FORM DA -1/88

APPLICATION FORM FOR REGISTRATION OF DRUGS

(WHICH ARE INCLUDED IN MONOGRAPH IN BP/BPC/USP-NF/INT. PH. AND
ALREADY INTRODUCED IN BANGLADESH)

1. Name & Address of the Manufacturer : Veritas Pharmaceuticals Ltd.

Muradpur, Vannara, Mouchak,
Kaliakoir, Gazipur
2. Manufacturing License No. : a) Biological : 288
b) Non-biological : 492
3. Name of the Drug : a) Generic name -
Tadalafil INN 10 mg per Tablet
: b) Brand name –
To be submitted at the time of inclusion
4. Product Data Sheet : Please see Annexure -I (enclosed)
5. Technical Data Sheet : Please see Annexure -II (enclosed)
6. a) Number of Manufacturers already : About 40 manufacturers
manufacturing the product in Bangladesh
b) Estimated market of this product/ : 1 million (approx.) Tablets are consumed per year
product group in Bangladesh
7. a) Proposed maximum retail price : To be submitted at the time of inclusion.
b) i) Estimated price per dose : To be submitted at the time of inclusion.
ii) Estimated price per day treatment : Depends on Physician’s advice.
iii) Cost for the recommended course of : Depends on Physician’s advice.
treatment
8. For Locally Manufacturing Drugs : Please see Annexure III (enclosed)
Particulars of Production Manager and
Quality Assurance Manager
9. Information regarding imported Drugs : Not applicable.
10. Date of submission :
11. Additional information (if any) : None

Annexure I

4. PRODUCT DATA SHEET

Composition
Each tablet contains Tadalafil 10 mg.

Descriptions
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Tadalafil is an oral drug that is used for treating impotence (the inability to attain or maintain a penile
erection). It is in a class of drugs called phosphodiesterase inhibitors.

Mode of Action
Does not directly cause penile erections, but affects the response to sexual stimulation. The
physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus
cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which
results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle
relaxation and inflow of blood to the corpus cavernosum. Tadalafil enhances the effect of NO by
inhibiting phosphodiesterase type 5 (PDE-5), which is responsible for degradation of cGMP in the
corpus cavernosum; when sexual stimulation causes local release of NO, inhibition of PDE-5 by
tadalafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle
relaxation and inflow of blood to the corpus cavernosum. At recommended doses, it has no effect in
the absence of sexual stimulation.

Indications and Uses

Treatment of erectile dysfunction.

Dosage and Administrations

May be administered with or without food, prior to anticipated sexual activity.
Adults: Erectile dysfunction- 10 mg prior to anticipated sexual activity (dosing range: 5-20 mg); to
be given as one single dose and not given more than once daily.
Note: Erectile function may be improved for up to 36 hours following a single dose.
Dosing adjustment with concomitant medications
CYP3A4 inhibitors: Dose reduction of tadalafil is recommended with strong CYP3A4 inhibitors.
The dose of tadalafil should not exceed 10 mg, and tadalafil should not be taken more frequently
than once every 72 hours. Examples of such inhibitors include azole antifungals, clarithromycin,
diclofenac, doxycycline, erythromycin, grapefruit juice, imatinib, isoniazid, nefazodone, nicardipine,
propofol, protease inhibitors, quinidine, and verapamil.
Dosage adjustment in renal impairment
Clcr 31-50 mL/minute: Initial dose 5 mg once daily; maximum dose 10 mg not to be given more
frequently than every 48 hours.
Clcr<30 mL/minute or hemodialysis: Maximum dose 5 mg.
Dosage adjustment in hepatic impairment
Mild-to-moderate hepatic impairment (Child-Pugh class A or B): Dose should not exceed 10 mg
once daily
Severe hepatic impairment: Use is not recommended

Pediatric Use
Tadalafil should not be used in individuals below 18 years of age.

