcapone 100 mg tid or 200 mg tid. The formal double-blind portion of the trial was 3 months long, and the primary outcome was a comparison between treatments in the change from baseline in the amount of time spent "On" (a period of relatively good functioning) and "Off" (a period of relatively poor functioning). Patients recorded periodically, throughout the duration of the trial, the time spent in each of these states.

In addition to the primary outcome, patients were also assessed using sub-parts of the Unified Parkinson's Disease Rating Scale (UPDRS), a frequently used multi-item rating scale intended to evaluate mentation (Part I), activities of daily living (Part II), motor function (Part III), complications of therapy (Part IV), and disease staging (Parts V and VI); an Investigator's Global Assessment of Change (IGA), a subjective scale designed to assess global functioning in 5 areas of Parkinson's disease; the Sickness Impact Profile (SIP), a multi-item scale in 12 domains designed to assess the patient's functioning in multiple areas; and the change in daily levodopa/carbidopa dose.

In one of the studies, 202 patients were randomized in 11 centers in the United States and Canada. In this trial, all patients were receiving concomitant levodopa and carbidopa. In the second trial, 177 patients were randomized in 24 centers in Europe. In this trial, all patients were receiving concomitant levodopa and benserazide.

The following tables display the results of these 2 trials:

Table 1. US/Canadian Fluctuator Study

* Compared to placebo. † Hours "Off" or "On" are based on the percent of waking day "Off" or "On",assuming a 16-hour waking day.
Primary Measure
	Baseline (hrs)	Change from Baseline at Month 3 (hrs)	p-value*
Hours of Wake Time "Off " †
Placebo	6.2	-1.2	—
100 mg tid	6.4	-2.0	0.169
200 mg tid	5.9	-3.0	<0.001
Hours of Wake Time "On" †
Placebo	8.7	1.4	—
100 mg tid	8.1	2.0	0.267
200 mg tid	9.1	2.9	0.008
Secondary Measures
	Baseline	Change from Baseline
		at Month 3	p-value*
Levodopa Total Daily Dose (mg)
Placebo	948	16	—
100 mg tid	788	-166	<0.001
200 mg tid	865	-207	<0.001
Global (overall) % Improved
Placebo	—	42	—
100 mg tid	—	71	<0.001
200 mg tid	—	91	<0.001
UPDRS Motor
Placebo	19.5	-0.4	—
100 mg tid	17.6	-1.9	0.217
200 mg tid	20.6	-2.0	0.210
UPDRS ADL
Placebo	7.5	-0.3	—
100 mg tid	7.7	-0.8	0.487
200 mg tid	8.3	0.2	0.412
SIP (total)
Placebo	14.7	-2.2	—
100 mg tid	14.9	-0.4	0.210
200 mg tid	17.6	-0.3	0.216

Table 2. European Fluctuator Study

Effects on "Off" time and levodopa dose did not differ by age or sex.
* Compared to placebo. † Hours "Off" or "On" are based on the percent of waking day "Off" or "On", assuming a 16-hour waking day.
Primary Measure
	Baseline (hrs)	Change from Baseline at Month 3 (hrs)	p-value*
Hours of Wake Time "Off " †
Placebo	6.1	-0.7	—
100 mg tid	6.5	-2.0	0.008
200 mg tid	6.0	-1.6	0.081
Hours of Wake Time "On" †
Placebo	8.5	-0.1	—
100 mg tid	8.1	1.7	0.003
200 mg tid	8.4	1.7	0.003
Secondary Measures
	Baseline	Change from Baseline
		at Month 3	p-value*
Levodopa Total Daily Dose (mg)
Placebo	660	-29	—
100 mg tid	667	-109	0.025
200 mg tid	675	-122	0.010
Global (overall) % Improved
Placebo	—	37	—
100 mg tid	—	70	0.003
200 mg tid	—	78	<0.001
UPDRS Motor
Placebo	24.0	-2.1	—
100 mg tid	22.4	-4.2	0.163
200 mg tid	22.4	-6.5	0.004
UPDRS ADL
Placebo	7.9	-0.5	—
100 mg tid	7.5	-0.9	0.408
200 mg tid	7.7	-1.3	0.097
SIP (total)
Placebo	21.6	-0.9	—
100 mg tid	16.6	-1.9	0.419
200 mg tid	18.4	-4.2	0.011

Non-fluctuating Patients

In this study, 298 patients with idiopathic Parkinson's disease on stable doses of levodopa/carbidopa who were not experiencing wearing-off phenomena were randomized to placebo, tolcapone 100 mg tid, or tolcapone 200 mg tid for 6 months at 20 centers in the United States and Canada. The primary measure of effectiveness was the Activities of Daily Living portion (Subscale II) of the UPDRS. In addition, the change in daily levodopa dose, other subscales of the UPDRS, and the SIP were assessed as secondary measures. The results are displayed in the following table:

Table 3. US/Canadian Non-fluctuator Study

Effects on Activities of Daily Living did not differ by age or sex.
* Compared to placebo.
Primary Measure
	Baseline	Change from Baseline
		at Month 6	p-value*
UPDRS ADL
Placebo	8.5	0.1	—
100 mg tid	7.5	-1.4	<0.001
200 mg tid	7.9	-1.6	<0.001
Secondary Measures
	Baseline	Change from Baseline
		at Month 6	p-value*
Levodopa Total Daily Dose (mg)
Placebo	364	47	—
100 mg tid	370	-21	<0.001
200 mg tid	381	-32	<0.001
UPDRS Motor
Placebo	19.7	0.1	—
100 mg tid	17.3	-2.0	0.018
200 mg tid	16.0	-2.3	0.008
SIP (total)
Placebo	6.9	0.4	—
100 mg tid	7.3	-0.9	0.044
200 mg tid	7.3	-0.7	0.078
Percent of Patients who
Developed Fluctuations
Placebo	—	26	—
100 mg tid	—	19	0.297
200 mg tid	—	14	0.047

INDICATIONS

Tasmar is indicated as an adjunct to levodopa and carbidopa for the treatment of the signs and symptoms of idiopathic Parkinson's disease. Because of the risk of potentially fatal, acute fulminant liver failure, Tasmar (tolcapone) should ordinarily be used in patients with Parkinson's disease on l-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to or are not appropriate candidates for other adjunctive therapies. Because of the risk of liver injury and because Tasmar, when it is effective, provides an observable symptomatic benefit, the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment, should be withdrawn from Tasmar.

