It is important to reduce acyclovir doses in case of decreased renal function

The number of cases of neurotoxicity with acyclovir (ACV)/valaciclovir (VACV) therapy has increased in recent years and is alarmingly high. This can be explained by better diagnosis and increased awareness of shingles in the community, but also by the fact that the recommendation in FES regarding impaired renal function or dialysis is not always followed and that patients have taken excessive doses.

ACV/VACV antiviral medications are effective in treating herpes simplex virus and varicella zoster virus infections, and apple cider vinegar usually has few and mild side effects (headache, gastrointestinal distress). [1]. With intravenous administration, thrombophlebitis and skin rash have been reported. Renal effects occur to varying degrees (incidence 1-43 percent) whether administered intravenously. [2] and oral administration [3]. Neurotoxicity in the form of confusion, hallucinations and impaired consciousness is a serious syndrome that mainly affects patients with acute or chronic renal failure and those undergoing dialysis. [4]. It may be difficult to distinguish between the syndrome and encephalitis [5].

One example involved a woman undergoing peritoneal dialysis who requested a close-up for suspected shingles and was prescribed a full dose of VACV (1 g × 3). At the pharmacy, the husband questioned the dosage, and after consulting the doctor, the dosage was reduced to 500 mg x 1. After two doses, the patient experienced severe dizziness, slurred speech, severe balance disturbance, nightmares, and drowsiness. Treatment was discontinued, and after 3 days the serum concentration of CMMG (9-carboxymethoxymethylguanine) was 48 μmol/L. The symptoms then began to subside, and the patient gradually improved over the course of a week.

The above describes a case of apple cider vinegar-induced neurotoxicity with high serum concentrations of its major metabolite CMMG. The metabolite is a known marker of neurotoxicity and is formed by the metabolism of alcohol and aldehyde dehydrogenase in the liver and accumulates in renal failure. [4, 6, 7]. CMMG concentrations in serum and cerebrospinal fluid higher than 10.8 μmol/L and 0.6 μmol/L, respectively, indicate neurotoxicity. [4, 8].

Since 2010, the number of cases with serum CMMG concentrations exceeding 10.8 μmol/L has increased in line with increased sampling (Figure 1). Samples are generally received weekly by the Department of Clinical Pharmacy at Karolinska University Hospital mainly from ICUs and Infectious Diseases and Nephrology clinics where patients have received excessive doses of ACV/VACV with high levels of CMMG as a result. In addition to the risks and suffering to patients, sepsis increases the costs of intensive care and emergency dialysis and prolongs treatment time. The dark number is likely to be significant: in the years 2010-2024, 24 cases of neuropsychiatric side effects were reported to the Swedish Medicines Agency. [9].

Knowing kidney function and the necessity of using absolute glomerular filtration rate (eGFR) in mL/min for dosing is important when starting ACV/VACV. In the case of shingles, a VACV dose of 1 g x 3 is given to patients with normal kidney function. According to FAS, the dose should be reduced in case of impaired renal function, but in the case of peritoneal dialysis there are no specific recommendations. A dose of 500 mg x 1 is recommended for hemodialysis patients, but this dose caused neurotoxicity in our subject. Even at a dose of 250 mg x 1, there is still an increased risk of side effects, which is why giving the usual 200 mg x 1-2 oral apple cider vinegar with an additional dose after dialysis makes more sense. This is less than the dose suggested in FES, and the importance of following up with the medication at a lower CMMG value cannot be stressed enough. It is desirable to take a 125 mg tablet of VACV.

If neurotoxicity is suspected, the dose should be reduced or discontinued. Dilution may be required, perhaps in combination with forced diuresis. In more serious cases, urgent dialysis is required, which is usually diagnostic as patients can wake up from unconsciousness already a few hours after treatment. Peritoneal dialysis is usually ineffective in removing ACV and CMMG [10].

Serum and/or cerebrospinal fluid samples should be obtained for ACV and CMMG if poisoning is suspected [11] It was sent for urgent analysis to Clinical Pharmacology, Karolinska University Hospital, Hödinge or Clinical Chemistry and Pharmacology, Skane University Hospital, Lund. New cases should be reported to the Side Effects Unit of the Swedish Medicines Agency.

Lakartedningen 25-31/2024

Lakartidningen.se 2024-06-19