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Drug Interactions between Lufyllin-EPG and Zepatier

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

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Interactions between your drugs

Major

PHENobarbital elbasvir

Applies to: Lufyllin-EPG (dyphylline / ephedrine / guaifenesin / phenobarbital) and Zepatier (elbasvir / grazoprevir)

CONTRAINDICATED: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of elbasvir and grazoprevir, both of which are substrates of the isoenzyme. In 10 study subjects, administration of elbasvir 50 mg once daily with efavirenz 600 mg once daily decreased elbasvir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 45%, 54% and 59%, respectively, compared to administration of elbasvir alone. Likewise, when grazoprevir 200 mg once daily and efavirenz 600 mg once daily were given together to 12 study subjects, grazoprevir Cmax, AUC and Cmin decreased by 87%, 83% and 69%, respectively. Efavirenz is generally considered a moderate inducer of CYP450 3A4. More potent inducers such as carbamazepine or phenytoin may interact to an even greater extent.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, concomitant use of elbasvir-grazoprevir with efavirenz or potent CYP450 3A4 inducers is considered contraindicated.

References (1)
  1. (2016) "Product Information. Zepatier (elbasvir-grazoprevir)." Merck & Co., Inc

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Major

PHENobarbital grazoprevir

Applies to: Lufyllin-EPG (dyphylline / ephedrine / guaifenesin / phenobarbital) and Zepatier (elbasvir / grazoprevir)

CONTRAINDICATED: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of elbasvir and grazoprevir, both of which are substrates of the isoenzyme. In 10 study subjects, administration of elbasvir 50 mg once daily with efavirenz 600 mg once daily decreased elbasvir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 45%, 54% and 59%, respectively, compared to administration of elbasvir alone. Likewise, when grazoprevir 200 mg once daily and efavirenz 600 mg once daily were given together to 12 study subjects, grazoprevir Cmax, AUC and Cmin decreased by 87%, 83% and 69%, respectively. Efavirenz is generally considered a moderate inducer of CYP450 3A4. More potent inducers such as carbamazepine or phenytoin may interact to an even greater extent.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, concomitant use of elbasvir-grazoprevir with efavirenz or potent CYP450 3A4 inducers is considered contraindicated.

References (1)
  1. (2016) "Product Information. Zepatier (elbasvir-grazoprevir)." Merck & Co., Inc

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Minor

ePHEDrine dyphylline

Applies to: Lufyllin-EPG (dyphylline / ephedrine / guaifenesin / phenobarbital) and Lufyllin-EPG (dyphylline / ephedrine / guaifenesin / phenobarbital)

Ephedrine-methylxanthine combinations are used for the treatment of asthma but the efficacy of the combination has been questioned. This combination may lead to increased xanthine side effects. The mechanism is unknown, but may be related to synergistic pharmacologic effects. Patients using this combination should be closely monitored for side effects such as nausea, vomiting, tachycardia, nervousness, or insomnia. If side effects are noted, the dosage of the xanthine may need to be decreased.

References (5)
  1. Weinberger M, Bronsky E, Bensch GW, Bock GN, Yecies JJ (1975) "Interaction of ephedrine and theophylline." Clin Pharmacol Ther, 17, p. 585-92
  2. Sims JA, doPico GA, Reed CE (1978) "Bronchodilating effect of oral theophylline-ephedrine combination." J Allergy Clin Immunol, 62, p. 15-21
  3. Tinkelman DG, Avner SE (1977) "Ephedrine therapy in asthmatic children. Clinical tolerance and absence of side effects." JAMA, 237, p. 553-7
  4. Weinberger MM, Brousky EA (1974) "Evaluation of oral bronchodilator therapy in asthmatic children: bronchodilators in asthmatic children." J Pediatr, 84, p. 421-7
  5. Badiei B, Faciane J, Sly M (1975) "Effect of throphylline, ephedrine and theri combination upon exercise-induced airway obstruction." Ann Allergy, 35, p. 32-6

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Drug and food interactions

Major

PHENobarbital food

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

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Moderate

ePHEDrine food

Applies to: Lufyllin-EPG (dyphylline / ephedrine / guaifenesin / phenobarbital)

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References (7)
  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company

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Minor

grazoprevir food

Applies to: Zepatier (elbasvir / grazoprevir)

Food does not appear to have clinically significant effects on the pharmacokinetics of elbasvir and grazoprevir. When a single 50 mg-100 mg dose of elbasvir-grazoprevir was administered to healthy study subjects with a high-fat meal (900 kcal; 500 kcal from fat), elbasvir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 15% and 11%, respectively, while grazoprevir Cmax and AUC increased by 2.8- and 1.5-fold, respectively, compared to administration under fasting conditions. According to the product labeling, elbasvir-grazoprevir may be administered with or without food.

References (1)
  1. (2016) "Product Information. Zepatier (elbasvir-grazoprevir)." Merck & Co., Inc

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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.