Frequently Asked Questions about ADCIRCA® (tadalafil)
For answers to common questions about ADCIRCA, please click the links below:
What is the indication for ADCIRCA?
What is the dosing for ADCIRCA?
Are there any drug-drug interactions with ADCIRCA?
Can ADCIRCA be taken with other PAH medications?
Can patients drink alcohol while taking ADCIRCA?
What are the most common side effects with ADCIRCA?
What is the mechanism of action for ADCIRCA?
How is ADCIRCA metabolized?
How does ADCIRCA affect systolic and diastolic blood pressure?
Can ADCIRCA be used safely in older patients?
Which classes of PAH can ADCIRCA be used to treat?
How should ADCIRCA be stored?
Are pharmacies equipped to answer questions about ADCIRCA?
What clinical benefits can be expected with ADCIRCA?
Does ADCIRCA offer clinical benefits beyond improved exercise ability?
Is there an assistance program for patients who cannot afford their co-pay?
Is there an assistance program for patients who are uninsured or who have inadequate insurance coverage?
What patient support programs are available for patients and their caregivers?
What is the indication for ADCIRCA?
ADCIRCA® (tadalafil) is a phosphodiesterase 5 inhibitor (PDE-5i) indicated
for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve
exercise ability. Studies establishing effectiveness included predominately patients
with NYHA Functional Class II–III symptoms and etiologies of idiopathic or heritable
PAH (61%) or PAH associated with connective tissue diseases (23%).2
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What is the dosing for ADCIRCA?
ADCIRCA is the only phosphodiesterase 5 inhibitor (PDE-5i) approved for PAH with
once-daily dosing. The recommended starting and maintenance dose for most patients
for ADCIRCA is 40 mg (two 20-mg tablets). ADCIRCA can be taken with or without food.
Dividing the 40-mg dose for ADCIRCA over the course of the day is not recommended.2
Tadalafil is metabolized predominately by CYP3A in the liver. Use of ADCIRCA with
potent CYP3A inhibitors, such as ketoconazole and itraconazole, should be avoided.
For patients on ADCIRCA therapy that require treatment with ritonavir, ADCIRCA should
be discontinued at least 24 hours prior to starting ritonavir. For patients on ritonavir
therapy that require treatment with ADCIRCA, start ADCIRCA at 20 mg once a day.
Use of ADCIRCA with potent inducers of CYP3A, such as rifampin, should be avoided.2
The use of ADCIRCA is not recommended for patients with severe renal or hepatic
impairment. Please see Full Prescribing Information for dosing recommendations for
patients with mild to moderate renal or hepatic impairment.2
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Are there any drug-drug interactions with ADCIRCA?
ADCIRCA may have interactions with2:
- Nitrates and guanylate cyclase (GC) stimulators (such as riociguat). Nitrates and GC stimulators
are contraindicated. Do not use nitrates within 48 hours of the last dose of ADCIRCA
- Alpha-blockers
- Antihypertensives
- Alcohol
- Ritovanir
- Potent inhibitors of CYP3A
- Potent inducers of CYP3A
Please see DRUG INTERACTIONS in Full Prescribing Information.
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Can ADCIRCA be taken with other PAH medications?
ADCIRCA has been studied in patients taking background bosentan therapy. Bosentan
(125 mg twice daily) reduced tadalafil (40 mg once daily) systemic exposure by 42%
and Cmax by 27% following multiple-dose co-administration. In the pivotal
trial for ADCIRCA, more than half (53%) of subjects were receiving concomitant bosentan
therapy. Tadalafil is not expected to cause clinically significant inhibition or
induction of the clearance of drugs metabolized by cytochrome P450 (CYP) isoforms
(eg, bosentan).2
ADCIRCA is contraindicated in patients taking guanylate cyclase (GC) stimulators. Do not use ADCIRCA in patients who are using a GC stimulator, such as riociguat. ADCIRCA may potentiate the hypotensive effects of GC stimulators.2
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Can patients drink alcohol while taking ADCIRCA?
Both alcohol and tadalafil are mild vasodilators. When mild vasodilators are taken
in combination, blood pressure-lowering effects are increased. Substantial consumption
of alcohol (eg, 5 units or greater) in combination with ADCIRCA can increase the
potential for orthostatic signs and symptoms, including increase in heart rate,
decrease in standing blood pressure, dizziness, and headache.2
Please see DRUG INTERACTIONS in Full Prescribing Information.
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What are the most common side effects with ADCIRCA?
The most common adverse events with ADCIRCA (reported by ≥9% of patients on ADCIRCA
and more frequently than placebo by 2%, respectively) include2:
- Headache (42% vs 15%)
- Myalgia (14% vs 4%)
- Nasopharyngitis (13% vs 7%)
- Flushing (13% vs 2%)
- Respiratory tract infection (13% vs 6%)
- Extremity pain (11% vs 2%)
- Nausea (11% vs 6%)
- Back pain (10% vs 6%)
- Dyspepsia (10% vs 2%)
- Nasal congestion (9% vs 1%)
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What is the mechanism of action for ADCIRCA?
ADCIRCA is an inhibitor of phosphodiesterase 5 (PDE-5), the enzyme responsible for
the degradation of cyclic guanosine monophosphate (cGMP). PAH is associated with
the impaired release of nitric oxide by the vascular endothelium in the pulmonary
vasculature. Inhibition of PDE-5 by tadalafil increases the concentrations of cGMP,
resulting in relaxation of pulmonary vascular smooth muscle cells and vasodilation
of the pulmonary vascular bed.2
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How is ADCIRCA metabolized?
ADCIRCA is predominately metabolized by CYP3A to a catechol metabolite. The catechol
metabolite undergoes extensive methylation and glucuronidation to form the methylcatechol
and methylcatechol glucuronide conjugate, respectively. The major circulating metabolite
is the methylcatechol glucuronide. Methylcatechol concentrations are less than 10%
of glucuronide concentrations. In vitro data suggest that metabolites are not expected
to be pharmacologically active at observed metabolite concentrations.
Use of ADCIRCA with potent CYP3A inhibitors, such as ketoconazole and itraconazole,
should be avoided. For patients on ADCIRCA therapy that require treatment with ritonavir,
ADCIRCA should be discontinued at least 24 hours prior to starting ritonavir. For
patients on ritonavir therapy that require treatment with ADCIRCA, start ADCIRCA
at 20 mg once a day. Use of ADCIRCA with potent inducers of CYP3A, such as rifampin,
should be avoided.2
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How does ADCIRCA affect systolic and diastolic blood pressure?
PDE-5 inhibitors, including tadalafil, have mild systemic vasodilatory properties
that may result in transient decreases in blood pressure.
Prior to prescribing ADCIRCA, carefully consider whether patients with underlying
cardiovascular disease could be affected adversely by such vasodilatory effects.
Patients with severely impaired autonomic control of blood pressure or with left
ventricular outflow obstruction (eg, aortic stenosis and idiopathic hypertrophic
subaortic stenosis) may be particularly sensitive to the actions of vasodilators,
including PDE-5 inhibitors.
Pulmonary vasodilators may significantly worsen the cardiovascular status of patients
with pulmonary veno-occlusive disease (PVOD). Since there are no clinical data on
administration of ADCIRCA to patients with veno-occlusive disease, administration
of ADCIRCA to such patients is not recommended. Should signs of pulmonary edema
occur when ADCIRCA is administered, the possibility of associated PVOD should be
considered.2
For effects on blood pressure when administered with nitrates, antihypertensives,
alcohol, or alpha-blockers, please see PHARMACODYNAMICS in Full Prescribing Information.
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Can ADCIRCA be used safely in older patients?
In the pivotal clinical study for ADCIRCA, 28% of the total number of subjects were
65 and over, while 8% were 75 and over. No overall differences in safety were observed
between subjects over 65 years of age compared with younger subjects or those over
75 years of age. No dose adjustment is warranted based on age alone; however, a
greater sensitivity to medication in some older individuals should be considered.2
Please see USE IN SPECIFIC POPULATIONS in Full Prescribing Information.
