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  • CLASSES

    Antimuscarinics

    DEA CLASS

    Rx

    DESCRIPTION

    Oral competitive selective M3 antimuscarinic agent
    Used for overactive bladder (OAB) in adult or pediatric patients 2 years and older; in adults may be used in combination with a beta-3 adrenoreceptor agonist
    Common side effects include dry mouth or constipation; monitor for urinary retention

    COMMON BRAND NAMES

    VESIcare

    HOW SUPPLIED

    Solifenacin/Solifenacin Succinate/VESIcare Oral Tab: 5mg, 10mg
    VESIcare Oral Susp: 1mg, 1mL

    DOSAGE & INDICATIONS

    For the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urinary urgency, and urinary frequency.
    Oral dosage (tablets)
    Adults

    5 mg PO once daily. May increase to 10 mg PO once daily if needed and tolerated. Max: 10 mg/day. In patients taking potent inhibitors of CYP3A4, do not exceed 5 mg PO once daily. USE WITH MIRABEGRON: The FDA-approved solifenacin dose is 5 mg PO once daily when given with mirabegron.

    For the treatment of neurogenic detrusor overactivity (neurogenic bladder).
    Oral dosage (oral suspension)
    Children and Adolescents 2 to 17 years weighing more than 60 kg

    5 mg PO once daily. The dose may be increased to 10 mg PO once daily if needed and tolerated.

    Children and Adolescents 2 to 17 years weighing 46 to 60 kg

    4 mg PO once daily. The dose may be increased to 8 mg PO once daily if needed and tolerated.

    Children and Adolescents 2 to 17 years weighing 31 to 45 kg

    3 mg PO once daily. The dose may be increased to 6 mg PO once daily if needed and tolerated.

    Children and Adolescents 2 to 17 years weighing 16 to 30 kg

    3 mg PO once daily. The dose may be increased to 5 mg PO once daily if needed and tolerated.

    Children and Adolescents 2 to 17 years weighing 9 to 15 kg

    2 mg PO once daily. The dose may be increased to 4 mg PO once daily if needed and tolerated.

    MAXIMUM DOSAGE

    Adults

    10 mg/day PO.

    Geriatric

    10 mg/day PO.

    Adolescents

    weighing more than 60 kg: 10 mg/day PO.
    weighing 46 to 60 kg: 8 mg/day PO.
    weighing 31 to 45 kg: 6 mg/day PO.
    weighing 16 to 30 kg: 5 mg/day PO.
    weighing 9 to 15 kg: 4 mg/day PO.

    Children

    2 to 12 years:
    weighing more than 60 kg: 10 mg/day PO.
    weighing 46 to 60 kg: 8 mg/day PO.
    weighing 31 to 45 kg: 6 mg/day PO.
    weighing 16 to 30 kg: 5 mg/day PO.
    weighing 9 to 15 kg: 4 mg/day PO.
    1 year: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Moderate hepatic impairment (Child-Pugh class B): Do not exceed 5 mg PO once daily in adults. Do not exceed the recommended starting dose in pediatric patients.
    Severe hepatic impairment (Child-Pugh class C): Use not recommended in adults or pediatric patients.

    Renal Impairment

    Adult patients:
    CrCl 30 mL/minute or more: No dosage adjustment needed.
    CrCl less than 30 mL/minute: Do not exceed 5 mg PO once daily.
     
    Pediatric patients:
    CrCl 30 mL/minute/1.73 m2 or more: No dosage adjustment needed.
    CrCl less than 30 mL/minute/1.73 m2: Do not exceed the recommended starting dose.

    ADMINISTRATION

    Oral Administration

    Solifenacin tablets are administered without regard to meals; administer with liquids and swallow whole.

    Oral Liquid Formulations

    Shake the bottle well before taking each dose.
    Measure the appropriate dose using a calibrated oral syringe.
    Follow each dose with liquid (e.g., water or milk).
    Take any missed doses as soon as possible, unless more than 12 hours have passed since the missed dose. If more than 12 hours have passed, skip the dose, and take the next dose at the usual time.
    Storage: Store at 20 to 25 degrees C (68 to 77 degrees F) with excursions permitted from 15 to 30 degrees C (59 to 86 degrees F). Store in the original bottle. Discard unused suspension 28 days after first opening the bottle.[65485]

    STORAGE

    VESIcare:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    History of angioedema

    Solifenacin is contraindicated in patients who have demonstrated solifenacin hypersensitivity or a history of angioedema with the drug. Reports of angioedema of the face, lips, tongue, and/or larynx have been associated with solifenacin administration. Angioedema has occurred, in some cases, after a single dose. Patients taking solifenacin should be informed of the risk of this adverse reaction and instructed to immediately discontinue solifenacin if swelling of the tongue, hypopharynx, or larynx occurs. Because upper airway swelling could be life threatening, patients may need emergent care to ensure a patent airway is promptly provided.

    Prostatic hypertrophy, renal failure, renal impairment, urinary retention, urinary tract obstruction

    Due to the anticholinergic effects, solifenacin is contraindicated in patients with urinary retention. In addition, anticholinergics may precipitate urinary retention in patients with preexisting urinary tract obstruction or prostatic hypertrophy, so caution is warranted. Altered pharmacokinetics of solifenacin occur in severe renal impairment (CrCl 30 mL/minute or less) and renal failure; dosages should be adjusted.

    Closed-angle glaucoma, contact lenses

    Use solifenacin with caution in patients with controlled glaucoma. Solifenacin is contraindicated in patients with uncontrolled narrow or closed-angle glaucoma. Solifenacin may increase intraocular pressure and aqueous outflow resistance in patients with closed-angle glaucoma; caution is advised in patients with treated disease of this type. The anticholinergic effects of solifenacin may make the eyes dry and this can cause irritation for wearers of contact lenses.

    Anticholinergic medications, autonomic neuropathy, gastroparesis, GI obstruction, ileus, myasthenia gravis, pyloric stenosis, ulcerative colitis

    Solifenacin should be administered with caution to patients with gastrointestinal (GI) obstructive disorders because of the risk of gastric retention. Solifenacin may delay gastric emptying and is contraindicated in patients with gastric retention (i.e., GI obstruction, ileus, gastroparesis, pyloric stenosis). Solifenacin, like other anticholinergic drugs, may decrease GI motility and should be used with caution in patients with conditions such as severe constipation, ulcerative colitis, and myasthenia gravis. Anticholinergics may, in general, aggravate conditions such as myasthenia gravis and autonomic neuropathy. Patients receiving solifenacin in combination with other anticholinergic medications may experience an increased frequency or severity of dry mouth, constipation, blurred vision, or other anticholinergic effects.[54021]

    Hepatic disease

    Hepatic disease (e.g., cirrhosis) can significantly alter the elimination of solifenacin. Patients with moderately reduced hepatic function should have a dosage modification. Patients with severe liver dysfunction should not receive solifenacin. Dosage reductions may also be required in patients receiving medications that inhibit CYP3A4.

    Driving or operating machinery

    Patients should be advised to use caution when driving or operating machinery while receiving solifenacin until the effects of the drug are known. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment. Anticholinergic drugs in general can cause blurred vision, dizziness, or somnolence in some patients.

    Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    The potential for solifenacin to cause QT prolongation was studied in a multidose, double-blind, and placebo- and positive-control trial. The median difference in heart rate from baseline compared to placebo for 10 mg and 30 mg doses was -2 and 0, respectively. A significant period effect on the QTc was observed. QT interval prolongation was greater with the 30 mg dose (3 times the solifenacin maximum dose) compared to the 10 mg dose, but less than when compared with the positive control. Avoid solifenacin use in patients at risk for torsade de pointes (TdP); QT prolongation and TdP have been reported during postmarketing use, although causality to the drug has not been determined. Use solifenacin with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

    Geriatric

    Use solifenacin with caution in the geriatric adult and adjust doses based on noted renal impairment, if present. In clinical trials, solifenacin-treated geriatric patients had safety and efficacy profiles similar to treated younger adults. Geriatric patients exhibit drug concentrations and exposures that are 20% to 25% higher than younger adults. Geriatric patients may also be at increased risk for developing a prolonged QT interval when using solifenacin.     According to the Beers Criteria, antimuscarinics with strong anticholinergic properties, such as solifenacin, are considered potentially inappropriate medications (PIMs) in geriatric patients with dementia/cognitive impairment (adverse CNS effects) or delirium/high risk of delirium (new-onset or worsening delirium), and it is recommended that use in these patient populations be avoided. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to the OBRA guidelines, solifenacin has specific and limited uses for urinary incontinence based on the cause and categorization of incontinence. Assessment of the underlying causes and identification of the type/category of urinary incontinence needs to be documented before or soon after the time of initiating treatment with a urinary incontinence medication. Patients should be assessed periodically for medication effects on urinary incontinence as well as lower urinary tract symptoms and treatment tolerability.[60742]

    Pregnancy

    There are no adequate and well-controlled studies of solifenacin in human pregnancy to be informative of a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes. Solifenacin should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. Animal studies indicate that solifenacin crosses the placental barrier of pregnant mice. No toxicities were noted with doses resulting in systemic exposure that was 1.2 times higher than exposure at the maximum recommended human dose (MRHD); however, fetal toxicity was noted with doses that were at least 3.6 times greater than the MRHD.

