Pain/fever/hay fever: Oral: Two tablets every 4 to 6 hours as needed (maximum: 10 tablets/day).
There are no dosage adjustments provided in the manufacturer’s labeling; monitor renal function with severe impairment.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
Avoid use (Ref).
(For additional information see "Acetaminophen (paracetamol) and phenyltoloxamine: Pediatric drug information")
Note: All sources of acetaminophen (eg, prescription, OTC, combination products) should be considered when evaluating a patient's maximum daily dose. To lower the risk for hepatotoxicity, limit daily dose to ≤75 mg/kg/day (maximum of 5 daily doses), not to exceed 4,000 mg/day; while recommended doses are generally considered safe, hepatotoxicity has been reported (rarely) even with doses below recommendations (Ref).
Pain (minor) or fever: Oral: Dolorex (acetaminophen 325 mg/phenyltoloxamine citrate 25 mg per tablet):
Children 6 to 11 years: 1 tablet every 4 to 6 hours as needed; maximum daily dose: 5 tablets/24 hours
Children ≥12 years and Adolescents: 2 tablets every 4 to 6 hours as needed; maximum daily dose: 10 tablets/24 hours
There are no dosage adjustments provided in the manufacturer's labeling; monitor renal function with severe impairment.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4,000 mg have been reported. Avoid chronic use in hepatic impairment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Central nervous system: Dizziness, drowsiness, lassitude
Dermatologic: Diaphoresis, pruritus, skin rash
Gastrointestinal: Nausea
Ophthalmic: Blurred vision
OTC labeling: When used for self-medication, do not use if allergic to acetaminophen, phenyltoloxamine, or any component of the formulation or with any other medicine containing acetaminophen or phenyltoloxamine.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hepatotoxicity: Acetaminophen has been associated with acute liver failure, at times resulting in liver transplant and death. Hepatotoxicity is usually associated with excessive acetaminophen intake and often involves >1 product that contains acetaminophen. Do not exceed the maximum recommended daily dose (>4 g daily in adults). In addition, long-term daily dosing may also result in liver damage in some patients.
• Skin reactions: Rarely, acetaminophen may cause serious and potentially fatal skin reactions such as acute generalized exanthematous pustulosis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Discontinue treatment if severe skin reactions develop.
Disease-related concerns:
• Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥3 alcoholic drinks/day may increase the risk of liver damage. Have patients avoid ethanol or limit to <3 drinks/day.
• Hepatic impairment: Use with caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.
Other warnings/precautions:
• Dosage limit: Limit acetaminophen dose to <4 g/day or <2.6 g/day (children <12 years of age).
• Self-medication (OTC use): When used for self-medication, patients should contact health care provider if they have liver disease and/or are currently taking a blood thinner. Discontinue use and notify health care provider if pain worsens or lasts >10 days in adults (or >5 days in children), fever worsens or lasts >3 days, if any new symptoms occur, or if redness or swelling is present.
Prophylactic use of acetaminophen to reduce fever and discomfort associated with vaccination is not recommended by the Advisory Committee on Immunization Practices (ACIP). Additionally, the ACIP does not recommend prophylactic acetaminophen to reduce risk of febrile seizure in infants and children with or without a history of febrile seizures. Antipyretics have not been shown to prevent febrile seizures (NCIRD/ACIP 2011). One study reported that routine prophylactic administration of acetaminophen to prevent fever prior to vaccination decreased the immune response of some vaccines; in the trial evaluating 459 infants (including 226 who received acetaminophen), antibody geometric mean concentrations (GMCs) for targeted vaccine immune response markers were lower in significantly more infants in the acetaminophen group compared with control. Before the booster dose, children who received prophylactic acetaminophen had lower antibody GMCs for all vaccine serotypes than children in the control group; this effect persisted after boosting even in the absence of additional acetaminophen doses. The clinical significance of this reduction in immune response has not been established (Prymula 2009). Antipyretics may be used to treat fever or discomfort following vaccination (NCIRD/ACIP 2011).
Hepatoxicity has been reported in patients using acetaminophen. In pediatric patients, this is most commonly associated with supratherapeutic dosing, more frequent administration than recommended, and use of multiple acetaminophen-containing products; however, hepatotoxicity has been rarely reported with recommended dosages (AAP [Sullivan 2011]; Heard 2014). All sources of acetaminophen (eg, prescription, OTC, combination) should be considered when evaluating a patient's maximum daily dose. To lower the risk for hepatotoxicity, the maximum daily acetaminophen dose should be limited to ≤75 mg/kg/day (maximum of 5 daily doses), not to exceed 4,000 mg/day (AAP [Sullivan 2011]; Heard 2014; Krenzelok 2012; Lavonas 2010). Acetaminophen avoidance or a lower total daily dose (2,000 to 3,000 mg/day) has been suggested for adults with increased risk for acetaminophen hepatotoxicity (eg, malnutrition, certain liver diseases, use of drugs that interact with acetaminophen metabolism); similar data are unavailable in pediatric patients (Hayward 2016; Larson 2007; Worriax 2007).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Dolorex: Acetaminophen 325 mg and phenyltoloxamine citrate 25 mg
Yes
Tablets (Dologesic Oral)
30-500 mg (per each): $0.22
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: May be administered without regard to food.
Pain/fever/hay fever: Temporary relief of minor aches and pains due to headache, backache, toothache, menstrual cramps, muscular aches, and minor pain of arthritis; temporarily reduces fever; temporarily reduces itchy and watery eyes due to hay fever.
