Atripla

Atripla may cause the following serious side effects:

• Lactic acidosis (buildup of an acid in the blood)
• Serious liver problems (hepatotoxicity), with liver enlargement (hepatomegaly) and fat in the liver (steatosis)
• "Flare-ups" of hepatitis B virus (HBV) infection
• Serious psychiatric problems
• Kidney problems (including decline or failure of kidney function)
• Changes in bone mineral density (thinning bones)

Common side effects:

• dizziness
• headache
• trouble sleeping
• drowsiness
• trouble concentrating
• unusual dreams 
• rash 
• tiredness
• upset stomach 
• vomiting
• gas
• diarrhea
• changes in body fat
• skin discoloration (small spots or freckles)
• symptoms of infection
• inflammation of the pancreas
• allergic reaction (including swelling of the face, lips, tongue, or throat), shortness of breath, pain, stomach pain, weakness and indigestion

This is not a complete list of Atripla drug interactions. Ask your doctor or pharmacist for more information.

Do not breastfeed if you are taking Atripla. Atripla may pass through the breast milk and cause serious harm to your baby. Also, it is known that the HIV can pass through the breast milk, therefore breastfeeding while on Atripla is not recommended.

If you take too much Atripla call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If Atripla is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

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 performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of efavirenz, emtricitabine, and tenofovir combination in children 12 years of age and older with a body weight of at least 40 kg. However, safety and efficacy have not been established in children younger than 12 years of age.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of efavirenz, emtricitabine, and tenofovir combination in the elderly. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution in patients receiving efavirenz, emtricitabine, and tenofovir combination.

Pregnancy

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.

• Amifampridine
• Amisulpride
• Bepridil
• Carbamazepine
• Cisapride
• Dasabuvir
• Dronedarone
• Elbasvir
• Grazoprevir
• Mesoridazine
• Paritaprevir
• Pimozide
• Piperaquine
• Ritonavir
• Saquinavir
• Sparfloxacin
• St John's Wort
• Terfenadine
• Thioridazine
• Voriconazole
• Ziprasidone

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.

• Alfuzosin
• Amiodarone
• Amitriptyline
• Amprenavir
• Anagrelide
• Apomorphine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Artemether
• Asenapine
• Astemizole
• Atazanavir
• Atovaquone
• Avanafil
• Axitinib
• Azithromycin
• Bedaquiline
• Bexarotene
• Boceprevir
• Bosutinib
• Bupropion
• Buserelin
• Chloroquine
• Chlorpromazine
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clomipramine
• Clozapine
• Cobimetinib
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Dabrafenib
• Daclatasvir
• Darunavir
• Dasatinib
• Deflazacort
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Deutetrabenazine
• Dexamethasone
• Didanosine
• Disopyramide
• Dofetilide
• Dolasetron
• Dolutegravir
• Domperidone
• Donepezil
• Doxepin
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Droperidol
• Ebastine
• Efavirenz
• Enzalutamide
• Eribulin
• Erythromycin
• Escitalopram
• Etravirine
• Famotidine
• Felbamate
• Fingolimod
• Flecainide
• Fluconazole
• Fluoxetine
• Formoterol
• Fosamprenavir
• Foscarnet
• Fosphenytoin
• Galantamine
• Gatifloxacin
• Gemifloxacin
• Ginkgo Biloba
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Histrelin
• Hydroquinidine
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Idelalisib
• Ifosfamide
• Iloperidone
• Imipramine
• Itraconazole
• Ivabradine
• Ketoconazole
• Lapatinib
• Ledipasvir
• Leuprolide
• Levofloxacin
• Levonorgestrel
• Linagliptin
• Lumefantrine
• Maraviroc
• Mefloquine
• Methadone
• Methotrimeprazine
• Metronidazole
• Mifepristone
• Mizolastine
• Moricizine
• Moxifloxacin
• Nafarelin
• Naloxegol
• Nelfinavir
• Netupitant
• Nevirapine
• Nifedipine
• Nilotinib
• Norfloxacin
• Octreotide
• Ofloxacin
• Olanzapine
• Olaparib
• Ondansetron
• Orlistat
• Paliperidone
• Panobinostat
• Papaverine
• Paroxetine
• Pasireotide
• Pazopanib
• Pentamidine
• Perphenazine
• Pimavanserin
• Pipamperone
• Pitolisant
• Ponatinib
• Posaconazole
• Probucol
• Procainamide
• Prochlorperazine
• Proguanil
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Ranolazine
• Ribociclib
• Rifabutin
• Rifampin
• Rifapentine
• Rilpivirine
• Risperidone
• Sertindole
• Sevoflurane
• Simeprevir
• Sirolimus
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sonidegib
• Sorafenib
• Sotalol
• Sulpiride
• Sultopride
• Sunitinib
• Tacrolimus
• Tamoxifen
• Telavancin
• Telithromycin
• Tetrabenazine
• Tizanidine
• Tolterodine
• Tolvaptan
• Toremifene
• Trazodone
• Trimipramine
• Triptorelin
• Ulipristal
• Vandetanib
• Vardenafil
• Velpatasvir
• Vemurafenib
• Venetoclax
• Venlafaxine
• Vilanterol
• Vilazodone
• Vinflunine
• Vorinostat
• Warfarin
• Zotepine
• Zuclopenthixol

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.

