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Drug Interactions between Akynzeo for Injection and clonazepam

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

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Interactions between your drugs

Moderate

clonazePAM fosnetupitant

Applies to: clonazepam and Akynzeo for Injection (fosnetupitant / palonosetron)

MONITOR: Coadministration with netupitant or its prodrug, fosnetupitant, may increase the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by netupitant and its desmethyl metabolite. When a single 7.5 mg oral dose of midazolam, a CYP450 3A4 probe substrate, was administered with netupitant 300 mg, mean midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 36% and 126%, respectively. When a 500 mg dose of erythromycin, another CYP450 3A4 substrate, was coadministered with netupitant 300 mg, the mean Cmax and AUC of erythromycin were increased by 92% and 56%, respectively, although the systemic exposure of erythromycin was highly variable.

MANAGEMENT: Caution is advised when netupitant or fosnetupitant is used concomitantly with drugs that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever netupitant or fosnetupitant is added to or withdrawn from therapy. The inhibitory effect on CYP450 3A4 can last for 6 days after administration of a single dose of netupitant or fosnetupitant.

References (3)
  1. Cerner Multum, Inc. "Australian Product Information."
  2. (2014) "Product Information. Akynzeo (netupitant-palonosetron)." Eisai Inc
  3. (2018) "Product Information. Akynzeo for Injection (fosnetupitant-palonosetron)." Helsinn Therapeutics Inc

Drug and food interactions

Moderate

clonazePAM food

Applies to: clonazepam

GENERALLY AVOID: Acute ethanol ingestion may potentiate the CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

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

References (7)
  1. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol, 11, p. 345-9
  2. Whiting B, Lawrence JR, Skellern GG, Meier J (1979) "Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide." Br J Clin Pharmacol, 7, p. 95-100
  3. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI (1981) "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl), 73, p. 381-3
  4. Juhl RP, Van Thiel DH, Dittert LW, Smith RB (1984) "Alprazolam pharmacokinetics in alcoholic liver disease." J Clin Pharmacol, 24, p. 113-9
  5. Ochs HR, Greenblatt DJ, Arendt RM, Hubbel W, Shader RI (1984) "Pharmacokinetic noninteraction of triazolam and ethanol." J Clin Psychopharmacol, 4, p. 106-7
  6. Staak M, Raff G, Nusser W (1979) "Pharmacopsychological investigations concerning the combined effects of dipotassium clorazepate and ethanol." Int J Clin Pharmacol Biopharm, 17, p. 205-12
  7. Nichols JM, Martin F, Kirkby KC (1993) "A comparison of the effect of lorazepam on memory in heavy and low social drinkers." Psychopharmacology (Berl), 112, p. 475-82

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.

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