These Highlights Do Not Include All The Information Needed To Use Tranexamic Acid Injection Safely And Effectively. See Full Prescribing Information For Tranexamic Acid Injection.

Tranexamic acid injection is for intravenous use only. Serious adverse reactions including seizures and cardiac arrythmias have occurred when tranexamic acid injection was inadvertently administered intrathecally instead of intravenously.

Confirm the correct route of administration for tranexamic acid injection and avoid confusion with other injectable solutions that might be administered at the same time as tranexamic acid injection. Syringes containing tranexamic acid injection should be clearly labeled with the intravenous route of administration.

Storage Conditions

Store at 20º to 25°C (68º to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.]

Discard unused portion.

Sterile, Nonpyrogenic, Preservative-free.

The container closure is not made with natural rubber latex.

Tranexamic acid may cause seizures, including focal and generalized seizures. The most common setting for tranexamic acid-induced seizures has been during cardiovascular surgery (a setting in which tranexamic acid is not FDA-approved and which uses doses of up to 10-fold higher than the recommended human dose and in patients inadvertently given tranexamic acid into the neuraxial system). Tranexamic acid is not approved and not recommended for neuraxial administration. Consider dose reduction during surgery and dose adjustments for patients with clinical conditions such as renal dysfunction. Closely monitor the patient during surgery. Consider electroencephalogram (EEG) monitoring for patients with history of seizures or who experience myoclonic movements, twitching, or show evidence of focal seizures. Discontinue tranexamic acid if seizures occur.

Cases of overdosage of tranexamic acid have been reported. Based on these reports, symptoms of overdosage may be gastrointestinal, e.g., nausea, vomiting, diarrhea; hypotensive, e.g., orthostatic symptoms; thromboembolic, e.g., arterial, venous, embolic; neurologic, e.g., visual impairment, convulsions, headache, mental status changes; myoclonus; and rash.

Tranexamic acid may cause dizziness. Concomitant use of other drugs that may also cause dizziness may worsen this effect. Advise patients to avoid driving or using machines until they know how tranexamic acid affects them.

Tranexamic acid is trans-4-(aminomethyl)cyclohexanecarboxylic acid, an antifibrinolytic agent. Tranexamic acid, USP is a white crystalline powder. The structural formula is

Empirical Formula: C₈H₁₅NO₂ Molecular Weight: 157.2

Each mL of the sterile solution for intravenous injection contains 100 mg tranexamic acid, USP and Water for Injection to 1 mL. The aqueous solution for injection has a pH of 6.5 to 8.0.

There are limited data concerning the use of tranexamic acid in pediatric patients with hemophilia who are undergoing tooth extraction. The limited data suggest that there are no significant pharmacokinetic differences between adults and pediatric patients.

Clinical studies of tranexamic acid did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

Tranexamic acid injection is contraindicated:

• In patients with subarachnoid hemorrhage. Anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by tranexamic acid injection in such patients.
• In patients with active intravascular clotting [see Warnings and Precautions (5.1)].
• In patients with hypersensitivity to tranexamic acid or any of the ingredients [see Warnings and Precautions (5.4)].

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Thromboembolic Risk [see Warnings and Precautions (5.1)]
• Seizures [see Warnings and Precautions (5.3)]
• Hypersensitivity Reactions [see Warnings and Precautions (5.4)]
• Visual Disturbances [see Warnings and Precautions (5.5)]
• Dizziness [see Warnings and Precautions (5.6)]

Prothrombotic Medical Products: Avoid concomitant use, can further increase the risk of thromboembolic adverse reactions associated with tranexamic acid. (5.1, 7.1, 8.3)

Reduce the dosage of tranexamic acid in patients with renal impairment, based on the patient's serum creatinine [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

Tranexamic acid, in concentrations of 1 mg/mL and 10 mg/mL prolongs the thrombin time. An antifibrinolytic concentration of tranexamic acid remains in different tissues for about 17 hours, and in the serum, up to 7 or 8 hours.

Tranexamic acid in concentrations up to 10 mg/mL blood has no influence on the platelet count, the coagulation time or various coagulation factors in whole blood or citrated blood from healthy subjects.

The recommended dose of tranexamic acid injection is 10 mg/kg actual body weight intravenously administered as a single-dose, immediately before tooth extractions. Infuse no more than 1 mL/minute to avoid hypotension [see Warnings and Precautions (5.1)]. Following tooth extraction, tranexamic acid injection may be administered for 2 to 8 days at a dose of 10 mg/kg actual body weight 3 to 4 times daily, intravenously.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

For intravenous infusion, tranexamic acid injection may be mixed with most solutions for infusion such as electrolyte solutions, carbohydrate solutions, amino acid solutions, and Dextran solutions. Heparin may be added to tranexamic acid injection. Tranexamic acid injection should NOT be mixed with blood. The drug is a synthetic amino acid and should NOT be mixed with solutions containing penicillin.