• Atorvastatin
• Caspofungin
• Darunavir
• Dienogest
• Diltiazem
• Estradiol
• Ethinyl Estradiol
• Ethynodiol
• Etonogestrel
• Indinavir
• Lopinavir
• Medroxyprogesterone
• Mestranol
• Norgestimate
• Ospemifene
• Pravastatin
• Ritonavir
• Sertraline
• Simvastatin
• Telaprevir
• Tipranavir

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:

• Allergic reaction to efavirenz (eg, Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions), history of—Should not be used in patients with this condition.

• Bone problems (eg, osteopenia), history of or
• Depression, history of or
• Fanconi syndrome (kidney disease), history of or
• Hepatitis B infection, history of or
• Heart rhythm problem (eg, QT prolongation) or
• Kidney failure, acute or
• Liver disease, mild or
• Seizures, history of—Use with caution. May make these conditions worse.

• Kidney disease, moderate or severe or
• Liver disease, moderate or severe—Use is not recommended in patients with these conditions.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Bone problems like bone pain, soft bones, and thin bones have happened with Atripla. This may lead to broken bones. You may need to have a test to check your bones. Talk with your doctor.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• Take calcium and vitamin D as you were told by your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take Atripla (efavirenz, emtricitabine, and tenofovir disoproxil fumarate).
• This medicine is not a cure for HIV. Stay under the care of your doctor.
• This medicine does not stop the spread of diseases like HIV or hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
• This medicine may help the immune system work. If you have an infection that you did not know you had, it may show up when you take this medicine. Tell your doctor right away if you notice any signs of infection like fever, sore throat, weakness, cough, or shortness of breath after you start Atripla.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking this medicine with your other drugs.
• This medicine may rarely cause swollen liver and an acid health problem in the blood. This may be deadly in some cases. The chance may be higher in women, in overweight people, and in people who have taken drugs like this one for a long time. Talk with your doctor.
• A type of abnormal heartbeat (prolonged QT interval) can happen with Atripla. Call your doctor right away if you have a fast heartbeat, a heartbeat that does not feel normal, or if you pass out.
• Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking this medicine.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• If you are able to get pregnant, a pregnancy test will be done to show that you are NOT pregnant before starting Atripla. Talk with your doctor.
• Use birth control that you can trust to prevent pregnancy while taking this medicine and for 3 months after care ends.
• If you get pregnant while taking Atripla or within 3 months after your last dose, call your doctor right away.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take on an empty stomach.
• Take with a full glass of water.
• Taking Atripla at bedtime may help with some side effects.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• It is important that you do not miss or skip a dose of Atripla during treatment.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.
• If you are not sure what to do if you miss a dose, call your doctor.

• Store in the original container at room temperature.
• Keep lid tightly closed.
• Store in a dry place. Do not store in a bathroom.
• 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.

Hypersensitivity

Atripla is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to efavirenz, a component of Atripla.

Contraindicated Drugs

Coadminstration of Atripla with voriconazole is contraindicated. Efavirenz, a component of Atripla, significantly decreases voriconazole plasma concentrations, and coadministration may decrease the therapeutic effectiveness of voriconazole. Also, voriconazole significantly increases efavirenz plasma concentrations, which may increase the risk of efavirenz-associated side effects. Because Atripla is a fixed-dose combination product, the dose of efavirenz cannot be altered [See Clinical Pharmacology (12.3) Tables 4 and 5].

If overdose occurs, the patient should be monitored for evidence of toxicity, including monitoring of vital signs and observation of the patient's clinical status; standard supportive treatment should then be applied as necessary. Administration of activated charcoal may be used to aid removal of unabsorbed efavirenz. Hemodialysis can remove both emtricitabine and tenofovir DF (refer to detailed information below), but is unlikely to significantly remove efavirenz from the blood.

Efavirenz: Some patients accidentally taking 600 mg twice daily have reported increased nervous system symptoms. One patient experienced involuntary muscle contractions.

Emtricitabine: Limited clinical experience is available at doses higher than the therapeutic dose of emtricitabine. In one clinical pharmacology trial single doses of emtricitabine 1200 mg were administered to 11 subjects. No severe adverse reactions were reported.

