Adipine XL 30mg & 60mg tablets

1. Name Of The Medicinal Product

Adipine XL 30mg Tablets

Adipine XL 60mg Tablets

2. Qualitative And Quantitative Composition

Each Adipine XL 30mg tablet contains 30mg of nifedipine

Each Adipine XL 60mg tablet contains 60mg of nifedipine

For excipients see 6.1

3. Pharmaceutical Form

Prolonged release tablet

Each pale red tablet is round and biconvex and embossed with "30" or "60" on one side.

4. Clinical Particulars

4.1 Therapeutic Indications

The tablets are indicated for:

- the treatment of all grades of hypertension

- the prophylaxis of chronic stable angina pectoris, either as monotherapy or in combination with a beta-blocker.

4.2 Posology And Method Of Administration

Route of Administration

For oral use

These tablets should be swallowed whole with a glass of water and not bitten, broken up or chewed.

Dosage Recommendations

It is recommended that each dose should be taken at approximately 24 hours intervals i.e. at the same time each day, preferably in the morning.

Adults: In mild to moderate hypertension, the recommended initial dose is one 20mg tablet once daily. In severe hypertension and the prophylaxis of angina pectoris, the recommended initial dose is one 30mg tablet once daily. The dose may be adjusted to a maximum of 90mg once daily.

Prophylactic anti-anginal efficacy is maintained when patients are switched from other calcium antagonists e.g. verapamil or diltiazem. When patients are switched, the recommended initial dose is 30mg nifedipine, once daily. Subsequent titration to a higher dosage should be according to clinical response.

Elderly: The pharmacokinetics of nifedipine may be altered in the elderly therefore, a lower maintenance dose may be necessary when treating elderly patients.

Patients with Renal Impairment: Dosage adjustments should not be required for patients with impaired renal function.

Patients with Hepatic Impairment: Nifedipine prolonged release tablets should not be administered to patients with impaired hepatic function.

Children: Nifedipine is not recommended for use in children.

Treatment with nifedipine may be continued long term.

4.3 Contraindications

Nifedipine XL Tablets are contraindicated:

- in patients with a known hypersensitivity to the drug or other constituents of the tablets

- in patients with a known hypersensitivity to other dihydropyridines calcium antagonists, because of the theoretical risk of cross-reactivity

- in women who are or may become pregnant, are capable of child bearing or to nursing mothers

- in patients with clinically significant aortic stenosis, in cardiogenic shock or unstable angina or for the treatment of acute attacks of angina

- in patients with inflammatory bowel disease, Crohn's disease or with a history of gastrointestinal obstruction, oesophageal obstruction or with decreased diameter of the gastrointestinal lumen

- in patients with hepatic impairment

- for secondary prevention of myocardial infarction or during or within one month of a myocardial infarction

Nifedipine XL Tablets should not be administered concomitantly with rifampicin since effective plasma levels of nifedipine may not be achieved owing to enzyme induction (see section 4.5).

The safety of nifedipine prolonged release tablets has not been established in patients with malignant hypertension.

4.4 Special Warnings And Precautions For Use

Nifedipine should be used with caution in patients with hypotension, as there is a risk of blood pressure decreasing further and in patients whose cardiac reserve is poor. Deterioration of heart failure has occasionally been observed with nifedipine.

Cardiac ischaemic pain has been reported to occur in a small proportion of patients following the introduction of nifedipine therapy. In such cases, treatment with nifedipine should be discontinued.

Caution should be exercised when nifedipine tablets are given to diabetic patients as they may require adjustment of their diabetic therapy.

In patients with malignant hypertension and hypovolaemia and who are on dialysis, a significant decrease in blood pressure can occur.

Nifedipine may be used in combined therapy with other antihypertensive agents including beta-blocker drugs, but the possibility of an additive effect resulting in postural hypotension should be borne in mind. Withdrawal of any previous antihypertensive agents should be gradual, as nifedipine will not prevent any possible rebound effects.

Nifedipine is contra-indicated in pregnancy. However, caution must be exercised when nifedipine with intravenous magnesium sulphate is given to pregnant women.

Nifedipine XL Tablets must not be administered to patients with Kock pouch (ileostomy after proctocolectomy).

A false positive effect may be obtained when carrying out a barium contrast X-ray.

Nifedipine XL Tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance e.g., galactosaemia, the Lapp lactase deficiency or glucose-galactose malabsorption, should be advised not to take these tablets.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Known Interactions

Nifedipine should not be taken with grapefruit juice because bioavailability is increased.

Cimetidine may potentiate the antihypertensive effect of nifedipine tablets if it is administered simultaneously.

It is reported that serum quinidine levels have been reduced when it is used in combination with nifedipine, irrespective of the quinidine dose taken.

The administration of nifedipine and digoxin concurrently may lead to reduced digoxin clearance and therefore, bring about an increase in the plasma digoxin level. Close monitoring of plasma digoxin levels should take place and, if necessary, a reduction in the dosage of digoxin.

Phenytoin induces the cytochrome P450 3A4 system. When nifedipine is co-administered with phenytoin, nifedipine's bioavailability is reduced and consequently, its efficacy is weakened. In such cases, the clinical response to nifedipine should be monitored following concomitant administration and, if necessary, consideration should be given to increasing the nifedipine dose. If the nifedipine dose is increased during the co-administration of both drugs, consideration should be given to reducing the nifedipine dose when phenytoin therapy is discontinued.

Diltiazem decreases the clearance of nifedipine and hence increases plasma nifedipine levels. Caution should be exercised when both drugs are given simultaneously. A reduction of nifedipine dose may be required when the two are used together.

Nifedipine may falsely increase the spectrophotometric values of urinary vanillylmandelic acid. HPLC measurements are not affected.

Nifedipine should not be administered concomitantly with rifampicin, as effective plasma levels of nifedipine may not be achieved as a result of enzyme induction.

Simultaneous administration of cisapride and nifedipine or quinupristin/dalfopristin and nifedipine may lead to increased plasma concentration of nifedipine. Hence, the blood pressure may need to be monitored and a reduction in the nifedipine dose may be necessary.

Nifedipine enhances the effect of non-polarising muscle relaxants.

Theoretical Interactions

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs such as erythromycin, ketoconazole, itraconazole, fluconazole, fluoxetine, indinavir, nelfinavir, ritonavir and saquinavir that are known to inhibit this enzyme system. Although no in vivo interaction studies with these drugs have been carried out, their co-administration with nifedipine in vitro, have shown increases in nifedipine plasma concentrations. Therefore, the blood pressure should be monitored and, if necessary, a reduction in the nifedipine dose should be considered.

Similarly, the potential interaction between nifedipine and nefazodone has not been clinically investigated. Nefazodone is known to inhibit the cytochrome P450 3A4 mediated metabolism of other drugs and therefore, co-administration with nifedipine may increase the plasma concentrations of nifedipine. Again, monitoring of the blood pressure is advised when both drugs are simultaneously administrated with, if necessary, a reduction in the nifedipine dose.

Tacrolimus is metabolised via the cytochrome P450 3A4 system. Upon co-administration with nifedipine, the plasma levels of tacrolimus should be monitored and, if necessary, consideration should be given to reducing the tacrolimus dose.