Discard any unused portion.

The diluted mixture may be stored for up to 4 hours at room temperature prior to patient administration.

Tranexamic acid injection is indicated in patients with hemophilia for short-term use (2 to 8 days) to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction.

Tranexamic acid is contraindicated in patients with active intravascular clotting.

Tranexamic acid is an antifibrinolytic and may increase the risk of thromboembolic events. Venous and arterial thrombosis or thromboembolism has been reported in patients treated with tranexamic acid. Avoid concomitant use of tranexamic acid and medical products that are pro-thrombotic, as the risk of thrombosis may be increased. These medications include but are not limited to, Factor IX Complex concentrates, Anti-inhibitor Coagulant concentrates, and hormonal contraceptives [see Drug Interactions (7.1), Use in Specific Populations (8.3)].

Although not seen in humans, focal areas of retinal degeneration have been observed in cats and dogs following oral or intravenous tranexamic acid at doses between 250 to 1600 mg/kg/day (1.6 to 22 times the recommended usual human dose based on body surface area) from 6 days to 1 year. No retinal changes have been observed in eye examinations of patients treated with tranexamic acid for up to 8 years. Patients expected to be treated for greater than 3 months may consider ophthalmic monitoring including visual acuity and optical coherence tomography at regular intervals.

Discontinue tranexamic acid if changes in ophthalmological examination occurs.

Tranexamic acid is a synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin. In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrin's matrix structure.

The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen. Native human plasminogen contains 4 to 5 lysine binding sites with low affinity for tranexamic acid (Kd = 750 μmol/L) and 1 with high affinity (Kd = 1.1 μmol/L). The high affinity lysine site of plasminogen is involved in its binding to fibrin. Saturation of the high affinity binding site with tranexamic acid displaces plasminogen from the surface of fibrin. Although plasmin may be formed by conformational changes in plasminogen, binding to and dissolution of the fibrin matrix is inhibited.

• Risk of Thrombosis with Concomitant Use of Factor IX: Avoid concomitant use. (5.1)
• Risk of Medication Errors Due to Incorrect Route of Administration: FOR INTRAVENOUS USE ONLY. (5.2)
• Seizures: Inadvertent injection into neuraxial system may result in seizures. (5.3)
• Hypersensitivity Reactions: In case of severe reaction, discontinue use and seek immediate medical attention. (5.4)
• Visual Disturbances: Visual or ocular adverse effects may occur. Discontinue use if visual or ocular symptoms occur. (5.5)
• Dizziness: Advise patients not to drive if dizziness occurs. (5.6)

• Before Extraction: Administer 10 mg/kg actual body weight of tranexamic acid injection intravenously with replacement therapy. (2.1)
• After Extraction: Administer 10 mg/kg actual body weight 3 to 4 times daily for 2 to 8 days. Infuse no more than 1 mL/minute to avoid hypotension. (2.1)
• Reduce the dosage for patients with renal impairment. (2.2, 8.6)

Injection: 1,000 mg tranexamic acid, USP (100 mg per mL) clear and colorless solution in 10 mL single-dose vials.

The following adverse reactions have been identified during postapproval use of tranexamic acid. 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.

Gastrointestinal disturbances (nausea, vomiting, diarrhea) may occur and may resolve with dose-reduction. Allergic dermatitis and giddiness have been reported. Hypotension has been reported when intravenous injection is too rapid.

Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acute renal cortical necrosis, and central retinal artery, vein obstruction and cases associated with concomitant use of combination hormonal contraceptives) have been rarely reported in patients receiving tranexamic acid for indications other than hemorrhage prevention in patients with hemophilia. Convulsion, cromatopsia, and visual impairment have also been reported.

Anaphylaxis or anaphylactoid reactions have been reported that are suggestive of a causal relationship.

Cases of hypersensitivity reactions, including anaphylactic reactions, have occurred with use of intravenous tranexamic acid. Discontinue treatment with tranexamic acid if serious reaction occurs, provide appropriate medical management, and do not restart treatment. Tranexamic acid is contraindicated in patients with a history of hypersensitivity to tranexamic acid.