Hemodialysis treatment removes approximately 30% of the emtricitabine dose over a 3-hour dialysis period starting within 1.5 hours of emtricitabine dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). It is not known whether emtricitabine can be removed by peritoneal dialysis.

Tenofovir DF: Limited clinical experience at doses higher than the therapeutic dose of tenofovir DF 300 mg is available. In one trial, 600 mg tenofovir DF was administered to 8 subjects orally for 28 days, and no severe adverse reactions were reported. The effects of higher doses are not known.

Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%. Following a single 300 mg dose of tenofovir DF, a 4-hour hemodialysis session removed approximately 10% of the administered tenofovir dose.

Atripla is a fixed-dose combination tablet containing efavirenz, emtricitabine, and tenofovir DF. SUSTIVA is the brand name for efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI). EMTRIVA is the brand name for emtricitabine, a synthetic nucleoside analog of cytidine. VIREAD is the brand name for tenofovir DF, which is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate. VIREAD and EMTRIVA are the components of TRUVADA.

Atripla tablets are for oral administration. Each tablet contains 600 mg of efavirenz, 200 mg of emtricitabine, and 300 mg of tenofovir DF (which is equivalent to 245 mg of tenofovir disoproxil) as active ingredients. The tablets include the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. The tablets are film coated with a coating material containing black iron oxide, polyethylene glycol, polyvinyl alcohol, red iron oxide, talc, and titanium dioxide.

Efavirenz: Efavirenz is chemically described as (S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one. Its molecular formula is C14H9ClF3NO2 and its structural formula is:

Efavirenz is a white to slightly pink crystalline powder with a molecular mass of 315.68. It is practically insoluble in water (less than 10 µg/mL).

Emtricitabine: The chemical name of emtricitabine is 5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. Emtricitabine is the (-) enantiomer of a thio analog of cytidine, which differs from other cytidine analogs in that it has a fluorine in the 5-position.

It has a molecular formula of C8H10FN3O3S and a molecular weight of 247.24. It has the following structural formula:

Emtricitabine is a white to off-white crystalline powder with a solubility of approximately 112 mg/mL in water at 25 °C.

Tenofovir DF: Tenofovir DF is a fumaric acid salt of the bis-isopropoxycarbonyloxymethyl ester derivative of tenofovir. The chemical name of tenofovir DF is 9-[(R)-2[[bis[[(isopropoxycarbonyl)oxy]- methoxy]phosphinyl]methoxy]propyl]adenine fumarate (1:1). It has a molecular formula of C19H30N5O10P ∙ C4H4O4 and a molecular weight of 635.52. It has the following structural formula:

Tenofovir DF is a white to off-white crystalline powder with a solubility of 13.4 mg/mL in water at 25 °C.

Clinical Study 934 supports the use of Atripla tablets in antiretroviral treatment-naïve HIV-1 infected patients. Additional data in support of the use of Atripla in treatment- naïve patients can be found in the prescribing information for VIREAD.

Clinical Study 073 provides clinical experience in subjects with stable, virologic suppression and no history of virologic failure who switched from their current regimen to Atripla.

In antiretroviral treatment-experienced patients, the use of Atripla tablets may be considered for patients with HIV-1 strains that are expected to be susceptible to the components of Atripla as assessed by treatment history or by genotypic or phenotypic testing [See Microbiology (12.4)].

Study 934: Data through 144 weeks are reported for Study 934, a randomized, open-label, active-controlled multicenter trial comparing emtricitabine + tenofovir DF administered in combination with efavirenz versus zidovudine/lamivudine fixed-dose combination administered in combination with efavirenz in 511 antiretroviral-naïve subjects. From Weeks 96 to 144 of the trial, subjects received emtricitabine/tenofovir DF fixed-dose combination with efavirenz in place of emtricitabine + tenofovir DF with efavirenz. Subjects had a mean age of 38 years (range 18–80); 86% were male, 59% were Caucasian, and 23% were Black. The mean baseline CD4+ cell count was 245 cells/mm3 (range 2–1191), and median baseline plasma HIV-1 RNA was 5.01 log10 copies/mL (range 3.56–6.54). Subjects were stratified by baseline CD4+ cell count (< or ≥200 cells/mm3), and 41% had CD4+ cell counts <200 cells/mm3. Fifty-one percent (51%) of subjects had baseline viral loads >100,000 copies/mL. Treatment outcomes through 48 and 144 weeks for those subjects who did not have efavirenz resistance at baseline (N=487) are presented in Table 8.