The effectiveness of Tasmar was demonstrated in randomized controlled trials in patients receiving concomitant levodopa therapy with carbidopa or another aromatic amino acid decarboxylase inhibitor who experienced end of dose wearing-off phenomena as well as in patients who did not experience such phenomena (see CLINICAL PHARMACOLOGY: Clinical Studies).

Contraindications

Tasmar tablets are contraindicated in patients with liver disease, in patients who were withdrawn from Tasmar because of evidence of Tasmar-induced hepatocellular injury or who have demonstrated hypersensitivity to the drug or its ingredients.

Tasmar is also contraindicated in patients with a history of nontraumatic rhabdomyolysis or hyperpyrexia and confusion possibly related to medication (see PRECAUTIONS: Events Reported With Dopaminergic Therapy).

Warnings

(SEE BOXED WARNING) Because of the risk of potentially fatal, acute fulminant liver failure, Tasmar (tolcapone) should ordinarily be used in patients with Parkinson's disease on l-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to or are not appropriate candidates for other adjunctive therapies (see INDICATIONS and DOSAGE AND ADMINISTRATION sections).

Because of the risk of liver injury and because Tasmar, when it is effective, provides an observable symptomatic benefit, the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment, should be withdrawn from Tasmar.

Tasmar therapy should not be initiated if the patient exhibits clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than the upper limit of normal. Patients with severe dyskinesia or dystonia should be treated with caution (see PRECAUTIONS: Rhabdomyolysis).

Patients who develop evidence of hepatocellular injury while on Tasmar and are withdrawn from the drug for any reason may be at increased risk for liver injury if Tasmar is reintroduced. Accordingly, such patients should not ordinarily be considered for retreatment.

In controlled Phase 3 trials, increases to more than 3 times the upper limit of normal in ALT or AST occurred in approximately 1% of patients at 100 mg tid and 3% of patients at 200 mg tid. Females were more likely than males to have an increase in liver enzymes (approximately 5% vs 2%). Approximately one third of patients with elevated enzymes had diarrhea. Increases to more than 8 times the upper limit of normal in liver enzymes occurred in 0.3% at 100 mg tid and 0.7% at 200 mg tid. Elevated enzymes led to discontinuation in 0.3% and 1.7% of patients treated with 100 mg tid and 200 mg tid, respectively. Elevations usually occurred within 6 weeks to 6 months of starting treatment. In about half the cases with elevated liver enzymes, enzyme levels returned to baseline values within 1 to 3 months while patients continued Tasmar treatment. When treatment was discontinued, enzymes generally declined within 2 to 3 weeks but in some cases took as long as 1 to 2 months to return to normal.

Monoamine oxidase (MAO) and COMT are the two major enzyme systems involved in the metabolism of catecholamines. It is theoretically possible, therefore, that the combination of Tasmar and a non-selective MAO inhibitor (eg, phenelzine and tranylcypromine) would result in inhibition of the majority of the pathways responsible for normal catecholamine metabolism. For this reason, patients should ordinarily not be treated concomitantly with Tasmar and a non-selective MAO inhibitor.

Tolcapone can be taken concomitantly with a selective MAO-B inhibitor (eg, selegiline).

Precautions

Hypotension/Syncope

Dopaminergic therapy in Parkinson's disease patients has been associated with orthostatic hypotension. Tolcapone enhances levodopa bioavailability and, therefore, may increase the occurrence of orthostatic hypotension. In Tasmar clinical trials, orthostatic hypotension was documented at least once in 8%, 14% and 13% of the patients treated with placebo, 100 mg and 200 mg Tasmar tid, respectively. A total of 2%, 5% and 4% of the patients treated with placebo, 100 mg and 200 mg Tasmar tid, respectively, reported orthostatic symptoms at some time during their treatment and also had at least one episode of orthostatic hypotension documented (however, the episode of orthostatic symptoms itself was invariably not accompanied by vital sign measurements). Patients with orthostasis at baseline were more likely than patients without symptoms to have orthostatic hypotension during the study, irrespective of treatment group. In addition, the effect was greater in tolcapone-treated patients than in placebo-treated patients. Baseline treatment with dopamine agonists or selegiline did not appear to increase the likelihood of experiencing orthostatic hypotension when treated with Tasmar. Approximately 0.7% of the patients treated with Tasmar (5% of patients who were documented to ha

Testosterone Transdermal

tes-TOS-ter-one

Commonly used brand name(s)

In the U.S.

• Androderm

In Canada

• Androplex

Available Dosage Forms:

• Patch, Extended Release

Therapeutic Class: Endocrine-Metabolic Agent

Pharmacologic Class: Androgen

Uses For testosterone

Testosterone transdermal patch is used for the treatment of males whose bodies do not make enough natural testosterone, a condition called hypogonadism. Testosterone is a male hormone responsible for the growth and development of the male sex organs and maintenance of secondary sex characteristics.

testosterone is available only with your doctor's prescription.

Before Using testosterone

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 testosterone, the following should be considered:

Allergies

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

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of testosterone transdermal patch in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies have not been performed on the relationship of age to the effects of testosterone transdermal patch in the geriatric population. However, elderly patients may be at an increased risk for developing prostate problems, including prostate cancer, which may require caution in patients receiving testosterone transdermal patch.

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 testosterone, 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 testosterone 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.

• Anisindione


• Bupropion


• Dicumarol


• Paclitaxel


• Paclitaxel Protein-Bound


• Phenprocoumon


• Warfarin

Using testosterone 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.

