1. NAME OF THE MEDICINAL PRODUCT

Cinnarizine Tablets 25mg Taj Pharma

Cinnarizine Tablets 75mg Taj Pharma

  1. QUALITATIVE AND QUANTITATIVE COMPOSITION
    a) Each uncoated modified-release tablet contains:

    Cinnarizine USP 25mg
    Excipients                                       q.s.b) Each uncoated modified-release tablet contains:
    Cinnarizine USP 75mg
    Excipients                                       q.s.
  2. PHARMACEUTICAL FORM

Tablet

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

Cinnarizine is used for the control of vestibular disorders such as vertigo, tinnitus, nausea and vomiting such as that seen in Meniere’s disease.

Cinnarizine is also effective in the control of motion sickness.

4.2 Posology and method of administration

Posology

Vestibular symptoms:

Adults, elderly and children over 12 years:

Two tablets three times a day.

Children 5-12 years:

One tablet three times a day.

The stated doses should not be exceeded.

Motion sickness:

Adults, elderly and children over 12 years:

Two tablets two hours before travel and one tablet every eight hours during journey if necessary.

Children 5-12 years:

One tablet two hours before travel and half a tablet every eight hours during journey if necessary.

Method of administration

For oral use.

Cinnarizine should preferably be taken after meals. The tablets may be sucked, chewed or swallowed whole with water.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

As with other antihistamines, cinnarizine may cause epigastric discomfort; taking it after meals may diminish gastric irritation. Cinnarizine should only be given to patients with Parkinson’s disease if the advantages outweigh the possible risk of aggravating this disease.

Use of cinnarizine should be avoided in porphyria.

There have been no specific studies in hepatic or renal dysfunction. Cinnarizine should be used with care in patients with hepatic or renal insufficiency.

Cinnarizine Tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Concurrent use of alcohol, CNS depressants or tricyclic antidepressants may potentiate the sedative effects of these drugs or of cinnarizine.

Cinnarizine may prevent an otherwise positive reaction to dermal reactivity indicators if used within 4 days prior to skin testing as it is an antihistamine.

4.6 Fertility, pregnancy and lactation

Pregnancy

The safety of cinnarizine in human pregnancy has not been established although studies in animals have not demonstrated teratogenic effects. As with other drugs, it is not advisable to administer cinnarizine in pregnancy.

Breast-feeding

There are no data on the excretion of cinnarizine in human breast milk. Taking cinnarizine whilst breast-feeding is not recommended.

4.7 Effects on ability to drive and use machines

Cinnarizine may cause drowsiness, especially at the start of treatment; patients affected in this way should not drive or operate machinery.

4.8 Undesirable effects

The safety of cinnarizine was evaluated in 372 cinnarizine-treated subjects who participated in 7 placebo-controlled trials for the indications peripheral circulatory disorders, cerebral circulatory disorders, vertigo and seasickness; and in 668 cinnarizine treated subjects who participated in six comparator and thirteen open label clinical trials for the indications peripheral circulatory disorders, cerebral circulatory disorders and vertigo. Based on pooled safety data from these clinical trials, the most commonly reported (>2% incidence) adverse drug reactions (ADRs) were: somnolence (8.3) and weight increased (2.1).

Including the above mentioned ADRs, the following ADRs have been observed from clinical trials and post-marketing experiences reported with the use of cinnarizine. Frequencies displayed use the following convention:

Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from the available data).

System organ class Adverse drug reactions
Frequency category
Common Uncommon Not known
Nervous system disorders Somnolence Lethargy Dyskinesia, extrapyramidal disorder (sometimes associated with depressive feelings), Parkinsonism, tremor
Gastrointestinal disorders Nausea, dyspepsia Vomiting, upper abdominal pain
Hepatobiliary disorders Cholestatic jaundice
Skin and subcutaneous tissue disorders Hyperhidrolysis, Lichenoid keratosis including lichen planus Subacute cutaneous lupus erythematosus
Musculoskeletal and connective tissue disorders Muscle rigidity
General disorders and administrative site conditions Fatigue
Investigations Weight increased

Cases of hypersensitivity, headache and dry mouth have also been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

Symptoms

The signs and symptoms are mainly due to the anticholinergic (atropine-like) activity of cinnarizine.

