Drug Interactions between Armour Thyroid and praziquantel

ADJUST DOSING INTERVAL: Administration with food increases the oral bioavailability of praziquantel. The mechanism has not been described. In nine healthy volunteers, administration of praziquantel (1800 mg single oral dose) following a high-fat meal increased the mean praziquantel peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 243% and 180%, respectively, compared to administration under fasting conditions. Administration with a high-carbohydrate meal increased these values by 515% and 271%, respectively, compared to fasting. Overall, the relative bioavailability was increased by a factor of 2.72 and 3.98 with the high-fat and high-carbohydrate meals, respectively. The time to reach peak concentration (Tmax) and elimination half-life (T1/2) were not significantly altered.

Coadministration with grapefruit juice may increase the oral bioavailability of praziquantel. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. In 18 healthy volunteers, administration of praziquantel (1800 mg single oral dose) with 250 mL of commercially squeezed grapefruit juice resulted in increases in the mean praziquantel Cmax and AUC of 63% and 90%, respectively, compared to administration with water. The Tmax and T1/2 were not significantly altered. The pharmacokinetics of praziquantel were subject to a high degree of interpatient variability with and without grapefruit juice.

MANAGEMENT: To ensure maximal oral absorption, praziquantel should be administered with meals. Administration with grapefruit juice may further increase pharmacologic effects of praziquantel, including adverse effects such dizziness, abdominal discomfort, and nausea.

ADJUST DOSING INTERVAL: Consumption of certain foods as well as the timing of meals relative to dosing may affect the oral absorption of T4 thyroid hormone (i.e., levothyroxine). T4 oral absorption is increased by fasting and decreased by foods such as soybean flour (e.g., infant formula), cotton seed meal, walnuts, dietary fiber, calcium, and calcium fortified juices. Grapefruit or grapefruit products may delay the absorption of T4 thyroid hormone and reduce its bioavailability. The mechanism of this interaction is not fully understood.

MANAGEMENT: Some manufacturers recommend administering oral T4 as a single daily dose, on an empty stomach, one-half to one hour before breakfast. In general, oral preparations containing T4 thyroid hormone should be administered on a consistent schedule with regard to time of day and relation to meals to avoid large fluctuations in serum levels. Foods that may affect T4 absorption should be avoided within several hours of dosing if possible. Consult local guidelines for the administration of T4 in patients receiving enteral feeding.

ADJUST DOSING INTERVAL: Concurrent administration of calcium-containing products may decrease the oral bioavailability of levothyroxine by one-third in some patients. Pharmacologic effects of levothyroxine may be reduced. The exact mechanism of interaction is unknown but may involve nonspecific adsorption of levothyroxine to calcium at acidic pH levels, resulting in an insoluble complex that is poorly absorbed from the gastrointestinal tract. In one study, 20 patients with hypothyroidism who were taking a stable long-term regimen of levothyroxine demonstrated modest but significant decreases in mean free and total thyroxine (T4) levels as well as a corresponding increase in mean thyrotropin (thyroid-stimulating hormone, or TSH) level following the addition of calcium carbonate (1200 mg/day of elemental calcium) for 3 months. Four patients had serum TSH levels that were higher than the normal range. Both T4 and TSH levels returned to near-baseline 2 months after discontinuation of calcium, which further supported the likelihood of an interaction. In addition, there have been case reports suggesting decreased efficacy of levothyroxine during calcium coadministration. It is not known whether this interaction occurs with other thyroid hormone preparations.

MANAGEMENT: Some experts recommend separating the times of administration of levothyroxine and calcium-containing preparations by at least 4 hours. Monitoring of serum TSH levels is recommended. Patients with gastrointestinal or malabsorption disorders may be at a greater risk of developing clinical or subclinical hypothyroidism due to this interaction.