• Licorice

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

• Blood disorder (e.g., polycythemia)—May increase risk for thromboembolic diseases.

• Breast cancer (males) or


• Prostate cancer, known or suspected—Should not be used in patients with these conditions.

• Drug abuse or dependence, history of or


• Enlarged prostate or


• Hypercalcemia (high calcium in the blood) or


• Problems in passing urine or


• Sleep apnea (breathing problem)—Use with caution. May make these conditions worse.

• Heart disease or


• Kidney disease or


• Liver disease—Use with caution. Testosterone may cause edema (fluid retention) in patients with these conditions.

• Lung disease or


• Obesity—May increase risk for sleep apnea.

Proper Use of testosterone

testosterone comes with a Medication Guide and patient instructions. Read and follow these instructions carefully. Ask your doctor or pharmacist if you have any questions.

Testosterone skin patch comes in four different doses and different patch sizes. Ask your doctor which is the right one for you.

Make sure that you wash your hands with soap and water before and after applying the patch.

For patients using the patch:

• After opening the pouch that contains the patch, apply the patch immediately.


• Apply the patch to a clean, dry area of the skin on your back, abdomen, thighs, or upper arm. Do not put the patch over burns, cuts, or irritated skin. Avoid putting the patch on oily or sweaty skin, or on areas covered with hair, since the patch may not stick tightly to these areas.


• Do not apply the patch to your scrotum or genital area. Avoid applying testosterone to a bony area (such as your shoulder) or to an area that might be under pressure for a long time (such as the back of your leg when you are sitting).


• The patch can be worn during sexual intercourse, or while taking a shower or bath. Wait for at least 3 hours after applying the medicine before you shower, swim, or wash the application site. However, heavy exercise and sweating may cause the patch to fall off.


• When replacing an old patch, make sure that you apply the new patch on a different spot. Do not put another patch back on the same spot for at least 7 days.


• Do not apply any type of ointment product on your skin before you put on the patch.


• If a patch comes off, just put it back on the same spot. If the patch will not stick and you have been wearing it for fewer than 12 hours, put on a new patch. Then stay on your regular schedule and replace it with a fresh patch at your next regular time. If you have already been wearing the patch for more than 12 hours, do not put on a new patch. Wait to put on a new patch at your next regular time. Do not use extra patches to make up for the one that came off.

Dosing

The dose of testosterone 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 testosterone. 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 transdermal dosage form (patch):
  
  • For hormone replacement:
    
    • Adults—At first, one 4-milligram (mg) or 5-mg, or two 2.5-mg patches applied nightly for 24 hours. Your doctor may adjust your dose as needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For non-virilized patients:
    
    • Adults—One 2.5-milligram patch applied nightly.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you forget to wear or change a patch, put one on as soon as you can. If it is almost time to put on your next patch, wait until then to apply a new patch and skip the one you missed. Do not apply extra patches to make up for a missed dose.

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

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

Precautions While Using testosterone

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and check for any problems or unwanted effects that may be caused by testosterone. Blood tests will be needed to check for unwanted effects.

testosterone should not be used by women. Testosterone may cause birth defects if a pregnant woman comes in contact with the patch or medicine. Make sure your doctor knows if your sexual partner is pregnant. If a pregnancy occurs while you are using testosterone, tell your doctor right away.

If a woman comes in contact with the patch, wash the skin area right away with soap and water to remove all the medicine. If the patch sticks to a woman, remove the patch right away and wash her skin thoroughly with soap and water.

If your female partner starts to have male-like changes such as unusual hair growth or increased acne, check with your doctor.

testosterone may increase the risk of prostate cancer, especially in older men. Make sure your doctor knows if you have prostate cancer, or if anyone in your family has prostate cancer.

In some cases, testosterone may decrease the amount of sperm men make and affect their ability to have children. If you plan to have children, talk with your doctor before using testosterone.

Tell your doctor if you experience too frequent erection of the penis, nausea, vomiting, yellowing of your skin or the whites of your eyes, or swelling of the ankle.

testosterone may cause swelling of the breasts (gynecomastia) and breast pain in some patients. If you have questions about this, talk to your doctor.

testosterone may cause changes in the level of cholesterol and fats in your blood. If this condition occurs, your doctor may give you a medicine to adjust the cholesterol and fats. Talk to your doctor if you have concerns.

testosterone contains aluminum that may cause skin burns at the patch site if you have a procedure called a magnetic resonance imaging (MRI) scan while you are wearing the patch. You must remove the patch before your MRI to prevent skin burns.

Check with your doctor immediately if mild, burn-like skin blisters, redness, itching, or swelling occurs at the site of application during or after treatment.

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

testosterone Side Effects

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

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

More common

• Skin itching, blistering, or redness at the application site

Less common

• Blistering, burning, crusting, dryness, or flaking of the skin


• bloody or black, tarry stools


• burning feeling at the application site


• constipation


• difficult urination


• hardening or thickening of the skin under patch


• itching, scaling, severe redness, soreness, or swelling of the skin


• pelvic pain


• severe stomach pain


• vomiting of blood or material that looks like coffee grounds

Rare

• Bladder pain


• bloody or cloudy urine


• blurred vision


• difficult, burning, or painful urination


• dizziness


• frequent urge to urinate


• headache


• lower back or side pain


• nervousness


• pounding in the ears


• slow or fast heartbeat


• testicular problems

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

• Discouragement


• feeling sad or empty


• irritability


• lack of appetite


• loss of interest or pleasure


• rash


• tiredness


• trouble concentrating


• trouble sleeping

Rare

• Accelerated growth


• blemishes on the skin


• body pain


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


• cold hands and feet


• contamination of the application site


• decreased interest in sexual intercourse


• fear


• feeling of constant movement of self or surroundings


• inability to have or keep an erection


• increased appetite


• lightheadedness


• loss in sexual ability, desire, drive, or performance


• loss of bladder control


• mood or mental changes


• pimples


• sensation of spinning


• thinking abnormalities


• weakness

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: testosterone Transdermal 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 testosterone Transdermal resources