Carbamazepine, phenobarbital or valproic acid have been shown to alter the plasma levels of a structurally similar calcium channel blocker, however, no interactive studies have been carried out with these drugs and nifedipine. A decrease (with carbamazepine or phenobarbital) or an increase (with valproic acid) in nifedipine plasma concentrations, leading to a change in efficacy, can therefore not be ruled out.

Drugs Shown Not to Interact With Nifedipine

Aspirin, benazepril, candesartan cilexetil, debrisoquine, doxazosin, irbesartan, omeprazole, orlistat, pantoprazole, ranitidine, rosiglitazone and triamterene hydrochlorothiazide are drugs known not to affect the pharmacokinetics of nifedipine when they are administered concomitantly with nifedipine.

4.6 Pregnancy And Lactation

Nifedipine is contraindicated in woman capable of child-bearing.

Safe use of nifedipine during human pregnancy has not been established. Animal studies have shown reproductive toxicity (embryotoxic and teratogenic effects) at maternally toxic doses.

Nifedipine may be present in breast milk and therefore, Nifedipine XL Tablets are contraindicated for use in nursing mothers.

In single reports of in vitro fertilisation, calcium antagonists like nifedipine have been associated with biochemical alterations in the head of the spermatozoa that may impair sperm function. Calcium antagonists like nifedipine should be considered as possible causes in those men who are repeatedly unsuccessful in fathering a child by in vitro fertilisation and where no other explanation can be found.

4.7 Effects On Ability To Drive And Use Machines

Reactions to nifedipine may vary in intensity in patients, especially at the onset of therapy, on changing medication or when combined with alcohol. Therefore, the patient should be warned of the possible effects and advised not to drive or operate machinery, if affected.

4.8 Undesirable Effects

Most undesirable effects are due to vasodilatory action of nifedipine and usually regress upon withdrawal of treatment.

Those commonly reported (at an incidence of> 1% < 10%) in clinical studies include headache, palpitations, vasodilatation (especially at the start of therapy), lethargy, constipation, dizziness and oedema particularly peripheral oedema not connected with weight gain or heart failure.

Other side effects associated with nifedipine therapy are named below:

	Uncommon Side Effects (> 0.1 % < 1 % )	Rare Side Effects (> 0.01 % < 0.1 % )	Spontaneous Reports ( < 0.01 % )
Body as a Whole	abdominal pain, chest pain, leg pain, malaise	allergic reaction, chest pain substernal, chills, hypersensitivity-type jaundice, facial oedema fever	anaphylactic reaction, weight loss
Cardiovascular	hypotension, postural hypotension, syncope, tachycardia	cardiovascular disorder
Digestive	diarrhoea, dry mouth, dyspepsia, flatulence, nausea	anorexia, eructation, gastrointestinal disorder, gingivitis, gingival hyperplasia, vomiting	bezoar, dysphagia, oesophagitis, gum disorder, intestinal obstruction, intestinal ulcer
Haematological			leucopenia, hyperglycaemia
Hepatic		liver function test abnormalities, increase in GGT	increase in ALT, jaundice
Musculoskeletal	leg cramps	arthralgia, joint disorder, myalgia	muscle cramps
Neurological	insomnia, nervousness, paraesthesia, somnolence, vertigo	hyperaesthesia, sleep disorder, tremor, mood changes
Respiratory	dyspnoea	epistaxis
Dermatological	pruritus, rash	angioedema, maculopapular, pustular and vesiculobullous rash, sweating, urticaria	purpura, exfoliative dermatitis, photosensitive dermatitis
Special Senses		abnormal vision, eye disorder, eye pain	blurred vision
Urogenital	nocturia, polyuria	dysuria, impotence

There have also been reports of gynaecomastia in older men on long-term therapy, but this usually regresses when treatment is withdrawn.

Exacerbation of angina pectoris has been observed at the start of treatment with modified-release preparations of dihydropyridines, including nifedipine. Myocardial infarction is also known to occur although it is not possible to distinguish it from the natural course of ischaemic heart disease.

4.9 Overdose

Symptoms

There are few reports of nifedipine overdose and the symptoms are not necessarily dose-related. The most likely manifestations of overdose are severe hypotension due to vasodilatation, tachycardia or bradycardia.

The metabolic disturbances may include hyperglycaemia, metabolic acidosis and hypo- or hyperkalaemia. The cardiac effects, which may occur, include heart block, AV dissociation and asystole and cardiogenic shock with pulmonary oedema.

Other toxic effects include drowsiness, dizziness, confusion, nausea, vomiting, lethargy, flushing, hypoxia, unconsciousness and coma.

Management

In the treatment of overdose it is important to restore stable cardiovascular conditions as soon as possible and achieve total elimination of nifedipine.

Gastric lavage and charcoal instillation may be of assistance if the patient is found early after the overdose. Gastric lavage may be necessary in combination with irrigation of the small intestine. Ipecacuanha should be given to children.

To prevent the subsequent absorption of nifedipine, elimination must be complete, including from the small intestine.

Activated charcoal should be given in 4 hourly doses of 25g for adults and 10g for children. The blood pressure, central arterial pressure, ECG, electrolytes, pulmonary wedge pressure and urea should be carefully monitored.

Placing the patient in the supine position with the feet raised and the use of plasma expanders, as appropriate, should treat the hypotension resulting from cardiogenic shock and arterial vasodilatation. If these measures are ineffective, hypotension may be treated with 10ml to 20ml of 10% calcium gluconate, administered intravenously over a period of 5 to 10 minutes. If ineffective, the therapy can be continued, with ECG monitoring.

Also, beta-sympathomimetics may be given e.g. 0.2mg of isoprenaline by slow intravenous or 5μg per minute as a continuous infusion. If the blood pressure response is inadequate with calcium and isoprenaline, vasoconstricting sympathomimetics such as dopamine or noradrenaline should be administered. The patient's response should determine the dosage of these drugs.

Bradycardia may be treated with atropine, beta-sympathomimetics or a temporary cardiac pacemaker.

Additional fluid should be administered with caution to avoid cardiac overload.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Anatomical Therapeutic Chemical (ATC) code: C08C A05

Selective calcium channel blocker

(dihydropyridine derivative), with mainly vascular effects

Nifedipine is a dihydropyridine and is a specific and potent antagonist of calcium influx through the slow channel of the cell membrane of cardiac and smooth muscle cells, both in coronary and peripheral circulation.

The antihypertensive effects of nifedipine are achieved by causing peripheral vasodilatation resulting in a reduction in peripheral resistance. Nifedipine administered once daily provides twenty-four hours control of elevated blood pressure. Nifedipine reduces blood pressure such that the percentage lowering is proportional to its initial level. In normotensive individuals, nifedipine has little or no effect.

Nifedipine produces its effects in the treatment of angina by reducing peripheral and coronary vascular resistance, leading to an increase in coronary blood flow, cardiac output and stroke volume and causing a decrease in after-load. Also, nifedipine submaximally dilates clear and atherosclerosis coronary arteries to protect the heart against coronary artery spasm and improve perfusion to the ischaemic myocardium. Nifedipine decreases the frequency of painful attacks and the ischaemic ECG changes regardless of the relative contribution from coronary artery spasm or atheroschlerosis.

