acyclovir and Hypertension

A randomized, double-blind study was conducted to evaluate the safety and pharmacokinetics of acyclovir following multiple-dose oral administration of valaciclovir (three times a day for 8 days) in geriatric volunteers (65 to 83 years of age). Pharmacokinetic evaluation was performed for three groups: normotensive subjects given 500-mg doses of valaciclovir (n = 11), normotensive subjects given, 1,000-mg doses of valaciclovir (n = 9), and thiazide diuretic-treated hypertensive subjects given 500-mg doses of valaciclovir (n = 9). Valaciclovir, the l-valyl ester of acylclovir, was rapidly absorbed and converted to acyclovir, with plasma valaciclovir concentrations generally undetectable or < or = 0.4 microgram/ml. The peak concentration of drug in plasma (Cmax) for acyclovir occurred at 1 to 2 h, and the half-life of acyclovir was 3 to 4 h in all three elderly groups. The Cmax and area under the concentration-time curve from 0 h to infinity (AUC0-infinity) values of acyclovir obtained on days 1 and 8 indicated no unexpected accumulation at steady state. The steady-state acyclovir Cmax (4.30 and 5.98 micrograms/ml) and daily AUC0-infinity (44 and 74 h.micrograms/ml) following dosing of valaciclovir (500 and 1,000 mg) three times a day were two to three times greater than those expected after high-dose oral acyclovir treatment (800 mg, five times daily). There were no valaciclovir-related changes or abnormalities in safety parameters and no reports of serious adverse experiences in these elderly volunteers. The plasma acyclovir concentration-time curves for the hypertensive and normotensive (500-mg valaciclovir treatment) elderly groups were almost superimposable, and acyclovir pharmacokinetic parameters for the two groups were not significantly different, indicating that concomitant thiazide diuretics do not alter acyclovir pharmacokinetics following valaciclovir dosing in the elderly. Compared with historical data for younger volunteers (creatinine clearance [CLCR] > 75 ml/min/1.73 m2), the elderly subjects (CLCR = 40 to 65 ml/min/1.73 m2) showed higher (approximately 15 to 20%) mean Cmaxs and higher (approximately 30 to 50%) mean AUC(0-infinity)s of acyclovir (P < 0.01), which were consistent with age-related decreases in CLCR. The increased acyclovir exposure from valaciclovir dosing will permit reduced dosing frequency and may result in improved efficacy in the management of herpesvirus diseases.

Topics: Acyclovir; Aged; Aged, 80 and over; Antiviral Agents; Diuretics; Double-Blind Method; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Prodrugs; Valacyclovir; Valine

To assess the incidence, predictive factors, and prognosis of acyclovir-induced nephrotoxicity. We conducted a historical prospective cohort study of patients treated with intravenous acyclovir in North Denmark Region from 2009 to 2016. Information on baseline demographics, co-morbidities, plasma creatinine, and treatment was obtained from the medical records. The primary outcome was an increase of ≥ 40 μmol/L in plasma creatinine level from baseline. We included 276 patients treated with intravenous acyclovir of which 29 (10.5%) met the primary outcome. In 14 cases, the treating physician considered acyclovir the main reason for nephrotoxicity, whereas a potential competing cause of renal impairment was present among the 15 remaining patients. Hypertension was the only predictive factor associated with nephrotoxicity (risk ratio (RR), 2.77; 95% confidence interval (CI), 1.41-5.46), while having no co-morbidities was protective (RR, 0.32; CI, 0.16-0.63). In all cases, the nephrotoxicity was reversible following rehydration and dose reduction or discontinuation of the drug. However, the normalized plasma creatinine upon treatment was significantly higher between cases with acyclovir-induced nephrotoxicity than cases with a potential competing cause (median [interquartile range (IQR)], 93.5 μmol/L [85-108] vs 75 μmol/L [66.5-88]; p = 0.019). Acyclovir-induced, reversible nephrotoxicity was observed in 5.1-10.5% of patients. It is difficult to predict who will develop acyclovir-induced nephrotoxicity; it may occur late in treatment and hypertension was the only independent predictive factor, while the absence of co-morbidities was protective. Ensuring hydration, frequent evaluations of renal function, and corresponding dose adjustment of intravenous acyclovir treatment seem prudent.

