Rectiv

Dosage Forms And Strengths

Ointment, 0.4% w/w (4 mg /1 g) in 30 g tubes.

Storage And Handling

RECTIV (nitroglycerin) Ointment 0.4% is available in 30 g (NDC 58914-301-80) aluminum tubes with polyethylene screw caps.

Store at 20°-25°C (68°-77°F); excursions permitted between 15°-30°C (59°-86°F). [See USP Controlled Room Temperature].

Keep the tube tightly closed. Use within 8 weeks of first opening.

Manufactured by: PHARBIL Waltrop GmbH, Im Wirrigen 25,45731 Waltrop, Germany. Manufactured for: Aptalis Pharma US, Inc., 100 Somerset Corporate Boulevard, Bridgewater, NJ 08807. Revised: July 2013

Nitroglycerin toxicity is generally mild. The estimated adult oral lethal dose of nitroglycerin is 200 mg to 1,200 mg. Infants may be more susceptible to toxicity from nitroglycerin. Consultation with a poison center should be considered.

Laboratory determinations of serum levels of nitroglycerin and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of nitroglycerin overdose.

No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of nitroglycerin and its active metabolites. Similarly, it is not known which if any of these substances can usefully be removed from the body by hemodialysis. No specific antagonist to the vasodilator effects of nitroglycerin is known, and no intervention has been subject to controlled study as a therapy of nitroglycerin overdose. Because the hypotension associated with nitroglycerin overdose is the result of venodilatation and arterial hypovolemia, prudent therapy in this situation should be directed toward increase in central fluid volume. Passive elevation of the patient's legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary.

The use of epinephrine or other arterial vasoconstrictors in this setting is not recommended.

In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of RECTIV overdose in these patients may be subtle and difficult, and invasive monitoring may be required.

Methemoglobinemia has been rarely reported with organic nitrates. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate arterial PO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.

If methemoglobinemia is present, intravenous administration of methylene blue, 1 to 2 mg/kg of body weight, may be required.

RECTIV®
[REC-tiv]
(Nitroglycerin) Ointment 0.4%

IMPORTANT: For intra-anal use only

Read the Patient Information that comes with RECTIV before you start using the product and each time you get a refill because there may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. If you have any questions about RECTIV, ask your healthcare provider.

What is RECTIV?

RECTIV is a prescription medicine used to treat moderate to severe pain caused by chronic anal fissures. An anal fissure is a tear in the skin lining the anal canal.

RECTIV is not suitable for children and adolescents under the age of 18 years because it has not been assessed in people in this age group.

Who should not use RECTIV?

Do not use RECTIV if you:

• are taking a medicine for erectile dysfunction (male impotence), for example Viagra (sildenafil), Cialis (tadalafil) or Levitra (vardenafil).
• have been told by your doctor that you have severe anemia (low numbers of red blood cells in your blood)
• have increased intracranial pressure or high pressure within your skull e.g. following head trauma or bleeding in your brain
• are allergic to any of the ingredients in RECTIV or if you have had allergic reactions to similar medicines in the past. See the end of this leaflet for a list of ingredients in RECTIV.

What should I tell my healthcare provider before using RECTIV?

Tell your healthcare provider about all your medical conditions, including if you:

• have low blood pressure
• have recently had a heart attack
• have heart or blood vessel disorders
• suffer from migraine or recurrent headaches
• are pregnant or plan to become pregnant. It is not known if RECTIV will harm your unborn baby.
• are breast-feeding or plan to breast-feed. It is not known if the components of RECTIV will harm your child if you breast-feed.

RECTIV may lower your blood pressure. When getting up from a lying or sitting position, you should get up slowly, otherwise you might feel faint.

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements. Other medicines may affect how RECTIV works. RECTIV may also affect how other medicines work.

Specifically, tell your doctor if you are taking any of the following:

• other nitroglycerin containing products
• a medicine for erectile dysfunction (male impotence), for example sildenafil, tadalafil or vardenafil (see the section above 'Who should not use RECTIV')
• medicines used to treat high blood pressure
• are taking aspirin, ergotamine (used to treat migraine) or are receiving tissue-type plasminogen activator (used to help dissolve blood clots formed in blood vessels in the heart, lungs and brain)
• are to be given heparin. If so, close monitoring of your blood will be required as your dose of heparin may need to be altered. Please discuss with your doctor before stopping RECTIV.

How should RECTIV be used?

Use RECTIV exactly as prescribed. See detailed Patient Instructions for Applying RECTIV at the end of this Patient Information leaflet.

Treatment may be continued for up to 3 weeks. If your anal pain does not get better after using RECTIV you should talk to your doctor.

What should I avoid while using RECTIV?

Do not drive or operate machinery immediately after applying RECTIV. If you feel dizzy or lightheaded after applying the ointment do not drive or operate machinery until the dizziness has stopped.

Avoid consuming alcohol while you are being treated with RECTIV as your blood pressure is more likely to be affected if you consume alcoholic beverages.

What are the possible side effects of RECTIV?

RECTIV can cause serious side-effects: Stop using the ointment and seek medical attention immediately if you have an allergic reaction. You may have swelling of the face, lips, tongue or throat, or difficulty breathing.

Common side-effects of RECTIV are:

• Headaches, which can be severe. You could take painkillers for this (such as acetaminophen). If the headaches are unpleasant, you may need to ask your doctor whether you should stop using RECTIV.
• Dizziness, faintness on standing, or light-headedness

These are not all the possible side effects of RECTIV. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store RECTIV?