5.2 Pharmacokinetic Properties

General Characteristics

Nifedipine XL Tablets are formulated as prolonged release products. They are designed to control the release of nifedipine over twenty-four hours so that a clinical effect is achieved when the tablets are swallowed, once a day.

The pharmacokinetic profile is characterised by low peak-trough fluctuation. Over twenty-four hours plasma concentration versus time profiles at steady state are plateau-like, rendering the Nifedipine XL Tablets suitable for once daily administration.

Absorption

Nifedipine is rapidly and almost completely absorbed from the gastrointestinal tract after oral administration. However, due to extensive hepatic first pass metabolism in the liver, the resultant bioavailability lies between 45% and 68%. The absorption rate is slightly changed when the tablets are taken after ingesting food but the extent of drug availability is not affected.

Distribution

Nifedipine is about 95% bound to plasma proteins.

Metabolism

Nifedipine is almost completely metabolised in the liver by oxidative and hydrolytic processes.

Elimination

The elimination half-life is 2 to 5 hours. About 70% to 80% of the administered dose of nifedipine is excreted via the kidneys, mostly as its active metabolites. The rest (5% to 15%) is excreted via the bile in the faeces. The non-metabolised drug substance is only found in traces (less than 1.0%) in the urine.

Characteristics in Patients

Patients with Renal Impairment

There are no significant differences in the pharmacokinetics of nifedipine in patients with renal impairment and in healthy subjects. Therefore, dosage adjustments should not be required for patients with impaired renal function.

Patients with Hepatic Impairment

Nifedipine is primarily metabolised in the liver. The elimination half-life is markedly prolonged and there is a reduction in total clearance. Therefore, owing to the duration of action, nifedipine should not be administered to patients with reduced hepatic function.

5.3 Preclinical Safety Data

The LD₅₀ values (in mg per kg) determined when nifedipine was given orally and intravenously to different animal species, are reported below:

Animal Species	Oral	Intravenous
Mouse	454 (401 - 572) *	4.2 (3.8 - 4.6) *
Rat	1022 (950 - 1087) *	15.5 (13.7 - 17.5) *
Rabbit	250 - 500	2 - 3
Cat	~ 100	0.5 - 8
Dog	> 250	2 - 3

* 95% confidence interval

Subacute & Subchronic Toxicity Studies (in Rats and Dogs)

Nifedipine doses of up to 50mg per kg in rats and 100mg per kg in dogs p.o were tolerated without any damage when administered orally over periods of thirteen and four weeks, respectively.

Nifedipine doses of 2.5mg per kg in rats and 0.1mg per kg in dogs were tolerated without any damage when administered intravenously over periods of three weeks and six days, respectively.

Chronic Toxicity Studies (in Rats and Dogs)

Nifedipine doses of up to and including 100 mg per kg in dogs p.o were tolerated without any damage when administered orally up to one year.

In rats, toxic effect occurred at nifedipine concentrations above 100 ppm in the feed (about 5mg to 7mg per kg body weight).

Carcinogenic Studies (in Rats)

Studies in rats over two years produced no evidence of carcinogenic effects caused by nifedipine.

Reproductive Studies (in Rats, Mice & Rabbits)

Studies in rats, mice and rabbits maternally toxic doses of nifedipine induced some teratogenic and embryotoxic effects.

Mutagenic Studies

In vivo and in vitro studies showed that nifedipine has no mutagenic properties.

6. Pharmaceutical Particulars

6.1 List Of Excipients

In Tablet Core

Povidone K30

Lactose monohydrate

Carbomer 974P

Silica, colloidal anhydrous

In Tablet Core & Coat

Talc

Hypromellose (E 464)

Magnesium stearate

In Tablet Coat

Dimethylaminoethyl methacrylate-Butyl methacrylate-Methyl methacrylate copolymer

Macrogol 4000

Red iron oxide (E 172)

Titanium dioxide (E 171)

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

Shelf Life of the Medicinal Product as Packaged for Sale

24 months

Shelf Life after Dilution or Reconstitution

Not applicable

Shelf Life after First Opening the Container

Not applicable

6.4 Special Precautions For Storage

Do not store above 25 ºC. Keep blister in the outer carton.

6.5 Nature And Contents Of Container

The tablets are enclosed in blisters composed of 25µm aluminium foil coated with 20gm^-2 PVDC film/250µm PVC foil coated with 40gm^-2 PVDC film

The blisters are boxed in cardboard cartons containing 28 tablets and a patient information leaflet.

6.6 Special Precautions For Disposal And Other Handling

Not applicable

7. Marketing Authorisation Holder

Chiesi Limited

Cheadle Royal Business Park

Highfield

Cheadle

SK8 3GY

United Kingdom

8. Marketing Authorisation Number(S)

Adipine XL 30 mg Tablets - PL 08829/0147

Adipine XL 60 mg Tablets - PL 08829/0148

9. Date Of First Authorisation/Renewal Of The Authorisation

28^th October 2004

10. Date Of Revision Of The Text

22/12/2008

11. LEGAL CATEGORY

POM

Tylenol Cough and Sore Throat Daytime

Generic Name: acetaminophen and dextromethorphan (a SEET a MIN oh fen and DEX troe me THOR fan)

Brand Names: Children's Triacting, Triaminic Cough & Sore Throat, Triaminic Cough & Sore Throat Softchews, Tylenol Cough and Sore Throat Daytime

What is Tylenol Cough and Sore Throat Daytime (acetaminophen and dextromethorphan)?

Acetaminophen is a pain reliever and fever reducer.

Dextromethorphan is a cough suppressant. It affects the signals in the brain that trigger cough reflex.

The combination of acetaminophen and dextromethorphan is used to treat cough and pain or fever caused by the common cold or flu.

Dextromethorphan will not treat a cough that is caused by smoking, asthma, or emphysema.

Acetaminophen and dextromethorphan may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Tylenol Cough and Sore Throat Daytime (acetaminophen and dextromethorphan)?

Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take acetaminophen. Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death. Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen. Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not use a cough or cold medicine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects. Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP.

What should I discuss with my healthcare provider before taking Tylenol Cough and Sore Throat Daytime (acetaminophen and dextromethorphan)?

Do not take this medication if you are allergic to acetaminophen or dextromethorphan. Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take acetaminophen. Do not use a cough or cold medicine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have liver disease or a history of alcoholism.

It is not known whether acetaminophen and dextromethorphan will harm an unborn baby. Do not use cold or cough medicine without medical advice if you are pregnant. It is not known whether acetaminophen and dextromethorphan will harm an unborn baby. Do not use cold or cough medicine without medical advice if you are pregnant.

Artificially sweetened liquid cough or cold medicine may contain phenylalanine. If you have phenylketonuria (PKU), check the medication label to see if the product contains phenylalanine.

How should I take Tylenol Cough and Sore Throat Daytime (acetaminophen and dextromethorphan)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death.

Cough or cold medicine is usually taken only for a short time until your symptoms clear up.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

Measure liquid medicine with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Drink extra fluids while you are taking this medication. Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash. If you need surgery, tell the surgeon ahead of time that you are using acetaminophen and dextromethorphan. You may need to stop using the medicine for a short time. Store at room temperature away from moisture, heat, and light.

What happens if I miss a dose?

