Valacyclovir
Generic: VALACYCLOVIR
Basic Information
Manufacturer
St. Mary's Medical Park Pharmacy
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
bed99bed-3904-5278-e053-2a95a90aeab6
Indications & Usage
1 INDICATIONS & USAGE Valacyclovir tablet, USP is a nucleoside analogue DNA polymerase inhibitor indicated for: Adult Patients (1.1) • Cold Sores (Herpes Labialis) • Genital Herpes • Treatment in immunocompetent patients (initial or recurrent episode) • Suppression in immunocompetent or HIV-infected patients • Reduction of transmission • Herpes Zoster Pediatric Patients (1.2) • Cold Sores (Herpes Labialis) • Chickenpox Limitations of Use (1.3) • The efficacy and safety of valacyclovir tablets, USP have not been established in immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients.
1.1 Adult patients Cold Sores (Herpes Labialis): Valacyclovir tablets, USP are indicated for treatment of cold sores (herpes labialis).
The efficacy of valacyclovir tablets, USP initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established.
Genital Herpes: Initial Episode: Valacyclovir tablets, USP are indicated for treatment of the initial episode of genital herpes in immunocompetent adults.
The efficacy of treatment with valacyclovir tablets, USP when initiated more than 72 hours after the onset of signs and symptoms has not been established.
Recurrent Episodes: Valacyclovir tablets, USP are indicated for treatment of recurrent episodes of genital herpes in immunocompetent adults.
The efficacy of treatment with valacyclovir tablets, USP when initiated more than 24 hours after the onset of signs and symptoms has not been established.
Suppressive Therapy: Valacyclovir tablets, USP are indicated for chronic suppressive therapy of recurrent episodes of genital herpes in immunocompetent and in HIV-infected adults.
The efficacy and safety of valacyclovir tablets, USP for the suppression of genital herpes beyond 1 year in immunocompetent patients and beyond 6 months in HIV-infected patients have not been established.
Reduction of Transmission: Valacyclovir tablets, USP are indicated for the reduction of transmission of genital herpes in immunocompetent adults.
The efficacy of valacyclovir tablets, USP for the reduction of transmission of genital herpes beyond 8 months in discordant couples has not been established.
The efficacy of valacyclovir tablets, USP for the reduction of transmission of genital herpes in individuals with multiple partners and non-heterosexual couples has not been established.
Safer sex practices should be used with suppressive therapy (see current Centers for Disease Control and Prevention [CDC] Sexually Transmitted Diseases Treatment Guidelines ).
Herpes Zoster: Valacyclovir tablets, USP are indicated for the treatment of herpes zoster (shingles) in immunocompetent adults.
The efficacy of valacyclovir tablets, USP when initiated more than 72 hours after the onset of rash and the efficacy and safety of valacyclovir tablets, USP for treatment of disseminated herpes zoster have not been established.
1.2 Pediatric Patients Cold Sores (Herpes Labialis): Valacyclovir tablets, USP are indicated for the treatment of cold sores (herpes labialis) in pediatric patients ≥12 years of age.
The efficacy of valacyclovir tablets, USP initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established.
Chickenpox: Valacyclovir tablets, USP are indicated for the treatment of chickenpox in immunocompetent pediatric patients 2 to <18 years of age.
Based on efficacy data from clinical studies with oral acyclovir, treatment with valacyclovir tablets, USP should be initiated within 24 hours after the onset of rash [see Clinical Studies (14.4)].
1.3 Limitations of Use The efficacy and safety of valacyclovir tablets, USP have not been established in: • Immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients with a CD4+ cell count ≥100 cells/mm 3 .
• Patients <12 years of age with cold sores (herpes labialis).
• Patients <2 years of age or ≥18 years of age with chickenpox.
• Patients <18 years of age with genital herpes.
• Patients <18 years of age with herpes zoster.
• Neonates and infants as suppressive therapy following neonatal herpes simplex virus (HSV) infection.
1.1 Adult patients Cold Sores (Herpes Labialis): Valacyclovir tablets, USP are indicated for treatment of cold sores (herpes labialis).
