Valtrex (valacyclovir HCl)

Dosage of valacyclovir hydrochloride is expressed in terms of valacyclovir.

Valacyclovir dosage modification according to renal function may be necessary in geriatric patients, depending on the underlying renal status of the patient. (See Dosage and Administration: Dosage in Renal and Hepatic Impairment.)

The manufacturer states that valacyclovir should be used with caution in patients receiving potentially nephrotoxic agents because this may increase the risk of renal dysfunction and/or reversible CNS manifestations. In patients with impaired renal function, doses and/or frequency of administration of valacyclovir must be modified in response to the degree of impairment.

For the treatment of first episodes of genital herpes in immunocompetent adults with impaired renal function, the manufacturer states that patients with creatinine clearances of 30 mL/minute per 1.73 m2 or greater may receive the usual oral valacyclovir dosage of 1 g every 12 hours; however, those with creatinine clearances of 10-29 or less than 10 mL/minute per 1.73 m2 should receive 1 g or 500 mg, respectively, once every 24 hours. For the episodic treatment of recurrent genital herpes in immunocompetent adults with impaired renal function, patients with creatinine clearances of 30 mL/minute per 1.73 m2 may receive the usual dosage of 500 mg every 12 hours, but those with clearances of 29 mL/minute per 1.73 m2 or less should receive 500 mg once every 24 hours.

For chronic suppression of recurrent episodes of genital herpes in immunocompetent adults with renal impairment, those with creatinine clearances of 30 mL/minute per 1.73 m2 or greater may receive the usually recommended dosage of oral valacyclovir. Patients with creatinine clearances less than 30 mL/minute per 1.73 m2 should receive 500 mg once every 24 hours; alternatively, those with a history of 9 or fewer recurrences per year may receive 500 mg once every 48 hours.

For chronic suppression of recurrent episodes of genital herpes in HIV-infected adults with renal impairment, those with creatinine clearances of 30 mL/minute per 1.73 m2 or greater may receive the usually recommended dosage of oral valacyclovir and those with creatinine clearances less than 30 mL/minute per 1.73 m2 should receive 500 mg once every 24 hours.

For the treatment of herpes labialis (cold sores) in patients with renal impairment, patients with creatinine clearances of 50 mL/minute or greater per 1.73 m2 may receive the usual oral valacyclovir dosage of 2 g every 12 hours for 1 day. Those with creatinine clearances of 30-49 mL/minute per 1.73 m2 should receive 1 g every 12 hours for 1 day, those with creatinine clearances of 10-29mL/minute per 1.73 m2 should receive 500 mg every 12 hours for 1 day, and those with creatinine clearances less than 10 mL/minute per 1.73 m2 should receive a single 500-mg dose.

For the treatment of acute, localized herpes zoster in adults, the manufacturer states that patients with creatinine clearances of 50 mL/minute or greater per 1.73 m2 may receive the usual oral valacyclovir dosage of 1 g every 8 hours. Those with creatinine clearances of 30-49 mL/minute per 1.73 m2 should receive 1 g every 12 hours, and those with creatinine clearances of 10-29 or less than 10 mL/minute per 1.73 m2 should receive 1 g or 500 mg, respectively, once every 24 hours.

Because acyclovir is removed by hemodialysis, the manufacturer states that patients undergoing hemodialysis may require a supplemental dose of valacyclovir after each dialysis period. However, if usual dosing coincides with a valacyclovir dose being administered soon after hemodialysis and subsequent dialysis takes place toward the end of the dosing interval, a supplemental dose would not be necessary.

Information regarding use of valacyclovir in patients undergoing peritoneal dialysis is not available. Based on experience with acyclovir, the manufacturer states that supplemental doses of valacyclovir do not appear to be necessary following peritoneal dialysis, either continuous ambulatory peritoneal dialysis (CAPD) or continuous arteriovenous hemofiltration/dialysis (CAVHD).

