Arixtra

Dosage Form: injection, solution
FULL PRESCRIBING INFORMATION

WARNING: SPINAL/EPIDURAL HEMATOMAS

Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH), heparinoids, or fondaparinux sodium and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

● use of indwelling epidural catheters

● concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants

● a history of traumatic or repeated epidural or spinal puncture

● a history of spinal deformity or spinal surgery

Monitor patients frequently for signs and symptoms of neurologic impairment. If neurologic compromise is noted, urgent treatment is necessary.

Consider the benefit and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis. [See Warnings and Precautions (5.5) and Drug Interactions (7).]

Indications and Usage for Arixtra

Prophylaxis of Deep Vein Thrombosis

Arixtra® is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE):

• in patients undergoing hip fracture surgery, including extended prophylaxis;


• in patients undergoing hip replacement surgery;


• in patients undergoing knee replacement surgery;


• in patients undergoing abdominal surgery who are at risk for thromboembolic complications.

Treatment of Acute Deep Vein Thrombosis

Arixtra is indicated for the treatment of acute deep vein thrombosis when administered in conjunction with warfarin sodium.

Treatment of Acute Pulmonary Embolism

Arixtra is indicated for the treatment of acute pulmonary embolism when administered in conjunction with warfarin sodium when initial therapy is administered in the hospital.

Arixtra Dosage and Administration

Do not mix other medications or solutions with Arixtra. Administer Arixtra only subcutaneously.

Deep Vein Thrombosis Prophylaxis Following Hip Fracture, Hip Replacement, and Knee Replacement Surgery

In patients undergoing hip fracture, hip replacement, or knee replacement surgery, the recommended dose of Arixtra is 2.5 mg administered by subcutaneous injection once daily after hemostasis has been established. Administer the initial dose no earlier than 6 to 8 hours after surgery. Administration of Arixtra earlier than 6 hours after surgery increases the risk of major bleeding. The usual duration of therapy is 5 to 9 days; up to 11 days of therapy was administered in clinical trials.

In patients undergoing hip fracture surgery, an extended prophylaxis course of up to 24 additional days is recommended. In patients undergoing hip fracture surgery, a total of 32 days (peri-operative and extended prophylaxis) was administered in clinical trials. [See Warnings and Precautions (5.6), Adverse Reactions (6), and Clinical Studies (14)].

Deep Vein Thrombosis Prophylaxis Following Abdominal Surgery

In patients undergoing abdominal surgery, the recommended dose of Arixtra is 2.5 mg administered by subcutaneous injection once daily after hemostasis has been established. Administer the initial dose no earlier than 6 to 8 hours after surgery. Administration of Arixtra earlier than 6 hours after surgery increases the risk of major bleeding. The usual duration of administration is 5 to 9 days, and up to 10 days of Arixtra was administered in clinical trials.

Deep Vein Thrombosis and Pulmonary Embolism Treatment

In patients with acute symptomatic DVT and in patients with acute symptomatic PE, the recommended dose of Arixtra is 5 mg (body weight <50 kg), 7.5 mg (body weight 50 to 100 kg), or 10 mg (body weight >100 kg) by subcutaneous injection once daily (Arixtra treatment regimen). Initiate concomitant treatment with warfarin sodium as soon as possible, usually within 72 hours. Continue treatment with Arixtra for at least 5 days and until a therapeutic oral anticoagulant effect is established (INR 2 to 3). The usual duration of administration of Arixtra is 5 to 9 days; up to 26 days of Arixtra injection was administered in clinical trials. [See Warnings and Precautions (5.6), Adverse Reactions (6), and Clinical Studies (14)].

Hepatic Impairment

No dose adjustment is recommended in patients with mild to moderate hepatic impairment, based upon single-dose pharmacokinetic data. Pharmacokinetic data are not available for patients with severe hepatic impairment. Patients with hepatic impairment may be particularly vulnerable to bleeding during Arixtra therapy. Observe these patients closely for signs and symptoms of bleeding. [See Clinical Pharmacology (12.4).]

Instructions for Use

Arixtra Injection is provided in a single-dose, prefilled syringe affixed with an automatic needle protection system. Arixtra is administered by subcutaneous injection. It must not be administered by intramuscular injection. Arixtra is intended for use under a physician’s guidance. Patients may self-inject only if their physician determines that it is appropriate and the patients are trained in subcutaneous injection techniques.

Prior to administration, visually inspect Arixtra to ensure the solution is clear and free of particulate matter.

To avoid the loss of drug when using the prefilled syringe, do not expel the air bubble from the syringe before the injection. Administration should be made in the fatty tissue, alternating injection sites (e.g., between the left and right anterolateral or the left and right posterolateral abdominal wall).

To administer Arixtra:

1. Wipe the surface of the injection site with an alcohol swab.
2. Hold the syringe with either hand and use your other hand to twist the rigid needle guard (covers the needle) counter-clockwise. Pull the rigid needle guard straight off the needle (Figure 1). Discard the needle guard. 3. Do not try to remove the air bubbles from the syringe before giving the injection. 4. Pinch a fold of skin at the injection site between your thumb and forefinger and hold it throughout the injection. 5. Hold the syringe with your thumb on the top pad of the plunger rod and your next 2 fingers on the finger grips on the syringe barrel. Pay attention to avoid sticking yourself with the exposed needle (Figure 2).
6. Insert the full length of the syringe needle perpendicularly into the skin fold held between the thumb and forefinger (Figure 3). 7. Push the plunger rod firmly with your thumb as far as it will go. This will ensure you have injected all the contents of the syringe (Figure 4).
8. When you have injected all the contents of the syringe, the plunger should be released. The plunger will then rise automatically while the needle withdraws from the skin and retracts into the security sleeve. Discard the syringe into the sharps container. 9. You will know that the syringe has worked when: The needle is pulled back into the security sleeve and the white safety indicator appears above the upper body. You may also hear or feel a soft click when the plunger rod is released fully.

Dosage Forms and Strengths

Single-dose, prefilled syringes containing either 2.5 mg, 5 mg, 7.5 mg, or 10 mg of fondaparinux.

Contraindications

Arixtra is contraindicated in the following conditions:

• Severe renal impairment (creatinine clearance [CrCl] <30 mL/min). [See Warnings and Precautions (5.2) and Use in Specific Populations (8.6).]


• Active major bleeding.


• Bacterial endocarditis.


• Thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of fondaparinux sodium.


• Body weight <50 kg (venous thromboembolism [VTE] prophylaxis only)  [see Warnings and Precautions (5.3)].

