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Zafirlukast: Drug information

Zafirlukast: Drug information
(For additional information see "Zafirlukast: Patient drug information" and see "Zafirlukast: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Accolate
Pharmacologic Category
  • Leukotriene Receptor Antagonist
Dosing: Adult
Asthma, maintenance therapy

Asthma, maintenance therapy (alternative agent):

Note: In patients with mild asthma, may be used as an alternative controller therapy in those who cannot take an inhaled corticosteroid (ICS). In patients with moderate to severe asthma, may be used as an adjunctive controller therapy in those with inadequate symptom control on an ICS (Ref).

Oral: 20 mg twice daily. Some experts suggest waiting 1 to 2 months before assessing efficacy (Ref).

Chronic urticaria

Chronic urticaria (off-label use): Oral: 20 mg twice daily (Ref).

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

Use is contraindicated.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Zafirlukast: Pediatric drug information")

Asthma, chronic

Asthma, chronic: Oral:

Children 5 to 11 years: 10 mg twice daily

Children ≥12 years and Adolescents: 20 mg twice daily

Dosing: Kidney Impairment: Pediatric

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Pediatric

Use is contraindicated.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences reported in children ≥12 years and adults unless otherwise specified.

>10%: Central nervous system: Headache (13%; children 5 to 11 years: 5%)

1% to 10%:

Central nervous system: Dizziness (2%), pain (2%)

Gastrointestinal: Nausea (3%), diarrhea (3%), abdominal pain (2%; children 5 to 11 years: 3%), vomiting (2%), dyspepsia (1%)

Hepatic: Increased serum ALT (2%)

Infection: Infection (4%)

Neuromuscular & skeletal: Back pain (2%), myalgia (2%), weakness (2%)

Miscellaneous: Fever (2%)

<1%, postmarketing, and/or case reports: Agranulocytosis, angioedema, arthralgia, bruise, depression, edema, eosinophilia (systemic), eosinophilic pneumonitis, hemorrhage, hepatic failure, hepatitis, hyperbilirubinemia, hypersensitivity reaction, insomnia, malaise, pruritus, skin rash, urticaria, vasculitis (with clinical features of eosinophilic granulomatosis with polyangiitis [formerly known as Churg-Strauss]; rare)

Contraindications

Hypersensitivity to zafirlukast or any component of the formulation; hepatic impairment (including hepatic cirrhosis)

Canadian labeling: Additional contraindications (not in US labeling): Patients in whom zafirlukast was discontinued due to treatment related hepatotoxicity

Warnings/Precautions

Concerns related to adverse effects:

• Eosinophilia and vasculitis: In rare cases, patients may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss), a condition which is often treated with systemic corticosteroid therapy. Healthcare providers should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between zafirlukast and these underlying conditions has not been established.

• Hepatotoxicity: Serious hepatic adverse events (including hepatitis, hyperbilirubinemia, and hepatic failure) have been reported with use; female patients may be at greater risk. Periodic testing of liver function may be considered (early detection coupled with therapy discontinuation is generally believed to improve the likelihood of recovery). Advise patients to be alert for and to immediately report symptoms (eg, anorexia, right upper quadrant abdominal pain, nausea). If hepatic dysfunction is suspected (due to clinical signs/symptoms), discontinue use immediately and measure liver function tests (particularly ALT); resolution observed in most but not all cases upon discontinuation of therapy. Do not resume or restart if hepatic function studies indicate dysfunction. Use in patients with hepatic impairment (including hepatic cirrhosis) is contraindicated.

• Infections: An increased proportion of patients >55 years of age reported infections as compared to placebo-treated patients. These infections were mostly mild or moderate in intensity and predominantly affected the respiratory tract. Infections occurred equally in both sexes, were dose-proportional to total milligrams of zafirlukast exposure, and were associated with coadministration of inhaled corticosteroids.

• Neuropsychiatric events: Postmarketing reports of behavioral changes (ie, depression, insomnia) have been noted. Instruct patients to report neuropsychiatric symptoms/events during therapy.

Concurrent drug therapy issues:

• Warfarin: Concomitant use with warfarin results in a clinically significant increase in INR; closely monitor INR with concurrent use.

Special populations:

• Older adult: Clearance is decreased in elderly patients; Cmax and AUC are increased approximately two- to threefold in adults ≥65 years compared to younger adults; however, no dosage adjustments are recommended in this age group.

