Apo-Nevirapine: Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

APO-NEVIRAPINE or APO-NEVIRAPINE XR is a medicine used to treat Human Immunodeficiency Virus (HIV) infection, the virus that causes AIDS (Acquired Immune Deficiency Syndrome).

APO-NEVIRAPINE or APO-NEVIRAPINE XR does not cure HIV or AIDS, and it is not known if it will help you live longer with HIV. People taking APO-NEVIRAPINE or APO-NEVIRAPINE XR may still get infections common in people with HIV (opportunistic infections). Therefore, it is very important that you stay under the care of your doctor.

What it does:

APO-NEVIRAPINE or APO-NEVIRAPINE XR is a type of anti-HIV medicine called a "non-nucleoside reverse transcriptase inhibitor" (NNRTI). It works by lowering the amount of HIV in the blood ("viral load"). You must take APO-NEVIRAPINE or APO-NEVIRAPINE XR with other anti-HIV medicines. When taken with other anti-HIV medicines, APO-

NEVIRAPINE or APO-NEVIRAPINE XR can reduce viral load and increase the number of CD4 cells ("T cells"). CD4 cells are a type of immune helper cell in the blood. APO-NEVIRAPINE or APO-NEVIRAPINE XR may not have these effects in every patient.

APO-NEVIRAPINE or APO-NEVIRAPINE XR is not a cure for HIV infection.

When it should not be used:

• If you are allergic (hypersensitive) to nevirapine or its components (see What the non-medicinal ingredients are).
• If you have a severe liver problem.
• If you have rare hereditary conditions of galactosemia, galactose intolerance, glucose/galactose malabsorption, Lapp lactase deficiency, as APO-NEVIRAPINE contains lactose.
• If you are allergic (hypersensitive) to nevirapine or its components (See What the non-medicinal ingredients are) or have used APO-NEVIRAPINE or APO-NEVIRAPINE XR and had a severe rash with associated symptoms such as malaise, fatigue, muscle/joint aches, blisters, facial edema (facial swelling), oral lesions, conjunctivitis, and/or hepatitis, eosinophilia(a lot of white blood cells called eosinophils in the blood), granulocytopenia(a decrease in white blood cells called granulocytes in the blood), lymphadenopathy (swelling of lymph nodes), and renal dysfunction (kidney not working properly), you must permanently discontinue APO-NEVIRAPINE or APO-NEVIRAPINE XR and seek medical evaluation immediately. (See WARNINGS AND PRECAUTIONS)

• Do not take APO-NEVIRAPINE or APO-

  NEVIRAPINE XR with St. John’s wort (Hypericum perforatum) as it will reduce APO-NEVIRAPINE or APO-NEVIRAPINE XR blood levels.

What the medicinal ingredient is:

APO-NEVIRAPINE or APO-NEVIRAPINE XR tablets contain the active ingredient nevirapine.

What the nonmedical ingredients are:

Apo-Nevirapine Immediate-Release:

Non-medicinal Ingredients (in alphabetical order): Anhydrous lactose, copovidone, crospovidone, magnesium stearate (Intragranular & Extragranular) and microcrystalline cellulose.

Apo-Nevirapine Extended-Release:

Non-medicinal Ingredients (in alphabetical order): hypromellose, magnesium stearate (Intragranular & Extragranular), methylcellulose, and yellow iron oxide.

What dosage forms it comes in:

APO-NEVIRAPINE (nevirapine) comes as an immediate-release white tablet containing 200 mg of nevirapine or as APO-NEVIRAPINE XR (nevirapine), an extended-release yellow tablet containing 400 mg of nevirapine.

WARNINGS AND PRECAUTIONS

Severe, life-threatening, and in some cases fatal liver toxicity, particularly in the first 18 weeks, has been reported in patients treated with nevirapine immediate release tablets, including pregnant women receiving chronic nevirapine immediate release tablets therapy in conjunction with other antiretroviral medication. Female gender and higher CD4 counts at the start of therapy may increase the risk of liver problems (see SIDE EFFECTS AND WHAT TO DO ABOUT THEM).

Severe skin and allergic reactions, including fatal cases have occurred with accompanying symptoms such as severe rash with fever, fatigue, muscle/joint pain, swelling of the face, hepatitis (liver inflammation), blood and kidney problems. If this occurs discontinue nevirapine immediate release tablets or nevirapine extended release tablets and contact your doctor immediately.

In rare cases liver problems have led to liver failure and can lead to a liver transplant or death. Therefore, if you develop any of the following symptoms of liver problems stop taking APO-NEVIRAPINE or APO-NEVIRAPINE XR and call your doctor right away:

• general ill feeling or “flu-like” symptoms
• yellowing skin or whites of your eyes
• tiredness
• dark urine (tea colored)
• nausea (feeling sick to your stomach)
• pale stools (bowel movements)
• lack of appetite

• pain, ache, or sensitivity to touch on your right

  side below your ribs

Your doctor should check you and do blood tests often to check your liver function during the first 18 weeks of therapy. Checks for liver problems should continue regularly during treatment with APO-NEVIRAPINE or APO-NEVIRAPINE XR.