Beers Criteria: Based on pharmacologic class concerns for first-generation antihistamines in the Beers Criteria, phenyltoloxamine may be a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its potent anticholinergic properties resulting in increased risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity; use should also be avoided due to reduced clearance with advanced age and tolerance associated with use as a hypnotic. Exposure to concurrent anticholinergic drugs also increases risk of falls, delirium, and dementia; consider total anticholinergic burden when conducting medication reviews (Beers Criteria [AGS 2023]).
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination
Agents with Clinically Relevant Anticholinergic Effects: May enhance the adverse/toxic effect of other Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the hepatotoxic effect of Acetaminophen. Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Amantadine: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Amezinium: Antihistamines may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Belumosudil: May increase the serum concentration of UGT1A1 Substrates. Management: Avoid coadministration of belumosudil with substrates of UGT1A1 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the UGT1A1 substrate may be required. Risk D: Consider therapy modification
Benperidol: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Benperidol. Risk C: Monitor therapy
Benzylpenicilloyl Polylysine: Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects. Risk D: Consider therapy modification
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Betahistine may diminish the therapeutic effect of Antihistamines. Risk C: Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Busulfan: Acetaminophen may increase the serum concentration of Busulfan. Risk C: Monitor therapy
Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Chlorprothixene: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy
Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
CloZAPine: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Dasatinib: Acetaminophen may enhance the hepatotoxic effect of Dasatinib. Dasatinib may increase the serum concentration of Acetaminophen. Management: Avoid coadministration of acetaminophen and dasatinib if possible. If coadministration is unavoidable, monitor for signs/symptoms of hepatotoxicity, particularly in patients with greater acetaminophen exposure. Risk D: Consider therapy modification
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Systemic): Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Dimethindene (Systemic). Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Eluxadoline: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flucloxacillin: May enhance the adverse/toxic effect of Acetaminophen. Specifically, the risk for high anion gap metabolic acidosis may be increased. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Fosphenytoin-Phenytoin: May decrease the serum concentration of Acetaminophen. Specifically, serum concentrations of acetaminophen may be decreased (leading to decreased efficacy), but the formation of the toxic N-acetyl-p-benzoquinone imine (NAPQI) metabolite may be increased (leading to increased hepatotoxicity). Risk C: Monitor therapy
Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination
Hyaluronidase: Antihistamines may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Imatinib: Acetaminophen may enhance the hepatotoxic effect of Imatinib. Risk C: Monitor therapy
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Acetaminophen may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Ipratropium (Nasal): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination
Isoniazid: May enhance the hepatotoxic effect of Acetaminophen. Isoniazid may increase the metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor therapy
Itopride: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
LamoTRIgine: Acetaminophen may decrease the serum concentration of LamoTRIgine. Risk C: Monitor therapy
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lorlatinib: May decrease the serum concentration of Acetaminophen. Risk C: Monitor therapy
Loxapine: CNS Depressants may enhance the CNS depressant effect of Loxapine. Risk D: Consider therapy modification
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyraPONE: May increase the serum concentration of Acetaminophen. More importantly, by inhibiting the conjugative metabolism of acetaminophen, metyrapone may shift the metabolism towards the oxidative route that produces a hepatotoxic metabolite. Risk X: Avoid combination
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Mianserin: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy
Mitapivat: May decrease the serum concentration of UGT1A1 Substrates. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxatomide: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
PHENobarbital: May increase the metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor therapy
Phenylephrine (Systemic): Acetaminophen may increase the serum concentration of Phenylephrine (Systemic). Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pitolisant: Antihistamines may diminish the therapeutic effect of Pitolisant. Risk X: Avoid combination
Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination
Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may enhance the ulcerogenic effect of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid combination
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor for signs of methemoglobinemia when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid use of these agents with prilocaine/lidocaine cream in infants less than 12 months of age. Risk C: Monitor therapy
Primidone: May increase the metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Acetaminophen. Probenecid may also limit the formation of at least one major non-toxic metabolite, possibly increasing the potential for formation of the toxic NAPQI metabolite. Management: Consider limiting acetaminophen use in combination with probenecid. Probenecid may reduce clearance of acetaminophen to one of its non-toxic metabolities, increasing the risk for acetaminophen toxicity, even a lower doses. Risk D: Consider therapy modification
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
QuiNIDine: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
RifAMPin: May enhance the hepatotoxic effect of Acetaminophen. RifAMPin may decrease the serum concentration of Acetaminophen. Risk C: Monitor therapy
Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Agents with Clinically Relevant Anticholinergic Effects. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Secretin: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification
Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
SORAfenib: Acetaminophen may enhance the hepatotoxic effect of SORAfenib. SORAfenib may increase the serum concentration of Acetaminophen. Management: Avoid coadministration of acetaminophen and sorafenib if possible. If coadministration is unavoidable, monitor for signs/symptoms of hepatotoxicity, particularly in patients with greater acetaminophen exposure. Risk D: Consider therapy modification
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Topiramate: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Tranylcypromine: May enhance the anticholinergic effect of Antihistamines, First Generation. Risk X: Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination
Vaccines: Acetaminophen may diminish the therapeutic effect of Vaccines. Management: Consider avoiding routine prophylactic use of acetaminophen before or during vaccine administration when possible. Acetaminophen is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider therapy modification
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. This appears most likely with daily acetaminophen doses exceeding 1.3 or 2 g/day for multiple consecutive days. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Refer to individual monographs.
Refer to individual monographs.
Acetaminophen: Although not fully elucidated, the analgesic effects are believed to be due to activation of descending serotonergic inhibitory pathways in the CNS. Interactions with other nociceptive systems may be involved as well (Smith 2009). Antipyresis is produced from inhibition of the hypothalamic heat-regulating center.
Phenyltoloxamine: An antihistamine (H1-blocking agent) that acts primarily to inhibit secretions in the nose, mouth, and pharynx, as well as causing CNS depression.
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