Other warnings/precautions:

• Reversal of bronchospasm: Not approved for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus; therapy can be continued during acute exacerbations of asthma.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Accolate: 10 mg, 20 mg

Generic: 10 mg, 20 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Accolate Oral)

10 mg (per each): $4.55

20 mg (per each): $4.55

Tablets (Zafirlukast Oral)

10 mg (per each): $2.05 - $4.10

20 mg (per each): $2.05 - $4.10

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

Oral: Administer at least 1 hour before or 2 hours after a meal.

Administration: Pediatric

Oral: Administer at least 1 hour before or 2 hours after a meal

Use: Labeled Indications

Asthma, maintenance therapy: Prophylaxis and chronic treatment of asthma in adults and children ≥5 years of age.

Use: Off-Label: Adult

Chronic urticaria

Medication Safety Issues
Sound-alike/look-alike issues:

Accolate may be confused with Accupril, Accutane, Aclovate

Metabolism/Transport Effects

Substrate of CYP2C9 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C9 (weak)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Erythromycin (Systemic): May decrease the serum concentration of Zafirlukast. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: CYP2C9 Inhibitors (Weak) may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Risk X: Avoid combination

Theophylline Derivatives: May decrease the serum concentration of Zafirlukast. Zafirlukast may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

TOLBUTamide: CYP2C9 Inhibitors (Weak) may increase the serum concentration of TOLBUTamide. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): CYP2C9 Inhibitors (Weak) may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Food Interactions

Food decreases bioavailability of zafirlukast by 40%. Management: Take on an empty stomach 1 hour before or 2 hours after meals.

Pregnancy Considerations

Outcome data following maternal use of zafirlukast in pregnancy are limited (Bakhireva 2007; Twaites 2007).

Uncontrolled asthma is associated with adverse events in pregnancy (increased risk of perinatal mortality, preeclampsia, preterm birth, low birth weight infants, cesarean delivery, and the development of gestational diabetes). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. Maternal treatment improves pregnancy outcomes by reducing the risk of some adverse events (eg, preterm birth, gestational diabetes) (ERS/TSANZ [Middleton 2020]; GINA 2023).

Agents other than zafirlukast are preferred for the treatment of asthma in pregnancy (ERS/TSANZ [Middleton 2020]; GINA 2023).

Data collection to monitor pregnancy and infant outcomes associated with asthma and the medications used to treat asthma in pregnancy is ongoing. Health care providers are encouraged to enroll exposed pregnant patients in the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (877-311-8972 or https://mothertobaby.org). Patients may also enroll themselves.

Breastfeeding Considerations

Zafirlukast is present in breast milk.

In women receiving zafirlukast 40 mg twice daily, maternal serum concentrations were 225 ng/mL and breast milk concentrations were 50 ng/mL. Due to the potential for adverse reactions in the breastfeeding infant, breastfeeding is not recommended by the manufacturer.

Monitoring Parameters

Monitor for improvements in air flow; monitor closely for sign/symptoms of hepatic injury; periodic monitoring of LFTs may be considered (not proved to prevent serious injury, but early detection may enhance recovery)

Mechanism of Action

Zafirlukast is a selectively and competitive leukotriene-receptor antagonist (LTRA) of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.

Pharmacokinetics (Adult Data Unless Noted)

Asthma symptom improvement:

Onset of action: Peak effect: 2 to 6 weeks

Duration: 12 hours

Absorption: Rapid

Distribution: Vdss: ~70 L

Protein binding: >99%, primarily to albumin

Metabolism: Extensively hepatic via CYP2C9

Bioavailability: Reduced 40% with food

Half-life elimination: ~10 hours (range: 8 to 16 hours)

Time to peak, serum: Children: 2 to 2.5 hours; Adults: 3 hours

Excretion: Feces (~90%); Urine (~10%)

Clearance: Children 5 to 6 years: 9.2 L/hour; Children 7 to 11 years: 11.4 L/hour; Adults: 20 L/hour

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: Approximately 50% to 60% greater Cmax and AUC compared with healthy subjects.