The rate but not the extent of conversion of valacyclovir to acyclovir may be reduced in patients with moderate (biopsy-proven cirrhosis) or severe (with and without ascites and biopsy-proven cirrhosis) hepatic impairment. Therefore, the manufacturer states that dosage modification is not necessary for patients with cirrhosis.

Valacyclovir hydrochloride is administered orally without regard to meals. Food does not affect systemic bioavailability of the drug.

Patients should maintain adequate hydration during valacyclovir treatment.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Cyp1a2 Inhibitors/Fezolinetant

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Inhibitors of CYP1A2 may inhibit the metabolism of fezolinetant.(1-4)

CLINICAL EFFECTS: Concurrent use of a CYP1A2 inhibitor may increase levels of and adverse effects from fezolinetant.(1-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Recommendations for concurrent use of fezolinetant with CYP1A2 inhibitors differ in different regions. The US manufacturer of fezolinetant states that concurrent use with strong, moderate, and weak CYP1A2 inhibitors is contraindicated.(1) The Australian, Canadian, and UK manufacturers of fezolinetant state that concurrent use with strong and moderate CYP1A2 inhibitors is contraindicated, while weak CYP1A2 inhibitors are not predicted to cause clinically relevant changes in fezolinetant exposure.(2-4)

DISCUSSION: In a study, fluvoxamine, a strong CYP1A2 inhibitor, increased fezolinetant maximum concentration (Cmax) and area-under-curve (AUC) by 80% and 840%, respectively. Mexiletine (400 mg every 8 hours), a moderate CYP1A2 inhibitor, increased fezolinetant Cmax and AUC by 40% and 360%, respectively. Cimetidine (300 mg every 6 hours), a weak CYP1A2 inhibitor, increased fezolinetant Cmax and AUC by 30% and 100%, respectively.(1) Strong CYP1A2 inhibitors linked to this monograph include angelica root, ciprofloxacin, enasidenib, enoxacin, fluvoxamine, and rofecoxib. Moderate CYP1A2 inhibitors linked to this monograph include capmatinib, centanafadine, dipyrone, fexinidazole, genistein, hormonal contraceptives, methoxsalen, mexiletine, osilodrostat, phenylpropanolamine, pipemidic acid, rucaparib, troleandomycin, vemurafenib, and viloxazine. Weak CYP1A2 inhibitors linked to this monograph include acyclovir, allopurinol, artemisinin, belumosudil, caffeine, cannabidiol, cimetidine, curcumin, dan-shen, deferasirox, disulfiram, Echinacea, famotidine, ginseng, norfloxacin, obeticholic acid, parsley, piperine, propafenone, propranolol, ribociclib, simeprevir, thiabendazole, ticlopidine, triclabendazole, valacyclovir, verapamil, and zileuton.(5-7)

Famciclo; Val; Acyclovir/Varicella; Zoster Live Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Acyclovir, famciclovir, and valacyclovir inhibit varicella zoster virus activity and may prevent the body from developing an immune response to the live vaccine.

CLINICAL EFFECTS: Administration of antiviral agents active against varicella zoster virus may decrease the efficacy of live, attenuated varicella or zoster vaccines.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: CDC immunization guidelines recommend acyclovir, famciclovir or valacyclovir discontinuation at least 24 hours prior to administration of varicella or zoster vaccines, if possible. Delay use or resumption of antiviral therapy for 14 days after vaccination.(1)

DISCUSSION: Acyclovir, famciclovir, valacyclovir inhibit varicella zoster virus activity and may prevent the body from developing an immune response to the live vaccine, decreasing the efficacy of efficacy of live, attenuated varicella or zoster vaccines.(1)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Acyclovir/Tizanidine

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Acyclovir may inhibit the metabolism of tizanidine by CYP1A2.(1)

CLINICAL EFFECTS: Concurrent use of acyclovir may result in elevated levels of and effects from tizanidine, including hypotension, bradycardia, drowsiness, sedation, and decreased psychomotor function.

