Roflumilast- Daliresp-@- Respiratory (Feb 2011)
Drug Name:Roflumilast- Daliresp-@- Respiratory (Feb 2011)
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Use with inhibitors of CYP3A4 or dual inhibitors of CYP3A4 and CYP1A2
(e.g., erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine)
will increase roflumilast systemic exposure and may result in increased
adverse reactions. The risk of such concurrent use should be weighed
carefully against benefit.
Indication:
DALIRESP® (roflumilast) tablets
Initial U.S. Approval: 2011
Weigh the risks and benefits of treatment with DALIRESP in patients with a
history of depression and/or suicidal thoughts or behavior.
Weight Decrease: Monitor weight regularly. If unexplained or clinically
significant weight loss occurs, evaluate weight loss and consider
discontinuation of DALIRESP.
Drug Name- Dalirep
Active Ingredient - Roflumilast
To decrease the frequency of flare-ups (exacerbations) or worsening
of symptoms from severe chronic obstructive pulmonary disease(COPD)
Indication-
To decrease the frequency of flare-ups (exacerbations) or worsening
of symptoms from severe chronic obstructive pulmonary disease(COPD)
Approved by FDA on 28-2-2011 (Ref- FDA approved List- 2011)
Roflumilast Tab 500mcg
Indication-
In the treatment of severe chronic obstructive pulmonary disease
(COPD) (FEVI post bronchodilator less than 50% predicted)
associated with chronic bronchitis in adult patients with a history
of frequent exacerbations as add on to bronchodilator treatment
Approved by FDA on 07-07--2014 (Ref- FDA approved List- 2014)
Repiratory ailment
Patent Expiry Date of drugs (Ref - IDMA Publication)
Chemical Category Manufacturer/ US Patent
Ingredient- Marketer Expiration Date
Roflumilast Respiratory Altana/Byk/Gulden 27-10-2015
New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Roflumilast Tablets 500mcg 17-07-2014
For the treatment of severe chronic obstuctive pulomonary disease (COPD)
(FEV1 post bronchodilator less than 50% predicted) associated with a
History of frequent exacerbations as add on to bronchodilator treatment
Adverse Reaction:
Most common adverse reactions (2%) are diarrhea, weight decrease,
nausea, headache, back pain, influenza, insomnia, dizziness and decreased appetite.
Contra-Indications:
CONTRAINDICATIONS
Moderate to severe liver impairment (Child-Pugh B or C)
WARNINGS AND PRECAUTIONS
Acute bronchospasm: Do not use for the relief of acute bronchospasm.
Psychiatric Events including Suicidality: Advise patients, their caregivers,
and families to be alert for the emergence or worsening of insomnia, anxiety,
depression, suicidal thoughts or other mood changes, and if such changes
occur to contact their healthcare provider.
Carefully weigh the risks and benefits of treatment with DALIRESP in patients
with a history of depression and/or suicidal thoughts or behavior.
Weight Decrease: Monitor weight regularly. If unexplained or clinically
significant weight loss occurs, evaluate weight loss and consider
discontinuation of DALIRESP.
Drug Interactions: Use with strong cytochrome P450 enzyme inducers
(e.g., rifampicin, phenobarbital, carbamazepine, phenytoin) is not recommended.
Dosages/ Overdosage Etc:
Indication-
To decrease the frequency of flare-ups (exacerbations) or worsening
of symptoms from severe chronic obstructive pulmonary disease(COPD)
INDICATIONS AND USAGE
DALIRESP is a selective phosphodiesterase 4 inhibitor indicated as a
treatment to reduce the risk of COPD exacerbations in patients with
severe COPD associated with chronic bronchitis and a history of exacerbations.
Limitations of Use: DALIRESP is not a bronchodilator and is not indicated
for the relief of acute bronchospasm.
DOSAGE AND ADMINISTRATION
The recommended dosage for patients with COPD is one 500 mcg tablet per day,
with or without food.