Since cough or cold medicine is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

Overdose symptoms may also include dizziness, drowsiness, feeling restless or nervous, diarrhea, loss of appetite, seizure (convulsions), or coma.

What should I avoid while taking Tylenol Cough and Sore Throat Daytime (acetaminophen and dextromethorphan)?

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP. Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen.

Avoid taking diet pills, caffeine pills, or other stimulants (such as ADHD medications) without your doctor's advice. Taking a stimulant together with cough medicine can increase your risk of unpleasant side effects.

Tylenol Cough and Sore Throat Daytime (acetaminophen and dextromethorphan) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have a serious side effect such as:

• 
  

  severe dizziness, anxiety, restless feeling, or nervousness;

  
  


• 
  

  confusion, hallucinations;

  
  


• 
  

  slow, shallow breathing;

  
  


• 
  

  easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms; or

  
  


• 
  

  nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

  
  

Less serious side effects may include:

• 
  

  upset stomach.

  
  


• 
  

  mild loss of appetite; or

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Tylenol Cough and Sore Throat Daytime (acetaminophen and dextromethorphan)?

Tell your doctor about all other medicines you use, especially:

• 
  

  celecoxib (Celebrex);

  
  


• 
  

  cinacalcet (Sensipar);

  
  


• 
  

  darifenacin (Enablex);

  
  


• 
  

  imatinib (Gleevec);

  
  


• 
  

  isoniazid;

  
  


• 
  

  quinidine (Quin-G);

  
  


• 
  

  ranolazine (Ranexa);

  
  


• 
  

  ritonavir (Norvir, Kaletra);

  
  


• 
  

  sibutramine (Meridia);

  
  


• 
  

  terbinafine (Lamisil);

  
  


• 
  

  zidovudine (Retrovir, AZT);

  
  


• 
  

  gout medication such as probenecid (Benemid);

  
  


• 
  

  medicines to treat high blood pressure;

  
  


• 
  

  seizure medication such as phenytoin (Dilantin) or phenobarbital (Luminal, Solfoton); or

  
  


• 
  

  an antidepressant such as amitriptyline (Elavil, Vanatrip, Limbitrol), bupropion (Wellbutrin, Zyban, Aplenzin), fluoxetine (Prozac, Sarafem, Symbyax), fluvoxamine (Luvox), imipramine (Janimine, Tofranil), paroxetine (Paxil), sertraline (Zoloft), and others.

  
  

This list is not complete and other drugs may interact with acetaminophen and dextromethorphan. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Tylenol Cough and Sore Throat Daytime resources

• Tylenol Cough and Sore Throat Daytime Side Effects (in more detail)
• Tylenol Cough and Sore Throat Daytime Use in Pregnancy & Breastfeeding
• Tylenol Cough and Sore Throat Daytime Drug Interactions
• 0 Reviews for Tylenol Cough and Sore Throat Daytime - Add your own review/rating

Compare Tylenol Cough and Sore Throat Daytime with other medications

• Cold Symptoms
• Cough
• Pain

Where can I get more information?

• Your pharmacist can provide more information about acetaminophen and dextromethorphan.

See also: Tylenol Cough and Sore Throat Daytime side effects (in more detail)

Norgalax Enema

NORGALAX rectal gel

Docusate Sodium

Read all of this leaflet carefully before you start taking this medicine

• Keep this leaflet. You may need to read it again.


• If you have any further questions, ask your doctor or pharmacist.


• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.


• If any of the side effects become serious, or you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

If you need the information on this leaflet in an alternative format, such as large text, or Braille please ring from the UK: 0800 198 5000.

In this leaflet:

• 1. What NORGALAX is and what it is used for


• 2. Before you use NORGALAX


• 3. How to use NORGALAX


• 4. Possible side effects


• 5. How to store NORGALAX


• 6. Further information

What Norgalax Is And What It Is Used For

NORGALAX softens the faeces (stools) to make your bowel movements easier. It will help you when you are constipated or can be used to empty the large intestine (gut) if the doctor wants to examine inside it.

Before You Use Norgalax

Do not use NORGALAX if:

• You have haemorrhoids (piles) or bleeding from your rectum (back passage).


• You have a pain in your abdomen (tummy).


• You feel sick or are being sick.


• Your doctor has told you that you have:
  
  
  • A blockage in your intestine (gut).
  
  
  • Sores around your anus (bottom) called anal fissures.
  
  
  • Inflammatory bowel disease such as ulcerative colitis or Crohn’s disease.
  
  
  • Inflammation of the back passage called Rectocolitis.
  
  

Taking/using other medicines

Do not use other laxatives while you are using NORGALAX as it may react with other medicines. Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Taking/using with food and drink

It does not matter if you use NORGALAX before or after meals.

Pregnancy and breast-feeding

NORGALAX may be used during pregnancy and whilst breast-feeding. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Using NORGALAX will not affect your ability to drive or use machinery.

How To Use Norgalax

Always use NORGALAX exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

• The usual dose is one tube and this is usually all you need. You can use a second tube later in the day, or the next day if needed.


• Do not use NORGALAX for more than a few days at a time.

To use NORGALAX pull the cap off the neck of the tube.

• Gently squeeze the tube and smear a drop around the neck of the tube to help it slide in.


• Push the neck of the tube all the way into your rectum (back passage). Squeeze the tube gently until it is empty.


• Stay near a toilet because you should need to use it about 5 to 20 minutes after using NORGALAX.

NORGALAX is not recommended for use in children under 12 years old.

If you use more NORGALAX than you should, contact your doctor.

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

Norgalax Enema Side Effects

Like all medicines, NORGALAX can cause side effects, although not everybody gets them.

Sometimes there is burning or pain around the anus (bottom). The wall of the rectum (back passage) may become reddish or it may bleed and you may suffer from diarrhoea but this soon goes.

Rarely the liver may be affected (signs include yellowing of the skin and eyes, bruising or itching) especially if other laxatives are being used as well as NORGALAX.

If any of the side effects become serious, or you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How To Store Norgalax

Keep all medicines out of the reach and sight of children.

Do not store above 25°C.

Do not use NORGALAX after the expiry date which is stated on the carton/tube as month/year. The expiry date refers to the last day of the month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further Information

What NORGALAX contains

The active substance is docusate sodium. Each tube contains 0.12g of docusate sodium.

The other ingredients are glycerol, sodium carboxymethyl cellulose and water.

What NORGALAX looks like and contents of the pack

NORGALAX comes in a tube containing 10g of gel. Each pack contains either 6 or 100 tubes.

Marketing Authorisation Holder and Manufacturer

The Marketing Authorisation Holder is

Norgine Ltd.

Harefield

Middlesex

UB9 6NS

UK

It is made by

Norgine Pharma

28102 Dreux

France

UK Marketing Authorisation Number: PL 00322/0065

The leaflet was last approved: 04/08/2008

Ticar

Generic Name: ticarcillin (tye KAR sil in)

Brand Names: Ticar

What is Ticar (ticarcillin)?

Ticarcillin is an antibiotic in a group of drugs called penicillins. Ticarcillin fights bacteria in the body.

The combination of ticarcillin is used to treat many different infections caused by bacteria, such as urinary tract infections, bone and joint infections, severe vaginal infections, stomach infections, and skin infections.