PREDISPOSING FACTORS: The risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(2)

PATIENT MANAGEMENT: The US manufacturer of tizanidine states that concurrent use of tizanidine with inhibitors of CYP1A2, such as acyclovir, should be avoided. If concurrent use is warranted, tizanidine should be initiated with a 2 mg dose and increased in 2-4 mg steps daily based on patient response to therapy.(1) If adverse reactions such as hypotension, bradycardia, or excessive drowsiness occur, reduce or discontinue tizanidine therapy.(1)

DISCUSSION: In a study in 10 healthy subjects, concurrent fluvoxamine, another inhibitor of CYP1A2, increased tizanidine maximum concentration (Cmax), area-under-curve (AUC), and half-life (T1/2) by 12-fold, 33-fold, and 3-fold, respectively. Significant decreases in blood pressure and increases in drowsiness and psychomotor impairment occurred.(1) In a study in 10 healthy subjects, concurrent ciprofloxacin, another inhibitor of CYP1A2, increase tizanidine Cmax and AUC by 7-fold and 10-fold, respectively. Significant decreases in blood pressure and and increases in drowsiness and psychomotor impairment occurred.(1)

Selected Antiviral Agents/Cladribine Oral

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Antiviral agents may inhibit the intracellular phosphorylation of cladribine by competitive inhibition of intracellular kinases.(1-4)

CLINICAL EFFECTS: Concurrent administration of antiviral agents with cladribine may result in decreased clinical efficacy of cladribine.(1-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of cladribine states that concurrent use of compounds that require activation by intracellular phosphorylation is not recommended.(1)

DISCUSSION: Cladribine undergoes a series of phosphorylations to its active metabolites.(1) Compounds phosphorylated by kinases linked to this monograph include: acyclovir, entecavir, ganciclovir, tenofovir, valacyclovir, and valganciclovir.

Selected Antivirals/Talimogene Laherparepvec

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Talimogene laherparepvec is a live, attenuated herpes simplex virus (HSV-1) which has been modified to express human GM-CSF.(1)

CLINICAL EFFECTS: Administration of antiviral agents with activity against HSV-1 may interfere with the effectiveness of talimogene laherparepvec.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid concomitant use when possible. Talimogene laherparepvec is a live, attenuated herpes simplex virus (HSV-1) which is injected into cancerous lesions where it replicates and produces GM-CSF, leading to lysis of tumors. It is sensitive to antiherpetic agents such as acyclovir, valacyclovir and famciclovir and so administration of these antivirals may impair talimogene laherparepvec effectiveness.(1)

DISCUSSION: Agents that inhibit herpes simplex virus activity may impair the ability of talimogene laherparepvec to replicate and produce GM-CSF in tumors. The impact of concurrent antiviral and talimogene laherparepvec therapy has not been studied; patients requiring antiviral prophylaxis or treatment with acyclovir, valacyclovir and famciclovir were excluded from clinical trials.(1) Agents linked to this monograph are systemic formulations of acyclovir, cidofovir, famciclovir, foscarnet, ganciclovir, valacyclovir and valganciclovir.

Selected Mate Substrates/Mate Inhibitors

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Inhibitors of the Multidrug and Toxin Extrusion (MATE) renal protein transporters in the kidneys may inhibit the transport of MATE substrates.(1) Acyclovir, cephalexin, and valacyclovir are MATE substrates.