Warnings and Precautions

Hemorrhage

Use Arixtra with extreme caution in conditions with increased risk of hemorrhage, such as congenital or acquired bleeding disorders, active ulcerative and angiodysplastic gastrointestinal disease, hemorrhagic stroke, uncontrolled arterial hypertension, diabetic retinopathy, or shortly after brain, spinal, or ophthalmological surgery. Isolated cases of elevated aPTT temporally associated with bleeding events have been reported following administration of Arixtra (with or without concomitant administration of other anticoagulants) [See Adverse Reactions (6.5)].

Do not administer agents that enhance the risk of hemorrhage with Arixtra unless essential for the management of the underlying condition, such as vitamin K antagonists for the treatment of VTE. If co-administration is essential, closely monitor patients for signs and symptoms of bleeding.

Do not administer the initial dose of Arixtra earlier than 6 to 8 hours after surgery. Administration earlier than 6 hours after surgery increases risk of major bleeding [see Dosage and Administration (2) and Adverse Reactions (6.1)].

Renal Impairment and Bleeding Risk

Arixtra increases the risk of bleeding in patients with impaired renal function due to reduced clearance [see Clinical Pharmacology (12.4)].

The incidence of major bleeding by renal function status reported in clinical trials of patients receiving Arixtra for VTE surgical prophylaxis is provided in Table 1. In these patient populations, the following is recommended:

• Do not use Arixtra for VTE prophylaxis and treatment in patients with CrCl <30 mL/min [see Contraindications (4)].


• Use Arixtra with caution in patients with CrCl 30 to 50 mL/min.

Table 1. Incidence of Major Bleeding in Patients Treated With Arixtra by Renal Function Status for Surgical Prophylaxis and Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)

		Degree of Renal Impairment
Population	Timing of Dose	Normal % (n/N)	Mild % (n/N)	Moderate % (n/N)	Severe % (n/N)
CrCl (mL/min)		≥80	≥50 - <80	≥30 - <50	<30
Orthopedic surgerya	Overall	1.6% (25/1,565)	2.4% (31/1,288)	3.8% (19/504)	4.8% (4/83)
	6-8 hours after surgery	1.8% (16/905)	2.2% (15/675)	2.3% (6/265)	0% (0/40)
Abdominal surgery	Overall	2.1% (13/606)	3.6% (22/613)	6.7% (12/179)	7.1% (1/14)
	6-8 hours after surgery	2.1% (10/467)	3.3% (16/481)	5.8% (8/137)	7.7% (1/13)
DVT and PE Treatment		0.4% (4/1,132)	1.6% (12/733)	2.2% (7/318)	7.3% (4/55)

CrCl = creatinine clearance.

a Hip fracture, hip replacement, and knee replacement surgery prophylaxis.

Assess renal function periodically in patients receiving Arixtra. Discontinue the drug immediately in patients who develop severe renal impairment while on therapy. After discontinuation of Arixtra, its anticoagulant effects may persist for 2 to 4 days in patients with normal renal function (i.e., at least 3 to 5 half-lives). The anticoagulant effects of Arixtra may persist even longer in patients with renal impairment [see Clinical Pharmacology (12.4)].

Body Weight <50 Kg and Bleeding Risk

Arixtra increases the risk for bleeding in patients who weigh less than 50 kg, compared to patients with higher weights.

In patients who weigh less than 50 kg:

• Do not administer Arixtra as prophylactic therapy for patients undergoing hip fracture, hip replacement, or knee replacement surgery and abdominal surgery [see Contraindications (4)].


• Use Arixtra with caution in the treatment of PE and DVT.

During the randomized clinical trials of VTE prophylaxis in the peri-operative period following hip fracture, hip replacement, or knee replacement surgery and abdominal surgery, major bleeding occurred at a higher rate among patients with a body weight <50 kg compared to those with a body weight >50 kg (5.4% versus 2.1% in patients undergoing hip fracture, hip replacement, or knee replacement surgery; 5.3% versus 3.3% in patients undergoing abdominal surgery).

Thrombocytopenia

Thrombocytopenia can occur with the administration of Arixtra. Thrombocytopenia of any degree should be monitored closely. Discontinue Arixtra if the platelet count falls below 100,000/mm3. Moderate thrombocytopenia (platelet counts between 100,000/mm3 and 50,000/mm3) occurred at a rate of 3.0% in patients given Arixtra 2.5 mg in the peri-operative hip fracture, hip replacement, or knee replacement surgery and abdominal surgery clinical trials. Severe thrombocytopenia (platelet counts less than 50,000/mm3) occurred at a rate of 0.2% in patients given Arixtra 2.5 mg in these clinical trials. During extended prophylaxis, no cases of moderate or severe thrombocytopenia were reported.

Moderate thrombocytopenia occurred at a rate of 0.5% in patients given the Arixtra treatment regimen in the DVT and PE treatment clinical trials. Severe thrombocytopenia occurred at a rate of 0.04% in patients given the Arixtra treatment regimen in the DVT and PE treatment clinical trials.

Isolated occurrences of thrombocytopenia with thrombosis that manifested similar to heparin-induced thrombocytopenia have been reported with the use of Arixtra in postmarketing experience. [See Adverse Reactions (6.5).]

Neuraxial Anesthesia and Post-operative Indwelling Epidural Catheter Use

Spinal or epidural hematomas, which may result in long-term or permanent paralysis, can occur with the use of anticoagulants and neuraxial (spinal/epidural) anesthesia or spinal puncture. The risk of these events may be higher with post-operative use of indwelling epidural catheters or concomitant use of other drugs affecting hemostasis such as NSAIDs [see Boxed Warning]. In the postmarketing experience, epidural or spinal hematoma has been reported in association with the use of Arixtra by subcutaneous (SC) injection. Monitor patients undergoing these procedures for signs and symptoms of neurologic impairment. Consider the potential risks and benefits before neuraxial intervention in patients anticoagulated or who may be anticoagulated for thromboprophylaxis.

Monitoring: Laboratory Tests

Routine coagulation tests such as Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) are relatively insensitive measures of the activity of Arixtra and international standards of heparin or LMWH are not calibrators to measure anti-Factor Xa activity of Arixtra. If unexpected changes in coagulation parameters or major bleeding occur during therapy with Arixtra, discontinue Arixtra. In postmarketing experience, isolated occurrences of aPTT elevations have been reported following administration of Arixtra [see Adverse Reactions (6.5)].

Periodic routine complete blood counts (including platelet count), serum creatinine level, and stool occult blood tests are recommended during the course of treatment with Arixtra.

The anti-Factor Xa activity of fondaparinux sodium can be measured by anti-Xa assay using the appropriate calibrator (fondaparinux). The activity of fondaparinux sodium is expressed in milligrams (mg) of the fondaparinux and cannot be compared with activities of heparin or low molecular weight heparins. [See Clinical Pharmacology (12.2, 12.3).]

Latex

The packaging (needle guard) of the prefilled syringe of Arixtra contains dry natural latex rubber that may cause allergic reactions in latex sensitive individuals.