Skin Reactions

Skin rash is the most common side effect of APO-NEVIRAPINE or APO-NEVIRAPINE XR. Most rashes occur in the first 6 weeks of treatment. In a small number of patients, rash can be serious and result in death. Therefore, if you develop a rash with any of the following symptoms, stop using APO-NEVIRAPINE or APO-NEVIRAPINE XR and call your doctor right away:

• general ill feeling or “flu-like” symptoms
• blisters
• fever
• mouth sores
• muscle or joint aches
• swelling of your face
• conjunctivitis (red or inflamed eyes, like “pink-eye”)
• tiredness
• any symptoms of liver problems discussed above

If your doctor tells you to stop treatment with APO-NEVIRAPINE or APO-NEVIRAPINE XR because you have experienced the serious liver or skin reactions described above, never take APO-NEVIRAPINE or APO-NEVIRAPINE XR again.

These are not all the side effects of APO-NEVIRAPINE or APO-NEVIRAPINE XR. See the section SIDE EFFECTS AND WHAT TO DO ABOUT THEM for more information. Tell your doctor if you have any side effects from APO-NEVIRAPINE or APO-NEVIRAPINE XR.

BEFORE you use APO-NEVIRAPINE or APO-NEVIRAPINE XR talk to your doctor or pharmacist:

• If you have or have had any diseases of the liver particularly hepatitis B or C infection;
• If you are pregnant or intend to become pregnant;
• If you are a breast-feeding mother. It is recommended that HIV infected women not breast-feed, to avoid transmission of the virus to the infant;
• If you are taking any medications, including prescription, non-prescription, herbal or homeopathic remedies;
• If you have any allergies to foods or drugs;
• If you are undergoing dialysis.

INTERACTIONS WITH THIS MEDICATION

Drugs that may interact with APO-NEVIRAPINE or APO-NEVIRAPINE XR include:

APO-NEVIRAPINE or APO-NEVIRAPINE XR may change the effect of other medicines, and other medicines can change the effect of APO-NEVIRAPINE or APO-NEVIRAPINE XR. Tell your doctors and pharmacists about all medicines you

take, including non-prescription medicines, vitamins and herbal supplements.

Do not take ketoconazole, rifampin efavirenz, delavirdine, etravirine, rilpivirine, elvitegravir (in combination with cobicistat), or boceprevir with APO-NEVIRAPINE or APO-NEVIRAPINE XR.

Tell your doctor if you take clarithromycin, fluconazole, methadone, rifabutin, indinavir, lopinavir/ritonavir combination, saquinavir or itraconazole.

APO-NEVIRAPINE or APO-NEVIRAPINE XR may not be right for you, or you may need careful monitoring.

You should be aware that APO-NEVIRAPINE or APO-NEVIRAPINE XR may change the effectiveness of oral contraceptives. Therefore oral contraceptives and other hormonal methods of birth control should not be used as a method of contraception in women taking APO-NEVIRAPINE or APO-NEVIRAPINE XR; other methods (barrier) must be used.

PROPER USE OF THIS MEDICATION

Usual dose:

Adult:

Follow the directions exactly as given to you by your doctor or pharmacist regarding the amount and frequency of dosing. The label will usually tell you this information as well. If you are not sure about dosing, ask your doctor or pharmacist.

APO-NEVIRAPINE Immediate-Release Tablets:

As a general guide, swallow one tablet (200 mg) once a day for the first 14 days (this lead-in period should be used because it has been found to lessen the frequency of rash) followed by one 200 mg tablet twice daily as part of a multi-drug treatment program. APO-NEVIRAPINE immediate release tablets can be taken with or without food.

APO-NEVIRAPINE XR Extended-Release Tablets:

Swallow one 200 mg tablet of nevirapine immediate release once daily for the first 14 days to lessen the frequency of rash followed by one 400 mg tablet of APO-NEVIRAPINE XR extended release once daily. The APO-NEVIRAPINE XR extended release tablets should not be broken or chewed. APO-NEVIRAPINE XR extended release tablets can be taken with or without food.

It is important to strictly follow the once daily dose for the first 14 days. Do not start taking the 200 mg APO-NEVIRAPINE twice daily or the 400 mg APO-NEVIRAPINE XR once daily if you have any symptoms of liver problems or skin rash (see SIDE EFFECTS AND WHAT TO DO ABOUT THEM). The manufacturer’s recommended dosage and monitoring for the other administered anti-retroviral drugs should be followed.