    Breast-feeding

    The developmental and health benefits of breast-feeding should be considered along with the clinical need of the mother for solifenacin and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. There is no information on the presence of solifenacin in human milk, the effects on a breastfed child, or the effects on milk production. Solifenacin is present in mouse milk, although it is not known if excretion into human milk occurs. Anticholinergic medications can inhibit lactation in animals and decrease serum prolactin concentrations in nonlactating women. Therefore, chronic solifenacin use may have adverse effects on milk production.  

    ADVERSE REACTIONS

    Severe

    ileus / Delayed / Incidence not known
    GI obstruction / Delayed / Incidence not known
    ocular hypertension / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    atrial fibrillation / Early / Incidence not known
    hyperkalemia / Delayed / Incidence not known

    Moderate

    constipation / Delayed / 5.4-13.4
    blurred vision / Early / 3.8-4.8
    cystitis / Delayed / 2.8-4.8
    urinary retention / Early / 0-1.4
    hypertension / Early / 0.5-1.4
    peripheral edema / Delayed / 0.3-1.1
    delirium / Early / Incidence not known
    hallucinations / Early / Incidence not known
    confusion / Early / Incidence not known
    depression / Delayed / Incidence not known
    dysphonia / Delayed / Incidence not known
    myasthenia / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    palpitations / Early / Incidence not known
    QT prolongation / Rapid / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known

