tiotropium/olodaterol inhaled (Rx)

Brand and Other Names:Stiolto Respimat
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tiotropium bromide/olodaterol inhaled

inhalation spray

  • (3.124mcg/2.736mcg)/actuation (equivalent to 2.5mcg/2.5mcg)

Chronic Obstructive Pulmonary Disease

Indicated for long-term, once-daily maintenance treatment in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema

Inhale 2 actuations PO qDay at the same time of the day

Dosage Modifications

Renal impairment

  • No dosage adjustment required
  • Moderate-to-severe (≤60 mL/min): Monitor closely for anticholinergic adverse effects

Hepatic impairment

  • Mild-to-moderate: No dose adjustment required
  • Severe: Not studied

Dosing Considerations

Not indicated to treat acute deteriorations of COPD

Not indicated to treat asthma

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and tiotropium/olodaterol inhaled

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            Incidence similar to individual components

            >10%

            Nasopharyngitis (12.4%)

            1-10%

            Cough (3.9%)

            Back pain (3.6%)

            ≤3%

            • Dehydration
            • Dizziness, insomnia
            • Glaucoma, intraocular pressure increased, vision blurred
            • Atrial fibrillation, palpitations, supraventricular tachycardia, tachycardia, hypertension
            • Epistaxis, pharyngitis, dysphonia, bronchospasm, laryngitis, sinusitis
            • Dry mouth, constipation, oropharyngeal candidiasis, dysphagia, gastroesophageal reflux disease, gingivitis, glossitis, stomatitis, intestinal obstruction including paralytic ileus
            • Rash, pruritus, angioneurotic edema, urticaria, skin infection, and skin ulcer, dry skin, hypersensitivity (including immediate reactions)
            • Arthralgia, joint swelling
            • Urinary retention, dysuria, and urinary tract infection
            Previous
            Next:

            Warnings

            Black Box Warnings

            Asthma-related death

            • Long-acting beta2-adrenergic agonists (LABAs), such as olodaterol, increase the risk for asthma-related death
            • A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths; this finding is considered a class effect of all LABAs, including olodaterol
            • Not to be used as a rescue therapy to treat acute bronchospasm; indicated for COPD maintenance therapy
            • Safety and efficacy not established in patients with asthma; NOT approved for treatment of asthma

            Contraindications

            Use of a LABA without an inhaled corticosteroid; tiotropium/olodaterol inhaled is not indicated for asthma

            Hypersensitivity to tiotropium ipratropium, olodaterol, or other ingredients

            Postmarketing experience with tiotropium, immediate hypersensitivity reactions, including angioedema (including swelling of the lips, tongue, or throat), itching, or rash reported; hypersensitivity reactions were also reported in clinical trials with tiotropium/olodaterol inhaled

            Cautions

            Safety and efficacy in patients with asthma not established; not indicated for asthma; monotherapy [without inhaled corticosteroids (ICS)] for asthma is associated with an increased risk of asthma-related death (see Black Box Warnings)

            Available data do not suggest an increased risk of death with use of LABA in patients with COPD

            Do not initiate in acutely deteriorating COPD

            Do not use for relief of acute symptoms; concomitant short-acting beta2­ agonists can be used as needed for acute relief

            Do not exceed the recommended dose; excessive use, or use in conjunction with other medications containing LABA, can result in clinically significant cardiovascular effects and may be fatal

            Immediate hypersensitivity reactions reported; discontinue immediately and consider alternatives if immediate hypersensitivity reactions, including angioedema, bronchospasm, or anaphylaxis, occur (see Contraindications)

            Life-threatening paradoxical bronchospasm can occur; discontinue immediately

            Caution with cardiovascular or convulsive disorders, thyrotoxicosis, or sensitivity to sympathomimetic drugs

            Worsening of narrow-angle glaucoma may occur; instruct patients to consult a physician immediately if this occurs

            Worsening of urinary retention may occur; caution with prostatic hyperplasia or bladder-neck obstruction and instruct patients to consult a physician immediately if this occurs

            May cause hypokalemia or hyperglycemia

            Monitor patients with moderate-to-severe renal impairment (≤60 mL/min) for anticholinergic adverse effects; tiotropium is predominantly excreted renally