CLINICAL EFFECTS: Concurrent use of MATE renal transporter inhibitors may result in increased levels of and toxicity from MATE substrates.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid concurrent use of acyclovir, cephalexin, or valacyclovir with MATE renal transporter inhibitors. If concurrent use cannot be avoided, monitor for toxicity of the MATE substrate and consider dosage reduction of the MATE substrate.(1)

DISCUSSION: Based upon in vitro data, risdiplam is expected to produce clinically significant inhibition of MATE1 and MATE2-K transporters at clinically relevant concentrations.(1) Selected MATE substrates linked include: acyclovir, cephalexin, and valacyclovir.(1,2) MATE inhibitors include: cimetidine, pyrimethamine, risdiplam, and vandetanib.(2)

Selected Nephrotoxic Agents/Foscarnet

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Foscarnet is nephrotoxic. Concurrent administration of other nephrotoxic agents may result in additive or synergistic effects on renal function.(1) Concurrent intravenous pentamidine may also result in hypocalcemia.(1)

CLINICAL EFFECTS: Concurrent use of foscarnet with nephrotoxic agents such as acyclovir, adefovir, intravenous aminoglycosides, amphotericin B, cyclosporine, methotrexate, non-steroidal anti-inflammatory agents, intravenous pentamidine, tacrolimus, tenofovir, vancomycin and voclosporin may result in renal toxicity.(1) Other nephrotoxic agents include capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, and streptozocin.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of foscarnet state that concurrent administration of potentially nephrotoxic agents such as acyclovir, intravenous aminoglycosides, amphotericin B, cyclosporine, methotrexate, tacrolimus, and intravenous pentamidine should be avoided.(1) Other nephrotoxic agents include adefovir, capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, non-steroidal anti-inflammatory agents, streptozocin, tenofovir, vancomycin and voclosporin. If concurrent therapy is warranted, monitor renal function closely. In patients receiving concurrent foscarnet and pentamidine, also monitor serum calcium levels and instruct patients to report severe muscle spasms, mental/mood changes, and/or seizures.(1)

DISCUSSION: The safety of foscarnet has not been studied in patients receiving other known potentially nephrotoxic agents. Renal impairment is the major toxicity of foscarnet.(1)

Selected Nephrotoxic Agents/Inotersen

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Inotersen can cause glomerulonephritis and renal toxicity. Concurrent administration of other nephrotoxic agents may result in additive or synergistic effects on renal function.(1)

CLINICAL EFFECTS: Concurrent use of inotersen with nephrotoxic agents such as acyclovir, adefovir, intravenous aminoglycosides, amphotericin B, cyclosporine, methotrexate, non-steroidal anti-inflammatory agents, intravenous pentamidine, tacrolimus, tenofovir, vancomycin and voclosporin may result in renal toxicity.(1) Other nephrotoxic agents include capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, and streptozocin.

PREDISPOSING FACTORS: Patients with pre-existing renal impairment.

PATIENT MANAGEMENT: The US manufacturer of inotersen state that caution should be used when administered concurrently with potentially nephrotoxic agents or agents that impair renal function.(1) If concurrent therapy is warranted, monitor renal function closely.(1)

DISCUSSION: The safety of inotersen has not been studied in patients receiving other known potentially nephrotoxic agents. Inotersen is only available through a Tegsedi REMS program because of the risk of glomerulonephritis and severe thrombocytopenia.(1)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Selected Antivirals/Vusolimogene Oderparepvec

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Vusolimogene oderparepvec is a genetically modified herpes simplex virus type 1 (HSV-1) oncolytic viral therapy.(1)

CLINICAL EFFECTS: Administration of antiviral agents with activity against HSV-1 may interfere with the effectiveness of vusolimogene oderparepvec.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving systemic antiviral treatment for herpetic infection should delay vusolimogene oderparepvec for 72 hours after completing antiviral therapy.(1)

DISCUSSION: Agents that inhibit herpes simplex virus activity may impair the ability of vusolimogene oderparepvec to replicate in tumors.(1) Antiviral agents with activity against HSV-1 include: acyclovir, cidofovir, famciclovir, foscarnet, ganciclovir, valacyclovir, and valganciclovir.

Selected Cyp1a2 Inhibitors/Theophylline Derivatives

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: CYP1A2 inhibitors may reduce the elimination rate of theophylline derivatives.