Adverse Reactions

The most serious adverse reactions reported with Arixtra are bleeding complications and thrombocytopenia [see Warnings and Precautions (5)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The adverse reaction information below is based on data from 8,877 patients exposed to Arixtra in controlled trials of hip fracture, hip replacement, major knee, or abdominal surgeries, and DVT and PE treatment. These trials consisted of the following:

• 2 peri-operative dose-response trials (n = 989)


• 4 active-controlled peri-operative VTE prophylaxis trials with enoxaparin sodium (n = 3,616), an extended VTE prophylaxis trial (n = 327), and an active-controlled trial with dalteparin sodium (n = 1,425)


• a dose-response trial (n = 111) and an active-controlled trial with enoxaparin sodium in DVT treatment (n = 1,091)


• an active-controlled trial with heparin in PE treatment (n = 1,092)

Hemorrhage

During administration of Arixtra, the most common adverse reactions were bleeding complications [see Warnings and Precautions (5.1)].

Hip Fracture, Hip Replacement, and Knee Replacement Surgery: The rates of major bleeding events reported during the hip fracture, hip replacement, or knee replacement surgery clinical trials with Arixtra 2.5 mg are provided in Table 2.

Table 2. Bleeding Across Randomized, Controlled Hip Fracture, Hip Replacement, and Knee Replacement Surgery Studies

	Peri-Operative Prophylaxis (Day 1 to Day 7 ± 1 post-surgery)		Extended Prophylaxis (Day 8 to Day 28 ± 2 post-surgery)
	Arixtra 2.5 mg SC once daily N = 3,616	Enoxaparin Sodiuma, b N = 3,956	Arixtra 2.5 mg SC once daily N = 327	Placebo SC once daily N = 329
Major bleedingc	96 (2.7%)	75 (1.9%)	8 (2.4%)	2 (0.6%)
Hip fracture	18/831 (2.2%)	19/842 (2.3%)	8/327 (2.4%)	2/329 (0.6%)
Hip replacement	67/2,268 (3.0%)	55/2,597 (2.1%)	—	—
Knee replacement	11/517 (2.1%)	1/517 (0.2%)	—	—
Fatal bleeding	0 (0.0%)	1 (<0.1%)	0 (0.0%)	0 (0.0%)
Non-fatal bleeding at critical site	0 (0.0%)	1 (<0.1%)	0 (0.0%)	0 (0.0%)
Re-operation due to bleeding	12 (0.3%)	10 (0.3%)	2 (0.6%)	2 (0.6%)
BI ≥2d	84 (2.3%)	63 (1.6%)	6 (1.8%)	0 (0.0%)
Minor bleedinge	109 (3.0%)	116 (2.9%)	5 (1.5%)	2 (0.6%)

a Enoxaparin sodium dosing regimen: 30 mg every 12 hours or 40 mg once daily.

b Not approved for use in patients undergoing hip fracture surgery.

c Major bleeding was defined as clinically overt bleeding that was (1) fatal, (2) bleeding at critical site (e.g. intracranial, retroperitoneal, intraocular, pericardial, spinal, or into adrenal gland), (3) associated with re-operation at operative site, or (4) with a bleeding index (BI) ≥2.

d BI ≥2: Overt bleeding associated only with a bleeding index (BI) ≥2 calculated as [number of whole blood or packed red blood cell units transfused + [(pre-bleeding) – (post-bleeding)] hemoglobin (g/dL) values].

e Minor bleeding was defined as clinically overt bleeding that was not major.

A separate analysis of major bleeding across all randomized, controlled, peri-operative, prophylaxis clinical studies of hip fracture, hip replacement, or knee replacement surgery according to the time of the first injection of Arixtra after surgical closure was performed in patients who received Arixtra only post-operatively. In this analysis, the incidences of major bleeding were as follows: <4 hours was 4.8% (5/104), 4 to 6 hours was 2.3% (28/1,196), 6 to 8 hours was 1.9% (38/1,965). In all studies, the majority (≥75%) of the major bleeding events occurred during the first 4 days after surgery.

Abdominal Surgery: In a randomized study of patients undergoing abdominal surgery, Arixtra 2.5 mg once daily (n = 1,433) was compared with dalteparin 5,000 IU once daily (n = 1,425). Bleeding rates are shown in Table 3.

Table 3. Bleeding in the Abdominal Surgery Study

	Arixtra 2.5 mg SC once daily	Dalteparin Sodium 5,000 IU SC once daily
	N = 1,433	N = 1,425
Major bleedinga	49 (3.4%)	34 (2.4%)
Fatal bleeding	2 (0.1%)	2 (0.1%)
Non-fatal bleeding at critical site	0 (0.0%)	0 (0.0%)
Other non-fatal major bleeding
Surgical site	38 (2.7%)	26 (1.8%)
Non-surgical site	9 (0.6%)	6 (0.4%)
Minor bleedingb	31 (2.2%)	23 (1.6%)

a Major bleeding was defined as bleeding that was (1) fatal, (2) bleeding at the surgical site leading to intervention, (3) non-surgical bleeding at a critical site (e.g. intracranial, retroperitoneal, intraocular, pericardial, spinal, or into adrenal gland), or leading to an intervention, and/or with a bleeding index (BI) ≥2.

b Minor bleeding was defined as clinically overt bleeding that was not major.

The rates of major bleeding according to the time interval following the first Arixtra injection were as follows: <6 hours was 3.4% (9/263) and 6 to 8 hours was 2.9% (32/1112).

Treatment of Deep Vein Thrombosis and Pulmonary Embolism: The rates of bleeding events reported during the DVT and PE clinical trials with the Arixtra injection treatment regimen are provided in Table 4.

Table 4. Bleedinga in Deep Vein Thrombosis and Pulmonary Embolism Treatment Studies

	Arixtra N = 2,294	Enoxaparin Sodium N = 1,101	Heparin aPTT adjusted IV N = 1,092
Major bleedingb	28 (1.2%)	13 (1.2%)	12 (1.1%)
Fatal bleeding	3 (0.1%)	0 (0.0%)	1 (0.1%)
Non-fatal bleeding at a critical site	3 (0.1%)	0 (0.0%)	2 (0.2%)
Intracranial bleeding	3 (0.1%)	0 (0.0%)	1 (0.1%)
Retro-peritoneal bleeding	0 (0.0%)	0 (0.0%)	1 (0.1%)
Other clinically overt bleedingc	22 (1.0%)	13 (1.2%)	10 (0.9%)
Minor bleedingd	70 (3.1%)	33 (3.0%)	57 (5.2%)

a Bleeding rates are during the study drug treatment period (approximately 7 days). Patients were also treated with vitamin K antagonists initiated within 72 hours after the first study drug administration.

b Major bleeding was defined as clinically overt: –and/or contributing to death – and/or in a critical organ including intracranial, retroperitoneal, intraocular, spinal, pericardial, or adrenal gland – and/or associated with a fall in hemoglobin level ≥2 g/dL – and/or leading to a transfusion ≥2 units of packed red blood cells or whole blood.

c Clinically overt bleeding with a 2 g/dL fall in hemoglobin and/or leading to transfusion of PRBC or whole blood ≥2 units.

d Minor bleeding was defined as clinically overt bleeding that was not major.