    Mild

    xerostomia / Early / 3.2-27.6
    dyspepsia / Early / 1.4-3.9
    nausea / Early / 1.7-3.3
    influenza / Delayed / 0.9-2.2
    fatigue / Early / 1.0-2.1
    abdominal pain / Early / 1.1-1.9
    dizziness / Early / 1.8-1.9
    xerophthalmia / Early / 0.3-1.6
    vomiting / Early / 0.2-1.1
    drowsiness / Early / 1.1-1.1
    pharyngitis / Delayed / 0.3-1.1
    cough / Delayed / 0.2-1.1
    gastroesophageal reflux / Delayed / Incidence not known
    dysgeusia / Early / Incidence not known
    headache / Early / Incidence not known
    nasal dryness / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    rash / Early / Incidence not known
    xerosis / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Acetaminophen; Caffeine: (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when dihydrocodeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of dihydrocodeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers. (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers. (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Acetaminophen; Chlorpheniramine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Acetaminophen; Codeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of codeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as doxylamine.
    Acetaminophen; Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as diphenhydramine.
    Acetaminophen; Hydrocodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Acetaminophen; Oxycodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oxycodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of oxycodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Acetaminophen; Pentazocine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when pentazocine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of pentazocine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Acrivastine; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Alfentanil: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of alfentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Alfuzosin: (Moderate) Use caution when administering alfuzosin with solifenacin due to the potential for QT prolongation. Both alfuzosin and solifenacin may prolong the QT interval in a dose-dependent manner. Additionally, torsade de pointes (TdP) has been reported with postmarketing use of solifenacin, although causality was not determined.
    Amiodarone: (Major) If possible, avoid coadministration of amiodarone and solifenacin as concurrent use may increase the risk of QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amisulpride: (Moderate) Monitor ECGs for QT prolongation when amisulpride is administered with solifenacin. Amisulpride causes dose- and concentration- dependent QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Amitriptyline: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with tricyclic antidepressants. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent. In addition, solifenacin is associated with dose-dependent QT prolongation, and torsades de pointes (TdP) has been reported with post-marketing use. Tricyclic antidepressants also are associated with QT prolongation and should be used cautiously and with close monitoring with solifenacin.
    Amoxapine: (Moderate) Additive anticholinergic effects may be seen when solifenacin is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects such as amoxapine. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin with solifenacin if possible due to the risk of QT prolongation; plasma concentrations of solifenacin may also increase. If concomitant use is unavoidable, do not administer more than than solifenacin 5 mg per day in adults; do not exceed the initial starting dose in pediatric patients. Periodically monitor ECGs and electrolytes; an interruption of clarithromycin therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Solifenacin is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold. Both drugs have been associated with dose- or concentration-dependent QT prolongation, and torsade de pointes (TdP) was reported in postmarketing experience with solifenacin although causality was not determined.
    Amprenavir: (Major) If coadministered with amprenavir, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with amprenavir. Solifenacin is a CYP3A4 substrate and amprenavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with anagrelide include solifenacin.
    Anticholinergics: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Apalutamide: (Minor) Monitor for decreased efficacy of solifenacin if coadministration with apalutamide is necessary. Solifenacin is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Studies have not been conducted to evaluate the effect of CYP3A4 inducers on solifenacin, but inducers of CYP3A4 may decrease solifenacin plasma concentrations.
    Apomorphine: (Moderate) Apomorphine and solifenacin should be coadministered cautiously and with close monitoring since concurrent use may increase the risk of QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality has not been established.
    Aprepitant, Fosaprepitant: (Moderate) Use caution if solifenacin and aprepitant are used concurrently and monitor for an increase in solifenacin-related adverse effects for several days after administration of a multi-day aprepitant regimen. Solifenacin is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of solifenacin. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Aripiprazole: (Moderate) Caution is advised when administering aripiprazole with solifenacin, as use of these drugs together may increase the risk for QT prolongation and torsade de pointes (TdP). Solifenacin has been associated dose-dependent prolongation of the QT interval. Torsades de pointes has been reported with post-marketing use, although causality was not determined. QT prolongation has also occurred during therapeutic use of aripiprazole and following overdose.
    Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval, such as solifenacin, should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Artemether; Lumefantrine: (Major) Solifenacin should be avoided with artemether; lumefantrine. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided. Consider ECG monitoring if solifenacin must be used with or after artemether; lumefantrine treatment.
    Asenapine: (Major) Solifenacin should be avoided in combination with asenapine. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect.
    Aspirin, ASA; Butalbital; Caffeine: (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of codeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Aspirin, ASA; Caffeine: (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when dihydrocodeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of dihydrocodeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of codeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Aspirin, ASA; Oxycodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oxycodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of oxycodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Atazanavir: (Major) If coadministered with atazanavir, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with atazanavir. Monitor for excessive anticholinergic effects.Solifenacin is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Atazanavir; Cobicistat: (Major) If coadministered with atazanavir, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with atazanavir. Monitor for excessive anticholinergic effects.Solifenacin is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold. (Major) If coadministered with cobicistat, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with cobicistat. Monitor for excessive anticholinergic effects. Solifenacin is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Atomoxetine: (Moderate) Use caution if atomoxetine is administered with solifenacin as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes has been reported with postmarketing use, although causality was not determined.
    Atropine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Atropine; Difenoxin: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur. (Moderate) Antidiarrheals (e.g. atropine; diphenoxylate, atropine; difenoxin, or loperamide) decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been rarely reported to induce toxic megacolon. Constipation and dry mouth are reported side effects of solifenacin. Additive GI, CNS, or other anticholinergic effects may occur if used concomitantly.
    Atropine; Edrophonium: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Azithromycin: (Major) Avoid coadministration of azithromycin with solifenacin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with solifenacin. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Solifenacin has also been associated with dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Belladonna; Opium: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when opium is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of opium and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Benzhydrocodone; Acetaminophen: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when benzhydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of benzhydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Benztropine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and solifenacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and solifenacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering solifenacin with boceprevir due to an increased potential for solifenacin-related adverse events. If solifenacin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of solifenacin. Solifenacin is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated solifenacin plasma concentrations.
    Bosentan: (Minor) Bosentan is a significant inducer of CYP2C9 and CYP3A4 hepatic isoenzymes. Theoretically, bosentan can increase the hepatic clearance of solifenacin, a CYP3A4 substrate. However, this interaction has not been studied.
    Botulinum Toxins: (Moderate) Systemic anticholinergic effects (e.g., blurred vision) may be potentiated if antimuscarinics are administered after administration of botulinum toxins.
    Brompheniramine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Brompheniramine; Phenylephrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Brompheniramine; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Buprenorphine: (Major) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval, such as solifenacin. Solifenacin has been associated dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined. Additionally, monitor patients for signs of urinary retention or reduced gastric motility when buprenorphine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of buprenorphine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Buprenorphine; Naloxone: (Major) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval, such as solifenacin. Solifenacin has been associated dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined. Additionally, monitor patients for signs of urinary retention or reduced gastric motility when buprenorphine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of buprenorphine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Butalbital; Acetaminophen; Caffeine: (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of codeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Butorphanol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Cabotegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with solifenacin as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Solifenacin has also been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Caffeine: (Minor) Beverages containing caffeine may aggravate bladder symptoms and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages. (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Caffeine; Sodium Benzoate: (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Carbetapentane; Chlorpheniramine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as diphenhydramine.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Carbetapentane; Pyrilamine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Carbidopa; Levodopa: (Minor) Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. Antimuscarinics, by slowing GI transit, may also decrease levodopa bioavailability; however, this mechanism appears to be of modest clinical significance. Antimuscarinic agents targeted specifically for urinary incontinence may be less likely to produce pronounced effects on levodopa response than those with more pronounced systemic action.
    Carbidopa; Levodopa; Entacapone: (Minor) Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. Antimuscarinics, by slowing GI transit, may also decrease levodopa bioavailability; however, this mechanism appears to be of modest clinical significance. Antimuscarinic agents targeted specifically for urinary incontinence may be less likely to produce pronounced effects on levodopa response than those with more pronounced systemic action.
    Carbinoxamine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Carbinoxamine; Phenylephrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Carbinoxamine; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Celecoxib; Tramadol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when tramadol is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of tramadol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Cenobamate: (Moderate) Monitor for decreased efficacy of solifenacin if coadministration with cenobamate is necessary. Solifenacin is a CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer. Studies have not been conducted to evaluate the effect of CYP3A4 inducers on solifenacin, but inducers of CYP3A4 may decrease solifenacin plasma concentrations.
    Ceritinib: (Major) Avoid coadministration of ceritinib with solifenacin if possible due to the risk of QT prolongation and increased exposure to solifenacin. If concomitant use is unavoidable, do not administer more than solifenacin 5 mg per day in adults; do not exceed the initial starting dose in pediatric patients. Periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Solifenacin is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold. Both drugs have been associated with dose- or concentration-dependent QT prolongation, and torsade de pointes (TdP) was reported in postmarketing experience with solifenacin although causality was not determined.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Chlorcyclizine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Chlordiazepoxide; Amitriptyline: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with tricyclic antidepressants. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent. In addition, solifenacin is associated with dose-dependent QT prolongation, and torsades de pointes (TdP) has been reported with post-marketing use. Tricyclic antidepressants also are associated with QT prolongation and should be used cautiously and with close monitoring with solifenacin.
    Chlordiazepoxide; Clidinium: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Chloroquine: (Major) Avoid coadministration of chloroquine with solifenacin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Chlorpheniramine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Chlorpheniramine; Codeine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of codeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Chlorpheniramine; Dextromethorphan: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when dihydrocodeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of dihydrocodeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when dihydrocodeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of dihydrocodeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Chlorpheniramine; Hydrocodone: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Chlorpheniramine; Phenylephrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Chlorpromazine: (Major) Chlorpromazine should be used cautiously and with close monitoring with solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use.
    Ciprofloxacin: (Moderate) Solifenacin should be used cautiously with ciprofloxacin. Solifenacin has been associated dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval.
    Cisapride: (Contraindicated) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, use of solifenacin with cisapride is contraindicated.
    Citalopram: (Major) According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval, such as solifenacin, is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined.
    Clarithromycin: (Major) Avoid coadministration of clarithromycin with solifenacin if possible due to the risk of QT prolongation; plasma concentrations of solifenacin may also increase. If concomitant use is unavoidable, do not administer more than than solifenacin 5 mg per day in adults; do not exceed the initial starting dose in pediatric patients. Periodically monitor ECGs and electrolytes; an interruption of clarithromycin therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Solifenacin is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold. Both drugs have been associated with dose- or concentration-dependent QT prolongation, and torsade de pointes (TdP) was reported in postmarketing experience with solifenacin although causality was not determined.
    Class IA Antiarrhythmics: (Moderate) Class IA antiarrhythmics (disopymide, procainamide, and quinidine) should be used cautiously and with close monitoring with solifenacin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval.Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. In addition, coadministration may result in additive anticholinergic effects. Anticholinergic agents administered concurrently with disopyramide, procainamide, or quinidine may produce additive antivagal effects on AV nodal conduction.