Avoid concomitant use of tranexamic acid with medical products that are prothrombotic because concomitant use can further increase the risk of thromboembolic adverse reactions associated with tranexamic acid [see Warnings and Precautions (5.1), Use in Specific Populations (8.3)].

Tranexamic Acid Injection, USP is a clear, colorless solution supplied as follows:

Nonclinical studies have shown a retinal toxicity associated with tranexamic acid. Toxicity is characterized by retinal atrophy commencing with changes to the retinal pigmented epithelium and progressing to retinal detachment in cats. The toxicity appears to be dose related, and changes are partially reversible at lower doses. Effects were observed in dogs at oral doses of 800 mg/kg/day and higher (multiple of 11 times the maximum human dose based on body surface area), and in cats at 250 mg/kg/day for 14 days (multiple of 1.6 times the maximum human dose based on body surface area). Some fully reversible changes in pigmentation were observed in cats at doses of 125 mg/kg/day (multiple of 0.8 times the maximum human dose based on body surface area). Studies suggest that the underlying mechanism may be related to a transient retinal ischemia at high exposures, linked to the known sympathomimetic effect of high plasma exposures of tranexamic acid.

Contraception

Concomitant use of tranexamic acid, which is an antifibrinolytic, with hormonal contraceptives may increase the risk for thromboembolic adverse reactions. Advise patients to use an effective alternative (nonhormonal) contraceptive method [see Warnings and Precautions (5.1), Drug Interactions (7.1)].

NDC 25021-415-10

Rx only

Tranexamic Acid Injection, USP

1,000 mg per 10 mL

(100 mg per mL)

For Intravenous Use Only

10 mL Single-Dose Vial

Tranexamic acid was not carcinogenic in a 2-year study in rats and mice at oral doses up to 3 and 5.3 g/kg/day, which are approximately 12 and 11 times the maximum recommended human dose based on body surface area, respectively.

Tranexamic acid was not genotoxic in the reverse mutation bacterial (Ames) test, and in vitro and in vivo cytogenetic test.

In a fertility and early embryonic development study, tranexamic acid was administered to male rats as 0.3% and 1% of drug in diet (average doses of 222 and 856 mg/kg/day) or to female rats at dose levels of 0.3% and 1.2% of drug in diet. Tranexamic acid had no effect on fertility or reproductive function of male or female rats at dose multiples of 4 or 5 times the maximum recommended human dose based on body surface area, respectively.

For patients with moderate to severe impaired renal function, the following dosages are recommended:

Tranexamic acid injection is for intravenous use only. Serious adverse reactions including seizures and cardiac arrythmias have occurred when tranexamic acid injection was inadvertently administered intrathecally instead of intravenously.

Confirm the correct route of administration for tranexamic acid injection and avoid confusion with other injectable solutions that might be administered at the same time as tranexamic acid injection. Syringes containing tranexamic acid injection should be clearly labeled with the intravenous route of administration.

Storage Conditions

Store at 20º to 25°C (68º to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.]

Discard unused portion.

Sterile, Nonpyrogenic, Preservative-free.

The container closure is not made with natural rubber latex.

Tranexamic acid may cause seizures, including focal and generalized seizures. The most common setting for tranexamic acid-induced seizures has been during cardiovascular surgery (a setting in which tranexamic acid is not FDA-approved and which uses doses of up to 10-fold higher than the recommended human dose and in patients inadvertently given tranexamic acid into the neuraxial system). Tranexamic acid is not approved and not recommended for neuraxial administration. Consider dose reduction during surgery and dose adjustments for patients with clinical conditions such as renal dysfunction. Closely monitor the patient during surgery. Consider electroencephalogram (EEG) monitoring for patients with history of seizures or who experience myoclonic movements, twitching, or show evidence of focal seizures. Discontinue tranexamic acid if seizures occur.

Cases of overdosage of tranexamic acid have been reported. Based on these reports, symptoms of overdosage may be gastrointestinal, e.g., nausea, vomiting, diarrhea; hypotensive, e.g., orthostatic symptoms; thromboembolic, e.g., arterial, venous, embolic; neurologic, e.g., visual impairment, convulsions, headache, mental status changes; myoclonus; and rash.

Tranexamic acid may cause dizziness. Concomitant use of other drugs that may also cause dizziness may worsen this effect. Advise patients to avoid driving or using machines until they know how tranexamic acid affects them.

Tranexamic acid is trans-4-(aminomethyl)cyclohexanecarboxylic acid, an antifibrinolytic agent. Tranexamic acid, USP is a white crystalline powder. The structural formula is

Empirical Formula: C₈H₁₅NO₂ Molecular Weight: 157.2

Each mL of the sterile solution for intravenous injection contains 100 mg tranexamic acid, USP and Water for Injection to 1 mL. The aqueous solution for injection has a pH of 6.5 to 8.0.