Local Reactions

Local irritation (injection site bleeding, rash, and pruritus) may occur following subcutaneous injection of Arixtra.

Elevations of Serum Aminotransferases

In the peri-operative prophylaxis randomized clinical trials of 7 ± 2 days, asymptomatic increases in aspartate (AST) and alanine (ALT) aminotransferase levels greater than 3 times the upper limit of normal were reported in 1.7% and 2.6% of patients, respectively, during treatment with Arixtra 2.5 mg once daily versus 3.2% and 3.9% of patients, respectively, during treatment with enoxaparin sodium 30 mg every 12 hours or 40 mg once daily enoxaparin sodium. These elevations are reversible and rarely associated with increases in bilirubin. In the extended prophylaxis clinical trial, no significant differences in AST and ALT levels between Arixtra 2.5 mg and placebo-treated patients were observed.

In the DVT and PE treatment clinical trials, asymptomatic increases in AST and ALT levels greater than 3 times the upper limit of normal of the laboratory reference range were reported in 0.7% and 1.3% of patients, respectively, during treatment with Arixtra. In comparison, these increases were reported in 4.8% and 12.3% of patients, respectively, in the DVT treatment trial during treatment with enoxaparin sodium 1 mg/kg every 12 hours and in 2.9% and 8.7% of patients, respectively, in the PE treatment trial during treatment with aPTT adjusted heparin.

Since aminotransferase determinations are important in the differential diagnosis of myocardial infarction, liver disease, and pulmonary emboli, elevations that might be caused by drugs like Arixtra should be interpreted with caution.

Other Adverse Reactions

Other adverse reactions that occurred during treatment with Arixtra in clinical trials with patients undergoing hip fracture, hip replacement, or knee replacement surgery are provided in Table 5.

Table 5. Adverse Reactions Across Randomized, Controlled, Hip Fracture Surgery, Hip Replacement Surgery, and Knee Replacement Surgery Studies

Adverse Reactions	Peri-Operative Prophylaxis (Day 1 to Day 7 ± 1 post-surgery)		Extended Prophylaxis (Day 8 to Day 28 ± 2 post-surgery)
	Arixtra 2.5 mg SC once daily	Enoxaparin Sodiuma, b	Arixtra 2.5 mg SC once daily	Placebo SC once daily
	N = 3,616	N = 3,956	N = 327	N = 329
Anemia	707 (19.6%)	670 (16.9%)	5 (1.5%)	4 (1.2%)
Insomnia	179 (5.0%)	214 (5.4%)	3 (0.9%)	1 (0.3%)
Wound drainage increased	161 (4.5%)	184 (4.7%)	2 (0.6%)	0 (0.0%)
Hypokalemia	152 (4.2%)	164 (4.1%)	0 (0.0%)	0 (0.0%)
Dizziness	131 (3.6%)	165 (4.2%)	2 (0.6%)	0 (0.0%)
Purpura	128 (3.5%)	137 (3.5%)	0 (0.0%)	0 (0.0%)
Hypotension	126 (3.5%)	125 (3.2%)	1 (0.3%)	0 (0.0%)
Confusion	113 (3.1%)	132 (3.3%)	4 (1.2%)	1 (0.3%)
Bullous eruptionc	112 (3.1%)	102 (2.6%)	0 (0.0%)	1 (0.3%)
Hematoma	103 (2.8%)	109 (2.8%)	7 (2.1%)	1 (0.3%)
Post-operative hemorrhage	85 (2.4%)	69 (1.7%)	2 (0.6%)	2 (0.6%)

a Enoxaparin sodium dosing regimen: 30 mg every 12 hours or 40 mg once daily.

b Not approved for use in patients undergoing hip fracture surgery.

c Localized blister coded as bullous eruption.

Adverse reactions in the abdominal surgery study and in the VTE treatment trials generally occurred at lower rates than in the hip and knee surgery trials described above. The most common adverse reaction in the abdominal surgery trial was post-operative wound infection (4.9%), and the most common adverse reaction in the VTE treatment trials was epistaxis (1.3%).

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Arixtra. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Isolated occurrences of thrombocytopenia with thrombosis that manifested similar to heparin-induced thrombocytopenia have been reported in the postmarketing experience and isolated cases of elevated aPTT temporally associated with bleeding events have been reported following administration of Arixtra (with or without concomitant administration of other anticoagulants) [see Warnings and Precautions (5.4)].

Drug Interactions

In clinical studies performed with Arixtra, the concomitant use of oral anticoagulants (warfarin), platelet inhibitors (acetylsalicylic acid), NSAIDs (piroxicam), and digoxin did not significantly affect the pharmacokinetics/pharmacodynamics of fondaparinux sodium. In addition, Arixtra neither influenced the pharmacodynamics of warfarin, acetylsalicylic acid, piroxicam, and digoxin, nor the pharmacokinetics of digoxin at steady state.

Agents that may enhance the risk of hemorrhage should be discontinued prior to initiation of therapy with Arixtra unless these agents are essential. If co-administration is necessary, monitor patients closely for hemorrhage. [See Warnings and Precautions (5.1).]

In an in vitro study in human liver microsomes, inhibition of CYP2A6 hydroxylation of coumarin by fondaparinux (200 micromolar i.e., 350 mg/L) was 17 to 28%. Inhibition of the other isozymes evaluated (CYPs 1A2, 2C9, 2C19, 2D6, 3A4, and 3E1) was 0 to 16%. Since fondaparinux does not markedly inhibit CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4) in vitro, fondaparinux sodium is not expected to significantly interact with other drugs in vivo by inhibition of metabolism mediated by these isozymes.

Since fondaparinux sodium does not bind significantly to plasma proteins other than ATIII, no drug interactions by protein-binding displacement are expected.

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category B. Reproduction studies have been performed in pregnant rats at subcutaneous doses up to 10 mg/kg/day (about 32 times the recommended human dose based on body surface area) and pregnant rabbits at subcutaneous doses up to 10 mg/kg/day (about 65 times the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to fondaparinux sodium. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Arixtra should be used during pregnancy only if clearly needed.

Nursing Mothers

Fondaparinux sodium was found to be excreted in the milk of lactating rats. However, it is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Arixtra is administered to a nursing mother.