Ticarcillin may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Ticar (ticarcillin)?

Do not use this medication if you are allergic to ticarcillin or to any other penicillin antibiotic, such as amoxicillin (Amoxil, Augmentin), ampicillin (Omnipen, Principen), carbenicillin (Geocillin), dicloxacillin (Dycill, Dynapen), oxacillin (Bactocill), penicillin (Beepen-VK, Ledercillin VK, Pen-V, Pen-Vee K, Pfizerpen, V-Cillin K, Veetids), and others.

Before using ticarcillin tell your doctor if you are allergic to cephalosporins such as Ceclor, Ceftin, Duricef, Keflex, and others, or if you have kidney disease, a bleeding or blood clotting disorder, low levels of potassium in your blood, a history of any type of allergy, or if you are on a salt-restricted diet.

Use this medication for the entire length of time prescribed by your doctor. Your symptoms may get better before the infection is completely treated. Ticarcillin will not treat a viral infection such as the common cold or flu. Ticarcillin can make birth control pills less effective. Use a second non-hormone method of birth control (such as a condom, diaphragm, spermicide) to prevent pregnancy while using ticarcillin.

What should I discuss with my healthcare provider before using Ticar (ticarcillin)?

Do not use this medication if you are allergic to ticarcillin or to any other penicillin antibiotic, such as:

• 
  

  amoxicillin (Amoxil, Augmentin);

  
  


• 
  

  ampicillin (Omnipen, Principen);

  
  


• 
  

  carbenicillin (Geocillin);

  
  


• 
  

  dicloxacillin (Dycill, Dynapen);

  
  


• 
  

  oxacillin (Bactocill); or

  
  


• 
  

  penicillin (Beepen-VK, Ledercillin VK, Pen-V, Pen-Vee K, Pfizerpen, V-Cillin K, Veetids, and others).

  
  

Before using ticarcillin, tell your doctor if you are allergic to any drugs (especially cephalosporins such as Ceclor, Ceftin, Duricef, Keflex, and others), or if you have:

• 
  

  kidney disease;

  
  


• 
  

  a bleeding or blood clotting disorder;

  
  


• 
  

  an electrolyte imbalance such as low levels of potassium in your blood;

  
  


• 
  

  a history of any type of allergy; or

  
  


• 
  

  if you are on a salt-restricted diet.

  
  

If you have any of these conditions, you may not be able to use ticarcillin, or you may need a dosage adjustment or special tests during treatment.

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Ticarcillin can make birth control pills less effective. Use a second non-hormone method of birth control (such as a condom, diaphragm, spermicide) to prevent pregnancy while using ticarcillin. It is not known whether ticarcillin passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I use Ticar (ticarcillin)?

Use this medication exactly as it was prescribed for you. Do not use the medication in larger amounts, or use it for longer than recommended by your doctor. Follow the instructions on your prescription label.

Ticarcillin is given as an injection through a needle placed into a vein. Your doctor, nurse, or other healthcare provider will give you this injection. You may be given instructions on how to inject your medicine at home. Do not use this medicine at home if you do not fully understand how to give the injection and properly dispose of needles and other items used in giving the medicine.

Ticarcillin must be mixed with a liquid (diluent) before injecting it. Do not mix the medicine until you are ready to give yourself an injection.

Ticarcillin is usually given for 10 to 14 days, depending on the infection being treated. Follow your doctor's instructions.

Use each needle only one time. Throw away used needles and syringes in a puncture-proof container. If your medicine does not come with such a container, ask your pharmacist where you can get one. Keep this container out of the reach of children and pets. Your pharmacist can tell you how to properly dispose of the container.

Use this medication for the entire length of time prescribed by your doctor. Your symptoms may get better before the infection is completely treated. Ticarcillin will not treat a viral infection such as the common cold or flu. Store unmixed ticarcillin, and the liquid diluent, at cool room temperature.

What happens if I miss a dose?

Use the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and use the medicine at the next regularly scheduled time. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

Symptoms of a ticarcillin overdose may include drowsiness, hyperactivity, or seizure (convulsions).

What should I avoid while using Ticar (ticarcillin)?

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or has blood in it, call your doctor. Do not use any medicine to stop the diarrhea unless your doctor has told you to.

Ticar (ticarcillin) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have any of these serious side effects:

• 
  

  diarrhea that is watery or bloody;

  
  


• 
  

  easy bruising or bleeding, unusual weakness;

  
  


• 
  

  dry mouth, increased thirst, confusion, increased urination, muscle pain or weakness, fast heart rate, feeling light-headed, fainting;

  
  


• 
  

  fever, chills, body aches, flu symptoms; or

  
  


• 
  

  skin rash, bruising, severe tingling, numbness, pain, muscle weakness.

  
  

Less serious side effects may be more likely to occur, such as:

• 
  

  mild diarrhea, gas, stomach pain;

  
  


• 
  

  nausea or vomiting;

  
  


• 
  

  headache;

  
  


• 
  

  skin rash or itching;

  
  


• 
  

  pain, swelling, or burning where the injection was given; or

  
  


• 
  

  vaginal yeast infection (itching or discharge).

  
  

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Ticar (ticarcillin)?

There may be other drugs that can affect ticarcillin. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Ticar resources

• Ticar Side Effects (in more detail)
• Ticar Use in Pregnancy & Breastfeeding
• Ticar Drug Interactions
• Ticar Support Group
• 0 Reviews for Ticar - Add your own review/rating

• Ticar Prescribing Information (FDA)


• Ticar Advanced Consumer (Micromedex) - Includes Dosage Information


• Ticar MedFacts Consumer Leaflet (Wolters Kluwer)


• Ticarcillin Disodium and Clavulanate Potassium Monograph (AHFS DI)

Compare Ticar with other medications

• Bone infection
• Febrile Neutropenia
• Intraabdominal Infection
• Joint Infection
• Kidney Infections
• Pelvic Inflammatory Disease
• Peritonitis
• Pneumonia
• Septicemia
• Skin Infection
• Urinary Tract Infection

Where can I get more information?

• Your doctor or pharmacist has information about ticarcillin written for health professionals that you may read.

See also: Ticar side effects (in more detail)

Tanafed DP Suspension

Pronunciation: dex-klor-fen-IR-a-meen/soo-doe-e-FED-rin
Generic Name: Dexchlorpheniramine/Pseudoephedrine
Brand Name: Duotan PD and Tanafed DP

Tanafed DP Suspension is used for:

Relieving congestion, sneezing, runny nose, nasal or throat itching, and itchy or watery eyes caused by colds, hay fever, or other allergic conditions. It may also be used for other conditions as determined by your doctor.

Tanafed DP Suspension is an antihistamine and decongestant combination. The antihistamine works by blocking the action of histamine, which helps reduce symptoms such as watery eyes and sneezing. The decongestant promotes sinus and nasal drainage, relieving congestion and pressure.

Do NOT use Tanafed DP Suspension if:

• you are allergic to any ingredient in Tanafed DP Suspension


• you are also taking droxidopa or sodium oxybate (GHB), or you have taken furazolidone or a monoamine oxidase (MAO) inhibitor (eg, phenelzine) within the last 14 days


• you have severe high blood pressure, severe heart blood vessel disease, rapid heartbeat, or severe heart problems


• you are unable to urinate or are having an asthma attack

Contact your doctor or health care provider right away if any of these apply to you.

