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Drug Interactions between Antrocol and dolutegravir

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

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Interactions between your drugs

Major

PHENobarbital dolutegravir

Applies to: Antrocol (atropine / phenobarbital) and dolutegravir

GENERALLY AVOID: Coadministration with potent inducers of UGT1A1 and CYP450 3A4 isoenzymes may significantly decrease the plasma concentrations of dolutegravir, which is primarily metabolized by UGT1A1 with some contribution from CYP450 3A4. Dolutegravir is also a substrate of UGT1A3, UGT1A9, and P-glycoprotein in vitro. In 16 study subjects, administration of dolutegravir 50 mg once daily with the potent CYP450 3A4 inducer carbamazepine at a dose of 300 mg twice daily decreased dolutegravir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin; 24 hours post-dose) by 33%, 49%, and 73%, respectively, compared to administration without carbamazepine. Data are not available for other potent CYP450 3A4 inducers phenytoin, phenobarbital (phenobarbitone), and St. John's wort.

MANAGEMENT: In patients with HIV-1 without integrase inhibitor (INI) resistance, some authorities recommend a dolutegravir dose of 50 mg twice daily for both adults and pediatric patients 12 years of age and older who weigh at least 40 kg when coadministered with potent UGT1A1 and CYP450 3A4 inducers including carbamazepine, phenytoin, phenobarbital, and St. John's Wort. However, other authorities advise that coadministration of dolutegravir with these inducers should be avoided. The safety and efficacy of dosages above 50 mg twice daily have not been evaluated. Alternative treatment combinations that do not include metabolic inducers should be considered whenever possible for INI-experienced patients with certain INI-associated resistance substitutions or clinically suspected INI resistance. In addition, concomitant use of potent UGT1A1 and CYP450 3A4 inducers with fixed-dose combination products containing dolutegravir is not recommended; however, when used in combination with carbamazepine, some authorities advise administration of an additional 50 mg daily dose of dolutegravir approximately 12 hours from the combination product. Local antiretroviral treatment experts should be consulted for current practice.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Tivicay (dolutegravir)." ViiV Healthcare (2013):
  4. "Product Information. Triumeq (abacavir/dolutegravir/lamivudine)." ViiV Healthcare (2014):
  5. "Product Information. Dovato (dolutegravir-lamivudine)." ViiV Healthcare (2019):
View all 5 references

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Drug and food interactions

Major

PHENobarbital food

Applies to: Antrocol (atropine / phenobarbital)

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J 94 (1966): 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med 51 (1971): 346-51
  3. Saario I, Linnoila M "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh) 38 (1976): 382-92
  4. Stead AH, Moffat AC "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol 2 (1983): 5-14
  5. Seixas FA "Drug/alcohol interactions: avert potential dangers." Geriatrics 34 (1979): 89-102
View all 5 references

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Moderate

atropine food

Applies to: Antrocol (atropine / phenobarbital)

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

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Minor

dolutegravir food

Applies to: dolutegravir

Food increases the extent of absorption and slows the rate of absorption of dolutegravir. When administered with a low-, moderate- or high-fat meal, dolutegravir peak plasma concentration (Cmax) increased by 46%, 52% and 67%, systemic exposure (AUC) increased by 33%, 41% and 66%, and time to reach Cmax (Tmax) increased from 2 hours to 3, 4 and 5 hours, respectively, compared to administration under fasted conditions. Dolutegravir may be taken with or without food.

References

  1. "Product Information. Tivicay (dolutegravir)." ViiV Healthcare (2013):

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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.

See also

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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

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