Drug Interactions between aminophylline / ephedrine / guaifenesin / phenobarbital and cabazitaxel

GENERALLY AVOID: Coadministration with potent CYP450 3A4 inducers may significantly decrease the plasma concentration and pharmacologic effects of cabazitaxel, which is primarily metabolized via the isoenzyme. A drug interaction study in patients with advanced cancers (n=21), revealed that repeated administration of rifampin (600 mg once daily), a potent CYP450 3A4 inducer, increased the clearance and decreased the systemic exposure (AUC) of cabazitaxel (15 mg/m2 intravenous) by 21% and 17%, respectively. In another study, adult patients with metastatic castration-resistant prostate cancer (n=14), received cabazitaxel (25 mg/m2 intravenous) at baseline (day 0) and then every 3 weeks for 3 doses. The potent CYP450 3A4 inducer enzalutamide (160 mg oral daily) was started at day 8 (+/- 1) and continued until 1 week after the 3rd dose of cabazitaxel (6 weeks of concurrent treatment). When compared to baseline, a 22% reduction in the AUC of cabazitaxel was observed, which investigators noted as potentially clinically relevant. They cautioned that subtherapeutic concentrations may occur when lower doses of cabazitaxel (e.g., 20 mg/m2) are utilized.

MANAGEMENT: Some authorities recommend avoiding concomitant use of cabazitaxel, a narrow therapeutic index drug, with potent CYP450 3A4 inducers. This may be particularly important in situations where reduced cabazitaxel dosing is utilized. If concomitant use is necessary, increased monitoring of cabazitaxel's efficacy may be advisable.

MONITOR: Barbiturates may decrease serum levels and therapeutic effects of the methylxanthines. The mechanism is barbiturate induction of CYP450 3A4 and 1A2 hepatic metabolism of methylxanthines.

MANAGEMENT: Close observation for clinical and laboratory evidence of decreased methylxanthine effect is indicated if these drugs must be used together. Patients should be advised to notify their physician if they experience a worsening of their respiratory symptoms.

Ephedrine-methylxanthine combinations are used for the treatment of asthma but the efficacy of the combination has been questioned. This combination may lead to increased xanthine side effects. The mechanism is unknown, but may be related to synergistic pharmacologic effects. Patients using this combination should be closely monitored for side effects such as nausea, vomiting, tachycardia, nervousness, or insomnia. If side effects are noted, the dosage of the xanthine may need to be decreased.