Topics: Acute Kidney Injury; Acyclovir; Administration, Intravenous; Adult; Aged; Antiviral Agents; Cohort Studies; Creatinine; Denmark; Female; Humans; Hypertension; Incidence; Kidney Diseases; Male; Middle Aged; Prognosis; Prospective Studies; Risk Factors

The relative effectiveness of acyclovir and famciclovir in the treatment of Bell's palsy is unclear. This study therefore compared recovery outcomes in patients with Bell's palsy treated with acyclovir and famciclovir. The study cohort consisted of patients with facial palsy who visited the outpatient clinic between January 2006 and January 2014. Patients were treated with prednisolone plus either acyclovir (n = 457) or famciclovir (n = 245). Patient outcomes were measured using the House-Brackmann scale according to initial severity of disease and underlying disease. The overall recovery rate tended to be higher in the famciclovir than in the acyclovir group. The rate of recovery in patients with initially severe facial palsy (grades V and VI) was significantly higher in the famciclovir than in the acyclovir group (p = 0.01), whereas the rates of recovery in patients with initially moderate palsy (grade III-IV) were similar in the two groups. The overall recovery rates in patients without hypertension or diabetes mellitus were higher in the famciclovir than in the acyclovir group, but the difference was not statistically significant. Treatment with steroid plus famciclovir was more effective than treatment with steroid plus acyclovir in patients with severe facial palsy. Famciclovir may be the antiviral agent of choice in the treatment of patients with severe facial palsy.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Bell Palsy; Diabetes Mellitus; Drug Therapy, Combination; Famciclovir; Female; Glucocorticoids; Humans; Hypertension; Male; Middle Aged; Prednisolone

A 97-year-old lady was hospitalized for left leg cellulitis. Comorbidity included hypertension and congestive heart failure. While in hospital, she developed a painless vesicular rash localized to the territory of the left trigeminal nerve (third branch), which evolved to pustules and crusts (Figure 1). A chickenpox-like disseminated eruption of vesicles followed within 4 days, with the same evolution pattern (Figure 2).The diagnosis of disseminated zoster was suspected. A PCR analysis confirmed the presence of varicella-zoster-virus (VZV) in an abdominal vesicle. The patient was treated with oral valacyclovir for 7 days. Clinical examination, laboratory tests (including HIV serology), and a chest radiograph revealed no evidence of underlying immunodeficiency or malignancy.

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Back; Face; Female; Heart Failure; Herpes Zoster; Herpesvirus 3, Human; Humans; Hypertension; Polymerase Chain Reaction; Valacyclovir; Valine

Topics: Acyclovir; Aged; Aged, 80 and over; Antiviral Agents; Brain Diseases, Metabolic; Diabetes Complications; Diagnosis, Differential; Herpes Zoster; Humans; Hypertension; Male; Myoclonus; Renal Dialysis; Renal Insufficiency; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Confusion; Diabetes Mellitus, Type 1; Female; Herpes Labialis; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Nausea

We report 31 cases of herpes zoster (HZ) with neurological complications: 14 with cranial nerve deficits, 1 with cranial nerve deficit associated with segmental motor disorder, 3 with segmental motor deficits, 2 with meningoencephalitis, 2 with meningoencephalitis associated with cranial neuropathy or myelitis, 2 with meningitis, 2 with hemiplegia contralateral to the ophthalmic HZ. 1 with hemiplegia and motor deficit and finally 1 with hemiplegia and a cranial neuropathy. Smoking was the putative risk factor in 53% of our patients together with diabetes, which has already been mentioned in the literature. We frequently observed more than one complication in succession (19.3%) that could not easily be related to the cutaneous distribution. Acyclovir had no demonstrable positive effects on neurological complication in our patients.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Cranial Nerve Diseases; Diabetes Complications; Female; Hemiplegia; Herpes Zoster; Humans; Hypertension; Male; Meningoencephalitis; Middle Aged; Risk Factors; Smoking