Singulair (Montelukast Sodium) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

Adults and Adolescents 15 Years of Age and Older with Asthma

SINGULAIR has been evaluated for safety in approximately 2950 adult and adolescent patients 15 years of age and older in clinical trials. In placebo-controlled clinical trials, the following adverse experiences reported with SINGULAIR occurred in greater than or equal to 1% of patients and at an incidence greater than that in patients treated with placebo, regardless of causality assessment:

Adverse Experiences Occurring in ≥1% of Patients with an Incidence Greater than that in Patients Treated with Placebo, Regardless of Causality Assessment

	SINGULAIR 10 mg/day (%) (n=1955)	Placebo (%) (n=1180)
Body As A Whole     Asthenia/fatigue     Fever     Pain, abdominal     Trauma	1.8 1.5 2.9 1.0	1.2 0.9 2.5 0.8
Digestive System Disorders     Dyspepsia     Gastroenteritis, infectious     Pain, dental	2.1 1.5 1.7	1.1 0.5 1.0
Nervous System/Psychiatric     Dizziness     Headache	1.9 18.4	1.4 18.1
Respiratory System Disorders     Congestion, nasal     Cough     Influenza	1.6 2.7 4.2	1.3 2.4 3.9
Skin/Skin Appendages Disorder     Rash	1.6	1.2
Laboratory Adverse Experiences 1     ALT increased     AST increased     Pyuria	2.1 1.6 1.0	2.0 1.2 0.9

The frequency of less common adverse events was comparable between SINGULAIR and placebo.

The safety profile of SINGULAIR when administered as a single dose for prevention of EIB in adult and adolescent patients 15 years of age and older was consistent with the safety profile previously described for SINGULAIR.

Cumulatively, 569 patients were treated with SINGULAIR for at least 6 months, 480 for one year, and 49 for two years in clinical trials. With prolonged treatment, the adverse experience profile did not significantly change.

Pediatric Patients 6 to 14 Years of Age with Asthma

SINGULAIR has been evaluated for safety in 476 pediatric patients 6 to 14 years of age. Cumulatively, 289 pediatric patients were treated with SINGULAIR for at least 6 months, and 241 for one year or longer in clinical trials. The safety profile of SINGULAIR in the 8-week, double-blind, pediatric efficacy trial was generally similar to the adult safety profile. In pediatric patients 6 to 14 years of age receiving SINGULAIR, the following events occurred with a frequency ≥2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: pharyngitis, influenza, fever, sinusitis, nausea, diarrhea, dyspepsia, otitis, viral infection, and laryngitis. The frequency of less common adverse events was comparable between SINGULAIR and placebo. With prolonged treatment, the adverse experience profile did not significantly change.

In studies evaluating growth rate, the safety profile in these pediatric patients was consistent with the safety profile previously described for SINGULAIR. In a 56-week, double-blind study evaluating growth rate in pediatric patients 6 to 8 years of age receiving SINGULAIR, the following events not previously observed with the use of SINGULAIR in this age group occurred with a frequency ≥2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: headache, rhinitis (infective), varicella, gastroenteritis, atopic dermatitis, acute bronchitis, tooth infection, skin infection, and myopia.

Pediatric Patients 2 to 5 Years of Age with Asthma

SINGULAIR has been evaluated for safety in 573 pediatric patients 2 to 5 years of age in single- and multiple-dose studies. Cumulatively, 426 pediatric patients 2 to 5 years of age were treated with SINGULAIR for at least 3 months, 230 for 6 months or longer, and 63 patients for one year or longer in clinical trials. SINGULAIR 4 mg administered once daily at bedtime was generally well tolerated in clinical trials. In pediatric patients 2 to 5 years of age receiving SINGULAIR, the following events occurred with a frequency ≥2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: fever, cough, abdominal pain, diarrhea, headache, rhinorrhea, sinusitis, otitis, influenza, rash, ear pain, gastroenteritis, eczema, urticaria, varicella, pneumonia, dermatitis, and conjunctivitis.

Pediatric Patients 6 to 23 Months of Age with Asthma

Safety and effectiveness in pediatric patients younger than 12 months of age with asthma have not been established.

