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Drug Interactions between Ocudox and remdesivir

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

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Interactions between your drugs

Moderate

doxycycline remdesivir

Applies to: Ocudox (doxycycline) and remdesivir

GENERALLY AVOID: Concomitant use of remdesivir with other agents that are known to induce hepatotoxicity may theoretically increase the risk of liver injury. Data from investigational use and clinical studies suggest that remdesivir may be associated with hepatotoxic effects. Transient treatment-emergent Grade 1 or Grade 2 elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed during multiple-dose Phase 1 studies in healthy volunteers. Some ALT and AST elevations were associated with graded PT elevations, but there were no graded changes in international normalized ratio (INR). Laboratory results for these subjects indicated no systemic sign of drug reaction. Liver transaminase elevations, including grade 3 or higher, were also observed in some participants during compassionate or investigational use of remdesivir and clinical studies for the treatment of COVID-19. The mechanism of potential hepatotoxicity is unknown and the contribution of remdesivir is difficult to determine, as transaminase elevations have also been reported as a component of COVID-19, including in patients receiving placebo in clinical trials of remdesivir.

MANAGEMENT: Until more information is available, concomitant use of remdesivir with known hepatotoxic drugs should be avoided when possible. Liver function should be evaluated prior to starting remdesivir and monitored during treatment as clinically appropriate. Remdesivir should not be initiated in patients with ALT greater than or equal to 5 times the upper limit of normal (ULN) at baseline. Likewise, remdesivir should be discontinued immediately if ALT increases to 5 times ULN or greater during treatment (may be restarted when ALT falls below 5 times ULN), or if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. Gilead Sciences, Inc (2020) About Remdesivir. https://www.gilead.com/purpose/advancing-global-health/covid-19/about-remdesivir
  4. European Medicines Agency (2020) Summary on compassionate use. Remdesivir Gilead. https://www.ema.europa.eu/en/documents/other/summary-compassionate-use-remdesivir-gilead_en.pdf
  5. US Food and Drug Administration (2020) Fact sheet for health care providers emergency use authorization (EUA) of remdesivir (GS-5734TM) https://www.fda.gov/media/137566/download
View all 5 references

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Drug and food interactions

Moderate

doxycycline food

Applies to: Ocudox (doxycycline)

GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%. In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%. Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg. Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline. Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally. It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.

MANAGEMENT: Coadministration of a tetracycline with any iron-containing product should be avoided if possible. Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.

References

  1. Neuvonen PJ (1976) "Interactions with the absorption of tetracyclines." Drugs, 11, p. 45-54
  2. Gothoni G, Neuvonen PJ, Mattila M, Hackman R (1972) "Iron-tetracycline interaction: effect of time interval between the drugs." Acta Med Scand, 191, p. 409-11
  3. Venho VM, Salonen RO, Mattila MJ (1978) "Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal." Eur J Clin Pharmacol, 14, p. 277-80
  4. (2002) "Product Information. Minocin (minocycline)." Lederle Laboratories
  5. Campbell NR, Hasinoff BB (1991) "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol, 31, p. 251-5
  6. Bateman FJ (1970) "Effects of tetracyclines." Br Med J, 4, p. 802
  7. Neuvonen PJ, Gothoni G, Hackman R, Bjorksten K (1970) "Interference of iron with the absorption of tetracyclines in man." Br Med J, 4, p. 532-4
  8. Greenberger NJ (1971) "Absorption of tetracyclines: interference by iron." Ann Intern Med, 74, p. 792-3
  9. Neuvonen PJ, Penttila O (1974) "Effect of oral ferrous sulphate on the half-life of doxycycline in man." Eur J Clin Pharmacol, 7, p. 361-3
  10. (2018) "Product Information. Seysara (sarecycline)." Allergan Inc
  11. (2018) "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc.
View all 11 references

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Minor

doxycycline food

Applies to: Ocudox (doxycycline)

Chronic alcohol consumption may enhance the elimination of doxycycline. The mechanism is induction of hepatic microsomal enzymes by alcohol. In one study, the half-life of doxycycline in six alcoholics was 10.5 hours, compared with 14.7 hours in six control patients. In addition, half the alcoholic patients had serum concentrations below what is generally considered the minimum therapeutic concentration (0.5 mcg/mL) at 12 to 24 hours after the dose. The investigators suggest that twice-a-day dosing may be indicated in these patients, especially if additional inducing drugs are used. The elimination of other tetracyclines probably is not affected by alcohol consumption.

References

  1. Neuvonen PJ, Penttila O, Roos M, Tirkkonen J (1976) "Effect of long-term alcohol consumption on the half-life of tetracycline and doxycycline in man." Int J Clin Pharmacol Biopharm, 14, p. 303-7

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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.