    Clemastine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Clofazimine: (Moderate) Monitor ECGs for QT prolongation when clofazimine is administered with solifenacin. QT prolongation and torsade de pointes (TdP) have been reported in patients receiving clofazimine in combination with QT prolonging medications. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Clomipramine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with tricyclic antidepressants. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent. In addition, solifenacin is associated with dose-dependent QT prolongation, and torsades de pointes (TdP) has been reported with post-marketing use. Tricyclic antidepressants also are associated with QT prolongation and should be used cautiously and with close monitoring with solifenacin.
    Clozapine: (Moderate) Use clozapine with caution in combination with solifenacin as concurrent use may increase the risk of QT prolongation. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Cobicistat: (Major) If coadministered with cobicistat, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with cobicistat. Monitor for excessive anticholinergic effects. Solifenacin is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Codeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of codeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Codeine; Guaifenesin: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of codeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of codeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Codeine; Phenylephrine; Promethazine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of codeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. (Moderate) Promethazine carries a possible risk of QT prolongation. Solifenacin is associated with a possible risk for QT prolongation and TdP and should be used cautiously with promethazine. Additive drowsiness and anticholinergic effects may also be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with promethazine. Additive antimuscarinic effects may be seen on GI smooth muscle, bladder function, the CNS, the eye, and temperature regulation.
    Codeine; Promethazine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of codeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. (Moderate) Promethazine carries a possible risk of QT prolongation. Solifenacin is associated with a possible risk for QT prolongation and TdP and should be used cautiously with promethazine. Additive drowsiness and anticholinergic effects may also be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with promethazine. Additive antimuscarinic effects may be seen on GI smooth muscle, bladder function, the CNS, the eye, and temperature regulation.
    Crizotinib: (Major) Avoid coadministration of crizotinib with solifenacin due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Solifenacin has also been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Cyclizine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as cyclizine.
    Cyproheptadine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Darunavir: (Major) If coadministered with darunavir, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with darunavir. Monitor for excessive anticholinergic effects. Solifenacin is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Darunavir; Cobicistat: (Major) If coadministered with cobicistat, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with cobicistat. Monitor for excessive anticholinergic effects. Solifenacin is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold. (Major) If coadministered with darunavir, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with darunavir. Monitor for excessive anticholinergic effects. Solifenacin is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) If coadministered with cobicistat, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with cobicistat. Monitor for excessive anticholinergic effects. Solifenacin is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold. (Major) If coadministered with darunavir, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with darunavir. Monitor for excessive anticholinergic effects. Solifenacin is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Use of ritonavir with solifenacin may increase exposure to solifenacin and risk for solifenacin-related side effects. If these drugs must be administered together, do not exceed solifenacin 5 mg per day in adults; do not exceed the initial solifenacin starting dose in pediatric patients. Ritonavir is a potent CYP3A4 inhibitor and solifenacin is a CYP3A4 substrate. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Dasatinib: (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) during concurrent use of dasatinib and solifenacin. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving solifenacin as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Delavirdine: (Major) If coadministered with delavirdine, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with delavirdine. Solifenacin is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Desflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with solifenacin. Halogenated anesthetics can prolong the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Desipramine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with tricyclic antidepressants. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent. In addition, solifenacin is associated with dose-dependent QT prolongation, and torsades de pointes (TdP) has been reported with post-marketing use. Tricyclic antidepressants also are associated with QT prolongation and should be used cautiously and with close monitoring with solifenacin.
    Deutetrabenazine: (Moderate) Consider the potential for additive QT prolongation if solifenacin is administered with deutetrabenazine. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
    Dexchlorpheniramine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as diphenhydramine.
    Dextromethorphan; Quinidine: (Moderate) Class IA antiarrhythmics (disopymide, procainamide, and quinidine) should be used cautiously and with close monitoring with solifenacin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval.Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. In addition, coadministration may result in additive anticholinergic effects. Anticholinergic agents administered concurrently with disopyramide, procainamide, or quinidine may produce additive antivagal effects on AV nodal conduction.
    Dicyclomine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when dihydrocodeine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of dihydrocodeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Diltiazem: (Moderate) Use caution and monitor for an increase in solifenacin-related adverse reactions with coadministration of diltiazem. Solifenacin is significantly metabolized via the CYP3A4 pathway; diltiazem is a CYP3A4 inhibitor. Coadministration may result in increased concentrations of solifenacin.
    Dimenhydrinate: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as dimenhydrinate.
    Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as diphenhydramine.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as diphenhydramine. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Diphenhydramine; Ibuprofen: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as diphenhydramine.
    Diphenhydramine; Naproxen: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as diphenhydramine.
    Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as diphenhydramine.
    Diphenoxylate; Atropine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur. (Moderate) Antidiarrheals (e.g. atropine; diphenoxylate, atropine; difenoxin, or loperamide) decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been rarely reported to induce toxic megacolon. Constipation and dry mouth are reported side effects of solifenacin. Additive GI, CNS, or other anticholinergic effects may occur if used concomitantly.
    Disopyramide: (Moderate) Class IA antiarrhythmics (disopymide, procainamide, and quinidine) should be used cautiously and with close monitoring with solifenacin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval.Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. In addition, coadministration may result in additive anticholinergic effects. Anticholinergic agents administered concurrently with disopyramide, procainamide, or quinidine may produce additive antivagal effects on AV nodal conduction.
    Dofetilide: (Major) Coadministration of dofetilide and solifenacin is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Dolasetron: (Moderate) Administer dolasetron with caution in combination with solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
    Dolutegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with solifenacin as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Solifenacin has also been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Donepezil: (Major) Avoid coadministration of solifenacin due to the potential for reduced therapeutic response to donepezil; the risk of QT prolongation and torsade de pointes (TdP) may also be increased. The therapeutic benefits of donepezil, a cholinesterase inhibitor, may be diminished during chronic coadministration with antimuscarinics/medications with anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Additionally, both drugs are associated with a risk of QT prolongation and TdP. Concurrent use may result in additive effects on the QT interval.
    Donepezil; Memantine: (Major) Avoid coadministration of solifenacin due to the potential for reduced therapeutic response to donepezil; the risk of QT prolongation and torsade de pointes (TdP) may also be increased. The therapeutic benefits of donepezil, a cholinesterase inhibitor, may be diminished during chronic coadministration with antimuscarinics/medications with anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Additionally, both drugs are associated with a risk of QT prolongation and TdP. Concurrent use may result in additive effects on the QT interval. (Moderate) The adverse effects of solifenacin may be enhanced with use of memantine; dosage adjustments of the solifenacin may be required when memantine is coadministered.
    Doxepin: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with tricyclic antidepressants. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent. In addition, solifenacin is associated with dose-dependent QT prolongation, and torsades de pointes (TdP) has been reported with post-marketing use. Tricyclic antidepressants also are associated with QT prolongation and should be used cautiously and with close monitoring with solifenacin.
    Doxylamine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as doxylamine.
    Doxylamine; Pyridoxine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as doxylamine.
    Dronabinol: (Moderate) Use caution if coadministration of dronabinol with an anticholinergic drug like solifenacin is necessary. Concurrent use of dronabinol, THC with anticholinergics may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
    Dronedarone: (Contraindicated) Coadministration of dronedarone and solifenacin is contraindicated, because of the potential for torsade de Pointes (TdP). Solifenacin has been associated dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. The concomitant use of dronedarone with other drugs that prolong the QTc may induce TdP and is contraindicated.
    Droperidol: (Major) Droperidol should be used cautiously and with close monitoring with solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and TdP. In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol.
    Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with solifenacin as concurrent use may increase the risk of QT prolongation; decreased solifenacin exposure is also possible. QTc prolongation has been observed with the use of efavirenz. Solifenacin has been associated with dose-dependent prolongation of the QT interval and TdP has been reported with post-marketing use, although causality was not determined. In addition, efavirenz may induce the CYP3A4 metabolism of solifenacin; potentially reducing the efficacy of solifenacin by decreasing its systemic exposure.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Consider alternatives to efavirenz when coadministering with solifenacin as concurrent use may increase the risk of QT prolongation; decreased solifenacin exposure is also possible. QTc prolongation has been observed with the use of efavirenz. Solifenacin has been associated with dose-dependent prolongation of the QT interval and TdP has been reported with post-marketing use, although causality was not determined. In addition, efavirenz may induce the CYP3A4 metabolism of solifenacin; potentially reducing the efficacy of solifenacin by decreasing its systemic exposure.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with solifenacin as concurrent use may increase the risk of QT prolongation; decreased solifenacin exposure is also possible. QTc prolongation has been observed with the use of efavirenz. Solifenacin has been associated with dose-dependent prolongation of the QT interval and TdP has been reported with post-marketing use, although causality was not determined. In addition, efavirenz may induce the CYP3A4 metabolism of solifenacin; potentially reducing the efficacy of solifenacin by decreasing its systemic exposure.
    Elagolix: (Minor) Monitor for decreased efficacy of solifenacin if coadministration with elagolix is necessary. Solifenacin is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Studies have not been conducted to evaluate the effect of CYP3A4 inducers on solifenacin, but inducers of CYP3A4 may decrease solifenacin plasma concentrations.
    Elagolix; Estradiol; Norethindrone acetate: (Minor) Monitor for decreased efficacy of solifenacin if coadministration with elagolix is necessary. Solifenacin is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Studies have not been conducted to evaluate the effect of CYP3A4 inducers on solifenacin, but inducers of CYP3A4 may decrease solifenacin plasma concentrations.
    Elbasvir; Grazoprevir: (Moderate) Administering solifenacin with elbasvir; grazoprevir may result in elevated solifenacin plasma concentrations. Solifenacin is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Eliglustat: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include solifenacin.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) If coadministered with cobicistat, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with cobicistat. Monitor for excessive anticholinergic effects. Solifenacin is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) If coadministered with cobicistat, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with cobicistat. Monitor for excessive anticholinergic effects. Solifenacin is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Caution is advised when administering rilpivirine with solifenacin as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Solifenacin has also been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering rilpivirine with solifenacin as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Solifenacin has also been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Encorafenib: (Major) Avoid coadministration of encorafenib and solifenacin due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Enflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with solifenacin. Halogenated anesthetics can prolong the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Entrectinib: (Major) Avoid coadministration of entrectinib with solifenacin due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Enzalutamide: (Minor) Monitor for decreased efficacy of solifenacin if coadministration with enzalutamide is necessary. Solifenacin is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Studies have not been conducted to evaluate the effect of CYP3A4 inducers on solifenacin, but inducers of CYP3A4 may decrease solifenacin plasma concentrations.
    Ergotamine; Caffeine: (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Eribulin: (Major) Solifenacin should be used cautiously and with close monitoring with eribulin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Eribulin has been associated with QT prolongation. If eribulin and solifenacin must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Erythromycin: (Major) Consider the potential risk for additive QT prolongation if solifenacin is administered with erythromycin. Erythromycin is associated with QT prolongation and torsade de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined. Also solifenacin may antagonize the stimulatory effects of erythromycin on the GI tract when erythromycin is used therapeutically for improving GI motility. If erythromycin is not being used to enhance GI motility, then these potential interactions are of little clinical significance.
    Erythromycin; Sulfisoxazole: (Major) Consider the potential risk for additive QT prolongation if solifenacin is administered with erythromycin. Erythromycin is associated with QT prolongation and torsade de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined. Also solifenacin may antagonize the stimulatory effects of erythromycin on the GI tract when erythromycin is used therapeutically for improving GI motility. If erythromycin is not being used to enhance GI motility, then these potential interactions are of little clinical significance.