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

Compare testosterone Transdermal with other medications

• Breast Cancer, Palliative
• Delayed Puberty, Male
• Hypogonadism, Male
• Postpartum Breast Pain

Sinus Pain & Pressure

Generic Name: acetaminophen and phenylephrine (a SEET a MIN oh fen and FEN il EFF rin)

Brand Names: Alka-Seltzer Plus Cold and Sinus, Excedrin Sinus Headache Caplet, Mapap Sinus Congestion and Pain, Robitussin Nasal Relief, Sinus Congestion and Pain Daytime Cool Ice, Sinus Pain & Pressure, Sudafed PE Sinus Headache, Theraflu Daytime Severe Cold, Tylenol Sinus Congestion Daytime

What is Sinus Pain & Pressure (acetaminophen and phenylephrine)?

Acetaminophen is a pain reliever and a fever reducer.

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

The combination of acetaminophen and phenylephrine is used to treat headache, fever, body aches, stuffy nose, and sinus congestion caused by allergies, the common cold, or the flu.

Acetaminophen and phenylephrine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Sinus Pain & Pressure (acetaminophen and phenylephrine)?

Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death. Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. Do not use this medicine if you have untreated or uncontrolled diseases such as glaucoma, asthma or COPD, high blood pressure, heart disease, coronary artery disease, or overactive thyroid. Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen. Do not use acetaminophen and phenylephrine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects. Ask a doctor or pharmacist before using any other pain, cold, allergy, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP.

What should I discuss with my healthcare provider before taking Sinus Pain & Pressure (acetaminophen and phenylephrine)?

Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take acetaminophen. Do not use this medicine if you have untreated or uncontrolled diseases such as glaucoma, asthma or COPD, high blood pressure, heart disease, coronary artery disease, or overactive thyroid. Do not use this medicine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

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

• 
  

  liver disease, cirrhosis, or a history of alcoholism;

  
  


• 
  

  diabetes;

  
  


• 
  

  glaucoma;

  
  


• 
  

  epilepsy or other seizure disorder;

  
  


• 
  

  enlarged prostate or urination problems; or

  
  


• 
  

  pheochromocytoma (an adrenal gland tumor).

  
  

It is not known whether acetaminophen and phenylephrine will harm an unborn baby. Do not use this medicine without a doctor's advice if you are pregnant. Acetaminophen and phenylephrine may pass into breast milk and may harm a nursing baby. Decongestants may also slow breast milk production. Do not use this medicine without a doctor's advice if you are breast-feeding a baby.

How should I take Sinus Pain & Pressure (acetaminophen and phenylephrine)?

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

Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death. Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

Dissolve one packet of the powder in at least 4 ounces of water. Stir this mixture and drink all of it right away.

Drop the effervescent tablets into a glass of water (at least 4 ounces, or one-half cup). Stir this mixture and drink all of it right away.

Do not take for longer than 7 days in a row. Stop taking the medicine and call your doctor if you still have a fever after 3 days of use, you still have pain after 7 days (or 5 days if treating a child), if your symptoms get worse, or if you have a skin rash, ongoing headache, or any redness or swelling. If you need surgery or medical tests, tell the surgeon or doctor ahead of time if you have taken this medicine within the past few days. Store at room temperature away from moisture and heat.

What happens if I miss a dose?

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

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of acetaminophen can be fatal.

The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

Overdose symptoms may also include severe forms of some of the side effects listed in this medication guide.

What should I avoid while taking Sinus Pain & Pressure (acetaminophen and phenylephrine)?

Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP. Avoid drinking alcohol. It may increase your risk of liver damage while you are taking acetaminophen. This medicine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Sinus Pain & Pressure (acetaminophen and phenylephrine) side effects

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

• 
  

  chest pain, fast, slow, or uneven heart rate;

  
  


• 
  

  confusion, hallucinations;

  
  


• 
  

  tremor, seizure (convulsions);

  
  


• 
  

  urinating less than usual or not at all;

  
  


• 
  

  nausea, pain in your upper stomach, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of your skin or eyes); or

  
  


• 
  

  dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, chest pain, uneven heartbeats, seizure).

  
  

Less serious side effects may include:

• 
  

  dizziness, weakness;

  
  


• 
  

  mild headache;

  
  


• 
  

  mild nausea, diarrhea, upset stomach;

  
  


• 
  

  runny nose;

  
  


• 
  

  feeling nervous, restless, or anxious; or

  
  


• 
  

  sleep problems (insomnia).

  
  

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

What other drugs will affect Sinus Pain & Pressure (acetaminophen and phenylephrine)?

Ask a doctor or pharmacist if it is safe for you to take acetaminophen and phenylephrine if you are also using any of the following drugs:

• 
  

  leflunomide (Arava);

  
  


• 
  

  an antibiotic, antifungal medicine, sulfa drug, or tuberculosis medicine;

  
  


• 
  

  birth control pills or hormone replacement therapy;

  
  


• 
  

  blood pressure medication;

  
  


• 
  

  cancer medicine;

  
  


• 
  

  cholesterol-lowering medications such as Lipitor, Niaspan, Zocor, Vytorin, and others;

  
  


• 
  

  gout or arthritis medications (including gold injections);

  
  


• 
  

  HIV/AIDS medication;

  
  


• 
  

  medicines to treat psychiatric disorders;

  
  


• 
  

  an NSAID such as Advil, Aleve, Arthrotec, Cataflam, Celebrex, Indocin, Motrin, Naprosyn, Treximet, Voltaren, others; or

  
  


• 
  

  seizure medication.

  
  

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

More Sinus Pain & Pressure resources

• Sinus Pain & Pressure Side Effects (in more detail)
• Sinus Pain & Pressure Use in Pregnancy & Breastfeeding
• Sinus Pain & Pressure Drug Interactions
• Sinus Pain & Pressure Support Group
• 1 Review for Sinus Pain & Pressure - Add your own review/rating

Compare Sinus Pain & Pressure with other medications

• Headache
• Nasal Congestion
• Sinus Symptoms

Where can I get more information?

