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Drug Interactions between amitriptyline / perphenazine and posaconazole

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

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Interactions between your drugs

Major

amitriptyline posaconazole

Applies to: amitriptyline / perphenazine and posaconazole

CONTRAINDICATED: Coadministration with posaconazole may increase the plasma concentrations of CYP450 3A4 substrates that can prolong the QT interval, possibly resulting in QT prolongation and cases of torsade de pointes (TdP). The underlying mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by posaconazole. 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 drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Coadministration of posaconazole with CYP450 3A4 substrates that can prolong the QT interval is considered contraindicated.

References (6)
  1. (2006) "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation
  2. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
  3. (2022) "Product Information. Posaconazole (AKM) (posaconazole)." Pharmacor Pty Ltd
  4. (2024) "Product Information. Posaconazole (posaconazole)." Morningside Healthcare Ltd
  5. (2023) "Product Information. Posaconazole (posaconazole)." Eugia US LLC
  6. (2023) "Product Information. Gln-Posaconazole (posaconazole)." Glenmark Pharmaceuticals Canada Inc
Moderate

amitriptyline perphenazine

Applies to: amitriptyline / perphenazine and amitriptyline / perphenazine

MONITOR: Coadministration of a phenothiazine with a tricyclic antidepressant (TCA) may result in elevated plasma concentrations of one or both drugs as well as additive adverse effects. Most phenothiazines and TCAs have been found to undergo metabolism by CYP450 2D6, thus competitive inhibition of the enzyme may occur when more than one of these agents are administered. Although these drugs have been used together clinically, the possibility of increased risk of serious adverse effects such as central nervous system depression, tardive dyskinesia, hypotension, and prolongation of the QT interval should be considered, as many of these agents alone can and have produced these effects. In addition, excessive anticholinergic effects may occur in combination use, which can result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of anticholinergic intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures.

MANAGEMENT: Concurrent use of phenothiazines and TCAs should be approached with caution, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication (e.g., abdominal pain, fever, heat intolerance, blurred vision, confusion, hallucinations) or cardiovascular toxicity (e.g., dizziness, palpitations, arrhythmias, syncope). Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A dosage reduction in one or both drugs may be necessary if excessive adverse effects develop.

References (16)
  1. Loga S, Curry S, Lader M (1981) "Interaction of chlorpromazine and nortriptyline in patients with schizophrenia." Clin Pharmacokinet, 6, p. 454-62
  2. Stadnyk AN, Glezos JD (1983) "Drug-induced heat stroke." Can Med Assoc J, 128, p. 957-9
  3. Bock JL, Nelson JC, Gray S, Jatlow PI (1983) "Desipramine hydroxylation: variability and effect of antipsychotic drugs." Clin Pharmacol Ther, 33, p. 322-8
  4. Gram LF, Overo KF (1972) "Drug interaction: inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man." Br Med J, 1, p. 463-5
  5. El-Yousef MK, Manier DH (1974) "Tricyclic antidepressants and phenothiazines." JAMA, 229, p. 1419
  6. Hirschowitz J, Bennett JA, Zemlan FP, Garver DL (1983) "Thioridazine effect on desipramine plasma levels." J Clin Psychopharmacol, 3, p. 376-9
  7. Vandel S, Sandoz M, Vandel B, Bonin B, Allers G, Volmat R (1986) "Biotransformation of amitriptyline in man: interaction with phenothiazines." Neuropsychobiology, 15, p. 15-9
  8. Zelman S, Guillan R (1970) "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry, 126, p. 1787-90
  9. Mann SC, Boger WP (1978) "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry, 135, p. 1097-100
  10. Warnes H, Lehmann HE, Ban TA (1967) "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J, 96, p. 1112-3
  11. Siris SG, Cooper TB, Rifkin AE, Brenner R, Lieberman JA (1982) "Plasma imipramine concentrations in patients receiving concomitant fluphenazine decanoate." Am J Psychiatry, 139, p. 104-6
  12. Johnson AL, Hollister LE, Berger PA (1981) "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry, 42, p. 313-7
  13. Lee BS (1986) "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry, 47, p. 571
  14. Moreau A, Jones BD, Banno V (1986) "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry, 31, p. 339-41
  15. Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA (1983) "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm, 2, p. 174-8
  16. Maynard GL, Soni P (1996) "Thioridazine interferences with imipramine metabolism and measurement." Ther Drug Monit, 18, p. 729-31
Moderate

perphenazine posaconazole

Applies to: amitriptyline / perphenazine and posaconazole

MONITOR: Theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. The risk of an individual agent or a combination of these 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 drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution and clinical monitoring are recommended if multiple agents associated with QT interval prolongation are prescribed together. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References (7)
  1. Glassman AH, Bigger JT Jr (2001) "Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death." Am J Psychiatry, 158, p. 1774-82
  2. Witchel HJ, Hancox JC, Nutt DJ (2003) "Psychotropic drugs, cardiac arrhythmia, and sudden death." J Clin Psychopharmacol, 23, p. 58-77
  3. Iannini PB (2002) "Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval." Expert Opin Drug Saf, 1, p. 121-8
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  5. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  6. Cerner Multum, Inc. "Australian Product Information."
  7. EMA. European Medicines Agency. European Union (2013) EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852