    Escitalopram: (Moderate) Use escitalopram with caution in combination with solifenacin as concurrent use may increase the risk of QT prolongation. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Ezogabine: (Moderate) Solifenacin should be used cautiously and with close monitoring with ezogabine as concurrent use may increase the risk of QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Ezogabine has been associated with QT prolongation.
    Fentanyl: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when fentanyl is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of fentanyl and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Fingolimod: (Moderate) Exercise caution when administering fingolimod concomitantly with solifenacin as concurrent use may increase the risk of QT prolongation. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking fingolimod.
    Flavoxate: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Flecainide: (Moderate) Solifenacin should be used cautiously with flecainide. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
    Fluconazole: (Contraindicated) Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP). The concurrent use of fluconazole, a moderate 3A4 inhibitor, and other drugs that prolong the QT interval and are CYP3A4 substrates, like solifenacin, is contraindicated due to the risk of TdP. Solifenacin is not usually contraindicated with moderate 3A4 inhibitors but because fluconazole is contraindicated with 3A4 substrates that prolong QT, these drugs should not be coadministered. Coadministration of fluconazole and solifenacin may result in an increased plasma concentration of solifenacin, causing an increased risk for adverse events, such as QT prolongation. It is not clear if single-dose fluconazole for vaginal candidiasis presents a lower risk for QT prolongation than other, multi-dose fluconazole regimens. Consider the risk vs. benefit of use of fluconazole versus alternative agents for the patients condition, particularly for vaginal yeast infection.
    Fluoxetine: (Moderate) Use fluoxetine with caution in combination with solifenacin. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Fluphenazine: (Moderate) Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with fluphenazine include solifenacin. Additive anticholinergic effects may also be seen with any of the antimuscarinics. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur in some patients.
    Fluvoxamine: (Moderate) Use fluvoxamine with caution with other drugs known to prolong the QT interval. QT prolongation and torsade de pointes (TdP) have been reported for both fluvoxamine and solifenacin with postmarketing use. Solifenacin has been associated with dose-dependent prolongation of the QT interval. In addition, solifenacin is significantly metabolized via the CYP3A4 pathway. Adult patients receiving potent CYP3A4 inhibitors should not receive solifenacin doses greater than 5 mg per day. Patients receiving moderate inhibitors, such as fluvoxamine, have not been assessed. It is possible that some patients taking fluvoxamine concurrently might need lower solifenacin doses.
    Fosamprenavir: (Major) If coadministered with fosamprenavir do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with fosamprenavir. Solifenacin is a CYP3A4 substrate and fosamprenavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as solifenacin. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval. In addition, TdP has been reported with postmarketing use of solifenacin, although causality was not determined. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fostemsavir: (Moderate) Consider the potential risk for additive QT prolongation if solifenacin is administered with fostemsavir. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Galantamine: (Moderate) The therapeutic benefits of the cholinesterase inhibitors for dementia or other neurologic conditions may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. Some of the common selective antimuscarinic drugs for bladder problems, (such as solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia.
    Gemifloxacin: (Moderate) Gemifloxacin should be used cautiously and with close monitoring with solifenacin as concurrent use may increase the risk of QT prolongation. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5-10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and solifenacin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has also been reported with postmarketing use, although causality was not determined.
    Gilteritinib: (Moderate) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and solifenacin is necessary. Gilteritinib has been associated with QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Glasdegib: (Major) Avoid coadministration of glasdegib with solifenacin due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Glycopyrronium: (Moderate) Although glycopyrronium is minimally absorbed into the systemic circulation after topical application, there is the potential for glycopyrronium to have additive anticholinergic effects when administered with other solfenacin. Per the manufaturer, avoid concomitant administration of glycopyrronium with other anticholinergic medications.
    Goserelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Granisetron: (Moderate) Use granisetron with caution in combination with solifenacin due to the risk of QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes has been reported with post-marketing use, although causality was not determined.
    Grapefruit juice: (Major) Patients should limit their intake of grapefruit or grapefruit juice while taking solifenacin. Consideration should be given to not exceed a 5 mg daily dose of solifenacin in adults who continue to regularly consume grapefruit juice; do not exceed the initial starting dose in pediatric patients. Solifenacin is significantly metabolized via the CYP3A4 pathway. Grapefruit and grapefruit juice may potently inhibit CYP3A4 metabolism in gut enterocytes. Potent CYP3A4 medications have been shown to increase solifenacin exposure by 2.7-fold.
    Green Tea: (Minor) Beverages containing caffeine may aggravate bladder symptoms and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
    Guaifenesin; Hydrocodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with solifenacin. Halogenated anesthetics can prolong the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Haloperidol: (Moderate) Consider the potential risk for additive QT prolongation if solifenacin is adminsitered with haloperidol. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
    Halothane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with solifenacin. Halogenated anesthetics can prolong the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Homatropine; Hydrocodone: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Hydrocodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Hydrocodone; Ibuprofen: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Hydrocodone; Phenylephrine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Hydrocodone; Pseudoephedrine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Hydromorphone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydromorphone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of hydromorphone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Hydroxychloroquine: (Major) Avoid coadministration of solifenacin and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Hydroxyzine: (Moderate) Caution is recommended if hydroxyzine is administered with solifenacin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Hyoscyamine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Ibuprofen; Oxycodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oxycodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of oxycodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Ibutilide: (Major) Ibutilide should be used cautiously and with close monitoring with solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with solifenacin, a CYP3A substrate, as solifenacin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Iloperidone: (Major) Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect.
    Imipramine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with tricyclic antidepressants. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent. In addition, solifenacin is associated with dose-dependent QT prolongation, and torsades de pointes (TdP) has been reported with post-marketing use. Tricyclic antidepressants also are associated with QT prolongation and should be used cautiously and with close monitoring with solifenacin.
    Indacaterol; Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Indinavir: (Major) If coadministered with indinavir, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with indinavir. Solifenacin is a CYP3A4 substrate and indinavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with solifenacin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has also been reported with postmarketing use, although causality was not determined.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with solifenacin may result in increased serum concentrations of solifenacin. Solifenacin is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
    Isoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with solifenacin. Halogenated anesthetics can prolong the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Itraconazole: (Major) Coadministration of solifenacin and itraconazole is contraindicated in patients with severe renal dysfunction or moderate/severe hepatic dysfunction due to the risk for QT prolongation. Further, solifenacin should not be administered within 2 weeks of itraconazole discontinuation in patients with renal or hepatic dysfunction. In patients with normal renal and hepatic function, do not exceed solifenacin 5 mg per day in adults; do not exceed the initial solifenacin starting dose in pediatric patients during use of itraconazole concurrently. Solifenacin is significantly metabolized by CYP3A4 and itraconazole is a potent CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold. Both drugs have been associated with dose- or concentration-dependent QT prolongation, and torsade de pointes (TdP) was reported in postmarketing experience with solifenacin although causality was not determined.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with solifenacin due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Ketoconazole: (Major) Avoid use of systemic ketoconazole with solifenacin if possible due to the potential for additive effects on the QT interval and increased exposure to solifenacin. If these drugs must be administered together, do not exceed solifenacin 5 mg per day in adults; do not exceed the initial solifenacin starting dose in pediatric patients. Ketoconazole is a potent CYP3A4 inhibitor and solifenacin is a CYP3A4 substrate. Following the administration of solifenacin 10 mg and ketoconazole 400 mg PO, the peak concentration and AUC of solifenacin increased 150% and 270%, respectively. Both drugs have been associated with dose- or concentration-dependent QT prolongation, and torsade de pointes (TdP) was reported in postmarketing experience with solifenacin although causality was not determined.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with solifenacin if possible due to the risk of QT prolongation; plasma concentrations of solifenacin may also increase. If concomitant use is unavoidable, do not administer more than than solifenacin 5 mg per day in adults; do not exceed the initial starting dose in pediatric patients. Periodically monitor ECGs and electrolytes; an interruption of clarithromycin therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Solifenacin is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold. Both drugs have been associated with dose- or concentration-dependent QT prolongation, and torsade de pointes (TdP) was reported in postmarketing experience with solifenacin although causality was not determined.
    Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with solifenacin. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Solifenacin has also been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Lefamulin: (Major) Avoid coadministration of lefamulin with solifenacin as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with solifenacin due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Solifenacin has also been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of solifenacin; monitor for potential reduction in efficacy. Solifenacin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of solifenacin; monitor for potential reduction in efficacy. Solifenacin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Letermovir: (Major) If coadministered with letermovir do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with letermovir. Solifenacin is a CYP3A4 substrate and letermovir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Levodopa: (Minor) Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. Antimuscarinics, by slowing GI transit, may also decrease levodopa bioavailability; however, this mechanism appears to be of modest clinical significance. Antimuscarinic agents targeted specifically for urinary incontinence may be less likely to produce pronounced effects on levodopa response than those with more pronounced systemic action.
    Levofloxacin: (Moderate) Levofloxacin should be used cautiously with solifenacin as concurrent use may increase the risk for QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined. Levofloxacin has been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin.
    Levoketoconazole: (Major) Avoid use of systemic ketoconazole with solifenacin if possible due to the potential for additive effects on the QT interval and increased exposure to solifenacin. If these drugs must be administered together, do not exceed solifenacin 5 mg per day in adults; do not exceed the initial solifenacin starting dose in pediatric patients. Ketoconazole is a potent CYP3A4 inhibitor and solifenacin is a CYP3A4 substrate. Following the administration of solifenacin 10 mg and ketoconazole 400 mg PO, the peak concentration and AUC of solifenacin increased 150% and 270%, respectively. Both drugs have been associated with dose- or concentration-dependent QT prolongation, and torsade de pointes (TdP) was reported in postmarketing experience with solifenacin although causality was not determined.
    Levorphanol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when levorphanol is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of levorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Lithium: (Moderate) Lithium should be used cautiously with solifenacin. Lithium has been associated with QT prolongation. Solifenacin has been associated dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Lofexidine: (Moderate) Monitor ECG if lofexidine is coadministered with solifenacin due to the potential for additive QT prolongation and torsade de pointes (TdP). Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Lonafarnib: (Major) Do not exceed a dose of 5 mg per day of solifenacin in patients receiving lonafarnib as concurrent use may increase solifenacin exposure. Solifenacin is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Loop diuretics: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms. Risk versus benefit should be addressed in patients receiving diuretics and solifenacin.
    Loperamide: (Moderate) Loperamide should be used cautiously and with close monitoring with solifenacin. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Loperamide; Simethicone: (Moderate) Loperamide should be used cautiously and with close monitoring with solifenacin. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with solifenacin due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. (Major) Use of ritonavir with solifenacin may increase exposure to solifenacin and risk for solifenacin-related side effects. If these drugs must be administered together, do not exceed solifenacin 5 mg per day in adults; do not exceed the initial solifenacin starting dose in pediatric patients. Ritonavir is a potent CYP3A4 inhibitor and solifenacin is a CYP3A4 substrate. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Lorlatinib: (Moderate) Monitor for decreased efficacy of solifenacin if coadministration with lorlatinib is necessary. Solifenacin is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer. Studies have not been conducted to evaluate the effect of CYP3A4 inducers on solifenacin, but inducers of CYP3A4 may decrease solifenacin plasma concentrations.
    Lubiprostone: (Moderate) Antimuscarinic drugs can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation, such as lubiprostone. The clinical significance of these potential interactions is uncertain.
    Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of solifenacin by decreasing its systemic exposure; if used together, monitor patients for adequate antimuscarinic response. Solifenacin is primarily metabolized by CYP3A4 and lumacaftor is a strong CYP3A inducer.
    Lurasidone: (Moderate) Antipsychotic agents may disrupt core temperature regulation; therefore, caution is recommended during concurrent use of lurasidone and medications with anticholinergic activity such as antimuscarinics. Concurrent use of lurasidone and medications with anticholinergic activity may contribute to heat-related disorders. Monitor patients for heat intolerance, decreased sweating, or increased body temperature if lurasidone is used with antimuscarinics.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as solifenacin. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Maprotiline: (Major) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with maprotiline include solifenacin. Additive anticholinergic effects may also be seen.
    Meclizine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as meclizine.
