A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Singulair Side Effects, and Drug Interactions - Montelukast
Singulair Side Effects, and Drug Interactions - Montelukast
SIDE EFFECTS
Adolescents and Adults 15 Years of Age and Older
Montelukast has been evaluated for safety in approximately 2600 adolescent
and adult patients 15 years of age and older in clinical trials. In placebo-controlled
clinical trials, the following adverse experiences reported with montelukast
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:
|
TABLE 3 Adverse Experiences Occurring
in ³1% of Patients with an Incidence
Greater than that in Patients Treated with Placebo, Regardless of
Causality Assessment
|
| |
Montelukast |
Placebo |
| 10 mg/day |
|
| (%) |
(%) |
| (n=1955) |
(n=1180) |
| Body as a Whole |
| |
Asthenia/fatigue |
1.8 |
1.2 |
| |
Fever |
1.5 |
0.9 |
| |
Pain, abdominal |
2.9 |
2.5 |
| |
Trauma |
1.0 |
0.8 |
| Digestive System Disorders |
| |
Dyspepsia |
2.1 |
1.1 |
| |
Gastroenteritis, infectious |
1.5 |
0.5 |
| |
Pain, dental |
1.7 |
1.0 |
| Nervous System/Psychiatric |
| |
Dizziness |
1.9 |
1.4 |
| |
Headache |
18.4 |
18.1 |
| Respiratory System Disorders |
| |
Congestion, nasal |
1.6 |
1.3 |
| |
Cough |
2.7 |
2.4 |
| |
Influenza |
4.2 |
3.9 |
| Skin/Skin Appendages Disorder |
| |
Rash |
1.6 |
1.2 |
| Laboratory Adverse Experiences* |
| |
ALT increased |
2.1 |
2.0 |
| |
AST increased |
1.6 |
1.2 |
| |
Pyuria |
1.0 |
0.9 |
| * Number of patients tested (Montelukast
and placebo, respectively): ALT and AST, 1935, 1170; pyuria, 1924,
1159. |
The frequency of less common adverse events was comparable between montelukast
and placebo.
Cumulatively, 569 patients were treated with montelukast 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
Montelukast has also been evaluated for safety in approximately 320 pediatric
patients 6 to 14 years of age. Cumulatively, 169 pediatric patients were
treated with montelukast for at least 6 months, and 121 for one year or
longer in clinical trials. The safety profile of montelukast versus placebo
in the double-blind, 8-week, pediatric efficacy trial was generally similar
to the adult safety profile with the exception of the adverse events listed
below. In pediatric patients receiving montelukast, the following events
occurred with a frequency ³2% and more
frequently than in pediatric patients who received placebo, regardless
of causality assessment: diarrhea, laryngitis, pharyngitis, nausea, otitis,
sinusitis, and viral infection. The frequency of less common adverse events
was comparable between montelukast and placebo. With prolonged treatment,
the adverse experience profile did not significantly change.
DRUG INTERACTIONS
Montelukast at a Dose of 10 mg Once Daily Dosed to Pharmacokinetic Steady
State
- did not cause clinically significant changes in the kinetics of a
single intravenous dose of theophylline (predominantly a cytochrome
P450 1A2 substrate).
- did not change the pharmacokinetic profile of warfarin (a substrate
of cytochromes P450 2A6 and 2C9) or influence the effect of a single
30-mg oral dose of warfarin on prothrombin time or the INR (International
Normalized Ratio).
- did not change the pharmacokinetic profile or urinary excretion of
immunoreactive digoxin.
- did not change the plasma concentration profile of terfenadine (a
substrate of cytochrome P450 3A4) or fexofenadine, its carboxylated
metabolite, and did not prolong the QTc interval following co-administration
with terfenadine 60 mg twice daily.
Montelukast at Doses of
³100 mg Daily Dosed
to Pharmacokinetic Steady State:
- did not significantly alter the plasma concentrations of either component
of an oral contraceptive containing norethindrone 1 mg/ethinyl estradiol
35 mcg.
- did not cause any clinically significant change in plasma profiles
of prednisone or prednisolone following administration of either oral
prednisone or intravenous prednisolone.
Phenobarbital, which induces hepatic metabolism, decreased the AUC of
montelukast approximately 40% following a single 10-mg dose of montelukast.
No dosage adjustment for montelukast is recommended. It is reasonable
to employ appropriate clinical monitoring when potent cytochrome P450
enzyme inducers, such as phenobarbital or rifampin, are co-administered
with montelukast.
Montelukast has been administered with other therapies routinely used
in the prophylaxis and chronic treatment of asthma with no apparent increase
in adverse reactions. In drug-interaction studies, the recommended clinical
dose of montelukast did not have clinically important effects on the pharmacokinetics
of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives
(norethindrone 1 mg/ethinyl estradiol 35 mcg), terfenadine, digoxin, and
warfarin.
Although additional specific interaction studies were not performed,
montelukast was used concomitantly with a wide range of commonly prescribed
drugs in clinical studies without evidence of clinical adverse interactions.
These medications included thyroid hormones, sedative hypnotics, non-steroidal
anti-inflammatory agents, benzodiazepines, and decongestants.
Phenobarbital, which induces hepatic
metabolism, decreased the AUC
of montelukast approximately
40% following a single 10-mg dose
of montelukast. No dosage adjustment
for montelukast is recommended.
It is reasonable to employ appropriate
clinical monitoring when
potent cytochrome
P450 enzyme inducers, such
as phenobarbital or
rifampin, are co-administered with montelukast.
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