Before using Tanafed DP Suspension:

Some medical conditions may interact with Tanafed DP Suspension. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a fast, slow, or irregular heartbeat


• if you have a history of asthma, lung problems (eg, emphysema), heart problems, blood vessel problems, ulcer, blockage of the stomach or intestines, difficulty urinating, blockage of the bladder, an overactive thyroid, diabetes, seizures, stroke, glaucoma, increased pressure in the eye, high blood pressure, adrenal gland problems, an enlarged prostate or other prostate problems, or trouble sleeping

Some MEDICINES MAY INTERACT with Tanafed DP Suspension. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Furazolidone, MAO inhibitors (eg, phenelzine), or tricyclic antidepressants (eg, amitriptyline) because side effects, such as severe headaches, high fever, and high blood pressure, may occur


• Digoxin or droxidopa because side effects, such as irregular heartbeat or heart attack, may occur


• Urinary alkalinizers (eg, sodium bicarbonate) because side effects of Tanafed DP Suspension may be increased


• Sodium oxybate (GHB) because side effects, such as severe drowsiness, may occur


• Bromocriptine or hydantoins (eg, phenytoin) because the risk of side effects and toxic effects may be increased by Tanafed DP Suspension


• Guanethidine, guanadrel, mecamylamine, methyldopa, or reserpine because effectiveness may be decreased by Tanafed DP Suspension

This may not be a complete list of all interactions that may occur. Ask your health care provider if Tanafed DP Suspension may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Tanafed DP Suspension:

Use Tanafed DP Suspension as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Tanafed DP Suspension may be taken with or without food. If stomach upset occurs, take with food to reduce stomach irritation.


• Shake well before using.


• Use a measuring device marked for medicine dosing. Ask your pharmacist for help if you are unsure of how to measure your dose.


• If you miss a dose of Tanafed DP Suspension and you are taking it regularly, take it as soon as possible. If several hours have passed or if it is nearing time for the next dose, do not double the dose to catch up, unless advised by your health care provider. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Tanafed DP Suspension.

Important safety information:

• Tanafed DP Suspension may cause drowsiness, dizziness, or blurred vision. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Tanafed DP Suspension. Using Tanafed DP Suspension alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.


• Avoid drinking alcohol or taking other medications that cause drowsiness (eg, sedatives, tranquilizers) while taking Tanafed DP Suspension. Tanafed DP Suspension will add to the effects of alcohol and other depressants. Ask your pharmacist if you have questions about which medicines are depressants.


• If you have trouble sleeping, ask your doctor or pharmacist about the best time of day to take Tanafed DP Suspension.


• If you are scheduled for allergy skin testing, do not take Tanafed DP Suspension for several days before the test because it may decrease your response to the skin tests.


• Tanafed DP Suspension contains dexchlorpheniramine and pseudoephedrine. Before you begin taking any new prescription or nonprescription medicine, read the ingredients to see if it also contains dexchlorpheniramine or pseudoephedrine. If it does or if you are uncertain if it does, contact your doctor or pharmacist.


• Do not exceed the recommended dose or take Tanafed DP Suspension for longer than prescribed without checking with your doctor.


• Do not take diet or appetite control medicines while you are taking Tanafed DP Suspension without checking with your doctor.


• Use Tanafed DP Suspension with caution in the ELDERLY because they may be more sensitive to its effects.


• Tanafed DP Suspension is not recommended for use in CHILDREN younger than 6 years of age. Safety and effectiveness in this age group have not been confirmed.


• Caution is advised when using Tanafed DP Suspension in CHILDREN because they may be more sensitive to its effects, especially excitability.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, discuss with your doctor the benefits and risks of using Tanafed DP Suspension during pregnancy. Tanafed DP Suspension is excreted in breast milk. Do not breast-feed while taking Tanafed DP Suspension.

Possible side effects of Tanafed DP Suspension:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; diarrhea; dizziness; drowsiness; dry mouth, throat, or nose; excitability; headache; loss of appetite; nausea; nervousness; restlessness; trouble sleeping; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blurred vision; chest pain; decreased coordination; difficulty urinating; fast or irregular heartbeat; fever; hallucinations; ringing in the ears; seizures; severe dizziness or drowsiness; severe nervousness, anxiety, or restlessness; tremors; unusual weakness.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Tanafed DP side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include bluish-colored skin; difficulty breathing; dilated pupils; fast or irregular heartbeat; fever; flushing; hallucinations; mental or mood changes; seizures; severe drowsiness or dizziness; severe excitability; severe nausea or vomiting; sweating; tremors; trouble breathing.

Proper storage of Tanafed DP Suspension:

Store Tanafed DP Suspension at room temperature, between 68 and 77 degrees F (20 and 25 degrees C), in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Tanafed DP Suspension out of the reach of children and away from pets.

General information:

• If you have any questions about Tanafed DP Suspension, please talk with your doctor, pharmacist, or other health care provider.


• Tanafed DP Suspension is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Tanafed DP Suspension. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Tanafed DP resources

• Tanafed DP Side Effects (in more detail)
• Tanafed DP Use in Pregnancy & Breastfeeding
• Tanafed DP Drug Interactions
• Tanafed DP Support Group
• 0 Reviews for Tanafed DP - Add your own review/rating

Compare Tanafed DP with other medications

• Nasal Congestion

Prolixin Decanoate

fluphenazine decanoate

Dosage Form: Injection, USP

Prolixin Decanoate Description

Prolixin Decanoate is the decanoate ester of a trifluoromethyl phenothiazine derivative. It is a highly potent behavior modifier with a markedly extended duration of effect. Prolixin Decanoate is available for intramuscular or subcutaneous administration, providing 25 mg fluphenazine decanoate per mL in a sesame oil vehicle with 1.2% (w/v) benzyl alcohol as a preservative. At the time of manufacture, the air in the vials is replaced by nitrogen.

Prolixin Decanoate - Clinical Pharmacology

The basic effects of fluphenazine decanoate appear to be no different from those of fluphenazine hydrochloride, with the exception of duration of action. The esterification of fluphenazine markedly prolongs the drug’s duration of effect without unduly attenuating its beneficial action.

Prolixin Decanoate has activity at all levels of the central nervous system as well as on multiple organ systems. The mechanism whereby its therapeutic action is exerted is unknown.

Fluphenazine differs from other phenothiazine derivatives in several respects: it is more potent on a milligram basis, it has less potentiating effect on central nervous system depressants and anesthetics than do some of the phenothiazines and appears to be less sedating, and it is less likely than some of the older phenothiazines to produce hypotension (nevertheless, appropriate cautions should be observed—see sections on PRECAUTIONS and ADVERSE REACTIONS).

Indications and Usage for Prolixin Decanoate

Prolixin Decanoate (Fluphenazine Decanoate Injection) is a long-acting parenteral antipsychotic drug intended for use in the management of patients requiring prolonged parenteral neuroleptic therapy (e.g., chronic schizophrenics).

Prolixin Decanoate has not been shown effective in the management of behavioral complications in patients with mental retardation.

Contraindications

Phenothiazines are contraindicated in patients with suspected or established subcortical brain damage.

