Drug Interactions between bromocriptine and palovarotene

GENERALLY AVOID: Grapefruit, pomelo, grapefruit hybrids, and juices or supplements containing these fruits may increase the plasma concentrations of palovarotene. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in these fruits. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with these fruits. Concomitant use of erythromycin, a moderate CYP450 3A4 inhibitor, with palovarotene at steady-state plasma levels increased its peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.6 and 2.5-fold, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased concentrations of palovarotene may increase the risk of adverse effects such as dry skin, dry lips, alopecia, pruritus, erythema, paronychia, cellulitis, decubitus ulcer, xerophthalmia, night blindness, depression, mood alterations, and pseudotumour cerebri (benign intracranial hypertension).

ADJUST DOSE: Food increases oral absorption of palovarotene.

MANAGEMENT: The manufacturer advises that concomitant use of palovarotene with grapefruit, pomelo, grapefruit hybrids and juices or supplements containing these fruits should be avoided. To ensure maximal absorption, palovarotene should be administered with food.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

MONITOR: Nicotine may cause vasoconstriction in some patients and potentiate the ischemic response to ergot alkaloids.

MANAGEMENT: Caution may be advisable when ergot alkaloids are used in combination with nicotine products. Patients should be advised to seek immediate medical attention if they experience potential symptoms of ischemia such as coldness, pallor, cyanosis, numbness, tingling, or pain in the extremities; muscle weakness; severe or worsening headache; visual disturbances; severe abdominal pain; chest pain; and shortness of breath.