Patients switching to APO-NEVIRAPINE XR Extended-Release Tablets:

Patients already on a regimen of nevirapine immediate release tablets 200 mg twice daily in combination with other antiretroviral agents can be switched to APO-NEVIRAPINE XR extended release 400 mg once daily in combination with other antiretroviral agents without a lead-in period of nevirapine immediate release.

Overdose:

In case of drug overdosage, contact a healthcare practitioner (e.g. doctor), hospital emergency department or regional Poison Control Centre, even if there are no symptoms.

Missed Dose:

If you miss a dose: If you forget to take your medicine, take it as soon as you remember. Then continue as before; do not double your next dosage.

If it is almost time for your next dose, do not take the missed dose. Instead, follow your regular dosing schedule by taking the next dose at its regular time.

If you stop taking APO-NEVIRAPINE or APO-NEVIRAPINE XR for more than 7 days, ask your doctor how much to take before you start taking it again. You may need to start with once-a-day 200 mg APO-NEVIRAPINE tablet dosing.

Avoid doing things that can spread HIV infection, as APO-NEVIRAPINE or APO-NEVIRAPINE XR does not stop you from passing HIV infection to others. Do not share needles, other injection equipment or personal items that can have blood or body fluids on them, like toothbrushes and razor blades. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.

This medicine is for you. Never give it to someone else, as it may harm them even if their symptoms are the same as yours.

Take your medications exactly as prescribed by your doctor. Do not change the dose without consulting your doctor.

Do not take any other medication including prescription, nonprescription, herbal or homeopathic remedies without your doctor’s advice. Also, inform any other doctor, dentist or pharmacist you consult that you are taking this medication.

Keep out of reach of children.

If you have any other questions about APO-NEVIRAPINE or APO-NEVIRAPINEXR, contact your doctor or pharmacist.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

APO-NEVIRAPINE or APO-NEVIRAPINE XR can cause serious liver damage and skin reactions that can cause death. Any patients can experience such side effects, but some patients are more at risk than others. See WARNINGS AND PRECAUTIONS.

Other common side effects of APO-NEVIRAPINE or APO-NEVIRAPINE XR include nausea, fatigue, fever, headache, vomiting, diarrhea, abdominal pain, skin rash and itching, myalgia (muscle pain) and arthralgia (joint pain). This list of side effects is not complete. Ask your doctor or pharmacist for more information.

Abnormal liver function test results, decrease in red blood cells or white blood cells called granulocytes, decrease in blood phosphorous, increase in blood pressure and hypersensitivity including severe allergic reaction with facial swelling may also occur.

If you feel unwell in any other way or have any symptoms that you do not understand, you should contact your doctor immediately.

Sleepiness can occur. Do not drive or operate machinery if you become drowsy.

Always tell your doctor or pharmacist about any undesirable effects you experience after taking APO-NEVIRAPINE or APO-NEVIRAPINE XR, even those not mentioned above.

Changes in body fat have been seen in some patients taking antiretroviral therapy. These changes may include increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the trunk. Loss of fat from the legs, arms and face may also happen. The cause and long term health effects of these conditions are not known at this time.

Occasionally, the inactive ingredients of APO-NEVIRAPINE XR extended release tablets may be eliminated in the stool as a soft hydrated mass that looks like a whole tablet. There is no cause for alarm.

Consult your doctor immediately if you experience any symptoms as listed above, or any symptoms that you do not understand.

This is not a complete list of side effects. For any unexpected effects while taking APO-NEVRAPINE or APO-NEVRAPINE XR, contact your doctor or pharmacist.

HOW TO STORE IT

Store APO-NEVIRAPINE or APO-NEVRAPINE XR tablets at normal room temperature (between 15°C and 30°C). As with all medicines, keep APO-NEVIRAPINE or APO-NEVRAPINE XR tightly closed and out of the reach of children. Do not take your medicine after the expiry date shown on the bottle.

REPORTING SUSPECTED SIDE EFFECTS

You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:

• Report online at www.healthcanada.gc.ca/medeffect
• Call toll-free at 1-866-234-2345

• Complete a Canada Vigilance Reporting Form and:

  Fax toll-free to 1-866-678-6789, or Mail to: Canada Vigilance Program Health Canada

  Postal Locator 0701E

  Ottawa, ON K1A 0K9

  Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect™ Canada Web site at www.healthcanada.gc.ca/medeffect

NOTE: Should you require information related to the management of side effects, contact your health professional. The Canada Vigilance Program does not provide medical advice.

MORE INFORMATION

This document plus the full product monograph, prepared for health professionals, can be found at: http://www.apotex.ca/products or by contacting DISpedia, Apotex's Drug Information Service at: 1-800-667-4708. Please visit our website to see if more up-to-date information has been posted.

Last revised: September 11, 2014