Phenothiazine compounds should not be used in patients receiving large doses of hypnotics.

Prolixin Decanoate (Fluphenazine Decanoate Injection) is contraindicated in comatose or severely depressed states.

The presence of blood dyscrasia or liver damage precludes the use of fluphenazine decanoate.

Fluphenazine decanoate is not intended for use in children under 12 years of age.

Prolixin Decanoate is contraindicated in patients who have shown hypersensitivity to fluphenazine; cross-sensitivity to phenothiazine derivatives may occur.

Warnings

Tardive Dyskinesia

Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with neuroleptic (antipsychotic) drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of neuroleptic treatment, which patients are likely to develop the syndrome. Whether neuroleptic drug products differ in their potential to cause tardive dyskinesia is unknown.

Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of neuroleptic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.

There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if neuroleptic treatment is withdrawn. Neuroleptic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying disease process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

Given these considerations, neuroleptics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic neuroleptic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to neuroleptic drugs, and, 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient on neuroleptics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.

(For further information about the description of tardive dyskinesia and its clinical detection, please refer to the sections on PRECAUTIONS, Information for Patients and ADVERSE REACTIONS,Tardive Dyskinesia.)

Neuroleptic Malignant Syndrome (NMS)

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias).

The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.

The management of NMS should include 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.

If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.

The use of this drug may impair the mental and physical abilities required for driving a car or operating heavy machinery.

Physicians should be alert to the possibility that severe adverse reactions may occur which require immediate medical attention.

Potentiation of the effects of alcohol may occur with the use of this drug.

Since there is no adequate experience in children who have received this drug, safety and efficacy in children have not been established.

Usage in Pregnancy

The safety for the use of this drug during pregnancy has not been established; therefore, the possible hazards should be weighed against the potential benefits when administering this drug to pregnant patients.

Precautions

General

Because of the possibility of cross-sensitivity, fluphenazine decanoate should be used cautiously in patients who have developed cholestatic jaundice, dermatoses, or other allergic reactions to phenothiazine derivatives.

Psychotic patients on large doses of a phenothiazine drug who are undergoing surgery should be watched carefully for possible hypotensive phenomena. Moreover, it should be remembered that reduced amounts of anesthetics or central nervous system depressants may be necessary.

The effects of atropine may be potentiated in some patients receiving fluphenazine because of added anticholinergic effects.

Fluphenazine decanoate should be used cautiously in patients exposed to extreme heat or phosphorus insecticides.

The preparation should be used with caution in patients with a history of convulsive disorders, since grand mal convulsions have been known to occur.

Use with caution in patients with special medical disorders such as mitral insufficiency or other cardiovascular diseases and pheochromocytoma.

The possibility of liver damage, pigmentary retinopathy, lenticular and corneal deposits, and development of irreversible dyskinesia should be remembered when patients are on prolonged therapy.

Outside state hospitals or other psychiatric institutions, fluphenazine decanoate should be administered under the direction of a physician experienced in the clinical use of psychotropic drugs, particularly phenothiazine derivatives. Furthermore, facilities should be available for periodic checking of hepatic function, renal function, and the blood picture. Renal function of patients on long-term therapy should be monitored; if BUN (blood urea nitrogen) becomes abnormal, treatment should be discontinued.

As with any phenothiazine, the physician should be alert to the possible development of “silent pneumonias” in patients under treatment with fluphenazine decanoate.

Neuroleptic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of neuroleptic drugs. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.

Information for Patients

Given the likelihood that a substantial proportion of patients exposed chronically to neuroleptics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided.

Adverse Reactions

Central Nervous System: The side effects most frequently reported with phenothiazine compounds are extrapyramidal symptoms including pseudoparkinsonism, dystonia, dyskinesia, akathisia, oculogyric crises, opisthotonos, and hyperreflexia. Muscle rigidity sometimes accompanied by hyperthermia has been reported following use of fluphenazine decanoate. Most often these extrapyramidal symptoms are reversible; however, they may be persistent (see below). The frequency of such reactions is related in part to chemical structure: one can expect a higher incidence with fluphenazine decanoate than with less potent piperazine derivatives or with straight-chain phenothiazines such as chlorpromazine. With any given phenothiazine derivative, the incidence and severity of such reactions depend more on individual patient sensitivity than on other factors, but dosage level and patient age are also determinants.

Extrapyramidal reactions may be alarming, and the patient should be forewarned and reassured. These reactions can usually be controlled by administration of antiparkinsonian drugs such as Benztropine Mesylate or intravenous Caffeine and Sodium Benzoate Injection, and by subsequent reduction in dosage.

Tardive Dyskinesia: See WARNINGS. The syndrome is characterized by involuntary choreoathetoid movements which variously involve the tongue, face, mouth, lips, or jaw (e.g., protrusion of the tongue, puffing of cheeks, puckering of the mouth, chewing movements), trunk and extremities. The severity of the syndrome and the degree of impairment produced vary widely.

The syndrome may become clinically recognizable either during treatment, upon dosage reduction, or upon withdrawal of treatment. Early detection of tardive dyskinesia is important. To increase the likelihood of detecting the syndrome at the earliest possible time, the dosage of neuroleptic drug should be reduced periodically (if clinically possible) and the patient observed for signs of the disorder. This maneuver is critical, since neuroleptic drugs may mask the signs of the syndrome.

Other CNS Effects: Occurrences of neuroleptic malignant syndrome (NMS) have been reported in patients on neuroleptic therapy (see WARNINGS, Neuroleptic Malignant Syndrome); leukocytosis, elevated CPK, liver function abnormalities, and acute renal failure may also occur with NMS.

Drowsiness or lethargy, if they occur, may necessitate a reduction in dosage; the induction of a catatonic-like state has been known to occur with dosages of fluphenazine far in excess of the recommended amounts. As with other phenothiazine compounds, reactivation or aggravation of psychotic processes may be encountered.

Phenothiazine derivatives have been known to cause, in some patients, restlessness, excitement, or bizarre dreams.

Autonomic Nervous System: Hypertension and fluctuations in blood pressure have been reported with fluphenazine.

Hypotension has rarely presented a problem with fluphenazine. However, patients with pheochromocytoma, cerebral vascular or renal insufficiency, or a severe cardiac reserve deficiency such as mitral insufficiency appear to be particularly prone to hypotensive reactions with phenothiazine compounds, and should therefore be observed closely when the drug is administered. If severe hypotension should occur, supportive measures including the use of intravenous vasopressor drugs should be instituted immediately. Levarterenol Bitartrate Injection is the most suitable drug for this purpose; epinephrine should not be used since phenothiazine derivatives have been found to reverse its action, resulting in a further lowering of blood pressure.

Autonomic reactions including nausea and loss of appetite, salivation, polyuria, perspiration, dry mouth, headache, and constipation may occur. Autonomic effects can usually be controlled by reducing or temporarily discontinuing dosage.

In some patients, phenothiazine derivatives have caused blurred vision, glaucoma, bladder paralysis, fecal impaction, paralytic ileus, tachycardia, or nasal congestion.

Metabolic and Endocrine: Weight change, peripheral edema, abnormal lactation, gynecomastia, menstrual irregularities, false results on pregnancy tests, impotency in men and increased libido in women have all been known to occur in some patients on phenothiazine therapy.

