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Calcium and Iron Supplements Lower Dolutegravir
Levels When Taken Between Meals
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15th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, May 19- 21, 2014, Washington, DC
Mark Mascolini
Calcium supplements taken with dolutegravir between meals lowered dolutegravir exposure by one third. Iron supplements with dolutegravir between meals approximately halved dolutegravir exposure. Supplements did not have this effect when taken with dolutegravir with a meal, or when dolutegravir was taken 2 hours before the supplement.
Antacids containing high levels metal cations significantly cut levels of dolutegravir, a 2-metal-binding integrase inhibitor, because of chelation. Current prescribing information recommends taking dolutegravir 2 hours before or 6 hours after cation-containing antacids or laxatives, sucralfate, oral iron supplements, oral calcium supplements, or buffered medications.
To learn more about calcium and iron supplement interactions with dolutegravir, GlaxoSmithKline researchers conducted an open-label four-period crossover study in healthy volunteers, half of them randomized to take 50 mg of dolutegravir with a calcium supplement (1200 mg of calcium carbonate) and half randomized to take the integrase inhibitor with an iron supplement (324 mg of ferrous fumarate).
Study participants took these agents in a four-step sequence: dolutegravir alone fasted; dolutegravir with a single dose of calcium or iron fasted; dolutegravir with a single dose of calcium or iron with a moderate (about 30%) fat meal; and dolutegravir fasted 2 hours before a single dose of calcium or iron. At least a 7-day washout separated each period.
Twelve people taking calcium and 11 taking iron could be evaluated. There were no grade 3 or 4 adverse events and no serious adverse events. Only one drug-related adverse event occurred--grade 1 nasal congestion.
Taking dolutegravir with a calcium supplement fasted lowered dolutegravir area under the concentration-time curve (AUC) 39%, maximum concentration (Cmax) 37%, and 24-hour concentration (C24) 39% when compared with dolutegravir alone fasted. Taking dolutegravir with an iron supplement fasted lowered dolutegravir AUC 54%, Cmax 57%, and C24 56%. Neither calcium nor iron affected dolutegravir concentrations when the supplement and the integrase inhibitor were taken together with a meal or when dolutegravir was taken 2 hours before the supplement.
"Dolutegravir and calcium or iron supplements can be co-administered if taken with a meal," the researchers concluded. "Under fasted conditions, dolutegravir should be given 2 hours prior or 6 hours after calcium or iron supplements."
Reference
1. Song I, Borland J, Arya N, Wynne B, Piscitelli S. The effect of calcium and iron supplements on the pharmacokinetics of Dolutegravir in healthy subjects. 15th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy. May 19-21, 2014. Washington, DC. Abstract P_13.
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