Acute cinnarizine overdoses have been reported with doses ranging from 90 to 2,250 mg. Vomiting, alterations in consciousness ranging from somnolence to stupor and coma, extrapyramidal symptoms and hypotonia are the most commonly reported signs and symptoms associated with a cinnarizine overdose. In a small number of young children, seizures developed. Clinical consequences were not severe in most cases, but deaths have been reported after single and polydrug overdoses involving cinnarizine.

Treatment

There is no specific antidote to cinnarizine and in the event of overdosage, treatment is symptomatic and supportive care. The administration of activated charcoal should only be considered in patients presenting within one hour of taking a potentially toxic overdose (i.e. more than 25mg/75mg/kg).

  1. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antivertigo preparations,

Mechanism of action

Cinnarizine is a piperazine derivative with the actions and uses of the antihistamines.

Cinnarizine has been shown to be a non-competitive antagonist of the smooth muscle contractions caused by various vasoactive agents including histamine. It acts on smooth muscle by selectively inhibiting the transport of calcium ions across cell membranes into depolarised cells, therefore reducing the availability of free Ca+ ions for the induction and maintenance of contraction.

Pharmacodynamic effects

Vestibular eye reflexes induced by caloric stimulation of the labyrinth in guinea pigs are markedly depressed by cinnarizine.

Cinnarizine has been shown to inhibit nystagmus.

5.2 Pharmacokinetic properties

Absorption

In man, after oral administration, absorption is relatively slow, peak serum concentrations occurring after 2.5 to 4 hours.

Distribution

The plasma protein binding of cinnarizine is 91%

Biotransformation

In animals, cinnarizine is extensively metabolised, N-dealkylation being the major pathway.

Cinnarizine undergoes extensive metabolism mainly via CYP2D6 but there is considerable interindividual variation in the extent of metabolism.

Elimination

Approximately two thirds of the metabolites are excreted with the faeces, the rest in the urine (unchanged as metabolites and glucuronide conjugates), mainly during the first five days after a single dose.

The reported elimination half-life for cinnarizine ranges from 4 to 24 hours.

5.3 Preclinical safety data

Nonclinical safety studies showed that effects were observed only after chronic exposures from approximately 7 to 35 times the recommended maximum daily human dose of 90 mg/day calculated on a body surface area basis. Cinnarizine blocked the cardiac hERG channel in vitro, however in isolated cardiac tissue and following intravenous application in guinea-pigs, no QTc prolongation or proarrhythmic effects were observed at substantially higher exposures than those expected clinically.

In reproductive studies in the rat, rabbit, and dog, there was no evidence of adverse effects on fertility and no teratogenicity. At high doses associated with maternal toxicity in the rat there was a decreased litter size, an increase in resorptions and a decrease in foetal birth weight.

In vitro mutagenicity studies indicated that the parent compound is not mutagenic however, after reacting with nitrite and forming the nitrosation product, a weak mutagenic activity was observed. Carcinogenicity studies have not been conducted however, no pre-neoplastic changes were evident during chronic 18-month oral administration in rats up to approximately 35 times the maximum human dose level.

  1. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Starch, maize, Lactose anhydrous, Mannitol, Magnesium stearate, Talc.

6.2 Incompatibilities

Not applicable

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

PVC/PVDC/Al blisters.

Pack sizes:

Blisters: 7, 14, 28, 30, 50, 90, 100 and 500mg modified-release tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements

  1. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of  Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com

 

Cinnarizine Tablets 25mg Taj Pharma

Package leaflet: Information for the Patient

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

Always take this medicine exactly as described in this leaflet or as your doctor or pharmacist has told you.

  • Keep this leaflet. You may need to read it
  • If you have any further questions, ask your doctor or
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as
  • If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section
WHAT IS IN THIS LEAFLET:
  1. What Cinnarizine is and what it is used
  2. What you need to know before you take
  3. How to take
  4. Possible side
  5. How to store
  6. Contents of the pack and other1. WHAT CINNARIZINE IS AND WHAT IT IS USED FOR

Cinnarizine belongs to a group of medicines called antihistamines.

Cinnarizine is used to control problems with balance (such as Meniere’s disease) which can cause vertigo (a spinning sensation or dizziness), ringing in the ears, nausea (feeling sick), vomiting (being sick) and loss of hearing.

Cinnarizine can also help to control travel sickness.

This medicine is for use in adults and children aged over 5 years.

