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Drug Interactions between cannabidiol and Dynacin

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

minocycline cannabidiol

Applies to: Dynacin (minocycline) and cannabidiol

MONITOR: Coadministration of cannabidiol with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Cannabidiol causes dose-related elevations of liver transaminases, both alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In controlled studies, the incidence of ALT elevations above 3 times the upper limit of normal (ULN) was 13% with cannabidiol versus 1% with placebo, and 17% in patients taking cannabidiol 20 mg/kg/day compared to 1% taking 10 mg/kg/day. Less than 1% of cannabidiol-treated patients had ALT or AST levels greater than 20 times the ULN. Some cases required hospitalization. In clinical trials, serum transaminase elevations typically occurred within the first two months of treatment initiation, but up to 18 months were reported in some cases, particularly in patients taking concomitant valproate. Resolution occurred with discontinuation or dosage reduction of cannabidiol and/or concomitant valproate in about two-thirds of the cases. In about one-third of the cases, transaminase elevations resolved during continued cannabidiol treatment, without dose reduction. The majority of ALT elevations occurred in patients taking concomitant valproate. Concomitant use of clobazam also increased the incidence of transaminase elevations, but to a lesser extent. In cannabidiol-treated patients, the incidence of ALT elevations greater than 3 times the ULN was 30% in patients taking both concomitant valproate and clobazam, 21% in patients taking concomitant valproate (without clobazam), 4% in patients taking concomitant clobazam (without valproate), and 3% in patients taking neither drug. Insufficient data are available to assess the risk of concomitant administration of other hepatotoxic drugs. Finally, patients with baseline transaminase levels above the ULN also had higher rates of transaminase elevations during cannabidiol treatment. In patients taking 20 mg/kg/day in controlled trials, the frequency of treatment-emergent ALT elevations greater than 3 times the ULN was 30% when ALT was above the ULN at baseline, compared to 12% when ALT was within the normal range at baseline. No patient taking cannabidiol 10 mg/kg/day experienced ALT elevations greater than 3 times the ULN when ALT was above the ULN at baseline, compared with 2% of patients in whom ALT was within the normal range at baseline.

MANAGEMENT: Caution is advised if cannabidiol is used in patients who are currently receiving or have recently received treatment with other hepatotoxic agents, and vice versa. Serum transaminases and total bilirubin levels should be obtained prior to initiating cannabidiol, and patients with elevated baseline transaminase levels above 3 times the ULN accompanied by elevations in bilirubin above 2 times the ULN should be evaluated. Repeat levels should be obtained at 1 month, 3 months, and 6 months after initiation of cannabidiol treatment, and periodically thereafter or as clinically indicated (e.g., within 1 month following changes in cannabidiol dosage or addition of/changes in medications that are known to impact the liver). Consider more frequent monitoring of serum transaminases and bilirubin in patients who are taking valproate or who have elevated liver enzymes at baseline. Patients who develop clinical signs or symptoms suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, right upper quadrant abdominal pain, fatigue, anorexia, jaundice, dark urine) should have serum transaminases and total bilirubin measured promptly, and cannabidiol treatment interrupted or discontinued as appropriate. Cannabidiol should be discontinued in patients with elevations of transaminase levels greater than 3 times the ULN and bilirubin levels greater than 2 times the ULN. Patients with sustained transaminase elevations of greater than 5 times the ULN should also have treatment discontinued. Patients with prolonged elevations of serum transaminases should be evaluated for other possible causes. Also consider dosage adjustment or discontinuation of any coadministered medication that is known to affect the liver.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2018) "Product Information. Epidiolex (cannabidiol)." Greenwich Biosciences LLC

Drug and food/lifestyle interactions

Moderate

cannabidiol food/lifestyle

Applies to: cannabidiol

ADJUST DOSING INTERVAL: Food may affect the plasma concentrations of cannabidiol. In healthy volunteers, administration of cannabidiol with a high-fat/high-calorie meal increased cannabidiol peak plasma concentration (Cmax) by 5-fold and systemic exposure (AUC) by 4-fold and reduced the total variability compared with administration in the fasted state.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of cannabidiol. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of cannabidiol by certain compounds present in grapefruit. The interaction has not been studied, but the product labeling for cannabidiol recommends consideration of a dosage reduction when used with strong or moderate inhibitors of CYP450 3A4. 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.

MANAGEMENT: Cannabidiol should be taken about the same time each day consistently either with or without food. Patients should limit the consumption of grapefruit and grapefruit juice. If they are coadministered, cannabidiol levels should be monitored and the dosage adjusted as necessary.

References (1)
  1. (2018) "Product Information. Epidiolex (cannabidiol)." Greenwich Biosciences LLC
Moderate

minocycline food/lifestyle

Applies to: Dynacin (minocycline)

GENERALLY AVOID: The oral bioavailability of quinolone and tetracycline antibiotics may be reduced by concurrent administration of preparations containing polyvalent cations such as aluminum, calcium, iron, magnesium, and zinc. Therapeutic failure may result. The proposed mechanism is chelation of quinolone and tetracycline antibiotics by di- and trivalent cations, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. Reduced gastrointestinal absorption of the cations should also be considered.

MANAGEMENT: Concomitant administration of oral quinolone and tetracycline antibiotics with preparations containing aluminum, calcium, iron, magnesium, and/or zinc salts should generally be avoided. Otherwise, the times of administration should be staggered by as much as possible to minimize the potential for interaction. Quinolones should typically be dosed either 2 to 4 hours before or 4 to 6 hours after polyvalent cation preparations, depending on the quinolone and formulation. Likewise, tetracyclines and polyvalent cation preparations should typically be administered 2 to 4 hours apart. The prescribing information for the antibiotic should be consulted for more specific dosing recommendations.

References (51)
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  4. Frost RW, Lasseter KC, Noe AJ, Shamblen EC, Lettieri JT (1992) "Effects of aluminum hydroxide and calcium carbonate antacids on the bioavailability of ciprofloxacin." Antimicrob Agents Chemother, 36, p. 830-2
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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.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

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