There are limited data concerning the use of tranexamic acid in pediatric patients with hemophilia who are undergoing tooth extraction. The limited data suggest that there are no significant pharmacokinetic differences between adults and pediatric patients.

Clinical studies of tranexamic acid did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

Tranexamic acid injection is contraindicated:

• In patients with subarachnoid hemorrhage. Anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by tranexamic acid injection in such patients.
• In patients with active intravascular clotting [see Warnings and Precautions (5.1)].
• In patients with hypersensitivity to tranexamic acid or any of the ingredients [see Warnings and Precautions (5.4)].

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Thromboembolic Risk [see Warnings and Precautions (5.1)]
• Seizures [see Warnings and Precautions (5.3)]
• Hypersensitivity Reactions [see Warnings and Precautions (5.4)]
• Visual Disturbances [see Warnings and Precautions (5.5)]
• Dizziness [see Warnings and Precautions (5.6)]

Prothrombotic Medical Products: Avoid concomitant use, can further increase the risk of thromboembolic adverse reactions associated with tranexamic acid. (5.1, 7.1, 8.3)

Reduce the dosage of tranexamic acid in patients with renal impairment, based on the patient's serum creatinine [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

Tranexamic acid, in concentrations of 1 mg/mL and 10 mg/mL prolongs the thrombin time. An antifibrinolytic concentration of tranexamic acid remains in different tissues for about 17 hours, and in the serum, up to 7 or 8 hours.

Tranexamic acid in concentrations up to 10 mg/mL blood has no influence on the platelet count, the coagulation time or various coagulation factors in whole blood or citrated blood from healthy subjects.

The recommended dose of tranexamic acid injection is 10 mg/kg actual body weight intravenously administered as a single-dose, immediately before tooth extractions. Infuse no more than 1 mL/minute to avoid hypotension [see Warnings and Precautions (5.1)]. Following tooth extraction, tranexamic acid injection may be administered for 2 to 8 days at a dose of 10 mg/kg actual body weight 3 to 4 times daily, intravenously.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

For intravenous infusion, tranexamic acid injection may be mixed with most solutions for infusion such as electrolyte solutions, carbohydrate solutions, amino acid solutions, and Dextran solutions. Heparin may be added to tranexamic acid injection. Tranexamic acid injection should NOT be mixed with blood. The drug is a synthetic amino acid and should NOT be mixed with solutions containing penicillin.

Discard any unused portion.

The diluted mixture may be stored for up to 4 hours at room temperature prior to patient administration.

Tranexamic acid injection is indicated in patients with hemophilia for short-term use (2 to 8 days) to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction.

Tranexamic acid is contraindicated in patients with active intravascular clotting.

Tranexamic acid is an antifibrinolytic and may increase the risk of thromboembolic events. Venous and arterial thrombosis or thromboembolism has been reported in patients treated with tranexamic acid. Avoid concomitant use of tranexamic acid and medical products that are pro-thrombotic, as the risk of thrombosis may be increased. These medications include but are not limited to, Factor IX Complex concentrates, Anti-inhibitor Coagulant concentrates, and hormonal contraceptives [see Drug Interactions (7.1), Use in Specific Populations (8.3)].

Although not seen in humans, focal areas of retinal degeneration have been observed in cats and dogs following oral or intravenous tranexamic acid at doses between 250 to 1600 mg/kg/day (1.6 to 22 times the recommended usual human dose based on body surface area) from 6 days to 1 year. No retinal changes have been observed in eye examinations of patients treated with tranexamic acid for up to 8 years. Patients expected to be treated for greater than 3 months may consider ophthalmic monitoring including visual acuity and optical coherence tomography at regular intervals.

Discontinue tranexamic acid if changes in ophthalmological examination occurs.

Tranexamic acid is a synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin. In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrin's matrix structure.

The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen. Native human plasminogen contains 4 to 5 lysine binding sites with low affinity for tranexamic acid (Kd = 750 μmol/L) and 1 with high affinity (Kd = 1.1 μmol/L). The high affinity lysine site of plasminogen is involved in its binding to fibrin. Saturation of the high affinity binding site with tranexamic acid displaces plasminogen from the surface of fibrin. Although plasmin may be formed by conformational changes in plasminogen, binding to and dissolution of the fibrin matrix is inhibited.