    Mefloquine: (Moderate) Mefloquine should be used with caution in patients receiving solifenacin as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Memantine: (Moderate) The adverse effects of solifenacin may be enhanced with use of memantine; dosage adjustments of the solifenacin may be required when memantine is coadministered.
    Mepenzolate: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Meperidine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when meperidine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of meperidine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Meperidine; Promethazine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when meperidine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of meperidine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. (Moderate) Promethazine carries a possible risk of QT prolongation. Solifenacin is associated with a possible risk for QT prolongation and TdP and should be used cautiously with promethazine. Additive drowsiness and anticholinergic effects may also be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with promethazine. Additive antimuscarinic effects may be seen on GI smooth muscle, bladder function, the CNS, the eye, and temperature regulation.
    Methadone: (Major) The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (more than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined. Additionally, monitor patients for signs of urinary retention or reduced gastric motility when methadone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of methadone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Methscopolamine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Metronidazole: (Moderate) Concomitant use of metronidazole and solifenacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Midostaurin: (Major) The concomitant use of midostaurin and solifenacin may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. QT prolongation and torsade de pointes have been reported during postmarketing surveillance of solifenacin.
    Mifepristone: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and solifenacin should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include solifenacin.
    Mirabegron: (Minor) There is no pharmacokinetic interaction with solifenacin and mirabegron, and the two drugs have been proven effective in combination treatment for overactive bladder. However, monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
    Mirtazapine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation. Mirtazapine exhibits weak anticholinergic activity that may be additive with the anticholinergic effects of solifenacin.
    Mitotane: (Moderate) Use caution if mitotane and solifenacin are used concomitantly, and monitor for decreased efficacy of solifenacin and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and solifenacin is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of solifenacin.
    Mobocertinib: (Major) Concomitant use of mobocertinib and solifenacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Morphine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when morphine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of morphine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Morphine; Naltrexone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when morphine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of morphine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Moxifloxacin: (Major) Concurrent use of moxifloxacin and solifenacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Prolongation of the QT interval has also been reported with moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
    Nabilone: (Moderate) Concurrent use of nabilone with anticholinergics may result in additive tachycardia and drowsiness, which may be pronounced.
    Nalbuphine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when nalbuphine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of nalbuphine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Nefazodone: (Moderate) Use caution and reduce the solifenacin dose to 5 mg per day when used concomitantly with nefazodone. Solifenacin is significantly metabolized via the CYP3A4 pathway; nefazodone is a strong CYP3A4 inhibitor. Pharmacokinetic studies of the use of solifenacin concomitantly with all CYP3A4 inhibitors have not been performed. The interaction between solifenacin and ketoconazole has been studied. Following the administration of solifenacin 10 mg and ketoconazole 400 mg PO, the peak concentration and AUC increased 150% and 270%, respectively.
    Nelfinavir: (Major) If coadministered with nelfinavir do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with nelfinavir. Monitor for excessive anticholinergic effects. Solifenacin is a CYP3A4 substrate and nelfinavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Nirmatrelvir; Ritonavir: (Major) Use of ritonavir with solifenacin may increase exposure to solifenacin and risk for solifenacin-related side effects. If these drugs must be administered together, do not exceed solifenacin 5 mg per day in adults; do not exceed the initial solifenacin starting dose in pediatric patients. Ritonavir is a potent CYP3A4 inhibitor and solifenacin is a CYP3A4 substrate. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Norfloxacin: (Moderate) Solifenacin has been associated dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with solifenacin include norfloxacin.
    Nortriptyline: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with tricyclic antidepressants. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent. In addition, solifenacin is associated with dose-dependent QT prolongation, and torsades de pointes (TdP) has been reported with post-marketing use. Tricyclic antidepressants also are associated with QT prolongation and should be used cautiously and with close monitoring with solifenacin.
    Octreotide: (Moderate) Consider the potential risk for additive QT prolongation if solifenacin is administered with octreotide. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Moderate) Ofloxacin should be used cautiously with solifenacin as concurrent use may increase the risk of QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined. Quinolones have been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Olanzapine: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering solifenacin with olanzapine. Solifenacin has been associated dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Olanzapine; Fluoxetine: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering solifenacin with olanzapine. Solifenacin has been associated dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval in rare instances. (Moderate) Use fluoxetine with caution in combination with solifenacin. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Olanzapine; Samidorphan: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering solifenacin with olanzapine. Solifenacin has been associated dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Use of ritonavir with solifenacin may increase exposure to solifenacin and risk for solifenacin-related side effects. If these drugs must be administered together, do not exceed solifenacin 5 mg per day in adults; do not exceed the initial solifenacin starting dose in pediatric patients. Ritonavir is a potent CYP3A4 inhibitor and solifenacin is a CYP3A4 substrate. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Ondansetron: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering solifenacin with ondansetron. If these drugs interval must be coadministered, ECG monitoring is recommended. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Ondansetron has also been associated with QT prolongation and post-marketing reports of TdP. Among 42 patients receiving a 4 mg bolus dose of intravenous ondansetron for the treatment of postoperative nausea and vomiting, the mean maximal QTc interval prolongation was 20 +/- 13 msec at the third minute after antiemetic administration (p < 0.0001). Risk for QT prolongation increases with increased dosage, and a 32 mg IV dose must no longer be used for prevention of chemotherapy induced emesis.
    Oritavancin: (Minor) Solifenacin is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of solifenacin may be reduced if these drugs are administered concurrently.
    Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with solifenacin. Osilodrostat is associated with dose-dependent QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes has been reported with postmarketing use, although causality was not determined.
    Osimertinib: (Major) Avoid coadministration of solifenacin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Solifenacin has also been associated with dose-dependent prolongation of the QT interval; TdP has been reported with postmarketing use, although causality was not determined.
    Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of solifenacin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Solifenacin has been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Oxybutynin: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Oxycodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oxycodone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of oxycodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Oxymorphone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oxymorphone is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of oxymorphone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Ozanimod: (Major) In general, do not initiate ozanimod in patients taking solifenacin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Pacritinib: (Major) Concomitant use of pacritinib and solifenacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Paliperidone: (Major) Concurrent use of paliperidone and solifenacin should be avoided if possible due to an increased risk for QT prolongation and torsade de pointes (TdP). Paliperidone has been associated with QT prolongation; TdP and ventricular fibrillation have been reported in the setting of overdose. Solifenacin has also been associated with dose-dependent prolongation of the QT interval; TdP has been reported during postmarketing use, although causality has not been determined. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
    Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include solifenacin.
    Pasireotide: (Moderate) Use caution when using pasireotide in combination with solifenacin as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and solifenacin, a CYP3A4 substrate, may cause an increase in systemic concentrations of solifenacin. Use caution when administering these drugs concomitantly.
    Pentamidine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering solifenacin with pentamidine. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Pentamidine has also been associated with QT prolongation.
    Pentazocine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when pentazocine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of pentazocine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Pentazocine; Naloxone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when pentazocine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of pentazocine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Perphenazine: (Moderate) Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with perphenazine include solifenacin. Additive anticholinergic effects may also be seen when phenothiazines are used concomitantly with any antimuscarinics. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Drowsiness or other additive CNS effects may also occur in some patients.
    Perphenazine; Amitriptyline: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with tricyclic antidepressants. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent. In addition, solifenacin is associated with dose-dependent QT prolongation, and torsades de pointes (TdP) has been reported with post-marketing use. Tricyclic antidepressants also are associated with QT prolongation and should be used cautiously and with close monitoring with solifenacin. (Moderate) Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with perphenazine include solifenacin. Additive anticholinergic effects may also be seen when phenothiazines are used concomitantly with any antimuscarinics. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Drowsiness or other additive CNS effects may also occur in some patients.
    Pexidartinib: (Moderate) Monitor for decreased efficacy of solifenacin if coadministration with pexidartinib is necessary. Solifenacin is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Phentermine; Topiramate: (Moderate) Through an additive effect, the use of topiramate with agents that may increase the risk for heat related disorders, such as solifenacin, may lead to oligohidrosis, hyperthermia, and/or heat stroke.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as solifenacin. Solifenacin has been associated dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Coadministration may increase the risk for QT prolongation.
    Pimozide: (Contraindicated) Because of the potential for torsade de pointes (TdP), concurrent use of pimozide and solifenacin is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. Solifenacin has been associated dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined.
    Pitolisant: (Major) Avoid coadministration of pitolisant with solifenacin as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Ponesimod: (Major) In general, do not initiate ponesimod in patients taking solifenacin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Posaconazole: (Contraindicated) The concurrent use of posaconazole and solifenacin is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of solifenacin. These drugs used in combination may result in elevated solifenacin plasma concentrations, causing an increased risk for solifenacin-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such solifenacin.
    Potassium-sparing diuretics: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms. Risk versus benefit should be addressed in patients receiving diuretics and solifenacin.
    Primaquine: (Moderate) Exercise caution when administering primaquine in combination with solifenacin as concurrent use may increase the risk of QT prolongation. Primaquine is associated with QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking primaquine.
    Procainamide: (Moderate) Class IA antiarrhythmics (disopymide, procainamide, and quinidine) should be used cautiously and with close monitoring with solifenacin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval.Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. In addition, coadministration may result in additive anticholinergic effects. Anticholinergic agents administered concurrently with disopyramide, procainamide, or quinidine may produce additive antivagal effects on AV nodal conduction.
    Prochlorperazine: (Moderate) Prochlorperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, the risk may be increased if coadministered with drugs with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with prochlorperazine include solifenacin. Additive anticholinergic effects may be seen with any antimuscarinics. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. With many antimuscarinics, additive drowsiness, hypotension or other additive CNS effects may also occur.
    Promethazine: (Moderate) Promethazine carries a possible risk of QT prolongation. Solifenacin is associated with a possible risk for QT prolongation and TdP and should be used cautiously with promethazine. Additive drowsiness and anticholinergic effects may also be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with promethazine. Additive antimuscarinic effects may be seen on GI smooth muscle, bladder function, the CNS, the eye, and temperature regulation.
    Promethazine; Dextromethorphan: (Moderate) Promethazine carries a possible risk of QT prolongation. Solifenacin is associated with a possible risk for QT prolongation and TdP and should be used cautiously with promethazine. Additive drowsiness and anticholinergic effects may also be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with promethazine. Additive antimuscarinic effects may be seen on GI smooth muscle, bladder function, the CNS, the eye, and temperature regulation.
    Promethazine; Phenylephrine: (Moderate) Promethazine carries a possible risk of QT prolongation. Solifenacin is associated with a possible risk for QT prolongation and TdP and should be used cautiously with promethazine. Additive drowsiness and anticholinergic effects may also be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with promethazine. Additive antimuscarinic effects may be seen on GI smooth muscle, bladder function, the CNS, the eye, and temperature regulation.
    Propafenone: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering solifenacin with propafenone. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Propafenone, a Class IC antiarrhythmic, also increases the QT interval largely due to prolongation of the QRS interval.
    Propantheline: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Proton pump inhibitors: (Moderate) The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Protriptyline: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with tricyclic antidepressants. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent. In addition, solifenacin is associated with dose-dependent QT prolongation, and torsades de pointes (TdP) has been reported with post-marketing use. Tricyclic antidepressants also are associated with QT prolongation and should be used cautiously and with close monitoring with solifenacin.