SINGULAIR has been evaluated for safety in 175 pediatric patients 6 to 23 months of age. The safety profile of SINGULAIR in a 6-week, double-blind, placebo-controlled clinical study was generally similar to the safety profile in adults and pediatric patients 2 to 14 years of age. SINGULAIR administered once daily at bedtime was generally well tolerated. In pediatric patients 6 to 23 months of age receiving SINGULAIR, the following events occurred with a frequency ≥2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: upper respiratory infection, wheezing; otitis media; pharyngitis, tonsillitis, cough; and rhinitis. The frequency of less common adverse events was comparable between SINGULAIR and placebo.

Adults and Adolescents 15 Years of Age and Older with Seasonal Allergic Rhinitis

SINGULAIR has been evaluated for safety in 2199 adult and adolescent patients 15 years of age and older in clinical trials. SINGULAIR administered once daily in the morning or in the evening was generally well tolerated with a safety profile similar to that of placebo. In placebo-controlled clinical trials, the following event was reported with SINGULAIR with a frequency ≥1% and at an incidence greater than placebo, regardless of causality assessment: upper respiratory infection, 1.9% of patients receiving SINGULAIR vs. 1.5% of patients receiving placebo. In a 4-week, placebo-controlled clinical study, the safety profile was consistent with that observed in 2-week studies. The incidence of somnolence was similar to that of placebo in all studies.

Pediatric Patients 2 to 14 Years of Age with Seasonal Allergic Rhinitis

SINGULAIR has been evaluated in 280 pediatric patients 2 to 14 years of age in a 2-week, multicenter, double-blind, placebo-controlled, parallel-group safety study. SINGULAIR administered once daily in the evening was generally well tolerated with a safety profile similar to that of placebo. In this study, the following events occurred with a frequency ≥2% and at an incidence greater than placebo, regardless of causality assessment: headache, otitis media, pharyngitis, and upper respiratory infection.

Adults and Adolescents 15 Years of Age and Older with Perennial Allergic Rhinitis

SINGULAIR has been evaluated for safety in 3357 adult and adolescent patients 15 years of age and older with perennial allergic rhinitis of whom 1632 received SINGULAIR in two, 6-week, clinical studies. SINGULAIR administered once daily was generally well tolerated, with a safety profile consistent with that observed in patients with seasonal allergic rhinitis and similar to that of placebo. In these two studies, the following events were reported with SINGULAIR with a frequency ≥1% and at an incidence greater than placebo, regardless of causality assessment: sinusitis, upper respiratory infection, sinus headache, cough, epistaxis, and increased ALT. The incidence of somnolence was similar to that of placebo.

Pediatric Patients 6 Months to 14 Years of Age with Perennial Allergic Rhinitis

The safety in patients 2 to 14 years of age with perennial allergic rhinitis is supported by the established safety in patients 2 to 14 years of age with seasonal allergic rhinitis. The safety in patients 6 to 23 months of age is supported by data from pharmacokinetic and safety and efficacy studies in asthma in this pediatric population and from adult pharmacokinetic studies.

Post-Marketing Experience

The following additional adverse reactions have been reported in post-marketing use:

Blood and lymphatic system disorders: increased bleeding tendency

Immune system disorders: hypersensitivity reactions including anaphylaxis, very rarely hepatic eosinophilic infiltration

Psychiatric disorders: agitation including aggressive behavior, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide), tremor

Nervous system disorders: drowsiness, paraesthesia/hypoesthesia, very rarely seizures

Cardiac disorders: palpitations

Gastrointestinal disorders: diarrhea, dyspepsia, nausea, very rarely pancreatitis, vomiting

Hepatobiliary disorders: Rare cases of cholestatic hepatitis, hepatocellular liver-injury, and mixed-pattern liver injury have been reported in patients treated with SINGULAIR. Most of these occurred in combination with other confounding factors, such as use of other medications, or when SINGULAIR was administered to patients who had underlying potential for liver disease such as alcohol use or other forms of hepatitis.

Skin and subcutaneous tissue disorders: angioedema, bruising, erythema nodosum, pruritus, urticaria

Musculoskeletal and connective tissue disorders: arthralgia, myalgia including muscle cramps

General disorders and administration site conditions: edema

In rare cases, patients with asthma on therapy with SINGULAIR may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between SINGULAIR and these underlying conditions has not been established (see PRECAUTIONS, Eosinophilic Conditions).

