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Drug Interactions between Aerolate SR and riociguat

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

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Interactions between your drugs

Major

theophylline riociguat

Applies to: Aerolate SR (theophylline) and riociguat

CONTRAINDICATED: Coadministration of riociguat with phosphodiesterase (PDE) inhibitors may cause significant hypotension. The mechanism involves peripheral vasodilation secondary to enhanced levels of cyclic guanosine monophosphate (cGMP) in vascular smooth muscle cells, as PDE inhibitors prevent degradation of cGMP while riociguat promotes its synthesis by stimulating soluble guanylate cyclase (sGC), an enzyme in the cardiopulmonary system that binds with nitric oxide (NO) to catalyze the synthesis of cGMP. In seven study patients with pulmonary arterial hypertension (PAH) on stable sildenafil treatment (20 mg three times a day), coadministration of single doses of riociguat (0.5 mg and 1 mg sequentially) demonstrated additive hemodynamic effects. One death has been reported in clinical studies of PAH patients on stable sildenafil treatment receiving riociguat 1 to 2.5 mg three times a day, and there was a high rate of discontinuation for hypotension. Riociguat does not affect the pharmacokinetics of sildenafil.

MANAGEMENT: Concomitant use of riociguat with PDE inhibitors, including specific PDE-5 inhibitors (e.g., avanafil, sildenafil, tadalafil, vardenafil) or nonspecific PDE inhibitors (e.g., dipyridamole, theophylline), is considered contraindicated. Riociguat should be discontinued at least 24 hours before administering a PDE-5 inhibitor, and avoidance of riociguat administration within 24 hours after sildenafil or within 48 hours after tadalafil is recommended. Limited data exists for other PDE inhibitors.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Adempas (riociguat)." Bayer Pharmaceutical Inc (2013):

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Drug and food interactions

Moderate

theophylline food

Applies to: Aerolate SR (theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

ADJUST DOSING INTERVAL: Administration of theophylline with continuous enteral nutrition may reduce the serum levels or the rate of absorption of theophylline. The mechanism has not been reported. In one case, theophylline levels decreased by 53% in a patient receiving continuous nasogastric tube feedings and occurred with both theophylline tablet and liquid formulations, but not with intravenous aminophylline.

MANAGEMENT: When administered to patients receiving continuous enteral nutrition , some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of theophylline is given; rapid-release formulations are preferable, and theophylline levels should be monitored.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8
  3. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67

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Moderate

riociguat food

Applies to: riociguat

ADJUST DOSE: Smoking may decrease the plasma concentrations of riociguat. The proposed mechanism is induction of the CYP450 1A1-mediated metabolism of riociguat by polycyclic aromatic hydrocarbons present in cigarette smoke. CYP450 1A1 is responsible for the formation of the major active metabolite, M1, which has just 1/3 to 1/10 the pharmacologic activity of riociguat. According to the product labeling, plasma concentrations of riociguat are reduced by 50% to 60% in smokers compared to nonsmokers.

MANAGEMENT: Riociguat dosages higher than 2.5 mg three times a day may be considered in cigarette smokers, if tolerated, so as to match the exposure seen in nonsmoking patients. However, safety and effectiveness of higher dosages have not been established. A dosage reduction should be considered in patients who stop smoking during treatment with riociguat.

References

  1. "Product Information. Adempas (riociguat)." Bayer Pharmaceutical Inc (2013):

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Moderate

theophylline food

Applies to: Aerolate SR (theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8

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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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