The efficacy of valacyclovir tablets, USP initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established.
Genital Herpes: Initial Episode: Valacyclovir tablets, USP are indicated for treatment of the initial episode of genital herpes in immunocompetent adults.
The efficacy of treatment with valacyclovir tablets, USP when initiated more than 72 hours after the onset of signs and symptoms has not been established.
Recurrent Episodes: Valacyclovir tablets, USP are indicated for treatment of recurrent episodes of genital herpes in immunocompetent adults.
The efficacy of treatment with valacyclovir tablets, USP when initiated more than 24 hours after the onset of signs and symptoms has not been established.
Suppressive Therapy: Valacyclovir tablets, USP are indicated for chronic suppressive therapy of recurrent episodes of genital herpes in immunocompetent and in HIV-infected adults.
The efficacy and safety of valacyclovir tablets, USP for the suppression of genital herpes beyond 1 year in immunocompetent patients and beyond 6 months in HIV-infected patients have not been established.
Reduction of Transmission: Valacyclovir tablets, USP are indicated for the reduction of transmission of genital herpes in immunocompetent adults.
The efficacy of valacyclovir tablets, USP for the reduction of transmission of genital herpes beyond 8 months in discordant couples has not been established.
The efficacy of valacyclovir tablets, USP for the reduction of transmission of genital herpes in individuals with multiple partners and non-heterosexual couples has not been established.
Safer sex practices should be used with suppressive therapy (see current Centers for Disease Control and Prevention [CDC] Sexually Transmitted Diseases Treatment Guidelines ).
Herpes Zoster: Valacyclovir tablets, USP are indicated for the treatment of herpes zoster (shingles) in immunocompetent adults.
The efficacy of valacyclovir tablets, USP when initiated more than 72 hours after the onset of rash and the efficacy and safety of valacyclovir tablets, USP for treatment of disseminated herpes zoster have not been established.
1.2 Pediatric Patients Cold Sores (Herpes Labialis): Valacyclovir tablets, USP are indicated for the treatment of cold sores (herpes labialis) in pediatric patients ≥12 years of age.
The efficacy of valacyclovir tablets, USP initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established.
Chickenpox: Valacyclovir tablets, USP are indicated for the treatment of chickenpox in immunocompetent pediatric patients 2 to <18 years of age.
Based on efficacy data from clinical studies with oral acyclovir, treatment with valacyclovir tablets, USP should be initiated within 24 hours after the onset of rash [see Clinical Studies (14.4)].
1.3 Limitations of Use The efficacy and safety of valacyclovir tablets, USP have not been established in: • Immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients with a CD4+ cell count ≥100 cells/mm 3 .
• Patients <12 years of age with cold sores (herpes labialis).
• Patients <2 years of age or ≥18 years of age with chickenpox.
• Patients <18 years of age with genital herpes.
• Patients <18 years of age with herpes zoster.
• Neonates and infants as suppressive therapy following neonatal herpes simplex virus (HSV) infection.
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: • Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome [see Warnings and Precautions (5.1)].
• Acute Renal Failure [see Warnings and Precautions (5.2)].
• Central Nervous System Effects [see Warnings and Precautions (5.3)].
The most common adverse reactions reported in at least 1 indication by >10% of adult patients treated with valacyclovir hydrochloride and observed more frequently with valacyclovir hydrochloride compared to placebo are headache, nausea, and abdominal pain.
The only adverse reaction reported in >10% of pediatric patients <18 years of age was headache.
• The most common adverse reactions reported in at least one indication by >10% of adult patients treated with valacyclovir hydrochloride and more commonly than in patients treated with placebo are headache, nausea, and abdominal pain.
(6.1) • The only adverse reaction occurring in >10% of pediatric patients <18 years of age was headache.(6.2) To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling 6.1 Clinical Trials Experience in Adult Patients Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Cold Sores (Herpes Labialis): In clinical studies for the treatment of cold sores, the adverse reactions reported by patients receiving valacyclovir hydrochloride 2 grams twice daily (n = 609) or placebo (n = 609) for 1 day, respectively, included headache (14%, 10%) and dizziness (2%, 1%).