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO SINGULAIR

Possible Singulair side effects / adverse reactions in 72 year old male

Reported by a physician from France on 2007-01-05

Patient: 72 year old male

Reactions: Amyotrophic Lateral Sclerosis

Adverse event resulted in: hospitalization, disablity

Suspect drug(s):
Singulair

Other drugs received by patient: Simvastatin; Cortisone

Possible Singulair side effects / adverse reactions in 64 year old female

Reported by a physician from United Kingdom on 2007-01-05

Patient: 64 year old female weighing 43.0 kg (94.6 pounds)

Reactions: Allergic Granulomatous Angiitis

Suspect drug(s):
Singulair

Other drugs received by patient: Fluticasone Propionate; Fluticasone Propionate and Salmeterol Xinafoate; Albuterol

Possible Singulair side effects / adverse reactions in 72 year old female

Reported by a physician from Belgium on 2007-01-09

Patient: 72 year old female weighing 51.0 kg (112.2 pounds)

Reactions: Asthmatic Crisis, Cough

Suspect drug(s):
Singulair

Other drugs received by patient: Fenoterol Hydrobromide and Ipratropium Bromide; Phenobarbital; Fosamax

Possible Singulair side effects / adverse reactions in 50 year old female

Reported by a consumer/non-health professional from France on 2007-01-11

Patient: 50 year old female weighing 38.0 kg (83.6 pounds)

Reactions: Chest Pain, General Physical Health Deterioration, Hypokalaemia

Adverse event resulted in: hospitalization

Suspect drug(s):
Ventolin
    Indication: Asthma

Paroxetine HCL

Zofran

Vfend
    Dosage: 200mg per day
    Administration route: Oral
    Indication: Aspergillosis
    Start date: 2006-05-24

Symbicort
    Dosage: 2puff per day

Cancidas
    Dosage: 50mg per day
    Indication: Aspergillosis
    Start date: 2006-06-12

Duragesic-100

Desloratadine

Singulair

Lyrica

Zolpidem Tartrate

Possible Singulair side effects / adverse reactions in 44 year old male

Reported by a health professional (non-physician/pharmacist) from France on 2007-01-11

Patient: 44 year old male

Reactions: Myositis, Gamma-Glutamyltransferase Increased, Hypothermia, Bradycardia, Cholinergic Syndrome, Transaminases Increased

Adverse event resulted in: hospitalization

Suspect drug(s):
Singulair
    Administration route: Oral
    Indication: Asthma

Valproate Sodium
    Administration route: Oral
    Indication: Epilepsy

Carbamazepine
    Administration route: Oral
    Indication: Epilepsy

Clobazam
    Administration route: Oral

Candesartan
    Administration route: Oral
    Indication: Hypertension

Desloratadine
    Administration route: Oral
    Indication: Rhinitis
    Start date: 2006-11-17
    End date: 2006-11-23

Possible Singulair side effects / adverse reactions in 50 year old female

Reported by a health professional (non-physician/pharmacist) from United Kingdom on 2007-01-11

Patient: 50 year old female

Reactions: Dyspnoea

Suspect drug(s):
Singulair
    Administration route: Oral
    Indication: Asthma
    Start date: 2006-12-11
    End date: 2006-12-12

Singulair

Other drugs received by patient: Alendronate Sodium; Aminophylline; Amiloride Hydrochloride and Hydrochlorothiazide; Dothiepin Hydrochloride; Hydroxyzine Hydrochloride; Metformin; Prednisolone

Possible Singulair side effects / adverse reactions in 9 year old male

Reported by a consumer/non-health professional from United States on 2007-01-11

Patient: 9 year old male weighing 49.0 kg (107.8 pounds)

Reactions: Anxiety, Psychomotor Hyperactivity, Palpitations, Insomnia, Depression, Aggression, Crying

Suspect drug(s):
Singulair
    Dosage: 1 tablet 1 x a day po
    Administration route: Oral
    Indication: Asthma
    Start date: 2007-01-05
    End date: 2007-01-07

Singulair
    Dosage: 1 tablet 1 x a day po
    Administration route: Oral
    Indication: Hypersensitivity
    Start date: 2007-01-05
    End date: 2007-01-07

Possible Singulair side effects / adverse reactions in 55 year old male

Reported by a physician from Ireland on 2007-01-16

Patient: 55 year old male

Reactions: Allergic Granulomatous Angiitis

Adverse event resulted in: hospitalization

Suspect drug(s):
Singulair

Other drugs received by patient: Calcium D3; Fosamax; Fortisip; Septrin; [therapy Unspecified]; Seretide; Lyrica; Tramadol HCL; Prochlorperazine; Deltacortril; Deltacortril; Deltacortril; Cyclophosphamide; Atrovent; Dexa-Rhinaspray