Pediatric Use

Safety and effectiveness of Arixtra in pediatric patients have not been established. Because risk for bleeding during treatment with Arixtra is increased in adults who weigh <50 kg, bleeding may be a particular safety concern for use of Arixtra in the pediatric population [see Warnings and Precautions (5.3)].

Geriatric Use

In clinical trials the efficacy of Arixtra in the elderly (65 years or older) was similar to that seen in patients younger than 65 years; however, serious adverse events increased with age. Exercise caution when using Arixtra in elderly patients, paying particular attention to dosing directions and concomitant medications (especially anti-platelet medication). [See Warnings and Precautions (5.1).]

Fondaparinux sodium is substantially excreted by the kidney, and the risk of adverse reactions to Arixtra may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, assess renal function prior to Arixtra administration. [See Contraindications (4), Warnings and Precautions (5.2), and Clinical Pharmacology (12.4).]

In the peri-operative hip fracture, hip replacement, or knee replacement surgery clinical trials with patients receiving Arixtra 2.5 mg, serious adverse events increased with age for patients receiving Arixtra. The incidence of major bleeding in clinical trials of Arixtra by age is provided in Table 6.

Megace Os

Generic Name: progestin (Oral route, Parenteral route, Vaginal route)

Commonly used brand name(s)

In the U.S.

• Aygestin


• Camila


• Crinone


• Errin


• First-Progesterone VGS


• Jolivette


• Megace


• Megace ES


• Next Choice


• Ovrette


• Plan B


• Prochieve


• Prometrium

In Canada

• Alti-Mpa


• Megace Os

Available Dosage Forms:

• Tablet


• Suspension


• Capsule, Liquid Filled


• Gel/Jelly


• Cream


• Kit


• Suppository

Uses For Megace Os

Progestins are hormones. They are used by both men and women for different purposes.

Progestins are prescribed for several reasons:

• To properly regulate the menstrual cycle and treat unusual stopping of the menstrual periods (amenorrhea). Progestins work by causing changes in the uterus. After the amount of progestins in the blood drops, the lining of the uterus begins to come off and vaginal bleeding occurs (menstrual period). Progestins help other hormones start and stop the menstrual cycle. .


• To help a pregnancy occur during egg donor or infertility procedures in women who do not produce enough progesterone. Also, progesterone is given to help maintain a pregnancy when not enough of it is made by the body.


• To prevent estrogen from thickening the lining of the uterus (endometrial hyperplasia) in women around menopause who are being treated with estrogen for ovarian hormone therapy (OHT). OHT is also called hormone replacement therapy (HRT) and estrogen replacement therapy (ERT).


• To treat pain that is related to endometriosis, a condition where the endometrial tissue which lines the uterus becomes displaced in other female organs.


• To treat a condition called endometriosis, to help prevent endometrial hyperplasia, or to treat unusual and heavy bleeding of the uterus (dysfunctional uterine bleeding) by starting or stopping the menstrual cycle.


• To help treat cancer of the breast, kidney, or uterus. Progestins help change the cancer cell's ability to react to other hormones and proteins that cause tumor growth. In this way, progestins can stop the growth of a tumor.


• To test the body's production of certain hormones such as estrogen.


• To treat loss of appetite and severe weight or muscle loss in patients with acquired immunodeficiency syndrome (AIDS) or cancer by causing certain proteins to be produced that cause increased appetite and weight gain.

Progestins may also be used for other conditions as determined by your doctor.

Depending on how much and which progestin you use or take, a progestin can have different effects. For instance, high doses of progesterone are necessary for some women to continue a pregnancy while other progestins in low doses can prevent a pregnancy from occurring. Other effects include causing weight gain, increasing body temperature, developing the milk-producing glands for breast-feeding, and relaxing the uterus to maintain a pregnancy.

Progestins can help other hormones work properly. Progestins may help to prevent anemia (low iron in blood), too much menstrual blood loss, and cancer of the uterus.

Progestins are available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, progestins are used in certain patients with the following medical conditions:

• Carcinoma of the prostate


• Corpus luteum insufficiency


• Hot flashes


• Polycystic ovary syndrome


• Precocious puberty

Before Using Megace Os

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.

Pediatric

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

Geriatric

This medicine has been tested and has not been shown to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

Progesterone, a natural hormone that the body makes during pregnancy, has not caused problems. In fact, it is sometimes used in women to treat a certain type of infertility and to aid in egg donor or infertility procedures.

Other progestins have not been studied in pregnant women. Be sure to tell your doctor if you become pregnant while using any of the progestins. It is best to use some kind of birth control method while you are receiving progestins in high doses. High doses of progestins are not recommended for use during pregnancy since there have been some reports that they may cause birth defects in the genitals (sex organs) of a male fetus. Also, some of these progestins may cause male-like changes in a female fetus and female-like changes in a male fetus, but these problems usually can be reversed. Low doses of progestins, such as those doses used for contraception, have not caused major problems when used accidentally during pregnancy.

Breast Feeding

Although progestins pass into the breast milk, they have not been shown to cause problems in nursing babies. However, progestins may change the quality or amount (increase or decrease) of the mother's breast milk. It may be necessary for you to take another medicine or to stop breast-feeding during treatment. Be sure you have discussed the risks and benefits of the medicine with your doctor.

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


• Dofetilide

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.

• Felbamate


• Isotretinoin


• 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 history of) or


• Heart or circulation problems or


• Kidney disease (severe) or


• Migraine headaches—Progestins may cause fluid retention which may cause these conditions to become worse.

• Bleeding problems, undiagnosed, such as blood in the urine or changes in vaginal bleeding—May make diagnosis of these problems more difficult.

• Blood clots, 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 history of or


• Liver disease, including jaundice, or history of or


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


• Stroke , active or history of or


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

• Breast disease (such as breast lumps or cysts), history of—May make this condition worse for diseases that do not react in a positive way to progestins.

• Diabetes mellitus—May cause an increase in your blood sugar and a change in the amount of medicine you take for diabetes; progestins in high doses are more likely to cause this problem.

• Memory loss (dementia)—May make this condition worse.

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

Proper Use of progestin

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

To make the use of a progestin as safe and reliable as possible, you should understand how and when to take it and what effects may be expected. Progestins usually come with patient directions. Read them carefully before taking or using 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 time than your doctor ordered. To do so may increase the chance of side effects. Try to take the medicine at the same time each day to reduce the possibility of side effects and to allow it to work better.

Progestins are often given together with certain medicines. If you are using a combination of medicines, make sure that you take each one at the proper time and do not mix them. Ask your health care professional to help you plan a way to remember to take your medicines at the right times.

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 medroxyprogesterone


• For oral dosage form (tablets):
  
  • For controlling unusual and heavy bleeding of the uterus (dysfunctional uterine bleeding) or treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults and teenagers—5 to 10 milligrams (mg) per day for five to ten days as directed by your doctor.
    