The frequencies of abnormal ALT (>2 x ULN) were 1.8% for patients receiving valacyclovir hydrochloride compared with 0.8% for placebo.
Other laboratory abnormalities (hemoglobin, white blood cells, alkaline phosphatase, and serum creatinine) occurred with similar frequencies in the 2 groups.
Genital Herpes: Initial Episode: In a clinical study for the treatment of initial episodes of genital herpes, the adverse reactions reported by ≥5% of patients receiving valacyclovir hydrochloride 1 gram twice daily for 10 days (n = 318) or oral acyclovir 200 mg 5 times daily for 10 days (n = 318), respectively, included headache (13%, 10%) and nausea (6%, 6%).
For the incidence of laboratory abnormalities see Table 2.
Recurrent Episodes: In 3 clinical studies for the episodic treatment of recurrent genital herpes, the adverse reactions reported by ≥5% of patients receiving valacyclovir hydrochloride 500 mg twice daily for 3 days (n = 402), valacyclovir hydrochloride 500 mg twice daily for 5 days (n = 1,136) or placebo (n = 259), respectively, included headache (16%, 11%, 14%) and nausea (5%, 4%, 5%).
For the incidence of laboratory abnormalities see Table 2.
Suppressive Therapy: Suppression of Recurrent Genital Herpes in Immunocompetent Adults: In a clinical study for the suppression of recurrent genital herpes infections, the adverse reactions reported by patients receiving valacyclovir hydrochloride 1 gram once daily (n = 269), valacyclovir hydrochloride 500 mg once daily (n = 266), or placebo (n = 134), respectively, included headache (35%, 38%, 34%), nausea (11%, 11%, 8%), abdominal pain (11%, 9%, 6%), dysmenorrhea (8%, 5%, 4%), depression (7%, 5%, 5%), arthralgia (6%, 5%, 4%), vomiting (3%, 3%, 2%), and dizziness (4%, 2%, 1%).
For the incidence of laboratory abnormalities see Table 2.
Suppression of Recurrent Genital Herpes in HIV-Infected Patients: In HIV-infected patients, frequently reported adverse reactions for valacyclovir hydrochloride (500 mg twice daily; n = 194, median days on therapy = 172) and placebo (n = 99, median days on therapy = 59), respectively, included headache (13%, 8%), fatigue (8%, 5%), and rash (8%, 1%).
Post-randomization laboratory abnormalities that were reported more frequently in valacyclovir subjects versus placebo included elevated alkaline phosphatase (4%, 2%), elevated ALT (14%, 10%), elevated AST (16%, 11%), decreased neutrophil counts (18%, 10%), and decreased platelet counts (3%, 0%), respectively.
Reduction of Transmission: In a clinical study for the reduction of transmission of genital herpes, the adverse reactions reported by patients receiving valacyclovir hydrochloride 500 mg once daily (n = 743) or placebo once daily (n = 741), respectively, included headache (29%, 26%), nasopharyngitis (16%, 15%), and upper respiratory tract infection (9%, 10%).
Herpes Zoster: In 2 clinical studies for the treatment of herpes zoster, the adverse reactions reported by patients receiving valacyclovir hydrochloride 1 gram 3 times daily for 7 to 14 days (n = 967) or placebo (n = 195), respectively, included nausea (15%, 8%), headache (14%, 12%), vomiting (6%, 3%), dizziness (3%, 2%), and abdominal pain (3%, 2%).
For the incidence of laboratory abnormalities see Table 2.
Table 2.