Possible Singulair side effects / adverse reactions in 9 year old female

Reported by a physician from Japan on 2007-01-16

Patient: 9 year old female

Reactions: Stevens-Johnson Syndrome

Adverse event resulted in: hospitalization

Suspect drug(s):
Singulair
    Administration route: Oral
    Indication: Asthma
    Start date: 2006-06-12
    End date: 2006-06-15

Clarithromycin
    Administration route: Oral
    Indication: Bronchitis
    Start date: 2006-06-12
    End date: 2006-06-15

Hokunalin
    Administration route: Topical
    Indication: Asthma
    Start date: 2006-06-12
    End date: 2006-06-15

Asverin
    Indication: Bronchitis
    Start date: 2006-06-12
    End date: 2006-06-15

Terbutaline Sulfate
    Indication: Bronchitis
    Start date: 2006-06-12
    End date: 2006-06-15

Possible Singulair side effects / adverse reactions in 28 year old male

Reported by a physician from France on 2007-01-16

Patient: 28 year old male

Reactions: Asthma, Allergic Granulomatous Angiitis

Adverse event resulted in: hospitalization

Suspect drug(s):
Singulair

Other drugs received by patient: Budesonide and Formoterol Fumarate; Albuterol Sulfate

Possible Singulair side effects / adverse reactions in 14 year old male

Reported by a physician from Spain on 2007-01-17

Patient: 14 year old male

Reactions: Mania, Prescribed Overdose

Adverse event resulted in: hospitalization

Suspect drug(s):
Singulair
    Administration route: Oral
    Indication: Asthma
    Start date: 2006-01-01
    End date: 2006-05-01

Singulair
    Administration route: Oral
    Start date: 2006-11-01
    End date: 2006-11-01

Other drugs received by patient: Salmeterol Xinafoate; Immunotherapy (Unspecified); Fluticasone Propionate; Fluticasone Propionate and Salmeterol Xinafoate; Fluticasone Propionate and Salmeterol Xinafoate; Fluticasone Propionate

Possible Singulair side effects / adverse reactions in 66 year old male

Reported by a physician from France on 2007-01-17

Patient: 66 year old male

Reactions: Leukocytoclastic Vasculitis, Hepatomegaly

Adverse event resulted in: hospitalization

Suspect drug(s):
Singulair

Other drugs received by patient: Fluticasone Propionate; [therapy Unspecified]; Fenofibrate

Possible Singulair side effects / adverse reactions in 44 year old male

Reported by a health professional (non-physician/pharmacist) from France on 2007-01-17

Patient: 44 year old male

Reactions: Myositis, Vomiting, Hypothermia, Alanine Aminotransferase Increased, Headache, Transaminases Increased, Gamma-Glutamyltransferase Increased, Aspartate Aminotransferase Increased, Photophobia, Dizziness, Blood Cholinesterase Increased, Bradycardia, Salivary Hypersecretion, Cholinergic Syndrome

Adverse event resulted in: hospitalization

Suspect drug(s):
Singulair
    Administration route: Oral
    Indication: Asthma
    Start date: 2004-01-01

Valproate Sodium
    Administration route: Oral
    Indication: Epilepsy
    Start date: 1996-01-01

Carbamazepine
    Administration route: Oral
    Indication: Epilepsy
    Start date: 1996-01-01

Clobazam
    Administration route: Oral

Candesartan
    Administration route: Oral
    Indication: Hypertension

Desloratidine
    Administration route: Oral
    Indication: Rhinitis
    Start date: 2006-11-17
    End date: 2006-11-23

Possible Singulair side effects / adverse reactions in 48 month old male

Reported by a health professional (non-physician/pharmacist) from United Kingdom on 2007-01-18

Patient: 48 month old male weighing 18.0 kg (39.6 pounds)