• Your pharmacist can provide more information about acetaminophen and phenylephrine.

See also: Sinus Pain & Pressure side effects (in more detail)

Toremifene

tore-EM-i-feen SIT-rate

Oral route(Tablet)

Toremifene prolongs the QTc interval in a dose- and concentration-related manner and may cause a type of ventricular tachycardia called Torsade de pointes. This could result in syncope, seizures, and/or death. Toremifene should not be prescribed to patients with congenital/acquired QT prolongation, uncorrected hypokalemia, or uncorrected hypomagnesemia. Drugs known to prolong the QT interval and strong CYP3A4 inhibitors should be avoided .

Commonly used brand name(s)

In the U.S.

• Fareston

Available Dosage Forms:

• Tablet

Therapeutic Class: Antiestrogen

Uses For toremifene

Toremifene is used to treat metastatic breast cancer (cancer that has spread) that is hormone-receptor positive in women who have already stopped menstruating (postmenopausal).

Many of the breast cancer tumors will grow when estrogen is available in the body. toremifene blocks the effects of the estrogen hormone in the body. As a result, the amount of estrogen that the tumor is exposed to is reduced, which will limit the growth of the tumor.

Before you begin treatment with toremifene, you and your doctor should talk about the good toremifene will do as well as the risks of using it.

toremifene is available only with your doctor's prescription.

Before Using toremifene

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 toremifene, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to toremifene 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

Toremifene is not indicated for use in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of toremifene in the elderly. However, elderly patients are more likely to have age-related liver problems, which may require an adjustment in the dose for patients receiving toremifene.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	D	Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking toremifene, 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 toremifene 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.

• Dronedarone


• Mesoridazine


• Pimozide


• Posaconazole


• Thioridazine


• Ziprasidone

Using toremifene 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.

• Alfuzosin


• Amiodarone


• Amitriptyline


• Amoxapine


• Apomorphine


• Arsenic Trioxide


• Asenapine


• Astemizole


• Atazanavir


• Azithromycin


• Chloroquine


• Chlorpromazine


• Ciprofloxacin


• Cisapride


• Citalopram


• Clarithromycin


• Clomipramine


• Clozapine


• Crizotinib


• Dasatinib


• Desipramine


• Disopyramide


• Dofetilide


• Dolasetron


• Droperidol


• Erythromycin


• Flecainide


• Fluconazole


• Gatifloxacin


• Gemifloxacin


• Granisetron


• Halofantrine


• Haloperidol


• Ibutilide


• Iloperidone


• Imipramine


• Indinavir


• Itraconazole


• Ketoconazole


• Lapatinib


• Levofloxacin


• Lopinavir


• Lumefantrine


• Mefloquine


• Methadone


• Moxifloxacin


• Nefazodone


• Nelfinavir


• Nilotinib


• Norfloxacin


• Nortriptyline


• Octreotide


• Ofloxacin


• Ondansetron


• Paliperidone


• Pazopanib


• Perflutren Lipid Microsphere


• Procainamide


• Prochlorperazine


• Promethazine


• Propafenone


• Protriptyline


• Quetiapine


• Quinidine


• Quinine


• Ranolazine


• Ritonavir


• Salmeterol


• Saquinavir


• Sodium Phosphate


• Sorafenib


• Sotalol


• Sparfloxacin


• Sunitinib


• Telavancin


• Telithromycin


• Terfenadine


• Tetrabenazine


• Trazodone


• Trifluoperazine


• Trimipramine


• Vandetanib


• Vardenafil


• Vemurafenib


• Venlafaxine


• Voriconazole

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.

Using toremifene with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use toremifene, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other Medical Problems

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

• Blood clots, or history of—Use is usually not recommended in patients with this condition.

• Bone problems or


• Congestive heart failure or


• Heart rhythm problems (e.g., QT prolongation) or


• Leukopenia (low white blood cells in the blood) or


• Thrombocytopenia (low platelets in the blood)—Use with caution. May make these conditions worse.

• Heart rhythm problems (e.g., congenital or acquired long QT syndrome) or


• Hypokalemia (low potassium in the blood), uncorrected or


• Hypomagnesemia (low magnesium in the blood), uncorrected—Should not be used in patients with these conditions.

• Liver disease (e.g., cirrhosis or fibrosis)—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Unusual growth of the lining of the uterus (womb)—Long-term use of toremifene is usually not recommended.

Proper Use of toremifene

Take toremifene only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

Toremifene sometimes causes mild nausea and vomiting. However, it may have to be taken for several weeks or months to be effective. Even if you begin to feel ill, do not stop using toremifene without first checking with your doctor. Ask your doctor for ways to lessen these effects.

You may take toremifene with or without food.

Dosing

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

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

• For oral dosage form (tablets):
  
  • For breast cancer:
    
    • Adults—60 milligrams (mg) once a day.
    
    
    • Children—Use is not recommended.
    
    
  
  

Missed Dose

If you miss a dose of toremifene, 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.

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

Precautions While Using toremifene

It is very important that your doctor check your progress at regular visits to make sure that toremifene is working properly. Blood tests may be needed to check for unwanted effects. It is important for women to have regular gynecologic check-ups while taking toremifene.

It is unlikely that a postmenopausal woman may become pregnant. But, you should know that using toremifene while you are pregnant could harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

toremifene can cause changes in heart rhythms, such as a condition called QT prolongation. It may change the way your heart beats and cause fainting or serious side effects in some patients. Contact your doctor right away if you have any symptoms of heart rhythm problems, such as fast, pounding, or uneven heartbeats.