Allergic Reactions: Skin disorders such as itching, erythema, urticaria, seborrhea, photosensitivity, eczema and even exfoliative dermatitis have been reported with phenothiazine derivatives. The possibility of anaphylactoid reactions occurring in some patients should be borne in mind.

Hematologic: Routine blood counts are advisable during therapy since blood dyscrasias including leukopenia, agranulocytosis, thrombocytopenic or nonthrombocytopenic purpura, eosinophilia, and pancytopenia have been observed with phenothiazine derivatives. Furthermore, if any soreness of the mouth, gums, or throat, or any symptoms of upper respiratory infection occur and confirmatory leukocyte count indicates cellular depression, therapy should be discontinued and other appropriate measures instituted immediately.

Hepatic: Liver damage as manifested by cholestatic jaundice may be encountered, particularly during the first months of therapy; treatment should be discontinued if this occurs. An increase in cephalin flocculation, sometimes accompanied by alterations in other liver function tests, has been reported in patients receiving the enanthate ester of fluphenazine (a closely related compound) who have had no clinical evidence of liver damage.

Others: Sudden, unexpected and unexplained deaths have been reported in hospitalized psychotic patients receiving phenothiazines. Previous brain damage or seizures may be predisposing factors; high doses should be avoided in known seizure patients. Several patients have shown sudden flare-ups of psychotic behavior patterns shortly before death. Autopsy findings have usually revealed acute fulminating pneumonia or pneumonitis, aspiration of gastric contents, or intramyocardial lesions.

Although this is not a general feature of fluphenazine, potentiation of central nervous system depressants (opiates, analgesics, antihistamines, barbiturates, alcohol) may occur.

The following adverse reactions have also occurred with phenothiazine derivatives: systemic lupus erythematosus-like syndrome, hypotension severe enough to cause fatal cardiac arrest, altered electrocardiographic and electroencephalographic tracings, altered cerebrospinal fluid proteins, cerebral edema, asthma, laryngeal edema, and angioneurotic edema; with long-term use—skin pigmentation, and lenticular and corneal opacities.

Injections of fluphenazine decanoate are extremely well tolerated, local tissue reactions occurring only rarely.

Prolixin Decanoate Dosage and Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Prolixin Decanoate (Fluphenazine Decanoate Injection) may be given intramuscularly or subcutaneously. A dry syringe and needle of at least 21 gauge should be used. Use of a wet needle or syringe may cause the solution to become cloudy.

To begin therapy with Prolixin Decanoate the following regimens are suggested:

For most patients, a dose of 12.5 to 25 mg (0.5 to 1 mL) may be given to initiate therapy. The onset of action generally appears between 24 and 72 hours after injection and the effects of the drug on psychotic symptoms becomes significant within 48 to 96 hours. Subsequent injections and the dosage interval are determined in accordance with the patient’s response. When administered as maintenance therapy, a single injection may be effective in controlling schizophrenic symptoms up to four weeks or longer. The response to a single dose has been found to last as long as six weeks in a few patients on maintenance therapy.

It may be advisable that patients who have no history of taking phenothiazines should be treated initially with a shorter-acting form of fluphenazine (see HOW SUPPLIED section for the availability of the shorter-acting fluphenazine hydrochloride dosage forms) before administering the decanoate to determine the patient’s response to fluphenazine and to establish appropriate dosage. For psychotic patients who have been stabilized on a fixed daily dosage of Prolixin Tablets (Fluphenazine Hydrochloride Tablets USP), Prolixin Elixir (Fluphenazine Hydrochloride Elixir USP), or Prolixin Oral Concentrate (Fluphenazine Hydrochloride Oral Solution), conversion of therapy from these short-acting oral forms to the long-acting injectable Prolixin Decanoate may be indicated.

Appropriate dosage of Prolixin Decanoate (Fluphenazine Decanoate Injection) should be individualized for each patient and responses carefully monitored. No precise formula can be given to convert to use of Prolixin Decanoate; however, a controlled multicentered study,* in patients receiving oral doses from 5 to 60 mg fluphenazine hydrochloride daily, showed that 20 mg fluphenazine hydrochloride daily was equivalent to 25 mg (1 mL) Prolixin Decanoate every three weeks. This represents an approximate conversion ratio of 0.5 mL (12.5 mg) of decanoate every three weeks for every 10 mg of fluphenazine hydrochloride daily.

*The Initiation of Long-Term Pharmacotherapy in Schizophrenia: Dosage and Side Effect Comparisons Between Oral and Depot Fluphenazine; N.R. Schooler; Pharmakopsych. 9:159-169, 1976.

Once conversion to Prolixin Decanoate is made, careful clinical monitoring of the patient and appropriate dosage adjustment should be made at the time of each injection.

Severely agitated patients may be treated initially with a rapid-acting phenothiazine compound such as Prolixin Injection (Fluphenazine Hydrochloride Injection USP—see package insert accompanying that product for complete information). When acute symptoms have subsided, 25 mg (1 mL) of Prolixin Decanoate may be administered; subsequent dosage is adjusted as necessary.

“Poor risk” patients (those with known hypersensitivity to phenothiazines, or with disorders that predispose to undue reactions): Therapy may be initiated cautiously with oral or parenteral fluphenazine hydrochloride (see package inserts accompanying these products for complete information). When the pharmacologic effects and an appropriate dosage are apparent, an equivalent dose of Prolixin Decanoate may be administered. Subsequent dosage adjustments are made in accordance with the response of the patient.

The optimal amount of the drug and the frequency of administration must be determined for each patient, since dosage requirements have been found to vary with clinical circumstances as well as with individual response to the drug.

Dosage should not exceed 100 mg. If doses greater than 50 mg are deemed necessary, the next dose and succeeding doses should be increased cautiously in increments of 12.5 mg.

How is Prolixin Decanoate Supplied

Prolixin Decanoate (Fluphenazine Decanoate Injection, USP) is available in 25 mg/mL:

1 mL Unimatic® single dose syringe	NDC 0003-0569-02 Each syringe is supplied with a 20-gauge 1-1/2 inch needle.
5 mL Multiple dose vial	NDC 0003-0569-15 At time of manufacture, the air in the vials is replaced by nitrogen.

Storage

Store at room temperature; avoid freezing and excessive heat. Protect from light.

APOTHECON®

Manufactured by Bristol-Myers Squibb Company

Princeton, NJ 08543 USA

Distributed by Geneva Pharmaceuticals, Inc.

Dayton, NJ 08810 USA

0569DIM-02

1081044A1

Prolixin Decanoate  fluphenazine decanoate  injection

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0003-0569 Route of Administration INTRAMUSCULAR, SUBCUTANEOUS DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength fluphenazine decanoate (fluphenazine) Active 25 MILLIGRAM  In 1 MILLILITER sesame oil Inactive   benzyl alcohol Inactive 12 MILLIGRAM  In 100 MILLILITER

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0003-0569-02 1 mL (MILLILITER) In 1 SYRINGE None 2 0003-0569-15 5 mL (MILLILITER) In 1 VIAL, MULTI-DOSE None

Revised: 08/2006Bristol-Myers Squibb Company

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