Reactions: Psychomotor Hyperactivity, Social Avoidant Behaviour

Suspect drug(s):
Singulair

Other drugs received by patient: Beclomethasone Dipropionate; Albuterol

Possible Singulair side effects / adverse reactions in 4 year old male

Reported by a physician from Sweden on 2007-01-18

Patient: 4 year old male

Reactions: Thirst, Urine Output Increased

Adverse event resulted in: hospitalization

Suspect drug(s):
Singulair

Other drugs received by patient: Airomir; Pulmicort

Possible Singulair side effects / adverse reactions in 34 year old female

Reported by a physician from Japan on 2007-01-19

Patient: 34 year old female

Reactions: Drug Eruption, Viral Infection, Rash Generalised, Pyrexia, Rash Morbilliform, Eosinophil Count Increased

Adverse event resulted in: hospitalization

Suspect drug(s):
Singulair

Other drugs received by patient: Clarithromycin; Carbocysteine; Medicon; Miradol; Alprazolam; Rivotril; Vegetamin B; Zolpidem Tartrate; Silece

Possible Singulair side effects / adverse reactions in 44 year old male

Reported by a health professional (non-physician/pharmacist) from France on 2007-01-22

Patient: 44 year old male weighing 61.0 kg (134.2 pounds)

Reactions: Gamma-Glutamyltransferase Increased, Hypothermia, Alanine Aminotransferase Increased, Miosis, Bradycardia, Cholinergic Syndrome

Adverse event resulted in: hospitalization

Suspect drug(s):
Kenzen 4 MG
    Administration route: Oral
    Indication: Hypertension
    Start date: 2004-01-01

Depakene
    Administration route: Oral
    Indication: Epilepsy
    Start date: 1996-01-01

Tegretol
    Administration route: Oral
    Indication: Epilepsy
    Start date: 1996-01-01

Urbanyl
    Administration route: Oral
    Indication: Epilepsy
    Start date: 1996-01-01

Singulair
    Administration route: Oral
    Indication: Asthma
    Start date: 2004-01-01

Desloratadine
    Administration route: Oral
    Indication: Rhinitis
    Start date: 2006-11-17
    End date: 2006-11-23

Possible Singulair side effects / adverse reactions in 9 year old female

Reported by a physician from Japan on 2007-01-22

Patient: 9 year old female

Reactions: Asthma, Oral Intake Reduced, Drug Ineffective, Stevens-Johnson Syndrome

Adverse event resulted in: hospitalization

Suspect drug(s):
Singulair
    Administration route: Oral
    Indication: Asthma
    Start date: 2006-06-12
    End date: 2006-06-15

Clarithromycin
    Administration route: Oral
    Indication: Bronchitis
    Start date: 2006-06-12
    End date: 2006-06-15

Asverin
    Administration route: Oral
    Indication: Bronchitis
    Start date: 2006-06-12
    End date: 2006-06-15

Terbutaline Sulfate
    Administration route: Oral
    Indication: Bronchitis
    Start date: 2006-06-12
    End date: 2006-06-15

Pasetocin
    Start date: 2006-06-10
    End date: 2006-06-12

Brocin
    Administration route: Oral
    Start date: 2006-06-10
    End date: 2006-06-12

Carbocysteine
    Administration route: Oral
    Start date: 2006-06-10
    End date: 2006-06-12

Codeine Phosphate
    Administration route: Oral
    Start date: 2006-06-10
    End date: 2006-06-12

Pontal
    Administration route: Oral
    Start date: 2006-06-10
    End date: 2006-06-12

Biofermin R
    Start date: 2006-06-10
    End date: 2006-06-12

Other drugs received by patient: Trimeprazine Tartrate

Possible Singulair side effects / adverse reactions in 9 year old female

Reported by a physician from Belgium on 2007-01-22

Patient: 9 year old female

Reactions: Balance Disorder, Abnormal Behaviour, Headache

Adverse event resulted in: hospitalization

Suspect drug(s):
Singulair
    Administration route: Oral
    Indication: Asthma
    Start date: 2003-11-05

Singulair
    Administration route: Oral
    Start date: 2006-11-02
    End date: 2006-11-07

Other drugs received by patient: Amoxicillin and Clavulanate Potassium; Fenoterol Hydrobromide and Ipratropium Bromide

Possible Singulair side effects / adverse reactions in 35 year old female

Reported by a physician from Switzerland on 2007-01-23

Patient: 35 year old female weighing 52.0 kg (114.4 pounds)

Reactions: Multi-Organ Failure, Allergic Granulomatous Angiitis

Adverse event resulted in: hospitalization

Suspect drug(s):
Singulair

Other drugs received by patient: [therapy Unspecified]