• Risk of Thrombosis with Concomitant Use of Factor IX: Avoid concomitant use. (5.1)
• Risk of Medication Errors Due to Incorrect Route of Administration: FOR INTRAVENOUS USE ONLY. (5.2)
• Seizures: Inadvertent injection into neuraxial system may result in seizures. (5.3)
• Hypersensitivity Reactions: In case of severe reaction, discontinue use and seek immediate medical attention. (5.4)
• Visual Disturbances: Visual or ocular adverse effects may occur. Discontinue use if visual or ocular symptoms occur. (5.5)
• Dizziness: Advise patients not to drive if dizziness occurs. (5.6)

• Before Extraction: Administer 10 mg/kg actual body weight of tranexamic acid injection intravenously with replacement therapy. (2.1)
• After Extraction: Administer 10 mg/kg actual body weight 3 to 4 times daily for 2 to 8 days. Infuse no more than 1 mL/minute to avoid hypotension. (2.1)
• Reduce the dosage for patients with renal impairment. (2.2, 8.6)

Injection: 1,000 mg tranexamic acid, USP (100 mg per mL) clear and colorless solution in 10 mL single-dose vials.

The following adverse reactions have been identified during postapproval use of tranexamic acid. 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.

Gastrointestinal disturbances (nausea, vomiting, diarrhea) may occur and may resolve with dose-reduction. Allergic dermatitis and giddiness have been reported. Hypotension has been reported when intravenous injection is too rapid.

Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acute renal cortical necrosis, and central retinal artery, vein obstruction and cases associated with concomitant use of combination hormonal contraceptives) have been rarely reported in patients receiving tranexamic acid for indications other than hemorrhage prevention in patients with hemophilia. Convulsion, cromatopsia, and visual impairment have also been reported.

Anaphylaxis or anaphylactoid reactions have been reported that are suggestive of a causal relationship.

Cases of hypersensitivity reactions, including anaphylactic reactions, have occurred with use of intravenous tranexamic acid. Discontinue treatment with tranexamic acid if serious reaction occurs, provide appropriate medical management, and do not restart treatment. Tranexamic acid is contraindicated in patients with a history of hypersensitivity to tranexamic acid.

Avoid concomitant use of tranexamic acid with medical products that are prothrombotic because concomitant use can further increase the risk of thromboembolic adverse reactions associated with tranexamic acid [see Warnings and Precautions (5.1), Use in Specific Populations (8.3)].

Tranexamic Acid Injection, USP is a clear, colorless solution supplied as follows:

Nonclinical studies have shown a retinal toxicity associated with tranexamic acid. Toxicity is characterized by retinal atrophy commencing with changes to the retinal pigmented epithelium and progressing to retinal detachment in cats. The toxicity appears to be dose related, and changes are partially reversible at lower doses. Effects were observed in dogs at oral doses of 800 mg/kg/day and higher (multiple of 11 times the maximum human dose based on body surface area), and in cats at 250 mg/kg/day for 14 days (multiple of 1.6 times the maximum human dose based on body surface area). Some fully reversible changes in pigmentation were observed in cats at doses of 125 mg/kg/day (multiple of 0.8 times the maximum human dose based on body surface area). Studies suggest that the underlying mechanism may be related to a transient retinal ischemia at high exposures, linked to the known sympathomimetic effect of high plasma exposures of tranexamic acid.

Contraception

Concomitant use of tranexamic acid, which is an antifibrinolytic, with hormonal contraceptives may increase the risk for thromboembolic adverse reactions. Advise patients to use an effective alternative (nonhormonal) contraceptive method [see Warnings and Precautions (5.1), Drug Interactions (7.1)].

NDC 25021-415-10

Rx only

Tranexamic Acid Injection, USP

1,000 mg per 10 mL

(100 mg per mL)

For Intravenous Use Only

10 mL Single-Dose Vial

Tranexamic acid was not carcinogenic in a 2-year study in rats and mice at oral doses up to 3 and 5.3 g/kg/day, which are approximately 12 and 11 times the maximum recommended human dose based on body surface area, respectively.

Tranexamic acid was not genotoxic in the reverse mutation bacterial (Ames) test, and in vitro and in vivo cytogenetic test.

In a fertility and early embryonic development study, tranexamic acid was administered to male rats as 0.3% and 1% of drug in diet (average doses of 222 and 856 mg/kg/day) or to female rats at dose levels of 0.3% and 1.2% of drug in diet. Tranexamic acid had no effect on fertility or reproductive function of male or female rats at dose multiples of 4 or 5 times the maximum recommended human dose based on body surface area, respectively.

For patients with moderate to severe impaired renal function, the following dosages are recommended: