TADALAFIL tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

TADALAFIL (UNII: 742SXX0ICT) (TADALAFIL - UNII:742SXX0ICT)

Available from:

Torrent Pharmaceuticals Limited

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Tadalafil tablets are 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%). Tadalafil is contraindicated in patients who are using any form of organic nitrate, either regularly or intermittently. Do not use nitrates within 48 hours of the lst dose of tadalafil. Tadalafil potentiates the hypotensive effect of nitrates. This potentiation is thought to result from the combined effects of nitrates and tadalafil on the nitric oxide/cGMP pathway [see Clinical Pharmacology ( 12.2)] . Coadministration of GC stimulators, such as riociguat with tadalafil is contraindicated. Tadalafil may potentiate the hypotensive effects of GC stimulators. Tadalafil is contraindicated in patients with a known serious hypersensitivity to tadalafil (Tadalafil tablets). Hypersensitivity reactions have been reported, including Stevens-Johnson syndrome and exfoliative dermatitis [see Adverse Reactions ( 6.2)] . Risk Summary 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. In animal reproduction studies, no adverse developmental effects were observed with oral administration of tadalafil to pregnant rats or mice during organogenesis at exposures 7 times the exposure at the maximum recommended human dose (MRHD) of 40 mg/day based on AUC (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death. Data Animal Data Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats. Animal reproduction studies showed no evidence of teratogenicity, embryotoxicity, or fetotoxicity when tadalafil was given to pregnant rats or mice at unbound tadalafil exposures up to 7 times the exposure at the maximum recommended human dose (MRHD) of 40 mg/day during organogenesis based on AUC. In one of two perinatal/postnatal developmental studies in rats, a reduction of postnatal pup survival was observed at dose levels of 60, 200 and 1,000 mg/kg. The no-observed effect-level (NOEL) for developmental toxicity was 30 mg/kg, which provided maternal exposure to unbound tadalafil concentrations approximately 5 times the exposure at the MRHD based on AUC. Signs of maternal toxicity occurred at doses greater than 200 mg/kg/day, which produced AUCs greater than 8 times the exposure at the MRHD. Surviving offspring had normal development and reproductive performance. Risk Summary There are no data on the presence of tadalafil and/or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Tadalafil and/or its metabolites are present in the milk of lactating rats at concentrations approximately 2.4-times that found in the plasma. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tadalafil tablets and any potential adverse effects on the breastfed child from tadalafil tablets or from the underlying maternal condition. Infertility Males Based on the data from 3 studies in adult males, tadalafil decreased sperm concentrations in the study of 10 mg tadalafil for 6 months and the study of 20 mg tadalafil for 9 months. This effect was not seen in the study of 20 mg tadalafil taken for 6 months. There was no adverse effect of tadalafil 10 mg or 20 mg on mean concentrations of testosterone, luteinizing hormone or follicle stimulating hormone. The clinical significance of the decreased sperm concentrations in the two studies is unknown. There have been no studies evaluating the effect of tadalafil on fertility in men or women [see Clinical Pharmacology ( 12.2)] . Safety and effectiveness of tadalafil tablets in pediatric patients have not been established. Of the total number of subjects in the clinical study of tadalafil for pulmonary arterial hypertension, 28 percent were 65 and over, while 8 percent were 75 and over. No overall differences in safety were observed between subjects over 65 years of age compared to younger subjects or those over 75 years of age. No dose adjustment is warranted based on age alone; however, a greater sensitivity to medications in some older individuals should be considered. [See Clinical Pharmacology ( 12.3)] . For patients with mild or moderate renal impairment, start tadalafil tablets at 20 mg once daily. Increase the dose to 40 mg once daily based upon individual tolerability [see Dosage and Administration ( 2.2), and Clinical Pharmacology ( 12.3)] . In patients with severe renal impairment, avoid use of tadalafil tablets because of increased tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis  [see Clinical Pharmacology ( 12.3)] . Because of limited clinical experience in patients with mild to moderate hepatic cirrhosis (Child-Pugh Class A or B), consider a starting dose of tadalafil tablets 20 mg once daily. Patients with severe hepatic cirrhosis (Child-Pugh Class C) have not been studied, thus avoid use of tadalafil tablets in such patients [see Dosage and Administration ( 2.3), and Clinical Pharmacology ( 12.3)] .

Product summary:

Tadalafil tablets USP 20 mg are yellow colored, oval shaped, biconvex beveled edge, film coated tablets with debossing "N9" on one side and plain on other side. Bottles of 30                                                  13668-581-30 Bottles of 60                                                  13668-581-60 Store at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature]. Keep this and all medication out of the reach of children.

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

Torrent Pharmaceuticals Limited
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SPL MEDGUIDE
Patient Information
Tadalafil (tah-DA-la-fil) tablets USP
Read this patient information before you start taking tadalafil
tablets and each time you get a refill. There
may be new information. This information does not take the place of
talking with your healthcare provider
about your medical condition or treatment.
What is the most important information I should know about tadalafil
tablets?
Never take tadalafil tablets with any nitrate or guanylate cyclase
stimulator medicines:
• Your blood pressure could drop quickly to an unsafe level
• You could get dizzy, faint and even have a heart attack or stroke.
Nitrates include:
• Medicines that treat chest pain (angina)
• Nitroglycerin in any form including tablets, patches, sprays, and
ointments
• Other nitrate medicines (isosorbide mononitrate or dinitrate)
• Street drugs that are inhaled, called "poppers" (amyl nitrate,
butyl nitrate or nitrite)
Guanylate cyclase stimulators include:
• Riociguat (Adempas ®) a medicine that treats pulmonary arterial
hypertension and chronic-
thromboembolic pulmonary hypertension
Ask your healthcare provider or pharmacist if you are not sure if you
take nitrate or guanylate cyclase
stimulator medicine.
What are tadalafil tablets?
Tadalafil tablets are a prescription medicine used to treat pulmonary
arterial hypertension (PAH, high blood
pressure in your lungs) to improve your ability to exercise.
It is not known if tadalafil tablets are safe or effective in
children.
Who should not take tadalafil tablets?
Do not take tadalafil tablets if you:
• take any medicines called nitrates.
• use recreational drugs called "poppers" like amyl nitrite and
butyl nitrite or nitrite.
• take any medicines called guanylate cyclase stimulators.
• are allergic to tadalafil or any other ingredients in tadalafil
tablets. See " What are the ingredients in
tadalafil tablets?" at the end of this leaflet.
See "What is the most important information I should know about
tadalafil tab

Summary of Product characteristics

TADALAFIL- TADALAFIL TABLET
TORRENT PHARMACEUTICALS LIMITED
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TADALAFIL TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR TADALAFIL
TABLETS.
TADALAFIL TABLETS, FOR ORAL ADMINISTRATION
INITIAL U.S. APPROVAL: 2003
INDICATIONS AND USAGE
Tadalafil tablets are phosphodiesterase 5 (PDE5) inhibitor 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%). (
1.1)
DOSAGE AND ADMINISTRATION
40 mg once daily, with or without food. ( 2.1).
Dividing the dose (40 mg) over the course of the day is not
recommended. ( 2.1)
Use with ritonavir requires dosage adjustments. ( 2.4)
DOSAGE FORMS AND STRENGTHS
Tablets (not scored): 20 mg ( 3).
CONTRAINDICATIONS
Concomitant organic nitrates ( 4.1)
Concomitant Guanylate Cyclase (GC) stimulators ( 4.2)
History of known serious hypersensitivity reaction to tadalafil or
CIALIS ( 4.3).
WARNINGS AND PRECAUTIONS
Hypotension: Carefully consider whether patients with certain
underlying cardiovascular disease could
be adversely affected by vasodilatory effects of tadalafil. Not
recommended in patients with pulmonary
veno-occlusive disease. ( 5.1, 5.2)
Effects on the eye: Sudden loss of vision could be a sign of
non-arteritic ischemic optic neuropathy
(NAION) and may be permanent . ( 5.3)
Hearing impairment: Cases of sudden decrease or loss of hearing have
been reported with CIALIS. (
5.4)
Concomitant PDE5 inhibitors: Avoid use with CIALIS or other PDE5
inhibitors. ( 5.5)
Prolonged erection: Advise patients to seek emergency treatment if an
erection lasts >4 hours. ( 5.6)
ADVERSE REACTIONS
The most common adverse reaction is headache. ( 6.1).
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT TORRENT