    
  
  
  • For preparing the uterus for the menstrual period:
    
    • Adults and teenagers—10 milligrams (mg) per day for five or ten days as directed by your doctor.
    
    
  
  
  • For preventing estrogen from thickening the lining of the uterus (endometrial hyperplasia) when taking estrogen for ovarian hormone therapy in postmenopausal women:
    
    • Adults—When taking estrogen each day on Days 1 through 25: Oral, 5 to 10 milligrams (mg) of medroxyprogesterone per day for ten to fourteen or more days each month as directed by your doctor. Or, your doctor may want you to take 2.5 or 5 mg per day without stopping. Your doctor will help decide the number of tablets that is best for you and when to take them.
    
    
  
  


• For intramuscular injection dosage form:
  
  • For treating cancer of the kidneys or uterus:
    
    • Adults and teenagers—At first, 400 to 1000 milligrams (mg) injected into a muscle as a single dose once a week. Then, your doctor may lower your dose to 400 mg or more once a month.
    
    
  
  


• For subcutaneous injection dosage form:
  
  • For treating pain related to endometriosis:
    
    • Adults and teenagers—104 milligrams (mg) injected under the skin of the anterior thigh or abdomen every three months (12 to 14 weeks) for not more than 2 years.
    
    
  
  

• For megestrol


• For oral dosage form (suspension):
  
  • For treating loss of appetite (anorexia), muscles (cachexia), or weight caused by acquired immunodeficiency syndrome (AIDS):
    
    • Adults and teenagers—800 milligrams (mg) a day for the first month. Then your doctor may want you to take 400 or 800 mg a day for three more months.
    
    
  
  


• For oral dosage form (tablets):
  
  • For treating cancer of the breast:
    
    • Adults and teenagers—160 milligrams (mg) a day as a single dose or in divided doses for two or more months.
    
    
  
  
  • For treating cancer of the uterus:
    
    • Adults and teenagers—40 to 320 milligrams (mg) a day for two or more months.
    
    
  
  
  • For treating loss of appetite (anorexia), muscles (cachexia), or weight caused by cancer:
    
    • Adults and teenagers—400 to 800 milligrams (mg) a day.
    
    
  
  

• For norethindrone


• For oral dosage form (tablets):
  
  • For controlling unusual and heavy bleeding of the uterus (dysfunctional uterine bleeding) or treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults and teenagers—2.5 to 10 milligrams (mg) a day from Day 5 through Day 25 (counting from the first day of the last menstrual cycle). Or, your doctor may want you to take the medicine only for five to ten days as directed.
    
    
  
  
  • For treating endometriosis:
    
    • Adults and teenagers—At first, 5 milligrams (mg) a day for two weeks. Then, your doctor may increase your dose slowly up to 15 mg a day for six to nine months. Let your doctor know if your menstrual period starts. Your doctor may want you to take more of the medicine or may want you to stop taking the medicine for a short period of time.
    
    
  
  

• For progesterone


• For oral dosage form (capsules):
  
  • For preventing estrogen from thickening the lining of the uterus (endometrial hyperplasia) when taking estrogen for ovarian hormone therapy in postmenopausal women:
    
    • Adults—200 milligrams (mg) per day at bedtime for 12 continuous days per 28-day cycle of estrogen treatment each month.
    
    
  
  
  • For treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults—400 milligrams (mg) per day at bedtime for ten days.
    
    
  
  


• For vaginal dosage form (gel):
  
  • For treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults and teenagers—45 milligrams (mg) (one applicatorful of 4% gel) once every other day for up to six doses. Dose may be increased to 90 mg (one applicatorful of 8% gel) once every other day for up to six doses if needed.
    
    
  
  
  • For use with infertility procedures:
    
    • Adults and teenagers—90 milligrams (mg) (one applicatorful of 8% gel) one or two times a day. If pregnancy occurs, treatment can continue for up to ten to twelve weeks.
    
    
  
  


• For injection dosage form:
  
  • For controlling unusual and heavy bleeding of the uterus (dysfunctional uterine bleeding) or treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults and teenagers—5 to 10 milligrams (mg) a day injected into a muscle for six to ten days. Or, your doctor may want you to receive 100 or 150 mg injected into a muscle as a single dose. Sometimes your doctor may want you first to take another hormone called estrogen. If your menstrual period starts, your doctor will want you to stop taking the medicine.
    
    
  
  


• For vaginal dosage form (suppositories):
  
  • For maintaining a pregnancy (at ovulation and at the beginning of pregnancy):
    
    • Adults and teenagers—25 mg to 100 milligrams (mg) (one suppository) inserted into the vagina one or two times a day beginning near the time of ovulation. Your doctor may want you to receive the medicine for up to eleven weeks.
    
    
  
  

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.

For all progestins, except for progesterone capsules for postmenopausal women: If you miss a dose of this medicine, take the missed dose 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.

For progesterone capsules for postmenopausal women: If you miss a dose of 200 mg of progesterone capsules at bedtime, take 100 mg in the morning then go back to your regular dosing schedule. If you take 300 mg of progesterone a day and you miss your morning and evening doses, you should not take the missed dose. Return to your regular dosing schedule.

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 Megace Os

It is very important that your doctor check your progress at regular visits. This will allow for your dosage to be adjusted and for any unwanted effects to be detected. These visits will usually be every 6 to 12 months, but some doctors require them more often.

The Prometrium® capsules contain peanut oil. If you have an allergy to peanuts, make sure your doctor knows this before you take this brand of progestin.

Progestins may cause some people to become dizzy. For oral or vaginal progesterone, dizziness or drowsiness may occur 1 to 4 hours after taking or using it. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are not alert.

Unusual or unexpected vaginal bleeding of various amounts may occur between your regular menstrual periods during the first 3 months of use. This is sometimes called spotting when slight, or breakthrough menstrual bleeding when heavier. If this should occur, continue on your regular dosing schedule. Check with your doctor:

• If unusual or unexpected vaginal bleeding continues for an unusually long time.


• If your menstrual period has not started within 45 days of your last period.

Missed menstrual periods may occur. If you suspect a pregnancy, you should stop taking this medicine immediately and call your doctor. Your doctor will let you know if you should continue taking the progestin.

If you are scheduled for any laboratory tests, tell your health care professional that you are taking a progestin. Progestins can change certain test results.

In some patients, tenderness, swelling, or bleeding of the gums may occur. Brushing and flossing your teeth carefully and regularly and massaging your gums may help prevent this. See your dentist regularly to have your teeth cleaned. Check with your medical doctor or dentist if you have any questions about how to take care of your teeth and gums, or if you notice any tenderness, swelling, or bleeding of your gums.