Older adult: In patients older than 65 years of age, there are about 2- to 3-fold greater Cmax and AUC compared with young adults.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Accolate;
  • (AR) Argentina: Accolate | Vanticon;
  • (AU) Australia: Accolate;
  • (BD) Bangladesh: Accolate | Freesy | Zafir | Zafnil | Zukast;
  • (BE) Belgium: Accolate | Resma;
  • (BG) Bulgaria: Accolate;
  • (BR) Brazil: Accolate;
  • (CH) Switzerland: Accolate;
  • (CL) Chile: Accolate;
  • (CN) China: Accolate;
  • (CO) Colombia: Accolate;
  • (CZ) Czech Republic: Accolate;
  • (DO) Dominican Republic: Accolate | Bronlukast | Lukast;
  • (EE) Estonia: Accolate;
  • (EG) Egypt: Alukast | Monocast;
  • (ES) Spain: Accolate | Aeronix | Olmoran;
  • (FI) Finland: Accolate;
  • (GB) United Kingdom: Accolate;
  • (HK) Hong Kong: Accolate;
  • (HU) Hungary: Accolate;
  • (ID) Indonesia: Accolate;
  • (IE) Ireland: Accolate;
  • (IL) Israel: Accolate;
  • (IN) India: Zuvair;
  • (IT) Italy: Accoleit | Zafirst;
  • (JO) Jordan: Accolate;
  • (JP) Japan: Accolate;
  • (KR) Korea, Republic of: Accolate;
  • (KW) Kuwait: Accolate;
  • (LB) Lebanon: Accolate;
  • (LT) Lithuania: Accolate;
  • (LU) Luxembourg: Accolate | Resma;
  • (LV) Latvia: Accolate;
  • (MX) Mexico: Accolate | Dralah;
  • (NO) Norway: Accolate;
  • (PE) Peru: Accolate;
  • (PH) Philippines: Accolate;
  • (PK) Pakistan: Accolate | Lokazaf | Zafirnex;
  • (PL) Poland: Accolate;
  • (PR) Puerto Rico: Accolate;
  • (PT) Portugal: Accolate;
  • (RU) Russian Federation: Accolate;
  • (SA) Saudi Arabia: Accolate;
  • (SG) Singapore: Accolate;
  • (SI) Slovenia: Accolate;
  • (SK) Slovakia: Accolate;
  • (TH) Thailand: Accolate;
  • (TR) Turkey: Accolate | Carrox;
  • (TW) Taiwan: Accolate;
  • (UY) Uruguay: Accolate;
  • (VE) Venezuela, Bolivarian Republic of: Accolate;
  • (ZA) South Africa: Accolate
  1. Accolate (zafirlukast) [prescribing information]. East Brunswick, NJ: Strides Pharma Inc; February 2022.
  2. Bagenstose SE, Levin L, Bernstein JA. The addition of zafirlukast to cetirizine improves the treatment of chronic urticaria in patients with positive autologous serum skin test results. J Allergy Clin Immunol. 2004;113(1):134-140. [PubMed 14713918]
  3. Bakhireva LN, Jones KL, Schatz M, et al; Organization of Teratology Information Specialists Collaborative Research Group. Safety of leukotriene receptor antagonists in pregnancy. J Allergy Clin Immunol. 2007;119(3):618-625. doi: 10.1016/j.jaci.2006.12.618 [PubMed 17336611]
  4. Bernstein JA, Lang DM, Khan DA, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014;133(5):1270-1277. [PubMed 24766875]
  5. Boyce JA. Antileukotriene agents in the management of asthma. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 7, 2021.
  6. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. https://ginasthma.org/2023-gina-main-report/. Updated 2023. Accessed August 23, 2023.
  7. Guidelines for the diagnosis and management of asthma. NAEPP Expert Panel Report 3. August 2007.
  8. Middleton PG, Gade EJ, Aguilera C, et al. ERS/TSANZ task force statement on the management of reproduction and pregnancy in women with airways diseases. Eur Respir J. 2020;55(2):1901208. doi:10.1183/13993003.01208-2019 [PubMed 31699837]
  9. Reimers A, Pichler C, Helbling A, Pichler WJ, Yawalkar N. Zafirlukast has no beneficial effects in the treatment of chronic urticaria. Clin Exp Allergy. 2002;32(12):1763-1768. [PubMed 12653169]
  10. Reinus JF, Persky S, Burkiewicz JS, et al, “Severe Liver Injury After Treatment With the Leukotriene Receptor Antagonist Zafirlukast,” Ann Intern Med, 2000, 133(12):964-8. [PubMed 11119397]
  11. Sánchez-Borges M, Asero R, Ansotegui IJ, et al; WAO Scientific and Clinical Issues Council. Diagnosis and treatment of urticaria and angioedema: a worldwide perspective. World Allergy Organ J. 2012;5(11):125-147. [PubMed 23282382]
  12. Twaites BR, Wilton LV, Shakir SA. Safety of zafirlukast: results of a postmarketing surveillance study on 7976 patients in England. Drug Saf. 2007;30(5):419-429. doi:10.2165/00002018-200730050-00005 [PubMed 17472420]
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