Hypercalcemia (high calcium in the blood) and tumor flare (increased size of a tumor) are more likely to occur in patients with bone problems who are taking toremifene. Stop using toremifene and check with your doctor right away if you have abdominal or stomach pain, confusion, constipation, depression, dry mouth, increased urination, loss of appetite, metallic taste, muscle weakness, pain and swelling in the bones and muscles surrounding a tumor, thirst, unusual tiredness, or weight loss.

Toremifene can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.


• Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in the urine or stools; or pinpoint red spots on your skin.


• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.


• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.


• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.


• Avoid contact sports or other situations where bruising or injury could occur.

toremifene may cause you to have bleeding from the vagina, especially when you first start using it. If the bleeding continues or is bothersome, check with your doctor right away.

Grapefruits and grapefruit juice may increase the effects of toremifene by increasing the amount of toremifene in your body. You should not eat grapefruit or drink grapefruit juice while you taking toremifene.

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

toremifene 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.

Also, because of the way toremifene acts on the body, there is a chance that it might cause other unwanted effects that may not occur until months or years after the medicine is used. Some patients who have used toremifene have developed cancer of the uterus (womb), although it is not known for sure if it was caused by the medicine. Discuss this possible effect with your doctor.

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

Less common

• Abdominal or stomach pain


• anxiety


• arm, back, or jaw pain


• blurred vision


• change in vaginal discharge


• changes in skin color


• changes in vision


• chest pain or discomfort


• chest tightness or heaviness


• confusion


• constipation


• cough


• decreased urine output


• depression


• dilated neck veins


• dizziness or lightheadedness


• dry mouth


• extreme fatigue


• fainting


• fast, slow, or irregular heartbeat


• headache


• inability to speak incoherent speech


• increased urination


• irregular breathing


• irregular heartbeat


• loss of appetite


• metallic taste


• muscle weakness


• nausea


• pain or discomfort in the arms, jaw, back, or neck


• pain or feeling of pressure in the pelvis


• pain, tenderness, or swelling of the foot or leg


• seizures


• severe or sudden headache


• shortness of breath


• slurred speech


• sudden shortness of breath or troubled breathing


• sweating


• swelling of the face, fingers, feet, or lower legs


• temporary blindness


• tenderness, pain, swelling, warmth, skin discoloration, and prominent superficial veins over the affected area


• thirst


• tightness in the chest


• troubled breathing


• unusual tiredness


• vaginal bleeding


• vomiting


• weakness in the arm and/or leg on one side of the body, sudden and severe


• weight gain


• weight loss


• wheezing

Rare

• Chest pain

Incidence not known

• Black, tarry stools


• bleeding gums


• blood in the urine or stools


• chills


• clay-colored stools


• dark urine


• dizziness


• fever


• headache


• itching


• painful or difficult urination


• pinpoint red spots on the skin


• rash


• sore throat


• sores, ulcers, or white spots on the lips or in the mouth


• swollen glands


• unpleasant breath odor


• unusual bleeding or bruising


• unusual tiredness or weakness


• vomiting of blood


• yellow eyes or skin

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

More common

• Blindness


• decreased vision


• dry eyes


• feeling of warmth


• redness of the face, neck, arms, and occasionally, upper chest


• sudden sweating


• sweating


• white or brownish vaginal discharge

Less common

• Bone pain


• changes in vision


• double vision


• eye pain


• tearing

Incidence not known

• Blistering, crusting, irritation, itching, or reddening of the skin


• cracked, dry, or scaly skin


• depression


• difficulty having a bowel movement (stool)


• dizziness or lightheadedness


• feeling of constant movement of self or surroundings


• feeling unusually cold


• hair loss


• itching skin


• lack or loss of strength


• partial or slight paralysis


• sensation of spinning


• shakiness in the legs, arms, hands, or feet


• shivering


• thinning of the hair


• trembling or shaking of the hands or feet

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: toremifene 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 toremifene resources

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• Toremifene Dosage
• Toremifene Use in Pregnancy & Breastfeeding
• Toremifene Drug Interactions
• Toremifene Support Group
• 0 Reviews for Toremifene - Add your own review/rating

• toremifene Concise Consumer Information (Cerner Multum)


• Toremifene MedFacts Consumer Leaflet (Wolters Kluwer)


• Fareston Prescribing Information (FDA)


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Saxagliptin and metformin

sax-a-GLIP-tin hye-droe-KLOR-ide, met-FOR-min hye-droe-KLOR-ide

Oral route(Tablet, Extended Release)

Lactic acidosis is a rare, but serious complication that can occur due to metformin accumulation. The risk of lactic acidosis increases with conditions such as sepsis, dehydration, excessive alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure. Discontinue therapy and hospitalize the patient immediately for suspected lactic acidosis .

Commonly used brand name(s)

In the U.S.

• Kombiglyze XR

Available Dosage Forms:

• Tablet, Extended Release

Therapeutic Class: Antidiabetic

Pharmacologic Class: Saxagliptin

Chemical Class: Metformin

Uses For saxagliptin and metformin

Saxagliptin and metformin combination is used to treat high blood sugar levels caused by type 2 diabetes. With this type of diabetes, insulin produced by the pancreas is not able to get sugar into the cells of the body where it can work properly. Using saxagliptin and metformin will help to lower blood sugar when it is too high and help restore the way you use food to make energy.

Many people can control type 2 diabetes with diet alone or diet and exercise. Following a specially planned diet and exercising will always be important when you have diabetes, even when you are taking medicines. To work properly, the amount of saxagliptin and metformin combination you take must be balanced against the amount and type of food you eat and the amount of exercise you do. If you change your diet, your exercise, or both, you will want to test your blood sugar to find out if it is too low. Your doctor will teach you what to do if this happens.

Saxagliptin and metformin combination does not help patients who have insulin-dependent or type 1 diabetes, because they cannot produce insulin from their pancreas. Their blood glucose is best controlled by insulin injections.

saxagliptin and metformin is available only with your doctor's prescription.