You will need to use a birth control method while taking progestins for noncontraceptive use if you are fertile and sexually active.

If you are using vaginal progesterone, avoid using other vaginal products for 6 hours before and for 6 hours after inserting the vaginal dose of progesterone.

Since it is possible that certain doses of progestins may cause temporary thinning of the bones by changing your hormone balance, it is important that your doctor know if you have an increased risk of osteoporosis. Some things that can increase your risk for having osteoporosis include cigarette smoking, abusing alcohol, taking or drinking large amounts of caffeine, and having a family history of osteoporosis or easily broken bones. Some medicines, such as glucocorticoids (cortisone-like medicines) or anticonvulsants (seizure medicine), can also cause thinning of the bones. However, it is thought that progestins can help protect against osteoporosis in postmenopausal women.

Megace Os Side Effects

Along with their needed effects, progestins used in high doses sometimes cause some unwanted effects such as blood clots, heart attacks, and strokes, or problems of the liver and eyes. Although these effects are rare, some of them can be very serious and cause death. It is not clear if these problems are due to the progestin. They may be caused by the disease or condition for which progestins are being used.

The following side effects may be caused by blood clots. Although not all of these side effects may occur, if they do occur they need immediate medical attention.

Get emergency help immediately if any of the following side effects occur:

Rare

• Symptoms of blood clotting problems, usually severe or sudden, such as:


• headache or migraine


• loss of or change in speech, coordination, or vision


• numbness of or pain in chest, arm, or leg


• unexplained shortness of breath

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

More common

• Changes in vaginal bleeding (increased amounts of menstrual bleeding occurring at regular monthly periods, lighter vaginal bleeding between menstrual periods, heavier vaginal bleeding between regular monthly periods, or stopping of menstrual periods)


• symptoms of blood sugar problems (dry mouth, frequent urination, loss of appetite, or unusual thirst)

Less common

• Mental depression


• skin rash


• unexpected or increased flow of breast milk

RareFor megestrol—During chronic treatment

• Backache


• dizziness


• filling or rounding out of the face


• irritability


• mental depression


• nausea or vomiting


• unusual decrease in sexual desire or ability in men


• unusual tiredness or weakness

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 pain or cramping


• bloating or swelling of ankles or feet


• blood pressure increase (mild)


• dizziness


• drowsiness (progesterone only)


• headache (mild)


• mood changes


• nervousness


• pain or irritation at place of injection site


• swelling of face, ankles, or feet


• unusual or rapid weight gain

Less common

• Acne


• breast pain or tenderness


• brown spots on exposed skin, possibly long-lasting


• hot flashes


• loss or gain of body, facial, or scalp hair


• loss of sexual desire


• trouble in sleeping

Not all of the side effects listed above have been reported for each of these medicines, but they have been reported for at least one of them. All of the progestins are similar, so any of the above side effects may occur with any of these medicines.

After you stop using this medicine, your body may need time to adjust. The length of time this takes depends on the amount of medicine you were using and how long you used it. During this period of time check with your doctor if you notice the following side effect:

For megestrol

• Dizziness


• nausea or vomiting


• unusual tiredness or weakness

• Delayed return to fertility


• stopping of menstrual periods


• unusual menstrual bleeding (continuing)

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.

AllerDur

Generic Name: dexchlorpheniramine and pseudoephedrine (dex klor fen EER a meen and soo doe e FED rin)

Brand Names: AllerDur, Duotan PD, Tanafed DP

What is AllerDur (dexchlorpheniramine and pseudoephedrine)?

Dexchlorpheniramine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

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

The combination of dexchlorpheniramine and pseudoephedrine is used to treat sneezing, cough, runny or stuffy nose, itchy or watery eyes, hives, skin rash, itching, and other symptoms of allergies and the common cold.

Dexchlorpheniramine and pseudoephedrine may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about AllerDur (dexchlorpheniramine and pseudoephedrine)?

Always ask a doctor before giving a cold or allergy medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not use any other over-the-counter cold, allergy, or sleep medication without first asking your doctor or pharmacist. If you take certain products together you may accidentally take too much of a certain drug. Read the label of any other medicine you are using to see if it contains an antihistamine or decongestant. Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body. Dexchlorpheniramine and pseudoephedrine can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol. It can increase some of the side effects of this medication.

What should I discuss with my healthcare provider before taking AllerDur (dexchlorpheniramine and pseudoephedrine)?

Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body.

Before taking this medication, tell your doctor if you are allergic to dexchlorpheniramine, or pseudoephedrine, or if you have:

• kidney disease;


• 
  

  diabetes;

  
  


• 
  

  glaucoma;

  
  


• 
  

  heart disease or high blood pressure;

  
  


• 
  

  diabetes;

  
  


• 
  

  a thyroid disorder;

  
  


• 
  

  an enlarged prostate; or

  
  


• 
  

  problems with urination.

  
  

If you have any of these conditions, you may not be able to use dexchlorpheniramine and pseudoephedrine, or you may need a dosage adjustment or special tests during treatment.

This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Dexchlorpheniramine and pseudoephedrine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Artificially-sweetened liquid forms of cold medicine may contain phenylalanine. This would be important to know if you have phenylketonuria (PKU). Check the ingredients and warnings on the medication label if you are concerned about phenylalanine.

How should I take AllerDur (dexchlorpheniramine and pseudoephedrine)?

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

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.

Measure the liquid form of this medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash.

If you need to have any type of surgery, tell the surgeon ahead of time if you have taken a cold medicine within the past few days.

This medication can cause you to have unusual results with allergy skin tests. Tell any doctor who treats you that you are taking an antihistamine.

Store the medication at room temperature away from moisture and heat.

What happens if I miss a dose?

Since cold or allergy medicine is usually taken only as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at your next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

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

Symptoms of an overdose may include feeling restless or nervous, nausea, vomiting, stomach pain, dizziness, drowsiness, dry mouth, warmth or tingly feeling, or seizure (convulsions).

What should I avoid while taking AllerDur (dexchlorpheniramine and pseudoephedrine)?

This medication can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol. It can increase some of the side effects of this medication.

Avoid using other medicines that make you sleepy (such as sleeping pills, pain medication, muscle relaxers, and medicine for seizures, depression or anxiety). They can add to sleepiness caused by dexchlorpheniramine and pseudoephedrine.

Avoid taking diet pills, caffeine pills, or other stimulants (such as ADHD medications) without your doctor's advice. Taking a stimulant together with a decongestant can increase your risk of unpleasant side effects.

Do not use any other over-the-counter cold, allergy, or sleep medication without first asking your doctor or pharmacist. If you take certain products together you may accidentally take too much of a certain drug. Read the label of any other medicine you are using to see if it contains an antihistamine or decongestant.

