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Drug Interaction Report

4 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Moderate

butabarbital tipranavir

Applies to: belladonna / butabarbital, tipranavir

MONITOR: Coadministration with drugs that are inducers of CYP450 3A4 may decrease the plasma concentrations of protease inhibitors (PIs), which are primarily metabolized by the isoenzyme.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, protease inhibitors should be used cautiously with agents that induce CYP450 3A4, particularly if only one PI is used in the antiretroviral regimen. Coadministration of atazanavir without ritonavir and carbamazepine, phenobarbital, or phenytoin is not recommended. Antiretroviral response should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the antiretroviral regimen adjusted as necessary.

References

  1. Product Information. Invirase (saquinavir). Roche Laboratories. 2001;PROD.
  2. Product Information. Crixivan (indinavir). Merck & Co., Inc. 2001;PROD.
  3. Product Information. Viracept (nelfinavir). Agouron Pharma Inc. 2001;PROD.
  4. Brooks J, Daily J, Schwamm L. Protease inhibitors and anticonvulsants. AIDS Clin Care. 1997;9:87,90.
  5. Barry M, Gibbons S, Back D, Mulcahy F. Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations. Clin Pharmacokinet. 1997;32:194-209.
  6. Product Information. Agenerase (amprenavir). Glaxo Wellcome. 2001;PROD.
  7. Acosta EP, Henry K, Baken L, Page LM, Fletcher CV. Indinavir concentrations and antiviral effect. Pharmacotherapy. 1999;19:708-12.
  8. Sommadossi JP. HIV protease inhibitors: pharmacologic and metabolic distinctions. AIDS. 1999;13:s29-40.
  9. Hugen PWH, Burger DM, Brinkman K, terHofstede HJM, Schuurman R, Koopmans PP, Hekster YA. Carbamazepine-indinavir interaction causes antiretroviral therapy failure. Ann Pharmacother. 2000;34:465-70.
  10. Durant J, Clevenbergh P, Garraffo R, Halfon P, Icard S, DelGiudice P, Montagne N, Schapiro JM, Dellamonica P. Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study. Aids. 2000;14:1333-9.
  11. Product Information. Fortovase (saquinavir). Roche Laboratories. 2001;PROD.
  12. Product Information. Reyataz (atazanavir). Bristol-Myers Squibb. 2003.
  13. Product Information. Lexiva (fosamprenavir). GlaxoSmithKline. 2003.
  14. Liedtke MD, Lockhart SM, Rathbun RC. Anticonvulsant and antiretroviral interactions. Ann Pharmacother. 2004;38:482-9.
  15. Product Information. Aptivus (tipranavir). Boehringer-Ingelheim. 2005.
  16. Product Information. Prezista (darunavir). Ortho Biotech Inc. 2006.
  17. Canadian Pharmacists Association. e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink 2006.
View all 17 references

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Drug and food interactions

Major

butabarbital food

Applies to: belladonna / butabarbital

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. 1966;94:863-5.
  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. 1971;51:346-51.
  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). 1976;38:382-92.
  4. Stead AH, Moffat AC. Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations. Hum Toxicol. 1983;2:5-14.
  5. Seixas FA. Drug/alcohol interactions: avert potential dangers. Geriatrics. 1979;34:89-102.
View all 5 references

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Moderate

tipranavir food

Applies to: tipranavir

ADJUST DOSING INTERVAL: Food does not appear to substantially alter the pharmacokinetics of tipranavir. When tipranavir capsules or oral solution was coadministered with ritonavir capsules at steady-state, no clinically significant changes in tipranavir peak plasma concentration (Cmax) and systemic exposure (AUC) were observed under fed conditions (500 to 682 kcal, 23% to 25% calories from fat) relative to fasted conditions. The effect of food on tipranavir exposure during coadministration with ritonavir tablets has not been evaluated. High-fat foods may enhance the gastrointestinal absorption of tipranavir. In a multiple-dose study, administration of tipranavir capsules with a high-fat meal (868 kcal, 53% from fat, 31% from carbohydrates) increased the oral bioavailability of tipranavir by 31% compared to administration with toast and skimmed milk, but did not significantly affect tipranavir Cmax. Thus, tipranavir may be safely taken with standard or high-fat meals.

MANAGEMENT: Tipranavir coadministered with low-dose ritonavir should be taken with food to improve the gastrointestinal tolerability of ritonavir. According to the product labeling, tipranavir coadministered with ritonavir capsules or solution can be taken with or without meals, whereas tipranavir coadministered with ritonavir tablets must be taken with meals.

References

  1. Product Information. Aptivus (tipranavir). Boehringer-Ingelheim. 2005.
  2. Cerner Multum, Inc. UK Summary of Product Characteristics.
  3. Canadian Pharmacists Association. e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink 2006.
  4. Cerner Multum, Inc. Australian Product Information.
View all 4 references

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Moderate

belladonna food

Applies to: belladonna / butabarbital

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. 1973;6:107-12.

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Therapeutic duplication warnings

No duplication 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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Further information

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