            Drug interactions overview

            • Additional adrenergic drugs by any route may potentiate sympathetic effects of olodaterol
            • Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate any hypokalemic effect of olodaterol
            • ECG changes and/or hypokalemia may result from non-potassium sparing diuretics administration (loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the beta-agonist dose exceeds the recommended dose
            • Exercise extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants or other drugs cause QT prolongation; drugs known to prolong the QTc interval may increase the risk of ventricular arrhythmias
            • Beta-blockers not only block the therapeutic effects of beta-agonists, but may produce severe bronchospasm in COPD patients; use with caution
            • May interact additively with concomitantly used anticholinergics; avoid use with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            There are no adequate and well-controlled clinical studies with or its individual components, tiotropium bromide and olodaterol, in pregnant women to inform of drug-associated risk of adverse pregnancy-related outcomes

            Use during pregnancy only if the potential benefit justifies the potential risk to the fetus

            Labor and delivery

            • There are no adequate and well-controlled human studies that have investigated effects on preterm labor or labor at term; because of potential for beta-agonist interference with uterine contractility, use during labor should be restricted to those patients in whom benefits clearly outweigh risks

            Animal data

            • Based on animal reproduction studies, no structural abnormalities observed when tiotropium was administered by inhalation to pregnant rats and rabbits during the period of organogenesis at doses 790 and 8 times, respectively, the maximum recommended human daily inhalation dose (MRHDID)
            • Increased postimplantation loss observed in rats and rabbits administered tiotropium at maternally toxic doses 430 times and 40 times the MRHDID, respectively
            • Based on animal studies, olodaterol was not teratogenic when administered to pregnant rats or rabbits during organogenesis at inhalation doses of approximately 2731 or 1353 times the MRHDID (on an AUC basis), in rats or rabbits, respectively

            Lactation

            There are no data on presence of tiotropium or olodaterol in human milk, effects on breastfed infant, or on milk production

            Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Tiotropium: Long-acting antimuscarinic agent, often referred to as anticholinergic; inhibits M3-receptors at smooth muscle, leading to bronchodilation

            Olodaterol: Long-acting beta2-adrenergic agonist (LABA); activates specific beta2-adrenergic receptors on the surface of smooth muscle cells, which increases intracellular cAMP and smooth muscle relaxation

            Absorption

            Tiotropium

            • ~33% of the inhaled dose reaches the systemic circulation
            • Absolute bioavailability (oral solution): 2-3%
            • Peak plasma time: 5-7 minutes after inhalation

            Olodaterol

            • ~30% of the inhaled dose reaches the systemic circulation
            • Absolute bioavailability (oral solution): <1%
            • Peak plasma time: 10-20 minutes after inhalation

            Distribution

            Tiotropium

            • Protein bound: 72%
            • Vd: 32 L/kg

            Olodaterol

            • Protein bound: 60%
            • Vd: 1110 L

            Metabolism

            Tiotropium: 25% metabolized by CYP2D6 and 3A4, then subsequent glutathione conjugation

            Olodaterol

            • Substantially metabolized by direct glucuronidation and by O-demethylation at the methoxy moiety followed by conjugation
            • Cytochrome P450 isozymes CYP2C9 and CYP2C8, with negligible contribution of CYP3A4, are involved in the O-demethylation of olodaterol
            • Uridine diphosphate glycosyl transferase isoforms UGT2B7, UGT1A1, 1A7, and 1A9 were shown to be involved in the formation of olodaterol glucuronides

            Elimination

            Tiotropium

            • Half-life (inhaled): 25 hr (terminal)
            • Total clearance: 880 mL/min (IV administration)
            • Excretion: 18.6% urine; remainder being mainly nonabsorbed drug in the gut that is eliminated via the feces

            Olodaterol

            • Half-life (inhaled): 45 hr (terminal); 7.5 hr (effective)
            • Total clearance: 872 mL/min
            • Renal clearance: 173 mL/min
            • Excretion: 9% urine; remainder being mainly nonabsorbed drug in the gut that is eliminated via the feces
            Previous
            Next:

            Administration

            Oral Inhalation Administration

            Oral inhalation only

            See prescribing information for full instructions

            Priming inhaler

            • When using the unit for the first time, insert the cartridge into inhaler and prime the unit by actuating the inhaler toward the ground until an aerosol cloud is visible and then repeat the process 3 more times
            • If not used for >3 days, patients are to actuate the inhaler once to prepare the inhaler for use
            • If not used for >21 days, patients are to actuate the inhaler until an aerosol cloud is visible and then repeat the process 3 more times to prepare the inhaler for use

            Missed dose: Take it as soon as possible; do not take more than 1 dose (2 puffs) in 24 hours

            Storage

            Store at controlled room temperature at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)

            Avoid freezing

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.