Drug Interactions between raltegravir and SlowMag Calm + Sleep
This report displays the potential drug interactions for the following 2 drugs:
- raltegravir
- SlowMag Calm + Sleep (magnesium citrate/melatonin)
Interactions between your drugs
magnesium citrate raltegravir
Applies to: SlowMag Calm + Sleep (magnesium citrate / melatonin) and raltegravir
GENERALLY AVOID: Coadministration with aluminum- and magnesium-containing antacids has been shown to reduce the oral bioavailability of raltegravir. The proposed mechanism is chelation of raltegravir by polyvalent cations, but changes in solubility and lipophilicity of raltegravir related to pH increases may also contribute. In drug interaction studies, raltegravir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) decreased by 44%, 49% and 63%, respectively, when a single 20 mL dose of aluminum and magnesium hydroxide antacid was administered simultaneously with raltegravir (400 mg twice daily). The Cmax, AUC and Cmin of raltegravir decreased by 51%, 51% and 56%, respectively, when the antacid was given 2 hours before raltegravir, and by 22%, 30% and 57%, respectively, when the antacid was given 2 hours after raltegravir. When given 4 hours apart, raltegravir Cmax, AUC and Cmin decreased by 22%, 19% and 60% with antacid administered first, and by 30%, 32% and 62% with raltegravir administered first. Minimal changes in raltegravir Cmax and AUC were observed when administration was staggered by 6 hours; however Cmin was still diminished by approximately 50% regardless of whether antacid was administered before or after raltegravir. When given with a single dose of antacid containing calcium carbonate 3000 mg, raltegravir Cmax, AUC and Cmin decreased by 52%, 55% and 32%, respectively. These changes are not considered clinically significant by the manufacturer.
MANAGEMENT: It is not known to what extent non-antacid aluminum and magnesium salts may interact with raltegravir. Until more information is available, it may be advisable to avoid taking raltegravir with any aluminum- and/or magnesium-containing product. Antacids containing calcium carbonate should not be used with once-daily raltegravir (HD formulation), but may be used without dose adjustment for other raltegravir products.
References (6)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- (2007) "Product Information. Isentress (raltegravir)." Merck & Co., Inc
- Cerner Multum, Inc. "Australian Product Information."
- Kiser JJ, Bumpass JB, Meditz AL, et al. (2010) "Effect of antacids on the pharmacokinetics of raltegravir in human immunodeficiency virus seronegative volunteers." Antimicrob Agents Chemother, 54, p. 4999-5003
- Moss DM, Siccardi M, Murphy M, et al. (2012) "Divalent metals and pH alter raltegravir disposition in vitro." Antimicrob Agents Chemother, 56, p. 3020-6
Drug and food interactions
melatonin food
Applies to: SlowMag Calm + Sleep (magnesium citrate / melatonin)
MONITOR: Oral caffeine may significantly increase the bioavailability of melatonin. The proposed mechanism is inhibition of CYP450 1A2 first-pass metabolism. After administration of melatonin 6 mg and caffeine 200 mg orally (approximately equivalent to 1 large cup of coffee) to 12 healthy subjects, the mean peak plasma concentration (Cmax) of melatonin increased by 137% and the area under the concentration-time curve (AUC) increased by 120%. The metabolic inhibition was greater in nonsmokers (n=6) than in smokers (n=6). The greatest effect was seen in subjects with the *1F/*1F genotype (n=7), whose melatonin Cmax increased by 202%. The half-life did not change significantly. The clinical significance of this interaction is unknown.
According to some authorities, alcohol may reduce the effect of melatonin on sleep. The mechanism of this interaction is not fully understood.
In addition, CYP450 1A2 inducers like cigarette smoking may reduce exogenous melatonin plasma levels. In a small clinical trial (n=8), habitual smokers had their melatonin plasma levels measured two times, each after a single oral dose of 25 mg of melatonin. They had smoked prior to the first measurement but had not smoked for 7 days prior to the second. Cigarette smoking significantly reduced melatonin plasma exposure (AUC) as compared to melatonin levels after 7 days of smoking abstinence (7.34 +/- 1.85 versus 21.07 +/- 7.28 nmol/L*h, respectively).
MANAGEMENT: Caution and monitoring are recommended if melatonin is used with inhibitors of CYP450 1A2 like caffeine or inducers of CYP450 1A2 like cigarette smoking. Consumption of alcohol should be avoided when taking melatonin.
References (3)
- Hartter S, Nordmark A, Rose DM, Bertilsson L, Tybring G, Laine K (2003) "Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity." Br J Clin Pharmacol, 56, p. 679-682
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Ursing C, Bahr CV, Brismar K, Rojdmark S (2005) "Influence of cigarette smoking on melatonin levels in man" Eur J Clin Pharmacol, 61, p. 197-201
Therapeutic duplication warnings
No warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
Further information
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