Kava

Absolute contraindication. Approximately 100 case reports of kava-associated liver injury have been documented worldwide, ranging from mild enzyme elevation to acute liver failure, transplantation, and death. Risk factors include organic solvent extracts, non-noble cultivars, and aerial plant material — but aqueous preparations have also been implicated. Pre-existing liver disease eliminates any safety margin.

Absolute contraindication. Concurrent heavy alcohol use compounds both hepatotoxicity risk and CNS depression. The Russmann 2001 index case of kava hepatotoxicity involved alcohol co-consumption. Alcohol's independent hepatotoxic burden plus kava's documented liver injury risk creates an unacceptable combined risk profile.

Relative contraindication. CYP2D6 poor metabolizer phenotype has been identified as a possible idiosyncratic susceptibility factor for kava hepatotoxicity based on a single case report (Russmann 2001). Impaired CYP2D6 metabolism may shunt kavalactone metabolism toward hepatotoxic pathways. Population prevalence of poor metabolizer phenotype varies by ethnicity (5–10% of European descent populations).

Absolute contraindication based on precautionary principle. No clinical study of kava in pregnancy has been published. Kavalactones' molecular weight and lipophilicity suggest placental transfer is likely. No human data on teratogenicity, fetal neurodevelopmental effects, or lactation transfer are available.

Absolute contraindication. No clinical trials, case series, or systematic safety data for kava use in children or adolescents have been published. The developing brain's sensitivity to GABAergic modulation warrants a precautionary absolute contraindication.

alprazolam, diazepam, lorazepam, clonazepam, benzodiazepine class

Absolute contraindication. A documented case of coma followed combined kava and alprazolam use (Almeida & Grimsley 1996). Kava potentiates GABAA receptors at a site distinct from the benzodiazepine binding pocket, creating additive or synergistic sedation when combined. Potentially life-threatening.

warfarin, phenytoin, omeprazole

Relative contraindication. In vitro pharmacokinetic data show CYP2C9/2C19 inhibition by several kavalactones at Ki 5–10 µM (Mathews 2005). No controlled human pharmacokinetic study or clinical case report has confirmed this interaction at standard kava doses. However, the narrow therapeutic indices of affected drugs (warfarin, phenytoin) mean even modest inhibition could produce clinically significant effects. Caution warranted; INR monitoring recommended for warfarin users.

opioids, sedating antihistamines, antipsychotics, barbiturates

Relative contraindication. Kava's GABAergic, sodium channel blocking, and monoaminergic activity creates additive CNS depression risk with opioids, sedating antihistamines, antipsychotics, and other depressants. Clinical data beyond the alprazolam coma case are limited to mechanistic inference. Respiratory depression risk is of particular concern with opioid co-administration. Dose reduction or avoidance recommended.