Before Using saxagliptin and metformin

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 saxagliptin and metformin, the following should be considered:

Allergies

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

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of saxagliptin and metformin combination in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of saxagliptin and metformin combination in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution for patients receiving saxagliptin and metformin. saxagliptin and metformin is not recommended in patients 80 years of age and older who have kidney problems.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	B	Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking saxagliptin and metformin, 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 saxagliptin and metformin 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.

• Acetrizoic Acid


• Diatrizoate


• Ethiodized Oil


• Iobenzamic Acid


• Iobitridol


• Iocarmic Acid


• Iocetamic Acid


• Iodamide


• Iodipamide


• Iodixanol


• Iodohippuric Acid


• Iodopyracet


• Iodoxamic Acid


• Ioglicic Acid


• Ioglycamic Acid


• Iohexol


• Iomeprol


• Iopamidol


• Iopanoic Acid


• Iopentol


• Iophendylate


• Iopromide


• Iopronic Acid


• Ioseric Acid


• Iosimide


• Iotasul


• Iothalamate


• Iotrolan


• Iotroxic Acid


• Ioversol


• Ioxaglate


• Ioxitalamic Acid


• Ipodate


• Metrizamide


• Metrizoic Acid


• Tyropanoate Sodium

Using saxagliptin and metformin 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.

• Acetazolamide


• Alatrofloxacin


• Balofloxacin


• Cimetidine


• Ciprofloxacin


• Clinafloxacin


• Dichlorphenamide


• Dofetilide


• Enoxacin


• Fleroxacin


• Flumequine


• Gatifloxacin


• Gemifloxacin


• Grepafloxacin


• Levofloxacin


• Lomefloxacin


• Moxifloxacin


• Norfloxacin


• Ofloxacin


• Pefloxacin


• Prulifloxacin


• Rufloxacin


• Sparfloxacin


• Temafloxacin


• Topiramate


• Tosufloxacin


• Trovafloxacin Mesylate


• Zonisamide

Using saxagliptin and metformin 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.

• Acebutolol


• Alprenolol


• Atenolol


• Betaxolol


• Bevantolol


• Bisoprolol


• Bitter Melon


• Bucindolol


• Carteolol


• Carvedilol


• Celiprolol


• Cephalexin


• Clorgyline


• Dilevalol


• Enalaprilat


• Enalapril Maleate


• Esmolol


• Fenugreek


• Glucomannan


• Guar Gum


• Iproniazid


• Isocarboxazid


• Labetalol


• Levobunolol


• Mepindolol


• Metipranolol


• Metoprolol


• Moclobemide


• Nadolol


• Nebivolol


• Nialamide


• Oxprenolol


• Pargyline


• Penbutolol


• Phenelzine


• Pindolol


• Procarbazine


• Propranolol


• Psyllium


• Rifampin


• Selegiline


• Sotalol


• Talinolol


• Tertatolol


• Timolol


• Toloxatone


• Tranylcypromine


• Trospium

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

• Alcohol, excessive use or


• Underactive adrenal glands or


• Underactive pituitary gland or


• Undernourished condition or


• Weakened physical condition—These conditions could make you more sensitive to the effects of low blood sugar.

• Alcoholism, history of or


• Gallstones or


• Hypertriglyceridemia (high triglycerides or fats in the blood)—May increase risk of having pancreatitis.

• Anemia (low levels of red blood cells) or


• Pancreatitis (inflammation and swelling of the pancreas) or


• Vitamin B12 deficiency—Use with caution. May make these conditions worse.

• Angioedema (swelling of the face, lips, tongue, or throat) to similar medicines (e.g., linagliptin, sitagliptin), history of—Use with caution. Patients who have experienced this condition may be at increased risk of getting angioedema with saxagliptin.

• Congestive heart failure, acute or unstable or


• Dehydration or


• Heart attack, acute or


• Hypoxemia (decreased oxygen in the blood) or


• Kidney disease or


• Liver disease or


• Sepsis (severe infection) or


• Shock (low blood pressure, blood circulation is poor)—A rare condition called lactic acidosis can occur. Talk with your doctor if you have concerns about this.

• Diabetic ketoacidosis (ketones in the blood) or


• Kidney disease, severe or


• Liver disease, severe or


• Metabolic acidosis (acid in the blood) or


• Type I diabetes—Should not be used in patients with these conditions.

• Fever or


• Infection or


• Surgery or


• Trauma—These conditions may cause temporary problems with blood sugar control and your doctor may want to treat you with insulin.

Proper Use of saxagliptin and metformin

saxagliptin and metformin usually comes with a Medication Guide. Read the information carefully and make sure you understand it before taking saxagliptin and metformin. If you have any questions, ask your doctor.

Carefully follow the special meal plan your doctor gave you. This is a very important part of controlling your condition, and is necessary if the medicine is to work properly. Also, exercise regularly and test for sugar in your blood or urine as directed.

Saxagliptin and metformin combination should be taken with the evening meal to help reduce stomach or bowel side effects that may occur during the first few weeks of treatment.

Swallow the extended-release tablet whole. Do not crush, break, or chew it.

While taking the extended-release tablet, part of the tablet may pass into your stools. This is normal and is nothing to worry about.

Dosing

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

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

• For oral dosage form (extended-release tablets):
  
  • For type 2 diabetes:
    
    • For patients taking metformin alone:
      
      • Adults—The metformin dose is the same as the dose you are already taking. Your doctor may adjust your dose until your blood sugar is controlled. However, the dose is usually not more than 5 milligrams (mg) of saxagliptin and 2000 mg of metformin once a day.
      
      
      • Children—Use and dose must be determined by your doctor.
      
      
    
    
    • For patients taking saxagliptin alone:
      
      • Adults—At first, one tablet containing 5 milligrams (mg) of saxagliptin and 500 mg of metformin once a day. Your doctor may gradually increase your dose until your blood sugar is controlled. However, the dose is usually not more than 5 mg of saxagliptin and 2000 mg of metformin once a day.
      
      
      • Children—Use and dose must be determined by your doctor.
      