Incidence (%) of Laboratory Abnormalities in Herpes Zoster and Genital Herpes Study Populations Laboratory Abnormality Herpes Zoster Genital Herpes Treatment Genital Herpes Suppression Valacyclovir Hydrochloride 1 gram 3 times daily (n = 967) Placebo (n = 195) Valacyclovir Hydrochloride 1 gram twice daily (n = 1,194) Valacyclovir Hydrochloride 500 mg twice daily (n = 1,159) Placebo (n = 439) Valacyclovir Hydrochloride 1 gram once daily (n = 269) Valacyclovir Hydrochloride 500 mg once daily (n = 266) Placebo (n = 134) Hemoglobin (<0.8 x LLN) 0.8% 0% 0.3% 0.2% 0% 0% 0.8% 0.8% White blood cells (<0.75 x LLN) 1.3% 0.6% 0.7% 0.6% 0.2% 0.7% 0.8% 1.5% Platelet count (<100,000/mm 3 ) 1.0% 1.2% 0.3% 0.1% 0.7% 0.4% 1.1% 1.5% AST (SGOT) (>2 x ULN) 1.0% 0% 1.0% a 0.5% 4.1% 3.8% 3.0% Serum creatinine (>1.5 x ULN) 0.2% 0% 0.7% 0% 0% 0% 0% 0% a Data were not collected prospectively.
LLN = Lower limit of normal.
ULN = Upper limit of normal.
6.2 Clinical Trials Experience in Pediatric Patients The safety profile of valacyclovir hydrochloride has been studied in 177 pediatric patients 1 month to <18 years of age.
Sixty-five pediatric patients, 12 to <18 years of age, received oral tablets for 1 to 2 days for treatment of cold sores.
The remaining 112 pediatric patients, 1 month to <12 years of age, participated in 3 pharmacokinetic and safety studies and received valacyclovir oral suspension.
Fifty-one of these 112 pediatric patients received oral suspension for 3 to 6 days.
The frequency, intensity, and nature of clinical adverse reactions and laboratory abnormalities were similar to those seen in adults.
Pediatric Patients 12 to <18 Years of Age (Cold Sores): In clinical studies for the treatment of cold sores, the adverse reactions reported by adolescent patients receiving valacyclovir hydrochloride 2 grams twice daily for 1 day, or valacyclovir hydrochloride 2 grams twice daily for 1 day followed by 1 gram twice daily for 1 day (n = 65, across both dosing groups), or placebo (n = 30), respectively, included headache (17%, 3%) and nausea (8%, 0%).
Pediatric Patients 1 Month to <12 Years of Age: Adverse events reported in more than 1 subject across the 3 pharmacokinetic and safety studies in children 1 month to <12 years of age were diarrhea (5%), pyrexia (4%), dehydration (2%), herpes simplex (2%), and rhinorrhea (2%).
No clinically meaningful changes in laboratory values were observed.
6.3 Postmarketing Experience In addition to adverse events reported from clinical trials, the following events have been identified during postmarketing use of valacyclovir hydrochloride.
Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made.
These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to valacyclovir hydrochloride.
General: Facial edema, hypertension, tachycardia.
Allergic: Acute hypersensitivity reactions including anaphylaxis, angioedema, dyspnea, pruritus, rash, and urticaria [see Contraindications (4)].
CNS Symptoms: Aggressive behavior; agitation; ataxia; coma; confusion; decreased consciousness; dysarthria; encephalopathy; mania; and psychosis, including auditory and visual hallucinations, seizures, tremors [see Warnings and Precautions (5.3), Use in Specific Populations (8.5), (8.6)].
Eye: Visual abnormalities.
Gastrointestinal: Diarrhea.
Hepatobiliary Tract and Pancreas: Liver enzyme abnormalities, hepatitis.
Renal: Renal failure, renal pain (may be associated with renal failure) [see Warnings and Precautions (5.2), Use in Specific Populations (8.5), (8.6)].
Hematologic: Thrombocytopenia, aplastic anemia, leukocytoclastic vasculitis, TTP/HUS [see Warnings and Precautions (5.1)].
Skin: Erythema multiforme, rashes including photosensitivity, alopecia.
• Acute Renal Failure [see Warnings and Precautions (5.2)].
• Central Nervous System Effects [see Warnings and Precautions (5.3)].
The most common adverse reactions reported in at least 1 indication by >10% of adult patients treated with valacyclovir hydrochloride and observed more frequently with valacyclovir hydrochloride compared to placebo are headache, nausea, and abdominal pain.
The only adverse reaction reported in >10% of pediatric patients <18 years of age was headache.
• The most common adverse reactions reported in at least one indication by >10% of adult patients treated with valacyclovir hydrochloride and more commonly than in patients treated with placebo are headache, nausea, and abdominal pain.
