Valaciclovir: Organs and Systems
Nervous system
Valaciclovir is a prodrug of aciclovir and can therefore cause similar effects, as two cases of nervous system effects have demonstrated.
- A 65-year-old man was given valaciclovir 1 g bd for 36 hours and had reduced concentration and was incoherent. All investigations were normal or negative. He improved rapidly on withdrawal of valaciclovir.
- A 44-year-old man was given valaciclovir 1 g tds for 5 days and developed a fever, disorientation, confusion, ataxia, dysarthria, and photophobia. All investigations were normal or negative. He was given antimicrobial drugs, including aciclovir, but his symptoms did not improve until the aciclovir was withdrawn.
Elderly patients and people with chronic renal insufficiency are most susceptible to the neurotoxic effects of aciclovir: confusion, hallucinations, dizziness, irritability, ataxia, tremor, myoclonus, and seizures. The symptoms usually occur within 3 days of the start of therapy and resolve within 5 days after withdrawal. Plasma aciclovir concentrations do not correlate with symptoms. Lumbar puncture and CT scans of the head are essentially unremarkable. The most common electroencephalographic abnormality is diffuse generalized slowing of brain wave activity.
Psychological, psychiatric
At high doses (8 g/day) hallucinations and confusion were a significant concern, but similar symptoms have also occurred at lower doses and in patients with renal insufficiency.
Ocular and auditory hallucinations have been reported in a 60-year-old female patient on CAPD.
A 58-year-old man with chronic renal insufficiency, who was hemodialysed twice a week, was treated with valaciclovir (1 g tds) for Herpes zoster. Two days later he became disoriented, dizzy, dysarthric, and experienced hallucinations. The serum aciclovir concentration was 21 µg/ml. Treatment was discontinued and he was treated with hemodialysis for 6 hours, resulting in marked clinical improvement. The next day his symptoms of dysarthria recurred, but immediately and completely resolved after a second hemodialysis.
Hematologic
In one study, high-dose valaciclovir was associated with an increased risk of a thrombotic microangiopathy-like syndrome, reported as thrombocytopenic purpura or hemolytic-uremic syndrome. This syndrome occurred in 14 of 523 patients who received valaciclovir and in only four of 704 patients who received aciclovir after a median of 54 (range weeks of treatment.
The precise relation to valaciclovir remains unclear, since eight of 14 patients who were treated with valaciclovir had stopped treatment at least 1 week before the onset of the syndrome. In addition, all patients with thrombotic microangiopathy-like syndromes had taken multiple concomitant medications, and most had other intercurrent illnesses, which could have explained the hematological and renal abnormalities. The authors concluded that additional data are required to understand the role of valaciclovir and other medications for thrombotic microangiopathy-like syndromes, which are recognized with increasing frequency in patients with advanced HIV disease.
Gastrointestinal
Nausea, vomiting, and abdominal pain were commonly reported in human volunteers, but only diarrhea was significantly associated with exposure.
Urinary tract
Aciclovir is excreted renally. High plasma concentrations of aciclovir can lead to precipitation in renal tubules, causing impaired renal function, which is generally reversible. Since oral valaciclovir can result in plasma aciclovir concentrations comparable to those attained with intravenous dosing, reversible impairment of renal function can also occur after prolonged use of high-dose valaciclovir. Indeed, in a study of high-dose valaciclovir for prevention of cytomegalovirus disease in HIV-infected people, there was an association between treatment with valaciclovir and moderate nephrotoxicity (serum creatinine more than 1.5 times the upper limit of normal; estimated creatinine clearance under 50 ml/ minute).