AllerDur (dexchlorpheniramine and pseudoephedrine) side effects

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

• 
  

  fast, pounding, or uneven heartbeat;

  
  


• 
  

  confusion, hallucinations, unusual thoughts or behavior;

  
  


• 
  

  severe dizziness, anxiety, restless feeling, or nervousness;

  
  


• 
  

  increased blood pressure (severe headache, blurred vision, trouble concentrating, chest pain, numbness, seizure);

  
  


• 
  

  confusion, hallucinations, unusual thoughts or behavior;

  
  


• 
  

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

  
  


• 
  

  urinating less than usual or not at all.

  
  

Keep taking the medication and talk to your doctor if you have any of these less serious side effects:

• 
  

  blurred vision;

  
  


• 
  

  dry mouth;

  
  


• 
  

  nausea, stomach pain, constipation;

  
  


• 
  

  mild loss of appetite, stomach upset;

  
  


• 
  

  warmth, tingling, or redness under your skin;

  
  


• 
  

  sleep problems (insomnia);

  
  


• 
  

  restless or excitability (especially in children);

  
  


• 
  

  skin rash or itching;

  
  


• 
  

  dizziness, drowsiness;

  
  


• 
  

  problems with memory or concentration; or

  
  


• 
  

  ringing in your ears.

  
  

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

What other drugs will affect AllerDur (dexchlorpheniramine and pseudoephedrine)?

Before taking this medication, tell your doctor if you are using any of the following drugs:

• 
  

  medicines to treat high blood pressure;

  
  


• 
  

  a diuretic (water pill);

  
  


• 
  

  medication to treat irritable bowel syndrome;

  
  


• 
  

  bladder or urinary medications such as oxybutynin (Ditropan, Oxytrol) or tolterodine (Detrol);

  
  


• 
  

  aspirin or salicylates (such as Disalcid, Doan's Pills, Dolobid, Salflex, Tricosal, and others);

  
  


• 
  

  a beta-blocker such as atenolol (Tenormin), carteolol (Cartrol), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal), sotalol (Betapace), timolol (Blocadren), and others; or

  
  


• 
  

  antidepressants such as amitriptyline (Elavil), clomipramine (Anafranil), imipramine (Janimine, Tofranil), and others.

  
  

If you are using any of these drugs, you may not be able to use dexchlorpheniramine and pseudoephedrine, or you may need dosage adjustments or special tests during treatment.

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

More AllerDur resources

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

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Where can I get more information?

• Your pharmacist has information about dexchlorpheniramine and pseudoephedrine written for health professionals that you may read.

Murine Tears Plus Drops

Pronunciation: te-tra-hye-DROZ-oh-leen
Generic Name: Tetrahydrozoline
Brand Name: Examples include Eye Moisturizing Relief and Murine Tears

Murine Tears Plus Drops are used for:

Temporarily relieving redness, burning, and irritation caused by dry eyes. It may also be used for other conditions as determined by your doctor.

Murine Tears Plus Drops are an eye decongestant and lubricant. It works by constricting the blood vessels in the eye and coating the eye, which relieves redness and dryness.

Do NOT use Murine Tears Plus Drops if:

• you are allergic to any ingredient in Murine Tears Plus Drops


• you have taken furazolidone or a monoamine oxidase (MAO) inhibitor (eg, phenelzine) within the past 14 days

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

Before using Murine Tears Plus Drops:

Some medical conditions may interact with Murine Tears Plus Drops. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have glaucoma, high blood pressure, diabetes, heart problems, or thyroid problems, or you are taking medicine for high blood pressure

Some MEDICINES MAY INTERACT with Murine Tears Plus Drops. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Tricyclic antidepressants (eg, amitriptyline) because they may decrease Murine Tears Plus Drops's effectiveness


• Cocaine, furazolidone, MAO inhibitors (eg, phenelzine), or tricyclic antidepressants (eg, amitriptyline) because they may increase the risk of Murine Tears Plus Drops's side effects, such as headache, fever, and high blood pressure


• Bromocriptine or cocaine because their actions and side effects may be increased by Murine Tears Plus Drops

This may not be a complete list of all interactions that may occur. Ask your health care provider if Murine Tears Plus Drops may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Murine Tears Plus Drops:

Use Murine Tears Plus Drops as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Murine Tears Plus Drops are for use in the eye only. Avoid contact with the nose, mouth, or other mucous membranes.


• To use Murine Tears Plus Drops, first, wash your hands. Tilt your head back. Using your index finger, pull the lower eyelid away from the eye to form a pouch. Drop the medicine into the pouch and gently close your eyes. Immediately use your finger to apply pressure to the inside corner of the eye for 1 to 2 minutes. Do not blink. Remove excess medicine around your eye with a clean tissue, being careful not to touch your eye. Wash your hands to remove any medicine that may be on them.


• To prevent germs from contaminating your medicine, do not touch the applicator tip to any surface, including your eye. Keep the container tightly closed.


• If you miss a dose of Murine Tears Plus Drops and you are using it regularly, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.

Ask your health care provider any questions you may have about how to use Murine Tears Plus Drops.

Important safety information:

• Remove contact lenses before using Murine Tears Plus Drops.


• Do not use Murine Tears Plus Drops if it becomes cloudy or changes color.


• Contact your doctor if you experience changes in your vision, eye pain, irritation, soreness, or continued redness, or if your condition does not improve after 3 days.


• Use Murine Tears Plus Drops with caution in CHILDREN because they may be more sensitive to its effects.


• PREGNANCY and BREAST-FEEDING: If you become pregnant while taking Murine Tears Plus Drops, discuss with your doctor the benefits and risks of using Murine Tears Plus Drops during pregnancy. It is unknown if Murine Tears Plus Drops are excreted in breast milk. If you are or will be breast-feeding while you are using Murine Tears Plus Drops, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Murine Tears Plus Drops:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Blurred vision; minor stinging when the medicine is dropped into the eye.

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

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); changes in vision; eye pain; worsening or persistent eye irritation or redness.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Murine Tears Plus Drops may be harmful if swallowed, especially in children.

Proper storage of Murine Tears Plus Drops:

Store Murine Tears Plus Drops at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Murine Tears Plus Drops out of the reach of children and away from pets.

General information:

• If you have any questions about Murine Tears Plus Drops, please talk with your doctor, pharmacist, or other health care provider.


• Murine Tears Plus Drops are to be used only by the patient for whom it is prescribed. Do not share it with other people.


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


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

This information is a summary only. It does not contain all information about Murine Tears Plus Drops. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Murine Tears Plus resources

• Murine Tears Plus Use in Pregnancy & Breastfeeding
• Murine Tears Plus Drug Interactions
• Murine Tears Plus Support Group
• 1 Review for Murine Tears Plus - Add your own review/rating

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• Eye Dryness/Redness