(6.1) • The only adverse reaction occurring in >10% of pediatric patients <18 years of age was headache.(6.2) To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling 6.1 Clinical Trials Experience in Adult Patients Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Cold Sores (Herpes Labialis): In clinical studies for the treatment of cold sores, the adverse reactions reported by patients receiving valacyclovir hydrochloride 2 grams twice daily (n = 609) or placebo (n = 609) for 1 day, respectively, included headache (14%, 10%) and dizziness (2%, 1%).
The frequencies of abnormal ALT (>2 x ULN) were 1.8% for patients receiving valacyclovir hydrochloride compared with 0.8% for placebo.
Other laboratory abnormalities (hemoglobin, white blood cells, alkaline phosphatase, and serum creatinine) occurred with similar frequencies in the 2 groups.
Genital Herpes: Initial Episode: In a clinical study for the treatment of initial episodes of genital herpes, the adverse reactions reported by ≥5% of patients receiving valacyclovir hydrochloride 1 gram twice daily for 10 days (n = 318) or oral acyclovir 200 mg 5 times daily for 10 days (n = 318), respectively, included headache (13%, 10%) and nausea (6%, 6%).
For the incidence of laboratory abnormalities see Table 2.
Recurrent Episodes: In 3 clinical studies for the episodic treatment of recurrent genital herpes, the adverse reactions reported by ≥5% of patients receiving valacyclovir hydrochloride 500 mg twice daily for 3 days (n = 402), valacyclovir hydrochloride 500 mg twice daily for 5 days (n = 1,136) or placebo (n = 259), respectively, included headache (16%, 11%, 14%) and nausea (5%, 4%, 5%).
For the incidence of laboratory abnormalities see Table 2.
Suppressive Therapy: Suppression of Recurrent Genital Herpes in Immunocompetent Adults: In a clinical study for the suppression of recurrent genital herpes infections, the adverse reactions reported by patients receiving valacyclovir hydrochloride 1 gram once daily (n = 269), valacyclovir hydrochloride 500 mg once daily (n = 266), or placebo (n = 134), respectively, included headache (35%, 38%, 34%), nausea (11%, 11%, 8%), abdominal pain (11%, 9%, 6%), dysmenorrhea (8%, 5%, 4%), depression (7%, 5%, 5%), arthralgia (6%, 5%, 4%), vomiting (3%, 3%, 2%), and dizziness (4%, 2%, 1%).
For the incidence of laboratory abnormalities see Table 2.
Suppression of Recurrent Genital Herpes in HIV-Infected Patients: In HIV-infected patients, frequently reported adverse reactions for valacyclovir hydrochloride (500 mg twice daily; n = 194, median days on therapy = 172) and placebo (n = 99, median days on therapy = 59), respectively, included headache (13%, 8%), fatigue (8%, 5%), and rash (8%, 1%).
Post-randomization laboratory abnormalities that were reported more frequently in valacyclovir subjects versus placebo included elevated alkaline phosphatase (4%, 2%), elevated ALT (14%, 10%), elevated AST (16%, 11%), decreased neutrophil counts (18%, 10%), and decreased platelet counts (3%, 0%), respectively.
Reduction of Transmission: In a clinical study for the reduction of transmission of genital herpes, the adverse reactions reported by patients receiving valacyclovir hydrochloride 500 mg once daily (n = 743) or placebo once daily (n = 741), respectively, included headache (29%, 26%), nasopharyngitis (16%, 15%), and upper respiratory tract infection (9%, 10%).
Herpes Zoster: In 2 clinical studies for the treatment of herpes zoster, the adverse reactions reported by patients receiving valacyclovir hydrochloride 1 gram 3 times daily for 7 to 14 days (n = 967) or placebo (n = 195), respectively, included nausea (15%, 8%), headache (14%, 12%), vomiting (6%, 3%), dizziness (3%, 2%), and abdominal pain (3%, 2%).
For the incidence of laboratory abnormalities see Table 2.
Table 2.