      
    
    
    • For patients using 2.5 milligrams (mg) of saxagliptin and extended-release metformin together:
      
      • Adults—One tablet containing 2.5 mg of saxagliptin and 1000 mg of metformin once a day.
      
      
      • Children—Use and dose must be determined by your doctor.
      
      
    
    
  
  

Missed Dose

If you miss a dose of saxagliptin and metformin, 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.

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

Precautions While Using saxagliptin and metformin

Your doctor will want to check your progress at regular visits, especially during the first few weeks that you take saxagliptin and metformin. Blood and urine tests may be needed to check for unwanted effects.

Let your doctor or dentist know you are taking saxagliptin and metformin. Your doctor may advise you to temporarily stop taking saxagliptin and metformin before you have major surgery or diagnostic tests including procedures that use contrast dye.

Under certain conditions, too much metformin can cause lactic acidosis. The symptoms of lactic acidosis are severe and quick to appear, and usually occur when other health problems not related to the medicine are present and are very severe, such as a heart attack or kidney failure. Symptoms of lactic acidosis include: abdominal or stomach discomfort; decreased appetite; diarrhea; fast or shallow breathing; a general feeling of discomfort; muscle pain or cramping; and unusual sleepiness, tiredness, or weakness.

If symptoms of lactic acidosis occur, you should get immediate emergency medical help.

Pancreatitis (swelling and inflammation of the pancreas) may occur while you are using saxagliptin and metformin. Stop using saxagliptin and metformin and check with your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

saxagliptin and metformin may cause serious types of allergic reactions, including anaphylaxis and angioedema. These conditions may be life-threatening and require immediate medical attention. Stop using saxagliptin and metformin and check with your doctor right away if you have a rash; itching; a large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs; trouble with breathing; or chest tightness while you are using saxagliptin and metformin.

It is very important to carefully follow any instructions from your health care team about:

• Alcohol—Drinking alcohol may cause severe low blood sugar. Discuss this with your health care team.


• Other medicines—Do not take other medicines unless they have been discussed with your doctor. This especially includes nonprescription medicines such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems.


• Counseling—Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, patients with diabetes may need special counseling about diabetes medicine dosing changes that might occur with lifestyle changes, such as changes in exercise or diet. Furthermore, counseling on contraception and pregnancy may be needed, because of the problems that can occur in patients with diabetes during pregnancy.


• Travel—Keep a recent prescription and your medical history with you. Be prepared for an emergency as you would normally. Make allowances for changing time zones and keep your meal times as close as possible to your usual meal times.


• In case of emergency—There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says you have diabetes and that lists all of your medicines.

Saxagliptin and metformin combination can cause low blood sugar. However, this can also occur if you delay or miss a meal or snack, drink alcohol, exercise more than usual, cannot eat because of nausea or vomiting, take certain medicines, or take saxagliptin and metformin combination with another type of diabetes medicine. The symptoms of low blood sugar must be treated before they lead to unconsciousness (passing out). Different people feel different symptoms of low blood sugar. It is important that you learn which symptoms of low blood sugar you usually have so you can treat it quickly.

Symptoms of hypoglycemia (low blood sugar) include: anxiety; behavior changes similar to being drunk; blurred vision; cold sweats; confusion; cool, pale skin; difficulty with thinking; drowsiness; excessive hunger; fast heartbeat; headache (continuing); nausea; nervousness; nightmares; restless sleep; shakiness; slurred speech; or unusual tiredness or weakness.

If symptoms of low blood sugar occur, eat glucose tablets or gel, corn syrup, honey, or sugar cubes; or drink fruit juice, non-diet soft drink, or sugar dissolved in water. Also, check your blood for low blood sugar. Glucagon is used in emergency situations when severe symptoms such as seizures (convulsions) or unconsciousness occur. Have a glucagon kit available, along with a syringe and needle, and know how to use it. The members of your household should also know how to use it.

Symptoms of hyperglycemia (high blood sugar) include: blurred vision; drowsiness; dry mouth; flushed, dry skin; fruit-like breath odor; increased urination (frequency and volume); ketones in the urine; loss of appetite; sleepiness; stomachache, nausea, or vomiting; tiredness; troubled breathing (rapid and deep); unconsciousness; or unusual thirst.

High blood sugar may occur if you do not exercise as much as usual, have a fever or infection, do not take enough or skip a dose of your diabetes medicine, or overeat or do not follow your meal plan.

If symptoms of high blood sugar occur, check your blood sugar level and then call your doctor for instructions.

saxagliptin and metformin is only part of a complete program for controlling diabetes. It is important that you always eat a healthy diet, watch your weight, and get regular exercise.

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

saxagliptin and metformin Side Effects

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

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

More common

• Anxiety


• bladder pain


• bloody or cloudy urine


• blurred vision


• body aches or pain


• chills


• cold sweats


• coma


• confusion


• cool, pale skin


• cough


• depression


• difficult, burning, or painful urination


• difficulty with breathing


• dizziness


• ear congestion


• fast heartbeat


• fever


• frequent urge to urinate


• headache


• increased hunger


• loss of voice


• lower back or side pain


• nasal congestion


• nausea


• nervousness


• nightmares


• runny nose


• seizures


• shakiness


• slurred speech


• sneezing


• sore throat


• unusual tiredness or weakness

Rare

• Cough or hoarseness

Incidence not known

• Black, tarry stools


• bleeding gums


• blood in the urine or stools


• constipation


• darkened urine


• difficulty with swallowing


• hives


• indigestion


• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs


• loss of appetite


• pains in the stomach, side, or abdomen, possibly radiating to the back


• pinpoint red spots on the skin


• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue


• shortness of breath


• skin rash


• tightness in the chest


• unusual bleeding or bruising


• vomiting


• wheezing


• yellow eyes or skin

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

More common

• Diarrhea


• muscle aches


• stuffy nose

Less common

• Abdominal or stomach pain


• itching


• pain or tenderness around the eyes and cheekbones


• redness of the skin


• weakness


• welts

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.

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.

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