CLINICAL EFFECTS: The concurrent administration of selected CYP1A2 inhibitors and theophylline or their derivatives may result in increased levels and toxicity of theophylline.(1-19)

PREDISPOSING FACTORS: Concomitant therapy with inhibitors of CYP3A4 (e.g. clarithromycin, itraconazole, ritonavir) which block a secondary metabolic pathway for theophylline, may increase the magnitude of this interaction.

PATIENT MANAGEMENT: Theophylline levels should be closely monitored in patients receiving concurrent therapy. The dosage of theophylline may need to be decreased after a CYP1A2 inhibitor is initiated. If the CYP1A2 inhibitor is discontinued in a patient stabilized on the combination, the theophylline level may fall. Monitor theophylline levels and adjust dose accordingly.

DISCUSSION: A study in 5 patients with active hepatitis B and 4 healthy subjects examined the effects of a single dose of interferon alpha (9 million units in 8 subjects, 18 million units in 1 subject). There was no effect on theophylline in 1 subject. In the other 8 subjects, interferon increased theophylline half-life by 70% and decreased theophylline clearance by 49% (range 33% to 81%).(1) A study in 11 healthy subjects examined the effects of interferon alpha (3 million International Units daily for 3 days) on a single aminophylline (4 mg/kg) infusion. Interferon increased the half-life, area-under-curve (AUC), and mean residence time by 13.7%, 17.9%, and 16.3%, respectively. Theophylline clearance decreased by 9.1%.(2) In a study in healthy males, peginterferon alfa-2a (180 mcg once weekly for 4 weeks) increased theophylline AUC by 25%.(3,4) Concurrent interferon alfa has been shown to increase theophylline levels by 100%.(5) A study in 7 patients with chronic hepatitis C examined the effects of interferon beta (3 million to 9 million International Units daily for 8 weeks) on theophylline ethylenediamine (single 250 mg infusion). Interferon decreased theophylline clearance by 26.3% and increased theophylline half-life by 39.3%. There was no correlation between interferon dose and effect. The greatest effect was seen in a patient who received 3 million International Units daily, while no effect was seen in a patient who received 9 million International Units daily.(6) Increased serum theophylline levels with signs and symptoms of theophylline toxicity have been reported in patients following the addition of mexiletine to their treatment.(7-15) In a study evaluated the combination of disulfiram and theophylline in 20 recovering alcoholics. Patients received a single IV dose of theophylline while being given either 250 mg or 500 mg of disulfiram daily. Both dosages of disulfiram decreased the clearance of theophylline. However, the effect was greatest in patients receiving disulfiram 500 mg daily.(16) Increases in serum theophylline concentration and half-life have been reported during concurrent administration of theophylline and ticlopidine.(17) In healthy subjects, rofecoxib (12.5 mg/day, 25 mg/day, or 50 mg/day for seven days) increased the area-under-curve (AUC) of a single dose of theophylline (300 mg) by 38% to 60%. Therefore, the manufacturer of rofecoxib recommends that theophylline levels be monitored if rofecoxib is initiated or changed in patients receiving theophylline.(18) Selected CYP1A2 inhibitors linked to this monograph include: acyclovir, Angelica dahurica, artemisinin, belumosudil, centanafadine, cannabidiol, curcumin, danshen, dipyrone, disulfiram, echinacea, enasidenib, fexinidazole, genistein, ginseng, interferons, methoxsalen, mexiletine, parsley, phenylpropanolamine, pipemidic acid, piperine, propafenone, ribociclib, rofecoxib, rucaparib, simeprevir, ticlopidine, triclabendazole, valacyclovir, and verapamil.(19)

Selected Nephrotoxic Agents/Tenofovir

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Tenofovir and other nephrotoxic agents may result in additive or synergistic effects on renal function and increase nephrotoxicity risk.(1)