Incidence (%) of Laboratory Abnormalities in Herpes Zoster and Genital Herpes Study Populations Laboratory Abnormality Herpes Zoster Genital Herpes Treatment Genital Herpes Suppression Valacyclovir Hydrochloride 1 gram 3 times daily (n = 967) Placebo (n = 195) Valacyclovir Hydrochloride 1 gram twice daily (n = 1,194) Valacyclovir Hydrochloride 500 mg twice daily (n = 1,159) Placebo (n = 439) Valacyclovir Hydrochloride 1 gram once daily (n = 269) Valacyclovir Hydrochloride 500 mg once daily (n = 266) Placebo (n = 134) Hemoglobin (<0.8 x LLN) 0.8% 0% 0.3% 0.2% 0% 0% 0.8% 0.8% White blood cells (<0.75 x LLN) 1.3% 0.6% 0.7% 0.6% 0.2% 0.7% 0.8% 1.5% Platelet count (<100,000/mm 3 ) 1.0% 1.2% 0.3% 0.1% 0.7% 0.4% 1.1% 1.5% AST (SGOT) (>2 x ULN) 1.0% 0% 1.0% a 0.5% 4.1% 3.8% 3.0% Serum creatinine (>1.5 x ULN) 0.2% 0% 0.7% 0% 0% 0% 0% 0% a Data were not collected prospectively.
LLN = Lower limit of normal.
ULN = Upper limit of normal.
6.2 Clinical Trials Experience in Pediatric Patients The safety profile of valacyclovir hydrochloride has been studied in 177 pediatric patients 1 month to <18 years of age.
Sixty-five pediatric patients, 12 to <18 years of age, received oral tablets for 1 to 2 days for treatment of cold sores.
The remaining 112 pediatric patients, 1 month to <12 years of age, participated in 3 pharmacokinetic and safety studies and received valacyclovir oral suspension.
Fifty-one of these 112 pediatric patients received oral suspension for 3 to 6 days.
The frequency, intensity, and nature of clinical adverse reactions and laboratory abnormalities were similar to those seen in adults.
Pediatric Patients 12 to <18 Years of Age (Cold Sores): In clinical studies for the treatment of cold sores, the adverse reactions reported by adolescent patients receiving valacyclovir hydrochloride 2 grams twice daily for 1 day, or valacyclovir hydrochloride 2 grams twice daily for 1 day followed by 1 gram twice daily for 1 day (n = 65, across both dosing groups), or placebo (n = 30), respectively, included headache (17%, 3%) and nausea (8%, 0%).
Pediatric Patients 1 Month to <12 Years of Age: Adverse events reported in more than 1 subject across the 3 pharmacokinetic and safety studies in children 1 month to <12 years of age were diarrhea (5%), pyrexia (4%), dehydration (2%), herpes simplex (2%), and rhinorrhea (2%).
No clinically meaningful changes in laboratory values were observed.
6.3 Postmarketing Experience In addition to adverse events reported from clinical trials, the following events have been identified during postmarketing use of valacyclovir hydrochloride.
Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made.
These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to valacyclovir hydrochloride.
General: Facial edema, hypertension, tachycardia.
Allergic: Acute hypersensitivity reactions including anaphylaxis, angioedema, dyspnea, pruritus, rash, and urticaria [see Contraindications (4)].
CNS Symptoms: Aggressive behavior; agitation; ataxia; coma; confusion; decreased consciousness; dysarthria; encephalopathy; mania; and psychosis, including auditory and visual hallucinations, seizures, tremors [see Warnings and Precautions (5.3), Use in Specific Populations (8.5), (8.6)].
Eye: Visual abnormalities.
Gastrointestinal: Diarrhea.
Hepatobiliary Tract and Pancreas: Liver enzyme abnormalities, hepatitis.
Renal: Renal failure, renal pain (may be associated with renal failure) [see Warnings and Precautions (5.2), Use in Specific Populations (8.5), (8.6)].
Hematologic: Thrombocytopenia, aplastic anemia, leukocytoclastic vasculitis, TTP/HUS [see Warnings and Precautions (5.1)].
Skin: Erythema multiforme, rashes including photosensitivity, alopecia.