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Drug Interactions between Para-Time S. R. and Probuphine

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

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Major

papaverine buprenorphine

Applies to: Para-Time S. R. (papaverine) and Probuphine (buprenorphine)

MONITOR CLOSELY: Intracoronary administration of papaverine has been associated with QT interval prolongation and torsade de pointes (TdP) arrhythmia. The risk may theoretically increase in patients receiving concomitant medications that can also prolong the QT interval or cause bradycardia. QT interval prolongation has not been reported following systemic or intracavernosal administration of papaverine. The precise mechanism of papaverine-induced ventricular tachyarrhythmias has not been delineated, but may involve inhibition of potassium currents and prolongation of the action potential duration. In a study involving 182 consecutive patients undergoing fractional flow reserve measurements, premature ventricular beats occurred in 15.9% of patients following administration of intracoronary papaverine. TdP occurred in 2.8% of patients, and of those, 1.7% developed ventricular fibrillation. The incidence of intracoronary papaverine-induced ventricular tachyarrhythmias has not been determined, but has ranged between <0.67% and 8.8% following intracoronary administration of 6 mg to 20 mg. Based on numerous reports, female gender, hypokalemia, alkalosis, bradycardia, administration of papaverine into the left coronary artery, and a prior history of drug-induced QT prolongation may be risk factors for papaverine-induced fatal ventricular tachyarrhythmias. Apart from isolated case reports, there are no published data regarding the potential interaction between intracoronary papaverine and its use with other QT-prolonging drugs. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drugs involved and dosages of the drugs.

MANAGEMENT: Caution and close monitoring are advised during intracoronary administration of papaverine, particularly in patients receiving concomitant drugs that can prolong the QT interval or cause bradycardia and in patients with other risk factors described above. Some QT prolonging medications have specific monitoring, dosing, and/or other recommendations present in their labeling to help mitigate or monitor this side effect; therefore, it may be advisable to consult the package labeling of the concomitant medication if coadministration with intracoronary papaverine is being considered or deemed necessary.

References

  1. Nakayama M, Tanaka N, Sakoda K, et al. "Papaverine-induced polymorphic ventricular tachycardia during coronary flow reserve study of patients with moderate coronary artery disease." Circ J 79 (2015): 530-6
  2. Goto M, Sato M, Kitzazawa H, et al. "Papaverine-induced QT interval prolongation and ventricular fibrillation in a patient with a history of drug-induced QT prolongation." Intern Med 53 (2014): 1629-31
  3. Nakayama M, Saito A, Kitazawa H, et al. "Papaverine-induced polymorphic ventricular tachycardia in relation to QTU and giant T-U waves in four cases." Intern Med 51 (2012): 351-6
  4. Inoue T, Asahi S, Takayanagi K, Morooka S, Takabatake Y "QT prolongation and possibility of ventricular arrhythmias after intracoronary papaverine." Cardiology 84 (1994): 9-13
  5. Vrolix M, Piessens J, De Geest H "Torsades de pointes after intracoronary papaverine." Eur Heart J 12 (1991): 273-6
  6. Kern MJ, Deligonul U, Serota H, Gudipati C, Buckingham T "Ventricular arrhythmia due to intracoronary papaverine: analysis of QT intervals and coronary vasodilatory reserve." Cathet Cardiovasc Diagn 19 (1990): 229-36
  7. Talman CL, Winniford MD, Rossen JD, Simonetti I, Kienzle MG, Marcus ML "Polymorphous ventricular tachycardia: a side effect of intracoronary papaverine." J Am Coll Cardiol 15 (1990): 275-8
  8. Jain A, Jenkins MG "Intracoronary electrocardiogram during torsade des pointes secondary to intracoronary papaverine." Cathet Cardiovasc Diagn 18 (1989): 255-7
View all 8 references

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Drug and food interactions

Major

buprenorphine food

Applies to: Probuphine (buprenorphine)