Drug and food interactions

Moderate

posaconazole food

Applies to: posaconazole

ADJUST DOSING INTERVAL: Food significantly increases the absorption of posaconazole from the oral suspension but only modestly from the delayed-release tablet. Following single-dose administration, posaconazole mean peak plasma concentration (Cmax) and systemic exposure (AUC) are approximately 2.5 to 3 times higher when the oral suspension is given with a nonfat meal or a nutritional supplement (14 grams of fat) than when given under fasting conditions, and approximately 3.5 to 4 times higher when given during or 20 minutes after a high-fat meal (50 grams of fat) than under fasting conditions. Acidic beverages may also increase posaconazole absorption. In 12 healthy volunteers, administration of a single 400 mg dose of posaconazole suspension with 12 ounces of ginger ale increased posaconazole Cmax by 92% and AUC by 70% compared to administration after fasting. In contrast, the Cmax and AUC of posaconazole increased by just 16% and 51%, respectively, when posaconazole tablets were given as a single 300 mg dose to healthy volunteers after a high-fat meal relative to a fasted state.

GENERALLY AVOID Concomitant use of alcohol and posaconazole administered in the form of delayed-release oral suspension may lead to a faster release of posaconazole. An in vitro dissolution study determined a potential for alcohol-induced dose-dumping with the delayed-release oral suspension of posaconazole.

MONITOR: In 5 study subjects, posaconazole Cmax decreased by 27% to 53% and AUC decreased by 33% to 51% when the oral suspension was administered via a nasogastric tube as opposed to orally.

MANAGEMENT: Posaconazole tablets should be taken with food, whereas posaconazole oral suspension should be administered during or immediately (i.e., within 20 minutes) following a full meal to enhance bioavailability. Patients who cannot eat a full meal should take the suspension with a liquid nutritional supplement or an acidic carbonated beverage such as ginger ale. In patients who cannot eat a full meal or tolerate an oral nutritional supplement or an acidic carbonated beverage and who do not have the option of taking another formulation of posaconazole, alternative antifungal therapy should be considered; otherwise, monitor patients closely for breakthrough fungal infections. Patients receiving posaconazole via a nasogastric tube should also be closely monitored due to increased risk of treatment failure associated with lower plasma exposure. Administration of alcohol with posaconazole from the delayed-release oral suspension formulation is not recommended.

References (4)
  1. (2006) "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation
  2. Sansone-Parsons A, Krishna G, Calzetta A, et al. (2006) "Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers." Antimicrob Agents Chemother, 50, p. 1881-3
  3. Krishna G, Moton A, Ma L, Malavade D, Medlock M, McLeod J (2008) "Effect of gastric pH, dosing regimen and prandial state, food and meal timing relative to dose, and gastro-intestinal motility on absorption and pharmacokinetics of the antifungal posaconazole." 18th European Congress of Clinical Microbiology and Infectious Diseases, April, p. 20
  4. Walravens J, Brouwers J, Spriet I, Tack J, Annaert P, Augustijns P (2011) "Effect of pH and Comedication on Gastrointestinal Absorption of Posaconazole: Monitoring of Intraluminal and Plasma Drug Concentrations." Clin Pharmacokinet, 50, p. 725-34
Moderate

amitriptyline food

Applies to: amitriptyline / perphenazine

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

References (7)
  1. Dorian P, Sellers EM, Reed KL, et al. (1983) "Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction." Eur J Clin Pharmacol, 25, p. 325-31
  2. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  3. Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R (1983) "Biotransformation of amitriptyline in alcoholic depressive patients." Eur J Clin Pharmacol, 24, p. 615-21
  4. Ciraulo DA, Barnhill JG, Jaffe JH (1988) "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther, 43, p. 509-18
  5. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M (1975) "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther, 17, p. 515-22
  6. Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF (1990) "Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls." J Stud Alcohol, 51, p. 366-72
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA (1982) "Imipramine disposition in alcoholics." J Clin Psychopharmacol, 2, p. 2-7
Moderate

perphenazine food

Applies to: amitriptyline / perphenazine

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.

References (2)
  1. Lutz EG (1976) "Neuroleptic-induced akathisia and dystonia triggered by alcohol." JAMA, 236, p. 2422-3
  2. Freed E (1981) "Alcohol-triggered-neuroleptic-induced tremor, rigidity and dystonia." Med J Aust, 2, p. 44-5
Moderate

amitriptyline food

Applies to: amitriptyline / perphenazine

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

References (4)
  1. (2024) "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd
  2. jeong sh, Newcombe D, sheridan j, Tingle M (2015) "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal, 7, p. 475-82
  3. Vaughan DP, Beckett AH, Robbie DS (1976) "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol, 3, p. 279-83
  4. Zevin S, Benowitz NL (1999) "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet, 36, p. 425-38

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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