DOSAGE FORMS AND STRENGTHS
Tablets: 500 mcg
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
1.Bronchospasm
DALIRESP is not a bronchodilator and should not be used for immediate relief of breathing
problems (i.e., as a rescue medication).
2.Psychiatric Events including Suicidality
Treatment with DALIRESP is associated with an increase in psychiatric adverse
reactions. Cases of suicidal ideation and behavior, including completed suicide,
have been observed in the post-marketing setting in patients with or without
a history of depression.
The risks and benefits of treatment with DALIRESP in patients with a history of
depression and/or suicidal thoughts or behavior should be carefully considered.
Advise patients, caregivers, and families to be alert for the emergence or
worsening of insomnia, anxiety, depression, suicidal thoughts or other mood changes,
and if such change continuing treatment with DALIRESP may be considered
3. Weight Decrease
Weight loss was a common adverse reaction in DALIRESP clinical trials
During follow-up after treatment discontinuation, the majority of patients
with weight loss regained some of the weight they had lost while receiving
DALIRESP.
Advise patients treated with DALIRESP to have their weight monitored regularly.
If unexplained weight loss occurs, patients should inform their healthcare provider
so that the weight loss can be evaluated, as discontinuation of DALIRESP may need
to be considered.
4.Drug Interactions
The use of cytochrome P450 enzyme inducers resulted in a reduction in exposure
which may result in decreased therapeutic effectiveness of DALIRESP.
The use of strong cytochrome P450 enzyme inducers (e.g., rifampicin,
phenobarbital, carbamazepine, phenytoin) with DALIRESP is not recommended
Pharmacology/ Pharmacokinetics:
1. Mechanism of Action
Roflumilast and its active metabolite (roflumilast N-oxide) are selective inhibitors
of phosphodiesterase 4 (PDE4). Roflumilast and roflumilast N-oxide inhibition
of PDE4 (a major cyclic-3Œ,5Œ-adenosine monophosphate (cyclic AMP)-metabolizing
enzyme in lung tissue) activity leads to accumulation of intracellular cyclic AMP.
While the specific mechanism(s) by which DALIRESP exerts its therapeutic
action in COPD patients is not well defined, it is thought to be related to the
effects of increased intracellular cyclic AMP in lung cells
2. Pharmacokinetics
Absorption
The absolute bioavailability of roflumilast following a 500 mcg oral dose is
approximately 80%. Maximum plasma concentrations (Cmax) of roflumilast
typically occur approximately one hour after dosing (ranging from
0.5 to 2 hours) in the fasted state while plateau-like maximum concentration
of the N-oxide metabolite are reached in approximately eight hours
(ranging from 4 to 13 hours).
Food has no effect on total drug absorption, but delays time to maximum
concentration (Tmax) of roflumilast by one hour and reduces Cmax by
approximately 40%, however, Cmax and Tmax of roflumilast N-oxide
did not inhibit P-gp transporter
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Teratogenic effects:
Pregnancy Category C:
There are no adequate and well controlled studies of DALIRESP in pregnant women.
DALIRESP was not teratogenic in mice, rats, or rabbits. DALIRESP should be used
during pregnancy only if the potential benefit justifies the potential risk to the fetus.
2. Nursing Mothers
Roflumilast and/or its metabolites are excreted into the milk of lactating rats.
Excretion of roflumilast and/or its metabolites into human milk is probable.
There are no human studies that have investigated effects of DALIRESP
on breast-fed infants. DALIRESP should not be used by women who are nursing.
3. Pediatric Use
COPD does not normally occur in children. The safety and effectiveness of
DALIRESP in pediatric patients have not been established.
4. Geriatric Use
Of the 4438 COPD subjects exposed to DALIRESP for up to 12 months in 8
controlled clinical trials, 2022 were >65 years of age and 471 were >75 years of age.
No overall differences in safety or effectiveness were observed between these
subjects and younger subjects and other reported clinical experience has not
identified differences in responses between the elderly and younger patients,
but greater sensitivity of some older individuals cannot be ruled out.
Based on available data for roflumilast, no adjustment of dosage in geriatric
patients is warranted