• Store at 20°-25°C (68°-77°F); excursions permitted between 15°-30°C (59°-86°F). [See USP Controlled Room Temperature].
• Keep the tube tightly closed.
• Use within 8 weeks of first opening.

Keep RECTIV out of the reach of children.

Do not use RECTIV after the expiry date which is stated on the label and carton after 'EXP.' The expiry date refers to the last day of that month.

General information about RECTIV

Medicines are sometimes prescribed for conditions that are not mentioned in Patient Information leaflets. Do not use RECTIV for a condition for which it is not prescribed. Do not give RECTIV to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information leaflet summarizes the most important information about RECTIV. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about RECTIV that is written for health professionals.

For more information call 1-800-472-2634 or visit www.RECTIV.com.

Patient Instructions for Use

When do I apply the ointment?

Apply the ointment every 12 hours exactly as your doctor has told you to.

How do I apply the ointment?

Cover your finger with plastic-wrap, a disposable surgical glove or a finger cot.

Lay the covered finger alongside the 1 inch dosing line marked on the side of the medicine box (see figure below) so that the tip of your finger is at one end of the dosing line. Starting at the tip of the finger, squeeze the ointment onto your finger for the same length marked on the box.

Refer to carton for accurate dosage guide.

Gently insert the finger with the ointment into the anal canal, up to the first finger joint. Carefully smear the ointment around the inner sides of the anal canal. If this cannot be achieved due to pain, application of the ointment should be made directly to the outside of the anus.

What do I do after I have applied the ointment?

Throw away the finger covering in the garbage, out of the reach of children and pets. Wash your hands.

What are the ingredients in RECTIV?

Active ingredient: nitroglycerin

Inactive ingredients: propylene glycol, lanolin, sorbitan sesquioleate, paraffin wax and white petrolatum.

You should not use this medication if you are allergic to nitroglycerin or any other nitrate medication. This includes isosorbide dinitrate (Dilatrate, Isordil, Isochron), isosorbide mononitrate (Imdur, ISMO, Monoket), or nitroglycerin used in a pill form or spray under the tongue, or as a skin patch or ointment (Minitran, Nitrek, Nitro-Bid, Nitro-Dur, Nitrolingual, Nitromist, Nitrostat, Nitro-Time, and others.)

Do not use nitroglycerin rectal if you are taking sildenafil (Viagra, Revatio), avanafil (Stendra), tadalafil (Cialis), or vardenafil (Levitra). Serious, life-threatening side effects can occur if you use nitroglycerin rectal while you are using sildenafil.

You also should not use nitroglycerin rectal if you have: severe anemia (a lack of red blood cells), or a brain injury, hemorrhage, or tumor.

Before using nitroglycerin rectal, tell your doctor if you have congestive heart failure, low blood pressure, glaucoma, liver disease, migraine headaches, or a history of heart attack, stroke, or circulation problems.

Do not use this medication without the advice of a doctor if you have early signs of a heart attack (chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling). Seek emergency medical attention if you have symptoms of a heart attack.

Nitroglycerin rectal can cause severe headaches, which may occur each time you use the medication. Your doctor may recommend treating fever and pain with an aspirin free pain reliever such as acetaminophen (Tylenol). Follow the label directions or your doctor's instructions about how much of this medicine to use.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most common adverse reaction of RECTIV (nitroglycerin) Ointment 0.4% applied to the anal canal is headache.

Headache may be recurrent following each dose. Headaches are typically of short duration and can be treated with an analgesic, e.g. acetaminophen, and are reversible upon discontinuation of treatment.

In Study REC-C-001, a double-blind, placebo-controlled trial in patients with a painful chronic anal fissure, the most frequent ( ≥ 2%) adverse reactions reported were as follows (Table 1):

Table 1: Incidence of Adverse Reactions ( ≥ 2%) in Study REC-C-001

Hypotension

Transient episodes of light-headedness, occasionally related to blood pressure changes, also may occur. Hypotension (including orthostatic hypotension) occurs infrequently, but in some patients may be severe enough to warrant discontinuation of therapy.

Allergic Reactions

Flushing, allergic reactions and application site reactions (including drug rash and exfoliative dermatitis) have been reported rarely.

Methemoglobinemia

In rare cases, therapeutic doses of organic nitrates have caused methemoglobinemia (see OVERDOSAGE).

Read the entire FDA prescribing information for Rectiv (Nitroglycerin)

Nitroglycerin rectal ointment is used to relieve moderate to severe pain caused by chronic anal fissures. An anal fissure is a tear in the skin around the opening for bowel movements, also known as the anus or rectal area. Nitroglycerin belongs to the group of medicines called nitrates. It works to relax the muscles around the anus so there is less pressure in the area.

This medicine is available only with your doctor's prescription.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of nitroglycerin in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of nitroglycerin in the elderly. However, elderly patients are more likely to have unwanted effects such as lightheadedness, dizziness, or fainting, which may require caution and an adjustment in the dose for patients receiving nitroglycerin.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Avanafil
• Riociguat
• Sildenafil
• Tadalafil
• Vardenafil

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alteplase, Recombinant

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acetylcysteine
• Aspirin
• Dihydroergotamine
• Pancuronium

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia, severe or
• Increased pressure in the head from an injury or bleeding—Should not be used in patients with these conditions.

• Congestive heart failure or
• Heart attack, recent or
• Heart or blood vessel disease (eg, cardiomyopathy) or
• Hypotension (low blood pressure) or
• Hypovolemia (low amount of blood)—Use with caution. May cause side effects to become worse.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep the tube tightly closed. Use within 8 weeks of first opening.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.