Geriatric Patients
Dosage adjustments are not required in elderly patients.
Contraindications

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Hypersensitivity to tadalafil or any component of the formulation; concurrent use of organic
nitrates (nitroglycerin) in any form; concurrent use of alpha-adrenergic antagonists (except
tamsulosin 0.4 mg/day)
Precautions and warning
There is a degree of cardiac risk associated with sexual activity; therefore, physicians may wish to
consider the cardiovascular status of their patients prior to initiating any treatment for erectile
dysfunction. Use caution in patients with left ventricular outflow obstruction (aortic stenosis or
IHSS); may be more sensitive to hypotensive actions. Use caution in patients receiving strong
CYP3A4 inhibitors, the elderly, or those with hepatic impairment or renal impairment; dosage
adjustment/limitation is needed. Use caution in patients with peptic ulcer disease.
Agents for the treatment of erectile dysfunction should be used with caution in patients with
anatomical deformation of the penis (angulation, cavernosal fibrosis, or Peyronie's disease), or in
patients who have conditions which may predispose them to priapism (sickle cell anemia, multiple
myeloma, leukemia). All patients should be instructed to seek medical attention if erection persists
>4 hours. The safety and efficacy of tadalafil with other treatments for erectile dysfunction have not
been studied and are, therefore, not recommended as combination therapy.
Precautions and warning (continued)
Safety and efficacy have not been studied in patients with the following conditions, therefore, use in
these patients is not recommended: Arrhythmias, hypotension, uncontrolled hypertension, unstable
angina or angina during intercourse, cardiac failure (NYHA Class II or greater), recent myocardial
infarction, or stroke within the last 6 months. A minority of patients with retinitis pigmentosa have
genetic disorders of retinal phosphodiesterases. There is no safety information on the administration
of tadalafil to these patients; administer with caution.
Side effects
Headache, dyspepsia, flushing, back pain, myalgia, nasal congestion, limb pain, abdominal pain
(upper), abnormal liver function tests, arthralgia, asthenia, angina pectoris, blurred vision, chest pain,
conjunctivitis, diaphoresis, diarrhea, dizziness, dysphagia, dyspnea, epistaxis, esophagitis, eye pain,
eyelid swelling, facial edema, fatigue, gastroesophageal reflux, gastritis, hypesthesia,
hyper-/hypotension, GGTP increased, insomnia, MI, nausea, pain, palpitation, paresthesia,
pharyngitis, postural hypotension, priapism (reported with drugs in this class), pruritus, rash,
somnolence, syncope, tachycardia, vertigo, visual changes (color vision), vomiting, xerostomia
Drug Interaction
Substrate of CYP3A4 (major)
Alpha-blockers: May lead to significant hypotension in some patients; concomitant use is
contraindicated (except tamsulosin at a dosage of 0.4 mg/day).
Antihypertensive agents: Tadalafil may increase the hypotensive effect of antihypertensive agents.
Use caution when coadministered with calcium channel blockers, diuretics, angiotensin-receptor
blockers, ACE-inhibitors, or adrenergic receptor-blocking agents.
CYP3A4 inhibitors: May increase the levels/effects of tadalafil. Dose reduction of tadalafil is
recommended with strong CYP3A4 inhibitors. The dose of tadalafil should not exceed 10 mg, and
tadalafil should not be taken more frequently than once every 72 hours. Example inhibitors include
azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, grapefruit juice, imatinib,
isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.
Nitroglycerin (or other nitrates): Concomitant use is contraindicated due to the potential for severe,
potentially fatal, hypotensive responses.
Ethanol/Nutrition/Herb Interactions:

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Ethanol: Substantial consumption of ethanol may increase the risk of hypotension and orthostasis.
Lower ethanol consumption has not been associated with significant changes in blood pressure or
increase in orthostatic symptoms.
Food: Rate and extent of absorption are not affected by food. Grapefruit juice may increase serum
levels/toxicity of tadalafil. Do not give more than a single 10 mg dose of tadalafil more frequently
than every 72 hours in patients who regularly consume grapefruit juice.
Over dosage
Symptoms similar to those seen at lower doses (headache, back pain, myalgias). Treatment is
symptomatic and supportive.
Storage
Store at room temperature at 770 F (250 C) away from light and moisture. Brief storage between 590
and 860 F (150-300 C) is permitted. Do not store in the bathroom. Keep all medicines away from
children and pets.
Package Quantities
Tadalafil Tablet: Box containing 2x10 or 3x10 tablets in blister pack.