CLINICAL EFFECTS: Concurrent use of tenofovir and other nephrotoxic agents may result in renal toxicity and acute renal failure.(1) Reports of acute renal failure and Fanconi syndrome have been reported with tenofovir use.(2,3) However, this has been reported in 3 case reports and the renal failure may have been complicated by other pre-existing conditions.(2)

PREDISPOSING FACTORS: Pre-existing renal dysfunction, long duration of use, low body weight, concomitant use of drugs that may increase tenofovir levels may increase the risk of nephrotoxicity.(1)

PATIENT MANAGEMENT: The US prescribing information for tenofovir recommends avoiding concurrent or recent use of a nephrotoxic agent.(3) Evaluate renal function prior to initiation of concurrent therapy and continue renal function monitoring during therapy. Dose adjustments may be required for impaired renal function. Tenofovir should be avoided with high-dose or multiple NSAIDs. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction.(3) Patients receiving concurrent NSAIDs with tenofovir should be monitored for possible renal toxicity.(1,2) The dosing interval should be adjusted in patients with a baseline creatinine clearance of less than 50 ml/min.(1-3)

DISCUSSION: From March 18, 2003 to December 1, 2005, Health Canada received 10 reports of nephrotoxic reactions with tenofovir. Three of these occurred following the addition of a NSAID to tenofovir therapy. In the first report, a patient maintained on tenofovir for 29 months developed acute renal failure and acute tubular necrosis requiring dialysis 5 days after beginning indomethacin (100 mg rectally twice daily). In the second report, a patient maintained on tenofovir for 7 months developed acute renal failure and acute tubular necrosis after taking 90 tablets of naproxen (375 mg) over 2 months. The patient died. In the third report, a patient maintained on tenofovir for over a year developed acute renal failure and nephrotic syndrome after 2 months of valdecoxib (20 mg daily) therapy. Symptoms subsided following discontinuation of valdecoxib.(1)

Known hypersensitivity or intolerance to valacyclovir, acyclovir, or any component of the formulation.

There are no contraindication contraindications for this drug.

• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Dehydration

• Kidney disease with likely reduction in glomerular filtration rate (GFr)

Headache, nausea, vomiting.

Less Frequent

• Dysmenorrhea
• Increased alanine transaminase

Rare or Very Rare

• Acute generalized exanthematous pustulosis
• Anaphylaxis
• Angioedema
• Aplastic anemia
• Coma
• DRESS syndrome
• Drug-induced psychosis
• Dyspnea
• Encephalopathy
• Erythema multiforme
• Facial edema
• Hemolytic uremic syndrome
• Hepatitis
• Hypertension
• Leukopenia
• Neutropenic disorder
• Renal failure
• Seizure disorder
• Stevens-johnson syndrome
• Thrombocytopenic disorder
• Thrombotic microangiography
• Thrombotic thrombocytopenic purpura
• Urticaria
• Visual changes

More Frequent

• Acute abdominal pain
• Headache disorder
• Nausea

Less Frequent

• Anorexia
• Arthralgia
• Constipation
• Diarrhea
• Dizziness
• Fatigue
• Vomiting

Rare or Very Rare

• Acute cognitive impairment
• Aggressive behavior
• Agitation
• Alopecia
• Ataxia
• Hallucinations
• Manic disorder
• Pruritus of skin
• Renal pain
• Skin photosensitivity
• Skin rash
• Tachycardia
• Toxic epidermal necrolysis
• Tremor

No enhanced messaging available.

Safety and efficacy not established in prepubertal children.

Category B.

Acyclovir distributed into human milk following oral administration of valacyclovir. Use valacyclovir with caution.

Increased risk of adverse renal or CNS effects. CNS effects reported more frequently in geriatric adults than in younger adults include agitation, hallucinations, confusion, delirium, and encephalopathy. In herpes zoster, longer duration of pain after healing (post-herpetic neuralgia) than in younger adults. Consider age-related decreases in renal function when selecting dosage and adjust dosage if necessary. (See Renal Impairment under Dosage and Administration.)