  1. WHAT YOU NEED TO KNOW BEFORE YOU TAKE CINNARIZINE

Do not take Cinnarizine if you:are allergic to cinnarizine or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before taking Cinnarizine if you:

  • Suffer from Parkinson’s disease (Cinnarizine may make your symptoms worse).
  • Need a skin allergy test, as Cinnarizine can affect the results. You will need to stop taking Cinnarizine 4 days before the
  • Have a blood problem called
  • Have problems with your liver or

Other medicines and Cinnarizine Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription, especially the following:

  • medicines for depression called tricyclic antidepressants (g. amitriptyline, dosulepin, imipramine)
  • Medicines that make you feel drowsy g. tranquillisers or painkillers.

Cinnarizine with alcohol

You should not drink alcohol during treatment as it may make you drowsier.

Pregnancy and breast-feeding

You should not take Cinnarizine if you are pregnant, think you may be pregnant or are trying to become pregnant. If you become pregnant while you are taking Cinnarizine you must stop taking the tablets immediately and tell your doctor. Cinnarizine may reach your baby through the breast milk. Therefore, you should not take Cinnarizine if you are breast-feeding.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines
This medicine occasionally causes drowsiness, especially at the start of treatment. If you feel drowsy do not drive or use machinery.
Cinnarizine contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
  1. HOW TO TAKE CINNARIZINE

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose is:

Problems with balance:
Use in adults, elderly and adolescents over 12 years – Two tablets three times a day.
Use in children 5 – 12 years old – One tablet three times a day.

Travel sickness:

Use in adults, elderly and adolescents over 12 years – Two tablets taken two hours before your journey and if necessary, one tablet taken every eight hours during your journey.

Use in children 5 – 12 years old – One tablet two hours before your journey and if necessary, half a tablet every eight hours during your journey.

Use in children under 5 years – Cinnarizine is not recommended for children under the age of 5. These tablets may be sucked, chewed or swallowed whole with water. Take these tablets after meals.

If you take more Cinnarizine than you should

If you accidentally take too many tablets or if a young child takes this medicine by accident, contact your doctor or nearest hospital emergency department immediately. You may be sick, feel sick or have an upset tummy, be shaking, have uncontrollable muscle spasms, weakness or floppy muscles, become drowsy or lose consciousness. Young children may also experience seizures.

If you forget to take Cinnarizine

Take the next dose as soon as you remember unless it is almost time for your next dose. Do not take a double dose to make up for a forgotten dose.

If you stop taking Cinnarizine

Do not stop taking your treatment without talking to your doctor, even though you may feel better or if you feel the tablets are not working.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

  1. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them

Stop taking Cinnarizine and seek medical help immediately if you have any of the following: Not known (cannot be estimated from the available data)

  • yellowing of the skin or whites of the eyes, dark urine, pale stools, tiredness, fever, nausea, weakness, drowsiness or abdominal pain. These may indicate you have serious problems with your liver
  • red, lumpy, itchy rash which may also have some silvery scales on areas of skin exposed to sunlight
  • allergic reactions such as a rash or swelling of the face, lips, tongue or throat, difficulty breathing

Other side effects:
Common (may affect up to 1 in 10 people)

  • drowsiness
  • feeling sick (nausea), indigestion
  • increase in weight

Uncommon (may affect up to 1 in 100 people)

  • lack of energy (lethargy), tiredness
  • being sick
  • pain in the upper stomach area
  • excessive sweating
  • patches of spots, red or pinkish skin, with a crust

Not known (cannot be estimated from the available data)

  • Shaking, uncontrollable twitching or twisting movements, muscle stiffness, restless legs, stiff posture with a slow shuffling walk. You may also feel depressed
  • headache
  • dry mouth
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
  1. HOW TO STORE CINNARIZINE
    Keep this medicine out of the sight and reach of children. This medicine does not require any special storage conditions. Do not use this medicine after the expiry date which is stated on the carton after ‘EXP’. The expiry date refers to the last day of that month. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

 

  1. CONTENTS OF THE PACK AND OTHER INFORMATION
    WHAT CINNARIZINE CONTAINS
    a) Each uncoated modified-release tablet contains:
    Cinnarizine 25mg
    Excipients                                       q.s.
    b) Each uncoated modified-release tablet contains:
    Cinnarizine 75mg
    Excipients                                       q.s.

 

What Cinnarizine looks like and contents of the pack

PVC/PVDC/Al blisters.

Pack sizes:

Blisters: 7, 14, 28, 30, 50, 90, 100 and 500mg modified-release tablets.

Not all pack sizes may be marketed.

  1. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of  Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com