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Drug Interactions between amitriptyline / perphenazine and ombitasvir / paritaprevir / ritonavir

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

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Interactions between your drugs

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

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

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Moderate

amitriptyline ritonavir

Applies to: amitriptyline / perphenazine and ombitasvir / paritaprevir / ritonavir

MONITOR: Coadministration with ritonavir may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to competitive inhibition of CYP450 2D6 activity by ritonavir. The systemic exposure (AUC) of some coadministered drugs has been reported to increase by up to twofold.

MANAGEMENT: Caution is advised if ritonavir must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ritonavir is added to or withdrawn from therapy.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):

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Moderate

perphenazine ritonavir

Applies to: amitriptyline / perphenazine and ombitasvir / paritaprevir / ritonavir

MONITOR: Coadministration with ritonavir may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to competitive inhibition of CYP450 2D6 activity by ritonavir. The systemic exposure (AUC) of some coadministered drugs has been reported to increase by up to twofold.

MANAGEMENT: Caution is advised if ritonavir must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ritonavir is added to or withdrawn from therapy.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):

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Drug and food interactions

Moderate

ritonavir food

Applies to: ombitasvir / paritaprevir / ritonavir

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):

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Moderate

paritaprevir food

Applies to: ombitasvir / paritaprevir / ritonavir

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of ombitasvir, paritaprevir, ritonavir, and dasabuvir. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a moderate-fat meal (approximately 600 Kcal; 20% to 30% calories from fat) increased the mean systemic exposure (AUC) by 82%, 211%, 49%, and 30%, respectively. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a high-fat meal (approximately 900 Kcal; with 60% calories from fat) increased the mean AUC by 76%, 180%, 44%, and 22%, respectively.

MANAGEMENT: Ombitasvir/paritaprevir/ritonavir plus dasabuvir should always be administered with a meal. The fat or calorie content does not matter.

References

  1. "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC (2022):

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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

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

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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

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

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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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