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Which classes of PAH can ADCIRCA be used to treat?
ADCIRCA can be used in all functional classes of PAH. Studies establishing effectiveness
included predominately patients with NYHA Functional Class II–III symptoms and etiologies
of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases
(23%).2
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How should ADCIRCA be stored?
ADCIRCA should be stored at 77°F (25°C); excursions permitted to 59°F-86°F (15°C-30°C)
[see USP Controlled Room Temperature]. ADCIRCA should be kept out of reach of children.2
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Are pharmacies equipped to answer questions about ADCIRCA?
ADCIRCA is available through retail and specialty pharmacies.
Retail pharmacies are capable of answering patients’ questions about ADCIRCA. Specialty
pharmacies typically provide the special services listed below:
- Scheduled home deliveries
- Monthly refill reminder call
- Help with billing insurance claims
- Access to additional PAH therapies as disease progresses
ADCIRCA is available through specialty pharmacies, including the specialty pharmacies
listed below (listed alphabetically)*:
* This is not an endorsement of any pharmacy or the quality of support it may provide.
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What clinical benefits can be expected with ADCIRCA?
The pivotal clinical study for ADCIRCA showed that ADCIRCA increases exercise capacity
in patients with PAH. The primary efficacy endpoint was the change from baseline
at week 16 in 6MWD. In the ADCIRCA 40-mg treatment group, the placebo-adjusted mean
increase in 6MWD was 33 meters (P=0.0004). The improvement in 6MWD was apparent
at 8 weeks of treatment and then maintained at week 12 and week 16.
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Does ADCIRCA offer clinical benefits beyond improved exercise ability?
The pivotal clinical study for ADCIRCA showed that ADCIRCA decreased clinical worsening
in patients with PAH. There was less clinical worsening at 16 weeks (defined as
death, lung transplantation, atrial septostomy, hospitalization because of worsening
PAH, initiation of new PAH therapy [prostacyclin or analog, endothelin receptor
antagonist, PDE-5 inhibitor], or worsening WHO functional class) in the ADCIRCA
40-mg group compared with the placebo group (p=0.041) and the groups that used lower doses
of ADCIRCA.
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Is there an assistance program for patients who cannot afford their co-pay?
Through the ADCIRCA Co-Pay Assistance Program, eligible patients on commercial/private insurance plans* have a $5 co-pay per prescription fill for 12 fills (program covers the difference in co-pay above $5 up to $800 monthly). Click for more information.
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Is there an assistance program for patients who are uninsured or who have inadequate insurance coverage?
Our ASSIST Advisors can provide information on assistance programs and eligibility requirements to your office staff or directly to your patients.* ASSIST Advisors can also provide information on insurance benefits, including prior authorization, claim denials, appeals, and step edit requirements. Click for more information.
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What patient support programs are available for patients and their caregivers?
The Pulmonary Hypertension Association (PHA)
The PHA is a leading community-based organization for patients with PAH. Its mission
is to find ways to prevent and cure PAH, while providing hope to the community of
affected individuals. To that end, the PHA offers the following services:
- Support groups, both local and online
- Educational programs for patients and families
- Tips on getting the most from your health insurance program
- Advocacy programs for lobbying members of Congress
- Updates on new developments in the field of PAH
For more information, visit www.PHAssociation.org.
The National Heart, Lung, and Blood Institute (NHLBI)
The NHLBI is part of the National Institutes of Health (NIH), the agency of the
US Department of Health and Human Services that is largely responsible for conducting
medical research. The NHLBI website has
easy-to-understand information about various
diseases that affect the heart and lungs. To learn more, visit www.nhlbi.nih.gov and search
for “PAH.”