    Pseudoephedrine; Triprolidine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating antihistamines.
    Pyrilamine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Quetiapine: (Major) Concurrent use of quetiapine and solifenacin should be avoided if possible due to an increased risk for QT prolongation and torsade de pointes (TdP) and an increased risk of anticholinergic side effects. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. If concurrent use is required, also monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents, such as solifenacin. Constipation may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Quinidine: (Moderate) Class IA antiarrhythmics (disopymide, procainamide, and quinidine) should be used cautiously and with close monitoring with solifenacin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval.Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. In addition, coadministration may result in additive anticholinergic effects. Anticholinergic agents administered concurrently with disopyramide, procainamide, or quinidine may produce additive antivagal effects on AV nodal conduction.
    Quinine: (Major) Avoid coadministration of quinine with solifenacin if possible due to the risk of QT prolongation and increased solfenacin exposure. If concomitant use is unavoidable, do not exceed more than solfenacin 5 mg per day in adults; do not exceed the initial starting dose in pediatric patients. Periodically monitor ECGs and electrolytes; an interruption of quinine therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Solifenacin is a CYP3A4 substrate and quinine is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold. Both drugs have been associated with dose- or concentration-dependent QT prolongation, and torsade de pointes (TdP) was reported in postmarketing experience with solifenacin although causality was not determined.
    Ranolazine: (Moderate) Use ranolazine with caution in combination with solifenacin as concurrent use may increase the risk of QT prolongation. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Rasagiline: (Moderate) MAOIs exhibit secondary anticholinergic actions. Additive anticholinergic effects may be seen when MAOIs are used concomitantly with antimuscarinics. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive CNS effects are also possible when many of these drugs are combined with MAOIs.
    Relugolix: (Moderate) Consider the potential risk for additive QT prolongation if solifenacin is administered with relugolix. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Relugolix; Estradiol; Norethindrone acetate: (Moderate) Consider the potential risk for additive QT prolongation if solifenacin is administered with relugolix. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Remifentanil: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when remifentanil is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of remifentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Ribociclib: (Major) Avoid coadministration of ribociclib with solifenacin due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of solifenacin may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Solifenacin is a CYP3A4 substrate that has also been associated with dose-dependent prolongation of the QT interval; TdP has been reported with postmarketing use, although causality was not determined. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with solifenacin due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of solifenacin may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Solifenacin is a CYP3A4 substrate that has also been associated with dose-dependent prolongation of the QT interval; TdP has been reported with postmarketing use, although causality was not determined. Concomitant use may increase the risk for QT prolongation.
    Rifapentine: (Moderate) Monitor for decreased efficacy of solifenacin if coadministration with rifapentine is necessary. Solifenacin is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Studies have not been conducted to evaluate the effect of CYP3A4 inducers on solifenacin, but inducers of CYP3A4 may decrease solifenacin plasma concentrations.
    Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with solifenacin as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Solifenacin has also been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Risperidone: (Moderate) Use risperidone and solifenacin together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Ritonavir: (Major) Use of ritonavir with solifenacin may increase exposure to solifenacin and risk for solifenacin-related side effects. If these drugs must be administered together, do not exceed solifenacin 5 mg per day in adults; do not exceed the initial solifenacin starting dose in pediatric patients. Ritonavir is a potent CYP3A4 inhibitor and solifenacin is a CYP3A4 substrate. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Rivastigmine: (Moderate) The therapeutic benefits of the cholinesterase inhibitors for dementia or other neurologic conditions may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. Some of the common selective antimuscarinic drugs for bladder problems, (such as solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia.
    Romidepsin: (Moderate) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with solifenacin as concurrent use may increase the risk of QT prolongation. Romidepsin has been reported to prolong the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Saquinavir: (Major) Solifenacin is a substrate for CYP3A4. Saquinavir boosted with ritonavir is a strong inhibitor of CYP3A4. Concurrent administration of solifenacin with a strong CYP3A4 inhibitor may cause an increase in systemic solifenacin concentrations. Additionally, saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsades de pointes (TdP). Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval, such as solifenacin. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations.
    Scopolamine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with solifenacin is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
    Sertraline: (Moderate) Use caution and monitor patients for QT prolongation when administering solifenacin with sertraline. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Sevoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with solifenacin. Halogenated anesthetics can prolong the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Simeprevir: (Moderate) Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of solifenacin, which is a CYP3A4 substrate. Monitor patients for adverse effects of solifenacin, such as antimuscarinic effects.
    Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving solifenacin due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes has been reported with postmarketing use, although causality was not determined.
    Sorafenib: (Major) Avoid coadministration of sorafenib with solifenacin due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Solifenacin has been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Sorafenib is also associated with QTc prolongation.
    Sotalol: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering solifenacin with sotalol. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Sotorasib: (Moderate) Monitor for decreased efficacy of solifenacin if coadministration with sotorasib is necessary. Solifenacin is a CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer.
    Sufentanil: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Sunitinib: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Sunitinib can prolong the QT interval.
    Tacrine: (Moderate) The therapeutic benefits of the cholinesterase inhibitors for dementia or other neurologic conditions may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. Some of the common selective antimuscarinic drugs for bladder problems, (such as solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia.
    Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with solifenacin. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Tamoxifen: (Moderate) Caution is advised with the concomitant use of tamoxifen and solifenacin due to an increased risk of QT prolongation and torsade de pointes (TdP). Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has also been reported with postmarketing use, although causality was not determined.
    Tapentadol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when tapentadol is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of tapentadol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Tegaserod: (Major) Solifenacin, as an antimuscarinic, may slow GI motility and thus may potentially antagonize the actions of drugs that enhance gastrointestinal motility, like tegaserod.
    Telaprevir: (Major) If coadministered with telaprevir, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with telaprevir. Solifenacin is a CYP3A4 substrate and telaprevir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Telavancin: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering solifenacin with telavancin. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Telavancin has also been associated with QT prolongation.
    Telithromycin: (Major) Avoid use of telithromycin with solifenacin if possible due to the potential for additive effects on the QT interval and increased exposure to solifenacin. If these drugs must be administered together, do not exceed solifenacin 5 mg per day in adults; do not exceed the initial solifenacin starting dose in pediatric patients. Telithromycin is a potent CYP3A4 inhibitor and solifenacin is a CYP3A4 substrate. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold. Solifenacin has been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Telithromycin is associated with QT prolongation and TdP.
    Tetrabenazine: (Major) Concurrent use of tetrabenazine and solifenacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Tetrabenazine also causes a small increase in the corrected QT interval (QTc).
    Thiazide diuretics: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms. Risk versus benefit should be addressed in patients receiving diuretics and solifenacin.
    Thioridazine: (Contraindicated) Because of the potential for torsades de pointes (TdP), concurrent use of solifenacin and thioridazine is contraindicated. Solifenacin has been associated dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Thiothixene: (Moderate) Additive anticholinergic effects may be seen when thiothixene is used concomitantly with other drugs having anticholinergic activity such as solifenacin. Monitor for anticholinergic-related adverse effects such as constipation, blurred vision, and urinary retention during concurrent use.
    Tipranavir: (Major) If coadministered with tipranavir do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with tipranavir. Monitor for excessive anticholinergic effects. Solifenacin is a CYP3A4 substrate and tipranavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Tolterodine: (Moderate) Tolterodine should be used cautiously with solifenacin. Solifenacin has been associated dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. In addition, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent.
    Topiramate: (Moderate) Through an additive effect, the use of topiramate with agents that may increase the risk for heat related disorders, such as solifenacin, may lead to oligohidrosis, hyperthermia, and/or heat stroke.
    Toremifene: (Major) Avoid coadministration of solifenacin with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Both drugs have been shown to prolong the QTc interval in a dose- and concentration-related manner. Torsade de pointes (TdP) has also been reported with postmarketing use of solifenacin, although causality was not determined.
    Tramadol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when tramadol is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of tramadol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Tramadol; Acetaminophen: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when tramadol is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of tramadol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Trazodone: (Major) Avoid coadministration of trazodone and solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of TdP. Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval.
    Triclabendazole: (Moderate) Monitor ECGs in patients receiving triclabendazole with solifenacin. Transient prolongation of the mean QTc interval was noted on the ECG recordings in dogs administered triclabendazole. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes has been reported with postmarketing use, although causality was not determined.
    Tricyclic antidepressants: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with tricyclic antidepressants. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent. In addition, solifenacin is associated with dose-dependent QT prolongation, and torsades de pointes (TdP) has been reported with post-marketing use. Tricyclic antidepressants also are associated with QT prolongation and should be used cautiously and with close monitoring with solifenacin.
    Trifluoperazine: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with trifluoperazine include solifenacin. Additive anticholinergic effects may also be seen with any antimuscarinics. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Drowsiness or other additive CNS effects may also occur in some patients.
    Trihexyphenidyl: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Trimipramine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with tricyclic antidepressants. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent. In addition, solifenacin is associated with dose-dependent QT prolongation, and torsades de pointes (TdP) has been reported with post-marketing use. Tricyclic antidepressants also are associated with QT prolongation and should be used cautiously and with close monitoring with solifenacin.
    Triprolidine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating antihistamines.
    Triptorelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Trospium: (Major) Additive anticholinergic effects may be seen when solifenacin is used concomitantly with other antimuscarinics, such as trospium. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent.
    Tucatinib: (Major) If coadministered with tucatinib, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. The plasma concentrations of solifenacin may be elevated when administered concurrently with tucatinib. Solifenacin is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold.
    Vandetanib: (Major) Avoid coadministration of vandetanib with solifenacin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Both drugs can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Torsade de pointes TdP has also been reported with postmarketing use of solifenacin, although causality was not determined.
    Vardenafil: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering solifenacin with vardenafil. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.
    Vemurafenib: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering solifenacin with vemurafenib. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Vemurafenib has also been associated with QT prolongation. In addition, solifenacin is a CYP3A4 substrate, while vemurafenib is CYP3A4 inducer. Decreased solifenacin concentrations may occur with concomitant use. Use caution, and monitor therapeutic effects of solifenacin when coadministered with vemurafenib.
    Venlafaxine: (Moderate) Solifenacin has been associated dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with solifenacin include venlafaxine.
    Vibegron: (Moderate) Vibegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as solifenacin, because of the risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
    Voclosporin: (Moderate) Concomitant use of voclosporin and solifenacin may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use of solifenacin, although causality was not determined.
    Voriconazole: (Major) When possible, avoid administering voriconazole with solifenacin due to the potential for additive effects on the QT interval and increased exposure to solifenacin. If these drugs must be administered together, do not exceed a 5 mg daily dose of solifenacin in adults; do not exceed the initial starting dose in pediatric patients. Voriconazole is a strong CYP3A4 inhibitor. Solifenacin is a CYP3A4 substrate. Coadministration of another strong CYP3A4 inhibitor increased the systemic exposure of solifenacin by 2.7-fold. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP), cardiac arrest, and sudden death. Solifenacin may cause dose-dependent prolongation of the QT interval; TdP has been reported with postmarketing use, although causality was not determined.
    Vorinostat: (Moderate) Solifenacin has been associated dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with solifenacin include vorinostat.
    Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as solifenacin.
    Ziprasidone: (Major) Concomitant use of ziprasidone and solifenacin should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies of solifenacin in human pregnancy to be informative of a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes. Solifenacin should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. Animal studies indicate that solifenacin crosses the placental barrier of pregnant mice. No toxicities were noted with doses resulting in systemic exposure that was 1.2 times higher than exposure at the maximum recommended human dose (MRHD); however, fetal toxicity was noted with doses that were at least 3.6 times greater than the MRHD.