Through Week 48, 84% and 73% of subjects in the emtricitabine + tenofovir DF group and the zidovudine/lamivudine group, respectively, achieved and maintained HIV-1 RNA <400 copies/mL (71% and 58% through Week 144). The difference in the proportion of subjects who achieved and maintained HIV-1 RNA <400 copies/mL through 48 weeks largely results from the higher number of discontinuations due to adverse events and other reasons in the zidovudine/lamivudine group in this open-label trial. In addition, 80% and 70% of subjects in the emtricitabine + tenofovir DF group and the zidovudine/lamivudine group, respectively, achieved and maintained HIV-1 RNA <50 copies/mL through Week 48 (64% and 56% through Week 144). The mean increase from baseline in CD4+ cell count was 190 cells/mm3 in the emtricitabine + tenofovir DF group and 158 cells/mm3 in the zidovudine/lamivudine group at Week 48 (312 and 271 cells/mm3 at Week 144).

Through 48 weeks, 7 subjects in the emtricitabine + tenofovir DF group and 5 subjects in the zidovudine/lamivudine group experienced a new CDC Class C event (10 and 6 subjects through 144 weeks).

Study 073: Study 073 was a 48-week open-label, randomized clinical trial in subjects with stable virologic suppression on combination antiretroviral therapy consisting of at least two NRTIs administered in combination with a protease inhibitor (with or without ritonavir) or a NNRTI.

To be enrolled, subjects were to have HIV-1 RNA <200 copies/mL for at least 12 weeks on their current regimen prior to trial entry with no known HIV-1 substitutions conferring resistance to the components of Atripla and no history of virologic failure.

The trial compared the efficacy of switching to Atripla or staying on the baseline antiretroviral regimen (SBR). Subjects were randomized in a 2:1 ratio to switch to Atripla (N=203) or stay on SBR (N=97). Subjects had a mean age of 43 years (range 22–73 years); 88% were male, 68% were white, 29% were Black or African-American, and 3% were of other races. At baseline, median CD4+ cell count was 516 cells/mm3, and 96% had HIV-1 RNA <50 copies/mL. The median time since onset of antiretroviral therapy was 3 years, and 88% of subjects were receiving their first antiretroviral regimen at trial enrollment.

At Week 48, 89% and 87% of subjects who switched to Atripla maintained HIV RNA <200 copies/mL and <50 copies/mL, respectively, compared to 88% and 85% who remained on SBR; this difference was not statistically significant. No changes in CD4+ cell counts from baseline to Week 48 were observed in either treatment arm.

Take Atripla exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take this medication on an empty stomach at bedtime.

While using Atripla, you may need frequent blood tests. Your liver function may also need to be tested.

This medication can cause you to have a false positive drug screening test. If you provide a urine sample for drug screening, tell the laboratory staff that you are taking Atripla.

Use this medication regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Store in the original container at room temperature, away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

If you have hepatitis B you may develop liver symptoms after you stop taking efavirenz, emtricitabine, and tenofovir, even months after stopping. Your doctor may want to check your liver function for several months after you stop using Atripla.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose symptoms may include uncontrolled muscle movements.

Animal studies have revealed evidence of fetal harm with efavirenz. Efavirenz crosses the placenta in animals and produces fetal blood levels similar to maternal blood levels. Efavirenz may cause fetal harm when used during the first trimester. There are no controlled data in human pregnancy. To monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral therapy, an Antiretroviral Pregnancy Registry (APR) has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: apregistry.com As of July 2014, the APR received prospective reports of about 1000 live births after exposure to efavirenz-containing regimens, over 800 of which were first-trimester exposures. Birth defects were observed in 19 of 825 live births with first-trimester exposure and 3 of 171 live births with second or third trimester exposure. One of these prospective reports with first-trimester exposure was a neural tube defect. Also, a single case of anophthalmia was prospectively reported with first-trimester efavirenz exposure; however, this case included severe oblique facial clefts and amniotic banding, a known association with anophthalmia. There have been 7 retrospective reports of findings consistent with neural tube defects (including meningomyelocele), all in infants of mothers with first-trimester exposure to efavirenz-containing regimens (not including this drug). Two cases (1 prospective, 1 retrospective) with findings consistent with neural tube defects were reported with this drug. Multiple defects (Dandy-Walker syndrome) in a fetus from a spontaneous abortion and neural tube defects in a fetus from a pregnancy terminated during the second trimester have also been reported. Both mothers had first-trimester exposure to efavirenz-containing regimens. Causality could not be clearly established in any of these cases. Pregnancy should be avoided during use of this drug. Barrier contraception should always be used in combination with other methods of contraception (e.g., hormonal). Use of adequate contraception for 12 weeks after drug discontinuation is recommended. Women of childbearing potential should undergo pregnancy testing before starting therapy and should be advised to notify their physician if they become pregnant during therapy. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

This drug should not be used during pregnancy unless there are no alternatives and the benefit outweighs the risk to the fetus. AU TGA pregnancy category: D US FDA pregnancy category: D Comments: -Effective contraception is recommended during therapy and for 12 weeks after the last dose; local protocol should be consulted regarding contraception timing. -If this drug is used during the first trimester of pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.