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Important Safety Information for ADCIRCA® (tadalafil) tablets
CONTRAINDICATIONS
- Nitrates and Guanylate Cyclase (GC) Stimulators: Do not use ADCIRCA in patients taking medicines
that contain nitrates or guanylate cyclase stimulators (such as riociguat), as the combination could cause a sudden,
unsafe drop in blood pressure. Do not use nitrates within 48 hours of the last dose of ADCIRCA.
- Hypersensitivity Reactions: Patients with a known serious hypersensitivity to tadalafil
should not take ADCIRCA
WARNINGS AND PRECAUTIONS
- Cardiovascular: Patients who experience anginal chest pain after taking ADCIRCA
should seek immediate medical attention
- Hypotension: Phosphodiesterase 5 inhibitors (PDE-5is), including tadalafil, have mild systemic
vasodilatory properties that may result in transient decreases in blood pressure. Before prescribing ADCIRCA, carefully
consider whether patients with underlying cardiovascular disease could be adversely affected by such actions.
- Worsening Pulmonary Vascular Occlusive Disease: Pulmonary vasodilators may significantly worsen the
cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD) and administration of ADCIRCA to these
patients is not recommended
- Vision/Hearing: Patients who experience a sudden loss of vision in one or both eyes, which could
be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), or sudden decrease or loss of hearing after taking
ADCIRCA should seek immediate medical attention
- Prolonged Erection: In rare instances, men taking PDE-5is (including tadalafil) for ED reported
an erection lasting more than four hours. Male patients who experience a prolonged erection should seek immediate medical
attention
SPECIAL POPULATIONS AND POTENTIAL DRUG INTERACTIONS:
- Special Populations (Pregnant or Expecting Pregnancy): Limited data from case series with
tadalafil use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse
maternal or fetal outcomes. Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure,
stroke, preterm delivery, and maternal and fetal death.
- Special Populations (Renal or Hepatic Impairment): The use of ADCIRCA is not recommended for
patients with severe renal or hepatic impairment. Please see Full Prescribing Information for dosing recommendations for
patients with mild to moderate renal or hepatic impairment
- Potential Drug Interactions: The use of ADCIRCA with alpha blockers, blood pressure medications,
or alcohol may lower blood pressure significantly and may lead to symptomatic hypotension (light-headedness or fainting)
- Potential Drug Interactions: Tadalafil is metabolized predominately by CYP3A in the liver. Use of
ADCIRCA with potent CYP3A inhibitors, such as ketoconazole and itraconazole, should be avoided. For patients on ADCIRCA
therapy that require treatment with ritonavir, ADCIRCA should be discontinued at least 24 hours prior to starting ritonavir.
For patients on ritonavir therapy that require treatment with ADCIRCA, start ADCIRCA at 20 mg once a day. Use of ADCIRCA with
potent inducers of CYP3A, such as rifampin, should be avoided
- Potential Drug Interactions: ADCIRCA contains the same ingredient (tadalafil) as Cialis®, which is
used to treat erectile dysfunction (ED) and the signs and symptoms of benign prostatic hyperplasia (BPH). The safety and
efficacy of combinations of ADCIRCA with Cialis or other PDE-5is have not been studied. Therefore, the use of such combinations
is not recommended
ADVERSE REACTIONS
- Adverse Reactions: The most common adverse event with ADCIRCA is headache (42% ADCIRCA
vs 15% placebo). Other common adverse events (reported by ≥9% of patients on ADCIRCA
and more frequent than placebo by 2%) include myalgia (14% vs 4%), nasopharyngitis
(13% vs 7%), flushing (13% vs 2%), respiratory tract infection (13% vs 6%), extremity
pain (11% vs 2%), nausea (11% vs 6%), back pain (10% vs 6%), dyspepsia (10% vs 2%),
and nasal congestion (9% vs 1%)
ADC.ISI.HCP.SEP2020
For more information about ADCIRCA, please see the Full Prescribing Information and
Patient Information or call 1-800-545-5979.
References:
- Data on file, June 2016.
- ADCIRCA [package insert]. Indianapolis, IN: Eli Lilly and Company; 2017.