    The developmental and health benefits of breast-feeding should be considered along with the clinical need of the mother for solifenacin and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. There is no information on the presence of solifenacin in human milk, the effects on a breastfed child, or the effects on milk production. Solifenacin is present in mouse milk, although it is not known if excretion into human milk occurs. Anticholinergic medications can inhibit lactation in animals and decrease serum prolactin concentrations in nonlactating women. Therefore, chronic solifenacin use may have adverse effects on milk production.  

    MECHANISM OF ACTION

    Solifenacin is a competitive M3 selective muscarinic receptor antagonist, but has effects on all muscarinic receptors. In general, antimuscarinic drugs depress both voluntary and involuntary bladder contractions, and also control secretion in the salivary glands, gastric ciliary muscle, and the CNS. The M2 and M3 muscarinic receptors are found in the human detrusor muscle. Even though there are a greater number of M2 receptors located in the detrusor muscle, it appears that M3 receptors are primarily responsible for normal micturition contraction. Muscarinic receptors that may also have a role in micturition are found on presynaptic nerve terminals (regulate transmitter release) and on bladder urothelium cells. Solifenacin has been clinically shown to inhibit bladder contraction, decrease detrusor pressure, and cause incomplete emptying of the bladder. Compared to tolterodine, solifenacin improves the volume of urine per void and reduces the frequency of incontinent and urgency episodes. Solifenacin has functional selectivity for the bladder compared to salivary muscarinic receptors, therefore, the antimuscarinic effects of solifenacin on the salivary gland are less pronounced compared to traditional anticholinergic agents.

    PHARMACOKINETICS

    Solifenacin is administered orally. Solifenacin is highly protein bound (98%) to human plasma proteins, principally to alpha1-acid glycoprotein. Solifenacin is also highly distributed to non-CNS tissues, having a mean steady-state volume of distribution (Vd) of 600 L in adults and 211 L in pediatric patients 2 to 17 years old. Solifenacin is metabolized primarily in the liver by CYP3A4. However, alternate metabolic pathways exist. The primary metabolic routes of solifenacin are through N-oxidation of the quinuclidin ring and 4R-hydroxylation of tetrahydroisoquinoline ring. One pharmacologically active metabolite (4R-hydroxy solifenacin), occurring at low concentrations and unlikely to contribute significantly to clinical activity, and 3 pharmacologically inactive metabolites (N-glucuronide and the N-oxide and 4R-hydroxy-N-oxide of solifenacin) have been found in human plasma. After a 10-mg radiolabeled dose in healthy adult patients, 69.2% of the radioactivity was recovered in the urine and 22.5% in the feces over 26 days. Less than 15% of the dose is recovered unchanged in the urine. The elimination half-life of solifenacin at steady-state is approximately 45 to 68 hours in adults and 26 hours in pediatric patients 2 to 17 years.[54021] [65485]
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4
    Solifenacin is metabolized primarily by CYP3A4. Drugs that potently inhibit CYP3A4 may increase concentrations. Drugs that induce CYP3A4 may alter the pharmacokinetic parameters. In vitro data show that solifenacin has no significant inhibitory effects on any CYP isoenzymes.[54021]

    Oral Route

    Solifenacin is well absorbed (90% oral bioavailability), and there is no effect of food on the pharmacokinetics. Solifenacin reaches peak concentrations of 32.3 and 62.9 ng/mL for the 5 and 10 mg tablets, respectively, at steady-state. Peak concentrations are attained in approximately 3 to 8 hours after administration of the oral tablet.[54021]