GENERALLY AVOID: Concomitant use of buprenorphine with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may increase the risk of buprenorphine overdose, severe respiratory depression, coma, and death. Reported cases have primarily occurred in the setting of buprenorphine maintenance treatment for opiate addiction, and many, but not all, involved abuse or misuse of buprenorphine including intravenous self-injection. The mechanism of interaction probably involves some degree of additive pharmacologic effects. Preclinical studies also suggest that benzodiazepines can alter the usual ceiling effect on buprenorphine-induced respiratory depression and render the respiratory effects of buprenorphine appear similar to those of full opioid agonists. Coadministration of buprenorphine with some CNS depressants such as alcohol, benzodiazepines, and phenothiazines may also increase the risk of hypotension.

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Extreme caution is advised when prescribing buprenorphine to patients who are addicted to opioids and also abusing benzodiazepines or alcohol. Due to potential risk of overdose and death, dependence on sedative-hypnotics such as benzodiazepines or alcohol is considered a relative contraindication for office-based buprenorphine treatment of opioid addiction. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

References

  1. "Product Information. Suboxone (buprenorphine-naloxone)." Reckitt and Colman Pharmaceuticals Inc (2002):
  2. Kilicarslan T, Sellers EM "Lack of interaction of buprenorphine with flunitrazepam metabolism." Am J Psychiatry 157 (2000): 1164-6
  3. Reynaud M, Petit G, Potard D, Courty P "Six deaths linked to concomitant use of buprenorphine and benzodiazepines." Addiction 93 (1998): 1385-92
  4. Tracqui A, Kintz P, Ludes B "Buprenorphine-related deaths among drug addicts in France: a report on 20 fatalities." J Anal Toxicol 22 (1998): 430-4
  5. Reynaud M, Tracqui A, Petit G, Potard D, Courty P "Six deaths linked to misuse of buprenorphine-benzodiazepine combinations." Am J Psychiatry 155 (1998): 448-9
  6. Kintz P "A new series of 13 buprenorphine-related deaths." Clin Biochem 35 (2002): 513-6
  7. Martin HA "The possible consequences of combining lorazepam and buprenorphine/naloxone: a case review." J Emerg Nurs 37 (2011): 200-2
  8. Hakkinen M, Launiainen T, Vuori E, Ojanpera I "Benzodiazepines and alcohol are associated with cases of fatal buprenorphine poisoning." Eur J Clin Pharmacol 68 (2012): 301-9
  9. Substance Abuse and Mental Health Services Administration (US) "Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series, No. 40 http://www.ncbi.nlm.nih.gov/books/NBK64245/" (2013):
  10. Schuman-Olivier Z, Hoeppner BB, Weiss RD, Borodovsky J, Shaffer HJ, Albanese MJ "Benzodiazepine use during buprenorphine treatment for opioid dependence: clinical and safety outcomes." Drug Alcohol Depend 132 (2013): 580-6
  11. Ferrant O, Papin F, Clin B, et al. "Fatal poisoning due to snorting buprenorphine and alcohol consumption." Forensic Sci Int 204 (2011): e8-11
  12. Pirnay S, Borron SW, Giudicelli CP, Tourneau J, Baud FJ, Ricordel I "A critical review of the causes of death among post-morten toxicological investigations: analysis of 34 buprenorphine-associated and 35 methadone-associated deaths." Addiction 99 (2004): 978-88
  13. Kintz P "Deaths involving buprenorphine: a compendium of French cases." Forensic Sci Int 121 (2001): 65-9
  14. Sekar M, Mimpriss TJ "Buprenorphine, benzodiazepines and prolonged respiratory depression." Anaesthesia 42 (1987): 567-8
  15. Gueye PN, Borron SW, Risede P, et al. "Buprenorphine and midazolalm act in combination to depress respiration in rats." Toxicol Sci 65 (2002): 107-14
  16. US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM518672.pdf" (2016):
View all 16 references

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Moderate

papaverine food

Applies to: Para-Time S. R. (papaverine)

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595
View all 8 references

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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.

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