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 Annexure II

5. TECHNICAL DATA
a) Composition/Formula: Each tablet contains

Active Substance Specifications Quantity Overage

Tadalafil INN 10.000 mg

Excipients
Lactose Monohydrate BP 76.000mg
Microcrystalline Cellulose BP 40.00 mg
(Avicel PH 101)
Povidone K 30 BP 2.800 mg
Sodium Starch Glycolate BP 5.600 mg
Sodium Lauryl Sulphate BP 2.100 mg
Magnesium Stearate BP 0.700 mg
Purified Talc 2.800 mg

Coating Materials
Hydroxypropyl Methyl Cellulose 6 USNF 2.800 mg
cps
Polyethylene Glycol 6000 BP 0.280 mg
Titanium Dioxide BP 0.168 mg
Purified Talc BP 0.168 mg
Quinolline Yellow Lake Ph. Grade 0.005 mg
**Purified Water BP 35.000 mg
** Solvent, will not present in final product

b) Manufacturing Process

Step-1: Weigh accurately Tadalafil, Lactose Monohydrate, Avicel PH 101 Sodium Lauryl
Sulphate and Sodium Strach Glycolate. Sieve through 30 mesh and mix for 10 minutes.
Step-2: Make Povidone K 30 binding solution with required amount of distilled water, transfer
to Step-1and granulate until to make a good granulating point.
Step- 3: Dry the granulated mass at 600C - 700C until LOD comes down to 2.50% - 3.00%.
Sieve the dried granules through 20 mesh.
Step-4: Weigh accurately Sodium Starch Glycolate, Talc and Magnesium Stearate, add to the
dried granules and mix for 5 minutes.
Step-5: After Q.A approval compress into tablets using appropriate tool.
Step-6: Compressed tablet after QA approval are ready for coating.

Film Coating
Step- 7: Mix all ingredients homogeneously to make a smooth suspension.
Step- 8: Spray the coating suspension on the tablets using a Film coating system.

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Packing:
Step- 9: Coated tablets after QA approval are packed in blister strips, each containing 10 tablets.
Step-10: Blister strips are further packed in printed cartons in 2 X 10’s & 3 X 10’s quantities.

c) Control data for Active Substances : As indicated under specification in 5 a).

d) Control data for Excipients : As indicated under specification in 5 a).
e) Control data for finished product

Appearance : A quinolline yellow lake colored, round shaped,

one side engraved with “V” and other side break
line tablet.
Average weight(mg) : Approx. 145 mg
Disintegration time : Not more than 30 minutes
Dissolution : Not less than 75% within 45 minutes
Assay : 90% to 110% of the label claim.
Claim : 10.0 mg 9.00 mg – 11.00 mg
f) Stability data : Will be submitted at the time of inclusion.
g) Proposed shelf life : Two years from the date of manufacturing.

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 Annexure III

8. PARTICULARS OF PRODUCTION MANAGER AND QA MANAGER

Plant Manager:

1. Full Name Md. Didarul Alam

2. Qualification M. Pharm

3. Date of joining to Veritas Pharma Ltd. 06th October 2020

4. Total Experience 18 Years

5. Registration Number A-2406

6. Signature

7. Date

QA In-Charge:

1. Full Name Md. Tawhidunnabi

2. Qualification M. Pharm

3. Date of joining to Veritas Pharma Ltd. 11th July 2019

4. Total Experience 06 Years

5. Registration Number A-12767

6. Signature

7. Date

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